,title,abstract
0,Cytotoxic T‐lymphocyte escape viral variants: how important are they in viral evasion of immune clearance in vivo?,"Summary: Although viral variants which are not recognized by epitope‐specific cytotoxic T lymphocytes (CTL) have been shown lo arise during a number of persistent virus infections, in many cases their significance remains controversial: it has been argued that the immune response is sufficiently plastic to contain their replication. In this review, we describe the mechanisms by which amino acid changes in viral proteins may affect epitope recognition by virus‐specific CTL, and discuss the viral and immunological basis for the emergence of viral variants bearing such amino acid changes during infection. We then consider the impact that viral variation may have on the host CTL response and its ability to contain virus replication. We argue that the emergence of a viral variant demonstrates that it must have an in vivo replicative advantage, and that as such, the variant must tip the balance between virus replication and immune control somewhat in favor of the virus. Further, we suggest that although the immune response can evolve to recognize new viral epitopes, the CTL generated following such evolution frequently have a reduced ability to contain virus replication. We conclude that this escape mechanism likely does make a significant contribution to persistence/pathogenesis during a number of different virus infections."
1,Fungal Speciation Using Quantitative Polymerase Chain Reaction (QPCR) in Patients With and Without Chronic Rhinosinusitis,"Objectives/Hypothesis: The objectives of this study were to determine the mycology of the middle meatus using an endoscopically guided brush sampling technique and polymerase chain reaction laboratory processing of nasal mucous; to compare the mycology of the middle meatus in patients with sinus disease with subjects without sinus disease; to compare the responses on two standardized quality‐of‐life survey forms between patients with and without sinusitis; and to determine whether the presence of fungi in the middle meatus correlates with responses on these data sets. Study Design: The authors conducted a single‐blind, prospective, cross‐sectional study. Methods: Patients with sinus disease and a control group without sinus disease were enrolled in the study. A disease‐specific, validated Sinonasal Outcomes Test survey (SNOT‐20) was completed by the subjects and a generalized validated Medical Outcomes Short Form 36 Survey (SF‐36) was also completed. An endoscopically guided brush sampling of nasal mucous was obtained from the middle meatus. Fungal specific quantitative polymerase chain reaction (QPCR) was performed on the obtained sample to identify one of 82 different species of fungus in the laboratory. Statistical analysis was used to categorize the recovered fungal DNA and to crossreference this information with the outcomes surveys. Results: The fungal recovery rate in the study was 45.9% in patients with sinus disease and 45.9% in control subjects. Patients with chronic rhinosinusitis had a mean SNOT‐20 score of 1.80 versus the control group mean score of 0.77 (P < .0001). SF‐36 data similarly showed a statistically significant difference between diseased and control populations with controls scoring a mean of 80.37 and patients with chronic rhinosinusitis scoring a mean of 69.35 for a P value of .02. However, no statistical significance could be ascribed to the presence or absence of fungi recovered, the type of fungi recovered, or the possible impact of fungi on the quality‐of‐life survey results. Conclusion: The recovery rate of fungi from the middle meatus of patients with chronic rhinosinusitis and a control population without chronic rhinosinusitis is 45.9% using QPCR techniques. No direct causation with regard to fungal species or presence was proven; however, a species grouping for future studies is proposed based on trends in this data and other reports. Disease‐specific outcomes surveys revealed a statistically significant difference between the two groups."
2,Role of aminopeptidase N (CD13) in tumor‐cell invasion and extracellular matrix degradation,"We have investigated the effect of monoclonal antibodies (MAbs) specific for aminopeptidase N/CD13 on the invasion of human metastatic tumor cells into reconstituted basement membrane (Matrigel). The invasion of human metastatic tumor cells (SN12M renal‐cell carcinoma, HT1080 fibrosarcoma and A375M melanoma) into Matrigel‐coated filters was inhibited by an anti‐CD 13 MAb, WM15, in a concentration‐dependent manner. However, this MAb did not have any effect on tumor‐cell adhesion and migration to the extracellular matrices, which may be involved in tumor‐cell invasion. MAb WM15 inhibited the degradation of type‐IV collagen by tumor cells in a concentration‐dependent manner. We also found that WM15 inhibited hydrolysing activities towards substrates of aminopeptidases in 3 different tumor cells. Since our previous study indicated that bestatin, an aminopeptidase inhibitor, was able to inhibit tumor‐cell invasion, as well as aminopeptidase activities of murine and human metastatic tumor cells, cell‐surface aminopeptidase N/CD13 may be partly involved in the activation mechanism for type‐IV collagenolysis to achieve tumor‐cell invasion, and anti‐CD13 MAb WM15 may inhibit tumor‐cell invasion through a mechanism involving its inhibitory action on the aminopeptidase N in tumor cells."
3,Virulent and attenuated canine distemper virus infects multiple dog brain cell types in vitro,"Canine Distemper Virus (CDV) produces an encephalitis in dogs that varies with viral strain. We have studied the cell tropisms of two virulent strains (CDV‐SH and CDV A75–17) and an attenuated strain, Rockborn (CDV‐RO), in cultured canine brain cells. Infected cell types were identified by double immunofluorescent labeling of specific cell markers and viral antigens. All viral strains studied produced infection in astrocytes, fibroblasts, and macrophages. Neurons were not infected by CDV A75–17 but were rapidly infected by CDV‐SH and CDV‐RO. Multipolar oligodendrocytes were very rarely infected by any of the virus strains. In contrast, a morphologically distinct subset of bipolar oligodendrocytes were commonly infected by CDV‐SH and CDV‐RO. The kinetics of infection in the astrocytes, oligodendrocytes, neurons, and macrophages varied between strains. Both CDV‐SH and CDV‐RO rapidly infected bipolar oligodendrocytes, astrocytes, neurons, and macrophages by 14 days post infection while infection by CDV A75–17 was delayed until after 28–35 days post infection. The differences in the growth kinetics and cell tropisms for some brain cells, exhibited by the three viral strains examined in this in vitro study, may relate to the different CNS symptoms that these strains produce in vivo."
4,Mortality factors affecting the leaf‐mining stages of Phyllonorycter (Lepidoptera: Gracillariidae) on oak and birch: 2. Biology of the parasite species,"Parasitic Hpenoptera attacking Phyllonorycter species mining leaves of oak and birch were studied at a Cheshire locality during 1974. The host developmental stages killed, and attacked, by each parasite species are analysed. Smaller species and males tend to kill earlier Phyllonorycter instars than do larger species and females, and certain of the endoparasites as well as the ectoparasites must discriminate between small hosts which receive haploid eggs and large hosts which receive diploid eggs. Host‐feeding is very widely practised, and facultative hyperparasitism is engaged in by all except the braconids and a few specialized chalcids. The biology of a parasite species generally allows its allocation to one of three groups according to the size of host larva that it attacks, whether it is endoparasitic or ectoparasitic, whether or not the host continues to develop after parasitization, the extent of its hyperparasitic behaviour, its reproductive capacity, and the width of its host range. Different strategies, together with different specific host and habitat preferences, provide the basis for parasite complexes of high species diversity."
5,Mycobacteria and the Skin,
6,Prevalence and Risk Factors for Bacterial Food‐Borne Zoonotic Hazards in Slaughter Pigs: A Review,"The Hygiene Package and Regulation EC‐2160/2003 require information flow from farm to slaughterhouse to enhance European consumers protection in a ‘farm to fork’ approach. This obligation especially concerns food‐borne zoonotic hazards transmitted to humans through pork consumption, such as thermophilic Campylobacter spp., Listeria monocytogenes, Salmonella enterica and Yersinia enterocolitica. Prevalence estimates of these four hazards are affected by the sampling strategy and diagnostic procedure. Individual prevalence estimates for pig carriage (from digestive contents or lymph nodes collected at slaughterhouse) were higher than individual prevalence estimates for pig shedding (from faeces). Among risk factors described in the literature, poor pen cleaning and disinfection after pig departure to slaughterhouse and poor bio‐security measures are of major significance. Moreover, whereas wet feed increases the risk of pig infection by L. monocytogenes, dry feed is a risk factor for Salm. enterica. Mixing batches of pigs, notably in fattening herds, represents a risk for the transmission of Salm. enterica and Y. enterocolitica. Whereas small herds are more infected by thermophilic campylobacters and Y. enterocolitica, higher prevalence of Salmonella is observed in large herds due to a more frequent mixing of batches. Antibiotic treatment during the finishing period increases the risk of transmission of Salm. enterica. The forenamed elements should be taken into account to characterize farms in a risk assessment approach and to improve zoonotic hazard management in the pork food chain."
7,Coronavirus y radiología. Consideraciones sobre la crisis,
8,Scalp Verruca from Barber Clippers: an Epidemiologic Assessment of a Common Fomite,
9,Inactivation of interleukin‐8 by aminopeptidase N (CD13),"Aminopeptidase (APN) was found to degrade interleukin‐8 (IL‐8) and inactivate its chemotactic activity. The chemotactic activity of IL‐8 was decreased by APN or neutrophil plasma membranes dose‐ and time‐dependently. The chemotactic activity was not inactivated in the presence of bestatin or WM15 monoclonal antibody. The expression of IL‐8 was measured by flow cytometry. On lipopolysaccharide (LPS) stimulation, IL‐8 expression increased for 60 min and then decreased markedly. In contrast, on treatment with LPS and bestatin, the expression of IL‐8 increased continuously for at least 120 min. These results suggest that the expression and release of IL‐8 from phagocytic cells are regulated by the proteolytic effect of APN on IL‐8. J. Leukoc. Biol. 57: 129–134; 1995."
10,Rat tracheal organ culture supports replication of parainfluenza 1 (6/94) virus and promotes 6/94 virus rescue from latently infected human brain cells,"Rat tracheal organ culture (TOC) supported replication of parainfluenza 1 (6/94) virus. Cell‐associated and cell‐free viruses were found after primary infection of TOC. In contrast to other mammalian systems, rat TOC was capable of maintaining 6/94 virus infectivity after primary infection. Rat TOC may be considered a potential indicator system that could be used to detect virus latent in human tissue."
11,Acute Respiratory Tract Infection in Daycare Centers for Older Persons,"OBJECTIVE: To evaluate the rate of specific pathogens and clinical syndromes associated with acute respiratory tract infections (ARTI) in frail older persons attending daycare. DESIGN: Prospective descriptive study, without intervention. SETTING: Two sites of a senior daycare program providing all‐inclusive care for the older persons in Rochester, New York. PARTICIPANTS: Staff members and participants of the daycare. MEASUREMENTS: Demographic, medical, and physical findings were collected from older subjects at baseline and while ill with respiratory illnesses. Nasopharyngeal specimens for viral and Chlamydia culture and sputum for bacterial culture were obtained from subjects when ill. Acute and convalescent sera were also collected with each illness and examined for viral, chlamydial, and mycoplasma infection. MAIN RESULTS: One hundred sixty‐five illnesses were documented in 165 older daycare participants as well as 113 illnesses among 67 staff members during the 15‐month study. The rate of ARTI in the elderly group was 10.8 per 100 person months. The most common etiologies in both the staff and elderly participants were respiratory syncytial virus (RSV), Influenza A, and coronavirus. The etiologies of illnesses in the staff compared with those in elderly group were similar except that bacterial infections were significantly more common among the elderly (7% vs. 0, P = 0.05). Multiple pathogens were found to cocirculate within centers, and no clear outbreak of a predominant organism was noted. Cough and nasal congestion characterized most illnesses. The elderly experienced significantly more cough, dyspnea, and sputum production than did the staff. There were 10 hospitalizations related to respiratory infections and four deaths during the acute illness among the elderly group and none in staff. CONCLUSIONS: Acute respiratory infections are a common occurrence in both the staff and participants of a senior daycare center and are the cause of substantial morbidity in frail older persons."
12,Evaluation of a new enzyme‐linked immunosorbent assay (ELISA) in the diagnosis of rhinovirus infection,"This study describes the evaluation of a newly developed ELISA for the direct detection of rhinovirus antigens in nasal washings. Of 54 volunteers inoculated with 100 TCID(50) of human rhinovirus type 2 (HRV‐2), 50 (96.6%) and 32 (59%) excreted antigen and virus on at least 1 of 3 days investigated, respectively. Thirty‐three (61%) had significant rises in rhinovirus‐specific IgA by ELISA. Twelve (22%) developed symptoms of colds. Generally the ELISA detected antigen more frequently in volunteers later in the course of infection and provided evidence of infection in a higher proportion of asymptomatic compared with symptomatic volunteers. On the other hand, virus isolation detected virus more frequently earlier in the course of infection and in a higher proportion of symptomatic compared with asymptomatic volunteers. We conclude that rhinovirus antigen detection by ELISA is a simple, rapid, sensitive, and practical test to diagnose a rhinovirus infection and potentially a viable alternative to virus isolation."
13,"Morphometric patterns in Recent and fossil penguins (Aves, Sphenisciformes)","A total of 622 skin specimens, 527 skeletons, and myological data compiled by Schreiweis (1972) were used to investigate morphometric patterns within and among the 18 Recent species of Spheniscidae, and to compare the family with a fighted species, the common diving‐petrel (Pelecanoides urinator), considered by some authorities to be similar to the flighted ancestor of penguins. Fossil penguins also were studied using measurements from 111 skeletal elements representing 18 species. Most external and skeletal measurements follow interspecific rankings in body mass; the latter span a 30‐fold range from 1 kg in Eudyptula minor to 30 kg in Aptenodytes forsteri. Flighted Pelecanoides is only one‐tenth the mass of the smallest spheniscid. Wing areas and body masses of penguins maintain approximate geometric similitude among species; the allometric coefficient is 0.62 ± 0.04. Several skeletal elements are less derived in conformation in the fossil penguins than in modern confamilials. Despite great variation in the lengths of wing and leg skeletons, penguins show relative consistency in proportions of wing elements; pelvic proportions were more variable within the Spheniscidae. Proportions within both limbs are distinctly different from those of Pelecanoides. Analysis of correlation structures within species of penguin revealed three major subsets of skeletal variables that are highly intercorrelated: trunk‐skull lengths, appendicular‐trunk widths, and appendicular lengths. Within these groups, measurements tend to separate by anatomical region and, to a lesser degree, by limb. Canonical analysis of skin and skeletal measurements revealed groupings of spheniscids on the basis of size and relatively complex shape variables. Cluster analyses of taxa on the canonical variates confirmed the similarity of congeners in Eudyptes, Eudyptula and Spheniscus; species of Aptenodytes and, to a lesser degree, Pygoscelis, are more heterogeneous. A cluster analysis of principal components of myological measurements tabulated by Schreiweis (1972) corresponded closely with phenetic groupings using external and skeletal variables. A canonical contrast between spheniscids and Pelecanoides indicated that the families differ in a relatively complex skeletal dimension that only in part reflects overall size. Multivariate assessment of sexual dimorphism in external and skeletal variables indicated that: Eudyptula is least dimorphic; Aptenodytes, Eudyptes, Megadyptes and Spheniscus are moderately dimorphic; and Pygoscelis is most dimorphic. Pelecanoides shows comparatively low dimorphism. Among‐species and within‐species first principal components of skeletal measurements (multivariate axes of skeletal ‘size’) differ from one another in their orientation, and both deviate from isometric size. The first principal component for skeletons of Pelecanoides also deviated from isometric size, but the direction of this allometry is fundamentally different from that in penguins. Estimates of body mass for fossil penguins, based on principal components of available skeletal measurements, indicate that fossil species ranged from 3 kg to 81 kg in total mass; the largest fossil species was approximately 2.5 times as massive as the largest extant spheniscid. Much of the morphometric variation in the Spheniscidae is explainable on locomotory, ecological and thermodynamic grounds, and the associated phenetic groupings conform broadly with traditional generic classifications. The evolutionary significance of mensural correlations, allometric trends and differences between fossil and Recent species are discussed, and the need for a phylogenetic analysis of this highly specialized family of winged‐propelled diving birds is stressed."
14,Introduction: why don't HIV/AIDS policies work?,
15,"21st Annual Symposium 25–27 September 2008 Rhodes, Greece Programme of the 21st annual meeting on: Peripheral Nerve, Neuromuscular and Muscle Disease",
16,Studies of an outbreak of acute hepatitis A: II. Antibody changes to cytomegalovirus and herpesvirus,The acute and convalescent sera from 14 schoolchildren with acute hepatitis A were tested for antibody changes to 70 viral antigens. Marked decreases were noted in the levels of antibody to cytomegalovirus in 5 of the 14 children and in the levels of antibody to herpesvirus type 1 in 3. No such changes were noted in 9 sex‐ and age‐matched healthy control children from the same classes.
17,European College of Veterinary Internal Medicine‐Companion Animals,
18,Two Nursing Home Outbreaks of Respiratory Infection with Legionella sainthelensi,"OBJECTIVE: To describe outbreaks of infection caused by Legionella sainthelensi occurring in older residents of two nursing homes and to determine risk factors for the development of infection. DESIGN: Descriptive epidemiology and a case‐control study. SETTING: Two nursing homes (140 beds and 254 beds in nursing homes A and B, respectively) located in southern Ontario, Canada, experiencing outbreaks of respiratory tract infection in July and August 1994. SUBJECTS: Case‐residents of the two nursing homes who met clinical and laboratory criteria for Legionella infection. Control‐residents were defined as those who were in the homes during the outbreaks and were asymptomatic. MEASUREMENTS: Active surveillance was conducted in both nursing homes to identify symptomatic residents. Residents with fever or respiratory tract symptoms had nasopharyngeal swabs taken for viral antigen detection and culture, urine for Legionella antigen detection, and acute and convalescent serology for viruses, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella. Chest X‐rays were performed, and an attempt was made to obtain blood and sputum cultures. Water samples from shower heads, faucets, and air conditioning units were collected for Legionella culture and polymerase chain reaction (PCR) assay. A case‐control study was done to assess possible risk factors for legionellosis. RESULTS: Twenty‐nine cases — 17 in nursing home A; 12 in nursing home B — were identified. Four (14%) case‐residents had documented pneumonia and four case‐residents died. Univariate analysis revealed that a history of stroke (odds ratio (OR) 2.3 (95% CI, 1.0–5.3)), eating pureed food (OR 4.6 (95% CI, 1.6–12.7)), and having fluids administered with medication (OR 2.5 (95% CI, 1.0–5.9)) were significant risk factors. Cases were less likely to wear dentures (OR .4 (95% CI, .2‐.9)) or to eat solid food (OR .3, (95% CI, .1‐.6)). Only eating pureed food remained significant in a multivariable analysis (OR 4.6 (95% CI, 1.6–13.0, P = .01)). CONCLUSION: This report describes outbreaks of legionellosis in two nursing homes, representing the first reported outbreaks of infection caused by Legionella sainthelensi. The association with illness of dietary characteristics indicative of swallowing disorders suggests that aspiration was the most likely mode of infection. The diagnosis of legionellosis should be considered during outbreaks of respiratory infection in nursing homes. J Am Geriatr Soc 47:547–552, 1999."
19,Localization of rhinovirus replication in vitro with in situ hybridization,"To facilitate understanding of human rhinovirus (HRV) pathogenesis, methods were developed for detection of HRV infection in vitro using in situ hybridization (ISH). HRV‐14 RNA probes and oligonucleotide probes representing conserved sequences in the 5′‐non‐translated region were labeled with (35)S and used to detect infected HeLa or WI‐38 strain human embryonic lung cells in cytological preparations. ISH was shown to be specific for detection of HRV on a single‐cell basis. Subsequently, in human nasal polyps infected in vitro, both oligonucleotide‐ and riboprobes produced a strong signal in association with ciliated epithelial cells. In human adenoids infected in vitro, a signal was observed in nonciliated epithelial cells. This study shows that HRV replicates in ciliated cells in the epithelium of human nasal polyps infected in vitro, and the presence of viral RNA in non‐ciliated cells of the human adenoid infected in vitro suggests that other cell types may also support rhinovirus replication."
20,Role of the golgi apparatus in cellular pathology,"The Golgi apparatus response to pathological disorders is predominantly as an intermediary component of membrane biogenesis where it is involved in processing, sorting and secretion of materials via secretory granules, and in the formation of lysosomes. A common initial response of the Golgi apparatus to any stress is an alteration or cessation of secretory activity. In the transformed cell, the Golgi apparatus is altered both morphologically and biochemically, suggesting a shift from a secretory to a membrane‐generating mode of functioning. However, since fewer or less well‐developed Golgi apparatus are frequently found in transformed cells, analytical methods of membrane isolation developed for normal tissues may not always yield equivalent results when applied to tumors. Cell surface alterations characteristic of malignant cells may result from modifications occurring at the level of the Golgi apparatus. Some lysosomal dysfunctions may result from underglycosylation of acid hydrolases by the Golgi apparatus. The use of cell‐free systems between endoplasmic reticulum and Golgi apparatus or within Golgi apparatus cisterane is providing a new approach to the elucidation of the role of the Golgi apparatus in normal as well as pathological states."
21,CHILDHOOD ASTHMA IN BRISBANE: EPIDEMIOLOGICAL OBSERVATIONS,"Analysis of hospital admissions for 20 years suggests that there has been an increase in childhood asthma in Brisbane. The characteristic seasonal pattern of asthma with waves in autumn and spring is evident from the second year of age and continues into adult life. It has not been explained, although respiratory infections, allergens and cold changes probably contribute to it. Unlike adults, children shown an increase in asthma in February‐March, ascribed to infections spread at school. Maximal asthma is associated with a mean temperature of 20–21°C. This may be optimal for the production of allergens. Further viral studies of asthmatic attacks are desirable."
22,IDENTIFICATION OF SEEDS FROM VARIOUS SPECIES OF STROPHANTHUS,"In a search for differential specific characters, the outer epidermis of the testa from Strophanthus seeds of 15 species has been examined. A “trichome index” has been defined, and the method of its determination described. It enabled the species studied to be divided into six groups."
23,A novel method for determination of inorganic oxyanions by electrospray ionization mass spectrometry using dehydration reactions,"Novel methods for the determination of inorganic oxyanions by electrospray (ES) ionization mass spectrometry have been developed using dehydration reactions between oxyanions and carboxylic acids at the ES interface. Twelve oxyanions (VO(3) (−), CrO(4) (2−), MoO(4) (2−), WO(4) (2−), BO(3) (3−), SiO(3) (2−), SiO(4) (4−), AsO(4) (4−), AsO(2) (−), SeO(4) (2−), SeO(3) (2−) and NO(2) (−)), out of 16 tested, reacted with at least one of four aminopolycarboxylic acids, i.e. iminodiacetic acid (IDA), nitrilotriacetic acid (NTA), trans‐1,2‐diaminocyclohexane‐N,N,N′,N′‐tetraacetic acid and triethylenetetramine‐N,N,N′,N″,N′″,N′″‐hexaacetic acid, at the ES interface to produce the dehydration products that gave intense mass ion responses, sufficient for trace analysis. As examples, trace determinations of Cr(VI) and silica in water samples were achieved after online ion exchange chromatography, where the dehydration product of CrO(4) (2−) and NTA (m/z 290) and that of SiO(4) (4−) and IDA (m/z 192) were measured. The limits of detection of the respective methods were 17 nM (0.83 ng Cr/ml) for Cr(VI) and 0.17 μM (4.8 ng Si/mL) for SiO(4) (4−). Copyright © 2016 John Wiley & Sons, Ltd."
24,Viral Respiratory Infections in the Institutionalized Elderly: Clinical and Epidemiologic Findings,"OBJECTIVE: To prospectively evaluate the incidence and impact of viral respiratory infection in the institutionalized elderly during a winter season. DESIGN: Prospective descriptive study, without intervention. METHOD: Patients with respiratory illnesses were evaluated by a directed history and physical examination. Nasopharyngeal secretions for viral culture were obtained, and acute and convalescent serum samples were obtained for analysis. Serologic evidence of infection with respiratory syncytial virus (RSV) and parainfluenza were determined by enzyme immunoassay (EIA), and influenza by hemagglutination‐inhibition assay and EIA. SETTING: A 591‐bed nursing home. PARTICIPANTS: Residents with signs or symptoms of acute respiratory illness (nasal congestion, pharyngitis, cough, wheezing, or respiratory difficulty) were eligible for study. RESULTS: A viral etiology was documented in 62 out of 149 illnesses (42%). RSV was the most common virus associated with illness; it was documented in 27% of respiratory illnesses, followed by rhinovirus (9%), parainfluenza (6%), and influenza (1%). RSV was associated with significantly more severe disease when compared with rhinovirus. Clustering of specific viral infections occurred, suggesting nosocomial transmission. CONCLUSIONS: Viruses are an important cause of acute respiratory infections in the institutionalized elderly during the winter months."
25,A novel real‐time PCR system for simultaneous detection of human viruses in clinical samples from patients with uncertain diagnoses,"A novel simultaneous detection system for human viruses was developed using a real‐time polymerase chain reaction (PCR) system to identify causes of infection in clinical samples from patients with uncertain diagnoses. This system, designated as the “multivirus real‐time PCR,” has the potential to detect 163 human viruses (47 DNA viruses and 116 RNA viruses) in a 96‐well plate simultaneously. The specificity and sensitivity of each probe–primer set were confirmed with cells or tissues infected with specific viruses. The multivirus real‐time PCR system showed profiles of virus infection in 20 autopsies of acquired immunodeficiency syndrome patients, and detected frequently TT virus, cytomegalovirus, human herpesvirus 6, and Epstein–Barr virus in various organs; however, RNA viruses were detected rarely except for human immunodeficiency virus‐1. Pathology samples from 40 patients with uncertain diagnoses were examined, including cases of encephalitis, hepatitis, and myocarditis. Herpes simplex virus 1, human herpesvirus 6, and parechovirus 3 were identified as causes of diseases in four cases of encephalitis, while no viruses were identified in other cases as causing disease. This multivirus real‐time PCR system can be useful for detecting virus in specimens from patients with uncertain diagnoses. J. Med. Virol. 83:322–330, 2011. © 2010 Wiley‐Liss, Inc."
26,Nitrogen fixing bacteria in the family Acetobacteraceae and their role in agriculture,"For centuries, the Acetobacteraceae is known as a family that harbors many species of organisms of biotechnological importance for industry. Nonetheless, since 1988 representatives of this family have also been described as nitrogen fixing bacteria able to plant growth promotion by a variety of mechanisms. Nitrogen fixation is a biological process that guarantees that the atmospheric N(2) is incorporated into organic matter by several bacterial groups. Most representatives of this group, also known as diazotrophic, are generally associated with soil rhizosphere of many plants and also establishing a more specific association living inside roots, leaves, and others plants tissues as endophyte. Their roles as plant growth‐promoting microorganisms are generally related to increase in plant biomass, phosphate and other mineral solubilization, and plant pathogen control. Here, we report many of these plant growth‐promoting processes related to nitrogen fixing species already described in Acetobacteraceae family, especially Gluconacetobacter diazotrophicus and their importance to agriculture. In addition, a brief review of the state of art of the phylogenetics, main physiological and biochemical characteristics, molecular and functional genomic data of this group of Acetobacteraceae is presented."
27,Development and evaluation of a real‐time nucleic acid sequence based amplification assay for rapid detection of influenza A,"The development and introduction of effective treatment for influenza A in the form of neuraminidase inhibitors have made the rapid diagnosis of infection important especially in high‐risk populations. The aim of this study was to develop a real‐time nucleic acid sequenced based amplification (NASBA) using a molecular beacon that could detect a wide range of influenza A subtypes and strains in a single reaction by targeting a conserved region of the influenza genome, and to evaluate its sensitivity and specificity against traditional laboratory techniques on a range of clinical samples usefulness during the 2003/2004 influenza season. The results demonstrated the assay to be highly sensitive and specific, detecting <0.1 TCID(50) of virus stock. Three hundred eighty‐nine clinical samples were tested in total from two patient groups. Overall, the real‐time NASBA assay detected 64% (66/103) more influenza positive samples than cell culture and direct immunofluorescence (IF) and, therefore, was shown to be more sensitive in detecting influenza A in a wide range of respiratory samples than traditional methods. In conclusion, the real‐time influenza A assay demonstrated clinical usefulness in both hospital and community populations. J. Med. Virol. 74:619–628, 2004. © 2004 Wiley‐Liss, Inc."
28,Oxidation of N‐heterocyclics: A green approach,"[Chemical structure: see text] Environmentally benign oxidation methods satisfy the postulates of green chemistry. Heterocyclic Noxides have applications in synthetic organic chemistry, chemotherapy and agrochemicals. Synthesis of Noxides using green oxidants will be attractive over the conventional methods. The presence of the N‐oxide group in the azine ring makes it more subject to electrophilic and nucleophilic attack and substantially expands the synthetic approaches for the modification of nitrogen‐containing heterocyclics. That is the reason for the increasing interest in the chemistry of heterocyclic N‐oxides. Some reactions adopted for oxidation of N‐heterocyclics have been discussed. Stereochemical and spectroscopic aspects have been mentioned. It will be advantageous if anchored catalysts are employed for industrial exploitation. Several physiochemical aspects of various methods have been discussed."
29,First detection of spring viraemia of carp virus in common carp (Cyprinus carpio L.) affected by a septicaemic disease in Mexico,"Spring viraemia of carp (SVC) is an infectious disease responsible for severe economic losses for various cyprinid species, particularly common carp (Cyprinus carpio carpio). The causative agent is the SVC virus (SVCV), a member of the Sprivivirus genus, Rhabdoviridae family, and a List 1 pathogen notifiable by the World Organization for Animal Health. This study describes the diagnosis of an SVCV pathogen isolated in October 2015 from wild common carp inhabiting a natural lagoon in central Mexico. While neither an epidemic nor fish mortalities were reported, the collected killed specimens exhibited clinical signs of disease (e.g., exopthalmia, moderate abdominal distension and haemorrhaging, as well as internal haemorrhages and adhesions). Histological results of injuries were consistent with the pathology caused by SVCV. This finding was supported by the isolation of a virus in EPC and BF‐2 cells and subsequent RT‐PCR confirmation of SVCV. The phylogenetic analyses of partial SVCV glycoprotein gene sequences classified the isolates into the Ia genogroup. These findings make this the first report of SVCV detection in Mexico, extending the southern geographical range of SVCV within North America. However, since this pathogen was detected in fish inhabiting a natural body of water without tributaries or effluents, it is difficult to estimate the risk of SVCV for other wild/feral cohabitating cyprinid species in the lagoon. The status of this virus is also unknown for other bodies of water within this region."
30,The role of the combination of IL‐2 and TGF‐β or IL‐10 in the generation and function of CD4(+) CD25(+) and CD8(+)regulatory T cell subsets,"Recently, considerable attention has been focused on thymus‐derived CD4(+) regulatory T cells that constitutively express CD25 and have a contact‐dependent, cytokine‐independent mechanism in vitro. However, peripheral CD4(+) and CD8(+) T cells can also be induced to become regulatory T cells. Here we review our studies using the combination of IL‐2 and transforming growth factor β (TGF‐β) to generate regulatory T cell subsets ex vivo, and the work of others using IL‐10 to induce suppressive activity. Under certain conditions, the autocrine effects of TGF‐β and IL‐10 induce peripheral T cells to produce immunosuppressive levels of each of these cytokines. This effect of TGF‐β is IL‐2 dependent. Under other conditions IL‐2 and TGF‐β can induce CD4(+) cells to develop potent contact‐dependent, cytokine‐independent regulatory activity. At present, there is considerable confusion concerning the mechanism of action of CD4(+) CD25(+) cells because cytokine‐producing regulatory T cells generated in the periphery can express CD25 and other markers displayed by naturally occurring, thymus‐derived regulatory T cells. We, therefore, propose a nomenclature that identifies thymus‐derived and peripheral regulatory cells, and that also differentiates T regulatory cells from T helper cells. Because T regulatory cells broadly control T helper cell reactivity, the mechanisms that control regulatory cell function are also reviewed. Finally, the potential use of regulatory T cells generated ex vivo as an adoptive immunotherapy for certain autoimmune diseases, to prevent organ graft rejection, or to prevent pathologic host responses to infectious agents is discussed."
31,Diseases of pet rodents,"The main pet rodent species are introduced with some brief notes on their suitability as pets and normal behaviour. The general clinical features of disease are discussed with some emphasis on species variation. The important diseases that occur in the United Kingdom are described under the headings of respiratory disease, diseases of the alimentary tract, diseases of the central nervous system, skin lesions, musculoskeletal disorders, palpable swellings, urinogenital disorders, diseases of pregnancy and injuries."
32,Tolerance of one‐month intranasal interferon,"Under double‐blind conditions, groups of volunteers (68 in total) were allocated at random to take intranasal solutions of placebo or one of three doses of highly purified leucocyte interferon by intranasal spray twice a day for 28 days. The highest dose would have been expected to protect against experimental colds. Treatment was discontinued because of upper respiratory symptoms as often in each of the interferon groups as in the placebo group. However, it was possible to distinguish clinically between “colds” on placebo and low‐dose interferon and “reactions to treatment” on high‐dose interferon. The features of the reactions to treatment were a protracted build‐up of local symptoms and minor epistaxis. None of the volunteers on the high‐dose interferon were thought to have a definite cold, but viruses were isolated from four out of six volunteers on low‐dose interferon who had definite colds. Previous experiments had also shown this dose to be insufficient to protect against experimental rhinovirus challenge. The dose of interferon that appeared to protect against virus infection caused significant unwanted effects. It is essential to find interferon preparations with less inflammatory activity before interferon can be considered for use as a long‐term prophylactic against the common cold."
33,Detection and identification of viruses by electron microscopy,"Electron microscopy can aid in the rapid diagnosis of viral diseases, as it can be performed in a matter of hours, but on a routine basis it should be used in conjunction with other techniques. Initially, the specimen source and patient symptoms should be ascertained, as these will lend suggestions of possible agents while eliminating others; however, this information should not be allowed to prejudice observation in such a way as to cause oversight of an unlikely pathogen. Second, selection of the method of preparation should be based on sample consistency; extraction, debris clarification, concentration, tissue culture amplification, or embedment may be necessary. Finally, false‐positive results must be avoided by differentiating viruses from cell organelles or debris, mycoplasmal or bacterial contamination, and bacteriophages."
34,SHELF‐LIFE EXTENSION OF FRESH FISH — A REVIEW PART I — SPOILAGE OF FISH,
35,Giardia lamblia in children and the child care setting: A review of the literature,
36,Ecto‐enzymes: physiology meets pathology,"Ecto‐enzymes are catalytic membrane proteins with their active sites outside the cell. They include cholinesterase, which inactivates acetylcholine, and angiotensin‐converting enzyme, which converts angiotensin I to biologically active angiotensin II, and numerous other peptidases, transpeptidases, nucleotidases, phosphodiesterases, and phosphatases. Many CD antigens of leukocytes are ecto‐enzymes; some CD antigens for which no function is currently known are probably ectoenzymes. Expression is highly regulated and correlated with differentiation and activation. Some are highly restricted in distribution; others are ubiquitous. Many are shared between leukocytes and non‐hematogenous cells. Biological functions appear to depend on the type and location of the cell in which expression occurs, and include recycling of nutrients, local control of response to cytokines and hormones, bone formation, cell mobility, invasion, and metastasis. Many novel regulatory functions of ecto‐enzymes remain to be discovered, and may reveal new mechanisms of local extracellular control of cellular function. J. Leukoc. Biol. 67: 285–311; 2000."
37,Inhibition of Phagocytosis and Interleukin‐1 Production in Pulmonary Macrophages From Rats With Sialodacryoadenitis Virus Infection,"To test whether or not sialodacryoadenitis virus (SDAV) infection in rats affects pulmonary macrophage function, we intranasally inoculated pathogen‐free F344 rats with SDAV and collected alveolar and interstitial macrophages 5 d later. We assessed Fc receptor‐mediated attachment and phagocytosis by phase‐contrast microscopic examination of monolayers of alveolar and interstitial macrophages incubated with zymosan, nonopsonized sheep erythrocytes, or erythrocytes opsonized with rabbit antisheeperythrocyte IgG. Alveolar macrophages from virus‐infected rats had significantly (P ≤ .05) lower indices of attachment and phagocytosis of opsonized erythrocytes than control macrophages, but there was no difference in attachment of zymosan particles. Interstitial macrophages were not affected. Alveolar macrophages from SDAV‐infected rats produced significantly less interleukin‐1 than those from control rats, as assessed by testing supematants from lipopolysaccharide‐stimulated macrophage cultures for induction of mouse thymocytes to take up tritiated thymidine. Effects of SDAV infection on lung macrophages could increase host susceptibility to other pathogens or complicate studies of respiratory tract immunity."
38,Body elongation and decreased reproductive output within a restricted clade of lizards (Reptilia: Scincidae),"Relationships between body shape and relative abdominal size were compared among differentially elongate species within the scincid lizard genus Brachymeles, to investigate how morphological evolution affects the proportion of body volume available to hold eggs and offspring. Relative abdominal size is inversely related to elongation, suggesting that relative clutch mass decreases with addition of abdominal body segments. Shape‐volume relationships contradict trends seen in comparisons among distantly related limbed and limbless squamates (lizards and snakes), in which snakes have relatively more abdominal volume. Comparison within a phylogenetically restricted group allows the identification of functional and ontogenetic factors potentially limiting reproductive output. In Bruchymeles, constraining factors include retention of anterior body segments bearing parasternal ribs, which prevents extension of the clutch anteriorly within the body, and reduction of allometry of abdominal segments, which provides extended series of uniformly‐sized vertebrae for limbless locomotion, but reduces the relative size of the abdomen. The latter trait is associated with overall size reduction, which affects relative egg‐size and packing. Factors constraining abdominal volume in this genus are probably common to other elongate lizards, a morphological group that has been rarely represented in comparative studies of life history."
39,Non‐Influenza Respiratory Viruses May Overlap and Obscure Influenza Activity,"OBJECTIVE: To report the number and timing of influenza A isolates, as well as overlapping respiratory viruses. Co‐circulating respiratory viruses may obscure the determination of influenza activity. DESIGN: Prospective clinical surveillance for the new onset of respiratory illness followed by viral cultures during seven separate influenza seasons. SETTING: The Wisconsin Veterans Home, a skilled nursing facility for veterans and their spouses. RESULTS: Influenza A isolates were encountered in greater numbers than non‐influenza A isolates during three seasons. Seasonal variability is striking. In December 1992, we identified a large outbreak of respiratory illness. Influenza type B was cultured from 102 residents. In December 1995, influenza A was cultured from 285 people in Wisconsin. At that time, we identified outbreaks of respiratory illness in two of our four buildings. Based on statewide data, we suspected an influenza outbreak; however, 26 isolates of parainfluenza virus type 1 were cultured with no influenza. The potential importance of culturing at the end of the season was demonstrated in 1991–1992 when an outbreak of respiratory syn‐cytial virus (RSV) overlapped and extended beyond influenza A activity. CONCLUSIONS: When interpreting new clinical respiratory illnesses as a basis for declaring an outbreak of influenza A, clinicians should realize that co‐circulating respiratory viruses can account for clinical illnesses. Clinicians might utilize healthcare dollars efficiently by performing cultures to focus the timing of influenza A chemoprophylaxis. Cultures could be performed when clinical outbreak criteria are approached to confirm an outbreak. Culturing of new respiratory illness could begin again before the anticipated discontinuation of prophylaxis (approximately 2 weeks). J Am Geriatr Soc 47:1087–1093,1999."
40,Astrocytic reaction predominance in chronic encephalitis of junin virus‐infected rats,"Junin virus antigen distribution and astrocytic reaction to prolonged infection were characterized in rat brain by the PAP technique. During the acute stage of neurologic disease following intracerebral inoculation, Junin antigen was detected in 100% of animals, strongly in most neurons but also to a much lesser degree in scattered astrocytes, dropping to 20% of rats at 540 days postinfection. Initially labeled in all brain areas, viral antigen gradually disappeared from hippocampus but persisted irregularly in cerebral cortex, basal ganglia, Purkinje cells, pons, and medulla oblongata. Such a pattern suggests that specific neuronal subpopulations, in spite of apparently unaltered cell morphology, may persistently harbor the virus, leading on occasion to a delayed neurologic syndrome. During both the acute and chronic stages of disease, a mild inflammatory exudate was observed, characterized by the presence of T and B lymphocytes, as well as macrophages and unidentified round cells. GFAP immunostaining showed increased astrocytic reaction as infection lapsed into chronicity. Corpus callosum, hippocampus, and cerebellum exhibited the sharpest reactive astrocytosis, followed by basal ganglia, pons, and medulla oblongata, whereas in cerebral cortex it was considerably less. Astrocyte activation, which failed to correlate with viral antigen presence in neurons, seems to result from a generalized condition, possibly including diffusible brain factors triggered by viral infection. Such widespread astroglial reaction may thus contribute to the outcome of the late neurologic syndrome."
41,Evaluation of an enzyme‐linked immunosorbent assay that measures rhinovirus‐specific antibodies in human sera and nasal secretions,"Rhinovirus‐specific antibodies have traditionally been detected by their ability to neutralise the homologous rhinovirus serotype in tissue culture. Recently, however, we have described an enzyme‐linked immunosorbent assay that detects rhinovirus‐specific antibodies in sera and nasal secretions [Barclay and Al‐Nakib, 1987]. Here we describe an evaluation of the ELISA in a study involving 71 adult volunteers inoculated intranasally with human rhinovirus type 2 (HRV‐2). Pre‐and post‐inoculation serum samples and pre‐inoculation nasal washings were tested for the presence of HRV‐2‐specific antibodies by ELISA. Such antibodies were associated with protection against infection when present locally in nasal secretions, but when also present in the serum they were associated with protection against both infection and the development of illness. The antibody concentrations showed strong correlation with each other and with that of antibodies detected by the neutralisation test. Following HRV‐2 infection, rises in HRV‐2‐specific IgA in sera detected by ELISA occurred more frequently than rises in neutralizing antibody. These results suggest that the ELISA is a sensitive and reliable indicator of recent infection, as well as a predictor of homologous immune status."
42,"Microstructure, evolution, and ontogeny of scale surfaces in cordylid and gerrhosaurid lizards","The distal oberhautchen and proximal beta layer of 41 species and every genus of cordylid and gerrhosaurid lizard were examined with a scanning electron microscope. Scale organs in these families are concentrated on the face, and scale organs occur singly or in pairs below the keel on the dorsals of cordylids but not gerrhosaurids. Most species examined possess primitive, lenticular scale organs. Unique and previously unknown, projecting scale organs occur in two species of Cordylus. Scale organs appear to be absent in species of Chamaesaura. The scale surfaces of cordylids are covered in macrohoneycomb. Individual compartments of cordylid macrohoneycomb are not intracellular structures but may be overlain by apparent oberhautchen cells. In some cordylid species, part of each cell is free and projects away from the scale surface as a pointed flap. Gerrhosaurids lack macrohoneycomb. Instead, their scale surfaces are covered in lamellae without dentate borders, 50–100 times as long as wide. The epidermis of Platysaurus is unique among cordylids in possessing lamellae 1–8 times as wide as long that overlap macrohoneycomb in some regions of the body. The scale surfaces of Cordylus cordylus undergo an ontogenetic change similar to that recently described for the xenosaurid genus Shinisaurus. Phylogenetic analysis of scale surface features allows the partitioning of Cordylus into three species groups and Chamaesaura into two species groups. Synapomorphies of the species of Chamaesaura, the species of Platysaurus, and the genera of the gerrhosaurids are also described. © 1995 Wiley‐Liss, Inc."
43,IN VITRO EFFECTS OF MONOLAURIN COMPOUNDS ON ENVELOPED RNA AND DNA VIRUSES,"Monolaurin alone and monolaurin with tert‐butylhydroxyanisole (BHA), methylparaben, or sorbic acid were tested for in vitro virucidal activity against 14 human RNA and DNA enveloped viruses in cell culture. At concentrations of 1% additive in the reaction mixture for 1 h at 23°C, all viruses were reduced in infectivity by >99.9%. Monolaurin with BHA was the most effective virucidal agent in that it removed all measurable infectivity from all of the viruses tested. The compounds acted similarly on all the viruses and reduced infectivity by disintegrating the virus envelope."
44,Evolution of the middle ear apparatus in talpid moles,"The middle ear structures of eight species of mole in the family Talpidae (Mammalia: Eulipotyphla) were studied under light and electron microscopy. Neurotrichus, Parascalops, and Condylura have a simple middle ear cavity with a loose ectotympanic bone, ossicles of a “microtype” morphology, and they retain a small tensor tympani muscle. These characteristics are ancestral for talpid moles. Talpa, Scalopus, Scapanus, and Parascaptor species, on the other hand, have a looser articulation between malleus and ectotympanic bone and a reduced or absent orbicular apophysis. These species lack a tensor tympani muscle, possess complete bullae, and extensions of the middle ear cavity pneumatize the surrounding basicranial bones. The two middle ear cavities communicate in Talpa, Scapanus, and Parascaptor species. Parascaptor has a hypertrophied malleus, a feature shared with Scaptochirus but not found in any other talpid genus. Differences in middle ear morphology within members of the Talpidae are correlated with lifestyle. The species with middle ears closer to the ancestral type spend more time above ground, where they will be exposed to high‐frequency sound: their middle ears appear suited for transmission of high frequencies. The species with derived middle ear morphologies are more exclusively subterranean. Some of the derived features of their middle ears potentially improve low‐frequency hearing, while others may reduce the transmission of bone‐conducted noise. By contrast, the unusual middle ear apparatus of Parascaptor, which exhibits striking similarities to that of golden moles, probably augments seismic sensitivity by inertial bone conduction. J. Morphol. © 2006 Wiley‐Liss, Inc."
45,Interactions of Pseudorabies Virus With Swine Alveolar Macrophages: Effects of Virus Infection on Cell Functions,"In order to assess the effect of Pseudorabies virus (PRV) infection on the function of swine alveolar macrophages (AM), lung lavage cells were cultured, infected with one of six strains of PRV, and various activities were measured. Activity measurement included viability, phagocytosis of yeast, phagosome‐lysosome fusion, phagocytosis of opsonized particles, and superoxide release. AM were infected with 5 × 10(‐3) PFU/cell, and the comparative assessment of functions was performed at 18‐20 h postinfection. Cell viability in PRV‐infected cultures ranged from 79 to 94% of the viability in noninfected cultures. Phagocytosis of yeast was significantly reduced only in the AM cultures infected with the strain S‐62. Phagosome‐lysosome fusion was depressed in cultures infected with the strains S‐62, 4892, 3816, and BUK. The phagocytosis of opsonized sheep red blood cells showed significant differences between noninfected and PRV‐infected cultures in all cases except cultures infected with the strain PRV‐C. The O(2) release after stimulation with opsonized zymosan was significantly reduced in all the PRV‐infected cultures. The effect of PRV infection on AM functions that are related to the bacterial activity of such cells suggests that PRV‐induced AM dysfunction might have a role in the increased susceptibility of PRV‐infected pigs to bacterial pneumonia."
46,Appearance of complement components and immunoglobulins on nasopharyngeal epithelial cells following naturally acquired infection with respiratory syncytial virus,"Nasopharyngeal epithelial cells (NPEC) were collected from 144 infants and children with respiratory syncytial virus (RSV) infection, and were analyzed by fluorescent antibody techniques for the presence of cell‐bound complement (C(/) (3)), IgA, IgC, and IgM class of immunoglobulins (Ig), and respiratory syncytial virus antigen. Viral antigen was present on the surface of NPEC in 100% of samples obtained in the first 3 days of illness. The percentage of patients positive for RSV antigen declined steadily, so that no patient still expressed viral antigen on NPEC by 57 days after the onset of illness. Cell‐bound IgA, IgC, and IgM could be detected in most of the samples tested in the first 13 days after the onset of illness. Subsequently, the frequency of detection of cell‐bound Ig gradually declined. Only 8–3 3 % of patients tested 57 days after the onset of illness expressed IgA, IgG, or IgM on NPEC. About 45% of samples tested in the first 8 weeks after the onset of illness exhibited complement binding to NPEC. The percentage of subjects showing cell‐bound C(/) (3) reached a maximum at 8–13 says after the onset of illness, while cell–bound C(/)(3) could not be detected in any of the samples collected 57–90 days after the onset of illness. Although cell‐bound C(/) (3) was generally present in association with cell‐bound Ig on NPEC, in a small percentage (4.6%) of patients cell‐bound C(/)(3) could be detected in the absence of any cell–bound Ig. Cell‐bound C(/)(3) and IgA, IgG, and IgM were present with equal frequency in patients with all forms of clinical disease caused by RSV, and in patients less than or greater than 6 months of age at the onset of illness."
47,SCIENTIFIC INFORMATION DOCUMENT: Campylobacter infection,
48,Innovative Drug Treatments for Viral and Autoimmune Myocarditis,"Myocarditis has been shown to be a common cause of cardiomyopathy and is believed to account for 25% of all cases in human beings. Unfortunately, the disease is difficult to detect before a myopathic process ensues. Treatment of myocarditis‐induced heart failure includes the standard regimen of diuretics, digoxin, angiotensin‐converting enzyme inhibitors, and currently, β‐adrenergic blockers. Treatment of myocarditis itself is dependent on the etiology of the illness. Treatments under investigation include immunosuppressants, nonsteroidal antiinflammatory agents, immunoglobulins, immunomodulation, antiadrenergics, calcium‐channel blockers, angiotensinconverting enzyme inhibitors, nitric oxide inhibition (e.g., aminoguanidine), and antiviral agents. Despite advances in treatment, more work needs to be done in the early detection of myocarditis. Additionally, better means need to be established for distinguishing between viral and autoimmune forms of the disease, so that appropriate treatment can be instituted."
49,"Program and Abstracts of the 11th INTERNATIONAL RES CONGRESS and 24th NATIONAL MEETING OF THE RETICULOENDOTHELIAL SOCIETY: Westin Kauai, Kauai, Hawaii, October 17–21, 1987",
50,Enzyme immunoassay for respiratory syncytial virus: Rapid detection in nasopharyngeal secretions and evaluation of isolates representing different RSV subgroups,"The presence of respiratory syncytial virus (RSV) was investigated by immunofluorescent antibody (IFA) technique and by an enzyme immunoassay (EIA) in 169 samples of nasopharyngeal secretions of infants and children with acute respiratory infections. Of 31 samples positive by EIA, 25 were positive by IFA. In 24 samples from a retrospective study, RSV positive by IFA and/or tissue culture isolation (TCI), 22 were also positive by EIA. The EIA was also evaluated with 111 RSV isolates in Hep2 cell cultures representing different RSV subgroups. All were positive by EIA. © 1993 Wiley‐Liss, Inc."
51,defensive publications in an r&d race,"This paper considers a multistage dynamic R&D race in which the competitors strategically publish research findings. Publications change the prior art, thus affecting patentability. Firms publish when they are behind in the race and their rival is close to winning it. Publication sets back both competitors and gives the follower a chance to catch up. Publications prolong the race. Firms are more likely to publish the more patient they are, and the higher their probability of success. Asymmetry between the firms generates additional incentives to publish such as protecting profits from a previous patent and increasing a strong firm's probability of winning. When firms face a joint decision on publications and the intensity of research, publications substitute investment."
52,Molecular biology of human pathogenic viruses,
53,Refining rare weed trait syndromes along arable intensification gradients,"QUESTION: How does the conservation (rarity) value of arable weed communities differ along intensification gradients? Which functional traits best distinguish the weed communities of more and less extensively managed fields? Can the same traits predict the rarity of individual weed species? LOCATION: Hungary. METHODS: Using relevé data from 60 cereal and 70 stubble fields, together with weed trait data, we characterized community responses to arable intensification using functional trait analyses based on trait‐convergence and trait‐divergence assembly patterns. We also examined how well the broad‐scale rarity status of species predicts their occurrence along intensification gradients, and how it maps onto our functional classifications describing intensification responses. RESULTS: The response of weeds to intensification in cereal fields was best described by a functional classification based on species' flowering duration, maximum height and seed weight: weeds of extensively managed fields have short flowering seasons (2–5 mo) and particularly large or small seeds. The highest proportions of rare species also happen to be found in these groups. The rarest weeds among these species tend to be late‐winter and early‐summer annuals, while the rare species of stubble fields tend to be broad‐leaved with low nitrogen requirements, small seeds and short height. Stubble fields showed a decline in weed cover with increasing application of fertilizer and distance from the field edge, but we could detect no strong associations of management factors with trait composition, perhaps because the intensification gradient across these fields was shorter. CONCLUSIONS: Many rare Hungarian weeds are associated with traditional extensive farming practices. They are particularly characterized by short, midsummer flowering periods and by preference for low nitrogen levels, but a range of trait syndromes must be considered to understand their ecology and conservation. Analyses based on trait‐divergence patterns, rather than trait‐convergence patterns, provide better insights into the functional composition of weed communities, emphasizing the importance of disruptive filters in weed community assembly and the need for improved methods to detect such effects."
54,The effect of plant species on soil nitrogen mineralization,"1.. To ascertain the influence of different plant species on nitrogen (N) cycling, we performed a long‐term garden experiment with six grasses and five dicots with different potential growth rates, that are adapted to habitats with different nutrient supplies. We measured in situ N mineralization and nitrification of the soil under monocultures of each species during the fourth year of the experiment. 2.. We focused on the effects of the different species on (i) annual net N mineralization; (ii) the seasonal pattern of N mineralization; and (iii) the fraction of the total N mineralization that is nitrified. Our hypothesis was that plant species of nutrient‐rich habitats would enhance the N mineralization compared with species of nutrient‐poor habitats. 3.. The results demonstrate a strong influence of the species on net N mineralization and net nitrification, both of which fluctuated strongly during the year. Overall, species from high fertility habitats increased N mineralization and nitrification more than species from low fertility habitats. About 90% of the mineralized ammonium was oxidized to nitrate. There was no significant difference in this proportion in the plots of species from nutrient‐rich, moderate and nutrient‐poor habitats."
55,Current issues and forthcoming events,
56,Enzyme‐Linked lmmunosorbent assay: A rapid reproducible test for the measurement of rabies antibody,"An enzyme‐linked immunosorbent assay (ELISA) was developed for detecting IgG antibodies to the Pitman Moore strain of rabies virus in sera from subjects immunised with HDCS vaccine. End‐point titres of antibody were determined using a pocket calculator preprogrammed to analyse absorbence values of test sera and negative controls. The assay was highly reproducible, and very close agreement was achieved when the results were compared with those of the mouse neutralization test. Rabies enzyme‐linked immunosorbent assay is easy to perform, the results are obtained within 48 hours, and because it employs inactivated virus, the test can be used safely without special containment facilities."
57,Polymerase chain reaction and sequencing for typing rhinovirus RNA,"Primers were designed and tested for their ability to distinguish rhinoviruses from enterovi‐ruses. A primer set derived from the 5′‐UTR/VP coding region junction was able to amplify all the rhinovirus serotypes tested. Enteroviruses were either not amplified by these primer pairs or produced a band of larger size that could easily be discriminated from the rhinovirus‐specific product. In contrast, primers embedded in the 5′‐UTR region alone were able to amplify both rhinovirus and enterovirus RNA. It is shown that rhino‐viruses could be specifically typed by sequencing the amplicon derived from this 5′‐UTR set. The sequences of the 5′‐UTR region often previously unsequenced rhinoviruses were derived. The sequences obtained cluster into two groups: 18,41, 15, 30, 63, 31,56, and 44; and 17, 69, and 70. Ampliconsfrom serotypes 17, 69, and 70 also group by sequence with the equivalent region of HRV14 from the genetic database, while the others group with 2 and 89. © 1994 Wiley‐Liss, inc."
58,Detection of enteric adenoviruses with synthetic oligonucleotide probes,"The abilities of hybridization probes to detect all human adenovirus types and to identify enteric adenovirus types were evaluated. The efficiency of hybridization was compared to other tests currently in routine laboratory use on clinical specimens from young children with gastroenteritis, Probes were derived from various regions of the adenovirus types 2 and 41 genomes, and were evaluated by hybridization with a series of DNA quantities from 1 μg to 10 pg of one adenovirus type from each human subgenus, lambda phage, and HEp 2 cells. The sensitivity of hybridization with the HPII probe (92.7%), containing the conserved hexon gene, compared well with EM (54.6%), culture and neutralization (45.5%), and enzyme immunoassay (61.8%). The sensitivity of detection of enteric adenovirus isolates by the cloned Bg/II D fragment probe (92.9%) and by a synthetic probe (85.7%), manufactured from type‐specific sequences of the Ad41 hexon gene were comparable to Ad40/Ad41 specific enzyme immunoassay (84.6%). Hybridization was found to be a sensitive method of adenovirus detection in comparison to traditional methods of laboratory diagnosis. Synthetic oligonucleotides enable specific detection of individual enteric adenovirus types. Hybridization had additional advantages over other tests in identifying cases of infection with more than one adenovirus type and in allowing an estimate of the concentration of adenovirus in the specimen."
59,"Mitotane (o, p‘‐DDD) treatment in a cat with hyperadrenocorticism",An 11‐year‐old male castrated Persian cat with spontaneous hyperadrenocorticism was presented. Both adrenals were grossly enlarged and calcified. A diagnosis of pituitary‐dependent hyperadrenocorticism was made. Signs of hyperadrenocorticism resolved with long‐term mitotane treatment. Concurrent diabetes mellitus resolved after 220 days of therapy. No severe adverse drug reactions were noted.
60,Detection of cytomegalovirus and Epstein‐Barr virus in labial salivary glands in Sjogren's syndrome and non‐specific sialadenitis,"To investigate the role of herpes viruses in Sjogren's syndrome, minor (labial) salivary gland tissues from Sjogren's syndrome and from non‐specific sialadenitis were examined for Epstein‐Barr virus (EBV) and human cytomegalovirus (HCMV) DNA by the polymerase chain reaction. Almost half of all salivary glands studied contained EBV and/or HCMV. There was, however, no significant difference between the detection of EBV or HCMV in salivary glands from patients with Sjogren's syndrome or non‐specific sialadenitis. The findings are consistent with the persistence of EBV and HCMV in minor salivary glands following primary infection, but do not indicate a direct role for either virus in the aetiology of Sjogren's syndrome, and do not exclude reactivation of the viruses in this disease."
61,Prospective Hematologic and Clinicopathologic Study of Asymptomatic Cats With Naturally Acquired Feline Immunodeficiency Virus Infection,"Prospective studies were performed over a 28‐ to 77‐month period (median, 66 months) on 5 cats with naturally acquired feline immunodeficiency virus (FIV) infection in an attempt to correlate hematologic and Clinicopathologic changes with the emergence of clinical disease. On presentation, all cats were asymptomatic; free of opportunistic infections; and had normal complete blood counts, bone marrow morphologies, marrow progenitor frequencies, and progenitor in vitro growth characteristics. During study, 2 cats remained healthy, 2 cats showed mild clinical signs, and 1 cat developed a malignant neoplasm (ie, bronchiolar‐alveolar adenocarcinoma). Although persistent hematologic abnormalities were not observed, intermittent peripheral leukopenias were common. In 3 of 5 FlV‐seropositive cats, lymphopenia (< 1,500 lymphs/μL; normal reference range, 1,500 to 7,000 lymphs/μL) was a frequent finding and the absolute lymphocyte counts had a tendency to progressively decline. One of the other 2 cats had consistently low to low‐normal absolute neutrophil counts (1,300 to 4,800 segs/μL; mean, 2,730 segs/μL; normal reference range, 2,500 to 12,500 segs/μL), and the remaining cat had consistently normal leukograms, except for a transient period (ie, 11 months) of benign lymphocytosis (7,200 to 13,430 lymphs/μL) early in the study. Periodic examinations of bone marrow aspirates revealed normal to slightly depressed myeloid‐to‐erythroid ratios with normal cellular morphology and maturation. Bone marrow abnormalities observed late in the study included mild dysmor‐phic changes (ie, megaloblastic features) in 2 cats, and a significant decrease (60% of controls, P < .001) in the frequencies of burst‐forming units erythroid (BFU‐E) in marrow cultures of FIV‐seropositive cats compared with uninfected control cats. Serum biochemical profiles were unremarkable throughout the study, with the exception of hyperglobulinemia (ie, polyclonal gammopathy) in 2 of 5 cats. Peripheral blood and bone marrow findings were of no apparent prognostic value. These results confirm the long latency between natural FIV infection and the development of life‐threatening clinical disease. Chronic FIV infection, like infection with human immunodeficiency virus, can be associated with derangements in peripheral blood cell counts, as well as pertubations in marrow cell morphologies and hematopoietic progenitor frequencies before the terminal symptomatic stages of retroviral disease, when persistent cytopenias are prominent."
62,The accuracy of nurses' estimates of their absenteeism,"gaudine a & gregory c (2010) Journal of Nursing Management 18, 599–605 The accuracy of nurses' estimates of their absenteeism Aim The purpose of the present study was to determine the accuracy of nurses’ self‐reports of absence by examining: (1) the correlation, intra‐class correlation, and Cronbach’s alpha for self‐reported absence and absence as reported in organizational records, (2) difference in central tendency for the two measures of absence and (3) the percentage of nurses who underestimate their absence. Background Research on nurses’ absenteeism has often relied on self‐reports of absence. However, nurses may not be aware of their actual absenteeism, or they may underestimate it. Method Self‐reported absence from questionnaires completed by 215 Canadian nurses was compared with their absence from organizational records. Results There is a strong positive correlation, a strong intra‐class correlation and Cronbach’s alpha for the two measures of absence. However, there is a difference in central tendency that is related to the majority of nurses in this study (51.1%) underestimating their days absent from work. Conclusions Research examining the predictors of absence may consider measuring absence with self‐reports. Nevertheless, nurses demonstrated a bias to underestimate their absence. Implications for nursing management Feedback interventions to reduce absenteeism can be developed to include providing nurses with accurate information about their absence."
63,Characterization of precipitates size distribution: validation of low‐voltage STEM,"The size distribution of second phase precipitates is frequently determined using conventional transmission electron microscopy (CTEM). However, other techniques, which present different advantages, can also be used for this purpose. In this paper, we focus on high angle annular dark field (HAADF) in TEM and scanning TEM (STEM) in scanning electron microscopy (SEM) imaging modes. The mentioned techniques will be first described, then compared to more conventional ones for the measurement of carbides size distribution in two FeCV and FeCVNb model alloys. This comparative study shows that STEM in SEM, a technique much easier to undertake compared to TEM, is perfectly adapted for size distribution measurements of second phase particles, with sizes ranging between 5 and 200 nm in these systems."
64,Can plant litter affect net primary production of a typical steppe in Inner Mongolia?,"Question: Litter (dead leaves or stems) affects production by conserving soil moisture. However, that role is not clear for grasslands where most precipitation falls during the growing season when the demand for water is high. Our question was: Does litter affect forage production in such an environment? Location: Typical steppe, Inner Mongolia. Methods: We examined the role of plant litter in two experiments where litter was either removed or added in a protected or heavily grazed site, respectively, in autumn and in spring in a split plot design. The treatments (control, moderate and heavy litter application) were applied once in five replications but repeated at new locations in each of 3 years. This was done to examine only the direct effect of litter on annual net primary production and selected plant characteristics and not potential secondary effects. We also measured soil moisture and soil temperature. Results: Removing litter caused a reduction in the amount of grass (Leymus chinensis) that was produced, but litter addition caused an inconsistent effect among years, with moderate applications producing the most positive effects. Litter removal resulted in shorter and less dense plants of L. chinensis and Carex duriuscula, while heavy litter addition in autumn reduced plant height of both Cleistogenes squarrosa and C. duriuscula. Conclusions: Litter was effective for enhancing soil moisture status and reducing soil heat units in the typical steppe of Inner Mongolia. Therefore, litter mass may serve as an index of grassland health in such environments."
65,Functional traits explain amphibian distribution in the Brazilian Atlantic Forest,"AIM: Species distributions are one of the most important ways to understand how communities interact through macroecological relationships. The functional abilities of a species, such as its plasticity in various environments, can determine its distribution, species richness and beta diversity patterns. In this study, we evaluate how functional traits influence the distribution of amphibians, and hypothesize which functional traits explain the current pattern of amphibian species composition. LOCATION: Atlantic Forest, Brazil. TAXON: Amphibia (Anura and Gymnophiona) METHODS: Using potential distributions of Brazilian amphibians from Atlantic Forest based on their functional traits, we analysed the influence of biotic and abiotic factors on species richness, endemism (with permutation multivariate analysis) and beta diversity components (i.e. total, turnover and nestedness dissimilarities). RESULTS: Environmental variables explained 59.5% of species richness, whereas functional traits explained 15.8% of species distribution (geographical species range) for Anuran and 88.8% for Gymnophiona. Body size had the strongest correlation with species distribution. Results showed that species with medium to large body size, and species that are adapted to living in open areas tended to disperse from west to east direction. Current forest changes directly affected beta diversity patterns (i.e. most species adapted to novel environments increase their ranges). Beta diversity partitioning between humid and dry forests showed decreased nestedness and increased turnover by increasing altitude in the south‐eastern region of the Atlantic Forest. MAIN CONCLUSIONS: Our study shows that functional traits directly influence the ability of the species to disperse. With the alterations of the natural environment, species more apt to these alterations have dispersed or increased their distribution, which consequently changes community structure. As a result, there are nested species distribution patterns and homogenization of amphibian species composition throughout the Brazilian Atlantic Forest."
66,Probable Vitamin K‐Deficient Bleeding in Two Cats With Malabsorption Syndrome Secondary to Lymphocytic Plasmacytic Enteritis,"Two cats with intestinal malabsorption developed a hemorrhagic diathesis. Although unsubstantiated, the probable cause of bleeding was a chronic malabsorption of fat and the fat‐soluble vitamin K. When treated_with vitamin Ki per os, one cat's clotting times were only partially corrected. Since vitamin K, is actively absorbed in the proximal small intestine, the incomplete response of this case to orally administered vitamin K, was predictable. The infrequent occurrence of bleeding in animals with malabsorption is, in part, attributable to the ileal and colonic absorption of bacterially derived vitamin K(2). For this reason, nonspecific use of antibiotics in these animals is contraindicated. Since long‐chain, polyunsaturated fats impair vitamin K absorption, dietary fat given to animals with malasorption should be restricted to medium‐ and short‐chain, saturated fats. Vitamin K should be administered subcutaneously to these animals if prolonged clotting times or active bleeding is present, and routinely prior to surgery. Oral supplementation with vitamin K(3), which is absorbed in the colon and less lipid soluble than vitamin Ki, should be given to animals with malabsorption that are maintained as outpatients. Adequate dosage levels of vitamin K(3), however, are yet to be established for the cat, and dose‐dependent hemolytic anemia is a probable toxic manifestation."
67,Ultrastructure of Euspermatozoa of cerithiacean gastropods (Prosobranchia: Mesogastropoda),"Euspermatozoa of selected cerithiacean gastropods have been studied using transmission electron microscopy and the results compared (primarily) with previous studies of mesogastropod and neogastropod euspermatozoa. Cerithiacean euspermatozoa each possess a well‐defined acrosome (extremely varied in shape), a short (2.25—3 μm), very electron‐dense nucleus, an elongate midpiece, and an elongate glycogen piece. A dense ring structure associated with the plasma membrane occurs at the junction of the midpiece and glycogen piece. While features such as the dense ring structure and the systematic periaxonemal arrangement of “glycogen” granules can be understood from a purely functional standpoint, it is suggested that euspermatozoon features also provide information of taxonomic and phylogenetic relevance. On the basis of euspermatozoon midpiece structure, true cerithiaceans can be easily distinguished from other mesogastropods and from neogastropods and are divided tentatively into two groups: Group 1 (Turritellidae, Cerithiidae, Australaba (family uncertain), Planaxidae, Potamididae (subfamily Batillariinae)), and Group 2 (Potamididae (subfamily Potamidinae), Modulidae, Obtortio (family uncertain)). Using midpiece and acrosomal features, group 1 can be further subdivided into two subgroups: Subgroup 1(i) (Turritellidae, Cerithiidae, Australaba) and Subgroup 1(ii) (Planaxidae, Potamididae (subfamily Batillariinae)). It is suggested that the pronounced differences existing between the two subfamilies of the Potamididae may indicate the necessity for a separate family for the Batillariinae."
68,Gastrointestinal Motility and Disease in Large Animals,"An understanding of the relationship between gastrointestinal (GI) motility and disease is imperative for the proper treatment of large animal patients, especially as new therapeutic agents become available. However, the abundance of information that has become available in the last 2 decades makes gaining this understanding a formidable task. This article summarizes the changes in GI motility caused by some common diseases and conditions encountered in large animal practice, such as GI obstruction, postoperative ileus, resection and anastomosis, diarrhea, endotoxemia, GI parasitism, hypocalcemia, and pregnancy. J Vet Intern Med 1996;10:51–59. Copyright © 1996 by the American College of Veterinary Internal Medicine."
69,Lymphocyte activation,
70,Aetiology and outcome in 90 cats presenting with dyspnoea in a referral population,"Objectives: Dyspnoea is an unspecific severe presenting sign, which can be life threatening and requires prompt treatment. Dyspnoeic cats often have significant underlying disease. Underlying aetiologies in cats that presented with dyspnoea were reviewed, and associations with patient signalment and outcome were investigated. Methods: The case records of 90 dyspnoeic cats were retrospectively reviewed and separated into different groups depending on aetiology (cardiac, respiratory, neoplastic and trauma). Duration of clinical signs, presentation, hospitalisation length and survival were analysed. Results: Cardiac (38 per cent), respiratory (32 per cent) and neoplastic (20 per cent) diseases were common causes of feline dyspnoea. Cats with respiratory causes had longer duration of clinical signs (P<0·001) before presentation. Cats with neoplasia were significantly older (P<0·001). No significant difference in respiratory rates was present between the groups (P = 0·154). High heart rates (P<0·001) and abnormalities on cardiac auscultation were more likely in the cardiac group. Clinical Significance: Frequent causes of dyspnoea in cats were cardiac disease followed by respiratory causes and neoplastic conditions. Heart rate on presentation and presence of heart murmurs or gallops are useful to identify cardiac causes. Improved proportion surviving was found in the respiratory group (P = 0·027), whereas cats with neoplasia had the worst outcome."
71,"Minireview The influence of season, photoperiod, and pineal melatonin on immune function","Abstract: In addition to the well‐documented seasonal cycles of mating and birth, there are also significant seasonal cycles of illness and death among many animal populations. Challenging winter conditions (i.e., low ambient temperature and decreased food availability) can directly induce death via hypothermia, starvation, or shock. Coping with these challenges can also indirectly increase morbidity and mortality by increasing glucocorticoid secretion, which can compromise immune function. Many environmental challenges are recurrent and thus predictable; animals could enhance survival, and presumably increase fitness, if they could anticipate immunologically challenging conditions in order to cope with these seasonal threats to health. The annual cycle of changing photoperiod provides an accurate indicator of time of year and thus allows immunological adjustments prior to the deterioration of conditions. Pineal melatonin codes day length information. Short day lengths enhance several aspects of immune function in laboratory studies, and melatonin appears to mediate many of the enhanced immunological effects of photoperiod. Generally, field studies report compromised immune function during the short days of autumn and winter. The conflict between laboratory and field data is addressed with a multifactor approach. The evidence for seasonal fluctuations in lymphatic tissue size and structure, as well as immune function and disease processes, is reviewed. The role of pineal melatonin and the hormones regulated by melatonin is discussed from an evolutionary and adaptive functional perspective. Finally, the clinical significance of seasonal fluctuations in immune function is presented. Taken together, it appears that seasonal fluctuations in immune parameters, mediated by melatonin, could have profound effects on the etiology and progression of diseases in humans and nonhuman animals. An adaptive functional perspective is critical to gain insights into the interaction among melatonin, immune function, and disease processes."
72,A New Disease Emerges: Severe Acute Respiratory Syndrome (SARS),
73,Effect of Gd‐DTPA‐BMA on blood and myocardial T(1) at 1.5T and 3T in humans,"PURPOSE: To compare T(1) values of blood and myocardium at 1.5T and 3T before and after administration of Gd‐DTPA‐BMA in normal volunteers, and to evaluate the distribution of contrast media between myocardium and blood during steady state. MATERIALS AND METHODS: Ten normal subjects were imaged with either 0.1 mmol/kg (N = 5) or 0.2 mmol/kg (N = 5) of Gd‐DTPA‐BMA contrast agent at 1.5T and 3T. T(1) measurements of blood and myocardium were performed prior to contrast injection and every five minutes for 35 minutes following contrast injection at both field strengths. Measurements of biodistribution were calculated from the ratio of ΔR(1) (ΔR (1myo)/ΔR (1blood)). RESULTS: Precontrast blood T(1) values (mean ± SD, N = 10) did not significantly differ between 1.5T and 3T (1.58 ± .13 sec, and 1.66 ± .06 sec, respectively; P > 0.05), but myocardium T(1) values were significantly different (1.07 ± .03 sec and 1.22 ± .07 sec, respectively; P < 0.05). The field‐dependent difference in myocardium T(1) postinjection (T(1)@3T – T(1)@1.5T) decreased by approximately 72% relative to precontrast T(1) values, while the field‐dependent difference of blood T(1) decreased only 30% postcontrast. Measurements of ΔR (1myo)/ΔR (1blood) were constant for 35 minutes postcontrast, but changed between 1.5T and 3T (0.46 ± .06 vs. 0.54 ± .06, P < 0.10). CONCLUSION: T(1) is significantly longer for myocardium (but not blood) at 3T compared to 1.5T. The differences in T(1) due to field strength are reduced following contrast administration, which may be attributed to changes in ΔR (1myo)/ΔR (1blood) with field strength. J. Magn. Reson. Imaging 2006. © 2006 Wiley‐Liss, Inc."
74,Meeting report on the 12th International Congress of Histochemistry and Cytochemistry (ICHC),"The International Congress of Histochemistry and Cytochemistry (ICHC) promoted in San Diego La Jolla (CA, USA), the 12th meeting where researchers of all over the world presented their work and the most innovative methods in histochemical disciplines. A summary of the last meeting is reported. © 2005 Wiley‐Liss, Inc."
75,Chikungunya disease and chloroquine treatment,
76,"Diversity and distribution of ferns in sub‐Saharan Africa, Madagascar and some islands of the South Atlantic","Aim This paper reports the diversity and endemism patterns of African ferns, and explores the potential role of diversity refuges and environmental and historical factors in the shaping of these patterns. Material and locations The extant fern taxa occupying Africa south of the Sahara, Madagascar and some islands of the South Atlantic. Methods The number of taxa in each area or operational geographical unit (OGU) was scored, and the correlation between this number and physical and climatic variables analysed by standard pairwise and stepwise multiple regression analysis (SPR and SMR). The effects of biological factors such as dispersal capacity, reproductive biology, genetic features and certain physiological adaptations were evaluated by comparing the number of species in each OGU. Floral affinities among OGUs were analysed using non‐metric multi‐dimensional scaling (NMS) and parsimonic analysis of dispersion (PAD), and compared with β‐turnover and inter‐OGU distances. Results OGU area, elevation and the distance between refuges determined the composition of local floras, but only greater OGU area and the existence of higher maximum elevations increased species richness. The distance between refuges also affected the number of endemic species, especially on islands. The biological features studied only slightly influenced fern distribution. The main climatic predictor of species number was humidity. SPR and SMR revealed three main groups of ferns with different ecological trends. NMS and PAD analyses separated the four areas of highest diversity in Africa, three of which are inhabited by ferns with distinct ecological requirements. The fourth area was Madagascar, which shows an accumulation of endemic and relict diversity that is not easy to explain. Main conclusions The distribution of ferns in Africa has been influenced by refuges. These probably allowed many species to recolonize the neighbouring areas after the extinctions of the Pleistocene. Three major components were detected in the African flora: Guinea‐Congolian thermophilous, cold‐tolerant Afro‐montane, and Southern drought‐tolerant elements. These are related to the three main refuge areas, i.e. the Gulf of Guinea area, the eastern tropical region, and the Cape region. Endemicity in ferns was found to be lower than that of seed plants due to the higher dispersability of fern spores. The distance between OGUs seems to be the main predictor of the number of endemic fern species these areas contain."
77,Plasmapheresis combined with interferon: An effective therapy for multiple sclerosis,"The rationale for the use of interferon (IFN) in the treatment of multiple sclerosis (MS) is based on its recognized antiviral and immunomodulating actions. The pathogenesis of MS is believed to be due to an immunologic response in a genetically predisposed individual, localized within the central nervous system white matter, and triggered by exposure to an environmental agent such as a virus. Based on our personal experience we find that the efficacy of IFN therapy is hampered in MS patients by the presence of an interferon inhibitor factor (IIF) in the patients' sera which we have isolated and characterized. When plasmapheresis (PP) was done on 24 MS patients with intermittent 3‐day administration of IFN‐a and human leukocyte IFN, marked increase of IFN in 18 patients and modest increase in three patients correlated with clinical improvement. Three clinical nonresponders showed no increase in IFN levels following therapy. The ability to remove IIF and lymphokine inhibitor factor (LIF) by PP may explain the successful treatment of our patients. We describe the evaluation of helper T cells, suppressor T cells, HLADR antigen, natural killer cells, and monocyte/macrophage cell populations by flow cytometry before and after PP. A significant increase in these immune‐competent cells correlated with marked improvement in Kurtzke disability status scale in 13 patients, while eight stabilized. Patients showing progression of the disease either showed decrease or no change in these parameters after therapy. Encouraging results from this pilot study suggest that PP combined with immunomodulatory regimens of IFN may be an effective therapy for MS."
78,Rhinovirus C is associated with wheezing and rhinovirus A is associated with pneumonia in hospitalized children in Morocco,"Human rhinovirus (RV) is commonly associated with severe acute lower respiratory infections (ALRI) in children. We aimed to describe the distribution of RV species and associations between RV species and clinical features in children hospitalized with clinically severe pneumonia (CSP) in Morocco. Nasopharyngeal aspirates (NPAs) were collected from 700 children, 2–59 months of age, admitted with CSP to the Hôpital d'Enfants de Rabat in Morocco. At least one respiratory virus was identified in 92% of children, of which RV was the most common (53%). PCR assays, sequencing, and phylogenetic tree analyses were carried out on 183 RV‐positive NPAs to determine RV species and genotypes. Of 157 successfully genotyped NPAs, 60 (38.2%) were RV‐A, 8 (5.1%) were RV‐B, and 89 (56.7%) were RV‐C. Wheezing and cyanosis were more common in RV‐C‐positive than RV‐A‐positive children (80.9% vs. 56.7%; P = 0.001 for wheezing and 10.1% vs. 0%; P = 0.011 for cyanosis). Physician's discharge diagnosis of pneumonia was more frequent among RV‐A‐positive (40.0%) than RV‐C‐positive children (20.2%; P = 0.009). RV‐A and RV‐C showed distinct seasonal patterns. Our findings suggest that RV‐C is associated with wheezing illness while RV‐A is associated with pneumonia. J. Med. Virol. 89:582–588, 2017. © 2016 Wiley Periodicals, Inc."
79,Protective effect of OK‐432 (streptococcal preparation) on murine fulminant hepatitis following mouse hepatitis virus infection,"The effects of OK‐432 (streptococcal preparation) on murine fulminant hepatitis were investigated. Hepatitis was induced by injection of mouse hepatitis virus type 2 (MHV‐2) at a strength of either 1 times 10(3) or 1 times 10(4) plaque‐forming units (PFU). Mice without OK‐432 treatment died within 5 days, whereas mice pre‐inoculated with OK‐432 showed survival rates of 50% (1 times 10(3)PFU) or 10% (1 times 10(4)PFU) after 60 days. Survival time was not prolonged if OK‐432 was injected after MHV‐2. Examined histologically, mice not treated with OK‐432 showed severe haemorrhagic necrosis of the liver, often panlobular. Treated mice showed less necrosis; the least necrosis was observed in those injected with OK‐432 before MHV‐2. In those mice injected first with OK‐432 and then with 1 times 10(3)PFU of MHV‐2 that survived 7 days, autopsy showed a very slight and focal hepatic necrosis, with follicular infiltration by lymphocytes and macrophages. Mitogenic reaction of spleen cells was remarkably less than normal in mice with MHV‐2 injection. However, mice injected with OK‐432 before MHV‐2 (same treatment as mice showing high survival rates) showed relatively high reactivity in comparison with mice not treated with OK‐432."
80,WSAVA Guidelines for the vaccination of dogs and cats,
81,Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function,"Recruitment and activation of leukocytes are important for elimination of microbes, including viruses, from infected areas. Chemokines constitute a group of bioactive peptides that regulate leukocyte migration and also contribute to activation of these cells. Chemokines are essential mediators of inflammation and important for control of viral infections. The profile of chemokine expression contributes to shaping the immune response during viral infection, whereas viral subversion of the chemokine system allows the virus to evade antiviral activities of the host. In this review, we discuss the role of chemokines in host‐defense against virus infections, and we also look deeper into the virus‐cell interactions that trigger chemokine expression as well as the cellular signaling cascades involved."
82,Clinical Practice Guideline for the Evaluation of Fever and Infection in Older Adult Residents of Long‐Term Care Facilities: 2008 Update by the Infectious Diseases Society of America,"Residents of long‐term care facilities (LTCFs) are at great risk for infection. Most residents are older and have multiple comorbidities that complicate recognition of infection; for example, typically defined fever is absent in more than one‐half of LTCF residents with serious infection. Furthermore, LTCFs often do not have the on‐site equipment or personnel to evaluate suspected infection in the fashion typically performed in acute care hospitals. In recognition of the differences between LTCFs and hospitals with regard to hosts and resources present, the Infectious Diseases Society of America first provided guidelines for evaluation of fever and infection in LTCF residents in 2000. The guideline presented here represents the second edition, updated by data generated over the intervening 8 years. It focuses on the typical elderly person institutionalized with multiple chronic comorbidities and functional disabilities (e.g., a nursing home resident). Specific topic reviews and recommendations are provided with regard to what resources are typically available to evaluate suspected infection, what symptoms and signs suggest infection in a resident of an LTCF, who should initially evaluate the resident with suspected infection, what clinical evaluation should be performed, how LTCF staff can effectively communicate about possible infection with clinicians, and what laboratory tests should be ordered. Finally, a general outline of how a suspected outbreak of a specific infectious disease should be investigated in an LTCF is provided."
83,Systemic Vasculitis with Severe Cutaneous Manifestation as a Suspected Idiosyncratic Hypersensitivity Reaction to Fenbendazole in a Cat,
84,BSAVA NEWS,
85,Feline Hybridoma Growth Factor/lnterleukin‐6 Activity,"An assay system was developed to measure feline hybridoma growth factor (HGF)/interleukin‐6 (IL‐6) activity in biological samples containing many kinds of cytokines by using the proliferation of the newly established mouse‐rat hybridoma clone. B3B1. The proliferative response of this B3B1 clone was IL‐6‐specific, and could not be promoted by other cytokines including IL‐1, IL‐2, IL‐3, and granulocyte‐colony‐stimulating factor (G‐CSF), The anti‐human B‐cell stimulatory factor 2 (BSF‐2)/IL‐6 antiserum did not neutralize feline HGF/IL‐6 activity in conditioned media prepared from feline con A‐stimulated splenocytes and unstimulated alveolar macrophages, indicating antigenic differences between species. Feline HGF/IL‐6 was eluted into the fractions corresponding to a molecular weight of 30,000–40,000 in gel filtration, and into the fractions at a salt concentration of 0.2–0.3 M NaCI in anion exchange chromatography. The physicochemical properties of feline HGF/IL‐6 were slightly different from those of murine and human IL‐6."
86,Direct detection of rhinoviruses by an enzyme‐linked immunosorbent assay,"This paper describes the first enzyme‐linked immunosorbent assay for the detection of rhinovirus antigens in clinical specimens (nasal washings), either directly or following overnight cell culture amplification. The assay takes approximately 48 hours to perform and utilizes the same rabbit antirhinovirus hyperimmune serum as both the capture and detecting antibody. The latter has been biotin‐labelled and is detected via a streptavidin 3‐galactosidase preformed complex. This new assay has been found to be very sensitive, detecting human rhinovirus (HRV)‐EL and HRV‐2 at titres as low as 10(1.8) TCID(50) 100 μl(−1) and < 10(1) TCID(50) 100 μl(−1), respectively. Furthermore, when 57 different human rhinovirus serotypes were tested in both the HRV‐EL and HRV‐2 ELISA systems a total of 49 (86%) were found to be cross‐reactive. Of 36 clinical specimens tested by virus isolation, cell‐culture‐amplified (CCA) ELISA, and direct ELISA, 15 were positive by isolation, 11 by CCA‐ELISA, and 11 by direct ELISA. The overall correlation of the CCA and direct ELISA techniques with virus isolation was found to be 88.9% and 66.7%, respectively. The present study demonstrates that the ELISA system developed is a sensitive technique for the diagnosis of rhinovirus infections."
87,Preliminary Characterisation of Torovirus‐Like Particles of Humans: Comparison With Berne Virus of Horses and Breda Virus of Calves,"Pleomorphic virus‐like particles have been observed by electron microscopy in the faeces of children and adults with diarrhoea. Some of these particles were approximately 100 nm in diameter and had a “fringe” of closely applied peplomers approximately 10 nm long; they closely resembled Berne virus of horses and Breda virus of calves, the two representatives of a newly proposed family called the Toroviridae. In one sample a toroidal nucleoprotein‐like structure was observed within the particles. For two samples a buoyant density of 1.14 g/ml was determined by centrifugation through a sucrose density gradient. One sample possessed a haemagglutination for rat erythrocytes. The serological relationship between these different viruses was observed by immune electron microscopy, haemagglutination inhibition, and serum neutralisation. The role of these viruslike particles as candidate pathogens of humans is discussed."
88,Two models of multiple sclerosis: Experimental allergic encephalomyelitis (EAE) and theiler's murine encephalomyelitis virus (TMEV) infection. A pathological and immunological comparison,"Theiler's murine encephalomyelitis virus (TMEV) infection and experimental allergic encephalomyelitis (EAE) are considered among the best models of human multiple sclerosis (MS). In both models, clinical disease is characterized by paralysis, while pathological changes consist of inflammatory demyelination. In both models there is a genetic influence on susceptibility/resistance to the development of disease. This has been thoroughly studied in TMEV infection, and it has been found to depend on both major histocompatibility complex (MHC) and non‐MHC genes. At least four genes have been so far identified. Because of this genetic influence, some strains of mice are more susceptible to both clinical and pathological changes than others, and susceptibility appears to best correlate with the ability of a certain murine strain to develop a delayed‐type hypersensitivity (DTH) response to viral antigens. We have also observed that even among mice which are equally susceptible clinically, striking differences may be seen under pathological examination. These consist of different gradients of severity of inflammation, particularly in regards to the macrophage component. There is an inverse relationship between the number of macrophages, and their length of stay in the CNS, and the ability of mice to remyelinate their lesions. The most severe lesions are in SJL/J mice, and remyelination in this strain is extremely poor. The least severe lesions in terms of macrophage invasion are in strains such as NZW and RIIIS/J, and these are able to remyelinate lesions very successfully. Murine chronic relapsing EAE (CR‐EAE) shows pathological changes in many ways similar to those in TMEV‐infected SJL/J mice, although less severe in terms of degrees of macrophage infiltration and tissue destruction. Mice with CR‐EAE have a correspondingly limited ability to remyelinate their lesions. In both models the pathology appears to be mediated through a DTH response. However, while in EAE the DTH response is clearly against neuroantigens, the response in TMEV infection is against the virus itself. The end result in both models would be that of myelin destruction through a lymphotoxincytokine‐mediated mechanism. The importance of the DTH response in both models is well illustrated by the effects of tolerance induction in EAE and TMEV infection to neuroantigens and virus, respectively. These are important models of human MS, since the current hypothesis is that a viral infection early in life, on the appropriate genetic background, may trigger a secondary misdirected immune response which could be directed either against myelin antigens and/or possible persistent virus(es). © 1995 Wiley‐Liss, Inc."
89,Genetic variability of alcohol dehydrogenase among Australian Drosophila species: Correlation of ADH biochemical phenotype with ethanol resource utilization,"Alcohol dehydrogenase (ADH) activities, electrophoretic phenotypes, and the extent of ethanol resource utilization are compared for three groups of species distinguishable on ecological criteria: 1) the cosmopolitan species D. melanogaster, a frequent inhabitant of wineries; 2) fruit‐baited species of the typically Australian subgenus Scaptodrosophila: D. lativittata, D. nitidithorax and D. howensis; and 3) Scaptodrosophila species not attracted to fermented‐fruit baits being collected by sweeping in temperate rain forests (D. inornata, D. collessi) or from Hibiscus flowers (D. hibisci). D. melanogaster showed the highest levels of ADH activity and an electrophoretic polymorphism with two active allelic forms, while group 2) species showed intermediate ADH activities and polymorphisms, which were consistent with “high activity” and “low activity” allelic forms in natural populations of these species, and group 3) species showed only “low activity” forms. Ethanol resource utilization follows the same sequence, being 1 > 2 > 3(D. howensis and D. collessi were not tested). Therefore the species considered shown an association of ADH biochemical phenotype, laboratory ethanol utilization, and resources utilized."
90,High protection of animals lethally infected with influenza virus by aprotinin‐rimantadine combination,"The successful therapeutic synergism of aprotinin and rimantadine, which are known to attack different viral targets, was demonstrated in influenza‐virus infected animals. Combined treatment with these drugs of mice infected with a highly lethal does of mouse‐adapted influenza virus prevented the development of separate administration of aprotinin and rimantadine induced 35% and 15% protection, respectively."
91,WSAVA Guidelines for the Vaccination of Dogs and Cats,
92,BSAVA Companion,
93,Therapeutic spectrum of interferon‐β in ischemic stroke,"Ischemic stroke is devastating and a major cause of morbidity and mortality worldwide. To date, only clot retrieval devices and/or intravenous tissue plasminogen activators (tPA) have been approved by the US‐FDA for the treatment of acute ischemic stroke. Therefore, there is an urgent need to develop an effective treatment for stroke that can have limited shortcomings and broad spectrum of applications. Interferon‐beta (IFN‐β), an endogenous cytokine and a key anti‐inflammatory agent, contributes toward obviating deleterious stroke outcomes. Therefore, exploring the role of IFN‐β may be a promising alternative approach for stroke intervention in the future. In the present review, we have discussed about IFN‐β along with its different mechanistic roles in ischemic stroke. Furthermore, therapeutic approaches targeting the inflammatory cascade with IFN‐β therapy that may be helpful in improving stroke outcome are also discussed."
94,RSV‐hRV co‐infection is a risk factor for recurrent bronchial obstruction and early sensitization 3 years after bronchiolitis,"To assess risk factors of recurrent bronchial obstruction and allergic sensitization 3 years after an episode of acute bronchiolitis, whether after ambulatory care treatment or hospitalization. A monocentric prospective longitudinal study including infants aged under 1 year with acute bronchiolitis was performed, with clinical (severity score), biological (serum Krebs von den Lungen 6 antigen), and viral (14 virus by naso‐pharyngeal suction detection) assessments. Follow‐up included a quaterly telephone interview, and a final clinical examination at 3 years. Biological markers of atopy were also measured in peripheral blood, including specific IgEs towards aero‐ and food allergens. Complete data were available for 154 children. 46.8% of them had recurrent wheezing (RW). No difference was found according to initial severity, care at home or in the hospital, respiratory virus involved, or existence of co‐infection. A familial history of atopy was identified as a risk factor for recurrent bronchial obstruction (60% for RW infants versus 39%, P = 0.02), as living in an apartment (35% versus 15%, P = 0.002). 18.6% of the infants were sensitized, with 48.1% of them sensitized to aeroallergens and 81.5% to food allergens. Multivariate analysis confirmed that a familial history of atopy (P = 0.02) and initial co‐infection RSV‐hRV (P = 0.02) were correlated with the risk of sensitization to aeroallergens at 3 years. Familial history of atopy and RSV‐hRV co‐infection are risk factors for recurrent bronchial obstruction and sensitization."
95,Toxicologic effects of ribavirin in cats,"Ribavirin, a broad‐spectrum antiviral agent active in vitro against a number of RNA and DNA viruses, has been associated with moderate toxicity in laboratory animals and humans. Clinically, ribavirin has been used effectively in persons primarily to treat life‐threatening viral diseases such as acute haemorrhagic fever or viral pneumonia of infants. In order to evaluate the feasibility of using this antiviral agent in cats, the effects of oral (p.o.), intramuscular (i.m.) and intravenous (i.v.) doses of ribavirin in 27 9‐month‐old specific‐pathogen‐free cats were evaluated by haematology, clinical chemistries, bone marrow biopsies and histopathology. Ribavirin was administered once daily for 10 consecutive days at a dose of either 11, 22, or 44 mg/kg after which all cats were euthanatized and necropsied. Most cats receiving 22 or 44 mg of ribavirin/kg became anorectic and suffered some degree of weight loss (0.2 to 0.6 kg), and about one‐third of the cats developed diarrhoea and/or mucous membrane pallor. Icterus or haemorrhage was not observed. The most profound and consistent haemato‐logic change, particularly among the moderate and high dosage groups regardless of route of administration, was a significant and severe thrombocytopenia (range, 33–78% reduction in mean platelet counts vs. baseline). Other changes, particularly reductions in total WBC and neutrophils and reductions in RBC and PCV, tended to occur at lower ribavirin dosages, but generally they were not statistically significant. Cats given 44 mg of ribavirin/kg i.v. showed significant decreases in leukocyte variables, including total WBC (P = 0.016), neutrophils (P= 0.026) and lymphocytes (P= 0.047). Mild‐to‐moderate increases in serum alanine aminotransferase and alkaline phosphatase activities occurred at doses of 22 and 44 mg/kg. Evaluation of bone marrow biopsies before and after treatment revealed that cats given 11 mg of ribavirin/kg had mild megakaryocytic (MK) hypoplasia, whereas cats receiving 22 or 44 mg/kg had progressively severe degrees of MK hypoplasia and dysplasia, asynchronous MK maturation, and increased myeloidrerythroid ratio. Pathologic changes in ribavirin‐treated cats generally were mild and included primarily enteritis (seven cats) and hepatocellular vacuolation and/or centrilobular necrosis (seven cats). Results of this study in cats indicated that daily administration of ribavirin at a dose range of 11 to 44 mg/kg induced a dose‐related toxic effect on bone marrow, primarily on megakaryocytes and erythroid precursors, and at the higher dosages it suppressed numbers of circulating leukocytes."
96,Occurrence in water of viruses of public health significance,
97,"Detection of human bocavirus in respiratory, fecal, and blood samples by real‐time PCR","Human bocavirus (HBoV) has been detected worldwide in respiratory samples. Two real‐time PCR assays, targeting the non‐structural protein (NP‐1) and viral protein (VP‐1) genes, were designed and validated to detect HBoV in patients with respiratory disease, gastroenteritis, or systemic illness. Sensitivity of the NP‐1 and VP‐1 assays were equal to the conventional PCR assay previously described by Allander et al. [2005: Proc Natl Acad Sci USA 102: 12891–12896] being 100%, and giving specificity of 94% and 93%, respectively. There was no cross‐reaction identified with unrelated respiratory agents, or to human DNA. The limits of detection were 10 copies of genomic DNA equivalents per reaction for both assays. The assays were used to screen three different sample populations, combined nose, and throat swabs (n = 96) from children with acute respiratory disease, fecal samples (n = 375) from adults, and children with gastroenteritis and whole blood (n = 229) collected from 31 immunocompromised children taken over an 18‐month period. In total 17 (18%) respiratory samples and 18 (4.8%) fecal samples were identified as having HBoV present. Of the pediatric whole blood specimens investigated, HBoV was detected in six (2.6%) samples from four patients. In summary, two real‐time PCR assays targeting different genes were designed and validated for use as screening methods for the detection of HBoV. HBoV was found in three different specimen types: parent‐collected combined nose–throat swabs, fecal samples collected from symptomatic individuals and whole blood from immunocompromised children. J. Med. Virol. 81:488–493, 2009. © 2009 Wiley‐Liss, Inc."
98,"ORIGINAL ARTICLE: Taxonomy and diversity of Afroalpine Chironomidae (Insecta: Diptera) on Mount Kenya and the Rwenzori Mountains, East Africa","Aim Anthropogenic climate change is expected to result in the complete loss of glaciers from the high mountains of tropical Africa, with profound impacts on the hydrology and ecology of unique tropical cold‐water lakes located downstream from them. This study examines the biodiversity of Chironomidae (Insecta: Diptera) communities in these scarce Afroalpine lake systems, in order to determine their uniqueness in relation to lowland African lakes and alpine lakes in temperate regions, and to evaluate the potential of Afroalpine Chironomidae as biological indicators to monitor future changes in the ecological integrity of their habitat. Location Mount Kenya (Kenya) and Rwenzori Mountains (Uganda). Methods The species composition of Afroalpine chironomid communities was assessed using recent larval death assemblages extracted from the surface sediments of 11 high‐mountain lakes between 2900 and 4575 m. Results were compared with similar faunal data from 68 East African lakes at low and middle elevation (750–2760 m), and with literature records of Chironomidae species distribution in sub‐Saharan Africa, the Palaearctic region and elsewhere. All recovered taxa were fully described and illustrated. Results The 11‐lake analysis yielded 1744 subfossil chironomid larvae belonging to 16 distinct taxa of full‐grown larvae, and three taxa of less differentiated juveniles. Eleven of these 16 are not known to occur in African lakes at lower elevation, and eight taxa (or 50% of total species richness) appear restricted to the specific habitat of cold lakes above 3900 m, where night‐time freezing is frequent year‐round. The faunal transition zone coincides broadly with the Ericaceous zone of terrestrial vegetation (c. 3000–4000 m). Snowline depression during the Quaternary ice ages must have facilitated dispersion of cold‐stenothermous species among the high mountains of equatorial East Africa, but less so from or to the Palaearctic region via the Ethiopian highlands. Main conclusions Chironomid communities in glacier‐fed lakes on Africa's highest mountains are highly distinct from those of lowland African lakes, and potentially unique on a continental scale. By virtue of excellent preservation and their spatial and temporal integration of local community dynamics, chironomid larval death assemblages extracted from surface sediments are powerful biological indicators for monitoring the hydrological and ecological changes associated with the current retreat and loss of Africa's glaciers."
99,Isolation and Identification of Enteric Adenoviruses,"Thirty‐four out of 64 faecal samples with adenovirus particles, as seen by electron microscopy, were found to contain adenovirus 40 or 41 by direct isolation and neutralization in Chang's conjunctival cells, mostly within one week. (Ad40 and 41 candidate viruses are serologically related.) 6 other adenovirus specics were isolated; 6 samples gave equivocal results, and 18 were negative. A genus‐specific ELISA with an antihexon coat yielded positive results in 40 out of 55 samples; the test failed to identify adenovirus antigen in 10 out of 17 specimens, which were found negative by culture. All of them were negative by immunfluorescence of inoculated Chang cell cultures. Hence the failures are probably due to insufficient amount of virus in the samples. The predominance of only two adenovirus species associated with gastroenteritis in children and the ease of cultivating and identifying them should help to elucidate their etiological significance."
100,Evaluation of the chemical and nutritional characteristics of almonds (Prunus dulcis (Mill). D.A. Webb) as influenced by harvest time and cultivar,"BACKGROUND: Several workers have studied the effect of harvest time on chemical and nutritional composition of almonds, but the results are partly conflicting, probably due to differences in the cultivars considered and to different agronomic and climatic conditions in the growing areas. In this paper, the influence of harvest time and cultivar on the chemical and nutritional composition of almonds (Prunus dulcis (Mill). D.A. Webb) were evaluated. Ten cultivars were considered, grown in the same orchard and subjected to the same agronomical regime. Almonds were collected at two different harvest times: (i) when the fruits were unripe, but already edible, and showed green and moist hull; and (ii) when the fruits were ripe, with dry brown hull. The analyses of proximate composition, fatty acid profile, total phenolic compounds, and antioxidant activity were carried out. RESULTS: Lipid content increased (P < 0.001) during ripening, while both protein and carbohydrate content decreased (P < 0.01). Fatty acid composition showed a not univocal behavior during ripening and was highly influenced by cultivar. Total phenolic compounds and antioxidant activity varied among cultivars but increased during ripening with the exception of cv Marcona. The ‘Genco’ and ‘Francolì’ cultivars were found to be phenolic rich. CONCLUSION: Harvest time and cultivar significantly influenced the chemical and nutritional composition of almonds. Genotype strongly influenced fatty acid composition and total phenolic compounds. The changes of bioactive compounds and antioxidant activity suggest that the synthesis of antioxidants also occurs in the last stage of ripening. Unripe almonds, a valuable niche product, showed interesting nutritional value. © 2018 Society of Chemical Industry"
101,Hemostatic Disorders in Feline Immunodeficiency Virus‐Seropositive Cats,"The hemostatic function of 40 feline immunodeficiency virus (FlV) seropositive and 8 FIV and feline leukemia virus (FeLV) seropositive cats was evaluated and compared with reference values from 30 clinically healthy cats. The FIVpositive cats were divided into 3 groups: group I included asymptomatic carriers; group II comprised sick FIV‐infected cats with illnesses not likely to influence the hemostatic system; and group III included FIV‐positive cats with diseases potentially associated with coagulopathies. Platelet counts in FIV/FeLV‐infected cats were significantly lower than in healthy cats (P < .003), whereas the differences in the 3 groups of FIV‐positive cats were variable (group I, P= .009; II, P= .05; III, P= .09). Thrombocytopenia (< 145,000 platelets/μL) was present in 4 FIV‐positive and 3 FIV/FeLV‐positive cats. Platelet aggregation induced by collagen (0.5 and 0.25 μg/mL), adenosine diphosphate (ADP) (1 and 0.6 μmol/L), and thrombin (0.4 and 0.25 IU/mL) was not significantly different from that of healthy cats. The plasma coagulation system was evaluated by measuring one‐stage prothrombin time (OSPT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen concentration, coagulation factor assays, fibrinogen and fibrin degradation products (FDP), and plasma exchange test. The OSPT was similar in FlV‐seropositive cats and in the healthy control group. Cats with FIV infection, however, had markedly shorter clotting times than healthy cats when using a modified test system (P < .05). In all groups of FIV‐infected cats and in those with FIV/FeLV infection, APTT measured with 2 different commercially available tests, and a modified plasma assay was markedly prolonged compared with healthy cats (APTT1 and 2:3 modification: P < .01; APTT2: P < .05 except group III). In 22 of 40 cats with FIV and in 5 of 8 cats with FIV/FeLV infection, plasma samples were beyond the reference range. The thrombin time was also significantly prolonged in cats with FIV and FIV/FeLV infection (P < .01); values in 17 of 40 FIV‐positive cats were above reference range. The mean fibrinogen concentration of cats with FIV and FIV/FeLV infection was higher than in the healthy control group (P < .001). Factor VIII activity of 4 cats with FIV infection was 1.5 times higher than that of healthy cats. Factor XII activity of 3 cats from a group of 20 cats with prolonged APTT was between 20% and 35%. Factor IX and XI activities ranged between 70% and 120%. The markedly prolonged APTT in 2 FIV‐positive cats could be shortened considerably in a plasma exchange test using 20% feline pooled plasma. The alterations in the coagulogram of FIV‐seropositive cats were not related to a clinical stage or concurrent diseases. A definite explanation of the distinct disorder within the intrinsic plasma coagulation system in FIV‐infected cats was not found."
102,Expression and distribution of cystic fibrosis transmembrane conductance regulator in neurons of the spinal cord,"To verify the hypothesis that cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in neurons of the human spinal cord, we investigated the presence and distribution of CFTR protein and mRNA in different segments of the human spinal cord obtained from autopsies. The techniques employed included reverse transcriptase‐polymerase chain reaction (RT‐PCR) to detect CFTR gene expression, in situ hybridization to detect mRNA distribution, and immunohistochemistry to detect protein distribution. The specificity of these experiments was established with extensive controls. We found widespread and abundant expression of CFTR in neurons of the human spinal cord. CFTR protein and mRNA are localized to the cytoplasm of neurons in all segments of the spinal cord but not to glial fibrillary acidic protein (GFAP)‐positive cells. CFTR is a very important molecule, acting as a chloride channel and regulating many physiological functions, including salt transport, fluid flow, and intracellular ion concentrations. Its mutation causes cystic fibrosis. Our finding of abundant CFTR in the spinal cord suggests that this molecule may be significant in the normal function and pathology of the spinal cord. © 2009 Wiley‐Liss, Inc."
103,Acute Tubulointerstitial Nephritis With Eosinophiluria in a Dog,
104,H(v)1 Proton Channels in Dinoflagellates: Not Just for Bioluminescence?,"Bioluminescence in dinoflagellates is controlled by H(V)1 proton channels. Database searches of dinoflagellate transcriptomes and genomes yielded hits with sequence features diagnostic of all confirmed H(V)1, and show that H(V)1 is widely distributed in the dinoflagellate phylogeny including the basal species Oxyrrhis marina. Multiple sequence alignments followed by phylogenetic analysis revealed three major subfamilies of H(V)1 that do not correlate with presence of theca, autotrophy, geographic location, or bioluminescence. These data suggest that most dinoflagellates express a H(V)1 which has a function separate from bioluminescence. Sequence evidence also suggests that dinoflagellates can contain more than one H(V)1 gene."
105,"European College of Veterinary Internal Medicine‐Companion Animals: Oral Research Communications of the 18th ECVIM‐CA Congress Ghent, Belgium, 4th to 6th September 2008",
106,Speakers Abstracts,
107,Detection of Human Rhinoviruses and Their Molecular Relationship Using cDNA Probes,"We describe here a cDNA: RNA hybridization system for the study of human rhinoviruses. We have constructed an M13 probe from the 5′ end of the genome of rhinovirus 14 (HRV‐14) and used this to detect directly viral RNA. Of the 56 human rhinoviruses so far investigated 54 or 96.4% gave clearly positive hybridization signals. However, the strength of this signal depended very much on the molecular relationship of these viruses. Thus, HRV‐3, 4, 17, 72, and, to a slightly lesser extent, HRV‐2, 6, 9, 13, 19, 31, 42, 49, 64, and 69 appear to be closely related to HRV‐14 whereas HRV‐5, 7, 8, 16, 32, 40, 45, 55, 56, 63, 80, 82, and 85 appear to be relatively divergent. Further, evidence is provided in this study that indicates that it would be feasible to use cDNA probes to detect human rhinoviruses in nasal washings. However, the sensitivity of detection was clearly affected by both the inclusion of inhibitors of endogenous RNase activity in the RNA extraction mixture and also in the method of extracting the viral RNA. From reconstruction experiments in nasal washings and under optimal conditions, we can detect virus at 10(2.8) TCID(50)/ml."
108,The safety of Bacillus species as insect vector control agents,
109,Introducing a Senior Course on Catastrophe Preparedness into the Dental School Curriculum,"This article describes an integrated fourth‐year course in catastrophe preparedness for students at the New York University College of Dentistry (NYUCD). The curriculum is built around the competencies proposed in “Predoctoral Dental School Curriculum for Catastrophe Preparedness,” published in the August 2004 Journal of Dental Education. We highlight our experience developing the program and offer suggestions to other dental schools considering adding bioterrorism studies to their curriculum."
110,Serotonin turnover rate in raphe and cortex of mice infected with Venezuelan equine encephalomyelitis virus,"The turnover of serotonin (5HT) was determined in the raphe area and cortex of mice infected with Pixuna, a strain of intermediate virulence of Venezuelan equine encephalomyelitis virus (VEEV). NMRI‐mice, 24 days old, were inoculated intracerebrally (ic) with 300 LDS0 of the virus. The animals were sacrificed 4, 7, 15, 21, 30, and 60 days postinoculation. 5HT and 5‐hydrodryindolacetic acid (SHIAA) in raphe and cortex were determined by high performance liquid chromatography (HPLC) with electrochemical detection. Turnover rate of 5HT was determined by the administration of pargyline, p‐chlorophenylalanine, and probenecid. The content of 5HT or SHIAA and 5HT/5HIAA ratios were not significantly different in infected compared with control mice. However, a decrease of 5HT turnover rate, determined after pargyline treatment, was observed in the raphe and not in the cortex of infected mice at 4 and 7 days after the inoculation. The turnover rate/(5HT)(0) in raphe is decreased in infected mice with signs of illness, suggesting a lower density of 5HT innervation in this brain area. The administration of p‐chlorophenylalanine and probenecid showed that the cortex is also affected, but the synthesis is less modified than metabolism or elimination. Cell bodies of 5HT neurons seem to be more susceptible than projections to infection by Pixuna strain of VEEV."
111,COMPILED BY THE VACCINATION GUIDELINES GROUP (VGG) OF THE WORLD SMALL ANIMAL VETERINARY ASSOCIATION (WSAVA),
112,Attitudes Toward People Living With HIV/AIDS: A Model of Attitudes to Illness,"This study examined attitudes toward people living with HIV/AIDS within a sample of 220 young men and women. As predicted, a multiple regression analysis revealed that the fear of contracting HIV/AIDS through casual contact was a significant predictor of both men's and women's willingness to interact with people living with HIV/AIDS. Attitudes toward homosexuality were also a significant predictor of attitudes toward people living with HIV/AIDS among women, who generally have a low risk of contracting the disease in Western societies. These results indicate that attitudes toward people with a serious illness may be strongly related to the perceived risk of contracting the disease."
113,Blastogenesis of Large Granular Lymphocytes in Nonlymphoid Organs,"High numbers of large granular lymphocytes (LGL) accumulate in the livers and peritoneal cavities of mice during the course of viral infection. Accumulation of natural killer (NK) cells at day 3 postinfection (p.i.) was shown to be radiation‐sensitive, implying that proliferation was required for this response. Accumulation occurred in splenectomized mice, indicating that the spleen, known to be an organ for mature NK cell proliferation, was not the major source for liver and peritoneal NK/LGL. Significant percentages (> 25%) of the LGL found in the liver and peritoneal cavity following viral infection or interferon induction with poly‐inosinic:pory‐cytidylic acid were defined morphologically as blasts (large cells with prominent nucleoli and intensely basophilic cytoplasms containing azurophilic granules). Most blast LGL at day 3 p.i. were sensitive to administration of anti‐asialo GM(1) serum in vivo, were Lyt‐2(‐), and were enriched in populations that lysed NK cell‐sensitive targets in vitro, indicating that these were NK/LGL. At day 3 p.i., leukocytes from the liver and peritoneal cavity incorporated (3)H‐thymidine and bound to and killed NK cell‐sensitive targets in single‐cell cytotoxicity assays. These data suggest that NK/LGL undergo at least one round of division in the liver and peritoneal cavity during viral infection. In contrast, blast LGL at day 7 p.i. were resistant to in vivo treatments with anti‐asialo GM(1) serum, were Lyt‐2(+), and were enriched in populations of cells that killed virus‐infected histocompatible targets, indicating that they were cytotoxic T lymphocytes (CTL). These results suggest that both NK/LGL and CTL/LGL are capable of blastogenesis and presumed proliferation at sites of virus infection, providing a means for the in situ augmentation of a host's cell‐mediated antiviral defenses."
114,Effect of persistent mouse hepatitis virus infection on MHC Class I expression in murine astrocytes,"Neurotropic strains of mouse hepatitis virus (MHV) have been used extensively for the study of viral pathogenesis in the central nervous system (CNS), serving as models for human neurological diseases such as multiple sclerosis (MS). MHV strains A59 and JHMV both cause acute and chronic encephalomyelitis and demyelination in susceptible strains of mice and rats. In acute disease, CNS damage is most likely the result of lytic infection in neurons and oligodendrocytes, and death can be prevented by the adoptive transfer of Class I‐restricted CD8+ T cells. However, in later stages of the disease induced by some MHV strains, virus tends to be restricted to astrocytes in a nonlytic infection, and the immune response appears to contribute to CNS damage. These data lead us to suggest that the astrocyte may play a central role in the neuropathogenesis of MHV infection. Consistent with this possibility, A59 has been reported to induce the expression of Class I molecules of the major histocompatibility complex (MHC) in glial cells following infection in vivo and in vitro. In this communication, we have examined the influence of persistent infection by both A59 and JHMV on MHC Class I expression in primary murine astrocytes. Persistence was characterized by the presence of intracellular viral antigen and mRNA in the absence of detectable infectious virus particles. Under these conditions, JHMV, but not A59, inhibited constitutive expression of the H‐2 K(b) molecule, with the magnitude of inhibition increasing with postinfection time. A59 was not able to induce Class I during persistence, presumably due to the lack of infectious virus particles. Class I expression was restored by the addition of gamma‐interferon (IFN‐γ) to astrocytes persistently infected with either A59 or JHMV. Thus, Class I inhibition is not a permanent consequence of JHMV persistence, and persistence does not interfere with normal signalling pathways for Class I induction. © 1995 Wiley‐Liss, Inc."
115,The biogeographical assignment of a west Kenyan rain forest remnant: further evidence from analysis of its reptile fauna,"Aim The Kakamega Forest, western Kenya, has been biogeographically assigned to both lowland and montane forest biomes, or has even been considered to be unique. Most frequently it has been linked with the Guineo‐Congolian rain forest block. The present paper aims to test six alternative hypotheses of the zoogeographical relationships between this forest remnant and other African forests using reptiles as a model group. Reptiles are relatively slow dispersers, compared with flying organisms (Aves and Odonata) on which former hypotheses have been based, and may thus result in a more conservative biogeographical analysis. Location Kakamega Forest, Kenya, Sub‐Saharan Africa. Methods The reptile diversity of Kakamega Forest was evaluated by field surveys and data from literature resources. Faunal comparisons of Kakamega Forest with 16 other African forests were conducted by the use of the ‘coefficient of biogeographic resemblance’ using the reptile communities as zoogeographic indicators. Parsimony Analysis of Endemism and Neighbour Joining Analysis of Endemism were used to generate relationship trees based on an occurrence matrix with paup*. Results The analysis clearly supports the hypothesis that the Kakamega Forest is the easternmost fragment of the Guineo‐Congolian rain forest belt, and thus more closely related to the forests of that Central–West African complex than to any forest further east, such as the Kenyan coastal forests. Many Kenyan reptile species occur exclusively in the Kakamega Forest and its associated forest fragments. Main conclusions The Kakamega Forest is the only remnant of the Guineo‐Congolian rain forest in the general area. We assume that the low degree of resemblance identified for the Guineo‐Congolian forest and the East African coastal forest reflect the long history of isolation of the two forest types from each other. Kenyan coastal forests may have been historically connected through forest ‘bridges’ of the southern highlands with the Congo forest belt, allowing reptile species to migrate between them. The probability of a second ‘bridge’ located in the region of southern Tanzanian inselbergs is discussed. Although not particularly rich in reptile species, the area should be considered of high national priority for conservation measures."
116,Mixed viral infections of the respiratory tract; an epidemiological study during consecutive winter seasons,"The current study aimed to describe the molecular epidemiology of mixed respiratory viral infections during consecutive winter seasons in a tertiary care hospital. Patients with symptoms of respiratory tract infection were evaluated during the 2009‐2011 and 2013‐15 winter seasons. A clinical microarray technique was used for viral detection. Clinical and epidemiological data were correlated with mixed viral detection and the need for hospitalization. In 332 out of 604 (54.4%) evaluated patients (17.6% children) a respiratory virus was identified. Mixed viral infections were diagnosed in 68/332 (20.5%) patients with virus detection (66.2% mixed Influenza‐RSV infections). Mixed viral infections were more commonly detected in children (OR 3.7; 95%CI 1.9‐5.6, P < 0.01) and patients with comorbidities. In logistic regression analyses, mixed viral infections were associated with younger age (mean age 30.4 years vs. 41.8 years, P ≤ 0.001) and increased rates of fever (OR: 2.7; 95%CI 1.04‐7.2, P < 0.05) but no adverse outcomes or increased rates of hospitalization. High rates of mixed viral infections were noted during all winter seasons (especially Influenza and RSV) and were more common in younger patients. The clinical significance of mixed respiratory viral infection needs further elucidation."
117,Pancreatic surgical biopsy in 24 dogs and 19 cats: postoperative complications and clinical relevance of histological findings,"OBJECTIVE: To assess the immediate postoperative complications associated with pancreatic biopsy in dogs and cats and review the clinical relevance of biopsy findings. METHODS: Retrospective review of clinical records from two referral institutions for cases undergoing pancreatic biopsy between 2000 and 2013. RESULTS: Twenty‐four dogs and 19 cats that had surgical pancreatic biopsy had sufficient detail in their clinical records and fulfilled the inclusion criteria. Postoperative complications were seen in 10 cases of which 5 were suggestive of post‐surgical pancreatitis. Two patients were euthanased within 10 days of surgery because of the underlying disease; neither suffered postoperative complications. Pancreatic pathology was found in 19 cases, 7 cases showed no change other than benign pancreatic nodular hyperplasia, and no abnormalities were seen in 18 cases. CLINICAL SIGNIFICANCE: Complications may be encountered following surgical pancreatic biopsy, although the risk should be minimal with good surgical technique. Pancreatic biopsy may provide a useful contribution to case management but it is not clear whether a negative pancreatic biopsy should be used to rule out pancreatic disease. Dogs were more likely to have no significant pathology found on pancreatic biopsy than cats, where chronic pancreatitis was the most common finding."
118,Published Only,
119,Viral infections in the acquired immunodeficiency syndrome,"The following communication is a tripartite synopsis of the role of viral infection in the acquired immunodeficiency syndrome (AIDS). The first section describes the impact of viral opportunistic infection in AIDS; for each virus, clinical presentation and diagnosis, laboratory diagnostic approaches (with emphasis on electron microscopy), and therapeutic interventions attempted to date are discussed. The second segment explores current theories on the pathogenesis of AIDS, and describes diagnostic and therapeutic approaches to the syndrome itself. The final section catalogues ultrastructural anomalies in the cells of AIDS patients, many of which have been mistakenly identified as etiologic agents."
120,Myelin‐ and microbe‐specific antibodies in guillain‐barré syndrome,"We surveyed the frequency of reported infections and target autoantigens in 56 Guillain Barré syndrome (GBS) patients by detecting antibodies to myelin and microbes. Sulfatide (43%), cardiolipin (48%), GD(1a) (15%), SGPG (11%), and GM(3) (11%) antibodies were the most frequently detected heterogenous autoantibodies. A wide spectrum of antimicrobial IgG and IgM antibodies were also detected; mumps‐specific IgG (66%), adenovirus‐specific IgG (52%), varicella‐zoster virus‐specific IgG (46%), and S. pneumoniae serotype 7‐specific IgG (45%) were the most prevalent. Our results indicate that polyclonal expansion of physiologic and pathologic antibodies and/or molecular mimicry likely occurs following infection and is related to other autoimmune factors in the etiology of GBS. Although no single definitive myelin‐specific autoantibody was identified, our results suggest a unique pattern of reactivity against autoantigens."
121,Rotavirus and other viruses in the stool of premature babies,"In a 12‐month study, 363 stools of 199 premature babies nursed in a separate ward of a paediatric clinic were examined by electron microscopy and on cell culture to detect virus. Twenty‐four (6.6%) were positive for rotavirus, in one winter epidemy. From four stools Echo 22 was isolated, and in six cases virus‐like particles were detected by electron microscopy. These virus infections are not a major problem in newborns, requiring special care, as they are mostly symptomless or mild."
122,Editor’s Perspectives – May 2020,
123,Development of an Efficient Bioprocess for Poultry Vaccines Using High‐density Insect Cell Culture,
124,Long‐term morbidity of respiratory viral infections during chemotherapy in children with leukaemia,"BACKGROUND: Respiratory viruses are a common cause of infection in immunosuppressed children undergoing cancer therapy. Pulmonary sequelae have been documented following respiratory viral infections (RVIs) in hematopoietic stem cell transplant (HSCT) recipients; however potential late effects in children undergoing nonmyeloablative chemotherapy have not been investigated. AIM: To evaluate the long‐term pulmonary morbidity of respiratory viral infections during chemotherapy in children with acute lymphoblastic leukemia (ALL). METHODS: Childhood ALL survivors, aged 7 to 18 years, greater than 6 months posttreatment were recruited. Exclusion criteria included HSCT or proven bacterial/fungal respiratory infection during treatment. Subjects were classified into “viral” or “control” groups according to retrospective medical records that documented the presence of laboratory‐proven RVIs during chemotherapy. Symptom questionnaires (Liverpool, ISAAC) and lung function testing (spirometry, plethysmography, diffusing capacity, forced oscillation technique to ATS/ERS standards) were then performed cross‐sectionally at the time of recruitment. RESULTS: Fifty‐four patients (31 viral, 23 control) were recruited: median (range) age 11.2 (7.2‐18.1) years, and at 4.9 (0.5‐13) years posttherapy. Abnormalities were detected in 17 (31%) individuals (8 viral, 9 control), with the most common being DLCO impairment (3 viral, 4 control) and reduced respiratory reactance at 5 Hz (5 viral, 6 control). Children with RVIs during chemotherapy reported more current respiratory symptoms, particularly wheeze (odds ratio [OR], 3.0; 95% confidence interval [CI]: 0.9‐10.0; P = .09) and cough (OR, 2.7; 95% CI: 0.8‐9.5; P = .11). No differences in lung function tests were observed between the two groups. CONCLUSIONS: Our study found children with RVIs during chemotherapy developed more long‐term respiratory symptoms than controls; however, differences did not reach statistical significance. No differences in static lung function were found between the two groups. Overall, pulmonary abnormalities and/or significant ongoing respiratory symptoms were detected in nearly a third of ALL survivors treated without HSCT. Larger, prospective studies are warranted to evaluate the etiology and clinical significance of these findings."
125,Conference Report,
126,Pharyngotonsillitis,
127,Flavor and odour characteristics of species of Allium in relation to their capacity to stimulate germination of sclerotia of Sclerotium cepivorum,"Of many species or cultivars of Allium tested only six ornamental species showed little or no capacity to stimulate germination of sclerotia of Sclerotium cepivorum. All six species had S‐methyl‐L‐cysteine sulphoxide as their principal flavour and odour precursor and their overall flavour and odour levels were low. All other species and cultivars were highly stimulatory, contained considerahle amounts of S‐1 or S‐2‐propenyl‐L‐cysteine sulphoxide as flavour and odour precursors and, with a few exceptions, they possessed high overall flavour and odour levels. These included several species which are thought to be related to cultivated edible forms. With the possible exception of A. caeruleum and A. cyaneum no evidence of resistance to infection by S. cepivorum was detected."
128,Molecular profiling of oral microbiota in jawbone samples of bisphosphonate‐related osteonecrosis of the jaw,"Oral Diseases (2012) 18, 602–612 Objective: Infection has been hypothesized as a contributing factor to bisphosphonate (BP)‐related osteonecrosis of the jaw (BRONJ). The objective of this study was to determine the bacterial colonization of jawbone and identify the bacterial phylotypes associated with BRONJ. Materials and methods: Culture‐independent 16S rRNA gene‐based molecular techniques were used to determine and compare the total bacterial diversity in bone samples collected from 12 patients with cancer (six, BRONJ with history of BP; six, controls without BRONJ, no history of BP but have infection). Results: Denaturing gradient gel electrophoresis profile and Dice coefficient displayed a statistically significant clustering of profiles, indicating different bacterial population in BRONJ subjects and control. The top three genera ranked among the BRONJ group were Streptococcus (29%), Eubacterium (9%), and Pseudoramibacter (8%), while in the control group were Parvimonas (17%), Streptococcus (15%), and Fusobacterium (15%). H&E sections of BRONJ bone revealed layers of bacteria along the surfaces and often are packed into the scalloped edges of the bone. Conclusion: This study using limited sample size indicated that the jawbone associated with BRONJ was heavily colonized by specific oral bacteria and there were apparent differences between the microbiota of BRONJ and controls."
129,Innovationen verbessern Lebensqualität von Patienten mit Hämophilie A,"Die Hämophilie gehört zu den am längsten bekannten Erbkrankheiten. Erst in den 60er Jahren ist es jedoch gelungen, Gerinnungskonzentrate aus Blutplasma herzustellen und damit eine Behandlung einzuführen, die Patienten vor schweren Blutungen und Verkrüppelungen bewahrt."
130,Role of chronic stress and depression in periodontal diseases,"An extensive body of experimental and clinical evidence documents the negative impact of chronic psychological stress and depression on the immune system and health. Chronic stress and depression can result in general dysregulation of the immune system, of both cellular and humoral pathways, which may contribute to pathogenic infection and concomitant periodontal tissue destruction. In general, the evidence is consistent with the hypothesis that stress can modify the host defense and progression of periodontal infections in patients susceptible to periodontitis. However, substantial evidence also indicates that these conditions can mediate risk for disease, including periodontitis, through changes in health‐related behaviors, such as oral hygiene, smoking and diet. The unequivocal interpretation of studies has also been hampered, in part, by issues related to conceptualization of stress and depression, as well as commonly associated comorbidities, such as diabetes, that can modify the onset and progression of periodontal disease. In addition, stress and depression appear to fall into a spectrum, ranging from mild to severe, involving a complex interaction of genetic background, coping strategies and environment. Differences in the conceptualization of stress and depression are probably important in assessing associations with other biologic and clinical measures. Future studies are necessary to clarify the complex interactions of chronic stress and depression in periodontal diseases."
131,Cost‐Effective Antibiotic Prescribing,"Antibiotics are often misused, resulting in a high frequency of adverse effects, emergence of drug‐resistant organisms, and excessive costs. The high cost of antibiotics is currently receiving the greatest attention. Considerable cost savings can be achieved by appropriate prescribing of antibiotics for patients receiving these drugs prophylactically as well as for those with established infections. This article cites specific examples of how cost‐effective antibiotic prescribing practices can realize substantial cost savings without any diminished quality in patient care."
132,Zytostatika aus dem Meer,Bodenbakterien aus der Gruppe der Actinomyceten sind seit langem Lieferanten für hoch wirksame Antibiotika. Dagegen sind Sekundärmetaboliten aus Actinomyceten des marinen Sediments noch eher selten.
133,"Plasticity for colour adaptation in vertebrates explained by the evolution of the genes pomc, pmch and pmchl","Different camouflages work best with some background matching colour. Our understanding of the evolution of skin colour is based mainly on the genetics of pigmentation (“background matching”), with little known about the evolution of the neuroendocrine systems that facilitate “background adaptation” through colour phenotypic plasticity. To address the latter, we studied the evolution in vertebrates of three genes, pomc, pmch and pmchl, that code for α‐MSH and two melanin‐concentrating hormones (MCH and MCHL). These hormones induce either dispersion/aggregation or the synthesis of pigments. We find that α‐MSH is highly conserved during evolution, as is its role in dispersing/synthesizing pigments. Also conserved is the three‐exon pmch gene that encodes MCH, which participates in feeding behaviours. In contrast, pmchl (known previously as pmch), is a teleost‐specific intron‐less gene. Our data indicate that in zebrafish, pmchl‐expressing neurons extend axons to the pituitary, supportive of an MCHL hormonal role, whereas zebrafish and Xenopus pmch+ neurons send axons dorsally in the brain. The evolution of these genes and acquisition of hormonal status for MCHL explain different mechanisms used by vertebrates to background‐adapt."
134,Use of Plant Viruses for Delivery of Vaccine Epitopes,
135,Temperature Dependence of Activation Energy in Stage II Recovery in Deformed Aluminium,The activation energy of recovery in 99.999% aluminium deformed at 4.2 K is investigated at temperatures between 50 to 180 K by means of the change of slope method. The activation energy varies from 0.15 to 0.60 eV with raising temperature. This behaviour is simulated by considering an overlapping of several first order processes within stage II. It is supposed that the variation of activation energy in stage II is due to recovery of vacancies and their small clusters by pipe diffusion mechanism.
136,Poster session abstracts,
137,Lessons learned,
138,An indicator‐based problem reduction scheme for coupled reactive transport models,"A number of effective models have been developed for simulating chemical transport in porous media; however, when a reactive chemical problem comprises multiple species within a substantial domain for a long period of time, the computational cost can become prohibitively expensive. This issue is addressed here by proposing a new numerical procedure to reduce the number of transport equations to be solved. This new problem reduction scheme (PRS) uses a predictor‐corrector approach, which “predicts” the transport of a set of non‐indicator species using results from a set of indicator species before “correcting” the non‐indicator concentrations using a mass balance error measure. The full chemical transport model is described along with experimental validation. The PRS is then presented together with an investigation, based on a 16‐species reaction‐advection‐diffusion problem, which determines the range of applicability of different orders of the PRS. The results of a further study are presented, in which a set of PRS simulations is compared with those from full model predictions. The application of the scheme to the intermediate‐sized problems considered in the present study showed reductions of up to 82% in CPU time, with good levels of accuracy maintained."
139,"Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction 2014 Winter Meeting February 25–March 1, 2014 Doral Golf Resort & Spa Miami, Florida",
140,Systematik und Biologie der Hepatitis‐Viren. Ähnliche Erkrankung – unterschiedliche Viren,"Hepatitis‐Viren wurden und werden dadurch gefunden und letztlich auch benannt, dass man die infektiösen Agenzien – meist in Form ihrer Nukleinsäuren – im Blut von Patienten mit Leberentzündungen nachweist. Die Nomenklatur folgt dann dem Alphabet. So ist es leicht nachvollziehbar, dass durchaus sehr unterschiedliche Virustypen gefunden wurden, die strukturell keine oder nur wenig Gemeinsamkeiten aufweisen. Umso interessanter ist es, sich die Biologie der verschiedenen Hepatitis‐Viren genauer anzusehen."
141,A comparative study of sex pheromone reception in the Hadeninae (Lepidoptera: Noctuidae),Abstract A comparative study of the olfactory responses to pheromone compounds was performed in twenty‐four species of Hadeninae. Electroantennograms (EAG) were recorded on male moths in response to thirty compounds and the response profiles of each species were analysed by factorial correspondence analysis. A limited number of molecules were found active and the most effective stimuli were Z9 tetradecenes and Z11 hexadecenes. The species of the Mythimna genus were most sensitive to aldehydes. Tholera decimalis did not respond to any of the molecules tested. The species belonging to the Mamestra and the Orthosia genera responded to a variety of molecules and no simple correlation was found between the genus and the EAG sensibility. Pheromone reception is discussed in relation to the taxonomy and the evolution of olfactory communication in Hadeninae.
142,Symposium Summaries,
143,A novel glucuronosyltransferase has an unprecedented ability to catalyse continuous two‐step glucuronosylation of glycyrrhetinic acid to yield glycyrrhizin,"Glycyrrhizin is an important bioactive compound that is used clinically to treat chronic hepatitis and is also used as a sweetener world‐wide. However, the key UDP‐dependent glucuronosyltransferases (UGATs) involved in the biosynthesis of glycyrrhizin remain unknown. To discover unknown UGATs, we fully annotated potential UGATs from Glycyrrhiza uralensis using deep transcriptome sequencing. The catalytic functions of candidate UGATs were determined by an in vitro enzyme assay. Systematically screening 434 potential UGATs, we unexpectedly found one unique GuUGAT that was able to catalyse the glucuronosylation of glycyrrhetinic acid to directly yield glycyrrhizin via continuous two‐step glucuronosylation. Expression analysis further confirmed the key role of GuUGAT in the biosynthesis of glycyrrhizin. Site‐directed mutagenesis revealed that Gln‐352 may be important for the initial step of glucuronosylation, and His‐22, Trp‐370, Glu‐375 and Gln‐392 may be important residues for the second step of glucuronosylation. Notably, the ability of GuUGAT to catalyse a continuous two‐step glucuronosylation reaction was determined to be unprecedented among known glycosyltransferases of bioactive plant natural products. Our findings increase the understanding of traditional glycosyltransferases and pave the way for the complete biosynthesis of glycyrrhizin."
144,II. Topic Sessions,
145,Veranstaltungskalender der DPhG,
146,Peramivir for Influenza A and B Viral Infections: A Pharmacokinetic Case Series,"OBJECTIVE: To describe the peramivir (PRV) pharmacokinetics in critically ill children treated for influenza A or B viral infections. DESIGN: Retrospective electronic medical record review of prospectively collected data from critically ill children receiving peramivir for influenza A or B viral infections in the pediatric intensive care unit (PICU). SETTING: A 189‐bed, freestanding children's tertiary care teaching hospital in Philadelphia, PA. PATIENTS: Critically ill children admitted to the PICU who were infected with influenza between January 1, 2016 and March 31, 2018. INTERVENTIONS: None. RESULTS: Eleven patients, two females (18%) and nine males (82%), accounted for 24 peramivir samples for therapeutic drug management. The median age was 5 years (interquartile range 1.5–6.5 yrs) with a median weight of 16.4 kg (interquartile range 14–24 kg). Ten (91%) patients demonstrated a larger volume of distribution, 11 (100%) patients demonstrated an increase in clearance, and 11 (100%) patients demonstrated a shorter half‐life estimate as compared with the package insert and previous pediatric trial data for peramivir. Eight (73%) patients tested positive for a strain of influenza A and 3 (27%) patients tested positive for influenza B; 4 of 11 (36%) patients tested positive for multiple viruses. All patients had adjustments made to their dosing interval to a more frequent interval. Ten (91%) patients were adjusted to an every‐12‐hour regimen and 1 (9%) patient was adjusted to an every‐8‐hour regimen. No adverse events were associated with peramivir treatment. CONCLUSION: The pharmacokinetics of PRV demonstrated in this PICU cohort differs in comparison to healthy pediatric and adult patients, and alterations to dosing regimens may be needed in PICU patients to achieve pharmacodynamic exposures. Additional investigations in the PICU population are needed to confirm these findings."
147,Transforming growth factor‐beta 1 in humidifier disinfectant‐associated children's interstitial lung disease,"BACKGROUND: Humidifier disinfectant‐associated children's interstitial lung disease has an unpredictable clinical course with a high morbidity and mortality. OBJECTIVES: To evaluate the differences in clinical findings between survivors and non‐survivors of humidifier disinfectant‐associated children's interstitial lung disease. To evaluate dynamic changes in serum cytokines related to inflammation and fibrosis in lung injury, and to determine whether these changes are predictive of survival in this disease. METHODS: We evaluated 17 children with humidifier disinfectant‐associated children's interstitial lung disease, from whom serum samples were obtained weekly during hospitalization. The severity of chest tomographic and lung pathologic findings was scored. Levels of several cytokines were measured in the serial serum samples. RESULTS: Seven of the 17 children were survivors. Compared to survivors, non‐survivors had greater ground‐glass attenuation on follow‐up chest tomography, higher admission neutrophil counts, and more macrophages on pathologic findings. Transforming growth factor‐beta 1 persisted at an elevated level (1,000–1,500 pg/ml) in survivors, whereas it decreased abruptly in non‐survivors. At the time of this decrease, non‐survivors had clinical worsening of their respiratory failure. Transforming growth factor‐beta 1 was positively correlated with PaO(2)/FiO(2) (r = 0.481, P < 0.0001). CONCLUSIONS: Non‐survivors exhibited more inflammatory clinical findings than survivors. Transforming growth factor‐beta 1 remained elevated in survivors, suggesting that it affected the clinical course of humidifier disinfectant‐associated children's interstitial lung disease. The prognosis of this lung disease may depend more on controlling excessive inflammation and repairing damaged lung than on fibrosis, and transforming growth factor‐beta 1 may play a key role in this process. Pediatr Pulmonol. 2016;51:173–182. © 2015 Wiley Periodicals, Inc."
148,SIOP ABSTRACTS,
149,Is SARS China's Chernobyl?,
150,Pediatric heart transplant from an incompletely treated influenza A‐positive donor,"There is a shortage of pediatric donor hearts for waitlisted children, and yet nearly 50% of organs offered are not transplanted. Donor quality is often cited as a reason for declining organs offered from donors infected with influenza, presumably due to concern about disease transmission at transplant leading to severe disease. We previously described an excellent outcome after heart transplant from a donor infected with influenza B that had been treated with a complete course of oseltamivir. In this report, we describe a similar outcome after transplantation of an organ from an influenza A‐positive donor with symptomatic disease incompletely treated with oseltamivir. Due to the availability of effective antiviral treatment, we suggest that influenza A is also a manageable donor infection that need not preclude heart placement."
151,"Selected hepatoprotective herbal medicines: Evidence from ethnomedicinal applications, animal models, and possible mechanism of actions","Insight into the hepatoprotective effects of medicinally important plants is important, both for physicians and researchers. Main reasons for the use of herbal medicine include their lesser cost compared with conventional drugs, lesser undesirable drug reactions and thus high safety, and reduced side effects. The present review focuses on the composition, pharmacology, and results of experimental trials of selected medicinal plants: Silybum marianum (L.) Gaertn., Glycyrrhiza glabra, Phyllanthus amarus Schumach. & Thonn., Salvia miltiorrhiza Bunge., Astragalus membranaceus (Fisch.) Bunge, Capparis spinosa (L.), Cichorium intybus (L.), Solanum nigrum (L.), Sapindus mukorossi Gaertn., Ginkgo biloba (L.), Woodfordia fruticosa (L.) Kurz, Vitex trifolia (L.), Schisandra chinensis (Turcz.) Baill., Cuscuta chinensis (Lam.), Lycium barbarum, Angelica sinensis (Oliv.) Diels, and Litsea coreana (H. Lev.). The probable modes of action of these plants include immunomodulation, stimulation of hepatic DNA synthesis, simulation of superoxide dismutase and glutathione reductase to inhibit oxidation in hepatocytes, reduction of intracellular reactive oxygen species by enhancing levels of antioxidants, suppression of ethanol‐induced lipid accumulation, inhibition of nucleic acid polymerases to downregulate viral mRNA transcription and translation, free radical scavenging and reduction of hepatic fibrosis by decreasing the levels of transforming growth factor beta‐1, and collagen synthesis in hepatic cells. However, further research is needed to identify, characterize, and standardize the active ingredients, useful compounds, and their preparations for the treatment of liver diseases."
152,Disulfide conformation and design at helix N‐termini,"To understand structural and thermodynamic features of disulfides within an α‐helix, a non‐redundant dataset comprising of 5025 polypeptide chains containing 2311 disulfides was examined. Thirty‐five examples were found of intrahelical disulfides involving a CXXC motif between the N‐Cap and third helical positions. GLY and PRO were the most common amino acids at positions 1 and 2, respectively. The N‐Cap residue for disulfide bonded CXXC motifs had average (ϕ,ψ) values of (−112 ± 25.2°, 106 ± 25.4°). To further explore conformational requirements for intrahelical disulfides, CYS pairs were introduced at positions N‐Cap‐3; 1,4; 7,10 in two helices of an Escherichia coli thioredoxin mutant lacking its active site disulfide (nSS Trx). In both helices, disulfides formed spontaneously during purification only at positions N‐Cap‐3. Mutant stabilities were characterized by chemical denaturation studies (in both oxidized and reduced states) and differential scanning calorimetry (oxidized state only). All oxidized as well as reduced mutants were destabilized relative to nSS Trx. All mutants were redox active, but showed decreased activity relative to wild‐type thioredoxin. Such engineered disulfides can be used to probe helix start sites in proteins of unknown structure and to introduce redox activity into proteins. Conversely, a protein with CYS residues at positions N‐Cap and 3 of an α‐helix is likely to have redox activity. Proteins 2010. © 2009 Wiley‐Liss, Inc."
153,Fragebogen zur PharmuZ “Arzneimittel gegen Tropenkrankheiten II”,
154,Review of Pharmacological Effects of Glycyrrhiza sp. and its Bioactive Compounds,"The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice root is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, and pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. A large number of components have been isolated from licorice, including triterpene saponins, flavonoids, isoflavonoids and chalcones, with glycyrrhizic acid normally being considered to be the main biologically active component. This review summarizes the phytochemical, pharmacological and pharmacokinetics data, together with the clinical and adverse effects of licorice and its bioactive components. Copyright © 2008 John Wiley & Sons, Ltd."
155,Meeting Report,
156,A Review of the Magnetic Relaxation and Its Application to the Study of Atomic Defects in α‐Iron and Its Diluted Alloys,"This review presents a comprehensive survey on intensive studies performed during the last decades on point defect reactions on α‐iron (α‐Fe) and its diluted alloys. Our intention is to give an actual account of the knowledge accumulated on this subject, as it has been obtained predominantly by means of the magnetic after‐effect (MAE) spectroscopy. After a concise introduction into the theoretical and experimental fundamentals of this technique, the main concern is focused on the presentation and detailed discussion of the MAE spectra arising — after low‐temperature electron (e(–))‐ or neutron(n)‐irradiation and subsequent annealing — in: (i) high‐purity α‐Fe and α‐Fe doped with (ii) substitutional solutes (like Ni, V, Al, Cu, Ti, Be, Si, Mn, …) or (iii) interstitial solutes (like O, H, C, N). During the course of systematic annealing treatments, these respective spectra undergo dramatic variations at specific temperatures thereby revealing in great detail the underlying intrinsic reactions of the radiation‐induced defects, i.e., reorientation, migration, clustering, dissolution and finally annihilation. In alloyed Fe systems the corresponding reaction sequences are even multiplied due to additional interactions between defects and solute atoms. Most valuable information concerning formation‐, dissociation‐ and binding enthalpies of small, mixed clusters (of the type C(i)V(k), N(i)V(k); i, k ≥ 1) has been obtained in high‐purity α‐Fe base material which, after charging with C or N, had been e(–)‐irradiated. Concerning the basic recovery mechanisms in α‐Fe, two complementary results are obtained from the analysis of the various systems: (i) in high‐purity and substitutionally alloyed α‐Fe the recovery in Stage‐III (200 K) is governed by a three‐dimensionally migrating (H (M) (I) = 0.56 eV) stable interstitial (dumb‐bell); (ii) following the formation and dissociation kinetics of small clusters (C(1)V(k), N(1)V(k)) in interstitially alloyed α‐Fe the migration enthalpy of the monovacancy must hold the following relation H (M) (N) (0.76 eV) < H (M) (C) (0.84 eV) < H (M) (V1). These results are in clear agreement with the so‐called two‐interstitial model (2IM) in α‐Fe – a conclusion being further substantiated by a systematic comparison with the results obtained from nonrelaxational techniques, like i.e. positron annihilation (PA), which by their authors are preferentially interpreted in terms of the one‐interstitial model (1IM)."
157,Scientific Content P1–P85,
158,Factors Influencing the Size Structure of Brook Trout and Brown Trout in Southeastern Wyoming Mountain Streams,"We used discriminant models to identify relations among size structures of stocks of brook trout Salvelinus fontinalis and brown trout Salmo trutta and features of their habitats in small mountain streams (2,377–2,975 m above mean sea level) in the Medicine Bow National Forest, Wyoming. Size structure was predicted from position of the study reach in the watershed, from channel gradient, and from composition of the salmonid community. Brook trout were predominantly small in high‐elevation, moderate‐gradient, forested reaches with allopatric populations; they were larger in mid‐elevation, low‐gradient, meadow reaches that contained some brown trout. Brown trout were mostly small in mid‐elevation, moderate‐gradient, forested reaches; however, more large brown trout occurred lower in the watersheds, in meadow or rangeland stream reaches that had low gradients and that supported allopatric populations."
159,2016 ASPHO ABSTRACTS,
160,THE FINE STRUCTURE OF THE CNS IN MULTIPLE SCLEROSIS. I. INTERPRETATION OF CYTOPLASMIC PAPOVAVIRUS‐LIKE AND PARAMYXOVIRUS‐LIKE INCLUSIONS,"During an electron microscopic study of the white matter in multiple sclerosis (MS), spheroidal reticular particles were found both in MS and in control brains. These particles have previously been described in the brain in MS and in brain‐derived cell cultures in subacute sclerosing panencephalitis. In both cases they were interpreted as papovaviruses, but in size, morphology and distribution they are identical to the reticulosomes and related particles which occur as proteinaceous artefacts in a variety of tissues and in subcellular fractions. Inclusions in endothelial cell cytoplasm, previously reported from the CNS in MS as paramyxovirus similar to measles, have also been found in the present study. They were present both in MS and in control brains and are identified as ‘rod‐shaped tubular bodies’, normally occurring organelles of endothelial cells. The necessity for a cautious interpretation of virus‐like inclusions is emphasized."
161,2018 ASPHO ABSTRACTS,
162,Urinary club cell protein 16 (CC16): Utility of its assay during acute bronchiolitis,"Acute bronchiolitis is responsible for high morbidity in infants. Club cell protein 16 kDa (CC16) is a major pneumoprotein secreted by club cells of the bronchial epithelium and eliminated by the renal pathway. CC16 seems to be a biomarker of epithelial damage in asthma. However, its value as a marker of acute bronchiolitis severity and later recurrent wheezing are uncertain, especially the value of its urinary assay for this purpose. A prospective, observational, analytical study was conducted at Clermont‐Ferrand University Hospital to correlate serum CC16 level with clinical severity of bronchiolitis in hospitalized infants aged less than 1 year. We analyzed correlations between serum and urinary CC16, CC16 levels and Wainwright score, immediate morbidity due to bronchiolitis, causal viruses, and recurrent wheezing 1 year after inclusion. In 166 infants, serum CC16 did not correlate with acute bronchiolitis severity (P = .49), but urinary CC16 did (P < .001). In multivariate analysis, urinary CC16 correlated mainly with urinary retinol binding protein (RBP; r = 0.70; P < .001). The logCC16u/logRBPu ratio correlated significantly with severity (P = .02). CC16 levels were not correlated with recurrent wheezing at 1 year. Urinary CC16 could be a useful biomarker in acute bronchiolitis for specific indications. This noninvasive assay would be particularly useful in the young infant population. Several factors must be taken into account in its interpretation, mainly tubular function. Further studies are needed to assess these factors."
163,Lipid transfer proteins from Brassica campestris and mung bean surpass mung bean chitinase in exploitability,"Antifungal peptides with a molecular mass of 9 kDa and an N‐terminal sequence demonstrating remarkable similarity to those of nonspecific lipid transfer proteins (nsLTPs) were isolated from seeds of the vegetable Brassica campestris and the mung bean. The purified peptides exerted an inhibitory action on mycelial growth in various fungal species. The antifungal activity of Brassica and mung bean nsLTPs were thermostable, pH‐stable, and stable after treatment with pepsin and trypsin. In contrast, the antifungal activity of mung bean chitinase was much less stable to changes in pH and temperature. Brassica LTP inhibited proliferation of hepatoma Hep G2 cells and breast cancer MCF 7 cells with an IC(50) of 5.8 and 1.6 µm, respectively, and the activity of HIV‐1 reverse transcriptase with an IC(50) of 4 µm. However, mung bean LTP and chitinase were devoid of antiproliferative and HIV‐1 reverse transcriptase inhibitory activities. In contrast to the mung bean LTP, which exhibited antibacterial activity, Brassica LTP was inactive. All three antifungal peptides lacked mitogenic activity toward splenocytes. These results indicate that the two LTPs have more desirable activities than the chitinase and that there is a dissociation between the antifungal and other activities of these antifungal proteins. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd."
164,Symposium Summaries,
165,"Anti‐HIV, Anti‐Poxvirus, and Anti‐SARS Activity of a Nontoxic, Acidic Plant Extract from the Trifollium Species Secomet‐V/anti‐Vac Suggests That It Contains a Novel Broad‐Spectrum Antiviral","Enveloped animal viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, human papillomavirus, Marburg, and influenza are major public health concerns around the world. The prohibitive cost of antiretroviral (ARV) drugs for most HIV‐infected patients in sub‐Saharan Africa and the serious side effects in those who have access to ARV drugs make a compelling case for the study of complementary and alternative therapies. Such therapies should have scientifically proved antiviral activity and minimal toxic effects. A plant extract, Secomet‐V, with an anecdotal indication in humans for promise as an anti‐HIV treatment, was investigated. Using a previously described attenuated vaccinia virus vGK5, we established the antiviral activity of Secomet‐V. Chemical analysis showed that it has an acidic pH, nontoxic traces of iron (<10 ppm), and almost undetectable levels of arsenic (<1.0 ppm). The color varies from colorless to pale yellow to dark brown. The active agent is heat stable at least up to sterilizing temperature of 121°C. The crude plant extract is a mixture of several small molecules separable by high‐pressure liquid chromatography. The HIV viral loads were significantly reduced over several months in a few patients monitored after treatment with Secomet‐V. Secomet‐V was also found to have antiviral activity against the SARS virus but not against the West Nile virus. Secomet‐V, therefore, is a broad‐spectrum antiviral, which possibly works by neutralizing viral infectivity, resulting in the prevention of viral attachment."
166,Mechanisms of Virus‐Induced Demyelination and Remyelination,
167,Specific RNA Drug Therapy of Hepatitis Viruses,
168,Mold contamination in schools with either high or low prevelance of asthma,"BACKGROUND: Mold exposures have been linked to the development and exacerbation of asthma. The purpose of this study was to determine whether the Environmental Relative Moldiness Index (ERMI) metric, developed to quantify mold exposures in homes, might be applied to evaluating the mold contamination in schools. METHODS: Settled dust samples (n = 10) were collected on each level of a water‐damaged school in Springfield, Massachusetts and two samples per level in five Idaho schools. Each dust sample was analyzed for the 36 molds that make up the ERMI. The concentration of 2.5‐μm particulate matter (PM (2.5)) was measured in each school at two locations during the spring of 2013. RESULTS: The average ERMI value in the Springfield school, 15.51, was significantly greater (p < 0.001) than the average ERMI value, −2.87, in the Idaho schools. Ten of the twenty‐six Group 1 molds, which are associated with water‐damaged environments, were in significantly greater concentrations in the Springfield school. The populations of Group 2 molds, which are common indoors even without water damage, were essentially the same in Springfield and Idaho schools. The average PM (2.5) concentration in the Springfield and Idaho schools was 11.6 and 3.4 μg/m(3), respectively. CONCLUSIONS: The ERMI scale might be useful in comparing the relative mold contamination in schools."
169,COMPARISON OF THE DEVELOPMENT OF RESISTANT STRAINS OF TYPE 1 HERPES SIMPLEX VIRUS TO IN VITRO ANTIVIRAL ACTIVITY OF 5‐IODO‐2‐ DEOXYURIDINE OR RIBAVIRIN.,
170,"Label‐free detection techniques for protein microarrays: Prospects, merits and challenges","Protein microarrays, on which thousands of discrete proteins are printed, provide a valuable platform for functional analysis of the proteome. They have been widely used for biomarker discovery and to study protein–protein interactions. The accomplishments of DNA microarray technology, which had enabled massive parallel studies of gene expression, sparked great interest for the development of protein microarrays to achieve similar success at the protein level. Protein microarray detection techniques are often classified as being label‐based and label‐free. Most of the microarray applications have employed labelled detection such as fluorescent, chemiluminescent and radioactive labelling. These labelling strategies have synthetic challenges, multiple label issues and may exhibit interference with the binding site. Therefore, development of sensitive, reliable, high‐throughput, label‐free detection techniques are now attracting significant attention. Label‐free detection techniques monitor biomolecular interactions and simplify the bioassays by eliminating the need for secondary reactants. Moreover, they provide quantitative information for the binding kinetics. In this article, we will review several label‐free techniques, which offer promising applications for the protein microarrays, and discuss their prospects, merits and challenges."
171,Influence of viral and bacterial respiratory infections on exacerbations and symptom severity in childhood asthma,
172,Hochkontagiöse Erkrankungen. Sind wir vorbereitet?,"Hochkontagiöse, gemeingefährliche, lebensbedrohliche Erkrankungen kommen in Deutschland bislang extrem selten vor, bergen aber ein hohes Gefahrenpotential für Patienten, Gesundheitspersonal und die allgemeine Bevölkerung. Sie können als importierte Infektionen, bei Laborunfällen oder im Rahmen bioterroristischer Anschläge vorkommen. Besondere Bedeutung haben die Mensch zu Mensch übertragbaren viralen hämorrhagischen Fieber (vor allem Ebola, Marburg, Lassa, Krim‐Kongo hämorrhagisches Fieber), Pockenerkrankungen und die Lungenpest. Anamnese und klinisches Bild erlauben Fachleuten, einen “begründeten Verdacht” auszusprechen, was eine Reihe spezifischer Maßnahmen nach sich ziehen muss. Diese sollten in Alarmplänen vorbereitet sein, deren Umsetzung ein enges Zusammenspiel zwischen Klinikern, Öffentlichem Gesundheitsdienst und Experten voraussetzt. Deutschland ist durch das Netzwerk der StAKoB im internationalen Vergleich sehr gut aufgestellt."
173,Arzt und Apotheker – vertrauensvolle Partner oder feindliche Brüder?,
174,Poly(N‐acylethylenimine) copolymers containing pendant pentamethyldisiloxanyl groups. I. Synthesis,"10‐(Pentamethyl disiloxanyl) decyl oxazoline (Si) was synthesized. It was copolymerized with either undecyl (U) or nonyl (N) oxazolines using methyl 4‐nitrobenzenesulfonate as initiator. Two series of random poly(N‐acylethylenimine) copolymers, U/Si and N/Si, were synthesized over the whole composition range of Si monomer with a total degree of polymerization of about 100. Narrow molecular weight distributions were obtained. At a monomer to initator ratio of about 1060, the final degree of polymerization was 374 with a polydispersity index of 1.93. This shows the effect of chain transfer in this system."
175,SIOP ABSTRACTS,
176,Optimizing Economic Outcomes in Acute Exacerbations of Chronic Bronchitis,"The treatment of community‐acquired respiratory tract infections, such as acute exacerbations of chronic bronchitis (AECB), constitutes a huge socioeconomic burden. In most cases, an antimicrobial agent is advocated to lessen morbidity and prevent serious clinical sequelae. Use of antimicrobial agents for AECB, however, is controversial, as it is difficult to distinguish between bacterial and nonbacterial AECB, and only marginal benefits have been reported. Antimicrobial agents, however, have reduced relapse rates, prolonged the time between exacerbations, shortened the duration of symptoms, and reduced the need for hospitalization. Microbiologic resistance and individual patient characteristics play important roles in determining the most appropriate antimicrobial agent for patients with AECB. More research on the effect of resistant bacteria on antimicrobial response rates will enable physicians to prescribe economically rational antimicrobial therapy for this common infection."
177,Measles Virus Infection Causes Expression of Class I and Class II MHC Antigens in Rat Brain,
178,EFFECT OF RIBAVIRIN ON VIRAL HEPATITIS IN LABORATORY ANIMALS,
179,Transfection of COS Cells with Human Cystatin cDNA and Its Effect on HSV‐1 Replication,
180,"CAN VIRAL ENVELOPE GLYCOLIPIDS PRODUCE AUTO‐IMMUNITY, WITH REFERENCE TO THE CNS AND MULTIPLE SCLEROSIS?","Many viruses, with lipid envelopes derived from the host cell membranes, have been implicated in the aetiology of multiple sclerosis (MS), and epidemiological studies support an infectious agent. Alternatively the disease is thought by other workers to be auto‐immune in nature, and recently much attention has been focused on immunological sensitivity to glycolipids in MS patients. In this paper it is proposed that CNS demyelination could arise in susceptible individuals (HLA type) from an immune response to glycolipids, triggered by the carrier effect of one or more enveloped neurotropic viruses."
181,Cell‐Mediated Immunity in Virus Infections of the Central Nervous System,
182,New insights into pediatric community‐acquired pneumonia gained from untargeted metabolomics: A preliminary study,"BACKGROUND: Available diagnostics often fail to distinguish viral from bacterial causes of pediatric community‐acquired pneumonia (pCAP). Metabolomics, which aims at characterizing diseases based on their metabolic signatures, has been applied to expand pathophysiological understanding of many diseases. In this exploratory study, we used the untargeted metabolomic analysis to shed new light on the etiology of pCAP. METHODS: Liquid chromatography coupled with mass spectrometry was used to quantify the metabolite content of urine samples collected from children hospitalized for CAP of pneumococcal or viral etiology, ascertained using a conservative algorithm combining microbiological and biochemical data. RESULTS: Fifty‐nine children with CAP were enrolled over 16 months. Pneumococcal and viral cases were distinguished by means of a multivariate model based on 93 metabolites, 20 of which were identified and considered as putative biomarkers. Among these, six metabolites belonged to the adrenal steroid synthesis and degradation pathway. CONCLUSIONS: This preliminary study suggests that viral and pneumococcal pneumonia differently affect the systemic metabolome, with a stronger disruption of the adrenal steroid pathway in pneumococcal pneumonia. This finding may lead to the discovery of novel diagnostic biomarkers and bring us closer to personalized therapy for pCAP."
183,Konzepte für die Hämophilie‐Behandlung. Gerinnungsfaktoren in der Therapie,Angeborene Blutungsleiden sind überwiegend durch genetische Defekte der im Blutplasma vorkommenden Gerinnungsfaktoren (I‐XIII) bedingt (Koagulopathien). Ursächlich kommen auch angeborene Störungen der Thrombozytenfunktion und extrem selten solche der Gefäßwand infrage.
184,Is an infectious trigger always required for primary hemophagocytic lymphohistiocytosis? Lessons from in utero and neonatal disease,"In this report, we evaluate the hypothesis that hemophagocytic lymphohistiocytosis in patients with defects of lymphocyte cytotoxicity is usually triggered by infections. We show that in the majority of patients, extensive virus PCR panels performed in addition to routine microbiological investigations remain negative and summarize 25 patients with onset of hemophagocytic lymphohistiocytosis in utero or within the first 10 days of life, in none of which an associated bacterial or viral infection was reported. These observations, even though preliminary, invite to consider a key role of lymphocyte cytotoxicity in controlling T‐cell homeostasis also in the absence of apparent infectious stimuli."
185,Tight junction‐related human diseases,"Tight junctions are intercellular junctions adjacent to the apical ends of paracellular spaces. They have two classical functions, the barrier function and the fence function. The former regulates the passage of ions, water and various molecules through paracellular spaces, and is thus related to edema, jaundice, diarrhea and blood‐borne metastasis. The latter function maintains cell polarity by forming a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell properties in terms of loss of cell polarity. Recently, two novel aspects of tight junctions have been reported. One is their involvement in signal transduction. The other is that fact that tight junctions are considered to be a crucial component of innate immunity. In addition, since some proteins comprising tight junctions work as receptors for viruses and extracellular stimuli, pathogenic bacteria and viruses target and affect the tight junction functions, leading to diseases. In this review, the relationship between tight junctions and human diseases will be described."
186,Negative Staining and Immune Electron Microscopy as Techniques for Rapid Diagnosis of Viral Agents,
187,"Severe, persistent, and fatal T‐cell immunodeficiency following therapy for infantile leukemia","We describe five cases of children who completed chemotherapy for infantile acute lymphoblastic leukemia (ALL) and soon after were diagnosed with severe T‐cell, non‐HIV immunodeficiency, with varying B‐cell and NK‐cell depletion. There was near absence of CD3(+), CD4(+), and CD8(+) cells. All patients developed multiple, primarily opportunistic infections. Unfortunately, four patients died, although one was successfully treated by hematopoietic stem cell transplantation. These immunodeficiencies appeared to be secondary to intensive infant ALL chemotherapy. Our report highlights the importance of the early consideration of this life‐threatening immune complication in patients who received chemotherapy for infantile ALL."
188,Microsensor Arrays for Saliva Diagnostics,"abstract: Optical fiber microarrays have been used to screen saliva from patients with end‐stage renal disease (ESRD) to ascertain the efficacy of dialysis. We have successfully identified markers in saliva that correlate with kidney disease. Standard assay chemistries for these markers have been converted to disposable test strips such that patients may one day be able to monitor their clinical status at home. Details of these developments are described. In addition, saliva from asthma and chronic obstructive pulmonary disease (COPD) patients is being screened for useful diagnostic markers. Our goal is to develop a multiplexed assay for these protein and nucleic acid biomarkers for diagnosing the cause and severity of pulmonary exacerbations, enabling more effective treatment to be administered. These results are reported in the second part of this article."
189,Trends in der Impfstoffentwicklung. DNA‐ und zellbasierte Impfstoffe,"Für eine Reihe von Infektionskrankheiten sowohl bakterieller, parasitärer als auch viraler Genese wurde vor allem im 20. Jahrhundert eine Vielzahl von Impfstoffen entwickelt, die Impflinge erfolgreich schützen konnten. Dies führte zu einer drastisch verminderten Krankheitslast in der Bevölkerung, zu einer deutlich verringerten Säuglingssterblichkeit und zu einer Erhöhung der Lebenserwartung. Aktuell werden die globalen Bemühungen intensiviert, das Poliomyelitis‐ und das Masern‐Virus auszurotten."
190,Academy News – April 2020 PM&R,
191,Dublin Pathology 2015. 8th Joint Meeting of the British Division of the International Academy of Pathology and the Pathological Society of Great Britain & Ireland,
192,"46(th) Congress of the International Society of Paediatric Oncology (SIOP) 2014: Toronto, Canada 22(nd)–25(th) October, 2014 SIOP abstracts",
193,Neither insects nor wind: ambophily in dioecious Chamaedorea palms (Arecaceae),"Pollination of Neotropical dioecious trees is commonly related to generalist insects. Similar data for non‐tree species with separated genders are inconclusive. Recent studies on pollination of dioecious Chamaedorea palms (Arecaceae) suggest that species are either insect‐ or wind‐pollinated. However, the wide variety of inflorescence and floral attributes within the genus suggests mixed pollination mode involving entomophily and anemophily. To evaluate this hypothesis, we studied the pollination of Chamaedorea costaricana,C. macrospadix,C. pinnatifrons and C. tepejilote in two montane forests in Costa Rica. A complementary morphological analysis of floral traits was carried out to distinguish species groups within the genus according to their most probable pollination mechanism. We conducted pollinator exclusion experiments, field observations on visitors to pistillate and staminate inflorescences, and trapped airborne pollen. A cluster analysis using 18 floral traits selected for their association with wind and insect pollination syndromes was carried out using 52 Chamaedorea species. Exclusion experiments showed that both wind and insects, mostly thrips (Thysanoptera), pollinated the studied species. Thrips used staminate inflorescences as brood sites and pollinated pistillate flowers by deception. Insects caught on pistillate inflorescences transported pollen, while traps proved that pollen is wind‐borne. Our empirical findings clearly suggest that pollination of dioecious Chamaedorea palms is likely to involve both insects and wind. A cluster analysis showed that the majority of studied species have a combination of floral traits that allow for both pollination modes. Our pollination experiments and morphological analysis both suggest that while some species may be completely entomophilous or anemophilous, ambophily might be a common condition within Chamaedorea. Our results propose a higher diversity of pollination mechanisms of Neotropical dioecious species than previously suggested."
194,Characterization of Bovine Parainfluenza Virus Type 3,"Bovine parainfluenza virus type 3 (PIV‐3) has a buoyant density of 1.197. The RNA of PIV‐3, like that of Sendai virus, is a single continuous chain which lacks polyadenylic acid sequences and tends to self‐anneal to a marked extent. It has a sedimentation coefficient of 42S and a molecular weight of 4.5 × 10(6), being slightly smaller than Sendai virus RNA (47S, 5.3 × 10(6)). PIV‐3 has 5 main structural proteins, of which 2 are glycoproteins. The molecular weights of protein(1), protein(2), protein(3), glycoprotein(1), and glycoprotein(2) were estimated to be 79,000, 68,000, 35,000, 69,000, and 55,000, respectively. Protein(2) was suggested to be nucleocapsid protein."
195,Comparison of Three Electron Microscopy Techniques for the Detection of Human Rotaviruses,"Rotavirus detection by direct electron microscopy was compared with direct and indirect immune electron microscopy techniques. The latter two approaches permitted the enumeration of 25 and 103 times more rotaviruses respectively, than direct electron microscopy. Also, 70% and 90% of the virus particles were aggregated by direct and indirect immune electron microscopy techniques respectively, thus facilitating their detection."
196,"Characterization of Small Plaque Mutants of Mouse Hepatitis Virus, JHM Strain","Two small plaque mutants designated as 1a and 2c were isolated from DBT cells persistently infected with the JHM strain of mouse hepatitis virus. Unlike the wild type JHM, these two mutant viruses grew more slowly with no prominent cell fusion. The buoyant densities of the mutants were slightly lower and 2c was revealed to have fewer peplomers than JHM by electron microscopy. The purified JHM contained five polypeptides with molecular weights (M.W.) of 260,000, 105,000 (GP105), 65,000, 60,000 (P60), and 23,000 (GP23). In addition to two polypeptides, P60 and GP23, which were common to JHM and the mutants, 1a was found to contain three other specific polypeptides with M.W. of 180,000 (GP160), 110,000, and 95,000 (GP95), while 2c had GP180, GP105, GP95, and one with a M.W. of 175,000. All of these polypeptides were shown to be glycosylated except for P60. After bromelain treatment, all these viruses lost the peplomers and contained P60 and another new 18,000 dalton polypeptide."
197,Flavivirus induces MHC antigen on human myoblasts: A model of autoimmune myositis?,"Infection of human embryonic myoblasts by West Nile virus (WNV), a flavivirus, caused significant upregulation of class I and II MHC expression as determined by flow cytometry. After 48 hours at a multiplicity of infection of 5 pfu/cell, a sixfold increase in MHC class I expression was induced from initially low levels of expression. In contrast, MHC class II was induced de novo to five times the control fluorescence level. At least 70% of the cells were infected as determined using fluorescence microscopy and anti‐WNV antibody labeling. Myoblasts were > 90% pure as shown by anti–Leu‐19 labeling. MHC class I (but not class II) was increased threefold after exposure to virus‐inactivated supernatant from 48‐hour–infected cells, indicating the presence of factor(s) contributing to the MHC class I increase. These findings may be important in establishing a link between viral infection of human cells and induction of inflammatory autoimmune disease. We discuss the possibility of using WNV as an in vivo model. © 1992 John Wiley & Sons, Inc."
198,"Tea and Health – Interview with Yukihiko Hara, Mitsui Norin Co., Ltd.",
199,Retracted: Immunological properties reveal the monovalent and bivalent recombinant dengue virus‐like particles as candidate vaccine for dengue,"Retraction statement: ‘Immunological properties reveal the monovalent and bivalent recombinant dengue virus‐like particles as candidate vaccine for dengue’ by Yan Liu, Junmei Zhou, Zhizhun Yu, Danyun Fang, Chunyun Fu, Xun Zhu, Zhenjian He, Huijun Yan, Wenquan Liu, Yunxia Tang, Mengfeng Li and Lifang Jiang. The above article in Microbiology and Immunology (doi: 10.1111/1348‐0421.12179), published online on 15 July 2014 in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the authors, the journal Editors‐in‐Chief, Akio Nakane, Takaji Wakita, Yasunobu Yoshikai, and Wiley Publishing Asia Pty Ltd. The retraction has been agreed as the article was submitted by Dr. Liu Y. without agreement of all co‐authors, including two listed corresponding authors."
200,Treatment of idiopathic spasmodic torticollis with botulinum‐A toxin: a pilot study of 19 patients,"Nineteen patients with spasmodic torticollis, unresponsive to standard therapy, were administered local injections of botulinum‐A toxin into the affected muscles. During an average follow‐up period of 11.5 months, a more than 25% improvement was noted in 14 of 19 patients. All those with purely focal dystonia and 9 of 10 patients with a disease history of less than three years benefited from treatment. Side effects were insignificant and transient. Botulinum toxin is a very effective and safe method of treatment for spasmodic torticollis."
201,A high frequency of allopolyploid speciation in the gymnospermous genus Ephedra and its possible association with some biological and ecological features,"The origin and evolution of polyploids have been studied extensively in angiosperms and ferns but very rarely in gymnosperms. With the exception of three species of conifers, all natural polyploid species of gymnosperms belong to Ephedra, in which more than half of the species show polyploid cytotypes. Here, we investigated the origin and evolution of polyploids of Ephedra distributed in the Qinghai–Tibetan Plateau (QTP) and neighbouring areas. Flow cytometry (FCM) was used to measure the ploidy levels of the sampled species that are represented by multiple individuals from different populations, and then, two single‐copy nuclear genes (LFY and DDB2) and two chloroplast DNA fragments were used to unravel the possible origins and maternal donors of the polyploids. The results indicate that the studied polyploid species are allopolyploids, and suggest that allotetraploidy is a dominant mode of speciation in Ephedra. The high percentage of polyploids in the genus could be related to some of its biological attributes such as vegetative propagation, a relatively high rate of unreduced gamete formation, and a small genome size relative to most other gymnosperms. Significant ecological divergences between allotetraploids and their putative progenitors were detected by PCAs and anova and Tukey's tests, with the exception of E. saxatilis. The overlap of geographical distributions and ecological niches of some diploid species could have provided opportunities for interspecific hybridization and allopolyploid speciation."
202,Distribution of split DnaE inteins in cyanobacteria,"Inteins are genetic elements found inside the coding regions of different host proteins and are translated in frame with them. The intein‐encoded protein region is removed by an autocatalytic protein‐splicing reaction that ligates the host protein flanks with a peptide bond. This reaction can also occur in trans with the intein and host protein split in two. After translation of the two genes, the two intein parts ligate their flanking protein parts to each other, producing the mature protein. Naturally split inteins are only known in the DNA polymerase III alpha subunit (polC or dnaE gene) of a few cyanobacteria. Analysing the phylogenetic distribution and probable genetic propagation mode of these split inteins, we conclude that they are genetically fixed in several large cyanobacterial lineages. To test our hypothesis, we sequenced parts of the dnaE genes from five diverse cyanobacteria and found all species to have the same type of split intein. Our results suggest the occurrence of a genetic rearrangement in the ancestor of a large division of cyanobacteria. This event fixed the dnaE gene in a unique two‐genes one‐protein configuration in the progenitor of many cyanobacteria. Our hypothesis, findings and the cloning procedure that we established allow the identification and acquisition of many naturally split inteins. Having a large and diverse repertoire of these unique inteins will enable studies of their distinct activity and enhance their use in biotechnology."
203,Could preventive intranasal interferon lower the morbidity in children prone to respiratory illness?,"Recent studies have demonstrated that rhinovirus infections can be prevented in the family setting through use of intranasal interferon sprays which are commenced when another family member develops a cold. One hundred and twenty‐seven children aged 4–9 years who had been hospitalized during their first year of life for severe infections caused by respiratory syncytial virus were studied virologically and epidemiologically during a seven‐month period which included the winter months. The hypothesis was that a significant part of their respiratory morbidity would be preventable by a contact prophylaxis approach using intranasal interferon. However, the findings suggest that a preventive approach of this kind would not substantially reduce the burden of respiratory illness in these children because: the target children themselves more often introduced illness into the family than did other household members; rhinovirus infections preventable by interferon were associated with little lower respiratory morbidity; and rhinoviruses were minor contributors to the total respiratory illness burden in these respiratory illness‐prone children."
204,Use of Protein A in the Serum‐in‐Agar Diffusion Method in Immune Electron Microscopy for Detection of Virus Particles in Cell Culture,"A modified technique using protein A in the serum‐in‐agar (SIA) method for immune electron microscopy (IEM) was presented. Grids coated with staphylococcal protein A were floated on samples mounted on agar containing 2% antiserum and incubated at 37 C, for 60 min. After washing and staining, the grids were observed in an electron microscope. The effects of protein A on virus detection were evaluated using poliovirus and bovine rotavirus infected cell culture fluids. The results showed that the technique using protein A (PA‐SIA) had at least 10‐fold higher sensitivity for virus detection than the original SIA. The optimal concentration of protein A was 1 to 10 μg/ml for coating the grids to trap virus particles. The PA‐SIA method was also compared with immunosorbent electron microscopy (ISEM). The former showed higher or at least the same sensitivity and some advantages in detecting antigen‐antibody reaction than the latter method. These results indicate that our PA‐SIA method may be superior to other IEM techniques presented previously for the detection and identification of viruses."
205,"The integral membrane protein from a virulent isolate of transmissible gastroenteritis virus: molecular characterization, sequence and expression in Escherichia coli","Subgenomic mRNA from a virulent isolate of porcine transmissible gastroenteritis virus (TGEV) was used to produce cDNA clones. Part of a new clone and a previously reported clone were sequenced and used to construct the viral gene for integral membrane protein. A single open reading frame (ORF) encoding a polypeptide of 262 amino acids, relative molecular mass (M(r)) 29459, was identified. The positive identification of the polypeptide as the integral membrane protein was demonstrated by the production in E. coli of a chimaeric protein comprising most of the ORF encoding the M(r) 29459 polypeptide and β‐galactosidase. The chimaeric protein reacted with a specific monoclonal antibody to viral integral membrane protein and antibodies raised against the chimaeric protein immune precipitated the viral protein. Comparison with the sequence of an avirulent isolate indicates amino acid residues that may be important in pathogenicity."
206,Looking Forward to Serving SID,
207,Differential Expression of the Major Histocompatibility Antigen Complex (MHC) on a Series of Burkitt's Lymphoma Lines,"We compared the expressions of class I and class II major histocompatibility antigen complex (MHC) on the surface of Jijoye and P3HR‐1 cells of Burkitt's lymphoma sublines. Jijoye cells had a large amount of class I and class II MHC antigens, whereas these antigens were less expressed on P3HR‐1 cells. On a subline of P3HR‐1 K cells the expression of class I antigen markedly diminished and class II antigen was undetectable. On the other hand, Jijoye, P3HR‐1, and P3HR‐1 K cell lines were confirmed to be Epstein‐Barr virus (EBV) nonproducer, low producer, and high producer, respectively. The chemical activation of EBV genome by treating P3HR‐1 cells with 12‐O‐tetradecanyl phorbol‐13 acetate (TPA) and n‐butyrate resulted in inhibition of the expression of class I and II antigens, while the addition of retinoic acid, an inhibitor of virus replication, blocked the decrease in the MHC antigen expression. These findings suggested that there might be an inverse correlation between the virus production and the expression of class I and II MHC antigens."
208,Australia was indeed the “lucky country” in the recent worldwide SARS epidemic,
209,Sequence of the nucleoprotein gene from a virulent British field isolate of transmissible gastroenteritis virus and its expression in Saccharomyces cerevisiae,"Subgenomic mRNA from a virulent isolate of porcine transmissible gastroenteritis virus (TGEV) was used to produce cDNA which was sequenced. Two non‐overlapping open reading frames (ORFs) were identified. The largest, encoding a polypeptide of 382 amino acids (relative molecular mass (M(r)) 43 483), was shown to be the viral nucleoprotein gene. The second ORF, found 3’to the larger ORF, encodes a polypeptide of 78 amino acids (M(r) 9068) which has yet to be assigned to a viral product. The nucleoprotein gene was expressed in yeast cells under the control of two types of yeast promoters: the constitutive PGK promoter, and the inducible GAL1 promoter. Yeast cells containing recombinant plasmids, with the nucleoprotein gene in the correct orientation, produced a polypeptide of M, 47000, identical to the viral product, that reacted with a specific monoclonal antibody."
210,Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2003–2004,"This review is the third update of the original review, published in 1999, on the application of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings the topic to the end of 2004. Both fundamental studies and applications are covered. The main topics include methodological developments, matrices, fragmentation of carbohydrates and applications to large polymeric carbohydrates from plants, glycans from glycoproteins and those from various glycolipids. Other topics include the use of MALDI MS to study enzymes related to carbohydrate biosynthesis and degradation, its use in industrial processes, particularly biopharmaceuticals and its use to monitor products of chemical synthesis where glycodendrimers and carbohydrate–protein complexes are highlighted. © 2009 Wiley Periodicals, Inc., Mass Spec Rev 28:273–361, 2009"
211,The dual role of thymidine phosphorylase in cancer development and chemotherapy,"Thymidine phosphorylase (TP), also known as “platelet‐derived endothelial cell growth factor” (PD‐ECGF), is an enzyme, which is upregulated in a wide variety of solid tumors including breast and colorectal cancers. TP promotes tumor growth and metastasis by preventing apoptosis and inducing angiogenesis. Elevated levels of TP are associated with tumor aggressiveness and poor prognosis. Therefore, TP inhibitors are synthesized in an attempt to prevent tumor angiogenesis and metastasis. TP is also indispensable for the activation of the extensively used 5‐fluorouracil prodrug capecitabine, which is clinically used for the treatment of colon and breast cancer. Clinical trials that combine capecitabine with TP‐inducing therapies (such as taxanes or radiotherapy) suggest that increasing TP expression is an adequate strategy to enhance the antitumoral efficacy of capecitabine. Thus, TP plays a dual role in cancer development and therapy: on the one hand, TP inhibitors can abrogate the tumorigenic and metastatic properties of TP; on the other, TP activity is necessary for the activation of several chemotherapeutic drugs. This duality illustrates the complexity of the role of TP in tumor progression and in the clinical response to fluoropyrimidine‐based chemotherapy. © 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 6, 903–953, 2009"
212,"Hydrocephalus in Suckling Rats Infected Intracerebrally with Mouse Hepatitis Virus, MHV‐A59","After intracerebral inoculation of mouse hepatitis virus, MHV‐A59 strain, into 3‐ to 5‐day‐old Wistar rats, some survivors at 14 days postinoculation (p.i.) were found to lack the cerebral cortex and to have an accumulation of a considerable amount of cerebrospinal fluid. The virus titer in the brain increased exponentially after inoculation, reaching a maximum 4 to 6 days p.i. when immunofluorescence revealed virus‐specific antigen within neurons in the cerebral cortex. A small amount of infectious virus was also detectable 14 days p.i. when the cerebral anomaly was evident. This brain malformation causing hydrocephalus was due to cerebral damage by viral infection."
213,"Ancestral acquisitions, gene flow and multiple evolutionary trajectories of the type three secretion system and effectors in Xanthomonas plant pathogens","Deciphering the evolutionary history and transmission patterns of virulence determinants is necessary to understand the emergence of novel pathogens. The main virulence determinant of most pathogenic proteobacteria is the type three secretion system (T3SS). The Xanthomonas genus includes bacteria responsible for numerous epidemics in agroecosystems worldwide and represents a major threat to plant health. The main virulence factor of Xanthomonas is the Hrp2 family T3SS; however, this system is not conserved in all strains and it has not been previously determined whether the distribution of T3SS in this bacterial genus has resulted from losses or independent acquisitions. Based on comparative genomics of 82 genome sequences representing the diversity of the genus, we have inferred three ancestral acquisitions of the Hrp2 cluster during Xanthomonas evolution followed by subsequent losses in some commensal strains and re‐acquisition in some species. While mutation was the main force driving polymorphism at the gene level, interspecies homologous recombination of large fragments expanding through several genes shaped Hrp2 cluster polymorphism. Horizontal gene transfer of the entire Hrp2 cluster also occurred. A reduced core effectome composed of xopF1, xopM, avrBs2 and xopR was identified that may allow commensal strains overcoming plant basal immunity. In contrast, stepwise accumulation of numerous type 3 effector genes was shown in successful pathogens responsible for epidemics. Our data suggest that capacity to intimately interact with plants through T3SS would be an ancestral trait of xanthomonads. Since its acquisition, T3SS has experienced a highly dynamic evolutionary history characterized by intense gene flux between species that may reflect its role in host adaptation."
214,Preventing local transmission of SARS: lessons from Singapore,
215,SARS and its effect on medical education in Hong Kong,
216,The receptor for Bacillus thuringiensis CrylA(c) delta‐endotoxin in the brush border membrane of the lepidopteran Manduca sexta is aminopeptidase N,"A 120 kDa glycoprotein in the larval midgut membrane of the Iepidopteran Manduca sexta, previously identified as a putative receptor for Bacillus thuringiensis CrylA(c) δ‐endotoxin, has been purified by a combination of protoxin affinity Chromatography and anion exchange chromatography. In immunoblotting experiments, the purified glycoprotein has the characteristics predicted of the receptor: it binds CrylA(c) toxin In the presence of GlcNAc but not GalNAc; it binds the lectin SBA; but it does not bind CrylB toxin. N‐terminal and internal amino acid sequences obtained from the protein show a high degree of similarity with the enzyme aminopeptidase N (EC 3.4.11.2). When assayed for aminopeptidase activity, purified receptor preparations were enriched 5.3‐fold compared to M. sexta brush border membrane vesicles. We propose that the receptor for CrylA(c) toxin in the brush border membrane of the lepidopteran M. sexta is the metalloprotease aminopeptidase N."
217,"Molecular characteristics and pathogenic assessment of porcine epidemic diarrhoea virus isolates from the 2018 endemic outbreaks on Jeju Island, South Korea","Since the 2013–2014 incursion of the virulent G2b porcine epidemic diarrhoea virus (PEDV) pandemic strains in South Korea, frequent moderate‐scale regional outbreaks have recurred. In particular, areas of Jeju Island with extensive swine production have faced repeated epidemics since the re‐emergence in 2014. The current study reports the complete genome sequences and molecular characterization of the representative PEDV strains responsible for the 2018 endemic outbreaks on Jeju Island. All isolates were determined to belong genetically to the highly pathogenic pandemic G2b group. Full‐length genome sizes of four isolates differed from that of the G2b epidemic field strain due to insertion or deletion (DEL) mutations in the non‐structural protein (nsp)‐ or spike (S) protein‐coding regions. The 2018 Jeju isolates shared 96.7%–98.7% and 98.5%–99.4% identity at the S gene and whole‐genome levels, respectively, compared to global G2b PEDV strains. Genetic and phylogenetic analyses indicated that the 2018 isolates were closest to the 2014 G2b re‐emergent Jeju strains, but appeared to have undergone substantial rapid independent evolution. Among the isolates, a notable nsp3 DEL variant strain, KOR/KNU‐1807/2018, was isolated and propagated by continuous passages in Vero cells, and displayed typical PEDV‐induced syncytia formation. Genomic sequencing identified a unique 8‐nt DEL in the extreme C‐terminal region of the S gene at the 4th passage (KNU‐1807‐P4) compared to its original sample. This DEL resulted in the premature termination of S by nine amino acid residues (EVFEKVHVQ), which contained a KxHxx motif that is a potential endoplasmic reticulum retrieval signal. In vivo animal studies showed that variant strain KNU‐1807 had decreased virulence in suckling piglets. These results advance our knowledge regarding the genetic variation and pathogenicity of the G2b PEDV endemic strains prevalent in Jeju swine herds in South Korea."
218,Emergence and adaptive evolution of Nipah virus,"Since its first emergence in 1998 in Malaysia, Nipah virus (NiV) has become a great threat to domestic animals and humans. Sporadic outbreaks associated with human‐to‐human transmission caused hundreds of human fatalities. Here, we collected all available NiV sequences and combined phylogenetics, molecular selection, structural biology and receptor analysis to study the emergence and adaptive evolution of NiV. NiV can be divided into two main lineages including the Bangladesh and Malaysia lineages. We formly confirmed a significant association with geography which is probably the result of long‐term evolution of NiV in local bat population. The two NiV lineages differ in many amino acids; one change in the fusion protein might be involved in its activation via binding to the G protein. We also identified adaptive and positively selected sites in many viral proteins. In the receptor‐binding G protein, we found that sites 384, 386 and especially 498 of G protein might modulate receptor‐binding affinity and thus contribute to the host jump from bats to humans via the adaption to bind the human ephrin‐B2 receptor. We also found that site 1645 in the connector domain of L was positive selected and involved in adaptive evolution; this site might add methyl groups to the cap structure present at the 5′‐end of the RNA and thus modulate its activity. This study provides insight to assist the design of early detection methods for NiV to assess its epidemic potential in humans."
219,Whether the GFR measured by renal scintigraphy under non-steady state conditions for critically ill patients with AKI can be used as a predictive parameter for clinical events,
220,Impact of intestinal parasites on microbiota and cobalamin gene sequences: a pilot study,"BACKGROUND: Approximately 30% of children worldwide are infected with gastrointestinal parasites. Depending on the species, parasites can disrupt intestinal bacterial microbiota affecting essential vitamin biosynthesis. METHODS: Stool samples were collected from 37 asymptomatic children from a previous cross-sectional Argentinian study. A multi-parallel real-time quantitative PCR was implemented for Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Trichuris trichiura, Cryptosporidium spp., Entamoeba histolytica and Giardia duodenalis. In addition, whole-genome sequencing analysis was conducted for bacterial microbiota on all samples and analyzed using Livermore Metagenomic Analysis Toolkit and DIAMOND software. Separate analyses were carried out for uninfected, Giardia-only, Giardia + helminth co-infections, and helminth-only groups. RESULTS: For Giardia-only infected children compared to uninfected children, DNA sequencing data showed a decrease in microbiota biodiversity that correlated with increasing Giardia burden and was statistically significant using Shannonʼs alpha diversity (Giardia-only > 1 fg/µl 2.346; non-infected group 3.253, P = 0.0317). An increase in diversity was observed for helminth-only infections with a decrease in diversity for Giardia + helminth co-infections (P = 0.00178). In Giardia-only infections, microbiome taxonomy changed from Firmicutes towards increasing proportions of Prevotella, with the degree of change related to the intensity of infection compared to uninfected (P = 0.0317). The abundance of Prevotella bacteria was decreased in the helminths-only group but increased for Giardia + helminth co-infections (P = 0.0262). Metagenomic analysis determined cobalamin synthesis was decreased in the Giardia > 1 fg/µl group compared to both the Giardia < 1 fg/µl and the uninfected group (P = 0.0369). Giardia + helminth group also had a decrease in cobalamin CbiM genes from helminth-only infections (P = 0.000754). CONCLUSION: The study results may provide evidence for an effect of parasitic infections enabling the permissive growth of anaerobic bacteria such as Prevotella, suggesting an altered capacity of vitamin B12 (cobalamin) biosynthesis and potential impact on growth and development in children [Image: see text]."
221,Initially elevated arterial lactate as an independent predictor of poor outcomes in severe acute pancreatitis,"BACKGROUND: The present study aimed to investigate the relationships between arterial lactate levels and outcomes in severe acute pancreatitis. METHODS: The study retrospectively analyzed the medical data of 329 patients with severe acute pancreatitis from January 2014 to February 2019. We compared baseline characteristics, laboratory data, severity scores, types of persistent organ failure, and primary and secondary outcomes of patients with and without elevated arterial lactate levels at admission. A multivariate logistic regression analysis model and receiver operating characteristic curve were adopted to evaluate the value of arterial lactate ≥4 mmol/L for identifying high-risk patients. Trends in arterial lactate levels were compared between patients in the survivor and nonsurvivor groups over a period of 7 days. RESULTS: Compared to normal arterial lactate levels, patients with elevated arterial lactate levels show significantly higher incidences of multiple persistent organ failure (3% vs 30%, P < 0.01), death (2% vs 11%, P < 0.01), septic shock (4% vs 24%, P < 0.01), pancreatic infection (12% vs 37%, P < 0.01), abdominal compartment syndrome (3% vs 20%, P < 0.01), pancreatic necrosis (41% vs 63%, P < 0.01), and a need for ventilator support (26% vs 54%, P < 0.01). For predicting mortality, arterial lactate levels ≥4 mmol/L had a high hazard ratio (10, 95% CI; 3.7–27; P < 0.01) and the highest area under the curve (0.78). CONCLUSIONS: Our results indicate that initially elevated arterial lactate is independently associated with poor outcomes and death in patients with severe acute pancreatitis and may serve as an early high-risk stratification indicator."
222,Non‐human viruses developed as therapeutic agent for use in humans,"Viruses usually infect a restricted set of host species, and only in rare cases does productive infection occur outside the natural host range. Infection of a new host species can manifest as a distinct disease. In this respect, the use of non‐human viruses in clinical therapy may be a cause for concern. It could provide the opportunity for the viruses to adapt to the new host and be transferred to the recipient's relatives or medical caretakers, or even to the normal host species. Such environmental impact is evidently undesirable. To forecast future clinical use of non‐human viruses, a literature study was performed to identify the viruses that are being considered for application as therapeutic agents for use in humans. Twenty‐seven non‐human virus species were identified that are in (pre)clinical development, mainly as oncolytic agents. For risk management, it is essential that the potential environmental consequences are assessed before initiating clinical use, even if the virus is not formally classified as a genetically modified organism. To aid such assessment, each of these viruses was classified in one of five relative environmental risk categories, ranging from “Negligible” to “Very High”. Canary pox virus and the Autographa californica baculovirus were assigned a “Negligible” classification, and Seneca Valley virus, murine leukemia virus, and Maraba virus to the “High” category. A complicating factor in the classification is the scarcity of publicly available information on key aspects of virus biology in some species. In such cases the relative environmental risk score was increased as a precaution. Copyright © 2011 John Wiley & Sons, Ltd."
223,From the Editors,
224,The ubiquitin‐proteasome system in positive‐strand RNA virus infection,"Positive‐stranded RNA viruses, like many other viruses, have evolved to exploit the host cellular machinery to their own advantage. In eukaryotic cells, the ubiquitin‐proteasome system (UPS) that serves as the major intracellular pathway for protein degradation and modification plays a crucial role in the regulation of many fundamental cellular functions. A growing amount of evidence has suggested that the UPS can be utilized by positive‐sense RNA viruses. The UPS eliminates excess viral proteins that prevent viral replication and modulates the function of viral proteins through post‐translational modification mediated by ubiquitin or ubiquitin‐like proteins. This review will discuss the current understanding of how positive RNA viruses have evolved various mechanisms to usurp the host UPS to modulate the function and stability of viral proteins. In addition to the pro‐viral function, UPS‐mediated viral protein degradation may also constitute a host defense process against some positive‐stranded RNA viral infections. This issue will also be discussed in the current review. Copyright © 2012 John Wiley & Sons, Ltd."
225,"Abstracts for the Annual Scientific Meeting of the Thoracic Society of Australia & New Zealand ‘Maintaining Lung Health from Cradle to Grave’ 7–12 April 2000, Melbourne, Australia",
226,Reasoned Decision Making Without Math? Adaptability and Robustness in Response to Surprise,"Many real‐world planning and decision problems are far too uncertain, too variable, and too complicated to support realistic mathematical models. Nonetheless, we explain the usefulness, in these situations, of qualitative insights from mathematical decision theory. We demonstrate the integration of info‐gap robustness in decision problems in which surprise and ignorance are predominant and where personal and collective psychological factors are critical. We present practical guidelines for employing adaptable‐choice strategies as a proxy for robustness against uncertainty. These guidelines include being prepared for more surprises than we intuitively expect, retaining sufficiently many options to avoid premature closure and conflicts among preferences, and prioritizing outcomes that are steerable, whose consequences are observable, and that do not entail sunk costs, resource depletion, or high transition costs. We illustrate these concepts and guidelines with the example of the medical management of the 2003 SARS outbreak in Vietnam."
227,Clinical relevance of necrotizing change in patients with community‐acquired pneumonia,"BACKGROUND AND OBJECTIVE: Few studies have analysed a large number of patients with necrotizing pneumonia (NP) diagnosed based on computed tomography (CT) scans. The aim of the present study was to document the incidence and clinical features of NP in patients with community‐acquired pneumonia (CAP). METHODS: This retrospective study was conducted on CAP patients who had been admitted to a tertiary referral centre and who had available enhanced CT scan images. Patients were allocated into NP and non‐NP groups, and they were compared with respect to various clinical variables. RESULTS: Of the 830 patients included in the present study, necrotizing change was observed in 103 patients (12%). Patients with NP experienced more symptoms of pneumonia, had higher blood levels of inflammatory markers and more often required pleural drainage compared to patients with non‐NP. Although the use of mechanical ventilation, vasopressor infusion, 30‐day mortality, in‐hospital mortality and clinical deterioration did not differ between the NP and non‐NP groups, the median length of hospital stay (LOS) was significantly longer in the NP group. Multivariate analysis using Cox proportional hazards model showed that necrotizing change independently predicted LOS in patients with CAP. CONCLUSION: NP affects approximately one‐tenth of hospitalized CAP patients. It may be associated with more severe clinical manifestations and may increase the need for pleural drainage. NP was found to be an independent predictor of LOS, but not of mortality in CAP patients."
228,EDITORIAL,
229,POSTER PRESENTATION,
230,AETIOLOGY OF COMMUNITY ACQUIRED PNEUMONIA WITH FEVER AND THE PRESENTATION AND PROGNOSIS OF VIRAL INFECTION: A PROSPECTIVE OBSERVATIONAL STUDY,
231,Viruses and autoimmunity: an affair but not a marriage contract,"Viruses are considered as causative agents and contributors to lesion expression in autoimmune disease, notions best supported by studies in animal model systems. This review discusses relationships between virus infection and autoimmunity focusing on mechanisms by which they could induce autoreactivity. The popular idea of molecular mimicry is viewed skeptically with the reviewers taking the viewpoint that viruses contribute to autoimmunity mainly by inducing several nonspecific inflammatory events that together are sufficient to trigger autoreactivity in genetically receptive hosts. Copyright © 2002 John Wiley & Sons, Ltd."
232,Loop mediated isothermal amplification (LAMP): a new generation of innovative gene amplification technique; perspectives in clinical diagnosis of infectious diseases,"Loop mediated isothermal amplification (LAMP) is a powerful innovative gene amplification technique emerging as a simple rapid diagnostic tool for early detection and identification of microbial diseases. The whole procedure is very simple and rapid wherein the amplification can be completed in less than 1 h under isothermal conditions employing a set of six specially designed primers spanning eight distinct sequences of a target gene, by incubating all the reagents in a single tube. Gene amplification products can be detected by agarose gel electrophoresis as well as by real‐time monitoring in an inexpensive turbidimeter. Gene copy number can also be quantified with the help of a standard curve generated from different concentrations of gene copy number plotted against time of positivity with the help of a real‐time turbidimeter. Alternatively, gene amplification can be visualised by the naked eye either as turbidity or in the form of a colour change when SYBR Green I, a fluorescent dsDNA intercalating dye, is employed. LAMP does not require a thermal cycler and can be performed simply with a heating block and/or water bath. Considering the advantages of rapid amplification, simple operation and easy detection, LAMP has potential applications for clinical diagnosis as well as surveillance of infectious diseases in developing countries without requiring sophisticated equipment or skilled personnel. Copyright © 2008 John Wiley & Sons, Ltd."
233,"Saffold virus, an emerging human cardiovirus","Saffold virus (SAFV) is an emerging human cardiovirus that has been shown to be ubiquitous. Initial studies of SAFV focused on respiratory and gastrointestinal infection; however, it has also recently been associated with diverse clinical symptoms including the endocrine, cardiovascular, and neurological systems. Given the systemic nature of SAFV, and its high prevalence, understanding its pathogenicity and clinical impact is of utmost importance. This comprehensive review highlights and discusses recent developments in epidemiology, human pathogenicity, animal, and molecular studies related to SAFV. It also provides detailed insights into the neuropathogenicity of SAFV. We argue that human studies have been confounded by coinfections and therefore require support from robust molecular and animal research. Thereby, we aim to provide foresight into further research to better understand this emerging virus."
234,Restoration Practices Have Positive Effects on Breeding Bird Species of Concern in the Chihuahuan Desert,"Woody plant encroachment into grasslands is a global concern. Efforts to restore grasslands often assume that removal of woody plants benefits biodiversity but assumptions are rarely tested. In the Chihuahuan Desert of the Southwestern United States, we tested whether abundances of grassland specialist bird species would be greater in plant communities resulting from treatment with herbicides to remove encroaching shrubs compared with untreated shrub‐dominated areas that represented pre‐treatment conditions. In 2010, we surveyed breeding birds and vegetation at 16 treated–untreated pairs. In 2011, we expanded the survey effort to 21 treated–untreated pairs, seven unpaired treatment areas, and five reference grassland areas. Vegetation in treatment areas had higher perennial grass foliar and basal cover and lower shrub foliar cover compared with untreated areas. Several regionally declining grassland specialists exhibited higher occurrence and relative abundance in treated areas. A shrubland specialist, however, was associated with untreated areas and may be negatively impacted by shrub removal. Bird community composition differed between treated and untreated areas in both years. Our results indicate that shrub removal can have positive effects on grassland specialist bird species, but that a mosaic of treated and untreated areas might be most beneficial for regional biodiversity."
235,"Abstracts for the 9th Congress of the Asian Pacific Society of Respirology 10‐13 December, Hong Kong",
236,COPD SIG: Poster Session 2,
237,Borna disease virus,"Borna disease virus (BDV) is unique amongst animal RNA viruses in its molecular biology and capacity to cause persistent, noncytolytic CNS‐infection in a wide variety of host species. Unlike other non‐segmented negative‐strand RNA animal viruses, BDV replicates in the nucleus of the host cell where splicing is employed for expression of a very compact genome. Epidemiological studies indicate a broad host range and geographical distribution, and some investigators have proposed that human infection may result in neuropsychiatric disorders. Experimental Borna disease in neonatal and adult rats provides an intriguing model for immune‐mediated disturbances of brain development and function. Copyright © 2001 John Wiley & Sons, Ltd."
238,Characterizing degradation products of peptides containing N‐terminal Cys residues by (off‐line high‐performance liquid chromatography)/matrix‐assisted laser desorption/ionization quadrupole time‐of‐flight measurements,"A transformation analogous to the well‐known conversion of an N‐terminal glutamine residue to pyroglutamic acid is the cyclization of an N‐terminal carboxamidomethylated cysteine residue (the normal product of alkylation with iodoacetamide). This yields 5‐oxothiomorpholine‐3‐carboxylic acid, with the same 17 Da mass loss observed in the Gln reaction. Nineteen tryptic peptides with Cys at the N‐terminal were identified for this study, and compared with eight with N‐terminal Gln. When examined by MALDI‐QqTOF and (off‐line HPLC)/MALDI‐QqTOF measurements, these were all found to undergo the cyclization reactions. The average degree of degradation during overnight digestion was found to be ∼51 and ∼34% for Cys and Gln, respectively; more detailed information on the time course of the reactions was obtained for the peptides CCTESLVNR and QYYTVFDR. Taking this modification into account while sequencing is likely to increase the probability of protein identification by peptide mass fingerprinting, especially for cysteine‐rich proteins. Copyright © 2003 John Wiley & Sons, Ltd."
239,Paediatric SIG: Poster Session,
240,1‐E3: COPD 4,
241,TSANZ Oral Presentations,
242,Invited Speakers,
243,The Effect of Mask Use on the Spread of Influenza During a Pandemic,"Face masks have traditionally been used in general infection control, but their efficacy at the population level in preventing transmission of influenza viruses has not been studied in detail. Data from published clinical studies indicate that the infectivity of influenza A virus is probably very high, so that transmission of infection may involve low doses of virus. At low doses, the relation between dose and the probability of infection is approximately linear, so that the reduction in infection risk is proportional to the reduction in exposure due to particle retention of the mask. A population transmission model was set up to explore the impact of population‐wide mask use, allowing estimation of the effects of mask efficacy and coverage (fraction of the population wearing masks) on the basic reproduction number and the infection attack rate. We conclude that population‐wide use of face masks could make an important contribution in delaying an influenza pandemic. Mask use also reduces the reproduction number, possibly even to levels sufficient for containing an influenza outbreak."
244,"Effects of Surface Material, Ventilation, and Human Behavior on Indirect Contact Transmission Risk of Respiratory Infection","Infectious particles can be deposited on surfaces. Susceptible persons who contacted these contaminated surfaces may transfer the pathogens to their mucous membranes via hands, leading to a risk of respiratory infection. The exposure and infection risk contributed by this transmission route depend on indoor surface material, ventilation, and human behavior. In this study, quantitative infection risk assessments were used to compare the significances of these factors. The risks of three pathogens, influenza A virus, respiratory syncytial virus (RSV), and rhinovirus, in an aircraft cabin and in a hospital ward were assessed. Results showed that reducing the contact rate is relatively more effective than increasing the ventilation rate to lower the infection risk. Nonfabric surface materials were found to be much more favorable in the indirect contact transmission for RSV and rhinovirus than fabric surface materials. In the cases considered in this study, halving the ventilation rate and doubling the hand contact rate to surfaces and the hand contact rate to mucous membranes would increase the risk by 3.7–16.2%, 34.4–94.2%, and 24.1–117.7%, respectively. Contacting contaminated nonfabric surfaces may pose an indirect contact risk up to three orders of magnitude higher than that of contacting contaminated fabric surfaces. These findings provide more consideration for infection control and building environmental design."
245,Pathogen inactivation/reduction of platelet concentrates: turning theory into practice,"Background Pathogen reduction technology (PRT) has been proven to reduce the residual risk of transmission of infectious agents. Reduction of various contaminating bacteriae, viruses and parasites by few to several log steps and efficiency to prevent GVHD has been shown. Aim To evaluate and compare advantages and disadvantages of PRT available for practical application in platelets. Materials and Methods PRT for the treatment of platelets is currently offered by two formats: Amotosalen (INTERCEPT, Cerus, Concord, CA, USA) and vitamin B2 (Mirasol, Caridian, Denver, USA). Results from different studies and our own experiences with the two techniques are compared and discussed. Results and Discussion For both technologies, different groups of investigators have shown acceptable in‐vitro results with respect to functional and storage data for platelets stored for up to 5 days after production and before transfusion. Initial clinical studies showed no inferiority of the treated platelets in comparison to untreated controls in thrombocytopenic patients. However for both techniques a tendency towards lower CCI has been reported, which may be more pronounced in the platelets treated with the Intercept process. For introduction of PRT many countries require not only CE mark but licensing with the respective authorities since treatment for pathogen reduction is regarded as creating a ‘new’ blood product. With respect to a platelet loss during pathogen reduction it seems recommendable to increase the lower limit of platelet content of the product to 2.5 × 10(11). Particularly for the Intercept system, where a considerable amount of platelets is lost in the purification of the product from Amotosalen, a change in the production process to increase the platelet yield may be necessary. Data from our group show a tendency for improved functional and storage parameters for platelets treated with the Mirasol process. Compared to conventional manufacturing of platelets by apheresis or pooling of buffy coats, pathogen reduction requires additional labour, space, and quality control. Shelf life of platelets is limited in most countries because of the risk of bacterial contamination (in Germany presently to 4 days). A prolongation to 5 or more days after pathogen reduction seems feasible but remains a topic for future studies. Conclusion Results of in vitro and clinical studies of pathogen reduced platelets are promising. Larger clinical trials will help to determine whether PRT proves to be beneficial (reduction of transmission of infections, less alloimmunisation) and overall cost effective (bearing in mind that additional costs may be compensated for by omission of gamma irradiation and potential longer shelf life)."
246,Serum Lipase Activity in Young Dogs With Acute Enteritis or Gastroenteritis,"Blood serum lipase activity was determined in 48 young dogs with acute enteritis or gastroenteritis due to canine parvovirus (16 cases) and presumably to other infectious agents (32 cases). Elevated serum lipase activity (> 500 U/L) was found in 13 dogs (27.1%) with values ranging from 800 to 2,780 U/L. The hyperlipasemia of these cases may be attributed to acute pancreatitis secondary to acute gastroenteritis or to gastrointestinal upset."
247,Print‐only Abstracts,
248,Threats to blood safety posed by emerging protozoan pathogens,
249,ULTRASONOGRAPHIC AND PATHOLOGIC FEATURES OF INTESTINAL SMOOTH MUSCLE HYPERTROPHY IN FOUR CATS,"The ultrasonographic findings for four cats with intestinal smooth muscle hypertrophy are described. In two cats, intestinal smooth muscle hypertrophy was associated with chronic enteritis. In the remaining two cats, intestinal smooth muscle hypertrophy affected the intestinal tract proximal to stenosis due to alimentary lymphoma and an intestinal foreign body, respectively. Moderate increased thickness of the affected intestinal wall, measuring 7–8 mm, was evident on abdominal ultrasonographic examination of all subjects. In addition, the ultrasonographic five‐layered feature of the intestinal wall was maintained, and only the muscular layer appeared thickened. Abdominal ultrasound allowed a presumptive diagnosis of intestinal smooth muscle hypertrophy that was confirmed histologically in all cats."
250,Globalization and blood safety,"Globalization may be viewed as the growing interdependence of countries worldwide through the increasing volume and variety of cross‐border transactions in goods and services, and also through the more rapid and widespread diffusion of technology. Globalization is not just an economic phenomenon, although it is frequently described as such, but includes commerce, disease and travel, and immigration, and as such it affects blood safety and supply in various ways. The relatively short travel times offered by modern aviation can result in the rapid spread of blood‐borne pathogens before measures to counteract transmission can be put in place; this would have happened with SARS if the basic life cycle of the SARS virus did not include an asymptomatic viraemia. This risk can be amplified by ecological factors which effect the spread of these pathogens once they are transferred to a naïve ecosystem, as happened with West Nile virus (WNV) in North America. The rationalization and contraction of the plasma products industry may be viewed as one aspect of globalization imposed by the remorseless inevitability of the market; the effect of this development on the safety and supply of products has yet to be seen, but the oversight and assurance of a shrinking number of players will present particular challenges. Similarly, the monopolization of technology, through patent enforcement which puts access beyond the reach of developing countries, can have an effect on blood safety. The challenges presented to blood safety by globalization are heightening the tensions between the traditional focus on the product safety – zero‐risk paradigm and the need to view the delivery of safe blood as an integrated process. As an illustration of this tension, donor deferral measures imposed by globalization‐induced risks such as vCJD and WNV have resulted in the loss of the safest and most committed portion of the blood donor population in many Western countries, leading to an increased risk to safety and supply. It is only through an appreciation of the basic needs of transfusion medicine, including the enunciation of appropriate principles to manage, rather than eliminate, risks, that the challenges imposed by globalization may be overcome."
251,CONTRAST‐ENHANCED ULTRASONOGRAPHY OF THE SMALL BOWEL IN HEALTHY CATS,"We characterized the pattern of ultrasonographic contrast enhancement of the small intestinal wall using a commercial contrast medium (Sonovue(®)) in 10 healthy awake cats. Subjectively, a rapid intense enhancement of the serosal and submucosal layers was followed by gradual enhancement of the entire wall section during the early phase. At peak enhancement, there was a subjective loss of demarcation between intestinal wall layers. In the late phase, there was a gradual wash out of signal from the intestinal wall. Submucosal wash out occurred last. Time‐intensity curves were generated for selected regions in the intestinal wall and multiple perfusion parameters were calculated for each cat. Perfusion parameters included arrival time (7.64 ± 2.23 s), baseline intensity (1.04 ± 0.04 a.u.), time to peak from injection (10.74 ± 2.08 s), time to peak from initial rise (3.1 ± 1.15), peak intensity (8.92 ± 3.72 a.u.), wash‐in rate (2.06 ± 0.70 a.u./s) and wash‐out rate (−1.07 ± 0.91 a.u./s). The perfusion pattern of normal feline small bowel may be useful for characterizing feline gastrointestinal disorders that involve the intestinal wall."
252,Oral Abstracts,
253,Oral abstracts,
254,"ABSTRACTS FROM THE 2014 EUROPEAN VETERINARY DIAGNOSTIC IMAGING ANNUAL CONFERENCE: Utrecht, The Netherlands, August 27 – August 30, 2014",
255,MAGNETIC RESONANCE IMAGING OF THE NORMAL AND DISEASED FELINE MIDDLE EAR,"The magnetic resonance imaging appearance of the feline middle ear is described in three healthy cats and in five cats with middle ear disease. Owing to the good spatial resolution, multiplanar slice orientation as well as display high contrast resolution of soft tissue, in particular fluids, MR imaging was helpful prior to surgery. It is superior to radiography which failed to allow identification of the abnormality in two of our five cats. MR imaging for middle ear disease should include dorsal and transverse plane images using T1‐ and T2‐ weighted sequences. In the presence of a mass within the bulla or the external ear canal application of contrast medium is helpful."
256,Abstract of 29th Regional Congress of the ISBT,
257,This won't hurt …: Tiny needles deliver drugs painlessly,
258,Environment: Toxic cleanups get a boost,
259,"Biomedicine: Acid blockers stop stomach ulcers, too",
260,Unbuttoning normalcy – on cosmopolitical events,"The history of social research can be read as a critical endeavour inasmuch as it unbuttons the normalcy of collective action by multiplying relevant actors and the imaginaries of social reality. I show how paying close sociological attention to what I call cosmopolitical events, offers one approach to such a conception of critical social science. In the paper, I explore the effects of the Japanese events at the Fukushima nuclear plant to unfold its significance as consequences that disrupt, question and alter common and taken for granted modes of ordering social life. Specifically, through approaching Fukushima as a cosmopolitical event we gain insight into the complex processes of normalizing social relations. Moreover, the Fukushima event and its effects demand to extend the history of the sociological imagination to the social and political relevance of the non‐human. What emerges is a practice that enriches the process of unfolding research agendas and conceptual space to include those that have been excluded, marginalized, forgotten, unconsidered, or disfigured in the process of normalizing social and political action."
261,Out of China: SARS virus' genome hints at independent evolution,
262,Biomedicine: SARS vaccine triggers immunity in monkeys,
263,Electronic thread: Fiber transistor may lead to woven circuits,
264,Environment: When testosterone gets down and dirty,
265,"Vaccines: Kids' vaccine guards adults too, for now",
266,Evaluating the ALERT algorithm for local outbreak onset detection in seasonal infectious disease surveillance data,"Estimation of epidemic onset timing is an important component of controlling the spread of seasonal infectious diseases within community healthcare sites. The Above Local Elevated Respiratory Illness Threshold (ALERT) algorithm uses a threshold‐based approach to suggest incidence levels that historically have indicated the transition from endemic to epidemic activity. In this paper, we present the first detailed overview of the computational approach underlying the algorithm. In the motivating example section, we evaluate the performance of ALERT in determining the onset of increased respiratory virus incidence using laboratory testing data from the Children's Hospital of Colorado. At a threshold of 10 cases per week, ALERT‐selected intervention periods performed better than the observed hospital site periods (2004/2005–2012/2013) and a CUSUM method. Additional simulation studies show how data properties may effect ALERT performance on novel data. We found that the conditions under which ALERT showed ideal performance generally included high seasonality and low off‐season incidence."
267,A revision of the western Palaearctic species of Urophora Robineau‐Desvoidy (Diptera: Tephritidae),"Abstract A key is provided to twenty‐four western Palaearctic species of Urophora Robineau‐Desvoidy. The hosts of twenty‐three species which attack Asteraceae are listed, including those being used or investigated as possible weed biocontrol agents. The species are divided into four species groups and the differing host relationships and types of galls induced by these groups are discussed. U.lopholomae sp.n. and U.affinis ssp. calcitrapae ssp.n., associated with Centaurea (Lopholoma) spp. and C. (Calcitrapa) spp. respectively, are described. U. algerica (Hering) and U.sjumorum (Rohdendorf) are both treated as subspecies of U. quadrifasciata (Meigen). U.pontica is given full specific status and U.hispanica is removed from synonymy. The following new synonymies are made (junior synonyms in parentheses): U. angustifascia (Hering) (=Euribia phaeocera Hering); U. cardui (Linnaeus) (=U. reaumurii Robineau‐Desvoidy, lectotype designated); U. jaceana (Hering) (=E.conyzae Hering); U.maura (Frauenfeld) (=E. tecta Hering); U. mauritanica Macquart (=U. lejura Rondani, Trypeta macrura Loew); U.solstitialis (Linnaeus) (=E.sonderupi Hering, U. veruata Rondani); U.stylata (Fabricius) (=E.pia Hering, U. vulcaanica Rondani); U. terebrans (Loew) (=E. approximata Hering, T. eriolepidis Loew, E. manni Hendel). The possibility that U. quadrifasciata is a species complex is discussed; it is also suggested that U.affinis and U.jaceana represent the morphological extremes of a complex. The misuse of the name Musca stylata Fabricius in the genus Myopites Blot is noted."
268,Identification and discrimination of Electrogena species by numerical methods (Ephemeroptera: Heptageniidae),"Abstract. Nine species of Electrogena from thirty‐one populations were investigated on the basis of five meristic and five ratio characters of the larvae. The attribution of populations to species was checked by a cluster analysis based on the generalized distances between pairs. Groups representing species were then subjected to a multiple discriminant analysis; discriminant functions and loadings were calculated. The correct attribution of individuals to species by the discriminant functions ranged from 97% to 100%. The analysis of discriminant loadings shows which characters contribute more to the discrimination of species. Although many species could be identified with some confidence by a sequential monothetic key based on meristic and qualitative characters, the discriminant analysis improves the effectiveness of identification of all species."
269,Biomedicine: SARs virus can spread in lab animals,
270,Phylogeny and classification of the Signiphoridae (Hymenoptera: Chalcidoidea),"Abstract. A data set consisting of twenty‐eight anatomical characters scored for twenty‐eight terminal taxa representing the world fauna of Signiphoridae was analysed using parsimony and compatibility methods. The Coccophaginae (Aphelinidae) and the Azotinae (Aphelinidae) were used as outgroups to establish polarity of character state changes. Relationships of Signiphoridae to other Chalcidoidea are discussed. Several multistate characters were treated in the parsimony analyses either as unordered or as ordered into transformation series using additive binary coding, which in some cases drastically reduced the number of equally parsimonious solutions. Monophyly of Signiphoridae is supported by seven synapomorphies. Four genera, Chartocerus, Thysanus, Clytina and Signiphora, are recognized within Signiphoridae based on synapomorphies. Rozanoviella syn.n. and Kerrichiella syn.n. are synonymized under Signiphora. Species of Signiphora are further assigned to four species groups, three of which are demonstrably monophyletic. Nine species or subspecies are transferred to Chartocerus from Signiphora (australicus comb.n., australiensis comb.n., australiensis orbiculatus comb.n., beethoveni comb.n., corvinus comb.n., funeralis comb.n., reticulata comb.n., ruskini comb.n., thusanoides comb.n.), one species to Thysanus from Signiphora (melancholicus comb.n.), and one species to Signiphora from Kerrichiella (coleoptratus comb.n.). A key to genera of Signiphoridae and species groups of Signiphora is presented. A diagnosis, relevant nomenclatural history, and a list of included species are given for each genus and species group, and the biology and distribution of each is summarized."
271,Astronomy: X‐ray images highlight galaxy collisions,
272,Biomedicine: Human antibody halts SARS in hamsters,
273,Books for late summer: From genius genes to tyrannosaur musings,
274,Fine toothcomb: New fossils add to primate‐origins debate,
275,Emerging pathogens: Drug‐resistant staph causes more pneumonia,
276,The next MTBE: Contamination from fuel additives could spread,
277,A Nanostructured Microfluidic Immunoassay Platform for Highly Sensitive Infectious Pathogen Detection,"Rapid and simultaneous detection of multiple potential pathogens by portable devices can facilitate early diagnosis of infectious diseases, and allow for rapid and effective implementation of disease prevention and treatment measures. The development of a ZnO nanorod integrated microdevice as a multiplex immunofluorescence platform for highly sensitive and selective detection of avian influenza virus (AIV) is described. The 3D morphology and unique optical property of the ZnO nanorods boost the detection limit of the H5N2 AIV to as low as 3.6 × 10(3) EID(50) mL(−1) (EID(50): 50% embryo infectious dose), which is ≈22 times more sensitive than conventional enzyme‐linked immunosorbent assay. The entire virus capture and detection process could be completed within 1.5 h with excellent selectivity. Moreover, this microfluidic biosensor is capable of detecting multiple viruses simultaneously by spatial encoding of capture antibodies. One prominent feature of the device is that the captured H5N2 AIV can be released by simply dissolving ZnO nanorods under slightly acidic environment for subsequent off‐chip analyses. As a whole, this platform provides a powerful tool for rapid detection of multiple pathogens, which may extent to the other fields for low‐cost and convenient biomarker detection."
278,Bacterial ecology: New bacteria linked to vaginal infections,
279,Significance of new lung infiltrates in outpatients after lung and heart–lung transplantation,"BACKGROUND: Infection and rejection represent major complications following lung transplantation and are often associated with pulmonary infiltrates. The differential diagnosis of these infiltrates depends on their timing after transplantation. The aim of this study was to characterize lung transplant recipients (LTR) presenting with new pulmonary infiltrates. METHODS: A retrospective analysis of all LTR and heart–lung transplant recipients attending outpatient follow‐up at our institution between September 1, 2006 and October 14, 2011 was performed. All patients presenting with new pulmonary infiltrates on chest x‐ray who underwent bronchoscopy were included. RESULTS: A total of 913 patients accounted for 13,156 attendances, with 3,912 bronchoscopies being performed. Seventy‐eight patients (9%) exhibited new pulmonary infiltrates and proceeded to bronchoscopy. Infiltrates occurred at a median 15 (interquartile range [IQR] 5–39) months after transplantation. Forty‐eight patients (62%) were male, and median patient age was 47 (IQR 29–57) years. Subsequent investigation revealed pneumonia to be the underlying cause in 63 patients (81%). In the remaining patients, chronic lung allograft dysfunction (CLAD) was responsible in 6 (8%), acute rejection in 5 (6%), and toxic pneumonitis in 4 (5%) patients. Overall 1‐year survival in LTR presenting with new infiltrates was 97%, compared with 96% for all LTR attending our Outpatient Department. CONCLUSIONS: New pulmonary infiltrates occurring after the first month in LTR are most likely due to infection. Through prompt diagnosis and treatment, early mortality appears unaffected. Late mortality remains attributable to CLAD."
280,Scientific Section,
281,Hepatitis E Virus and Related Viruses in Animals,"Hepatitis E is an acute human liver disease in healthy individuals which may eventually become chronic. It is caused by the hepatitis E virus (HEV) and can have a zoonotic origin. Nearly 57,000 people die yearly from hepatitis E‐related conditions. The disease is endemic in both developing and developed countries with distinct epidemiologic profiles. In developing countries, the disease is associated with inadequate water treatment, while in developed countries, transmission is associated with animal contact and the ingestion of raw or uncooked meat, especially liver. All human HEV are grouped into at least four genotypes, while HEV or HEV‐related viruses have been identified in an increasing number of domestic and wild animal species. Despite a high genetic diversity, only one single HEV serotype has been described to date for HEV genotypes 1–4. The discovery of new HEV or HEV‐related viruses leads to a continuing increase in the number of genotypes. In addition, the genome organization of all these viruses is variable with overlapping open reading frames (ORF) and differences in the location of ORF3. In spite of the role of some domestic and wild animals as reservoir, the origin of HEV and HEV‐related viruses in humans and animals is still unclear. This review discusses aspects of the detection, molecular virology, zoonotic transmission and origin of HEV and HEV‐related viruses in the context of ‘One Health’ and establishes a link between the previous and the new taxonomy of this growing virus family."
282,"Abstract Presentations from the AABB Annual Meeting San Diego, CA ctober 7‐10, 2017",
283,Ribosomal frameshifting in yeast viruses,"Proper maintenance of translational reading frame by ribosomes is essential for cell growth and viability. In the last 10 years it has been shown that a number of viruses induce ribosomes to shift reading frame in order to regulate the expression of gene products having enzymatic functions. Studies on ribosomal frameshifting in viruses of yeast have been particularly enlightening. The roles of viral mRNA sequences and secondary structures have been elucidated and a picture of how these interact with host chromosomal gene products is beginning to emerge. The efficiency of ribosomal frameshifting is important for viral particle assembly, and has identified ribosomal frameshifting as a potential target for antiviral agents. The availability of mutants of host chromosomal gene products involved in maintaining the efficiency of ribosomal frameshifting bodes well for the use of yeast in future studies of ribosomal frameshifting."
284,Relationships between Floodplain Lake Fish Communities and Environmental Variables in a Large River‐Floodplain Ecosystem,"Floodplain lakes of large river systems contain fish habitats that are not found elsewhere within the river, and these lakes have a diversity of environmental conditions that vary in space and time. Our objective was to examine relationships between floodplain lake fish communities and environmental variables associated with lake morphology, water chemistry, and river‐floodplain connectivity in a large river‐floodplain ecosystem. Multivariate direct‐gradient analyses indicated that lake surface area, lake depth, water clarity, and (to a lesser extent) dissolved oxygen were the most important factors in the structuring of lake fish communities. Results further suggested that floodplain lakes could be placed into groups that contained distinctive fish communities. Fish community structure was not strongly related to river‐floodplain connectivity, though fish species richness in individual lakes was positively correlated with degree of flooding in those lakes. Fish species diversity in lakes was positively correlated with linear distance between lakes and the main river channel; lakes that were furthest from the main river channel had more diverse fish communities. The diversity of environmental conditions in floodplain lakes is essential for maintaining net ecosystem diversity in large river ecosystems."
285,Viral attacks on the blood supply: the impact of severe acute respiratory syndrome in Beijing,
286,"Infectivity of Cryptosporidium parvum oocysts is retained upon intestinal passage through a migratory water‐fowl species (Canada goose, Branta canadensis)","Summary Five Cryptosporidium‐free Canada geese (Branta canadensis) were individually orally dosed with 3–5 × 10(6) Cryptosporidium parvum oocysts infectious to neonatal BALB/c mice. After intestinal passage, inoculum‐derived oocysts extracted from goose faeces established severe infection in 14 neonatal BALB/c mice (inoculum dose 2.5 × 10(5)/mouse). The inoculum‐derived oocysts were detected in goose faeces up to 9 days post‐inoculation (PI); the number of intact oocysts and oocyst shells shed during the first 3 days PI was significantly higher than for the remaining 6 days PI (P<0.01). Based on acid‐fast stained air‐dried direct wet smears, 62% of the oocysts in goose faeces were intact (oocyst shells constituted 38%) and conformed to morphological features of viable and infectious inoculum oocysts. The fluorescence scores of the inoculated oocysts, obtained by use of the MERIFLUOR test, were identical to those obtained for the faeces‐recovered oocysts (majority 3 + to 4 +). The dynamics of oocyst shedding showed that overall, the birds released a significantly higher number of intact oocysts than oocyst shells (P<0.01) Retention of the viability and infectivity of C. parvum oocysts following intestinal passage through a migratory water‐fowl species has serious epidemiological implications. Water‐fowl can serve as mechanical vectors for the water‐borne oocysts and can contaminate surface waters with C. parvum. As the concentration of Cryptosporidium oocysts in source waters is attributable to water‐shed management practices, water‐shed protection programme officials should consider water‐fowl as a potential factor enhancing contamination of the source water with Cryptosporidium."
287,"Abstracts of the Joint Conference of the Canadian Society for Transfusion Medicine, Canadian Blood Services and Héma‐Québec, Banff, Alberta, Canada, 21–24 April 2005",
288,Classification of Texas Reservoirs in Relation to Limnology and Fish Community Associations,"I used cluster analysis to examine associations among 20 fish species to develop a classification scheme for 132 large Texas reservoirs. Five major groups of reservoirs were identified by cluster analysis based on species associations. Of 29 reservoirs surveyed previously, 76% were classified into the same species associations from one survey to the next. When 19 environmental variables were used in canonical correlation analysis of the five reservoir groups, I found a general east‐to‐west separation of species associations by water quality and a northwest‐to‐southeast separation by surface elevation and growing season. A discriminant functions model based on a reduced set of nine environmental variables had an unbiased error rate of 18% for predicting the species association in unclassified reservoirs. A stratified sampling scheme based on the classification model decreased the variance of statewide electrofishing catch per effort up to 43% for bluegill Lepomis macrochirus and 23% for largemouth bass Micropterus salmoides over a simple random sample of reservoirs."
289,Current awareness on yeast,"In order to keep subscribers up‐to‐date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly‐published material on yeasts. Each bibliography is divided into 10 sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (4 weeks journals ‐ search completed 10th. Nov. 2004)"
290,"Molecular delimitation of clades within New World species of the ""spiny solanums"" (Solanum subg. Leptostemonum)","Solanum subg. Leptostemonum contains approximately 350–450 species, including the cultivated eggplant, S. melongena. Most species placed in this subgenus form a monophyletic group, the Leptostemonum clade, characterized by the presence of stellate hairs and prickles, leading to the common name of ""spiny solanums"". Here we present a phylogenetic analysis that circumscribes the major clades within the spiny solanums and examines the relationships among them, with an emphasis on New World species. Of particular interest is the clarification of the clade limits and species composition of groups that have not been well‐sampled. We also increase sampling of taxa that have been previously analyzed in molecular studies, namely those in the Torva, Micracantha, and Erythrotrichum clades. These groups have convergent morphological characteristics that have challenged taxonomists, making classification difficult. Results from our study delimit 14 clades within the spiny solanums, including the newly designated Asterophorum, Gardneri, Sisymbriifolium, and Thomasiifolium clades. We also establish the placement of species not previously sampled, especially those endemic to Brazil. These results give an increased understanding of the evolution of the Leptostemonum clade by defining monophyletic groups within it and identify areas of the phylogenetic tree that remain unresolved and require further taxon sampling."
291,Tempering the risk: Rift Valley fever and bioterrorism,
292,"Seasonal Diversity, Abundance, and Distribution of Ichthyoplankton in Tamiahua Lagoon, Western Gulf of Mexico","The ichthyoplanktonic community of Tamiahua Lagoon, Veracruz, Mexico, was studied throughout an annual cycle. Major concentrations of larvae occurred in the central portion of the lagoon, occasionally along the channels, but never at the inlets. The cycle of larva abundance was correlated with cycles of salinity and temperature. In spite of the greater number of species then, the spring and summer periods had low species diversity and evenness, due to the marked domination by larvae of Anchoa mitchilli. The number of larval fish species and individuals entering the lagoon from the adjacent offshore waters was minimal. The greatest portion of species diversity is generated within the lagoon itself. The community structure identified corresponds to the physically controlled type, as indicated by the poor diversity values obtained."
293,Infections after T‐replete haploidentical transplantation and high‐dose cyclophosphamide as graft‐versus‐host disease prophylaxis,"BACKGROUND: Recently, a platform of T‐cell replete haploidentical hematopoietic stem cell transplantation (haplo‐HSCT) using post‐transplant cyclophosphamide (Cy) has shown high reproducibility and acceptable safety profile. METHOD: This prospective cohort analysis allowed us to collect data on infections among 70 consecutive recipients of haplo‐HSCT affected by various hematologic malignancies. RESULTS: After a median follow‐up of 23 months, cumulative incidence of viral infections was 70% (95% confidence interval [CI] 59–81) at 100 days and 77% (95% CI 67–87) at 1 year; 35 of 65 patients at risk had CMV reactivation (54%) and the rate of polyomavirus‐virus‐associated cystitis was 19% (13/70). Cumulative incidence of bacterial and fungal infections at 1 year were 63% (95% CI 51–75) and 12% (95% CI 4–19), respectively. Of note, only 1 invasive fungal infection occurred beyond 1 year after transplant (day +739). CONCLUSION: In conclusion, despite a high rate of viral infections in the early period, present data suggest a satisfactory infectious profile after T‐cell replete haplo‐HSCT using post‐transplant Cy. These results may help clinicians to improve both prophylactic and therapeutic antimicrobial strategies in this emerging haploidentical setting."
294,"Design, Synthesis, and Evaluation of Bioactive Small Molecules","Collaborative research projects between chemists, biologists, and medical scientists have inevitably produced many useful drugs, biosensors, and medical instrumentation. Organic chemistry lies at the heart of drug discovery and development. The current range of organic synthetic methodologies allows for the construction of unlimited libraries of small organic molecules for drug screening. In translational research projects, we have focused on the discovery of lead compounds for three major diseases: Alzheimer's disease (AD), breast cancer, and viral infections. In the AD project, we have taken a rational‐design approach and synthesized a new class of tricyclic pyrone (TP) compounds that preserve memory and motor functions in amyloid precursor protein (APP)/presenilin‐1 (PS1) mice. TPs could protect neuronal death through several possible mechanisms, including their ability to inhibit the formation of both intraneuronal and extracellular amyloid β (Aβ) aggregates, to increase cholesterol efflux, to restore axonal trafficking, and to enhance long‐term potentiation (LTP) and restored LTP following treatment with Aβ oligomers. We have also synthesized a new class of gap‐junction enhancers, based on substituted quinolines, that possess potent inhibitory activities against breast‐cancer cells in vitro and in vivo. Although various antiviral drugs are available, the emergence of viral resistance to existing antiviral drugs and various understudied viral infections, such as norovirus and rotavirus, emphasizes the demand for the development of new antiviral agents against such infections and others. Our laboratories have undertaken these projects for the discovery of new antiviral inhibitors. The discussion of these aforementioned projects may shed light on the future development of drug candidates in the fields of AD, cancer, and viral infections."
295,Oral Presentation Sessions,
296,Risks associated with red blood cell transfusions: potential benefits from application of pathogen inactivation,"BACKGROUND: Red blood cell (RBC) transfusion risks could be reduced if a robust technology for pathogen inactivation of RBC (PI‐RBCs) were to be approved. MATERIALS AND METHODS: Estimates of per‐unit and per‐patient aggregate infectious risks for conventional RBCs were calculated; the latter used patient diagnosis as a determinant of estimated lifetime exposure to RBC units. Existing in vitro data for the two technologies under development for producing PI‐RBCs and the status of current clinical trials are reviewed. RESULTS: Minimum and maximum per‐unit risk were calculated as 0.0003% (1 in 323,000) and 0.12% (1 in 831), respectively. The minimum estimate is for known lower‐risk pathogens while the maximal estimate also includes an emerging infectious agent (EIA) and endemic area Babesia risk. Minimum and maximum per‐patient lifetime risks by diagnosis grouping were estimated as 1.5 and 3.3%, respectively, for stem cell transplantation (which includes additional risk for cytomegalovirus transmission); 1.2 and 3.7%, respectively, for myelodysplastic syndrome; and 0.2 and 44%, respectively, for hemoglobinopathy. DISCUSSION: There is potential for PI technologies to reduce infectious RBC risk and to provide additional benefits (e.g., prevention of transfusion‐associated graft‐versus‐host disease and possible reduction of alloimmunization) due to white blood cell inactivation. PI‐RBCs should be viewed in the context of having a fully PI‐treated blood supply, enabling a blood safety paradigm shift from reactive to proactive. Providing insurance against new EIAs. Further, when approved, the use of PI for all components may catalyze operational changes in blood donor screening, laboratory testing, and component manufacturing."
297,"Abstract Presentations from the AABB Annual Meeting Boston, MA, October 13–16, 2018",
298,An approach to the control of disease transmission in pig‐to‐human xenotransplantation,"Abstract: Although several major immunologic hurdles need to be overcome, the pig is currently considered the most likely source animal of cells, tissues and organs for transplantation into humans. Concerns have been raised with regard to the potential for the transfer of infectious agents with the transplanted organ to the human recipient. This risk is perceived to be increased as it is likely that the patient will be iatrogenically immunocompromised and the organ‐source pig may be genetically engineered in such a way to render its organs particularly susceptible to infection with human viruses. Furthermore, the risk may not be restricted to the recipient, but may have consequences for the health of others in the community. The identification of porcine endogenous retroviruses and of hitherto unknown viruses have given rise to the most concern. We document here the agents we believe should be excluded from the organ‐source pigs. We discuss the likelihood of achieving this aim and outline the potential means by which it may best be achieved."
299,Nosocomial Infection in the Intensive Care Unit,
300,The Immunology of Bovine Respiratory Disease: Recent Advancements,"Bovine respiratory disease (BRD) remains a leading cause of morbidity, mortality, and economic loss to the cattle industry. The continued high prevalence of the disease underlines a gap in understanding of the host immune response to respiratory infection. The host immune response is beneficial and detrimental, required for clearing the disease but often leading to tissue damage and long-term defects in lung function. This article highlights advancements made in understanding innate and adaptive immunity in BRD, factors that predispose animals to BRD, and novel intervention strategies that may lead to changes in the approach to treating and controlling BRD."
301,Veranstaltungstipps,
302,Use of high frequency oscillatory ventilator in neonates with respiratory failure: the clinical practice in Taiwan and early multimodal outcome prediction,"High-frequency oscillatory ventilation (HFOV) can be a rescue for neonates with refractory respiratory failure or an early elective therapy for preterm infants with severe respiratory distress syndrome (RDS). However, little is known about the current evolution and therapeutic limitations of HFOV. We therefore aimed to describe its use in clinical practice and predict the risk of mortality for neonates receiving HFOV. A retrospective observational study of all neonates treated with HFOV in a quaternary referral NICU between January 2007 and December 2016 was conducted. We classified these patients into five subgroups based on primary respiratory diagnoses. We performed the logistic regression and decision tree regression analyses to identify independent factors of 30-day mortality following HFOV. A total of 1125 patients who were ever supported on HFOV were enrolled, of whom 64.1% received HFOV as a rescue therapy, 27.2% received it as an elective therapy, and 8.7% received it for air leak. An average oxygenation index (OI) greater than 25 in the first 24 hours after the initiation of HFOV and patients with secondary pulmonary hypertension were found to have the greatest risk of in-hospital mortality (p < 0.0001). The overall in-hospital mortality rate was 25.8% (290/1125). Decision tree regression analysis revealed that neonates with refractory respiratory failure who had a pre-HFOV OI value higher than 20.5 and OI values higher than 21.5, 23.5 and 34 at 2 hours, 6 hours, and 12 hours after the use of HFOV, respectively, had a significantly increased risk of 30-day mortality. We identified the predictors and cutoff points of OI before and after the initiation of HFOV in neonates with respiratory failure, which can be clinically used as a reference for 30-day mortality. Further efforts are still needed to optimize the outcomes."
303,Antibodies against a short region of PfRipr inhibit Plasmodium falciparum merozoite invasion and PfRipr interaction with Rh5 and SEMA7A,"Plasmodium falciparum merozoite invasion into erythrocytes is an essential step of the blood-stage cycle, survival of parasites, and malaria pathogenesis. P. falciparum merozoite Rh5 interacting protein (PfRipr) forms a complex with Rh5 and CyRPA in sequential molecular events leading to erythrocyte invasion. Recently we described PfRipr as a conserved protein that induces strain-transcending growth inhibitory antibodies in in vitro assays. However, being a large and complex protein of 1086 amino acids (aa) with 87 cysteine residues, PfRipr is difficult to express in conventional expression systems towards vaccine development. In this study we sought to identify the most potent region of PfRipr that could be developed to overcome difficulties related to protein expression, as well as to elucidate the invasion inhibitory mechanism of anti-PfRipr antibodies. Using the wheat germ cell-free system, Ecto- PfRipr and truncates of approximately 200 aa were expressed as soluble proteins. We demonstrate that antibodies against PfRipr truncate 5 (PfRipr_5: C(720)-D(934)), a region within the PfRipr C-terminal EGF-like domains, potently inhibit merozoite invasion. Furthermore, the antibodies strongly block PfRipr/Rh5 interaction, as well as that between PfRipr and its erythrocyte-surface receptor, SEMA7A. Taken together, PfRipr_5 is a potential candidate for further development as a blood-stage malaria vaccine."
304,Nonantibiotic Adjunctive Therapies for Community-Acquired Pneumonia (Corticosteroids and Beyond): Where Are We with Them?,"Community-acquired pneumonia (CAP) is a leading cause of hospitalization, morbidity, and mortality. Despite advances in antibiotic treatments, mortality among patients with CAP is still high. For this reason, interest has been focused on nonantibiotic therapeutic measures directed to the host response rather than the microorganism. The development of an efficacious adjunctive treatment has important implications for reducing mortality in CAP. Some clinical studies performed in the last decade have shown a clinically beneficial effect of corticosteroids, possibly by diminishing local and systemic inflammatory host response. Recent meta-analyses showed faster resolution of symptoms, shorter time to clinically stability, reduction of mechanical ventilation needed, and reduction of mortality in the most severe population, although some methodological limitations must be taken into account. In addition, some studies using statins also suggested improved outcomes due to its anti-inflammatory effect in CAP, although this requires further research. Other adjunctive therapies such as immunoglobulins and stem cells are being explored, but are not yet in the stage of clinical trials. In summary, the use of corticosteroids and other adjuvant treatments are promising in CAP, but more studies are needed to determine their impact on mortality."
305,Community-Acquired Pneumonia in the Asia-Pacific Region,"Community-acquired pneumonia (CAP) is an important cause of mortality and morbidity worldwide. Aging population, dense urbanization, and poor access to health care make the Asia-Pacific region vulnerable to CAP. The high incidence of CAP poses a significant health and economic burden in this region. Common etiologic agents in other global regions including Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Staphylococcus aureus, and respiratory viruses are also the most prevalent pathogens in the Asia-Pacific region. But the higher incidence of Klebsiella pneumoniae and the presence of Burkholderia pseudomallei are unique to the region. The high prevalence of antimicrobial resistance in S. pneumoniae and M. pneumoniae has been raising the need for more prudent use of antibiotics. Emergence and spread of community-acquired methicillin-resistant S. aureus deserve attention, while the risk has not reached significant level yet in cases of CAP. Given a clinical and socioeconomic importance of CAP, further effort to better understand the epidemiology and impact of CAP is warranted in the Asia-Pacific region."
306,"Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention","Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The disease is more severe and dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection. The predominant serotypes circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been conducted. Cidofovir is the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States, but currently are not available to civilians."
307,Avian Influenza A Viruses: Evolution and Zoonotic Infection,"Although efficient human-to-human transmission of avian influenza virus has yet to be seen, in the past two decades avian-to-human transmission of influenza A viruses has been reported. Influenza A/H5N1, in particular, has repeatedly caused human infections associated with high mortality, and since 1998 the virus has evolved into many clades of variants with significant antigenic diversity. In 2013, three (A/H7N9, A/H6N1, and A/H10N8) novel avian influenza viruses (AIVs) breached the animal-human host species barrier in Asia. In humans, roughly 35% of A/H7N9-infected patients succumbed to the zoonotic infection, and two of three A/H10N8 human infections were also lethal; however, neither of these viruses cause influenza-like symptoms in poultry. While most of these cases were associated with direct contact with infected poultry, some involved sustained human-to-human transmission. Thus, these events elicited concern regarding potential AIV pandemics. This article reviews the human incursions associated with AIV variants and the potential role of pigs as an intermediate host that may hasten AIV evolution. In addition, we discuss the known influenza A virus virulence and transmission factors and their evaluation in animal models. With the growing number of human AIV infections, constant vigilance for the emergence of novel viruses is of utmost importance. In addition, careful characterization and pathobiological assessment of these novel variants will help to identify strains of particular concern for future pandemics."
308,Enterovirus D68 and Human Respiratory Infections,"Enterovirus D68 (EV-D68) is a member of the species Enterovirus D in the genus Enterovirus of the Picornaviridae family. EV-D68 was first isolated in the United States in 1962 and is primarily an agent of respiratory disease. Infections with EV-D68 have been rarely reported until recently, when reports of EV-D68 associated with respiratory disease increased notably worldwide. An outbreak in 2014 in the United States, for example, involved more than 1,000 cases of severe respiratory disease that occurred across almost all states. Phylogenetic analysis of all EV-D68 sequences indicates that the circulating strains of EV-D68 can be classified into two lineages, lineage 1 and lineage 2. In contrast to the prototype Fermon strain, all circulating strains have deletions in their genomes. Respiratory illness associated with EV-D68 infection ranges from mild illness that just needs outpatient service to severe illness requiring intensive care and mechanical ventilation. To date, there are no specific medicines and vaccines to treat or prevent EV-D68 infection. This review provides a detailed overview about our current understanding of EV-D68-related virology, epidemiology and clinical syndromes, pathogenesis, and laboratory diagnostics."
309,Human Respiratory Syncytial Virus: Infection and Pathology,"The human respiratory syncytial virus (hRSV) is by far the major cause of acute lower respiratory tract infections (ALRTIs) worldwide in infants and children younger than 2 years. The overwhelming number of hospitalizations due to hRSV-induced ALRTI each year is due, at least in part, to the lack of licensed vaccines against this virus. Thus, hRSV infection is considered a major public health problem and economic burden in most countries. The lung pathology developed in hRSV-infected individuals is characterized by an exacerbated proinflammatory and unbalanced Th2-type immune response. In addition to the adverse effects in airway tissues, hRSV infection can also cause neurologic manifestations in the host, such as seizures and encephalopathy. Although the origins of these extrapulmonary symptoms remain unclear, studies with patients suffering from neurological alterations suggest an involvement of the inflammatory response against hRSV. Furthermore, hRSV has evolved numerous mechanisms to modulate and evade the immune response in the host. Several studies have focused on elucidating the interactions between hRSV virulence factors and the host immune system, to rationally design new vaccines and therapies against this virus. Here, we discuss about the infection, pathology, and immune response triggered by hRSV in the host."
310,Parainfluenza Virus Infection,"Human parainfluenza viruses (HPIVs) are single-stranded, enveloped RNA viruses of the Paramyoviridaie family. There are four serotypes which cause respiratory illnesses in children and adults. HPIVs bind and replicate in the ciliated epithelial cells of the upper and lower respiratory tract and the extent of the infection correlates with the location involved. Seasonal HPIV epidemics result in a significant burden of disease in children and account for 40% of pediatric hospitalizations for lower respiratory tract illnesses (LRTIs) and 75% of croup cases. Parainfluenza viruses are associated with a wide spectrum of illnesses which include otitis media, pharyngitis, conjunctivitis, croup, tracheobronchitis, and pneumonia. Uncommon respiratory manifestations include apnea, bradycardia, parotitis, and respiratory distress syndrome and rarely disseminated infection. Immunity resulting from disease in childhood is incomplete and reinfection with HPIV accounts for 15% of respiratory illnesses in adults. Severe disease and fatal pneumonia may occur in elderly and immunocompromised adults. HPIV pneumonia in recipients of hematopoietic stem cell transplant (HSCT) is associated with 50% acute mortality and 75% mortality at 6 months. Though sensitive molecular diagnostics are available to rapidly diagnose HPIV infection, effective antiviral therapies are not available. Currently, treatment for HPIV infection is supportive with the exception of croup where the use of corticosteroids has been found to be beneficial. Several novel drugs including DAS181 appear promising in efforts to treat severe disease in immunocompromised patients, and vaccines to decrease the burden of disease in young children are in development."
311,"Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes","Among immunocompromised individuals, members of the human Herpesviridae family are frequently encountered pathogens. Cytomegalovirus, herpes simplex virus 1 and 2, varicella zoster virus, Epstein–Barr virus, and human herpesvirus-6, -7, and -8 all establish latency after infection and can reactivate during periods of immunosuppression, leading to both direct and indirect adverse effects on the host including severe organ dysfunction as well as allograft rejection and loss after transplantation. While not all herpesviruses are primary respiratory pathogens, many of their manifestations include involvement of the respiratory tract. This article discusses the individual viruses, their epidemiology, and clinical manifestations as well as recommended treatment and preventive strategies."
312,Phylogeography and genetic diversity of the copepod family Cyclopidae (Crustacea: Cyclopoida) from freshwater ecosystems of Southeast Nigeria,"BACKGROUND: Copepods are key components of aquatic ecosystems and can help regulate the global carbon cycle. Much attention has been paid to the species diversity of copepods worldwide, but the phylogeography and genetic diversity of copepods in Nigeria is unexplored. RESULTS: Using a mitochondrial cytochrome c oxidase subunit I marker, we preformed phylogenetic and phylogeographic analyses for Cyclopidae copepods in Southeast Nigeria. A high species diversity of Cyclopidae in Nigeria: 5 species of Tropocyclops, 5 species of Mesocyclops and 2 species of Thermocyclops from Cyclopidae were identified in 15 populations. Moreover, we detected 18 unique haplotypes, which fell into two distinct clades. Pairwise genetic distances (uncorrected p-distances) among the species of Cyclopidae ranged from 0.05 to 0.257. Several species co-existed in the same lake, and some haplotypes were shared among different geographic populations, suggesting a dispersal of Cyclopidae in our sampling region. Finally, we found that the population genetic diversity for each species of Cyclopidae was low in Nigeria. CONCLUSIONS: Our findings explored the species diversity and distribution of copepods within the family Cyclopidae for 15 Nigerian freshwater ecosystems: a high species diversity of Cyclopidae copepods was detected over a small geographic sampling range. Results from this study contribute to a better understanding of copepod diversity of Nigerian freshwater ecosystems."
313,Monitoring Leishmania infection and exposure to Phlebotomus perniciosus using minimal and non-invasive canine samples,"BACKGROUND: In endemic areas of zoonotic leishmaniosis caused by L. infantum, early detection of Leishmania infection in dogs is essential to control the dissemination of the parasite to humans. The aim of this study was to evaluate the serological and/or molecular diagnostic performance of minimally and non-invasive samples (conjunctiva cells (CS) and peripheral blood (PB)) for monitoring Leishmania infection/exposure to Phlebotomus perniciosus salivary antigens in dogs at the beginning and the end of sand fly seasonal activity (May and October, respectively) and to assess associated risks factors. METHODS: A total of 208 sheltered dogs from endemic areas of leishmaniosis were screened. Leishmania DNA detection in PB on filter paper and CS was performed by nested-PCR (nPCR), while the detection of anti-Leishmania antibodies was performed using IFAT and ELISA. The exposure to P. perniciosus salivary antigens (SGH, rSP01 and rSP03B + rSP01) was measured by ELISA. RESULTS: Ninety-seven (46.6%) and 116 (55.8%) of the 208 dogs were positive to Leishmania antibodies or DNA by at least one test at the beginning and end of the sand fly season, respectively. IFAT and ELISA presented a substantial agreement in the serodiagnosis of leishmaniosis. Discrepant PB nPCR results were obtained between sampling points. Leishmania DNA was detected in CS of 72 dogs at the end of the phlebotomine season. The presence of antibodies to the parasite measured by ELISA was significantly higher in dogs presenting clinical signs compatible with leishmaniosis at both sampling points. Phlebotomus perniciosus salivary antibodies were detected in 179 (86.1%) and 198 (95.2%) of the screened dogs at the beginning and end of the phlebotomine season, respectively. CONCLUSIONS: The association between ELISA positivity and clinical signs suggests its usefulness to confirm a clinical suspicion. CS nPCR seems to be an effective and non-invasive method for assessing early exposure to the parasite. PB nPCR should not be used as the sole diagnostic tool to monitor Leishmania infection. The correlation between the levels of antibodies to P. perniciosus saliva and Leishmania antibodies suggests the use of a humoral response to sand fly salivary antigens as biomarkers of L. infantum infection. [Image: see text]"
314,The role of molecular diagnosis in acute respiratory tract infection,
315,Clustering of Feline Coronaviruses in Multicat Households,
316,Simultaneous detection and typing of human metapneumovirus strains in nasopharyngeal secretions and cell cultures by monoclonal antibodies,
317,Seasonal respiratory virus testing in management of adult cystic fibrosis patients,
318,Absence of Melaka-virus in European children with respiratory disease,
319,Respiratory Viral and Atypical Pneumonias,
320,Comments on “Impact of bronchoalveolar lavage multiplex polymerase chain reaction on microbiological yield and therapeutic decisions in severe pneumonia in intensive care unit”,
321,A highly efficient in vivo plasmid editing tool based on CRISPR-Cas12a and phage λ Red recombineering,
322,Respiratory viruses and acute asthma in children,
323,Broad reactivity of the Luminex xTAG Respiratory Virus Panel (RVP) assay for the detection of human rhinoviruses,
324,"IV, 6. Calicivirus RNA recombination","RNA recombination apparently contributed to the evolution of CVs. Nucleic acid sequence homology or identity and similar RNA secondary structure of CVs and non-CVs may provide a locus for recombination within CVs or with non-CVs should co-infections of the same cell occur. Natural recombinants have been demonstrated among other enteric viruses, including Picornaviridae (Kirkegaard and Baltimore, 1986; Furione et al., 1993), Astroviridae (Walter et al., 2001), and possibly rotaviruses (e.g., Desselberger, 1996; Suzuki et al., 1998), augmenting the natural diversity of these pathogens and complicating viral gastroenteritis prevention strategies based upon traditional vaccines. Such is the case for CVs and Astroviridae, whose recombinant strains may be a common portion of naturally circulating strains. The taxonomic — and perhaps biologic — limits of recombination are defined by the suggested recombination of Nanovirus and CV, viruses from hosts of different biologic orders; the relationship of picornaviruses and CVs, viruses in different families, as recombination partners; and the intra-generic recombination between different clades of NLVs."
325,Atypical respiratory pathogens,"The main atypical pathogens in respiratory tract infections are classified on the basis of their ability to cause atypical pneumonia. This is not a well-defined clinical entity, and it is evident that atypical pathogens can sometimes cause ‘typical’ pneumonias and vice versa. This emphasizes the need for microbiological diagnosis, since it affects the selection of proper treatment, in which β-lactam antibiotics and aminoglycosides are not effective. Moreover, mixed infections caused by atypical and typical pathogens together are common. At this moment rapid and sensitive diagnostic methods are lacking. Besides numerous viruses, the main bacterial pathogens causing atypical pneumonias are Mycoplasma pneumoniae, two chlamydial species, Chlamydia pneumoniae and C. psittaci, one rickettsia, Coxiella burnetti, and several Legionella species. The majority of these pathogens cause upper respiratory tract infections more often than overt pneumonias. An atypical agent, Chlamydia pneumoniae, has also been associated with chronic inflammatory conditions in the cardiovascular system. The most recently discovered pathogen in atypical pneumonias is a hantavirus causing hantavirus pulmonary syndrome."
326,First report of two consecutive respiratory syncytial virus outbreaks by the novel genotypes ON-1 and NA-2 in a neonatal intensive care unit(),"OBJECTIVE: Respiratory syncytial virus is a pathogen frequently involved in nosocomial outbreaks. Although several studies have reported nosocomial outbreaks in neonatal intensive care units, molecular epidemiology data are scarce. Here, the authors describe two consecutive respiratory syncytial virus outbreaks caused by genotypes ON-1 and NA-2 in a neonatal intensive care unit in São Paulo, Brazil. METHODS: A prospective search for respiratory syncytial virus was performed after diagnosing the index case and four other symptomatic newborns in the neonatal intensive care unit. Nasopharyngeal aspirate samples of all patients in the neonatal intensive care unit were tested for 17 respiratory viruses using real-time reverse transcriptase polymerase chain reaction. Genotyping was performed using nucleotide sequencing. RESULTS: From May to August 2013, two different outbreaks were detected in the neonatal intensive care unit. A total of 20 infants were infected with respiratory syncytial virus-A (ten and 14 with ON-1 and NA-2 genotypes, respectively). The mean age of the infants was 10 days, mean birth weight was 1,961 g, and the mean gestational age was 33 weeks. Risk factors (heart disease, lung disease, and prematurity) were present in 80% and 85.7% of infants in the ON-1 and NA-2 groups, respectively. In total, 45.8% of infants were asymptomatic and 20.8% required mechanical ventilation. Coinfections were not detected during the outbreaks. CONCLUSIONS: Infants in a neonatal intensive care unit who develop abrupt respiratory symptoms should be tested for respiratory viruses, especially respiratory syncytial virus. Even in the absence of severe symptoms, respiratory syncytial virus detection can prevent nosocomial transmission through infection control measures. A better understanding of respiratory syncytial virus molecular epidemiology is essential for developing new vaccines and antiviral drugs against respiratory syncytial virus."
327,Bronchiectasis: working together for better evidence,
328,Feline infectious diseases: Our curiosity could be their salvation,
329,Food-borne and water-borne diseases under climate change in low- and middle-income countries: Further efforts needed for reducing environmental health exposure risks,"This paper provides a view of the major facts and figures related to infectious diseases with a focus on food-borne and water-borne diseases and their link with environmental factors and climate change. The global burden of food-borne diseases for 31 selected hazards was estimated by the World Health Organization at 33 million disability-adjusted life years (DALYs) in 2010 with 40% of this burden concentrated among children under 5 years of age. The highest burden per population of food-borne diseases is found in Africa, followed by Southeast Asia and the Eastern Mediterranean sub-regions. Unsafe water used for the cleaning and processing of food is a key risk factors contributing to food-borne diseases. The role of quality and quantity of water to the general burden of infectious diseases deserves attention, particularly in low- and middle-income countries, as its effects go beyond the food chain. Water-related infectious diseases are a major cause of mortality and morbidity worldwide, and climate change effects will exacerbate the challenges for the public health sector for both food-borne and water-borne diseases. Selected case studies from Africa and Asia show that (i) climate change extreme events, such as floods, may exacerbate the risks for infectious diseases spreading through water systems, and (ii) improvements related to drinking water, sanitation and hygiene could result in a significant reduction of intestinal parasitic infections among school-aged children. There is a need to better anticipate the impacts of climate change on infectious diseases and fostering multi-stakeholder engagement and multi-sectoral collaborations for integrated interventions at schools, community and household levels. The paper calls for giving priority to improving the environmental conditions affecting food-borne and water-borne infectious diseases under climate change."
330,Viral pharyngitis,
331,Classical and molecular techniques for the diagnosis of viral gastroenteritis(),
332,Ribavirin,
333,"Randomised, controlled trial of effectiveness of ampicillin in mild acute respiratory infections in Indonesian children","The recommended treatment for mild acute respiratory infections (ARI) in children is supportive care only, but many physicians, especially in developing countries, continue to prescribe antibiotic treatment because they believe it prevents progression to more severe ARI. To find out whether ampicillin treatment conferred any benefit over supportive care alone, a randomised, controlled trial was carried out among 889 children (under 5 years) with mild ARI in Indonesia. 447 were randomly allocated ampicillin (25-30 mg/kg body weight three times daily for 5 days) plus supportive care (continued breastfeeding, clearing of the nose, and paracetamol to control fever); 442 were allocated supportive care only. The treatment groups were almost identical after randomisation in terms of age, sex, level of parental education, history of measles immunisation, and fever. After 1 week the percentages cured were nearly identical (204 [46%] ampicillin; 209 [47%] control), as were the percentages of cases progressing to moderate ARI (56 [13%] vs 53 [12%]). The effect of treatment was not modified by age, sex, measles immunisation status, or the educational level of the parents. At the 2-week follow-up, the percentages cured were 62% (277) in the ampicillin group and 58% (256) in the control group; 14% of both groups had progressed to moderate ARI; and 24% (107) and 28% (123), respectively, still had mild ARI. None of the differences in outcome between the ampicillin and control groups was statistically significant. Thus, ampicillin plus supportive care offers no benefit over supportive care alone for treatment of mild ARI in young Indonesian children."
334,The wheezing infant,"Wheeze is a symptom and not a diagnosis. It is extremely common in infancy; 20-30% of children have experienced recurrent episodic wheezing by the age of 12 months. Wheezing may result from widespread peripheral airway narrowing or, less commonly, from localized central disease. Excluding recurrent viral wheezing and asthma-like symptoms, all other specific causes of wheezing (e.g. cystic fibrosis, congenital airway disorders, chronic lung disease of prematurity) affect only 2-3% of the population. Although wheezing disease preceded by acute viral bronchiolitis early in infancy features prominently in most articles on childhood asthma, it affects, at most, 1% of the population. The increased prevalence of reported wheezing in industrialized countries until the mid-1990s, accompanied by an increase in the number of hospital admissions for wheezing, represents a true increase in the problem rather than simply increased awareness. In the UK, wheezing in pre-school children accounts for about 25% of acute hospital admissions in childhood, and almost 50% during epidemics of respiratory syncytial virus (RSV) infection."
335,"Virus-virus and virus-bacterium associations in the etiology of tuberculous and nontuberculous pneumopatia, during influenza season",
336,Impact of a poorly performing point-of-care test during the 2017-2018 influenza season,
337,T cell sensitization to proteolipid protein in myelin basic protein-induced relapsing experimental allergic encephalomyelitis,"(SJL/J × PL/J)F(1) mice immunized with myelin basic protein (MBP) develop an autoimmune demyelinating disease termed relapsing experimental allergic encephalomyelitis (rEAE). The acute stage of disease is mediated by CD4(+) T cells specific for MBP amino acids 1–9. To determine the immunologic bases for disease relapse, host sensitization to additional autoantigens of the central nervous system was measured. Results indicate that most animals develop T cell reactivity to endogenous myelin proteolipid protein (PLP) during rEAE. However, PLP-specific immunity does not appear to accound for expression of relapse episodes of demyelination. relapse episodes of demyelination."
338,GASTROINTESTINAL AND NUTRITIONAL PROBLEMS IN CHILDREN WITH IMMUNODEFICIENCY AND AIDS,
339,SCANDINAVIAN EPIDEMIC NEPHROPATHY AND KOREAN HÆMORRHAGIC FEVER,
340,Infectious wastes: Myths and realities,
341,Virus evolution,
342,The epidemiology of respiratory infections in children(),
343,Viral cytopathogenicity correlated with integration of ubiquitin-coding sequences(),"The RNA genomes of cytopathogenic bovine viral diarrhea virus (BVDV) isolates contain insertions highly homologous to cellular sequences. For two of them the insert was identified as ubiquitin coding sequence. The genome of BVDV Osloss contains exactly one ubiquitin gene monomer. In the case of BVDV CP1 the cellular insertion comprises one complete ubiquitin gene and part of a second monomer. The host cell-derived element in the CP1 genome is embedded in a large duplication of about 2.4 kb of viral sequences. Cellular insertion and duplication were not found in the genome of NCP1, the noncytopathogenic counterpart of CP1. These results strongly suggest that recombination between viral and cellular RNA is responsible for development of the cytopathogenic viruses, which is linked to pathogenesis of a lethal disease in cattle."
344,VIRUS-LIKE PARTICLES IN INFECTIOUS HEPATITIS,
345,Cold calling,Vaccination against flu viruses is well established and reasonably successful…
346,Contrasting effects of immunosuppression on herpes simplex virus type I (HSV I) induced central nervous system (CNS) demyelination in mice,"We previously reported that lip inoculation of Herpes simplex virus type I (HSV I) in specific strains of mice would induce multifocal brain demyelination (MBD). The mechanisms mediating the development of MBD are unknown. In this study, five inbred strains of mice (C57BL/6J, Balb/cByJ, A/J, SJL/J, PL/J) immunosuppressed with either irradiation (IR), cyclophosphamide (CY), or cyclosporin A (CP) along with three immune deficient strains (C57BL/6J nu/nu, Balb/cByJ nu/nu, C57BL/6J bg/bg) were lip inoculated with HSV I to determine the effect of immunosuppression on viral spread throughout the brain and the development of demyelination during the acute stage of infection. Mortality increased in all groups when compared with controls but was greatest in A/J, SJL/J, and PL/J strains, where all mice died before day 6 PI. In contrast with immunocompetent C57BL/6J mice where virus is restricted to the brainstem, virus spread throughout the brain of immunosuppressed C57BL/6J, C57BL/6J nu/nu, and C57BL/6J bg/bg mice. Despite viral spread throughout the brain of immunosuppressed C57BL/6J, C57BL/6J nu/nu, Balb/cByJ and Balb/cByJ nu/nu mice, MBD did not develop. MBD did develop however, in both HSV I infected C57BL/6J bg/bg and CP treated Balb/cByJ mice. Immunosuppression of HSV I infected Balb/cByJ mice prevents the development of demyelination at the trigeminal root entry zone (TREZ) of the brainstem while in Balb/cByJ nu/nu mice, the extent of demyelination at TREZ was reduced and delayed when compared with immunocompetent controls. These results suggest that the immune system plays an important role in limiting viral spread in the brain as well as in the development of demyelination at TREZ and of MBD throughout the brain during the acute phase of infection. Virus alone does not induce MBD in this animal model of virus induced CNS demyelination but is a prerequisite for its development."
347,How ‘hidden’ reading frames are expressed,"Secondary reading frames, ‘hidden’ under other reading frames, are used for coordinated expression of proteins in several eukaryotic viruses. In some genes, ribosomal frameshifting and initiation or reinitiation of protein synthesis on internal AUG codons are translational mechanisms allowing access to such ‘hidden’ reading frames. In others, secondary reading frames are translated from alternatively spliced or edited mRNAs."
348,Expression patterns of the ectopeptidases aminopeptidase N/CD13 and dipeptidyl peptidase IVICD26: immunoultrastructural topographic localization on different types of cultured cells,"Aminopeptidase N/CD13 and dipeptidyl peptidase IV/CD26 are widespread membrane-bound peptidases involved in fundamental biological processes. Using cryo-ultramicrotomy of cultured cells followed by indirect immunogold labelling, both enzymes appeared to be strongly and regularly labelled on the cell surfaces of human synovial fibroblasts, T-Iymphocytes and colon carcinoma cells Caco-2. In the cytoplasm of the synovial fibroblasts gold-labelled vesicle-like structures were found, which we consider to be potential transport vesicles. An abundant and regular expression of CD13 was detected on cultured renal parenchymal cells. On the renal carcinoma cell line Caki-l cells we found a low, non-homogeneous and clustered CD13-labelling. On cultured renal parenchymal cells and the Caki-l cells CD26 could not be observed. The expression pattern of CD26 on renal carcinoma cell line Caki-2 cells showed also a slightly clustered distribution. A low density CD26-labelling was present on the squamous cell carcinoma cell line UM-SCC-22B. CD13 was absent in Caki-2 and UMSCC-22B cells. The presence of both enzymes on the cultured cells enables their ultrastructural investigation under different growth conditions and their involvement in cell-cell interactions. For this purpose, however, further investigations are necessary."
349,Avsunviroidae family: Viroids containing hammerhead ribozymes,"This chapter focuses on the second viroid family, whose members are also referred to as hammerhead viroids, taking into account their most outstanding feature. If the word “small” is the first to come to mind when considering viroids, perhaps the second word is “hammerhead,” because this class of ribozymes, which because of its structural simplicity has an enormous biotechnological potential, is described in avocado sunblotch viroid (ASBVd) as well as in a viroid-like satellite RNA. The most outstanding feature of the Avsunviroidae members is their potential to adopt hammerhead structures in both polarity strands and to self-cleave in vitro accordingly. Viroids differ from viruses not only in their genome size but also in other fundamental aspects, prominent among which is the lack of messenger activity of both viroid RNAs and their complementary strands."
350,Mouse neuropathogenic poliovirus strains cause damage in the central nervous system distinct from poliomyelitis,"Poliomyelitis as a consequence of poliovirus infection is observed only in primates. Despitea host range restricted to primates, experimental infection of rodents with certain genetically well defined poliovirus strains produces neurological disease. The outcome of infection of mice with mouse-adapted poliovirus strains has been described previously mainly in terms of paralysis and death, and it was generally assumed that these strains produce the same disease syndromes in normal mice and in mice transgenic for the human poliovirus receptor (hPVR-tg mice). We report a comparison of the clinical course and the histopathological features of neurological disease resulting from intracerebral virus inoculation in normal micewith those of murine poliomyelitis in hPVR-tg mice. The consistent pattern of clinical deficits in poliomyelitic transgenic mice contrasted with highly variable neurologic disease that developed in mice infected with different mouse-adapted polioviruses. Histopathological analysis showed a diffuse encephalomyelitis induced by specific poliovirus serotype 2 isolates in normal mice, that affected neuronal cell populations without discrimination, whereas in hPVR-tg animals, damage was restricted to spinal motor neurons. Mouse neurovirulent strains of poliovirus type 2 differed from mouse neurovirulent poliovirus type 1 derivatives in their ability to induce CNS lesions. Our findings indicate that the characteristic clinical appearance and highly specific histopathological features of poliomyelitis are mediated by the hPVR. Our data lead us to conclude that the tissue tropism of mouse-adapted poliovirus strains in normal mice is fundamentally different from that of poliovirus in hPVR-tg mice and primates, and that this is indicative of an as yet unknown mechanism of adsorption and uptake of the virus into cells of the murine CNS."
351,Alphaviruses — vectors for the expression of heterologous genes,"DNA viruses and retroviruses are well established as vectors for the expression of heterologous genes, but there is increasing interest in the possibilities of using RNA viruses, which do not replicate through a DNA intermediate, for this purpose. This article summarizes some of the general properties of RNA viruses and concentrates on one class of RNA viruses — the alphaviruses — and their potential as expression vectors."
352,"VI, 3. Molecular biology and epidemiology of Aichi virus and other diarrhoeogenic enteroviruses","The virion of the Aichi virus contains a single-stranded RNA molecule as the genome. The homology of Aichi virus structural proteins (VP0, VP3, and VP1) with corresponding polypeptides of other picornaviruses varies between 19% and 32%. The epidemiology of the Aichi virus as a medically important pathogen has not been well defined. Stool samples from adult patients in six oyster-associated gastroenteritis outbreaks were examined for variation, based on their reactivity with a monoclonal antibody raised against the standard strain (A486/88) and on reverse transcription–polymerase chain reactions (RT-PCR) of three genomic regions. Antibody to the Aichi virus could be detected using a neutralization test and an enzyme-linked immunosorbent assay (ELISA). These methods were used for the identification of Aichi virus infection in paired serum samples. The chapter concludes with a discussion on other diarrheagenic enteroviruses."
353,The disruption of infectious bronchitis virus (IBV-41 strain) with Triton X-100 detergent,
354,Immunoblotting and dot blotting,
355,Effects of immunopotentiating agents on alveolar macrophage properties,"Infectious respiratory diseases in man and in domestic animals are characterized by the presence of a large number of different microorganisms: viruses, bacterias, mycoplasmas. It is therefore necessary to stimulate non-specific defense mechanisms in the lung and especially alveolar macrophages (AM). These cells, located in the alveolar air-spaces, play a major role in the lung clearance mechanisms and exert antibacterial, antiviral and antitumoral activities. Activation of alveolar macrophages was studied in vitro with lipopolysaccharide (LPS), lymphokines or mycobacterial derivatives (MDP). Rodent alveolar macrophages were rendered cytotoxic by in vitro exposure to LPS, free MDP or liposome-encapsulated MDP derivatives. In vivo, intravenously administered liposomes containing lipophilic MDP derivatives induced cytotoxic alveolar macrophages and protected mice against the development of pulmonary metastases."
356,Ambisense Rna Genomes of Arenaviruses and Phleboviruses,"This chapter reviews the evidence that shows that arenaviruses and members of one genus of the Bunyaviridae (phleboviruses) have some proteins coded in subgenomic, viral-sense mRNA species and other proteins coded in subgenomic, viral-complementary mRNA sequences. This unique feature is discussed in relation to the implications it has on the intracellular infection process and how such a coding arrangement may have evolved. The chapter presents a list of the known members of the arenaviridae, their origins, and the vertebrate hosts from which isolates have been reported. It discusses the structural components, the infection cycle, and genetic attributes of arenaviruses. In order to determine how arenaviruses code for gene products, the S RNA species of Pichinde virus and that of a viscerotropic strain of LCM virus (LCM-WE) have been cloned into DNA and sequenced. The arenavirus S RNA is described as having an ambisense strategy, to denote the fact that both viral and viral-complementary sequences are used to make gene products. The chapter discusses the infection cycle, the structural and genetic properties of bunyaviridae member."
357,Viral-Bacterial Synergistic Interaction in Respiratory Disease,"Humans and animals are constantly inoculated with various microorganisms resident in the upper respiratory tract and by inhaled aerosols, yet pneumonia is a relatively rare event. This implies the existence of very efficient defense mechanisms that are capable of eliminating the vast majority of microorganisms before they colonize and multiply to sufficient levels, resulting in clinical diseases. In order to overcome this continuous barrage of microorganisms, there is a complex array of defense mechanisms present in the upper and lower respiratory tract capable of eradicating these organisms. However, in individuals suffering from a variety of diseases, including virus infections, colonization occurs rapidly with subsequent development of pneumonia. Thus, it is estimated that 90% of bacterial pneumonias develop after a viral infection. Furthermore, individuals suffering from a viral pneumonia have a 40% chance of developing bacterial pneumonia. The reasons for the increased colonization of the lung by bacteria following virus infections are related to the surface properties of epithelial cells lining the respiratory tract, the physiological environment of the respiratory tract, and the alteration of the specific and nonspecific defense mechanisms of the lung that occurs as a result of virus infection."
358,Viral Enteritis,"Viral enteritis, rotavirus enteritis in particular, has emerged as the major cause of infant diarrhea throughout the world. A new understanding of the causes and mechanisms of viral diarrhea has provided the basis for new approaches to active and preventive therapy. The administration of rational oral fluids and early provisions of nutrients have been beneficial in acute cases. Work to develop vaccines for human rotavirus has been promising, but a safe vaccine of proven effectiveness is not yet available."
359,299S1 DGHM Abstracts,
360,"Clinical, virologic, and serologic evidence of Epstein-Barr virus infection in association with childhood pneumonia()","To explore the association of Epstein-Barr virus infection with childhood pneumonia we studied two patients whose mononucleosis-like illnesses were accompanied by pneumonia; both had virologic and serologic evidence of current or recent EBV infection. We then analyzed the sera of 71 children (age range, 14 months to 9 years) with pulmonary infiltrates for the presence of four classes of antibody to EBV. Antibody responses consistent with current or recent EB virus infection were found in 15. Two children had IgM antibodies to the EBV viral antigen at titers ≥1:160, indicating current infection, and all 15 patients had antibody to components of the early antigen complex, suggesting recent infection. A fourfold rise or drop in one or more EBV-specific antibody classes was noted in eight patients within 30 days following onset of clinical illness. Few patients had clinical features suggesting infectious mononucleosis. Eight of the 15 with serologic evidence of current or recent EBV infection also had clinical or serologic evidence of infection with another pathogen-bacterial, viral, or mycoplasmal. Thus, in childhood pneumonia, EBV may be a primary, co-primary, or secondary pathogen; it may be reactivated in the course of infection with another agent, or possibly, by suppressing immune function, it may precipitate infection with some other organism."
361,Colostral transfer of bovine immunoglobulin E and dynamics of serum IgE in calves,"The role of IgE in protective immunity is becoming understood, therefore the colostral transfer of IgE and the age-dependent changes of IgE levels may be important for neonatal immunity. To investigate this question, serum samples were collected from range-fed Hereford cows and their calves from birth through 9 months of age. The sera were assayed for total IgE by enzyme-linked immunosorbent assay (ELISA). Calves were found to have significant levels of IgE during the first week postpartum, indicating colostral transfer of IgE. Thereafter, serum levels declined rapidly within 3 weeks from birth. The IgE levels began to increase after 12 weeks of age, and in some cases reached adult levels. The passive transfer of maternal IgE through colostrum may be important in providing early protection from disease, especially against intestinal parasites."
362,"Viral respiratory diseases in children: Classification, etiology, epidemiology, and risk factors()()()","The epidemiology, molecular structure, cell tropism, and pathophysiology of many human disease-causing viruses have been painstakingly and elegantly characterized during the past 50 years. Vaccines and antiviral drugs of varying efficacy were developed and tested. Despite the relegation of smallpox to a freezer chest and the progress in the control of measles and hepatitis B, the viruses that cause respiratory tract infections remain significant causes of illness and death in pediatric populations worldwide. This discussion surveys the virus groups that contain nearly 200 distinct viruses that cause sporadic and epidemic respiratory infections in children. The epidemiology of infection with the influenza A and B, parainfluenza, and respiratory syncytial viruses and adenoviruses and their impact on infants and children and the groups at highest risk for morbid outcomes are discussed. (J PEDIATR 1994;124:S13-S6)"
363,Effective Use of the Diagnostic Laboratory in Dairy Practice,
364,Infectious disease in athletes,
365,Multiplex RT-nested PCR differentiation of gill-associated virus (Australia) from yellow head virus (Thailand) of Penaeus monodon,"A multiplex RT-nested PCR has been developed to detect and differentiate the closely related prawn viruses, gill-associated virus (GAV) from Australia and yellow head virus (YHV) from Thailand. RT-PCR using primers to conserved sequences in the ORF1b gene amplified a 794 bp region of either GAV or YHV. Nested PCR using a conserved sense primer and either a GAV- or YHV-specific antisense primer to a divergent sequence differentially amplified a 277 bp region of the primary PCR amplicon. Multiplexing the YHV antisense primer with a GAV antisense primer to another divergent sequence allowed the viruses to be distinguished in a single nested PCR. Nested PCR enhanced detection sensitivity between 100- and 1000-fold and GAV or YHV RNA was detectable in ∼10 fg lymphoid organ total RNA. The multiplex RT-nested PCR was also able to co-detect GAV and YHV RNA mixed over a wide range of concentrations to simulate potential dual-infection states. The robustness of the test was examined using RNA samples from Penaeus monodon prawns infected either chronically or acutely with GAV or YHV and collected at different locations in Eastern Australia and Thailand between 1994 and 1998. GAV- (406 bp) or YHV-specific (277 bp) amplicons were differentially generated in all cases, including five YHV RNA samples in which no primary RT-PCR amplicon was detected. Sequence analysis of GAV and YHV PCR amplicons identified minor variations in the regions targeted by the virus-specific antisense primers. However, none occurred at positions that critically affected the PCR."
366,Viral proteases as targets for chemotherapeutic intervention,"Many viruses encode proteinases that are essential for infectivity, and are consequently attractive chemotherapeutic targets. The biochemistry and structure of the human immunodeficiency virus proteinase have been characterized extensively, and potent peptide-mimetic inhibitors have been developed. Techniques and strategies used to improve the efficiency of these compounds are likely to be applicable to other viral proteinases."
367,Laboratory Diagnosis of Swine Diseases,
368,Evidence for the existence of IL-4 and IFNγ secreting cells in the T cell repertoire of naive mice,"The kinetics with which IgE responses develop in vivo following immunization of experimental animals indirectly support the existence of IL-4-secreting T cells as a normal component of the T cell repertoire. At the same time, studies of IL-4-secreting cell frequencies directly ex vivo have argued that T cells with the potential to become IL-4 secretors exist in vivo, in the form of precursors requiring stimulation and 4 – 12 days of culture as well as restimulation with mitogen or Ag before they become detectable as lymphokine-secreting cells. We demonstrate here that intravenous administration of low doses of anti-CD3 mAb 145-2C11 results in IL-4 production within 60 min of stimulation as demonstrated by Northern analysis of mRNA and a sensitive, selective bioassay (CT.4S cell proliferation) of biologically active IL-4 protein. Production of IL-4 is paralleled by IFNγ synthesis, displaying similar kinetics. These findings, consistent with the presence of mature cells capable of IL-4 and IFNγ synthesis in the T cell repertoire of naive mice, are supported by the observation that stimulation of spleen cells from naive mice with anti-CD3 mAb in vitro for 12 h also results in strong IL-4 and IFNγ mRNA and protein synthesis. The data support and extend those obtained through analysis of cytokine mRNA synthesis alone, thereby providing evidence that “fresh” T cells are indeed capable of producing IL-4 directly ex vivo and are consistent with the existence of IL-4-secreting cells as a normal component of the T cell repertoire of naive mice."
369,Ste24: An Integral Membrane Protein Zinc Metalloprotease with Provocative Structure and Emergent Biology,"Ste24, an integral membrane protein zinc metalloprotease, is found in every kingdom of eukaryotes. It was discovered approximately 20 years ago by yeast genetic screens identifying it as a factor responsible for processing the yeast mating a-factor pheromone. In animals, Ste24 processes prelamin A, a component of the nuclear lamina; mutations in the human ortholog of Ste24 diminish its activity, giving rise to genetic diseases of accelerated aging (progerias). Additionally, lipodystrophy, acquired from the standard highly active antiretroviral therapy used to treat AIDS patients, likely results from off-target interactions of HIV (aspartyl) protease inhibitor drugs with Ste24. Ste24 possesses a novel “α-barrel” structure, consisting of a ring of seven transmembrane α-helices enclosing a large (> 12,000 Å(3)) interior volume that contains the active-site and substrate-binding region; this “membrane-interior reaction chamber” is unprecedented in integral membrane protein structures. Additionally, the surface of the membrane-interior reaction chamber possesses a strikingly large negative electrostatic surface potential, adding additional “functional mystery.” Recent publications implicate Ste24 as a key factor in several endoplasmic reticulum processes, including the unfolded protein response, a cellular stress response of the endoplasmic reticulum, and removal of misfolded proteins from the translocon. Ste24, with its provocative structure, enigmatic mechanism, and recently emergent new biological roles including “translocon unclogger” and (non-enyzmatic) broad-spectrum viral restriction factor, presents far differently than before 2016, when it was viewed as a “CAAX protease” responsible for cleavage of prenylated (farnesylated or geranylgeranylated) substrates. The emphasis of this review is on Ste24 of the “Post-CAAX-Protease Era.”"
370,Design of the first highly potent and selective aminopeptidase N (EC 3.4.11.2) inhibitor,A series of phosphinic compounds mimicking the transition state of substrates hydrolysed by aminopeptidase N (EC 3.4.11.2) were synthesized. These new compounds have potent inhibitory activities with Ki values in the nanomolar range. These derivatives behave as the most potent APN inhibitors designed to date.
371,Vγ9Vδ2 T cell-mediated non-cytolytic antiviral mechanisms and their potential for cell-based therapy,"In healthy adult Homo sapiens, the most frequent circulating γδ T cells (Vγ9Vδ2) respond to pyrophosphomonoesters, alkylamines (together referred to as non-peptidic antigens, NpAgs) and nitrogen-containing bisphosphonates. The seemingly very low toxicity of bisphosphonate and pyrophosphomonoester drugs in vivo, may allow novel approaches to the immunotherapy of viral infections. For example, these drugs can be used to stimulate Vγ9Vδ2 T cells to release antiviral molecules that directly suppress virus replication without destroying the virus-replicating cells. In addition, the soluble molecules released by γδ T cells could boost the antiviral potency of cytotoxic T lymphocytes (CTLs) and promote antigen presentation. The relative therapeutic value of drug-induced direct antiviral and immunoregulatory activities may depend on the infecting virus as well as on the nature of protective immune responses."
372,OTC product: Kleenex Anti-Viral tissue,
373,An invited commentary on: “Evidence based management guideline for the COVID-19 pandemic - Review article”,
374,Opportunities for rapid viral diagnosis,
375,"A rapid, quantitative assay for titration of bovine virus diarrhoea-mucosal disease virus()","An end point dilution microtitration assay is described that can be used for the titration of both cytopathic and non-cytopathic isolates of bovine virus diarrhoea-mucosal disease virus. Indirect immunofluorescence is used to detect infected MDBK cells in the wells of Terasaki plates. The virus titre is derived from the number of uninfected wells, using the Poisson distribution. The assay is simple, fast and economical. Titres of cytopathic virus determined by the microtitration assay and standard plaque assay are equivalent."
376,"Seasonality and prevalence of rotavirus in Al-Ain, United Arab Emirates","Background: Rotaviruses are the single most important causative agent of acute neonatal enteritis in most avian and mammalian species including humans. Rotaviruses infections have also been shown to be associated with the elderly, immunocompromised individuals and more recently with epidemic diarrheal illness in adults. Objectives: To study the incidence and the effect of seasonality on the prevalence of rotaviruses in Al-Ain, United Arab Emirates. Study design: A total of 650 stool samples submitted to the laboratories of two University Teaching Hospitals (Al-Ain and Tawam) and a private hospital (Oasis) were examined for the presence of rotaviruses from January 1990–December, 1992, using a commercially available latex agglutination assay. The meteorological data (temperature, relative humidity and rainfall) recorded during the sampling period was analyzed statistically to examine the effect of seasonality on the prevalence of rotavirus cases in Al-Ain, United Arab Emirates. Results: Rotavirus was detected in 21.4% of the samples examined. The predominant number of positive cases (35%) were in the 7–12 months age group. It was interesting to find rotavirus-positive cases in as low an age group as <3 months (3.6%) and as high as 10 years (8.04%). There was no significant difference on infection rates between male and female groups in the study. However, there was a significant difference between the national (38.18%) and non-national children (61.28%). The higher rate of the latter may be due to import of infections. There appeared to be a seasonal pattern of rotavirus occurrence in the cases studied, with a marked increase in the number of positive cases during the months when the relative humidity was low (25–45%) and there was no rainfall. Conclusions: Rotavirus was detected in all age groups with a predominance in 7–12 month age groups, and a higher incidence in non-nationals. There was a marked increase in the number of positive cases during the months when the relative humidity was low (25–45%) and there was no rainfall. These findings are discussed in relation to the epidemiology and prophylaxis of rotavirus infections."
377,HIV genetic variation: Life at the edge,
378,New Developments in Fungal Virology,"Although viruses are widely distributed in fungi, their biological significance to their hosts is still poorly understood. A large number of fungal viruses are associated with latent infections of their hosts. With the exception of the killer-immune character in the yeasts, smuts, and hypovirulence in the chestnut blight fungus, fungal properties that can specifically be related to virus infection are not well defined. Mycoviruses are not known to have natural vectors; they are transmitted in nature intracellularly by hyphal anastomosis and heterokaryosis, and are disseminated via spores. Because fungi have a potential for plasmogamy and cytoplasmic exchange during extended periods of their life cycles and because they produce many types of propagules (sexual and asexual spores), often in great profusion, mycoviruses have them accessible to highly efficient means for transmission and spread. It is no surprise, therefore, that fungal viruses are not known to have an extracellular phase to their life cycles. Although extracellular transmission of a few fungal viruses have been demonstrated, using fungal protoplasts, the lack of conventional methods for experimental transmission of these viruses have been, and remains, an obstacle to understanding their biology. The recent application of molecular biological approaches to the study of mycoviral dsRNAs and the improvements in DNA-mediated fungal transformation systems, have allowed a clearer understanding of the molecular biology of mycoviruses to emerge. Considerable progress has been made in elucidating the genome organization and expression strategies of the yeast L-A virus and the unencapsidated RNA virus associated with hypovirulence in the chestnut blight fungus. These recent advances in the biochemical and molecular characterization of the genomes of fungal viruses and associated satellite dsRNAs, as they relate to the biological properties of these viruses and to their interactions with their hosts are the focus of this chapter."
379,Reovirus infection in adult mice: the virus hemagglutinin determines the site of intestinal disease,"Reovirus type 1, strain Lang, and type 3, strain Dearing, induced site-specific intestinal lesions in the adult mouse after intravenous inoculation. Reovirus type 1 caused inflammation and epithelial changes such as loss of nuclear polarity, villus blunting and crypt hyperplasia restricted to the ileum. In contrast, reovirus type 3 induced duodenitis, jejunitis, and ulcerative colitis. In the duodenum and jejunum, the epithelial cells appeared normal, but hemorrhage and inflammation in the lamina propria was present. In the colon, superficial ulceration, crypt abscesses, and intraluminal hemorrhage was observed. Segregation analysis using reassorant clones derived from reoviruses 1 and 3, suggested the viral hemagglutinin, encoded by genome segment S1, to be the major viral determinant of site specific intestinal disease following intravenous inoculation."
380,Amantadine for chronic hepatitis C: a magic bullet or yet another dead duck?,
381,[32] Families of cysteine peptidases,"This chapter presents families of cysteine peptidases. The activity of all cysteine peptidases depends on a catalytic dyad of cysteine and histidine. The order of the cysteine and histidine residues (Cys/His or His/Cys) in the linear sequence differs between families and this is among the lines of evidence suggesting that cysteine peptidases have had many separate evolutionary origins. The families C1, C2, and C10 can be described as “papainlike,” and form clan CA. The papain family contains peptidases with a wide variety of activities, including endopeptidases with broad specificity, endopeptidases with narrow specificity, aminopeptidases, and peptidases with both endopeptidase and exopeptidase activities. Papain homologs are generally either lysosomal or secreted proteins. The calpain family includes the calcium-dependent cytosolic endopeptidase calpain, which is known from birds and mammals, and the product of the sol gene in Drosophila. Calpain is a complex of two peptide chains. Picornains are a family of polyprotein-processing endopeptidases from single-stranded RNA viruses. Each picornavirus has two picornains (2A and 3C)."
382,Improved cutaneous genetic immunization by microneedle array delivery of an adjuvanted adenovirus vaccine,
383,Clinically distinguishable syndromes caused by viruses,
384,Ribavirin efficacy in an in vivo model of Crimean-Congo hemorrhagic fever virus (CCHF) infection(),"After intraperitoneal (i.p.) infection of infant mice with CCHF virus, virus titers in liver remained significantly higher than in other organs except blood (serum). Within the liver, virus antigen was first found by immunofluorescence (IFA) in Kupffer cells followed by more extensive hepatic spread. Later, virus was found in other organs including brain and heart. Ribavirin treatment significantly reduced infant mouse mortality and extended the geometric mean time to death. Ribavirin treatment reduced CCHF virus growth in liver and significantly decreased, but did not prevent, viremia. Despite a substantial viremia, infection of other organs including brain and heart was not detected in ribavirin-treated mice. A hepatotropic virus subpopulation with less neurovirulence than the parent was isolated from liver of ribavirin-treated mice (single dose, 100 mg/kg). After serial passage in placebo-treated mice, the exclusive hepatotropism was lost."
385,Virus-induced autoimmunity: Molecular mimicry as a route to autoimmune disease,
386,Improvements in obtaining and characterizing mouse cerebrospinal fluid(): Application to mouse hepatitis virus-induced encephalomyelitis,"This report describes advances in techniques for analyzing cellular and humoral immune components in the cerebrospinal fluid (CSF) of the mouse that are applicable to other laboratory animals. CSF studies undertaken during experimental infection of mice with JHM strain virus (JHMV) of mouse hepatitis virus are presented. A critical pitfall which can lead to erroneous or invalid results is contamination of the CSF by even minute quantities of blood. Means of avoiding this contamination are attention to anatomical reference points, the use of a micropipet, and prior intracardiac perfusion of animals with phosphate-buffered saline. Cells in the CSF were typed as either B, T, polymorphonuclear, or mononuclear cells by the combination of a microcytotoxicity assay and histologic stains. A radioimmunoassay (RIA) allowed quantification of antibodies to JHMV in the CSF and indicated the presence of intrathecal synthesis of antibody in chronically infected mice. The combined use of these sensitive methods makes possible CSF analysis in individual mice rather than in pooled groups."
387,Does muscle activation occur by direct mechanical coupling of transverse tubules to sarcoplasmic reticulum?,"Our knowledge of the physiological and biochemical constituents of skeletal muscle excitation has increased greatly during the last few years but this has not led to a consensus of the physiological mode of muscle activation. Three hypotheses of transmission, involving either transmitter-receptor interaction or direct mechanical coupling, are still under active consideration. The hypothesis of direct mechanical coupling currently being evaluated proposes that the dihydropyridine receptor in the transverse tubules serves as a voltage sensor that communicates directly with the junctional foot protein/Ca(2+) channel of sarcoplasmic reticulum to initiate opening of the channel."
388,The spectrum of severe wheezing in childhood(),
389,Chapter 8 Paramyxoviruses,"The paramyxoviruses are a heterogeneous group of viruses causing a variety of clinical diseases in humans, animals, and birds. This chapter examines in more detail the structure and properties of the important human viruses in this group, namely measles, respiratory syncytial virus (RSV), mumps and parainfluenza viruses I-V. They are all enveloped, negative-stranded, riboviruses of helical symmetry. It is suggested that susceptible children, adolescents, and adults should be vaccinated against mumps, unless vaccination is contraindicated. Mumps vaccine can be of particular value to children approaching puberty and for adolescents and adults, especially males who have not had mumps in childhood. Ribavirin therapy may be particularly beneficial for children at risk for severe and often fatal RSV infection, such as infants with congenital heart disease. Attenuated measles vaccines have been developed empirically by selection of host range mutants, and are widely and successfully used throughout the world. Using the vaccine, some countries may soon eliminate measles as an endogenous virus but continued problems are anticipated, particularly in adults with viruses re-introduced by visitors from abroad. Basic studies on new antivirals are continuing (particularly with oligopeptides) but antiviral compounds are unlikely to have extended use in the clinic, except perhaps in tropical areas where the disease may be life threatening. However, a vaccination programme in these areas is preferable, and is an urgent need."
390,O manejo do absorvedor de CO(2) durante o uso do aparelho de anestesia como respirador mecânico em pacientes com COVID-19,
391,Crossed immunoelectrophoresis: Qualitative and quantitative considerations,"Invented 20 years ago, crossed immunoelectrophoresis (X-IEP) today is a technique of unusual power and myriad application. It combines very high resolution with exquisite specificity by alloying 2-dimensional electrophoresis with immunoprecipitation for symbiotic new potentialities. The consequent matchless quantitative/qualitative capabilities of X-IEP for analyzing antigens in complex mixtures, particularly by their idiomatic internal comparisons, are still not widely recognized. Because of this and the supposed complications of its use and interpretation, X-IEP is more rarely used than it should be. This essay discusses contemporary X-IEP with the particular aims of demonstrating that it is not difficult to use and of explaining with selected examples why it is peculiarly powerful for analyzing antigen mixtures like the body fluids, tissue and cell extracts, and microbial homogenates."
392,Greater frequency of viral respiratory infections in asthmatic children as compared with their nonasthmatic siblings(),"A longitudinal clinical and microbiologic surveillance was conducted from October to May, 1971–1972, on 16 children with infectious asthma and 15 of their nonasthmatic siblings. Asthmaticchildren experienced a significantly greater frequency of viral respiratory infections than did nonasthmatic ones (5.1 vs. 3.8 per subject). This increased incidence appeared to be largely the result of a greater number of rhinovirus infections. While respiratory infections of identical etiology that occurred concurrently in an asthmatic and his sibling were equivalent in severity, illnesses were longer (but not significantly so) in asthmatic children."
393,Master author index,
394,Expression in Escherichia coli and purification of biologically active L proteinase of foot-and-mouth disease virus,The foot-and-mouth disease virus (FMDV) Lb gene was cloned into bacterial expression vectors under the control of a T7 RNA polymerase promoter. The Lb protein was expressed in both an in vitro transcription-translation system and in Escherichia coli. In vitro expression of a construct containing the Lb gene fused to a portion of the VP4 and 3D genes demonstrated cis cleavage activity that could be blocked by the thiol protease inhibitor E-64. Lb expressed in E. coli was purified from the soluble fraction by metal chelation chromatography. Purified Lb had trans cleavage activity at the L/P1 junction and cleaved the p220 component of the cap-binding protein complex.
395,VIRUSES AND GASTROENTERITIS,
396,Respiratory illness caused by picornavirus infection: a review of clinical outcomes,"Background: Respiratory infections result from invasion of the respiratory tract, mainly by viruses, and are the leading cause of acute morbidity in individuals of all ages worldwide. During peak season, picornaviruses cause 82% of all episodes of acute nasopharyngitis (the common cold), the most frequent manifestation of acute respiratory infection, and produce more restriction of activity and physician consultations annually than any other viral or bacterial source of respiratory illness. Objective: This article reviews the clinical impact and outcomes of picornavirus-induced respiratory infections in specific populations at risk for complications. It also discusses the potential economic impact of the morbidity associated with picornavirus-induced respiratory infection. Methods: Relevant literature was identified through searches of MEDLINE, OVID, International Pharmaceutical Abstracts, and Lexis-Nexis. The search terms used were picornavirus, rhinovirus, enterovirus, viral respiratory infection, upper respiratory infection, disease burden, economic, cost, complications, asthma, COPD, immunocompromised, elderly, otitis media, and sinusitis. Additional publications were identified from the reference lists of the retrieved articles. Conclusions: Based on the clinical literature, picornavirus infections are associated with severe morbidity as well as considerable economic and societal costs. Future research should focus on identifying patterns of illness and the costs associated with management of these infections. New treatments should be assessed not only in terms of their ability to produce the desired clinical outcome, but also in terms of their ability to reduce the burden of disease, decrease health care costs, and improve productivity."
397,[33] Using confocal microscopy to study virus binding and entry into cells,"The chapter presents a discussion on the study of virus binding and entry into cells by using confocal microscopy. For the study new approaches to study vaccinia virus (VV), binding and entry based on confocal microscopy are developed. These techniques do not require virus purification or labeling and generate data that reveal the absolute numbers of virus particles that have bound to or have entered into individual cells. The chapter describes these techniques and then illustrates with some of the results obtained. These methods should be applicable to any virus larger than 50 nm. The chapter discusses the way these techniques have generated data that cannot be obtained with classical binding or entry assays. Vaccina virus is the prototype of the poxvirus family. These are DNA viruses that replicate in the cell cytoplasm and have genomes between 150 and 300 kbp. These techniques are presented with a study of the binding and entry of VV. The methods have been particularly useful for studying VV because this virus produces two different forms of infectious virion that are antigenically and biologically distinct and are produced in widely differing amounts. Moreover, the extracellular enveloped virus (EEV) form of VV cannot be purified from contaminating IMV without disrupting the integrity of the outer envelope."
398,Nonculturable agents of viral gastroenteritis,
399,Regulation of Tobamovirus Gene Expression,"This chapter discusses tobacco mosaic virus (TMV) strains U1, OM, L, CGMMV, 0, and Cc. The production of each TMV protein is regulated differently, both in amounts and times of production. The chapter discusses some of the strategies that tobamoviruses uses to control gene expression: (1) different subgenomic RNA promoter/leader sequences control timing of expression of genes, (2) genes expressed via subgenomic mRNAs are expressed in decreasing amounts with increasing distances from the 3' terminus, and (3) TMV mRNAs appear to be translationally regulated differently from host mRNAs. Genome organization affects gene expression, but it appears to be equally important for the efficiency of replication and the ability of the genomic structure to be stably propagated. Different virus groups have evolved different gene arrangements. Tobamovirus genes expressed via subgenomic mRNAs appear to be expressed in increasing amounts when positioned nearer the 3’ terminus."
400,Antiviral agents against respiratory viruses,
401,Outcomes of Three- Versus Six-Monthly Dispensing of Antiretroviral Treatment (ART) for Stable HIV Patients in Community ART Refill Groups: A Cluster-Randomized Trial in Zimbabwe,"INTRODUCTION: Multimonth dispensing (MMD) of antiretroviral treatment (ART) aims to reduce patient-related barriers to access long-term treatment and improve health system efficiency. However, randomized evidence of its clinical effectiveness is lacking. We compared MMD within community ART refill groups (CARGs) vs. standard-of-care facility-based ART delivery in Zimbabwe. METHODS: A three-arm, cluster-randomized, pragmatic noninferiority trial was performed. Thirty health care facilities and associated CARGs were allocated to either ART collected three-monthly at facility (3MF, control); ART delivered three-monthly in CARGs (3MC); or ART delivered six-monthly in CARGs (6MC). Stable adults receiving ART ≥six months with baseline viral load (VL) <1000 copies/ml were eligible. Retention in ART care (primary outcome) and viral suppression (VS) 12 months after enrollment were compared, using regression models specified for clustering (ClinicalTrials.gov: NCT03238846). RESULTS: 4800 participants were recruited, 1919, 1335, and 1546 in arms 3MF, 3MC, and 6MC, respectively. For retention, the prespecified noninferiority limit (-3.25%, risk difference [RD]) was met for comparisons between all arms, 3MC (94.8%) vs. 3MF (93.0%), adjusted RD = 1.1% (95% CI: -0.5% to 2.8%); 6MC (95.5%) vs. 3MF: aRD = 1.2% (95% CI: -1.0% to 3.6%); and 6MC vs. 3MC: aRD = 0.1% (95% CI: -2.4% to 2.6%). VL completion at 12 months was 49%, 45%, and 8% in 3MF, 3MC, and 6MC, respectively. VS in 3MC (99.7%) was high and not different to 3MF (99.1%), relative risk = 1.0 (95% CI: 1.0-1.0). VS was marginally reduced in 6MC (92.9%) vs. 3MF, relative risk = 0.9 (95% CI: 0.9-1.0). CONCLUSION: Retention in CARGs receiving three- and six-monthly MMD was noninferior versus standard-of-care facility-based ART delivery. VS in 3MC was high. VS in six-monthly CARGs requires further evaluation."
402,Correlation of urine pH with the detection of cytomegalovirus by the shell vial technique,The influence of the pH of urine on the detection of cytomegalovirus (CMV) by the shell vial assay was evaluated. The pH values of 295 urine specimens ranged from 4.7 to 8.5 (mean 6.3) and were not significantly different in culture-positive versus culture-negative samples. None of the urine specimens appeared to be toxic for the cells used in the shell vial assay. We recommend inoculation of urine specimens into shell vials without adjustment of pH.
403,Viral infections and recurrences of febrile convulsions(),"To determine whether complicated febrile seizures occur more often in children with a proven viral infection, we performed viral examinations on 144 children with febrile convulsions, of whom 112 had simple and 32 had complicated seizures. A diagnosis of virus infection was verified in 46% of the former patients and 53% of the latter. Three adenoviruses, one parainfluenza virus type 2 and one type 3, one respiratory syncytial virus, one echovirus type 11, one herpes simplex virus type 2, and one influenza B virus were isolated from the cerebrospinal fluid. A simple febrile convulsion occurred in seven children with a positive cerebrospinal fluid viral isolation, and two had a complex febrile seizure. In a follow-up of 2 to 4 years (mean 3.3 years), 21 of the 107 children with simple seizures (19.6%) and 3 of the 32 children with complicated seizures (9.4%) had recurrent febrile seizures. The children with positive evidence for a viral infection, even with a virus isolated from the cerebrospinal fluid, had no more recurrences than those without any proven viral infection. We conclude that children with a proven viral infection have no worse prognosis than those without."
404,O14 Has the 7-valent pneumococcal conjugate vaccine (PCV7) reduced hospital visits and admissions for pneumonia in young children in Calgary?,
405,"Avian flu virus H5N1: No proof for existence, pathogenicity, or pandemic potential; non-“H5N1” causation omitted",
406,The Morphology of Virus-Antibody Interaction,"In the field of virus study, the electron microscope technique of negative staining is now more than 10 years old, and during these years the knowledge of virus fine structure has changed beyond all recognition. This chapter describes that the immune aggregate should be incubated for 1 hour at 37°C and then left in the cold overnight. This is the optimum approach for a system, where the concentration of neither the antigen nor the antiserum is known, and maximum clumping is needed. However, with many systems these parameters have been established, and if it is known that clumping can be obtained readily, for example, as with the avian infectious bronchitis system, then incubation for 1 hour at 37°C is sufficient, followed by spinning at 10,000 rpm for half an hour. Viruses in the small to intermediate size range are ideal for immune studies, as the particles are not disproportionately larger than the antibody molecules attached to them, and interaction between them can be visualized with better than 10 a resolution. Particles as large as the poxviruses are becoming too large for good resolution of antibody molecules to be obtained, and aggregates of poxvirus particles are usually too dense to be recorded photographically except at low power. In the field of clinical virology, there is a possibility that the electron microscope technique of negative staining will become a standard method of diagnosis. As far as research is concerned, the present article seems to have described the beginnings that have been made in the visualization of several aspects of antigen-antibody interaction. Each line investigated has yielded a few answers, but of much greater importance, has led to a better understanding of what questions should be asked. At present, viral antigens can only occasionally be obtained in pure form, such that there are only a very few systems where controlled and specific virus-antigen-antibody systems can be visualized."
407,Tailed Bacteriophages: The Order Caudovirales,"This chapter discusses the common properties of tailed phages and potential criteria for their classification as an order and situating tailed phages with respect to other viruses. Tailed bacteriophages have a common origin and constitute an order with three families, named Caudovirales. Their structured tail is unique. Tailed phages share a series of high-level taxonomic properties and show many facultative features that are unique or rare in viruses—for example, tail appendages and unusual bases. They share with other viruses, especially herpesviruses, elements of morphogenesis and lifestyle that are attributed to convergent evolution. Tailed phages present three types of lysogeny, exemplified by phages λ, Mu, and P1. Lysogeny appears as a secondary property acquired by horizontal gene transfer. Amino acid sequence alignments (notably of DNA polymerases, integrases, and peptidoglycan hydrolases) indicate frequent events of horizontal gene transfer in tailed phages. Common capsid and tail proteins have not been detected. Present-day tailed phages appear as chimeras, but their monophyletic origin is still inscribed in their morphology, genome structure, and replication strategy. It may also be evident in the three-dimensional structure of capsid and tail proteins. It is unlikely to be found in amino acid sequences because constitutive proteins must be so old that relationships were obliterated and most or all replication-, lysogeny-, and lysis-related proteins appear to have been borrowed."
408,Phosphorylation of the mouse hepatitis virus nucleocapsid protein,"Analysis of the radiolabeled tryptic peptides derived from the nucleocapsid proteins of two serotypes of mouse hepatitis virus showed each to have a small number of unique peptides; however, twobiologically distinct variants of the JHM strain appeared identical. Analysis of [(32)P]-labeled nucleocapsid-derived peptides showed that phosphorylation occurs at only a few sites and that all three viruses differed in the sites of phosphorylation. No differences in the sites of phosphorylation were found between the nucleocapsid proteins derived from purified virions and the membranes or the cytosol of infected cells, suggesting that post-translational phosphorylation plays no role in the regulation of viral assembly. These data show unequivocal evidence that the nucleocapsid proteins of mouse hepatitis virus strains differ in the sites of phosphorylation."
409,Biological studies of the fusion function of California serogroup Bunyaviruses,"Like other enveloped viruses, La Crosse virus is capable of inducing membrane fusion after exposure to mild acid. This function is known to have biological significance at the level of the whole organism, since it has been related to infection in a mouse model. In this report the process of fusion-from-within (FFWI) for LAC and other members of the California serogroup of Bunyaviruses is characterized. Like fusion-from-without, FFWI is dependent on pH, temperature, and number of virus particles present in the supernatant of fusing cells. Electron micrographs demonstrate that LAC mediated cell membrane fusion is a rapid, multi-point event, and that other than fusion of their plasma membranes, the cells do not show any morphological change. In agreement with theory, lysosomotropic agents were capable of inhibiting La Crosse virus infection. This inhibition was not due to non-specific toxic effects on infected cells. Finally, fusion studies of other California serogroup members revealed minor differences in the pH of fusion induction in some strains. These differences were consistent with the known subtyping within the serogroup."
410,An ELISA system for evaluating antiretroviral activity against Rauscher murine leukemia virus,"A system for evaluating the activity of antiviral agents against Rauscher murine leukemia virus (R-MuLV) has been developed using an enzyme linked immunosorbent assay technique. The activity of various antiviral compounds demonstrated in this assay system has been compared to their activity in the UV-XC plaque reduction assay, which has been used historically for evaluating anti-R-MuLV compounds. The assay is based upon detection of R-MuLV encoded p30 protein production in virus infected murine cells. The assay reagents are readily available and the assay system is amenable to automated data collection systems. Cytotoxicity evaluations are conducted in parallel to the Rauscher MuLV ELISA assay in order to assess drug-induced reductions in cell viability. Cytotoxicity evaluations are important to interpretation of the ELISA results since reductions in cell viability reduce viral protein production which would indicate an antiviral drug effect. This system is less sensitive than the classical UV-XC plaque reduction assay; however, it does offer an alternative to the time-consuming and labor-intensive plaque assay."
411,Antibody-Mediated Destruction of Virus-Infected Cells,"This chapter describes the effect of antibody on virus-infected cells with special reference to the human system. The destruction by antibody of the infected cells through the mediation of complement is described in detail based in considerable part on the contributions of the authors. Activation of the alternative pathway by the various infected cells is of special interest. The interesting effect of the antibody-dependent cell-mediated cytotoxicity (ADCC) system involving viral antigens in cell killing is also presented. Multiple additional topics are also covered, such as the effect of antibody on the expression of viral proteins both on the surface of the cell and intracellularly. Serum antibody, produced in response to virus infections, is of major importance in preventing the spread of infection by virtue of neutralizing free virus in extracellular fluids. Virus neutralization by antibody is enhanced by complement. Antibody binding to the surface of virus-infected cells can affect virus production and release in the absence of an effector system. Immunoglobulin (IgG) antibody can mediate the destruction of virus-infected cells in conjunction with complement or cytotoxic lymphocytes. In addition, at a conceptual level there is evidence to suggest that antibody may enhance and confer specificity on basic nonspecific humoral and cell-mediated defense mechanisms."
412,Human bocavirus 1 may suppress rhinovirus-associated immune response in wheezing children,
413,Modulation of MHC antigen expression by viruses and oncogenes,"It is becoming increasingly clear that regulation of MHC antigen expression by viruses and oncogenes, leading to either immune evasion or autoimmunity, is widespread and important in disease. At a recent meeting, which brought together workers interested in tumour immunology, viral infection and the MHC, a number of mechanisms for the regulation of MHC antigen expression were revealed and the importance of balanced expression of MHC gene products to effective immunity was underlined."
414,The potential use of liposome-mediated antiviral therapy,"The natural targeting of liposomes to cells of the reticuloendothelial system should be exploited to examine whether selective delivery of antiviral or immunomodulatory agents could be beneficial for the treatment of viral diseases. In this review we discuss the potential use of liposomes in the treatment of virus diseases, the targeting of liposome-encapsulated immunomodulators to macrophages in order to render these cells cytolytic for virus-infected cells, and the targeting of liposome-encapsulated antiviral drugs to macrophages to achieve direct suppression of virus replication within these cells."
415,Muramyl peptides confer hepatoprotection against murine viral hepatitis,"The hepatoprotection induced by synthetic muramyl peptides was investigated using a model of lethal murine mouse hepatitis MHV-3 virus infection. MDP and a nonpyrogenic analog, Murametide, inhibited the steep elevation of serum transaminases induced by MHV-3 irrespective of whether the immunomodulators were administered before or after the infection. A significant proportion of MDP or Murametide-treated animals, in contrast to controls, survived the MHV-3 infection. The histopathological examination of the liver revealed marked necrosis of the hepatic parenchymal cells and infiltration of the inflammatory cells in controls but not in MDP-treated animals."
416,Complex Carbohydrates in Drug Development,"Recent advances in carbohydrate chemistry and biochemistry afford the opportunity to develop bioactive complex carbohydrates, per se, as drugs or as lead compounds in drug development. Complex carbohydrates are unique among biopolymers in their inherent potential to generate diverse molecular structures. While proteins vary only in the linear sequence of their monomer constituents, individual monosaccharides can combine at any of several sites on each carbohydrate ring, in linear or branched arrays, and with varied stereochemistry at each linkage bond. This chapter addresses some salient features of mammalian glycoconjugate structure and biosynthesis, and presents examples of the biological activities of complex carbohydrates. The chapter presents selected examples that will provide an accurate introduction to their pharmacological potential. In addition to their independent functions, oligosaccharides can modify the activities of proteins to which they are covalently attached. Many glycoprotein enzymes and hormones require glycosylation for expression and function. The chapter discusses the ancillary role of carbohydrates that is of great importance to the use of engineered glycoproteins as pharmaceuticals."
417,Increased susceptibility of aged rats to haemorrhage and intravascular hypercoagulation following endotoxin administered in a generalized Shwartzman regime,"Ageing rats are known to have an increased incidence of myocardial fibrosis and dyspnoea caused by pulmonary intravascular coagulation. In order to determine whether endotoxin can be responsible for such responses in ageing rats we have exposed rats of differing ages (2 months, 16 months and 24 months) to single or repeated (two doses 24 h apart; generalized Shwartzman regime) intravenous doses of endotoxin (E. coli 0111134). Only the 2-year-old rats reacted adversely. Two doses of endotoxin produced death, with focal myocardial necrosis, haemorrhage and pulmonary and hepatic intravascular coagulation. The increased susceptibility of aged rats to the toxic effects of endotoxin explains some of the changes found in the tissues of old rats. The sporadic nature of both cardiac failure and dyspnoea as a cause of morbidity and mortality in ageing rats may be related to the need for two endotoxin episodes in a period of 24 h to provoke a generalized Shwartzman reaction, an occurrence likely to be relatively uncommon under natural conditions."
418,ASYMPTOMATIC ENDEMIC ROTAVIRUS INFECTIONS IN THE NEWBORN,"Between May 1, 1976, and May 14, 1977, 343 (32·5%) of 1056 5-day-old babies in newborn nurseries excreted rotaviruses. The infection-rate was highest during winter (49%). 76% of infected babies at this time were bottle-fed. 41% of neonates excreted low amounts of virus (10(8) particles/g fæces); older children tended to excrete >10(10) particles/g fæces. Infected breast-fed babies excreted less virus than those who were bottle-fed. Stools of breast-fed babies often contained clumps of complete ""smooth"" rotavirus particles. When the newborn nurseries were transferred to a newly built hospital wing, infection appeared in the new wards, including those admitting only new patients, within a short period. Infection was either mild (8%) or symptomless (92%), and even babies with symptoms required no treatment."
419,Semliki Forest Virus: A Probe for Membrane Traffic in the Animal Cell,"The traffic among the cellular compartments is thought to be mediated by membrane vesicles, which bud from one compartment and fuse with the next. Despite the continuous exchange of membrane components among them, the organelles maintain their characteristic protein and lipid compositions such that the traffic remains selective, thus, avoiding intermixing of components. This membrane traffic recycles components from the cell surface to the interior of the cell and back to the cell surface again. The membrane traffic between the ER and the cell surface involves a major sorting problem. Little is known of how the animal cell has solved this problem in molecular terms. One experimental tool in this direction is provided by some enveloped animal viruses, which mature at the cell surface of infected cells. Such viruses include influenza virus, Semliki Forest virus (SFV), Sindbis virus, and vesicular stomatitis virus (VSV). They are extremely simple in makeup and hence are very well characterized. The purpose of this article is to illustrate the use of the enveloped viruses as tools in the study of membrane traffic in the animal cell. This is done in the context of the life cycle of the virus in the host cell. The article will be concerned mainly with Semliki Forest virus (SFV), which is the virus that has been worked upon in the chapter. SFV belongs to the alphaviruses, a genus of the togavirus family."
420,DIAGNOSIS AND MANAGEMENT OF RHINITIS,"The complaint of rhinitis is one of the most frequent reasons why patients seek a physician's evaluation. Rhinitis is an inflammatory response of the nasal mucosa to various stimuli (both allergic or nonallergic). It is characterized by symptoms of nasal congestion, sneezing, nasal pruritis, and rhinorrhea.(49) The prevalence of rhinitis and the economic impact for both patient and managed care organizations dictate that clinicians carefully consider the medications available to them."
421,Recent Developments in Viral Gastroenteritis,"In recent years impressive advances have been made in understanding viral gastroenteritis. A specific causative agent has been identified in infants and young children, and studies of a similar but distinct enteritis in piglets have given new insight into the pathogenesis of viral diarrhea. This article discusses these recent findings in veterinary and human medicine."
422,CLINICAL VIRAL INFECTIONS AND MULTIPLE SCLEROSIS,"Over an 8 year period, 170 patients with multiple sclerosis (MS) and 134 healthy controls were assessed at monthly intervals in order to ascertain environmental factors which might be important in producing exacerbation or progression of the illness, and to compare the frequency of common viral infections in the two groups. During cumulative periods designated ""at risk"" (2 weeks before the onset of infection until 5 weeks afterwards) annual exacerbation rates were almost 3-fold greater than those during periods not at risk. Approximately 9% of infections were temporally related to exacerbations, whereas 27% of exacerbations were related to infections. Frequency of common infections was approximately 20-50% less in MS patients than controls; it was progressively less in those with greater disability. Even in minimally disabled patients with similar potential for infectious contacts, the infection rate was significantly less than in controls, suggesting that MS patients could have superior immune defences against common viruses."
423,The blind watchmaker and rational protein engineering,"In the present review some scientific areas of key importance for protein engineering are discussed, such as problems involved in deducting protein sequence from DNA sequence (due to posttranscriptional editing, splicing and posttranslational modifications), modelling of protein structures by homology, NMR of large proteins (including probing the molecular surface with relaxation agents), simulation of protein structures by molecular dynamics and simulation of electrostatic effects in proteins (including pH-dependent effects). It is argued that all of these areas could be of key importance in most protein engineering projects, because they give access to increased and often unique information. In the last part of the review some potential areas for future applications of protein engineering approaches are discussed, such as non-conventional media, de novo design and nanotechnology."
424,Early coagulopathy in severe iron poisoning,
425,WHAT CLINICIANS NEED TO KNOW ABOUT ANTIVIRAL DRUGS AND VIRAL RESISTANCE,"During the last decade, significant advances have been made in the development and use of antiviral agents for the successful treatment of a number of viral infections.8, 51, 57 An expanding array of antiviral drugs are currently available for the management of infections caused by herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), cytomegalovirus (CMV), varicella-zoster virus (VZV), influenza A virus, respiratory syncytial virus (RSV), human immunodeficiency virus type 1 (HIV-1), papillomaviruses, and hepatitis B and C viruses. The increased number and use of antiviral agents, however, has led to the emergence of drug-resistant viruses, particularly in immunocompromised patients such as those with acquired immunodeficiency syndrome (AIDS) or hematologic malignancy or those who have undergone organ transplantation. For comprehensive reviews on specific viruses, see references 26, 41, 64, 81–83, and 102. Clinical situations that favor the development of resistance include long-term suppressive therapy, recurrent intermittent therapy, and the use of less than optimum doses of an antiviral agent. Generally, the emergence and isolation of drug-resistant viruses is associated more so with the therapeutic use of antiviral agents and does not seem to be caused by prophylactic treatment. As more patients fail to respond to appropriate therapy and additional antiviral agents are produced, it will also become important for diagnostic virology laboratories to provide rapid and practical antiviral susceptibility testing to assist physicians in defining drug resistance and choosing appropriate alternative therapies. This review describes the major antiviral agents, their mechanisms of action, and the development of drug resistance following antiviral therapy. A brief overview of the available phenotypic and genotypic susceptibility assays for detecting antiviral resistance is also discussed."
426,The Molecular Biology of Influenza Virus Pathogenicity,"It is an accepted concept that the pathogenicity of a virus is of polygenic nature. Because of their segmented genome, influenza viruses provide a suitable system to prove this concept. The studies employing virus mutants and reassortants have indicated that the pathogenicity depends on the functional integrity of each gene and on a gene constellation optimal for the infection of a given host. As a consequence, virtually every gene product of influenza virus has been reported to contribute to pathogenicity, but evidence is steadily growing that a key role has to be assigned to hemagglutinin. As the initiator of infection, hemagglutinin has a double function: (1) promotion of adsorption of the virus to the cell surface, and (2) penetration of the viral genome through a fusion process among viral and cellular membranes. Adsorption is based on the binding to neuraminic acid-containing receptors, and different virus strains display a distinct preference for specific oligosaccharides. Fusion capacity depends on proteolytic cleavage by host proteases, and variations in amino acid sequence at the cleavage site determine whether hemagglutinin is activated in a given cell. Differences in cleavability and presumably also in receptor specificity are important determinants for host tropism, spread of infection, and pathogenicity. The concept that proteolytic activation is a determinant for pathogenicity was originally derived from studies on avian influenza viruses, but there is now evidence that it may also be relevant for the disease in humans because bacterial proteases have been found to promote the development of influenza pneumonia in mammals."
427,Mouse hepatitis virus infection of mice causes long-term depletion of lactate dehydrogenase-elevating virus-permissive macrophages and T lymphocyte alterations,"Intraperitoneal injection of pathogen-free B10.A mice with mouse hepatitis virus (MHV)-A59 resulted in a short subclinical infection which was terminated by a rapid antiviral immune response. The infection resulted in a rapid, but transient, about 10-fold increase in the number of macrophages and total cells in the peritoneum of the mice. This increase was preceded by a complete depletion of the peritoneum of the subpopulation of macrophages that supports a productive infection by lactate dehydrogenase-elevating virus (LDV). The depletion of LDV-permissive macrophages was a long-term effect; at 50 days post-infection with MHV, the proportion of LDV-permissive macrophages in the peritoneum had reached only 20% of that observed in the peritoneum of uninfected mice, whereas the total number of macrophages in the peritoneum had returned to normal. Furthermore, MHV infection resulted in a long-term alteration in the proliferative response of spleen T cells to concanavalin A (ConA) and in their ability to produce interferon γ; several times higher concentrations of ConA were required to induce a maximum proliferative response in spleen T cell populations from 5-week MHV-infected B10.A mice than in spleen T cell populations from infected companion mice but the former produced 5 times more interferon γ than the T cells from unifected mice."
428,Inflammation: Patterns and new concepts,
429,Ethical aspects of vaccines and vaccination,
430,Microbial nomenclature: A list of names and origins,Microbial nomenclature underwent a large number of changes in the 1970s. Many species of pathogens were added and many others experienced name changes. These modifications primarily were due to two unrelated factors: the use of new DNA hybridization techniques and the advent of computerized literature searches to establish historical precedence. In 1980 an approved list of microbial names was published. This list fixed and legitimized bacterial nomenclature. All future additions or alterations to it had to pass international scientific committees. This list has now been accepted by the scientific community. The derivation of these names are presented in this review.
431,Viral Pathogens of the Penaeid Shrimp,"While significant advances that have been made in determining the role of viruses involved in various epizootics occurring in penned shrimp aquaculture, viral diseases will continue to plague the industry. A major obstacle to the study of these diseases is the lack of convenient and quantitative methodologies, such as in vitro cell culture systems to grow and study (characterize) the virus. A beginning has been made with the recent development of protocols for the consistent preparation of primary shrimp lymphoid cells, which were employed for the quanta1 assay of some of the shrimp viral pathogens. The primary cell lines have also been used to analyze the synthesis of viral proteins at the cellular level and to study viral pathogenesis. With the further successful development of additional primary cell lines from other shrimp tissues and the establishment of continuous diploid and transformed shrimp cell lines, this problem is being solved. The value of cell culture systems is becoming increasingly clear. They present several obvious advantages because (1) they are more cost effective, sensitive, and convenient than whole animals, particularly for rapid monitoring of infectivity, (2) they yield quantitatively reproducible results, and (3) viral growth kinetics, biochemical and genetic characteristics, and so on can be studied more easily. Their biggest potential use is in future molecular biology and genetic studies of shrimp viruses."
432,AN ENVELOPED VIRUS IN STOOLS OF CHILDREN AND ADULTS WITH GASTROENTERITIS THAT RESEMBLES THE BREDA VIRUS OF CALVES,Pleomorphic virus-like particles about 100 nm in diameter with a fringe of closely applied peplomers (7-9 nm in length) were observed by electron microscopy in the stools of 20 children and adults with gastroenteritis. In most of the samples no other viral or bacterial pathogens were detected. In form and under immune electron microscopy these virus-like particles resembled the Breda virus isolated from diarrhoeic calves. These objects may be a viral pathogen of humans.
433,The microbiology associated with cystic fibrosis,
434,Summary of the II international consensus symposium on combined antiviral therapy and implications for future therapies,
435,Persistent Viral Infections as Models for Research in Virus Chemotherapy,"The acute systemic virus infection is commonly used as an experimental model in chemotherapy research despite the fact that the chance for an effective chemotherapy of acute virus infections is small. In most acute infections, virus multiplication is well advanced before the disease is expressed and treatment will, in many cases, come too late. However, control by chemotherapy might be promising for persistent virus infections, where, owing to the slow progression of the disease, sufficient time for treatment is available. Although there are various ways in which viruses can persist in their hosts, comparative studies in vitro and in vivo reveal common features that shall be briefly reviewed. Animal models with persistent virus infections are usually difficult to experiment with because of the varying length of the incubation period brought about by the complex relationship among virus replication, immune reactions, and disease."
436,Virology of hepatitis C virus,"Hepatitis C virus (HCV) has been identified as the main causative agent of post-transfusion non-A, non-B hepatitis. Through recently developed diagnostic assays, routine serologic screening of blood donors has prevented most cases of post-transfusion hepatitis. The purpose of this paper is to comprehensively review current information regarding the virology of HCV. Recent findings on the genome organization, its relationship to other viruses, the replication of HCV ribonucleic acid, HCV translation, and HCV polyprotein expression and processing are discussed. Also reviewed are virus assembly and release, the variability of HCV and its classification into genotypes, the geographic distribution of HCV genotypes, and the biologic differences between HCV genotypes. The assays used in HCV genotyping are discussed in terms of reliability and consistency of results, and the molecular epidemiology of HCV infection is reviewed. These approaches to HCV epidemiology will prove valuable in documenting the spread of HCV in different risk groups, evaluating alternative (nonparenteral) routes of transmission, and in understanding more about the origins and evolution of HCV."
437,Epidemiology and Treatment of Chronic Bronchitis and Its Exacerbations,
438,Veterinary vaccines,"Vaccination of animals for the prevention of infectious diseases has been practised for a number of years with little change in product composition. Recent advances in molecular biology, pathogenesis and immunology have laid the groundwork for the development of a new generation of veterinary vaccines based on pure subunits as well as live vectored bacteria and viruses. Along with novel methods of antigen preparation, the use of new adjuvants and delivery systems will permit targeting of the appropriate immune response as well as offering flexibility in terms of vaccination protocols. These new technologies are also being applied to the development of vaccines to enhance animal productivity and to control reproduction."
439,"Distinctive features of foot-and-mouth disease virus, a member of the picornavirus family; aspects of virus protein synthesis, protein processing and structure",
440,Diversity of coding strategies in influenza viruses,"Influenza viruses have exploited a variety of strategies to increase their genome coding capacities. These include unspliced, spliced, alternatively spliced and bicistronic mRNAs, translation from overlapping reading frames and a coupled stop-start translation of tandem cistrons."
441,"Structural organization, expression and chromosomal mapping of the mouse cystatin-C-encoding gene (Cst3)","Cystatin C (CstC) is a potent cysteine-proteinase inhibitor. The structure of the mouse CstC-encoding gene (Cst3) was examined by sequencing a 6.1-kb genomic DNA containing the entire gene, as well as 0.9 kb of 5′ flanking and 1.7 kb of its 3′ flanking region. The sequence revealed that the overall organization of the gene is very similar to those of the genes encoding human CstC and other type-2 Cst, with two introns at positions identical to those in the human gene. The promoter area does not contain typical TATA or CAAT ☐es. Two copies of a Spl-binding motif, GGGCGG, are present in the 5′ flanking region within 300 bp upstream from the initiation codon. A hexa-nucleotide, TGTTCT, which is a core sequence of the androgen-responsive element (ARE), is found in the promoter region. This region also contains a 21-nucleotide sequence, 5′-AGACTAGCAGCTGACTGAAGC, which contains two potential binding sites for the transcription factor, AP-1. The mouse Cst3 mRNA was detected in all of thirteen tissues examined by Northern blot analysis. Cst3 was mapped in the mouse to a position on distal chromosome 2."
442,Inactivation of viral antigens for vaccine preparation with particular reference to the application of binary ethylenimine,Viral antigens for human and veterinary vaccines are still inactivated with formaldehyde. This is not an ideal inactivant and the problems of formaldehyde inactivation of vaccines are discussed. Vaccines inactivated with aziridines are superior in safety and antigenicity. Aziridines inactivate viruses in a first-order reaction and the inactivation rate and endpoint can be determined. The preparation and application of the aziridine compound binary ethylenimine (BEI) and the necessary conditions for and controls of the inactivation process are described and discussed. A computer program has been written for assistance in the use of BEI for controlled inactivation of viral antigens.
443,Binding of Plasmodium falciparum 175-kilodalton erythrocyte binding antigen and invasion of murine erythrocytes requires N-acetylneuraminic acid but not its O-acetylated form,"Sialic acid on human erythrocytes is involved in invasion by the human malaria parasite, Plasmodium falciparum. Mouse erythrocytes were used as a reagent to explore the question of whether erythrocyte sialic acid functions as a nonspecific negative charge or whether the sialic acid is a necessary structural part of the receptor for merozoites. Human erythrocytes contain N-acetylneuraminic acid (Neu5Ac), whereas mouse erythrocytes, which are also invaded by P. falciparum merozoites, contain 9-O-acetyl-N-acetylneuraminic acid (Neu5,9Ac(2)) and N-glycoloylneuraminic acid (Neu5Gc), in addition to Neu5Ac. We compared the effects of sialidase and influenza C virus esterase treatments of mouse erythrocytes on invasion and the binding of a 175-kDa P. falciparum protein (EBA-175), a sialic acid-dependent malaria ligand implicated in the invasion process. Sialidase-treated mouse erythrocytes were refractory to invasion by P. falciparum merozoites and failed to bind EBA-175. Influenza C virus esterase, which converts Neu5,9Ac(2) to Neu5Ac, increased both invasion efficiency and EBA-175 binding to mouse erythrocytes. Thus, the parasite and EBA-175 discriminate between Neu5Ac and Neu5,9Ac(2), that is, the C-9 acetyl group interferes with EBA-175 binding and invasion by P.falciparum merozoites. This indicates that sialic acid is part of a receptor for invasion."
444,Increased influenza A virus sialidase activity with N-acetyl-9-O-acetylneuraminic acid-containing substrates resulting from influenza C virus O-acetylesterase action(),"Influenza virus type C (Johannesburg/1/66) was used as a source for the enzyme O-acetylesterase (EC 3.1.1.53) with several natural sialoglycoconjugates as substrates. The resulting products were immediately employed as substrates using influenza virus type A [(Singapore/6/86) (H1N1) or Shanghai/11/87 (H3N2)] as a source for sialidase (neuraminidase, EC 3.2.1.18). A significant increase in the percentage of sialic acid released was found when the O-acetyl group was cleaved by O-acetylesterase activity from certain substrates (bovine submandibular gland mucin, rat serum glycoproteins, human saliva glycoproteins, mouse erythrocyte stroma, chick embryonic brain gangliosides and bovine brain gangliosides). A common feature of all these substrates is that they contain N-acetyl-9-O-acetylneuraminic acid residues. By contrast, no significant increase in the release of sialic acid was detected when certain other substrates could not be de-O-acetylated by the action of influenza C esterase, either because they lacked O-acetylsialic acid (human glycophorin A, α(1)-acid glycoprotein from human serum, fetuin and porcine submandibular gland mucin) or because the 4-O-acetyl group was scarcely cleaved by the viral O-acetylesterase (equine submandibular gland mucin). The biological significance of these facts is discussed, relative to the infective capacity of influenza C virus."
445,Interaction of Viruses with Cell Surface Receptors,"This chapter discusses the interaction of viruses with cell surface receptors. The rigorous characterizations of receptor–ligand interactions have been derived from binding studies of radiolabeled ligands in neuropharmacology and endocrinology. The definition of viral recognition sites as receptors involves three major criteria that are derived from models of ligand–receptor interactions: saturability, specificity, and competition. A variety of approaches have been used to study the interaction of viral particles with cell surface receptors or reception sites. A rigorous study of viral–receptor interactions requires the use of more than one technique as different approaches provide complementary information about viral binding. The chapter discusses membrane components that interact with viruses. The identification of the subviral components that are responsible for the binding of viruses to cell surfaces has preceded the structural understanding of the cellular receptors themselves. The chapter summarizes current data concerning the viral attachment protein (VAP) of selected viruses."
446,Preparation of Components,
447,Committed to Care: Research Submitted to the National Abortion Federation’s 44th Annual Meeting,
448,Touch Me Not: Physical Distancing in Radiology during COVID-19,
449,There’s So Much More to Cats…,
450,What’s next for nudging and choice architecture?,
451,The Influence of the Variation in Sepsis Rate between Neonatal Intensive Care Units on Neonatal Outcomes in Very-Low-Birth-Weight Infants,"Sepsis is commonly known to affect neonatal outcomes. We assessed how much center-to-center variability of the sepsis rate affects the outcomes of very-low-birth-weight infants (VLBWIs). 7,493 VLBWIs registered in the Korean Neonatal Network from 2013 to 2016 were classified into three groups according to the sepsis rate: low sepsis group (LS) < 25(th) percentile versus intermediate sepsis group (IS) 25(th)–75(th) versus high sepsis group (HS) ≥ 75(th). The incidence density of sepsis for the LS, IS, and HS groups were 1.17, 3.17, and 8.88 cases/1,000 person-days. After propensity score matching was done for multiple antenatal and perinatal factors, the odds ratio of death, moderate to severe bronchopulmonary dysplasia and/or death, periventricular leukomalacia, and survival without major morbidities for the HS group were 2.0 (95% confidence interval 1.4–2.8), 1.9 (1.5–2.4), 1.5 (1.1–2.3) and 0.7 (0.5–0.8) when compared with the IS group, and 2.2 (1.6–3.2), 2.3 (1.8–2.9), 2.0 (1.3–2.9), and 0.7 (0.6–0.9) when compared with the LS group. There were no significant differences in those outcomes between the LS and IS groups. Hence, nationwide quality improvements to control the sepsis rate especially in units with a high sepsis rate will be helpful to improve the outcomes of VLBWIs."
452,Corona-Krise trifft auf Strukturprobleme im Gesundheitswesen,
453,Wirtschaft unter Schock — Finanzpolitik hält dagegen,"According to the leading German economic research institutes, the German economy is experiencing a drastic slump as a result of the corona pandemic. In order to slow down the wave of infection, the state has severely restricted economic activity in Germany. As a result, GDP is expected to shrink by 4.2% this year. The recession is leaving clear traces on the labour market and the national budget. At its peak, the unemployment rate will soar to 5.9% and the number of short-time workers to 2.4 million. This year, the fiscal policy stabilisation measures will lead to a record deficit in the general government budget of 159 billion euro. After the shutdown, the economy will gradually recover. Accordingly, the increase in GDP next year will be strong at 5.8%. This forecast is associated with considerable downside risks, e.g. because the pandemic can be slowed faster or because the recovery of economic activity will be less successful than expected or there may be a new wave of infection."
454,Vermögensverteilung und Wirtschaftskrisen,
455,Nachfrageorientierte Klimapolitik — Evidenz aus der Corona-Krise,
456,Human Influenza Virus Infections,"Seasonal and pandemic influenza are the two faces of respiratory infections caused by influenza viruses in humans. As seasonal influenza occurs on an annual basis, the circulating virus strains are closely monitored and a yearly updated vaccination is provided, especially to identified risk populations. Nonetheless, influenza virus infection may result in pneumonia and acute respiratory failure, frequently complicated by bacterial coinfection. Pandemics are, in contrary, unexpected rare events related to the emergence of a reassorted human-pathogenic influenza A virus (IAV) strains that often causes increased morbidity and spreads extremely rapidly in the immunologically naive human population, with huge clinical and economic impact. Accordingly, particular efforts are made to advance our knowledge on the disease biology and pathology and recent studies have brought new insights into IAV adaptation mechanisms to the human host, as well as into the key players in disease pathogenesis on the host side. Current antiviral strategies are only efficient at the early stages of the disease and are challenged by the genomic instability of the virus, highlighting the need for novel antiviral therapies targeting the pulmonary host response to improve viral clearance, reduce the risk of bacterial coinfection, and prevent or attenuate acute lung injury. This review article summarizes our current knowledge on the molecular basis of influenza infection and disease progression, the key players in pathogenesis driving severe disease and progression to lung failure, as well as available and envisioned prevention and treatment strategies against influenza virus infection."
457,BvDU Kurz notiert,
458,In Vivo Assembly of Nanoparticles Achieved through Synergy of Structure‐Based Protein Engineering and Synthetic DNA Generates Enhanced Adaptive Immunity,"Nanotechnologies are considered to be of growing importance to the vaccine field. Through decoration of immunogens on multivalent nanoparticles, designed nanovaccines can elicit improved humoral immunity. However, significant practical and monetary challenges in large‐scale production of nanovaccines have impeded their widespread clinical translation. Here, an alternative approach is illustrated integrating computational protein modeling and adaptive electroporation‐mediated synthetic DNA delivery, thus enabling direct in vivo production of nanovaccines. DNA‐launched nanoparticles are demonstrated displaying an HIV immunogen spontaneously self‐assembled in vivo. DNA‐launched nanovaccines induce stronger humoral responses than their monomeric counterparts in both mice and guinea pigs, and uniquely elicit CD8+ effector T‐cell immunity as compared to recombinant protein nanovaccines. Improvements in vaccine responses recapitulate when DNA‐launched nanovaccines with alternative scaffolds and decorated antigen are designed and evaluated. Finally, evaluation of functional immune responses induced by DLnanovaccines demonstrates that, in comparison to control mice or mice immunized with DNA‐encoded hemagglutinin monomer, mice immunized with a DNA‐launched hemagglutinin nanoparticle vaccine fully survive a lethal influenza challenge, and have substantially lower viral load, weight loss, and influenza‐induced lung pathology. Additional study of these next‐generation in vivo‐produced nanovaccines may offer advantages for immunization against multiple disease targets."
459,"1H-Imidazole-2,5-Dicarboxamides as NS4A Peptidomimetics: Identification of a New Approach to Inhibit HCV-NS3 Protease","The nonstructural (NS) protein NS3/4A protease is a critical factor for hepatitis C virus (HCV) maturation that requires activation by NS4A. Synthetic peptide mutants of NS4A were found to inhibit NS3 function. The bridging from peptide inhibitors to heterocyclic peptidomimetics of NS4A has not been considered in the literature and, therefore, we decided to explore this strategy for developing a new class of NS3 inhibitors. In this report, a structure-based design approach was used to convert the bound form of NS4A into 1H-imidazole-2,5-dicarboxamide derivatives as first generation peptidomimetics. This scaffold mimics the buried amino acid sequence Ile-25` to Arg-28` at the core of NS4A(21`–33`) needed to activate the NS3 protease. Some of the synthesized compounds (Coded MOC) were able to compete with and displace NS4A(21`–33`) for binding to NS3. For instance, N(5)-(4-guanidinobutyl)-N(2)-(n-hexyl)-1H-imidazole-2,5-dicarboxamide (MOC-24) inhibited the binding of NS4A(21`–33`) with a competition half maximal inhibitory concentration (IC(50)) of 1.9 ± 0.12 µM in a fluorescence anisotropy assay and stabilized the denaturation of NS3 by increasing the aggregation temperature (40% compared to NS4A(21`–33`)). MOC-24 also inhibited NS3 protease activity in a fluorometric assay. Molecular dynamics simulations were conducted to rationalize the differences in structure–activity relationship (SAR) between the active MOC-24 and the inactive MOC-26. Our data show that MOC compounds are possibly the first examples of NS4A peptidomimetics that have demonstrated promising activities against NS3 proteins."
460,Therapeutic management of severe hypothermia with veno-arterial ECMO: where do we stand? Case report and review of the current literature,"BACKGROUND: Severe accidental hypothermia is associated with high morbidity and mortality. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides an efficient rewarming method with complete cardiopulmonary support. The use of VA-ECMO for this indication has greatly improved the vital and functional prognosis of patients. CASE PRESENTATION: We report a case of a 46-year-old patient who was treated for severe hypothermia with a temperature of 22.4 °C along with initial cardiac arrest, whose progression was favorable after the implementation of VA-ECMO support. Two months after initial cardiac arrest, the patient was reassessed and showed signs of complete recovery with regard to his mental and physical capacities. CONCLUSIONS: The recent international publications and groups of experts recommend the use of VA ECMO as the gold standard therapy to treat severe hypothermia. Therefore, it seems suitable to update the current knowledge on the topic by analysing the latest international publications. The performance of this technique calls into question ethical and economic factors. Two distinct medical teams tried to identify and regroup prognosis factors in predictive survival scores. They raise the question of the utility of these scores in clinical practice. Indeed, according to which survival rate should we proceed to prolonged resuscitation and implement VA-ECMO? Additional studies will be needed for external approval of these survival scores, and additional reflection by experts will be required."
461,Clinical efficacy and safety of polymyxins based versus non-polymyxins based therapies in the infections caused by carbapenem-resistant Acinetobacter baumannii: a systematic review and meta-analysis,"BACKGROUND: The prevalence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) is on the rise worldwide. Polymyxins are considered as last-resort drugs for CRAB infections, but there is still controversy regarding the efficacy and safety of polymyxins based therapies in CRAB infections. The present systematic review was designed to compare the efficacy and safety of polymyxins based therapies versus non-polymyxins based therapies in CRAB infections. METHODS: We performed a systematic literature search in PubMed, Embase, CINAHL, Cochrane Library, and clinicaltrials.gov to identify eligible studies reporting the clinical outcomes of patients with CRAB infections. The meta-analysis employed a random-effects model to estimate the odds ratio (OR) and standardized mean difference (SMD) with 95% confidence interval (CI). The primary outcome was 1-month mortality for any cause. We also examined clinical response, microbiological response, length of stay in hospital, and adverse events. RESULTS: Eleven eligible studies were analyzed (1052 patients in total), including 2 randomized clinical trials. Serious risk of bias was found in 8 out of the 11 studies. There was no statistically significant difference between polymyxins based therapies and non-polymyxins based therapies in 1-month mortality for any cause (OR, 0.95; 95% CI, 0.59 to 1.53), microbiological response (OR, 3.83; 95% CI, 0.90 to 16.29) and length of stay in hospital (SMD, 0.24; 95% CI, − 0.08 to 0.56). The pooled OR of clinical response indicated a significant difference in favor of polymyxin based therapies (OR, 1.99; 95% CI, 1.31 to 3.03). The pooled OR of adverse events showed that non-polymyxins based therapies were associated with fewer adverse events (OR, 4.32; 95% CI, 1.39 to 13.48). CONCLUSION: The performance of polymyxins based therapies was better than non-polymyxin based therapies in clinical response rate and similar to non-polymyxin based therapies in terms of 1-month mortality and microbiological response in treating CRAB infections. Due to the limitations of our study, we cannot draw a firm conclusion on the optimal treatment of CRAB infections, but polymyxins would be a relatively effective treatment for CRAB infections. Adequate and well-designed large scale randomized controlled trials are required to clarify the relative efficacy of polymyxins based and non-polymyxins based therapies."
462,"Severity and outcomes of influenza-related pneumonia in type A and B strains in China, 2013–2019","BACKGROUND: Inconsistencies exist regarding the severity of illness caused by different influenza strains. The aim of this study was to compare the clinical outcomes of hospitalized adults and adolescents with influenza-related pneumonia (Flu-p) from type A and type B strains in China. METHODS: We retrospectively reviewed data from Flu-p patients in five hospitals in China from January 2013 to May 2019. Multivariate logistic and Cox regression models were used to assess the effects of influenza virus subtypes on clinical outcomes, and to explore the risk factors of 30-day mortality for Flu-p patients. RESULTS: In total, 963 laboratory-confirmed influenza A-related pneumonia (FluA-p) and 386 influenza B-related pneumonia (FluB-p) patients were included. Upon adjustment for confounders, multivariate logistic regression models showed that FluA-p was associated with an increased risk of invasive ventilation (adjusted odds ratio [aOR]: 3.824, 95% confidence interval [CI]: 2.279–6.414; P < 0.001), admittance to intensive care unit (aOR: 1.630, 95% CI: 1.074–2.473, P = 0.022) and 30-day mortality (aOR: 2.427, 95% CI: 1.568–3.756, P < 0.001) compared to FluB-p. Multivariate Cox regression models confirmed that influenza A virus infection (hazard ratio: 2.637, 95% CI: 1.134–6.131, P = 0.024) was an independent predictor for 30-day mortality in Flu-p patients. CONCLUSIONS: The severity of illness and clinical outcomes of FluA-p patients are more severe than FluB-p. This highlights the importance of identifying the virus strain during the management of severe influenza."
463,"Latest trends in L. infantum infection in dogs in Spain, Part II: current clinical management and control according to a national survey of veterinary practitioners","BACKGROUND: Canine leishmaniosis (CanL) is a parasitic zoonotic disease, endemic in the Mediterranean basin including Spain. While knowledge about CanL, its management, treatment, prevention and control mounts, it remains unclear whether all clinical veterinarians follow the same international recommendations, such as those of the LeishVet group. This study was thus designed to assess recent trends in the clinical management of CanL in veterinary clinics across Spain through a questionnaire-based survey. Results were compared with those of a prior national multicenter questionnaire administered by our research team in 2005. METHODS: A questionnaire consisting of 28 questions about CanL was developed using Google Forms and distributed by email to 1428 veterinary clinics in Spain. Questions were designed to obtain data on common clinical signs, techniques and complementary exams used to diagnose the disease, and on its monitoring, treatment and control measures. Data were collected in a database for statistical analysis. RESULTS: Completed questionnaires were returned by 295 clinics. Compared to the situation in 2005, responses indicate that clinical signs of CanL have not changed significantly, cutaneous lesions being still the most prevalent sign observed by practitioners. Quantitative serological techniques are considered an adequate approach to diagnosis, provided their results are supported by the findings of a thorough physical exam, as well as complementary tests (complete blood count, biochemical profile, plasma protein electrophoretogram and complete urinalysis). Treatment protocols and check-ups follow international recommendations. Finally, a multimodal approach is being endorsed to adequately control CanL including preventive measures such as annual serological check-ups and the combination of repellents and vaccines. Additionally, owners are being better informed about CanL by veterinarians, which translates to the improved control of this zoonosis. CONCLUSIONS: The clinical management of CanL has recently undergone significant changes owing to improvements in clinical knowledge of the disease, more unified international criteria, improved diagnostic techniques and their adequate interpretation, as well as a greater awareness of the disease transmitted to owners. [Image: see text]"
464,Infektionen als Notfall der Onkologie: Übersicht über die aktuellen Leitlinien,"BACKGROUND: Patients with oncologic diseases, particularly those with hematologic malignancies, are at an increased risk of common infections and unique treatment-related complications with high mortality and morbidity. The annual incidence and prevalence of cancer in Germany is rising. Although modern treatments have generally led to improved survival, increasing age, comorbidities, and frailty of the patients require multidisciplinary strategies for handling complex therapeutic concepts and treatment of the associated complications. METHODS: A selective literature search and guidelines from the European Society for Medical Oncology (ESMO), the German Society of Hematology and Medical Oncology (Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie, DGHO), the Infectious Diseases Working Group of the DGHO (Arbeitsgemeinschaft Infektionen in der Hämatologie und Onkologie, AGIHO), and the American Society of Clinical Oncology (ASCO) formed the basis of this study. CONCLUSION: Recognition of severe infections in cancer patients and their discrimination from treatment-associated complications is a challenge. Neutropenic fever is the most frequent infectious emergency in oncology. Early empiric treatment with broad-spectrum antibiotics and escalated diagnostic strategies are needed to successfully treat this vulnerable patient group. In this article, a range of potentially life-threatening infections in immunocompromised patients are discussed."
465,"Public health response to two imported, epidemiologically related cases of Lassa fever in the Netherlands (ex Sierra Leone), November 2019","On 20 November 2019, Lassa fever was diagnosed in a physician repatriated from Sierra Leone to the Netherlands. A second physician with suspected Lassa fever, repatriated a few days later from the same healthcare facility, was confirmed infected with Lassa virus on 21 November. Comprehensive contact monitoring involving high- and low-risk contacts proved to be feasible and follow-up of the contacts did not reveal any case of secondary transmission in the Netherlands."
466,Mulling over meetings,
467,"Net woody vegetation increase confined to seasonally inundated lowlands in an Australian tropical savanna, Victoria River District, Northern Territory","Abstract Georeferenced digital aerial photographs were used to assess changes in overstorey vegetation cover since 1948 in the Victoria River District, Northern Territory, Australia, across a range of lowland tropical savanna habitats and with explicit consideration of known and variable site‐specific grazing and fire management histories. Vegetation surveys at corresponding locations on the ground identified five distinct woody vegetation communities defined primarily by water drainage and secondarily by soil characteristics. Air‐photo analyses revealed that, contrary to popular perceptions and in contrast to results from other habitats, there has been no generalized net increase in overstorey woody vegetation cover across the full range of lowland savanna habitats. Rather, different habitats exhibited distinctly different vegetation change mechanisms: low‐lying seasonally inundated ‘wet’ habitats have experienced woody vegetation increase since 1948, whereas well‐drained ‘dry’ habitats have experienced overstorey vegetation stability or loss. In almost every instance woody vegetation increase could be attributed to the invasion or proliferation of a single species, Melaleuca minutifolia F.Muell. The extent of M. minutifolia increase was unrelated to historical grazing/fire regime. Demographic analyses for this species revealed that recruitment was often episodic and that synchronized recruitment events occurred uniformly across the full range of historical management treatments, most likely as a consequence of favourable climatic conditions in years with an extended wet season. Heavy grazing facilitated juvenile survival and/or recruitment, most likely by reducing grassy fuel loads and eliminating landscape fire. We conclude that while there has been no generalized net increase in overstorey woody vegetation cover in lowland environments, savanna dynamics are complex, and multiple change mechanisms have occurred simultaneously in different habitats, some of which have been significantly transformed since 1948. Where net woody vegetation increase has occurred it is primarily a natural consequence of episodic M. minutifolia establishment in climatically favourable years, but the extent and magnitude of this effect is likely mediated by fire/grazing regime."
468,"Habitat structure is more important than vegetation composition for local‐level management of native terrestrial reptile and small mammal species living in urban remnants: A case study from Brisbane, Australia","Abstract As urban areas continue to expand and replace natural and agricultural landscapes, the ability to manage and conserve native wildlife within urban environments is becoming increasingly important. To do so we first need to understand species' responses to local‐level habitat attributes in order to inform the decision‐making process and on‐ground conservation actions. Patterns in the occurrence of native terrestrial reptile and small mammal species in 59 sites located in remnant urban habitat fragments of Brisbane City were assessed against local‐level environmental characteristics of each site. Cluster analysis, multidimensional scaling ordination, and principal axis correlation were used to investigate relationships between species' occurrences and environmental characteristics. Native reptiles were most strongly associated with the presence of termite mounds, a high amount of fallen woody material, and a moderate amount of weed cover. Native small mammals were most strongly associated with the presence of grass trees (Xanthorrhoea spp.), and both reptiles and small mammals were negatively influenced by increased soil compaction. Significant floristic characteristics were considered to be important as structural, rather than compositional, habitat elements. Therefore, habitat structure, rather than vegetation composition, appears to be most important for determining native, terrestrial reptile and small mammal species assemblages in urban forest fragments. We discuss the management implications in relation to human disturbances and local‐level management of urban remnants."
469,The loss of aquatic and riparian plant communities: Implications for their consumers in a riverine food web,"Abstract Human induced alterations to rivers and steams have resulted in significant changes to the structure and diversity of riparian and aquatic plant communities. These changes will impact on the dynamics of riverine carbon cycles and food web structure and function. Here we investigate the principal sources of organic carbon supporting local shredder communities across a gradient in different levels of anthropogenic development along riverine reaches, in South Australia. In forested/wooded reaches with minimum to limited development, semi‐emergent macrophytes were the principal sources of organic carbon supporting the local shredder communities. However, in developed reaches, course particulate organic matter and filamentous algae were the principal food sources. The C:N ratios of the food sources in developed reaches were higher than those of their consumers indicating a stoichiometric mismatch. This imbalanced consumer‐resource nutrient ratio in those developed reaches is likely to impose constraints on the growth and reproduction of their aquatic shredder communities with probable knock‐on effects to higher trophic levels."
470,Structure and environmental relationships of insectivorous bat assemblages in tropical Australian savannas,"Abstract Patterns in the composition of assemblages of microbat species sampled during the late dry season (the ‘build‐up’) in north Australian savannas were assessed against a range of environmental factors as well as four a priori defined habitat types (riparian, escarpments, coastal and woodlands). Distinct species assemblages were most strongly associated with topographic and climatic variables. There were also limited associations with vegetation structure, fire and local roost potential but no associations with insects or water availability. Total species diversity at sample sites was associated with distance to rivers and rainfall. In general, species assemblages were not clearly defined and the number of significant environmental associations was relatively few. We compare these associations with those reported for bat assemblages elsewhere in Australia."
471,"Relationship between species in the genus Rosa, section Pimpinellifoliae","The morphology of twelve species of Rosa is described and similarities between these species are assessed. Possible origins of the tetraploid species from diploid species are indicated on grounds of comparative morphology. The wild origins of living and herbarium specimens are given in order to supplement published data on geographical distribution. Meiosis in pollen mother cells, viability of pollen grains at anthesis and ability to set seed was studied in several F(1) hybrids: no indication of complete or even partial sterility was found. Reproductive isolation is therefore unlikely to be maintained by reduced fertility of interspecific hybrids. Three species are reduced to synonymy with three other species, being retained as subspecific taxa. Two species are transferred from section Pimpinellifoliae to section Cinnamomeae."
472,Study on Prediction Model of HIV Incidence Based on GRU Neural Network Optimized by MHPSO,"Acquired Immune Deficiency Syndrome (AIDS) is still one of the most life-threatening diseases in the world. Moreover, new infections are still potentially increasing. This difficult problem must be solved. Early warning is the most effective way to solve this problem. Here, we aim to determine the best performing model to track the epidemic of AIDS, which will provide a methodological basis for testing the time characteristics of the disease. From January 2004 to January 2018, we built four computing methods based on AIDS dataset: BPNN model, RNN model, LSTM model and MHPSO-GRU model. Compare the final estimated performance to determine the preferred method. Result. Considering the root mean square error (RMSE), mean absolute error (MAE), mean error rate (MER) and mean absolute percentage error (MAPE) in the simulation and prediction subsets, the MHPSO-GRU model is determined as the best performance technology. Estimates for the period from May 2018 to December 2020 suggest that the event appears to continue to increase and remain high."
473,Next Generation Technology for Epidemic Prevention and Control: Data-Driven Contact Tracking,"Contact tracking is one of the key technologies in prevention and control of infectious diseases. In the face of a sudden infectious disease outbreak, contact tracking systems can help medical professionals quickly locate and isolate infected persons and high-risk individuals, preventing further spread and a large-scale outbreak of infectious disease. Furthermore, the transmission networks of infectious diseases established using contact tracking technology can aid in the visualization of actual virus transmission paths, which enables simulations and predictions of the transmission process, assessment of the outbreak trend, and further development and deployment of more effective prevention and control strategies. Exploring effective contact tracking methods will be significant. Governments, academics, and industries have all given extensive attention to this goal. In this paper, we review the developments and challenges of current contact tracing technologies regarding individual and group contact from both static and dynamic perspectives, including static individual contact tracing, dynamic individual contact tracing, static group contact tracing, and dynamic group contact tracing. With the purpose of providing useful reference and inspiration for researchers and practitioners in related fields, directions in multi-view contact tracing, multi-scale contact tracing, and AI-based contact tracing are provided for next-generation technologies for epidemic prevention and control."
474,Modeling Behavioral Response to Vaccination Using Public Goods Game,"Epidemics of infectious disease can be traced back to the early days of mankind. Only in the last two centuries vaccination has become a viable strategy to prevent such epidemics. In addition to the clinical efficacy of this strategy, the behavior and public attitudes affect the success of vaccines. This paper describes modeling the efficacy of vaccination considering the cost and benefit of vaccination to individual players. The model is based on the public goods game and is presented as a spatial game on a lattice. Using this model, individuals can contribute to the public health by paying the cost of vaccination or choose to be protected by the public who is vaccinated rather than pay the cost and share the risk of vaccination. Thus, in this model individuals can choose to stay susceptible, can become infected, or choose to vaccinate once in each episode. This paper presents the behavioral changes of the population and the cost to the society as a function of the cost of vaccines, cost of being infected, and the “fear factor” created by the public media."
475,Uncertainty Assisted Robust Tuberculosis Identification With Bayesian Convolutional Neural Networks,"Tuberculosis (TB) is an infectious disease that can lead towards death if left untreated. TB detection involves extraction of complex TB manifestation features such as lung cavity, air space consolidation, endobronchial spread, and pleural effusions from chest x-rays (CXRs). Deep learning based approach named convolutional neural network (CNN) has the ability to learn complex features from CXR images. The main problem is that CNN does not consider uncertainty to classify CXRs using softmax layer. It lacks in presenting the true probability of CXRs by differentiating confusing cases during TB detection. This paper presents the solution for TB identification by using Bayesian-based convolutional neural network (B-CNN). It deals with the uncertain cases that have low discernibility among the TB and non-TB manifested CXRs. The proposed TB identification methodology based on B-CNN is evaluated on two TB benchmark datasets, i.e., Montgomery and Shenzhen. For training and testing of proposed scheme we have utilized Google Colab platform which provides NVidia Tesla K80 with 12 GB of VRAM, single core of 2.3 GHz Xeon Processor, 12 GB RAM and 320 GB of disk. B-CNN achieves 96.42% and 86.46% accuracy on both dataset, respectively as compared to the state-of-the-art machine learning and CNN approaches. Moreover, B-CNN validates its results by filtering the CXRs as confusion cases where the variance of B-CNN predicted outputs is more than a certain threshold. Results prove the supremacy of B-CNN for the identification of TB and non-TB sample CXRs as compared to counterparts in terms of accuracy, variance in the predicted probabilities and model uncertainty."
476,Variable-Gain Control for Respiratory Systems,"In this paper, we introduce a variable-gain control strategy for mechanical ventilators in the respiratory systems. Respiratory systems assist the patients who have difficulty breathing on their own. For the comfort of the patient, fast pressure buildup (and release) and a stable flow response are desired. However, linear controllers typically need to balance between these conflicting objectives. In order to balance this tradeoff in a more desirable manner, a variable-gain controller is proposed, which switches the controller gain based on the magnitude of the patient flow. The effectiveness of the control strategy is demonstrated in experiments on different test lungs."
477,Information Diffusion on Social Media During Natural Disasters,"Social media analytics has drawn new quantitative insights of human activity patterns. Many applications of social media analytics, from pandemic prediction to earthquake response, require an in-depth understanding of how these patterns change when human encounter unfamiliar conditions. In this paper, we select two earthquakes in China as the social context in Sina-Weibo (or Weibo for short), the largest Chinese microblog site. After proposing a formalized Weibo information flow model to represent the information spread on Weibo, we study the information spread from three main perspectives: individual characteristics, the types of social relationships between interactive participants, and the topology of real interaction networks. The quantitative analyses draw the following conclusions. First, the shadow of Dunbar’s number is evident in the “declared friends/followers” distributions, and the number of each participant’s friends/followers who also participated in the earthquake information dissemination show the typical power-law distribution, indicating a rich-gets-richer phenomenon. Second, an individual’s number of followers is the most critical factor in user influence. Strangers are very important forces for disseminating real-time news after an earthquake. Third, two types of real interaction networks share the scale-free and small-world property, but with a looser organizational structure. In addition, correlations between different influence groups indicate that when compared with other online social media, the discussion on Weibo is mainly dominated and influenced by verified users."
478,"Development and validation of a portable, point-of-care canine distemper virus qPCR test","Canine distemper virus (CDV) is a multi-host pathogen that can cause significant mortality in domestic, wild terrestrial and marine mammals. It is a major conservation threat in some endangered species. Infection can result in severe respiratory disease and fatal encephalitis. Diagnosis and disease monitoring in wildlife, and differentiation of CDV from rabies (a life-threatening zoonotic disease that can produce similar neurologic signs), would benefit from the availability of a portable, point-of-care (POC) diagnostic test. We therefore developed a quantitative RT-PCR assay for CDV using shelf-stable, lyophilized reagents and target-specific primers and probes for use with the handheld Biomeme two3(™) qPCR thermocycler. Biomeme’s extraction methodology, lyophilized reagents, and thermocycler were compared to our standard laboratory-based methods to assess sensitivity, efficiency and overall test performance. Results using a positive control plasmid for CDV showed comparable sensitivity (detection of 50 copies) and PCR efficiency between the two platforms, and CDV detection was similar between platforms when tested using a modified live CDV vaccine. Significantly higher Ct values (average Ct = 5.1 cycles) were observed using the Biomeme platform on known CDV positive animal samples. CDV detection using the Biomeme platform was similar in 25 of 26 samples from suspect CDV cases when compared to standard virology laboratory testing. One false positive was observed that was negative upon retest. The Biomeme methodology can be adapted for detection of specific targets, and this portable technology saves time by eliminating the need for local or international sample transport for laboratory-based diagnostics. However, results of our testing suggest that decreased diagnostic sensitivity (higher Ct values) relative to laboratory-based methods was observed using animal samples, so careful validation and optimization are essential. Portable qPCR platforms can empower biologists and wildlife health professionals in remote and low-resource settings, which will greatly improve our understanding of CDV disease ecology and associated conservation threats in wildlife."
479,Protecting Medical Trainees on the Coronavirus Disease 2019 (COVID-19) Frontlines Saves Us All,
480,The fight against stroke must go on,
481,Obesity-related stigma—hiding in plain sight,
482,A Unified Approach for EIT Imaging of Regional Overdistension and Atelectasis in Acute Lung Injury,"Patients with acute lung injury or acute respiratory distress syndrome (ALI/ARDS) are vulnerable to ventilator-induced lung injury. Although this syndrome affects the lung heterogeneously, mechanical ventilation is not guided by regional indicators of potential lung injury. We used electrical impedance tomography (EIT) to estimate the extent of regional lung overdistension and atelectasis during mechanical ventilation. Techniques for tidal breath detection, lung identification, and regional compliance estimation were combined with the Graz consensus on EIT lung imaging (GREIT) algorithm. Nine ALI/ARDS patients were monitored during stepwise increases and decreases in airway pressure. Our method detected individual breaths with 96.0% sensitivity and 97.6% specificity. The duration and volume of tidal breaths erred on average by 0.2 s and 5%, respectively. Respiratory system compliance from EIT and ventilator measurements had a correlation coefficient of 0.80. Stepwise increases in pressure could reverse atelectasis in 17% of the lung. At the highest pressures, 73% of the lung became overdistended. During stepwise decreases in pressure, previously-atelectatic regions remained open at sub-baseline pressures. We recommend that the proposed approach be used in collaborative research of EIT-guided ventilation strategies for ALI/ARDS."
483,Impact of Model Shape Mismatch on Reconstruction Quality in Electrical Impedance Tomography,"Electrical impedance tomography (EIT) is a low-cost, noninvasive and radiation free medical imaging modality for monitoring ventilation distribution in the lung. Although such information could be invaluable in preventing ventilator-induced lung injury in mechanically ventilated patients, clinical application of EIT is hindered by difficulties in interpreting the resulting images. One source of this difficulty is the frequent use of simple shapes which do not correspond to the anatomy to reconstruct EIT images. The mismatch between the true body shape and the one used for reconstruction is known to introduce errors, which to date have not been properly characterized. In the present study we, therefore, seek to 1) characterize and quantify the errors resulting from a reconstruction shape mismatch for a number of popular EIT reconstruction algorithms and 2) develop recommendations on the tolerated amount of mismatch for each algorithm. Using real and simulated data, we analyze the performance of four EIT reconstruction algorithms under different degrees of shape mismatch. Results suggest that while slight shape mismatch is well tolerated by all algorithms, using a circular shape severely degrades their performance."
484,A SARS Method for Reliable Spectrum Sensing in Multiband Communication Systems,"This paper introduces a novel method of spectrum sensing in communication systems that utilizes nonuniform sampling in conjunction with a suitable spectral analysis tool. It is referred to here as spectral analysis for randomized sampling (SARS). Owing to the deployment of nonuniform sampling, the proposed technique can accomplish the sensing task by using sampling rates well below the ones demanded by uniform-sampling-based digital signal processing (DSP). The effect of the cyclostationary nature of the incoming digital communication signal on the adequacy of the adopted periodogram-type estimator for the spectrum sensing operation is addressed. The statistical characteristics of the estimator are presented. General reliability conditions on the length of the required signal observation window, i.e., sensing time, for a chosen sampling rate or vice versa are provided amid a sought system performance. The impact of the presence of noise and processing transmissions with various power levels on the derived dependability recommendations is given. The analytical results are illustrated by numerical examples. This paper establishes a new framework for efficient spectrum sensing where considerable savings on the sampling rate and number of processed samples can be attained."
485,Absolute Electrical Impedance Tomography (aEIT) Guided Ventilation Therapy in Critical Care Patients: Simulations and Future Trends,"Thoracic electrical impedance tomography (EIT) is a noninvasive, radiation-free monitoring technique whose aim is to reconstruct a cross-sectional image of the internal spatial distribution of conductivity from electrical measurements made by injecting small alternating currents via an electrode array placed on the surface of the thorax. The purpose of this paper is to discuss the fundamentals of EIT and demonstrate the principles of mechanical ventilation, lung recruitment, and EIT imaging on a comprehensive physiological model, which combines a model of respiratory mechanics, a model of the human lung absolute resistivity as a function of air content, and a 2-D finite-element mesh of the thorax to simulate EIT image reconstruction during mechanical ventilation. The overall model gives a good understanding of respiratory physiology and EIT monitoring techniques in mechanically ventilated patients. The model proposed here was able to reproduce consistent images of ventilation distribution in simulated acutely injured and collapsed lung conditions. A new advisory system architecture integrating a previously developed data-driven physiological model for continuous and noninvasive predictions of blood gas parameters with the regional lung function data/information generated from absolute EIT (aEIT) is proposed for monitoring and ventilator therapy management of critical care patients."
486,Computational Study of Interdependence Between Hemagglutinin and Neuraminidase of Pandemic 2009 H1N1,"Influenza type A viruses are classified into subtypes based on their two surface proteins, hemagglutinin (HA) and neuraminidase (NA). The HA protein facilitates the viral binding and entering a host cell and the NA protein helps the release of viral progeny from the infected cell. The complementary roles of HA and NA entail their collaboration, which has important implications for viral replication and fitness. The HA protein from early strains of pandemic 2009 H1N1 of swine origin preferentially binds to human type receptors with a weak binding to avian type receptors. This virus caused several human deaths in December 2013 in Texas, USA, which motivated us to investigate the changes of genetic features that might contribute to the surged virulence of the virus. Our time series analysis on the strains of this virus collected from 2009 to 2013 implied that the HA binding preference of this virus in USA, Europe, and Asia has been the characteristic of swine H1N1 virus since 2009. However, its characteristic of seasonal human H1N1 and its binding avidity for avian type receptors both were on steady rise and had a clear increase in 2013 with American strains having the sharpest surge. The first change could enhance the viral transmission and replication in humans and the second could increase its ability to cause infection deep in lungs, which might account for the recent human deaths in Texas. In light of HA and NA coadaptation and evolutionary interactions, we also explored the NA activity of this virus to reveal the functional balance between HA and NA during the course of virus evolution. Finally we identified amino acid substitutions in HA and NA of the virus that were critical for the observed evolution."
487,Pandemic Influenza Detection by Electrically Active Magnetic Nanoparticles and Surface Plasmon Resonance,"Influenza A virus (FLUAV), the causative agent of influenza infection, has received extensive attention due to the recent swine-origin H1N1 pandemic. FLUAV has long been the cause of annual epidemics as well as less frequent but more severe global pandemics. Here, we describe a biosensor utilizing electrically active magnetic (EAM) polyaniline-coated nanoparticles as the transducer in an electrochemical biosensor for rapidly identifying FLUAV strains based on receptor specificity, which will be useful to monitor animal influenza infections and to characterize pandemic potential of strains that have transmitted from animals to humans. Pandemic potential requires human-to-human transmissibility, which is dependent upon FLUAV hemagglutinin (HA) specificity for host glycan receptors. Avian FLUAV preferentially bind to α2,3-linked receptors, while human FLUAV bind to α2,6-linked receptors. EAM nanoparticles were prepared by synthesizing aniline monomer around gamma iron (III) oxide (γ-Fe(2)O(3)) cores, yielding 25–100-nm diameter nanoparticles that were structurally characterized by transmission electron microscopy and electron diffraction. The EAM nanoparticles were coated with monoclonal antibodies specific to H5N1 (A/Vietnam/1203/04). Specificity of binding between glycans and H5 was demonstrated. The biosensor results were correlative to supporting data from a surface plasmon resonance assay that characterized HA/glycan binding and α-H5 antibody activity. This novel study applies EAM nanoparticles as the transducer in a specific, portable, easy-to-use biosensor with great potential for disease monitoring and biosecurity applications."
488,Identification of Adequate Neurally Adjusted Ventilatory Assist (NAVA) During Systematic Increases in the NAVA Level,"Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (P(aw)) in proportion to the electrical activity of the diaphragm (EAdi) using an adjustable proportionality constant (NAVA level, cm⋅H (2)O/ [Formula: see text] V). During systematic increases in the NAVA level, feedback-controlled down-regulation of the EAdi results in a characteristic two-phased response in P(aw) and tidal volume (Vt). The transition from the 1st to the 2nd response phase allows identification of adequate unloading of the respiratory muscles with NAVA (NAVA(AL)). We aimed to develop and validate a mathematical algorithm to identify NAVA(AL). P(aw), Vt, and EAdi were recorded while systematically increasing the NAVA level in 19 adult patients. In a multistep approach, inspiratory P(aw) peaks were first identified by dividing the EAdi into inspiratory portions using Gaussian mixture modeling. Two polynomials were then fitted onto the curves of both P(aw) peaks and Vt. The beginning of the P(aw) and Vt plateaus, and thus NAVA (AL), was identified at the minimum of squared polynomial derivative and polynomial fitting errors. A graphical user interface was developed in the Matlab computing environment. Median NAVA(AL) visually estimated by 18 independent physicians was 2.7 (range 0.4 to 5.8) cm⋅H (2)O/ [Formula: see text] V and identified by our model was 2.6 (range 0.6 to 5.0) cm⋅H (2)O/ [Formula: see text] V. NAVA(AL) identified by our model was below the range of visually estimated NAVA(AL) in two instances and was above in one instance. We conclude that our model identifies NAVA(AL) in most instances with acceptable accuracy for application in clinical routine and research."
489,Unobtrusive Sensing and Wearable Devices for Health Informatics,"The aging population, prevalence of chronic diseases, and outbreaks of infectious diseases are some of the major challenges of our present-day society. To address these unmet healthcare needs, especially for the early prediction and treatment of major diseases, health informatics, which deals with the acquisition, transmission, processing, storage, retrieval, and use of health information, has emerged as an active area of interdisciplinary research. In particular, acquisition of health-related information by unobtrusive sensing and wearable technologies is considered as a cornerstone in health informatics. Sensors can be weaved or integrated into clothing, accessories, and the living environment, such that health information can be acquired seamlessly and pervasively in daily living. Sensors can even be designed as stick-on electronic tattoos or directly printed onto human skin to enable long-term health monitoring. This paper aims to provide an overview of four emerging unobtrusive and wearable technologies, which are essential to the realization of pervasive health information acquisition, including: 1) unobtrusive sensing methods, 2) smart textile technology, 3) flexible-stretchable-printable electronics, and 4) sensor fusion, and then to identify some future directions of research."
490,Ensuring Equitable Access to School Meals,
491,Plasma Donors in the Southwestern United States Positively Contribute to the Diverse Therapeutic Antibody Profile of Immune Globulin Products,"Human-plasma-derived immune globulin (IG) is used in augmentation therapy to provide protective levels of antibodies to patients with primary immune deficiency diseases (PIDD) and for prophylaxis against infectious diseases. To maintain the breadth of antibodies necessary for clinical protection, it is important to understand regional patterns of antibody seroprevalence in source plasma from which IG products are manufactured. In this study, source plasma from donation centers in various locations of the Southwestern quarter of the United States was surveyed for antibody titers to hepatitis A virus (HAV), measles virus (MeV), and cytomegalovirus (CMV). A broad range of anti-HAV Ig plasma titers was observed among these centers, with some centers exhibiting 3–5 times the titers of the others. Minor to no differences were observed for levels of anti-MeV and anti-CMV, respectively. Importantly, elevated anti-HAV Ig titers were broadly observed across plasma units obtained from the centers exhibiting high titers, indicative of a potential regional phenomenon among donors as opposed to few donors with singularly high titers. Plasma from these high-titer centers conferred significantly greater neutralization against HAV in vitro. The outcomes of this study give a glimpse of the antibody diversity inherent in human plasma used to manufacture IG products.."
492,Development of a Yeast Two-Hybrid Screen for Selection of Human Ras-Raf Protein Interaction Inhibitors,A yeast two-hybrid screening system was developed to screen for small molecules that inhibit the interaction of the Ras and the Raf proteins. Hyperpermeable yeast strains useful for high-throughput screening (HTS) for the two-hybrid system were created. Differential inhibition of the Ras-Raf vs the hsRPB4-hsRPB7 interaction allowed the identification of selective inhibitors.
493,Acute Hemorrhagic Rectal Ulcer Syndrome: A New Clinical Entity? Report of 19 Cases and Review of the Literature,"PURPOSE: Acute hemorrhagic rectal ulcer syndrome is characterized by sudden onset, painless, and massive hemorrhage from rectal ulcer(s) in patients with serious underlying illnesses. It is a matter of controversy whether acute hemorrhagic rectal ulcer syndrome is a distinct clinical entity. This is the first Asian report on acute hemorrhagic rectal ulcer syndrome to be made outside Japan. METHODS: From January 1989 to December 1999, 8,085 patients underwent total colonoscopy at our institution. We retrospectively analyzed the medical records and colonoscopic files. The diagnosis of acute hemorrhagic rectal ulcer syndrome was made by means of the clinical, histologic, and colonoscopic findings. RESULTS: Among the 8,085 patients, 19 patients (11 males; mean age, 71.2 ± 10.1 years) were diagnosed with acute hemorrhagic rectal ulcer syndrome, which accounted for 2.8 percent of the patients with massive lower gastrointestinal bleeding. The duration from hospitalization to the onset of massive bleeding ranged from 3 to 14 (mean, 9 ± 3.3) days. Characteristics of colonoscopic appearance were solitary or multiple rectal ulcer(s), with round, circumferential, geographical, or Dieulafoy-like lesions located within a mean of 4.7 cm ± 1.5 cm from the dentate line. Histopathologically, the lesions appeared as necrosis with denudation of covering epithelium, hemorrhage, and multiple thrombi in the vessels of the mucosa and underlying stroma, which is considered to be similar to stress-related mucosa injury. Successful hemostasis was obtained in 74 percent (14/19) of patients with direct therapeutic maneuvers. Prognosis was largely dependent on accurate diagnosis and management of the underlying disorders. CONCLUSIONS: We assert that acute hemorrhagic rectal ulcer syndrome is a rare but important entity and stress that awareness of this clinical entity should lead to a high index of suspicion resulting in early detection, diagnosis, and appropriate therapy."
494,"Culture, institutions and democratization*","We construct a model of revolution and transition to democracy under individualistic and collectivist cultures. The main result is that, despite facing potentially more challenging collective action problems, countries with individualistic cultures are more likely to end up adopting democracy earlier than countries with collectivist cultures. Our empirical analysis suggests a strong and robust association between individualistic cultures and average polity scores and durations of democracy, even after controlling for other determinants of democracy emphasized in the literature. We provide evidence that countries with collectivist cultures also are more likely to experience autocratic breakdowns and transitions from autocracy to autocracy."
495,"Reply to the letter to the editor by Tuuminen et al. (2020), “Indoor air nontoxicity should be proven with special techniques prior claiming that it may cause a variety of mental disorders.”",
496,Investigating the Strategies Adopted by Emergency Nurses to Address Uncertainty and Change in the Event of Emerging Infectious Diseases: A Grounded Theory Study,"Emergency nurses frequently encounter uncertainty and changes during the management of emerging infectious diseases, which challenge their capability to perform their duties in a well-planned and systematic manner. To date, little is known about the coping strategies adopted by emergency nurses in addressing uncertainty and changes during an epidemic event. The present study explored emergency nurses’ behaviours and strategies in handling uncertainty and practice changes during an epidemic event. A qualitative study based on the Straussian grounded theory approach was established. Semi-structured, face-to-face, individual interviews were conducted with 26 emergency nurses for data collection. Adapting protocol to the evolving context of practice was revealed as the core category. Four interplaying subcategories were identified: (1) Completing a comprehensive assessment, (2) continuing education for emerging infectious disease management, (3) incorporating guideline updates and (4) navigating new duties and competencies. The nurses demonstrated the prudence to orientate themselves to an ambiguous work situation and displayed the ability to adapt and embrace changes in their practice and duties. These findings offer insights into the need for education and training schemes that allow emergency nurses to acquire and develop the necessary decision-making and problem-solving skills to handle a public health emergency."
497,The Relationship Exploration between Public Migration Attention and Population Migration from a Perspective of Search Query,"Rapid population migration has been viewed as a critical factor impacting urban network construction and regional sustainable development. The supervision and analysis of population migration are necessary for guiding the optimal allocation of urban resources and for attaining the high efficiency development of region. Currently, the explorations of population migration are often restricted by the limitation of data. In the information era, search engines widely collect public attention, implying potential individual actions, and freely provide open, timelier, and large-scope search query data for helping explore regional phenomena and problems. In this paper, we endeavor to explore the possibility of adopting such data to depict population migration. Based on the search query from Baidu search engine, three migration attention indexes (MAIs) are constructed to capture public migration attention in cyber space. Taking three major urban agglomerations in China as case study, we conduct the correlation analysis among the cyber MAIs and population migration in geographical space. Results have shown that external-MAI and local-MAI can positively reflect the population migration inner regions and across regions from a holistic lens and that intercity-MAI can be a helpful supplement for the delineation of specific population flow. Along with the accumulation of cyber search query data, its potential in exploring population migration can be further reinforced."
498,"Validation of age, PaO(2)/FlO(2) and plateau pressure score in Korean patients with acute respiratory distress syndrome: a retrospective cohort study","BACKGROUND: A predictive scoring system for acute respiratory distress syndrome (ARDS) patients, which incorporates age, PaO(2)/FlO(2), and plateau pressure, APPS, was developed recently. It was validated externally in a Caucasian population but has not been studied in Asian populations. The aim of this study was to validate APPS in Korean ARDS patients. METHODS: We retrospectively reviewed the medical records of patients who were diagnosed with ARDS using the Berlin criteria and admitted to the medical ICU at Seoul National University Hospital from January 2015 to December 2016. The validation of the APPS was performed by evaluating its calibration and predictive accuracy. Its calibration was plotted and quantified using the Hosmer–Lemeshow test. Its predictive accuracy was assessed by calculating the area under the receiver operating characteristics (AUC–ROC) curve. RESULTS: A total of 116 patients were analyzed, 32 of whom survived. Of the 116 patients, 11 (9.5%) were classified as APPS grade 1 (score 3–4), 88 (75.9%) as grade 2 (score 5–7) and 17 (14.6%) as grade 3 (score 8–9). In-hospital mortality was 27.3% for grade 1, 73.9% for grade 2 and 94.1% for grade 3 (P for trend < 0.001). The APPS was well calibrated (Hosmer–Lemeshow test, P = 0.578) and its predictive accuracy was acceptable (AUC–ROC 0.704, 95% confidence interval 0.599–0.809). CONCLUSIONS: The APPS predicted in-hospital mortality in Korean patients with ARDS with similar power to its application in a Western population and with acceptable predictive accuracy. TRIAL REGISTRATION: Retrospectively registered."
499,H2 influenza A virus is not pathogenic in Tmprss2 knock-out mice,"The host cell protease TMPRSS2 cleaves the influenza A virus (IAV) hemagglutinin (HA). Several reports have described resistance of Tmprss2(−/−) knock-out (KO) mice to IAV infection but IAV of the H2 subtype have not been examined yet. Here, we demonstrate that TMPRSS2 is able to cleave H2-HA in cell culture and that Tmprss2(−/−) mice are resistant to infection with a re-assorted PR8_HA(H2) virus. Infection of KO mice did not cause major body weight loss or death. Furthermore, no significant increase in lung weights and no virus replication were observed in Tmprss2(−/−) mice. Finally, only minor tissue damage and infiltration of immune cells were detected and no virus-positive cells were found in histological sections of Tmprss2(−/−) mice. In summary, our studies indicate that TMPRSS2 is required for H2 IAV spread and pathogenesis in mice. These findings extend previous results pointing towards a central role of TMPRSS2 in IAV infection and validate host proteases as a potential target for antiviral therapy."
500,Immunization with a fusion protein vaccine candidate generated from truncated peptides of human enterovirus 71 protects mice from lethal enterovirus 71 infections,"BACKGROUND: Prophylactic vaccines are critical in preventing hand, foot, and mouth disease (HFMD) primarily caused by human enterovirus 71 (EV71) infection. Children aged less than 5 years are especially susceptible to EV71 infections. In addition to the development of vaccines containing the inactivated virus, those containing virus-like particles (VLPs) with repeated antigens also constitute an effective preventive strategy for EV71 infections, with safety and productivity advantages. We previously developed a fusion protein composed with truncated peptides of the EV71 capsid protein, which assembled into spherical particles. This study aimed to assess the immunoprotective effects of this fusion protein as a vaccine candidate in a mouse model of EV71 infection. METHODS: To evaluate the protective effect of fusion protein vaccine candidate, neonatal mice born by immunized female mice, as well as normal neonatal mice immunized twice were infected with EV71 virus. Whereafter, the survival rates, clinical scores and viral loads were measured. RESULTS: The high dosage and booster immunization helped induce specific serum antibodies with high neutralization titers, which were transferred to neonatal mice, thereby facilitating effective resistance towards EV71 infection. An active immune response was also observed in neonatal mice which generated following immunization. CONCLUSIONS: The present results suggest that this fusion protein is a suitable vaccine candidate in treating EV71 infections."
501,Synthesis and Bioactivity Assessment of Novel Spiro Pyrazole-Oxindole Congeners Exhibiting Potent and Selective in vitro Anticancer Effects,"The present work aims to design and synthesize novel series of spiro pyrazole-3,3’-oxindoles analogues and investigate their bioactivity as antioxidant and antimicrobial agents, as well as antiproliferative potency against selected human cancerous cell lines (i.e., breast, MCF-7; colon, HCT-116 and liver, HepG-2) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and proapoptotic protein markers. The analytical and spectral data of the all synthesized target congeners were compatible with their structures. Synthesized compounds showed diverse moderate to powerful antimicrobial and antioxidant activities. Results of MTT assay revealed that seven synthesized compounds (i.e., 11a, 11b, 12a, 12b, 13b, 13c and 13h) particularly exhibited significant cytotoxicity against the three cancerous cell lines under investigation. Ranges of IC(50) values obtained were 5.7–21.3 and 5.8–37.4 µg/mL against HCT-116 and MCF-7, respectively; which is 3.8 and 6.5-fold (based on the least IC(50) values) more significant relative to the reference chemotherapeutic drug doxorubicin. In HepG-2 cells, the analogue 13h exhibited the highest cytotoxicity with IC(50) value of 19.2µg/mL relative to doxorubicin (IC(50) = 21.6µg/mL). The observed cytotoxicity was specific to cancerous cells, as evidenced by the minimal toxicity in the noncancerous control skin-fibroblast cells. ELISA results indicated that the observed antiproliferative effect against examined cancer cell lines is mediated via engaging the activation of apoptosis as illustrated by the significant increase in proapoptotic protein markers (p53, bax and caspase-3) and reduction in the antiapoptotic marker bcl-2. Taken together, results of the present study emphasize the potential of spiro pyrazole-oxindole analogues as valuable candidate anticancer agents against human cancer cells."
502,Mitteilungen des Berufsverbands der Pneumologen in Baden-Württemberg,
503,Agenda,
504,"Deep phenotyping: Embracing complexity and temporality—Towards scalability, portability, and interoperability",
505,Remote Treatment Delivery in Response to the COVID-19 Pandemic,
506,Resistance of Enteric Viruses on Fomites,"Human enteric viruses are associated with several clinical features, especially gastroenteritis. Large amounts of these viruses can be released in the environment and spread to people. Enteric viruses are nonenveloped viruses and have displayed good survival in the environment. They can be significantly resistant in food and water but also on fomites, and this is thought to play a role in transmission, leading to sporadic cases or outbreaks. The survival of enteric viruses on fomites relies on many factors including the virus itself, fomite properties, and extrinsic environmental factors such as temperature or relative humidity. Several reports in the literature have found an association with gastroenteritis cases or outbreaks and fomites naturally contaminated by enteric viruses. However, the study of virus survival following natural contamination is challenging, and most published studies are laboratory based, using experimental contamination. In addition, recent and detailed data on the resistance of each of the main enteric viruses on fomites are scarce. Many approaches, both physical and chemical, can be used to inactivate enteric viruses, the efficacy of which depends on the virus and the disinfection conditions."
507,Effects of Age on Voice Onset Time and Variability in Children with Repaired Cleft Palate,"OBJECTIVE: To examine the effect of age on voice onset time (VOT) and VOT variability in children with repaired cleft palate. METHODS: Twenty-two children with repaired cleft palate were allocated into two age groups: younger children (YC: n = 13) and older children (OC: n = 9). VOT measurements from monosyllabic words (/pa/, /ta/, and /ka/) and intraspeaker VOT variability estimated by coefficients of variation (CoV) of two age groups were compared. RESULTS: Age was found to have a statistically significant effect on VOT and VOT variability. Specifically, OC had significantly longer VOT (F(1,66) = 4.196, p < 0.05) and less VOT variability (F(1,66) = 6.007, p < 0.05) for English voiceless stops than YC. No statistically significant main effect for speech sample or age by speech sample interaction was observed. CONCLUSIONS: Our data supplement the existing literature by adding VOT and VOT variability information for older children/adolescents with repaired cleft palate. Findings from the study suggest VOT patterns acquired at younger age appear to be further exaggerated and stabilized during the adolescent period among children with repaired cleft palate. A future study is necessary to determine different sources of VOT variability in children with a history of cleft palate, which may have clinical therapeutic implications."
508,"Prognostic factors for ARDS: clinical, physiological and atypical immunodeficiency","BACKGROUND: Risk factors affecting the prognosis of acute respiratory distress syndrome (ARDS) in adults were investigated. The aim was to identify new predictors for ARDS patient prognosis, including those with clinical, pathophysiological, and atypical immunodeficiency. METHODS: ARDS patients were retrospectively included. The patients were grouped and analysed according to different oxygenation index grades and prognosis, and factors influencing prognosis and survival were examined. Adolescent patients, patients with typical immunodeficiency and patients who died within 24 h after being diagnosed with ARDS were excluded. The predictive value for mortality was determined by Cox proportional hazard analysis. RESULTS: In total, 201 patients who fulfilled the Berlin definition of ARDS were included. The severity of critical illness on the day of enrolment, as measured by the Acute Physiology and Chronic Health Evaluation (APACHE) II score (P = 0.016), Sequential Organ Failure Assessment (SOFA) score (P = 0.027), and PaO(2)/FiO(2) (P = 0.000), worsened from mild to severe ARDS cases. Compared with survivors, non-survivors were significantly older and had higher APACHE II and SOFA scores. Moreover, significantly lower lymphocyte/neutrophil ratios and leukocyte counts were found among non-survivors than survivors (P = 0.008, P = 0.012). A moderate positive correlation between the lymphocyte/neutrophil and PaO(2)/FiO(2) ratios (P = 0.023) was observed. In predicting 100-day survival in patients with ARDS, the area under the curve (AUC) for the lymphocyte/neutrophil ratio was significantly higher than those for the PaO(2)/FiO(2) ratio alone, body mass index (BMI) alone, and the lymphocyte count alone (P = 0.0062, 0.0001, and 0.0154). Age (per log(10) years), BMI < 24, SOFA score, leukocyte count, and the lymphocyte/neutrophil ratio were independent predictors of 28-day mortality in ARDS patients. Additionally, ARDS patients with a lymphocyte/neutrophil ratio < 0.0537 had increased 28-day mortality rates (P = 0.0283). Old age affected both 28-day and 100-day mortality rates (P = 0.0064,0.0057). CONCLUSIONS: Age (per log(10) years), BMI < 24, SOFA score, lymphocytes, and the lymphocyte/neutrophil ratio were independent predictors of 100-day mortality in patients with ARDS. The lymphocyte/neutrophil ratio may represent a potential molecular marker to evaluate atypical immunosuppression or impairment in patients with ARDS."
509,India under COVID-19 lockdown,
510,'We will have a lot to do when this is over',
511,'I do not know when I will practise again',
512,Online resource created to support redeployed dentists,
513,BDJ offers support to dental companies,
514,Alternative teaching aids,
515,Caution with NSAIDs,
516,Initial experience of DCTs,
517,'We are all awaiting our call to the frontline',
518,Head Dental Officer appointed,
519,Remain positive and proactive,
520,Young colleagues need support,
521,Out of our comfort zone,
522,Skincare experts offer advice for those wearing face masks for long periods,
523,Mitteilungen der Gesellschaft für Gastroenterologie in NRW,
524,Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection,"Despite being a leading cause of severe respiratory disease, there remains no licensed respiratory syncytial virus (RSV) vaccine. Neutralizing antibodies reduce the severity of RSV-associated disease, but are not sufficient for preventing reinfection. In contrast, the role of memory CD8 T cells in protecting against a secondary RSV infection is less established. We recently demonstrated that high-magnitude memory CD8 T cells efficiently reduced lung viral titers following RSV infection, but induced fatal immunopathology that was mediated by IFN-γ. To evaluate the ability of RSV-specific neutralizing antibodies to prevent memory CD8 T cell-mediated immunopathology, mice with high-magnitude memory CD8 T cell responses were treated with neutralizing antibodies prior to RSV challenge. Neutralizing antibody treatment significantly reduced morbidity and prevented mortality following RSV challenge compared with IgG-treated controls. Neutralizing antibody treatment restricted early virus replication, which caused a substantial reduction in memory CD8 T cell activation and IFN-γ production, directly resulting in survival. In contrast, therapeutic neutralizing antibody administration did not impact morbidity, mortality, or IFN-γ levels, despite significantly reducing lung viral titers. Therefore, only pre-existing neutralizing antibodies prevent memory CD8 T cell-mediated immunopathology following RSV infection. Overall, our results have important implications for the development of future RSV vaccines."
525,Protect Healthcare Workers and Patients from COVID-19: The Experience of Two Tertiary Ophthalmology Care Referral Centers in Italy,
526,Effectiveness comparison of indocyanine green retention test with the cirrhotic severity scoring in evaluating the pathological severity of liver cirrhosis in patients with hepatocellular carcinoma and Child-Pugh grade A liver function,"BACKGROUND: Evaluating cirrhotic severity is essential for individualizing surgical modalities for patients with hepatocellular carcinoma (HCC). Our previous study proposed a non-invasive method named cirrhotic severity scoring (CSS) to stage liver cirrhosis. Indocyanine green retention rate at 15 min (ICG-R15) has been widely used for the preoperative evaluation of hepatic functional reserve; however, whether ICG-R15 is well correlated with cirrhotic severity, and especially whether comparable with CSS in predicting cirrhotic severity in HCC patients with Child-Pugh grade A liver function remains unknown. METHODS: Overall, 510 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between January 2011 and December 2014 were retrospectively studied. Cirrhotic severity was pathologically assessed using the Laennec staging system. The correlations between ICG-R15, CSS, and cirrhotic severity were analyzed. Furthermore, the performance of ICG-R15 and CSS in predicting posthepatectomy liver failure (PHLF) and 90-day mortality was compared. RESULTS: Patients with no, mild, moderate, and severe cirrhosis accounted for 15.9%, 29.2%, 35.9%, and 19.0%, respectively, in the entire cohort. ICG-R15 was found to be less than 10% in 100%, 93.3%, 86.3%, and 70.1% of the patients with no, mild, moderate, and severe cirrhosis, respectively. There was only a weak correlation between ICG-R15 and the pathological severity of liver cirrhosis (r = 0.325; P < 0.001). However, CSS showed a strong correlation with the pathological severity of liver cirrhosis (r = 0.788; P < 0.001). For those with ICG-R15 in the normal range, the accuracy of CSS in diagnosing no/mild, moderate, and severe cirrhosis was 89.1%, 72.8%, and 72.1%, respectively. In addition, CSS was superior to ICG-R15 in predicting PHLF and 90-day mortality. CONCLUSIONS: CSS was more useful than ICG-R15 in the preoperative assessment of cirrhotic severity in HCC patients with Child-Pugh grade A liver function. More studies are needed to further validate CSS in patients with different Child-Pugh grades."
527,Pilot test of an online training module on near-infrared spectroscopy monitoring for the randomised clinical trial SafeBoosC-III,"BACKGROUND: SafeBoosC-III is an international randomised clinical trial to evaluate the effect of treatment of extremely preterm infants during the first 3 days of life based on cerebral near-infrared spectroscopy (NIRS) monitoring versus treatment and monitoring as usual. To ensure high quality of the trial intervention as well as of patient care, we have developed a multilingual web-based training program to train relevant staff and test their competence. As we enter an under-explored area of e-learning, we have conducted a pilot study on the first of the five modules comprising the web-based training program to test the feasibility of developing such a program for an international trial with limited resources. METHODS: The module in this study focuses on the principles and practice of NIRS monitoring. The pedagogical idea was to integrate training and certification. One-hundred doctors and nurses from five Neonatal Intensive Care Units across China, Spain and Denmark were invited to participate in the pilot study. Upon completion of the NIRS module, participants were invited to evaluate their experience by completing an online survey. Data from closed-ended questions were analysed using descriptive statistics while data from open-ended questions underwent thematic analysis. RESULTS: In total, 81 of 100 invited staff members entered the training module and completed the online survey. The median time and the number of questions to pass the module was 15 minutes and seven questions, respectively. Most staff found the academic level of the learning material and quiz appropriate (85% and 93% of all staff members, respectively), as well as agreeing that the module was relevant to prepare them to ‘use the NIRS device’ (90%). Thematic analysis revealed issues such as a discrepancy between learning material and quiz questions, lack of clarity, and technical issues. CONCLUSION: We provide evidence of the feasibility of developing a multilingual web-based training program for an international trial, despite challenges such as low budget, language barriers and possibly differences in the clinical training of staff. Exploring the integration of training and certification for international trials, the positive results of this study motivate further developments. TRIAL REGISTRATION: ClinicalTrial.gov, NCT03770741. Registered 10 December 2018."
528,"Update on Ebola Treatment Center Costs and Sustainability, United States, 2019","We surveyed 56 Ebola treatment centers (ETCs) in the United States and identified costs incurred since 2014 ($1.76 million/ETC) and sustainability strategies. ETCs reported heavy reliance on federal funding. It is uncertain if, or for how long, ETCs can maintain capabilities should federal funding expire in 2020."
529,New trends in Manufacturing Systems Research 2020,
530,"Update to Our Reader, Reviewer, and Author Communities—April 2020",
531,"Association of early viral lower respiratory infections and subsequent development of atopy, a systematic review and meta-analysis of cohort studies","INTRODUCTION: Existing evidence on the relationship between childhood lower respiratory tract infections (LRTI) and the subsequent atopy development is controversial. We aimed to investigate an association between viral LRTI at <5 years and the development of atopy at > 2 years. METHODS: We conducted a search at Embase, Pubmed, Web of Science, and Global Index Medicus. We collected data from the included articles. We estimated the odds ratio and the 95% confidence intervals with a random effect model. We determined factors associated with atopy development after childhood LRTI using univariate and multivariate meta-regression analyses. We recorded this systematic review at PROSPERO with the number CRD42018116955. RESULTS: We included 24 studies. There was no relationship between viral LRTI at <5 years and skin prick test-diagnosed-atopy (OR = 1.2, [95% CI = 0.7–2.0]), unknown diagnosed-atopy (OR = 0.7, [95% CI = 0.4–1.3]), atopic dermatitis (OR = 1.2, [95% CI = 0.9–1.6]), hyperreactivity to pollen (OR = 0.8, [95% CI = 0.3–2.7]), food (OR = 0.8, [95% CI = 0.3–2.5]), or house dust mite (OR = 1.1, [95% CI = 0.6–2.2]). Although not confirmed in all studies with a symmetric distribution of the 23 confounding factors investigated, the overall analyses showed that there was a relationship between childhood viral LRTI at < 5 years and serum test diagnosed-atopy (OR = 2.0, [95% CI = 1.0–4.1]), allergic rhinoconjunctivitis (OR = 1.7, [95% CI = 1.1–2.9]), hyperreactivity diagnosed by serum tests with food (OR = 5.3, [1.7–16.7]) or inhaled allergens (OR = 4.2, [95% CI = 2.1–8.5]), or furred animals (OR = 0.6, [95% CI = 0.5–0.9]). CONCLUSION: These results suggest that there is no association between viral LRTI at < 5 years and the majority of categories of atopy studied during this work. These results, however, are not confirmed for the remaining categories of atopy and more particularly those diagnosed by serum tests. There is a real need to develop more accurate atopy diagnostic tools."
532,Comparative characterization of flavivirus production in two cell lines: Human hepatoma-derived Huh7.5.1-8 and African green monkey kidney-derived Vero,"The Flaviviridae is a family of enveloped viruses with a positive-sense single-stranded RNA genome. It contains many viruses that threaten human health, such as Japanese encephalitis virus (JEV) and yellow fever virus (YFV) of the genus Flavivirus as well as hepatitis C virus of the genus Hepacivirus. Cell culture systems highly permissive for the Flaviviridae viruses are very useful for their isolation, propagation, and diagnosis, an understanding of their biology, and the development of vaccines and antiviral agents. Previously, we isolated a human hepatoma HuH-7-derived cell clone, Huh7.5.1–8, which is highly permissive to hepatitis C virus infection. Here, we have characterized flavivirus infection in the Huh7.5.1–8 cell line by comparing with that in the African green monkey kidney-derived Vero cell line, which is permissive for a wide spectrum of viruses. Upon infection with JEV, Huh7.5.1–8 cells produced a higher amount of virus particles early in infection and were more susceptible to virus-induced cell death than Vero cells. Similar outcomes were obtained when the cells were infected with another flavivirus, YFV (17D-204 strain). Quantification of cellular and extracellular viral RNA revealed that high JEV production in Huh7.5.1–8 cells can be attributed to rapid viral replication kinetics and efficient virus release early in infection. In a plaque assay, Huh7.5.1–8 cells developed JEV plaques more rapidly than Vero cells. Although this was not the case with YFV plaques, Huh7.5.1–8 cells developed higher numbers of YFV plaques than Vero cells. Sequence analysis of cDNA encoding an antiviral RNA helicase, RIG-I, showed that Huh7.5.1–8 cells expressed not only a full-length RIG-I mRNA with a known dominant-negative missense mutation but also variants without the mutation. However, the latter mRNAs lacked exon 5/6−12, indicating functional loss of RIG-I in the cells. These characteristics of the Huh7.5.1–8 cell line are helpful for flavivirus detection, titration, and propagation."
533,The CD1 family and T cell recognition of lipid antigens,"Abstract: For many years it was thought that T lymphocytes recognized only peptide antigens presented by MHC class I or class II molecules. Recently, it has become clear that a wide variety of lipids and glycolipids are also targets of the T cell response. This novel form of cell‐mediated immune recognition is mediated by a family of lipid binding and presenting molecules known as CD1. The CD1 proteins represent a small to moderate sized family of β2‐microglobulin‐associated transmembrane proteins that are distantly related to MHC class I and class II molecules. They are conserved in most or all mammals, and control the development and function of T cell populations that participate in innate and adaptive immune responses through the recognition of self and foreign lipid antigens. Here we review the current state of our understanding of the structure and function of CD1 proteins, and the role of CD1‐restricted T cell responses in the immune system."
534,Detection of blood‐transmissible agents: can screening be miniaturized?,"Transfusion safety relating to blood‐transmissible agents is a major public health concern, particularly when faced with the continuing emergence of new infectious agents. These include new viruses appearing alongside other known reemerging viruses (West Nile virus, Chikungunya) as well as new strains of bacteria and parasites (Plasmodium falciparum, Trypanosoma cruzi) and finally pathologic prion protein (variant Creutzfeldt‐Jakob disease). Genomic mutations of known viruses (hepatitis B virus, hepatitis C virus, human immunodeficiency virus) can also be at the origin of variants susceptible to escaping detection by diagnostic tests. New technologies that would allow the simultaneous detection of several blood‐transmissible agents are now needed for the development and improvement of screening strategies. DNA microarrays have been developed for use in immunohematology laboratories for blood group genotyping. Their application in the detection of infectious agents, however, has been hindered by additional technological hurdles. For instance, the variability among and within genomes of interest complicate target amplification and multiplex analysis. Advances in biosensor technologies based on alternative detection strategies have offered new perspectives on pathogen detection; however, whether they are adaptable to diagnostic applications testing biologic fluids is under debate. Elsewhere, current nanotechnologies now offer new tools to improve the sample preparation, target capture, and detection steps. Second‐generation devices combining micro‐ and nanotechnologies have brought us one step closer to the potential development of innovative and multiplexed approaches applicable to the screening of blood for transmissible agents."
535,"Letter to the editor concerning “Guidelines for clinical diagnosis and treatment of osteonecrosis of the femoral head in adults (2019 version)” by Zhao et al., Journal of Orthopaedic Translation, 2019, https://doi.org/10.1016/j.jot.2019.12.004",
536,Retinopathy of prematurity in Rwanda: a prospective multi-centre study following introduction of screening and treatment services,"OBJECTIVES: To investigate risk factors for retinopathy of prematurity (ROP) in a newly established ROP screening and management programme in Rwanda, Africa. METHODS: In this multi-centre prospective study 795/2222 (36%) babies fulfilled the inclusion criteria (gestational age (GA) < 35 weeks or birth weight (BW) < 1800 g or unstable clinical course), 424 (53%) of whom were screened for ROP. 270 died before the first screening. ROP and treatment-warranted ROP were classified using the revised International Classification of ROP (2005). Data on maternal and perinatal risk factors were collected from daily neonatal notes. RESULTS: 31 babies (7.3%, CI 5.0–10.2) developed any ROP, 13 of whom (41.9%, CI 24.5–60.9) required treatment. ROP was seen in six neonates with GA > 30 weeks and BW > 1500 g, one of whom required treatment. In univariate analysis the following were associated with any ROP: increasing number of days on supplemental oxygen (OR 2.1, CI 1.5–3.0, P < 0.001), low GA (OR 3.4, CI 1.8–6.4, P < 0.001), low BW (OR 2.3, CI 1.5–3.4, P < 0.001), at least one episode of hyperglycaemia ≥ 150 mg/dl (OR 6.6, CI 2.0–21.5, P < 0.001), blood transfusion (OR 3.5, CI 1.6–7.4, P < 0.001) or sepsis (OR 3.2, CI 1.2–8.6, P = 0.01). In multivariate analysis longer exposure to supplemental oxygen (OR 2.1, CI 1.2–3.6, P = 0.01) and hyperglycaemia (OR 3.5, CI 1.0–12.4, P = 0.05) remained significant. CONCLUSIONS: ROP has become an emerging health problem in Rwanda, requiring programmes for screening and treatment. ROP screening is indicated beyond the 2013 American Academy guidelines. Improved quality of neonatal care, particularly oxygen delivery and monitoring is needed."
537,Coronaviridae1,"The family Coronavirtdae comprises a monogeneric group of 11 viruses which infect vertebrates. The main characteristics of the member viruses are: (i) Morphological: Enveloped pleomorphic particles typically 100 nm in diameter (range 60-220 nm), bearing about 20 nm long club-shaped surface projections, (ii) Structural: A single-stranded infectious molecule of genomic RNA of about (5-7) × 10(6) molecular weight. A phosphorylated nucleocapsid protein [mol.wt. (50-60) × 10(3)] complexed with the genome as a helical ribonucleoprotein; a surface (peplomer) protein, associated with one or two glycosylated polypeptides [mol.wt. (90-180) × 10(3)]; a transmembrane (matrix) protein, associated with one polypeptide which may be glycosylated to different degrees [mol.wt. (20-35) × 10(3)]. (iii) Replicative: Production in infected cells of multiple 3′ coterminal sub genomic mRNAs extending for different lengths in the 5′ direction. Virions bud intracytoplasmically. (iv) Antigenic: 3 major antigens, each corresponding to one class of virion protein, (v) Biological: Predominantly restricted to infection of natural vertebrate hosts by horizontal transmission via the fecal/oral route. Responsible mainly for respiratory and gastrointestinal disorders."
538,Predictive factors for successful INTELLiVENT-ASV® use: a retrospective observational study,"BACKGROUND: INTELLiVENT-ASV® (I-ASV) is a closed-loop ventilation mode that automatically controls the ventilation settings. Although a number of studies have reported the usefulness of I-ASV, the clinical situations in which it may be useful have not yet been clarified. We aimed to report our initial 3 years of experience using I-ASV, particularly the clinical conditions and the technical and organizational factors associated with its use. Furthermore, we evaluated the usefulness of I-ASV and determined the predictive factors for successful management with I-ASV. METHODS: This single-center, retrospective observational study included patients who were ventilated using the Hamilton G5® ventilator (Hamilton Medical AG, Rhäzüns, Switzerland) from January 2016 to December 2018. The patients were categorized into the “I-ASV success” group and “I-ASV failure” group (those receiving mechanical ventilation with I-ASV along with any other mode). Multivariate analysis was performed to identify factors associated with successful I-ASV management. RESULTS: Of the 189 patients, 135 (71.4%) were categorized into the I-ASV success group. In the I-ASV success group, the reasons for ICU admission included post-elective surgery (94.1%), post-emergent surgery (81.5%), and other medical reasons (55.6%). I-ASV failure was associated with a low P/F ratio (278 vs. 167, P = 0.0003) and high Acute Physiology and Chronic Health Evaluation (APACHE) II score (21 vs. 26, P < 0.0001). The main reasons for not using I-ASV included strong inspiratory effort and asynchrony. The APACHE II score was an independent predictive factor for successful management with I-ASV, with an odds ratio of 0.92 (95% confidential interval 0.87–0.96, P = 0.0006). The area under the receiver operating curve for the APACHE II score was 0.722 (cut-off: 24). CONCLUSIONS: In this study, we found that 71.4% of the fully mechanically ventilated patients could be managed successfully with I-ASV. The APACHE II score was an independent factor that could help predict the successful management of I-ASV. To improve I-ASV management, it is necessary to focus on patient-ventilator interactions."
539,Effect of mechanical ventilation versus spontaneous breathing on abdominal edema and inflammation in ARDS: an experimental porcine model,"BACKGROUND: Mechanical ventilation (MV), compared to spontaneous breathing (SB), has been found to increase abdominal edema and inflammation in experimental sepsis. Our hypothesis was that in primary acute respiratory distress syndrome (ARDS) MV would enhance inflammation and edema in the abdomen. METHODS: Thirteen piglets were randomized into two groups (SB and MV) after the induction of ARDS by lung lavage and 1 h of injurious ventilation. 1. SB: continuous positive airway pressure 15 cmH(2)O, fraction of inspired oxygen (FIO(2)) 0.5 and respiratory rate (RR) maintained at about 40 cycles min(− 1) by titrating remifentanil infusion. 2. MV: volume control, tidal volume 6 ml kg(− 1), positive end-expiratory pressure 15 cmH(2)O, RR 40 cycles min(− 1), FIO(2) 0.5. Main outcomes: abdominal edema, assessed by tissues histopathology and wet-dry weight; abdominal inflammation, assessed by cytokine concentration in tissues, blood and ascites, and tissue histopathology. RESULTS: The groups did not show significant differences in hemodynamic or respiratory parameters. Moreover, edema and inflammation in the abdominal organs were similar. However, blood IL6 increased in the MV group in all vascular beds (p < 0.001). In addition, TNFα ratio in blood increased through the lungs in MV group (+ 26% ± 3) but decreased in the SB group (− 17% ± 3). CONCLUSIONS: There were no differences between the MV and SB group for abdominal edema or inflammation. However, the systemic increase in IL6 and the TNFα increase through the lungs suggest that MV, in this model, was harmful to the lungs."
540,Leptospirosis as an important differential of pulmonary haemorrhage on the intensive care unit: a case managed with VV-ECMO,"BACKGROUND: Leptospirosis is a potentially fatal zoonosis. It can cause a wide range of symptoms, including diffuse alveolar haemorrhage which occurs in a minority of cases but carries a mortality of over 70%. These patients may present with severe acute respiratory failure. The differential diagnosis for diffuse alveolar haemorrhage is broad whereas prompt diagnosis and treatment can be lifesaving. CASE PRESENTATION: A 20-year-old previously fit and well trout farm worker presented with a 3-day history of malaise, fevers, diarrhoea, vomiting and jaundice. He developed haemoptysis, severe headaches, neck stiffness and photophobia on the day of emergency admission. He was anaemic and thrombocytopenic. Anuric acute kidney injury (urea 32, creat 507) required immediate haemofiltration. In view of progressive respiratory failure with four-quadrant lung infiltrates on imaging, he was given broad spectrum antibiotics and pulsed methylprednisolone empirically, in case of a vasculitic pulmonary-renal presentation. He was intubated within 48 h of admission. Despite attempted protective ventilatory management, he remained hypoxaemic and developed pneumomediastinum. He was retrieved to a specialist cardiorespiratory intensive care unit on femoro-femoral mobile VV-ECMO. Three days from admission, results showed positive Leptospira IgM and real-time PCR. Serial bronchoscopies showed old and fresh clots, but not the classical progressive late red tinge of the returned lavage fluid. After eight days, VV-ECMO was weaned, he was extubated three days later, and made a full recovery. At 9 months follow-up, he was clinically better, with resolution of the CT scan findings and near normal lung function, albeit with low normal gas transfer. CONCLUSIONS: Leptospirosis is a rare but important differential to be considered in diffuse alveolar haemorrhage presenting to the ICU, especially in young males. A thorough history for occupational or recreational risk factors may offer the diagnostic clue. Most patients recover fully with antibiotics. However, resulting acute severe respiratory failure can ensue. In this situation, early consideration for respiratory ECMO support offers time for clearance of endobronchial clot, parenchymal recovery, and prevention of ventilator-induced lung injury. Steroids have no clear evidence but may be used to avoid delay in treating suspected vasculitic or autoimmune causes of diffuse alveolar haemorrhage."
541,Low occurrence of extended-spectrum cephalosporinase producing Enterobacteriaceae and no detection of methicillin-resistant coagulase-positive staphylococci in healthy dogs in Sweden,"Sweden has a long tradition of monitoring occurrence of antibiotic resistant bacteria in both animals and humans, but there currently is no organised and harmonized monitoring on carriage of Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL), plasmid-mediated AmpC beta-lactamase (pAmpC), or methicillin-resistant coagulase positive staphylococci e.g. methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs. The aim of the current study was therefore to determine the prevalence of ESBL/pAmpC producing Enterobacteriaceae and methicillin-resistant coagulase positive staphylococci in healthy dogs in Sweden, and to phenotypically and genotypically characterize any identified isolates. It was shown that 0.9% (95% confident interval 0.3–2.7%) of the dogs (n = 325) carried multi-resistant ESBL-producing Escherichia coli, but that no methicillin-resistant coagulase positive staphylococci could be detected. In conclusion, the occurrence of multi-drug resistant bacteria remains rare among healthy dogs in Sweden. In addition, the ESBL-producing E. coli identified showed genetic characteristics related to those reported from humans."
542,Diagnostic Experience from an Epidemic of Canine Parvoviral Enteritis,SUMMARY: Hemagglutination (HA) test and electron microscopy (EM) were used to diagnose canine parvoviral enteritis on fecal samples from 58 hospitalized dogs of a huge epidemic. By HA‐tests the presence of the canine parvovirus (CPV) involved was shown in samples from 15 dogs (∼ 26%). A reference antiserum was used to identify the virus of each sample by hemagglutination inhibition (HI). By EM parvovirus‐like particles were seen in samples from 28 dogs (∼ 48%). Particles in six samples were identified as CPV by immunoaggregation. Sera from 17 out of 19 dogs examined showed specific HI titers during the acute stage of illness. A high incidence of concomitant infection with Campylobacter spp was found by the bacteriologists. ZUSAMMENFASSUNG: Diagnostische Erfahrungen während einer Epidemie von Parvovirus‐Enteritis der Hunde Während einer grossen Epidemie von Parvovirus‐Enteritis der Hunde (in Schweden) wurde der Nachweis von Virus in Kotproben mit Hilfe der Hëmagglutination (HA) und Elektronenmikroskopie (EM) versucht; die Kotproben stammten von 58 hospitalisierten Hunden. Mit dem HA‐Test ließ sich das ursächliche Parvovirus in den Proben von 15 Hunden nachweisen (= ∼ 26%). In jeder von diesen Proben wurde das Virus durch Hämagglutination‐Hemmung (HAH) mit einem Referenzserum identifiziert. Mit der EM waren Parvovirus‐ähnliche Partikel in den Proben von 28 Hunden zu finden (= ∼ 48%). In 6 von diesen Proben wurden die Partikel mittels der Immunaggregation als das ursächlichen Parvovirus identifiziert. In 17 Serumproben von 19 untersuchten Hunden wurden spezifische HAH‐Titer während der akuten Krankheitsphase festgestellt. Die Bakteriologen wiesen ein gehäuftes Vorkommen von gleichzeitiger Infektion mit Campylobacter spp nach. RÉSUMÉ: Expériences de diagnostic durant une épidémie d'entérite à Parvovirus chez des chiens On a recherché la mise en évidence du virus dans des matières fécales à l'aide de l'hémagglutination (HA) et de la microscopie électronique (EM) durant une forte épidémie d'entérite à Parvovirus chez des chiens en Suède. Les échantillons d'excréments provenaient de 58 chiens hospitalisés. Le Parvovirus a été mis en évidence par test HA dans les échantillons de 15 chiens (∼ 26%). Le virus a été identifié dans chacun de ces échantillons au moyen de l'inhibition de l'hémagglutination (HAH) avec un sérum de référence. On a trouvé des particules identiques au microscope électronique dans les échantillons de 28 chiens (∼ 48%). Les particules dans 6 de ces prélèvements furent identifiées comme Parvovirus au moyen de l'immunoaggrégation. Un titre HAH spécifique a été établi durant la phase aiguë de la maladie dans 17 échantillons sérologiques sur 19 chiens examinés. La bactériologie a montré la présence fréquente d'une infection simultanée à Campylobacter spp. RESUMEN: Experiencias en el diagnóstico de una epidemia de parvovirus‐enteritis en caninos Mediante pruebas de hemaglutinación y microscopía electrónica se diagnosticó parvovirus‐enteritis en caninos en muestras fecales de 58 caninos hospitalizados a raiz de una extensa epidemia. Con la prueba de hemaglutinación se detectó la presencia de virus en muestras fecales de 15 caninos (∼ 26%). Un antisuero de referencia se utilizó para la identificación del virus (prueba de inhibición de la hemaglutinación). Con microscopía electrónica se identificó parvovirus en muestras fecales de 28 caninos (∼ 48%). El virus fué identificado en seis muestras fecales utilizando la prueba de inmunoagregación. Sueros de 17 de 19 caninos examinados demostraron títulos específicos de inhibición de la hemaglutinación durante la etapa aguda de la enfermedad. Se demostró también una alta incidencia de infección concomitante con Campylobacter spp.
543,Telehealth’s Time Has Come,
544,Bladder Cancer Guidelines: Let Not the Cure Be Worse than the Disease,
545,The Wuhan COVID-19 intubation experience,
546,Infektionsschutzrecht nach Inkrafttreten des Masernschutzgesetzes,"On 1 March 2020, the amendments to the German Protection Against Infection Act that were introduced by the act to protect against measles and strengthen vaccination prevention (Measles Protection Act) entered into force. The reason for the changes is that the number of individuals with measles has significantly increased in recent years. To protect public health, the Measles Protection Act has implemented regulations requiring that persons in certain institutions must either have adequate protection against measles or have immunity to measles. In this article the current legal situation with regard to health care facilities is presented."
547,Safety Considerations in the Laboratory Testing of Specimens Suspected or Known to Contain the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2),
548,Self-reported Olfactory and Taste Disorders in Patients With Severe Acute Respiratory Coronavirus 2 Infection: A Cross-sectional Study,
549,Inhaltsverzeichnis,
550,COVID-19: Keine Entwarnung im Sommer?,
551,Hydrops fetalis and neonatal abdominal compartment syndrome continuum from immature gastric teratoma: a case report,"BACKGROUND: Hydrops fetalis as well as abdominal compartment syndrome (ACS) are conditions that are associated with high mortality rates. A rare case of immature gastric teratoma causing fetal hydrops and subsequent ACS is presented. The related pathophysiologic mechanisms are discussed, and the importance of timely recognition and appropriate interventions are highlighted. CASE PRESENTATION: The male patient was born preterm, weighing 3.9 kg., by Cesarean section. Prior prenatal ultrasounds were normal, but a scan done just before delivery had findings indicating polyhydramnios, fetal ascites, and meconium peritonitis. Upon delivery, the patient had respiratory distress, anasarca and a massively distended abdomen. Resuscitation measures, including ventilatory support, were instituted. Imaging studies showed ascites as well as a large, complex intra-abdominal lesion with calcifications. In the succeeding hours, anuria persisted, anasarca worsened, the abdomen became more distended, and inotrope requirements increased. The occurrence of ACS, from what was presumed to be a retroperitoneal teratoma, was therefore considered. Laparotomy was done on the 28th hour of life, with en bloc excision of a massive tumor and attached section of the greater curvature of the stomach. Passage of urine occurred intra-operatively, and the patient was soon after weaned off inotropes and ventilator support. The histopathologic result was immature gastric teratoma. No chemotherapy was given, and the patient’s serum AFP is at normal levels 15 months following surgery. CONCLUSION: The presence of a massive intra-abdominal lesion can result in the pathophysiologic continuum of hydrops fetalis and neonatal ACS. The early recognition of such an association can enable appropriate expectant management of similarly affected neonates, including emergent decompression laparotomy."
552,Noninvasive oxygenation strategies in adult patients with acute respiratory failure: a protocol for a systematic review and network meta-analysis,"BACKGROUND: Acute hypoxemic respiratory failure is one of the leading causes of intensive care unit admission and is associated with high mortality. Noninvasive oxygenation strategies such as high-flow nasal cannula, standard oxygen therapy, and noninvasive ventilation (delivered by either face mask or helmet interface) are widely available interventions applied in these patients. It remains unclear which of these interventions are more effective in decreasing rates of invasive mechanical ventilation and mortality. The primary objective of this network meta-analysis is to summarize the evidence and compare the effect of noninvasive oxygenation strategies on mortality and need for invasive mechanical ventilation in patients with acute hypoxemic respiratory failure. METHODS: We will search key databases for randomized controlled trials assessing the effect of noninvasive oxygenation strategies in adult patients with acute hypoxemic respiratory failure. We will exclude studies in which the primary focus is either acute exacerbations of chronic obstructive pulmonary disease or cardiogenic pulmonary edema. The primary outcome will be all-cause mortality (longest available up to 90 days). The secondary outcomes will be receipt of invasive mechanical ventilation (longest available up to 30 days). We will assess the risk of bias for each of the outcomes using the Cochrane Risk of Bias Tool. Bayesian network meta-analyses will be conducted to obtain pooled estimates of head-to-head comparisons. We will report pairwise and network meta-analysis treatment effect estimates as risk ratios and 95% credible intervals. Subgroup analyses will be conducted examining key populations including immunocompromised hosts. Sensitivity analyses will be conducted by excluding those studies with high risk of bias and different etiologies of acute respiratory failure. We will assess certainty in effect estimates using GRADE methodology. DISCUSSION: This study will help to guide clinical decision-making when caring for adult patients with acute hypoxemic respiratory failure and improve our understanding of the limitations of the available literature assessing noninvasive oxygenation strategies in acute hypoxemic respiratory failure. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121755"
553,Age Limit in Bronchiolitis Diagnosis: 6 or 12 Months?,"Aim: The most frequent cause of lower respiratory tract infection in infants is bronchiolitis. Up to now there is no agreement on the upper limit age of bronchiolitis. Our aim was to identify if there are clinical differences in infants hospitalized for bronchiolitis between 0–6 months and 6–12 months of age. A secondary aim was to establish whether there was differences in terms of recurrent wheezing at 12, 24, and 36 months of follow-up. Methods: We retrospectively analyzed clinical and virological records of 824 infants hospitalized for bronchiolitis during 11 consecutive epidemic seasons. From each infant at admission to the hospital nasopharyngeal washing was collected, clinical severity was assessed and clinical data were extracted from a structured questionnaire. At 12–24–36 months after discharge, parents were interviewed seeking information on recurrent wheezing. Results: A total of 773 infants (Group1) were ≤6 months of age, while 51 were >6 months (Group 2). No differences between family history for atopy and passive smoking exposure were observed between the two groups. Respiratory syncyzial virus was detected more frequently in Group 1 and human bocavirus in Group 2. The clinical severity score (p = 0.011) and the use of intravenous fluids (p = 0.0001) were higher in Group 1 with respect to Group 2 infants. At 36 months follow-up 163/106 (39.4%) Group 1 and 9/9 Group 2 infants experienced recurrent wheezing (p = 0.149). Conclusion: We demonstrated that 0-6 months old infants bronchiolitis differs from > 6 months bronchiolitis."
554,Esperanza de vida al nacer. Contribuciones y desafíos de la microbiología,
555,Immunocytochemical Localization of the Menkes Copper Transport Protein (ATP7A) to the Trans-Golgi Network,"We have generated polyclonal antibodies against the amino-terminal third of the Menkes protein (ATP7A; MNK) by immunizing rabbits with a histidine-tagged MNK fusion construct containing metal-binding domains 1–4. The purified antibodies were used in Western analysis of cell lysates and in indirect immunofluorescence experiments on cultured cells. On Western blots, the antibodies recognized the ∼165 kDa MNK protein in CHO cells and human fibroblasts. No MNK signal could be detected in fibroblasts from a patient with Menkes disease or in Hep3B hepatocellular carcinoma cells, confirming the specificity of the antibodies. Immunocytochemical analysis of CHO cells and human fibroblasts showed a distinct perinuclear signal corresponding to the pattern of the Golgi complex. This staining pattern was similar to that of α-mannosidase II which is a known resident enzyme of the Golgi complex. Using brefeldin A, a fungal inhibitor of protein secretion, we further demonstrated that the MNK protein is localized to the trans-Golgi network. This data provides direct evidence for a subcellular localization of the MNK protein which is similar to the proposed vacuolar localization of Ccc2p, the yeast homolog of MNK and WND (ATP7B), the Wilson disease gene product. In light of the proposed role of MNK both in subcellular copper trafficking and in copper efflux, these data suggest a model for how these two processes are linked and represent an important step in the functional analysis of the MNK protein."
556,"Confronting infectious diseases is a perpetual struggle, top official says",
557,Amenity Migration and Public Lands: Rise of the Protected Areas,"Rural amenity migration, or the relocation for quality of life purposes as opposed to monetary enhancement, has been occurring for decades and has been particularly pronounced in the American West where the phenomenon peaked in the 1990s. Researchers have illustrated that some places are more attractive for migrants than others and that certain regional amenities hold considerable influence on where migrants relocate. Increased migration levels typically result in increased economic growth indicators, making amenity migration an attractive rural development strategy. But comprehensive econometric analysis focused on amenity migration in the American West has been lacking. To address this, we conducted an econometric analysis of attributes that influenced migration to rural Western counties from 1980 to 2010. Over 20 potential amenity supply categories were collated for 356 rural counties from 11 Western states, with a focus on public lands. Descriptive statistics and OLS regressions were estimated and interpreted. Traditional amenities of climate, water area, and regional access were highly associated with migration levels, while designated natural amenities of Wilderness and National Monuments were the most influential public lands for migration to rural Western counties. Farming and oil and gas dependency were negatively associated with migration levels. Increasing the amount of protected areas, and branding campaigns based on natural amenities, can be a critical development strategy for rural communities."
558,Harnessing Cross-Reactive CD8(+) T(RM) Cells for Long-Standing Protection Against Influenza A Virus,
559,Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN,"CIRE/mDC-SIGN is a C-type lectin we originally identified as a molecule differentially expressed by mouse dendritic cell (DC) populations. Immunostaining with a CIRE/mDC-SIGN-specific mAb revealed that CIRE/mDC-SIGN is indeed on the surface of some CD4(+), CD4(−)8(−) DCs and plasmacytoid pre-DCs, but not on CD8(+) DCs. It has been proposed that CIRE/mDC-SIGN is the functional orthologue of human DC-SIGN (hDC-SIGN), a molecule that both enhances T cell responses and facilitates antigen uptake. We assessed if CIRE/mDC-SIGN and hDC-SIGN exhibit functional similarities. CIRE/mDC-SIGN is down-regulated upon activation, but unlike hDC-SIGN, incubation with IL-4 and IL-13 did not enhance CIRE/mDC-SIGN expression, indicating differences in gene regulation. Like hDC-SIGN, CIRE/mDC-SIGN bound mannosylated residues. However, we could detect no role for CIRE/mDC-SIGN in T cell–DC interactions and the protein did not bind to pathogens known to interact with hDC-SIGN, including Leishmania mexicana, cytomegalovirus, HIV and lentiviral particles bearing the Ebolavirus glycoprotein. The binding of CIRE/mDC-SIGN to hDC-SIGN ligands was not rescued when CIRE/mDC-SIGN was engineered to express the stalk region of hDC-SIGN. We conclude that there are significant differences in the fine specificity of the C-type lectin domains of hDC-SIGN and CIRE/mDC-SIGN and that these two molecules may not be functional orthologues."
560,Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9,"Remyelination failure plays an important role in the pathophysiology of multiple sclerosis, but the underlying cellular and molecular mechanisms remain poorly understood. We now report actively demyelinating lesions in patients with multiple sclerosis are associated with increased glial expression of fibroblast growth factor 9 (FGF9), which we demonstrate inhibits myelination and remyelination in vitro. This inhibitory activity is associated with the appearance of multi-branched ‘pre-myelinating’ MBP(+)/PLP(+) oligodendrocytes that interact with axons but fail to assemble myelin sheaths; an oligodendrocyte phenotype described previously in chronically demyelinated multiple sclerosis lesions. This inhibitory activity is not due to a direct effect of FGF9 on cells of the oligodendrocyte lineage but is mediated by factors secreted by astrocytes. Transcriptional profiling and functional validation studies demonstrate that these include effects dependent on increased expression of tissue inhibitor of metalloproteinase-sensitive proteases, enzymes more commonly associated with extracellular matrix remodelling. Further, we found that FGF9 induces expression of Ccl2 and Ccl7, two pro-inflammatory chemokines that contribute to recruitment of microglia and macrophages into multiple sclerosis lesions. These data indicate glial expression of FGF9 can initiate a complex astrocyte-dependent response that contributes to two distinct pathogenic pathways involved in the development of multiple sclerosis lesions. Namely, induction of a pro-inflammatory environment and failure of remyelination; a combination of effects predicted to exacerbate axonal injury and loss in patients."
561,Perspectives on Fatigue from the Study of Chronic Fatigue Syndrome and Related Conditions,"Fatigue is a symptom whose causes are protean and whose phenotype includes physical, mood, and behavioral components. Chronic fatigue syndrome (CFS) is an illness that has strong biological underpinnings and no definite etiology. Diagnostic criteria established by the Centers for Disease Control and Prevention have helped classify CFS as an overlap of mood, behavioral, and biological components. These include the presence of fatigue for more than 6 months associated with a diminution of functional activity and somatic symptoms, and pain not attributable to a specific diagnosis or disease. Four of the following criteria need to be present: sore throat, impaired memory or cognition, unrefreshing sleep, postexertional fatigue, tender glands, aching stiff muscles, joint pain, and headaches. Many researchers have observed that CFS shares features in common with other somatic syndromes, including irritable bowel syndrome, fibromyalgia, and temporomandibular joint dysfunction. Correlations between inflammation and infection, augmented sensory processing, abnormalities of neurotransmitters, nerve growth factors, low levels of serotonin and norepinephrine, abnormalities of homeostasis of the stress system, and autonomic dysfunction may be hallmarks of CFS. The relative contributions of each of these abnormalities to the profound fatigue associated with CFS need to be explored further to better evaluate and treat the syndrome."
562,Pediatric Patient Safety in the Ambulatory Setting,
563,LRRK2 Expression in Normal and Pathologic Human Brain and in Human Cell Lines,"Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been recently identified in families with autosomal-dominant late-onset Parkinson disease. We report that by reverse transcriptase-polymerase chain reaction, the mRNA of LRRK2 is expressed in soluble extracts of human brain, liver, and heart and in cultured human astrocytes, microglia, and oligodendroglia as well as in human neuroblastoma cell lines. We find by Western blotting using a polyclonal antibody of the leucine-rich repeat kinase 2 protein (Lrrk2) specific for C-terminal residues 2511-2527 that an apparent full-length protein and several of its fractions are expressed in soluble extracts of normal human brain. By immunocytochemistry, the antibody recognizes neurons, and more weakly astrocytes and microglia, in normal brain tissue. It intensely labels Lewy bodies in Parkinson disease and related neurodegenerative disorders. It also labels a subset of neurofibrillary tangles in Alzheimer disease and the Parkinsonism dementia complex of Guam (PDCG). It labels thorn-shaped astrocytes and oligodendroglial coiled bodies in PDCG; oligodendroglial inclusions in multiple system atrophy; Pick bodies in Pick disease; nuclear and cytoplasmic inclusions in Huntington disease; and intraneuronal and glial inclusions in amyotrophic lateral sclerosis. In summary, LRRK2 is constitutively expressed in neurons and also in glial cells of human brain. It strongly associates with pathological inclusions in several neurodegenerative disorders."
564,Similarity relations of DNA and RNA polymerases investigated by the principal component analysis of amino acid sequences,"The principal component analysis based on the physicochemical properties of amino acid residues is applied to DNA and RNA polymerases to assign the sequence motifs for the polymerization activities of these proteins. After the reconfirmation of the sequence motifs of families A and B of DNA polymerases indicated previously, it elucidates the sequence motifs for the polymerization activity of DNA polymerase III (family C) by the similarity to the polymerization center of multimeric DNA dependent RNA polymerases. This identification proceeds to clarify the sequence motifs for polymerization activities of primases; eukaryotic and archaebacterial primases carry motifs similar to those of family C, while the motifs of eubacterial primase fall into the category of the motifs in family B DNA polymerases such as α, δ, ϵ and II. This finding means that DNA dependent RNA polymerases are also divided into groups corresponding to three families, A, B and C, because the monomeric DNA dependent RNA polymerases in phages are reconfirmed to carry sequence motifs similar to those of family A DNA polymerases. Furthermore, the three families of polymerization motifs are found to fall within the variation range of polymerization motifs displayed by many RNA dependent RNA polymerases, suggesting a close evolutionary relation between them. The sequence motifs for polymerization activities of reverse transcriptase and telomerase seem to be the intermediate between family A DNA polymerase and some RNA dependent RNA polymerases, e.g., from Leviviridae. On the contrary, the sequence fragments similar to the nucleotidyltransferase superfamily including DNA polymerase β are not found in any RNA dependent RNA polymerase, suggesting their other lineage of polymerization motifs."
565,FULL ISSUE PDF,
566,Editorial statement,
567,Regional Lung Perfusion as Determined by Electrical Impedance Tomography in Comparison With Electron Beam CT Imaging,"The aim of the experiments was to check the feasibility of pulmonary perfusion imaging by functional electrical impedance tomography (EIT) and to compare the EIT findings with electron beam computed tomography (EBCT) scans. In three pigs, a Swan-Ganz catheter was positioned in a pulmonary artery branch and hypertonic saline solution or a radiographic contrast agent were administered as boli through the distal or proximal openings of the catheter. During the administration through the proximal opening, the balloon at the tip of the catheter was either deflated or inflated. The latter case represented a perfusion defect. The series of EIT scans of the momentary distribution of electrical impedance within the chest were obtained during each saline bolus administration at a rate of 13/s. EBCT scans were acquired at a rate of 3.3/s during bolus administrations of the radiopaque contrast material under the same steady-state conditions. The EIT data were used to generate local time-impedance curves and functional EIT images showing the perfusion of a small lung region, both lungs with a perfusion defect and complete both lungs during bolus administration through the distal and proximal catheter opening with an inflated or deflated balloon, respectively. The results indicate that EIT imaging of lung perfusion is feasible when an electrical impedance contrast agent is used."
568,Reassortment Networks and the Evolution of Pandemic H1N1 Swine-Origin Influenza,"Prior research developed Reassortment Networks to reconstruct the evolution of segmented viruses under both reassortment and mutation. We report their application to the swine-origin pandemic H1N1 virus (S-OIV). A database of all influenza A viruses, for which complete genome sequences were available in Genbank by October 2009, was created and dynamic programming was used to compute distances between all corresponding segments. A reassortment network was created to obtain the minimum cost evolutionary paths from all viruses to the exemplar S-OIV A/California/04/2009. This analysis took 35 hours on the Cray Extreme Multithreading (XMT) supercomputer, which has special hardware to permit efficient parallelization. Six specific H1N1/H1N2 bottleneck viruses were identified that almost always lie on minimum cost paths to S-OIV. We conjecture that these viruses are crucial to S-OIV evolution and worthy of careful study from a molecular biology viewpoint. In phylogenetics, ancestors are typically medians that have no functional constraints. In our method, ancestors are not inferred, but rather chosen from previously observed viruses along a path of mutation and reassortment leading to the target virus. This specificity and functional constraint render our results actionable for further experiments in vitro and in vivo."
569,System for Infectious Disease Information Sharing and Analysis: Design and Evaluation,"Motivated by the importance of infectious disease informatics (IDI) and the challenges to IDI system development and data sharing, we design and implement BioPortal, a Web-based IDI system that integrates cross-jurisdictional data to support information sharing, analysis, and visualization in public health. In this paper, we discuss general challenges in IDI, describe BioPortal's architecture and functionalities, and highlight encouraging evaluation results obtained from a controlled experiment that focused on analysis accuracy, task performance efficiency, user information satisfaction, system usability, usefulness, and ease of use."
570,Design and Control of a Mechatronic Tracheostomy Tube for Automated Tracheal Suctioning,"Goal: Mechanical ventilation is required to aid patients with breathing difficulty to breathe more comfortably. A tracheostomy tube inserted through an opening in the patient neck into the trachea is connected to a ventilator for suctioning. Currently, nurses spend millions of person-hours yearly to perform this task. To save significant person-hours, an automated mechatronic tracheostomy system is needed. This system allows for relieving nurses and other carers from the millions of person-hours spent yearly on tracheal suctioning. In addition, it will result in huge healthcare cost savings. Methods: We introduce a novel mechatronic tracheostomy system including the development of a long suction catheter, automatic suctioning mechanisms, and relevant control approaches to perform tracheal suctioning automatically. To stop the catheter at a desired position, two approaches are introduced: 1) Based on the known travel length of the catheter tip; 2) Based on a new sensing device integrated at the catheter tip. It is known that backlash nonlinearity between the suction catheter and its conduit as well as in the gear system of the actuator are unavoidable. They cause difficulties to control the exact position of the catheter tip. For the former case, we develop an approximate model of backlash and a direct inverse scheme to enhance the system performances. The scheme does not require any complex inversions of the backlash model and allows easy implementations. For the latter case, a new sensing device integrated into the suction catheter tip is developed and backlash compensation controls are avoided. Results: Automated suctioning validations are successfully carried out on the proposed experimental system. Comparisons and discussions are also introduced. Significance: The results demonstrate a significant contribution and potential benefits to the mechanical ventilation areas."
571,Automatic Control of Arterial Carbon Dioxide Tension in Mechanically Ventilated Patients,This paper presents a method of controlling the arterial carbon dioxide tension of patients receiving mechanical ventilation. Controlling of the CO(2) tension is achieved by regulating the ventilator initiated breath frequency and also volume per breath.
572,Temporal and Spatial Monitoring and Prediction of Epidemic Outbreaks,"This paper introduces a nonlinear dynamic model to study spatial and temporal dynamics of epidemics of susceptible-infected-removed type. It involves modeling the respective collections of epidemic states and syndromic observations as random finite sets. Each epidemic state consists of the number of infected individuals in an isolated population system and the corresponding partially known parameters of the epidemic model. The infectious disease could spread between population systems with known probabilities based on prior knowledge of ecological and biological features of the environment. The problem is then formulated in the context of Bayesian framework and estimated via a probability hypothesis density filter. Each population system under surveillance is assumed to be homogenous and fixed, with daily reports on the number of infected people available for monitoring and prediction. When model parameters are partially known, results of numerical studies indicate that the proposed approach can help early prediction of the epidemic in terms of peak and duration."
573,Characterization and Use of a Fiber Optic Sensor Based on PAH/SiO(2) Film for Humidity Sensing in Ventilator Care Equipment,"Objective: To develop a compact probe that can be used to monitor humidity in ventilator care equipment. A mesoporous film of alternate layers of Poly(allylamine hydrochloride) (PAH) and silica (SiO2) nanoparticles (bilayers), deposited onto an optical fibre was used. The sensing film behaves as a Fabry-Perot cavity of low-finesse where the absorption of water vapour changes the optical thickness and produces a change in reflection proportional to humidity. Methods: The mesoporous film was deposited upon the cleaved tip of an optical fibre using the layer-by-layer method. The sensor was calibrated in a bench model against a commercially available capacitive sensor. The sensitivity and response time were assessed in the range from 5 % relative humidity (RH) to 95%RH for different numbers of bilayers up to a maximum of nine. Results: The sensitivity increases with the number of bilayers deposited; sensitivity of 2.28 mV/%RH was obtained for nine bilayers. The time constant of the response was 1.13 s ± 0.30 s which is faster than the commercial device (measured as 158 s). After calibration, the optical fibre humidity sensor was utilised in a bench top study employing a mechanical ventilator. The fast response time enabled changes in humidity in individual breaths to be resolved. Conclusion: Optical fibre sensors have the potential to be used to monitor breath to breath humidity during ventilator care. Significance: Control of humidity is an essential part of critical respiratory care and the developed sensor provides a sensitive, compact and fast method of humidity monitoring."
574,A Strategic Plan for Strengthening America’s Families: A Brief from the Coalition of Behavioral Science Organizations,"Despite significant progress in research on the treatment and prevention of psychological, behavioral, and health problems, the translation of this knowledge into population-wide benefit remains limited. This paper reviews the state of America’s children and families, highlighting the influence of stressful contextual and social conditions on child and family well-being and the concentration of disadvantage in numerous neighborhoods and communities throughout the nation. It then briefly reviews the progress that has been made in pinpointing policies that can reduce stressful contextual conditions such as poverty, discrimination, and the marketing of unhealthful foods and substances. It also describes numerous family and school interventions that have proven benefit in preventing psychological and behavioral problems as diverse as tobacco, alcohol, and other drug use; depression; antisocial behavior; academic failure; obesity prevention; and early childbearing. We argue that progress in translating existing knowledge into widespread benefit will require a nationwide effort to intervene comprehensively in neighborhoods and communities of concentrated disadvantage. We present a strategic plan for how such an effort could be organized. The first step in this organizing would be the creation of a broad and diverse coalition of organizations concerned with advancing public health and well-being. Such a coalition could increase public support both for the policies needed to focus on these disadvantaged areas and the research needed to incrementally improve our ability to help these areas."
575,Revue de presse,
576,Defining trained immunity and its role in health and disease,"Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed ‘trained immunity’, a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define ‘trained immunity’ as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity."
577,"The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route","BACKGROUND: Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions. RESULTS: Fifty-two healthy, community dwelling elderly adults (65–82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alum-adjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ≥10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21–34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%, p = 0.008). The low seroconversion rate in the IM group progressively declined with increasing age, and responders had significantly lower HBsAb titers and limited isotype responses. Moreover, T-CMI (proliferation and cytokine production) were significantly reduced in both percentage of responders and intensity of the response for both Th1 and Th2 subsets in the elderly. CONCLUSIONS: Our data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B- and T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04162223. Registered 14 November 2019. Retrospectively registered."
578,A Single-Copy IS5-Like Transposon in the Genome of a Bdelloid Rotifer,"In the course of sequencing telomeric chromosomal regions of the bdelloid rotifer Adineta vaga, we encountered an unusual DNA transposon. Unlike other bdelloid and, more generally, eukaryotic transposable elements (TEs), it exhibits similarity to prokaryotic insertion sequences (ISs). Phylogenetic analysis indicates that this transposon, named IS5_Av, is related to the ISL2 group of the IS5 family of bacterial IS elements. Despite the apparent intactness of the single open reading frame coding for a DDE transposase and the perfect identity of its 213-bp terminal inverted repeats (TIRs), the element is present in only one copy per diploid genome. It does not exhibit any detectable levels of transcription, so that its transposase gene appears to be silent in the bdelloid host. Although horizontal transfers of TEs between kingdoms are not known to happen in nature, it appears likely that IS5_Av underwent integration into the A. vaga genome relatively recently, but was not successful in adapting to the new host and failed to increase in copy number. Alternatively, it might be the only known member of a novel eukaryotic DNA TE superfamily which is so rare that its other members, if any, have not yet been identified in eukaryotic genomes sequenced to date."
579,Alternative Regimens of Neuraminidase Inhibitors for Therapy of Hospitalized Adults with Influenza: A Systematic Review of Randomized Controlled Trials,"INTRODUCTION: Influenza in hospitalized intensive care unit (ICU) patients with respiratory failure is associated with 25% mortality, despite timely oseltamivir treatment. A systematic review of randomized controlled trials (RCTs) was conducted to evaluate the efficacy and safety of alternative neuraminidase inhibitor (NAI) regimens compared to standard of care in patients hospitalized for H1N1, H3N2, or B influenza. METHODS: The Cochrane collaboration searching methods were followed in Cochrane Library, PubMed, and Web of Science databases (2009–2019). Eligibility criteria were RCTs comparing different regimens of NAIs in hospitalized patients (at least 1 year old) for clinically diagnosed influenza (H1N1, H3N2, or B). Pre-defined endpoints were time to clinical resolution (TTCR), overall mortality, hospital discharge, viral clearance, drug-related adverse events (AEs), and serious adverse events. RESULTS: Seven trials (1579 patients) were included. Two trials compared two regimens of oral oseltamivir therapy, and one trial compared two regimens of intravenous zanamivir therapy vs oral oseltamivir therapy. Four trials focused on intravenous peramivir therapy: two trials compared two different regimens and two trials compared two different regimens vs oral oseltamivir therapy. Overall, the different regimens were well tolerated, with no significant differences in AEs; nonetheless non-significant differences were reported among different regimens regarding TTCR, mortality, and viral clearance. CONCLUSION: Higher compared to standard doses of NAIs or systemic peramivir therapy compared to oral oseltamivir therapy did not demonstrate benefit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12325-020-01347-5) contains supplementary material, which is available to authorized users."
580,Toxigenic type D Pasteurella multocida in New South Wales pig herds—prevalence and factors associated with infection,"Between March and July 1987, a study was undertaken to determine the prevalence of and factors associated with toxigenic type D Pasteurella multocida infection in New South Wales pig herds. Toxigenic type D P. multocida was isolated from the nasal cavities of pigs in one (2%) of 50 randomly selected herds. Toxigenic isolates were also recovered from 2 (8%) of a separate group of 25 herds that had purchased pigs from a known infected piggery in South Australia (herd SA). Snout abnormalities were present in 9.4%, 3.2% and 1.8% of grower pigs in the 3 affected herds. Isolation of toxigenic P. multocida was significantly associated (p < 0.0001) with the occurrence of clinically affected pigs in the herd. Purchase of at least 5 pigs from herd SA was associated with an elevated risk (p < 0.05) of isolation of toxigenic P. multocida."
581,Investigations of an enteric infection of cockatoos caused by an enterovirus‐like agent,"An enteric infection in cockatoos associated with a 30nm diameter enterovirus‐like agent seen in faeces and intestinal epithelial cells is described. The disease is characterised by intractable, profuse, mucoid diarrhoea, weight loss, dehydration and death. Lesions in the intestine consist of villous atrophy, villous fusion, enterocyte hyperplasia and, in some cases, chronic inflammation. Affected birds so far examined have concurrent psittacine beak and feather disease."
582,Characteristics and prognosis of hospital‐treated obstructive bronchitis in children aged less than two years,"In a prospective study 101 children aged less than 2 years (median age 10 months), were examined the first time they were admitted to a paediatric ward for asthmatic symptoms. Two‐thirds were boys and 58 had parents or siblings with allergic symptoms. During winter‐spring, respiratory syncytial (RS) virus was verified in 50% of children. Other viral agents were adenovirus, parainfluenza 3, coxsackie B 2, ECHO 6 and rotavirus. At the acute stage, 54% of the children displayed changes on pulmonary X‐ray. The total IgE value was + 2 SD score units in 14 children. At reinvestigation after 3–4.5 years, when the children were aged 3.3–6.3 years, 53% were free from asthmatic symptoms; the median age for the last episode was 2 years. A total of 33% had mild asthma, 8% moderate and 6% severe asthma. The factors which correlated significantly with persistent asthma were: (1) The need for daily medication for at least 6 months. (2) A young age in conjunction with the first wheezing episode and on the first admission to a paediatric ward because of asthmatic symptoms. (3) Other past or present atopic symptoms. Heredity, tobacco smoking at home, having a furry pet, RS virus infection, or high total IgE at the time of the first admission did not correlate significantly with the persistence of asthma 3–4.5 years later. The results emphasize the good overall prognosis of wheezing in early childhood, even when the wheezing is severe enough to lead to inpatient treatment."
583,UNEXPECTED ISOLATION OF A NEWCASTLE DISEASE VIRUS,
584,ω-3 vs. ω-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation,"OBJECTIVE: To compare the effects of a conventional ω-6 lipid infusion and a fish oil based (ω-3) lipid infusion for parenteral nutrition on neutrophil function, lipid mediators, and plasma free fatty acids. DESIGN AND SETTING: Open-label, randomized, pilot study in a university hospital medical intensive care unit and experimental laboratory. PATIENTS AND PARTICIPANTS: Ten patients with septic shock and eight healthy controls. INTERVENTIONS: Patients (five per group) requiring parenteral nutrition received intravenously either a ω-3 or a ω-6 lipid emulsion for a 10-day period. MEASUREMENTS AND RESULTS: At baseline levels of plasma free fatty acids were elevated several-fold, including high concentrations of the ω-6 lipid precursor arachidonic acid (AA). Neutrophils isolated from septic patients displayed markedly reduced responsiveness to ex vivo stimulation, including lipid mediator generation [leukotrienes (LT), PAF], respiratory burst, and phosphoinositide hydrolysis signaling. Under the ω-6 lipid infusion regimen abnormalities in plasma free fatty acids and impairment of neutrophil functions persisted or worsened. In contrast, a rapid switch in the plasma free fatty acid fraction to predominance of the ω-3 acids eicosapentaenoic acid and docosahexaenoic acid over AA occurred in response to ω-3 lipid infusion. LTB(5), in addition to LTB(4), appeared upon neutrophil stimulation originating from these patients, and neutrophil function was significantly improved in the ω-3 lipid group. CONCLUSIONS: ω-3 vs. ω-6 lipid emulsions differentially influence the plasma free fatty acid profile with impact on neutrophil functions. Lipid-based parenteral nutrition in septic patients may thus exert profound influence on sequelae and status of immunocompetence and inflammation. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00134-003-1900-2."
585,Modeling the helicase domain of Brome mosaic virus 1a replicase,"Brome mosaic virus (BMV) is a representative member of positive-strand RNA viruses. The 1a replicase from BMV is a membrane protein of unknown structure with a methyltransferase N-terminal domain and a putative helicase activity in the C-terminal domain. In order to make a functional prediction of the helicase activity of the BMV 1a C-terminal domain, we have built a model of its structure. The use of fold recognition servers hinted at two different superfamilies of helicases [superfamily 1 (SF1) and superfamily 2 (SF2)] as putative templates for the C-terminal fragment of BMV 1a. A structural model of BMV 1a in SF2 was obtained by means of a fold recognition server (3D-PSSM). On the other hand, we used the helicase motifs described in the literature to construct a model of the structure of the BMV 1a C-terminal domain as a member of the SF1. The biological functionality and statistic potentials were used to discriminate between the two models. The results illustrate that the use of sequence profiles and patterns helps modeling. Accordingly, the C-terminal domain of BMV 1a is a potential member of the SF1 of helicases, and it can be modeled with the structure of a member of the UvrD family of helicases. The helicase mechanism was corroborated by the model and this supports the hypothesis that BMV 1a should have helicase activity."
586,Images in Clinical ECT: Immediate impact of COVID-19 on ECT Practice,
587,Nurses transforming systems of care: The bicentennial of Florence Nightingale's legacy,Lessons from Florence Nightingale are just as relevant today as they were more than 150 years ago. Learn how nurse leaders can follow her lead and embrace the importance of nurturing highly motivated nurses who are critical thinkers.
588,"Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial","OBJECTIVE: To assess the efficacy and safety of ultra-low dose 0.005% estriol vaginal gel in women with breast cancer receiving nonsteroidal aromatase inhibitors (NSAIs) and experiencing treatment-related vulvovaginal symptoms and signs. METHODS: Women with hormone receptor-positive early breast cancer receiving NSAIs were randomized to either estriol vaginal gel or placebo for 12 weeks. Vaginal maturation, vaginal pH, and total and individual scores of symptoms and signs of vulvovaginal atrophy were assessed at baseline and at weeks 3 and 12; sexual functioning was also evaluated using the Female Sexual Functioning Index (FSFI) questionnaire, as well as circulating estrogens, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). RESULTS: Sixty-one women with a mean age of 59 years were included: 50 received 0.005% estriol vaginal gel and 11 received placebo. Active treatment significantly improved maturation value and pH, vaginal dryness and global scores of symptoms and signs. Active treatment also increased the total FSFI score and all the FSFI domains, with the exception of pain. Small oscillations were observed in FSH and LH, which remained within the postmenopausal range. Estriol levels increased initially and normalized by week 12, and estradiol and estrone remained mostly undetectable throughout the study. CONCLUSIONS: Ultra-low dose 0.005% estriol vaginal gel showed efficacy in improving the symptoms and signs of vulvovaginal atrophy. These results, together with minimal oscillations in hormonal levels throughout the treatment, support the use of ultra-low dose 0.005% estriol vaginal gel as a treatment option for vulvovaginal atrophy in women with breast cancer receiving NSAIs with an indication for treatment with vaginal estrogens."
589,Telemedicine Home-Based Cardiac Rehabilitation: A CASE SERIES,"In this case series report, we review 2 patients who were among the first to participate in the Henry Ford telemedicine home-based cardiac rehabilitation (TM-HBCR) program. These patients had barriers to full participation in a facility-based cardiac rehabilitation (CR) program due to return to work and access to transportation. However, they were willing and able to participate in the TM-HBCR program. DISCUSSION: The two cases discussed herein are examples of individuals who likely would not have fully participated in CR if the only option available was a facility-based program. While HBCR is not an option for all patients, it does address several barriers that are known to limit participation in facility-based CR for some individuals. SUMMARY: Technology has made it possible to provide the key components of a facility-based CR program through a TM-HBCR model using a secure connection to the patients via their personal mobile device."
590,"Effects of NT-814, a dual neurokinin 1 and 3 receptor antagonist, on vasomotor symptoms in postmenopausal women: a placebo-controlled, randomized trial","OBJECTIVES: To evaluate the safety, pharmacokinetics, and preliminary efficacy of NT-814, a dual neurokinin 1,3 antagonist, in postmenopausal women with vasomotor symptoms (hot flashes). METHODS: We completed a double-blind, randomized, placebo-controlled trial in three US clinical research units in 76 postmenopausal women with moderate/severe hot flashes. Participants were randomized to 14 days of once-daily NT-814 or placebo within each of four sequential dose cohorts; 50, 100, 150, and 300 mg. Participants completed diaries of hot flash frequency and severity and waking due to night sweats before (baseline) and during treatment. RESULTS: All prespecified efficacy parameters (24-h hot flash frequency and severity, frequency of waking due to night sweats) decreased in all groups (including placebo). Mean reduction from baseline at week 2 in moderate/severe hot flash frequency was 37% in the placebo group and, respectively, 24% (P = 0.048 vs placebo), 59% (P = 0.155), 84% (P < 0.001) and 66% (P = 0.022) in the 50 mg, 100 mg, 150 mg, and 300 mg NT-814 groups; in waking due to night sweats reduction was 20% (P = 0.059), 55% (P = 0.135), 81% (P < 0.001), and 63% (P = 0.031) in the NT-814 groups and 32% in the placebo group. The improvement with NT-814 ≥150 mg was also evident in the first week of treatment. The most common treatment-related adverse events were mild somnolence and headache, more frequently in the 300 mg group. Safety monitoring identified no concerns. CONCLUSIONS: Once-daily NT-814 (≥150 mg/d) resulted in a rapid, marked improvement in hot flashes and waking due to night sweats. No safety concerns were identified. Doses up to 300 mg were well tolerated."
591,ECT during COVID-19: An Essential Medical Procedure – Maintaining Service Viability and Accessibility,
592,"The association between hormone therapy and sarcopenia in postmenopausal women: the Korea National Health and Nutrition Examination Survey, 2008-2011","OBJECTIVE: Menopausal transition contributes to sarcopenia, but the effects of hormone therapy (HT) on sarcopenia in postmenopausal women have not been determined. This study assessed the effect of HT on sarcopenia in postmenopausal women. METHODS: The present study included 4,254 postmenopausal women who participated in the Korea National Health and Nutritional Examination Surveys from 2008 to 2011. Appendicular skeletal muscle mass divided by weight (ASM/Wt) and the prevalence of sarcopenia were analyzed in groups of women stratified by duration of HT use. RESULTS: ASM/Wt was higher and the prevalence of sarcopenia was lower in participants with a history of prolonged (≥13 mo) HT use than in participants with a shorter duration of HT use or no HT use. After adjusting for multiple confounding factors, prolonged use of HT remained significantly associated with estimated mean ASM/Wt and the prevalence of sarcopenia (odds ratio: 0.60; 95% confidence interval: 0.41-0.88; P = 0.01). In addition, the prevalence of sarcopenia was linearly associated with history of hypertension, duration of hypertension, physical activity, and duration of HT use. Subgroup analysis showed that the association between duration of HT use and the prevalence of sarcopenia was maintained in younger (<65 y old) and leaner (body mass index <25 kg/m(2)) postmenopausal women. CONCLUSIONS: The present study showed that the prolonged use of HT was associated with high muscle mass and a low prevalence of sarcopenia in postmenopausal women."
593,ECT in a time of COVID-19,
594,Double-Edged Spike: Are SARS-CoV-2 Serologic Tests Safe Right Now?,
595,"Knowledge, awareness and practices towards seasonal influenza and its vaccine: implications for future vaccination campaigns in Jordan","BACKGROUND. Influenza is an underestimated contributor to morbidity and mortality. Population knowledge regarding influenza and its vaccination has a key role in enhancing vaccination coverage. OBJECTIVES. This study aimed to identify the gaps of knowledge among Jordanian population towards influenza and its vaccine, and to identify the major determinants of accepting seasonal influenza vaccine in adults and children in Jordan. METHODS. This was a cross-sectional study that enrolled 941 randomly selected adults in Amman, Jordan. A four-section questionnaire was used which included questions about the sociodemographic characteristics, knowledge about influenza and the factors that affect seasonal influenza vaccine acceptance and refusal. RESULTS. Only 47.3% of the participants were considered knowledgeable. About half of the participants (51.9%) correctly identified the main influenza preventative measures. Lack of knowledge about the important role of seasonal influenza vaccine in disease prevention was observed. Low vaccination rate (20% of adults) was reported. The most critical barrier against vaccination in adults and children was the concern about the safety and the efficacy of the vaccine, while the most important predictors for future vaccination in adults and children were physician recommendation and government role. In children, the inclusion of the vaccine within the national immunization program was an important determinant of vaccine acceptance. CONCLUSION. Formulating new strategies to improve the population’s level of knowledge, assuring the population about the safety and the efficacy of the vaccine and the inclusion of the vaccine within the national immunization program are the essential factors to enhance vaccination coverage in Jordan."
596,Compliance in teenagers with coeliac disease—a Swedish follow‐up study,"A group of 47 children with coeliac disease, born between 1973 and 1978 in the Swedish county of Västmanland, participated in a controlled questionnaire study. Health, self‐esteem, knowledge of the disease and dietary compliance were investigated. The children with coeliac disease were otherwise just as healthy as the control children. Growth and self‐esteem were normal. Good knowledge of coeliac disease and dietary treatment was found in 87% of children and dietary compliance was 81%. Girls and younger children (12–14 years) were more compliant than boys and older children (15–17 years). Compliance correlated positively to knowledge."
597,Mixed Infection Is Common in Children with Respiratory Adenovirus Infection,"ABSTRACT. The presence of concomitant viral or bacterial infection was evaluated in 20 patients hospitalized for adenovirus infection of the middle or lower airways by using new serological methods for detection of both antigens and antibodies. Adenovirus infection was identified by measurement of antibodies with complement fixation test or by direct detection of viral antigen in nasopharyngeal aspirates. Mixed infection was present in 11 (55%) of the 20 patients. Viral coinfection was demonstrated in five (25%) and bacterial in nine (45%) patients. Bacterial coinfection was common, 67%, in children with an infection focus, pneumonia or acute otitis media, but rare, 13%, in those without it. Seroconversion to nontypable Haemophilus influenzae was indicated in six children; four of them were infants, four had pneumonia and three acute otitis media. Pneumococcal infection was indicated in two patients with pneumonia, both aged over two years. Chlamydia trachomatis was involved in one case. The results indicate that bacterial coinfection is common in respiratory adenovirus infection affecting lower airways, especially if pneumonia is present."
598,Multiple sclerosis in the Faroe Islands,"Detailed questionnaires were completed in 1978–79 by 23 of the 28 then known resident Faroese multiple sclerosis (MS) patients and 127 controls. These controls were divided into 69 Group A (patient sibs and other relatives), 37 Group B (matched neighbor controls, their spouses and sibs, plus patient's spouse), and 21 Group C (distant matched controls, spouses, relatives living where MS patients never resided and British troops were not encamped during the war). No differences between cases and controls were found for education, occupation, types of residence, bathing, sanitary or drinking facilities, and nature of house construction or heating. Detailed dietary histories, available for half the subjects, revealed no difference, cases versus controls, for four age periods between age 0 and 30 years, and for 16 specified foodstuffs. Animal exposures showed overall no consistent differences by location or type of animal. There was a tendency to greater exposure to British troops during the war for cases versus Groups A and B, but this did not attain statistical significance. Vaccinations for smallpox, tetanus and diphtheria were less common in the MS; no difference was found for other vaccinations. Except for a relative deficit in the cases for rubella and (insignificantly) for measles, mumps and chicken pox, reported illnesses were equally common among all groups. Operations, hospitalizations and injuries did not differentiate the groups, nor did age at menarche for women. Neurologic symptoms were significantly more common in the cases than in the controls."
599,Endemism in Tasmanian cool temperate rainforest: alternative hypotheses,Endemism in Tasmanian cool temperate rainforest: alternative hypotheseS. Evidence is presented which suggests that hypotheses presented by Kirkpatrick & Brown relating to endemic species in Tasmania are either invalid or of limited importance for woody rainforest species. In their place three hypotheses are presented to account for the presence of endemic species in Tasmanian cool temperate rainforest on the basis of the fossil record and the distribution of species which are closely related to the endemics. The first two hypotheses relate to the presence of the endemic species in the general Tasmanian region. They are: 1.. Some species evolved in southeastern Australia during the Tertiary in response to the changing climate. Some of the ancestral species still occur in temperate rainforest at lower latitudes in Australia. 2.. Some species have remained essentially unchanged in Tasmania during the Tertiary and Quaternary climatic changes. The third hypothesis relates to the restriction of these cool temperate rainforest species to Tasmania: 1.. Post‐glacial climatic changes (especially a decrease in rainfall) and the human influence (especially land clearing and fire) may have combined to eliminate some cool temperate rainforest species from mainland Australia.
600,"Derivation and dispersal of Acacia (Leguminosae), with particular reference to Australia, and the recognition of Senegalia and Racosperma","The morphology of seedlings, leaves, flowers and inflorescences, anatomy of the pod, the occurrence of extra‐floral nectaries, free amino acids of the seeds, flavonoid compounds in heartwoods, cyanogenic compounds and porate, colporate and extraporate pollen, and susceptibility to rusts, all indicate that three genera, Acacia Miller, Senegalia Raf. and Racosperma Martius, should be recognized. These correspond to currently accepted subgenera of Acacia. The size of these more narrowly circumscribed genera is in keeping with the size of genera of other tribes of low diversity in Leguminosae. Acacia and Senegalia arose independently from the Ingeae, with Racosperma being derived from Senegalia. Section Filicinae is more advanced than section Senegalia of Senegalia, and sections Racosperma and Pukhella, both with at least some species with bipinnate foliage, are the most advanced of Racosperma, while the other sections Pleurinervia and Lycopodiifolia have only phyllodinous species. Long‐range dispersal of Racosperma from the Australian region has occurred, but the broad pattern of distribution is interpreted in terms of plate tectonics. Racosperma was present in Australia in the late Cretaceous but did not become widespread until the general drying of the continent in the Miocene. The flora of SW Australia has been isolated from the rest of the continent by climatic barriers since the late Tertiary and has a high proportion of endemic species. Barriers to plant migration in the east have operated only intermittently and there is no area comparable in endemism to the southwest."
601,"Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence","PURPOSE: AE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year overall disease-free survival (DFS) but possible benefit in subgroups. Here, we present the final landmark analysis. METHODS: In this 4-arm, prospective, randomized, single-blinded, multi-center phase II trial, disease-free node positive and high-risk node negative breast cancer patients enrolled after standard of care therapy. Six monthly inoculations of vaccine (VG) vs. control (CG) were given as the primary vaccine series with 4 boosters at 6-month intervals. Demographic, safety, immunologic, and DFS data were evaluated. RESULTS: 456 patients were enrolled; 154 patients in the VG and 147 in CG for AE37, 89 patients in the VG and 91 in CG for GP2. The AE37 arm had no difference in DFS as compared to CG, but pre-specified exploratory subgroup analyses showed a trend towards benefit in advanced stage (p = 0.132, HR 0.573 CI 0.275–1.193), HER2 under-expression (p = 0.181, HR 0.756 CI 0.499–1.145), and triple-negative breast cancer (p = 0.266, HR 0.443 CI 0.114–1.717). In patients with both HER2 under-expression and advanced stage, there was significant benefit in the VG (p = 0.039, HR 0.375 CI 0.142–0.988) as compared to CG. The GP2 arm had no significant difference in DFS as compared to CG, but on subgroup analysis, HER2 positive patients had no recurrences with a trend toward improved DFS (p = 0.052) in VG as compared to CG. CONCLUSIONS: This phase II trial reveals that AE37 and GP2 are safe and possibly associated with improved clinical outcomes of DFS in certain subgroups of breast cancer patients. With these findings, further evaluations are warranted of AE37 and GP2 vaccines given in combination and/or separately for specific subsets of breast cancer patients based on their disease biology."
602,Vitamin B and Vitamin C Affect DNA Methylation and Amino Acid Metabolism in Mycobacterium bovis BCG,"Vitamins are essential nutrients and key cofactors of enzymes that regulate cellular metabolism, and also activate the immune system. Recent studies have shown that vitamin B1 (V(B)(1)) and vitamin C (Vc) can inhibit Mycobacterium tuberculosis growth, but the precise mechanism is still not well understood. In the present study, we have used RNA-sequencing (RNA-seq), liquid chromatography coupled to mass spectrometry (LC-MS) and single-molecule real-time (SMRT) sequencing to analyze the transcriptional, metabolic and methylation profiles of Mycobacterium bovis BCG when treated with V(B)(1) and Vc. Our results show that, after vitamin treatment, variant metabolites were mainly clustered in pathways related to amino acid metabolism. Treatment with both vitamins significantly up-regulated the gene encoding cysteine synthase A. Additionally, only BCG that was treated with V(C) showed m4c modifications. Genes harboring this methylation were up-regulated, suggesting that m4c methylation can promote gene transcription to some extent. Overall, this study contributes to the understanding of the effects of V(B)(1) and V(C), and suggests that these vitamins constitute potential anti-tuberculosis drugs."
603,Management in der Behandlung von Patienten nach Einsatz biologischer Agenzien,"The risk of terrorist attacks with weapons of mass destruction like biological agents is increasing. Biological agents can be disseminated as aerosols or by contaminating food and beverages. The multitude of agents and the different pathways of transmission cause very different clinical presentations. Natural infections with potential biological agents in Germany are rare and in most cases imported from endemic areas abroad. It is crucial to include these diseases in the spectrum of differential diagnosis. Local and state health departments have to be notified as early as possible in dubious cases. Public health management can be efficient only, if there is high reporting discipline and all epidemic measures are well coordinated."
604,Chloroquine and bafilomycin A mimic lysosomal storage disorders and impair mTORC1 signalling,"Autophagy is dependent upon lysosomes, which fuse with the autophagosome to complete the autophagic process and whose acidic interior permits the activity of their intraluminal degradative enzymes. Chloroquine (CQ) and bafilomycin A1 (BafA) each cause alkalinisation of the lumen and thus impair lysosomal function, although by distinct mechanisms. CQ diffuses into lysosomes and undergoes protonation, while BafA inhibits the ability of the vacuolar type H(+)-ATPase (v-ATPase) to transfer protons into the lysosome. In the present study, we examine the impact of CQ and BafA on the activity of mammalian target of rapamycin complex 1 (mTORC1), inhibition of which is an early step in promoting autophagy. We find each compound inhibits mTORC1 signalling, without affecting levels of protein components of the mTORC1 signalling pathway. Furthermore, these effects are not related to these agents’ capacity to inhibit autophagy or the reduction in amino acid supply from lysosomal proteolysis. Instead, our data indicate that the reduction in mTORC1 signalling appears to be due to the accumulation of lysosomal storage material. However, there are differences in responses to these agents, for instance, in their abilities to up-regulate direct targets of transcription factor EB (TFEB), a substrate of mTORC1 that drives transcription of many lysosomal and autophagy-related genes. Nonetheless, our data imply that widely used agents that alkalinise intralysosomal pH are mimetics of acute lysosomal storage disorders (LSDs) and emphasise the importance of considering the result of CQ and BafA on mTORC1 signalling when interpreting the effects of these agents on cellular physiology."
605,Preparing undergraduate students for clinical work in a complex environment: evaluation of an e-learning module on physiotherapy in the intensive care unit,"BACKGROUND: Intensive Care Units (ICUs) are daunting environments for physiotherapy (PT) students performing clinical rotations. To prepare students for this environment, a newly developed, evidence-based e-learning module was designed and implemented in the undergraduate curriculum. The aim of this study was to investigate whether e-learning is a feasible method in preparing PT students for clinical work in complex ICU environments, as perceived by students and experts. METHODS: A mixed methods proof of concept study was undertaken. Participants were final-year students of an international curriculum, and experts from didactic and clinical fields. An e-learning module consisting of 7 separate chapters based on the latest scientific evidence and clinical expertise was developed, piloted and incorporated into the undergraduate curriculum as a compulsory course to be completed prior to clinical ICU rotations. Data were collected through 3 focus group meetings and 5 semi-structured interviews; these meetings and interviews were audio recorded, transcribed verbatim and analyzed. RESULTS: The study sample comprised of 14 students and 5 experts. Thematic analysis revealed three themes: expected competencies of PT students in ICU, feeling prepared for ICU clinical work and dealing with local variety. The e-learning module enabled students to anticipate clinical situations and PT tasks in the ICU. Higher level clinical reasoning skills, handling of lines and wires and dealing with out-of-textbook situations could not be achieved with the e-learning module alone. CONCLUSIONS: An e-learning module can sufficiently prepare PT students for their clinical tasks in the ICU, as long as it is integrated with, or closely connected to, the students’ clinical placement."
606,General Adaptation in Critical Illness: Glucocorticoid Receptor-alpha Master Regulator of Homeostatic Corrections,"In critical illness, homeostatic corrections representing the culmination of hundreds of millions of years of evolution, are modulated by the activated glucocorticoid receptor alpha (GRα) and are associated with an enormous bioenergetic and metabolic cost. Appreciation of how homeostatic corrections work and how they evolved provides a conceptual framework to understand the complex pathobiology of critical illness. Emerging literature place the activated GRα at the center of all phases of disease development and resolution, including activation and re-enforcement of innate immunity, downregulation of pro-inflammatory transcription factors, and restoration of anatomy and function. By the time critically ill patients necessitate vital organ support for survival, they have reached near exhaustion or exhaustion of neuroendocrine homeostatic compensation, cell bio-energetic and adaptation functions, and reserves of vital micronutrients. We review how critical illness-related corticosteroid insufficiency, mitochondrial dysfunction/damage, and hypovitaminosis collectively interact to accelerate an anti-homeostatic active process of natural selection. Importantly, the allostatic overload imposed by these homeostatic corrections impacts negatively on both acute and long-term morbidity and mortality. Since the bioenergetic and metabolic reserves to support homeostatic corrections are time-limited, early interventions should be directed at increasing GRα and mitochondria number and function. Present understanding of the activated GC-GRα's role in immunomodulation and disease resolution should be taken into account when re-evaluating how to administer glucocorticoid treatment and co-interventions to improve cellular responsiveness. The activated GRα interdependence with functional mitochondria and three vitamin reserves (B1, C, and D) provides a rationale for co-interventions that include prolonged glucocorticoid treatment in association with rapid correction of hypovitaminosis."
607,Mitteilungen des GRC,
608,Mitteilungen der agswn,
609,Nebenwirkungen neuer onkologischer Immuntherapien,"Systemic treatment with immune checkpoint inhibitors (ICI) has revolutionized the treatment of hematological and oncological diseases in recent years. The mechanism of action hinges on enhancing the natural ability of the immune system to eliminate malignant cells. The most important substances in this arena include inhibitors of PD‑1, PD-L1 and CTLA‑4. As a consequence, the spectrum of treatment-associated adverse reactions is shifting away from classical cytotoxic effects (e.g. pancytopenia and polyneuropathy) towards novel entities of immune-mediated complex diseases. These so-called immune-related adverse events (irAEs) can involve any organ system and mimic known classical autoimmune conditions. Timely recognition of irAEs is the key for rapid initiation of a suitable treatment and is especially challenging in the clinical routine as it requires an intensive interdisciplinary management. Nephrologists are particularly confronted with this kind of problem due to the highly interdisciplinary nature of their work. This article summarizes the broad spectrum of currently known renal and more frequently occuring non-renal forms of irAEs and aims to prime the reader on diagnostic and therapeutic options."
610,A Mathematical Framework for Predicting Lifestyles of Viral Pathogens,"Despite being similar in structure, functioning, and size, viral pathogens enjoy very different, usually well-defined ways of life. They occupy their hosts for a few days (influenza), for a few weeks (measles), or even lifelong (HCV), which manifests in acute or chronic infections. The various transmission routes (airborne, via direct physical contact, etc.), degrees of infectiousness (referring to the viral load required for transmission), antigenic variation/immune escape and virulence define further aspects of pathogenic lifestyles. To survive, pathogens must infect new hosts; the success determines their fitness. Infection happens with a certain likelihood during contact of hosts, where contact can also be mediated by vectors. Besides structural aspects of the host-contact network, three parameters appear to be key: the contact rate and the infectiousness during contact, which encode the mode of transmission, and third the immunity of susceptible hosts. On these grounds, what can be said about the reproductive success of viral pathogens? This is the biological question addressed in this paper. The answer extends earlier results of the author and makes explicit connection to another basic work on the evolution of pathogens. A mathematical framework is presented that models intra- and inter-host dynamics in a minimalistic but unified fashion covering a broad spectrum of viral pathogens, including those that cause flu-like infections, childhood diseases, and sexually transmitted infections. These pathogens turn out as local maxima of numerically simulated fitness landscapes. The models involve differential and integral equations, agent-based simulation, networks, and probability."
611,Mitteilungen der DGINA,
612,Toward minimal bacterial cells: evolution vs. design,"Recent technical and conceptual advances in the biological sciences opened the possibility of the construction of newly designed cells. In this paper we review the state of the art of cell engineering in the context of genome research, paying particular attention to what we can learn on naturally reduced genomes from either symbiotic or free living bacteria. Different minimal hypothetically viable cells can be defined on the basis of several computational and experimental approaches. Projects aiming at simplifying living cells converge with efforts to make synthetic genomes for minimal cells. The panorama of this particular view of synthetic biology lead us to consider the use of defined minimal cells to be applied in biomedical, bioremediation, or bioenergy application by taking advantage of existing naturally minimized cells."
613,The curious case of COVID-19 in children,
614,The distress of Iranian adults during the Covid-19 pandemic – More distressed than the Chinese and with different predictors,
615,Bacterial insertion sequences: their genomic impact and diversity,"Insertion sequences (ISs), arguably the smallest and most numerous autonomous transposable elements (TEs), are important players in shaping their host genomes. This review focuses on prokaryotic ISs. We discuss IS distribution and impact on genome evolution. We also examine their effects on gene expression, especially their role in activating neighbouring genes, a phenomenon of particular importance in the recent upsurge of bacterial antibiotic resistance. We explain how ISs are identified and classified into families by a combination of characteristics including their transposases (Tpases), their overall genetic organisation and the accessory genes which some ISs carry. We then describe the organisation of autonomous and nonautonomous IS‐related elements. This is used to illustrate the growing recognition that the boundaries between different types of mobile element are becoming increasingly difficult to define as more are being identified. We review the known Tpase types, their different catalytic activities used in cleaving and rejoining DNA strands during transposition, their organisation into functional domains and the role of this in regulation. Finally, we consider examples of prokaryotic IS domestication. In a more speculative section, we discuss the necessity of constructing more quantitative dynamic models to fully appreciate the continuing impact of TEs on prokaryotic populations."
616,Candidemia following solid organ transplantation in the era of antifungal prophylaxis: the Australian experience,"Abstract: Solid organ transplant (SOT) recipients have high rates of invasive fungal infections, with Candida species the most commonly isolated fungi. The aim of this study was to identify differences between incidence rates, risk factors, clinical presentations, and outcomes of candidemia in SOT recipients and non‐SOT patients. Data from the multicenter prospective Australian Candidaemia Study were examined. From August 2001 to July 2004, 24 episodes (2.2%; 24/1068) of candidemia were identified in SOT recipients. During this period, the numbers of transplanted organs included liver (n=455), kidney (n=1605), single lung (n=57), bilateral lung (n=183), heart and lung (n=18), heart (n=157), and pancreas (n=62). The overall annual estimated incidence of candidemia in SOT recipients was higher (3 per 1000 transplant admissions) than in non‐SOT patients (incidence 0.21 per 1000 admissions; P<0.001). The incidence and timing of candidemia post transplant was influenced by the transplanted organ type, with the majority of episodes (n=14, 54%) occurring >6 months after renal transplantation. Risk factors for candidemia in the month preceding diagnosis were similar to non‐SOT recipients except for corticosteroid therapy (P<0.001). Antifungal prophylaxis did not select for more resistant or non‐albicans Candida species in the SOT group. The 30‐day all‐cause mortality was similar to non‐SOT patients with candidemia and remains high at 21%. All deaths in SOT recipients occurred early (within 5 days of diagnosis), underlining a need for better diagnostic tests, targeted prevention, and early treatment strategies."
617,New ethnicities online: reflexive racialisation and the internet,"In this article we analyse the emergence of Internet activity addressing the experiences of young people in two British communities: South Asian and Chinese. We focus on two web sites: http://www.barficulture.com and http://www.britishbornchinese.org.uk, drawing on interviews with site editors, content analysis of the discussion forums, and E‐mail exchanges with site users. Our analysis of these two web sites shows how collective identities still matter, being redefined rather than erased by online interaction. We understand the site content through the notion of reflexive racialisation. We use this term to modify the stress given to individualisation in accounts of reflexive modernisation. In addition we question the allocation of racialised meaning from above implied by the concept of racialisation. Internet discussion forums can act as witnesses to social inequalities and through sharing experiences of racism and marginalisation, an oppositional social perspective may develop. The online exchanges have had offline consequences: social gatherings, charitable donations and campaigns against adverse media representations. These web sites have begun to change the terms of engagement between these ethnic groups and the wider society, and they have considerable potential to develop new forms of social action."
618,"Immunoglobulin G, A, and M Light Chain Ratios in some Humoral Immunological Disorders","The total kappa/lambda immunoglobulin light chain ratio and the kappa/lambda ratios within each of the serum immunoglobulin classes G. A. and M were measured in thirteen patients with humoral immunological disorders. Of those patients, eight had common variable immunodeficiency whereas live patients had other forms of humoral immunological deficiencies. Eleven patients had abnormal antibody response in vivo. All but three of the thirteen patients had clearly abnormal light chain ratios in one or more of the immunoglobulin classes. We conclude that humoral immunological disorders, usually characterized by abnormal heavy chain production and a disturbed antibody response, may frequently have a concomitant abnormal synthesis of the light chains resulting in an abnormal kappa/lambda light chain ratio."
619,Interferon‐α Production and Tissue Localization of Interferon‐α/β Producing Cells after Intradermal Administration of Aujeszky's Disease Virus–Infected Cells in Pigs,"Intradermal administration of glutaraldehyde–fixed Aujeszky's disease virus (ADV) infected autologous or allogeneic cells resulted in the induction of an interferon(IFN)–α/β response in pigs. Using a sensitive dissociation–enhanced lanthanide fluoroimmunoassay (DELFIA), IFN–α/β was detected in blood at 8 and 24 h after injection of ADV–infected cells. In parallel, by means of in situ hybridization, IFN–α/β mRNA containing cells were demonstrated in regional lymph nodes. Occasional IFN–α/β mRNA positive cells were also seen in injected dermal areas, but not in contralateral lymph nodes, spleen, bone marrow, blood or liver. The ability of leucocytes in whole blood cultures to produce IFN–α/β upon stimulation by ADV was markedly diminished 3–7 days after intradermal injection of ADV–infected cells. In contrast, cultures of purified peripheral blood mononuclear cells (PBMC) had intact IFN–α/β responses. Further, serum from ADV–injected pigs inhibited the in vitro ADV–induced IFN‐α/β responses in PBMC from control pigs, most likely due to the demonstrated presence of anti–ADV antibodies. We suggest that the IFN‐α/β producing cells in lymph nodes may participate in the development of antiviral immunity and could be equivalent to Natural IFN–α/β producing (NIP) cells."
620,Apneic Oxygenation for Emergency Intubations in the Pediatric Emergency Department—A Quality Improvement Initiative,"INTRODUCTION: Emergency airway management of critically ill children in the Emergency Department (ED) is associated with the risk of intubation-related desaturation, which can be minimized by apneic oxygenation. We evaluated the use of apneic oxygenation in the pediatric ED and reported a quality improvement initiative to incorporate apneic oxygenation as a routine standard of care during rapid sequence intubations (RSIs). METHODS: A baseline period from June 2016 to April 2017 highlighted the practice gaps. Quality improvement interventions were subsequently developed and implemented as a care bundle consisting of a pre-intubation checklist, placing reminders and additional oxygen source in resuscitation bays, incorporating into the responsibilities of the airway doctor and the airway nurse (copiloting), education during airway workshops and simulation training for doctors and nurses, as well as enhancing documentation of the intubation process. We monitored a post-intervention observation period from May 2017 to April 2018 for the effectiveness of the care bundle. RESULTS: Apneic oxygenation was not performed in all 22 RSIs during the baseline period. Among 25 RSIs in the post-intervention observation period, providers performed apneic oxygenation in 17 (68%) cases. There was no significant difference in the utilization of apneic oxygenation among emergency physicians and pediatric anesthetists performing RSIs in the pediatric ED. CONCLUSIONS: We successfully implemented a care bundle targeted at incorporating apneic oxygenation as a routine standard of care during emergency intubations performed in ED. This method could be adopted by other pediatric EDs to improve airway management in critically ill children."
621,Schedule-based Family-centered Rounds: A Novel Approach to Achieve High Nursing Attendance and Participation,"INTRODUCTION: Bedside nurse (RN) presence during family-centered rounds (FCR) enhances communication and collaboration for safer, higher-quality care.1–3 At our institution, RN participation in FCR was variable and lower than desired. The content discussed at each bedside during rounds was inconsistent, contributing to the irregular achievement of established FCR checklist items. METHODS: Using a scheduling tool with a prioritization algorithm and set time allotment/patient, we implemented schedule-based family-centered rounds (SBFCR) on a pediatric acute care unit. Primary outcome metrics included RN attendance and participation. We tracked rounding checklist compliance, parent presence on rounds, and adherence to the schedule. Surveys provided information on provider and family satisfaction. Perceived impact on teaching was the balancing measure because the structure discouraged spending extra time at the cost of team tardiness for the next patient. RESULTS: We created a schedule for 95% workweek days, with the rounding order kept for 93%. Mean RN attendance increased from 69% to 87% and participation increased from 48% to 80% with SBFCR (P < 0.001 for each). FCR checklist compliance increased from 60% to 94% (P < 0.001). Families felt more informed and able to attend; their presence at rounds rose from 66% to 85% (P < 0.001). Most faculty and trainees felt SBFCR was efficient and observed increased teaching with SBFCR. CONCLUSIONS: SBFCR provides an organizational framework for increased RN attendance and participation as well as greater family presence during rounds. The system elevated provider satisfaction with rounding without degrading the perceived educational experience."
622,Key Drivers in Reducing Hospital-acquired Pressure Injury at a Quaternary Children’s Hospital,"INTRODUCTION: Despite being a participating Solutions for Patient Safety (SPS) children’s hospital and having attempted implementation of the SPS hospital-acquired pressure injuries (HAPIs) prevention bundle, our hospital remained at a HAPI rate that was 3 times the mean for SPS participating children’s hospitals. This performance led to the launch of an enterprise-wide HAPI reduction initiative in our organization. The purpose of this article is to describe the improvement initiative, the key drivers, and the resulting decrease in the SPS-reportable HAPI rate. METHODS: We designed a hospital-wide HAPI reduction initiative with actions grouped into 3 key driver areas: standardization, data transparency, and accountability. We paused all individual hospital unit-based HAPI reduction initiatives. We calculated the rate of SPS-reportable HAPIs per 1,000 patient days during both the pre- and postimplementation phases and compared mean rates using a 2-sided t test assuming unequal variances. RESULTS: The mean SPS-reportable HAPI rate for the preimplementation phase was 0.3489, and the postimplementation phase was 0.0609. The difference in rates was statistically significant (P < 0.00032). This result equates to an 82.5% reduction in HAPI rate. CONCLUSIONS: Having an institutional pause and retooled initiative to reduce HAPI with key drivers in the areas of standardization, data transparency, and accountability had a statistically significant reduction in our organization’s SPS-reportable HAPI rate."
623,Retrospective Review of the Safety and Efficacy of Virtual Reality in a Pediatric Hospital,"INTRODUCTION: Virtual reality (VR) is an emerging tool for anxiety and fear reduction in pediatric patients. VR use is facilitated by Certified Child Life Specialists (CCLS) at pediatric hospitals. The primary aim of this study was to retrospectively review the safety of VR by analyzing adverse events after the utilization of VR under CCLS supervision. Secondary objectives were to characterize the efficacy of VR in enhancing patient cooperation, describe the integration of VR into Child Life services, and identify interventions that accompanied VR. METHODS: The Stanford Chariot Program developed VR applications, customized VR interfaces, and patient head straps, and distributed these to CCLS. Chart review analyzed VR utilization through CCLS patient notes. Inclusion criteria were all patients ages 6 to 18-years-old who received a Child Life intervention. RESULTS: From June 2017 to July 2018, 31 CCLS saw 8,098 patients, 3,696 of which met age criteria with pre- and post-intervention cooperation data. Two hundred thirteen patients received VR with an accompanying intervention, while 34 patients received only VR. Adverse events were rare, and included increased anxiety (3.8%, n=8), dizziness (0.5%, n=1), and nausea (0.5%, n=1). Patients were more likely to be cooperative after receiving VR (99.5%, n=212) compared to pre-intervention (96.7%, n=206, p=0.041). VR use was most common in the perioperative setting (60%, n=128), followed by outpatient clinics (15%, n=32). CONCLUSION: VR is safe in pediatric patients with appropriate hardware, software, and patient selection. Side effects were rare and self-limited. VR appears to be associated with improvements in cooperation."
624,A Three-part Quality Improvement Initiative to Increase Patient Satisfaction and Reduce Appointment Time,"INTRODUCTION: PediPlace, a busy pediatric not-for-profit clinic in Lewisville, Tex., struggles with prolonged patient wait times. This quality improvement (QI) project aimed to reduce appointment lengths and improve the patient experience. METHODS: PediPlace introduced 3 interventions: improved patient tracking to measure timing on the electronic health record interface, elimination of script repetition between medical assistants and providers, and patient art kits. RESULTS: From over 2,000 surveys indicated that patients were more satisfied; the percentage of negative survey comments decreased from 20% in 2017 and 2018 to under 10% in 2019. The overall rating of the clinic rose from 3.8 to 4.75 (on a scale of 1–5) after QI interventions as well. The number of patients not checked out declined from 49 errors in October–December 2018 to 25 errors in January–March 2019, indicating that this part of the initiative was initially successful. However, subsequent months experienced higher error rates. Analysis of over 20,000 appointments from June 2018 to July 2019 showed that appointment length did not change after interventions. CONCLUSIONS: There was no difference in appointment lengths between Hispanic/Latino patients and other patients, and an encouraging finding that suggests PediPlace providers are effective bilingual communicators. Furthermore, anecdotal evidence indicated that the art kits were positively received. The interventions appeared to improve the patient experience but did not impact appointment length. PediPlace plans to continue QI initiatives in the future."
625,Establishing Standardized Documentation for Anaphylaxis Treatment in a Tertiary Care Pediatric Allergy Clinic,"INTRODUCTION: Anaphylaxis is a potentially life-threatening allergic reaction. Common allergy clinic procedures, including oral food challenges and subcutaneous immunotherapy, carry a risk of anaphylaxis, the treatment for which is epinephrine. Our goal was to develop a standardized process for the management and documentation of allergic reactions that occur in a tertiary care pediatric allergy clinic. METHODS: This was a single institution quality improvement pilot study. A multidisciplinary team from the allergy department designed, implemented, and studied the use of a standardized form for the documentation and treatment of allergic reactions within the clinic. RESULTS: A standardized form was developed based on evidence-based guidelines for the management of allergic reactions and included space for documentation. Both clinic providers and staff approved the form. One year after the introduction, we reached 100% adherence for the use of the form in visits during which a patient experienced a severe allergic reaction requiring epinephrine. Two patients required transfer to the emergency room; the quality improvement form was utilized in these cases to document treatment and assist with the hand-off to emergency room personnel before transfer. CONCLUSIONS: We successfully implemented a standardized form for the treatment and documentation of anaphylaxis within our allergy clinic. The next steps focus on further integrating this form into the electronic medical record, determining compliance with evidence-based management of anaphylaxis, and formally assessing the use of the form as a handoff tool in the event of patient transfer."
626,Pediatric Clinician Comfort Discussing Diagnostic Errors for Improving Patient Safety: A Survey,"INTRODUCTION: Meaningful conversations about diagnostic errors require safety cultures where clinicians are comfortable discussing errors openly. However, clinician comfort discussing diagnostic errors publicly and barriers to these discussions remain unexplored. We compared clinicians’ comfort discussing diagnostic errors to other medical errors and identified barriers to open discussion. METHODS: Pediatric clinicians at 4 hospitals were surveyed between May and June 2018. The survey assessed respondents’ comfort discussing medical errors (with varying degrees of system versus individual clinician responsibility) during morbidity and mortality conferences and privately with peers. Respondents reported the most significant barriers to discussing diagnostic errors publicly. Poststratification weighting accounted for nonresponse bias; the Benjamini–Hochberg adjustment was applied to control for false discovery (significance set at P < 0.018). RESULTS: Clinicians (n = 838; response rate 22.6%) were significantly less comfortable discussing all error types during morbidity and mortality conferences than privately (P < 0.004) and significantly less comfortable discussing diagnostic errors compared with other medical errors (P < 0.018). Comfort did not differ by clinician type or years in practice; clinicians at one institution were significantly less comfortable discussing diagnostic errors compared with peers at other institutions. The most frequently cited barriers to discussing diagnostic errors publicly included feeling like a bad clinician, loss of reputation, and peer judgment of knowledge base and decision-making. CONCLUSIONS: Clinicians are more uncomfortable discussing diagnostic errors than other types of medical errors. The most frequent barriers involve the public perception of clinical performance. Addressing this aspect of safety culture may improve clinician participation in efforts to reduce harm from diagnostic errors."
627,Decreasing Usage of Lights and Sirens in an Urban Environment: A Quality Improvement Project,"INTRODUCTION: The risk of lights and sirens use in emergency medical services has been well documented. Our critical care transport team performs over 1,800 interfacility nonemergency medical services transports annually into a dense urban environment. Historically, we have utilized lights and sirens to navigate traffic patterns. The use exceeded industry standards. This quality improvement project was undertaken to decrease the use of lights and sirens. METHODS/RESULTS: The baseline use of lights and sirens in 2011 was 76% en route and 73% on return to the facility. We revised the internal policy guiding the appropriate usage of lights and sirens. In 2012, without an improvement in usage, a use justification process was implemented. By 2013, the use of lights and sirens was still high en route, but had decreased to 53% on the return trip. In 2014, we added accountability measures requiring justification, with a subsequent drop in 2015 to 14% en route and 13% on return. In the following 3 years, the transport teams have sustained lights and sirens use to 20% or below. CONCLUSIONS: This quality improvement initiative impacted team behavior and decreased the use of lights and sirens over 5 years, with sustained improvement at or below 20%. This improvement was accomplished through ongoing evaluation, education, data gathering, and open communication. There was no negative impact on patient outcomes during this time. Lights and sirens continue to be used when indicated."
628,ED RAPID: A Novel Children’s Hospital Direct Admission Process Utilizing the Emergency Department,"INTRODUCTION: Direct hospital admission of children without evaluation in the emergency department (ED) is common, but few guidelines exist to maximize safety by assessing patient stability. This report describes a novel approach to support patient safety. METHODS: An interdisciplinary children’s hospital team developed a brief ED-based evaluation process called the ED Rapid Assessment of Patients Intended for Inpatient Disposition (ED RAPID). It entails a brief evaluation of vital signs and clinical stability by the ED attending physician and nurse. Children deemed stable are admitted to inpatient wards, whereas those requiring immediate intervention undergo full ED evaluation and disposition. We assessed outcomes for all children evaluated through this process from March 2013 through February 2015. RESULTS: During the study period, we identified 715 patients undergoing ED RAPID evaluation. Of these, we directly admitted 691 (96.4%) to the hospital ward after ED RAPID evaluation; median ED treatment time was 4.0 minutes. We transitioned 24 (3.4%) to full ED evaluation, 14 (2.0%) because a ward bed was unavailable, and 10 (1.4%) for clinical reasons identified in the evaluation. We admitted four of the 10 stopped (40% of stops, 0.6% of total) to an intensive care unit, and 6 (60% of stops, 0.8% of total) to the hospital ward after ED care. Eight children (1.1%) admitted to the hospital ward after ED RAPID evaluation required a transfer to an intensive care unit within 12 hours. CONCLUSION: The ED RAPID evaluation process for children directly admitted to the hospital was feasible and effective in this setting."
629,AutoPEWS: Automating Pediatric Early Warning Score Calculation Improves Accuracy Without Sacrificing Predictive Ability,"INTRODUCTION: Pediatric early warning scores (PEWS) identify hospitalized children at risk for deterioration. Manual calculation is prone to human error. Electronic health records (EHRs) enable automated calculation, removing human error. This study’s objective was to compare the accuracy of automated EHR-based PEWS calculation (AutoPEWS) to manual calculation and evaluate the non-inferiority of AutoPEWS in predicting deterioration. METHODS: We performed a retrospective cohort study inclusive of non-intensive care unit inpatients at a freestanding children’s hospital over 4.5 months in Fall 2018. AutoPEWS mapped the historical manual PEWS scoring rubric to frequently used EHR documentation. We determined accuracy by comparing the expected respiratory subset score based on the current respiratory rate to the actual respiratory score of AutoPEWS and the manual PEWS. The agreement was determined using kappa statistics. We used predicted probabilities from a generalized linear mixed model to calculate areas under the curve for each combination of scores (AutoPEWS, manual) and deterioration outcome (rapid response team activation, unplanned intensive care unit transfer, critical deterioration event). We compared the adjusted difference in areas under the curves between the scores. Non-inferiority was defined as a difference of <0.05. RESULTS: There were 23,514 total PEWS representative of 5,384 patients. AutoPEWS respiratory scores were 99.97% accurate, while the manual PEWS respiratory scores were 86% accurate. AutoPEWS were higher overall than the manual PEWS (mean 0.65 versus 0.34). They showed a fair-to-good agreement (weighted kappa 0.42). Non-inferiority of AutoPEWS compared with the manual PEWS was demonstrated for all deterioration outcomes. CONCLUSIONS: Automation of PEWS calculation improved accuracy without sacrificing predictive ability."
630,Economic Evaluation: Onsite HSV PCR Capabilities for Pediatric Care,"OBJECTIVE: Herpes simplex virus (HSV) encephalitis has an overall mortality rate of 11%–29% with treatment. Although rare, HSV encephalitis is frequently tested for and empirically treated, especially in the neonatal population. HSV infection can be diagnosed with polymerase chain reaction (PCR) testing, although this frequently requires sending samples to reference laboratories. The inherent delay in results may lead to prolonging empiric treatment and hospital stay, resulting in increased costs. This study investigates whether onsite HSV PCR testing decreases hospitalization duration, acyclovir treatment duration, and financial cost on an institution. PROJECT DESIGN: This single-center project utilized the IHI model for improvement to evaluate third-party HSV PCR processing versus an implemented onsite PCR-based meningitis–encephalitis panel for HSV central nervous system evaluation. The primary outcome was hospital cost differential with secondary outcomes, including duration of acyclovir administration and time to result. RESULTS: We identified 96 children age 0–18 from 2010 to 2016, 74 patients utilizing offsite third-party testing, and 22 patients utilizing onsite. We observed a per-patient cost savings of $428 ($618.43–$190.43, P = 0.029) upon the implementation of onsite testing. The mean duration of acyclovir therapy decreased from 3.7 to 0.26 days per patient (P < 0.001). Time to result decreased from 4.6 to 0.13 days (P < 0.001). CONCLUSIONS: Acquisition of real-time local HSV PCR capabilities significantly decreased time to result and empiric medication use while significantly reducing hospital costs in a military treatment facility."
631,Decreasing Chronic Lung Disease Associated with Bubble CPAP Technology: Experience at Five Years,"INTRODUCTION: Bubble continuous positive airway pressure (bCPAP) is associated with a decreased risk for chronic lung disease (CLD) in preterm neonates. This report examined the effectiveness of adopting bCPAP to reduce respiratory complications and medication usage in a community hospital NICU. METHODS: The efficacy of bCPAP was assessed by retrospective examination and comparison of 45 neonates who received bCPAP and 87 neonates who received conventional ventilation only. Data on medication usage were also collected and analyzed. RESULTS: After introduction of the bCPAP protocol, the median number of days on oxygen decreased in the bCPAP group compared with the conventional ventilation only group (median = 33 days, IQR = 7.5–66 vs median = 0, IQR = 0–0; P < 0.001). The exposure to conventional ventilation decreased in the bCPAP group compared with the conventional ventilation only group (median = 18 days, IQR = 5–42.5 vs median = 0, IQR = 0–7; P < 0.001). Postimplementation of bCPAP revealed decreases in CLD from 26 (30%) in the conventional ventilation only group to 2 (4%) in the bCPAP group (P = 0.002); there was also a significant decrease in the use of sedative medications in the bCPAP group compared with the conventional ventilation only group (mean = 5.20 doses, SD = 31.97 vs mean = 1.43, SD = 9.98; P < 0.001). CONCLUSION: The use of bCPAP results in significant decreases in the use of conventional ventilation, the risk for CLD, and the need for sedative medication."
632,A Quality Improvement Intervention Bundle to Reduce 30-Day Pediatric Readmissions,"INTRODUCTION: Pediatric hospital readmissions can represent gaps in care quality between discharge and follow-up, including social factors not typically addressed by hospitals. This study aimed to reduce the 30-day pediatric readmission rate on 2 general pediatric services through an intervention to enhance care spanning the hospital stay, discharge, and follow-up process. METHODS: A multidisciplinary team developed an intervention bundle based on a needs assessment and evidence-based models of transitional care. The intervention included pre-discharge planning with a transition coordinator, screening and intervention for adverse social determinants of health (SDH), medication reconciliation after discharge, communication with the primary care provider, access to a hospital-based transition clinic, and access to a 24-hour direct telephone line staffed by hospital attending pediatricians. These were implemented sequentially from October 2013 to February 2017. The primary outcome was the readmission rate within 30 days of index discharge. The length of stay was a balancing measure. RESULTS: During the intervention, the included services discharged 4,853 children. The pre-implementation readmission rate of 10.3% declined to 7.4% and remained stable during a 4-month post-intervention observation period. Among 1,394 families screened for adverse SDH, 48% reported and received assistance with ≥ 1 concern. The length of stay increased from 4.10 days in 2013 to 4.30 days in 2017. CONCLUSIONS: An intervention bundle, including SDH, was associated with a sustained reduction in readmission rates to 2 general pediatric services. Transitional care that addresses multiple domains of family need during a child’s health crisis can help reduce pediatric readmissions."
633,Survey-based Work System Assessment to Facilitate Large-scale Dissemination of Healthcare Quality Improvement Programs,"INTRODUCTION: The dissemination of quality improvement (QI) interventions to a broader range of healthcare settings requires a proactive assessment of local work systems and processes. The objective of this study was to examine the feasibility of using a survey-based work system assessment (WSA) tool to facilitate the dissemination of a program for optimizing blood culture (BC) use. METHODS: Informed by findings from an onsite, interview-based WSA at 2 hospitals, a 50-item WSA survey was devised and administrated to 15 hospitals participating in a QI collaborative. WSA survey data were summarized, shared, and discussed with individual hospitals to inform the adaptation and implementation of the BC program. Physician champions leading the local QI team assessed the use of the WSA survey by completing an 8-item survey. RESULTS: A total of 347 clinicians completed the WSA survey, and physician champions at 12 hospitals evaluated the use of the WSA survey. Both the WSA survey data and the evaluation of the WSA survey showed that the survey-based WSA tool could help participating hospitals understand their current BC ordering practices and identify potential barriers to implementing the program from the perspectives of different clinicians. CONCLUSIONS: We demonstrated how a survey-based tool could be used to facilitate WSA in the dissemination of a program for improving BC use to a multisite collaborative. A survey-based WSA tool can be used to facilitate future large-scale intervention dissemination efforts."
634,Qualitative Study to Understand Pediatric Hospitalists and Emergency Medicine Physicians’ Perspectives of Clinical Pathways,"INTRODUCTION: Healthcare costs are rising, and clinical pathways (CPW) are one means to promote high-value care by standardizing care and improving outcomes without compromising cost or quality. However, providers do not always follow CPW, and our understanding of their perceptions is limited. Our objective was to examine pediatric hospital medicine (PHM) and pediatric emergency medicine (PEM) physician perspectives of CPW. METHODS: We conducted semistructured, in-depth, one-on-one qualitative interviews with PHM and PEM physicians between February 2017 and August 2017. Interviews were audio-recorded, professionally transcribed, and accuracy verified. Using an inductive analytic strategy, we systematically coded the data to identify themes. RESULTS: We interviewed 15 PHM and 15 PEM physicians. These providers identified many benefits and limitations of CPW, which positively or negatively impact resource utilization, communication, education of personnel, patients, and families, as well as practice behaviors and attitudes. Perceived benefits included (1) reduction of unnecessary utilization, (2) standardization of care, (3) improved communication, (4) education of oneself and others, and (5) confidence and validation when actions align with CPW. Limitations of CPW were (1) resource utilization for revisions, updates, and dissemination; (2) “tunnel vision” and cognitive biases; (3) loss of autonomy; (4) prescriptive medicine; (5) information overload; (6) pressure to adhere; and (7) guilt if actions do not align with CPW. CONCLUSIONS: CPW are tools with advantages and disadvantages that are used and viewed differently by providers. Such insight into how physicians perceive CPW may help to optimize hospital improvement work and enhance high-value care."
635,Handoff Communication between Remote Healthcare Facilities,"INTRODUCTION: Handoffs and transitions of care are common weak points in healthcare provider communication as patients move between sites. With no consistent pattern of communication between St. Jude Children’s Research Hospital (St. Jude) and its affiliated clinics, the Affiliate Program Office at St. Jude developed and implemented a standardized communication tool to facilitate patient transitions between different healthcare sites. METHODS: Each team of providers created flow diagrams to define the current state of communication when patients were transitioning between remote sites. Fishbone diagrams identified the common barriers to effective communication as a lack of consistent communication and ownership. We developed a communication tool to address these barriers, which was disseminated by secure email. We measured the percent usage of the completed hand-off tool before a patient transitioned, staff experience, and the number of errors. RESULTS: The time to send or receive the communication bundle was <10 minutes. Within 3 months of implementing the SMART bundle at 3 pilot sites, the bundle was used completely in 6 of 8 patient transitions and was associated with somewhat improved staff satisfaction. We identified no adverse events related to the communication bundle. CONCLUSIONS: In this small pilot study, we accomplished closed-loop communication between geographically remote healthcare sites by using an electronically transmitted standardized communication bundle."
636,The Vitals Risk Index—Retrospective Performance Analysis of an Automated and Objective Pediatric Early Warning System,"INTRODUCTION: Pediatric in-hospital cardiac arrests and emergent transfers to the pediatric intensive care unit (ICU) represent a serious patient safety concern with associated increased morbidity and mortality. Some institutions have turned to the electronic health record and predictive analytics in search of earlier and more accurate detection of patients at risk for decompensation. METHODS: Objective electronic health record data from 2011 to 2017 was utilized to develop an automated early warning system score aimed at identifying hospitalized children at risk of clinical deterioration. Five vital sign measurements and supplemental oxygen requirement data were used to build the Vitals Risk Index (VRI) model, using multivariate logistic regression. We compared the VRI to the hospital’s existing early warning system, an adaptation of Monaghan’s Pediatric Early Warning Score system (PEWS). The patient population included hospitalized children 18 years of age and younger while being cared for outside of the ICU. This dataset included 158 case hospitalizations (102 emergent transfers to the ICU and 56 “code blue” events) and 135,597 control hospitalizations. RESULTS: When identifying deteriorating patients 2 hours before an event, there was no significant difference between Pediatric Early Warning Score and VRI’s areas under the receiver operating characteristic curve at false-positive rates ≤ 10% (pAUC(10) of 0.065 and 0.064, respectively; P = 0.74), a threshold chosen to compare the 2 approaches under clinically tolerable false-positive rates. CONCLUSIONS: The VRI represents an objective, simple, and automated predictive analytics tool for identifying hospitalized pediatric patients at risk of deteriorating outside of the ICU setting."
637,Improving Accuracy and Timeliness of Nursing Documentation of Pediatric Early Warning Scores,"INTRODUCTION: Accurate and timely documentation of pediatric early warning scores (PEWS) by the bedside nurse into the electronic health record (EHR) is important to promote early identification of patients in stages of deterioration. Through the implementation of a PEWS calculator embedded in the EHR, we hope to improve the accuracy of the recorded score and reduce the time between vital sign collection and final documentation in the EHR. METHODS: Identification of the highest PEWS value in the 24 hours before all unplanned transfers or rapid response activations without a transfer occurred between the period November 1, 2013, through December 31, 2016. The accuracy of the calculated cardiac or respiratory subscore based on heart rate or the respiratory rate at the time of PEWS calculation was determined. We tracked the calculation of the time to chart via the difference between nursing documentation of PEWS compared to vital sign collection. Before September 3, 2015, PEWS was calculated mentally by the bedside nurse; afterward, the nurse entered the unique PEWS features into the EHR, and the EHR automatically calculated PEWS. RESULTS: This study evaluated 2,409 PEWS scores, 1,411 before and 998 after initiation of the PEWS calculator. Accuracy before the EHR calculator was 71%, and the median time to document was 55 minutes. Following the implementation of the calculator, no scores were incorrectly calculated too low, and the median time to document was 20 minutes. CONCLUSIONS: Transition to an EHR-based PEWS calculator eliminated inaccurately low PEWS values and reduced time to document."
638,Improving Disposition Decision-Making for Pediatric Diabetic Ketoacidosis: A Quality Improvement Study,"INTRODUCTION: In many centers, children with diabetic ketoacidosis (DKA) receive care either in an endocrinology ward or a pediatric intensive care unit (PICU). We conducted a quality improvement (QI) initiative to reduce potentially avoidable PICU admissions of children with DKA without increasing endocrinology ward-to-PICU transfers. METHODS: A survey of providers demonstrated opportunities to increase awareness of institutional criteria for PICU admissions of children with DKA. We created an electronic health record (EHR) dot-phrase, prepopulated with these criteria, and placed a note in the EHR for all patients with DKA as a reference for all providers. An EHR-based data report was created to monitor the disposition of DKA patients and the use of the dot-phrase (process measure). The primary outcome measure was the potentially avoidable PICU admissions for patients with DKA. Endocrinology ward-to-PICU transfers were tracked as a balancing measure to ensure safe disposition. RESULTS: After the implementation of the dot-phrase, use was variable, but averaged 33.4% over 1 year. The percentage of DKA admissions classified as potentially avoidable PICU stays decreased from 4.1% to 0.5%, with a concurrent decrease in the total percentage of PICU admissions for DKA from 19.1% to 8.4%. The percentage of endocrinology ward-to-PICU transfers also declined from 0.8% to 0%. CONCLUSIONS: A novel EHR-based intervention increasing awareness and documentation of established pediatric DKA management guidelines can be used to safely reduce PICU admissions for DKA without increasing the rate of endocrinology ward-to-intensive care unit transfers."
639,Optimizing Analgesic Use During Infant Lumbar Puncture in the Emergency Department,"INTRODUCTION: Lumbar puncture (LP) for the collection of cerebrospinal fluid is an important diagnostic tool for the evaluation of febrile or ill-appearing infants. This invasive procedure is painful for patients; inadequate analgesia may have lasting effects. The American Academy of Pediatrics recommends analgesia during all LP procedures, and oral sucrose alone does not offer sufficient analgesia. Our objective was to identify analgesic use trends during infant LP in our emergency department and create a system of analgesic administration. We aimed for complete compliance with one method of analgesia and an increase in our use of 2 or more methods to 85% over 12 months. METHODS: We utilized Plan-Do-Study-Act cycle methodology and retrospective chart review. Five interventions focused on staff communication, collaboration, and education. Inclusion criteria: infants <60 days who underwent LP procedure due to fever >38°C, hypothermia <36.5°C of unknown origin, or ill-appearance. RESULTS: One hundred infant LPs analyzed: 52 preintervention and 48 intervention. The use of one analgesic increased from 98% preintervention to 100%. The use of 2 or more analgesics increased from 58% preintervention to 87%. Topical lidocaine use increased from 56% preintervention to 73%. LP success rates were high in both groups, with no statistically significant change in the success rate. CONCLUSION: We created a streamlined process to ensure all infants undergoing lumbar puncture received at least 1 analgesic and increased the proportion of infants treated with 2 or more analgesics. This work could be expanded to improve analgesia during other invasive procedures in the emergency department."
640,A Front-end Redesign With Implementation of a Novel “Intake” System to Improve Patient Flow in a Pediatric Emergency Department,"INTRODUCTION: Children’s Hospital Colorado is an academic, tertiary-care Level 1 Trauma Center with an emergency department (ED) that treats >70,000 patients/year. Patient volumes continue to increase, leading to worsening wait times and left-without-being-seen (LWBS) rates. In 2015, the ED’s median door-to-provider time was 49 minutes [interquartile range (IQR) = 26–90], with a 3.2% LWBS rate. ED leadership, staff, and providers aimed to improve patient flow with specific goals to (1) decrease door-to-provider times to a median of <30 minutes and (2) decrease annual LWBS rate to <1%. METHODS: An inter-professional team utilized quality improvement and Lean methodology to study, redesign, and implement significant changes to ED front-end processes. Key process elements included (1) new Flow Nurse/EMT roles, (2) elimination of traditional registration and triage processes, (3) immediate “quick registration” and nurse assessment upon walk-in, (4) direct-bedding of patients, and (5) a novel “Intake” system staffed by a pediatric emergency medicine physician. RESULTS: In the 12 months following full implementation of the new front-end system, the median door-to-provider time decreased 49% to 25 minutes (IQR = 13–50), and the LWBS rate decreased from 3.2% to 1.4% (a 56% relative decrease). Additionally, the percentage of patients seen within 30 minutes of arrival increased, overall ED length-of-stay decreased, patient satisfaction improved, and no worsening of the unexpected 72-hour return rate occurred. CONCLUSIONS: Using quality improvement and Lean methodology, an inter-professional team decreased door-to-provider times and LWBS rates in a large pediatric ED by redesigning its front-end processes and implementing a novel pediatric emergency medicine-led Intake system."
641,Screening With Reticulocyte Hemoglobin Increased Iron Sufficiency Among NICU Patients,"INTRODUCTION: To increase the rate of iron sufficiency among neonatal intensive care unit (NICU) patients from 16% to >35% within 12 months of implementing standardized assessment of reticulocyte hemoglobin (retHE). METHODS: We implemented a quality improvement (QI) study to improve iron sufficiency in our out-born level III/IV NICU. We screened 2,062 admissions, of which 622 were eligible based on feeding status at discharge. QI interventions included educational efforts and guideline implementation. Our primary outcome measure was the percentage of patients with their discharge retHE measure within the normal range. We also tracked the process measure of the number of retHE tests performed and a balancing measure of the incidence of elevated retHE among patients receiving iron supplementation. Statistical process control (SPC) charts assessed for special cause variation. RESULTS: The percentage of patients with a retHe within the normal range was significantly increased from a mean of 20% to 39% on SPC chart analysis. We measured significantly more retHE values after guideline implementation (11/mo to 24/mo) and found no cases of elevated retHE among patients receiving iron supplementation. CONCLUSIONS: After the implementation of a standardized guideline, a higher rate of iron sufficiency was found in NICU patients at discharge. This work is generalizable to neonatal populations with the potential for a significant impact on clinical practice."
642,Improving the Compliance of Intraoperative Antibiotic Redosing: A Quality Improvement Initiative,"INTRODUCTION: At Children’s Hospital and Medical Center in Omaha, Nebraska, the intraoperative antibiotic redosing guidelines and the time frame considered compliant for redosing were unclear. This lack of clarity plus an ill-defined process for ensuring intraoperative antibiotic redosing resulted in a compliance rate of 11%. The organization’s surgical site infection (SSI) rate was 3.19%, above the national benchmark of 1.87%. The primary project goal was to increase intraoperative antibiotic redosing compliance. The secondary project goal was to decrease SSIs. METHODS: With recommendations from the Infectious Disease Society of America, we developed new organizational redosing guidelines, as well as a new antibiotic-specific reminder alert in the electronic medical record. Implementation of the new guidelines and processes occurred after providing education to the anesthesiologists, surgeons, and circulating nurses. Monthly evaluation of data allowed for quick recognition of oversights followed by the initiation of process updates. RESULTS: Data showed that the initial compliance rate for the intraoperative redosing of antibiotics was 11%. Following interventions, compliance has reached and sustained an average of 99%. Survey results show that provider knowledge of the guidelines and process has improved. Though not directly related, the National Surgical Quality Improvement Program observed that the SSI rate decreased from 3.19% in 2014 to 2.3% in 2018. CONCLUSIONS: This project demonstrates that comprehensive education along with antibiotic-specific electronic medical record alerts significantly increased the compliance of intraoperative antibiotic redosing at Children’s Hospital & Medical Center. Continuous education and monthly updates sustained results for over 40 months."
643,Impact of a Multidisciplinary Sepsis Initiative on Knowledge and Behavior in a Pediatric Center,"OBJECTIVE: Our institution performed an educational initiative targeting previously identified barriers to pediatric sepsis recognition and treatment. We hypothesized that provider knowledge, attitude, and behavior would be improved 1 year after implementation. METHODS: This was a prospective, observational study of a multi-faceted quality initiative introduced to providers in the Emergency Department, inpatient wards, and Pediatric Intensive Care Unit of a tertiary care children’s hospital. Educational platforms consisted of quarterly electronic sepsis “newsletters,” brightly colored posters highlighting protocol and screening strategies displayed throughout the hospital, and low-fidelity simulation sessions (drills) led by trained staff and incorporated into daily workflows. The content was driven by feedback from a baseline needs assessment of sepsis education. One year after implementation, the needs assessment was repeated. RESULTS: Over 3 months, facilitators conducted 197 drills and captured a majority of nurses (89%), pediatrics residents (96%), and respiratory therapists (62%). By 6 months, 241 sessions had been completed. Approximately 55.4% of the 442 eligible staff participated in our post-intervention survey. Overall, knowledge of diagnostic criteria for pediatric sepsis and septic shock increased from pre-intervention levels (P = 0.015). Among post-implementation respondents, drill participants outperformed their colleagues (P = 0.001). A greater percentage of post-intervention respondents indicated comfort with sepsis recognition (P < 0.001), and fewer reported hesitating to bring sepsis concerns to their care team (P < 0.01). CONCLUSIONS: Our findings suggest that a multidisciplinary curriculum balancing active education—through brief, targeted simulation—and general awareness—through electronic resources and a poster campaign—can improve sepsis-related knowledge, attitude, and behavior among pediatric practitioners."
644,"Reduction of Central Line-associated Bloodstream Infection Through Focus on the Mesosystem: Standardization, Data, and Accountability","INTRODUCTION: Efforts to reduce central line-associated bloodstream infection (CLABSI) rates require strong microsystems for success. However, variation in practices across units leads to challenges in ensuring accountability. We redesigned the organization’s mesosystem to provide oversight and alignment of microsystem efforts and ensure accountability in the context of the macrosystem. We implemented an A3 framework to achieve reductions in CLABSI through adherence to known evidence-based bundles. METHODS: We conducted this CLABSI reduction improvement initiative at a 395-bed freestanding, academic, university-affiliated children’s hospital. A mesosystem-focused A3 emphasized bundle adherence through 3 key drivers (1) practice standardization, (2) data transparency, and (3) accountability. We evaluated the impact of this intervention on CLABSI rates during the pre-intervention (01/15-09/17) and post-intervention (07/18–06/19) periods using a Poisson model controlling for baseline trends. RESULTS: Our quarterly CLABSI rates during the pre-intervention period ranged from 1.0 to 2.3 CLABSIs per 1,000 central line-days. With the mesosystem in place, CLABSI rates ranged from 0.4 to 0.7 per 1,000 central line days during the post-intervention period. Adjusting for secular trends, we observed a statistically significant decrease in the post versus pre-intervention CLABSI rate of 71%. CONCLUSION: Our hospital-wide CLABSI rate declined for the first time in many years after the redesign of the mesosystem and a focus on practice standardization, data transparency, and accountability. Our approach highlights the importance of alignment across unit-level microsystems to ensure high-fidelity implementation of practice standards throughout the healthcare-delivery system."
645,Actualités profession,
646,Lassa fever outbreak continues across Nigeria,
647,The resurgence of convalescent plasma therapy,
648,Rebalancing Redux: the Final NICE Guidelines on Abdominal Aortic Aneurysm (AAA) Disease,
649,Redistributing working schedules using the infective principle in the response to COVID-19,
650,STELLAR 3 and STELLAR 4: Lessons From the Fall of Icarus,
651,Evolution of ARDS biomarkers: Will metabolomics be the answer?,"To date, there is no clinically agreed-upon diagnostic test for acute respiratory distress syndrome (ARDS): the condition is still diagnosed on the basis of a constellation of clinical findings, laboratory tests, and radiological images. Development of ARDS biomarkers has been in a state of continuous flux during the past four decades. To address ARDS heterogeneity, several studies have recently focused on subphenotyping the disease on the basis of observable clinical characteristics and associated blood biomarkers. However, the strong correlation between identified biomarkers and ARDS subphenotypes has yet to establish etiology; hence, there is a need for the adoption of other methodologies for studying ARDS. In this review, we will shed light on ARDS metabolomics research in the literature and discuss advances and major obstacles encountered in ARDS metabolomics research. Generally, the ARDS metabolomics studies focused on identification of differentiating metabolites for diagnosing ARDS, but they were performed to different standards in terms of sample size, selection of control cohort, type of specimens collected, and measuring technique utilized. Virtually none of these studies have been properly validated to identify true metabolomics biomarkers of ARDS. Though in their infancy, metabolomics studies exhibit promise to unfold the biological processes underlying ARDS and, in our opinion, have great potential for pushing forward our present understanding of ARDS."
652,Letter to the Editor: Resources and recommendations for a quick transition to online instruction in physiology,
653,Fever: Role of Pyrogens and Cryogens,
654,Chemokines in acute respiratory distress syndrome,"A characteristic feature of all inflammatory disorders is the excessive recruitment of leukocytes to the site of inflammation. The loss of control in trafficking these cells contributes to inflammatory diseases. Leukocyte recruitment is a well-orchestrated process that includes several protein families including the large cytokine subfamily of chemotactic cytokines, the chemokines. Chemokines and their receptors are involved in the pathogenesis of several diseases. Acute lung injury that clinically manifests as acute respiratory distress syndrome (ARDS) is caused by an uncontrolled systemic inflammatory response resulting from clinical events including major surgery, trauma, multiple transfusions, severe burns, pancreatitis, and sepsis. Systemic inflammatory response syndrome involves activation of alveolar macrophages and sequestered neutrophils in the lung. The clinical hallmarks of ARDS are severe hypoxemia, diffuse bilateral pulmonary infiltrates, and normal intracardiac filling pressures. The magnitude and duration of the inflammatory process may ultimately determine the outcome in patients with ARDS. Recent evidence shows that activated leukocytes and chemokines play a key role in the pathogenesis of ARDS. The expanding number of antagonists of chemokine receptors for inflammatory disorders may hold promise for new medicines to combat ARDS."
655,Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury,"Acute respiratory distress syndrome (ARDS) is a common cause of death in the intensive care unit, with mortality rates of ~30–40%. To reduce invasive diagnostics such as bronchoalveolar lavage and time-consuming in-hospital transports for imaging diagnostics, we hypothesized that particle flow rate (PFR) pattern from the airways could be an early detection method and contribute to improving diagnostics and optimizing personalized therapies. Porcine models were ventilated mechanically. Lipopolysaccharide (LPS) was administered endotracheally and in the pulmonary artery to induce ARDS. PFR was measured using a customized particles in exhaled air (PExA 2.0) device. In contrast to control animals undergoing mechanical ventilation and receiving saline administration, animals who received LPS developed ARDS according to clinical guidelines and histologic assessment. Plasma levels of TNF-α and IL-6 increased significantly compared with baseline after 120 and 180 min, respectively. On the other hand, the PFR significantly increased and peaked 60 min after LPS administration, i.e., ~30 min before any ARDS stage was observed with other well-established outcome measurements such as hypoxemia, increased inspiratory pressure, and lower tidal volumes or plasma cytokine levels. The present results imply that PFR could be used to detect early biomarkers or as a clinical indicator for the onset of ARDS."
656,Human lung extracellular matrix hydrogels resemble the stiffness and viscoelasticity of native lung tissue,"Chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are associated with changes in extracellular matrix (ECM) composition and abundance affecting the mechanical properties of the lung. This study aimed to generate ECM hydrogels from control, severe COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) IV], and fibrotic human lung tissue and evaluate whether their stiffness and viscoelastic properties were reflective of native tissue. For hydrogel generation, control, COPD GOLD IV, and fibrotic human lung tissues were decellularized, lyophilized, ground into powder, porcine pepsin solubilized, buffered with PBS, and gelled at 37°C. Rheological properties from tissues and hydrogels were assessed with a low-load compression tester measuring the stiffness and viscoelastic properties in terms of a generalized Maxwell model representing phases of viscoelastic relaxation. The ECM hydrogels had a greater stress relaxation than tissues. ECM hydrogels required three Maxwell elements with slightly faster relaxation times (τ) than that of native tissue, which required four elements. The relative importance (R(i)) of the first Maxwell element contributed the most in ECM hydrogels, whereas for tissue the contribution was spread over all four elements. IPF tissue had a longer-lasting fourth element with a higher R(i) than the other tissues, and IPF ECM hydrogels did require a fourth Maxwell element, in contrast to all other ECM hydrogels. This study shows that hydrogels composed of native human lung ECM can be generated. Stiffness of ECM hydrogels resembled that of whole tissue, while viscoelasticity differed."
657,Worldwide clinical practices in perioperative antibiotic therapy for lung transplantation,"BACKGROUND: Infection is the most common cause of mortality within the first year after lung transplantation (LTx). The management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices. METHODS: We sent by email a survey dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy to 180 LTx centers around the world. The invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center during a 3-month period. RESULTS: We received a total of 99 responses from 24 countries, mostly from Western Europe (n = 46) and the USA (n = 34). Systematic screening for bronchial recipient colonization before LTx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. In recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin / tazobactam, cefepime, ceftazidime, carbapenems) were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant Staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. For these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). In recipients with previous colonization, antibiotics were adapted to the susceptibility of the most resistant strain and given for at least 14 days (67%). CONCLUSION: Practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. The antibiotic duration reported was longer for colonized recipients."
658,Potential prognostic roles of serum lactate and Creatine kinase levels in poisoned patients,"BACKGROUND: Examination of serum lactate level and its changes, as an indicator of tissue oxygenation, as well as level of creatine kinase (CK) inhibitors, as a factor of mortality which partially expresses heart, brain, and muscle damage, may be considered as tools to determine prognosis in critically ill patients. We aimed to evaluate these two factors as potential prognostic factors in critically poisoned patients admitted to our toxicology ICU. METHOD: This is a cross-sectional descriptive-analytic study that was performed on poisoned patients referred to emergency department of Loghman Hakim Hospital. One-hundred critically poisoned patients who had been admitted to ICU were conveniently chosen using a random number table and included into the study after obtaining consent forms from their next of kin. Their serum lactate and CK levels were checked on admission. These levels were compared subsequently between survivors and non-survivors to seek for their potential prognostic role. RESULTS: In a total of 100 patients enrolled, 61 were male. Serum level of lactate (with a cut off of 26 mg/dL) and serum CK with a cutoff point of 169 U/L could have prognosticated death with sensitivity and specificity of 78 and 77% (for lactate) and 74 and 62% (for serum CK), respectively. CONCLUSIONS: In poisoned patients, serum lactate and CK can be used as possible prognostic factors because they rapidly increase in the serum and are easily detectable."
659,"A tribute to Stephen M. Schwartz, MD, PhD",
660,Point-of-Care Technologies for Health Care,"The increasingly global focus on health care issues continues to underline the importance of point-of-care technologies and their ability to provide cost-effective solutions that address many unmet health care needs. Further, the current crisis in health care costs has critically underscored the need for research and development into highly effective, but low cost means of delivering health care. With a focus on providing clinically actionable information at or near the patient, point-of-care devices provide clinicians with information that is critical to the management of patient care while they are still with the patient. Rapid information results in various advantages for POC testing in different kinds of health care settings. In primary care settings in developed countries, the shortened timeline between testing and availability of results reduces the need for extra office visits or follow-up phone calls to convey testing results and adjust clinical intervention. This strategy can reduce cost and increase access of otherwise underserved populations to medical care. For diseases that are infectious, such as sexually transmitted infections or respiratory diseases, POC testing can facilitate treatment modalities quickly, thus preventing further spread of the infection for better and timely clinical management. In acute care settings, timely access to diagnostic information is most critical for providing an effective medical response. In disaster settings, POC diagnostics can speed triage and enable rapid establishment and delivery of medical services."
661,Pandemic response lessons from influenza H1N1 2009 in Asia,"During April 2009, a novel H1N1 influenza A virus strain was identified in Mexico and the USA. Within weeks the virus had spread globally and the first pandemic of the 21st Century had been declared. It is unlikely to be the last and it is crucial that real lessons are learned from the experience. Asia is considered a hot spot for the emergence of new pathogens including past influenza pandemics. On this occasion while preparing for an avian, highly virulent influenza virus (H5N1 like) originating in Asia in fact the pandemic originated from swine, and was less virulent. This discrepancy between what was planned for and what emerged created its own challenges. The H1N1 pandemic has tested national health‐care infrastructures and exposed shortcomings in our preparedness as a region. Key health challenges include communication throughout the region, surge capacity, access to reliable information and access to quality care, health‐care worker skills, quality, density and distribution, access to essential medicines and lack of organizational infrastructure for emergency response. Despite years of preparation the public health and clinical research community were not ready to respond and opportunities for an immediate research response were missed. Despite warm words and pledges efforts to engage the international community to ensure equitable sharing of limited resources such as antivirals and vaccines fell short and stockpiles in the main remained in the rich world. This manuscript with authors from across the region describes some of the major challenges faced by Asia in response to the pandemic and draws lessons for the future."
662,The function of a ribosomal frameshifting signal from human immunodeficiency virus‐1 in Escherichia coli,"A 15‐17 nucleotide sequence from the gag‐pol ribosome frameshift site of HIV‐1 directs analogous ribosomal frameshifting in Escherichia coli. Limitation for leucine, which is encoded precisely at the frameshift site, dramatically increased the frequency of leftward frameshifting. Limitation for phenylaianine or arginine, which are encoded just before and just after the frameshift, did not significantly affect frameshifting. Protein sequence analysis demonstrated the occurrence of two closeiy related frameshift mechanisms. In the first, ribosomes appear to bind leucyl‐tRNA at the frameshift site and then slip leftward. This is the 'simultaneous slippage’mechanism. In the second, ribosomes appear to slip before binding amlnoacyl‐tRNA, and then bind phenylaianyl‐tRNA, which is encoded in the left‐shifted reading frame. This mechanism is identicai to the‘overlapping reading’we have demonstrated at other bacterial frameshift sites. The HIV‐1 sequence is prone to frame‐shifting by both mechanisms in E. coli."
663,Limited polymorphism at major histocompatibility complex (MHC) loci in the Swedish moose A. alces,"The Swedish moose was analysed for genetic variability at major histocompatibility complex (MHC) class I and class II DQA, DQB and DRB loci using restriction fragment length polymorphism (RFLP) and single strand conformation polymorphism (SSCP) techniques. Both methods revealed limited amounts of polymorphism. Since the SSCP analysis concerned an expressed DRB gene it can be concluded that the level of functional MHC class II polymorphism, at least at the DRB locus, is low in Swedish moose. DNA fingerprinting was used to determine if the unusual pattern of low MHC variability could be explained by a low degree of genome‐wide genetic diversity. Hybridizations with two minisatellite probes gave similarity indices somewhat higher than the average for other natural population, but the data suggest that the low MHC variability cannot be explained by a recent population bottleneck. However, since minisatellite sequences evolve more rapidly than MHC sequences, the low levels of MHC diversity may be attributed to a bottleneck of more ancient origin. The selection pressure for MHC variability in moose may also be reduced and we discuss the possibility that its solitary life style may reduce lateral transmission of pathogens in the population."
664,Analysis of Benthic Communities in the Cyclades Plateau (Aegean Sea) Using Ecological and Paleoecological Data Sets,"Abstract. In the Cyclades plateau (Aegean Sea), a qualitative and quantitative analysis of macro‐benthic fauna was carried out in 1986. Standard multivariate analysis techniques were applied to both ecological (living benthic fauna) and paleoecological data sets in order to distinguish distribution patterns. Results showed that caution must prevail in drawing conclusions from a limited data set. The clearest classification was obtained using total living fauna, while the dead molluscan fauna gave a similar pattern; this indicates similar response to the environmental conditions of the area. In the analysis of the living molluscan fauna, the groups failed to show any clusters, probably as an effect of some impoverished sites. In the two groups delineated, depth seems to be the major factor in the distribution of species. The fact that two distinct data sets (subfossil assemblages and living communities), when treated separately, produce similar grouping indicates that the subfossil assemblages could be reliably used as a first approach for determination of the living communities' distribution patterns."
665,Mycelial compatibility groups and pathogenic diversity in Sclerotium rolfsii populations from sugar beet crops in Mediterranean‐type climate regions,"The population structure of Sclerotium rolfsii from autumn‐sown sugar beet crops in Mediterranean‐type climate regions of Chile, Italy, Portugal and Spain was determined by analyses of mycelial compatibility groups (MCGs) and pathogenicity to 11 economically important plant species. Twelve MCGs (i–xii) were identified among 459 S. rolfsii isolates. MCG iii was the most prevalent group in all countries except Italy. MCG i, the most abundant group (64·7% of isolates) was identified in Portugal and Spain. The remaining MCGs were restricted to various regions within one country (ii, vi, ix) or different countries (v), or to specific localities (iv, vii, viii, x, xi, xii). MCGs iv, vii and x each comprised one isolate. Fields extensively sampled in southern Spain were infected with one to three MCGs. Plant species differed in susceptibility to MCG tester isolates with a MCG by species interaction. Cluster analyses allowed selection into five MCG groupings and grouped plant species into species‐groups 1 (broccoli, chickpea, sunflower, tomato) and 2 (cotton, pepper, sugar beet, watermelon). MCG groupings 1 (i, ix), 2 (ii, iii, vi, viii) and 5 (x, xii) were moderately virulent to species‐group 1 and mildly virulent to species‐group 2. MCG groupings 3 (iv, v, xi) and 4 (vii) were mildly virulent to both species‐groups. Across MCG groups, species were rated highly susceptible (chickpea, sunflower), susceptible (cotton, pepper, tomato, watermelon), moderately resistant (broccoli, melon, sugar beet) and resistant (corn, wheat). Establishing the MCG population structure and virulence variability among S. rolfsii isolates should help in the management of sclerotium root rot diseases."
666,Correlation between relative growth rate and specific leaf area requires associations of specific leaf area with nitrogen absorption rate of roots,"• . Close correlations between specific leaf area (SLA) and relative growth rate (RGR) have been reported in many studies. However, theoretically, SLA by itself has small net positive effect on RGR because any increase in SLA inevitably causes a decrease in area‐based leaf nitrogen concentration (LNC(a)), another RGR component. It was hypothesized that, for a correlation between SLA and RGR, SLA needs to be associated with specific nitrogen absorption rate of roots (SAR), which counteracts the negative effect of SLA on LNC(a). • . Five trees and six herbs were grown under optimal conditions and relationships between SAR and RGR components were analyzed using a model based on balanced growth hypothesis. • . SLA varied 1.9‐fold between species. Simulations predicted that, if SAR is not associated with SLA, this variation in SLA would cause a 47% decrease in LNC(a) along the SLA gradient, leading to a marginal net positive effect on RGR. In reality, SAR was positively related to SLA, showing a 3.9‐fold variation, which largely compensated for the negative effect of SLA on LNC(a). Consequently, LNC(a )values were almost constant across species and a positive SLA–RGR relationship was achieved. • . These results highlight the importance of leaf–root interactions in understanding interspecific differences in RGR."
667,Seasonal and pandemic influenza during pregnancy and risk of fetal death: A Norwegian registry-based cohort study,"Previous studies of fetal death with maternal influenza have been inconsistent. We explored the effect of maternal influenza-like illness (ILI) in pregnancy on the risk of fetal death, distinguishing between diagnoses during regular influenza seasons and the 2009/2010 pandemic and between trimesters of ILI. We used birth records from the Medical Birth Registry of Norway to identify fetal deaths after the first trimester in singleton pregnancies (2006–2013). The Norwegian Directorate of Health provided dates of clinical influenza diagnoses by primary-health-care providers, whereas dates of laboratory-confirmed influenza A (H1N1) diagnoses were provided by the Norwegian Surveillance System for Communicable Diseases. We obtained dates and types of influenza vaccinations from the Norwegian Immunisation Registry. Cox proportional-hazards regression models were fitted to estimate hazard ratios (HRs) of fetal death, with associated 95% confidence intervals (CIs), comparing women with and without an ILI diagnosis in pregnancy. There were 2510 fetal deaths among 417,406 eligible pregnancies. ILI during regular seasons was not associated with increased risk of fetal death: adjusted HR = 0.90 (95% CI 0.64–1.27). In contrast, ILI during the pandemic was associated with substantially increased risk of fetal death, with an adjusted HR of 1.75 (95% CI 1.21–2.54). The risk was highest following first-trimester ILI (adjusted HR = 2.28 [95% CI 1.45–3.59]). ILI during the pandemic—but not during regular seasons—was associated with increased risk of fetal death in the second and third trimester. The estimated effect was strongest with ILI in first trimester. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10654-020-00600-z) contains supplementary material, which is available to authorized users."
668,Neutrophil chemoattractant receptors in health and disease: double-edged swords,"Neutrophils are frontline cells of the innate immune system. These effector leukocytes are equipped with intriguing antimicrobial machinery and consequently display high cytotoxic potential. Accurate neutrophil recruitment is essential to combat microbes and to restore homeostasis, for inflammation modulation and resolution, wound healing and tissue repair. After fulfilling the appropriate effector functions, however, dampening neutrophil activation and infiltration is crucial to prevent damage to the host. In humans, chemoattractant molecules can be categorized into four biochemical families, i.e., chemotactic lipids, formyl peptides, complement anaphylatoxins and chemokines. They are critically involved in the tight regulation of neutrophil bone marrow storage and egress and in spatial and temporal neutrophil trafficking between organs. Chemoattractants function by activating dedicated heptahelical G protein-coupled receptors (GPCRs). In addition, emerging evidence suggests an important role for atypical chemoattractant receptors (ACKRs) that do not couple to G proteins in fine-tuning neutrophil migratory and functional responses. The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation, with a pivotal modulatory role for the (inflammatory) environment. Here, we provide an overview of chemoattractant receptors expressed by neutrophils in health and disease. Depending on the (patho)physiological context, specific chemoattractant receptors may be up- or downregulated on distinct neutrophil subsets with beneficial or detrimental consequences, thus opening new windows for the identification of disease biomarkers and potential drug targets."
669,Polymorphisms in PARP1 predict disease-free survival of triple-negative breast cancer patients treated with anthracycline/taxane based adjuvant chemotherapy,"Triple-negative breast cancer (TNBC) is a highly aggressive disease and of poor prognosis. It is very important to identify novel biomarkers to predict therapeutic response and outcome of TNBC. We investigated the association between polymorphisms in PARP1 gene and clinicopathological characteristics or survival of 272 patients with stage I-III primary TNBC treated with anthracycline/taxane based adjuvant chemotherapy. We found that after adjusted by age, grade, tumor size, lymph node status and vascular invasion, rs7531668 TA genotype carriers had significantly better DFS rate than TT genotype carriers, the 5 y DFS was 79.3% and 69.2% (P = 0.046, HR 0.526 95% CI 0.280–0.990). In lymph node negative subgroup, DFS of rs6664761 CC genotype carriers was much better than TT genotype carriers (P = 0.016, HR 0.261 95% CI 0.088–0.778) and DFS of rs7531668 AA genotype carriers was shorter than TT genotype carriers (P = 0.015, HR 3.361 95% CI 1.259–8.969). In subgroup of age ≤ 50, rs6664761 TC genotype predicted favorable DFS than TT genotype (P = 0.042, HR 0.405 95% CI 0.170–0.967). Polymorphisms in PARP1 gene had no influence on treatment toxicities. After multivariate analysis, tumor size (P = 0.037, HR = 2.829, 95% CI: 1.063–7.525) and lymph node status (P < 0.001, HR = 9.943, 95% CI: 2.974–33.243) were demonstrated to be independent prognostic factors. Our results suggested that polymorphisms in PARP1 gene might predict the DFS of TNBC patients treated with anthracycline/taxane based adjuvant chemotherapy."
670,Under-the-Radar Dengue Virus Infections in Natural Populations of Aedes aegypti Mosquitoes,"The incidence of locally acquired dengue infections increased during the last decade in the United States, compelling a sustained research effort concerning the dengue mosquito vector, Aedes aegypti, and its microbiome, which has been shown to influence virus transmission success. We examined the “metavirome” of four populations of Aedes aegypti mosquitoes collected in 2016 to 2017 in Manatee County, FL. Unexpectedly, we discovered that dengue virus serotype 4 (DENV4) was circulating in these mosquito populations, representing the first documented case of such a phenomenon in the absence of a local DENV4 human case in this county over a 2-year period. We confirmed that all of the mosquito populations carried the same DENV4 strain, assembled its full genome, validated infection orthogonally by reverse transcriptase PCR, traced the virus origin, estimated the time period of its introduction to the Caribbean region, and explored the viral genetic signatures and mosquito-specific virome associations that potentially mediated DENV4 persistence in mosquitoes. We discuss the significance of prolonged maintenance of the DENV4 infections in A. aegypti that occurred in the absence of a DENV4 human index case in Manatee County with respect to the inability of current surveillance paradigms to detect mosquito vector infections prior to a potential local outbreak. IMPORTANCE Since 1999, dengue outbreaks in the continental United States involving local transmission have occurred only episodically and only in Florida and Texas. In Florida, these episodes appear to be coincident with increased introductions of dengue virus into the region through human travel and migration from countries where the disease is endemic. To date, the U.S. public health response to dengue outbreaks has been largely reactive, and implementation of comprehensive arbovirus surveillance in advance of predictable transmission seasons, which would enable proactive preventative efforts, remains unsupported. The significance of our finding is that it is the first documented report of DENV4 transmission to and maintenance within a local mosquito vector population in the continental United States in the absence of a human case during two consecutive years. Our data suggest that molecular surveillance of mosquito populations in high-risk, high-tourism areas of the United States may enable proactive, targeted vector control before potential arbovirus outbreaks."
671,Epitope-Based Peptide Vaccine against Glycoprotein G of Nipah Henipavirus Using Immunoinformatics Approaches,"BACKGROUND: Nipah belongs to the genus Henipavirus and the Paramyxoviridae family. It is an endemic most commonly found at South Asia and has first emerged in Malaysia in 1998. Bats are found to be the main reservoir for this virus, causing disease in both humans and animals. The last outbreak has occurred in May 2018 in Kerala. It is characterized by high pathogenicity and fatality rates which varies from 40% to 70% depending on the severity of the disease and on the availability of adequate healthcare facilities. Currently, there are no antiviral drugs available for NiV disease and the treatment is just supportive. Clinical presentations for this virus range from asymptomatic infection to fatal encephalitis. OBJECTIVE: This study is aimed at predicting an effective epitope-based vaccine against glycoprotein G of Nipah henipavirus, using immunoinformatics approaches. METHODS AND MATERIALS: Glycoprotein G of the Nipah virus sequence was retrieved from NCBI. Different prediction tools were used to analyze the epitopes, namely, BepiPred-2.0: Sequential B Cell Epitope Predictor for B cell and T cell MHC classes II and I. Then, the proposed peptides were docked using Autodock 4.0 software program. Results and Conclusions. The two peptides TVYHCSAVY and FLIDRINWI have showed a very strong binding affinity to MHC class I and MHC class II alleles. Furthermore, considering the conservancy, the affinity, and the population coverage, the peptide FLIDRINWIT is highly suitable to be utilized to formulate a new vaccine against glycoprotein G of Nipah henipavirus. An in vivo study for the proposed peptides is also highly recommended."
672,Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine,"BACKGROUND: There is a dearth of drug therapies available for the treatment of acute respiratory distress syndrome (ARDS). Certain metabolites play a key role in ARDS and could serve as potential targets for developing therapies against this respiratory disorder. The present study was designed to determine such “functional metabolites” in ARDS using metabolomics and in vivo experiments in a mouse model. METHODS: Metabolomic profiles of blood plasma from 42 ARDS patients and 28 healthy controls were captured using Ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) assay. Univariate and multivariate statistical analysis were performed on metabolomic profiles from blood plasma of ARDS patients and healthy controls to screen for “functional metabolites”, which were determined by variable importance in projection (VIP) scores and P value. Pathway analysis of all the metabolites was performed. The mouse model of ARDS was established to investigate the role of “functional metabolites” in the lung injury and mortality caused by the respiratory disorder. RESULTS: The metabolomic profiles of patients with ARDS were significantly different from healthy controls, difference was also observed between metabolomic profiles of the non-survivors and the survivors among the ARDS patient pool. Levels of Phenylalanine, D-Phenylalanine and Phenylacetylglutamine were significantly increased in non-survivors compared to the survivors of ARDS. Phenylalanine metabolism was the most notably altered pathway between the non-survivors and survivors of ARDS patients. In vivo animal experiments demonstrated that high levels of Phenylalanine might be associated with the severer lung injury and increased mortality of ARDS. CONCLUSION: Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma Phenylalanine. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800015930. Registered 29 April 2018, http://www.chictr.org.cn/edit.aspx?pid=25609&htm=4"
673,Erratum,
674,In vivo evidence for extracellular DNA trap formation,"Extracellular DNA trap formation is a cellular function of neutrophils, eosinophils, and basophils that facilitates the immobilization and killing of invading microorganisms in the extracellular milieu. To form extracellular traps, granulocytes release a scaffold consisting of mitochondrial DNA in association with granule proteins. As we understand more about the molecular mechanism for the formation of extracellular DNA traps, the in vivo function of this phenomenon under pathological conditions remains an enigma. In this article, we critically review the literature to summarize the evidence for extracellular DNA trap formation under in vivo conditions. Extracellular DNA traps have not only been detected in infectious diseases but also in chronic inflammatory diseases, as well as in cancer. While on the one hand, extracellular DNA traps clearly exhibit an important function in host defense, it appears that they can also contribute to the maintenance of inflammation and metastasis, suggesting that they may represent an interesting drug target for such pathological conditions."
675,"Tolerance of coffee (Coffea spp.) seeds to ultra‐low temperature exposure in relation to calorimetric properties of tissue water, lipid composition, and cooling procedure","The effect of exposure to ultra‐low temperature (liquid nitrogen, LN) on viability of seeds desiccated to various water contents was investigated in 9 coffee species. Three groups of species could be distinguished based on seed survival after LN exposure. In group 1 species, no seedling production could be obtained after LN exposure due to endosperm injury. In group 2 species, recovery was very low or nil after rapid cooling, and only moderate after slow cooling. In group 3 species, very high percentages of seedling development were observed after both rapid and slow cooling. A high interspecific variability for the high moisture freezing limit was observed within the species of groups 2 and 3, since it ranged from 0.14 to 0.26 g H(2)O g(−1) dry weight. A very highly significant correlation was found for those species between the unfreezable water content, as determined from DSC analysis, and the high moisture freezing limit of their seeds. No significant correlation was found between seed lipid content, which varied from 9.8 to 34.6% dry weight, and survival after LN exposure. However, a negative relationship was found between seed unfreezable water content and lipid content. Interspecific differences in fatty acid composition of seed lipids resulted in a high variability in the percentage of unsaturated fatty acids, which ranged from 28.7 to 54.4% among the 9 species studied. For all species studied, a highly significant correlation was found between the percentage of unsaturated fatty acids and the percentage of seedling recovery after rapid or slow cooling."
676,Resource Allocation and Priority Setting,"There has been much discussion of resource allocation in medical systems, in the United States and elsewhere. In large part, the discussion is driven by rising costs and the resulting budget pressures felt by publicly funded systems and by both public and private components of mixed health systems. In some publicly funded systems, resource allocation is a pressing issue because resources expended on one disease or person cannot be spent on another disease or person. Some of the same concern arises in mixed medical systems with multiple funding sources."
677,International Collaboration for Global Public Health,There is a long tradition of global collaboration in biomedicine and public health. Examples range from medical outposts in rural communities run by foreign missionaries (Good 1991) to the early infectious disease programs of the Rockefeller Foundation (Fosdick 1989) and from medical services and training programs for indigenous populations set up by colonial authorities (Marks 1997) to the Pan American Health Organization (PAHO) established by a collective of sovereign governments (Cueto 2007).
678,Addressing Burnout: Symptom Management Versus Treating the Cause,
679,To our global neonatal nursing community,
680,"Functional richness of local hoverfly communities (Diptera, Syrphidae) in response to land use across temperate Europe","Environmental change is not likely to act on biodiversity in a random manner, but rather according to species traits that affect assembly processes, thus, having potentially serious consequences on ecological functions. We investigated the effects of anthropogenic land use on functional richness of local hoverfly communities of 24 agricultural landscapes across temperate Europe. A multivariate ordination separated seven functional groups based on resource use, niche characteristics and response type. Intensive land use reduced functional richness, but each functional group responded in a unique way. Species richness of generalist groups was nearly unaffected. Local habitat quality mainly affected specialist groups, while land use affected intermediate groups of rather common species. We infer that high species richness within functional groups alone is no guarantee for maintaining functional richness. Thus, it is not species richness per se that improves insurance of functional diversity against environmental pressures but the degree of dissimilarity within each functional group."
681,"Character‐ and tree‐based delimitation of species in the ‘Cichlasoma’ facetum group (Teleostei, Cichlidae) with the description of a new genus","The ‘Cichlasoma’ facetum group is part of the taxonomically complex group of Neotropical cichlid fishes of the tribe Heroini. Many species groups and unplaced species of heroines are still left without a generic name following the revision of the genus Cichlasoma. We describe here the ‘Cichlasoma’ facetum group as a new genus, Australoheros, and provide evidence for its monophyly based on phylogenetic analyses of morphological and mtDNA characters. Australoheros is morphologically characterized by the lowest values in meristic characters among heroines and by three apomorphic characters in coloration pattern. In addition to the three described species of Australoheros, our results of species delimitation based on a combination of tree‐ and character‐based approaches identify seven putatively new species of Australoheros. Several coding schemes of morphological characters are used to recover the intrageneric relationships within the genus, resulting in very similar topologies. Discovery of additional species within the genus is expected once material from the whole distribution area is studied."
682,In vitro susceptibility of Escherichia coli strains isolated from diarrhoeic lambs and goat kids to 14 antimicrobial agents,"The in vitro activities of 14 anti‐microbial agents were determined against 92 strains of E. coli isolated from lambs (60 strains) and kids (32 strains) affected by neonatal diarrhoea. The overall percentage of resistant strains to streptomycin, sulphadimethoxine and tetracycline was very high (above 70%). A high level of resistance (from 30% to 50%) to ampicillin, kanamycin, neomycin and chloramphenicol was also detected. The E. coli strains were highly susceptible to cephalosporins, polymyxin and quinolones. Most of the strains showed multiresistance: 77.2% of isolates were resistant to at least two antibiotics, 55.4% were resistant to at least four antibiotics and 33.7% were resistant to at least six antibiotics. A total of 34 antibiotypes could be distinguished."
683,"Graptoloid feeding efficiency, rotation and astogeny","Two methods are used to examine feeding strategies in graploloids; the first profiles different sets of zooids on the colony, the second treats the colony as a whole. Both of these techniques have advantages. The choice between them brings into question our concepts of the degree of coloniality shown by graptoloids. Using a whole colony model. graptoloids can be shown to have sampled the water with variable efficiency. as defined in this paper. Planar forms were relatively inefficient, generally sampling less than 10% of the available water. Inclined forms frequently approached 75% efficiency. Biserial forms and strdight monograptids roulinely exceeded 100%. sampling each unit of water more than once. Rotation of the rhabdosome during movement increased the efficiency of horizontal and inclined forms. It reduced the efficiency of scandent biserials and straight monograptids. These were both advantageous effects. Astogenetic changes in colony size and form would have had a profound effect on feeding efficiency.□Graptoloid, ecology, astogeny"
684,Propagation of Hemagglutinating Encephalomyelitis Virus in Porcine Cell Cultures,"SUMMARY: This study reports some cultural characteristics of the VW 572 strain of hemagglutinating encephalomyelitis virus (HEV) in primary pig kidney (PPK) cells, primary pig testicle (PPT) cells, secondary pig thyroid (SPTh) cells and the cell lines PK‐15 (pig kidney), SK−6 (swine kidney) and ST (swine testicle). A growth curve, based on cytopathic effect (CPE), immunofluorescence (IF), hemadsorption (Hads) and hemagglutination (HA), showed that SPTh and PPK cells were most susceptible for cultivation and quantitation of the virus. For the detection of replication in tubes inoculated with small amounts of virus, CPE, Hads and HA appeared to be useful and sensitive criteria. Repeated virus quantitation trials revealed a high variation in titration end‐points, even in the most susceptible cell types. The optimal procedure for the isolation of HEV from clinical specimens is preferably to inoculate the material on SPTh or PPK cells and to make a blind passage if the HA test at 7 days post inoculation is negative. ZUSAMMENFASSUNG: Züchtung von Hemagglutinating Encephalomyelitis Virus (HEV) in porcinen Zellkulturen Kulturelle Eigenschaften des HEV‐Stammes VW 572 in primären Schweinenierenzellen (PPK), primären Schweinehodenzellen (PPT), sekundären Schweineschilddrüsenzellen (SPTh) und in den Zellinien PK‐15 (Schweinenieren), SK−6 (Schweinenieren) und ST (Schweinehoden) werden beschrieben. Vermehrungskurven, die mit Hilfe des cytopatischen Effektes (CPE), der Immunofluoreszenz (IF), der Hämadsorption (Hads) und der Hämagglutination als Kriterien für die Virusreplikation erstellt wurden, zeigten, daß SPTh und PPK‐Zellen am empfindlichsten für die Züchtung und Titration des Virus sind. Zum Nachweis der Virusvermehrung in Röhrchen, die mit kleinen Virusmengen beimpft wurden, waren CPE, Hads und HA empfindliche und brauchbare Kriterien. Wiederholte Virustitrationen zeigten eine hohe Variation der Titerendpunkte auch in hochempfänglichen Zellkulturen. Die optimale Methode für die Isolierung von HEV von klinischem Material ist die Verimpfung auf SPTh oder PPK mit anschließender Blindpassage, wenn der HA‐Test sieben Tage p. inf. negativ ist. RÉSUMÉ: Culture du virus hémagglutinant de l'encéphalomyélite (HEV) dans des cultures de cellules de porc On décrit les propriétés de culture de la souche HEV VW 572 dans des cellules primaires de reins de pores (PPK), dans des cellules primaires de testicules de porcs (PPT), dans des cellules secondaires de glandes tyroïdes de porcs (SPTh) et dans les lignées cellulaires PK‐15 (reins de porcs), SK−6 (reins de porcs) et ST (testicules de porcs). Les courbes de multiplication établies avec l'effet cytopathique (CPE), l'immunofluorescence (IF), l'hémadsorption (Hads) et l'hémagglutination (HA) comme critères pour la réplication du virus ont montré que les cellules SPTh et PPK étaient les plus sensibles pour la culture et la titration du virus. CPE, Hads et HA furent les critères sensibles et utilisables pour la mise en évidence de la multiplication virale en tubes inoculés avec de petites quantités de virus. Des titrations du virus répétées ont montré une forte variation du titre final également dans les cultures cellulaires hautement réceptrices. La méthode optimale pour l'isolement de HEV à partir d'un matériel clinique est l'inoculation sur SPTh ou PPK avec passages à l'aveugle si le test HA est négatif 7 jours après l'infection. RESUMEN: Propagación del virus hemoaglutinante de la encefalomielitis (HEV) en los cultivos de células de cerdos Se describen las propiedades culturales de la estirpe HEV VW 572 en células renales primarias de cerdo (PPK), células testiculares primarias de cerdo, células tiroideas secundarias de cerdo (SPTh) y en las líneas celulares PK‐15 (riñones de cerdo), SK−6 (riñones porcinos) y ST (testículos de cerdo). Las curvas de multiplicación, las cuales se establecieron con ayuda del efecto citopático (CPE), la inmunofluorescencia (IF), la hemoadsorción (Hads) y la hemoaglutinación como criterios para la replicación virósica, mostraban que las células SPTh y PPK son las más sensibles para el cultivo y titulación del virus. Para la puesta en evidencia de la multiplicación virósica en tubitos, los cuales se inocularon con cantidades pequeñas de virus, eran CPE, Hads y HA criterios sensibles y útiles. Titulaciones repetidas de virus mostraban una variación elevada de los puntos finales de títulos incluso en cultivos celulares harto receptibles. El método óptimo para el aislamiento de HEV a partir de material clínico consiste en la inoculación a SPTH o PPK con pase ciego inmediato si la prueba HA es negativa 7 días después de la infección."
685,Necrotizing enterocolitis in very low birthweight infants: a four‐year experience,"Fifty (13%) of 375 infants who weighed 1500 g or less at birth had necrotizing enterocolitis (NEC). Haematological changes suggestive of sepsis occurred in 83% and positive bacteriological cultures were found in 38%, the most common organism isolated being Clostridium perfringens. Complications included intestinal perforation in six patients and recurrence of NEC in five, of whom one subsequently developed an intestinal stricture. Five of the eight nursery deaths were secondary to peritonitis and overwhelming sepsis from NEC. In spite of the discontinuation of milk feeds for prolonged periods, satisfactory caloric intake and weight gain were achieved with parenteral nutrition in the survivors. Of the 41 long‐term survivors, six (15%) were found to have a disability at 2 years of ago, corrected for prematurity, compared with 48 (20%) of 241 very low birthweight survivors from the same study period who did not have NEC. None had evidence of gastrointestinal dysfunction. Six (15%) children remained below the 10th percentile for both weight and height. This study showed that early diagnosis and therapy for NEC in very tow birthweight infants were associated with a favourable short‐ and long‐term outcome."
686,The Evolutionary History of the Genus Acanthamoeba and the Identification of Eight New 18S rRNA Gene Sequence Types,"ABSTRACT The 18S rRNA gene (Rns) phylogeny of Acanthamoeba is being investigated as a basis for improvements in the nomenclature and taxonomy of the genus. We previously analyzed Rns sequences from 18 isolates from morphological groups 2 and 3 and found that they fell into four distinct evolutionary lineages we called sequence types T1‐T4. Here, we analyzed sequences from 53 isolates representing 16 species and including 35 new strains. Eight additional lineages (sequence types T5‐T12) were identified. Four of the 12 sequence types included strains from more than one nominal species. Thus, sequence types could be equated with species in some cases or with complexes of closely related species in others. The largest complex, sequence type T4, which contained six closely related nominal species, included 24 of 25 keratitis isolates. Rns sequence variation was insufficient for full phylogenetic resolution of branching orders within this complex, but the mixing of species observed at terminal nodes confirmed that traditional classification of isolates has been inconsistent. One solution to this problem would be to equate sequence types and single species. Alternatively, additional molecular information will be required to reliably differentiate species within the complexes. Three sequence types of morphological group 1 species represented the earliest divergence in the history of the genus and, based on their genetic distinctiveness, are candidates for reclassification as one or more novel genera."
687,Influences of El Niño on assemblages of mesopelagic fish larvae along the Pacific coast of Baja California Sur,"Seasonal assemblages of mesopelagic fish larvae and changes related with environmental factors (plankton biomass, sea surface temperature anomaly, upwelling, and the multivariate El Niño index) were investigated. From 1982 to 1987, 16 oceanographic cruises were carried out along the Pacific coast of Baja California Sur, Mexico. Larvae of 42 mesopelagic fish taxa were collected. Larval abundance was highly variable during the studied period, but summer months coincided with higher abundance (>200 larvae under 10 m(2)). Larval assemblages were dominated by three of the most common species of tropical (Vinciguerria lucetia, Diogenichthys laternatus) and subtropical affinity (Triphoturus mexicanus). A group of species of tropical affinity (Diplophos proximus, Diaphus pacificus, Benthosema panamense) was useful for distinguishing the 1982–84 El Niño event, and an assemblage of larvae of temperate affinity (Symbolophorus californiensis, Melamphaes lugubris, Bathylagus ochotensis, Leuroglossus stilbius, Protomyctophum crockeri) characterized ‘normal’ years (mid‐1984 to mid‐1987)."
688,Land use affects the relationship between species diversity and productivity at the local scale in a semi‐arid steppe ecosystem,"1.. The accelerating extinction rate of plant species and its effect on ecosystem functioning is a hotly debated topic in ecological research. Most research projects concerning the relationship between species diversity and productivity have been conducted in artificial plant communities, with only a few in natural ecosystems. In this study we examined the relationship between species diversity and above‐ground net primary productivity (ANPP) over two consecutive growth seasons (2004 and 2005) in a semi‐arid steppe ecosystem of northern China, that were subjected to different land uses. 2.. Land use affected the relationship between species diversity and ANPP in this semi‐arid steppe ecosystem. Exclusion of grazing without or with biomass removal by mowing increased ANPP, species richness and species diversity compared with free grazing; the effect was reflected mainly as enhanced importance of the perennial forbs functional group in terms of their relative contributions to ANPP, plant cover and plant abundance. 3.. Many mechanisms regulate the relationship between species diversity and productivity. Differential effects of anthropogenic activities on biodiversity and ecosystem functioning greatly complicate the analysis of such relationships. On grazing‐exclusion sites the relationship between ANPP and species richness can be best described as an exponential growth function (R (2) = 0·99, P < 0·001, n = 24); whereas on the free‐grazing site the relationship takes the form of exponential decay (R (2) = 0·96, P < 0·001, n = 24). Our study concludes that the mode and severity of disturbance are important factors for interpreting the relationship between species diversity and productivity in semi‐arid steppe ecosystems."
689,Assessment of periradicular microbiota by DNA‐DNA hybridization,"Abstract – In the present study the “checkerboard” DNA‐DNA hybridization technique was used to identify bacteria in periapical endodontic lesions of asymptomatic teeth. Thirty‐four patients with root‐filled teeth and apical periodontitis were divided into two groups, each containing 17 patients. In Group 1, a marginal incision was performed during surgery to expose the lesion, and in Group 2, a submarginal incision was applied. The gingiva and mucosa were swabbed with an 0.2% chlorhexidine gluconate solution prior to surgery. Bacterial DNA was identified in all samples from the two groups using 40 different whole genomic probes. The mean number (±SD) of species detected was 33.7±3.3 in Group 1 and 21.3±6.3 in Group 2 (P<0.001). The majority of the probe‐detected bacteria were present in more lesions from Group1 than from Group 2. The differences were most notable for Campylobacter gracilis, Porphyromonas endodontalis, Propionibacterium acnes, Capnocytophaga gingivalis, Fusobacterium nucleatum ssp. nucleatum, Fusobacterium nucleatum ssp. polymorphum, Prevotella intermedia, Treponema denticola, Streptococcus constellatus and Actinomyces naeslundii I. Bacterial species such as Actinobacillus actinomycetemcomitans and Bacteroides forsythus were detected in more than 60% of the lesions from both groups. Also, P. endodontalis was abundant in periapical tissue. The data supported the idea that following a marginal incision, bacteria from the periodontal pocket might reach the underlying tissues by surgeon‐released bacteremia. The study provided solid evidence that bacteria invade the periapical tissue of asymptomatic teeth with apical periodontitis. The detection of much more bacteria with the “checkerboard” DNA‐DNA hybridization method than has previously been recovered by anaerobic culture indicated that the endodontic (and periodontal) microfloras should be redefined using molecular methods."
690,Immunogenicity and Efficacy of a Commercial Feline Leukemia Virus Vaccine,"Twenty young adult specific pathogen‐free cats were randomly divided into two groups of 10 animals each. One group was vaccinated with two doses of feline leukemia virus vaccine according to the manufacturer's recommendations. All 20 cats were challenge exposed oronasally (4 times over a 1‐week period), beginning 3 weeks after immunization, with a virulent subgroup A strain of FeLV (CT600‐FeLV). The severity of the FeLV infection was enhanced by treating the cats with methylprednisolone acetate at the time of the last FeLV exposure. Ten of 10nonvaccinated cats became persistently viremic compared with 0/10 of the vaccinates. ELISA antibodies to whole FeLV were present at high concentrations after immunization in all of the vaccinated cats, and there was no observable anamnestic antibody response after challenge exposure. ELISA antibodies to whole FeLV appeared at low concentrations in the serum of nonvaccinated cats after infection but disappeared as the viremia became permanently established. Virus neutralizing antibodies were detected in 3/10 vaccinates and 0/10 nonvaccinates immediately before FeLV challenge exposure, and in 8/10 vaccinates and 1/10 nonvaccinates 5 weeks later. Although vaccination did not consistently evoke virus neutralizing antibodies, it appeared to immunologically prime cats for a virus‐neutralizing antibody response after infection. Active FeLV infection was detected in bone marrow cells taken 14 weeks after infection from 10/10 nonvaccinates and 0/10 vaccinates. Latent FeLV infection was not detected in bone marrow cells from any of the vaccinated cats 14 weeks after challenge exposure."
691,Monotonicity properties for a ratio of finite many gamma functions,"In the paper, the authors consider a ratio of finite many gamma functions and find its monotonicity properties such as complete monotonicity, the Bernstein function property, and logarithmically complete monotonicity."
692,Urbanization interferes with the use of amphibians as indicators of ecological integrity of wetlands,"1. Wetlands are ecologically and economically important ecosystems but are threatened globally by many forms of human disturbance. Understanding the responses of wetland species to human disturbance is essential for effective wetland management and conservation. 2. We undertook a study to determine (i) whether anurans can be used effectively to assess the ecological integrity of wetlands affected by groundwater withdrawal and, if so, (ii) what effect increasing urbanization might have on the utility of anurans as wetland indicators. We monitored the intensity of anuran calls at 42 wetlands in south‐western Florida throughout 2001–2002 and 2005–2009. 3. We first validated the use of anurans to assess wetland integrity using a small group of wetlands by comparing anuran calling and subsequent tadpole development with an established index employing vegetation composition and structure. We then verified that the results could be expanded to a variety of sites throughout the region. Finally, we focused on urbanized wetlands to determine whether urbanization could interfere with the use of anurans to assess wetland integrity. 4. We used PRESENCE to estimate occupancy and detection probabilities and to examine the relationship between occupancy and five covariates expected to influence individual species occurrence. We used FRAGSTATS to calculate the mean proximity index for urbanized wetlands, which assesses the size and distribution of land use types within a specified area. 5. Our results showed that the group of species including oak toad Anaxyrus quercicus, southern cricket frog Acris gryllus, pinewoods treefrog Hyla femoralis, barking treefrog Hyla gratiosa, and little grass frog Pseudacris ocularis is a reliable indicator of wetland integrity. However, this same group of species, which is sensitive to wetland health, is selectively excluded from urbanized wetlands. 6. Synthesis and applications. Although anurans are effective indicators of wetland health and complement vegetation surveys, the usefulness of this group for monitoring the ecological integrity of wetlands can be substantially reduced, or eliminated, as a consequence of urbanization. We urge for careful consideration of confounding factors in any studies examining the utility of indicator species."
693,"Acanthamoeba healyi N. Sp. and the Isoenzyme and Immunoblot Profiles of Acanthamoeba spp., Groups 1 and 3","ABSTRACT Two strains of Acanthamoeba isolated from human brain tissue and a strain of Acanthamoeba isolated from a fish were compared with 10 species of Acanthamoeba belonging to groups 1, 2 and 3 based on their isoenzyme profiles and antigenic characteristics. A total of 12 enzymes were studied. The isoenzymes and antigens were electrophoretically separated on polyacrylamide gradient gels, and the patterns obtained were compared after appropriate staining for particular enzymes and reactivities with homologous and heterologous rabbit anti‐Acanthamoeba antisera. One of the human strains (CDC:1283:V013) was identified as A. healyi n. sp. because of its unique isoenzyme profiles for 11 of the 12 enzymes tested. The other human isolate was reidentified as A. culbertsoni because its isoenzyme profiles for 10 of 12 enzymes resembled those of A. culbertsoni, Lilly A‐1 strain. Since the isoenzyme profiles and the antigenic patterns of the fish isolate as well were remarkably similar to those of A. royreba, it was considered as a strain of A. royreba. Polyacrylamide gradient gel electrophoresis appears to be a powerful technique for the study of isoenzymes and antigens of Acanthamoeba."
694,"An Ultrastructural Study of Vairimorpha necatrix (Microspora, Microsporida) with Particular Reference to Episporontal Inclusions During Octosporogony","ABSTRACT. The life cycle of Vairimorpha necatrix was studied by electron microscopy. Disporous development has two distinct stages: 1) diplokaryotic meronts which are actively mitotic, and 2) diplokaryotic sporonts which are distinguished by reduced ribosome density and a thickened plasmalemma. After final division of the sporont, sporoblasts form spores which are ovocylindrical and measure 4.4 ± 0.08 × 2.3 ± 0.05 μm (mean ± SE). Octosporous development results in eight haploid spores being formed in a sporophorous vesicle. The uninucleate octospores were smaller than the binucleate dispores and the exospore was thicker but less crenulate in outline. Early in octosporogony, tubules are produced from the sporont plasmalemma and electron‐dense material accumulates in the episporontal space. The latter may be amorphous, vesiculated, or vacuolated in appearance and in later stages may take a stacked, lamellar form. At sporoblast formation, exospore material coats the plasmalemma and attached tubules; all inclusions in the episporontal space gradually disappear as spores are formed. These secretory products may have application to taxonomic distinction at the species level."
695,Multiplication of rubella and measles viruses in primary rat neural cell cultures: relevance to a postulated triggering mechanism for multiple sclerosis,"Rubella virus multiplied to low titre and produced a partial cytopathic effect in rat glial cell cultures. Anti‐galactocerebroside staining showed that this cytopathic effect involved the disintegration of oligodendrocytes. A similar effect was produced following infection of myelinating neural cell cultures with rubella virus, but virus multiplication could not be detected in pure neuron cultures. Measles virus was found to multiply and produce a cytopathic effect in primary cultures of both neurons and glial cells. These results are discussed in relation to the ability of measles and rubella viruses to trigger human multiple sclerosis."
696,Aspects of canine distemper virus and measles virus encephalomyelitis,"Canine distemper (CD) is a frequently fatal, systemic morbillivirus infection in the dog and other carnivores: encephalomyelitis is the common cause of death. Susceptibility to canine distemper virus (CDV) is now recognized in a wide range of non–domestic animals, most recently in captive lions, tigers and leopards. Furthermore, closely related viruses have produced CD–like diseases in marine mammals. CDV induces an inclusion–body encephalomyelitis in the dog and demyelination is often a conspicuous feature. Myelin injury is associated with the presence of virus but the mechanism of demyelination remains incompletely understood. Oligodendrocyte infection may be defective, as has been shown in vitro. CDV and measles virus (MV) produce similar systemic disorders in their respective hosts but differ markedly in the frequency of central nervous system (CNS) involvement, and in the pathogenesis of the more common neurological sequelae. Both CDV and MV have been considered as multiple sclerosis agents, and the association of CDV with other human disease has been suggested."
697,Considerations for Drug Interactions on QTc in Exploratory COVID-19 (Coronavirus Disease 2019) Treatment,
698,COVID-19 cacophony: is there any orchestra conductor?,
699,"Clinical characteristics and imaging manifestations of the 2019 novel coronavirus disease (COVID-19): A multi-center study in Wenzhou city, Zhejiang, China",
700,Practice recommendations for lung cancer radiotherapy during the COVID-19 pandemic: An ESTRO-ASTRO consensus statement,
701,Department of Error,
702,Correction to Lancet Glob Health 2020; 8: e452–53,
703,Multiple parameters required for diagnosis of COVID-19 in clinical practice,
704,Avian macrophage and immune response: an overview,"Macrophages belong to the mononuclear phagocytic system lineage. This cell type is unique in that it is a crucial player in both the innate and adaptive immune responses. The material described in this overview is a brief description of what I presented as a World's Poultry Science Association-sponsored lecture at the annual meetings of the Poultry Science Association in 2002. Therefore, I have not attempted to present an up-to-date review of literature on this topic. Rather, I have summarized some salient research accomplishments made by our research group over the years in the area of avian macrophage biology and function."
705,Letter from the Guest Editors,
706,Clinical and CT imaging features of 2019 novel coronavirus disease (COVID-19),
707,HEALTH STATUS OF LIVER TRANSPLANTED PATIENTS DURING THE CORONAVIRUS OUTBREAK IN ITALY: A LARGE SINGLE CENTER EXPERIENCE FROM MILAN,
708,A non-static quantum inspired spacetime in f(R) gravity: Gravity's rainbow,"In this note we explore a non-static spacetime in quantum regime in the background of [Formula: see text] gravity. The time dependent Vaidya metric which represents the spacetime of a radiating body like star is studied in an energy dependent gravity's rainbow, which is a UV completion of General Relativity. In our quest we have used gravitational collapse as the main tool. The focus is to probe the nature of singularity (black hole or naked singularity) formed out of the collapsing procedure. This is achieved via a geodesic study. For our investigation we have considered two different models of [Formula: see text] gravity, namely the inflationary Starobinsky's model and the power law model. Our study reveals the fact that naked singularity is as good a possibility as black hole as far as the central singularity is concerned. Via a proper fine tuning of the initial data, we may realize both black hole or naked singularity as the end state of the collapse. Thus this study is extremely important and relevant in the light of the Cosmic Censorship hypothesis. The most important result derived from the study is that gravity's rainbow increases the tendency of formation of naked singularities. We have also deduced the conditions under which the singularity will be a strong or weak curvature singularity. Finally in our quest to know more about the model we have performed a thermodynamical study. Throughout the study we have obtained results which involve deviation from the classical set-up. Such deviations are expected in a quantum evolution and can be attributed to the quantum fluctuations that our model suffers from. It is expected that this study will enhance our knowledge about quantization of gravity and subsequently about the illusive theory of quantum gravity."
709,Physical activity for immunity protection: Inoculating populations with healthy living medicine in preparation for the next pandemic(),
710,Artificial Intelligence (AI) applications for COVID-19 pandemic,"BACKGROUND AND AIMS: Healthcare delivery requires the support of new technologies like Artificial Intelligence (AI), Internet of Things (IoT), Big Data and Machine Learning to fight and look ahead against the new diseases. We aim to review the role of AI as a decisive technology to analyze, prepare us for prevention and fight with COVID-19 (Coronavirus) and other pandemics. METHODS: The rapid review of the literature is done on the database of Pubmed, Scopus and Google Scholar using the keyword of COVID-19 or Coronavirus and Artificial Intelligence or AI. Collected the latest information regarding AI for COVID-19, then analyzed the same to identify its possible application for this disease. RESULTS: We have identified seven significant applications of AI for COVID-19 pandemic. This technology plays an important role to detect the cluster of cases and to predict where this virus will affect in future by collecting and analyzing all previous data. CONCLUSIONS: Healthcare organizations are in an urgent need for decision-making technologies to handle this virus and help them in getting proper suggestions in real-time to avoid its spread. AI works in a proficient way to mimic like human intelligence. It may also play a vital role in understanding and suggesting the development of a vaccine for COVID-19. This result-driven technology is used for proper screening, analyzing, prediction and tracking of current patients and likely future patients. The significant applications are applied to tracks data of confirmed, recovered and death cases."
711,Leadership Evolution: The Academy's Sustained and Growing Contribution,
712,Pandemic school closures: risks and opportunities,
713,Validation of RESP and PRESERVE score for ARDS patients with pumpless extracorporeal lung assist (pECLA),"BACKGROUND: RESP score and PRESERVE score have been validated for veno-venous Extracorporeal Membrane Oxygenation in severe ARDS to assume individual mortality risk. ARDS patients with low-flow Extracorporeal Carbon Dioxide Removal, especially pumpless Extracorporeal Lung Assist, have also a high mortality rate, but there are no validated specific or general outcome scores. This retrospective study tested whether these established specific risk scores can be validated for pumpless Extracorporeal Lung Assist in ARDS patients in comparison to a general organ dysfunction score, the SOFA score. METHODS: In a retrospective single center cohort study we calculated and evaluated RESP, PRESERVE, and SOFA score for 73 ARDS patients with pumpless Extracorporeal Lung Assist treated between 2002 and 2016 using the XENIOS iLA Membrane Ventilator. Six patients had a mild, 40 a moderate and 27 a severe ARDS according to the Berlin criteria. Demographic data and hospital mortality as well as ventilator settings, hemodynamic parameters, and blood gas measurement before and during extracorporeal therapy were recorded. RESULTS: Pumpless Extracorporeal Lung Assist of mechanical ventilated ARDS patients resulted in an optimized lung protective ventilation, significant reduction of P(aCO2), and compensation of acidosis. Scoring showed a mean score of alive versus deceased patients of 3 ± 1 versus − 1 ± 1 for RESP (p < 0.01), 3 ± 0 versus 6 ± 0 for PRESERVE (p < 0.05) and 8 ± 1 versus 10 ± 1 for SOFA (p < 0.05). Using receiver operating characteristic curves, area under the curve (AUC) was 0.78 (95% confidence interval (CI) 0.67–0.89, p < 0.01) for RESP score, 0.80 (95% CI 0.70–0.90, p < 0.0001) for PRESERVE score and 0.66 (95% CI 0.53–0.79, p < 0.05) for SOFA score. CONCLUSIONS: RESP and PRESERVE scores were superior to SOFA, as non-specific critical care score. Although scores were developed for veno-venous ECMO, we could validate RESP and PRESERVE score for pumpless Extracorporeal Lung Assist. In conclusion, RESP and PRESERVE score are suitable to estimate mortality risk of ARDS patients with an arterio-venous pumpless Extracorporeal Carbon Dioxide Removal."
714,The Generation of Virtual Defenders,
715,Maurizio Galderisi. In Memoriam,
716,Comparison of ATP Bioluminescence and Aerobic Bacterial Count for Evaluating Surface Cleanliness in an Italian Hospital,"Contaminated hospital surfaces have been demonstrated to be an important environmental reservoir of microorganisms that can increase the risk of nosocomial infection in exposed patients. As a consequence, cleaning and disinfecting hospital environments play an important role among strategies for preventing healthcare-associated colonization and infections. The aim of the present study was to evaluate whether adenosine triphosphate (ATP) presence, measured by bioluminescence methods, can predict microbiological contamination of hospital surfaces. The study was carried out between September and December 2012 at the University Hospital “P. Giaccone” of Palermo. A total of 193 randomly selected surfaces (tables, lockers, furnishings) were sampled and analyzed in order to assess ATP levels (expressed as relative light units or RLU) and aerobic colony count (ACC) or presence of S. aureus. ACC had median values of 1.85 cfu/cm(2) (interquartile range = 4.16) whereas ATP median was 44.6 RLU/cm(2) (interquartile range = 92.3). Overall, 85 (44.0%) surfaces exceeded the established microbial benchmark: 73 (37.8%) exceeded the 2.5 cfu/cm(2) ACC standard, 5 (2.6%) surfaces were positive for S. aureus and 7 (3.6%) showed both the presence of S. aureus and an ACC of more than 2.5 cfu/cm(2). ACC and bioluminescence showed significant differences in the different surface sites (p < 0.001). A significant correlation was found between ACC and RLU values (p-value < 0.001; R(2) = 0.29) and increasing RLU values were significantly associated with a higher risk of failing the benchmark (p < 0.001). Our data suggest that bioluminescence could help in measuring hygienic quality of hospital surfaces using a quick and sensitive test that can be an useful proxy of microbial contamination; however, further analysis will be necessary to assess the cost-efficacy of this methodology before requiring incorporation in hospital procedures."
717,Analysis of Residual Chemicals on Filtering Facepiece Respirators After Decontamination,"The N95 filtering facepiece respirator (FFR) is commonly used to protect individuals from infectious aerosols. Health care experts predict a shortage of N95 FFRs if a severe pandemic occurs, and an option that has been suggested for mitigating such an FFR shortage is to decontaminate and reuse the devices. Before the effectiveness of this strategy can be established, many parameters affecting respiratory protection must be measured: biocidal efficacy of the decontamination treatment, filtration performance, pressure drop, fit, and toxicity to the end user post treatment. This research effort measured the amount of residual chemicals created or deposited on six models of FFRs following treatment by each of 7 simple decontamination technologies. Measured amounts of decontaminants retained by the FFRs treated with chemical disinfectants were small enough that exposure to wearers will be below the permissible exposure limit (PEL). Toxic by-products were also evaluated, and two suspected toxins were detected after ethylene oxide treatment of FFR rubber straps. The results provide encouragement to efforts promoting the evolution of effective strategies for decontamination and reuse of FFRs."
718,Health Care Workers’ Mobile Phones: A Potential Cause of Microbial Cross-Contamination Between Hospitals and Community,"This study evaluated the microbial contamination of health care workers’ (HCWs) mobile phones. The study was conducted at a secondary referral hospital in July 2010. Samples were taken from all surfaces of the mobile phones using a sterile swab, and incubated on Brain Heart Infusion agar at 37.5°C for 24 hr. Any isolated microorganisms were grown aerobically on 5% sheep blood agar and eosin methylene-blue agar medium at 37.5°C for 24–48 hr. The Sceptor microdilution system was used to identify the microorganisms, together with conventional methods. The oxacillin disc diffusion test and double-disc synergy test were used to identify methicillin-resistant Staphylococcus aureus (MRSA) and expanded-spectrum beta-lactamase (ESBL)-producing Gram-negative bacilli, respectively. The mobile phones were also categorized according to whether the HCWs used them in the intensive care unit (ICU). Overall, 183 mobile phones were screened: 94 (51.4%) from nurses, 32 (17.5%) from laboratory workers, and 57 (31.1%) from health care staff. In total, 179 (97.8%) culture-positive specimens were isolated from the 183 mobile phones, including 17 (9.5%) MRSA and 20 (11.2%) ESBL-producing Escherichia coli, which can cause nosocomial infections. No statistical difference was observed in the recovery of MRSA (p = 0.3) and ESBL-producing E. coli (p = 0.6) between the HCW groups. Forty-four (24.6%) of the 179 specimens were isolated from mobile phones of ICU workers, including two MRSA and nine ESBL-producing E. coli. A significant (p = 0.02) difference was detected in the isolation of ESBL-producing E. coli between ICU workers and non-ICU workers. HCWs’ mobile phones are potential vectors for transferring nosocomial pathogens between HCWs, patients, and the community."
719,Inactivation of Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus faecium (VRE) on Various Environmental Surfaces by Mist Application of a Stabilized Chlorine Dioxide and Quaternary Ammonium Compound-Based Disinfectant,"Contaminated environmental surfaces are important reservoirs in the transmission of many human pathogens. Although several options exist for disinfecting contaminated environmental surfaces, few are compatible with use on both hard smooth non-porous (hard) and soft porous surfaces (soft) while still offering significant disinfection of the contaminating organisms. This study evaluated the efficacy of mist application of a stabilized chlorine dioxide and quaternary ammonium compound-based disinfectant (Cryocide20) for inactivation of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) on various environmental surfaces. MRSA and VRE were applied to hard and soft surfaces (glass, steel, tile, carpet, and cotton fabric), allowed to dry, and exposed to a uniform mist application of the disinfectant solution. After 1 hr of contact time, the residual disinfectant was neutralized, and the bacteria were recovered and enumerated on brain heart infusion (BHI) agar. Reduction of both test bacteria was observed on most of the hard and soft surfaces tested. Log(10) reduction of the organisms tended to be higher on steel, tile, and carpet than glass or cotton. Overall, these results suggest that mist application of Cryocide20 disinfectant may be an effective option for reduction of low levels of infectious bacterial pathogens from contaminated environmental surfaces."
720,A Study Quantifying the Hand-to-Face Contact Rate and Its Potential Application to Predicting Respiratory Tract Infection,"A substantial portion of human respiratory tract infection is thought to be transmitted via contaminated hand contact with the mouth, eyes, and/or nostrils. Thus, a key risk factor for infection transmission should be the rate of hand contact with these areas termed target facial membranes. A study was conducted in which 10 subjects were each videotaped for 3 hr while performing office-type work in isolation from other persons. The number of contacts to the eyes, nostrils, and lips was scored during subsequent viewing of the tapes. The total contacts per subject had sample mean x = 47 and sample standard deviation s = 34. The average total contact rate per hour was 15.7. The authors developed a relatively simple algebraic model for estimating the dose of pathogens transferred to target facial membranes during a defined exposure period. The model considers the rate of pathogen transfer to the hands via contact with contaminated environmental surfaces, and the rate of pathogen loss from the hands due to pathogen die-off and transfer from the hands to environmental surfaces and to target facial membranes during touching. The estimation of infection risk due to this dose also is discussed. A hypothetical but plausible example involving influenza A virus transmission is presented to illustrate the model."
721,Discomfort and Exertion Associated with Prolonged Wear of Respiratory Protection in a Health Care Setting,"The nature of discomfort and level of exertion associated with wearing respiratory protection in the health care workplace are not well understood. Although a few studies have assessed these topics in a laboratory setting, little is known about the magnitude of discomfort and the level of exertion experienced by workers while they deliver health care to patients for prolonged periods. The purpose of this study was to determine the magnitude of discomfort and level of exertion experienced by health care workers while wearing respiratory protection for periods up to 8 hr when performing their typical occupational duties. This project was a multiple cross-over field trial of 27 health care workers, aged 24–65, performing their typical, hospital-based occupational duties. Each participant served as his/her own control and wore one of seven respirators or a medical mask for 8 hr (or as long as tolerable) with interposed doffing periods every 2 hr. Self-perceived discomfort and exertion were quantified before each doffing: self-perceived level of discomfort using a visual analog scale, and self-perceived level of exertion using a Borg scale. Overall, and as would be expected, discomfort increased over time with continual respirator use over an 8-hr period. Interestingly, exertion increased only marginally over the same time period. The relatively low level of exertion associated with eight respiratory protective devices, including models commonly used in the U.S. health care workplace, is not likely to substantially influence workers’ tolerability or occupational productivity. However, the magnitude of discomfort does appear to increase significantly over time with prolonged wear. These results suggest that respirator-related discomfort, but not exertion, negatively influences respirator tolerance over prolonged periods. Discomfort may also interfere with the occupational duties of workers."
722,ATP as a Marker for Surface Contamination of Biological Origin in Schools and as a Potential Approach to the Measurement of Cleaning Effectiveness,"To address the need for a quantitative approach to the measurement of cleaning effectiveness, related to biologically derived surface contamination, three commercially available adenosine triphosphate (ATP) test systems were used to collect multiple samples measured in relative light units (RLUs) from 27 elementary schools in the southwestern United States before and after a standardized cleaning protocol. The database consisted of 6480 ATP measurements from four critical surfaces (student desktops, cafeteria tabletops, and restroom sinks and stall doors). Data was assessed according to ranges of ATP values before and after cleaning. Results showed the potential for such data to provide the basis for a standardized approach to the measurement of cleaning effectiveness, based on detection and quantification of pollutant loads of biological origin, across critical surfaces in school building environments. It is anticipated that verification of this data in school buildings across different geographic and climatic regions will lead to the establishment of “acceptable” ranges of ATP values that can be used as a practice-based approach to improving cleaning practices and contributing to healthier school environments."
723,Toward Understanding the Risk of Secondary Airborne Infection: Emission of Respirable Pathogens,"Certain respiratory tract infections are transmitted through air. Coughing and sneezing by an infected person can emit pathogen-containing particles with diameters less than 10 μm that can reach the alveolar region. Based on our analysis of the sparse literature on respiratory aerosols, we estimated that emitted particles quickly decrease in diameter due to water loss to one-half the initial values, and that in one cough the volume in particles with initial diameters less than 20 μm is 6 × 10(−8) mL. The pathogen emission rate from a source case depends on the frequency of expiratory events, the respirable particle volume, and the pathogen concentration in respiratory fluid. Viable airborne pathogens are removed by exhaust ventilation, particle settling, die-off, and air disinfection methods; each removal mechanism can be assigned a first-order rate constant. The pathogen concentration in well-mixed room air depends on the emission rate, the size distribution of respirable particles carrying pathogens, and the removal rate constants. The particle settling rate and the alveolar deposition fraction depend on particle size. Given these inputs plus a susceptible person's breathing rate and exposure duration to room air, an expected alveolar dose μ is estimated. If the infectious dose is one organism, as appears to be true for tuberculosis, infection risk is estimated by the expression: R = 1 − exp(−μ). Using published tuberculosis data concerning cough frequency, bacilli concentration in respiratory fluid, and die-off rate, we illustrate the model via a plausible scenario for a person visiting the room of a pulmonary tuberculosis case. We suggest that patients termed “superspreaders” or “dangerous disseminators” are those infrequently encountered persons with high values of cough and/or sneeze frequency, elevated pathogen concentration in respiratory fluid, and/or increased respirable aerosol volume per expiratory event such that their pathogen emission rate is much higher than average."
724,Performance of an N95 Filtering Facepiece Particulate Respirator and a Surgical Mask During Human Breathing: Two Pathways for Particle Penetration,"The protection level offered by filtering facepiece particulate respirators and face masks is defined by the percentage of ambient particles penetrating inside the protection device. There are two penetration pathways: (1) through the faceseal leakage, and the (2) filter medium. This study aimed at differentiating the contributions of these two pathways for particles in the size range of 0.03–1 μm under actual breathing conditions. One N95 filtering facepiece respirator and one surgical mask commonly used in health care environments were tested on 25 subjects (matching the latest National Institute for Occupational Safety and Health fit testing panel) as the subjects performed conventional fit test exercises. The respirator and the mask were also tested with breathing manikins that precisely mimicked the prerecorded breathing patterns of the tested subjects. The penetration data obtained in the human subject- and manikin-based tests were compared for different particle sizes and breathing patterns. Overall, 5250 particle size- and exercise-specific penetration values were determined. For each value, the faceseal leakage-to-filter ratio was calculated to quantify the relative contributions of the two penetration pathways. The number of particles penetrating through the faceseal leakage of the tested respirator/mask far exceeded the number of those penetrating through the filter medium. For the N95 respirator, the excess was (on average) by an order of magnitude and significantly increased with an increase in particle size (p < 0.001): ∼7-fold greater for 0.04 μm, ∼10-fold for 0.1 μm, and ∼20-fold for 1 μm. For the surgical mask, the faceseal leakage-to-filter ratio ranged from 4.8 to 5.8 and was not significantly affected by the particle size for the tested submicrometer fraction. Facial/body movement had a pronounced effect on the relative contribution of the two penetration pathways. Breathing intensity and facial dimensions showed some (although limited) influence. Because most of the penetrated particles entered through the faceseal, the priority in respirator/mask development should be shifted from improving the efficiency of the filter medium to establishing a better fit that would eliminate or minimize faceseal leakage."
725,St. Corona – eine Fürsprecherin gegen Seuchen?: Eine Miszelle aus der Medizin- und Urologiegeschichte,"The knowledge of hagiography and hagiotherapy still plays an important role in the history of science, especially when focusing on specific aspects of history. While knowledge about St. Liborius persists in urology, knowledge about patron saints for pandemics, especially those who were called upon to treat venereal diseases, has diminished due to the association with nonappropriate sexual behavior."
726,Gold nanoparticles for preparation of antibodies and vaccines against infectious diseases,"Introduction: Vaccination remains very effective in stimulating protective immune responses against infections. An important task in antibody and vaccine preparation is to choose an optimal carrier that will ensure a high immune response. Particularly promising in this regard are nanoscale particle carriers. An antigen that is adsorbed or encapsulated by nanoparticles can be used as an adjuvant to optimize the immune response during vaccination. a very popular antigen carrier used for immunization and vaccination is gold nanoparticles, with are being used to make new vaccines against viral, bacterial, and parasitic infections. Areas covered: This review summarizes what is currently known about the use of gold nanoparticles as an antigen carrier and adjuvant to prepare antibodies in vivo and design vaccines against viral, bacterial, and parasitic infections. The basic principles, recent advances, and current problems in the use of gold nanoparticles are discussed. Expert opinion: Gold nanoparticles can be used as adjuvants to increase the effectiveness of vaccines by stimulating antigen-presenting cells and ensuring controlled antigen release. Studying the characteristics of the immune response obtained from the use of gold nanoparticles as a carrier and an adjuvant will permit the particles’ potential for vaccine design to be increased."
727,Pathogenic variants in CDC45 on the remaining allele in patients with a chromosome 22q11.2 deletion result in a novel autosomal recessive condition,"PURPOSE: The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion in humans, with highly variable phenotypic expression. Whereas congenital heart defects, palatal anomalies, immunodeficiency, hypoparathyroidism, and neuropsychiatric conditions are observed in over 50% of patients with 22q11DS, a subset of patients present with additional “atypical” findings such as craniosynostosis and anorectal malformations. Recently, pathogenic variants in the CDC45 (Cell Division Cycle protein 45) gene, located within the LCR22A–LCR22B region of chromosome 22q11.2, were noted to be involved in the pathogenesis of craniosynostosis. METHODS: We performed next-generation sequencing on DNA from 15 patients with 22q11.2DS and atypical phenotypic features such as craniosynostosis, short stature, skeletal differences, and anorectal malformations. RESULTS: We identified four novel rare nonsynonymous variants in CDC45 in 5/15 patients with 22q11.2DS and craniosynostosis and/or other atypical findings. CONCLUSION: This study supports CDC45 as a causative gene in craniosynostosis, as well as a number of other anomalies. We suggest that this association results in a condition independent of Meier–Gorlin syndrome, perhaps representing a novel condition and/or a cause of features associated with Baller–Gerold syndrome. In addition, this work confirms that the phenotypic variability observed in a subset of patients with 22q11.2DS is due to pathogenic variants on the nondeleted chromosome."
728,Targeted tumour theranostics in mice via carbon quantum dots structurally mimicking large amino acids,"Strategies for selectively imaging and delivering drugs to tumours typically leverage differentially upregulated surface molecules on cancer cells. Here, we show that intravenously injected carbon quantum dots, functionalized with multiple paired α-carboxyl and amino groups that bind to the large neutral amino acid transporter 1 (which is expressed in most tumours), selectively accumulate in human tumour xenografts in mice and in an orthotopic mouse model of human glioma. The functionalized quantum dots, which structurally mimic large amino acids and can be loaded with aromatic drugs through π–π stacking interactions, enabled—in the absence of detectable toxicity—near-infrared fluorescence and photoacoustic imaging of the tumours and a reduction in tumour burden after the targeted delivery of chemotherapeutics to the tumours. The versatility of functionalization and high tumour selectivity of the quantum dots make them broadly suitable for tumour-specific imaging and drug delivery."
729,Outcome of patients with cirrhosis requiring intensive care unit support: Prospective assessment of predictors of mortality,"Determinants of outcome and the utility of the Child-Pugh score and the acute physiology and chronic health evaluation (APACHE) II score as predictors of outcome were prospectively assessed in 54 consecutive patients with cirrhosis requiring intensive care unit (ICU) management. Overall mortality in the ICU was 43% (23/54). Child-Pugh scores did not differ between survivors or nonsurvivors (12.8 versus 12.3, P = 0.26), however APACHE II scores (P = 0.007), acute physiology scores (P = 0.006), and Karnofsky scores (P = 0.001) were significant predictors of outcome. By univariate analysis, requirement of mechanical ventilation analysis (P = 0.001), duration of mechanical ventilation (P = 0.001), pulmonary infiltrates (P = 0.0001), infections (P = 0.047), gastrointestinal bleeding (P = 0.005), and serum creatinine ≥1.5 mg/dl (P = 0.0005) were significantly associated with mortality. By logistic regression analysis only pulmonary infiltrates (P = 0.0001) and renal dysfunction (P = 0.041) were independent predictors of mortality. When controlled for the severity of illness (APACHE II scores), the mortality in patients with cirrhosis caused by alcohol was significantly lower than that in patients with liver disease not caused by alcohol (P = 0.01). Our study not only identified predictors of poor outcome in patients with cirrhosis requiring ICU care but also provided data that may have implications for optimal timing for transplantation."
730,Vaping induced pneumonitis: a small community hospital’s case series and analysis,"BACKGROUND: Electronic cigarettes/e-cigarettes (ECs), or vaping, is currently the most popular form of smoking amongst youth in the United States. ECs are battery-powered devices that vaporize a liquid that comes in small cartridges, or pods, that contain various chemicals, nicotine, and an array of flavors that can be modified to include cannabinoids (THC). With increasing popularity, however, there is an epidemic of pulmonary and gastrointestinal illnesses associated with vaping in the continental U.S.A. METHODS: We analyzed medical charts of three patients who were active users of ECs and presented with pneumonitis to our community medical center between January and August 2019. RESULTS: We report three cases of vaping pneumonitis in young adults, ages 18 to 21, who presented with similar symptoms, profiles, imaging studies, and disease progression. The average length of stay was approximately one week, and all patients had an extensive work-up in addition to a relapsing and remitting course of their condition. CONCLUSIONS: Early recognition and diagnosis of vaping pneumonitis are essential in the treatment of the ongoing epidemic. Extensive unnecessary work up may lead to increased healthcare costs. Our case series echoes the concerns of the CDC such that ECs should be avoided, and those with any pulmonary or gastrointestinal symptoms should seek medical attention promptly."
731,Adjuvant Immunotherapy of Feline Fibrosarcoma with Recombinant Feline Interferon‐ω,"Background: Recombinant feline interferon‐ω (rFeIFN‐ω) was tested as a treatment option for cats with fibrosarcoma to assess safety and feasibility. Hypothesis: Treatment with rFeIFN‐ω in cats with fibrosarcoma is safe and feasible. Animals: Twenty domestic cats. Methods: In an open‐labeled uncontrolled clinical trial 12 injections of 1 × 10(6) U/kg rFeIFN‐ω were administered over a 5‐week period: the 1st through 4th injections were given intratumorally, and the 5th through 12th injections were administered subcutaneously at the tumor excision site. Wide surgical excision of the tumors was carried out after the 4th injection and before the 5th injection of rFeIFN‐ω. A Common Terminology Criteria for Adverse Events (CTCAE) analysis was conducted. Flow cytometry of fibrosarcoma cells after incubation with rFeIFN‐ω and recombinant feline interferon‐γ was performed to assess the biological effect of rFeIFN‐ω. Results: Changes in blood cell count, increases in serum aspartate‐amino‐transferase activity, serum bilirubin concentration, serum creatinine and serum electrolyte concentrations, weight loss, anorexia, increased body temperature, and reduced general condition were observed but were mostly minor (grade 1 and 2) and self limiting. Eosinophilia (P= .025), neutropenia (P= .021), and weight loss (P < .001) were statistically correlated with rFeIFN‐ω‐treatment (analysis of parameters before treatment and after 3 injections of rFeIFN‐ω). Flow cytometry of 5 unrelated feline fibrosarcoma cell lines showed increased expression of major histocompatibility complex (MHC) class I molecules (P= .026) in response to in vitro incubation with rFeIFN‐ω, whereas expression of MHC class II molecules was not affected significantly. Conclusions and Clinical Importance: RFeIFN‐ω for the treatment of feline fibrosarcoma is safe, well tolerated, and can be easily performed in practice. To assess the efficacy of the treatment, it should be tested in a placebo‐controlled trial."
732,"Shutting Up Infected Houses: Infectious Disease Control, Past and Present",
733,Return to the Past: The Case for Antibody-Based Therapies in Infectious Diseases,"In the preantibiotic era, passive antibody administration (serum therapy) was useful for the treatment of many infectious diseases. The introduction of antimicrobial chemotherapy in the 1940s led to the rapid abandonment of many forms of passive antibody therapy. Chemotherapy was more effective and less toxic than antibody therapy. In this last decade of the 20th century the efficacy of antimicrobial chemotherapy is diminishing because of the rapidly escalating number of immunocompromised individuals, the emergence of new pathogens, the reemergence of old pathogens, and widespread development of resistance to antimicrobial drugs. This diminishment in the effectiveness of chemotherapy has been paralleled by advances in monoclonal antibody technology that have made feasible the generation of human antibodies. This combination of factors makes passive antibody therapy an option worthy of serious consideration. We propose that for every pathogen there exists an antibody that will modify the infection to the benefit of the host. Such antibodies are potential antimicrobial agents. Antibody-based therapies have significant advantages and disadvantages relative to standard chemotherapy. The reintroduction of antibody-based therapy would require major changes in the practices of infectious disease specialists."
734,Hot hearts on bone scintigraphy are not all amyloidosis: hydroxychloroquine-induced restrictive cardiomyopathy,
735,Selection of an aminoglycoside antibiotic for administration to horses,"The serum concentrations of the aminoglycosides neomycin, kanamycin and streptomycin were determined after intravenous (iv) and intramuscular (im) administration. These values were then related to the minimum inhibitory concentrations (MIC) of a number of equine pathogenic bacteria to determine the duration of therapeutic serum concentrations of the aminoglycosides in the horse. Pharmacokinetic analysis of the data using neomycin as the example revealed a mean (± sd) peak serum concentration of 23.2 ± 10.2 μg/ml present at 30 mins, and at 8 h the serum concentration was 2.8 ± 0.8 μg/ml. From the pharmacological analysis of concentration‐time data it was shown that neomycin was very rapidly absorbed from the im injection site, with an absorption half‐time of 0.16 ± 0.05 and was well absorbed (systemic availability was 73.7 ± 26.9 per cent). A peak tissue level, which represented 40 per cent of the amount of drug in the body, was obtained at 32 mins after injection of the drug. At 8 h, the fractions of the dose in the central and peripheral compartments of the model were 1.5 per cent and 2.5 per cent respectively, and 96 per cent was the cumulative amount eliminated up to that time. Based on the MIC values of the majority of isolates of Corynebacterium equi, and only a few isolates of Klebsiella pneumoniae, Escherichia coli, Salmonella typhimurium and Streptococcus equi, one would expect a serum concentration of more than 2 μg neomycin/ml up to 8 h following im dosage (10 mg/kg) to be therapeutically effective."
736,Ingestion of sugar beet fiber enhances irradiation-induced aberrant crypt foci in the rat colon under an apoptosis-suppressed condition,"The induction of aberrant crypt foci (ACF) by irradiation of γ-rays ((60)Co), and the effect of dietary sugar beet fiber (SBF) on irradiation-induced ACF were examined. We found that abdominal irradiation of γ-rays could induce ACF in the rat colon. The irradiation was performed once a week at a dose rate of 2 or 3 Gy per irradiation. Irradiation-induced ACF were observed in the colon at 10 weeks after the first irradiation at dose of 2 Gy for six times or 3 Gy for four times. Dietary SBF had no effect on the number of ACF, aberrant crypts (AC) or AC/focus induced by abdominal γ-irradiation. However, an ingestion of SBF resulted in an increase in the number of these parameters in apoptosis-suppressed rats by cycloheximide (CHX). An injection of CHX suppressed irradiation-induced apoptosis of the colonic epithelial cells for at least 6 h after the irradiation. In CHX-injected rats, an ingestion of SBF significantly increased the number of ACF, AC and AC/focus compared with fiber-free fed rats at 9 weeks after the first irradiation. On the other hand, in saline-injected rats, no significant difference was found between SBF and fiber-free diets in the number of ACF, AC and AC/focus through the experimental period. These results suggest that dietary SBF may be involved in the elimination of abnormal cells from an irradiated colon through the apoptosis of colonic epithelial cells. In this study, we have shown a new method for inducing ACF by using γ-rays which were not influenced by luminal contents such as bacterial enzyme, at least in the initiation stage."
737,Hyperkalemic Atrial Standstill in Neonatal Calf Diarrhea,"Hyperkalemia has been associated with cardiac abnormalities and muscular disorders. Hyperkalemia is a common problem associated with the acid‐base and electrolyte disturbances that occur in neonatal calves having acute diarrhea. Occasional calves with acute neonatal diarrhea, metabolic acidosis, and hyperkalemia have cardiac rate or rhythm abnormalities. Bradycardia observed in three such calves was found to represent atrial standstill and was attributed to hyperkalemia. (Journal of Veterinary Internal Medicine 1992; 6:294–297)"
738,Evaluation of murine norovirus as a surrogate for human norovirus and hepatitis A virus in heat inactivation studies,"Aims: To determine the suitability of murine norovirus (MNV) as a surrogate for human norovirus (HuNoV) in heat inactivation studies. Methods and Results: MNV, hepatitis A virus (HAV) and HuNoV genogroup I and II (GI and GII) specific real‐time quantitative reverse transcription (qRT)‐PCR assays were used to determine the effects of heat exposure (63 and 72°C) for up to 10 min in water and milk. Using culture assays, MNV and HAV showed similar reductions in infectivity over time. Both HuNoV GI and GII showed lower log reductions in qRT‐PCR titre following heat exposure than either MNV or HAV. No significant protective effect of milk was observed for any virus. Conclusions: MNV is as suitable a surrogate for HuNoV as HAV. In heat inactivation studies at 63 and 72°C, qRT‐PCR results indicate that HuNoV is less susceptible to heat than either HAV or MNV and so neither virus may be an appropriate surrogate for HuNoV. Significance and Impact of the Study: Caution should be used when extrapolating surrogate virus data for HuNoV. Although not conclusive, our results suggest that HuNoV may be more resistant to heat than either HAV or MNV."
739,ARHGAP24 inhibits cell proliferation and cell cycle progression and induces apoptosis of lung cancer via a STAT6-WWP2-p27 axis,"Rho GTPase-activating proteins (RhoGAPs) have been reported to be of great importance in the initiation and development of many different cancers. However, their biological roles and regulatory mechanisms in lung cancer development and progression are poorly defined. Real-time PCR or western blotting analysis was used to detect Rho GTPase-activating protein 24 (ARHGAP24), WWP2, p27, p-STAT6 and STAT6 expression levels as well as the activity of RhoA and Rac1 in lung cancer. Cell proliferation, apoptosis and cell cycle were measured by CCK-8 and flow cytometry analysis. Tumor growth of lung cancer cells was measured using a nude mouse xenograft experiment model in vivo. The correlation between WWP2 and p27 was measured by co-immunoprecipitation and ubiquitination analysis. We found that ARHGAP24 expression was lower in lung cancer tissues collected from the The Cancer Genome Atlas and independent hospital database. Overexpression of ARHGAP24 significantly suppressed cell proliferation and the activity of RhoA and Rac1, induced cell apoptosis and arrested cell cycle at the G(0)–G(1) phase. ARHGAP24 overexpression also inhibited tumor growth in nude mice, whereas knockdown of ARHGAP24 significantly promoted cell proliferation and WWP2 expression and inhibited cell cycle arrest at G(1) phase through activating STAT6 signaling. ARHGAP24 overexpression inhibited WWP2 overexpression-induced cell proliferation, cell cycle progression and the decreased p27 expression. Moreover, WWP2 was found interacted with p27, and WWP2 overexpression promoted the ubiquitination of p27. In conclusion, our findings suggest that ARHGAP24 inhibits cell proliferation and cell cycle progression and induces cell apoptosis of lung cancer via a STAT6-WWP2-p27 axis."
740,Microbial contamination in kitchens and bathrooms of rural Cambodian village households,"Aims: To quantify microbial contamination on kitchen and bathroom surfaces (fomites) in rural Cambodian homes and to compare these concentrations to similar data from the United States and Japan. Methods and Results: This study monitored the numbers of faecal coliforms (i.e. thermotolerant coliforms), total coliforms, Escherichia coli and heterotrophic plate count bacteria on household surfaces in a rural village of Cambodia. Faecal coliform levels in Cambodia were highest on moist locations such as the plastic ladle used for sink water, the toilet seat surface and the cutting board surface with 100‐fold higher levels of faecal coliform bacteria than E. coli and 100‐fold higher levels of faecal coliforms than the US and Japanese studies. Conclusions: A single public health intervention barrier, such as an improved latrine, is only partially effective for household sanitation. For complete sanitation, multiple environmental barriers may be necessary. These barriers occur in a house constructed with easily washable surfaces, a chlorinated water distribution system, house climate control and cleaning product availability. Significance and Impact of the Study: Results of this study can be used to emphasize the importance of increasing household environmental sanitation barriers."
741,Seroepidemiology of Chronic Fatigue Syndrome: A Case-Control Study,"We performed serological testing for a large number of infectious agents in 26 patients from Atlanta who had chronic fatigue syndrome (CFS) and in 50 controls matched by age, race, and sex. We did not find any agent associated with CFS. In addition, we did not find elevated levels of antibody to any of a wide range of agents examined. In particular, we did not find elevated titers of antibody to any herpesvirus, nor did we find evidence of enteroviral exposure in this group of patients."
742,Correction to Lancet Oncol 2020; published online April 30. https://doi.org/10.1016/S1470-2045(20)30265-5,
743,Correction to Lancet Infect Dis 2020; published online March 30. https://doi.org/10.1016/S1473-3099(20)30243-7,
744,Issue Highlights,
745,Safe Reintroduction of Cardiovascular Services during the COVID-19 Pandemic: Guidance from North American Society Leadership,
746,Cancelling a Major Meeting is never an Easy Decision,
747,Leadership Essentials During a Disaster,
748,Chloroquine-induced torsade de pointes in a COVID-19 patient,
749,Inflammatory dilated cardiomyopathy: Etiology and clinical management,"Inflammatory dilated cardiomyopathy (DCMi) is a syndrome, not an etiological disease entity. The infective etiology and the immunopathology can be best determined through endomyocardial biopsy with a complete work-up by light microscopy, immunohistology, and polymerase chain reaction for microbial agents. This review focuses on the methodological advances in diagnosis in the past few years and exemplifies the importance of an etiology-orientated treatment in different case scenarios. In fulminant nonviral myocarditis, immunosuppressive treatment together with hemodynamic stabilization of the patient via mechanical circulatory support (e.g., microaxial pumps, extracorporeal membrane oxygenation, left ventricular assist device) can be life-saving. For viral inflammatory cardiomyopathy, intravenous immunoglobulin treatment can resolve inflammation and often eradicate the virus."
750,Analysis of Expression Profiles of Long Noncoding RNAs and mRNAs in A549 Cells Infected with H3N2 Swine Influenza Virus by RNA Sequencing,"Long noncoding RNAs (lncRNAs) participate in regulating many biological processes. However, their roles in influenza A virus (IAV) pathogenicity are largely unknown. Here, we analyzed the expression profiles of lncRNAs and mRNAs in H3N2-infected cells and mock-infected cells by high-throughput sequencing. The results showed that 6129 lncRNAs and 50,031 mRNA transcripts in A549 cells displayed differential expression after H3N2 infection compared with mock infection. Among the differentially expressed lncRNAs, 4963 were upregulated, and 1166 were downregulated. Functional annotation and enrichment analysis using gene ontology and Kyoto Encyclopedia of Genes and Genomes databases (KEGG) suggested that target genes of the differentially expressed lncRNAs were enriched in some biological processes, such as cellular metabolism and autophagy. The up- or downregulated lncRNAs were selected and further verified by quantitative real-time polymerase chain reaction (RT-qPCR) and reverse transcription PCR (RT-PCR). To the best of our knowledge, this is the first report of a comparative expression analysis of lncRNAs in A549 cells infected with H3N2. Our results support the need for further analyses of the functions of differentially expressed lncRNAs during H3N2 infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-019-00170-9) contains supplementary material, which is available to authorized users."
751,Structural equation modeling the “control of gut overgrowth” in the prevention of ICU-acquired Gram-negative infection,"BACKGROUND: Conceptually, the “control of gut overgrowth” (COGO) is key in mediating prevention against infection with Gram-negative bacilli by topical antibiotic prophylaxis, a common constituent of selective digestive decontamination (SDD) regimens. However, the relative importance of the other SDD components, enteral and protocolized parenteral antibiotic prophylaxis, versus other methods of infection prevention and versus other contextual exposures cannot be resolved within individual studies. METHODS: Seven candidate generalized structural equation models founded on COGO concepts were confronted with Pseudomonas and Acinetobacter bacteremia as well as ventilator-associated pneumonia data derived from > 200 infection prevention studies. The following group-level exposures were included in the models: use and mode of antibiotic prophylaxis, anti-septic and non-decontamination methods of infection prevention; proportion receiving mechanical ventilation; trauma ICU; mean length of ICU stay; and concurrency versus non-concurrency of topical antibiotic prophylaxis study control groups. RESULTS: In modeling Pseudomonas and Acinetobacter gut overgrowth as latent variables, anti-septic interventions had the strongest negative effect against Pseudomonas gut overgrowth but no intervention was significantly negative against Acinetobacter gut overgrowth. Strikingly, protocolized parenteral antibiotic prophylaxis and concurrency each have positive effects in the model, enteral antibiotic prophylaxis is neutral, and Acinetobacter bacteremia incidences are high within topical antibiotic prophylaxis studies, moreso with protocolized parenteral antibiotic prophylaxis exposure. Paradoxically, topical antibiotic prophylaxis (moreso with protocolized parenteral antibiotic prophylaxis) appears to provide the strongest summary prevention effects against overall bacteremia and overall VAP. CONCLUSIONS: Structural equation modeling of published Gram-negative bacillus infection data enables a test of the COGO concept. Paradoxically, Acinetobacter and Pseudomonas bacteremia incidences are unusually high among studies of topical antibiotic prophylaxis."
752,An automated aquatic rack system for rearing marine invertebrates,"BACKGROUND: One hundred years ago, marine organisms were the dominant systems for the study of developmental biology. The challenges in rearing these organisms outside of a marine setting ultimately contributed to a shift towards work on a smaller number of so-called model systems. Those animals are typically non-marine organisms with advantages afforded by short life cycles, high fecundity, and relative ease in laboratory culture. However, a full understanding of biodiversity, evolution, and anthropogenic effects on biological systems requires a broader survey of development in the animal kingdom. To this day, marine organisms remain relatively understudied, particularly the members of the Lophotrochozoa (Spiralia), which include well over one third of the metazoan phyla (such as the annelids, mollusks, flatworms) and exhibit a tremendous diversity of body plans and developmental modes. To facilitate studies of this group, we have previously described the development and culture of one lophotrochozoan representative, the slipper snail Crepidula atrasolea, which is easy to rear in recirculating marine aquaria. Lab-based culture and rearing of larger populations of animals remain a general challenge for many marine organisms, particularly for inland laboratories. RESULTS: Here, we describe the development of an automated marine aquatic rack system for the high-density culture of marine species, which is particularly well suited for rearing filter-feeding animals. Based on existing freshwater recirculating aquatic rack systems, our system is specific to the needs of marine organisms and incorporates robust filtration measures to eliminate wastes, reducing the need for regular water changes. In addition, this system incorporates sensors and associated equipment for automated assessment and adjustment of water quality. An automated feeding system permits precise delivery of liquid food (e.g., phytoplankton) throughout the day, mimicking real-life feeding conditions that contribute to increased growth rates and fecundity. CONCLUSION: This automated system makes laboratory culture of marine animals feasible for both large and small research groups, significantly reducing the time, labor, and overall costs needed to rear these organisms."
753,Long Noncoding RNA NRAV Promotes Respiratory Syncytial Virus Replication by Targeting the MicroRNA miR-509-3p/Rab5c Axis To Regulate Vesicle Transportation,"Respiratory syncytial virus (RSV) is an enveloped RNA virus which is responsible for approximately 80% of lower respiratory tract infections in children. Current lines of evidence have supported the functional involvement of long noncoding RNA (lncRNA) in many viral infectious diseases. However, the overall biological effect and clinical role of lncRNAs in RSV infection remain unclear. In this study, lncRNAs related to respiratory virus infection were obtained from the lncRNA database, and we collected 144 clinical sputum specimens to identify lncRNAs related to RSV infection. Quantitative PCR (qPCR) detection indicated that the expression of lncRNA negative regulator of antiviral response (NRAV) in RSV-positive patients was significantly lower than that in uninfected patients, but lncRNA psoriasis-associated non-protein coding RNA induced by stress (PRINS), nuclear paraspeckle assembly transcript 1 (NEAT1), and Nettoie Salmonella pas Theiler’s (NeST) showed no difference in vivo and in vitro. Meanwhile, overexpression of NRAV promoted RSV proliferation in A549 and BEAS-2B cells, and vice versa, indicating that the downregulation of NRAV was part of the host antiviral defense. RNA fluorescent in situ hybridization (FISH) confirmed that NRAV was mainly located in the cytoplasm. Through RNA sequencing, we found that Rab5c, which is a vesicle transporting protein, showed the same change trend as NRAV. Subsequent investigation revealed that NRAV was able to favor RSV production indirectly by sponging microRNA miR-509-3p so as to release Rab5c and facilitate vesicle transportation. The study provides a new insight into virus-host interaction through noncoding RNA, which may contribute to exploring potential antivirus targets for respiratory virus. IMPORTANCE The mechanism of interaction between RSV and host noncoding RNAs is not fully understood. In this study, we found that the expression of long noncoding RNA (lncRNA) negative regulator of antiviral response (NRAV) was reduced in RSV-infected patients, and overexpression of NRAV facilitated RSV production in vitro, suggesting that the reduction of NRAV in RSV infection was part of the host antiviral response. We also found that NRAV competed with vesicle protein Rab5c for microRNA miR509-3p in cytoplasm to promote RSV vesicle transport and accelerate RSV proliferation, thereby improving our understanding of the pathogenic mechanism of RSV infection."
754,"Korotnevella hemistylolepis N. Sp. and Korotnevella monacantholepis N. Sp. (Paramoebidae), Two New Scale‐covered Mesohaline Amoebae","ABSTRACT. Two new species of Korotnevella Goodkov, 1988, Korotnevella hemistylolepis n. sp. and Korotnevella monacantholepis n. sp., are described from mesohaline ecosystems. The amoebae are characterized on the basis of light and electron microscopy with special emphasis on the structure of the basket scales, which have species‐specific architecture. The two new species are the second and third ones recovered from environments other than freshwater. In terms of scale morphology they most closely resemble a freshwater species, Korotnevella bulla (Schaeffer, 1926) Goodkov, 1988. Two genus names, Dactylamoeba Korotnev, 1880 and Korotnevella Goodkov, 1988, are in current use. The latter name is preferred, pending rediscovery and characterization of Dactylamoeba elongata Korotnev, 1880, the type species of the genus. Korotnevella species can be divided into three groups on the basis of scale morphology, suggesting that the genus may not be monophyletic. A key to species is provided."
755,A case of cow's milk allergy in the neonatal period‐evidence for intrauterine sensitization?,"Clinical manifestations of cow's milk allergy rarely occur in the first days after birth. We report on a newborn presenting with hemorrhagic mecon‐ium in the first hour of life followed by bloody diarrhea in the next few days. At day 14, an elevaled total IgE, specific IgE to cow's milk and an eosinophilia in peripheral blood were found. Symptoms disappeared when the milk feed was changed to an extensively hydrolyzed casein formula. Two challenges with cow's milk formula (on day 30 and at 7 months of age) were followed by recurrence of vomiting, watery diarrhea and failure to thrive. At the age of 17 months cow's milk was tolerated well. Although other pathogenetic mechanisms cannot completely be ruled out, there is strong evidence that cow's milk allergy— induced by intrauterine sensiti‐zation—explains the symptoms in our patient. In conclusion, cow's milk allergy can occur even in the first days of life, and our clinical observation supports the concept of intra‐uterine sensitization to allergens."
756,The importance of ultrasonographic pneumatosis intestinalis in equine neonatal gastrointestinal disease,"Reasons for performing study: Recognising the presence of a necrotising component of the gastrointestinal disease may be clinically useful in ill equine neonates. Objectives: To study the importance of abdominal sonograms in neonatal foals suffering from gastrointestinal conditions and to describe the clinical features of necrotising gastrointestinal disease. Hypothesis: There is a subgroup of neonates with sonographically detectable pneumatosis intestinalis (PI), reflecting a necrotising disease. Methods: Records of foals aged ≤7 days hospitalised from 2005 to 2009 with signs of gastrointestinal disease were evaluated (n = 89). The association of sonographic, clinical and clinicopathological signs with necrotising gastrointestinal disease and outcome was determined. Results: PI was imaged in 19 foals. Twenty‐seven foals were classified as having necrotising gastrointestinal disease based on the presence of gastrointestinal signs (colic, diarrhoea, gastric reflux or abdominal distension) and sonographic PI (n = 19), surgical (n = 2) or pathological (n = 6) evidence of gastrointestinal necrosis. There was a difference between survival rate in foals with and without necrotising disease (33.3 and 69.4%, respectively, P = 0.005) or foals with and without PI detected sonographically (36.8 and 72.1%, respectively, P = 0.023). PI was the only sonographic finding associated with outcome. Prematurity, the presence of blood in the faeces, gastric reflux, abdominal distension, abnormal echogenicity of the colon and the lowest white blood cell count during hospitalisation were associated with necrotising gastrointestinal disease (P<0.05). Conclusions and potential relevance: Abdominal sonograms have prognostic value in neonatal gastrointestinal disease. PI and the presence of necrotising gastrointestinal disease were common and associated with a poor prognosis."
757,Caring for Pediatric Patients with Diabetes amidst the COVID-19 Storm,
758,Managing FPIES during the COVID-19 pandemic-expert recommendations,
759,The use of PET in COVID 19 cases,
760,Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI)-Associated Interstitial Lung Disease During the COVID-19 Pandemic,
761,The Clinical Observation of a CVID Patient Infected with COVID-19,
762,"Efficacy and Safety of Oral Pleconaril for Treatment of Colds Due to Picornaviruses in Adults: Results of 2 Double-Blind, Randomized, Placebo-Controlled Trials","The novel capsid-binding antiviral pleconaril inhibits in vitro replication of most rhinoviruses and enteroviruses. Oral pleconaril treatment was studied in 2 parallel randomized, double-blind, placebo-controlled trials. Among 1363 picornavirus-infected participants (65%) in the studies combined, the median time to alleviation of illness was 1 day shorter for pleconaril recipients than for placebo recipients (P > .001). Cold symptom scores and frequency of picornavirus cultured from nasal mucus specimens were lower among pleconaril recipients by day 2 of treatment. No treatment effects were seen in those without picornavirus infection. Pleconaril was associated with a higher incidence of nausea (6% vs. 4%) and diarrhea (9% vs. 7%) and with small increases in mean serum cholesterol levels and platelet counts, compared with baseline measurements. A subsequent 6-week prophylaxis study found that pleconaril induces cytochrome P-450 3A enzymes, which metabolize a variety of drugs, including ethinyl estradiol. Early pleconaril treatment was well tolerated and significantly reduced the duration and severity of colds due to picornaviruses in adults."
763,Sinensetin suppresses influenza a virus-triggered inflammation through inhibition of NF-κB and MAPKs signalings,"BACKGROUND: Human respiratory system infected with influenza A virus (IAV) elicited a robust pro-inflammatory response that resulted in severe illness and even death. Currently, limited immunomodulator is available to counteract IAV-associated pneumonia in the clinic. Sinensetin, a polymethoxylated flavone with five methoxy groups, has been found to possess anti-agiogenesis, anti-inflammatory and anti-diabetic activities. However, the effects of sinensetin on IAV-triggered pro-inflammatory response remain unclear. In the present study, the anti-inflammatory effects and corresponding possible mechanism of sinensetin in IAV-infected A549 cells were subjected to investigations. METHODS: The cytotoxic effects of sinensetin towards A549 cells was detected by MTT and LDH assays. The antiviral activity of sinensetin against influenza A virus was assayed in A549 cells with an engineered replication-competent influenza A virus carrying Gaussia luciferase reporter gene infection. The effect of sinensetin on influenza A virus-triggered inflammatory reaction was determined by qRT-PCR, Luminex assays, ELISA and Western blot. RESULTS: Our results showed that sinensetin did not exhibit antiviral activity against A/PR/8/34 (H1N1). Meanwhile, sinensetin treatment significantly decreased IAV-induced expression of pro-inflammatory mediators at mRNA and protein levels, including IL-6, TNF-α, IP-10, IL-8 and MCP-1. Additionally, levels of cyclooxygenase (COX)-2 and the downstream product prostaglandin E(2) (PGE(2)) up-regulated by IAV infection were dramatically suppressed by sinensetin. The mechanistic investigation revealed that sinensetin treatment suppressed the NF-κB transcriptional activity using the NF-κB reporter stable HEK293 cell line stimulated with TNF-α (20 ng/mL) or influenza H1N1 virus. Furthermore, sinensetin abrogated influenza H1N1 virus-induced activation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings. CONCLUSION: Collectively, our results indicated that sinensetin has potential capacity to attenuate IAV-triggered pro-inflammatory response via inactivation of NF-κB, ERK1/2 MAPK and p38 MAPK signalings, which implied that sinensetin may be a promising candidate drug for influenza H1N1 virus infection therapeutics."
764,A role for CIM6P/IGF2 receptor in memory consolidation and enhancement,"Cation-independent mannose-6-phosphate receptor, also called insulin-like growth factor two receptor (CIM6P/IGF2R), plays important roles in growth and development, but is also extensively expressed in the mature nervous system, particularly in the hippocampus, where its functions are largely unknown. One of its major ligands, IGF2, is critical for long-term memory formation and strengthening. Using CIM6P/IGF2R inhibition in rats and neuron-specific knockdown in mice, here we show that hippocampal CIM6P/IGF2R is necessary for hippocampus-dependent memory consolidation, but dispensable for learning, memory retrieval, and reconsolidation. CIM6P/IGF2R controls the training-induced upregulation of de novo protein synthesis, including increase of Arc, Egr1, and c-Fos proteins, without affecting their mRNA induction. Hippocampal or systemic administration of mannose-6-phosphate, like IGF2, significantly enhances memory retention and persistence in a CIM6P/IGF2R-dependent manner. Thus, hippocampal CIM6P/IGF2R plays a critical role in memory consolidation by controlling the rate of training-regulated protein metabolism and is also a target mechanism for memory enhancement."
765,Witch-hunt Cannot Eradicate COVID-19,
766,Management of Travel-Related Infectious Diseases in the Emergency Department,"PURPOSE OF REVIEW: Emergency physicians generally have limited exposure to internationally acquired illnesses. However, travelers can present quite ill, and delays in recognition and treatment can lead to increased morbidity and mortality. This paper aims to summarize typical presentations of common international diseases and provide the emergency physician with a practical approach based on current guidelines. RECENT FINDINGS: In the treatment of traveler’s diarrhea, azithromycin has become the treatment of choice due to the growing antibiotic resistance. Intravenous artesunate was approved in 2019 under investigational new drug protocol for the treatment of severe malaria, and artemisinin-based combination therapies (ACTs) have become the first-line treatment for most cases of uncomplicated malaria. Since the 2015 outbreak, Zika has become a concern to many travelers, but the current treatment is supportive. SUMMARY: Clinicians should be aware of a few noteworthy updates in the treatment of internationally acquired illnesses, but more importantly, they must recognize warning signs of severe illness and treat promptly. Future research on workup and disposition could help emergency physicians identify which patients need admission in well-appearing febrile travelers."
767,Post-translational modifications and stress adaptation: the paradigm of FKBP51,"Adaptation to stress is a fundamental requirement to cope with changing environmental conditions that pose a threat to the homeostasis of cells and organisms. Post-translational modifications (PTMs) of proteins represent a possibility to quickly produce proteins with new features demanding relatively little cellular resources. FK506 binding protein (FKBP) 51 is a pivotal stress protein that is involved in the regulation of several executers of PTMs. This mini-review discusses the role of FKBP51 in the function of proteins responsible for setting the phosphorylation, ubiquitination and lipidation of other proteins. Examples include the kinases Akt1, CDK5 and GSK3β, the phosphatases calcineurin, PP2A and PHLPP, and the ubiquitin E3-ligase SKP2. The impact of FKBP51 on PTMs of signal transduction proteins significantly extends the functional versatility of this protein. As a stress-induced protein, FKBP51 uses re-setting of PTMs to relay the effect of stress on various signaling pathways."
768,"ECR 2020 Book of Abstracts: Vienna, Austria. 15 March 2020",
769,Mitteilungen der DGRh – Veranstaltungen der Rheumaakademie,
770,Mitteilungen der DGRh,
771,"Real-time, MinION-based, amplicon sequencing for lineage typing of infectious bronchitis virus from upper respiratory samples","Infectious bronchitis (IB) causes significant economic losses in the global poultry industry. Control of IB is hindered by the genetic diversity of the causative agent, infectious bronchitis virus (IBV), which has led to the emergence of several serotypes that lack complete serologic cross-protection. Although serotyping requires immunologic characterization, genotyping is an efficient means to identify IBVs detected in samples. Sanger sequencing of the S1 subunit of the spike gene is currently used to genotype IBV; however, the universal S1 PCR was created to work from cultured IBV, and it is inefficient at detecting multiple viruses in a single sample. We describe herein a MinION-based, amplicon-based sequencing (AmpSeq) method that genetically categorized IBV from clinical samples, including samples with multiple IBVs. Total RNA was extracted from 15 tracheal scrapings and choanal cleft swab samples, randomly reverse transcribed, and PCR amplified using modified S1-targeted primers. Amplicons were barcoded to allow for pooling of samples, processed per manufacturer’s instructions into a 1D MinION sequencing library, and then sequenced on the MinION. The AmpSeq method detected IBV in 13 of 14 IBV-positive samples. AmpSeq accurately detected and genotyped both IBV lineages in 3 of 5 samples containing 2 IBV lineages. Additionally, 1 sample contained 3 IBV lineages, and AmpSeq accurately detected 2 of the 3 lineages. Strain identification, including detection of different IBVs from the same lineage, was also possible with this AmpSeq method. Our results demonstrate the feasibility of using MinION-based AmpSeq for rapid and accurate identification and lineage typing of IBV from oral swab samples."
772,Mitteilungen der DGG,
773,Successful treatment of mycobacterial infection associated hemophagocytic lymphohistiocytosis with etoposide and anti-tuberculous therapy: a case report,"BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening disorder characterized by an exacerbated but ineffective inflammatory response, which can be classified as primary and secondary HLH. HLH associated with Mycobacterium tuberculosis is uncommon. This case report accounted an immunocompetent patient who was confirmed to be Mycobacterium infection, or rather, highly suspected tuberculosis (TB) associated HLH, with a favorable outcome. CASE PRESENTATION: A 36-year-old man presented with persistent fever, pancytopenia, and hyperferritinemia. A bone marrow smear demonstrated hemophagocytosis, and pathological examination of lung biopsy was positive for acid-fast bacilli, which established the diagnosis of Mycobacterium infection and HLH. Then the patient treated successfully with anti-TB therapy, along with 8 weeks of etoposide. CONCLUSION: This case emphasizes that HLH should be kept in mind when clinicians encounter a patient with severe infection presenting with pancytopenia and hyperferritinemia. Given the high mortality, early diagnosis and appropriate therapy can provide patients with a favorable prognosis."
774,Scrub typhus as a rare cause of acute pyelonephritis: case report,"BACKGROUND: Scrub typhus can present with atypical signs and symptoms such as those of acute kidney injury, gastroenteritis, pneumonitis, and acute respiratory distress syndrome. Meningitis, encephalitis, and hepatic dysfunction have also been reported, particularly in severe cases with multisystem involvement. Scrub typhus has never been reported in the literature to cause urinary tract infections (UTIs) which includes cystitis and pyelonephritis. CASE PRESENTATION: A 45-year old male presenting to the outpatient unit with fever, right flank pain, and burning micturition for three days was initially treated for UTI. However, he returned to the hospital on the fourth day of illness with persistent symptoms. He was hospitalized, with intravenous (IV) ceftriaxone. Computerized tomography scan of his abdomen-pelvis showed features of acute pyelonephritis, so his antibiotics were upgraded to meropenem and teicoplanin. Despite this, the patient’s condition deteriorated. Laboratory investigations showed multisystem involvement: decreasing platelets, raised creatinine, and deranged liver panel. As Kathmandu was hit by dengue epidemic during the patient’s hospitalization, on the seventh day of his illness, blood samples were sent for tropical fever investigation. All tests came out negative except for scrub typhus—IgM antibodies positive on rapid diagnostic test. The patient’s symptoms subsided after 48 h of starting doxycycline and he became fully asymptomatic four days later. Fever did not recur even after discontinuing other IV antibiotics, favoring scrub typhus disease rather than systemic bacterial sepsis. CONCLUSIONS: Scrub typhus is an emerging infectious disease of Nepal. Therefore, every unexplained fever cases (irrespective of clinical presentation) should be evaluated for potential Rickettsiosis. Moreover, for cases with acute pyelonephritis, atypical causative agents should be investigated, for example scrub typhus in this case."
775,Combining the use of Nuss procedure and rib fixation for severe flail chest: a case report,"BACKGROUND: Severe flail chest is a life-threatening situation. The Nuss procedure is a new effective treatment for severe flail chest patients who cannot be weaned from prolonged mechanical ventilation in the last few years. However, the procedure is not suitable when there are multiple fractures in both the anterior and lateral chest walls. Here, we reported a rare case of severe flail chest in a patient who suffered multiple fractures in both the anterior and lateral chest walls in a traffic accident. CASE PRESENTATION: A 49-year-old patient suffered severe flail chest by a steering wheel in a traffic accident with multiple fractures in both the anterior and lateral chest walls. In the beginning, the patient was administrated with mechanical ventilation because of acute respiratory distress syndrome (ARDS) for more than 1 week. Then the patient suffered from a severe lung infection and decreased blood oxygen saturation. After a multidiscipline discussion (MDT), three rib fixation plates were first used to rebuild the stability of lateral chest walls, then two Nuss bars were inserted to eliminate paradoxical movement in the anterior chest wall. Finally, the patient recovered smoothly after the combining procedure. CONCLUSIONS: Severe flail chest patients with both the anterior and lateral chest walls after trauma are in a life-threatening situation, and require an appropriate procedure to get out of danger in time. Rib fixation is an effective treatment when the fractured sites are few and the fractured area is small. The Nuss procedure is a new effective method for severe flail chest with multiple fractures in an anterior chest wall, which is also a minimally invasive and short time-consuming procedure. However, it does not suitable for the patient with multiple fractures in lateral chest walls. Combining the use of Nuss procedure and rib fixation can solve severe flail chest with multiple ribs and sternum fractures in both the anterior and lateral chest walls, and the outcome of this procedure is satisfying in the present rare case."
776,Convalescent transfusion for pandemic influenza: preparing blood banks for a new plasma product?,"Due to the potential of a severe pandemic to limit efficacy or availability of medical countermeasures, some researchers have begun a search for new interventions that could complement the planned antiviral‐ and vaccine‐based response to an influenza pandemic. One such countermeasure—the transfusion of pandemic influenza‐specific antibodies from surviving patients to the clinically ill—is the focus of this commentary. Passive immunotherapy, which includes the use of monoclonal antibodies (MoAbs), hyperimmune globulin, or convalescent plasma, had been used before the advent of antibiotics and has recently reentered the limelight due to the accelerating development of MoAb therapies against cancer, a number of microbes, allograft rejection, and a host of other conditions. After the plausible biologic mechanism and somewhat limited data supporting the efficacy for this modality against influenza are reviewed, safety and logistical concerns for utilization of this potential new product (fresh convalescent plasma against influenza [FCP‐Flu]) are discussed. FCP‐Flu could indeed prove useful in a response to a pandemic, but two necessary items must first be satisfied. Most importantly, more research should be conducted to establish FCP‐Flu efficacy against the current and other pandemic strains. Second, and also importantly, blood banks and donor centers should examine whether offering this new product would be feasible in a pandemic and begin planning before a more severe pandemic forces us to respond without adequate preparation."
777,Nineteen years of experience with autotransfusion for elective surgery in children: more troublesome than we expected,"BACKGROUND: Under the rationale that children undergoing elective surgery are the best candidates for autologous blood donors because of their long life expectancy, aggressive donations of autologous blood, even from infants, have been reported. A number of problems are associated with the procedure, however, whereas the risks of homologous blood are very low. STUDY DESIGN AND METHODS: From 1987 through 2005, of 5792 patients referred to blood transfusion services at two Japanese university hospitals for autologous blood donations, 314 children younger than 16 years old served as subjects for assessment. RESULTS: Of 314 children, 7 were not suitable as autologous donors. In most cases this was due to uncooperative behavior. Over a follow‐up period of 19 years, the authors encountered 53 cases (17.3%) of donation‐related problems, and this rate was higher than the 6 percent rate recorded for adult cases (316/5305). Nine children suffered crucial complications such as vasovagal reactions, and one 14‐year‐old boy required a vasopressor drug. Important findings were that 6 of these were first‐time donors, and the amount of blood drawn was under 10 percent of their estimated blood volume. CONCLUSION: Of 53 donation‐related problems, 9 (17.0%) were accompanied by marked hypotension. Drawing autologous blood from children has become easier with advanced devices; however, lessening of anxiety and tension are essential for the safety of children's autologous blood donation programs. Aggressive donation should be avoided."
778,A phylogeographical study of the Turnip mosaic virus population in East Asia reveals an ‘emergent’ lineage in Japan,"The genetic structure of populations of Turnip mosaic virus (TuMV) in East Asia was assessed by making host range and gene sequence comparisons of 118 isolates utilizing a population genetic approach. Most, but not all, isolates collected from Brassica plants in China infected only Brassica plants, whereas those from Japan infected both Brassica and Raphanus (BR) plants. Analyses of the positions of recombination sites in five regions of the genomes (one third of the full sequence) of the many recombinant isolates were fully congruent with the results of phylogenetic analysis, and at least one recombination type pattern was shared between Chinese and Japanese populations. One lineage of nonrecombinant isolates from the basal‐BR lineage was found in 2000 in Kyushu, Japan but none in China, and have since been found over the whole island. The sudden expansion of this basal‐BR population was strongly supported by calculations showing the deviations from the neutral equilibrium model for the individual geographical lineages with overall lack of nucleotide diversity, and by analysis of mismatch distribution. Our study shows that the recent Chinese and Japanese TuMV isolates are part of the same population but are discrete lineages."
779,Regeneration of monsoon rain forest in northern Australia: the sapling bank,"Abstract. As part of a wider study examining regeneration pathways in monsoon rain forest vegetation in northern Australia, a one‐off, dry season census of saplings was undertaken along transects sampled at each of 33 relatively undisturbed sites broadly representative of the range of regional monsoon rain forest vegetation. Four floristic quadrat groups were derived through TWINSPAN classification. Subsequent analyses involved: (1) comparison of mean dry season stockings of juveniles occurring in different rain forest types, and their structural and environmental correlates; (2) comparison of the contributions of different life forms, and the influence of clonal reproduction in the sapling regeneration banks of different forest types; and (3) exploration of relationships between the distributions of saplings of common tree species with respect to seed bank, floristic, structural, and environmental variables. While data presented here require cautious interpretation given that processes of seedling/sapling recruitment and mortality are highly dynamic, sapling banks were found to be most dense on coarse‐textured, moist soils, and least dense on coarse‐textured, seasonally dry soils. Canopy cover and fire impact were shown to be highly influential on sapling distribution, especially for saplings of tree species and those growing on seasonally dry sites. Sapling densities were little influenced by proximity to rain forest margins, except for shrubs. The potential for clonal reproduction was significantly greater on dry sites, especially for trees. The majority of saplings sampled were derived from relatively few common, non‐clonal, canopy tree species. Sapling distributions of 20 out of 23 common tree species were clumped in the vicinity of conspecific adults; for most species the strength of this relationship was greater than that for any other variable. These data support observations in the literature concerning the distribution of sapling banks in moist and dry tropical forests."
780,In situ regeneration of Pinus strobus and P. resinosa in the Great Lakes forest communities of Canada,"Abstract. Two extensive forest vegetation survey datasets are explored, using ordination and classification, for evidence of in situ regeneration by Pinus strobus (Eastern white pine) and P. resinosa (Red pine). Ordination of tree species contributions to total basal area in 320 upland northern hardwood‐ conifer stands produced distinct stand groups for P.banksiana, P. resinosa, P. strobus and mesic hardwoods in an ascending sequence along the first axis. Quercus rubra (red oak), Q. alba (white oak) and tolerant conifer groups formed segregates from the hardwood complex along the second axis. P. strobus mixes with all other forest types, but P. resinosa is restricted to its own group. Seedlings and trees of P. strobus are more abundant than saplings, which are restricted to the pine and oak forests. Therefore, seed production, dispersal and seedling establishment seem to be less of a barrier to in situ regeneration by P. strobus than subsequent survival and growth. Canonical correspondence analysis of 170 pine‐dominated stands from the Canadian Shield of Ontario, in which tree species variables are segmented into height‐class pseudo‐ species, yielded no linear relationship between environmental features or stand structure and seedling densities of P. strobus. However, total tree basal area appears to impose an upper limit to seedling density on the forest floor. Strong correlations emerged between pine seedling density and understorey vegetation. Stand classification of the understorey vegetation, using constrained indicator species analysis, yielded distinct high and low seedling groups. Low pine seedling density was associated with abundant broadleaved shrubs, herbs and seedlings as well as feathermosses and tolerant conifers. High seedling density could not be ascribed to the presence of seedbed taxa, such as Polytrichum, but is ascribed to the absence of competition and other forms of inhibition in the understorey vegetation and down through the canopy profile. In situ regeneration of P. strobus does, therefore, occur but conditions over the forest landscape are largely restrictive."
781,Reversion of vegetation following the cessation of fertilizer application,"Abstract. Tadham Moor in Somerset, England, is an exceptionally rich wetland site which has been mown for hay for many years, with stock grazing the aftermath, but with no history of any fertilizer use. A randomized blocks field experiment (1986–1989) was used to study the effects of five levels of nitrogen input treatments: 0 = control, 25, 50, 100 and 200 kg of N fertilizer per ha per yr. In Phase II of the experiment (1990–1993), each plot was split into two subplots. The allocated fertilizer treatment for the plot was continued in one, randomly selected, subplot but the treatment was discontinued in the other subplot. The experiment not only identified and quantified the changes occurring in the vegetation of hay meadows under different levels of N input, it also provided valuable insight into the dynamics of the sward upon the discontinuance of the treatments. The data for Phase II were used to estimate the time required by the changed vegetation (under different nitrogen treatments) to revert to a state comparable to that prevailing in the control plots. A method for estimating reversion times is described. The main difficulties in estimating the reversion times are identified, the choice of robust vegetation variables being critical. Reversion time estimation methods are presented and used to obtain working estimates for the four nitrogen treatments, applied for 5 yr. These estimates are 3, 5, 7 and 9 yr respectively. The validity of the estimates of 3 yr for the lowest nitrogen input treatment (25 kg /ha/yr) was checked using the available post cessation data."
782,Mediterranean pasture dynamics: the role of germination,Abstract. Meteorological patterns have a decisive influence on the inter‐annual dynamics of therophyte pastures under Mediterranean climatic conditions. The germination behaviour of annual pasture species was studied by subjecting two collections of seeds taken from plants and soil‐seed banks to two phytotron‐simulated weather patterns: early and late autumn rains. Species from these pastures were arranged along a gradient of sensitivity to temperature on the arrival of the first persistent rain. This sensitivity was manifested in both the total germination success of the species and the germination time profile. The different germination patterns of the species can provide competitive advantages depending on the autumn weather conditions.
783,"Nitrate reductase activity in vegetation below an arctic bird cliff, Svalbard, Norway","Abstract. Vegetated sites below bird‐nesting cliffs are uniquely nutrient‐rich habitats in the otherwise nutrient‐poor arctic environment. Plants from six distinct vegetation zones below such a cliff at 79° N, Svalbard, Norway, were collected for analysis under greenhouse conditions. Leaf nitrate reductase activity (NRA) was analysed in 42 species representing 25 % of the Svalbard vascular flora. The species mean NRA values ranged from 0.37 to 8.34 μmols of nitrite ions formed per gram of plant fresh weight per hour. Species in the vegetated zone growing closest to recent guano deposits had the highest NRA values, (mean = 4.47) whereas plants growing farther below the cliff had significantly lower values (mean = 0.55). A similar pattern was detected in a duplicate set of plants induced with 15 mM KNO(3); vegetation zone means for NRA ranged from 5.08 to 0.98 μmols of nitrite ions formed per gram of plant fresh weight per hour. Maximally induced species NRA values were highest in the first zones below the cliff and decreased downslope. This gradient paralleled the steep soil nitrate gradient, which decreased from 13.84 mg/l at the cliffbase to 1.03 mg/l downslope. Correspondingly, soil ammonium ions in the vegetation zones ranged between 1.96 mg/l at the cliff‐base to 0.03 mg/l downslope. Correlations between NRA and soil nitrate provide a systematic basis for assigning scalar ‘nitrogen figures’ as indicators of habitat preference, here for the first time applied to arctic species."
784,Assessing allergenic fungi in house dust by floor wipe sampling and quantitative PCR,"Abstract In the present study, we modified an existing surface wipe sampling method for lead and other heavy metals to create a protocol to collect fungi in floor dust followed by real‐time quantitative PCR (qPCR)‐based detection. We desired minimal inconvenience for participants in residential indoor environmental quality and health studies. Accuracy, precision, and method detection limits (MDLs) were investigated. Overall, MDLs ranged from 0.6 to 25 cell/cm(2) on sampled floors. Overall measurement precisions expressed as the coefficient of variation because of sample processing and qPCR ranged 6–63%. Median and maximum fungal concentrations in house dust in study homes in Visalia, Tulare County, California, were 110 and 2500 cell/cm(2), respectively, with universal fungal primers (allergenic and nonallergenic species). The field study indicated samplings in multiple seasons were necessary to characterize representative whole‐year fungal concentrations in residential microenvironments. This was because significant temporal variations were observed within study homes. Combined field and laboratory results suggested this modified new wipe sampling method, in conjunction with growth‐independent qPCR, shows potential to improve human exposure and health studies for fungal pathogens and allergens in dust in homes of susceptible, vulnerable population subgroups. PRACTICAL IMPLICATIONS: Fungi are ubiquitous in indoor and outdoor environments, and many fungi are known to cause allergic reactions and exacerbate asthma attacks. This study established—by modifying an existing—a wipe sampling method to collect fungi in floor dust followed by real‐time quantitative PCR (qPCR)‐based detection methodologies. Results from this combined laboratory and field assessment suggested the methodology’s potential to inform larger human exposure studies for fungal pathogens and allergens in house dust as well as epidemiologic studies of children with asthma and older adults with chronic respiratory diseases."
785,"Resource utilization, overlap and temporal dynamics in a guild of mountain stream insects","SUMMARY 1. Resource utilization was quantified for six mayfly (Ephemeroptera) and one caddis (Trichoptera) species comprising a lotic scraper/collector‐gatherer guild across three niche dimensions (temporal, trophic and spatial). Based on trophic differences and inferred microspatial utilization, the members of this guild separated into two groups: (1) cryptic detritivores and (2) exposed algivores. 2. Each species demonstrated a slow seasonal univoltine life cycle except for Epeorus longimanus (Eaton) and Baetis iricaudatus (Dodds) which were fast seasonal univoltine and multivoltine, respectively. 3. Temporal sequencing of periods of peak resource utilization were not demonstrated by the members of this guild. A null analysis indicated that periods of peak resource utilization were aggregated."
786,The search for reference conditions for stream vegetation in northern Europe,"1. The European Water Framework Directive provides a framework for improving the ecological quality of stream ecosystems, with deviation from reference used as a measure of ecological status. 2. Here we examine the possibility of using less impacted stream sites from Latvia, Lithuania and Poland to establish a Danish reference network for macrophyte assemblages, and as a guiding image for identification of possible references sites within Denmark. Both approaches were evaluated using historical Danish records. 3. Four different macrophyte assemblages were identified for mid‐sized streams in the Central and Eastern Lowland ecoregions. Macrophyte assemblages could not be delineated using physical stream site characteristics; however a gradual change in assemblage composition was attributed to differences in alkalinity and human impact. 4. Assemblages of contemporary vegetation in Denmark were quite similar to those found in Polish, Latvian and Lithuanian streams (26–35%). However, more importantly, from species‐based predictions we noted higher similarity, particularly with Latvian and Lithuanian streams, before intensive land use commenced in Denmark (c. 1900). These results show that stream sites from these three countries can be considered in a Danish reference network. 5. Two of the four macrophyte assemblages comprised species such as Fontinalis antipyretica, Myriophyllum spicatum, Nuphar lutea, Potamogeton alpinus and P. perfoliatus that have a very scattered occurrence in the contemporary vegetation in Denmark. These groups were closely associated with the predictions from historic records, thereby lending support the conjecture that these assemblages could be part of the guiding image for the identification of potential reference sites within Denmark."
787,Ecological and historical filters constraining spatial caddisfly distribution in Mediterranean rivers,"1. Contemporary species distributions are determined by a mixture of ecological and historical filters acting on several spatial and temporal scales. Mediterranean climate areas are one of the world's biodiversity hotspots with a high level of endemicity, which is linked to complex ecological and historical factors. 2. This paper explores the ecological and historical factors constraining the distribution of caddisfly species on a large regional scale. A total of 69 taxa were collected from 140 sampling sites in 10 Iberian Mediterranean river basins. Approximately 74% of taxa can be considered rare, with the southern basins (the Baetic–Riffian region) having greater endemicity. The greatest richness, involving a mixture of northern and southern species, was found in the transitional area between the Baetic–Riffian region and the Hesperic Massif. 3. The historical processes occurring during the Tertiary (i.e. the junction of the Eurasian and African plates) explained 3.1% of species distribution, whereas ecological factors accounted for 20.7%. Only 0.3% was explained by the interaction of history and ecology. A set of multi‐scale ecological variables (i.e. basin, reach and bedform characteristics) defined five river types with specific caddisfly assemblages. The commonest caddisfly species accounted for the regional distribution pattern, while rare taxa contributed to the explanation of subtle patterns not shown by common species. 4. Despite the importance of historical factors for biogeography and the large scale used in our study, ecological variables better explained caddisfly distribution. This may be explained by the length of time since the historical process we are considering, the high dispersion and colonisation capacity of many caddisfly species, and the strong environmental gradient in the area. Because of the historical and environmental complexity of Mediterranean areas, rare taxa should be included in ecological studies so that the singularity of these ecosystems is not missed."
788,An Extraordinary Issue for Extraordinary Times,
789,"A chromosomal analysis of some water beetle species recently transferred from Agabus Leach to Ilybius Erichson, with particular reference to the variation in chromosome number shown by I. montanus Stephens (Coleoptera: Dytiscidae)","The karyotypes of seven Ilybius species are described and illustrated. All except I. wasastjernae have a basic karyotype of 34 autosomes plus sex chromosomes which are X0 (♂), XX (♀), with the X chromosome among the largest in the nucleus. This karyotype appears to be the norm for Ilybius and supports the transfer of the species concerned from Agabus to Ilybius. I. wasastjernae has 36 autosomes and the X chromosome is the smallest in the nucleus and its karyotype is unlike any other known karyotype in either Ilybius or Agabus. In most of the species studied no intraspecific variation has been detected. Exceptions are I. chalconatus, where there is one inversion polymorphism in one of the autosomes, and I. montanus whose autosome number has been found to vary from 29 to 34. Such variation is highly unusual among Coleoptera. The variation results from fusion‐fission polymorphisms involving three different pairs of autosomes. In each case the fusions may be homozygous, heterozygous or absent. All populations investigated were polymorphic for some of the fusions, but only one (La Salceda, Spain) included individuals lacking all fusions. The frequencies of fused and unfused chromosomes were analysed in three English populations. In only one case was there a departure from the values expected from the Hardy‐Weinberg equilibrium, and this population also showed a significant difference from the other two. Meiosis in males heterozygous for fusions involves the production of trivalents in first division, but results in the production of abundant sperm, with no evidence of chromosomal abnormalities in second metaphase, or of degenerating cells as a result of failed meiosis. The three fusions sites are consistent in all the populations studied, and it is concluded that these fusions represent unique historical events rather than current chromosomal instability."
790,Nutrition and feeding of African ungulates during quarantine at Dvur Kralove Zoo,
791,Studies on the Ephemeroptera of a Northumbrian river system: I. Serial distribution and relative abundance,"The River Coquet is a clean, fast flowing, moderately calcareous river. It is young to mature in development and supports a typical torrential fauna. Marked trends in successional replacement along the river course are confined to the scarce species of Ephemeroptera and the absence of longitudinal zonation in the distribution of some common species is related to the topographical characteristics of the system. A distinct successional trend by one species is attributed to its intolerance to the lower temperatures at high altitudes. Major discontinuities in distribution are found between the Ephemeroptera of the main river and certain tributaries. The paucity of certain otherwise abundant species in one region is related to silt deposition resulting from sand and gravel excavation."
792,Infectious Diseases and Extinction Risk in Wild Mammals,"Abstract: Parasite‐driven declines in wildlife have become increasingly common and can pose significant risks to natural populations. We used the IUCN Red List of Threatened and Endangered Species and compiled data on hosts threatened by infectious disease and their parasites to better understand the role of infectious disease in contemporary host extinctions. The majority of mammal species considered threatened by parasites were either carnivores or artiodactyls, two clades that include the majority of domesticated animals. Parasites affecting host threat status were predominantly viruses and bacteria that infect a wide range of host species, including domesticated animals. Counter to our predictions, parasites transmitted by close contact were more likely to cause extinction risk than those transmitted by other routes. Mammal species threatened by parasites were not better studied for infectious diseases than other threatened mammals and did not have more parasites or differ in four key traits demonstrated to affect parasite species richness in other comparative studies. Our findings underscore the need for better information concerning the distribution and impacts of infectious diseases in populations of endangered mammals. In addition, our results suggest that evolutionary similarity to domesticated animals may be a key factor associated with parasite‐mediated declines; thus, efforts to limit contact between domesticated hosts and wildlife could reduce extinction risk."
793,"IMMUNOPATHOLOGY OF RHINO MOUSE, AN AUTOSOMAL RECESSIVE MUTANT WITH MURINE LUPUS‐LIKE DISEASE","Detection of high incidence of antinuclear antibodies (ANA) was reported in young homozygous rhino mice employing formalinized chicken erythrocyte nuclei as substrate for indirect immunofluorescence (IF) assay. The titers of ANA heightened with increasing age, and attained to 1:1024 by the time mice reached 5 months of age. The occurrence of ANA was associated with development of splenic and hepatic fibrosis, glomerulonephritis and abnormalities of lymphoreticular tissue. The granular deposits of IgG and C3 detected by direct IF were initially found at the basement membrane of dermal‐epidermal junction of rhino mice aged 2.5 months. These deposits distributed progressively in the fibrotic areas of spleen and liver, and renal glomerular tufts at 5 months of age. Dense deposits revealed by electron microscopy were found in the regions where IF of IgG and G3 was observed. Acid buffer eluates from liver and kidney contained IgG reactive with nuclear antigens. Importance of homozygous rhino gene was discussed in relation to development of autoimmune disorders of these mice."
794,Looking Back at TMS2020: Setting Records and Starting Trends,
795,Pulmonary Thromboembolism in Cats,"Pulmonary thromboembolism (PTE) is rarely diagnosed in cats, and the clinical features of the disease are not well known. PTE was diagnosed at postmortem examination in 17 cats, a prevalence of 0.06% over a 24‐year period. The age of affected cats ranged from 10 months to 18 years, although young (<4 years) and old (10 years) cats were more commonly affected than were middleaged cats. Males and females were equally affected. The majority of cats with PTE (n = 16) had concurrent disease, which was often severe. The most common diseases identified in association with PTE were neoplasia, anemia of unidentified cause, and pancreatitis. Cats with glomerulonephritis, encephalitis, pneumonia, heart disease, and hepatic lipidosis were also represented in this study. Most cats with PTE demonstrated dyspnea and respiratory distress before death or euthanasia, but PTE was not recognized ante mortem in any cat studied. In conclusion, PTE can affect cats of any age and is associated with a variety of systemic and inflammatory disorders. It is recommended that the same clinical criteria used to increase the suspicion of PTE in dogs should also be applied to cats."
796,"A comparison of some classification methods used to determine benthic macro‐invertebrate species associations in river survey work based on data obtained from the River Ely, South Wales","SUMMARY. The results of a survey of the macro‐invertebrates of the polluted River Ely, South Wales, are used as a basis for comparing several classification methods which have been used previously in river survey work to determine species groupings. The methods compared are product‐moment correlation (clustered by the nearest neighbour technique), Kendall's tau coefficient (clustered by the nearest neighbour and average linkage techniques), and Squared Euclidean‐Distance coefficient (clustered by nearest neighbour and Ward's techniques). The species groupings determined by these methods were influenced both by the association coefficient and the technique used to cluster it. Some species were grouped together by all or most of the methods. The ecological validity of these robust groups is examined. A clear recommendation regarding the most appropriate method is frustrated by incomplete knowledge of the ecological requirements of most of the aquatic macro‐invertebrates used in the data‐set. However, Kendall's tau coefficient clustered by the average linkage technique appeared to produce ecologically meaningful species groups. Product‐moment correlation was also reasonably successful and since it is based on absolute abundance data whereas Kendall's tau coefficient is based on relative abundance data, the use of the two together is recommended for determining robust groups."
797,Ciliate populations in temporary freshwater ponds: seasonal dynamics and influential factors,"SUMMARY 1. The ciliate populations of two temporary ponds in southern Ontario were studied throughout their aquatic phases in 2001. Pond I (∼1 ha) held water for 98 days, whereas Pond II (∼0.25 ha) held water for 34 days. Populations were assessed both within the ponds themselves and within a series of enclosures in which invertebrate predator pressure was manipulated. 2. In the natural pond water, total ciliate abundance in Pond II rose rapidly from day 1 increasing two orders of magnitude by day 7. In contrast, total abundance in Pond I began at the same level as in Pond II but increased much more slowly, reached a plateau of around 500 individuals L(−1), and increased again late in the hydroperiod. 3. Despite being only 500 m apart, the two ponds were fairly dissimilar in terms of their species richness and species composition. Pond I contained 50 species compared with 70 species for Pond II, with only 24 species shared. Additional species occurred within the enclosures raising the total species richness to 145 species; 88 from Pond I, 104 from Pond II, with 47 species (30%) in common. Pond II contained more mid‐sized ciliates (50–200 μm), whereas Pond I was dominated by smaller ciliates, especially in mid‐May and early June. In Pond I, cumulative species richness throughout the hydroperiod was highest in the predator addition enclosures (65 ± 4 species), followed by the partial‐predator exclusion enclosures (50 ± 4). Lowest species richness was found in the control enclosures (39 ± 2) and in the pondwater controls (39 ± 0). Differences between the ciliates in the natural pond water and the enclosures appeared to be related to a greater concentration of phytoplankton within the enclosures (perhaps resulting from extensive growth of duckweed, Lemna, outside), and higher densities of zooplankters in the pond. 4. The physicochemical environment influenced species richness, total abundance and the number of rare species (27 in Pond II versus 13 in Pond I). Variation in ciliate abundance in Pond I could be explained by the number of days after filling (39%) and enclosure treatment (23%). These two parameters also explained 72% of the variation in species richness in Pond I (46 and 26%, respectively). Sixty‐five per cent of the variation in abundance in Pond II could be explained by the measured parameters: number of days after filling 27%, pH 19%, and nitrate levels 12%. Fifty‐two per cent of the variation in species richness was explained by the environmental parameters, of which pH was the most influential. Species succession was a strong feature of both ponds and its relationship to environmental variables and the presence of other organisms is discussed. 5. Addition of invertebrate predators resulted in higher abundance and higher species richness for a limited time period in one of the ponds – suggesting that differences in foodweb dynamics may influence ciliate community composition."
798,Interferon and Interferon-Induced Chemokine Expression Is Associated with Control of Acute Viremia in West Nile Virus-Infected Blood Donors,"To understand early host responses controlling West Nile virus (WNV) infection, acutely viremic blood donors, identified by nucleic acid amplification testing, were enrolled and monitored for RNA-clearance and WNV-specific IgM and IgG antibodies. Viral load and chemokine and cytokine assays were performed on serial samples from donors whose index and first follow-up samples tested negative for IgM. A total of 84% of the specimens obtained from viremic donors before IgM/IgG seroconversion demonstrated a decreasing viral load. Levels of interferon (IFN)-α ere significantly increased before IgM seroconversion, relative to those in control specimens. CXCL10 and CCL2 were significantly elevated in donor specimens obtained before IgM seroconversion, compared with those obtained after IgM seroconversion. These findings suggest that IFN-mediated innate immunity plays a key role in initial control of WNV replication."
799,A Systematic Review of Tracheostomy Modifications and Swallowing in Adults,"Dysphagia occurs in 11% to 93% of patients following tracheostomy. Despite its benefits, the tracheostomy often co-exists with dysphagia given its anatomical location, the shared pathway of the respiratory and alimentary systems, and the medical complexities necessitating the need for the artificial airway. When tracheostomy weaning commences, it is often debated whether the methods used facilitate swallowing recovery. We conducted a systematic review to determine whether tracheostomy modifications alter swallowing physiology in adults. We searched eight electronic databases, nine grey literature repositories and conducted handsearching. We included studies that reported on oropharyngeal dysphagia as identified by instrumentation in adults with a tracheostomy. We accepted case series (n > 10), prospective or retrospective observational studies, and randomized control trials. We excluded patients with head and neck cancer and/or neurodegenerative disease. Two independent and blinded reviewers rated abstracts and articles for study inclusion. Data abstraction and risk of bias assessment was conducted on included studies. Discrepancies were resolved by consensus. A total of 7079 citations were identified, of which, 639 articles were reviewed, with ten articles meeting our inclusion criteria. The studies were heterogeneous in study design, patient population, and outcome measures. For these reasons, we presented our findings descriptively. All studies were limited by bias risk. This study highlights the limitations of the evidence and therefore the inability to conclude whether tracheostomy modifications alter swallowing physiology."
800,Cytokine Profiles Induced by the Novel Swine-Origin Influenza A/H1N1 Virus: Implications for Treatment Strategies,"Background. Given the apparent high mortality associated with the novel swine-origin influenza A/H1N1 virus (S-OIV) in Mexico, we aimed to study the cytokine profiles induced by S-OIV and the effect of immunomodulators. Methods. We assayed cytokines and their messenger RNA (mRNA) levels in culture supernatants of human macrophages infected with H5N1, S-OIV California/04/2009 (S-OIV-CA), S-OIV Hong Kong/415742 (S-OIV-HK), or seasonal H1N1 with or without celecoxib and mesalazine. Results. Among the 12 cytokines showing detectable levels, levels of 8 proinflammatory cytokines (interleukin [IL] 2R, IL-6, interferon [IFN] α, macrophage inflammatory protein [MIP] α, MIP-1b, IFN-induced protein 10, regulated on activation, normal T cell expressed and secreted [RANTES], and monocyte chemotactic protein [MCP] 1) were higher in cells infected by H5N1 but similar among cells infected with H1N1, S-OIV-CA, or SOIV- HK. The levels of the other 4 cytokines were similar for H5N1, H1N1, S-OIV-CA and S-OIV-HK. Among the 8 cytokines induced by H5N1, 6 were suppressed by celecoxib and mesalazine. The mRNA levels of tumor necrosis factor a, IFN-γ, IL-6, and MCP-1 induced by H5N1 were higher than the levels of other cytokines at 12 and/or 24 h. Conclusions. No major cytokine storm, as seen in H5N1 infection, is associated with S-OIV infection of cell lines. The mainstay of treatment for uncomplicated S-OIV infections should be antiviral agents without immunomodulators. For individual S-OIV-infected patients with severe primary viral pneumonia, severe sepsis, and multiorgan failure, immunomodulators may be considered as an adjunctive therapy in clinical trials."
801,Nonspecific Proctitis: Association with Human Immunodeficiency Virus Infection in Homosexual Men,"In a cross-sectional study of 140 homosexual men attending a sexually transmissible diseases clinic, the association between the presence of antibody to the human immunodeficiency virus (HIV) and the presence of proctitis, as determined by histologic examination, as well as past or present exposure to other pathogens and details of sexual practices was analyzed. Significant associations with HIV seropositivity were found with the number of lifetime partners, positive treponemal serology, and evidence of previous infection with herpes simplex virus. However the major and unique finding was the strong and independent association between proctitis diagnosed by histologic criteria and seropositivity for HIV. Whether this is cause or effect awaits further elucidation."
802,Medical Students’ Clinical Reasoning During a Simulated Viral Pandemic: Evidence of Cognitive Integration and Insights on Novices’ Approach to Diagnostic Reasoning,"INTRODUCTION: Cognitive integration from multiple disciplines is essential to clinical problem-solving. Because it is not directly observable, demonstrating evidence of learners’ cognitive integration remains a challenge. In addition, little is known about preclinical medical students’ approach to diagnostic reasoning despite widespread implementation of clinical reasoning curricula for these early learners. The objectives of this study were to characterize how first-year medical students integrated knowledge to problem-solve during a simulated viral pandemic and to characterize students’ diagnostic reasoning approach to this clinical scenario. MATERIALS AND METHODS: Student teams analyzed clinical data to formulate hypotheses for the pandemic’s source and submitted reports justifying their hypotheses and treatment recommendations. A content analysis on students’ reports identified codes and themes characterizing the learning content integrated and students’ approaches to diagnostic reasoning tasks. RESULTS: Sixteen problem-solving codes were identified, demonstrating integration of new and previously encountered content from multiple disciplines. A compare-contrast analytical approach was the most commonly employed diagnostic reasoning approach (100%), with a smaller subset of teams also using a causal approach (20%). DISCUSSION: Content analysis of preclinical students’ diagnostic justification tasks provided insights into their approach to diagnostic reasoning, which was most consistent with the search-inference framework rather than a causal approach, likely due to limited pathophysiological knowledge at that point in training. CONCLUSIONS: Evidence of cognitive integration can be made explicit through learners’ narrative justification of diagnostic reasoning tasks. Preclinical students’ diagnostic reasoning development has implications for curricular design and implementation for this learner group."
803,In-silico identification of the vaccine candidate epitopes against the Lassa virus hemorrhagic fever,"Lassa virus (LASV), a member of the Arenaviridae, is an ambisense RNA virus that causes severe hemorrhagic fever with a high fatality rate in humans in West and Central Africa. Currently, no FDA approved drugs or vaccines are available for the treatment of LASV fever. The LASV glycoprotein complex (GP) is a promising target for vaccine or drug development. It is situated on the virion envelope and plays key roles in LASV growth, cell tropism, host range, and pathogenicity. In an effort to discover new LASV vaccines, we employ several sequence-based computational prediction tools to identify LASV GP major histocompatibility complex (MHC) class I and II T-cell epitopes. In addition, many sequence- and structure-based computational prediction tools were used to identify LASV GP B-cell epitopes. The predicted T- and B-cell epitopes were further filtered based on the consensus approach that resulted in the identification of thirty new epitopes that have not been previously tested experimentally. Epitope-allele complexes were obtained for selected strongly binding alleles to the MHC-I T-cell epitopes using molecular docking and the complexes were relaxed with molecular dynamics simulations to investigate the interaction and dynamics of the epitope-allele complexes. These predictions provide guidance to the experimental investigations and validation of the epitopes with the potential for stimulating T-cell responses and B-cell antibodies against LASV and allow the design and development of LASV vaccines."
804,Strain-specific transcriptional and posttranscriptional regulation of heat-labile toxin expression by enterotoxigenic Escherichia coli,"Enterotoxigenic Escherichia coli (ETEC) represents one of the most important etiological agents of diarrhea in developing countries and characteristically produces at least one of two enterotoxins: heat-labile toxin (LT) and heat-stable toxin (ST). It has been previously shown that the production and release of LT by human-derived ETEC strains are variable. Although the natural genetic polymorphisms of regulatory sequences of LT-encoding (eltAB) genes may explain the variable production of LT, the knowledge of the transcriptional and posttranscriptional aspects affecting LT expression among ETEC strains is not clear. To further understand the factors affecting LT expression, we evaluated the impact of the natural polymorphism in noncoding regulatory sequences of eltAB among clinically derived ETEC strains. Sequence analyses of seven clinically derived strains and the reference strain H10407 revealed polymorphic sites at both the promoter and upstream regions of the eltAB operon. Operon fusion assays with GFP revealed that specific nucleotide changes in the Pribnow box reduce eltAB transcription. Nonetheless, the total amounts of LT produced by the tested ETEC strains did not strictly correspond to the detected LT-specific mRNA levels. Indeed, the stability of LT varied according to the tested strain, indicating the presence of posttranscriptional mechanisms affecting LT expression. Taken together, our results indicate that the production of LT is a strain-specific process and involves transcriptional and posttranscriptional mechanisms that regulate the final amount of toxin produced and released by specific strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42770-020-00231-2) contains supplementary material, which is available to authorized users."
805,"Tracheostomy in patients with acute respiratory distress syndrome is not related to quality of life, symptoms of psychiatric disorders or return-to-work: the prospective DACAPO cohort study","BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition that often requires prolonged mechanical ventilation. Tracheostomy is a common procedure with some risks, on the other hand with potential advantages over orotracheal intubation in critically ill patients. This study investigated the association of tracheostomy with health-related quality of life (HRQoL), symptoms of psychiatric disorders and return-to-work of ARDS survivors. METHODS: Data were collected in the context of the prospective observational German-wide DACAPO study. Clinical and demographic patient data and treatment characteristics were obtained from the participating intensive care units (ICU). HRQoL and return-to-work were assessed using patient-reported questionnaires 3, 6 and 12 months after ICU discharge. HRQoL was measured with the Physical and Mental Component Scale of the Short-Form 12 Questionnaire (PCS-12, MCS-12). The prevalence of psychiatric symptoms (depression and post-traumatic stress disorder [PTSD]) was assessed using the Patient Health Questionnaire-9 and the Post-Traumatic Stress Syndrome-14. Physician-diagnosed anxiety and obsessive–compulsive disorder were recorded by patient self-report in the follow-up questionnaires. The associations of tracheostomy with HRQoL, psychiatric symptoms and return-to-work after 12 months were investigated by means of multivariable linear and logistic regression models. RESULTS: Primary 877 ARDS patients (mean ± standard deviation: 54 ± 16 years, 68% male) survived and were discharged from ICU. Out of these patients, 478 (54.5%) were tracheotomised during ICU treatment. After 12 months, patient-reported outcomes could be analysed of 388 (44.2%) respondents, 205 with tracheostomy and 183 without. One year after ICU discharge, tracheostomy showed no significant association with physical or mental health-related quality of life (PCS-12: − 0.73 [− 3.96, 2.51]; MCS-12: − 0.71 [− 4.92, 3.49]), symptoms of psychiatric disorders (depression: 0.10 [− 1.43, 1.64]; PTSD: 3.31 [− 1.81, 8.43]; anxiety: 1.26 [0.41, 3.86]; obsessive–compulsive disorder: 0.59 [0.05, 6.68]) or return-to-work (0.71 [0.31, 1.64]) in the multivariable analysis (OR [95%-CI]). CONCLUSIONS: Up to 1 year after ICU discharge, neither HRQoL nor symptoms of psychiatric disorders nor return-to-work was affected by tracheostomy. Trial registration NCT02637011 (ClinicalTrials.gov, Registered 15 December 2015, retrospectively registered)"
806,Infektionsschutzrecht nach Inkrafttreten des Masernschutzgesetzes,"On 1 March 2020, the amendments to the German Protection Against Infection Act that were introduced by the act to protect against measles and strengthen vaccination prevention (Measles Protection Act) entered into force. The reason for the changes is that the number of individuals with measles has significantly increased in recent years. To protect public health, the Measles Protection Act has implemented regulations requiring that persons in certain institutions must either have adequate protection against measles or have immunity to measles. In this article the current legal situation with regard to health care facilities is presented."
807,Physiology in Medicine: Understanding dynamic alveolar physiology to minimize ventilator-induced lung injury,"Acute respiratory distress syndrome (ARDS) remains a serious clinical problem with the main treatment being supportive in the form of mechanical ventilation. However, mechanical ventilation can be a double-edged sword: if set improperly, it can exacerbate the tissue damage caused by ARDS; this is known as ventilator-induced lung injury (VILI). To minimize VILI, we must understand the pathophysiologic mechanisms of tissue damage at the alveolar level. In this Physiology in Medicine paper, the dynamic physiology of alveolar inflation and deflation during mechanical ventilation will be reviewed. In addition, the pathophysiologic mechanisms of VILI will be reviewed, and this knowledge will be used to suggest an optimal mechanical breath profile (MB(P): all airway pressures, volumes, flows, rates, and the duration that they are applied at both inspiration and expiration) necessary to minimize VILI. Our review suggests that the current protective ventilation strategy, known as the “open lung strategy,” would be the optimal lung-protective approach. However, the viscoelastic behavior of dynamic alveolar inflation and deflation has not yet been incorporated into protective mechanical ventilation strategies. Using our knowledge of dynamic alveolar mechanics (i.e., the dynamic change in alveolar and alveolar duct size and shape during tidal ventilation) to modify the MB(P) so as to minimize VILI will reduce the morbidity and mortality associated with ARDS."
808,Lung Parenchymal Mechanics in Health and Disease,"The mechanical properties of lung tissue are important determinants of lung physiological functions. The connective tissue is composed mainly of cells and extracellular matrix, where collagen and elastic fibers are the main determinants of lung tissue mechanical properties. These fibers have essentially different elastic properties, form a continuous network along the lungs, and are responsible for passive expiration. In the last decade, many studies analyzed the relationship between tissue composition, microstructure, and macrophysiology, showing that the lung physiological behavior reflects both the mechanical properties of tissue individual components and its complex structural organization. Different lung pathologies such as acute respiratory distress syndrome, fibrosis, inflammation, and emphysema can affect the extracellular matrix. This review focuses on the mechanical properties of lung tissue and how the stress-bearing elements of lung parenchyma can influence its behavior."
809,A case report of fatal disseminated fungal sepsis in a patient with ARDS and extracorporeal membrane oxygenation,"BACKGROUND: With the following report we want to present an unusual case of a patient suffering from acute respiratory distress syndrome with early discovery of bacterial pathogens in bronchoalveolar liquid samples that developed a fatal undiscovered disseminated fungal infection. CASE PRESENTATION: A 67-year-old man was admitted to our university hospital with dyspnea. Progressive respiratory failure developed leading to admission to the intensive care unit, intubation and prone positioning was necessary. To ensure adequate oxygenation and lung protective ventilation veno-venous extracorporeal membrane oxygenation was established. Despite maximal therapy and adequate antiinfective therapy of all discovered pathogens the condition of the patient declined further and he deceased. Postmortem autopsy revealed Mucor and Aspergillus mycelium in multiple organs such as lung, heart and pancreas as the underlying cause of his deterioration and death. CONCLUSION: Routine screening re-evaluation of every infection is essential for adequate initiation and discontinuation of every antiinfective therapy. In cases with unexplained deterioration and unsuccessful sampling the possibility for diagnostic biopsies should be considered."
810,Improvement cues of lesion absorption using the adjuvant therapy of traditional Chinese medicine Qinbudan tablet for retreatment pulmonary tuberculosis with standard anti-tuberculosis regimen,"BACKGROUND: China is the second highest pulmonary tuberculosis (PTB) burden country worldwide. However, retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs. The cure rate (approximately 50.0–73.3%) and management of retreatment of PTB in China needs to be improved. Qinbudan decoction has been widely used to treat PTB in China since the 1960s. Previously clinical studies have shown that the Qinbudan tablet (QBDT) promoted sputum-culture negative conversion and lesion absorption. However, powerful evidence from a randomized controlled clinical trial is lacking. Therefore, the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial in China. People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013. The treatment group received an anti-TB regimen and QBDT, and the control group was administered an anti-TB regimen plus placebo. Anti-TB treatment options included isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months (2HRZES), followed by isoniazid, rifampicin, ethambutol for 6 months (6HRE), daily for 8 months. Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method. Secondary outcomes included lung lesion absorption and cavity closure. Adverse events and reactions were observed after treatment. A structured questionnaire was used to record demographic information and clinical symptoms of all subjects. Data analysis was performed by SPSS 25.0 software in the full analysis set (FAS) population. RESULTS: One hundred eighty-one cases of retreatment PTB were randomly divided into two groups: the placebo group (88 cases) and the QBDT group (93 cases). A total of 166 patients completed the trial and 15 patients lost to follow-up. The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences (79.6% vs 69.3%; rate difference = 0.10, 95% confidence interval (CI): - 0.02–0.23; F = 2.48, P = 0.12) after treatment. A significant 16.6% increase in lesion absorption was observed in the QBDT group when compared with the placebo group (67.7% vs 51.1%; rate difference = 0.17, 95% CI: 0.02–0.31; χ(2) = 5.56, P = 0.02). The intervention and placebo group did not differ in terms of cavity closure (25.5% vs 21.1%; rate difference = 0.04, 95% CI: - 0.21–0.12; χ(2) = 0.27, P = 0.60). Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting. CONCLUSIONS: No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen. However, QBDT as an adjunct therapy significantly promoted lesion absorption, thereby reducing lung injury due to Mycobacterium tuberculosis infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT02313610."
811,Live-attenuated Salmonella enterica serotype Choleraesuis vaccine with regulated delayed fur mutation confer protection against Streptococcus suis in mice,"BACKGROUND: Recombinant Salmonella enterica serotype Choleraesuis (S. Choleraesuis) vaccine vector could be used to deliver heterologous antigens to prevent and control pig diseases. We have previously shown that a live-attenuated S. Choleraesuis vaccine candidate strain rSC0011 (ΔP(crp527)::TT araC P(BAD)crp Δpmi-2426 ΔrelA199::araC P(BAD)lacI TT ΔasdA33, Δ, deletion, TT, terminator) delivering SaoA, a conserved surface protein in most of S. suis serotypes, provided excellent protection against S. suis challenge, but occasionally lead to morbidity (enteritidis) in vaccinated mice (approximately 1 in every 10 mice). Thus, alternated attenuation method was sought to reduce the reactogenicity of strain rSC0011. Herein, we described another recombinant attenuated S. Choleraesuis vector, rSC0012 (ΔP(fur88):: TT araC P(BAD)fur Δpmi-2426 ΔrelA199:: araC P(BAD)lacI TT ΔasdA33) with regulated delayed fur mutation to avoid inducing disease symptoms while exhibiting a high degree of immunogenicity. RESULTS: The strain rSC0012 strain with the ΔP(fur88)::TT araC P(BAD)fur mutation induced less production of inflammatory cytokines than strain rSC0011 with the ΔP(crp527)::TT araC P(BAD)crp mutation in mice. When delivering the same pS-SaoA plasmid, the intraperitoneal LD(50) of rSC0012 was 18.2 times higher than that of rSC0011 in 3-week-old BALB/C mice. rSC0012 with either pS-SaoA or pYA3493 was cleared from spleen and liver tissues 7 days earlier than rSC0011 with same vectors after oral inoculation. The strain rSC0012 synthesizing SaoA induced high titers of anti-SaoA antibodies in both systemic (IgG in serum) and mucosal (IgA in vaginal washes) sites, as well as increased level of IL-4, the facilitator of Th2-type T cell immune response in mice. The recombinant vaccine rSC0012(pS-SaoA) conferred high percentage of protection against S. suis or S. Choleraesuis challenge in BALB/C mice. CONCLUSIONS: The live-attenuated Salmonella enterica serotype Choleraesuis vaccine rSC0012(pS-SaoA) with regulated delayed fur mutation provides a foundation for the development of a safe and effective vaccine against S. Choleraesuis and S. suis."
812,Zebrafish as an alternative animal model in human and animal vaccination research,"Much of medical research relies on animal models to deepen knowledge of the causes of animal and human diseases, as well as to enable the development of innovative therapies. Despite rodents being the most widely used research model worldwide, in recent decades, the use of the zebrafish (Danio rerio) model has exponentially been adopted among the scientific community. This is because such a small tropical freshwater teleost fish has crucial genetic, anatomical and physiological homology with mammals. Therefore, zebrafish constitutes an excellent experimental model for behavioral, genetic and toxicological studies which unravels the mechanism of various human diseases. Furthermore, it serves well to test new therapeutic agents, such as the safety of new vaccines. The aim of this review was to provide a systematic literature review on the most recent studies carried out on the topic. It presents numerous advantages of this type of animal model in tests of efficacy and safety of both animal and human vaccines, thus highlighting gains in time and cost reduction of research and analyzes."
813,The immune response to influenza in older humans: beyond immune senescence,"Despite widespread influenza vaccination programs, influenza remains a major cause of morbidity and mortality in older adults. Age-related changes in multiple aspects of the adaptive immune response to influenza have been well-documented including a decline in antibody responses to influenza vaccination and changes in the cell-mediated response associated with immune senescence. This review will focus on T cell responses to influenza and influenza vaccination in older adults, and how increasing frailty or coexistence of multiple (≥2) chronic conditions contributes to the loss of vaccine effectiveness for the prevention of hospitalization. Further, dysregulation of the production of pro- and anti-inflammatory mediators contributes to a decline in the generation of an effective CD8 T cell response needed to clear influenza virus from the lungs. Current influenza vaccines provide only a weak stimulus to this arm of the adaptive immune response and rely on re-stimulation of CD8 T cell memory related to prior exposure to influenza virus. Efforts to improve vaccine effectiveness in older adults will be fruitless until CD8 responses take center stage."
814,Congenital diaphragmatic hernia presenting with symptoms within the first day of life; outcomes from a non-ECMO centre in Denmark,"BACKGROUND: Between 1998 and 2015, we report on the survival of congenital diaphragmatic hernia (CDH)-infants presenting with symptoms within the first 24 h of life, treated at Odense University Hospital (OUH), a tertiary referral non-extracorporeal membrane oxygenation (ECMO) hospital for paediatric surgery. METHODS: We performed a retrospective cohort study of prospectively identified CDH-infants at our centre. Data from medical records and critical information systems were obtained. Baseline data included mode of delivery and infant condition. Outcome data included 24-h, 28-day, and 1 year mortality rates and management data included intensive care treatment, length of stay in the intensive care unit, time of discharge from hospital, and surgical intervention. Descriptive analyses were performed for all variables. Survivors and non-survivors were compared for baseline and treatment data. RESULTS: Ninety-five infants were identified (44% female). Of these, 77% were left-sided hernias, 52% were diagnosed prenatally, and 6.4% had concurrent malformations. The 28-day mortality rate was 21.1%, and the 1 year mortality rate was 22.1%. Of the 21 non-survivors, nine died within the first 24 h, and 10 were sufficiently stabilised to undergo surgery. A statistically significant difference was observed between survivors and non-survivors regarding APGAR score at 1 and 5 min., prenatal diagnosis, body length at birth, and delivery at OUH. CONCLUSIONS: Our outcome results were comparable to published data from other centres, including centres using ECMO."
815,Modern diagnostics in emergency medicine,
816,A Spontaneous Lower Motor Neuron Disease Apparently Caused by Indigenous Type-C RNA Virus in Wild Mice,A high incidence of spontaneous lower-limb paralysis occurred in a population of wild mice (Mus musculus) which had a high incidence of naturally occurring lymphoma and elevated indigenous type-C virus activity. Experimental transmission evidence indicated that both the neurologic and lymphomatous disorders almost certainly were caused by the indigenous type-C virus. The virus appeared to have a direct neurotropic effect on anterior horn neurons in the lower spinal cord.
817,Type C Virus Expression in Lymphoma-Paralysis-Prone Wild Mice,"Wild mice trapped near Lake Casitas (LC) in southern California showed a high prevalence of infectious type C virus in the liver, spleen, and thymus within the first few weeks of life. By young adulthood about 80% of LC mice (including their genital tissues) were infected. Virus isolates from these mice cause lymphoma and lower limb paralysis under both natural and experimental conditions. Mice destined to develop paralysis showed higher levels of serum gs antigen early in life, whereas mice destined to develop lymphoma or remain free of these diseases could not be distinguished by this test. The individual variation in virus expression suggested that differences in virus type or in the immune or other host defense mechanisms greatly influenced susceptibility or resistance to indigenous type C virus-caused disease in LC wild mice."
818,Differential Distribution of Mouse Mammary Tumor Virus-Related Sequences in the DNA’s of Rats,"Radioactively labeled mouse mammary tumor virus (MuMTV) 60-70S RNA, obtained from virions grown In both murine and feline cells, was employed In molecular hybridization experiments to detect MuMTV-related sequences In the DNA’s of rats (Rattus norveglcus). With the use of relaxed conditions of hybridization and assay for RNA-DNA duplexes, all strains of laboratory rats and feral rats examined were shown to possess endogenous MuMTV-related DNA sequences In the low repetitive range. These sequences were related to approximately 20% of the MuMTV genome and exhibited a melting temperature (Tm) approximately 5° C lower than MuMTV-specific proviral sequences In murine (Mus musculus) DNA’s. Certain colonies of the F344 strain of rat (Fischer) contained animals whose DNA’s possessed additional MuMTV-related sequences. These sequences were related to the non-germ-line-transmitted, tumorassociated (TA) sequences of the highly oncogenic MuMTV (C3H). They were found In the DNA of some F344 rats and a cloned established F344 rat embryo cell line at a frequency of approximately one copy per haploid genome and exhibited a Tm 9° C lower than that of hybrid duplexes formed between radioactive MuMTV TA-sequence RNA and C3H mouse mammary tumor DNA. The DNA’s of rats, therefore, contained two sets of sequences that were related to sequences of the MuMTV genome: One set was germ-line transmitted, whereas the other set appeared to be transmitted in some rats via a non-germ line or infectious process."
819,Determinants of Susceptibility and Resistance to Feline Leukemia Virus Infection. I. Role of Macrophages,"The role of autochthonous peritoneal feline macrophages (Mθ) in the age-related resistance of cats to feline leukemia virus (FeLV) was investigated by a study of the functional properties and FeLV susceptibility of Mθ from kittens and adult cats and the effect of hydrocortisone (HC) and silica on Mθ-FeLV interactions. Although the phagocytic functions of isolated Mθ from kittens and adults were equivalent, the mean FeLV susceptibility of Mθ from kittens was five times that of Mθ from adult cats, thus establishing a direct correlation between the age-related susceptibility of cats and Mθ from cats to FeLV. Mθ of viremic cats were found to be infected with FeLV in vivo; virus titers were slightly higher than those obtained after in vitro infection of Mθ. Mθ from cats that had experienced regressive FeLV infection were not significantly more resistant to FeLV infection in vitro than were Mθ from naive adult specific-pathogen-free cats. HC, which has been shown to enhance the in vivo FeLV susceptibility of cats, also enhanced the permissiveness of Mθ from cats to FeLV in vitro (600-fold for Mθ from adult cats and 200-fold for Mθ) from kittens. Mθ permissiveness to FeLV was highly sensitive to HC and occurred in Mθ infected in vivo or in vitro. In parallel with the effect of HC on the natural resistance of cats to FeLV, administration of silica before virus inoculation also markedly enhanced the FeLV susceptibility of adult cats. Silica was toxic for isolated Mθ but not for lymphocytes in vitro, and silica produced monocytopenia and neutrophilia, delayed skin allograft rejection, and augmented feline oncovirus-associated cell membrane antigen antibody responses in vivo. These experiments indicate that Mθ were linked to the natural resistance of cats to FeLV and that the temporary elimination of Mθ functions (e.g., by silica) and/or the conversion of the Mθ-FeLV relationship from a nonpermissive to a permissive state (e.g., by corticosteroids) resulted in failure of early virus containment, in persistent virus amplification in hemolymphatic tissues, and in subsequent FeLV-related proliferative or antiproliferative disease."
820,Pathogenesis of Lesions Induced in Rat Lung by Chronic Tobacco Smoke Inhalation,"Lesions were induced in the lungs of specific-pathogen-free F344 rats by chronic tobacco smoke exposure. Animals exposed to 7 cigarettes/day were killed after 1, 1.5, or 2 years of exposure. Parallel lifetime exposures induced pulmonary tumors in 9% of the animals. In serially killed animals, four types of lesions were found: 1) perivascular or peribronchiolar accumulation of lymphoreticular cells, 2) fibrotic and cellular enlargement of peribronchiolar septa, 3) type II cell hyperplasia with septal fibrosis, and 4) air-space enlargement (emphysema). However, emphysema occurred only in animals exposed to a higher (10 cigarettes) dose of tobacco smoke. Ultrastructural studies showed all of the focal lesions to be infiltrated by cells typical of the inflammatory response. The type II hyperplastic and peribronchiolar alveolar lesions involved larger portions of the parenchyma in fibrotic changes but differed in structure, location, and frequency. The incidence of the peribronchiolar alveolar lesions was temporally related to tumor incidence."
821,PC-FACS May 2020 for July 2020 Issue,
822,SARS-CoV-2 in pregnancy: symptomatic pregnant women are only the tip of the iceberg,
823,Coronavirus disease: challenges for psychiatry,"Coronavirus disease (COVID-19) presents two urgent health problems: the illness caused by the virus itself and the anxiety, panic and psychological problems associated with the pandemic. Both problems present substantial challenges for our patients, their families, our multidisciplinary teams and our psychiatrist colleagues. We need good psychiatry, now more than ever."
824,Triple combination therapy of favipiravir plus two monoclonal antibodies eradicates influenza virus from nude mice,"Prolonged treatment of immunocompromised influenza patients with viral neuraminidase (NA) inhibitors is required, because the immune system of such patients fails to eradicate the viruses. Here, we attempted to eradicate influenza virus from the respiratory organs of nude mice, which is a model of immunocompromised hosts, by using combination therapy of the viral polymerase inhibitor favipiravir and monoclonal antibodies (mAbs) against the receptor-binding site (RBS) and stem of viral hemagglutinin (HA). Although monotherapy or combination therapy of two antivirals (two mAbs or favipiravir plus a mAb) suppressed virus replication, they failed to eradicate viruses from nude mice. In contrast, the triple combination therapy of favipiravir plus anti-Stem and anti-RBS mAbs completely stopped virus replication in nude mice, resulting in virus clearance. Triple combination approaches should be considered for the treatment of human immunocompromised patients with severe influenza."
825,Protecting Clinicians from Civil Liability During a Public Health Crisis: Legislative & Professional Organizational Efforts,
826,The structure–activity relationship review of the main bioactive constituents of Morus genus plants,"ABSTRACT: Morus genus plants are mainly distributed in the temperate to tropical areas over the world and include 17 species and two subspecies. Due to their excellent pharmacological activity, security in food additives and high value in the national economy, Morus genus plants have drawn more and more attention in recent years. In the light of the references published over the last few decades, flavonoids, benzofurans, stilbenes, and Diels–Alder adducts have been reported to be the main bioactive constituents of Morus genus plants. This review summarizes the compounds with excellent bioactivities isolated from Morus genus plants as well as their structure–activity relationships (SARs), which might be useful for the further research and development of Morus genus plants. GRAPHIC ABSTRACT: [Image: see text] The aromatic heterocycles with excellent bioactivities isolated from Morus genus plants as well as their structure–activity relationships (SARs) were summarized."
827,"Advances in cytomegalovirus (CMV) biology and its relationship to health, diseases, and aging","Cytomegalovirus (CMV) is one of the largest and most ubiquitous latent persistent viruses. Most humans are infected with CMV early in life, and all immunocompetent humans spend several decades living with CMV. In the vast majority of the hosts, CMV does not cause manifest disease, and CMV therefore can be considered part of normal aging for 50–90% of the human population worldwide. Experimental, clinical, and epidemiological studies suggest that CMV carriage can have nuanced outcomes, including both potentially harmful and potentially beneficial impacts on the host. We here present a summary of the 7th International Workshop on CMV and Immunosenescence, covering various aspects of the interplay between CMV and its mammalian hosts in the context of virus spread, immune evasion, antiviral immunity, as well as the impact on health span and aging."
828,The dynamic change of serum S100B levels from day 1 to day 3 is more associated with sepsis-associated encephalopathy,"We investigated the role of dynamic changes of serum levels S100B protein in brain injury and poor outcome of sepsis. This is a prospective cohort study designed to include 104 adult patients with sepsis who are admitted to ICU from Jan 2015 to Aug 2016. Sepsis was defined as sepsis 3.0. Patients with a GCS score of <15, or at least one positive CAM-ICU score were thought to have brain dysfunction. 59 patients were diagnosed with SAE and the rest 45 patients were diagnosed with non-SAE. Serum S100B was measured on day 1 and 3 after ICU admission. Primary outcomes included brain dysfunction and 28-day/180-day mortality. The SAE group showed a significantly higher APACHE II score, SOFA scores, length of ICU stay, 28-day and 180-day mortality, serum S100B levels on day 1 and day 3. S100B levels on day 1 of 0.226 μg/L were diagnostic for SAE with 80.0% specificity and 66.1% sensitivity, and the area under (AUC) the curve was 0.728, S100B levels on day 3 of 0.144 μg/L were diagnostic for SAE with 84.44% specificity and 69.49% sensitivity, and the AUC was 0.819. In addition, the AUC for S100B on day 3 for predicting 180-day mortality was larger than for S100B on day 1 (0.731 vs. 0.611). Multiple logistic regression analysis showed that S100B3 (p = 0.001) but not S100B1 (p = 0.927) were independently correlated with SAE. Kaplan-Meier survival analysis showed that patients with S100B levels higher than 0.144 μg/L had a lower probability of survival at day 180. There were more patients with encephalopathy and a higher 28-day or 180-day mortality in the ΔS100B + group than in the ΔS100B- group. Multiple logistic regression analysis showed that SAE and IL-6 on day 3 were independently correlated with S100B dynamic increase. These findings suggest that elevated serum S100B levels on day 3 and the dynamic changes of serum S100B levels from day three to one were more associated with brain dysfunction and mortality than that on day 1 in patients with sepsis."
829,"Whose crisis? Pandemic flu, ‘communication disasters’ and the struggle for hegemony","Public health authorities in Germany regard communication as a crucial part of infectious disease prevention and control strategies. Communication becomes even more important during public health crises such as pandemics. Drawing on Briggs and Hallin’s concept of biocommunicability, we analysed the German National Pandemic Plan and key informant interviews with public health experts, critical infrastructure providers and ambulance services. We examined the projected expectations towards the behaviour of the audiences and the projected ways of information circulation informing public health communication strategies during a pandemic. Participants shared the expectation that the population would react towards an influenza pandemic with panic and fear due to a lack of information or a sensationalist media coverage. They associated the information uptake of their target audience with trust in their expertise. While our informants from public health conceptualised trust in terms of a face-to-face interaction, they sought to gain trust through transparency in their respective institutional settings. Our analysis suggests that this moved health information into a political register where their medical authority was open to debate. In response to this, they perceived the field of communication as a struggle for hegemony."
830,Early signs of right ventricular systolic and diastolic dysfunction in acute severe respiratory failure: the importance of diastolic restrictive pattern,"BACKGROUND: The incidence and pathophysiology of right ventricular failure in patients with severe respiratory insufficiency has been largely investigated. However, there is a lack of early signs suggesting right ventricular systolic and diastolic dysfunction prior to acute cor pulmonale development. METHODS: We conducted a retrospective analytical cohort study of patients for acute respiratory distress syndrome undertaking an echocardiography during admission in the cardiothoracic intensive care unit. Patients were divided according to treatment: conventional protective ventilation (38 patients, 38%); interventional lung assist (23 patients, 23%); veno-venous extracorporeal membrane oxygenation (37 patients, 37%). Systolic and diastolic function was studied assessing, respectively: right ventricular systolic longitudinal function (tricuspid annular plane systolic excursion) and systolic contraction duration (tricuspid annular plane systolic excursion length); right ventricular diastolic filling time and right ventricular diastolic restrictive pattern (presence of pulmonary valve presystolic ejection wave). Correlation between the respiratory mechanics and systo-diastolic parameters were analysed. RESULTS: In 98 patients studied, systolic dysfunction (tricuspid annular plane systolic excursion <16 mm) was present in 33.6% while diastolic restrictive pattern was present in 64%. A negative correlation was found between tricuspid annular plane systolic excursion and tricuspid annular plane systolic excursion length (P<0.0001; r −0.42). Tricuspid annular plane systolic excursion and tricuspid annular plane systolic excursion length correlated with right ventricular diastolic filling time (P<0.001; r −0.39). Pulmonary valve presystolic ejection wave was associated with tricuspid annular plane systolic excursion (P<0.0001), tricuspid annular plane systolic excursion length (P<0.0001), right ventricular diastolic filling time (P<0.0001), positive end-expiratory pressure (P<0.0001) and peak inspiratory pressure (P<0.0001). CONCLUSION: Diastolic restrictive pattern is present in a remarkable percentage of patients with respiratory distress syndrome. Bedside echocardiography allows a mechanistic evaluation of systolic and diastolic interaction of the right ventricle."
831,FluA-p score: a novel prediction rule for mortality in influenza A-related pneumonia patients,"BACKGROUND: The pneumonia severity index (PSI) and the CURB-65 (confusion, urea, respiratory rate, blood pressure, age ≥ 65 years) score have been shown to predict mortality in community-acquired pneumonia. Their ability to predict influenza-related pneumonia, however, is less well-established. METHODS: A total of 693 laboratory-confirmed FluA-p patients diagnosed between Jan 2013 and Dec 2018 and recruited from five teaching hospitals in China were included in the study. The sample included 494 patients in the derivation cohort and 199 patients in the validation cohort. The prediction rule was established based on independent risk factors for 30-day mortality in FluA-p patients from the derivation cohort. RESULTS: The 30-day mortality of FluA-p patients was 19.6% (136/693). The FluA-p score was based on a multivariate logistic regression model designed to predict mortality. Results indicated the following significant predictors (regression statistics and point contributions toward total score in parentheses): blood urea nitrogen > 7 mmol/L (OR 1.604, 95% CI 1.150–4.492, p = 0.040; 1 points), pO(2)/F(i)O(2) ≤ 250 mmHg (OR 2.649, 95% CI 1.103–5.142, p = 0.022; 2 points), cardiovascular disease (OR 3.967, 95% CI 1.269–7.322, p < 0.001; 3 points), arterial PH < 7.35 (OR 3.959, 95% CI 1.393–7.332, p < 0.001; 3 points), smoking history (OR 5.176, 95% CI 2.604–11.838, p = 0.001; 4 points), lymphocytes < 0.8 × 10(9)/L (OR 8.391, 95% CI 3.271–16.212, p < 0.001; 5 points), and early neurominidase inhibitor therapy (OR 0.567, 95% CI 0.202–0.833, p = 0.005; − 2 points). Seven points was used as the cut-off value for mortality risk stratification. The model showed a sensitivity of 0.941, a specificity of 0.762, and overall better predictive performance than the PSI risk class (AUROC = 0.908 vs 0.560, p < 0.001) and the CURB-65 score (AUROC = 0.908 vs 0.777, p < 0.001). CONCLUSIONS: Our results showed that a FluA-p score was easy to derive and that it served as a reliable prediction rule for 30-day mortality in FluA-p patients. The score could also effectively stratify FluA-p patients into relevant risk categories and thereby help treatment providers to make more rational clinical decisions."
832,Prehospital reversal of profound respiratory acidosis and hypercapnic coma by non-invasive ventilation: a report of two cases,"BACKGROUND: In chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF), non-invasive ventilation (NIV) is generally recommended and has proven its benefits by reducing endotracheal intubation (ETI) rates, intensive care unit (ICU) admissions, complications, and mortality. Choosing between immediate ETI or NIV trial is often difficult when such patients present with an altered mental status. Some guidelines recommend avoiding NIV when consciousness is impaired given the risk of aspiration, and some authors suggest that a pH < 7.25 is highly predictive of NIV failure. Though clinical response to a well-adjusted NIV treatment can be both swift and spectacular, these contraindications probably encourage physicians to proceed to immediate ETI. Some studies indeed report that NIV was not even considered in as many as 60% of patients who might have benefited from this therapy, though ETI related complications might have been avoided had NIV been successfully applied. CASE PRESENTATION: We report two cases of ARF in COPD patients who were successfully treated by NIV in prehospital setting and avoided ETI despite contraindications (altered mental status with a Glasgow Coma Scale < 8) and failure risk factors (severe respiratory acidosis with pH < 7.25). CONCLUSION: In COPD patients presenting ARF, NIV trial could be considered even when relative contraindications such as an altered level of consciousness or a severe respiratory acidosis are present."
833,Phenotypic heterogeneity by site of infection in surgical sepsis: a prospective longitudinal study,"BACKGROUND: The role of site of infection in sepsis has been poorly characterized. Additionally, sepsis epidemiology has evolved. Early mortality has decreased, but many survivors now progress into chronic critical illness (CCI). This study sought to determine if there were significant differences in the host response and current epidemiology of surgical sepsis categorized by site of infection. STUDY DESIGN: This is a longitudinal study of surgical sepsis patients characterized by baseline predisposition, insult characteristics, serial biomarkers, hospital outcomes, and long-term outcomes. Patients were categorized into five anatomic sites of infection. RESULTS: The 316 study patients were predominantly Caucasian; half were male, with a mean age of 62 years, high comorbidity burden, and low 30-day mortality (10%). The primary sites were abdominal (44%), pulmonary (19%), skin/soft tissue (S/ST, 17%), genitourinary (GU, 12%), and vascular (7%). Most abdominal infections were present on admission and required source control. Comparatively, they had more prolonged proinflammation, immunosuppression, and persistent organ dysfunction. Their long-term outcome was poor with 37% CCI (defined as > 14 in ICU with organ dysfunction), 49% poor discharge dispositions, and 30% 1-year mortality. Most pulmonary infections were hospital-acquired pneumonia. They had similar protracted proinflammation and organ dysfunction, but immunosuppression normalized. Long-term outcomes are similarly poor (54% CCI, 47% poor disposition, 32% 1-year mortality). S/ST and GU infections occurred in younger patients with fewer comorbidities, less perturbed immune responses, and faster resolution of organ dysfunction. Comparatively, S/ST had better long-term outcomes (23% CCI, 39% poor disposition, 13% 1-year mortality) and GU had the best (10% CCI, 20% poor disposition, 10% 1-year mortality). Vascular sepsis patients were older males, with more comorbidities. Proinflammation was blunted with baseline immunosuppression and organ dysfunction that persisted. They had the worst long-term outcomes (38% CCI, 67% poor disposition, 57% 1-year mortality). CONCLUSION: There are notable differences in baseline predisposition, host responses, and clinical outcomes by site of infection in surgical sepsis. While previous studies have focused on differences in hospital mortality, this study provides unique insights into the host response and long-term outcomes associated with different sites of infection."
834,"Propofol versus placebo (with rescue with ketamine) before less invasive surfactant administration: study protocol for a multicenter, double-blind, placebo controlled trial (PROLISA)","BACKGROUND: One major limitation for less invasive surfactant administration (LISA) is the difficulty in providing sedation before this procedure and the competitive risk of respiratory depression versus avoidance of intubation for most sedative or analgesic drugs used in this context. The objective of this study is to compare the need for mechanical ventilation within 72 h of life following premedication with propofol, versus placebo (rescue with ketamine), for the LISA procedure in preterm neonates born before 32 weeks gestational age (wGA). METHODS: ProLISA is a phase III, non-inferiority, multicenter, double blind, randomized, placebo controlled trial designed according to the SPIRIT Statement. Neonates born before 32 wGA in 12 geographically dispersed Neonatal Intensive Care Units in France needing surfactant will be included from September 2019 to September 2022. A sample of 542 patients is needed. The neonate is randomized to the intervention (propofol) or control placebo group. Open label rescue treatment with ketamine is possible in both groups if FANS (Faceless Acute Neonatal pain Scale) is ≥6. To guide drug administration, FANS is scored before attempting laryngoscopy. Once an adequate score has been obtained, LISA is performed according to a standardized protocol. The primary outcome is the need for mechanical ventilation within 72 h of life. Secondary outcomes are tolerance of the procedure, pain evaluation, hemodynamic and neurologic parameters after the intervention, morbidities before discharge and neurodevelopmental assessment at 2 years of age. DISCUSSION: This paper describes the first multicenter, double-blind, randomized, placebo-controlled trial on this topic and will provide crucial information to support implementation of the LISA procedure. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04016246. Registered 06 June 2019, N°EUDRACT: 2018–002876-41."
835,"Inhibition of complement pathway activation with Pozelimab, a fully human antibody to complement component C5","Complement is a key component of the innate immune system. Inappropriate complement activation underlies the pathophysiology of a variety of diseases. Complement component 5 (C5) is a validated therapeutic target for complement-mediated diseases, but the development of new therapeutics has been limited by a paucity of preclinical models to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) properties of candidate therapies. The present report describes a novel humanized C5 mouse and its utility in evaluating a panel of fully human anti-C5 antibodies. Surprisingly, humanized C5 mice revealed marked differences in clearance rates amongst a panel of anti-C5 antibodies. One antibody, pozelimab (REGN3918), bound C5 and C5 variants with high affinity and potently blocked complement-mediated hemolysis in vitro. In studies conducted in both humanized C5 mice and cynomolgus monkeys, pozelimab demonstrated prolonged PK and durable suppression of hemolytic activity ex vivo. In humanized C5 mice, a switch in dosing from in-house eculizumab to pozelimab was associated with normalization of serum C5 concentrations, sustained suppression of hemolytic activity ex vivo, and no overt toxicity. Our findings demonstrate the value of humanized C5 mice in identifying new therapeutic candidates and treatment options for complement-mediated diseases."
836,Changing care pathways and between-center practice variations in intensive care for traumatic brain injury across Europe: a CENTER-TBI analysis,"PURPOSE: To describe ICU stay, selected management aspects, and outcome of Intensive Care Unit (ICU) patients with traumatic brain injury (TBI) in Europe, and to quantify variation across centers. METHODS: This is a prospective observational multicenter study conducted across 18 countries in Europe and Israel. Admission characteristics, clinical data, and outcome were described at patient- and center levels. Between-center variation in the total ICU population was quantified with the median odds ratio (MOR), with correction for case-mix and random variation between centers. RESULTS: A total of 2138 patients were admitted to the ICU, with median age of 49 years; 36% of which were mild TBI (Glasgow Coma Scale; GCS 13–15). Within, 72 h 636 (30%) were discharged and 128 (6%) died. Early deaths and long-stay patients (> 72 h) had more severe injuries based on the GCS and neuroimaging characteristics, compared with short-stay patients. Long-stay patients received more monitoring and were treated at higher intensity, and experienced worse 6-month outcome compared to short-stay patients. Between-center variations were prominent in the proportion of short-stay patients (MOR = 2.3, p < 0.001), use of intracranial pressure (ICP) monitoring (MOR = 2.5, p < 0.001) and aggressive treatments (MOR = 2.9, p < 0.001); and smaller in 6-month outcome (MOR = 1.2, p = 0.01). CONCLUSIONS: Half of contemporary TBI patients at the ICU have mild to moderate head injury. Substantial between-center variations exist in ICU stay and treatment policies, and less so in outcome. It remains unclear whether admission of short-stay patients represents appropriate prudence or inappropriate use of clinical resources. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-05965-z) contains supplementary material, which is available to authorized users."
837,A management algorithm for adult patients with both brain oxygen and intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC),"BACKGROUND: Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place. METHODS: Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting. RESULTS: We established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms. CONCLUSIONS: These protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05900-x) contains supplementary material, which is available to authorized users."
838,"Sero-epidemiological study of the rotavirus VP8* protein from different P genotypes in Valencia, Spain","The aims of the present work were to determine the prevalence and titer of serum antibodies against several rotavirus VP8* proteins from different P genotypes in children and adults in Valencia, Spain; and to determine the role of the secretor status (FUT2(G428A) polymorphism) in the antibody response. The VP8* protein from the P[4], P[6], P[8], P[9], P[11], P[14] and P[25] genotypes were produced in E. coli. These proteins were tested with 88 serum samples from children (n = 41, 3.5 years old in average) and from adults (n = 47, 58 years old in average) by ELISA. A subset of 55 samples were genotyped for the FUT2(G428A) polymorphism and the antibody titers compared. The same subset of samples was also analysed by ELISA using whole rotavirus Wa particles (G1P[8]) as antigen. Ninety-three per cent of the samples were positive for at least one of the VP8* antigens. Differences in the IgG seroprevalence were found between children and adults for the P[4], P[8] and P[11] genotypes. Similarly, significant differences were found between adults and children in their antibody titers against the P[4], P[8], and P[11] VP8* genotypes, having the children higher antibody titers than adults. Interestingly, positive samples against rare genotypes such as P[11] (only in children), P[14] and P[25] were found. While no statistical differences in the antibody titers between secretors and non-secretors were found for any of the tested P genotypes studied, a higher statistic significant prevalence for the P[25] genotype was found in secretors compared to non-secretors. Significant differences in the antibody titers between secretors and non-secretors were found when the whole viral particles from the Wa rotavirus strain (G1P[8]) were used as the antigen."
839,Structural basis of transmembrane coupling of the HIV-1 envelope glycoprotein,"The prefusion conformation of HIV-1 envelope protein (Env) is recognized by most broadly neutralizing antibodies (bnAbs). Studies showed that alterations of its membrane-related components, including the transmembrane domain (TMD) and cytoplasmic tail (CT), can reshape the antigenic structure of the Env ectodomain. Using nuclear magnetic resonance (NMR) spectroscopy, we determine the structure of an Env segment encompassing the TMD and a large portion of the CT in bicelles. The structure reveals that the CT folds into amphipathic helices that wrap around the C-terminal end of the TMD, thereby forming a support baseplate for the rest of Env. NMR dynamics measurements provide evidences of dynamic coupling across the TMD between the ectodomain and CT. Pseudovirus-based neutralization assays suggest that CT-TMD interaction preferentially affects antigenic structure near the apex of the Env trimer. These results explain why the CT can modulate the Env antigenic properties and may facilitate HIV-1 Env-based vaccine design."
840,Error in Discussion,
841,Predicting the global mammalian viral sharing network using phylogeography,"Understanding interspecific viral transmission is key to understanding viral ecology and evolution, disease spillover into humans, and the consequences of global change. Prior studies have uncovered macroecological drivers of viral sharing, but analyses have never attempted to predict viral sharing in a pan-mammalian context. Using a conservative modelling framework, we confirm that host phylogenetic similarity and geographic range overlap are strong, nonlinear predictors of viral sharing among species across the entire mammal class. Using these traits, we predict global viral sharing patterns of 4196 mammal species and show that our simulated network successfully predicts viral sharing and reservoir host status using internal validation and an external dataset. We predict high rates of mammalian viral sharing in the tropics, particularly among rodents and bats, and within- and between-order sharing differed geographically and taxonomically. Our results emphasize the importance of ecological and phylogenetic factors in shaping mammalian viral communities, and provide a robust, general model to predict viral host range and guide pathogen surveillance and conservation efforts."
842,Rapid colorimetric loop-mediated isothermal amplification for hypersensitive point-of-care Staphylococcus aureus enterotoxin A gene detection in milk and pork products,"Staphylococcus aureus strains carrying enterotoxin A gene (sea) causes food poisoning and cannot be distinguished from non-pathogenic strains by the culture method. Here, we developed a rapid, specific and sensitive visual detection of sea using loop-mediated isothermal amplification (LAMP) combined with nanogold probe (AuNP) or styryl dye (STR). LAMP-AuNP and LAMP-STR can detect as low as 9.7 fg (3.2 sea copies) and 7.2 sea copies, respectively, which were lower than PCR (97 fg or 32 sea copies). The excellent performance of these new assays was demonstrated in food samples using crude DNA lysates. While the culture method detected 10(4) CFU/g in ground pork and 10 CFU/mL in milk in 5–7 days, LAMP-AuNP could detect down to 10 CFU/g for both samples in 27 minutes. Analyzing 80 pork and milk samples revealed that the LAMP-AuNP showed 100% sensitivity, 97–100% specificity and 97.5–100% accuracy, which were superior to the culture method, and comparable to PCR but without requirement of a thermal cycler. Furthermore, our LAMP-AuNP detect sea at a range below the food safety control (<100 CFU/g). The LAMP-STR quantitated sea in 10–1,000 CFU (7.2–720 copies). Our crude DNA lysis combined with LAMP-AuNP/STR present effective point-of-care detection and facilitate appropriate control strategies."
843,In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies,"Antibody immunotherapy is revolutionizing modern medicine. The field has advanced dramatically over the past 40 years, driven in part by major advances in isolation and manufacturing technologies that have brought these important biologics to the forefront of modern medicine. However, the global uptake of monoclonal antibody (mAb) biologics is impeded by biophysical and biochemical liabilities, production limitations, the need for cold-chain storage and transport, as well as high costs of manufacturing and distribution. Some of these hurdles may be overcome through transient in vivo gene delivery platforms, such as non-viral synthetic plasmid DNA and messenger RNA vectors that are engineered to encode optimized mAb genes. These approaches turn the body into a biological factory for antibody production, eliminating many of the steps involved in bioprocesses and providing several other significant advantages, and differ from traditional gene therapy (permanent delivery) approaches. In this review, we focus on nucleic acid delivery of antibody employing synthetic plasmid DNA vector platforms, and RNA delivery, these being important approaches that are advancing simple, rapid, in vivo expression and having an impact in animal models of infectious diseases and cancer, among others."
844,Cell-Free Protein Synthesis: A Promising Option for Future Drug Development,"Proteins are the main source of drug targets and some of them possess therapeutic potential themselves. Among them, membrane proteins constitute approximately 50% of the major drug targets. In the drug discovery pipeline, rapid methods for producing different classes of proteins in a simple manner with high quality are important for structural and functional analysis. Cell-free systems are emerging as an attractive alternative for the production of proteins due to their flexible nature without any cell membrane constraints. In a bioproduction context, open systems based on cell lysates derived from different sources, and with batch-to-batch consistency, have acted as a catalyst for cell-free synthesis of target proteins. Most importantly, proteins can be processed for downstream applications like purification and functional analysis without the necessity of transfection, selection, and expansion of clones. In the last 5 years, there has been an increased availability of new cell-free lysates derived from multiple organisms, and their use for the synthesis of a diverse range of proteins. Despite this progress, major challenges still exist in terms of scalability, cost effectiveness, protein folding, and functionality. In this review, we present an overview of different cell-free systems derived from diverse sources and their application in the production of a wide spectrum of proteins. Further, this article discusses some recent progress in cell-free systems derived from Chinese hamster ovary and Sf21 lysates containing endogenous translocationally active microsomes for the synthesis of membrane proteins. We particularly highlight the usage of internal ribosomal entry site sequences for more efficient protein production, and also the significance of site-specific incorporation of non-canonical amino acids for labeling applications and creation of antibody drug conjugates using cell-free systems. We also discuss strategies to overcome the major challenges involved in commercializing cell-free platforms from a laboratory level for future drug development."
845,Mitteilungen des BDI,
846,"Direct RNA Sequencing for the Study of Synthesis, Processing, and Degradation of Modified Transcripts","It has been known for a few decades that transcripts can be marked by dozens of different modifications. Yet, we are just at the beginning of charting these marks and understanding their functional impact. High-quality methods were developed for the profiling of some of these marks, and approaches to finely study their impact on specific phases of the RNA life-cycle are available, including RNA metabolic labeling. Thanks to these improvements, the most abundant marks, including N(6)-methyladenosine, are emerging as important determinants of the fate of marked RNAs. However, we still lack approaches to directly study how the set of marks for a given RNA molecule shape its fate. In this perspective, we first review current leading approaches in the field. Then, we propose an experimental and computational setup, based on direct RNA sequencing and mathematical modeling, to decipher the functional consequences of RNA modifications on the fate of individual RNA molecules and isoforms."
847,Editorial: Immunopathology of Chronic Bacterial and Viral Diseases Prevalent in Latin America,
848,Practical Considerations When Performing Neurodiagnostic Studies on Patients with COVID-19 and Other Highly Virulent Diseases,"The coronavirus disease 2019, SARS-COV-2 (the cause of COVID-19), has led to a worldwide shortage of personal protective equipment (PPE) and an increased stress on hospital resources, which has resulted in a spike in the anxiety of the frontline healthcare workers. News reports and information about the virus are rapidly changing. We present a case of a patient with COVID-19 who had a seizure-like spell for which an EEG was performed. In early to mid-March, there were no clear guidelines or recommendations available from neurodiagnostic-related organizations or hospitals on how to adapt procedure workflow to those with COVID-19. When caring for COVID-19 patients, as when caring for any patient with an infectious disease, it is hospital protocol to follow contact, droplet/airborne precautions by wearing appropriate PPE. However, because we knew very little about the coronavirus, this case was different. In this article, we discuss our experience with our EEG workflow and concerns for staff exposure. We then discuss our adaptations and modifications to our standard procedures and protocols. A time analysis comparing our standard EEG protocol with our modified COVID-19 protocol revealed a significant decrease in technologist exposure time (99 minutes versus 51 minutes), which theoretically would reduce the chance of virus transmission to our technologist. At this critical moment in time, we hope such modifications will allow us to continue delivering high quality patient care while optimizing resource utilization and above all keeping our technologists safe."
849,Diverse CD8 T Cell Responses to Viral Infection Revealed by the Collaborative Cross,"Enhanced host protection against re-infection requires generation of memory T cells of sufficient quantity and functional quality. Unlike well-studied inbred mice, T cell responses of diverse size and quality are generated following infection of humans and outbred mice. Thus, additional models are needed that accurately reflect variation in immune outcomes in genetically diverse populations and to uncover underlying genetic causes. The Collaborative Cross (CC), a large recombinant inbred panel of mice, is an ideal model in this pursuit for the high degree of genetic variation present, because it allows for assessment of genetic factors underlying unique phenotypes. Here, we advance the utility of the CC as a tool to analyze the immune response to viral infection. We describe variability in resting immune cell composition and adaptive immune responses generated among CC strains following systemic virus infection and reveal quantitative trait loci responsible for generation of CD62L+ memory CD8 T cells."
850,Primum non nocere,
851,Mesenchymal stem/stromal cells: the therapeutic effects in animal models of acute pulmonary diseases,"The pulmonary diseases are one of the most important causes of death in the world. The successful therapies in the field of lung diseases are very limited and the medical treatments available are ineffective in many of the lung diseases. Many studies have evaluated the new therapies in the acute pulmonary diseases, and the transplantation of mesenchymal stem/stromal cells (MSCs), which is a branch of cell therapy, has a special place among the new medical techniques. The MSCs are present throughout the body and are thought to play a role in tissue regeneration and inflammation control. In the event of injury, the local MSCs traverse the shortest possible distance from the tissue or blood vessels to reach the affected site. But, there are few undifferentiated cells in the tissues. The exogenous MSCs are used to immunity modify or regenerative treatments in preclinical models of acute pulmonary diseases. Several studies have shown the positive effects of MSCs replacement in the acute lung disorders. The effection mechanism of the MSCs include the differentiation ability and the secretion of paracrine agents such as the anti-inflammatory mediators. Many studies suggest that this treatment method is safe and is probably to be widely used in future clinical trials. This review will describe the therapeutic effects of the MSCs in the experimental models of the acute pulmonary diseases for use as a method of treatment in clinical trials in future."
852,"Synthetic strategies, SAR studies, and computer modeling of indole 2 and 3-carboxamides as the strong enzyme inhibitors: a review","ABSTRACT: Indole derivatives have been the focus of many researchers in the study of pharmaceutical compounds for many years. Researchers have investigated the effect of carboxamide moiety at positions 2 and 3, giving unique inhibitory properties to these compounds. The presence of carboxamide moiety in indole derivatives causes hydrogen bonds with a variety of enzymes and proteins, which in many cases, inhibits their activity. In this review, synthetic strategies of indole 2 and 3-carboxamide derivatives, the type, and mode of interaction of these derivatives against HLGP, HIV-1, renin enzyme, and structure–activity studies of these compounds were investigated. It is hoped that indole scaffolds will be tested in the future for maximum activity in pharmacological compounds. GRAPHIC ABSTRACT: [Image: see text]"
853,Association between risk factors of metabolic syndrome with lung function,"BACKGROUND/OBJECTIVES: Increased evidence suggests that metabolic syndrome (MetS) is correlated with lung function impairment. This study aimed to explore the associations between MetS risk factors and the lung function. SUBJECTS/METHODS: The cross-sectional study included 6945 participants attending health examination between 2010 and 2012 in Taiwan. MetS was assessed according to the criteria of National Cholesterol Education Program III. Spirometric parameters were measured to define lung function. The relationships were tested using multiple linear regression and logistic regression analyses. RESULTS: The prevalence of MetS was significantly higher in males (16.2%) than females (3.8%). Although the prevalence of restrictive lung disease (RLD) was comparable between genders (20.7 and 21.0%), males with co-existent MetS had a higher prevalence of RLD than females (27.4 vs. 18.0%). Abdominal obesity, indicated by waist circumference (WC) and weight-to-height ratio (WHtR), was the most significant factor associated with lung function decline. Other components of MetS also showed statistically significant relationships, but very weak, with lung function. There was a trend toward an increased prevalence of RLD with the increasing number of MetS scores in males, independent of age, smoking, and body mass index. CONCLUSIONS: Abdominal obesity was the key component of MetS associated with mechanical effect on lung function impairment in a prime-age adult population. Although RLD was not associated with increased probability of having MetS, the participants with more MetS scores were at a higher risk of losing lung function."
854,"Sans-abri, sans-papiers et confinés ?",
855,A deubiquitylase with an unusually high-affinity ubiquitin-binding domain from the scrub typhus pathogen Orientia tsutsugamushi,"Ubiquitin mediated signaling contributes critically to host cell defenses during pathogen infection. Many pathogens manipulate the ubiquitin system to evade these defenses. Here we characterize a likely effector protein bearing a deubiquitylase (DUB) domain from the obligate intracellular bacterium Orientia tsutsugamushi, the causative agent of scrub typhus. The Ulp1-like DUB prefers ubiquitin substrates over ubiquitin-like proteins and efficiently cleaves polyubiquitin chains of three or more ubiquitins. The co-crystal structure of the DUB (OtDUB) domain with ubiquitin revealed three bound ubiquitins: one engages the S1 site, the second binds an S2 site contributing to chain specificity and the third binds a unique ubiquitin-binding domain (UBD). The UBD modulates OtDUB activity, undergoes a pronounced structural transition upon binding ubiquitin, and binds monoubiquitin with an unprecedented ~5 nM dissociation constant. The characterization and high-resolution structure determination of this enzyme should aid in its development as a drug target to counter Orientia infections."
856,NLRP6 Plays an Important Role in Early Hepatic Immunopathology Caused by Schistosoma mansoni Infection,"Schistosomiasis is a debilitating parasitic disease that affects more than 200 million people worldwide and causes approximately 280,000 deaths per year. Inside the definitive host, eggs released by Schistosoma mansoni lodge in the intestine and especially in the liver where they induce a granulomatous inflammatory process, which can lead to fibrosis. The molecular mechanisms initiating or promoting hepatic granuloma formation remain poorly understood. Inflammasome activation has been described as an important pathway to induce pathology mediated by NLRP3 receptor. Recently, other components of the inflammasome pathway, such as NLRP6, have been related to liver diseases and fibrotic processes. Nevertheless, the contribution of these components in schistosomiasis-associated pathology is still unknown. In the present study, using dendritic cells, we demonstrated that NLRP6 sensor is important for IL-1β production and caspase-1 activation in response to soluble egg antigens (SEA). Furthermore, the lack of NLRP6 has been shown to significantly reduce periovular inflammation, collagen deposition in hepatic granulomas and mRNA levels of α-SMA and IL-13. Livers of Nlrp6(–/–) mice showed reduced levels of CXCL1/KC, CCL2, CCL3, IL-5, and IL-10 as well as Myeloperoxidase (MPO) and Eosinophilic Peroxidase (EPO) enzymatic activity. Consistently, the frequency of macrophage and neutrophil populations were lower in the liver of NLRP6 knockout mice, after 6 weeks of infection. Finally, it was further demonstrated that the onset of hepatic granuloma and collagen deposition were also compromised in Caspase-1(–/–), IL-1R(–/–) and Gsdmd(–/–) mice. Our findings suggest that the NLRP6 inflammasome is an important component for schistosomiasis-associated pathology."
857,"The Impact of Non-optimum Ambient Temperature on Years of Life Lost: A Multi-county Observational Study in Hunan, China","The ambient temperature–health relationship is of growing interest as the climate changes. Previous studies have examined the association between ambient temperature and mortality or morbidity, however, there is little literature available on the ambient temperature effects on year of life lost (YLL). Thus, we aimed to quantify the YLL attributable to non-optimum ambient temperature. We obtained data from 1 January 2013 to 31 December 2017 of 70 counties in Hunan, China. In order to combine the effects of each county, we used YLL rate as a health outcome indicator. The YLL rate was equal to the total YLL divided by the population of each county, and multiplied by 100,000. We estimated the associations between ambient temperature and YLL with a distributed lag non-linear model (DNLM) in a single county, and then pooled them in a multivariate meta-regression. The daily mean YLL rates were 22.62 y/(p·100,000), 10.14 y/(p·100,000) and 2.33 y/(p·100,000) within the study period for non-accidental, cardiovascular, and respiratory disease death. Ambient temperature was responsible for advancing a substantial fraction of YLL, with attributable fractions of 10.73% (4.36–17.09%) and 16.44% (9.09–23.79%) for non-accidental and cardiovascular disease death, respectively. However, the ambient temperature effect was not significantly for respiratory disease death, corresponding to 5.47% (−2.65–13.60%). Most of the YLL burden was caused by a cold temperature than the optimum temperature, with an overall estimate of 10.27% (4.52–16.03%) and 15.94% (8.82–23.05%) for non-accidental and cardiovascular disease death, respectively. Cold and heat temperature-related YLLs were higher in the elderly and females than the young and males. Extreme cold temperature had an effect on all age groups in different kinds of disease-caused death. This study highlights that general preventative measures could be important for moderate temperatures, whereas quick and effective measures should be provided for extreme temperatures."
858,The burden of laboratory-confirmed influenza infection in Lebanon between 2008 and 2016: a single tertiary care center experience,"BACKGROUND: Influenza is a major cause of morbidity and mortality worldwide. Following the 2009 pandemic, there was widened interest in studying influenza burden in all regions. However, since data from the World Health Organization (WHO) Middle East and North Africa (MENA) region remain limited, we aimed to contribute to the understanding of influenza burden in Lebanon. METHODS: A retrospective chart review extending over a period of 8 seasons from Jan 1st, 2008 till June 30th, 2016 at a tertiary care center in Beirut was performed. All cases confirmed to have influenza based on rapid antigen detection or/and polymerase chain reaction on a respiratory sample were included for analysis. Data on epidemiology, clinical presentation, complications, antiviral use and mortality were collected for analysis. RESULTS: A total of 1829 cases of laboratory-confirmed influenza were identified. Average annual positivity rate was 14% (positive tests over total requested). Both influenza A and B co-circulated in each season with predominance of influenza A. Influenza virus started circulating in December and peaked in January and February. The age group of 19–50 years accounted for the largest proportion of cases (22.5%) followed by the age group of 5–19 years (18%). Pneumonia was the most common complication reported in 33% of cases. Mortality reached 3.8%. The two extremes of age (< 2 years and ≥ 65 years) were associated with a more severe course of disease, hospitalization, intensive care unit (ICU) admission, complications, and mortality rate. Of all the identified cases, 26% were hospitalized. Moderate-to-severe disease was more likely in influenza B cases but no difference in mortality was reported between the two types. Antivirals were prescribed in 68.8% and antibiotics in 41% of cases. There seemed to be an increasing trend in the number of diagnosed and hospitalized cases over the years of the study. CONCLUSION: Patients with laboratory-confirmed influenza at our center had a high rate of hospitalization and mortality. A population based prospective surveillance study is needed to better estimate the burden of Influenza in Lebanon that would help formulate a policy on influenza control."
859,First Molecular Identification of Canine Parvovirus Type 2 (CPV2) in Chile Reveals High Occurrence of CPV2c Antigenic Variant,"Canine parvovirus type 2 (CPV2) is one of the most important intestinal pathogens in dogs and puppies. CPV2 has been evolved into three genetic and antigenic variants (2a, 2b, and 2c), which are distributed worldwide. We reported the first study of genetic diversity of CPV2 in Chile. Sixty-five samples were collected from puppies presenting with severe gastroenteritis and different vaccination statuses. PCR, restriction fragment length polymorphism (RFLP), and partial sequencing of the coding region of the structural viral protein VP2 was performed. Thirty of a total of 65 samples tested positive by PCR out of which 19 were further classified as CPV2c and one as CPV2a using RFLP and Sanger sequencing. The phylogeny was in concordance with the RFLP analysis. This is the first report of the genetic characterization of CPV2 in Chile and reveals a high occurrence of CPV2c."
860,Pulmonary complications associated with veno-arterial extra-corporeal membrane oxygenation: a comprehensive review,"Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving technology that provides transient respiratory and circulatory support for patients with profound cardiogenic shock or refractory cardiac arrest. Among its potential complications, VA-ECMO may adversely affect lung function through various pathophysiological mechanisms. The interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response which may increase pulmonary vascular permeability and promote the sequestration of polymorphonuclear neutrophils within the lung parenchyma. Also, VA-ECMO increases the afterload of the left ventricle (LV) through reverse flow within the thoracic aorta, resulting in increased LV filling pressure and pulmonary congestion. Furthermore, VA-ECMO may result in long-standing pulmonary hypoxia, due to partial shunting of the pulmonary circulation and to reduced pulsatile blood flow within the bronchial circulation. Ultimately, these different abnormalities may result in a state of persisting lung inflammation and fibrotic changes with concomitant functional impairment, which may compromise weaning from VA-ECMO and could possibly result in long-term lung dysfunction. This review presents the mechanisms of lung damage and dysfunction under VA-ECMO and discusses potential strategies to prevent and treat such alterations."
861,Multi-task learning sparse group lasso: a method for quantifying antigenicity of influenza A(H1N1) virus using mutations and variations in glycosylation of Hemagglutinin,"BACKGROUND: In addition to causing the pandemic influenza outbreaks of 1918 and 2009, subtype H1N1 influenza A viruses (IAVs) have caused seasonal epidemics since 1977. Antigenic property of influenza viruses are determined by both protein sequence and N-linked glycosylation of influenza glycoproteins, especially hemagglutinin (HA). The currently available computational methods are only considered features in protein sequence but not N-linked glycosylation. RESULTS: A multi-task learning sparse group least absolute shrinkage and selection operator (LASSO) (MTL-SGL) regression method was developed and applied to derive two types of predominant features including protein sequence and N-linked glycosylation in hemagglutinin (HA) affecting variations in serologic data for human and swine H1N1 IAVs. Results suggested that mutations and changes in N-linked glycosylation sites are associated with the rise of antigenic variants of H1N1 IAVs. Furthermore, the implicated mutations are predominantly located at five reported antibody-binding sites, and within or close to the HA receptor binding site. All of the three N-linked glycosylation sites (i.e. sequons NCSV at HA 54, NHTV at HA 125, and NLSK at HA 160) identified by MTL-SGL to determine antigenic changes were experimentally validated in the H1N1 antigenic variants using mass spectrometry analyses. Compared with conventional sparse learning methods, MTL-SGL achieved a lower prediction error and higher accuracy, indicating that grouped features and MTL in the MTL-SGL method are not only able to handle serologic data generated from multiple reagents, supplies, and protocols, but also perform better in genetic sequence-based antigenic quantification. CONCLUSIONS: In summary, the results of this study suggest that mutations and variations in N-glycosylation in HA caused antigenic variations in H1N1 IAVs and that the sequence-based antigenicity predictive model will be useful in understanding antigenic evolution of IAVs."
862,Cervical and oral human papillomavirus infection in women living with human immunodeficiency virus (HIV) and matched HIV-negative controls in Brazil,"BACKGROUND: Despite the demonstrated role of human Papillomavirus (HPV) in the etiology of cervical cancer and the strong evidence suggesting the importance of HPV in the development of oropharyngeal cancer, several aspects of the interrelationship between HPV infection in both body sites remain unknown, specifically in female human immunodeficiency virus (HIV)-positive (HIV+) patients. We aimed to assess the prevalence, distribution, and concordance of cervical and oral HPV in HIV+ women and matched HIV-negative (HIV-) controls in Brazil. MATERIAL AND METHODS: Cervical and endocervical samples for cytological screening and HPV detection and oral samples were collected from 115 HIV+ women using highly active antiretroviral therapy (HAART) and 139 HIV-matched controls (HIV-) in Maringá City, Brazil. Risk factors were assessed using a standardized questionnaire, and the data regarding HIV infection were obtained from the patients’ medical records. HPV detection and typing were performed using the Kit Multiplex XGEN Multi HPV Chip HS12. RESULTS: HIV infection was well controlled in this cohort, but women who exhibited detectable HIV loads were significantly associated with HPV-positive status overall (P = 0.03) and in cervical mucosa (P = 0.01). HIV+ women had significantly more abnormal cytological findings (P = 0.04) than HIV- women. Of the 115 HIV+ women, 48.7% were positive for cervical and/or oral HPV DNA; of the 139 HIV- women, 41% were positive for cervical and/or oral HPV (P = 0.25). Both HIV+ and HIV- women had a statistically higher prevalence of cervical HPV infection than oral infection. The concurrent HPV infection in two anatomical sites was similar in HIV+ and HIV- women; however, HPV type concordance was not observed. HPV type distribution was different between the anatomical sites in both groups, and HIV+ women presented less common types, mainly in oral mucosa. CONCLUSION: Our data support the importance of testing HPV infection in HIV+ women, even when the HIV infection is well controlled. Prospective studies are required to better understand the natural history of HPV infection in both anatomical sites, specifically in HIV+ women."
863,Brain natriuretic peptide to predict successful liberation from mechanical ventilation in critically ill patients: a systematic review and meta-analysis,"BACKGROUND: Predicting successful liberation from mechanical ventilation (MV) in critically ill patients is challenging. Brain natriuretic peptide (BNP) has been proposed to help guide decision-making for readiness to liberate from MV following a spontaneous breathing trial (SBT). METHODS: We performed a systematic review and meta-analysis of randomized and prospective observational studies that measured BNP levels at the time of SBT in patients receiving MV. The primary endpoint was successful liberation from MV (absence of reintubation or non-invasive ventilation at 48 h). Statistical analyses included bi-variate and Moses-Littenberg models and DerSimonian-Laird pooling of areas under ROC curve (AUROC). RESULTS: A total of 731 articles were screened. Eighteen adult and 2 pediatric studies were fulfilled pre-specified eligibility. The measure of the relative variation of BNP during SBT (ΔBNP%) after exclusion of SBT failure by clinical criteria in adults yielded a sensitivity and specificity of 0.889 [0.831–0.929] and 0.828 [0.730–0.896] for successful liberation from MV, respectively, with a pooled AUROC of 0.92 [0.88–0.97]. The pooled AUROC for any method of analysis for absolute variation of BNP (ΔBNP), pre-SBT BNP, and post-SBT BNP were 0.89 [0.83–0.95], 0.77 [0.63–0.91], and 0.85 [0.80–0.90], respectively. CONCLUSION: The relative change in BNP during a SBT has potential value as an incremental tool after successful SBT to predict successful liberation from MV in adults. There is insufficient data to support the use of BNP in children or as an alternate test to clinical indices of SBT, or the use of ΔBNP, BNP-pre, and BNP-post as an alternate or incremental test. TRIAL REGISTRATION: PROSPERO CRD42018087474 (6 February 2018)"
864,Neue intensivmedizinische Herausforderungen durch Klimawandel und globale Erderwärmung,"BACKGROUND: In the last five decades a continuous increase in the average global temperature has been recorded. Furthermore, natural disasters (e.g. heat waves, severe storms, floods and large forest fires) are becoming more frequent. The impact of global warming and climate change on health involves an increase in respiratory, cardiovascular, renal and cognitive mental diseases. Furthermore, a change in the frequency and patterns of infectious diseases can also be observed in Europe. MATERIAL AND METHODS: This article presents the most important studies that investigated diseases associated with the climate change, with special reference to those that represent a challenge for intensive care medicine. RESULTS: Currently available epidemiological data and statistical extrapolations indicate that diseases resulting from the climate change (acute infection-related respiratory and intestinal diseases, exacerbation of pre-existing pulmonary lesions, heat-related dehydration, cerebral insults and myocardial infarction) are relevant for intensive care medicine. Particular emphasis is placed on a significant increase in acute kidney damage during heat waves. A previously unknown pattern of infectious diseases necessitates new knowledge and targeted management. In some studies, persisting mental impairments were registered during heat waves and natural disasters, e.g. posttraumatic stress disorder. CONCLUSION: Intensive care medicine must be prepared for the challenges due to global warming and climate change. Slow but continuous changes (e.g. rise in temperature) as well as acute changes (e.g. heat waves and natural disasters) will induce an increased need for intensive medical care services (e.g. an increase in the need for renal replacement procedures). Intensive care physicians will need to be familiar with the diagnostics and management of diseases associated with the climate change. An initiative of the specialist societies involved would be welcomed."
865,Visiting Sub-Interships in Wake of the Covid-19 Crisis: An Opportunity for Improvement,
866,Inherited Thoracic Aortic Disease: New Insights and Translational Targets,"Inherited thoracic aortopathies denote a group of congenital conditions that predispose to disease of the thoracic aorta. Aortic wall weakness and abnormal aortic hemodynamic profiles predispose these patients to dilatation of the thoracic aorta, which is generally silent but can precipitate aortic dissection or rupture with devastating and often fatal consequences. Current strategies to assess the future risk of aortic dissection or rupture are based primarily on monitoring aortic diameter. However, diameter alone is a poor predictor of risk, with many patients experiencing dissection or rupture below current intervention thresholds. Developing tools that improve the risk assessment of those with aortopathy is internationally regarded as a research priority. A robust understanding of the molecular pathways that lead to aortic wall weakness is required to identify biomarkers and therapeutic targets that could improve patient management. Here, we summarize the current understanding of the genetically determined mechanisms underlying inherited aortopathies and critically appraise the available blood biomarkers, imaging techniques, and therapeutic targets that have shown promise for improving the management of patients with these important and potentially fatal conditions."
867,Differential expression of interferon-lambda receptor 1 splice variants determines the magnitude of the antiviral response induced by interferon-lambda 3 in human immune cells,"Type III interferons (IFN-lambdas(λ)) are important cytokines that inhibit viruses and modulate immune responses by acting through a unique IFN-λR1/IL-10RB heterodimeric receptor. Until now, the primary antiviral function of IFN-λs has been proposed to be at anatomical barrier sites. Here, we examine the regulation of IFN-λR1 expression and measure the downstream effects of IFN-λ3 stimulation in primary human blood immune cells, compared with lung or liver epithelial cells. IFN-λ3 directly bound and upregulated IFN-stimulated gene (ISG) expression in freshly purified human B cells and CD8(+) T cells, but not monocytes, neutrophils, natural killer cells, and CD4(+) T cells. Despite similar IFNLR1 transcript levels in B cells and lung epithelial cells, lung epithelial cells bound more IFN-λ3, which resulted in a 50-fold greater ISG induction when compared to B cells. The reduced response of B cells could be explained by higher expression of the soluble variant of IFN-λR1 (sIFN-λR1), which significantly reduced ISG induction when added with IFN-λ3 to peripheral blood mononuclear cells or liver epithelial cells. T-cell receptor stimulation potently, and specifically, upregulated membrane-bound IFNLR1 expression in CD4(+) T cells, leading to greater antiviral gene induction, and inhibition of human immunodeficiency virus type 1 infection. Collectively, our data demonstrate IFN-λ3 directly interacts with the human adaptive immune system, unlike what has been previously shown in published mouse models, and that type III IFNs could be potentially utilized to suppress both mucosal and blood-borne viral infections."
868,Dynamical correlations and pairwise theory for the symbiotic contact process on networks,"The two-species symbiotic contact process (2SCP) is a stochastic process in which each vertex of a graph may be vacant or host at most one individual of each species. Vertices with both species have a reduced death rate, representing a symbiotic interaction, while the dynamics evolves according to the standard (single species) contact process rules otherwise. We investigate the role of dynamical correlations on the 2SCP on homogeneous and heterogeneous networks using pairwise mean-field theory. This approach is compared with the ordinary one-site theory and stochastic simulations. We show that our approach significantly outperforms the one-site theory. In particular, the stationary state of the 2SCP model on random regular networks is very accurately reproduced by the pairwise mean-field, even for relatively small values of vertex degree, where expressive deviations of the standard mean-field are observed. The pairwise approach is also able to capture the transition points accurately for heterogeneous networks and provides rich phase diagrams with transitions not predicted by the one-site method. Our theoretical results are corroborated by extensive numerical simulations."
869,Role of structural holes in containing spreading processes,"Structural holes are channels or paths spanned by a group of indirectly connected nodes and their intermediary in a network. In this work we emphasize the interesting role of structural holes as brokers for information propagation. Based on the distribution of the structural hole numbers associated with each node, we propose a simple yet effective approach for choosing the most influential nodes to immunize in containing the spreading processes. Using a wide spectrum of large real-world networks, we demonstrate that the proposed approach outperforms conventional methods in a remarkable way. In particular, we find that the performance gains of our approach are particularly prominent for networks with high transitivity and assortativity, which verifies the vital role of structural holes in information diffusion on networked systems."
870,Collective versus hub activation of epidemic phases on networks,"We consider a general criterion to discern the nature of the threshold in epidemic models on scale-free (SF) networks. Comparing the epidemic lifespan of the nodes with largest degrees with the infection time between them, we propose a general dual scenario, in which the epidemic transition is either ruled by a hub activation process, leading to a null threshold in the thermodynamic limit, or given by a collective activation process, corresponding to a standard phase transition with a finite threshold. We validate the proposed criterion applying it to different epidemic models, with waning immunity or heterogeneous infection rates in both synthetic and real SF networks. In particular, a waning immunity, irrespective of its strength, leads to collective activation with finite threshold in scale-free networks with large degree exponent, at odds with canonical theoretical approaches."
871,Intervention threshold for epidemic control in susceptible-infected-recovered metapopulation models,"Metapopulation epidemic models describe epidemic dynamics in networks of spatially distant patches connected via pathways for migration of individuals. In the present study, we deal with a susceptible-infected-recovered (SIR) metapopulation model where the epidemic process in each patch is represented by an SIR model and the mobility of individuals is assumed to be a homogeneous diffusion. We consider two types of patches including high-risk and low-risk ones under the assumption that a local patch is changed from a high-risk one to a low-risk one by an intervention. We theoretically analyze the intervention threshold which indicates the critical fraction of low-risk patches for preventing a global epidemic outbreak. We show that an intervention targeted to high-degree patches is more effective for epidemic control than a random intervention. The theoretical results are validated by Monte Carlo simulations for synthetic and realistic scale-free patch networks. The theoretical results also reveal that the intervention threshold depends on the human mobility network and the mobility rate. Our approach is useful for exploring better local interventions aimed at containment of epidemics."
872,Traffic-driven epidemic spreading in multiplex networks,"Recent progress on multiplex networks has provided a powerful way to abstract the diverse interaction of a network system with multiple layers. In this paper, we show that a multiplex structure can greatly affect the spread of an epidemic driven by traffic dynamics. One of the interesting findings is that the multiplex structure could suppress the outbreak of an epidemic, which is different from the typical finding of spread dynamics in multiplex networks. In particular, one layer with dense connections can attract more traffic flow and eventually suppress the epidemic outbreak in other layers. Therefore, the epidemic threshold will be larger than the minimal threshold of the layers. With a mean-field approximation, we provide explicit expressions for the epidemic threshold and for the onset of suppressing epidemic spreading in multiplex networks. We also provide the probability of obtaining a multiplex configuration that suppresses the epidemic spreading when the multiplex is composed of: (i) two Erdős-Rényi layers and (ii) two scale-free layers. Therefore, compared to the situation of an isolated network in which a disease may be able to propagate, a larger epidemic threshold can be found in multiplex structures."
873,Backbone reconstruction in temporal networks from epidemic data,"Many complex systems are characterized by time-varying patterns of interactions. These interactions comprise strong ties, driven by dyadic relationships, and weak ties, based on node-specific attributes. The interplay between strong and weak ties plays an important role on dynamical processes that could unfold on complex systems. However, seldom do we have access to precise information about the time-varying topology of interaction patterns. A particularly elusive question is to distinguish strong from weak ties, on the basis of the sole node dynamics. Building upon analytical results, we propose a statistically-principled algorithm to reconstruct the backbone of strong ties from data of a spreading process, consisting of the time series of individuals' states. Our method is numerically validated over a range of synthetic datasets, encapsulating salient features of real-world systems. Motivated by compelling evidence, we propose the integration of our algorithm in a targeted immunization strategy that prioritizes influential nodes in the inferred backbone. Through Monte Carlo simulations on synthetic networks and a real-world case study, we demonstrate the viability of our approach."
874,Epidemic spreading with awareness and different timescales in multiplex networks,"One of the major issues in theoretical modeling of epidemic spreading is the development of methods to control the transmission of an infectious agent. Human behavior plays a fundamental role in the spreading dynamics and can be used to stop a disease from spreading or to reduce its burden, as individuals aware of the presence of a disease can take measures to reduce their exposure to contagion. In this paper, we propose a mathematical model for the spread of diseases with awareness in complex networks. Unlike previous models, the information is propagated following a generalized Maki-Thompson rumor model. Flexibility on the timescale between information and disease spreading is also included. We verify that the velocity characterizing the diffusion of information awareness greatly influences the disease prevalence. We also show that a reduction in the fraction of unaware individuals does not always imply a decrease of the prevalence, as the relative timescale between disease and awareness spreading plays a crucial role in the systems' dynamics. This result is shown to be independent of the network topology. We finally calculate the epidemic threshold of our model, and show that it does not depend on the relative timescale. Our results provide a new view on how information influence disease spreading and can be used for the development of more efficient methods for disease control."
875,Limitations of discrete-time approaches to continuous-time contagion dynamics,"Continuous-time Markov process models of contagions are widely studied, not least because of their utility in predicting the evolution of real-world contagions and in formulating control measures. It is often the case, however, that discrete-time approaches are employed to analyze such models or to simulate them numerically. In such cases, time is discretized into uniform steps and transition rates between states are replaced by transition probabilities. In this paper, we illustrate potential limitations to this approach. We show how discretizing time leads to a restriction on the values of the model parameters that can accurately be studied. We examine numerical simulation schemes employed in the literature, showing how synchronous-type updating schemes can bias discrete-time formalisms when compared against continuous-time formalisms. Event-based simulations, such as the Gillespie algorithm, are proposed as optimal simulation schemes both in terms of replicating the continuous-time process and computational speed. Finally, we show how discretizing time can affect the value of the epidemic threshold for large values of the infection rate and the recovery rate, even if the ratio between the former and the latter is small."
876,Equivalence of several generalized percolation models on networks,"In recent years, many variants of percolation have been used to study network structure and the behavior of processes spreading on networks. These include bond percolation, site percolation, [Formula: see text]-core percolation, bootstrap percolation, the generalized epidemic process, and the Watts threshold model (WTM). We show that—except for bond percolation—each of these processes arises as a special case of the WTM, and bond percolation arises from a small modification. In fact “heterogeneous [Formula: see text]-core percolation,” a corresponding “heterogeneous bootstrap percolation” model, and the generalized epidemic process are completely equivalent to one another and the WTM. We further show that a natural generalization of the WTM in which individuals “transmit” or “send a message” to their neighbors with some probability less than 1 can be reformulated in terms of the WTM, and so this apparent generalization is in fact not more general. Finally, we show that in bond percolation, finding the set of nodes in the component containing a given node is equivalent to finding the set of nodes activated if that node is initially activated and the node thresholds are chosen from the appropriate distribution. A consequence of these results is that mathematical techniques developed for the WTM apply to these other models as well, and techniques that were developed for some particular case may in fact apply much more generally."
877,Hysteresis loop of nonperiodic outbreaks of recurrent epidemics,"Most of the studies on epidemics so far have focused on the growing phase, such as how an epidemic spreads and what are the conditions for an epidemic to break out in a variety of cases. However, we discover from real data that on a large scale, the spread of an epidemic is in fact a recurrent event with distinctive growing and recovering phases, i.e., a hysteresis loop. We show here that the hysteresis loop can be reproduced in epidemic models provided that the infectious rate is adiabatically increased or decreased before the system reaches its stationary state. Two ways to the hysteresis loop are revealed, which is helpful in understanding the mechanics of infections in real evolution. Moreover, a theoretical analysis is presented to explain the mechanism of the hysteresis loop."
878,Outbreaks in susceptible-infected-removed epidemics with multiple seeds,"We study a susceptible-infected-removed (SIR) model with multiple seeds on a regular random graph. Many researchers have studied the epidemic threshold of epidemic models above which a global outbreak can occur, starting from an infinitesimal fraction of seeds. However, there have been few studies of epidemic models with finite fractions of seeds. The aim of this paper is to clarify what happens in phase transitions in such cases. The SIR model in networks exhibits two percolation transitions. We derive the percolation transition points for the SIR model with multiple seeds to show that as the infection rate increases epidemic clusters generated from each seed percolate before a single seed can induce a global outbreak."
879,Discrete-time dynamic network model for the spread of susceptible-infective-recovered diseases,"We propose a discrete-time dynamic network model describing the spread of susceptible-infective-recovered diseases in a population. We consider the case in which the nodes in the network change their links due to social mixing dynamics as well as in response to the disease. The model shows the behavior that, as we increase social mixing, disease spread is inhibited in certain cases, while in other cases it is enhanced. We also extend this dynamic network model to take into account the case of hidden infection. Here we find that, as expected, the disease spreads more readily if there is a time period after contracting the disease during which an individual is infective but is not known to have the disease."
880,Epidemic spreading in random rectangular networks,The use of network theory to model disease propagation on populations introduces important elements of reality to the classical epidemiological models. The use of random geometric graphs (RGGs) is one of such network models that allows for the consideration of spatial properties on disease propagation. In certain real-world scenarios—like in the analysis of a disease propagating through plants—the shape of the plots and fields where the host of the disease is located may play a fundamental role in the propagation dynamics. Here we consider a generalization of the RGG to account for the variation of the shape of the plots or fields where the hosts of a disease are allocated. We consider a disease propagation taking place on the nodes of a random rectangular graph and we consider a lower bound for the epidemic threshold of a susceptible-infected-susceptible model or a susceptible-infected-recovered model on these networks. Using extensive numerical simulations and based on our analytical results we conclude that (ceteris paribus) the elongation of the plot or field in which the nodes are distributed makes the network more resilient to the propagation of a disease due to the fact that the epidemic threshold increases with the elongation of the rectangle. These results agree with accumulated empirical evidence and simulation results about the propagation of diseases on plants in plots or fields of the same area and different shapes.
881,Influence of trust in the spreading of information,"The understanding and prediction of information diffusion processes on networks is a major challenge in network theory with many implications in social sciences. Many theoretical advances occurred due to stochastic spreading models. Nevertheless, these stochastic models overlooked the influence of rational decisions on the outcome of the process. For instance, different levels of trust in acquaintances do play a role in information spreading, and actors may change their spreading decisions during the information diffusion process accordingly. Here, we study an information-spreading model in which the decision to transmit or not is based on trust. We explore the interplay between the propagation of information and the trust dynamics happening on a two-layer multiplex network. Actors' trustable or untrustable states are defined as accumulated cooperation or defection behaviors, respectively, in a Prisoner's Dilemma setup, and they are controlled by a memory span. The propagation of information is abstracted as a threshold model on the information-spreading layer, where the threshold depends on the trustability of agents. The analysis of the model is performed using a tree approximation and validated on homogeneous and heterogeneous networks. The results show that the memory of previous actions has a significant effect on the spreading of information. For example, the less memory that is considered, the higher is the diffusion. Information is highly promoted by the emergence of trustable acquaintances. These results provide insight into the effect of plausible biases on spreading dynamics in a multilevel networked system."
882,Memory effects on epidemic evolution: The susceptible-infected-recovered epidemic model,"Memory has a great impact on the evolution of every process related to human societies. Among them, the evolution of an epidemic is directly related to the individuals' experiences. Indeed, any real epidemic process is clearly sustained by a non-Markovian dynamics: memory effects play an essential role in the spreading of diseases. Including memory effects in the susceptible-infected-recovered (SIR) epidemic model seems very appropriate for such an investigation. Thus, the memory prone SIR model dynamics is investigated using fractional derivatives. The decay of long-range memory, taken as a power-law function, is directly controlled by the order of the fractional derivatives in the corresponding nonlinear fractional differential evolution equations. Here we assume “fully mixed” approximation and show that the epidemic threshold is shifted to higher values than those for the memoryless system, depending on this memory “length” decay exponent. We also consider the SIR model on structured networks and study the effect of topology on threshold points in a non-Markovian dynamics. Furthermore, the lack of access to the precise information about the initial conditions or the past events plays a very relevant role in the correct estimation or prediction of the epidemic evolution. Such a “constraint” is analyzed and discussed."
883,Sampling methods for the quasistationary regime of epidemic processes on regular and complex networks,"A major hurdle in the simulation of the steady state of epidemic processes is that the system will unavoidably visit an absorbing, disease-free state at sufficiently long times due to the finite size of the networks where epidemics evolves. In the present work, we compare different quasistationary (QS) simulation methods where the absorbing states are suitably handled and the thermodynamical limit of the original dynamics can be achieved. We analyze the standard QS (SQS) method, where the sampling is constrained to active configurations, the reflecting boundary condition (RBC), where the dynamics returns to the pre-absorbing configuration, and hub reactivation (HR), where the most connected vertex of the network is reactivated after a visit to an absorbing state. We apply the methods to the contact process (CP) and susceptible-infected-susceptible (SIS) models on regular and scale free networks. The investigated methods yield the same epidemic threshold for both models. For CP, that undergoes a standard collective phase transition, the methods are equivalent. For SIS, whose phase transition is ruled by the hub mutual reactivation, the SQS and HR methods are able to capture localized epidemic phases while RBC is not. We also apply the autocorrelation time as a tool to characterize the phase transition and observe that this analysis provides the same finite-size scaling exponents for the critical relaxation time for the investigated methods. Finally, we verify the equivalence between RBC method and a weak external field for epidemics on networks."
884,Impact of environmental colored noise in single-species population dynamics,"Variability on external conditions has important consequences for the dynamics and the organization of biological systems. In many cases, the characteristic timescale of environmental changes as well as their correlations play a fundamental role in the way living systems adapt and respond to it. A proper mathematical approach to understand population dynamics, thus, requires approaches more refined than, e.g., simple white-noise approximations. To shed further light onto this problem, in this paper we propose a unifying framework based on different analytical and numerical tools available to deal with “colored” environmental noise. In particular, we employ a “unified colored noise approximation” to map the original problem into an effective one with white noise, and then we apply a standard path integral approach to gain analytical understanding. For the sake of specificity, we present our approach using as a guideline a variation of the contact process—which can also be seen as a birth-death process of the Malthus-Verhulst class—where the propagation or birth rate varies stochastically in time. Our approach allows us to tackle in a systematic manner some of the relevant questions concerning population dynamics under environmental variability, such as determining the stationary population density, establishing the conditions under which a population may become extinct, and estimating extinction times. We focus on the emerging phase diagram and its possible phase transitions, underlying how these are affected by the presence of environmental noise time-correlations."
885,Clustering determines the dynamics of complex contagions in multiplex networks,"We present the mathematical analysis of generalized complex contagions in a class of clustered multiplex networks. The model is intended to understand spread of influence, or any other spreading process implying a threshold dynamics, in setups of interconnected networks with significant clustering. The contagion is assumed to be general enough to account for a content-dependent linear threshold model, where each link type has a different weight (for spreading influence) that may depend on the content (e.g., product, rumor, political view) that is being spread. Using the generating functions formalism, we determine the conditions, probability, and expected size of the emergent global cascades. This analysis provides a generalization of previous approaches and is especially useful in problems related to spreading and percolation. The results present nontrivial dependencies between the clustering coefficient of the networks and its average degree. In particular, several phase transitions are shown to occur depending on these descriptors. Generally speaking, our findings reveal that increasing clustering decreases the probability of having global cascades and their size, however, this tendency changes with the average degree. There exists a certain average degree from which on clustering favors the probability and size of the contagion. By comparing the dynamics of complex contagions over multiplex networks and their monoplex projections, we demonstrate that ignoring link types and aggregating network layers may lead to inaccurate conclusions about contagion dynamics, particularly when the correlation of degrees between layers is high."
886,Mutually cooperative epidemics on power-law networks,"The spread of an infectious disease can, in some cases, promote the propagation of other pathogens favoring violent outbreaks, which cause a discontinuous transition to an endemic state. The topology of the contact network plays a crucial role in these cooperative dynamics. We consider a susceptible-infected-removed-type model with two mutually cooperative pathogens: An individual already infected with one disease has an increased probability of getting infected by the other. We present a heterogeneous mean-field theoretical approach to the coinfection dynamics on generic uncorrelated power-law degree-distributed networks and validate its results by means of numerical simulations. We show that, when the second moment of the degree distribution is finite, the epidemic transition is continuous for low cooperativity, while it is discontinuous when cooperativity is sufficiently high. For scale-free networks, i.e., topologies with diverging second moment, the transition is instead always continuous. In this way we clarify the effect of heterogeneity and system size on the nature of the transition, and we validate the physical interpretation about the origin of the discontinuity."
887,Efficiency of prompt quarantine measures on a susceptible-infected-removed model in networks,"This study focuses on investigating the manner in which a prompt quarantine measure suppresses epidemics in networks. A simple and ideal quarantine measure is considered in which an individual is detected with a probability immediately after it becomes infected and the detected one and its neighbors are promptly isolated. The efficiency of this quarantine in suppressing a susceptible-infected-removed (SIR) model is tested in random graphs and uncorrelated scale-free networks. Monte Carlo simulations are used to show that the prompt quarantine measure outperforms random and acquaintance preventive vaccination schemes in terms of reducing the number of infected individuals. The epidemic threshold for the SIR model is analytically derived under the quarantine measure, and the theoretical findings indicate that prompt executions of quarantines are highly effective in containing epidemics. Even if infected individuals are detected with a very low probability, the SIR model under a prompt quarantine measure has finite epidemic thresholds in fat-tailed scale-free networks in which an infected individual can always cause an outbreak of a finite relative size without any measure. The numerical simulations also demonstrate that the present quarantine measure is effective in suppressing epidemics in real networks."
888,Control of epidemics via social partnership adjustment,"Epidemic control is of great importance for human society. Adjusting interacting partners is an effective individualized control strategy. Intuitively, it is done either by shortening the interaction time between susceptible and infected individuals or by increasing the opportunities for contact between susceptible individuals. Here, we provide a comparative study on these two control strategies by establishing an epidemic model with nonuniform stochastic interactions. It seems that the two strategies should be similar, since shortening the interaction time between susceptible and infected individuals somehow increases the chances for contact between susceptible individuals. However, analytical results indicate that the effectiveness of the former strategy sensitively depends on the infectious intensity and the combinations of different interaction rates, whereas the latter one is quite robust and efficient. Simulations are shown to verify our analytical predictions. Our work may shed light on the strategic choice of disease control."
889,Takeover times for a simple model of network infection,"We study a stochastic model of infection spreading on a network. At each time step a node is chosen at random, along with one of its neighbors. If the node is infected and the neighbor is susceptible, the neighbor becomes infected. How many time steps [Formula: see text] does it take to completely infect a network of [Formula: see text] nodes, starting from a single infected node? An analogy to the classic “coupon collector” problem of probability theory reveals that the takeover time [Formula: see text] is dominated by extremal behavior, either when there are only a few infected nodes near the start of the process or a few susceptible nodes near the end. We show that for [Formula: see text] , the takeover time [Formula: see text] is distributed as a Gumbel distribution for the star graph, as the convolution of two Gumbel distributions for a complete graph and an Erdős-Rényi random graph, as a normal for a one-dimensional ring and a two-dimensional lattice, and as a family of intermediate skewed distributions for [Formula: see text]-dimensional lattices with [Formula: see text] (these distributions approach the convolution of two Gumbel distributions as [Formula: see text] approaches infinity). Connections to evolutionary dynamics, cancer, incubation periods of infectious diseases, first-passage percolation, and other spreading phenomena in biology and physics are discussed."
890,Three faces of node importance in network epidemiology: Exact results for small graphs,"We investigate three aspects of the importance of nodes with respect to susceptible-infectious-removed (SIR) disease dynamics: influence maximization (the expected outbreak size given a set of seed nodes), the effect of vaccination (how much deleting nodes would reduce the expected outbreak size), and sentinel surveillance (how early an outbreak could be detected with sensors at a set of nodes). We calculate the exact expressions of these quantities, as functions of the SIR parameters, for all connected graphs of three to seven nodes. We obtain the smallest graphs where the optimal node sets are not overlapping. We find that (i) node separation is more important than centrality for more than one active node, (ii) vaccination and influence maximization are the most different aspects of importance, and (iii) the three aspects are more similar when the infection rate is low."
891,Griffiths phase on hierarchical modular networks with small-world edges,"The Griffiths phase has been proposed to induce a stretched critical regime that facilitates self-organizing of brain networks for optimal function. This phase stems from the intrinsic structural heterogeneity of brain networks, i.e., the hierarchical modular structure. In this work, the Griffiths phase is studied in modified hierarchical networks with small-world connections based on the 3-regular Hanoi network. Through extensive simulations, the hierarchical level-dependent inter-module wiring probabilities are identified to determine the emergence of the Griffiths phase. Numerical results and the complementary spectral analysis of the relevant networks can be helpful for a deeper understanding of the essential structural characteristics of finite-dimensional networks to support the Griffiths phase."
892,Effect of risk perception on epidemic spreading in temporal networks,"Many progresses in the understanding of epidemic spreading models have been obtained thanks to numerous modeling efforts and analytical and numerical studies, considering host populations with very different structures and properties, including complex and temporal interaction networks. Moreover, a number of recent studies have started to go beyond the assumption of an absence of coupling between the spread of a disease and the structure of the contacts on which it unfolds. Models including awareness of the spread have been proposed, to mimic possible precautionary measures taken by individuals that decrease their risk of infection, but have mostly considered static networks. Here, we adapt such a framework to the more realistic case of temporal networks of interactions between individuals. We study the resulting model by analytical and numerical means on both simple models of temporal networks and empirical time-resolved contact data. Analytical results show that the epidemic threshold is not affected by the awareness but that the prevalence can be significantly decreased. Numerical studies on synthetic temporal networks highlight, however, the presence of very strong finite-size effects, resulting in a significant shift of the effective epidemic threshold in the presence of risk awareness. For empirical contact networks, the awareness mechanism leads as well to a shift in the effective threshold and to a strong reduction of the epidemic prevalence."
893,Accurate ranking of influential spreaders in networks based on dynamically asymmetric link weights,"We propose an efficient and accurate measure for ranking spreaders and identifying the influential ones in spreading processes in networks. While the edges determine the connections among the nodes, their specific role in spreading should be considered explicitly. An edge connecting nodes [Formula: see text] and [Formula: see text] may differ in its importance for spreading from [Formula: see text] to [Formula: see text] and from [Formula: see text] to [Formula: see text]. The key issue is whether node [Formula: see text] , after infected by [Formula: see text] through the edge, would reach out to other nodes that [Formula: see text] itself could not reach directly. It becomes necessary to invoke two unequal weights [Formula: see text] and [Formula: see text] characterizing the importance of an edge according to the neighborhoods of nodes [Formula: see text] and [Formula: see text]. The total asymmetric directional weights originating from a node leads to a novel measure [Formula: see text] , which quantifies the impact of the node in spreading processes. An [Formula: see text]-shell decomposition scheme further assigns an [Formula: see text]-shell index or weighted coreness to the nodes. The effectiveness and accuracy of rankings based on [Formula: see text] and the weighted coreness are demonstrated by applying them to nine real-world networks. Results show that they generally outperform rankings based on the nodes' degree and [Formula: see text]-shell index while maintaining a low computational complexity. Our work represents a crucial step towards understanding and controlling the spread of diseases, rumors, information, trends, and innovations in networks."
894,Fundamental difference between superblockers and superspreaders in networks,"Two important problems regarding spreading phenomena in complex topologies are the optimal selection of node sets either to minimize or maximize the extent of outbreaks. Both problems are nontrivial when a small fraction of the nodes in the network can be used to achieve the desired goal. The minimization problem is equivalent to a structural optimization. The “superblockers,” i.e., the nodes that should be removed from the network to minimize the size of outbreaks, are those nodes that make connected components as small as possible. “Superspreaders” are instead the nodes such that, if chosen as initiators, they maximize the average size of outbreaks. The identity of superspreaders is expected to depend not just on the topology, but also on the specific dynamics considered. Recently, it has been conjectured that the two optimization problems might be equivalent, in the sense that superblockers act also as superspreaders. In spite of its potential groundbreaking importance, no empirical study has been performed to validate this conjecture. In this paper, we perform an extensive analysis over a large set of real-world networks to test the similarity between sets of superblockers and of superspreaders. We show that the two optimization problems are not equivalent: superblockers do not act as optimal spreaders."
895,Stochastic dynamics for reinfection by transmitted diseases,"The use of stochastic models to study the dynamics of infectious diseases is an important tool to understand the epidemiological process. For several directly transmitted diseases, reinfection is a relevant process, which can be expressed by endogenous reactivation of the pathogen or by exogenous reinfection due to direct contact with an infected individual (with smaller reinfection rate [Formula: see text] than infection rate [Formula: see text]). In this paper, we examine the stochastic susceptible, infected, recovered, infected (SIRI) model simulating the endogenous reactivation by a spontaneous reaction, while exogenous reinfection by a catalytic reaction. Analyzing the mean-field approximations of a site and pairs of sites, and Monte Carlo (MC) simulations for the particular case of exogenous reinfection, we obtained continuous phase transitions involving endemic, epidemic, and no transmission phases for the simple approach; the approach of pairs is better to describe the phase transition from endemic phase (susceptible, infected, susceptible (SIS)-like model) to epidemic phase (susceptible, infected, and removed or recovered (SIR)-like model) considering the comparison with MC results; the reinfection increases the peaks of outbreaks until the system reaches endemic phase. For the particular case of endogenous reactivation, the approach of pairs leads to a continuous phase transition from endemic phase (SIS-like model) to no transmission phase. Finally, there is no phase transition when both effects are taken into account. We hope the results of this study can be generalized for the susceptible, exposed, infected, and removed or recovered ([Formula: see text]) model, for which the state exposed (infected but not infectious), describing more realistically transmitted diseases such as tuberculosis. In future work, we also intend to investigate the effect of network topology on phase transitions when the SIRI model describes both transmitted diseases ([Formula: see text]) and social contagions ([Formula: see text])."
896,Critical behavior of a two-step contagion model with multiple seeds,"A two-step contagion model with a single seed serves as a cornerstone for understanding the critical behaviors and underlying mechanism of discontinuous percolation transitions induced by cascade dynamics. When the contagion spreads from a single seed, a cluster of infected and recovered nodes grows without any cluster merging process. However, when the contagion starts from multiple seeds of [Formula: see text] where [Formula: see text] is the system size, a node weakened by a seed can be infected more easily when it is in contact with another node infected by a different pathogen seed. This contagion process can be viewed as a cluster merging process in a percolation model. Here we show analytically and numerically that when the density of infectious seeds is relatively small but [Formula: see text] , the epidemic transition is hybrid, exhibiting both continuous and discontinuous behavior, whereas when it is sufficiently large and reaches a critical point, the transition becomes continuous. We determine the full set of critical exponents describing the hybrid and the continuous transitions. Their critical behaviors differ from those in the single-seed case."
897,Epidemic spreading on activity-driven networks with attractiveness,"We study SIS epidemic spreading processes unfolding on a recent generalization of the activity-driven modeling framework. In this model of time-varying networks, each node is described by two variables: activity and attractiveness. The first describes the propensity to form connections, while the second defines the propensity to attract them. We derive analytically the epidemic threshold considering the time scale driving the evolution of contacts and the contagion as comparable. The solutions are general and hold for any joint distribution of activity and attractiveness. The theoretical picture is confirmed via large-scale numerical simulations performed considering heterogeneous distributions and different correlations between the two variables. We find that heterogeneous distributions of attractiveness alter the contagion process. In particular, in the case of uncorrelated and positive correlations between the two variables, heterogeneous attractiveness facilitates the spreading. On the contrary, negative correlations between activity and attractiveness hamper the spreading. The results presented contribute to the understanding of the dynamical properties of time-varying networks and their effects on contagion phenomena unfolding on their fabric."
898,Tuning the overlap and the cross-layer correlations in two-layer networks: Application to a susceptible-infectious-recovered model with awareness dissemination,"We study the properties of the potential overlap between two networks [Formula: see text] sharing the same set of [Formula: see text] nodes (a two-layer network) whose respective degree distributions [Formula: see text] are given. Defining the overlap coefficient [Formula: see text] as the Jaccard index, we prove that [Formula: see text] is very close to 0 when [Formula: see text] and [Formula: see text] are random and independently generated. We derive an upper bound [Formula: see text] for the maximum overlap coefficient permitted in terms of [Formula: see text] , and [Formula: see text]. Then we present an algorithm based on cross rewiring of links to obtain a two-layer network with any prescribed [Formula: see text] inside the range [Formula: see text]. A refined version of the algorithm allows us to minimize the cross-layer correlations that unavoidably appear for values of [Formula: see text] beyond a critical overlap [Formula: see text]. Finally, we present a very simple example of a susceptible-infectious-recovered epidemic model with information dissemination and use the algorithms to determine the impact of the overlap on the final outbreak size predicted by the model."
899,Interplay between cost and benefits triggers nontrivial vaccination uptake,"The containment of epidemic spreading is a major challenge in science. Vaccination, whenever available, is the best way to prevent the spreading, because it eventually immunizes individuals. However, vaccines are not perfect, and total immunization is not guaranteed. Imperfect immunization has driven the emergence of antivaccine movements that totally alter the predictions about the epidemic incidence. Here, we propose a mathematically solvable mean-field vaccination model to mimic the spontaneous adoption of vaccines against influenzalike diseases and the expected epidemic incidence. The results are in agreement with extensive Monte Carlo simulations of the epidemics and vaccination coevolutionary processes. Interestingly, the results reveal a nonmonotonic behavior on the vaccination coverage that increases with the imperfection of the vaccine and after decreases. This apparent counterintuitive behavior is analyzed and understood from stability principles of the proposed mathematical model."
900,Infection dynamics on spatial small-world network models,"The study of complex networks, and in particular of social networks, has mostly concentrated on relational networks, abstracting the distance between nodes. Spatial networks are, however, extremely relevant in our daily lives, and a large body of research exists to show that the distances between nodes greatly influence the cost and probability of establishing and maintaining a link. A random geometric graph (RGG) is the main type of synthetic network model used to mimic the statistical properties and behavior of many social networks. We propose a model, called REDS, that extends energy-constrained RGGs to account for the synergic effect of sharing the cost of a link with our neighbors, as is observed in real relational networks. We apply both the standard Watts-Strogatz rewiring procedure and another method that conserves the degree distribution of the network. The second technique was developed to eliminate unwanted forms of spatial correlation between the degree of nodes that are affected by rewiring, limiting the effect on other properties such as clustering and assortativity. We analyze both the statistical properties of these two network types and their epidemiological behavior when used as a substrate for a standard susceptible-infected-susceptible compartmental model. We consider and discuss the differences in properties and behavior between RGGs and REDS as rewiring increases and as infection parameters are changed. We report considerable differences both between the network types and, in the case of REDS, between the two rewiring schemes. We conclude that REDS represent, with the application of these rewiring mechanisms, extremely useful and interesting tools in the study of social and epidemiological phenomena in synthetic complex networks."
901,Rapid decay in the relative efficiency of quarantine to halt epidemics in networks,"Several recent studies have tackled the issue of optimal network immunization by providing efficient criteria to identify key nodes to be removed in order to break apart a network, thus preventing the occurrence of extensive epidemic outbreaks. Yet, although the efficiency of those criteria has been demonstrated also in empirical networks, preventive immunization is rarely applied to real-world scenarios, where the usual approach is the a posteriori attempt to contain epidemic outbreaks using quarantine measures. Here we compare the efficiency of prevention with that of quarantine in terms of the tradeoff between the number of removed and saved nodes on both synthetic and empirical topologies. We show how, consistent with common sense, but contrary to common practice, in many cases preventing is better than curing: depending on network structure, rescuing an infected network by quarantine could become inefficient soon after the first infection."
902,Bursting endemic bubbles in an adaptive network,"The spread of an infectious disease is known to change people's behavior, which in turn affects the spread of disease. Adaptive network models that account for both epidemic and behavioral change have found oscillations, but in an extremely narrow region of the parameter space, which contrasts with intuition and available data. In this paper we propose a simple susceptible-infected-susceptible epidemic model on an adaptive network with time-delayed rewiring, and show that oscillatory solutions are now present in a wide region of the parameter space. Altering the transmission or rewiring rates reveals the presence of an endemic bubble—an enclosed region of the parameter space where oscillations are observed."
903,Impact of the infectious period on epidemics,"The duration of the infectious period is a crucial determinant of the ability of an infectious disease to spread. We consider an epidemic model that is network based and non-Markovian, containing classic Kermack-McKendrick, pairwise, message passing, and spatial models as special cases. For this model, we prove a monotonic relationship between the variability of the infectious period (with fixed mean) and the probability that the infection will reach any given subset of the population by any given time. For certain families of distributions, this result implies that epidemic severity is decreasing with respect to the variance of the infectious period. The striking importance of this relationship is demonstrated numerically. We then prove, with a fixed basic reproductive ratio ([Formula: see text]), a monotonic relationship between the variability of the posterior transmission probability (which is a function of the infectious period) and the probability that the infection will reach any given subset of the population by any given time. Thus again, even when [Formula: see text] is fixed, variability of the infectious period tends to dampen the epidemic. Numerical results illustrate this but indicate the relationship is weaker. We then show how our results apply to message passing, pairwise, and Kermack-McKendrick epidemic models, even when they are not exactly consistent with the stochastic dynamics. For Poissonian contact processes, and arbitrarily distributed infectious periods, we demonstrate how systems of delay differential equations and ordinary differential equations can provide upper and lower bounds, respectively, for the probability that any given individual has been infected by any given time."
904,Spontaneous repulsion in the [Formula: see text] reaction on coupled networks,"We study the transient dynamics of an [Formula: see text] process on a pair of randomly coupled networks, where reactants are initially separated. We find that, for sufficiently small fractions [Formula: see text] of cross couplings, the concentration of [Formula: see text] (or [Formula: see text]) particles decays linearly in a first stage and crosses over to a second linear decrease at a mixing time [Formula: see text]. By numerical and analytical arguments, we show that for symmetric and homogeneous structures [Formula: see text] where [Formula: see text] is the mean degree of both networks. Being this behavior is in marked contrast with a purely diffusive process, where the mixing time would go simply like [Formula: see text] , we identify the logarithmic slowing down in [Formula: see text] to be the result of a spontaneous mechanism of repulsion between the reactants [Formula: see text] and [Formula: see text] due to the interactions taking place at the networks' interface. We show numerically how this spontaneous repulsion effect depends on the topology of the underlying networks."
905,Autocorrelation of the susceptible-infected-susceptible process on networks,"In this paper, we focus on the autocorrelation of the susceptible-infected-susceptible (SIS) process on networks. The [Formula: see text]-intertwined mean-field approximation (NIMFA) is applied to calculate the autocorrelation properties of the exact SIS process. We derive the autocorrelation of the infection state of each node and the fraction of infected nodes both in the steady and transient states as functions of the infection probabilities of nodes. Moreover, we show that the autocorrelation can be used to estimate the infection and curing rates of the SIS process. The theoretical results are compared with the simulation of the exact SIS process. Our work fully utilizes the potential of the mean-field method and shows that NIMFA can indeed capture the autocorrelation properties of the exact SIS process."
906,Two golden times in two-step contagion models: A nonlinear map approach,"The two-step contagion model is a simple toy model for understanding pandemic outbreaks that occur in the real world. The model takes into account that a susceptible person either gets immediately infected or weakened when getting into contact with an infectious one. As the number of weakened people increases, they eventually can become infected in a short time period and a pandemic outbreak occurs. The time required to reach such a pandemic outbreak allows for intervention and is often called golden time. Understanding the size-dependence of the golden time is useful for controlling pandemic outbreak. Using an approach based on a nonlinear mapping, here we find that there exist two types of golden times in the two-step contagion model, which scale as [Formula: see text] and [Formula: see text] with the system size [Formula: see text] on Erdős-Rényi networks, where the measured [Formula: see text] is slightly larger than [Formula: see text]. They are distinguished by the initial number of infected nodes, [Formula: see text] and [Formula: see text] , respectively. While the exponent [Formula: see text] of the [Formula: see text]-dependence of the golden time is universal even in other models showing discontinuous transitions induced by cascading dynamics, the measured [Formula: see text] exponents are all close to [Formula: see text] but show model-dependence. It remains open whether or not [Formula: see text] reduces to [Formula: see text] in the asymptotically large- [Formula: see text] limit. Our method can be applied to several models showing a hybrid percolation transition and gives insight into the origin of the two golden times."
907,Correlations between thresholds and degrees: An analytic approach to model attacks and failure cascades,"Two node variables determine the evolution of cascades in random networks: a node's degree and threshold. Correlations between both fundamentally change the robustness of a network, yet they are disregarded in standard analytic methods as local tree or heterogeneous mean field approximations, since order statistics are difficult to capture analytically because of their combinatorial nature. We show how they become tractable in the thermodynamic limit of infinite network size. This enables the analytic description of node attacks that are characterized by threshold allocations based on node degree. Using two examples, we discuss possible implications of irregular phase transitions and different speeds of cascade evolution for the control of cascades."
908,Optimization of targeted node set in complex networks under percolation and selection,"Most of the existing methods for the robustness and targeted immunization problems can be viewed as greedy strategies, which are quite efficient but readily induce a local optimization. In this paper, starting from a percolation perspective, we develop two strategies, the relationship-related (RR) strategy and the prediction relationship (PR) strategy, to avoid a local optimum only through the investigation of interrelationships among nodes. Meanwhile, RR combines the sum rule and the product rule from explosive percolation, and PR holds the assumption that nodes with high degree are usually more important than those with low degree. In this manner our methods have a better capability to collapse or protect a network. The simulations performed on a number of networks also demonstrate their effectiveness, especially on large real-world networks where RR fragments each of them into the same size of the giant component; however, RR needs only less than [Formula: see text] of the number of nodes which are necessary for the most excellent existing methods."
909,Robustness and fragility of the susceptible-infected-susceptible epidemic models on complex networks,"We analyze two alterations of the standard susceptible-infected-susceptible (SIS) dynamics that preserve the central properties of spontaneous healing and infection capacity of a vertex increasing unlimitedly with its degree. All models have the same epidemic thresholds in mean-field theories but depending on the network properties, simulations yield a dual scenario, in which the epidemic thresholds of the modified SIS models can be either dramatically altered or remain unchanged in comparison with the standard dynamics. For uncorrelated synthetic networks having a power-law degree distribution with exponent [Formula: see text] , the SIS dynamics are robust exhibiting essentially the same outcomes for all investigated models. A threshold in better agreement with the heterogeneous rather than quenched mean-field theory is observed in the modified dynamics for exponent [Formula: see text]. Differences are more remarkable for [Formula: see text] , where a finite threshold is found in the modified models in contrast with the vanishing threshold of the original one. This duality is elucidated in terms of epidemic lifespan on star graphs. We verify that the activation of the modified SIS models is triggered in the innermost component of the network given by a [Formula: see text]-core decomposition for [Formula: see text] while it happens only for [Formula: see text] in the standard model. For [Formula: see text] , the activation in the modified dynamics is collective involving essentially the whole network while it is triggered by hubs in the standard SIS. The duality also appears in the finite-size scaling of the critical quantities where mean-field behaviors are observed for the modified but not for the original dynamics. Our results feed the discussions about the most proper conceptions of epidemic models to describe real systems and the choices of the most suitable theoretical approaches to deal with these models."
910,Role of hubs in the synergistic spread of behavior,"The spread of behavior in a society has two major features: the synergy of multiple spreaders and the dominance of hubs. While strong synergy is known to induce mixed-order transitions (MOTs) at percolation, the effects of hubs on the phenomena are yet to be clarified. By analytically solving the generalized epidemic process on random scale-free networks with the power-law degree distribution [Formula: see text] , we clarify how the dominance of hubs in social networks affects the conditions for MOTs. Our results show that, for [Formula: see text] , an abundance of hubs drive MOTs, even if a synergistic spreading event requires an arbitrarily large number of adjacent spreaders. In particular, for [Formula: see text] , we find that a global cascade is possible even when only synergistic spreading events are allowed. These transition properties are substantially different from those of cooperative contagions, which are another class of synergistic cascading processes exhibiting MOTs."
911,Emergence of power laws in noncritical neuronal systems,"Experimental and computational studies provide compelling evidence that neuronal systems are characterized by power-law distributions of neuronal avalanche sizes. This fact is interpreted as an indication that these systems are operating near criticality, and, in turn, typical properties of critical dynamical processes, such as optimal information transmission and stability, are attributed to neuronal systems. The purpose of this Rapid Communication is to show that the presence of power-law distributions for the size of neuronal avalanches is not a sufficient condition for the system to operate near criticality. Specifically, we consider a simplistic model of neuronal dynamics on networks and show that the degree distribution of the underlying neuronal network may trigger power-law distributions for neuronal avalanches even when the system is not in its critical regime. To certify and explain our findings we develop an analytical approach based on percolation theory and branching processes techniques."
912,Morphological inversion of complex diffusion,"Epidemics, neural cascades, power failures, and many other phenomena can be described by a diffusion process on a network. To identify the causal origins of a spread, it is often necessary to identify the triggering initial node. Here, we define a new morphological operator and use it to detect the origin of a diffusive front, given the final state of a complex network. Our method performs better than algorithms based on distance (closeness) and Jordan centrality. More importantly, our method is applicable regardless of the specifics of the forward model, and therefore can be applied to a wide range of systems such as identifying the patient zero in an epidemic, pinpointing the neuron that triggers a cascade, identifying the original malfunction that causes a catastrophic infrastructure failure, and inferring the ancestral species from which a heterogeneous population evolves."
913,Effective distances for epidemics spreading on complex networks,We show that the recently introduced logarithmic metrics used to predict disease arrival times on complex networks are approximations of more general network-based measures derived from random walks theory. Using the daily air-traffic transportation data we perform numerical experiments to compare the infection arrival time with this alternative metric that is obtained by accounting for multiple walks instead of only the most probable path. The comparison with direct simulations reveals a higher correlation compared to the shortest-path approach used previously. In addition our method allows to connect fundamental observables in epidemic spreading with the cumulant-generating function of the hitting time for a Markov chain. Our results provides a general and computationally efficient approach using only algebraic methods.
914,Objective measures for sentinel surveillance in network epidemiology,"Assume one has the capability of determining whether a node in a network is infectious or not by probing it. Then problem of optimizing sentinel surveillance in networks is to identify the nodes to probe such that an emerging disease outbreak can be discovered early or reliably. Whether the emphasis should be on early or reliable detection depends on the scenario in question. We investigate three objective measures from the literature quantifying the performance of nodes in sentinel surveillance: the time to detection or extinction, the time to detection, and the frequency of detection. As a basis for the comparison, we use the susceptible-infectious-recovered model on static and temporal networks of human contacts. We show that, for some regions of parameter space, the three objective measures can rank the nodes very differently. This means sentinel surveillance is a class of problems, and solutions need to chose an objective measure for the particular scenario in question. As opposed to other problems in network epidemiology, we draw similar conclusions from the static and temporal networks. Furthermore, we do not find one type of network structure that predicts the objective measures, i.e., that depends both on the data set and the SIR parameter values."
915,Hipsters on networks: How a minority group of individuals can lead to an antiestablishment majority,"The spread of opinions, memes, diseases, and “alternative facts” in a population depends both on the details of the spreading process and on the structure of the social and communication networks on which they spread. One feature that can change spreading dynamics substantially is heterogeneous behavior among different types of individuals in a social network. In this paper, we explore how antiestablishment nodes (e.g., hipsters) influence the spreading dynamics of two competing products. We consider a model in which spreading follows a deterministic rule for updating node states (which indicate which product has been adopted) in which an adjustable probability [Formula: see text] of the nodes in a network are hipsters, who choose to adopt the product that they believe is the less popular of the two. The remaining nodes are conformists, who choose which product to adopt by considering which products their immediate neighbors have adopted. We simulate our model on both synthetic and real networks, and we show that the hipsters have a major effect on the final fraction of people who adopt each product: even when only one of the two products exists at the beginning of the simulations, a small fraction of hipsters in a network can still cause the other product to eventually become the more popular one. To account for this behavior, we construct an approximation for the steady-state adoption fractions of the products on [Formula: see text]-regular trees in the limit of few hipsters. Additionally, our simulations demonstrate that a time delay [Formula: see text] in the knowledge of the product distribution in a population, as compared to immediate knowledge of product adoption among nearest neighbors, can have a large effect on the final distribution of product adoptions. Using a local-tree approximation, we derive an analytical estimate of the spreading of products and obtain good agreement if a sufficiently small fraction of the population consists of hipsters. In all networks, we find that either of the two products can become the more popular one at steady state, depending on the fraction of hipsters in the network and on the amount of delay in the knowledge of the product distribution. Our simple model and analysis may help shed light on the road to success for antiestablishment choices in elections, as such success—and qualitative differences in final outcomes between competing products, political candidates, and so on—can arise rather generically in our model from a small number of antiestablishment individuals and ordinary processes of social influence on normal individuals."
916,Understanding the temporal pattern of spreading in heterogeneous networks: Theory of the mean infection time,"For a reliable prediction of an epidemic or information spreading pattern in complex systems, well-defined measures are essential. In the susceptible-infected model on heterogeneous networks, the cluster of infected nodes in the intermediate-time regime exhibits too large fluctuation in size to use its mean size as a representative value. The cluster size follows quite a broad distribution, which is shown to be derived from the variation of the cluster size with the time when a hub node was first infected. On the contrary, the distribution of the time taken to infect a given number of nodes is well concentrated at its mean, suggesting the mean infection time is a better measure. We show that the mean infection time can be evaluated by using the scaling behaviors of the boundary area of the infected cluster and use it to find a nonexponential but algebraic spreading phase in the intermediate stage on strongly heterogeneous networks. Such slow spreading originates in only small-degree nodes left susceptible, while most hub nodes are already infected in the early exponential-spreading stage. Our results offer a way to detour around large statistical fluctuations and quantify reliably the temporal pattern of spread under structural heterogeneity."
917,Meldepflichten für Infektionskrankheiten und Infektionserreger in Deutschland: Entwicklung und Verbesserungsvorschläge,"With the entry into force of the Infection Protection Act (IfSG) in 2001, the reporting obligations for infectious diseases and infectious agents were placed on a new foundation. For the first time, a distinction was made between an obligation for the notification of infectious diseases by physicians and a notification obligation for infectious agents by laboratories. The aim was to reduce the notification burden on physicians and thus to improve the quality of the notifications. Since then, numerous new obligations for notifications have been added. The aim of this work is to describe and discuss the mandatory notification of infectious diseases in Germany on the basis of their development – compared to previous regulations in Germany (Federal Communicable Diseases Act) as well as international and Europe-wide recommendations (IHR; decisions of the EU Commission 1999, 2018) – and to submit suggestions for improvement. Regarding the considerable increase in reporting requirements and reports in recent years, and the fact that the IfSG provides other surveillance systems in addition to mandatory reporting, the mandatory reporting system should be focused on the necessary reporting requirements. In a first step, the proposed abolition of the mandatory reporting of noroviruses and rotaviruses could relieve both the notifiers and the health authorities, thus enabling more efficient reporting and more intensive and better investigation by the health authorities."
918,Seasonal fluctuation of beak and feather disease virus (BFDV) infection in wild Crimson Rosellas (Platycercus elegans),"Understanding patterns of pathogen emergence can help identify mechanisms involved in transmission dynamics. Beak and feather disease virus (BFDV) poses a major threat world-wide to wild and captive parrots. Yet data from wild birds on seasonal fluctuations in prevalence and infection intensity, and thereby the potential high-risk times for virus transmission, have been lacking. We screened wild Crimson Rosellas (Platycercus elegans) for BFDV in blood and cloacal swabs. Prevalence in blood samples and cloacal swabs, as well as viral load varied with Julian date and in blood, were highest after the breeding season. Breeding birds had lower viral load and lower BFDV prevalence in blood than non-breeding birds (10.1% prevalence in breeding vs. 43.2% in non-breeding birds). BFDV prevalence was much higher in younger (<3 years) than older (≥3 years) birds for both blood samples (42.9% vs. 4.5%) and cloacal swabs (56.4% vs. 12.3%). BFDV status in blood and cloacal samples was not correlated within individuals. We show that, at least in P. elegans, BFDV infection seems to occur year-round, with seasonal changes in prevalence and load found in our samples. Our analyses suggest that the seasonal changes were associated primarily with the breeding season. We also discuss age and sex as important predictors of BFDV infection."
919,Epidemic Extinction and Control in Heterogeneous Networks,"We consider epidemic extinction in finite networks with a broad variation in local connectivity. Generalizing the theory of large fluctuations to random networks with a given degree distribution, we are able to predict the most probable, or optimal, paths to extinction in various configurations, including truncated power laws. We find that paths for heterogeneous networks follow a limiting form in which infection first decreases in low-degree nodes, which triggers a rapid extinction in high-degree nodes, and finishes with a residual low-degree extinction. The usefulness of our approach is further demonstrated through optimal control strategies that leverage the dependence of finite-size fluctuations on network topology. Interestingly, we find that the optimal control is a mix of treating both high- and low-degree nodes based on theoretical predictions, in contrast to methods that ignore dynamical fluctuations."
920,Critical Behaviors in Contagion Dynamics,"We study the critical behavior of a general contagion model where nodes are either active (e.g., with opinion [Formula: see text] , or functioning) or inactive (e.g., with opinion [Formula: see text] , or damaged). The transitions between these two states are determined by (i) spontaneous transitions independent of the neighborhood, (ii) transitions induced by neighboring nodes, and (iii) spontaneous reverse transitions. The resulting dynamics is extremely rich including limit cycles and random phase switching. We derive a unifying mean-field theory. Specifically, we analytically show that the critical behavior of systems whose dynamics is governed by processes (i)–(iii) can only exhibit three distinct regimes: (a) uncorrelated spontaneous transition dynamics, (b) contact process dynamics, and (c) cusp catastrophes. This ends a long-standing debate on the universality classes of complex contagion dynamics in mean field and substantially deepens its mathematical understanding."
921,Epidemic Threshold in Continuous-Time Evolving Networks,"Current understanding of the critical outbreak condition on temporal networks relies on approximations (time scale separation, discretization) that may bias the results. We propose a theoretical framework to compute the epidemic threshold in continuous time through the infection propagator approach. We introduce the weak commutation condition allowing the interpretation of annealed networks, activity-driven networks, and time scale separation into one formalism. Our work provides a coherent connection between discrete and continuous time representations applicable to realistic scenarios."
922,Finite Temperature Phase Behavior of Viral Capsids as Oriented Particle Shells,"A general phase plot is proposed for discrete particle shells that allows for thermal fluctuations of the shell geometry and of the inter-particle connectivities. The phase plot contains a first-order melting transition, a buckling transition, and a collapse transition and is used to interpret the thermodynamics of microbiological shells."
923,Degree Dispersion Increases the Rate of Rare Events in Population Networks,"There is great interest in predicting rare and extreme events in complex systems, and in particular, understanding the role of network topology in facilitating such events. In this Letter, we show that degree dispersion—the fact that the number of local connections in networks varies broadly—increases the probability of large, rare fluctuations in population networks generically. We perform explicit calculations for two canonical and distinct classes of rare events: network extinction and switching. When the distance to threshold is held constant, and hence stochastic effects are fairly compared among networks, we show that there is a universal, exponential increase in the rate of rare events proportional to the variance of a network’s degree distribution over its mean squared."
924,Critical Stretching of Mean-Field Regimes in Spatial Networks,"We study a spatial network model with exponentially distributed link lengths on an underlying grid of points, undergoing a structural crossover from a random, Erdős-Rényi graph, to a [Formula: see text]-dimensional lattice at the characteristic interaction range [Formula: see text]. We find that, whilst far from the percolation threshold the random part of the giant component scales linearly with [Formula: see text] , close to criticality it extends in space until the universal length scale [Formula: see text] , for [Formula: see text] , before crossing over to the spatial one. We demonstrate the universal behavior of the spatiotemporal scales characterizing this critical stretching phenomenon of mean-field regimes in percolation and in dynamical processes on [Formula: see text] networks, and we discuss its general implications to real-world phenomena, such as neural activation, traffic flows or epidemic spreading."
925,A conformation-based intra-molecular initiation factor identified in the flavivirus RNA-dependent RNA polymerase,"The flaviviruses pose serious threats to human health. Being a natural fusion of a methyltransferase (MTase) and an RNA-dependent RNA polymerase (RdRP), NS5 is the most conserved flavivirus protein and an important antiviral target. Previously reported NS5 structures represented by those from the Japanese encephalitis virus (JEV) and Dengue virus serotype 3 (DENV3) exhibit two apparently different global conformations, defining two sets of intra-molecular MTase-RdRP interactions. However, whether these NS5 conformations are conserved in flaviviruses and their specific functions remain elusive. Here we report two forms of DENV serotype 2 (DENV2) NS5 crystal structures representing two conformational states with defined analogies to the JEV-mode and DENV3-mode conformations, respectively, demonstrating the conservation of both conformation modes and providing clues for how different conformational states may be interconnected. Data from in vitro polymerase assays further demonstrate that perturbing the JEV-mode but not the DENV3-mode intra-molecular interactions inhibits catalysis only at initiation, while the cell-based virological analysis suggests that both modes of interactions are important for virus proliferation. Our work highlights the role of MTase as a unique intra-molecular initiation factor specifically only through the JEV-mode conformation, providing an example of conformation-based crosstalk between naturally fused protein functional modules."
926,"What’s Important: Weathering the COVID-19 Crisis: Time for Leadership, Vigilance, and Unity",
927,Rethinking Sedation During Prolonged Mechanical Ventilation for Coronavirus Disease 2019 Respiratory Failure,
928,Interacting opinion and disease dynamics in multiplex networks: Discontinuous phase transition and nonmonotonic consensus times,"Opinion formation and disease spreading are among the most studied dynamical processes on complex networks. In real societies, it is expected that these two processes depend on and affect each other. However, little is known about the effects of opinion dynamics over disease dynamics and vice versa, since most studies treat them separately. In this work we study the dynamics of the voter model for opinion formation intertwined with that of the contact process for disease spreading, in a population of agents that interact via two types of connections, social and contact. These two interacting dynamics take place on two layers of networks, coupled through a fraction [Formula: see text] of links present in both networks. The probability that an agent updates its state depends on both the opinion and disease states of the interacting partner. We find that the opinion dynamics has striking consequences on the statistical properties of disease spreading. The most important is that the smooth (continuous) transition from a healthy to an endemic phase observed in the contact process, as the infection probability increases beyond a threshold, becomes abrupt (discontinuous) in the two-layer system. Therefore, disregarding the effects of social dynamics on epidemics propagation may lead to a misestimation of the real magnitude of the spreading. Also, an endemic-healthy discontinuous transition is found when the coupling [Formula: see text] overcomes a threshold value. Furthermore, we show that the disease dynamics delays the opinion consensus, leading to a consensus time that varies nonmonotonically with [Formula: see text] in a large range of the model's parameters. A mean-field approach reveals that the coupled dynamics of opinions and disease can be approximately described by the dynamics of the voter model decoupled from that of the contact process, with effective probabilities of opinion and disease transmission."
929,"Schlechte Luft, miese Stimmung: Depression","Statistiken zeigen, dass Luftverschmutzung neben Gefäßen und Atemwegen wohl auch das Gehirn schädigt. Eine Metaanalyse zeigt eine Häufung von Depressionen und Suiziden im Zusammenhang mit Feinstaubbelastung."
930,COVID-19: Rätsel um den Verlauf bei Kindern: Coronavirus-Pandemie,Auch ein halbes Jahr nach dem Auftauchen von SARS-CoV-2 weiß die Fachwelt wenig über den Verlauf der Infektion bei Kindern. Schwere Verläufe sind bei ihnen trotz normaler Ansteckungsraten offenbar sehr selten. Aber warum?
931,Behandlung von Patienten in Corona-Ambulanzen: COVID-19-Pandemie,"Die Kassenärztlichen Vereinigungen haben dazu aufgerufen, Corona-Ambulanzen aufzubauen. Dort sollen gezielt Patienten mit einer möglichen Corona-Infektion behandelt werden. Im Folgenden wird der Aufbau einer Corona-Ambulanz beschrieben und ein Ausblick gegeben, wie die weitere Entwicklung der ambulanten Behandlung in der Corona-Krise aussehen könnte."
932,Congenital diaphragmatic eventration and hernia sac compared to CDH with true defects: a retrospective cohort study,"Congenital diaphragmatic eventration (CDE) and congenital diaphragmatic hernia (CDH) with or without hernia sac are three different types of congenital diaphragmatic malformations, which this study evaluates. All surgically treated patients with CDE or Bochdalek type CDH between 2000 and 2016 were included in this retrospective analysis. Demographics, CDH-characteristics, treatment, and clinical outcome were evaluated. In total, 200 patients were included. Patients with an eventration or hernia sac had no significant differences and were compared as patients without a true defect to patients with a true defect. The 1-year survival of patients with a true defect was significantly lower than patients with no true defect (76% versus 97%, p = 0.001). CDH with no true defect had significantly better short-term outcomes than CDH with true defect requiring patch repair. However, at 30 days, they more often required oxygen supplementation (46% versus 26%, p = 0.03) and had a higher recurrence rate (8% versus 0%, p = 0.006) (three eventration and two hernia sac patients). Conclusion: Patients without a true defect seem to have a more similar clinical outcome than CDH patients with a true defect, with a better survival. However, the recurrence rate and duration of oxygen supplementation at 30 days are higher than CDH patients with a true defect."
933,Proportional assist ventilation (PAV) versus neurally adjusted ventilator assist (NAVA): effect on oxygenation in infants with evolving or established bronchopulmonary dysplasia,"Both proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA) provide pressure support synchronised throughout the respiratory cycle proportional to the patient’s respiratory demand. Our aim was to compare the effect of these two modes on oxygenation in infants with evolving or established bronchopulmonary dysplasia. Two-hour periods of PAV and NAVA were delivered in random order to 18 infants born less than 32 weeks of gestation. Quasi oxygenation indices (“OI”) and alveolar-arterial (“A-a”) oxygen gradients at the end of each period on PAV, NAVA and baseline ventilation were calculated using capillary blood samples. The mean “OI” was not significantly different on PAV compared to NAVA (7.8 (standard deviation (SD) 3.2) versus 8.1 (SD 3.4), respectively, p = 0.70, but lower on both than on baseline ventilation (mean baseline “OI” 11.0 (SD 5.0)), p = 0.002, 0.004, respectively). The “A-a” oxygen gradient was higher on PAV and baseline ventilation than on NAVA (20.8 (SD 12.3) and 22.9 (SD 11.8) versus 18.5 (SD 10.8) kPa, p = 0.015, < 0.001, respectively). Conclusion: Both NAVA and PAV improved oxygenation compared to conventional ventilation. There was no significant difference in the mean “OI” between the two modes, but the mean “A-a” gradient was better on NAVA."
934,Beneficial effect modification on survival outcome of sepsis between ART-123 and polymyxin B‑immobilised haemoperfusion: a nationwide Japanese registry study,"BACKGROUND: Although recently published randomised controlled trials did not confirm significant positive effect of ART-123 or polymyxin B‑immobilised haemoperfusion (PMX-HP) on survival outcome, previous studies using a dataset of 3195 patients with sepsis registered at 42 intensive care units throughout Japan revealed significantly reduced mortality following these treatments. A study has suggested the efficacy of combination therapy with ART-123 and PMX-HP; however, it did not evaluate the effect modification between them. We hypothesised that coadministration of ART-123 and PMX-HP has a significant positive effect modification on survival outcome. The purpose of this study was to evaluate the effect modification between ART-123 and PMX-HP treatment on the survival outcome of sepsis using post hoc analysis of the dataset of the Japan Septic Disseminated Intravascular Coagulation registry. RESULTS: Of the 3195 patients recorded in the registry, 2350 were analysed. The product term between ART-123 and PMX-HP was analysed by the Cox regression model to evaluate significance. The primary outcome of this study was hospital mortality. Although the administration of ART-123 was independently positively associated with survival outcome (adjusted hazard ratio [HR]: 0.834, 95% confidence interval [CI] 0.695–0.999; P = 0.049) in the model prior to the introduction of the product term, a significant effect modification on survival outcome was observed between the administration of ART-123 and PMX-HP treatment (adjusted HR: 0.667, 95% CI 0.462–0.961; P = 0.030). CONCLUSIONS: The main effect of the administration of ART-123 may be beneficial for survival outcome in patients with sepsis. In addition, a significant beneficial effect modification on survival outcome was observed between the administration of ART-123 and PMX-HP treatment."
935,In vitro characterization of PrismaLung+: a novel ECCO(2)R device,"BACKGROUND: Invasive mechanical ventilation is lifesaving in the setting of severe acute respiratory failure but can cause ventilation-induced lung injury. Advances in extracorporeal CO(2) removal (ECCO(2)R) technologies may facilitate more protective lung ventilation in acute respiratory distress syndrome, and enable earlier weaning and/or avoid invasive mechanical ventilation entirely in chronic obstructive pulmonary disease exacerbations. We evaluated the in vitro CO(2) removal capacity of the novel PrismaLung+ ECCO(2)R device compared with two existing gas exchangers. METHODS: The in vitro CO(2) removal capacity of the PrismaLung+ (surface area 0.8 m(2), Baxter) was compared with the PrismaLung (surface area 0.35 m(2), Baxter) and A.L.ONE (surface area 1.35 m(2), Eurosets) devices, using a closed-loop bovine blood–perfused extracorporeal circuit. The efficacy of each device was measured at varying pCO(2) inlet (p(in)CO(2)) levels (45, 60, and 80 mmHg) and blood flow rates (Q(B)) of 200–450 mL/min; the PrismaLung+ and A.L.ONE devices were also tested at a Q(B) of 600 mL/min. The amount of CO(2) removed by each device was assessed by measurement of the CO(2) infused to maintain circuit equilibrium (CO(2) infusion method) and compared with measured CO(2) concentrations in the inlet and outlet of the CO(2) removal device (blood gas analysis method). RESULTS: The PrismaLung+ device performed similarly to the A.L.ONE device, with both devices demonstrating CO(2) removal rates ~ 50% greater than the PrismaLung device. CO(2) removal rates were 73 ± 4.0, 44 ± 2.5, and 72 ± 1.9 mL/min, for PrismaLung+, PrismaLung, and A.L.ONE, respectively, at Q(B) 300 mL/min and p(in)CO(2) 45 mmHg. A Bland–Altman plot demonstrated that the CO(2) infusion method was comparable to the blood gas analysis method for calculating CO(2) removal. The resistance to blood flow across the test device, as measured by pressure drop, varied as a function of blood flow rate, and was greatest for PrismaLung and lowest for the A.L.ONE device. CONCLUSIONS: The newly developed PrismaLung+ performed more effectively than PrismaLung, with performance of CO(2) removal comparable to A.L.ONE at the flow rates tested, despite the smaller membrane surface area of PrismaLung+ versus A.L.ONE. Clinical testing of PrismaLung+ is warranted to further characterize its performance."
936,"Infectious Complications Following CD19 Chimeric Antigen Receptor T-cell Therapy for Children, Adolescents, and Young Adults","BACKGROUND: Infectious complications of chimeric antigen receptor (CAR) T-cell immunotherapy in children and young adults have not been well described. METHODS: Medical records of patients ≤26 years old receiving CD19 CAR T-cell infusion (CTI) at a single institution between 2014 and 2017 were reviewed. The number of infections per 100 days-at-risk (infection density) in the 90 days preceding and 0–28 and 29–90 days after CTI was calculated. Poisson regression and Cox analyses were utilized to identify risk factors for infections. RESULTS: Eighty-three patients received CTI during the study period. Most patients (98%) had refractory or relapsed acute lymphoblastic leukemia (ALL). Infections occurred in 54% of patients in the 90 days before CTI (infection density, 1.23) and in 40% of patients in the first 28 days following CTI (infection density, 2.89). Infection density decreased to 0.55 in the 29–90 days post-CTI. Most infections were bacteremias (39%) or respiratory viral infections (43%). Pre-CTI risk factors associated with infection included prior hematopoietic cell transplantation (HCT), immunoglobulin G (IgG) level <400 mg/dL, and lymphodepletion other than cyclophosphamide plus fludarabine; post-CTI risk factors included higher-severity CRS and IgG <400 mg/dL. CONCLUSIONS: Infection rates in children and young adults receiving CD19 CAR T-cell therapy increase in the first month and then decline. Understanding types and timing of infections and contributing risk factors may help inform prophylactic and monitoring strategies. Specific attention should be given to patients with prior HCT, severe hypogammaglobulinemia, and severe CRS."
937,Pervasive refusal syndrome: systematic review of case reports,"Pervasive refusal syndrome (PRS) is a complex condition that affects young people leading to social withdrawal, inability or refusal to eat, drink, mobilise or speak. The affected individual regresses and is unable to self-care and quite characteristically will resist rehabilitation, worsen with praise or remain entirely passive. This systematic review was aimed at describing clinical features of PRS, current interventions and to summarise some of the nosological aspects of the condition. Without language restriction, an electronic search was conducted in Embase, PsychInfo, Medline, Cochrane library, and PubMed databases yielding 29 articles with a total of 79 cases. We performed a risk of assessment bias using an adapted Newcastle–Ottawa Scale and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. 124 articles were identified, of which 29 were included and these yielded 79 cases. Seventy-six percent of the studies had a low rate of risk of assessment bias (good quality). Our results show that PRS overlaps with several conditions, mainly affects young females aged 7–15 years and has a recovery rate of 78% if diagnosed and treated early but the duration of inpatient treatment may last up to 9.44 months (8.82 SD). The patients had multiple inter-dependent risks. The major predisposing factors included vulnerable premorbid personality and pre-existing mental disorder. Precipitating factors were stressors such as infection and traumatic experiences. Enmeshed parent–child relationship served as a maintaining factor. The themes of treatment approach are essentially rehabilitative: (1) working collaboratively with patient and family, (2) having access to multidisciplinary team, and (3) peer/group supervision. This study has systematically evaluated a large sample of patients with PRS to ascertain its clinical features and the core elements of its treatment. Its key treatment approach is a multi-modal rehabilitative strategy that is compassionate, transparent and inclusive. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00787-020-01536-1) contains supplementary material, which is available to authorized users."
938,Less daily oral hygiene is more in the ICU: not sure,
939,Optimization and One-Step Purification of Recombinant V Antigen Production from Yersinia pestis,"The purpose of this study was to develop an efficient and inexpensive method for the useful production of recombinant protein V antigen, an important virulence factor for Yersinia pestis. To this end, the synthetic gene encoding the V antigen was subcloned into the downstream of the intein (INT) and chitin-binding domain (CBD) from the pTXB1 vector using specific primers. In the following, the produced new plasmid, pTX-V, was transformed into E. coli ER(2566) strain, and the expression accuracy was confirmed using electrophoresis and Western blotting. In addition, the effects of medium, inducer, and temperature on the enhancement of protein production were studied using the Taguchi method. Finally, the V antigen was purified by a chitin affinity column using INT and CBD tag. The expression was induced by 0.05 mM IPTG at 25 °C under optimal conditions including TB medium. It was observed that the expression of the V-INT–CBD fusion protein was successfully increased to more than 40% of the total protein. The purity of V antigen was as high as 90%. This result indicates that V antigen can be produced at low cost and subjected to one-step purification using a self-cleaving INT tag."
940,Pulmonary non-tuberculous mycobacterial infections: current state and future management,"Currently, there is a trend of increasing incidence in pulmonary non-tuberculous mycobacterial infections (PNTM) together with a decrease in tuberculosis (TB) incidence, particularly in developed countries. The prevalence of PNTM in underdeveloped and developing countries remains unclear as there is still a lack of detection methods that could clearly diagnose PNTM applicable in these low-resource settings. Since non-tuberculous mycobacteria (NTM) are environmental pathogens, the vicinity favouring host-pathogen interactions is known as important predisposing factor for PNTM. The ongoing changes in world population, as well as socio-political and economic factors, are linked to the rise in the incidence of PNTM. Development is an important factor for the improvement of population well-being, but it has also been linked, in general, to detrimental environmental consequences, including the rise of emergent (usually neglected) infectious diseases, such as PNTM. The rise of neglected PNTM infections requires the expansion of the current efforts on the development of diagnostics, therapies and vaccines for mycobacterial diseases, which at present, are mainly focused on TB. This review discuss the current situation of PNTM and its predisposing factors, as well as the efforts and challenges for their control."
941,Australia’s Gambling Epidemic: The Role of Neighbourhood Ethnic Diversity,"Gambling is a popular leisure activity but also a significant public health issue in Australia. The severity of gambling in Australia is characterised by unprecedented gambling expenditures and losses representing the highest gambling rates in the world, which has led to renewed interests in understanding the factors influencing gambling behaviours. We contribute to the debate on the determinants of gambling by providing the first study that examines the impact of ethnic diversity on gambling. Using data from the Household, Income and Labour Dynamics in Australia survey, we find that ethnic diversity is positively associated with gambling. This result is robust to alternative estimation approaches, alternative ways of measuring ethnic diversity and irrespective of whether gambling is measured using the Problem Gambling Severity Index, gambling expenditures or number of gambling activities. Our results also suggest stronger effects of ethnic diversity for problem gamblers compared to gamblers in other risk categories. These results support the need for policies that promote social capital in diverse communities to reduce the risks of social isolation, which is an important motivator of gambling behaviour."
942,"The Evaluation of a Health-Based Education and Behavioral Change Retreat on Quality of Life, Physical Activity and Psychosocial Health in Adult Cancer Survivors: An Exploratory Analysis","Knights Cabin Cancer retreats may represent an ideal opportunity and environment to fill the gap in health education and behavioral change. It is unknown, however, whether the program improves quality of life, physical activity, and psychosocial health. Cancer survivors who enrolled in a retreat completed online questionnaires prior to and 3 months post to assess health-related quality of life, physical activity, and psychosocial variables; perceived stress, depression, and self-esteem. Paired t tests were utilized to compare changes pre and 3 months post the retreat. The majority of the 51 cancer survivors were female with a mean age of 53. The mental component summary of health-related quality of life (p < 0.016) and physical activity score (p = 0.048) was significantly improved at follow-up, while the physical component summary of health-related quality of life was not (p = 0.139). In addition, participants showed an improvement in psychosocial variables of self-esteem (p = 0.016) and depression (p = 0.016) after 3 months but did not show a significant improvement in perceived stress (p = 0.054). Improvements were seen following a Knights Cabin Cancer retreat in mental health-related quality of life and physical activity as well as some psychosocial variables. Further research is needed to evaluate the individual program components and the sustainability of the program in the community."
943,Hydrocortisone and bronchopulmonary dysplasia: variables associated with response in premature infants,"OBJECTIVE: The primary objective was to evaluate hydrocortisone’s efficacy for decreasing respiratory support in premature infants with developing bronchopulmonary dysplasia (BPD). Secondary objectives included assessment of the impact of intrauterine growth restriction (IUGR), maternal history of chorioamnionitis, side effects and route of administration associated with hydrocortisone’s efficacy. Dexamethasone as second-line treatment to decrease respiratory support was reviewed. METHODS: Retrospective chart review of preterm infants requiring respiratory support receiving hydrocortisone. RESULTS: A total of 48 patients were included. Successful extubation was achieved in 50% of intubated patients after hydrocortisone treatment with no major complications. In our small study, history of maternal chorioamnionitis, IUGR or route of administration did not affect the response. Rescue dexamethasone after hydrocortisone therapy was ineffective in the ten patients who failed extubation following hydrocortisone. CONCLUSION: Hydrocortisone is effective in decreasing respiratory support in patients with developing BPD without major complications. Randomized studies are warranted to confirm our findings."
944,"Detection of Group A Beta Hemolytic Streptococci Species, emm, and Exotoxin Genes Isolated from Patients with Tonsillopharyngitis","Group A Beta Hemolytic Streptococci (GAS) is the most critical human pathogen that leads to tonsillopharyngitis. The aims of this study were to identify GAS isolates and to determine emm typing, the coverage rate of available vaccines, and the distribution of superantigen gene profiles. 15 GAS isolates were isolated from throat cultures of 200 patients with tonsillopharyngitis, who were admitted to Canakkale Health Application and Research Hospital between October 2017 and May 2018. Identification of the isolates was performed by conventional methods and 16S rRNA sequence analysis. emm typing and exotoxin profiling of the isolates were performed by polymerase chain reaction. 7.5% GAS was detected in 200 patients. All the GAS isolates were identified as S. pyogenes. emm typing can be carried out in 13 S. pyogenes isolates. emm89 (33.3%), emm44 (20%), emm6 (13.3%), emm84 (6.7%), emm1 (6.7%), and emm18.1 (6.7%) were found to be six emm types. The coverage rate of S. pyogenes strains for 26-valent vaccine was 61.5% and for the 30-valent vaccine 84.6%. The most common exotoxin was speB (86.7%), followed by speC (60%), speF (33.3%), ssa (26.7%), speA (20%), speM (20%), speJ (13.3%), speL (6.7%), and speI (6.7%). As a result of determining the emm types of S. pyogenes species in Canakkale, it was concluded that the potential of 30-valent vaccine should be considered in Turkey and development of vaccines containing exotoxin types may be beneficial."
945,Incidence and risk factors for acquired colonization and infection due to extended-spectrum beta-lactamase-producing Gram-negative bacilli: a retrospective analysis in three ICUs with low multidrug resistance rate,"The purpose of this study is to assess risk factors for the acquisition of extended-spectrum β-lactamase-producing Gram-negative bacilli (ESBL-GNB) colonization and infection (AI) in ICUs with low ESBL-GNB prevalence rate. We conducted a retrospective observational study in three ICUs in Bretagne, France. All patients admitted from January 2016 to September 2017 with a length of stay of 2 days or more were included. Universal screening for ESBL-GNB colonization was performed in all participating ICUs. Of the 3250 included patients, 131 (4.0%) were colonized at admission, 59 acquired colonization while hospitalized (1.9%; 95% CI [1.5–2.5%]), and 15 (0.5%; 95% CI [0.3–0.8%]) acquired ESBL-GNB infections. In the case of infection, the specificity and the negative predictive values of preexistent colonization for the ESBL-GNB etiology were 93.2% [91.5–95.1%] and 95.2% [93.5–97.1%], respectively. Colonization was the main risk factor for ESBL-GNB AI (OR = 9.61; 95% CI [2.86–32.29]; p < 0.001). Antimicrobial susceptibility of non-ESBL-GNB isolates responsible for AI was similar for any non-carbapenem β-lactam (95%) and imipenem (94%). ESBL-GNB AIs were rare in ICUs with low ESBL-GNB prevalence rate. Prior colonization was the main risk factor for subsequent infection. Empirical carbapenem therapy could be avoided in non ESBL-GNB colonized patients with suspected AI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-019-03800-y) contains supplementary material, which is available to authorized users."
946,Long-term outcome of surgical excision for treatment of cervicofacial granulomatous lymphadenitis in children,"PURPOSE: Granulomatous inflammation is a common cause of subacute cervicofacial lymphadenitis in children. Nontuberculous mycobacterial (NTM) infections and cat-scratch disease (CSD) are the most frequent causes. Optimal treatment, which may include surgery, antibiotic treatment or wait-and-see approach, is debatable. The goal of this study was to compare the short- and long-term outcome of various surgical procedures. METHODS: Case series with a chart review of all children treated by surgical excision of granulomatous lymph nodes in the cervicofacial area from 2000 to 2016 at two tertiary care centers. RESULTS: Forty patients were included in this study. The median age at first symptoms was 3.7 years (13 months–14 years). Mean follow-up was 5.8 years (6 months–15.3 years). 25 patients fit with diagnosis of NTM infection, 6 with CSD while diagnosis remained uncertain in 9 patients. The primary surgical procedure consisted of total excision (n = 27), incision/drainage (n = 9) or incomplete excision (n = 4). None of the patients treated by primary complete excision needed further intervention contrary to the group of patients with incomplete surgical procedures where additional surgical management was required in 54%. At follow-up, all patients were healthy without evidence of recurrence. CONCLUSION: We advocate early surgical intervention with complete excision to reach quick resolution and reduce the need for additional surgery. The long-term outcome was favorable."
947,Integrity of plasma DNA is inversely correlated with vaccine-induced antitumor immunity in ovarian cancer patients,"Cancer immunotherapy including vaccine therapy is a promising modality for cancer treatment, but few patients show its clinical benefits currently. The identification of biomarkers that can identify patients who will benefit from cancer immunotherapy is thus important. Here, we investigated the potential utility of the circulating cell-free DNA (cfDNA) integrity—a ratio of necrotic cell-derived, longer DNA fragments versus apoptotic cell-derived shorter fragments of Alu gene—as a biomarker of vaccine therapy for patients with ovarian cancer. We analyzed plasma samples from 39 patients with advanced or recurrent ovarian cancer enrolled in clinical trials for personalized peptide vaccinations. We observed that (1) the cfDNA integrity was decreased after the first cycle of vaccination, and (2) the decreased levels of cfDNA integrity were correlated with vaccine-induced immune responses; i.e., decreased cfDNA integrity was observed in 91.7% and 59.3% of the IgG-positive and negative patients, respectively (p = 0.0445). Similarly, decreased cfDNA integrity was observed in 92.9% and 56.0% of CTL response-positive and negative patients, respectively (p = 0.0283). These results suggest that the circulating cfDNA integrity is a possible biomarker for cancer vaccine therapy."
948,Neue Impfstoffe gegen Tuberkulose,"With about 10 million active disease cases and 1.5 million deaths in 2018, tuberculosis (TB) remains one of the most threatening infectious diseases. Yet, the World Health Organization (WHO) aims to reduce morbidity and mortality by 90 and 95%, respectively, between 2015 and 2035. Although diagnostics, therapeutics, and a vaccine are available, it is beyond doubt that better intervention measures are needed to accomplish this ambitious goal. The vaccine bacille Calmette-Guérin (BCG) partially protects infants against TB, but it is virtually ineffective against pulmonary TB in adolescents and adults. The efficacy of this vaccine, however, has not yet been fully exploited. In addition, new vaccine candidates are currently being assessed in clinical trials. Because a quarter of all people are latently infected with Mycobacterium tuberculosis (Mtb), new vaccines must be applied not only prior to infection (pre-exposure vaccination) but also after infection (postexposure vaccination). Prevention of infection, prevention of disease, and prevention of recurrence are currently assessed as clinical endpoints. Because protection against TB is primarily mediated by T lymphocytes, TB vaccine development focuses on protective T cell responses. Protein adjuvant formulations, viral vectors, and killed and live bacterial vaccines are currently being assessed in clinical trials. Moreover, therapeutic vaccination is clinically tested, notably in adjunct to canonical drug therapy to multiresistant TB. It is likely that a single vaccine cannot accomplish the various indications and that different vaccination strategies are required."
949,Hospitalization following influenza infection and pandemic vaccination in multiple sclerosis patients: a nationwide population-based registry study from Norway,"Patients with multiple sclerosis (MS) are at increased risk of infections and related worsening of neurological function. Influenza infection has been associated with increased risk of various neurological complications. We conducted a population-based registry study to investigate the risk of acute hospitalization of MS patients in relation to influenza infection or pandemic vaccination in Norway. The entire Norwegian population in the years 2008–2014 was defined as our study population (N = 5,219,296). Information on MS diagnosis, influenza infection and vaccination were provided by Norwegian national registries. The self-controlled case series method was used to estimate incidence rate ratios (IRRs) with 95% confidence intervals (95% CI) in defined risk periods. 6755 MS patients were identified during the study period. Average age at first registration of an MS diagnosis was 51.8 years among men and 49.9 years among females (66.9%). The IRR for emergency hospitalization among MS patients the first week after an influenza diagnosis was 3.4 (95% CI 2.4–4.8). The IRR was 5.6 (95% CI 2.7–11.3) after pandemic influenza, and 4.8 (95% CI 3.1–7.4) after seasonal influenza. Pandemic vaccination did not influence risk of hospitalization [IRR within the first week: 0.7 (95% CI 0.5–1.0)]. Among MS patients, influenza infection was associated with increased risk for acute hospitalization while no increased risk was observed after pandemic vaccination. Influenza vaccination could prevent worsening of MS-related symptoms as well as risk of hospitalization."
950,Determination of Compassion Levels of Nurses Working at a University Hospital,"This study was conducted to determine the compassion levels of nurses working in a university hospital. The study sample consists of 227 nurses who were available and participated in the research voluntarily during the study. The study data were collected by using “Nurse Description Form” and “Compassion Scale (CS).” In the analysis of the study data, number, percentage, mean and independent T test and ANOVA test were used. The total mean score of CS of the nurses was found as 97.02 ± 10.67. There was no statistically significant difference between gender, marital status and weekly work hours of the nurses and their total CS score means and total sub-scale score means. On the other hand, there was a statistically significant difference between the age variable of the nurses and the sub-scale of “separation,” between the education level of the nurses and their total CS score means. As a result, it was found that the level of compassion of the nurses was moderate and the level of education affected the compassion levels of the nurses."
951,Effect of adjunctive tobramycin inhalation versus placebo on early clinical response in the treatment of ventilator-associated pneumonia: the VAPORISE randomized-controlled trial,
952,The Utility of Diaphragm Ultrasound in Reducing Time to Extubation,"PURPOSE: Prediction of optimal timing for extubation of mechanically ventilated patients is challenging. Ultrasound measures of diaphragm thickness or diaphragm dome excursion have been used to aid in predicting extubation success or failure. The aim of this study was to determine if incorporating results of diaphragm ultrasound into usual ICU care would shorten the time to extubation. METHODS: We performed a prospective, randomized, controlled study at three Brown University teaching hospitals. Included subjects underwent block randomization to either usual care (Control) or usual care enhanced with ultrasound measurements of the diaphragm (Intervention). The primary outcome was the time to extubation after ultrasound, and the secondary outcome was the total days on the ventilator. Only intensivists in the Intervention group would have the ultrasound information on the likelihood of successful extubation available to incorporate with traditional clinical and physiologic measures to determine the timing of extubation. RESULTS: A total of 32 subjects were studied; 15 were randomized into the Control group and 17 into the Intervention group. The time from ultrasound to extubation was significantly reduced in the Intervention group compared to the Control group in patients with a ∆tdi% ≥ 30% (4.8 ± 8.4 vs 35.0 ± 41.0 h, p = 0.04). The time from ultrasound to extubation was shorter in subjects with a normally functioning diaphragm (∆tdi% ≥ 30%) compared to those with diaphragm dysfunction (∆tdi% < 30%) (23.2 ± 35.2 vs 57.3 ± 52.0 h p = 0.046). When combining the Intervention and Control groups, a value of ∆tdi% ≥ 30% for extubation success at 24 h provided a sensitivity, specificity, PPV and NPV of 90.9%, 86.7%, 90.9%, and 86.7%, respectively. CONCLUSIONS: Diaphragm ultrasound evaluation of ∆tdi% aids in reducing time to extubation."
953,"Characterization of HIV-1 subtypes and drug resistance mutations in Henan Province, China (2017–2019)","Human immunodeficiency virus type 1 (HIV-1) infection remains a severe public health problem worldwide. In this study, we investigated the distribution of HIV-1 subtypes and the prevalence of drug resistance mutations (DRMs) among patients with HIV-1 infection in Henan Province, China. HIV-1 strains in blood samples taken from inpatients and outpatients visiting the Sixth People’s Hospital of Zhengzhou from August 2017 to July 2019 with a viral load (VL) greater than 1000 copies/ml were subjected to subtype and DRMs analysis. Out of a total of 769 samples, subtype and DRM data were obtained from 657 (85.43%) samples. Phylogenetic analysis based on partial pol gene sequences indicated that the most commonly found genotype was subtype B (45.51%, 299/657), followed by CRF01_AE (28.61%, 188/657), CRF07_BC (15.68%, 103/657), CRF08_BC (0.76%, 5/657), C (0.61%, 4/657), A (0.30%, 2/657), and others (8.52%, 56/657). Circulating recombinant forms (CRFs) were most commonly found in patients who were naïve to antiretroviral treatment (ART) (68.67%, 160/233). The percentage of patients with one or more major drug-resistance mutations was 50.99% (335/657), and it was 6.44% (15/233) in ART-naive patients that were primarily infected with subtype B (17.74%). Resistance mutations were most common at codons 65, 103, 106, 184, and 190 of the reverse transcriptase gene and codon 46 of the protease gene. Our study provides detailed information about the distribution of HIV-1 subtypes and the incidence of drug resistance mutations of different subtypes in ART-experienced and naïve patients. This can guide policymakers in making decisions about treatment strategies against HIV-1."
954,Pressure support ventilation-pro decreases propofol consumption and improves postoperative oxygenation index compared with pressure-controlled ventilation in children undergoing ambulatory surgery: a randomized controlled trial,"PURPOSE: The PSVPro mode is increasingly being used for surgeries under laryngeal mask airway owing to improved ventilator-patient synchrony and decreased work of breathing. We hypothesized that PSVPro ventilation mode would reduce consumption of anesthetic agents compared with pressure control ventilation (PCV). METHODS: Seventy children between three and eight years of age undergoing elective lower abdominal and urological surgery were randomized into PCV group (n = 35) or PSVPro group (n = 35). General anesthesia was induced with sevoflurane and a Proseal LMA™ was inserted. Anesthesia was maintained with propofol infusion to maintain the entropy values between 40 and 60. In the PCV mode, the inspiratory pressure was adjusted to obtain an expiratory tidal volume of 8 mL·kg(−1) and a respiratory rate of 12–20/min. In the PSVPRO group, the flow trigger was set at 0.4 L·min(−1) and pressure support was adjusted to obtain expiratory tidal volume of 8 mL·kg(−1). Consumption of anesthetic agent was recorded as the primary outcome. Emergence time and discharge time were recorded as secondary outcomes. RESULTS: The PSVPro group showed significant reduction in propofol consumption compared with the PCV group (mean difference, 33.3 µg(−1)·kg(−1)·min(−1); 95% confidence interval [CI], 24.2 to 42.2). There was decrease in the emergence time in the PSVPro group compared with the PCV group (mean difference, 3.5 min; 95% CI, 2.8 to 4.2) and in time to achieve modified Aldrete score > 9 (mean difference, 3.6 min; 95% CI, 1.9 to 5.2). CONCLUSION: The PSVPro mode decreases propofol consumption and emergence time, and improves oxygenation index in children undergoing ambulatory surgery. TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI/2017/12/010942); registered 21 December, 2017."
955,Obesity associated with increased postoperative pulmonary complications and mortality after trauma laparotomy,"BACKGROUND: Patient-related risk factors for the development of postoperative pulmonary complications (PPCs) include age ≥ 60-years, congestive heart failure, hypoalbuminemia and smoking. The effect of obesity is unclear and has not been shown to independently increase the likelihood of PPCs in trauma patients undergoing trauma laparotomy. We hypothesized the likelihood of mortality and PPCs would increase as body mass index (BMI) increases in trauma patients undergoing trauma laparotomy. METHODS: The Trauma Quality Improvement Program (2010–2016) was queried to identify trauma patients ≥ 18-years-old undergoing trauma laparotomy within 6-h of presentation. A multivariable logistic regression analysis was used to determine the likelihood of PPCs and mortality when stratified by BMI. RESULTS: From 8,330 patients, 2,810 (33.7%) were overweight (25–29.9 kg/m(2)), 1444 (17.3%) obese (30–34.9 kg/m(2)), 580 (7.0%) severely obese (35–39.9 kg/m(2)), and 401 (4.8%) morbidly obese (≥ 40 kg/m(2)). After adjusting for covariates including age, injury severity score, chronic obstructive pulmonary disease, smoking, and rib/lung injury, the likelihood of PPCs increased with increasing BMI: overweight (OR = 1.37, CI 1.07–1.74, p = 0.012), obese (OR = 1.44, CI 1.08–1.92, p = 0.014), severely obese (OR = 2.20, CI 1.55–3.14, p < 0.001), morbidly obese (OR = 2.42, CI 1.67–3.51, p < 0.001), compared to those with normal BMI. In addition, the adjusted likelihood of mortality increased for the morbidly obese (OR = 2.60, CI 1.78–3.80, p < 0.001) compared to those with normal BMI. CONCLUSION: Obese trauma patients undergoing emergent trauma laparotomy have a high likelihood for both PPCs and mortality, with morbidly obese trauma patients having the highest likelihood for both. This suggests obesity should be accounted for in risk prediction models of trauma patients undergoing laparotomy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00068-020-01329-w) contains supplementary material, which is available to authorized users."
956,A Prospective Cohort Study of Factors Associated with Empiric Antibiotic De-escalation in Neonates Suspected with Early Onset Sepsis (EOS),"BACKGROUND: Prolonged empiric antibiotic use, resulting from diagnostic uncertainties, in suspected early onset sepsis (EOS) cases constitutes a significant problem. Unnecessary antibiotic use increases the risk of antibiotic resistance. Furthermore, prolonged antibiotic use increases the risk of mortality and morbidity in neonates. Proactive measures including empiric antibiotic de-escalation are crucial to overcome these problems. METHODS: This was a prospective cohort study conducted in the neonatal intensive care units of two public hospitals in Malaysia. Neonates with a gestational age greater than 34 weeks who were started on empiric antibiotics within 72 h of life were screened. The data were then stratified according to de-escalation and non-de-escalation practices, where de-escalation practice was defined as narrowing down or discontinuation of empiric antibiotic within 72 h of treatment. RESULTS: A total of 1045 neonates were screened, and 429 were included. The neonates were then divided based on de-escalation (n = 207) and non-de-escalation (n = 222) practices. Neonates under non-de-escalation practices showed significantly longer durations of antibiotic use compared to those under de-escalation practices (p < 0.05), with no difference in treatment outcomes. Five factors were found to be associated with de-escalation of antibiotics. They are cesarean section delivery, exposure to antenatal steroids, nil history of maternal pyrexia, absence of meconium-stained amniotic fluid, and normal C-reactive protein ≤ 0.5 mg/dL (p < 0.05). CONCLUSIONS: Empiric antibiotic de-escalation appears feasible as a routine form of treatment for EOS in late preterm and term neonates."
957,"Polymorphism analysis and supertype definition of swine leukocyte antigen class I molecules in three-way crossbred (Landrace, Duroc, and Yorkshire) pigs: implications for the vaccine development of African swine fever virus",
958,Early oral colostrum administration in preterm infants,"BACKGROUND: Early administration of colostrum may provide preterm infants with immune components. Previous studies illustrating the effects of oral colostrum (OC) have been confounded by the coincidence of enteral feedings. OBJECTIVE: To quantify OC absorption, as measured by urinary sIgA and lactoferrin, in preterm infants prior to enteral feedings. MATERIALS AND METHODS: Colostrum was obtained from mothers delivering infants ≤32 weeks and ≤1500 g. sIgA and lactoferrin were measured in infant urine, and microflora in saliva and tracheal aspirates were characterized. RESULTS: Urinary sIgA and lactoferrin were significantly greater in infants receiving OC by syringe compared to swab (p < 0.002). Urinary sIgA correlated with the total number of doses in 72 h (R(2) = 43%, p < 0.01). CONCLUSIONS: Administration of OC by syringe and higher cumulative dose are associated with increased absorption of sIgA and lactoferrin, and early dosing may contribute to a more diverse tracheal microbiome."
959,Antimicrobial de-escalation is part of appropriate antibiotic usage in ICU,
960,"Nitrosourea, etoposide and cyclophosphamide followed by autologous stem cell transplantation for pediatric lymphoma patients","Treatment outcomes in pediatric lymphoma have improved substantially over the past 2 decades; however, the prognosis for patients with high risk or relapsed disease remains poor. We evaluated outcomes of high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) in 56 pediatric lymphoma patients. Patients received nitrosourea (51 BCNU; 5 ACNU), etoposide, and cyclophosphamide (BEC; AEC). Median age at HDC/auto-SCT was 12 years (range 2–17 years). Forty-four patients underwent HDC/auto-SCT because they did not achieve complete remission after induction chemotherapy. Eight patients showed relapse and four NK/T-cell lymphoma patients also underwent HDC/auto-SCT. BCNU pneumonitis was diagnosed in nine (16.0%) patients. Eight (14.3%) relapsed after HDC/auto-SCT. Treatment-related mortality occurred in three cases. Five-year event-free survival and overall survival rates were 74.8% [72.7% non-Hodgkin’s lymphoma (NHL); 83.3% Hodgkin’s disease (HD); 72.7%] and 83.6% (81.6% NHL; 91.7% HD), respectively. HDC/auto-SCT with BEC or AEC regimen for pediatric high-risk lymphoma patients showed feasible outcomes. However, treatment modifications are warranted to reduce relapse and toxicity."
961,Predictive impact of early mobilization on rehospitalization for elderly Japanese heart failure patients,"The aim of this study was to determine whether early mobilization was associated with rehospitalization among elderly heart failure patients. We measured the time from admission to mobilization and other clinical characteristics for 190 heart failure patients (mean age, 80.7 years). The primary outcome was heart failure rehospitalization. Kaplan–Meier survival curves were plotted and the hazard ratios for rehospitalization were determined using Cox proportional hazards regression models. During a median follow-up period of 750 days, 58 patients underwent rehospitalization. The time from admission to mobilization was significantly longer for these patients than for those who were not rehospitalized. Univariate and multivariate Cox proportional hazards analyses showed that the time from admission to mobilization was an independent predictor of rehospitalization, and receiver-operating characteristic analysis determined an optimal cutoff value of 3 days for differentiating the patients more likely to experience a subsequent cardiac event (sensitivity, 76%; specificity, 69%; area under the curve, 0.667). Kaplan–Meier survival curve analysis showed a significantly lower event rate in the ≤ 3-day group (p = 0.001, log-rank test). In conclusion, the time from admission to mobilization may be one of the strongest predictors of rehospitalization in elderly heart failure patients. Early mobilization within 3 days may be an initial target for the acute phase treatment of heart failure."
962,Thoracoscopic repair of esophageal atresia with distal tracheoesophageal fistula: is it a safe procedure in infants weighing less than 2000 g?,"BACKGROUND: Since Rothenberg first performed thoracoscopic repair for esophageal atresia with distal tracheoesophageal fistula (EA/TEF) successfully in 2000, thoracoscopic repair has achieved status as a routine procedure worldwide. Previously, an international multicenter study reported that this procedure was not inferior to conventional open surgery. However, thoracoscopic surgery is a highly difficult operation for surgeons and anesthesiologists; as a result, the safety and efficacy of the surgery is still under debate. Considering these circumstances, the purpose of this study was to analyze the results of single-center thoracoscopic surgery and to compare the outcomes relative to the patient’s weight at the time of surgery. METHODS: We retrospectively analyzed patients with EA/TEF who underwent thoracoscopic surgery in a single center between October 2008 and February 2017. RESULTS: In total, 41 cases of thoracoscopic repair of EA/TEF were performed. Upon subgrouping by over and under 2000 g of body weight at the time of operation, 34 were found to be over 2000 g and seven were under 2000 g. Intraoperative factors and events were not significantly different between the two groups. Additionally, most of the postoperative outcomes, including the rate of postoperative leakage and strictures, showed no difference. On the other hand, the under 2000 g group had more gastroesophageal reflux requiring fundoplication than did the heavier group (P = 0.04). CONCLUSIONS: The results of this center’s thoracoscopic repair of EA/TEF were not inferior to other centers’ outcomes. Additionally, the intraoperative and postoperative outcomes were similar despite differences in weight at operation. Therefore, thoracoscopic repair might be a feasible surgical option for infants weighing less than 2000 g when performed by a surgeon and anesthesiologist team who are experienced in pediatric thoracoscopic surgery."
963,Collaborative Management Strategies for Drug Shortages in Neurocritical Care,"Drug shortages have become all too familiar in the health care environment, with over 200 drugs currently on shortage. In the wake of Hurricane Maria in September 2017, hospitals across the USA had to quickly and creatively adjust medication preparation and administration techniques in light of decreased availability of intravenous (IV) bags used for compounding a vast amount of medications. Amino acid preparations, essential for compounding parenteral nutrition, were also directly impacted by the hurricane. Upon realization of the impending drug shortages, hospitals resorted to alternative methods of drug administration, such as IV push routes, formulary substitutions, or alternative drug therapies in hopes of preserving the small supply of IV bags available and prioritizing them for them most critical needs. In some cases, alternative drug therapies were required, which increased the risk of medication errors due to the use of less-familiar treatment options. Clinical pharmacists rounding with medical teams provided essential, patient-specific drug regimen alternatives to help preserve a dwindling supply while ensuring use in the most critical cases. Drug shortages also frequently occur in the setting of manufacturing delays or discontinuation and drug recalls, with potential to negatively impact patient care. The seriousness of the drug shortage crisis reached public attention by December 2017, when political and pharmacy organizations called for response to the national drug shortage crisis. In this article, we review institutional mitigation strategies in response to drug shortages and discuss downstream effects of these shortages, focusing on medications commonly prescribed in neurocritical care patients."
964,MELD–Na Is More Strongly Associated with Risk of Infection and Outcomes Than Other Characteristics of Patients with Cirrhosis,"BACKGROUND AND AIMS: The nature and outcomes of infection among patients with cirrhosis in safety-net hospitals are not well described. We aimed to characterize the rate of and risk factors for infection, both present on admission and nosocomial, in this unique population. We hypothesized that infections would be associated with adverse outcomes such as short-term mortality. METHODS: We used descriptive statistics to characterize infections within a retrospective cohort characterized previously. We used multivariable logistic regression models to assess potential risk factors for infection and associations with key outcomes such as short-term mortality and length of stay. RESULTS: The study cohort of 1112 patients included 33% women with a mean age of 56 ± 10 years. Infections were common (20%), with respiratory and urinary tract infections the most frequent. We did not observe a difference in the incidence of infection on admission based on patient demographic factors such as race/ethnicity or estimated household income. Infections on admission were associated with greater short-term mortality (12% vs 4% in-hospital and 14% vs 7% 30-day), longer length of stay (6 vs 3 days), intensive care unit admission (28% vs 18%), and acute-on-chronic liver failure (10% vs 2%) (p < 0.01 for all). Nosocomial infections were relatively uncommon (4%), but more frequent among patients admitted to the intensive care unit. Antibiotic resistance was common (38%), but not associated with negative outcomes. CONCLUSION: We did not identify demographic risk factors for infection, but did confirm its morbid effect among patients with cirrhosis in safety-net hospitals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10620-020-06164-y) contains supplementary material, which is available to authorized users."
965,Urgent intubation without neuromuscular blocking agents and the risk of tracheostomy,"Neuromuscular blocking agents play a significant role in improving the success rate for urgent intubation, although there is limited evidence about the effect on subsequent outcomes, such as the incidence of tracheostomy. In this retrospective cohort study, we aimed to examine the association between avoidance of neuromuscular blocking agents for urgent tracheal intubation and incidence of tracheostomy among patients in the intensive care unit (ICU). The setting of this study was an eight-bed ICU at a tertiary-care hospital in Okayama, Japan. We included patients who underwent urgent tracheal intubation at the emergency department or the ICU and were admitted to the ICU between April 2013 and November 2017. We extracted data on methods and medications of intubation, predictors for difficult intubation, Cormack–Lehane grade, patient demographics, primary diagnoses, reintubation. We estimated odds ratios and their 95% confidence intervals for elective tracheostomy during the ICU stay using logistic regression models. Of 411 patients, 46 patients underwent intubation without neuromuscular blocking agents and 61 patients underwent tracheostomy. After adjusting for potential confounders, patients who avoided neuromuscular blocking agents had more than double the odds of tracheostomy (odds ratio 2.59, 95% confidence interval 1.06–6.34, p value = 0.04). When stratifying the subjects by risk status for tracheostomy, the association was more pronounced in high-risk group, while we observed less significant association in the low-risk group. Avoidance of neuromuscular blocking agents for urgent intubation increases the risk of tracheostomy among emergency patients, especially those who have a higher risk for tracheostomy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11739-019-02214-0) contains supplementary material, which is available to authorized users."
966,Comparison of the use of AnaConDa® versus AnaConDa-S® during the post-operative period of cardiac surgery under standard conditions of practice,"Changes have been made to the AnaConDa device (Sedana Medical, Stockholm, Sweden), decreasing its size to reduce dead space and carbon dioxide (CO(2)) retention. However, this also involves a decrease in the surface area of the activated carbon filter. The CO(2) elimination and sevoflurane (SEV) reflection of the old device (ACD-100) were thus compared with the new version (ACD-50) in patients sedated after coronary artery bypass graft surgery. After ERC approval and written informed consent, 23 patients were sedated with SEV, using first the ACD-100 and then the ACD-50 for 60 min each. With each device, patients were ventilated with tidal volumes (TV) of 5 ml/kg of ideal body weight for the first 30 min, and with 7 ml/kg for the next 30 min. Ventilation parameters, arterial blood gases, Bispectral-Index™ (BIS, Aspect Medical Systems Inc., Newton, MA, USA), SEV concentrations exhaled by the patient (SEV-exhaled) and from the expiratory hose (SEV-lost) were recorded every 30 min. A SEV reflection index was calculated: SRI [%] = 100 × (1 − (SEV-lost/SEV-exhaled)). Data were compared using ANOVA with repeated measurements and Student’s T-tests for pairs. Respiratory rates, tidal and minute volumes were not significantly different between the two devices. End tidal and arterial CO(2) partial pressures were significantly higher with the ACD-100 as compared with the ACD-50. SEV infusion rate remained constant. SEV reflection was higher (SRI: ACD-100 vs. ACD-50, TV 5 ml/kg: 95.29 ± 6.45 vs. 85.54 ± 11.15, p = 0.001; 7 ml/kg: 93.42 ± 6.55 vs. 88.77 ± 12.26, p = 0.003). BIS was significantly lower when using the higher TV (60.91 ± 9.99 vs. 66.57 ± 8.22, p = 0.012), although this difference was not clinically relevant. During postoperative sedation, the use of ACD-50 significantly reduced CO(2) retention. SEV reflection was slightly reduced. However, patients remained sufficiently sedated without increasing SEV infusion."
967,Cardiorespiratory behavior of preterm infants receiving continuous positive airway pressure and high flow nasal cannula post extubation: randomized crossover study,"BACKGROUND: Nasal continuous positive airway pressure (NCPAP) and high flow nasal cannula (HFNC) are modes of non-invasive respiratory support commonly used after extubation in extremely preterm infants. However, the cardiorespiratory physiology of these infants on each mode is unknown. METHODS: Prospective, randomized crossover study in infants with birth weight ≤1250 g undergoing their first extubation attempt. NCPAP and HFNC were applied randomly for 45 min each, while ribcage and abdominal movements, electrocardiogram, oxygen saturation, and fraction of inspired oxygen (FiO(2)) were recorded. Respiratory signals were analyzed using an automated method, and differences between NCPAP and HFNC features and changes in FiO(2) were analyzed. RESULTS: A total of 30 infants with median [interquartile range] gestational age of 27 weeks [25.7, 27.9] and birth weight of 930 g [780, 1090] were studied. Infants were extubated at 5 days [2, 13] of life with 973 g [880, 1170] and three failed (10%). No differences in cardiorespiratory behavior were noted, except for longer respiratory pauses (9.2 s [5.0, 11.5] vs. 7.3 s [4.6, 9.3]; p = 0.04) and higher FiO(2) levels (p = 0.02) during HFNC compared to NCPAP. CONCLUSIONS: In extremely preterm infants studied shortly after extubation, the use of HFNC was associated with longer respiratory pauses and higher FiO(2) requirements."
968,ECLS-associated infections in adults: what we know and what we don’t yet know,"Extracorporeal life support (ECLS) is increasingly used in the management of patients with severe cardiopulmonary disease. Infections are frequently the etiologies underlying the respiratory, and occasionally cardiac, failure that necessitates ECLS. Just as importantly, infections are among the most commonly reported adverse events during ECLS. Infections in this setting may be the sequelae of prolonged critical illness or of underlying immune dysregulation; they may be hospital-acquired infections, and they may or may not be attributable to the presence of ECLS itself, the latter being an aspect that can be difficult to determine. Current registry data and evidence from the literature offer some insights, but also leave open many questions regarding the nature and significance of infections reported both before and during ECLS, including the question of any causal link between ECLS and the development of infections. An ongoing lack of consistency in the identification, diagnosis, management, and prevention of infections during ECLS is limiting our ability to interpret literature data and thus highlighting the need for more rigorous investigation and standardization of definitions. This review aims to characterize the current understanding of infections associated with the use of ECLS, taking into account data from the updated Extracorporeal Life Support Organization Registry, which provides important context for understanding the epidemiology and outcomes of these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05847-z) contains supplementary material, which is available to authorized users."
969,Does additional coronary artery bypass grafting to aortic valve replacement in elderly patients affect the early and long-term outcome?,"Early and long-term outcomes in elderly patients who underwent isolated aortic valve replacement (iAVR) are well defined. Conflicting data exist in elderly patients who underwent AVR plus coronary artery bypass grafting (CABG). We sought to evaluate the early and long-term outcomes of combined AVR + CABG in patients older than 75 years of age. From June 1999 to June 2018, 402 patients ≥ 75 years who underwent iAVR (n = 200; 49.7%) or combined AVR plus CABG (n = 202; 50.3%) were retrospectively analysed. AVR + CABG patients were older than iAVR patients (78.5 ± 2.5 vs 77.6 ± 2.8 years; p < 0.0001), with greater co-morbidities and more urgent/emergency surgery. 30-day mortality was 6.5% in the AVR + CABG and 4.5% in the iAVR group (p = 0.38). Multivariate analysis identified EuroSCORE II [odd ratio (OR) 1.13] postoperative stroke (OR 12.53), postoperative low cardiac output syndrome (OR 8.72) and postoperative mechanical ventilation > 48 h (OR 8.92) as independent predictors of 30-day mortality; preoperative cerebrovascular events (OR 3.43), creatinine (OR 7.27) and extracorporeal circulation time (OR 1.01) were independent predictors of in-hospital major adverse cardiovascular and cerebral events (MACCE). Treatment was not an independent predictor of 30-day mortality and in-hospital MACCE. Survival at 1, 5 and 10 years was 94.7 ± 1.6%, 72.6 ± 3.6% and 31.7 ± 4.8% for iAVR patients and 89.1 ± 2.3%, 73.9 ± 3.5% and 37.2 ± 4.8% for AVR + CABG subjects (p = 0.99). Using adjusted Cox regression model, creatinine [hazard ration (HR) 1.50; p = 0.018], COPD (HR 1.97; p = 0.003) and NYHA class (HR 1.39; p < 0.0001) were independent predictors of late mortality; the combined AVR + CABG was not associated with increased risk of late mortality (HR 0.83; p = 0.30). In patients aged ≥ 75 years, combined AVR + CABG was not associated with increased 30-day mortality, in-hospital MACCE and long-term mortality. Surgical revascularization can be safely undertaken at the time of AVR in elderly patients."
970,Spinal-cardiac crosstalk,
971,Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability,"PURPOSE: Exome and genome sequencing (ES/GS) are performed frequently in patients with congenital anomalies, developmental delay, or intellectual disability (CA/DD/ID), but the impact of results from ES/GS on clinical management and patient outcomes is not well characterized. A systematic evidence review (SER) can support future evidence-based guideline development for use of ES/GS in this patient population. METHODS: We undertook an SER to identify primary literature from January 2007 to March 2019 describing health, clinical, reproductive, and psychosocial outcomes resulting from ES/GS in patients with CA/DD/ID. A narrative synthesis of results was performed. RESULTS: We retrieved 2654 publications for full-text review from 7178 articles. Only 167 articles met our inclusion criteria, and these were primarily case reports or small case series of fewer than 20 patients. The most frequently reported outcomes from ES/GS were changes to clinical management or reproductive decision-making. Two studies reported on the reduction of mortality or morbidity or impact on quality of life following ES/GS. CONCLUSION: There is evidence that ES/GS for patients with CA/DD/ID informs clinical and reproductive decision-making, which could lead to improved outcomes for patients and their family members. Further research is needed to generate evidence regarding health outcomes to inform robust guidelines regarding ES/GS in the care of patients with CA/DD/ID."
972,Racial Disparity in 30-Day Outcomes of Metabolic and Bariatric Surgery,"BACKGROUND: There is evidence of racial disparity in the long-term weight loss outcomes of bariatric surgery. However, there has been a more limited evaluation of the impact of race on immediate perioperative outcomes. The aim of this study was to compare 30-day postoperative outcomes among different races. STUDY DESIGN: The 2016 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried to identify patients aged ≥ 18 and body mass index ≥ 35 who underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) with known information on race. We then evaluated the effect of five different races on four different 30-day outcomes. RESULTS: Of the total 106,932 patients (79.5% White, 19.3% African American (AA), 0.5% Asian, 0.4% American Indian or Alaska Native, 0.3% Native Hawaiian or other Pacific Islander), 30-day rates of postoperative complication, readmission, re-intervention, and reoperation were 6, 3.8, 1.3, and 1.2%, respectively. After controlling for other covariates in multivariate logistic regression and selecting White as reference, AA was the only race associated with a higher risk of postoperative complications (odds ratio [OR] 1.13; confidence interval [CI] 1.06–1.2) and readmissions (OR 1.47; CI 1.3–1.6). AA and American Indian or Alaska Native were also associated with higher re-interventions (OR 1.31; CI 1.15–1.51 and OR 2.11; CI 1.03–4.34). Furthermore, AA was associated with lower 30-day reoperations (OR 0.83; CI 0.7–0.9). CONCLUSION: This study found significant racial differences in short-term outcomes following bariatric surgery. Factors underlying these disparities are unclear and warrant further investigation."
973,Sepsis-Induced Cardiomyopathy: a Comprehensive Review,"PURPOSE OF REVIEW: To briefly review epidemiology and pathophysiology of SICM and provide a more extensive review of the data on diagnostic and management strategies. RECENT FINDINGS: SICM is likely underdiagnosed and that has mortality implications. Current evidence supports speckle tracking echocardiography to identify decreased contractility irrespective of left ventricular ejection fraction for the diagnosis of SICM. There continues to be a dearth of large clinical trials evaluating the treatment of SICM and current consensus focuses on supportive measures such as vasopressors and inotropes. SUMMARY: Sepsis is a significant cause of mortality, and sepsis-induced cardiomyopathy has both prognostic and management implications for these patients. Individualized work-up and management of these patients is crucial to improving outcomes."
974,Inter-country variability over time in the mortality of mechanically ventilated patients,"PURPOSE: Variations in clinical characteristics and management and in the mortality of mechanically ventilated patients have not been sufficiently evaluated. We hypothesized that mortality shows a variability associated with country after adjustment for clinical characteristics and management. METHODS: Analysis of four studies carried out at 6-year intervals over an 18-year period. The studies included 26,024 patients (5183 in 1998, 4968 in 2004, 8108 in 2010, and 7765 in 2016) admitted to 1253 units from 38 countries. The primary outcome was 28-day mortality. We performed analyses using multilevel logistic modeling with mixed-random effects, including country as a random variable. To evaluate the effect of management strategies on mortality, a mediation analysis was performed. RESULTS: Adjusted 28-day mortality decreased significantly over time (first study as reference): 2004: odds ratio 0.82 (95% confidence interval [CI] 0.72–0.93); 2010: 0.63 (95% CI 0.53–0.75); 2016: 0.49 (95% CI 0.39–0.61). A protective ventilatory strategy and the use of continuous sedation mediated a moderate fraction of the effect of time on mortality in patients with moderate hypoxemia and without hypoxemia, respectively. Logistic multilevel modeling showed a significant effect of country on mortality: median odds ratio (MOR) in 1998: 2.02 (95% CI 1.57–2.48); in 2004: 1.76 (95% CI 1.47–2.06); in 2010: 1.55 (95% CI 1.37–1.74), and in 2016: 1.39 (95% CI 1.25–1.54). CONCLUSIONS: These findings suggest that country could contribute, independently of confounder variables, to outcome. The magnitude of the effect of country decreased over time. Clinical trials registered with http://www.clinicaltrials.gov (NCT02731898). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05867-9) contains supplementary material, which is available to authorized users."
975,The effect of patent ductus arteriosus on coronary artery blood flow in premature infants: a prospective observational pilot study,"OBJECTIVE: To compare coronary flows between premature infants with and without hemodynamically significant patent ductus arteriosus (hsPDA) and to determine if coronary flow is influenced by medical PDA treatment. DESIGN: Prospective, observational pilot study. Forty-three infants <32 weeks gestation underwent echocardiography when routinely indicated. Study group included infants with hsPDA requiring treatment. Comparison groups included infants with nonsignificant PDA and infants without PDA. RESULTS: The study group (n = 13), compared with the comparison groups with nonsignificant PDA (n = 12) and without PDA (n = 18) had higher troponin levels (p = 0.003 and 0.004, respectively). In infants with hsPDA compared with infants with no PDA there was a significant increase in myocardial oxygen demand and decrease in left main coronary artery flow, with nonsignificant increase in cardiac output. CONCLUSIONS: Decrease in coronary artery flows and higher troponin values may suggest a “steal effect,” not allowing to meet the elevated myocardial oxygen demand in infants with hsPDA."
976,Effect of early cognitive interventions on delirium in critically ill patients: a systematic review,"PURPOSE: A systematic review of the literature was conducted to determine the effects of early cognitive interventions on delirium outcomes in critically ill patients. SOURCE: Search strategies were developed for MEDLINE, EMBASE, Joanna Briggs Institute, Cochrane, Scopus, and CINAHL databases. Eligible studies described the application of early cognitive interventions for delirium prevention or treatment within any intensive care setting. Study designs included randomized-controlled trials, quasi-experimental trials, and pre/post interventional trials. Two reviewers independently extracted data and assessed risk of bias using Cochrane methodology. PRINCIPAL FINDINGS: Four hundred and four citations were found. Seven full-text articles were included in the final review. Six of the included studies had an overall serious, high, or critical risk of bias. After application of cognitive intervention protocols, a significant reduction in delirium incidence, duration, occurrence, and development was found in four studies. Feasibility of cognitive interventions was measured in three studies. Cognitive stimulation techniques were described in the majority of studies. CONCLUSION: The study of early cognitive interventions in critically ill patients was identified in a small number of studies with limited sample sizes. An overall high risk of bias and variability within protocols limit the utility of the findings for widespread practice implications. This review may help to promote future large, multi-centre trials studying the addition of cognitive interventions to current delirium prevention practices. The need for robust data is essential to support the implementation of early cognitive interventions protocols."
977,Treatment of ventilator-associated pneumonia (VAP) caused by Acinetobacter: results of prospective and multicenter ID-IRI study,"Ventilator-associated pneumonia (VAP) due to Acinetobacter spp. is one of the most common infections in the intensive care unit. Hence, we performed this prospective-observational multicenter study, and described the course and outcome of the disease. This study was performed in 24 centers between January 06, 2014, and December 02, 2016. The patients were evaluated at time of pneumonia diagnosis, when culture results were available, and at 72 h, at the 7th day, and finally at the 28th day of follow-up. Patients with coexistent infections were excluded and only those with a first VAP episode were enrolled. Logistic regression analysis was performed. A total of 177 patients were included; empiric antimicrobial therapy was appropriate (when the patient received at least one antibiotic that the infecting strain was ultimately shown to be susceptible) in only 69 (39%) patients. During the 28-day period, antibiotics were modified for side effects in 27 (15.2%) patients and renal dose adjustment was made in 38 (21.5%). Ultimately, 89 (50.3%) patients died. Predictors of mortality were creatinine level (OR, 1.84 (95% CI 1.279–2.657); p = 0.001), fever (OR, 0.663 (95% CI 0.454–0.967); p = 0.033), malignancy (OR, 7.095 (95% CI 2.142–23.500); p = 0.001), congestive heart failure (OR, 2.341 (95% CI 1.046–5.239); p = 0.038), appropriate empiric antimicrobial treatment (OR, 0.445 (95% CI 0.216–0.914); p = 0.027), and surgery in the last month (OR, 0.137 (95% CI 0.037–0.499); p = 0.003). Appropriate empiric antimicrobial treatment in VAP due to Acinetobacter spp. was associated with survival while renal injury and comorbid conditions increased mortality. Hence, early diagnosis and appropriate antibiotic therapy remain crucial to improve outcomes."
978,Utility of echocardiography in predicting mortality in infants with severe bronchopulmonary dysplasia,"OBJECTIVE: To determine the relationship between interventricular septal position (SP) and right ventricular systolic pressure (RVSP) and mortality in infants with severe BPD (sBPD). STUDY DESIGN: Infants with sBPD in the Children’s Hospitals Neonatal Database who had echocardiograms 34–44 weeks’ postmenstrual age (PMA) were included. SP and RVSP were categorized normal, abnormal (flattened/bowed SP or RVSP > 40 mmHg) or missing. RESULTS: Of 1157 infants, 115 infants (10%) died. Abnormal SP or RVSP increased mortality (SP 19% vs. 8% normal/missing, RVSP 20% vs. 9% normal/missing, both p < 0.01) in unadjusted and multivariable models, adjusted for significant covariates (SP OR 1.9, 95% CI 1.2–3.0; RVSP OR 2.2, 95% CI 1.1–4.7). Abnormal parameters had high specificity (SP 82%; RVSP 94%), and negative predictive value (SP 94%, NPV 91%) for mortality. CONCLUSIONS: Abnormal SP or RVSP is independently associated with mortality in sBPD infants. Negative predictive values distinguish infants most likely to survive."
979,Peptide Phage Display: Molecular Principles and Biomedical Applications,"Phage display (PD) is a technology based on the presentation of functional exogenous peptides on the capsid surface of bacteriophages. PD is performed by introducing a DNA sequence of interest at a specific position within a functional viral gene. In addition, peptide phage libraries are powerful tools for expressing a wide range of random peptides and for specific peptide screening. Specifically, PD applications include the analysis of binding and interactions between proteins, the identification of bioactive peptides that bind to receptors, the identification of disease-associated antigens, and the identification of cell-specific peptides. Since its emergence, PD technology has revolutionized several fields in the biological sciences, such as oncology, cell biology, and pharmacology, the innumerable applications for which will be described throughout this review."
980,Correction to: Ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: understanding nebulization of aminoglycosides and colistin,
981,Respiratory outcomes of late preterm infants of mothers with early and late onset preeclampsia,"OBJECTIVE: To study the effect of early and late onset preeclampsia (EOPE, LOPE, respectively) on outcomes of late preterm infants. STUDY DESIGN: Cohort study of late preterm infants admitted to a tertiary care NICU from January 2014–July 2015. Outcomes of late preterm infants of EOPE mothers were compared with the next late preterm infant of a LOPE mother and the next two late preterm infants of normotensive non-PE mothers. Primary outcome comprised use of continuous positive airway pressure, mechanical ventilation and/or surfactant in the 24 h after birth. RESULTS: Compared to normotensives (n = 131), adjusted odds ratio (AORs) of the primary outcome was higher in the EOPE (n = 64) and LOPE (n = 65) groups but reached statistical significance only in the EOPE group, AORs 12.9, 95% CI 3.5–37 and 2.7, 95% CI 0.95–8.1, respectively. CONCLUSIONS: Compared to late preterm infants of normotensive and LOPE mothers, infants of mothers with EOPE have significantly higher respiratory morbidity."
982,Do not drink and lyse: alcohol intoxication increases fibrinolysis shutdown in injured patients,"INTRODUCTION: High alcohol consumption has been associated with decreased fibrinolysis and enhanced thrombosis risk in cardiovascular disease. In trauma, alcohol has been associated with poor clot formation; however, its effect on fibrinolysis has not been fully investigated. We assessed the association of blood alcohol levels and fibrinolysis in trauma activation patients. METHODS: We queried our prospective registry of trauma activations from 2014 to 2016. Associations between viscoelastic measurements [rapid thrombelastography (rTEG)] and blood alcohol level (BAL) were determined and adjusted for confounders by a multinomial logistic regression. Lysis phenotypes were defined by the % lysis in 30 min (LY30) as follows: hyperfibrinolysis ≥ 3%, physiologic 0.9–2.9%, and fibrinolysis shutdown < 0.9%. RESULTS: Overall, 191 (43.8%) had BAL measured. There were 65 (34%) patients that had no detectable BAL, 32 (16.8%) had BAL of 10–150 mg/dL, and 94 (49.2%) patients had BAL > 150 mg/dL. BAL had a moderate, but significant inverse correlation with LY30 (Rho = − 0.315, p < 0.001), while there were no significant correlations between BAL and other TEG values. The distribution of fibrinolysis phenotypes varied significantly by BAL levels (p < 0.009, with high BAL having more shutdown and less hyperfibrinolysis than the other two BAL level groups. Multinomial logistic regression showed that after adjustment for confounders, BAL levels > 150 mg/dL were independently associated with a threefold increase in the odds of shutdown compared to undetectable BAL (OR 3.37, 95% CI 1.04–8.05, p = 0.006). High BAL was also significantly associated with higher odds of shutdown compared to low BAL (OR 2.63, 95% CI 1.15–6.06). Compared to physiologic fibrinolysis, fibrinolysis shutdown was associated with increased mortality (OR 2.87, 95% CI 1.41–5.83) and VFD < 28 (OR 2.54, 95% CI 1.47–4.39). CONCLUSION: In the injured patient, high blood alcohol levels are associated with increased incidence of fibrinolysis shutdown. This finding has implications for postinjury hemostatic resuscitation as these patients may be harmed by anti-fibrinolytics. Further research is needed to assess whether the association with fibrinolysis is modified by the chronicity and type of alcohol consumed and whether anti-fibrinolytic therapy in intoxicated patients produces adverse effects."
983,A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age,"Raine Syndrome (RS) is caused by biallelic loss-of-function mutations in FAM20C gene and characterized by hypophosphatemia, typical facial and skeletal features. Subperiosteal bone formation and generalized osteosclerosis are the most common radiological findings. Here we present a new case with RS. A 9-month-old male patient on a home-type ventilator was referred for hypophosphatemia. He was born with a weight of 3800 g to non-consanguineous parents. Prenatal ultrasound had demonstrated nasal bone agenesis. A large anterior fontanel, frontal bossing, exophthalmos, hypoplastic nose, high arched palate, low set ears, triangular mouth, and corneal opacification were detected on physical examination. Serial skeletal X-rays revealed diffuse osteosclerosis at birth which was gradually decreased by the age of 5 months with subperiosteal undermineralized bone formation and medullary space of long bone could be distinguishable with bone-within-a-bone appearance. At 9 months of age, hand X-ray revealed cupping of the ulna with loose radial bone margin with minimal fraying and osteopenia. Cranial computed tomography scan showed bilateral periventricular calcification and hydrocephalus in progress. The clinical, laboratory, and radiological examinations were consistent with RS. Molecular analyses revealed a compound heterozygous mutation in FAM20C gene (a known pathogenic mutation, c.1645C > T, p.Arg549Trp; and a novel c.863 + 5 G > C variant). The patient died due to respiratory failure at 17 months of age. This case allowed us to demonstrate natural progression of skeletal features in RS. Furthermore, we have described a novel FAM20C variant causing RS. Previous literature on RS is also reviewed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00223-020-00694-3) contains supplementary material, which is available to authorized users."
984,Coupling the Macroscale to the Microscale in a Spatiotemporal Context to Examine Effects of Spatial Diffusion on Disease Transmission,"There are many challenges to coupling the macroscale to the microscale in temporal or spatial contexts. In order to examine effects of an individual movement and spatial control measures on a disease outbreak, we developed a multiscale model and extended the semi-stochastic simulation method by linking individual movements to pathogen’s diffusion, linking the slow dynamics for disease transmission at the population level to the fast dynamics for pathogen shedding/excretion at the individual level. Numerical simulations indicate that during a disease outbreak individuals with the same infection status show the property of clustering and, in particular, individuals’ rapid movements lead to an increase in the average reproduction number [Formula: see text] , the final size and the peak value of the outbreak. It is interesting that a high level of aggregation the individuals’ movement results in low new infections and a small final size of the infected population. Further, we obtained that either high diffusion rate of the pathogen or frequent environmental clearance lead to a decline in the total number of infected individuals, indicating the need for control measures such as improving air circulation or environmental hygiene. We found that the level of spatial heterogeneity when implementing control greatly affects the control efficacy, and in particular, an uniform isolation strategy leads to low a final size and small peak, compared with local measures, indicating that a large-scale isolation strategy with frequent clearance of the environment is beneficial for disease control."
985,"Effects of oropharyngeal administration of colostrum on the incidence of necrotizing enterocolitis, late-onset sepsis, and death in preterm infants: a meta-analysis of RCTs","Necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) are two major contributors to death among preterm infants. Oropharyngeal administration of colostrum (OAC) has been proved as an easy, safe, and economically viable technique to help preterm neonates to build up their immunity. In this review, we assessed the effects of OAC on preterm infants. Several mainstream databases were searched including PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and a website of clinical trials. Randomized controlled trials (RCTs) comparing OAC vs. placebo or no intervention in preterm infants (gestation age <34 weeks or birth weight <1500 g) were eligible. Overall, nine RCTs (n = 689) were included in the review. Meta-analysis showed no statistical significance in terms of the incidence of NEC (RR = 0.59, 95% CI = 0.33–1.06, p = 0.08), LOS (RR = 0.78, 95% CI = 0.60–1.03, p = 0.08) and mortality rate (RR = 0.63, 95% CI = 0.38–1.05, p = 0.07). No significant difference was found in the subgroup analysis, apart from the group of the undeveloped region in NEC and mortality. In addition, time was significantly reduced in terms of achieving full enteral feeding (MD = −3.60, 95% CI = −6.55–0.64, p = 0.02) and hospital stay (MD = −10.38, 95% CI = −18.47–2.29, p = 0.01). The results show that OAC does not reduce the incidences of NEC, LOS, and death in preterm infants, but there is a trend toward a positive effect. It is therefore recommended as routine care for preterm infants in the NICU."
986,Ionizing Radiation Exposure in NICU,"The authors prospectively studied ionizing radiation exposure in consecutive 107 very low birth weight (VLBW) neonates, admitted to their Level III neonatal intensive care unit (NICU). Number of X-rays, their indications and calculated dose of radiation were documented. Their mean birth weight (+SD) and gestational age (+SD) were 1077 (±219.8) g and 29.7 (+2.57) wk respectively. Extremely low birth weight (ELBW) neonates underwent significantly higher radiographs when compared with VLBW neonates; 7.5(5–13.25) vs. 2(1–6); p < 0.0001. ELBW neonates received 3 times higher dose of radiation, when compared with VLBW neonates; 139.4 μsv (81.6–256.15) vs. 46.6 μsv (14.4–115.7); p < 0.0001. Seven percent of ELBW neonates received >1msv radiation. Lifetime risk associated with high radiation exposure during neonatal period is unknown. Every effort should be taken to reduce number of radiographs. Imaging modalities without radiation exposure such as, point of care ultrasound should be used wherever possible."
987,The Role of Networks in Racial Disparities in HIV Incidence Among Men Who Have Sex with Men in the United States,"Network factors have been proposed as potential drivers of racial disparities in HIV among Black and Latino men who have sex with men (MSM). This review aimed to synthesize the extant literature on networks and racial disparities in HIV among MSM and identify potential directions for future research. We searched databases for peer-reviewed articles published between January 1, 2008 and July 1, 2018. Articles were included if the sample was comprised primarily of racial/ethnic minority MSM and measured one or more network characteristics. (n = 25). HIV prevalence in networks, social support, and structural barriers were linked to disparities in HIV for Black MSM. Future research should focus on intervention development around social support and other strategies for risk reduction within networks. Given the contribution of structural factors to racial/ethnic HIV disparities, network-level interventions should be paired with policies that improve access to housing, jobs, and education for MSM."
988,Characterization of the highly immunogenic VP2 protrusion domain as a diagnostic antigen for members of Birnaviridae family,"Birnaviridae is a family of viruses (birnaviruses) which consists of four genera, members of which cause diseases in fish, birds, mollusks, and insects. The genome of birnaviruses encodes the highly immunogenic VP2 capsid protein. In order to demonstrate that the VP2 protein can be exploited as a diagnostic antigen for birnaviruses, we developed a lateral flow assay based on the surface-exposed VP2 protrusion domain of a representative birnavirus, infectious bursal disease virus (IBDV) of serotype 1 which causes the highly devastating infectious bursal disease in chickens. The biophysical characterization of the purified domain reveals that the domain predominantly consists of β-sheets, exists in a trimeric form, and remains folded at high temperatures, making it suitable for diagnostic purposes. Owing to its highly immunogenic nature and excellent biophysical properties, we employed the VP2 protrusion domain in a gold nanoparticle-based lateral flow assay for rapid detection of anti-IBDV antibodies in serum samples of infected chickens. Our results indicate that the domain binds anti-IBDV antibodies with high specificity during laboratory testing and on-site testing. The lateral flow assay reported here yields comparable results in a qualitative manner as obtained through a commercial enzyme-linked immunosorbent assay (ELISA). As VP2 is a common capsid protein of birnaviruses, the lateral flow assay can be generalized for other birnaviruses, and members of Tetraviridae and Nodaviridae families which contain homologous VP2 capsid proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-020-10458-6) contains supplementary material, which is available to authorized users."
989,"Whole-Transcriptome Analysis of Dermal Fibroblasts, Derived from Three Pairs of Monozygotic Twins, Discordant for Parkinson’s Disease","Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. In most cases, the development of the disease is sporadic and is not associated with any currently known mutations associated with PD. It is believed that changes associated with the epigenetic regulation of gene expression may play an important role in the pathogenesis of this disease. The study of individuals with an almost identical genetic background, such as monozygotic twins, is one of the best approaches to the analysis of such changes. A whole-transcriptome analysis of dermal fibroblasts obtained from three pairs of monozygotic twins discordant for PD was carried out in this work. Twenty-nine differentially expressed genes were identified in the three pairs of twins. These genes were included in seven processes within two clusters, according to the results of an enrichment analysis. The cluster with the greatest statistical significance included processes associated with the regulation of the differentiation of fat cells, the action potential, and the regulation of glutamatergic synaptic transmission. The most significant genes, which occupied a central position in this cluster, were PTGS2, SCN9A, and GRIK2. These genes can be considered as potential candidate genes for PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12031-019-01452-3) contains supplementary material, which is available to authorized users."
990,Current understanding of the therapeutic benefits of mesenchymal stem cells in acute respiratory distress syndrome,"The acute respiratory distress syndrome (ARDS) is a multifaceted lung disorder in which no specific therapeutic intervention is able to effectively improve clinical outcomes. Despite an improved understanding of molecular mechanisms and advances in supportive care strategies, ARDS remains associated with high mortality, and survivors usually face long-term morbidity. In recent years, preclinical studies have provided mounting evidence of the potential of mesenchymal stem cell (MSC)-based therapies in lung diseases and critical illnesses. In several models of ARDS, MSCs have been demonstrated to induce anti-inflammatory and anti-apoptotic effects, improve epithelial and endothelial cell recovery, and enhance microbial and alveolar fluid clearance, thus resulting in improved lung and distal organ function and survival. Early-stage clinical trials have also demonstrated the safety of MSC administration in patients with ARDS, but further, large-scale investigations are required to assess the safety and efficacy profile of these therapies. In this review, we summarize the main mechanisms whereby MSCs have been shown to exert therapeutic effects in experimental ARDS. We also highlight questions that need to be further elucidated and barriers that must be overcome in order to efficiently translate MSC research into clinical practice."
991,Impact of Sleep Deprivation in the Neurological Intensive Care Unit: A Narrative Review,"Sleep is fundamental for everyday functioning, yet it is often negatively impacted in critically ill patients by the intensive care setting. With a focus on the neurological intensive care unit (NeuroICU), this narrative review summarizes methods of measuring sleep and addresses common causes of sleep disturbance in the hospital including environmental, pharmacological, and patient-related factors. The effects of sleep deprivation on the cardiovascular, pulmonary, immune, endocrine, and neuropsychological systems are discussed, with a focus on short-term deprivation in critically ill populations. Where evidence is lacking in the literature, long-term sleep deprivation studies and the effects of sleep deprivation in healthy individuals are also referenced. Lastly, strategies for the promotion of sleep in the NeuroICU are presented."
992,"Neurological Manifestations of Influenza A (H1N1): Clinical Features, Intensive Care Needs, and Outcome","OBJECTIVES: To describe neurological manifestations in children with Influenza A (H1N1). METHODS: This retrospective study was conducted in the Pediatric intensive care unit (PICU) and Pediatric Neurology unit of a tertiary care teaching hospital in North India involving children with PCR confirmed Influenza A (H1N1) with neurological manifestations during 2019 outbreak. RESULTS: Six children (5 females, 1 male) were enrolled. All presented with neurological symptoms (seizures and altered sensorium) accompanied with fever and respiratory symptoms with duration of illness of 2–7 d. The admission Glasgow Coma Scale ranged from 4 to 12. Only 2 cases showed cerebrospinal fluid pleocytosis. Neuroimaging was suggestive of diffuse cerebral edema, acute necrotizing encephalopathy of childhood, and acute disseminated encephalomyelitis. All were treated with Oseltamivir. Four cases had clinical features of raised intracranial pressure (ICP) and were managed in PICU, 3 of them needed mechanical ventilation, 3 needed vasoactive drugs, 3 received 3% saline infusion, 1 underwent invasive ICP monitoring, and 3 (cases 4, 5 and 6) received intravenous methylprednisolone (30 mg/kg) for 5 d. Total duration of hospital stay was 10–30 d. Case 2 expired due to refractory raised ICP. Among survivors, 3 children had residual neurological deficits and the remaining 2 had achieved premorbid condition. CONCLUSIONS: Influenza A (H1N1) can present with isolated or predominant neurological manifestations which can contribute to poor outcome. The authors suggest to rule out H1N1 in any child who presents with unexplained neurological manifestations during seasonal outbreaks of H1N1."
993,Semi-quantitative cultures of throat and rectal swabs are efficient tests to predict ESBL-Enterobacterales ventilator-associated pneumonia in mechanically ventilated ESBL carriers,"PURPOSE: In ICU patients with carriage of extended spectrum beta-lactamase producing Enterobacterales (ESBL-E) and suspected Gram-negative bacilli ventilator-associated pneumonia (GNB-VAP), the quantification of the rectal and throat ESBL-E carriage might predict the ESBL-E involvement in GNB-VAP. Our aim was to evaluate whether a semi-quantitative assessment of rectal/throat ESBL-E carriage can predict ESBL-E-associated VAP in medical ICU patients. METHODS: From May 2014 to May 2017, all ESBL-E carriers had a semi-quantitative assessment of ESBL-E density in swabs cultures. For those who developed GNB-VAP (diagnosed using bronchoalveolar lavage or plugged telescopic catheter with significant quantitative culture), the last positive swab collected at least 48 h before GNB-VAP onset was selected. Clinical data were extracted from a prospectively collected database. RESULTS: Among 365 ESBL-E carriers, 82 developed 107 episodes of GNB-VAP (ESBL-E VAP, n = 50; and non-ESBL-E GNB-VAP, n = 57) after 13 days of mechanical ventilation in median. Antimicrobials use before VAP onset was similar between groups. The last swabs were collected 5 days in median before VAP onset. ESBL-E. coli carriers developed ESBL-E VAP less frequently (n = 13, 34%) than others (n = 32, 67.3%, p < .01). Throat swab positivity (39 (78%) vs. 12 (23%), p < .01) was more frequent for ESBL-E VAP. ESBL-E VAP was associated with significantly higher ESBL-E density in rectal swabs. In multivariate models, non-E. coli ESBL-E carriage and rectal ESBL-E carriage density, or throat carriage, remained associated with ESBL-E VAP. CONCLUSION: In carriers of ESBL-E other than E. coli, ESBL-E throat carriage or a high-density ESBL-E rectal carriage are risk factors of ESBL-E VAP in case of GNB-VAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06029-y) contains supplementary material, which is available to authorized users."
994,Prolonged Outbreak of Candida krusei Candidemia in Paediatric Ward of Tertiary Care Hospital,"BACKGROUND: A sudden rise of Candida krusei candidemia cases was noticed in our hospital within 1 year with maximum cases from paediatric unit. The present study reports the results of epidemiological investigation of possible outbreak of candidemia by C. krusei in paediatric unit at our tertiary care centre. METHODS: Clinical characteristics and risk factors associated with C. krusei candidemia were evaluated. Yeast identification and antifungal susceptibility testing was performed according to standard protocol. To find the potential source of C. krusei in hospital environment and hand colonization, swabs were collected from different fomites (n = 40) and hand washings from 24 health care workers (HCW), respectively. Infection control and prevention practices were intensified following the recognition of outbreak. Genetic typing was done by fluorescent amplified fragment length polymorphism (FAFLP) technique. Case–control comparison was performed with C. tropicalis and C. pelliculosa cases. RESULTS: Candida krusei fungaemia significantly affected paediatric group (82/186, 44%) as compared to adults (14/130, 10.8%; p < 0.001). Among paediatric group, maximum isolation was reported from neonatal unit of paediatric emergency (NUPE). C. krusei was isolated from hands of one HCW and washbasin in NUPE. FAFLP revealed clonality between blood and environmental isolates indicating cross-transmission of C. krusei. Gastrointestinal disease (p = 0.018), previous antibiotics (p = 0.021) especially to carbapenems (p = 0.039), was significant among C. krusei candidemia cases compared to C. pelliculosa cases. CONCLUSION: We report the largest outbreak of C. krusei candidemia in paediatric unit within 1 year with isolation of related strains from environment and hands of HCW. Routine screening of hand hygiene practices revealed non-compliance to standard practices leading to the increase in C. krusei candidemia cases."
995,Recombination Between High-Risk Human Papillomaviruses and Non-Human Primate Papillomaviruses: Evidence of Ancient Host Switching Among Alphapapillomaviruses,"We use all the currently known 405 Papillomavirus (PV) sequences, 343 curated PV sequences from both humans and animals from the PAVE data base, to analyse the recombination dynamics of these viruses at the whole genome levels. After showing some evidence of human and non-human primate PV recombination, we report a comprehensive recombination analysis of all currently known 82 Alphapapillomaviruses (Alpha-PVs). We carried out an exploratory study and found novel recombination events between High-Risk HPV Types and Macaca fascicularis PV1 (MfPV1), Macaca Fuscata PV2 (MfuPV2) and Pan Paniscus PV1 (PpPV1) Papillomaviruses. This is the first evidence of interactions between PVs from different hosts and hence postulates the likelihood of ancient host switching among Alpha-PVs. Notwithstanding these results should be interpreted with caution because the major and minor parents indicated by RDP4 program are simply the sequences in the alignment that most closely resemble the actual parents. We found statistically significant differences between the phylogenies of the PV sequences with recombination regions and PV sequences without recombination regions using the Shimodaira–Hasegawa phylogenetic incongruence testing. We show that not more than 76MYA Alpha-PVs were in the same biological niche, a pre-requisite for recombination, and as the hosts evolved and diversified, the viruses adapted to specific host niches which eventually led to coevolution with specific hosts before speciation of primate species. Thus providing evidence that in ancient times no earlier than the Cretaceous period of the Mesozoic age, Alpha-PVs recombined and switched hosts, but whether this host switching is occurring currently is unknown. However, a clearer picture of the PVs evolutionary landscape can only be achieved with the incremental discovery of PV sequences, especially from the animal kingdom. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00239-020-09946-0) contains supplementary material, which is available to authorized users."
996,Junctional and somatic hypermutation-induced CX(4)C motif is critical for the recognition of a highly conserved epitope on HCV E2 by a human broadly neutralizing antibody,"Induction of broadly neutralizing monoclonal antibodies (bNAbs) that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus (HCV) vaccine research. The study of bNAbs arising in natural infection is essential in this endeavor. We generated a human antibody, 8D6, recognizing the E2 protein of HCV isolated from a chronic hepatitis C patient. This antibody shows broadly neutralizing activity, which covers a pan-genotypic panel of cell culture-derived HCV virions (HCVcc). Functional and epitope analyses demonstrated that 8D6 can block the interaction between E2 and CD81 by targeting a highly conserved epitope on E2. We describe how the 8D6 lineage evolved via somatic hypermutation to achieve broad neutralization. We found that the V(D)J recombination-generated junctional and somatic hypermutation-induced disulfide bridge (C-C) motif in the CDRH3 is critical for the broad neutralization and binding activity of 8D6. This motif is conserved among a series of broadly neutralizing HCV antibodies, indicating a common binding model. Next, the 8D6 inferred germline (iGL) was reconstructed and tested for its binding affinity and neutralization activity. Interestingly, 8D6 iGL-mediated relatively strong inhibition of the 1b genotype PR79L9 strain, suggesting that PR79L9 may serve as a potential natural viral strain that provides E2 sequences that induce bNAbs. Overall, our detailed epitope mapping and genetic studies of the HCV E2-specific mAb 8D6 have allowed for further refinement of antigenic sites on E2 and reveal a new mechanism to generate a functional CDRH3, while its iGL can serve as a probe to identify potential HCV vaccine strains."
997,Developing metrics for nursing quality of care for low- and middle-income countries: a scoping review linked to stakeholder engagement,"BACKGROUND: The use of appropriate and relevant nurse-sensitive indicators provides an opportunity to demonstrate the unique contributions of nurses to patient outcomes. The aim of this work was to develop relevant metrics to assess the quality of nursing care in low- and middle-income countries (LMICs) where they are scarce. MAIN BODY: We conducted a scoping review using EMBASE, CINAHL and MEDLINE databases of studies published in English focused on quality nursing care and with identified measurement methods. Indicators identified were reviewed by a diverse panel of nursing stakeholders in Kenya to develop a contextually appropriate set of nurse-sensitive indicators for Kenyan hospitals specific to the five major inpatient disciplines. We extracted data on study characteristics, nursing indicators reported, location and the tools used. A total of 23 articles quantifying the quality of nursing care services met the inclusion criteria. All studies identified were from high-income countries. Pooled together, 159 indicators were reported in the reviewed studies with 25 identified as the most commonly reported. Through the stakeholder consultative process, 52 nurse-sensitive indicators were recommended for Kenyan hospitals. CONCLUSIONS: Although nurse-sensitive indicators are increasingly used in high-income countries to improve quality of care, there is a wide heterogeneity in the way indicators are defined and interpreted. Whilst some indicators were regarded as useful by a Kenyan expert panel, contextual differences prompted them to recommend additional new indicators to improve the evaluations of nursing care provision in Kenyan hospitals and potentially similar LMIC settings. Taken forward through implementation, refinement and adaptation, the proposed indicators could be more standardised and may provide a common base to establish national or regional professional learning networks with the common goal of achieving high-quality care through quality improvement and learning."
998,Proteomic analysis revealed T cell hyporesponsiveness induced by Haemonchus contortus excretory and secretory proteins,"Haemonchus contortus has evolved highly integrated and sophisticated mechanisms to promote coexistence with hosts. The excretory-secretory (ES) products generated by this parasite contribute to the regulation of the host immune response to facilitate immune evasion and induce chronicity, but the proteins responsible for this process and the exact cellular mechanisms have yet to be defined. In this study, we identified 114 H. contortus ES proteins (HcESPs) interacting with host T cells and 15 T cell binding receptors via co-immunoprecipitation and shotgun liquid chromatography-tandem mass spectrometry analysis. Based on bioinformatics analysis, we demonstrated that HcESPs could inhibit T cell viability, induce cell apoptosis, suppress T cell proliferation and cause cell cycle arrest. Furthermore, the stimulation of HcESPs exerted critical control effects on T cell cytokine production profiles, predominantly promoting the secretion of interleukin (IL)-10, IL-17A and transforming growth factor-β1 and inhibiting IL-2, IL-4 and interferon-γ production. Collectively, these findings may provide insights into the interaction between ES proteins and key host effector cells, enhancing our understanding of the molecular mechanism underlying parasite immune evasion and providing new clues for novel vaccine development."
999,Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection,"BACKGROUND: Accurate etiology diagnosis is crucial for central nervous system infections (CNS infections). The diagnostic value of metagenomic next-generation sequencing (mNGS), an emerging powerful platform, remains to be studied in CNS infections. METHODS: We conducted a single-center prospective cohort study to compare mNGS with conventional methods including culture, smear and etc. 248 suspected CNS infectious patients were enrolled and clinical data were recorded. RESULTS: mNGS reported a 90.00% (9/10) sensitivity in culture-positive patients without empirical treatment and 66.67% (6/9) in empirically-treated patients. Detected an extra of 48 bacteria and fungi in culture-negative patients, mNGS provided a higher detection rate compared to culture in patients with (34.45% vs. 7.56%, McNemar test, p < 0.0083) or without empirical therapy (50.00% vs. 25.00%, McNemar test, p > 0.0083). Compared to conventional methods, positive percent agreement and negative percent agreement was 75.00% and 69.11% separately. mNGS detection rate was significantly higher in patients with cerebrospinal fluid (CSF) WBC > 300 * 10(6)/L, CSF protein > 500 mg/L or glucose ratio ≤ 0.3. mNGS sequencing read is correlated with CSF WBC, glucose ratio levels and clinical disease progression. CONCLUSION: mNGS showed a satisfying diagnostic performance in CNS infections and had an overall superior detection rate to culture. mNGS may held diagnostic advantages especially in empirically treated patients. CSF laboratory results were statistically relevant to mNGS detection rate, and mNGS could dynamically monitor disease progression."
1000,Improving transitions in care for children with complex and medically fragile needs: a mixed methods study,"BACKGROUND: Children with medical complexity are a small yet resource intensive population in the Canadian health care system. The process for discharging these children from hospital to home is not yet optimal. The overall goal of this project was to develop recommendations to be included in a provincial strategy to support transitions in care for children with complex and medically fragile needs. METHODS: A wide assortment of stakeholders participated in this mixed method, multiphase project. During Phase 1, data was gathered from a range of sources to document families’ experiences transitioning from an inpatient hospital stay back to their home communities. In Phase 2, pediatricians, nurses, and health administrators participated in key stakeholder interviews to identify barriers and facilitators to a successful transition in care for children and families with complex care needs. A multi-sector consensus meeting was held during Phase 3 to discuss study findings and refine key recommendations for inclusion in a provincial strategy. RESULTS: Six case studies were developed involving children and families discharged home with a variety of complex care needs. Children ranged in age from 15 days to 9 years old. Nine telephone interviews were conducted in Phase 2 with pediatricians, nurses, and administrators from across the province. A variety of inter-institutional communication challenges were described as a major barrier to the transition process. A consistent message across all interviews was the need for improved coordination to facilitate transitions in care. The consensus meeting to review study findings included physicians, nurses, paramedics, senior administrators, and policy analysts from different health and government sectors and resulted in six recommendations for inclusion in a provincial strategy. CONCLUSIONS: This project identified policy and practice gaps that currently exist related to transitions in care for children with complex and medically fragile needs and their families. Our collaborative patient-centred approach to understanding how children and families currently navigate transitions in care provided a foundation for developing recommendations for a provincial wide strategy."
1001,Chlamydia psittaci Triggers the Invasion of H9N2 Avian Influenza Virus by Impairing the Functions of Chicken Macrophages,"SIMPLE SUMMARY: Chlamydia psittaci, an obligate, intracellular, Gram-negative bacterium and economically relevant pathogen in poultry and pet bird, could cause psittacosis/ornithosis, and is also a human pathogen causing atypical pneumonia after zoonotic transmission. H9N2 influenza virus, a low pathogenic avian influenza viruses’ subtype, has become endemic in different types of domestic poultry in lots of countries, resulting in great economic loss due to reduced egg production or high mortality associated with coinfection with other pathogens. These two pathogens are easily mixed with other pathogens to aggravate the disease, and often cause mixed infection in clinics. Co-infection of C. psittaci with H9N2 commonly induces severe pneumonia and high mortality in specific pathogen-free (SPF) chickens. According to previous studies, we postulated that C. psittaci infection may beneficial for the replication of H9N2 in HD11. Consequently, in this study, we clarify the pathogenic mechanism of coinfection with C. psittaci and H9N2 in the chicken macrophage cell line HD11, which is the first study of the coinfection of C. psittaci and H9N2 in vitro. ABSTRACT: In a pilot study, simultaneous infection with Chlamydia psittaci (C. psittaci) and H9N2 virus induced 20% mortality and severe avian airsacculitis, shedding light on animal models of poultry respiratory diseases. However, the pathogenesis is still unclear. In the current study, we hypothesized that C. psittaci infection execrates macrophage function and facilitates H9N2 infection. To explore the potential mechanism, we studied the effect of C. psittaci and H9N2 on the functions of HD11 cells in vitro by simultaneous infection of C. psittaci and H9N2. At the same time, we used infection with C. psittaci or H9N2 alone as the control groups. The results showed that coinfection with C. psittaci and H9N2 could significantly aggravate the mortality of HD11 cells compared to C. psittaci or H9N2 infection alone. In addition, coinfection with C. psittaci and H9N2 did not induce high C. psittaci loads compared to C. psittaci infection alone at 12- and 24-hours post-inoculation (hpi), but coinfection with C. psittaci and H9N2 could increase the loads of H9N2 compared to H9N2 alone in HD11 cells at 12 hpi. More importantly, inducible nitric oxide synthase (iNOS) expression levels, enzyme activity, nitric oxide (NO) production, and phagocytosis were reduced significantly in the group with C. psittaci and H9N2 coinfection compared to those of H9N2 or C. psittaci alone at 24 hpi. Finally, C. psittaci infection induced robust expressions of type Th2 cytokines interleukin (IL)-4 and IL-10, while interferon gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) displayed a significant decrease compared to H9N2 infection alone at 24 hpi. All the above data indicate that C. psittaci infection can facilitate H9N2 invasion and to aggravate severe avian airsacculitis by impairing macrophage functions."
1002,Residual Neuromuscular Blockade and Postoperative Pulmonary Complications: What Does the Recent Evidence Demonstrate?,"PURPOSE OF REVIEW: The purpose of this review is to assess how residual neuromuscular block impacts postoperative pulmonary complications and whether we can modify the risk by improving certain aspects in daily clinical care. RECENT FINDINGS: Postoperative respiratory impairment may be due to various causes, such as age, surgery type, comorbidity, smoking, preoperative anemia, and general anesthesia. However, increasing evidence suggests that residual neuromuscular block is an important risk factor for postoperative pulmonary complications and may affect the outcome. Conflicting data from some recent reports show that the use of quantitative neuromuscular monitoring alone does not preclude residual neuromuscular block and that improvements in the interpretation of neuromuscular monitoring may be required. Pulmonary complications seem to be reduced for train-of-four ratios > 0.95 before tracheal extubation compared with > 0.9. SUMMARY: This review stresses the need for appropriate management of neuromuscular block in the prevention of postoperative pulmonary complications but acknowledges that the causes are multifactorial."
1003,Critical Issues in Leadership Development for Peer Support Specialists,"This paper is a qualitative analysis of perspectives on leadership development among working peer support specialists and highlights the challenges, needs and efficacy these individuals experience in their work settings. Six participants engaged in a 2 h semi-structured focus group. Participants were guided through a series of nine questions regarding their transition to leadership, professional communication and relationships. Seven themes emerged: managing dual relationships; having difficult conversations; push and pull of leadership; taking responsibility for others; taking responsibility for self-care; addressing stigma in the workplace, and, spirituality/a calling to help. These professionals integrate their personal experiences of recovery into their direct care and leadership approaches in the workplace. This blending of recovery concepts and supervision approaches reflect some of the powerful elements that peer recovery specialists are uniquely qualified to lead in the healthcare workforce. These findings provide important implications for leadership development among this growing segment of the healthcare workforce."
1004,Hypersensitivity Reactions to Biologicals: from Bench to Bedside,"PURPOSE OF REVIEW: Biologic agents are new treatment options for chronic inflammatory diseases and cancers. As a result of their unique mechanism of action, they are more effective and less toxic treatment option and their clinical usage is increasing. While they are more commonly used, various adverse effects have been observed including life-threatening ones, including anaphylaxis. The aim of this review is to distinguish the anaphylaxis from other hypersensitivity reactions (HSR) and provide a management algorithm for the anaphylactic reactions induced by biological agents. RECENT FINDINGS: Many case reports and series have been published regarding anaphylaxis and other hypersensitivity reactions (concerning cytokine release syndrome, acute infusion–related reactions) due to biologic agents. Although acute treatment of HSR varies according to the clinical presentation, desensitization with the drug is the major management option for subsequent administrations in the case of anaphylactic reactions. SUMMARY: Anaphylaxis and other immediate onset hypersensitivity reactions are occasionally difficult to differentiate from each other, and mixed-type reactions may be observed. Immediate management of anaphylaxis includes discontinuation of infusion, immediate administration of adrenaline, antihistamines, corticosteroids, and other treatment options depending on the symptoms. After 30–120 min of the reaction, a blood sample for serum tryptase levels should be obtained and after 4–6 weeks skin testing with the culprit drug should be performed for decision of long-term management via either graded challenge or desensitization."
1005,"Occupational traumatic injuries rarely affect genitourinary organs: a retrospective, comparative study","PURPOSE: To determine the mechanisms of injury associated with occupational injuries (OI) to genitourinary (GU) organs and compare GU OIs with GU non-OIs. METHODS: A single institution, retrospective study was conducted at a level 1 trauma center between 2010 and 2016 of all patients with GU injuries. OI was defined as any traumatic event that occurred in the workplace requiring hospital admission. Types of occupations were recorded in addition to the location of injury, mechanisms of injury, concomitant injuries, operative interventions, total cost, and mortality. GU OI patients were then compared to GU non-OI patients. RESULTS: 623 patients suffered a GU injury, of which 39 (6.3%) had a GU OI. Fall (43%) was the most common mechanism of injury; followed by motor vehicle collision/motorcycle crash (31%), crush injury (18%), and pedestrian struck (8%). The adrenal gland (38%) and kidney (38%) were the most commonly injured organs. There was no difference in mortality (13% GU OI vs. 15% GU non-OI, p = 0.70) or total direct cost ($21,192 ± 28,543 GU OI vs. $28,215 ± 32,332 GU non-OI, p = 0.45). Total costs were decreased with mortality from a GU injury (odds ratio (OR) 0.3, CI 0.26–0.59; p = < 0.001) and increased with higher injury severity scores (OR 1.1, CI 1.09–1.2; p = < 0.0001). Total costs were not affected by OI status. CONCLUSIONS: Occupational GU trauma presents with similar patterns of injury, hospital course, and direct cost as GU trauma that occurs in non-occupational settings."
1006,Development of a Hospital Medical Surge Preparedness Index using a national hospital survey,"To generate a Hospital Medical Surge Preparedness Index that can be used to evaluate hospitals across the United States in regard to their capacity to handle patient surges during mass casualty events. Data from the American Hospital Association’s annual survey, conducted from 2005 to 2014. Our sample comprised 6239 hospitals across all 50 states, with an annual average of 5769 admissions. An extensive review of the American Hospital Association survey was conducted and relevant variables applicable to hospital inpatient services were extracted. Subject matter experts then categorized these items according to the following subdomains of the “Science of Surge” construct: staff, supplies, space, and system. The variables within these categories were then analyzed through exploratory and confirmatory factor analyses, concluding with the evaluation of internal reliability. Based on the combined results, we generated individual (by hospital) scores for each of the four metrics and an overall score. The exploratory factor analysis indicated a clustering of variables consistent with the “Science of Surge” subdomains, and this finding was in agreement with the statistics generated through the confirmatory factor analysis. We also found high internal reliability coefficients, with Cronbach’s alpha values for all constructs exceeding 0.9. A novel Hospital Medical Surge Preparedness Index linked to hospital metrics has been developed to assess a health care facility’s capacity to manage patients from mass casualty events. This index could be used by hospitals and emergency management planners to assess a facility’s readiness to provide care during disasters."
1007,Nonoperative treatment of traumatic spinal injuries in Tanzania: who is not undergoing surgery and why?,"STUDY DESIGN: Retrospective, cohort study of a prospectively collected database. OBJECTIVES: In a cohort of patients with traumatic spine injury (TSI) in Tanzania who did not undergo surgery, we sought to: (1) describe this nonoperative population, (2) compare outcomes to operative patients, and (3) determine predictors of nonoperative treatment. SETTING: Tertiary referral hospital. METHODS: All patients admitted for TSI over a 33-month period were reviewed. Variables included demographics, fracture morphology, neurologic exam, indication for surgery, length of hospitalization, and mortality. Regression analyses were used to report outcomes and predictors of nonoperative treatment. RESULTS: 270 patients met inclusion criteria, of which 145 were managed nonoperatively. Demographics between groups were similar. The nonoperative group was young (mean = 35.5 years) and primarily male (n = 125, 86%). Nonoperative patients had 7.39 times the odds of death (p = 0.003). Patients with AO type A0/1/2/3 fractures (p < 0.001), ASIA E exams (p = 0.016), cervical spine injuries (p = 0.005), and central cord syndrome (p = 0.016) were more commonly managed nonoperatively. One hundred and twenty-four patients (86%) had indications for but did not undergo surgery. After multivariate analysis, the only predictor of nonoperative management was sustaining a cervical injury (p < 0.001). CONCLUSIONS: Eighty-six percent of nonoperative TSI patients had an indication for surgery. Nonoperative management was associated with an increased risk of mortality. Cervical injury was the single independent risk factor for not undergoing surgery. The principle reason for nonoperative management was cost of implants. While a causal relationship between nonoperative management and inferior outcomes cannot be made, efforts should be made to provide surgery when indicated, regardless of a patient’s ability to pay."
1008,Diagnosis and Management of Tuberculous Pericarditis: What Is New?,"PURPOSE OF REVIEW: This review provides an update on the immunopathogenesis of tuberculous pericarditis (TBP), investigations to confirm tuberculous etiology, the limitations of anti-tuberculous therapy (ATT), and recent efficacy trials. RECENT FINDINGS: A profibrotic immune response characterizes TBP, with low levels of AcSDKP, high levels of γ-interferon and IL-10 in the pericardium, and high levels of TGF-β and IL-10 in the blood. These findings may have implications for future therapeutic targets. Despite advances in nucleic acid amplification approaches, these tests remain disappointing for TBP. Trials of corticosteroids and colchicine have had mixed results, with no impact on mortality, evidence of a reduction in rates of constrictive pericarditis and potential harm in those with advanced HIV. Small studies suggest that ATT penetrates the pericardium poorly. Given that there is a close association between high bacillary burden and mortality, a rethink about the optimal drug doses and duration may be required. SUMMARY: The high mortality and morbidity from TBP despite use of anti-tuberculous drugs call for researches targeting host-directed immunological determinants of treatment outcome. There is also a need for the identification of steps in clinical management where interventions are needed to improve outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11886-020-1254-1) contains supplementary material, which is available to authorized users."
1009,Transthyretin at Admission and Over Time as a Marker for Clinical Outcomes in Critically Ill Trauma Patients: A Prospective Single-Center Study,"BACKGROUND: Transthyretin (TTR) has been described as a predictor for outcomes in medical and surgical patients. However, the association of TTR on admission and over time on outcomes has not yet been prospectively assessed in trauma patients. METHODS: This is a prospective observational study including trauma patients admitted to the intensive care unit (ICU) of a large Level I trauma center 05/2014–05/2015. TTR levels at ICU admission and all subsequent values over time were recorded. Patients were observed for 28 days or until hospital discharge. The association of outcomes and TTR levels at admission and over time was assessed using multivariable regression and generalized estimating equation (GEE) analysis, respectively. RESULTS: A total of 237 patients with TTR obtained at admission were included, 69 of whom had repeated TTR measurements. Median age was 40.0 years and median ISS 16.0; 83.1% were male. Below-normal TTR levels at admission (41.8%) were independently associated with higher in-hospital mortality (p = 0.042), more infectious complications (p = 0.032), longer total hospital length of stay (LOS) (p = 0.013), and ICU LOS (p = 0.041). Higher TTR levels over time were independently associated with lower in-hospital mortality (p = 0.015), fewer infections complications (p = 0.028), shorter total hospital and ICU LOS (both p < 0.001), and fewer ventilator days (0.004). CONCLUSIONS: In critically ill trauma patients, below-normal TTR levels at admission were independently associated with worse outcomes and higher TTR levels over time with better outcomes, including lower in-hospital mortality, less infectious complications, shorter total hospital and ICU LOS, and fewer ventilator days. Based on these results, TTR may be considered as a prognostic marker in this patient population."
1010,Guidelines to the Practice of Anesthesia – Revised Edition 2020,"The Guidelines to the Practice of Anesthesia Revised Edition 2020 (the Guidelines) were prepared by the Canadian Anesthesiologists’ Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2020 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgement in determining the proper course of action for any patient’s circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12630-019-01507-4) contains supplementary material, which is available to authorized users."
1011,Continuous feeding versus intermittent bolus feeding for premature infants with low birth weight: a meta-analysis of randomized controlled trials,"BACKGROUND/OBJECTIVES: Clinical risks and advantages of both continuous feeding and intermittent feeding for preterm infants have been presented in previous studies. To determine the most appropriate feeding method for low-birth-weight infants, a meta-analysis was conducted. SUBJECTS/METHODS: Articles related to this topic were searched in PubMed, EMBASE, and Cochrane Library electronic database from the onset to May 2019. Heterogeneity analysis was performed with Chi-square and I(2) test. Pooled analysis was based on fixed effects model, if heterogeneity between the eligible studies was negligible (I(2) < 50%, P > 0.05). In contrast, a random effects model was carried out. The quality of including studies were evaluated by Cochrane assessment tool. RESULTS: A total of 1030 articles identified. Altogether, eight articles including 707 infants were included in final analysis based on eligibility criteria. In continuous feeding infants, time to achieving full feeds was longer (weight mean difference 0.98 (95% CI 0.26–1.71, P = 0.008) days) compared with intermittent feeding infants. Pooled analysis indicated there were no significant difference in other variables such as feeding intolerance, duration of hospitalization, days to regain birth weight, days to first successful oral feeding, duration of parenteral feeding, weight growth, length increment, head circumference growth, proven necrotizing enterocolitis, and probable necrotizing enterocolitis. In subgroup analysis for birth weight (<1000 g and >1000 g), we did not identify significant difference in time to full feeds, time to regain birth weight, and duration of hospitalization. CONCLUSIONS: Intermittent feeding may be more beneficial for low-birth weight infants, However, well-designed studies and evidenced-based clinical practice are required to determine the most appropriate feeding method for premature infants with low birth weight."
1012,Who’s Your Enemy?: Incorporating Stories of Trauma into a Medical Humanities Course,"This article discusses the theoretical and practical experiment of creating, promoting and co-teaching a medical humanities course: Medicine, War and the Arts at a School of Medicine in the United States from the viewpoint of the students who took the class. Specifically, it analyses how three themes emerged in students’ responses to the oral, literary and visual stories of war and trauma in the course and how they revealed the subjective and ambivalent nature of all medical encounters with patients. The conclusion is that actively encouraging students to view the role of the physician through the lens of historical and contemporary trauma enables them to contemplate the difficult question, “Who’s Your Enemy?” when caring for the sick and themselves."
1013,Noninvasive ventilation for pediatric interfacility transports: a retrospective study,"BACKGROUND: To characterize pediatric patients supported with continuous positive airway pressure and bilevel positive airway pressure (CPAP/BiPAP) or high-flow nasal cannula (HFNC) during interfacility transport (IFT). METHODS: A retrospective study with a provincial pediatric transport team from a tertiary hospital pediatric intensive care unit. Pediatric patients aged 28 days to < 17 years, who required IFT between January 2017 and December 2018, were identified through a transport registry and were included in the study. RESULTS: A total of 118 (26.7%) patients received CPAP/BIPAP or HFNC support for IFT. The most common respiratory diagnosis was bronchiolitis (46%). These patients were placed on respiratory support, 31.4 minutes after the transport team’s arrival. None required intubation during their IFT, despite mean transport times of 163 minutes. CONCLUSIONS: This study may provide important information for programs with large catchment areas, in which large distances and transport times should not be barriers to NIV implementation."
1014,Significance of norovirus in occupational health: a review of published norovirus outbreaks in Central and Northern Europe,"OBJECTIVES: Globally, norovirus (NoV) is the leading cause of gastroenteritis infection among all ages. The development of prevention strategies in the field of occupational health requires a detailed knowledge about the impact of the disease on employees. This review article aims not only at evaluating the burden of NoV outbreaks on staff but also at discussing implications for future prevention strategies. METHODS: Published NoV outbreaks in Central and Northern Europe were identified via a systematic literature search. Additionally, published NoV outbreaks in Germany were detected via a manual literature search. Key epidemiological data, as the number of symptomatic staff, was then extracted. The proportion of affected employees was calculated for each dataset (single NoV outbreaks or aggregated data of multiple outbreaks). RESULTS: Overall, 116 datasets were extracted from 72 relevant articles. 144,852 persons were affected by NoV gastroenteritis, 25,408 out of them (17.5%) were employees. 23,874 (94.0%) of them fell sick during outbreaks in hospitals and related settings. NoV cases among personnel in food establishments were reported only sporadically (mean ratio: 0.01). CONCLUSIONS: Employees in hospitals and community facilities seem quantitatively to be most vulnerable towards NoV epidemics. Therefore, high quality of prevention measures in these settings, respective compliance with prevention strategies should have the highest priority. The disease can be considered as an occupational disease, even regularly without long-term consequences. Following work safety rules, a vaccination for vulnerable groups should be recommended if the vaccine development turns out to be successful. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00420-020-01543-4) contains supplementary material, which is available to authorized users."
1015,Impact of tracheostomy on language and cognitive development in infants with severe bronchopulmonary dysplasia,"OBJECTIVE: The impact of tracheostomy on language and cognitive development in infants with severe bronchopulmonary dysplasia (BPD) is not known. We hypothesize that tracheostomy has an independent negative impact on language and cognitive development in infants with severe BPD. STUDY DESIGN: This is a retrospective cohort study of de-identified data of infants with severe BPD who received tracheostomy at <2 years of age, compared with infants with severe BPD without tracheostomy. The primary outcomes measured were total language and cognitive scores at 2–3 years of age as determined by Bayley Scales of Infant and Toddler Development, 3rd Edition. RESULTS: A total of 26 patients with tracheostomies and 28 patients without tracheostomies were analyzed. There was no significant difference in total language development or cognitive development between patients with tracheostomies and those without. Insurance status had an effect on language and cognition while controlling for trach status. CONCLUSIONS: Tracheostomy does not independently impact the language and cognitive development of infants with severe BPD."
1016,Acquisition of Information About Innovative Practices in Outpatient Mental Health Clinics,"This study uses qualitative interviews with leaders of 34 mental health clinics in the context of a statewide rollout of clinical and business innovations to explore how clinics first learn about innovations and which external sources of information they access. Clinic leaders reported accessing information about innovations mainly from government agencies, professional associations, peer organizations, and research literature. Leaders mentioned an average of two external sources of information. There was evidence of variation in how leaders accessed information and how information about innovations was communicated within clinics. Findings have implications for improving dissemination of information about innovations in mental health systems."
1017,Zielgruppengerechte Krisenintervention – Angehörige und Team,"Families find themselves in an exceptional situation after the sudden death of someone close. Anxiety, aggression, rage, incomprehension, and distraction are only a few feelings of the concerned people which intensive care staff must take care of. Crisis intervention, developed in the middle of the last century, offers a framework with its concepts for the healthcare staff of how to work with the bereaved people during the first few hours. The BASIS model is a sort of counseling technique that guides nurses and physicians: bonding and urging the acceptance of the facts, providing structure and information, and securing backup support networks. Professionals who offer help need a high level of empathy and compassion for their work. But it is essential to offer help only in situations where advice is possible. Otherwise, physicians and nurses are at high risk to develop compassion fatigue. The right training, advanced education, and supervision are necessary, so that healthcare professionals can support people in crisis."
1018,"An increasing prevalence of non-GII.4 norovirus genotypes in acute gastroenteritis outbreaks in Huzhou, China, 2014-2018","Since 2014, novel non-GII.4 norovirus (NoV) genotypes continue to be reported as the main cause of outbreaks worldwide. In this study, we analyzed the epidemiological and genetic features of NoV outbreaks from July 2014 to June 2018 in Huzhou, China. A total of 450 stool samples collected from 51 AGE outbreaks were tested for NoVs by real-time RT PCR. Partial polymerase and capsid sequences of NoV-positive samples were amplified and sequenced for phylogenetic analysis. NoVs were found to be responsible of 84.3% of AGE outbreaks in Huzhou over the past 5 years. Most NoV outbreaks were reported in the cool months (November-March) and occurred in primary schools and kindergartens. Changes in the diversity of genotypes and the distribution of predominant types were observed in recent years. At least eight genotypes were identified, and 91.9% of the genotyped outbreaks were caused by non-GII.4 strains. The top three circulating genotypes during the study period were GII.2[P16], GII.3[P12], and GII.17[P17]. The predominant NoV genotypes in outbreaks have changed from GII.4 variants to GII.17[P17] in 2014-2015, GII.3[P12] in 2015-2016, and then GII.2[P16] in 2016-2018. Non-GII.4 NoVs play an increasingly important role in outbreaks in Huzhou. Continuous surveillance is needed to monitor the emergence of novel NoV strains and help control NoV outbreaks in the next epidemic season."
1019,An audit to analyse the two-week wait pathway at an oral cancer specialist district general hospital,"Background The incidence of head and neck cancers is increasing, alongside a decrease in associated mortality. Currently, medical and dental practitioners can refer patients to be seen urgently within two weeks. The appropriateness of these referrals has been disputed. In 2020, the Department of Health aims for patients to be given cancer diagnoses within 28 days from referral. Methods A retrospective audit was conducted for all patients referred under the two-week wait pathway in a six-month period. In the first cycle of this audit, one month's worth of urgent referrals were analysed; given the small sample size, very few recommendations could be made. The audit cycle was repeated and it analysed six months' worth of data, which gave a much more representative study. All patients were analysed to see if the 14-day period had been breached. Positive cancer patients were further assessed to see if their diagnosis had been given within 28 days and treatments within 62 days. Results Of the 569 patients seen, there was a positive malignancy diagnostic yield of 7.38%. Nineteen patients breached the 14-day wait. Of the positive patients, 45.2% received their diagnosis more than 28 days from referral, and 22.2% of these patients received treatment after 62 days. Conclusion The department performed well despite the high number of referrals. This audit has touched on some key issues which have been discussed in detail in this article. Furthermore, this audit recommends a concerted effort to improve oral cancer detections skills among GDPs and GMPs. While all referrals may be appropriate from a primary care point of view, this audit makes it apparent that better differentiation is needed between malignant and routinely manageable lesions. All secondary care units alongside general practitioners can learn from the findings of this audit."
1020,Outcomes of Severe PARDS on High-Frequency Oscillatory Ventilation – A Single Centre Experience,"OBJECTIVE: To describe experience with high-frequency oscillatory ventilation (HFOV) in children with acute respiratory distress syndrome (ARDS) transitioned from conventional mechanical ventilation (CMV) due to refractory hypoxemia and to assess factors associated with survival and also compare outcomes of patients who were managed with early HFOV (within 24 h of intubation) vs. late HFOV. METHODS: This retrospective, observational study was conducted in a tertiary care hospital's pediatric intensive care unit. Thirty-four children with pediatric acute respiratory distress syndrome (PARDS) managed with HFOV were included. RESULTS: Of 34 children with PARDS managed with HFOV after failure of conventional ventilation to improve oxygenation, 8 survived. Improvement in the Oxygenation Index (OI) at 48 h of initiation of HFOV along with percent increase in PaO(2)/FiO(2) (P/F ratio) at 24 h of HFOV were predictors of survival. The response to HFOV, based on OI and P/F ratio, between 24 and 48 h of ventilation identified potential survivors. Also, lower positive end-expiratory pressure (PEEP) on CMV and shorter duration of CMV before initiation of HFOV were associated with survival. CONCLUSIONS: Survival in pediatric ARDS patients treated with HFOV could be predicted by using trends of OI – with survivors showing a more rapid decline in OI between 24 and 48 h of initiation compared to non-survivors."
1021,Effects of intraoperative positive end-expiratory pressure optimization on respiratory mechanics and the inflammatory response: a randomized controlled trial,"Applying lung protective mechanical ventilation (LPV) during general anaesthesia even in patients with non-injured lungs is recommended. However, the effects of an individual PEEP-optimisation on respiratory mechanics, oxygenation and their potential correlation with the inflammatory response and postoperative complications have not been evaluated have not been compared to standard LPV in patients undergoing major abdominal surgery. Thirty-nine patients undergoing open radical cystectomy were enrolled in this study. In the study group (SG) optimal PEEP was determined by a decremental titration procedure and defined as the PEEP value resulting the highest static pulmonary compliance. In the control group (CG) PEEP was set to 6 cmH2O. Primary endpoints were intraoperative respiratory mechanics and gas exchange parameters. Secondary outcomes were perioperative procalcitonin kinetics and postoperative pulmonary complications. Optimal PEEP levels (median = 10, range: 8–14 cmH2O), PaO2/FiO2 (451.24 ± 121.78 mmHg vs. 404.15 ± 115.87 mmHg, P = 0.005) and static pulmonary compliance (52.54 ± 13.59 ml cmH2O-1 vs. 45.22 ± 9.13 ml cmH2O-1, P < 0.0001) were significantly higher, while driving pressure (8.26 ± 1.74 cmH2O vs. 9.73 ± 4.02 cmH2O, P < 0.0001) was significantly lower in the SG as compared to the CG. No significant intergroup differences were found in procalcitonin kinetics (P = 0.076). Composite outcome results indicated a non-significant reduction of postoperative complications in the SG. Intraoperative PEEP-optimization resulted in significant improvement in gas exchange and pulmonary mechanics as compared to standard LPV. Whether these have any effect on short and long term outcomes require further investigations. Trial registration: Clinicaltrials.gov, identifier: NCT02931409."
1022,Compassionate Love among Catholic Priests: its Antecedents and its Influence on Affect toward Pastoral Ministry in Indonesia,"What drives Catholic priests to continue to serve people? That is the main question behind this psychological study. Based on a working model of compassionate love (Underwood 2008), the priestly compassionate love model was tested to determine whether spirituality, social support, priestly commitment, and well-being simultaneously influence compassionate love, which in turn brings out a positive affect in those doing pastoral ministry. The participants were 256 Catholic priests in Indonesia. Using structural equation modeling, the results of the study showed a good fit. Spirituality was the factor that contributed most strongly to compassionate love. Receiving adequate support from multiple sources motivated the priests to love others. Moreover, priestly commitment also influenced the priests to love others compassionately. Although well-being did not significantly influence compassionate love, it still played an important role in the model because it was correlated with all factors. Finally, the results showed that compassionate love powerfully influenced the priests to be enthusiastic and eager in doing pastoral ministry. These findings are discussed theoretically and practically in the context of priestly life and ministry in Indonesia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11089-019-00888-z) contains supplementary material, which is available to authorized users."
1023,Satisfaction with Care and Satisfaction with Decision Making are Similar Regardless of Staffing Model in a Neurocritical Care Unit,"INTRODUCTION: Patient-centered care, particularly shared medical decision making, is difficult to measure in critically ill patients where decisions are often made by a designated surrogate, often receiving information from multiple providers with varying degrees of training. The purpose of this study was to compare short-term satisfaction with care and decision making in patients or surrogates between two neurocritical care units [one staffed by a neurocritical care attending and advanced practice providers (APPs) and one staffed by a neurocritical care attending and resident/fellow trainees] using the Family Satisfaction in the ICU (FS-ICU) survey. METHODS: Over a 6-month period, the FS-ICU was administered on a tablet device to patients or surrogates at least 24 h after admission and stored on REDCap database. RESULTS: One hundred and thirty-four patients or surrogates completed the FS-ICU. The response rates were 59.97% and 46.58% in the APP and trainee units, respectively. There were no differences in patient age, sex, ventilator days or ICU length of stay. Overall, there were no differences in satisfaction with care or perceived shared medical making between the units. Respondents who identified their relationship with the patient as “other” (not a spouse, parent, nor a sibling) were less satisfied with care. Additionally, surrogates who identified as parents of the patient were more satisfied with degree of shared medical decision making. CONCLUSION: This study showed that: (1) collecting FS-ICU in a neurocritical care unit is feasible, (2) overall there is no difference in short-term satisfaction with care or shared decision making between a NICU staffed with trainees compared to one staffed with APPs, and (3) parents of patients have a higher short-term satisfaction with degree of shared medical decision making."
1024,Bariatric Surgery Outcomes in Patients with Prior Solid Organ Transplantation: an MBSAQIP Analysis,"INTRODUCTION: Obesity is a risk factor for poor patient outcomes after organ transplantation (TXP). While metabolic and bariatric surgery (MBS) is safe and effective in treating severe obesity, the role of MBS in transplant patients continues to evolve. METHODS: A retrospective analysis was performed of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) patients in the 2017 Metabolic and Bariatric Surgery Accreditation Quality and Improvement Project (MBSAQIP) database. Propensity and case-control matching, and multivariable logistic regression were performed for 30-day post-operative outcomes. RESULTS: A total of 336 transplant patients were compared with 157,413 patients without transplant. Propensity and case-control matching reveal no significant differences in mortality (p > 0.2). However, case-control matching revealed longer operative time (104 min versus 76 min, p < 0.001), increased length of stay (2 days versus 1 day, p < 0.05), perioperative transfusions (2% versus 0.22%, p = 0.009), and leak rates (2.2% versus 0.55%, p = 0.02) in the transplant cohort. On multivariable regression analysis, prior transplantation was associated with higher rates of overall (OR 1.6, p = 0.007) and bariatric-related morbidity (OR 1.78, p = 0.004), leak (OR 3.47, p = 0.0027), and surgical site infection (OR 3.32, p = 0.004). Prior transplantation did not predict overall (p = 0.55) nor bariatric-related mortality (p = 0.99). CONCLUSION: MBS in prior solid organ transplantation patients is overall safe, but is associated with increased operative time and length of stay, as well as higher rates of some post-operative morbidity."
1025,Molecular Modelling and Insilico Engineering of PapMV-CP Towards Display and Development of Capripox Viral Like Particles Based on Immunogenic P32 Envelop Protein is the Homologous of the Vaccinia-Viral H3L Gene: An Insilico Approach,"Viral-like particles are assembled from capsid protein structural subunits of different viruses and have ability to establish research in biomedicals, like construction of novel safety vaccines, gene therapy vectors by delivering systems for nucleic acids, small biomolecules and diagnostics. Papaya Mosaic Viral nanoparticals can provide as a vaccine candidate helps to increase the immunity by fusing the epitope based peptide antigen. Capripox viruses are the genus comprises Lymphy skin-disease, Sheep and Goat pox Viruses are notified by The World Animal Health Organization (OIE) based on their economic impotence act as a transboundary animal diseases viruses of sheep, goat, and cattle’s respectively. Plant viral based innovative vaccines have been emerged ineffective vaccine development. This research describes the engineering and development of a new vaccine candidate by display immunogenic peptide using the carrier capsid protein of Papaya Mosaic Virus. The Capripox virus P32 immunogenic protein is homologous of the vaccinia virus H3L gene displayed PapMV CP. The antigenicity of P32 protein epitope lowest score among epitopes C-terminally docked epitopes are EP6 > EP3 > EP8 as well the lowest score among epitopes N-terminally docked epitopes are EP8 > EP3 > EP6 presented on the N-terminus of PMV CP region which are found to be suitable for epitope display. And these modelled immunogenic peptide could be used to develop a viral like particles. Epitope based Antibody developed against immunogenic epitopic regions can contribute to a novel and robust protection from infection. As well might be used for developing cost effective detection kits for Transboundary animal disease viruses."
1026,The Golden Hour: a quality improvement initiative for extremely premature infants in the neonatal intensive care unit,"BACKGROUND: Following delivery, extremely premature infants are vulnerable to rapid development of hypothermia and hypoglycemia. To reduce local rates of these morbidities, a multidisciplinary team developed a protocol standardizing evidence-based care practices during the first hour after birth. METHODS: Using quality improvement methodology, the Golden Hour protocol was implemented for all inborn infants <27 weeks’ gestation. Data were collected (2012–2017) over three phases; pre-protocol (n = 80), Phase I (n = 42), and Phase II (n = 92). RESULTS: There were no significant differences in infant characteristics. Improvements in hypothermia (59% vs 26% vs 38%; p = 0.001), hypoglycemia (18% vs 7% vs 4%; p = 0.012), and minutes to completion of stabilization [median (Q1,Q3) 110 (89,138) vs 111 (94,135) vs 92 (74,129); p = 0.0035] were observed. CONCLUSIONS: Implementation of an evidence-based, Golden Hour protocol is an effective intervention for reducing hypothermia and hypoglycemia in extremely premature infants."
1027,Rate and risk factors for rehospitalisation in sepsis survivors: systematic review and meta-analysis,"PURPOSE: Sepsis survivors have a higher risk of rehospitalisation and of long-term mortality. We assessed the rate, diagnosis, and independent predictors for rehospitalisation in adult sepsis survivors. METHODS: We searched for non-randomized studies and randomized clinical trials in MEDLINE, Cochrane Library, Web of Science, and EMBASE (OVID interface, 1992–October 2019). The search strategy used controlled vocabulary terms and text words for sepsis and hospital readmission, limited to humans, and English language. Two authors independently selected studies and extracted data using predefined criteria and data extraction forms. RESULTS: The literature search identified 12,544 records. Among 56 studies (36 full and 20 conference abstracts) that met our inclusion criteria, all were non-randomised studies. Studies most often report 30-day rehospitalisation rate (mean 21.4%, 95% confidence interval [CI] 17.6–25.4%; N = 36 studies reporting 6,729,617 patients). The mean (95%CI) rehospitalisation rates increased from 9.3% (8.3–10.3%) by 7 days to 39.0% (22.0–59.4%) by 365 days. Infection was the most common rehospitalisation diagnosis. Risk factors that increased the rehospitalisation risk in sepsis survivors were generic characteristics such as older age, male, comorbidities, non-elective admissions, hospitalisation prior to index sepsis admission, and sepsis characteristics such as infection and illness severity, with hospital characteristics showing inconsistent associations. The overall certainty of evidence was moderate for rehospitalisation rates and low for risk factors. CONCLUSIONS: Rehospitalisation events are common in sepsis survivors, with one in five rehospitalisation events occurring within 30 days of hospital discharge following an index sepsis admission. The generic and sepsis-specific characteristics at index sepsis admission are commonly reported risk factors for rehospitalisation. REGISTRATION: PROSPERO CRD 42016039257, registered on 14-06-2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05908-3) contains supplementary material, which is available to authorized users."
1028,Probiotics in hospitalized adult patients: a systematic review of economic evaluations,"PURPOSE: Probiotics may prevent healthcare-associated infections, such as ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and other adverse outcomes. Despite their potential benefits, there are no summative data examining the cost-effectiveness of probiotics in hospitalized patients. This systematic review summarized studies evaluating the economic impact of using probiotics in hospitalized adult patients. METHODS: We searched MEDLINE, EMBASE, CENTRAL, ACP Journal Club, and other EBM reviews (inception to January 31, 2019) for health economics evaluations examining the use of probiotics in hospitalized adults. Independently and in duplicate, we extracted data study characteristics, risk of bias, effectiveness and total costs (medications, diagnostics/procedures, devices, personnel, hospital) associated with healthcare-associated infections (ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea and antibiotic-associated diarrhea). We used Grading of Recommendations Assessment, Development and Evaluation methods to assess certainty in the overall cost-effectiveness evidence. RESULTS: Of 721 citations identified, we included seven studies. For the clinical outcomes of interest, there was one randomized-controlled trial (RCT)-based health economic evaluation, and six model-based health economic evaluations. Probiotics showed favourable cost-effectiveness in six of seven (86%) economic evaluations. Three of the seven studies were manufacturer-supported, all which suggested cost-effectiveness. Certainty of cost-effectiveness evidence was very low because of risk of bias, imprecision, and inconsistency. CONCLUSION: Probiotics may be an economically attractive intervention for preventing ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and antibiotic-associated diarrhea in hospitalized adult patients. Nevertheless, certainty about their cost-effectiveness evidence is very low. Future RCTs examining probiotics should incorporate cost data to inform bedside practice, clinical guidelines, and healthcare policy. Trial registration: PROSPERO CRD42019129929; Registered 25 April, 2019. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12630-019-01525-2) contains supplementary material, which is available to authorized users."
1029,"Outcomes in conventional laparoscopic versus robotic-assisted primary bariatric surgery: a retrospective, case–controlled study of the MBSAQIP database","INTRODUCTION: Robotic-assisted bariatric surgery is increasingly performed. There remains controversy about the overall benefit of robotic-assisted (RBS) compared to conventional laparoscopic (LBS) bariatric surgery. In this study, we used a large national risk-stratified bariatric clinical database to compare outcomes between robotic and laparoscopic gastric bypass (RNYGB) and sleeve gastrectomy (SG). METHODS: A retrospective analysis of the 2015 and 2016 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Participant Use Data File (PUF) was performed. Primary robotic and laparoscopic RYNGB and SG were analyzed. Descriptive analysis was performed of the unmatched cohorts, followed by 1:3 case-controlled matching. Cases and controls were matched by patient demographics and pre-operative comorbidities, and peri-operative outcomes compared. RESULTS: 77,991 Roux-en-Y gastric bypass (RnYGB) (7.5% robotic-assisted) and 189,503 SG (6.8% robotic-assisted) cases were identified. Operative length was significantly higher in both the robotic-assisted RnYGB and SG cohorts (p < 0.0001). Outcomes were similar between the robotic-assisted and laparoscopic RnYGB cohorts, except a lower mortality rate (p = 0.05), transfusion requirement (p = 0.005), aggregate bleeding (p = 0.04), and surgical site infections (SSI) (p = 0.006) in the robotic-assisted cohort. Outcomes were also similar between robotic-assisted and laparoscopic SG, except for a longer length of stay (p < 0.0001) and higher rates of conversion (p < 0.0001), 30-day intervention (p = 0.01), operative drain present (p < 0.0001), sepsis (p = 0.01), and organ space SSI (p = 0.0002) in the robotic cohort. Bleeding was lower in the robotic SG cohort and mortality was similar. CONCLUSION: Both robotic-assisted and laparoscopic RnYGB and SG are overall very safe. Robotic-assisted gastric bypass is associated with a lower mortality and morbidity; however, a clear benefit for robotic-assisted SG compared to laparoscopic SG was not seen. Given the longer operative and hospital duration, robotic SG is not cost-effective. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00464-019-06915-7) contains supplementary material, which is available to authorized users."
1030,The zero-VAP sophistry and controversies surrounding prevention of ventilator-associated pneumonia,
1031,Fast tracking after repair of congenital heart defects,"Fast tracking after repair of congenital heart defects (CHD) is a process involving the reduction of perioperative period by timely admission, early extubation after surgery, short intensive care unit (ICU) stay, early mobilisation, and faster hospital discharge. It requires a coordinated multidisciplinary team involvement. In the last 2 decades, many centres have adopted the fast tracking strategy in paediatric cardiac population, safely and successfully extubating patients in the OR with reported benefits in terms of reduced morbidity and ICU/hospital stay. In this manuscript, we will review the literature available on early extubation after repair of CHD and share our experience with this approach."
1032,Patients who develop post-operative atrial fibrillation have reduced survival after off-pump coronary artery bypass grafting,"OBJECTIVE: Post-operative atrial fibrillation (POAF) increases hospital stay, resource utilization, morbidity, and mortality. However, there is paucity of data about its effect in Indian patients undergoing off-pump coronary artery bypass grafting (CABG). METHODS: Seven hundred forty-eight patients underwent off-pump CABG from January 2015 to December 2016 (24 months). One hundred twenty-seven patients (16.7%) developed POAF. In an effort to mitigate the effects of wider risk factors on perioperative outcomes, a separate sub-analysis of patients based on risks quantified by EuroSCORE II (<> 3) was also performed. RESULTS: Age > 60 years and development of sepsis were the independent predictors for the development of POAF. Thirty-day/mortality rate was higher in the POAF group (7.1% vs. 1.4%; p value < 0.001). POAF was associated with increased ICU and hospital stay and increased incidence of stroke and renal dysfunction. The survival was significantly lower in the POAF group compared with the normal sinus rhythm (NSR) (3-year survival in POAF was 81.3% vs. 94.4% in the NSR group; Hazard ratio (HR) 3.867 (1.989–7.516)). Intra-aortic balloon pump (IABP) usage, age ≥ 60 years and sepsis were independent predictors for the development of POAF in low-risk patients. For the NSR group, 1-year survival was 98% and 3-year survival was 95.7%. For the POAF group, 1-year survival was 94.4% and 3-year survival was 84.0% (HR. 3.794 (1.897–7.591)). CONCLUSION: The incidence of POAF was lower than reported in the wider global literature. Increasing age and development of post-operative sepsis were strong independent predictors of POAF. POAF increases the morbidity; length of hospital stay and these patients show decreased survival after off-pump CABG."
1033,Comparison of extubation success using noninvasive positive pressure ventilation (NIPPV) versus noninvasive neurally adjusted ventilatory assist (NI-NAVA),"OBJECTIVE: Compare rates of initial extubation success in preterm infants extubated to NIPPV or NI-NAVA. STUDY DESIGN: In this pilot study, we randomized 30 mechanically ventilated preterm infants at the time of initial elective extubation to NI-NAVA or NIPPV in a 1:1 assignment. Primary study outcome was initial extubation success. RESULTS: Rates of continuous extubation for 120 h were 92% in the NI-NAVA group and 69% in the NIPPV group (12/13 vs. 9/13, respectively, p = 0.14). Infants extubated to NI-NAVA remained extubated longer (median 18 vs. 4 days, p = 0.02) and experienced lower peak inspiratory pressures (PIP) than infants managed with NIPPV throughout the first 3 days after extubation. Survival analysis through 14 days post extubation showed a sustained difference in the primary study outcome until 12 days post extubation. CONCLUSIONS: Our study is the first to suggest that a strategy of extubating preterm infants to NI-NAVA may be more successful."
1034,Ultrasonographic evaluation of lung and heart in predicting successful weaning in mechanically ventilated neurosurgical patients,"In critically ill neurosurgical patients, delayed and premature extubation increases the risk of morbidity and mortality. Assessment of critically ill patients before and during spontaneous breathing trial (SBT) is crucial in predicting weaning failure. We explored the trend of changes with integrated lung and cardiac ultrasonography in predicting success of weaning in neurosurgical patients. Lung ultrasound and cardiac ultrasound was performed before and after 30 min and 120 min of SBT. Lung ultrasound score (LUS, range 0–36) was calculated using a predefined method of assessment of six chest regions on either side. The left ventricular function was evaluated by measuring fractional area change. The maximum velocities of mitral inflow E and A waves (E/A), deceleration time of E wave (DTE) and tissue doppler based E′ wave at lateral annulus to calculate E/E′, were measured to assess left ventricular filling pressure. Twenty seven patients underwent SBT, among these 22 had success and five had failure of SBT. The SBT failure group had higher baseline LUS and progressively higher LUS during SBT compared to the success group, suggesting significant lung de-recruitment. There was significant increase in the LV filling pressure (increase E/A and E/E′, decrease in DTE) after 30 and 120 min of SBT in failure group compared to the success group. Point of care lung and cardiac ultrasonography may be useful in detecting cardiopulmonary changes induced by SBT. Higher lung aeration loss and LV filling pressure were observed with SBT failure group."
1035,Conceptualizing LGBT Stigma and Associated HIV Vulnerabilities Among LGBT Persons in Lesotho,"Social marginalization harms lesbian, gay, bisexual, and transgender (LGBT) persons’ wellbeing in Lesotho. Socio-cultural mechanisms linking LGBT stigma, depression, substance use, and HIV among LGBT persons in Lesotho are understudied. We explore associations between LGBT stigma, mental health stressors, and HIV vulnerabilities among LGBT persons in Lesotho. We conducted in-depth, semi-structured interviews with 46 LGBT persons and six key informants (e.g. healthcare providers). Participants described depression, substance use, and HIV as mutually reinforcing and situated in larger social contexts of stigma. Alcohol use was a stigma coping strategy and a way to build LGBT connections. At the same time, alcohol use elevated HIV vulnerabilities by lowering condom use uptake. Pervasive stigma reinforced barriers to healthcare engagement. Community-led support and services were leveraged to navigate stigma, reduce HIV vulnerabilities, and ultimately improve health. Findings emphasize the key role contexts play in shaping sexual and mental health among LGBT persons in Lesotho."
1036,"Multidomain Interventions to Prevent Cognitive Impairment, Alzheimer’s Disease, and Dementia: From FINGER to World-Wide FINGERS","Alzheimer’s disease (AD) and dementia are a global public health priority, and prevention has been highlighted as a pivotal component in managing the dementia epidemic. Modifiable risk factors of dementia and AD include lifestyle-related factors, vascular and metabolic disorders, and psychosocial factors. Randomized controlled clinical trials (RCTs) are needed to clarify whether modifying such factors can prevent or postpone cognitive impairment and dementia in older adults. Given the complex, multifactorial, and heterogeneous nature of late-onset AD and dementia, interventions targeting several risk factors and mechanisms simultaneously may be required for optimal preventive effects. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is the first large, long-term RCT to demonstrate that a multidomain lifestyle-based intervention ameliorating vascular and lifestyle-related risk factors can preserve cognitive functioning and reduce the risk of cognitive decline among older adults at increased risk of dementia. To investigate the multidomain intervention in other populations and diverse cultural and geographical settings, the World-Wide FINGERS (WW-FINGERS) network was recently launched (https://alz.org/wwfingers). Within this network, new FINGER-type trials with shared core methodology, but local culture and context-specific adaptations, will be conducted in several countries. The WW-FINGERS initiative facilitates international collaborations, provides a platform for testing multidomain strategies to prevent cognitive impairment and dementia, and aims at generating high-quality scientific evidence to support public health and clinical decision-making. Furthermore, the WW-FINGERS network can support the implementation of preventive strategies and translation of research findings into practice."
1037,The Obesity Paradox in the Trauma Patient: Normal May not Be Better,"OBJECTIVE: The obesity paradox is the association of increased survival for overweight and obese patients compared to normal and underweight patients, despite an increased risk of morbidity. The obesity paradox has been demonstrated in many disease states but has yet to be studied in trauma. The objective of this study is to elucidate the presence of the obesity paradox in trauma patients by evaluating the association between BMI and outcomes. METHODS: Using the 2014–2015 National Trauma Database (NTDB), adults were categorized by WHO BMI category. Logistic regression was used to assess the odds of mortality associated with each category, adjusting for statistically significant covariables. Length of stay (LOS), ICU LOS and ventilator days were also analyzed, adjusting for statistically significant covariables. RESULTS: A total of 415,807 patients were identified. Underweight patients had increased odds of mortality (OR 1.378, p < 0.001 95% CI 1.252–1.514), while being overweight had a protective effect (OR 0.916, p = 0.002 95% CI 0.867–0.968). Class I obesity was not associated with increased mortality compared to normal weight (OR 1.013, p = 0.707 95% CI 0.946–1.085). Class II and Class III obesity were associated with increased mortality risk (Class II OR 1.178, p = 0.001 95% CI 1.069–1.299; Class III OR 1.515, p < 0.001 95% CI 1.368–1.677). Hospital and ICU LOS increased with each successive increase in BMI category above normal weight. Obesity was associated with increased ventilator days; Class I obese patients had a 22% increase in ventilator days (IRR 1.217 95% CI 1.171–1.263), and Class III obese patients had a 54% increase (IRR 1.536 95% CI 1.450–1.627). CONCLUSION: The obesity paradox exists in trauma patients. Further investigation is needed to elucidate what specific phenotypic aspects confer this benefit and how these can enhance patient care. LEVEL OF EVIDENCE: Level III, prognostic study"
1038,Wide variation in caffeine discontinuation timing in premature infants,"OBJECTIVE: To assess site variability and concomitant respiratory support related to the timing of caffeine discontinuation, and compare clinical characteristics of infants who discontinued caffeine before vs. within the last week of hospitalization. STUDY DESIGN: Cohort study of 81,110 infants <35 weeks gestational age and <1500 g birth weight discharged from 304 neonatal intensive care units from 2001–2016. RESULTS: The mean postmenstrual age at caffeine discontinuation ranged from 32 to 37 weeks among sites. Respiratory support at the time of discontinuation was common, but variable, with 0–57% of infants receiving positive airway pressure at caffeine discontinuation by site. Infants who discontinued caffeine within the last week of hospitalization had longer total duration of caffeine, but were discharged from the hospital at an earlier postmenstrual age. CONCLUSION: There was substantial variability among sites in the timing of caffeine discontinuation before discharge and respiratory support at the time of caffeine discontinuation."
1039,Novel vaccine technologies for the 21st century,"Novel approaches to vaccine development include structure-based immunogen design, gene-based vaccine platforms and formulation of recombinant antigens with potent adjuvants. These technologies are producing encouraging results in the development of vaccines for globally important diseases such as tuberculosis, influenza and respiratory syncytial virus. Here we highlight the most important developments in these areas over the past 18 months."
1040,Diffuse varicella zoster virus reactivation in critically ill immunocompromised patient,
1041,Comparison of ATG-thymoglobulin with ATG-Fresenius for Epstein-Barr virus infections and graft-versus-host-disease in patients with hematological malignances after haploidentical hematopoietic stem cell transplantation: a single-center experience,"Two anti-thymocyte globulin (ATG) forms are used in graft-versus-host disease (GVHD) prophylaxis during haploidentical hematopoietic stem cell transplantations (haplo-HSCTs): ATG-thymoglobulin (ATG-T) and ATG-fresenious (ATG-F). However, comparable dosages for haplo-HSCT remain unclear. We compared and evaluated the effects of ATG-T (7.5 mg/kg) or ATG-F (20 mg/kg) dosages in a relatively homogenous population in haplotype HSCT settings. Patients administered ATG-T 7.5 mg/kg (n = 81) or ATG-F 20 mg/kg (n = 35) as part of GVHD prophylaxis during haplo-HSCT were enrolled. Incidence and severity of GVHD, Epstein–Barr virus (EBV) infection, and immune cell recovery were compared using the Mann-Whitney U rank test and chi-square test. Cumulative incidences of GVHD, EBV infection and its subgroups, and relapse mortality were computed; overall survival (OS) was analyzed using the Kaplan-Meier method, with the log-rank test used for univariate comparison. Risk factors for OS were analyzed by the Cox proportional hazards model. Incidence and cumulative incidence of all grades of acute GVHD and subgroups were comparable in both groups (all p > 0.05); however, cumulative incidence of any grade and limited chronic GVHD was significantly higher in the ATG-T group (p = 0.002, p = 0.007, respectively). Cumulative incidences of EBV infections, EBV-DNAemia, and EBV-related diseases were similar; relapse mortality and OS rates were comparable between both groups (all p > 0.05). ATG-T dosage (7.5 mg/kg) appeared comparable to ATG-F dosage (20 mg/kg) for haplo-HSCT. Currently approved ATG-T and ATG-F doses appear efficient to balance the risk–benefit ratio of GVHD, OS, relapse mortality, and EBV infection in haplo-HSCT."
1042,Vaccination during pregnancy: current and possible future recommendations,"Immunizing pregnant women to protect the mother, fetus and infant from infection has increasingly been used over the last decade. Protection against infectious diseases in neonates is mainly provided by maternal antibodies transferred from mother to infant during pregnancy through transplacental transport or after delivery via breastfeeding. Both the transplacental- and breast milk–derived maternal antibodies function as the primary source of protection against infectious diseases in neonates during the first vulnerable weeks of life. During recent infectious disease outbreaks (influenza, pertussis, Zika…) and for other infectious diseases (CMV, GBS…), pregnant women are increasingly identified as an important target for vaccination. For some of these diseases, vaccines are already on the market, and recommended during pregnancy. For others, vaccines are currently under development; furthermore, some are even specifically designed to be administered during pregnancy. Conclusion: This review article provides an overview on the rationale and main mechanism of the maternal vaccination strategy and gives a summary about the current and possible future recommendations for maternal vaccination."
1043,Influence of a temporary stabilization device on respiratory status in patients with severe trauma with a femoral shaft fracture treated by damage control strategy,"BACKGROUND: There are few studies on the safety and respiratory consequences of the use of a skeletal traction (ST) device in the management of femoral shaft fractures with damage control orthopaedics (DCO) strategy, particularly in cases of prolonged use. The aim of this study was to assess the influence of ST compared with an external fixator (EF) on respiratory complications and mechanical ventilation requirements in patients with severe trauma with a femoral shaft fracture managed by DCO strategy. METHODS: We retrospectively reviewed all patients with severe trauma patients with a unilateral femoral shaft fracture admitted to our institution from 2010 to 2015. Patients who did not undergo definitive osteosynthesis during the first 24 h were included and divided into two groups: DCO-ST group and DCO-EF group. In addition to trauma severity, global management of respiratory complications, the incidence of acute respiratory distress syndrome (ARDS) and mechanical ventilation requirements and outcome were compared. RESULTS: Fifty-five patients were managed with DCO strategy (mean Injury Severity Score, 28.4); there were 31 in the DCO-ST group and 24 in the DCO-EF group. No significant difference in terms of the main characteristics, initial severity and associated injuries was observed between the two groups. In contrast, ARDS was found more frequently in the DCO-ST group (81% versus 54%; P = 0.035). Number of ventilation days also tended to be higher in the DCO-ST group (9 days [IQR 3–15 days] versus 7 [IQR 2–16 days]; P = 0.24). No difference was found for mortality and hospitalization duration between the DCO-ST and DCO-EF groups. CONCLUSION: The prolonged use of an ST device in the present cohort was associated with a higher incidence of impaired respiratory function. Therefore, our findings suggest that EF is preferable to ST in the DCO setting for femoral shaft fracture, especially in trauma patients at high risk of developing delayed respiratory failure."
1044,Treatment of An Acute Severe Cadmium Poisoning Patient Combined with Multiple Organ Dysfunction Syndromes by Integrated Chinese and Western Medicines: A Case Report,
1045,Clinical relevance and impact of Corynebacterium isolation in lower respiratory tract of critically ill patients requiring mechanical ventilation,"PURPOSE: Corynebacterium spp. (C. spp.) is commonly considered as a contaminant in respiratory specimens. No study has ever focused on its clinical relevance in the lower respiratory tract of patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation. The aims were to describe the characteristics of ICU patients with a C. spp. positive deep respiratory specimen, to investigate the impact of C. spp. on the occurrence of pneumonia, and to evaluate the outcomes of these pneumonia. METHODS: We retrospectively included all adult patients admitted to ICU in a 1000-bed University Hospital (2007–2017) who had a C. spp. positive lower respiratory tract specimen at a significant quantitative level. We used clinical, radiological, and microbiological criteria to classify the likelihood of such pneumonia. RESULTS: Among the 31 patients included, acute respiratory failure and postoperative care after major surgery were the main reasons of admission. SAPS II was 47 [34–60]. C. spp. pneumonia was considered as probable, possible and unlikely in 10, 14, and 7 patients, respectively. Fifty-two and 94% of C. spp. strains were sensitive to amoxicillin, and vancomycin/linezolid, respectively. Seventeen patients had a complete course of antibiotic against C. spp. The overall ICU mortality was 58%. CONCLUSION: Corynebacterium spp seems to be responsible for authentic pneumonia in mechanically ventilated patients. It should be considered as clinically relevant when predominantly present in respiratory specimen from patients suspected with pneumonia in ICU, and empirically treated."
1046,Intracranial pressure monitors associated with increased venous thromboembolism in severe traumatic brain injury,"BACKGROUND: Utilization of intracranial pressure monitors (ICPMs) has not been consistently shown to improve mortality in patients with severe traumatic brain injury (TBI). A single-center analysis concluded that venous thromboembolism (VTE) chemoprophylaxis (CP) posed no significant bleeding risk in patients following ICPM implementation; however, there is still debate about the optimal use and timing of CP in patients with ICPMs for fear of worsening intracranial hemorrhage. We hypothesized that ICPM use is associated with increased time to VTE CP and thus increased VTE in patients with severe TBI. METHODS: A retrospective analysis of the Trauma Quality Improvement Program (2010–2016) was performed to compare severe TBI patients with and without ICPMs. A multivariable logistic regression analysis was completed. RESULTS: From 35,673 patients with severe TBI, 12,487 (35%) had an ICPM. Those with ICPMs had a higher rate of VTE CP (64.3% vs. 49.4%, p < 0.001) but a longer median time to CP initiation (5 vs. 4 days, p < 0.001) as well as a longer hospital length of stay (LOS) (18 vs. 9 days, p < 0.001) compared to those without ICPMs. After adjusting for covariates, ICPM use was found to be associated with a higher risk of VTE (9.2% vs 4.3%, OR = 1.75, CI = 1.42–2.15, p < 0.001). CONCLUSIONS: Compared to patients without ICPMs, those with ICPMs had a longer delay to initiation of CP leading to an increase in VTE. In addition, there was a nearly two-fold higher associated risk for VTE in patients with ICPMs even when controlling for known VTE risk factors. Improved adherence to initiation of CP in the setting of ICPMs may help decrease the associated risk of VTE with ICPMs."
1047,Cumulative Antenatal Risk and Kindergarten Readiness in Preterm-Born Preschoolers,"A suboptimal intrauterine environment is thought to increase the probability of deviation from the typical neurodevelopmental trajectory, potentially contributing to the etiology of learning disorders. Yet the cumulative influence of individual antenatal risk factors on emergent learning skills has not been sufficiently examined. We sought to determine whether antenatal complications, in aggregate, are a source of variability in preschoolers’ kindergarten readiness, and whether specific classes of antenatal risk play a prominent role. We recruited 160 preschoolers (85 girls; ages 3–4 years), born ≤33(6)/(7) weeks’ gestation, and reviewed their hospitalization records. Kindergarten readiness skills were assessed with standardized intellectual, oral-language, prewriting, and prenumeracy tasks. Cumulative antenatal risk was operationalized as the sum of complications identified out of nine common risks. These were also grouped into four classes in follow-up analyses: complications associated with intra-amniotic infection, placental insufficiency, endocrine dysfunction, and uteroplacental bleeding. Linear mixed model analyses, adjusting for sociodemographic and medical background characteristics (socioeconomic status, sex, gestational age, and sum of perinatal complications) revealed an inverse relationship between the sum of antenatal complications and performance in three domains: intelligence, language, and prenumeracy (p = 0.003, 0.002, 0.005, respectively). Each of the four classes of antenatal risk accounted for little variance, yet together they explained 10.5%, 9.8%, and 8.4% of the variance in the cognitive, literacy, and numeracy readiness domains, respectively. We conclude that an increase in the co-occurrence of antenatal complications is moderately linked to poorer kindergarten readiness skills even after statistical adjustment for perinatal risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10802-019-00577-8) contains supplementary material, which is available to authorized users."
1048,Global Regulatory Landscape for Aggregate Safety Assessments: Recent Developments and Future Directions,"Notwithstanding successful harmonization efforts, the global regulatory framework governing product safety is complex and continually evolving, as evidenced by additional regional guidance and regulations. In this regulatory review, we provide an overview from both global and regional perspectives. A historical perspective, with a focus on recent developments, enables identification of important long–term trends, such as a shift from single–case medical review of serious adverse events to an interdisciplinary evaluation of aggregate data for the purpose of judging product causality and informing benefit–risk assessments. We will show how these trends lead to opportunities for closer interdisciplinary collaboration, for bridging the gap between preand postmarketing surveillance, and for a more proactive determination of patient populations with a positive benefit–risk profile for product use. We will conclude by pointing to ongoing and future work that seeks to provide specific solutions for ongoing aggregate safety evaluation."
1049,Adaptive immunity: an emerging player in the progression of NAFLD,"In the past decade, nonalcoholic fatty liver disease (NAFLD) has become a leading cause of chronic liver disease and cirrhosis, as well as an important risk factor for hepatocellular carcinoma (HCC). NAFLD encompasses a spectrum of liver lesions, including simple steatosis, steatohepatitis and fibrosis. Although steatosis is often harmless, the lobular inflammation that characterizes nonalcoholic steatohepatitis (NASH) is considered a driving force in the progression of NAFLD. The current view is that innate immune mechanisms represent a key element in supporting hepatic inflammation in NASH. However, increasing evidence points to the role of adaptive immunity as an additional factor promoting liver inflammation. This Review discusses data regarding the role of B cells and T cells in sustaining the progression of NASH to fibrosis and HCC, along with the findings that antigens originating from oxidative stress act as a trigger for immune responses. We also highlight the mechanisms affecting liver immune tolerance in the setting of steatohepatitis that favour lymphocyte activation. Finally, we analyse emerging evidence concerning the possible application of immune modulating treatments in NASH therapy."
1050,Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets,"Neurological disorders such as Alzheimer’s disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and vascular dementia (VCID) have no disease-modifying treatments to date and now constitute a dementia crisis that affects 5 million in the USA and over 50 million worldwide. The most common pathological hallmark of these age-related neurodegenerative diseases is the accumulation of specific proteins, including amyloid beta (Aβ), tau, α-synuclein (α-syn), TAR DNA-binding protein 43 (TDP43), and repeat-associated non-ATG (RAN) peptides, in the intra- and extracellular spaces of selected brain regions. Whereas it remains controversial whether these accumulations are pathogenic or merely a byproduct of disease, the majority of therapeutic research has focused on clearing protein aggregates. Immunotherapies have garnered particular attention for their ability to target specific protein strains and conformations as well as promote clearance. Immunotherapies can also be neuroprotective: by neutralizing extracellular protein aggregates, they reduce spread, synaptic damage, and neuroinflammation. This review will briefly examine the current state of research in immunotherapies against the 3 most commonly targeted proteins for age-related neurodegenerative disease: Aβ, tau, and α-syn. The discussion will then turn to combinatorial strategies that enhance the effects of immunotherapy against aggregating protein, followed by new potential targets of immunotherapy such as aging-related processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00853-2) contains supplementary material, which is available to authorized users."
1051,Selenium and selenoproteins: it’s role in regulation of inflammation,"ABSTRACT: Selenium is an essential immunonutrient which holds the human’s metabolic activity with its chemical bonds. The organic forms of selenium naturally present in human body are selenocysteine and selenoproteins. These forms have a unique way of synthesis and translational coding. Selenoproteins act as antioxidant warriors for thyroid regulation, male-fertility enhancement, and anti-inflammatory actions. They also participate indirectly in the mechanism of wound healing as oxidative stress reducers. Glutathione peroxidase (GPX) is the major selenoprotein present in the human body, which assists in the control of excessive production of free radical at the site of inflammation. Other than GPX, other selenoproteins include selenoprotein-S that regulates the inflammatory cytokines and selenoprotein-P that serves as an inducer of homeostasis. Previously, reports were mainly focused on the cellular and molecular mechanism of wound healing with reference to various animal models and cell lines. In this review, the role of selenium and its possible routes in translational decoding of selenocysteine, synthesis of selenoproteins, systemic action of selenoproteins and their indirect assimilation in the process of wound healing are explained in detail. Some of the selenium containing compounds which can acts as cancer preventive and therapeutics are also discussed. These compounds directly or indirectly exhibit antioxidant properties which can sustain the intracellular redox status and these activities protect the healthy cells from reactive oxygen species induced oxidative damage. Although the review covers the importance of selenium/selenoproteins in wound healing process, still some unresolved mystery persists which may be resolved in near future. GRAPHIC ABSTRACT: [Image: see text]"
1052,A study of comorbidities in myasthenia gravis,"Management of myasthenia gravis (MG) in the presence of comorbidities may be difficult. We report the effect of comorbidities in the outcome of MG. The patients with MG during 1991–2016 were included and evaluated including their demographic variables, clinical findings, Myasthenia Gravis Foundation of America (MGFA) score. The patients were categorized into early onset (≤ 40 years) and late onset (> 40 years) MG. The comorbidities (autoimmune and miscellaneous) and iatrogenic complications were compared between early and late onset, and in good and poor outcome groups. Out of 81 patients with MG, 48 patients had early and 33 late onset. In 71 (88%) patients, comorbidities were present and were autoimmune in 8 (10%) and miscellaneous in all the patients (88%). Iatrogenic complications were present in 54 (67%) patients. Thymectomy was done in 19 patients; 16 had thymoma and 3 thymic hyperplasia. Myasthenic crisis occurred in 28 patients; 5 (18%) had autoimmune and all had miscellaneous comorbidities. The patients with poor outcome had ≥ 2 comorbidities, myasthenic crisis, leukocytosis, elevated serum bilirubin and creatinine, and increased number of hospital admissions (P < 0.05). Myasthenia gravis is associated with comorbidities in majority of patients especially in late onset group, and more than two comorbidities are related to poor outcome."
1053,Frailty Predicts Morbidity and Mortality After Laparoscopic Cholecystectomy for Acute Cholecystitis: An ACS-NSQIP Cohort Analysis,"BACKGROUND: Current guidelines recommend laparoscopic cholecystectomy be offered for patients with acute cholecystitis except those deemed as high risk. Few studies have examined the impact of frailty on outcomes for patients undergoing laparoscopic cholecystectomy. Therefore, the aim of this study was to determine the association of frailty with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis. METHODS: Patients undergoing laparoscopic cholecystectomy for acute cholecystectomy were identified from 2005 to 2010 in the American College of Surgeons National Surgical Quality Improvement Project (NSQIP). The Modified Frailty Index (mFI) was used a surrogate for frailty, and patients were stratified as non-frail (mFI 0), low frailty (mFI 1–2), intermediate frailty (mFI 3–4) and high frailty (mFI ≥ 5). Univariable and multivariable analyses were performed. Receiver operator curves (ROC) and an area under the curve (AUC) were generated to determine accuracy of mFI in predicting postoperative morbidity and mortality. RESULTS: Of the 6898 patients undergoing laparoscopic cholecystectomy, 3245 (47%) patients were non-frail. There were 2913 (42%) patients with low-frailty, 649 (9%) patients with intermediate frailty, and 91 (2%) with high frailty. Clavien IV complications were higher for intermediate frail patients (OR 1.81, 95% CI 1.00–3.28, p = 0.050) and high-frail patients (OR 4.59, 95% CI 1.98–10.7, p < 0.001). Additionally, mortality was higher for patients with intermediate frailty (OR 4.69, 95% CI 1.37–16.0, p = 0.014) and high frailty (OR 12.2, 95% CI 2.67–55.5, p = 0.001). The mFI had excellent accuracy for mortality (AUC = 0.83) and Clavien IV complications (AUC = 0.73). CONCLUSION: Frailty is associated with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis."
1054,Healthcare needs of vulnerable patient groups: available data and existing gaps in Germany with respect to long-term mechanical ventilation,"AIM: Long-term invasively ventilated patients exhibit exceptional and resource-intensive healthcare needs. However, major knowledge gaps in Germany complicate appropriate approaches to best address these demands. This paper evaluates available information on the patient group and their healthcare needs from German data sources and derives implications for healthcare planning and regulation by national/federal self-governing bodies, political decision-makers, and specialized providers. METHODS: Based on the concept of needs, we addressed the normative dimension typically characterized by epidemiological data. Based on existing German health system data resources, an explorative approach was utilized to identify and characterize available databases providing information on the patient group and/or their healthcare. RESULTS: To date, no available database provides information on the healthcare needs of this patient group. As of the reporting year 2017, the diagnosis-related groups (DRG) statistics will provide hospital-specific data on home invasive ventilation interventions, but the data do not provide information on long-term care. Claims data may be a promising source for cross-sectoral evaluation of healthcare needs but feature methodological challenges. These results call for efforts to address limited data eligibility, adopt a broader understanding of healthcare needs, and identify actions needed to evidence informed and needs-oriented healthcare. CONCLUSION: Future approaches on needs-oriented specialized healthcare should close the existing knowledge gap based on reliable data. In addition to normative information, they should consider subjective dimensions on a life course perspective and quantitative and qualitative service performance characteristics across multiple sectors and professions."
1055,Immunophenotypic analysis of cerebrospinal fluid reveals concurrent development of ATL in the CNS of a HAM/TSP patient,"Both adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) can be induced by HTLV-1, but concurrent development has been rarely reported. We present the case of a 55-year-old female who developed cranial nerve symptoms after a 20-year history of HAM/TSP. Although multiple white matter lesions were observed on brain magnetic resonance imaging, no abnormalities were seen on a systemic computed tomography scan. Quantitative flow-cytometric analysis of cell populations in the cerebrospinal fluid (CSF) revealed that most of the infiltrating cells were not inflammatory cells, but HTLV-1-infected CD4(+) CADM-1(+) T-cells completely lacking CD7 expression. As stepwise downregulation of CD7 is correlated with disease progression from HTLV-1 carrier to aggressive ATL, the CSF cells were classified as aggressive ATL; these cells exhibited a more progressed phenotype than those in peripheral blood (PB). HAM/TSP disease activity was estimated to be low. From these and other examinations, we made a diagnosis of acute-type ATL, which unusually developed in the central nervous system at initial onset prior to systemic progression. In ATL cases with a challenging diagnosis, immunophenotypic characterization of CSF and PB is valuable for differential diagnosis and understanding disease status."
1056,"CD8(+) T cells in HIV control, cure and prevention","HIV infection can be effectively treated by lifelong administration of combination antiretroviral therapy, but an effective vaccine will likely be required to end the HIV epidemic. Although the majority of current vaccine strategies focus on the induction of neutralizing antibodies, there is substantial evidence that cellular immunity mediated by CD8(+) T cells can sustain long-term disease-free and transmission-free HIV control and may be harnessed to induce both therapeutic and preventive antiviral effects. In this Review, we discuss the increasing evidence derived from individuals who spontaneously control infection without antiretroviral therapy as well as preclinical immunization studies that provide a clear rationale for renewed efforts to develop a CD8(+) T cell-based HIV vaccine in conjunction with B cell vaccine efforts. Further, we outline the remaining challenges in translating these findings into viable HIV prevention, treatment and cure strategies."
1057,Society of Surgical Oncology SSO 2020 – International Conference on Surgical Cancer Care,
1058,A Change of Course: The Case for a Neurorecovery Clinic,
1059,An extensive field study reveals the circulation of new genetic variants of subtype 1a of bovine viral diarrhea virus in Uruguay,"Bovine viral diarrhea virus (BVDV) is a major pathogen worldwide, causing significant economic losses to the livestock sector. In Uruguay, BVDV seroprevalence at the farm level is >80%. In this work, 2546 serum, blood or tissue samples collected from animals suspected of being affected by BVD between 2015 and 2017 were analyzed by reverse transcription PCR and sequencing. Analysis of the BVDV genomic regions 5’UTR/N(pro), N(pro) and E2 revealed that BVDV-1a, 1i and 2b circulate in the country, with BVDV-1a being the most prevalent subtype. Population dynamics studies revealed that BVDV-1a has been circulating in our herds since ~1990. This subtype began to spread and evolve, accumulating point mutations at a rate of 3.48 × 10(−3) substitutions/site/year, acquiring specific genetic characteristics that gave rise to two local genetic lineages of BVDV-1a. These lineages are divergent from those circulating worldwide, as well as the vaccine strain currently used in Uruguay. The most notable differences between field and vaccine strains were found in the E2 glycoprotein, suggesting that the amino acid substitutions could result in failure of cross-protection/neutralization after vaccination. This is the first study that compares Uruguayan BVDV field and vaccine strains with other BVDV strains from throughout the world. The results obtained in this study will be very useful for developing a suitable immunization program for BVDV in Uruguay by identifying local field strains as candidates for vaccine development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04446-z) contains supplementary material, which is available to authorized users."
1060,"Colletotrichum species causing cassava (Manihot esculenta Crantz) anthracnose in different eco-zones within the Recôncavo Region of Bahia, Brazil","A survey to investigate the occurrence of cassava anthracnose disease (CAD) and distribution of Colletotrichum spp. in cassava plantations in different eco-zones of the Reconcavo Region in Bahia, Brazil, investigated during the rainy season of 2014. A total of 50 cassava fields distributed among 18 municipalities were visited and intensity of anthracnose evaluated. The highest disease incidence (DI) (83.3%) was in samples collected in São Félix, and the lowest (34.4%), in Varzedo. Municipalities that presented the highest values for DI were located within the ‘Af’ Köppen–Geiger eco-zone, also presenting the highest values for the estimated McKinney disease index. Based on previous studies of multilocus phylogeny, seven different species of Colletotrichum were identified (Colletotrichum fructicola, Colletotrichum tropicale, Colletotrichum gloeosporioides s.s, Colletotrichum theobromicola, Colletotrichum siamense, Colletotrichum brevisporum and Colletotrichum plurivorum) and a new approach based on ERIC-PCR was used aiming to group the 82 isolates according to these findings. The highest percentage of genetic variance (> 78%) was among isolates within fields. Based on the survey and genetic analysis, C. fructicola is probably the main causal agent of cassava anthracnose in the Recôncavo Region, since this species was present with highest incidence in all eco-zones, 47.61, 42.86 and 57.14% for Af (tropical rainforest climate), As (tropical dry savanna climate) and Aw (tropical wet savanna climate), respectively. This study is the first report of C. fructicola lineages as the most likely pathogen causing anthracnose disease of cassava in Brazil, and these findings may be used to guide the selection of resistant varieties."
1061,Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study,"An accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p < 0.01). S. pneumoniae remains the most common pathogen in patients hospitalized with CAP. Multinational CPG recommendations for patients with CAP seem to appropriately cover the most common pathogens and should be strongly encouraged for the management of CAP patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-020-03870-3) contains supplementary material, which is available to authorized users."
1062,High-resolution melting curve analysis: a novel method for identification of Mycoplasma species isolated from clinical cases of bovine and porcine respiratory disease,"Mycoplasma species cause wide ranges of infectious diseases in human and animals. The aim of the present study was to evaluate a real-time polymerase chain reaction (RT-PCR) followed by a high-resolution melting curve assay (HRM) for rapid differentiation of Mycoplasma species isolated from clinical cases of bovine and porcine respiratory disease. Lung samples from suspected cases to respiratory infections from cows and pigs were cultured on specific media, and the extracted DNA were tested by conventional polymerase chain reaction (PCR) assays for Mycoplasma. A set of universal primers specific for the 16S ribosomal RNA gene was designed and used for RT-PCR and HRM. The HRM analysis was able to differentiate between five different species of Mycoplasmas, namely, M. hyopneumoniae, M. bovis, M. hyorhinis, M. hyosynoviae and other uncultured Mycoplasma. All results were confirmed based on 16S rRNA gene sequencing. This rapid and reliable assay was as a simple alternative to PCR and sequencing, differentiating bovine and porcine mycoplasmas in species level."
1063,Bioinformatics design and experimental validation of influenza A virus multi-epitopes that induce neutralizing antibodies,"Pandemics caused by influenza A virus (IAV) are responsible for the deaths of millions of humans around the world. One of these pandemics occurred in Mexico in 2009. Despite the impact of IAV on human health, there is no effective vaccine. Gene mutations and translocation of genome segments of different IAV subtypes infecting a single host cell make the development of a universal vaccine difficult. The design of immunogenic peptides using bioinformatics tools could be an interesting strategy to increase the success of vaccines. In this work, we used the predicted amino acid sequences of the neuraminidase (NA) and hemagglutinin (HA) proteins of different IAV subtypes to perform multiple alignments, epitope predictions, molecular dynamics simulations, and experimental validation. Peptide selection was based on the following criteria: promiscuity, protein surface exposure, and the degree of conservation among different medically relevant IAV strains. These peptides were tested using immunological assays to test their ability to induce production of antibodies against IAV. We immunized rabbits and mice and measured the levels of IgG and IgA antibodies in serum samples and nasal washes. Rabbit antibodies against the peptides P11 and P14 (both of which are hybrids of NA and HA) recognized HA from both group 1 (H1, H2, and H5) and group 2 (H3 and H7) IAV and also recognized the purified NA protein from the viral stock (influenza A Puerto Rico/916/34). IgG antibodies from rabbits immunized with P11 and P14 were capable of recognizing viral particles and inhibited virus hemagglutination. Additionally, intranasal immunization of mice with P11 and P14 induced specific IgG and IgA antibodies in serum and nasal mucosa, respectively. Interestingly, the IgG antibodies were found to have neutralizing capability. In conclusion, the peptides designed through in silico studies were validated in experimental assays. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04537-2) contains supplementary material, which is available to authorized users."
1064,Preoperative Assessment and Management of Patients with Pain and Anxiety Disorders,"PURPOSE OF REVIEW: This review summarizes selected recent evidence on issues important for preoperative pain evaluation. RECENT FINDINGS: Opioids, though a mainstay of postoperative pain management, are associated with both short and increasingly recognized long-term risks, including persistent opioid use. Risk factors for high levels of acute postoperative pain as well as chronic postsurgical pain may overlap, including psychological factors such as depression, anxiety, and catastrophizing. Tools to predict those at risk for poor postoperative pain outcomes are being studied. SUMMARY: Preoperative pain and psychological factors can affect postoperative pain outcomes. More work is needed in the future to develop practical interventions in the preoperative period to address these factors."
1065,Novel targets and strategies to combat borreliosis,"Lyme borreliosis is a bacterial infection that can be spread to humans by infected ticks and may severely affect many organs and tissues. Nearly four decades have elapsed since the discovery of the disease agent called Borrelia burgdorferi. Although there is a plethora of knowledge on the infectious agent and thousands of scientific publications, an effective way on how to combat and prevent Lyme borreliosis has not been found yet. There is no vaccine for humans available, and only one active vaccine program in clinical development is currently running. A spirited search for possible disease interventions is of high public interest as surveillance data indicates that the number of cases of Lyme borreliosis is steadily increasing in Europe and North America. This review provides a condensed digest of the history of vaccine development up to new promising vaccine candidates and strategies that are targeted against Lyme borreliosis, including elements of the tick vector, the reservoir hosts, and the Borrelia pathogen itself."
1066,Development of Population and Bayesian Models for Applied Use in Patients Receiving Cefepime,"BACKGROUND AND OBJECTIVE: Understanding pharmacokinetic disposition of cefepime, a β-lactam antibiotic, is crucial for developing regimens to achieve optimal exposure and improved clinical outcomes. This study sought to develop and evaluate a unified population pharmacokinetic model in both pediatric and adult patients receiving cefepime treatment. METHODS: Multiple physiologically relevant models were fit to pediatric and adult subject data. To evaluate the final model performance, a withheld group of 12 pediatric patients and two separate adult populations were assessed. RESULTS: Seventy subjects with a total of 604 cefepime concentrations were included in this study. All adults (n = 34) on average weighed 82.7 kg and displayed a mean creatinine clearance of 106.7 mL/min. All pediatric subjects (n = 36) had mean weight and creatinine clearance of 16.0 kg and 195.6 mL/min, respectively. A covariate-adjusted two-compartment model described the observed concentrations well (population model R(2), 87.0%; Bayesian model R(2), 96.5%). In the evaluation subsets, the model performed similarly well (population R(2), 84.0%; Bayesian R(2), 90.2%). CONCLUSION: The identified model serves well for population dosing and as a Bayesian prior for precision dosing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40262-020-00873-3) contains supplementary material, which is available to authorized users."
1067,A Comprehensive Review of Cutaneous Leishmaniasis in Sri Lanka and Identification of Existing Knowledge Gaps,"PURPOSE: Sri Lanka is endemic to cutaneous leishmaniasis and reported as the latest focus of leishmaniasis in the Asian subcontinent. Annually, the number of leishmaniasis cases is increasing; therefore, more efficient diagnostic tools, treatment methods and effective prevention measures are indispensable. For this reason, many studies were conducted regarding leishmaniasis infections in Sri Lanka; however, some areas need more attention. Thus, in this review, we comprehensively discussed the studies on leishmaniasis carried out in Sri Lanka. METHODS: Published articles on leishmaniasis in Sri Lanka were searched on PubMed, Google Scholar and ResearchGate databases. Inclusion criteria for the articles were based on keyword searches including ‘Leishmaniasis in Sri Lanka’, ‘Leishmaniasis vector in Sri Lanka’, ‘Sandfly species in Sri Lanka’, ‘Leishmaniasis epidemiology in Sri Lanka’ which are publicly accessible as of 15th July 2019. RESULTS: In this study, we evaluated and summarized the leishmaniasis reports in Sri Lanka and mainly focused on clinical presentation of leishmaniasis infection, genetic characteristics of Leishmania donovani Sri Lankan strain, geographical distribution and associated environmental factors, immunological aspects of the infection, vector, reservoir host, risk factors, diagnosis and treatment, and prevention and control. Furthermore, we identified the areas where further research is needed to fill the essential knowledge gaps. CONCLUSIONS: Leishmaniasis has become a critically important parasitic infection in Sri Lanka, whereas the significant clinical form is cutaneous leishmaniasis. Prevalence of the leishmaniasis infections is reported from all the districts of the country. Therefore, more studies are essential to be carried out to fill the existing knowledge gaps emphasized in this review."
1068,Validity and reliability of pocket-sized ultrasound devices in measurement of optic nerve sheath diameter in ICU patients,"The measurement of the optic nerve sheath diameter (ONSD) by ultrasonography (USG) is particularly important for intracranial pressure (ICP) monitoring when invasive measurements are not possible or are contraindicated. Standard USG (SUDs) devices can be bulky and may break down the workflow. The validity and reliability of pocket-sized USG devices (PSUDs) compared to SUDs for ONSD measurement has not been investigated, yet. We compared the reliability and validity of PSUDs with SUDs for ONSD measurement. 35 patients were included in the study. ONSD measurements with PSUDs and SUDs were performed by two clinicians as three different measurements in both sagittal and transverse axis of the eye. There was agreement between mean transverse ONSD (mtONSD), mean sagittal ONSD (msONSD), and mean ONSD(mONSD) values measured with each device according to Bland–Altman test (p = 0.166, p = 0.135, p = 0.066, respectively) with no proportional bias (p = 0.544, p = 0.868, p = 0.929, respectively). Intraclass correlation coefficients (ICC) were found to be greater than 0.7 for mtONSD, msONSD, and mONSD values measured by SUD (ICC = 0.790, ICC = 0.817, and ICC = 0.844, respectively). Similarly, for mtONSD, msONSD, and mONSD values measured by PSUD, ICC were found greater than 0.7 (ICC = 0.763, ICC = 0.814, and ICC = 0.843, respectively). There was no statistically significant difference between mtONSD and msONSD (p = 0.441 for SUD and p = 0.893 for PSUD). There was a good correlation between mtONSD and msONSD (r = 0.767 for SUD and r = 0.816 for PSUD). The total variance between three different measurements in the transverse and sagittal axis was ± 0.6 mm. PSUDs can be used with similar validity and reliability as SUDs for ONSD measurement."
1069,"Green synthesis of zinc oxide nanoparticles from the leaf, stem and in vitro grown callus of Mussaenda frondosa L.: characterization and their applications","Biosynthesis of zinc oxide nanoparticles (ZnO-NPs) was achieved by utilizing the reducing and capping potential of leaf, stem and callus aqueous extracts of Mussaenda frondosa.The bioreduced ZnO-NPs were characterized using powder X-ray diffraction (XRD), ultraviolet–visible spectroscopy (UV–Vis spectroscopy), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), fourier transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS) techniques. UV–visible spectra of ZnO-NPs showed a strong absorption peak at 370, 376 and 373 nm corresponding to the band gap energy of 3.33, 3.27 and 3.30 eV for ZnO-NPs obtained from leaf (L-ZnO-NP), stem (S-ZnO-NP) and callus (C-ZnO-NP) aqueous extracts, respectively. XRD analysis confirmed the formation of hexagonal wurtzite structures having an average grain size between 5 and 20 nm in diameter. FTIR spectra revealed the presence of stretching vibrations of –O–H, C–H, C–N, C = O groups involved in reduction and stabilization of nanoparticles. SEM images recognize the presence of spongy, spherical, porous agglomerated nanoparticles. DLS analysis and zeta potential values validated the stability of ZnO-NPs. The present investigation puts light on the photocatalytic activity and biological (antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancerous) applications of ZnO-NPs. The current study is an attempt to describe an effective, simple and eco-friendly method of ZnO-NP synthesis and to evaluate its potential for various industrial and medical applications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13204-020-01382-2) contains supplementary material, which is available to authorized users."
1070,New markers for sepsis caused by Pseudomonas aeruginosa during burn infection,"INTRODUCTION: Sepsis is a leading cause of mortality in burn patients. One of the major causes of sepsis in burn patients is Pseudomonas aeruginosa. We hypothesized that during dissemination from infected burn wounds and subsequent sepsis, P. aeruginosa affects the metabolome of the blood resulting in changes to specific metabolites that would serve as biomarkers for early diagnosis of sepsis caused by P. aeruginosa. OBJECTIVES: To identify specific biomarkers in the blood after sepsis caused by P. aeruginosa infection of burns. METHODS: Gas chromatography with time-of-flight mass spectrometry was used to compare the serum metabolome of mice that were thermally injured and infected with P. aeruginosa (B–I) to that of mice that were neither injured nor infected, mice that were injured but not infected, and mice that were infected but not injured. RESULTS: Serum levels of 19 metabolites were significantly increased in the B–I group compared to controls while levels of eight metabolites were significantly decreased. Thymidine, thymine, uridine, and uracil (related to pyrimidine metabolism), malate and succinate (a possible sign of imbalance in the tricarboxylic acid cycle), 5-oxoproline (related to glutamine and glutathione metabolism), and trans-4-hydroxyproline (a major component of the protein collagen) were increased. Products of amino acid metabolism were significantly decreased in the B–I group, including methionine, tyrosine, indole-3-acetate, and indole-3-propionate. CONCLUSION: In all, 26 metabolites were identified, including a unique combination of five metabolites (trans-4-hydroxyproline, 5-oxoproline, glycerol-3-galactoside, indole-3-acetate, and indole-3-propionate) that could serve as a set of biomarkers for early diagnosis of sepsis caused by P. aeruginosa in burn patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11306-020-01658-2) contains supplementary material, which is available to authorized users."
1071,The performance of biological and tertiary wastewater treatment procedures for rotaviruses A removal,"Enteric viruses, generally found in sewage, are recognized as the main cause of waterborne and foodborne public health outbreaks. Among leading enteric viruses, the Rotavirus A (RVA) detection in wastewater appeared to be a novel approach to monitor the emergence of these viruses in some countries where the viral gastroenteritis surveillance is almost absent such as in Tunisia. The RVA detection and quantification in an industrial sewage purification plant of Charguia I (Tunis, Tunisia) were achieved to evaluate the performance of activated sludge procedures coupled to a macrofiltration monolamp ultraviolet irradiation type C (UV-C(254)) disinfection reactor. This UV-C(254) system was preceded by a fiberglass cartridge filter system with an average porosity of 45 μm to clarify the water and thus increase its UV transmittance. A total of 140 composite sewage samples was collected from this line of treatment and analyzed for RVA detection. The detection and the viral load quantification of RVA were performed using real-time reverse transcription polymerase chain reaction (RT-PCR). The virological results showed in general that RVA were detected at high frequency of 98% (137/140). In fact, the RVA detection rates at the exit of the two studied wastewater treatment were about 100% at the exit of the activated sludge procedure. It means that all wastewater sampled at this last step of treatment was positive for RVA detection. On the other hand, 92.5% of the wastewater samples taken at the exit of the monolamp UV-C(254) reactor were positive for the RVA. However, the RVA quantification results expressed as viral load showed a significant reduction in the means of RVA viral loads at the exit of the biological activated sludge procedure and the tertiary UV-C(254) treatment, showing in general an improved treated wastewater virological quality. Therefore, the RVA load removal rates recorded at the two successive stages of treatment, the activated sludge and the UV-C(254) treatment, were around 85% and 73%, respectively, as compared to the one with 100% registered for the raw wastewater. In addition, good physical-chemical and bacteriological qualities of the treated sewage were found at the exit of the two considered wastewater treatment procedures. The present investigation represents the first Tunisian environmental report showing the good effectiveness and performance of the biological and the tertiary treatments for RVA removal. Therefore, an improved and an optimized tertiary disinfection treatment was needed since it could be a good means for getting better viral water quality and for minimizing the transmission and dissemination of human infectious viral diseases."
1072,Enhanced oral hygiene interventions as a risk mitigation strategy for the prevention of non-ventilator-associated pneumonia: a systematic review and meta-analysis,"Background Healthcare-acquired pneumonias are a significant risk for nursing home and hospital patients. While oral care interventions (OCIs) have been found to be effective in reducing the risk of ventilator-associated pneumonia (VAP), their utility in mitigating non-ventilator-associated pneumonias (NVAP) remains unknown. We performed a structured meta-analysis of randomised and non-randomised clinical trials of enhanced oral hygiene procedures on NVAP. Methods We searched PubMed and Embase to include clinical trials (randomised and non-randomised), and observational (retrospective and prospective) and quasi-experimental studies examining the effect of any method of OCI on incidence of NVAP. Results After quality assessment and consensus agreement between authors, we synthesised six randomised clinical trials (3,891 patients), two non-randomised trials (2,993 patients), and separately assessed a retrospective trial (143 patients) and a quasi-experimental study (83 patients). Most studies, performed in nursing homes, did not show a significant association between OCI and NVAP prevention (RR random 0.89, 95% CI 0.64-1.25, p value 0.50). Likewise, the non-randomised trials failed to show an association between NVAP risk and OCI (RR random 1.42, 95% CI, 0.70-2.88, p value 0.32). However, in the subgroup analysis comparing dental professional involvement in care vs usual care, reduced NVAP risk was demonstrated (RR random 0.65, 95% CI 0.43-0.98, p value 0.03). Conclusions Study results suggest that professional dental care may confer some benefit among NVAP patients. The lack of consistent OCI protocols, data in hospitalised patients and robust randomised clinical trials do not allow definitive conclusions about the contribution of OCI in mitigating NVAP risk. Zusatzmaterial online: Zu diesem Beitrag sind unter 10.1038/s41415-020-1452-7 für autorisierte Leser zusätzliche Dateien abrufbar."
1073,Macrophage-like THP-1 cells show effective uptake of silica nanoparticles carrying inactivated diphtheria toxoid for vaccination,"Nanoparticles may be used in vaccinology as an antigen delivery and/or an immunostimulant to enhance immunity. Porous silica has been identified as an effective adjuvant for more than a decade, and we have therefore investigated the take up rate by an immortalized macrophage-like cell line of a number of mesoporous silica nanoparticles (MSNPs) with differing diameter and pore size. The MSNPs were synthesized using a sol-gel reaction and post-synthesis removal of the template. The MSNPs showed a clear distribution in take up rate peaking at 217 nm, whereas a comparison with solid spherical nanoparticles showed a similar distribution peaking at 377 nm. The MSNPs were investigated before and after loading with antigen. Diphtheria toxoid was used as a proof-of-concept antigen and showed a peak macrophage internalization of 53.42% for loaded LP3 particles which had a diameter of 217.75 ± 5.44 nm and large 16.5 nm pores. Optimal MSNP sizes appeared to be in the 200–400 nm range, and larger pores showed better antigen loading. The mesoporous silica particles were shown to be generally biocompatible, and cell viability was not altered by the loading of particles with or without antigen. [Figure: see text]"
1074,Bubble bilevel ventilation facilitates gas exchange in anesthetized rabbits,"BACKGROUND: Bubble continuous positive airway pressure is an established therapy for infants in respiratory distress. In resource-limited settings, few treatment options exist for infants requiring further respiratory support. A bubble bilevel device has been developed to provide nonelectric, time-cycled, pressure-limited respiratory support. We compared the efficacy of bubble bilevel ventilation with conventional mechanical ventilation in sedated rabbits. METHODS: Six adult rabbits under inhaled isoflurane general anesthesia were ventilated by alternating intervals of conventional and bubble bilevel ventilation for three 10−15-min periods. During each period, interval arterial blood gas (ABG) measurements were obtained after at least 10 min on the respective mode of ventilation. RESULTS: The bubble bilevel system was able to deliver the following pressures: 20/7, 15/5, 12/5, 8/5 cm H(2)O. The estimated differences in arterial blood gas values on bubble bilevel vs. ventilator were as follows (normalized values): pH 7.41 vs. 7.40, pCO(2) 37.7 vs. 40, pO(2) 97.6 vs. 80. In addition, the bubble bilevel ventilation delivered consistent pressure waveforms without interruption for over 60 min on two rabbits. CONCLUSION: This study demonstrates promising in vivo results on the efficacy of a novel bubble bilevel device, which may prove useful for infants in respiratory distress. IMPACT: Given the lack of personnel, funds or infrastructure to provide neonatal mechanical ventilation in resource-limited settings, additional low-cost, low-tech treatments are necessary to save infant lives. Bubble bilevel ventilation reliably delivers two levels of airway pressure to anesthetized rabbits resulting in normalization of blood gases comparable to those achieved on a traditional ventilator. If proven effective, simple technologies like this device have the potential to significantly impact neonatal mortality due to respiratory distress globally."
1075,"Streptovertimycins A–H, new fasamycin-type antibiotics produced by a soil-derived Streptomyces morookaense strain","Eight new fasamycin-type polyketides, streptovertimycins A–H (1−8), were isolated from soil-derived Streptomyces morookaense SC1169 cultivated on wheat grains. Their structures were established by extensive spectroscopic analysis and theoretical computations of ECD spectra. Compounds 1−8 have a fasamycin-type pentacyclic structure featuring a 15-O-methyl group. They exhibited potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) with MIC values in the range of 0.63–5.0 μg/ml. The activity profile provided new insights into the structure–activity relationships of fasamycin-type antibiotics."
1076,Selecting the dosage of ceftazidime–avibactam in the perfect storm of nosocomial pneumonia,"PURPOSE: Ceftazidime–avibactam is a novel β-lactam/β-lactamase inhibitor combination recently approved in Europe and the USA for the treatment of adults with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), among other indications. In the phase III REPROVE trial (NCT01808092), ceftazidime–avibactam demonstrated non-inferiority to meropenem for the treatment of patients with nosocomial pneumonia (NP), including VAP. As ceftazidime–avibactam was not studied in patients with NP prior to REPROVE, selecting an appropriate dosage regimen in the “perfect storm” of NP required careful consideration of potential determinants and confounders of response specific to the NP patient population. METHODS: This review describes the series of preclinical studies and pharmacokinetic/pharmacodynamic (PK/PD) analyses that supported ceftazidime–avibactam dosage selection for patients with NP/VAP (2000/500 mg by 2-h intravenous infusion every 8 h, adjusted for renal function). In parallel, important considerations for antibiotic dosage selection in patients with NP are highlighted, including adequate drug penetration into the lungs, the suitability of murine-derived plasma PK/PD targets, evaluation of MIC distributions against clinical bacterial isolates from patients with NP, and consideration of PK in patients with NP, who are often critically ill. These analyses also supported the European approval of ceftazidime–avibactam for adults with HAP, including VAP, before the completion of REPROVE. CONCLUSIONS: This work serves as a successful practical example of dosage design for a new antibacterial drug therapy in the indication of NP, including VAP, where previous drug therapies have failed, possibly as a result of evaluation of too few variables, thereby limiting the accuracy of pharmacodynamic predictions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00228-019-02804-z) contains supplementary material, which is available to authorized users."
1077,Peculiarities of biofilm formation by Paracoccus denitrificans,"Most bacteria form biofilms, which are thick multicellular communities covered in extracellular matrix. Biofilms can become thick enough to be even observed by the naked eye, and biofilm formation is a tightly regulated process. Paracoccus denitrificans is a non-motile, Gram-negative bacterium that forms a very thin, unique biofilm. A key factor in the biofilm formed by this bacterium is a large surface protein named biofilm-associated protein A (BapA), which was recently reported to be regulated by cyclic diguanosine monophosphate (cyclic-di-GMP or c-di-GMP). Cyclic-di-GMP is a major second messenger involved in biofilm formation in many bacteria. Though cyclic-di-GMP is generally reported as a positive regulatory factor in biofilm formation, it represses biofilm formation in P. denitrificans. Furthermore, quorum sensing (QS) represses biofilm formation in this bacterium, which is also reported as a positive regulator of biofilm formation in most bacteria. The QS signal used in P. denitrificans is hydrophobic and is delivered through membrane vesicles. Studies on QS show that P. denitrificans can potentially form a thick biofilm but maintains a thin biofilm under normal growth conditions. In this review, we discuss the peculiarities of biofilm formation by P. denitrificans with the aim of deepening the overall understanding of bacterial biofilm formation and functions."
1078,Noninvasive respiratory support in the hypoxaemic peri-operative/periprocedural patient: a joint ESA/ESICM guideline,"Hypoxaemia is a potential life-threatening yet common complication in the peri-operative and periprocedural patient (e.g. during an invasive procedure at risk of deterioration of gas exchange, such as bronchoscopy). The European Society of Anaesthesiology (ESA) and the European Society of Intensive Care Medicine (ESICM) developed guidelines for the use of noninvasive respiratory support techniques in the hypoxaemic patient in the peri-operative and periprocedural period. The panel outlined five clinical questions regarding treatment with noninvasive respiratory support techniques [conventional oxygen therapy (COT), high flow nasal cannula, noninvasive positive pressure ventilation (NIPPV) and continuous positive airway pressure (CPAP)] for hypoxaemic patients with acute peri-operative/periprocedural respiratory failure. The goal was to assess the available literature on the various noninvasive respiratory support techniques, specifically studies that included adult participants with hypoxaemia in the peri-operative/periprocedural period. The literature search strategy was developed by a Cochrane Anaesthesia and Intensive Care trial search specialist in close collaboration with the panel members and the ESA group methodologist. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the level of evidence and to grade recommendations. The final process was then validated by both ESA and ESICM scientific committees. Among 19 recommendations, the two grade 1B recommendations state that: in the peri-operative/periprocedural hypoxaemic patient, the use of either NIPPV or CPAP (based on local expertise) is preferred to COT for improvement of oxygenation; and that the panel suggests using NIPPV or CPAP immediately post-extubation for hypoxaemic patients at risk of developing acute respiratory failure after abdominal surgery. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-05948-0) contains supplementary material, which is available to authorized users."
1079,14 Years’ experience of esophageal replacement surgeries,"BACKGROUND: Esophageal replacement is a challenge to the therapeutic skills of surgeons and a technically demanding operation in the pediatric age group. Various conduits and routes have been described in the literature, each with their specific advantages and disadvantages. We carried out this retrospective study to share our experience of esophageal replacement. METHODOLOGY: This study was conducted at the department of pediatric surgery The Children’s Hospital and The Institute of Child Health, Lahore. The records of patients treated for esophageal replacement were reviewed. The patients under follow-up were called for clinical evaluation and assessed of long terms complications if any. RESULTS: A total of 93 patients with esophageal replacement were included in the study. Esophageal replacement was done with gastric transposition in 84 cases (90%), colon interposition in 7 cases (7.5%) including one case of redo colonic interposition, and jejunal interposition in 2 cases (2%). Routes of esophageal replacement were trans-hiatal in 71 (76%), retrosternal in 13 (14%), and trans-hiatal with thoracotomy in 9 (10%) patients. Postoperatively, all of the conduits maintained viability. Wound infection was seen in 10 (11%), wound dehiscence in 5 (5%), anastomotic leak in 9 (10%), anastomotic stenosis in 12 (13%), fistula formation in 4 (4%), aortic injury 1 (1%), dumping syndrome 8 (9%), reflux 18 (19%), dysphagia 15 (16%) and death occurred in 12 patients (13%). CONCLUSION: There are problems with esophageal replacement in developing countries. In this context, gastric conduit appeared as the best conduit for esophageal replacement, using the trans-hiatal route for replacement, in the authors’ experience."
1080,Treatment of Ebola-related critical illness,"PURPOSE: To explore contemporary clincial case management of patients with Ebola virus disease. METHODS: A narrative review from a clinical perspective of clinical features, diagnostic tests, treatments and outcomes of patients with Ebola virus disease. RESULTS: Substantial advances have been made in the care of patients with Ebola virus disease (EVD), precipitated by the unprecedented extent of the 2014–2016 outbreak. There has been improved point-of-care diagnostics, improved characterization of the clinical course of EVD, improved patient-optimized standards of care, evaluation of effective anti-Ebola therapies, administration of effective vaccines, and development of innovative Ebola treatment units. A better understanding of the Ebola virus disease clinical syndrome has led to the appreciation of a central role for critical care clinicians—over 50% of patients have life-threatening complications, including hypotension, severe electrolyte imbalance, acute kidney injury, metabolic acidosis and respiratory failure. Accordingly, patients often require critical care interventions such as monitoring of vital signs, intravenous fluid resuscitation, intravenous vasoactive medications, frequent diagnostic laboratory testing, renal replacement therapy, oxygen and occasionally mechanical ventilation. CONCLUSION: With advanced training and adherence to infection prevention and control practices, clinical interventions, including critical care, are feasible and safe to perform in critically ill patients. With specific anti-Ebola medications, most patients can survive Ebola virus infection."
1081,Incidence and Profile of Severe Cycling Injuries After Bikeway Infrastructure Changes,"The objective of this study was to evaluate whether bicycling infrastructure changes in the city of Minneapolis effectively reduced the incidence or severity of traumatic bicycling related injuries sustained by patients admitted to our Level 1 Trauma Center. Data for this retrospective cohort study was obtained from the trauma database at our institution and retrospective chart review. The total number of miles of bikeway in the city on a yearly basis was used to demonstrate the change in cycling infrastructure. Adjusted regression analysis demonstrated a significant reduction in ISS when total bike lane miles increased (Coef. − 0.04, P < 0.001). Increasing bike lane miles was also associated with a significant reduction in severe head injury (OR 0.99, P < 0.001) and ICU LOS (Coef. − 0.17, P = 0.013). The miles of bike lanes were not associated with any significant changes in mortality or mechanical ventilation days when adjusted for other factors. We were able to demonstrate a reduction in the severity of injuries incurred by cyclists in the setting of a significant increase in the total number of bicycle lane miles. Our data lends credence to the existing evidence that the addition of bicycle lane miles increases cyclist safety."
1082,Impfen im Kontext globaler Herausforderungen,
1083,Oxidative stress markers in neonatal respiratory distress syndrome: advanced oxidation protein products and 8-hydroxy-2-deoxyguanosine in relation to disease severity,"OBJECTIVE: We assessed oxidant–antioxidant status and evaluated the role of lipid peroxidation, oxidative DNA damage, and protein oxidation in the development and severity of neonatal respiratory distress syndrome (RDS). METHODS: Forty preterm neonates with RDS were compared with another 40 preterm neonates without RDS enrolled as controls. Total antioxidant capacity (TAC), malondialdehyde (MDA), advanced oxidation protein products (AOPPs), 8-hydroxy-2-deoxyguanosine (8-OHdG), and trace elements (copper and zinc) were measured in cord blood (day 0) for all neonates and repeated on day 3 for the RDS group. RESULTS: Day 0 serum levels of MDA, AOPPs, and 8-OHdG were significantly higher in neonates with RDS than controls with a further increase on day 3. Days 0 and 3 levels of TAC, copper, and zinc were significantly lower in the RDS group compared with controls. Elevated serum levels of 8-OHdG and AOPPs were associated with severe RDS, invasive mechanical ventilation, and high mortality rate. 8-OHdG and AOPPs were positively correlated with MDA, oxygenation index, duration of ventilation, and duration of hospitalization. CONCLUSIONS: Increased lipid, protein, and DNA oxidation is accompanied by alterations in the antioxidant defense status, which may play a role in the pathogenesis and severity of RDS."
1084,Dexmedetomidine in Enhanced Recovery After Surgery (ERAS) Protocols for Postoperative Pain,"PURPOSE OF REVIEW: Effective acute pain management has evolved considerably in recent years and is a primary area of focus in attempts to defend against the opioid epidemic. Persistent postsurgical pain (PPP) has an incidence of up to 30–50% and has negative outcome of quality of life and negative burden on individuals, family, and society. The 2016 American Society of Anesthesiologists (ASA) guidelines states that enhanced recovery after surgery (ERAS) forms an integral part of Perioperative Surgical Home (PSH) and is now recommended to use a multimodal opioid-sparing approach for management of postoperative pain. As such, dexmedetomidine is now being used as part of ERAS protocols along with regional nerve blocks and other medications, to create a satisfactory postoperative outcome with reduced opioid consumption in the Post anesthesia care unit (PACU). RECENT FINDINGS: Dexmedetomidine, a selective alpha(2) agonist, possesses analgesic effects and has a different mechanism of action when compared with opioids. When dexmedetomidine is initiated at the end of a procedure, it has a better hemodynamic stability and pain response than ropivacaine. Dexmedetomidine can be used as an adjuvant in epidurals with local anesthetic sparing effects. Its use during nerve blocks results in reduced postoperative pain. Also, local infiltration of IV dexmedetomidine is associated with earlier discharge from PACU. SUMMARY: Perioperative use of dexmedetomidine has significantly improved postoperative outcomes when used as part of ERAS protocols. An in-depth review of the use of dexmedetomidine in ERAS protocols is presented for clinical anesthesiologists."
1085,Zooplankton invasions in the early 21st century: a global survey of recent studies and recommendations for future research,"We present a comprehensive survey of the scientific literature pertaining to non-indigenous and invasive zooplankton published across the first decades of the twenty-first century (i.e., 2000–2018). We provide a concise summary of the manner in which the scientific community has allocated its efforts to this issue in recent decades, and to illuminate trends that emerge from the literature. Our search yielded 620 publications encompassing 139 invasive zooplankton species, with invasive zooplankton reported from every region of the planet—including the Arctic and Antarctic. Most taxa were reported in a small number of publications, with the majority being mentioned in only a single paper. In contrast, approximately half of the surveyed publications concerned just four species: Bythotrephes longimanus, Mnemioposis leidyi, Cercopagis pengoi, and Daphnia lumholtzi. Our survey reveals strong geographic patterns among the literature, with most publications arising from economically developed western nations. We found that the majority of publications pertained to holoplanktonic organisms from freshwater habitats, especially from the North American Great Lakes. Based on these results, we present several recommendations for future research topics that may hold considerable opportunity for growth in our understanding of the invasion process. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10750-019-04096-x) contains supplementary material, which is available to authorized users."
1086,Photocatalytic activity and antibacterial behavior of TiO(2) coatings co-doped with copper and nitrogen via sol–gel method,"The sol–gel process is used to prepare photocatalytic coatings with antibacterial properties. Also, doping with metallic or non-metallic elements has an impact on the antibacterial and photocatalytic activity of these coatings. Although there are many studies in this field, the effect of co-doping with Cu and N and their concentrations on the antibacterial properties of TiO(2) coatings against the E. coli and S. aureus bacteria has not been studied. In the present investigation, the sol–gel method was employed to deposit both undoped and Cu-N co-doped TiO(2) photocatalytic coatings on glass surface, which are expected to degrade bacterial and chemical contaminants in water while exposed to visible sunlight wavelengths. Before the coating process, an appropriate heat treatment was applied on the samples and the quality of coatings, band gap energy, and also photocatalytic and antibacterial properties were evaluated. Results showed that, in the presence of dopants, the band gap become narrower and the absorption spectrum is transferred from the ultraviolet to the visible light range. Also, it was demonstrated that, under the visible light radiation, all of the co-doped samples show higher photocatalytic activity than the undoped ones. Meanwhile, the antibacterial characteristics of TiO(2) coatings was enhanced by increasing the dopant concentration when exposing to sunlight. [Image: see text]"
1087,Capacity Building for Refugee Mental Health in Resettlement: Implementation and Evaluation of Cross-Cultural Trauma-Informed Care Training,"Refugee mental health needs are heightened during resettlement but are often neglected due to challenges in service provision, including lack of opportunities for building capacity and partnership among providers. We developed and implemented culturally-responsive refugee mental health training, called Cross-Cultural Trauma-Informed Care (CC-TIC) training. We evaluated CC-TIC, using a free listing and semi-structured retrospective pre- and post-training evaluation with five localities in two states in the U.S. The results showed significant improvement in providers’ knowledge of trauma impacts, cultural expressions of trauma/stress-related symptoms, and culturally-responsive trauma-informed care. Trauma-informed care specific to refugee resettlement was regarded as the most helpful topic and community partnership building as the most requested area for future training. This study emphasizes that culturally-responsive trauma-informed approaches can help bridge gaps between mental health care and resettlement services and promote exchanges of knowledge and expertise to build collaborative care and community partnership."
1088,The effects of weather on daily emergency ambulance service demand in Taipei: a comparison with Hong Kong,"Numerous studies have examined the effects of weather on emergency ambulance service (EAS) demand. Given Taipei’s unique physical and social environments, empirical evidence collected from other regions may not be applicable. Collecting more information about the characteristics of vulnerable groups and the effects of weather could help the EAS managing authority in formulating cost-effective EAS policies. This study aims to look at the effects of weather on EAS demand in Taipei and to make a comparison with Hong Kong, which is also an Asian city and has a similar cultural context. The study analyzed over 370,000 EAS usage records from the Taipei City Fire Department. These records were aggregated into time series data according to patients’ characteristics and then regressed on meteorological data via multivariate forward regression. The effect size differences of the variance explained by different groups of EAS users’ regression models were compared. Afterward, the results of the regression analysis from Taipei were compared with those from a Hong Kong study. Elderly and critical patients in both cities showed significantly more sensitivity to weather than other patients. Further analysis showed that non-trauma cases were related to weather in Taipei. Although both cities had similar results, the Taipei study clearly showed that elderly and critical patients were more sensitive to weather than other patient subgroups. Health education programs should focus on the vulnerable groups identified in this study in order to increase their awareness and help them protect themselves before the onset of adverse weather conditions. By generating results that are directly applicable to Taipei, the formulation of inappropriate EAS policies can be prevented."
1089,Behavioral Health Emergencies Encountered by Community Paramedics: Lessons from the Field and Opportunities for Skills Advancement,Note: This statement is mandatory. Please provide.
1090,Human encephalitis caused by pseudorabies virus infection: a case report,"Pseudorabies virus (PRV) primarily infects swine but can infect cattle, dogs, and cats. Several studies have reported that PRV can cross the specie barrier and induce human encephalitis, but a definitive diagnosis of human PRV encephalitis is debatable due to the lack of PRV DNA detection. Here, we report a case of human PRV encephalitis diagnosed by the next-generation sequencing (NGS) of PRV sequences in the cerebrospinal fluid (CSF) of a patient. A male pork vendor developed fever and seizures for 6 days. NGS results showed PRV sequences in his CSF and blood. Sanger sequencing showed that PRV DNA in the CSF and PRV antibodies in both the CSF and blood were positive. MRI results revealed multiple inflammatory lesions in the bilateral hemisphere. Based on the clinical and laboratory data, we diagnosed the patient with PRV encephalitis. This case suggests that PRV can infect humans, causing severe viral encephalitis. People at risk of PRV infection should improve their self-protection awareness."
1091,A Rotavirus Virus-Like Particle Confined Palladium Nanoreactor and Its Immobilization on Graphene Oxide for Catalysis,"ABSTRACT: In this work, a new viral protein cage based nanoreactor was successfully constructed via encapsulating Tween 80 stabilized palladium nanoparticles (NPs) into rotavirus capsid VP2 virus-like particles (i.e. Pd@VP2). The effects of stabilizers including CTAB, SDS, Tween 80 and PVP on controlling the particle size of Pd NPs were investigated. They were further immobilized on graphene oxide (i.e. Pd@VP2/GO) by a simple mixing method. Some characterizations including FT-IR and XPS were conducted to study adsorption mode of Pd@VP2 on GO sheets. Their catalytic performance was estimated in the reduction of 4-nitrophenol (4-NP). Results showed that Tween 80 stabilized Pd NPs with the molar ratio of Pd to Tween 80 at 1:0.1 possessed the smallest size and the best stability as well. They were encapsulated into viral protein cages (mean size 49 ± 0.26 nm) to assemble confined nanoreactors, most of which contained 1–2 Pd NPs (mean size 8.15 ± 0.26 nm). As-prepared Pd@VP2 indicated an enhanced activity (apparent reaction rate constant k(app) = (3.74 ± 0.10) × 10(−3) s(−1)) for the reduction of 4-NP in comparison to non-confined Pd-Tween80 colloid (k(app) = (2.20 ± 0.06) × 10(−3) s(−1)). It was logically due to confinement effects of Pd@VP2 including high dispersion of Pd NPs and high effective concentration of substrates in confined space. Pd@VP2 were further immobilized on GO surface through C-N bond. Pd@VP2/GO exhibited good reusability after recycling for four runs, confirming the strong anchoring effects of GO on Pd@VP2. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10562-020-03252-6) contains supplementary material, which is available to authorized users."
1092,Reference guide for management of adult immune thrombocytopenia in Japan: 2019 Revision,
1093,B cell memory: building two walls of protection against pathogens,"Surviving a single infection often results in lifelong immunity to the infecting pathogen. Such protection is mediated, in large part, by two main B cell memory ‘walls’ — namely, long-lived plasma cells and memory B cells. The cellular and molecular processes that drive the production of long-lived plasma cells and memory B cells are subjects of intensive research and have important implications for global health. Indeed, although nearly all vaccines in use today depend on their ability to induce B cell memory, we have not yet succeeded in developing vaccines for some of the world’s most deadly diseases, including AIDS and malaria. Here, we describe the two-phase process by which antigen drives the generation of long-lived plasma cells and memory B cells and highlight the challenges for successful vaccine development in each phase."
1094,Different effects of acetyl-CoA carboxylase inhibitor TOFA on airway inflammation and airway resistance in a mice model of asthma,"BACKGROUND AND OBJECTIVE: Acetyl CoA carboxylase (ACC) regulates the differentiation of Th1, Th2, Th17 cells and Treg cells, which play a critical role in airway inflammation of asthma. Here we investigated the role of ACC in the pathogenesis of asthma. METHODS: Chicken Ovalbumin-sensitized and -challenged mice were divided into three groups, PBS group, DMSO (solvent of TOFA) group and ACC inhibitor 5-tetradecyloxy-2-furoic acid (TOFA) + DMSO group. Airway inflammation was assessed with histology, percentages of CD4(+)T cell subsets in lung and spleen was assessed with flow cytometry, and airway responsiveness was assessed with FinePointe RC system. The expression of characteristic transcription factors of CD4(+)T cell subsets was evaluated with real-time PCR. Cytokine levels in bronchoalveolar lavage fluid (BALF) and serum was determined with ELISA. RESULTS: In asthma mice, the expression of ACC increased, while the expression of phosphorylated ACC (pACC) decreased. TOFA had no significant effect on pACC expression. TOFA reduced serum IgE, airway inflammatory cells infiltration and goblet cell hyperplasia, but dramatically increased airway responsiveness. TOFA significantly reduced the percentages of Th1, Th2, Th17 cells in lung and spleen, the expression of GATA3 and RORγt in lung, and IFN-γ, IL-4, IL-17A levels in BALF and serum. TOFA had no significant effect on the percentage of Treg cells, IL-10 level and the expression of T-bet and Foxp3. CONCLUSION: Acetyl-CoA carboxylase inhibitor TOFA might have a distinct effect on asthmatic airway inflammation and airway hyperresponsiveness."
1095,Phylogenetic analysis of rabies viruses isolated from cattle in southern Brazil,"Bats and dogs are the main reservoirs of rabies virus (RABV) in Latin America and are responsible for the maintenance of different cycles of infection. In the two neighbour and most southern Brazilian states of Rio Grande do Sul (RS) and Santa Catarina (SC), rabies in dogs has been successfully controlled for more than 30 years. However, rabies associated to the rural cycle remains endemic, with a significant, though oscillating—annual incidence of rabies in cattle. Despite the plethora of studies on genetic analyses of Brazilian RABV, isolates from southern Brazil have only scarcely been investigated. This work was performed to identify the genetic lineages of RABVs circulating in states of RS and SC. Fifty-nine RABV cattle isolates from RS and SC were selected and submitted to reverse transcription/polymerase chain reaction (RT-PCR) followed by sequencing of the nucleoprotein gene. In RS, the circulation of two sublineages (1A and 1B) of RABV was detected, both with characteristics of lineages usually detected in vampire bats (Desmodus rotundus). In SC, only one sublineage of RABV (1B) was detected. Nevertheless, the findings reported here are expected to contribute to the understanding of the biology of the virus in the region and its interactions with the natural host D. rotundus."
1096,Theoretical bounds and approximation of the probability mass function of future hospital bed demand,"Failing to match the supply of resources to the demand for resources in a hospital can cause non-clinical transfers, diversions, safety risks, and expensive under-utilized resource capacity. Forecasting bed demand helps achieve appropriate safety standards and cost management by proactively adjusting staffing levels and patient flow protocols. This paper defines the theoretical bounds on optimal bed demand prediction accuracy and develops a flexible statistical model to approximate the probability mass function of future bed demand. A case study validates the model using blinded data from a mid-sized Massachusetts community hospital. This approach expands upon similar work by forecasting multiple days in advance instead of a single day, providing a probability mass function of demand instead of a point estimate, using the exact surgery schedule instead of assuming a cyclic schedule, and using patient-level duration-varying length-of-stay distributions instead of assuming patient homogeneity and exponential length of stay distributions. The primary results of this work are an accurate and lengthy forecast, which provides managers better information and more time to optimize short-term staffing adaptations to stochastic bed demand, and a derivation of the minimum mean absolute error of an ideal forecast."
1097,Lessons from Medicine,
1098,Study of Antiviral Activity of Metabolites of a New Serratia species K-57 Strain,"The results of studies of a newly isolated Serratia species K-57 strain are presented. The strain is characterized by antiviral activity towards human influenza A/Aichi/2/68/H3N2, vaccinia, mouse smallpox, and herpes simplex-2 viruses. The detected characteristics of the strain, including the data on activities on nucleolytic enzymes, recommend it for the development of therapeutic and preventive antiviral drugs."
1099,Burnout and Leadership Style in Behavioral Health Care: a Literature Review,"Burnout among behavioral health care providers and employees is associated with poor patient and provider outcomes. Leadership style has generally been identified as a means of reducing burnout, yet it is unclear whether some leadership styles are more effective than others at mitigating burnout. Additionally, behavioral health care is provided in a variety of contexts and a leadership style employed in one context may not be effective in another. The purpose of this paper was to review the literature on leadership style and burnout in behavioral health care contexts to identify the different leadership styles and contexts in which the relationship between the two constructs was studied. Studies were categorized based on the leadership style, study design, research methods, and study context. Findings of this review provide insights into potential approaches to prevent employee burnout and its attending costs, as well as ways to improve future research in this critical area."
1100,Tuberculosis vaccine development: from classic to clinical candidates,"Bacillus Calmette-Guérin (BCG) has been in use for nearly 100 years and is the only licensed TB vaccine. While BCG provides protection against disseminated TB in infants, its protection against adult pulmonary tuberculosis (PTB) is variable. To achieve the ambitious goal of eradicating TB worldwide by 2050, there is an urgent need to develop novel TB vaccines. Currently, there are more than a dozen novel TB vaccines including prophylactic and therapeutic at different stages of clinical research. This literature review provides an overview of the clinical status of candidate TB vaccines and discusses the challenges and future development trends of novel TB vaccine research in combination with the efficacy of evaluation of TB vaccines, provides insight for the development of safer and more efficient vaccines, and may inspire new ideas for the prevention of TB."
1101,Epitope-Based Vaccine Designing of Nocardia asteroides Targeting the Virulence Factor Mce-Family Protein by Immunoinformatics Approach,"Nocardia asteroides is the main causative agent responsible for nocardiosis disease in immunocompromised patient viz. Acquired Immunodeficiency Syndrome (AIDS), malignancy, diabetic, organ recipient and genetic disorders. The virulence factor and outer membrane protein pertains immense contribution towards the designing of epitopic vaccine and limiting the robust outbreak of diseases. While epitopic based vaccine element carrying B and T cell epitope along with adjuvant is highly immunoprophylactic in nature. Present research equips immunoinformatics to figure out the suitable epitopes for effective vaccine designing. The selected epitopes VLGSSVQTA, VNIELKPEF and VVPSNLFAV amino acids sequence are identified by HLA-DRB alleles of both MHC class (MHC-I and II) molecules. Simultaneously, these also accessible to B-cell, confirmed through the ABCPred server. Antigenic property expression is validated by the Vaxijen antigenic prediction web portal. Molecular docking between the epitopes and T cell receptor delta chain authenticate the accurate interaction between epitope and receptor with significantly low binding energy. Easy access of epitopes to immune system also be concluded as transmembrane nature of the protein verified by using of TMHMM server. Appropriate structural identity of the virulence factor Mce-family protein generated through Phyre2 server and subsequently validated by ProSA and PROCHECK program suite. The structural configuration of theses epitopes also shaped using DISTILL web server. Both the structure of epitopes and protein will contribute a significant step in designing of epitopic vaccine against N. asteroides. Therefore, such immunoinformatics based computational drive definitely provides a conspicuous impel towards the development of epitopic vaccine as a promising remedy of nocardiosis"
1102,Parents’ acceptance and regret about end of life care for children who died due to malignancy,"PURPOSE: To analyse the preference of end of life care place in paediatric oncology patients, and to understand the end of life care needs and regrets among the care givers. METHOD: This was an observational qualitative study. Parents of in-curable paediatric malignancy patients who died during the years 2016–2018 were interviewed using a pre-formed open-ended questionnaire. Fears during the last phase of child’s life, most disturbing symptoms, choice of end of life care plan, regret of care givers and reasons for such choices were noted and analysed. RESULT: Twenty six families were interviewed. A median of 3 months of discordance was noted between declaration of in-curability and acceptance of the same by the family. During terminal months, pain (84.62%) was described as the most bothersome symptom followed by respiratory distress (73.08%). Eighteen families (69%) opted for home-based terminal care, 8 (31%) for hospital-based terminal care. Regret of choice was noted in 62.5% families of the hospital-based care group (separation from home environment being the main reason) and 38.89% of the home-based care group (lack of access to health care personnel and pain medication being the main reasons). CONCLUSION: Home-based care is the preferred option for end of life care by the care givers. Lack of community-based terminal care support system and availability of analgesics are the main areas to work on in India."
1103,Trends in Drain Utilization in Bariatric Surgery: an Analysis of the MBSAQIP Database 2015–2017,"BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (SG) are the two most common bariatric operations. With the implementation of enhanced recovery protocols, the use of drains should decrease. METHODS: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database was queried for the years 2015–2017. Our inclusion criteria included all patients undergoing a primary LRYGB, SG, and revisions. We examined demographics, operative characteristics, the use of drains, and postoperative complications. Continuous variables were summarized using means and standard deviations (SD). Categorical variables were summarized using frequencies and proportions. Student’s T test (Wilcoxon sum rank test in the case of skewed data) and chi-squared analysis were used to assess the baseline differences in drain utilization. RESULTS: From 2015 to 2017, there were 388,239 bariatric cases performed without drains and 100,221 performed with drains. Twenty-nine percent of LRYGB patients had a drain placed but only 16.7% of SG patients. The percentage of LRYGB that had a drain dropped from 33.1 to 24.6% during the study period and that of SG dropped from 20.3 to 13.6%. Patients that had drains placed were more likely to have a provocative test at the time of surgery (prevalence ratio (PR) 2.24) and to have a postoperative swallow study (PR 1.93). CONCLUSIONS: Drains are still commonly used in bariatric patients. Over the study period, there was a decrease in the use of drains in both bypass and sleeve patients. Patients with a drain were more likely to have had a provocative test and a swallow study and have a higher rate of complications and mortality. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11695-019-04215-6) contains supplementary material, which is available to authorized users."
1104,Assessment of the benefits of head-up preoxygenation using near-infrared spectroscopy with pulse oximetry in a swine model,"Compared with supine positioning, head-up positioning improves preoxygenation and prolongs the time to oxygen desaturation. We reevaluated benefits of head-up positioning using near-infrared spectroscopy (NIRS) with pulse oximetry in a pig model. Six pigs (mean ± SD weight: 25.3 ± 0.6 kg) were anesthetized with isoflurane and evaluated in four positions—supine, head-up, head-down, head-up to supine—just before apnea (positions’ order after “supine” was randomized). In each position, after 5 min of preoxygenation with 100% oxygen, apnea was induced and the time to SpO(2) < 70% measured. Hemodynamic and blood-gas variables and the cerebral tissue oxygenation index (TOI) were evaluated using NIRS and recorded. Hypovolemia was induced by collecting 600 mL blood. Apnea experiment was performed again in each position. The times (seconds) ± SD to SpO(2) < 70% were 108 ± 13 (supine), 138 ± 15 (head-up; P < 0.0001 vs all other positions); 101 ± 12 (head-down) and 106 ± 15 (head-up to supine) during normovolemia, and 110 ± 29, 120 ± 7 (not significant vs all other positions), 101 ± 16, and 106 ± 11, respectively, during hypovolemia. Although the TOI was not associated with the positions during normovolemia, the head-up position during hypovolemia decreased TOI from 62% ± 6% (supine) to 50% ± 9% (head-up; P = 0.0019) before preoxygenation, and it remained low during apnea. The head-up position improves preoxygenation, but repositioning to supine negates the benefits. Head-up positioning during evident hypovolemia should be avoided because the cerebral oxygenation could decrease."
1105,Care competencies in adolescents: Development of a new measure and relationships with well-being,"Worldwide, we observe an increasing focus on fostering well-being in adolescents. This is reflected in growing research in the field of care. However, empirical research is lacking that focuses on the relationship between components of care: receiving care, self-care and extending care. This lack of research is mirrored in the lack of valid measures for assessing care competencies in educational contexts. The present research, therefore, has four goals: 1) to create a valid and reliable scale assessing levels of care competencies based on the multifaceted and multidimensional concept of care; 2) to explore the relationship between socio-demographic characteristics and care competencies in adolescents; 3) to examine the psychological outcomes associated with different levels of care competencies in adolescents; 4) to explore the interaction of the three care dimensions in predicting adolescents’ well-being. Based on data from 742 adolescents, a reliable and valid scale could be developed with six subscales: Receiving care, self-care and extending care, with each of them falling apart in care competencies and care failures. Gender, age and academic achievement were related to care competencies/failures. Findings support the link between adolescents’ well-being and care competencies/failures. These results have implications for promoting adolescents’ well-being through school-based care-cultivation programs."
1106,Nanobiotechnological modules as molecular target tracker for the treatment and prevention of malaria: options and opportunity,"Malaria is one of the major infectious diseases that remains a constant challenge to human being mainly due to the emergence of drug-resistant strains of parasite and also the availability of drugs, which are non-specific for their pharmacodynamic activity and known to be associated with multiple side effects. The disease has acquired endemic proportions in tropical countries where the hygienic conditions are not satisfactory while the environmental conditions favor the proliferation of parasite and its transmission, particularly through the female anopheles. It is obvious that to square up the problems, there is a need for designing and development of more effective drugs, which can combat the drug-resistant strains of the parasite. Molecular biology of the parasite and its homing into host cellular tropics provide multiple drug targets that could judiciously be considered for engineering and designing of new generation antimalarial drugs and also drug delivery systems. Though the recent reports document that against malaria parasite the vaccine could be developed, nevertheless, due to smart mutational change overs by the parasite, it is able to bypass the immune surveillance. The developed vaccine therefore failed to assure absolute protection against the malarial infection. In the conventional mode of treatment antimalarial drugs, the dose and dosage regimen that is followed at large crops up the contraindicative manifestations, and hence compromising the effective treatment. The emerging trends and new updates in contemporary biological sciences, material sciences, and drug delivery domain have enabled us with the availability of a multitude of mode and modules which could plunge upon the nanotechnology in particular to treat this challenging infection. The nanotechnology-based option may be tuned or customized as per the requirements to mark and target i.e. the infected RBCs, for targeted drug delivery. [Figure: see text]"
1107,Anti-viral activity of Zingiber officinale (Ginger) ingredients against the Chikungunya virus,"Chikungunya is one of the highly infectious viral disease without vaccine and anti-viral. Aim of present study is to check the anti-chikungunya activities of Zingiber officinale (Ginger) in the animal cell culture model. The medicinal plant extract was prepared from Z. officinale rhizome. Median tissue culture infective dose (TCID(50)) of Chikungunya virus (CHIKV) and Maximum non-toxic dose (MNTD) of Z. officinale extract was determined in Vero cell-line on the basis of cell viability followed by MTT assay. In vitro anti-chikungunya activity was performed in Vero cell-line with MNTD and half of MNTD of Z. officinale medicinal plant extract. The anti-viral effect of Z. officinale was studied by observing the cytopathic effects and cell viability measured by MTT assay. Maximum non-toxic dose of Z. officinale plant extract was found 62.5 μg/ml. During anti-chikungunya experimentation, cell viability increased to 51.05% and 35.10%, when Vero cells were pre-treated with MNTD and half of MNTD of Z. officinale extract respectively. Similarly, in co-treatment, when MNTD, half of MNTD of Z. officinale and Median tissue culture infective dose CHIKV were inoculated simultaneously, then the viability of Vero cell-line was increases by 52.90% and 49.02% respectively. The rhizome extracts of Z. officinale have high potential to treat CHIKV. Medicinal plants and their metabolites are most important sources of antimicrobial and can be utilized for the development of new drugs. In view of the rapid expansion of CHIKV at the global level, there is an urgent need to develop newer anti-chikungunya drugs."
1108,Reporting of acute pancreatitis by radiologists-time for a systematic change with structured reporting template,Acute pancreatitis has a wide array of imaging presentations. Various classifications have been used in the past to standardize the terminology and reduce confusing and redundant terms. We aim to review the historical and current classifications of acute pancreatitis and propose a new reporting template which can improve communication between various medical teams by use of appropriate terminology and structured radiology template. The standardized reporting template not only conveys the most important imaging findings in a simplified yet comprehensive way but also allows structured data collection for future research and teaching purposes.
1109,Preclinical Evaluation of Vaccines to Treat Opioid Use Disorders: How Close are We to a Clinically Viable Therapeutic?,"The ongoing opioid crisis, now into its second decade, represents a global public health challenge. Moreover, the opioid crisis has manifested despite clinical access to three approved opioid use disorder medications: the full opioid agonist methadone, the partial opioid agonist buprenorphine, and the opioid antagonist naltrexone. Although current opioid use disorder medications are underutilized, the ongoing opioid crisis has also identified the need for basic research to develop both safer and more effective opioid use disorder medications. Emerging preclinical evidence suggests that opioid-targeted vaccines or immunopharmacotherapies may be promising opioid use disorder therapeutics. One premise for this article is to critically examine whether vaccine effectiveness evaluated using preclinical antinociceptive endpoints is predictive of vaccine effectiveness on abuse-related endpoints such as drug self-administration, drug discrimination, and conditioned place preference. A second premise is to apply decades of knowledge in the preclinical evaluation of candidate small-molecule therapeutics for opioid use disorder to the preclinical evaluation of candidate opioid use disorder immunopharmacotherapies. We conclude with preclinical experimental design attributes to enhance preclinical-to-clinical translatability and potential future directions for immunopharmacotherapies to address the dynamic illicit opioid environment."
1110,Gut microbiota in neonates with congenital gastrointestinal surgical conditions: a prospective study,"BACKGROUND: There is limited information on gut microbiota of neonates with congenital gastrointestinal surgical conditions (CGISCs) available. METHODS: This study compared stool microbiota and short-chain fatty acids (SCFAs) of 37 term infants with CGISCs with 36 term healthy infants (HIs). Two stool samples were collected from each infant: as soon as possible after birth (week 1) and 10–14 days of life (week 2). RESULTS: Bacterial richness and alpha diversity were comparable between CGISCs and HIs at week 1 and week 2 (all p > 0.05). Beta diversity analysis revealed that at week 1, CGISCs had similar community structures to HIs (p = 0.415). However, by week 2, community structures of CGISCs were significantly different from HIs (p = 0.003). At week 1, there were no significant differences in the relative abundances of genera Bifidobacterium and Bacteroides between CGISCs and HIs. At week 2, the relative abundance of Bifidobacterium was significantly lower in CGISCs (mean percentage 7.21 ± 13.49 vs. 28.96 ± 19.6; p = 0.002). Bacteroides were also less abundant in the CGISC group (mean percentage 0.12 ± 0.49 vs. 6.59 ± 8.62; p = 0.039). Relative abundance of genera Pseudomonas and Escherichia–Shigella were higher in CGISCs. At week 2, stool concentrations of all SCFAs were lower in CGISCs (all p < 0.001). CONCLUSIONS: During hospitalization, neonates with CGISCs develop gut dysbiosis and deficiency of SCFAs. IMPACT: During hospitalisation, neonates with congenital gastrointestinal surgical conditions develop gut dysbiosis with deficiency of Bifidobacteria and Bacteroides and increased abundance of Escherichia-Shigella and Pseudomonas. They also have low levels of short chain fatty acids in their stools compared to healthy infants. This is the first study evaluating the gut microbiota using 16S ribosomal RNA sequencing methods and stool short chain fatty acids in neonates with congenital gastrointestinal surgical conditions and comparing them to healthy infants. The findings of this study will pave the way for randomised trials of bifidobacterial supplementation in neonates with congenital gastrointestinal surgical conditions."
1111,Refeeding syndrome: multimodal monitoring and clinical manifestation of an internal severe neurotrauma,"Refeeding syndrome (RFS) is a rare, potentially life-threatening, condition seen in malnourished patients starting refeeding. RFS may provoke seizures and acute encephalopathy and can be considered an internal severe neurotrauma in need of specific treatment. The objective was to describe course of disease, treatment and, for the first time, multimodal monitoring output in a comatose patient suffering RFS. After gastric-banding and severe weight loss, the patient initiated self-starving and was transferred to our intensive care unit (ICU) following rapid refeeding. At arrival, seizures, decrease in consciousness (GCS 7) and suspected acute encephalitis was presented. Serum albumin was 8 g/l. Intracranial pressure (ICP), invasive blood pressure and electrocardiography (ECG) were monitored. Pressure reactivity (PR(x)) and compliance (RAP) were calculated. The patient developed congestive heart failure, anuria and general oedema despite maximal neuro- and general ICU treatment. Global cerebral oedema and hypoperfusion areas with established ischemia were seen. ECG revealed massive cardiac arrhythmia and disturbed autonomic regulation. PR(x) indicated intact autoregulation (−0.06 ± 0.18, mean ± SD) and relatively normal compliance (RAP = 0.23 ± 0.13). After 15 days the clinical state was improved, and the patient returned to the primary hospital. RFS was associated with serious deviations in homeostasis, high ICP levels, ECG abnormalities, kidney and lung affections. It is of utmost importance to recognize this rare syndrome and to treat appropriately. Despite the severe clinical state, cerebral autoregulation and compensatory reserve were generally normal, questioning the applicability of indirect measurements such as PR(x) and RAP during neuro-intensive care treatment of RFS patients with cerebral engagement."
1112,Sepsis and ECMO,"Sepsis is being recognized as an important complication of extracorporeal membrane oxygenation (ECMO) and its presence is a poor prognostic marker and increases the overall mortality. The survival rate differs in the various types of cannulation techniques. Adult patients with prolonged duration of ECMO constitute the major risk population. Ventilator-associated pneumonia and bloodstream infections form the main sources of sepsis in these patients. It is important to know the most common etiological agents for sepsis in ECMO, which varies partly with the local epidemiology of the hospitals. A high index of suspicion, drawing adequate volumes for blood culture and early and timely administration of appropriate empirical antimicrobials can substantially decrease the morbidity and mortality in this high-risk population. The dosing of antimicrobials is influenced by the pharmacological variations on ECMO machine and is an important consideration. Infection control practices are of paramount importance and need to be followed meticulously to prevent sepsis in ECMO."
1113,Perioperative Considerations in Endoscopic Skull Base Surgery,"PURPOSE OF THE REVIEW: Present an overview of perioperative considerations specific to endoscopic skull base surgery necessary to maximize successful outcomes. RECENT FINDINGS: The majority of perioperative considerations for endoscopic skull base surgery lack strong supporting evidence and frequently have varied use or implementation amongst institutions. A notable exception comes from a recent randomized controlled trial demonstrating the benefit of lumbar drainage in high-risk cerebrospinal fluid leaks. SUMMARY: Skull base surgeons must consider a multitude of perioperative factors. While many components of perioperative management are extrapolated from related fields such as endoscopic sinus surgery or open cranial base surgery, additional high-quality studies are needed to delineate best practices specific to endoscopic skull base surgery."
1114,Surgical Options for Pulmonary Atresia with Ventricular Septal Defect in Neonates and Young Infants,"BACKGROUND: The optimal surgical strategy for pulmonary atresia with ventricular septal defect (PA/VSD) in neonates and young infants is controversial. Staged repair may be associated with a higher risk of inter-stage mortality, while primary repair may lead to frequent post-repair re-interventions. METHODS: From 2004 to 2017, 65 patients with PA/VSD who underwent surgical intervention before 90 days of age were identified and enrolled in this retrospective study. The cohort was divided into two groups: group-SR, who underwent initial palliation with staged repair (n = 50), and group-PR who underwent primary repair (n = 15). RESULTS: There were three post-palliation in-hospital mortalities, four inter-stage mortalities, and one post-repair in-hospital mortality in group-SR. In group-PR, there was one in-hospital death and one late death. Five-year survival rates were comparable between the two groups (group-SR: 83.6%; group-PR: 86.7%; p = 0.754). During the median follow-up duration of 44.7 months (Inter-quartile range, 19–109 months), 40 post-repair re-interventions (22 in group-SR, 18 in group-PR) were performed in 26 patients (18 in group-SR, 8 in group-PR). On Cox proportional hazards model, primary repair was identified as the only risk factor for decreased time to death/1st post-repair re-intervention (Hazard ratio (HR): 2.3, p = 0.049) and death/2nd post-repair re-intervention (HR 2.91, p = 0.033). CONCLUSIONS: A staged repair strategy, compared with primary repair, was associated with comparable overall survival with less frequent re-interventions after repair in young infants with PA/VSD. Lowering the inter-stage mortality after initial palliation by vigilant outpatient care and aggressive home monitoring may be the key to better surgical outcomes in this subset. GRAPHIC ABSTRACT: Surgical outcomes of PA with VSD according to the surgical strategies. Patient 1 (birth weight: 2.7 kg) underwent primary Rastelli-type repair at post-natal day # 50 (body weight: 3.8 kg) using Contegra® 12 mm. The postoperative course was rocky, with long ventilatory support (10 days), ICU stay (14 days), and hospital stay (20 days). Cardiac CT scan at 9 months post-repair showed severe branch pulmonary artery stenosis, which necessitated LPA stenting at 12 months post-repair and RV-PA conduit replacement with extensive pulmonary artery reconstruction at 25 months post-repair. Patient 2 (birth weight: 2.5 kg) underwent RMBT at post-natal day #30 (body weight: 3.4 kg) using 4 mm PTFE vascular graft and staged Rastelli-type repair at post-natal 11 months using a hand-made Gore-Tex valved conduit (14 mm). No post-repair re-intervention has been performed. Cardiac CT scan at 90 months post-repair showed no branch pulmonary artery stenosis. [Image: see text] CT computed tomography, ICU intensive care unit, LPA left pulmonary artery, PA pulmonary atresia, PTFE polytetrafluoroethylene, RMBT right modified Blalock–Taussig shunt, RV-PA right ventricle to pulmonary artery, VSD ventricular septal defect."
1115,A Comprehensive Review on Human Aichi Virus,"Although norovirus, rotavirus, adenovirus and Astrovirus are considered the most important viral agents transmitted by food and water, in recent years other viruses, such as Aichi virus (AiV), have emerged as responsible for gastroenteritis outbreaks associated with different foods. AiV belongs to the genus Kobuvirus of the family Picornaviridae. It is a virus with icosahedral morphology that presents a single stranded RNA genome with positive sense (8280 nucleotides) and a poly (A) chain. AiV was first detected from clinical samples and in recent years has been involved in acute gastroenteritis outbreaks from different world regions. Furthermore, several studies conducted in Japan, Germany, France, Tunisia and Spain showed a high prevalence of AiV antibodies in adults (between 80% and 99%), which is indicative of a large exposure to this virus. The aim of this review is to bring together all the discovered information about the emerging pathogen human Aichi virus (AiV), discussing the possibles routes of transmission, new detection techniques and future research. Although AiV is responsible for a low percentage of gastroenteritis outbreaks, the high seroprevalence shown by human populations indicates an evident role as an enteric agent. The low percentage of AiV detection could be explained by the fact that the pathogen is more associated to subclinical infections. Further studies will be needed to clarify the real impact of AiV in human health and its importance as a causative gastroenteritis agent worldwide."
1116,Comparable Effect of Two-Step Versus Extended Infusions on the Pharmacokinetics of Imipenem in Patients with Sepsis and Septic Shock,"INTRODUCTION: The present study aimed to compare the pharmacokinetic/pharmacodynamic (PK/PD) parameters of imipenem administered by two-step (50% delivered in a 30-min bolus, 50% for the following 90 min) or extended (administered continuously for 2 h) infusion. METHODS: Patients with sepsis and septic shock were prospectively enrolled and randomized into four groups. Subjects in the two-step or extended groups were given two doses of imipenem (0.5 g q6h and 1.0 g q8h). The plasma imipenem concentrations were measured at given time points after the fifth dose. The PK/PD target was defined as the achievement of a fractional time above the minimal inhibitory concentration (MIC) of > 40%. RESULTS: Thirty-five patients were eventually enrolled. No significant difference was observed in the percentage of patients achieving 40% T > MIC between the different infusion modes with the same dosage, although the two-step groups exhibited a significantly shorter T(max) compared with the extended groups (0.5 g q6h: 1.5 ± 0.8 vs. 2.0 ± 0.0 h; 1.0 g q8h: 1.0 ± 0.6 vs. 2.0 ± 0.0 h; both, p < 0.05). All four groups achieved 40% T > MIC when MIC was 0.5–4.0 μg/ml, but only regimens with a higher dose (1.0 g q8h) achieved target when MIC was 8 μg/ml. CONCLUSION: The two-step and extended regimens of imipenem are comparable to the PK/PD target in the treatment of sepsis and septic shock. A higher dose (1.0 g q8h) should be considered for target achievement at an MIC of > 8 μg/ml. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02616354. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12325-020-01339-5) contains supplementary material, which is available to authorized users."
1117,Synergistic Activity of Ceragenins Against Carbapenem-Resistant Acinetobacter baumannii Strains in Both Checkerboard and Dynamic Time-Kill Assays,"Acinetobacter baumannii is an emerging opportunistic pathogen that primarily infects critically ill patients in nosocomial settings and there is a need for identifying new alternative therapeutic agents against these organisms. Ceragenins are non-peptide, membrane-active agents that mimic the antimicrobial properties of antimicrobial peptides (AMPs) and affect the membrane permeability of microorganisms. The in vitro activities of CSA-8, CSA-13, CSA-44, CSA-131, CSA-138 either alone or in combination with colistin (sulphate) were determined against 25 carbapenem-resistant A. baumannii strains. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of selected ceragenins and colistin against these isolates were measured by in vitro microbroth dilution techniques. Checkerboard techniques and time-kill assays were performed to determine the activities of combinations. The MIC(50) values (mg/L) of CSA-8, CSA-13, CSA-44, CSA-131, CSA-138 and colistin were 32, 4, 8, 2, 4 and 0.5, respectively. The MIC(90) (mg/L) of CSA-8, CSA-13, CSA-44, CSA-131, CSA-138 and colistin were 128, 8, 16, 8, 16 and 16, respectively. At 6 h, 1×MIC and 2×MIC of CSA-13 were bactericidal. CSA-13 + colistin combination displayed synergistic interaction. Antagonism between antimicrobials was not observed. According to the results, CSA-13 and CSA-131 can be good alternatives for infections caused by carbapenem-resistant A. baumannii."
1118,"Impfen bei Immundefizienz: Anwendungshinweise zu den von der Ständigen Impfkommission empfohlenen Impfungen. (III) Impfen bei hämatologischen und onkologischen Erkrankungen (antineoplastische Therapie, Stammzelltransplantation), Organtransplantation und Asplenie",
1119,Hypersensitivity reactions to biologics (part I): allergy as an important differential diagnosis in complex immune-derived adverse events,"PURPOSE: Biotechnological substances (BSs) are strongly relied upon to prevent rejection of transplanted organs, and to treat oncological, allergological, and other inflammatory diseases. Allergic reactions to partly foreign biologics can occur due to their potential immunogenicity. The severity of an immune response to a biological drug may range from no clinical significance to a severe, life-threatening anaphylactic reaction. METHODS: Detailed searches were performed on Pubmed, Web of Science, and Google Scholar to include all available publications. In addition, the Food and Drug Administration, the European Medicines Agency, and British Columbia Cancer Agency Drug Manual databases were screened for hypersensitivity reaction (HSR), infusion reaction, injection site reaction, urticaria, and anaphylaxis for individual BSs. RESULTS: Treatment with BSs can cause various types of HSR. These are mentioned in the literature with definitions such as allergic reactions, anaphylactoid reactions, anaphylaxis, HSR, infusion reactions, injection site reactions, cytokine release syndrome, and urticaria. Due to the overlap in signs and symptoms in the reported descriptions, it is not always possible to differentiate these reactions properly according to their pathomechanism. Similarly, many data reported as anaphylaxis actually describe severe anaphylactic reactions (grades III or IV). CONCLUSION: There is an urgent need for a simpler symptom- or system-based classification and scoring system to create an awareness for HSRs to BSs. A better understanding of the pathophysiology of HSRs and increased clinical experience in the treatment of side effects will provide timely control of unexpected reactions. As a result, immunotherapy with BSs will become safer in the future."
1120,Symposia,
1121,Diabetes-associated infections: development of antimicrobial resistance and possible treatment strategies,"Diabetes mellitus is associated with various types of infections notably skin, mucous membrane, soft tissue, urinary tract, respiratory tract and surgical and/or hospital-associated infections. The reason behind this frequent association with infections is an immunocompromised state of diabetic patient because uncontrolled hyperglycemia impairs overall immunity of diabetic patient via involvement of various mechanistic pathways that lead to the diabetic patient as immunocompromised. There are specific microbes that are associated with each type of infection and their presence indicates specific type of infections. For instance, E. coli and Klebsiella are the most common causative pathogens responsible for the development of urinary tract infections. Diabetic-foot infections commonly occur in diabetic patients. In this article, we have mainly focused on the association of diabetes mellitus with various types of bacterial infections and the pattern of resistance against antimicrobial agents that are frequently used for the treatment of diabetes-associated infections. Moreover, we have also summarized the possible treatment strategies against diabetes-associated infections."
1122,Influenza and antiviral resistance: an overview,"Influenza affects approximately 1 billion individuals each year resulting in between 290,000 and 650,000 deaths. Young children and immunocompromised individuals are at a particularly high risk of severe illness attributable to influenza and these are also the groups of individuals in which reduced susceptibility to neuraminidase inhibitors is most frequently seen. High levels of resistance emerged with previous adamantane therapy for influenza A and despite no longer being used to treat influenza and therefore lack of selection pressure, high levels of adamantane resistance continue to persist in currently circulating influenza A strains. Resistance to neuraminidase inhibitors has remained at low levels to date and the majority of resistance is seen in influenza A H1N1 pdm09 infected immunocompromised individuals receiving oseltamivir but is also seen less frequently with influenza A H3N2 and B. Rarely, resistance is also seen in the immunocompetent. There is evidence to suggest that these resistant strains (particularly H1N1 pdm09) are able to maintain their replicative fitness and transmissibility, although there is no clear evidence that being infected with a resistant strain is associated with a worse clinical outcome. Should neuraminidase inhibitor resistance become more problematic in the future, there are a small number of alternative novel agents within the anti-influenza armoury with different mechanisms of action to neuraminidase inhibitors and therefore potentially effective against neuraminidase inhibitor resistant strains. Limited data from use of novel agents such as baloxavir marboxil and favipiravir, does however show that resistance variants can also emerge in the presence of these drugs."
1123,Incidence of post-traumatic pneumonia in poly-traumatized patients: identifying the role of traumatic brain injury and chest trauma,"PURPOSE: Traumatic brain injury (TBI) and chest trauma are common injuries in severely injured patients. Both entities are well known to be associated with severe post-traumatic complications, including pneumonia, a common complication with a significant impact on the further clinical course. However, the relevance of TBI, chest trauma and particularly their combination as risk factors for the development of pneumonia and its impact on outcomes are not fully elucidated. METHODS: A retrospective analysis of poly-traumatized patients treated between 2010 and 2015 at a level I trauma centre was performed. Inclusion criteria were: Injury Severity Score ≥ 16 and age ≥ 18 years. TBI and chest trauma were classified according to the Abbreviated Injury Scale. Complications (i.e. acute respiratory distress syndrome (ARDS), multi-organ dysfunction syndrome (MODS) and pneumonia) were documented by a review of the medical records. The primary outcome parameter was in-hospital mortality. RESULTS: Over the clinical course, 19.9% of all patients developed pneumonia, and in-hospital mortality was 25.3%. Pneumonia (OR 5.142, p = 0.001) represented the strongest independent predictor of in-hospital mortality, followed by the combination of chest injury and TBI (OR 3.784, p = 0.008) and TBI (OR 3.028, p = 0.010). Chest injury alone, the combination of chest injury and TBI, and duration of ventilation were independent predictors of pneumonia [resp. OR 4.711 (p = 0.004), OR 4.193 (p = 0.004), OR 1.002 (p < 0.001)]. CONCLUSIONS: Chest trauma alone and especially its combination with TBI represent high-risk injury patterns for the development of pneumonia, which forms the strongest predictor of mortality in poly-traumatized patients."
1124,Development and bioanalytical method validation of an LC-MS/MS assay for simultaneous quantitation of 2-alkyl-4(1H)-quinolones for application in bacterial cell culture and lung tissue,"Pseudomonas aeruginosa is an opportunistic pathogen that produces numerous exoproducts during infection that help it evade the host immune system and procure nutrients from the host environment. Among these products are a family of secreted 2-alkyl-4(1H)-quinolone metabolites (AQs), which exhibit a range of biological activities. Here, we describe the validation of a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method for quantifying multiple AQ congeners in complex biological matrices. The assay was validated for selectivity, sensitivity, linearity, accuracy, precision, carryover, dilution integrity, recovery, matrix effects, and various aspects of stability (freeze-thaw, bench-top, long-term storage, and autosampler/post-preparative). Using authentic standards for 6 distinct AQ congeners, we report accurate quantitation within a linear range between 25 and 1000 nmol/L for all of the validated AQ standards. This method was successfully applied to quantify AQ concentrations in P. aeruginosa cell culture and in the lungs of mice infected with P. aeruginosa. Further, we confirmed the presence of unsaturated forms of several AQ congeners in cell culture. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00216-019-02374-0) contains supplementary material, which is available to authorized users."
1125,A glass half-full: defining ventilator-associated pneumonia in the neonatal intensive care unit,
1126,False-positive anti-NMDA receptor antibodies in severe case of Lyme neuroborreliosis,
1127,Comparative thermostability analysis of zoonotic and human influenza virus A and B neuraminidase,"Neuraminidase (NA) thermostability of influenza A and B viruses isolated from birds, swine and humans was measured to evaluate its variability associated with host body temperature. The highest 50% inactivation temperature (IT(50)) was observed with H3N8 avian influenza virus (74 °C), and the lowest IT(50) was observed with the seasonal human H3N2 virus (45.5 °C). The IT(50) values of A(H1N1)pdm09 viruses 56.4-58.5 °C were statistically higher than that of the prepandemic strain A/Solomon Islands/03/06 (52.5 °C). An analysis of Ca(2+) binding sites revealed the correspondence of amino acid changes to NA thermostability. This study demonstrates that changes in NA thermostability correspond to differences in host body temperature."
1128,Loneliness in Old Age: An Unaddressed Health Problem,
1129,Characterization of 100 extended major histocompatibility complex haplotypes in Indonesian cynomolgus macaques,"Many medical advancements—including improvements to anti-rejection therapies in transplantation and vaccine development—rely on preclinical studies conducted in cynomolgus macaques (Macaca fascicularis). Major histocompatibility complex (MHC) class I and class II genes of cynomolgus macaques are orthologous to human leukocyte antigen complex (HLA) class I and class II genes, respectively. Both encode cell-surface proteins involved in cell recognition and rejection of non-host tissues. MHC class I and class II genes are highly polymorphic, so comprehensive genotyping requires the development of complete databases of allelic variants. Our group used PacBio circular consensus sequencing of full-length cDNA amplicons to characterize MHC class I and class II transcript sequences for a cohort of 293 Indonesian cynomolgus macaques (ICM) in a large, pedigreed breeding colony. These studies allowed us to expand the existing database of Macaca fascicularis (Mafa) alleles by identifying an additional 141 MHC class I and 61 class II transcript sequences. In addition, we defined co-segregating combinations of allelic variants as regional haplotypes for 70 Mafa-A, 78 Mafa-B, and 45 Mafa-DRB gene clusters. Finally, we defined class I and class II transcripts that are associated with 100 extended MHC haplotypes in this breeding colony by combining our genotyping analyses with short tandem repeat (STR) patterns across the MHC region. Our sequencing analyses and haplotype definitions improve the utility of these ICM for transplantation studies as well as infectious disease and vaccine research. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00251-020-01159-5) contains supplementary material, which is available to authorized users."
1130,Voices from the Field: Addressing Job Burnout in School Psychology Training Programs,"Job burnout among school psychologists represents a potentially serious issue given widespread shortages of practitioners. It is then important to identify effective strategies for both preventing and responding to feelings of burnout when they occur to ultimately ensure a healthy workforce. The current study examined written responses provided by 122 practicing school psychologists in the Southeastern United States to the question, “What do you think training programs can do about the issue of burnout in school psychology.” A qualitative thematic analysis of responses resulted in the identification of three main themes: develop specific personal/professional skills, modify professional/training components, and modify administrative/organizational policies and seven associated sub-themes. Resulting themes are discussed in reference to specific recommendations training programs can take in the future to better address job burnout in the field."
1131,Neonatal Organ and Tissue Donation for Research: Options Following Death by Natural Causes,"The donation of organs and tissues from neonates (birth to 28 days) for transplantation has been a relatively infrequent occurrence. Less common has been the use of neonatal organs and tissues for research. Specific ethical and legal questions beg for rational and transparent guidelines with which to evaluate referrals of potential donors. Donation of organs and tissues from a neonate can play a key role in the care and support provided to families by health care professionals around the time of a neonate’s death. We report on the recovery of neonatal organs and tissues for research. A working group made up of bioethicists, neonatologists, lawyers, obstetric practioners as well as organ procurement and tissue banking professionals evaluated legal, ethical and medical issues. Neonatal donor family members were also consulted. Our primary goals were (a) to ensure that referrals were made in compliance with all applicable federal and state laws, regulations and institutional protocols, and (b) to follow acceptable ethical standards. Algorithms and policies designed to assist in the evaluation of potential neonatal donors were developed. Neonatal donation is proving increasingly valuable for research into areas including diabetes, pulmonary, gastrointestinal, genitourinary and neurological development, rheumatoid arthritis, autism, childhood psychiatric and neurologic disorders, treatment of MRSA infection and pediatric emergency resuscitation. The development of policies and procedures will assist medical professionals who wish to offer the option of donation to family members anticipating the death of a neonate."
1132,Infection and atherosclerosis: TLR-dependent pathways,"Atherosclerotic vascular disease (ASVD) is a chronic process, with a progressive course over many years, but it can cause acute clinical events, including acute coronary syndromes (ACS), myocardial infarction (MI) and stroke. In addition to a series of typical risk factors for atherosclerosis, like hyperlipidemia, hypertension, smoking and obesity, emerging evidence suggests that atherosclerosis is a chronic inflammatory disease, suggesting that chronic infection plays an important role in the development of atherosclerosis. Toll-like receptors (TLRs) are the most characteristic members of pattern recognition receptors (PRRs), which play an important role in innate immune mechanism. TLRs play different roles in different stages of infection of atherosclerosis-related pathogens such as Chlamydia pneumoniae (C. pneumoniae), periodontal pathogens including Porphyromonas gingivalis (P. gingivalis), Helicobacter pylori (H. pylori) and human immunodeficiency virus (HIV). Overall, activation of TLR2 and 4 seems to have a profound impact on infection-related atherosclerosis. This article reviews the role of TLRs in the process of atherosclerosis after C. pneumoniae and other infections and the current status of treatment, with a view to providing a new direction and potential therapeutic targets for the study of ASVD."
1133,Evaluation of diaphragm ultrasound in predicting extubation outcome in mechanically ventilated patients with COPD,"BACKGROUND: To explore the value of the right hemi-diaphragmatic excursion (DE) and its variation in predicting extubation outcome in mechanically ventilated patients with COPD. METHODS: All included patients with COPD received mechanical ventilation (MV) and were ready to wean from MV. After patients passed the 30 min spontaneous breathing trail (SBT), extubation was considered to be feasible, and the right DE measured by ultrasound at 0 min, 5 min, and 30 min of SBT were named as DE(0), DE(5), and DE(30), respectively. RESULTS: Twenty-five patients succeeded extubation; 12 patients failed. The area under receiver operator characteristic curve (AUC(ROC)) of DE(30) and ΔDE(30−5) (the variation between 30 and 5 min) were 0.762 and 0.835; a cutoff value of DE(30) > 1.72 cm and ΔDE(30−5) > 0.16 cm were associated with a successful extubation with a sensitivity of 76% and 84%, a specificity of 75% and 83.3%, respectively. The predictive probability equation of the DE(30) plus ∆DE(30−5) was P = 1/[1 + e(−(−5.625+17.689×∆DE)(30−5)(+1.802×DE)(30)())], a cutoff value of P > 0.626 was associated with a successful extubation with the AUC(ROC) of 0.867, a sensitivity of 92%, and a specificity of 83.3%. CONCLUSION: The combination of DE(30) and ∆DE(30−5) could improve the predictive value and could be used as the predictor of extubation outcome in mechanically ventilated patients with COPD."
1134,Vibrio harveyi: a serious pathogen of fish and invertebrates in mariculture,"Vibrio harveyi, which belongs to family Vibrionaceae of class Gammaproteobacteria, includes the species V. carchariae and V. trachuri as its junior synonyms. The organism is a well-recognized and serious bacterial pathogen of marine fish and invertebrates, including penaeid shrimp, in aquaculture. Diseased fish may exhibit a range of lesions, including eye lesions/blindness, gastro-enteritis, muscle necrosis, skin ulcers, and tail rot disease. In shrimp, V. harveyi is regarded as the etiological agent of luminous vibriosis in which affected animals glow in the dark. There is a second condition of shrimp known as Bolitas negricans where the digestive tract is filled with spheres of sloughed-off tissue. It is recognized that the pathogenicity mechanisms of V. harveyi may be different in fish and penaeid shrimp. In shrimp, the pathogenicity mechanisms involved the endotoxin lipopolysaccharide, and extracellular proteases, and interaction with bacteriophages. In fish, the pathogenicity mechanisms involved extracellular hemolysin (encoded by duplicate hemolysin genes), which was identified as a phospholipase B and could inactivate fish cells by apoptosis, via the caspase activation pathway. V. harveyi may enter the so-called viable but nonculturable (VBNC) state, and resuscitation of the VBNC cells may be an important reason for vibriosis outbreaks in aquaculture. Disease control measures center on dietary supplements (including probiotics), nonspecific immunostimulants, and vaccines and to a lesser extent antibiotics and other antimicrobial compounds."
1135,Pediatric trauma venous thromboembolism prediction algorithm outperforms current anticoagulation prophylaxis guidelines: a pilot study,"PURPOSE: Venous thromboembolism (VTE) in injured children is rare, but sequelae can be morbid and life-threatening. Recent trauma society guidelines suggesting that all children over 15 years old should receive thromboprophylaxis may result in overtreatment. We sought to evaluate the efficacy of a previously published VTE prediction algorithm and compare it to current recommendations. METHODS: Two institutional trauma registries were queried for all pediatric (age < 18 years) patients admitted from 2007 to 2018. Clinical data were applied to the algorithm and the area under the receiver operating characteristic (AUROC) curve was calculated to test algorithm efficacy. RESULTS: A retrospective review identified 8271 patients with 30 episodes of VTE (0.36%). The VTE prediction algorithm classified 51 (0.6%) as high risk (> 5% risk), 322 (3.9%) as moderate risk (1–5% risk) and 7898 (95.5%) as low risk (< 1% risk). AUROC was 0.93 (95% CI 0.89–0.97). In our population, prophylaxis of the ‘moderate-’ and ‘high-risk’ cohorts would outperform the sensitivity (60% vs. 53%) and specificity (96% vs. 77%) of current guidelines while anticoagulating substantially fewer patients (373 vs. 1935, p < 0.001). CONCLUSION: A VTE prediction algorithm using clinical variables can identify injured children at risk for venous thromboembolic disease with more discrimination than current guidelines. Prospective studies are needed to investigate the validity of this model. LEVEL OF EVIDENCE: III—Clinical decision rule evaluated in a single population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00383-019-04613-y) contains supplementary material, which is available to authorized users."
1136,Molecular and antigenic characterization of bovine herpesvirus type 1 (BoHV-1) strains from cattle with diverse clinical cases in Turkey,"The present study reports the molecular and antigenic characterization of 13 bovine herpesvirus type 1 (BoHV-1) field viruses obtained from cattle with different clinical cases in Turkey between 1992 and 2017. We selected glycoprotein C (gC) of BoHV-1 as a target to detect and/or verify presence of the virus in suspect materials followed by virus isolation (VI) in MDBK cells. In seven out of 13 BoHV-1 positive samples, cytophatic effects (CPEs) were observed in MDBK cell cultures, although only four virus samples reached a sufficient titer to use in phylogenetic assay, restriction endonuclease analysis (REA), and virus neutralization test (VNT). According to the results of sequence analysis of the 13 BoHV-1 positive samples, nine BoHV-1 field viruses were determined as BoHV-1.1 and four as BoHV-1.2. Using REA, we demonstrated that two of our isolated viruses could be categorized as BoHV-1.1 while the other two isolates were BoHV-1.2 subtypes. Differences between the BoHV-1.1 and BoHV-1.2 isolates were also detected in the VNT results by assaying 125 suspected serum samples after testing with isolated (KY748023, KY748022, KY748020, and KY748021) and reference viruses (BoHV-1 Cooper and BoHV-5 Texas 89). These results are indicating the need to correctly identify BoHV-1 field isolates to better understand the epidemiology and pathogenesis of infection. In addition, it would be useful to identify the subtypes circulating in the specific geographical area while determining vaccination preferences."
1137,Rural–Urban Disparities in Intracerebral Hemorrhage Mortality in the USA: Preliminary Findings from the National Inpatient Sample,"OBJECTIVES: To compare in-hospital mortality between intracerebral hemorrhage (ICH) patients in rural hospitals to those in urban hospitals of the USA. METHODS: We used the National Inpatient Sample to retrospectively identify all cases of ICH in the USA over the period 2004–2014. We used multivariable-adjusted models to compare odds of mortality between rural and urban hospitals. Joinpoint regression was used to evaluate trends in age- and sex-adjusted mortality in rural and urban hospitals over time. RESULTS: From 2004 to 2014, 5.8% of ICH patients were admitted in rural hospitals. Rural patients were older (mean [SE] 76.0 [0.44] years vs. 68.8 [0.11] years in urban), more likely to be white and have Medicare insurance. Age- and sex-adjusted mortality was greater in rural hospitals (32.2%) compared to urban patients (26.5%) (p value < 0.001). After multivariable adjustment, patients hospitalized in rural hospitals had two times the odds of in-hospital death compared to patients in urban hospitals (OR 2.07, 95% CI 1.77–2.41. p value < 0.001). After joinpoint regression, mortality declined in urban hospitals by an average of 2.8% per year (average annual percentage change, [AAPC] − 2.8%, 95% CI − 3.7 to − 1.8%), but rates in rural hospitals remained unchanged (AAPC − 0.54%, 95% CI − 1.66 to 0.58%). CONCLUSIONS: Despite current efforts to reduce disparity in stroke care, ICH patients hospitalized in rural hospitals had two times the odds of dying compared to those in urban hospitals. In addition, the ICH mortality gap between rural and urban centers is increasing. Further studies are needed to identify and reverse the causes of this disparity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-020-00950-2) contains supplementary material, which is available to authorized users."
1138,C1 esterase inhibitor in pediatric cardiac surgery with cardiopulmonary bypass plays a vital role in activation of the complement system,"Our prospective study was therefore designed to determine which part of the systemic inflammatory response after cardiac operations resulted from Cardiopulmonary bypass (CPB) in neonates and infants. After approval by the human ethical committee of the Gunma Children’s Medical Center (GCMC) and informed consent of the parents, 40 consecutive term congenital heart disease patients aged until 1 year who underwent long CPB time (> 3 h) at surgery were included in the prospective study between January 2012 and December 2014. C1 esterase inhibitor (C1-inh) drug (@Berinert) was generously provided by CSL Behring (King of Prussia, PA). The C1-inh (20 IU/kg) was given intravenously 60 min after CPB. Blood samples for complement factors were obtained before and 48 h after administration of C1-inh. Six patients did not survive and their data were not included. Of 34 patients included, median age was 6.5 months, median body weight was 6050 g, and 16 (47%) were female. According to the Mann–Whitney U test, there were no differences between the two groups concerning demographic and intraoperative data, postoperative chemical data. C1q concentration was only significant lower in patients with C1-inh non-treated group than in patients with C1-inh treated group. But, the consumption of C1q, C3, C4, CH(50), and C1-inh in patients with C1-inhibitor non-treated group was observed early postoperatively. There is a significant difference in the values before and after C1-inh treatment between the two groups. The lower value in the C1-inh-treated group is explained by the activation of the classical pathway through the replenishment of complements by C1-inh treatment. This study proposes the administration of C1-inh is an effective therapy to reduce the activation and improve the clinical capillary leak syndrome."
1139,"Pseudomonas syringae pv. actinidiae: Ecology, Infection Dynamics and Disease Epidemiology","Since 2008, the kiwifruit industry has been devastated by a pandemic outbreak of Pseudomonas syringae pv. actinidiae (Psa), the causal agent of bacterial canker. This disease has become the most significant limiting factor in kiwifruit production. Psa colonizes different organs of the host plant, causing a specific symptomatology on each of them. In addition, the systemic invasion of the plant may quickly lead to plant death. Despite the massive risk that this disease poses to the kiwifruit industry, studies focusing on Psa ecology have been sporadic, and a comprehensive description of the disease epidemiology is still missing. Optimal environmental conditions for infection, dispersal and survival in the environment, or the mechanisms of penetration and colonization of host tissues have not been fully elucidated yet. The present work aims to provide a synthesis of the current knowledge, and a deeper understanding of the epidemiology of kiwifruit bacterial canker based on new experimental data. The pathogen may survive in the environment or overwinter in dormant tissues and be dispersed by wind or rain. Psa was observed in association with several plant structures (stomata, trichomes, lenticels) and wounds, which could represent entry points for apoplast infection. Environmental conditions also affect the bacterial colonization, with lower optimum values of temperature and humidity for epiphytic than for endophytic growth, and disease incidence requiring a combination of mild temperature and leaf wetness. By providing information on Psa ecology, these data sets may contribute to plan efficient control strategies for kiwifruit bacterial canker. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00248-019-01459-8) contains supplementary material, which is available to authorized users."
1140,Translational Genomics in Neurocritical Care: a Review,"Translational genomics represents a broad field of study that combines genome and transcriptome-wide studies in humans and model systems to refine our understanding of human biology and ultimately identify new ways to treat and prevent disease. The approaches to translational genomics can be broadly grouped into two methodologies, forward and reverse genomic translation. Traditional (forward) genomic translation begins with model systems and aims at using unbiased genetic associations in these models to derive insight into biological mechanisms that may also be relevant in human disease. Reverse genomic translation begins with observations made through human genomic studies and refines these observations through follow-up studies using model systems. The ultimate goal of these approaches is to clarify intervenable processes as targets for therapeutic development. In this review, we describe some of the approaches being taken to apply translational genomics to the study of diseases commonly encountered in the neurocritical care setting, including hemorrhagic and ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and status epilepticus, utilizing both forward and reverse genomic translational techniques. Further, we highlight approaches in the field that could be applied in neurocritical care to improve our ability to identify new treatment modalities as well as to provide important information to patients about risk and prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00838-1) contains supplementary material, which is available to authorized users."
1141,Die Urologie wird elektrisch – Elektrotherapie: Moderne Therapien zur Behandlung moderner Erkrankungen – Beispiele aus der Urologie,"The significance of electricity for medicine in the modern industrial age should not be underestimated. Particularly in connection with neurasthenia, electrotherapeutic approaches also experienced a boom for domestic use. Thus, electrotherapy reached urology just as it was becoming established as a medical specialty. We analyzed urological manuals and textbooks and objects in the W. P. Didusch Center for Urologic History and the Museum zur Geschichte der Urologie in Berlin to present the wide range of indications for electrotherapy in the emerging field of urology from impotence to urethral strictures and try to highlight the variability of their importance over time."
1142,Bacterial biopolymers: from pathogenesis to advanced materials,"Bacteria are prime cell factories that can efficiently convert carbon and nitrogen sources into a large diversity of intracellular and extracellular biopolymers, such as polysaccharides, polyamides, polyesters, polyphosphates, extracellular DNA and proteinaceous components. Bacterial polymers have important roles in pathogenicity, and their varied chemical and material properties make them suitable for medical and industrial applications. The same biopolymers when produced by pathogenic bacteria function as major virulence factors, whereas when they are produced by non-pathogenic bacteria, they become food ingredients or biomaterials. Interdisciplinary research has shed light on the molecular mechanisms of bacterial polymer synthesis, identified new targets for antibacterial drugs and informed synthetic biology approaches to design and manufacture innovative materials. This Review summarizes the role of bacterial polymers in pathogenesis, their synthesis and their material properties as well as approaches to design cell factories for production of tailor-made bio-based materials suitable for high-value applications."
1143,ECTES Abstracts 2020,
1144,"Establishing Context to Build Capacity: A Qualitative Study to Determine the Feasibility, Utility, and Acceptability of a Complex Trauma Training for Psychologists Working in Urban Migrant Communities in Northern Peru","Across Latin America, increasing access to mental health care has become a priority. Management of common mental disorders is shifting to primary care, and community mental health centers (CMHCs) are being established to treat severe needs. In urban migrant communities on the outskirts of Trujillo, Peru, five new CMHCs have been built to treat complex mental health concerns, partially in response to high rates of domestic violence and child maltreatment. However, psychologists have no training in the treatment of interpersonal trauma. This study sought to determine the utility of such a training and identify areas for cultural adaptation. Six focus groups were conducted with CMHC psychologists. Findings revealed that, while a culturally-adapted training in trauma-focused treatment is desired, sociocultural barriers to ensuring the physical and psychological safety of the service user must be considered, as well as provider barriers including short treatment packages, insufficient physical infrastructure, and unstable work conditions."
1145,A classical swine fever virus E2 fusion protein produced in plants elicits a neutralizing humoral immune response in mice and pigs,"Classical swine fever (CSF) is one of the most important viral diseases of swine worldwide. Although live or attenuated virus vaccines have been used to control CSFV, it is difficult to distinguish vaccinated pigs from infected pigs; this leads to restrictions on import and export. Subunit vaccines based on the CSFV E2 glycoprotein have been developed using baculovirus or insect cell systems, but some weaknesses remain. Here, we describe production of an E2 recombinant protein using a Nicotiana benthamiana plant expression system. To do this, we took advantage of the ability of the swine Fc domain to increase solubility and stability of the fusion protein and to strengthen immune responses in target animals. N. benthamiana expressed high amounts of pFc2-fused E2 proteins, which were isolated and purified by affinity chromatography to yield a high pure recombinant protein in a cost-effective manner. Native-polyacrylamide gel electrophoresis and size exclusion chromatography confirmed that the pmE2:pFc2 fusion exists as a multimer rather than as a dimer. Injection of recombinant pmE2 protein into mice or piglets generated anti-pmE2 antibodies with efficient neutralizing activity against CSFV. These results suggest that a purified recombinant E2 protein produced in N. benthamiana generates high titers of neutralizing antibodies in vivo; as such, the protein could be developed as a subunit vaccine against CSFV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10529-020-02892-3) contains supplementary material, which is available to authorized users."
1146,Programmed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation,"The antimicrobial functions of neutrophils are facilitated by a defensive armamentarium of proteins stored in granules, and by the formation of neutrophil extracellular traps (NETs). However, the toxic nature of these structures poses a threat to highly vascularized tissues, such as the lungs. Here, we identified a cell-intrinsic program that modified the neutrophil proteome in the circulation and caused the progressive loss of granule content and reduction of the NET-forming capacity. This program was driven by the receptor CXCR2 and by regulators of circadian cycles. As a consequence, lungs were protected from inflammatory injury at times of day or in mouse mutants in which granule content was low. Changes in the proteome, granule content and NET formation also occurred in human neutrophils, and correlated with the incidence and severity of respiratory distress in pneumonia patients. Our findings unveil a ‘disarming’ strategy of neutrophils that depletes protein stores to reduce the magnitude of inflammation."
1147,Author Correction: A Engineered immunogen binding to alum adjuvant enhances humoral immunity,
1148,Severe blunt trauma in Finland and Estonia: comparison of two regional trauma repositories,"PURPOSE: Evolving trauma system of Estonia has undergone several reforms; however, performance and outcome indicators have not been benchmarked previously. Thus, we initiated a baseline study to compare demographics, management and outcomes of severely injured patients between Southern Finland and Northern Estonia utilizing regional trauma repositories. METHODS: A comparison of data fields of the Helsinki University Hospital trauma registry (HTR) and trauma registry at the North Estonia Medical Centre in Tallinn (TTR) between 1/1/2015 and 31/12/2016 was performed. The inclusion criterion was Injury Severity Score > 15. Transferred patients, patients with penetrating injuries, and pediatric patients were excluded. The data for comparison included demographics, Trauma Score-Injury Severity Score (TRISS), mortality, and standardized mortality ratio (SMR). Primary outcome was mortality and SMR per TRISS methodology. RESULTS: During the 2-year study period, 324 patients from the HTR and 152 from the TTR were included. Demographic profile was similar between the repositories with the exception of severe abdominal injuries being more prevalent at the TTR (25.0% vs. 13.3%, p = 0.002). Predominant injury mechanism was non-ground level fall in both repositories. Mortality was similar at 14.5% and 13.6% at the TTR and HTR, respectively (adj. p = 0.762; OR 1.13, 95% CI 0.64–1.99). SMR was lower at the HTR compared to the TTR (0.65 vs. 0.77, p > 0.05), however, the difference did not reach statistical significance. CONCLUSION: Benchmarking trauma repositories at a national level provides opportunities for quality and performance improvements. We observed comparable demographic profile and outcome indicators in the compared regional trauma systems."
1149,"Canine parvovirus 2b in fecal samples of asymptomatic free-living South American coatis (Nasua nasua, Linnaeus, 1766)","Canine parvovirus type 2 (CPV-2) is classified into three subtypes (CPV-2a, CPV-2b, and CPV-2c) and is the main cause of enteritis and myocarditis in young domestic and wild animals. This study aimed to evaluate the presence of CPV-2 in the feces of asymptomatic free-living coatis from Garden Forest Reserve, Palmital city, SP, Brazil. Fecal samples from 21 coatis (both sexes, different ages, and different aspects of feces) were collected in August 2014 and March 2015. The nucleic acid extracted was submitted to a polymerase chain reaction (PCR) assay to amplify a fragment of the VP2 gene of CPV-2. Eight (38%) fecal samples were positive in the PCR assay and were confirmed by sequencing. The 7 nucleotide (nt) sequences analyzed showed 100% nt identity with the prototype strain of CPV-2b (CPV-39 strain). The analysis of the deduced amino acid (aa) sequence revealed the presence of the GAT codon (aa D-Asp) at position 426 of the VP2 viral protein (subtype 2b). This study describes for the first time the identification of CPV-2b in asymptomatic free-living coatis (Nasua nasua) and suggests that coatis are susceptible to Carnivore protoparvovirus 1 infection and are important as a reservoir and an asymptomatic carrier to other wild and domestic animal species."
1150,Complex abdominal wall hernia repair with biologic mesh in elderly: a propensity matched analysis,"BACKGROUND: Complex abdominal wall reconstruction (CAWR) has become a common surgical procedure both in non-elderly and elderly patients. OBJECTIVE: The aim of this study is to analyze the outcomes of the elderly compared to nonelderly undergoing CAWR using propensity score matching. METHODS: All patients who underwent CAWR using porcine-derived, non-crosslinked acellular dermal matrix (ADM) (Strattice™) between January 2014 and July 2017 were studied retrospectively. Propensity matched analysis was performed for risk adjustment in multivariable analysis and for one-to-one matching. The outcomes were analyzed for differences in postoperative complications, reoperations, mortality, hospital length of stay and adverse discharge disposition. RESULTS: One hundred-thirty-six patients were identified during the study period. Non-elderly (aged 18–64 years) constituted 70% (n = 95) and elderly (aged ≥ 65 years) comprised 30% of the overall patient population (n = 41). Seventy-three (56.7%) were females. After adjustment through the propensity score, which included 35 pairs, the surgical site infection (p = 1.000), wound necrosis (p = 1.000), the need for mechanical ventilation (p = 0.259), mortality (p = 0.083), reoperation rate (p = 0.141), hospital length of stay (p = 0.206), and discharge disposition (p = 0.795) were similar. CONCLUSION: Elderly patients undergoing CAWR with biological mesh have comparable outcomes with non-elderly patients when using propensity matching score."
1151,Surfactant replacement therapy: from biological basis to current clinical practice,"This review summarizes the current knowledge on the physiological action of endogenous and exogenous pulmonary surfactant, the role of different types of animal-derived and synthetic surfactants for RDS therapy, different modes of administration, potential risks and strategies of ventilation, and highlights the most promising aims for future development. Scientists have clarified the physicochemical properties and functions of the different components of surfactant, and part of this successful research is derived from the characterization of genetic diseases affecting surfactant composition or function. Knowledge from functional tests of surfactant action, its immunochemistry, kinetics and homeostasis are important also for improving therapy with animal-derived surfactant preparations and for the development of modified surfactants. In the past decade newly designed artificial surfactants and additives have gained much attention and have proven different advantages, but their particular role still has to be defined. For clinical practice, alternative administration techniques as well as postsurfactant ventilation modes, taking into account alterations in lung mechanics after surfactant placement, may be important in optimizing the potential of this most important drug in neonatology."
1152,Longer term hemodialysis-dependent chronic renal failure increases the risk of post-cardiac surgery vasoplegic syndrome,"PURPOSE: We evaluated whether longer term hemodialysis (HD) is associated with a higher incidence of vasoplegic syndrome (VS) after cardiac surgery. METHODS: This retrospective, single-center cohort study included 562 consecutive patients who underwent cardiac surgery in a tertiary hospital from January 2015 to December 2016. We assessed VS occurrence and its relationship with HD duration and other risk factors. To assess the effect of the HD duration on VS occurrence, we constructed ordinal variables: HD = 0 (non-HD), 0 < HD ≤ 5 (HD ≤ 5 years), 5 < HD ≤ 10, and 10 < HD. RESULTS: The overall mean (± standard deviation) age of patients was (73 ± 11) years, and there were 60.9% men. Forty-one patients (7.3%) were HD dependent. Cardiac surgeries included all coronary artery bypass graft procedures, all valvular procedures, and aortic surgery involving cardiopulmonary bypass (CPB). Sixty-six patients (10%) developed VS. Most preoperative patient characteristics were comparable between the VS and no-VS groups; a chronic HD status and a total CPB time of > 180 min were significantly more common in the VS group (P < 0.0001 and P = 0.02, respectively). Longer term HD significantly correlated with VS incidence (P < 0.0001). Ordinal variables for the HD duration and age and known risk factors for VS (preoperative use of angiotensin-converting enzyme inhibitors and beta-blockers, low left-ventricular ejection fraction, and CPB time > 180 min) were subjected to multivariate regression analysis. Long-term HD was identified as an independent predictor of VS (odds ratio, 2.29, 95% confidence interval, 1.66–3.18). CONCLUSIONS: Longer term HD may be associated with a higher VS incidence after cardiac surgery. VS should be given attention after cardiac surgery in chronic HD-dependent patients."
1153,A multi-epitope plant-made chimeric protein (LTBentero) targeting common enteric pathogens is immunogenic in mice,"KEY MESSAGE: A plant-based multiepitopic protein (LTBentero) containing epitopes from ETEC, S. typhimurium, and V. parahaemolyticus was produced in plants cells and triggered systemic and intestinal humoral responses in immunized mice. ABSTRACT: Around 200 million people suffer gastroenteritis daily and more than 2 million people die annually in developing countries due to such pathologies. Vaccination is an alternative to control this global health issue, however new low-cost vaccines are needed to ensure proper vaccine coverage. In this context, plants are attractive hosts for the synthesis and delivery of subunit vaccines. Therefore, in this study a plant-made multiepitopic protein named LTBentero containing epitopes from antigens of enterotoxigenic E. coli, S. typhimurium, and V. parahaemolyticus was produced and found immunogenic in mice. The LTBentero protein was expressed in tobacco plants at up to 5.29 µg g(−1) fresh leaf tissue and was deemed immunogenic when administered to BALB/c mice either orally or subcutaneously. The plant-made LTBentero antigen induced specific IgG (systemic) and IgA (mucosal) responses against LTB, ST, and LptD epitopes. In conclusion, multiepitopic LTBentero was functionally produced in plant cells, being capable to trigger systemic and intestinal humoral responses and thus it constitutes a promising oral immunogen candidate in the fight against enteric diseases."
1154,Antibodies generated against dextransucrase exhibit potential anticariostatic properties in Streptococcus mutans,"Streptococcus mutans is a common principal causative agent of dental caries. In this communication, we describe that the antibodies raised against purified dextransucrase effectively inhibited the growth of S. mutans. The purified enzyme showed 58-fold enrichment, 17.5% yield and a specific activity of 3.96 units/mg protein. Purified IgG fraction of the antibody showed significant affinity with the antigenic protein. Immunotritation of the enzyme with dextransucrase antibody showed a gradual increase in inhibition of dextransucrase activity. The growth of S. mutans was also inhibited by 85% in the presence of 28 μg of IgG fraction of the antibody. Antibodies also impaired glucosyltransferase activity (72.8%) and biofilm formation by 92.6% in S. mutans. Western blot analysis revealed no cross reactivity with the various tissues of mice, rat, rabbit and humans. Dot blot analysis showed little reactivity with Lactobacillus acidophilus and Staphylococcus aureus and there was no reactivity with other bacterial strains like Enterococcus faecalis, Escherichia coli and Salmonella typhimurium. These findings suggest that antibody raised against dextransucrase exhibit inhibitory effects on the growth of S. mutans and biofilm formation with no reactivity with various mammalian tissues, thus it could be an effective anticariogenic agent."
1155,Atorvastatin-loaded solid lipid nanoparticles as eye drops: proposed treatment option for age-related macular degeneration (AMD),"Statins, widely prescribed for cardiovascular diseases, are also being eyed for management of age-related macular degeneration (AMD). Poor bioavailability and blood-aqueous barrier may however limit significant ocular concentration of statins following oral administration. We for the first time propose and investigate local application of atorvastatin (ATS; representative statin) loaded into solid lipid nanoparticles (SLNs), as self-administrable eye drops. Insolubility, instability, and high molecular weight > 500 of ATS, and ensuring that SLNs reach posterior eye were the challenges to be met. ATS-SLNs, developed (2339/DEL/2014) using suitable components, quality-by-design (QBD) approach, and scalable hot high-pressure homogenization, were characterized and evaluated comprehensively for ocular suitability. ATS-SLNs were 8 and 12 times more bioavailable (AUC) in aqueous and vitreous humor, respectively, than free ATS. Three-tier (in vitro, ex vivo, and in vivo) ocular safety, higher corneal flux (2.5-fold), and improved stability (13.62 times) including photostability of ATS on incorporation in ATS-SLNs were established. Autoclavability and aqueous nature are the other highlights of ATS-SLNs. Presence of intact fluorescein-labeled SLNs (F-SLNs) in internal eye tissues post–in vivo application as eye drops provides direct evidence of successful delivery. Perinuclear fluorescence in ARPE-19 cells confirms the effective uptake of F-SLNs. Prolonged residence, up to 7 h, was attributed to the mucus-penetrating nature of ATS-SLNs. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13346-020-00733-4) contains supplementary material, which is available to authorized users."
1156,Bacterial vaccines in poultry,"BACKGROUND: Poultry bacterial pathogens are mainly controlled by using high-cost sanitary measures and medical treatment. However, the drug-resistant strains of pathogens continuously emerge, and medical treatments are often ineffective. Moreover, there is increasing public objections to drug residues in poultry products. The other important type of control is the vaccination which depends on immunity. This immunological control is the major practical alternative to chemotherapy. Success of vaccines in combating poultry diseases depends mainly on the choice of the proper type of vaccines, correct time of its usage, and method of administration. The types of vaccines include attenuated live vaccines, and these vaccines were shown to be effective in inducing protection. The second type is killed vaccine or whole bacteria extracts which is less successful in providing protection compared to live vaccines. The metabolic product vaccine (toxoids) is the third type of vaccine. The recombinant DNA technique was adopted to produce the protective antigens in a sufficient amount and in cost-effective ways. CONCLUSIONS: Protection studies against bacterial diseases were performed by using several trials: living vaccines (live attenuated vaccines; live, non-pathogenic microorganisms; live, low virulence microorganism), inactivated (killed) vaccines (heat-inactivated, chemical inactivates, radiation), metabolic product vaccines (toxoids), subunit vaccines (whole cell proteins, outer membrane proteins, purified flagellar proteins (flagellin), fimbrial proteins, pilus proteins, lipopolysaccharides), vaccines produced by recombinant deoxyribonucleic acid (DNA) technology, and DNA vaccines."
1157,"Nicorandil, a K(ATP) Channel Opener, Attenuates Ischemia–Reperfusion Injury in Isolated Rat Lungs","PURPOSE: Nicorandil is a hybrid between nitrates and K(ATP) channel opener activators. The aim of this study was to evaluate the nicorandil’s effects on ischemia–reperfusion (IR) lung injury and examine the mechanism of its effects. METHODS: Isolated rat lungs were divided into 6 groups. In the sham group, the lungs were perfused and ventilated for 150 min. In the IR group, after perfusion and ventilation for 30 min, they were interrupted (ischemia) for 60 min, and then resumed for 60 min. In the nicorandil (N) + IR group, nicorandil 6 mg was added before ischemia (nicorandil concentration was 75 µg ml(−1)). In the glibenclamide + N + IR group, the L-NAME (N(ω)-Nitro-l-arginine methyl ester) + N + IR group and ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) + N + IR group, glibenclamide 3 µM, L-NAME 100 µM, and ODQ 30 µM were added 5 min before nicorandil administration, respectively. We measured the coefficient of filtration (Kfc) of the lungs, total pulmonary vascular resistance, and the wet-to-dry lung weight ratio (WW/DW ratio). RESULTS: Kfc was significantly increased after 60 min reperfusion compared with baseline in the IR group, but no change in the sham group. An increase in Kfc was inhibited in the N + IR group compared with the IR group (0.92 ± 0.28 vs. 2.82 ± 0.68 ml min(−1) mmHg(−1) 100 g(−1); P < 0.01). Also, nicorandil attenuated WW/DW ratio was compared with IR group (8.3 ± 0.41 vs. 10.9 ± 2.5; P < 0.05). Nicorandil’s inhibitory effect was blocked by glibenclamide and ODQ (P < 0.01), but not by L-NAME. CONCLUSIONS: Nicorandil attenuated IR injury in isolated rat lungs. This protective effect appears to involve its activation as K(ATP) channel opener as well as that of the sGC-cGMP pathway."
1158,Is Protocolised Weaning that Includes Early Extubation Onto Non-Invasive Ventilation More Cost Effective Than Protocolised Weaning Without Non-Invasive Ventilation? Findings from the Breathe Study,"BACKGROUND: Optimising techniques to wean patients from invasive mechanical ventilation (IMV) remains a key goal of intensive care practice. The use of non-invasive ventilation (NIV) as a weaning strategy (transitioning patients who are difficult to wean to early NIV) may reduce mortality, ventilator-associated pneumonia and intensive care unit (ICU) length of stay. OBJECTIVES: Our objectives were to determine the cost effectiveness of protocolised weaning, including early extubation onto NIV, compared with weaning without NIV in a UK National Health Service setting. METHODS: We conducted an economic evaluation alongside a multicentre randomised controlled trial. Patients were randomised to either protocol-directed weaning from mechanical ventilation or ongoing IMV with daily spontaneous breathing trials. The primary efficacy outcome was time to liberation from ventilation. Bivariate regression of costs and quality-adjusted life-years (QALYs) provided estimates of the incremental cost per QALY and incremental net monetary benefit (INMB) overall and for subgroups [presence/absence of chronic obstructive pulmonary disease (COPD) and operative status]. Long-term cost effectiveness was determined through extrapolation of survival curves using flexible parametric modelling. RESULTS: NIV was associated with a mean INMB of £620 ($US885) (cost-effectiveness threshold of £20,000 per QALY) with a corresponding probability of 58% that NIV is cost effective. The probability that NIV is cost effective was higher for those with COPD (84%). NIV was cost effective over 5 years, with an estimated incremental cost-effectiveness ratio of £4618 ($US6594 per QALY gained). CONCLUSIONS: The probability of NIV being cost effective relative to weaning without NIV ranged between 57 and 59% overall and between 82 and 87% for the COPD subgroup. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s41669-020-00210-1) contains supplementary material, which is available to authorized users."
1159,"Coinfection, Altered Vector Infectivity, and Antibody-Dependent Enhancement: The Dengue–Zika Interplay","Although dengue and Zika cocirculation has increased within the past 5 years, very little is known about its epidemiological consequences. To investigate the effect of dengue and Zika cocirculation on the spread of both pathogens, we create a deterministic dengue and Zika coinfection model, the first to incorporate altered infectivity of mosquitoes (due to coinfection). The model also addresses increased infectivity due to antibody-dependent enhancement (ADE) within the human population. Central to our analysis is the derivation and interpretation of the basic reproductive number and invasion reproductive number of both pathogens. In addition, we investigate how model parameters impact the persistence of each disease. Our results identify threshold conditions under which one disease facilitates the spread of the other and show that ADE has a greater impact on disease persistence than altered vector infectivity. This work highlights the importance of ADE and illustrates that while the endemic presence of dengue facilitates the spread of Zika, it is possible for high Zika prevalence to prevent the establishment of dengue."
1160,Event-Driven ECG Sensor in Healthcare Devices for Data Transfer Optimization,"The long-term monitoring of cardiovascular signs requires a wearable and connected electrocardiogram (ECG) healthcare device. It increases user’s comfort and diagnosis quality of chronic cardiac and/or high-risk patients. This paper covers the enormous data to be transmitted from the ECG device to the physician’s, namely the cardiologist’s, control unit. Existent ECG devices uniformly sample analog signals and convert them to digital samples which are compressed before data transmission. However, event-driven sampling simultaneously compresses and samples. Therefore, this paper quantitatively compares successive approximation register analog-to-digital converter (SAR ADC) with discrete wavelet transform (DWT) compression and level-crossing analog-to-digital converter (LC-ADC). Evaluation metrics are the percent root-mean-square difference ([Formula: see text] ), bit compression ratio ([Formula: see text] ) and data length in bits. When a 12-bit reconstruction is operated on the outputs of an 8-bit LC-ADC with 12-bit and 10-kHz reference counter, the [Formula: see text] is equal to 80% for 75% of test ECG signals. That is better than the 71.87% [Formula: see text] of the 12-bit 1-kHz SAR ADC with DWT compression. The modeled LC-ADC guarantees a signal quality in terms of [Formula: see text] comparable to the [Formula: see text] of the SAR ADC with DWT compression. The data length in bits of the LC-ADC is lower than the data length in bits of the SAR ADC with more than 14-bit resolution with DWT compression for 82% of the test ECG signals. However, for lower resolutions, to obtain lower power consumption for radiofrequency transmission, a better alternative remains the SAR ADC with DWT compression."
1161,In silico prediction of toxicity and its applications for chemicals at work,"OBJECTIVE AND METHODS: This study reviewed the concept of in silico prediction of chemical toxicity for prevention of occupational cancer and future prospects in workers’ health. In this review, a new approach to determine the credibility of in silico predictions with raw data is explored, and the method of determining the confidence level of evaluation based on the credibility of data is discussed. I searched various papers and books related to the in silico prediction of chemical toxicity and carcinogenicity. The intention was to utilize the most recent reports after 2015 regarding in silico prediction. RESULTS AND CONCLUSION: The application of in silico methods is increasing with the prediction of toxic risks to human and the environment. The various toxic effects of industrial chemicals have triggered the recognition of the importance of using a combination of in silico models in the risk assessments. In silico occupational exposure models, industrial accidents, and occupational cancers are effectively managed and chemicals evaluated. It is important to identify and manage hazardous substances proactively through the rigorous evaluation of chemicals."
1162,Making Medical Decisions for Incapacitated Patients Without Proxies: Part II,"In the United States, there is no consensus about who should make decisions in acute but non-emergent situations for incapacitated patients who lack surrogates. For more than a decade, our academic medical center has utilized community volunteers from the hospital ethics committee to engage in shared decision-making with the medical providers for these patients. In order to add a different point of view and minimize conflict of interest, the volunteers are non-clinicians who are not employed by the hospital. Using case examples and interviews with the community members, this paper describes how the protocol has translated into practice over the years since its inception. Members reported comfort with the role as well as satisfaction with the thoroughness of their discussions with the medical team. They acknowledged feelings of moral uncertainty, but expressed confidence in the process. Questions raised by the experience are discussed. Overall, the protocol has provided oversight, transparency, and protection from conflict of interest to the decision-making process for this vulnerable patient population."
1163,The CSF Diversion via Lumbar Drainage to Treat Dialysis Disequilibrium Syndrome in the Critically Ill Neurological Patient,
1164,Schistosomiasis—from immunopathology to vaccines,"Schistosomiasis (bilharzia) is a neglected tropical disease caused by trematode worms of the genus Schistosoma. The transmission cycle involves human (or other mammalian) water contact with surface water contaminated by faeces or urine, as well as specific freshwater snails acting as intermediate hosts. The main disease-causing species are S. haematobium, S. mansoni and S. japonicum. According to the World Health Organisation, over 250 million people are infected worldwide, leading to considerable morbidity and the estimated loss of 1.9 million disability-adjusted life years (DALYs), a likely underestimated figure. Schistosomiasis is characterised by focal epidemiology and an over-dispersed population distribution, with higher infection rates in children. Complex immune mechanisms lead to the slow acquisition of immune resistance, but innate factors also play a part. Acute schistosomiasis, a feverish syndrome, is most evident in travellers following a primary infection. Chronic schistosomiasis affects mainly individuals with long-standing infections residing in poor rural areas. Immunopathological reactions against schistosome eggs trapped in host tissues lead to inflammatory and obstructive disease in the urinary system (S. haematobium) or intestinal disease, hepatosplenic inflammation and liver fibrosis (S. mansoni and S. japonicum). An effective drug—praziquantel—is available for treatment but, despite intensive efforts, no schistosomiasis vaccines have yet been accepted for public use. In this review, we briefly introduce the schistosome parasites and the immunopathogenic manifestations resulting from schistosomiasis. We then explore aspects of the immunology and host-parasite interplay in schistosome infections paying special attention to the current status of schistosomiasis vaccine development highlighting the advancement of a new controlled human challenge infection model for testing schistosomiasis vaccines."
1165,Howard Grey 1932–2019,
1166,Accidental Burn in a Neonate in Neonatal Intensive Care Unit: What Could be the Cause?,
1167,Cognitive Function in Liver Transplantation,"PURPOSE OF REVIEW: Liver transplantation (LT) remains the only way to cure patients with severe liver diseases. Important questions about neurological sequelae and quality of life after LT have emerged. In this review, we discuss the neurocognitive changes associated with LT and we conclude with recommendations in this regard for patients, caregivers, and physicians. RECENT FINDINGS: Compared with other solid organ recipients, LT patients tend to have a higher incidence (up to 30%) of neurological complications post-LT. Even in absence of previous episodes of hepatic encephalopathy (HE), some patients display new onset of neurological symptoms post-LT, raising the concern about the role of other factors that may have a direct impact on cognitive function. SUMMARY: Different mechanisms have been postulated to explain these postoperative neurological symptoms. They include sequelae of HE, persistent impairment of cognitive function due to cirrhosis, or postoperative decompensation of an unknown or undiagnosed neurodegenerative disorder."
1168,Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs. 3 doses in young women,"A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9–14 years were randomized to receive 2 doses at months 0 and 6 (n=301) or 3 doses at months 0, 1 and 6 (n=304). Girls aged 15–17 years (n=149) and women aged 18–26 years (n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9–17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9–14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-019-9547-7 and is accessible for authorized users."
1169,Study of the Binding Pattern of HLA Class I Alleles of Indian Frequency and cTAP Binding Peptide for Chikungunya Vaccine Development,"Chikungunya is a mosquito-borne disease, caused by the member of the Togaviridae family belongs to the genus alphavirus, making it a major threat in all developing countries as well as some developed countries. The mosquito acts as a vector for the disease and carries the CHIK-Virus. To date there is no direct treatment available and that demands the development of more effective vaccines. In this study author employed Immune Epitope Database and Analysis Resource, a machine learning-based algorithm principally working on the Artificial Neural Network (ANN) algorithm, also known as (IEDB-ANN) for the prediction and analysis of Epitopes. A total of 173 epitopes were identified on the basis of IC50 values, among them 40 epitopes were found, sharing part with the linear B-cell epitopes and exposed to the cTAP1protein, and out of 40, 6 epitopes were noticed to show interactions with the cTAP with their binding energy ranging from − 3.61 to − 1.22 kcal/mol. The six epitopes identified were exposed to the HLA class I alleles and from this all revealed interaction with the HLA alleles and minimum binding energy that ranges from − 4.12 to − 5.88 kcal/mol. Besides, two T cell epitopes i.e. (145)KVFTGVYPE(153) and (395)STVPVAPPR(403) were found most promiscuous candidates. These promiscuous epitopes-HLA complexes were further analyzed by the molecular dynamics simulation to check the stability of the complex. Results obtained from this study suggest that the identified epitopes i.e. and (395)STVPVAPPR(403), are likely to be capable of passing through the lumen of ER to bind withthe HLA class I allele and provide new insights and potential application in the designing and development of peptide-based vaccine candidate for the treatment of chikungunya."
1170,Xentry-Gap19 inhibits Connexin43 hemichannel opening especially during hypoxic injury,"Hypoxic injury results in cell death, tissue damage and activation of inflammatory pathways. This is mediated by pathological Connexin43 (Cx43) hemichannel (HC) opening resulting in osmotic and ionic imbalances as well as cytokine production perpetuating the inflammatory environment. Gap19 is an intracellularly acting Cx43 mimetic peptide that blocks HC opening and thus promotes cell survival. However, native Gap19, which must enter the cell in order to function, exhibits low cell permeability. In this study, Gap19 was conjugated to the cell-penetrating peptide, Xentry, to investigate if cellular uptake could be improved while maintaining peptide function. Cellular uptake of Xentry-Gap19 (XG19) was much greater than that of native Gap19 even under normal cell culture conditions. Peptide function was maintained post uptake as shown by reduced ethidium homodimer influx and ATP release due to Cx43 HC block. While XG19 blocked pathologic HC opening though, normal gap junction communication required for cell repair and survival mechanisms was not affected as shown in a dye scrape-load assay. Under hypoxic conditions, increased expression of Syndecan-4, a plasma membrane proteoglycan targeted by Xentry, enabled even greater XG19 uptake leading to higher inhibition of ATP release and greater cell survival. This suggests that XG19, which is targeted specifically to hypoxic cells, can efficiently and safely block Cx43 HC and could therefore be a novel treatment for hypoxic and inflammatory diseases. [Figure: see text]"
1171,An unusual case of Aspergillus endocarditis of native aortic valve following ECMO,"Fungal endocarditis following Extracorporeal membrane oxygenation (ECMO) is rare and very rarely reported. Though rare it has a high mortality rate. A 49-year-old male patient who had venovenous ECMO presented with aortic valve endocarditis after 40 days. He underwent sutureless bioprosthehtic valve placement and debridement of abscess. Abscess fluid grew aspergillus species and was started on dual antifungal intravenous amphotericin and variconazole. He was discharged after 1 month with oral variconazole. Incidence of aseptic endocarditis (AE) has been on rise due to increase in invasive procedures. Blood culture is mostly sterile, and fever may be absent. Abscess debridement and aggressive dual antifungal treatment helped our patient in his road to recovery. In current era with increasing use of ECMO, newer rarer complications should be kept in mind. High index of suspicion is required for diagnosing fungal endocarditis after ECMO."
1172,Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy,"Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell–cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies."
1173,Intensivist coverage and patient outcomes,
1174,What drives change in neonatal intensive care units? A qualitative study with physicians and nurses in six European countries,"BACKGROUND: Innovation is important to improve patient care, but few studies have explored the factors that initiate change in healthcare organizations. METHODS: As part of the European project EPICE on evidence-based perinatal care, we carried out semi-structured interviews (N = 44) with medical and nursing staff from 11 randomly selected neonatal intensive care units in 6 countries. The interviews focused on the most recent clinical or organizational change in the unit relevant to the care of very preterm infants. Thematic analysis was performed using verbatim transcripts of recorded interviews. RESULTS: Reported changes concerned ventilation, feeding and nutrition, neonatal sepsis, infant care, pain management and care of parents. Six categories of drivers to change were identified: availability of new knowledge or technology; guidelines or regulations from outside the unit; need to standardize practices; participation in research; occurrence of adverse events; and wish to improve care. Innovations originating within the unit, linked to the availability of new technology and seen to provide clear benefit for patients were more likely to achieve consensus and rapid implementation. CONCLUSIONS: Innovation can be initiated by several drivers that can impact on the success and sustainability of change."
1175,Production and immunogenicity of Fubc subunit protein redesigned from DENV envelope protein,"Dengue virus (DENV) is a vector-borne human pathogen that usually causes dengue fever; however, sometime it leads to deadly complications such as dengue with warning signs (DWS+) and severe dengue (SD). Several studies have shown that fusion (Fu) and bc loop of DENV envelope domain II are highly conserved and consist some of the most dominant antigenic epitopes. Therefore, in this study, Fu and bc loops were joined together to develop a short recombinant protein as an alternative of whole DENV envelope protein, and its immunogenic potential as fusion peptide was estimated. For de novo designing of the antigen, Fu and bc peptides were linked with an optimised linker so that the three dimensional conformation was maintained as it is in DENV envelope protein. The redesigned Fubc protein was expressed in E. coli and purified. Subsequently, structural integrity of the purified protein was verified by CD spectroscopy. To characterise immune responses against recombinant Fubc protein, BALB/c mice were subcutaneously injected with emulsified antigen preparation. It was observed by ELISA that Fubc fusion protein elicited higher serum IgG antibody response either in the presence or in absence of Freund’s adjuvant in comparison to the immune response of Fu and bc peptides separately. Furthermore, the binding of Fubc protein with mice antisera was validated by SPR analysis. These results suggest that Fu and bc epitope-based recombinant fusion protein could be a potential candidate towards the development of the effective subunit vaccine against DENV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-020-10541-y) contains supplementary material, which is available to authorized users."
1176,"Seasonal and pandemic influenza: 100 years of progress, still much to learn","Influenza viruses are highly transmissible, both within and between host species. The severity of the disease they cause is highly variable, from the mild and inapparent through to the devastating and fatal. The unpredictability of epidemic and pandemic outbreaks is accompanied but the predictability of seasonal disease in wide areas of the Globe, providing an inexorable toll on human health and survival. Although there have been great improvements in understanding influenza viruses and the disease that they cause, our knowledge of the effects they have on the host and the ways that the host immune system responds continues to develop. This review highlights the importance of the mucosa in defence against infection and in understanding the pathogenesis of disease. Although vaccines have been available for many decades, they remain suboptimal in needing constant redesign and in only providing short-term protection. There are real prospects for improvement in treatment and prevention of influenza soon, based on deeper knowledge of how the virus transmits, replicates and triggers immune defences at the mucosal surface."
1177,Early Surgical Closure of Atrial Septal Defect Improves Clinical Status of Symptomatic Young Children with Underlying Pulmonary Abnormalities,"Elective closure of atrial septal defect (ASD) is usually recommended during preschool ages. However, ASD may contribute to deteriorating health in the presence of significant comorbidity and, thus, may need earlier closure. There is a lack of clarity regarding the indications for and outcomes after ASD closure in infancy and early childhood. We investigated the benefits and safety of surgical ASD closure in symptomatic patients under 2 years of age. Retrospective chart review was conducted in patients who underwent surgical ASD closure within the first 2 years of life. Of 31 symptomatic ASD patients, 22 had persistent respiratory symptoms, 24 failure to thrive, and 9 pulmonary hypertension. Overall, 26 patients (84.0%) showed clinical improvement after ASD closure, including improved respiratory status (17/22; 77.3%), resumption of normal growth (15/24; 62.5%), and resolution of pulmonary hypertension (7/7; 100%, 2 patients unable to assess postoperatively). Two medically complicated patients died a few months after surgery unrelated to surgical complications. Four out of 8 ventilator-dependent patients were weaned from mechanical ventilation within 1 month after ASD closure. Closure of ASD did not improve those patients with highly advanced lung disease and/or medically complex conditions including underlying genetic abnormalities. Surgical complications were uncommon. Postoperative hospital stay was 4 to 298 days (median 8 days). The majority of our patients demonstrated significant clinical improvement after ASD closure. Early ASD closure is safe and beneficial for symptomatic infants and young children with associated underlying pulmonary abnormalities, especially bronchopulmonary dysplasia."
1178,Higher virulence of swine H1N2 influenza viruses containing avian-origin HA and 2009 pandemic PA and NP in pigs and mice,"Pigs are capable of harbouring influenza A viruses of human and avian origin in their respiratory tracts and thus act as an important intermediary host to generate novel influenza viruses with pandemic potential by genetic reassortment between the two viruses. Here, we show that two distinct H1N2 swine influenza viruses contain avian-like or classical swine-like hemagglutinins with polymerase acidic (PA) and nucleoprotein (NP) genes from 2009 pandemic H1N1 influenza viruses that were found to be circulating in Korean pigs in 2018. Swine H1N2 influenza virus containing an avian-like hemagglutinin gene had enhanced pathogenicity, causing severe interstitial pneumonia in infected pigs and mice. The mortality rate of mice infected with swine H1N2 influenza virus containing an avian-like hemagglutinin gene was higher by 100% when compared to that of mice infected with swine H1N2 influenza virus harbouring classical swine-like hemagglutinin. Further, chemokines attracting inflammatory cells were strongly induced in lung tissues of pigs and mice infected by swine H1N2 influenza virus containing an avian-like hemagglutinin gene. In conclusion, it is necessary for the well-being of humans and pigs to closely monitor swine influenza viruses containing avian-like hemagglutinin with PA and NP genes from 2009 pandemic H1N1 influenza viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04572-z) contains supplementary material, which is available to authorized users."
1179,Comparing MMPI-2-Restructured Form Scores by Service Era for Veterans Assessed Within the Veteran Affairs Healthcare System,"This study compares profiles of Minnesota Multiphasic Personality Inventory-2-Restructured Form (MMPI-2-RF) scale scores from 1492 VA test-takers who served during the Vietnam or Gulf War service eras. The sample includes all such cases collected at any VA posttraumatic stress disorder Clinical Teams across the United States between January 1, 2008 and May 31, 2015 using the MMPI-2 or MMPI-2-RF (via the VA Mental Health Assistant suite). Associations between gender and score differences were also examined. In contrast to past research using the MMPI-2, results of this study suggest that veterans are generally homogeneous in their MMPI-2-RF profiles across different periods of service. Specifically, the magnitudes of mean differences are small and not clinically significant. Thus, responses on the MMPI-2-RF do not appear influenced by service era. Implications for the clinical use of, and research with, the MMPI-2-RF are discussed within the VA healthcare system."
1180,Efficient smooth muscle cell differentiation of iPS cells on curcumin-incorporated chitosan/collagen/polyvinyl-alcohol nanofibers,"Bladder dysfunction is one of the most common diseases that occur for a number of reasons and the current treatment modalities do not improve much in its recovery process. Tissue engineering in the last two decades has given great hope for the treatment of these disorders. In this study, a composite nanofibrous scaffold was fabricated from chitosan, collagen, and polyvinyl-alcohol polymer blend while curcumin incorporated in scaffold fibers. The scaffold supportive functions from smooth muscle cell differentiation were studied when human-induced pluripotent stem cells were cultured on the scaffolds under differentiation medium. Biocompatibility of the fabricated scaffold increased significantly by incorporating curcumin in the scaffold fibers, where protein adsorption, cell attachment, and viability were increased in the nanofiber/curcumin group compared with the other groups. In addition, the expression level of smooth muscle cell-related genes, including alpha-smooth muscle actin (αSMA), smooth muscle 22 alpha (SM-22a), Caldesmon1, and Calponin1in the stem cells upregulated while cultured in the presence of curcumin, but this increase was significantly improved while cells cultured on the nanofibers/curcumin. In addition, αSMA protein in the cells cultured on the nanofibers/curcumin expressed significantly higher than those cells cultured on the nanofibers without curcumin. It can be concluded that smooth muscle cell differentiation of the induced pluripotent stem cells promoted by curcumin and this promotion was synergistically improved while curcumin incorporated in the nanofibers. [Figure: see text]"
1181,Engineering strategies to overcome the current roadblocks in CAR T cell therapy,"T cells genetically engineered to express chimeric antigen receptors (CARs) have proven — and impressive — therapeutic activity in patients with certain subtypes of B cell leukaemia or lymphoma, with promising efficacy also demonstrated in patients with multiple myeloma. Nevertheless, various barriers restrict the efficacy and/or prevent the widespread use of CAR T cell therapies in these patients as well as in those with other cancers, particularly solid tumours. Key challenges relating to CAR T cells include severe toxicities, restricted trafficking to, infiltration into and activation within tumours, suboptimal persistence in vivo, antigen escape and heterogeneity, and manufacturing issues. The evolution of CAR designs beyond the conventional structures will be necessary to address these limitations and to expand the use of CAR T cells to a wider range of malignancies. Investigators are addressing the current obstacles with a wide range of engineering strategies in order to improve the safety, efficacy and applicability of this therapeutic modality. In this Review, we discuss the innovative designs of novel CAR T cell products that are being developed to increase and expand the clinical benefits of these treatments in patients with diverse cancers."
1182,Early versus late tracheostomy in patients with traumatic brain injury,
1183,Pre-hospital trauma care in Switzerland and Germany: do they speak the same language?,"PURPOSE: Swiss and German (pre-)hospital systems, distribution and organization of trauma centres differ from each other. It is unclear if outcome in trauma patients differs as well. Therefore, this study aims to determine differences in characteristics, therapy and outcome of trauma patients between both German-speaking countries. METHODS: The TraumaRegister DGU(®) (TR-DGU) was used. Patients with Injury Severity Score ≥ 9 admitted to a level 1 trauma centre between 01/2009 and 12/2017 were included if they required ICU care or died. Trauma pattern, pre-hospital procedures and outcome were compared between Swiss (CH, n = 4768) and German (DE, n = 66,908) groups. RESULTS: Swiss patients were older than German patients (53 vs. 50 years). ISS did not differ between groups (CH 23.8 vs. DE 23.0 points). There were more low falls < 3 m (34% vs. 21%) at the expense of less traffic accidents (37% vs. 52%) in the Swiss population. In Switzerland 30% of allocations were done without physician involvement, whereas this occurred in 4% of German cases. Despite a comparable number of patients with a GCS ≤ 8 (CH 29.6%; DE 26.4%), differences in pre-hospital intubation rates occurred (CH 31% vs. DE 40%). Severe traumatic brain injuries were diagnosed most frequently in Switzerland (CH 62% vs. DE 49%). Admission vital signs were similar, and standardized mortality ratios were close to one in both countries. CONCLUSION: This study demonstrates that patients’ age, trauma patterns and pre-hospital care differ between Germany and Switzerland. However, adjusted mortality was almost similar. Further benchmarking studies are indicated to optimize trauma care in both German-speaking countries."
1184,Sequence analysis of the first B5 subgenogroup strain of enterovirus 71 isolated in Korea,"Enterovirus A71 (EV71), the main etiological agent of handfoot- mouth disease (HFMD), circulates in many areas of the world and has caused large epidemics since 1997, especially in the Asia-Pacific region. In this study, we determined the full-genome sequence of CMC718, a newly isolated EV71 strain in Korea. The CMC718 genome was 7,415 nucleotides in length and was confirmed by whole-genome phylogenetic analysis to belong to the B5 genotype. In particular, CMC718 demonstrated maximum identity with strain M988 of the B5 genotype and numerous amino acid variants were detected in the 3D domain of the viral protein P3, which is consistent with the mutation pattern of a B5 strain isolated in 2012–2013. Comparison of the CMC718 sequence with other EV71 reference strains confirmed the relationship and genetic variation of CMC718. Our study was a full-genome sequence analysis of the first EV71 strain of the B5 genotype isolated in South Korea. This information will be a valuable reference for the development of methods for the detection of recombinant viruses, the tracking of infections, and the diagnosis of EV71."
1185,HER2-Positive Breast Cancer Immunotherapy: A Focus on Vaccine Development,"Clinical progress in the field of HER2-positive breast cancer therapy has been dramatically improved by understanding of the immune regulatory mechanisms of tumor microenvironment. Passive immunotherapy utilizing recombinant monoclonal antibodies (mAbs), particularly trastuzumab and pertuzumab has proved to be an effective strategy in HER2-positive breast cancer treatment. However, resistance to mAb therapy and relapse of disease are still considered important challenges in clinical practice. There are increasing reports on the induction of cellular and humoral immune responses in HER2-positive breast cancer patients. More recently, increasing efforts are focused on using HER2-derived peptide vaccines for active immunotherapy. Here, we discuss the development of various HER2-derived vaccines tested in animal models and human clinical trials. Different formulations and strategies to improve immunogenicity of the antigens in animal studies are also discussed. Furthermore, other immunotherapeutic approaches to HER2 breast cancer including, CTLA-4 inhibitors, immune checkpoint inhibitors, anti PD-1/PD-L1 antibodies are presented."
1186,The Conundrums of Counselling Women in Violent Intimate Partner Relationships in South Africa: Implications for Practice,"Little research focuses on how counsellors experience counselling encounters concerning intimate partner violence. This study reports on narrative research conducted with eight South African non-governmental organisation counsellors. Participants spoke of creating productive and caring counselling dynamics, and providing non-directive counselling. However, they also indicated providing moral guidance, particularly in cases where pregnancy or children were involved. Success was viewed rather narrowly as the women leaving the relationship, setting up ‘all-or-nothing’ outcomes. Such ‘success’ led to counsellor happiness, whilst failure in this regard led to counsellors experiencing anger and burn-out. We conclude that the conundrums evident in these data are grounded in patriarchal systems, limiting the efficacy of counselling based on a bondage and deliverance narrative. Implications for practice and training are also outlined."
1187,Bio-electrical impedance analysis in critically ill patients: are we ready for prime time?,
1188,Repair of ventricular septal defect through anterolateral thoracotomy with central cannulation: our experience,"BACKGROUND: At present thoracotomy with femoro-femoral bypass is an established approach for minimally invasive open heart surgeries, but thoracotomy with conventional cannulation is yet to be established. We performed 54 cases of ventricular septal defect (VSD) closure via anterolateral thoracotomy approach with central cannulation. Here we are describing our results and experience of VSD closure via anterolateral thoracotomy approach. AIM AND OBJECTIVE: The aim of our study was to evaluate early outcomes of VSD repair via anterolateral thoracotomy with central cannulation. METHODS: This is a retrospective, observational, descriptive type of study. Fifty four patients (31 males, 23 females) underwent VSD repair from November 2016 to November 2018 via anterolateral thoracotomy with age ranges from 3 to 22 years (mean age 10.57 + 8.88 years). Mean body weight was 22.29 + 13.44 kg (range 10 to 48 kg). The VSD was perimembranous in 47 patients, subpulmonic in 2, muscular in 2, and inlet in 3 patients. RESULTS: There was no operative or late mortality. The mean incision length was 7.16 ± 02.08 cm (range, 5 cm to 9 cm). Average duration of cardiopulmonary bypass (CPB) was 61.72 ± 14.20 min (range, 48–78 min), and aortic cross-clamp time was 38.51 ± 13.08 min (range, 26–56 min). The average postoperative intensive care unit (ICU) stay was 1.83 ± 1.32 days (range, 1–3 days), and hospital stay was 4.92 ± 1.82 days (range, 4–7 days). CONCLUSION: Anterolateral thoracotomy with conventional central cannulation can be a safe alternative to median sternotomy with superior cosmetic results for the repair of VSDs."
1189,"Smp76, a Scorpine-Like Peptide Isolated from the Venom of the Scorpion Scorpio maurus palmatus, with a Potent Antiviral Activity Against Hepatitis C Virus and Dengue Virus","Growing global viral infections have been a serious public health problem in recent years. This current situation emphasizes the importance of developing more therapeutic antiviral compounds. Hepatitis C virus (HCV) and dengue virus (DENV) belong to the Flaviviridae family and are an increasing global health threat. Our previous study reported that the crude venom of Scorpio maurus palmatus possessed anti-HCV and anti-DENV activities in vitro. We report here the characterization of a natural antiviral peptide (scorpion-like peptide Smp76) that prevents HCV and DENV infection. Smp76 was purified from S. m. palmatus venom and contains 76 amino acids with six residues of cysteine. Smp76 antiviral activity was evaluated using a cell culture technique utilizing Huh7it-1, Vero/SLAM, HCV (JFH1, genotype 2a) and DENV (Trinidad 1751, type 2). A potential antiviral activity of Smp76 was detected in culture cells with an approximate IC(50) of 0.01 μg/ml. Moreover, Smp76 prevents HCV infection and suppresses secondary infection, by inactivating extra-cellular infectious particles without affecting viral replication. Interestingly, Smp76 is neither toxic nor hemolytic in vitro at a concentration 1000-fold higher than that required for antiviral activity. Conclusively, this report highlights novel anti-HCV and anti-DENV activities of Smp76, which may lay the foundation for developing a new therapeutic intervention against these flaviviruses."
1190,Oxygen saturation histograms predict nasal continuous positive airway pressure-weaning success in preterm infants,"BACKGROUND: Continuous positive airway pressure (CPAP) is widely used in preterm infants. Identification of readiness for weaning from CPAP can balance benefits with risks of CPAP exposure. We tested the hypothesis that preterm infants that successfully transition off CPAP have higher oxygen saturations prior to weaning compared with infants who fail weaning from CPAP. METHODS: This was a single-center-matched case–control study in infants ≤30 weeks’ gestation receiving ≤30% FiO(2) weaned off CPAP during the first postnatal week. Cases were infants placed back on CPAP within 7 days of being taken off CPAP, whereas control infants remained off CPAP for 7 consecutive days following CPAP discontinuation. Infants were matched on gestational age at birth (±10 days). Prospectively collected histograms detailing the distribution of oxygen saturations prior to CPAP discontinuation were compared between cases and controls. RESULTS: Over a 12-month monitoring period, 36 infants met inclusion criteria. Baseline characteristics, morbidities, and clinical variables did not differ between cases and controls. Controls achieved oxygen saturations of 95–97 and 97–100% for longer duration compared to cases (p < 0.05). CONCLUSIONS: In preterm infants with RDS receiving CPAP and ≤30% FiO(2), infants with higher oxygen saturations had greater success in transitioning off CPAP."
1191,What is new in non-ventilated ICU-acquired pneumonia?,
1192,Improving the prognostic value of ∆PCO(2) following cardiac surgery: a prospective pilot study,"Conflicting results have been published on prognostic significance of central venous to arterial PCO(2) difference (∆PCO(2)) after cardiac surgery. We compared the prognostic value of ∆PCO(2) on intensive care unit (ICU) admission to an original algorithm combining ∆PCO(2), ERO(2) and lactate to identify different risk profiles. Additionally, we described the evolution of ∆PCO(2) and its correlations with ERO(2) and lactate during the first postoperative day (POD1). In this monocentre, prospective, and pilot study, 25 patients undergoing conventional cardiac surgery were included. Central venous and arterial blood gases were collected on ICU admission and at 6, 12 and 24 h postoperatively. High ∆PCO(2) (≥ 6 mmHg) on ICU admission was found to be very frequent (64% of patients). Correlations between ∆PCO(2) and ERO(2) or lactate for POD1 values and variations were weak or non-existent. On ICU admission, a high ∆PCO(2) did not predict a prolonged ICU length of stay (LOS). Conversely, a significant increase in both ICU and hospital LOS was observed in high-risk patients identified by the algorithm: 3.5 (3.0–6.3) days versus 7.0 (6.0–8.0) days (p = 0.01) and 12.0 (8.0–15.0) versus 8.0 (8.0–9.0) days (p < 0.01), respectively. An algorithm incorporating ICU admission values of ∆PCO(2), ERO(2) and lactate defined a high-risk profile that predicted prolonged ICU and hospital stays better than ∆PCO(2) alone."
1193,Moving Past Ganciclovir and Foscarnet: Advances in CMV Therapy,"PURPOSE OF REVIEW: CMV DNA polymerase inhibitors such as ganciclovir and foscarnet have dramatically reduced the burden of CMV infection in the HCT recipient. However, their use is often limited by toxicities and resistance. Agents with novel mechanisms and favorable toxicity profiles are critically needed. We review recent developments in CMV antivirals and immune-based approaches to mitigating CMV infection. RECENT FINDINGS: Letermovir, an inhibitor of the CMV terminase complex, was approved in 2017 for primary CMV prophylaxis in adult seropositive allogeneic HCT recipients. Maribavir, an inhibitor of the CMV UL97 kinase, is currently in two phase 3 treatment studies. Adoptive immunotherapy using third-party T cells has proven safe and effective in preliminary studies. Vaccine development continues, with several promising candidates currently under study. SUMMARY: No longer limited to DNA polymerase inhibitors, the prevention and treatment of CMV infections in the HCT recipient is a rapidly evolving field which should translate into improvements in CMV-related outcomes."
1194,Interventions to improve wellbeing among obstetricians and midwives at Cork University Maternity Hospital,"BACKGROUND: There is an increasing body of research demonstrating stress, burnout, and compassion fatigue among those working in obstetrics and gynaecology. The literature is lacking with respect to targeted interventions aimed at improving staff wellbeing. AIMS: To investigate whether an intervention which increases support for staff is feasible to implement and effective at improving staff wellbeing. METHODS: This study was conducted in a tertiary university teaching maternity hospital. All doctors in training (DITs) (N = 28) and midwives (N = 69) working in the delivery suite were invited to participate. Wellbeing was assessed by measuring burnout, compassion fatigue, and perceived stress using validated questionnaires. These were distributed pre-intervention and 6 months after implementation of the interventions. The support interventions consisted of posters promoting self-care, team bonding sessions, and end of shift meetings. RESULTS: Eighteen (64%) DITs and 22 (31%) midwives returned pre-intervention questionnaires. Thirteen (18%) midwives retuned post-intervention questionnaires, of which five midwives (7%) returned both the pre-intervention questionnaire and the post-intervention questionnaire. Eighty-seven percent of participants were experiencing emotional exhaustion pre-intervention. There was a statistically significant decrease in the Professional Quality of Life burnout score from pre-intervention (M = 25.8) to post-intervention (M = 21.4), p = 0.02. End of shift meetings were discontinued after 5 weeks due to low attendance. End of shift meetings provided an opportunity for support and debriefing; however, the timing of these sessions impaired their long-term feasibility. CONCLUSION: DITs and midwives of this sample are experiencing high levels of burnout and compassion fatigue. End of shift meetings for midwives and team bonding sessions for DITs may positively impact on wellbeing, but in current format, they are not feasible for long-term implementation. The low level of participation highlights a challenge in implementing institution-wide support interventions."
1195,Pneumocystis jirovecii Pneumonia and Other Infections in Idiopathic Inflammatory Myositis,"PURPOSE OF REVIEW: The management of patients with idiopathic inflammatory myositis (IIM) can be complex and challenging due to the myriad of complications they can experience. The continued use of corticosteroids, in addition to the rise of combination immunosuppressive therapy, has contributed to the ongoing concern for infection. Perhaps the most feared infection in IIM patients is Pneumocystis jirovecii pneumonia (PJP) given its infrequent occurrence yet high mortality. The field has been, and continues to be, without evidence-based guidelines to help clinicians determine which patients with IIM to prescribe prophylaxis. Herein, we review this literature to provide the clinician with an up-to-date view of infections in IIM. RECENT FINDINGS: In the past 5 years, a number of studies have been reported highlighting various infectious complications, which help us better understand their frequency and associated risk factors. In addition, data has been published on the potential harms of PJP prophylaxis, to better inform the risk/benefit of our decision-making. SUMMARY: Infection remains a major contributor to morbidity and mortality in IIM. A better understanding of which patient subgroups are at risk for particular infections will inform optimal management strategies."
1196,Pretreatment with glucose–insulin–potassium improves ventricular performances after coronary artery bypass surgery: a randomized controlled trial,"Heart failure is the main cause of poor outcome following open heart surgery and experimental studies have demonstrated that glucose–insulin–potassium (GIK) infusion exerts cardioprotective effects by reducing myocardial ischemia–reperfusion injuries. This randomized controlled trial was designed to assess the effects of GIK on left ventricular function in moderate-to-high risk patients undergoing on-pump isolated coronary artery bypass surgery (CABGS), or combined with aortic valve replacement. The primary outcomes were the effects of GIK on two- and three-dimensional left ventricular ejection fraction (2D and 3D-LVEF), and on transmitral flow propagation velocity (Vp), that occurred between the pre- and post-CPB periods. GIK administration was associated with favorable interaction effects (p < 0.001) on 2D-LVEF, 3D-LVEF and Vp changes over the study periods. In GIK pretreated patients (N = 54), 2-D and 3D-LVEF and Vp increased slightly during surgery (mean difference [MD] + 3.5%, 95% confidence interval [95% CI] − 0.2 to 7.1%, MD + 4.0%, 95% CI 0.6–7.4%, and MD + 22.2%, 95% CI 16.0–28.4%, respectively). In contrast, in the Placebo group (N = 46), 2D-and 3D-LVEF, as well as Vp all decreased after CPB (MD − 7.5% [− 11.6 to − 3.4%], MD − 12.0% [− 15.2 to − 8.8%] and MD − 21.3% [− 25.7 to − 16.9%], respectively). In conclusion, the administration of GIK resulted in better preservation of systolic and diastolic ventricular function in the early period following weaning from CPB."
1197,Recent advances in radiotracers targeting norepinephrine transporter: structural development and radiolabeling improvements,"The norepinephrine transporter (NET) is a major target for the evaluation of the cardiac sympathetic nerve system in patients with heart failure and Parkinson's disease. It is also used in the therapeutic applications against certain types of neuroendocrine tumors, as exemplified by the clinically used (123/131)I-MIBG as theranostic single-photon emission computed tomography (SPECT) agent. With the development of more advanced positron emission tomography (PET) technology, more radiotracers targeting NET have been reported, with superior temporal and spatial resolutions, along with the possibility of functional and kinetic analysis. More recently, fluorine-18-labelled NET tracers have drawn increasing attentions from researchers, due to their longer radiological half-life relative to carbon-11 (110 min vs. 20 min), reduced dependence on on-site cyclotrons, and flexibility in the design of novel tracer structures. In the heart, certain NET tracers provide integral diagnostic information on sympathetic innervation and the nerve status. In the central nervous system, such radiotracers can reveal NET distribution and density in pathological conditions. Most radiotracers targeting cardiac NET-function for the cardiac application consistent of derivatives of either norepinephrine or MIBG with its benzylguanidine core structure, e.g. (11)C-HED and (18)F-LMI1195. In contrast, all NET tracers used in central nervous system applications are derived from clinically used antidepressants. Lastly, possible applications of NET as selective tracers over organic cation transporters (OCTs) in the kidneys and other organs controlled by sympathetic nervous system will also be discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00702-020-02180-4) contains supplementary material, which is available to authorized users."
1198,Factors associated with development of early and late pulmonary hypertension in preterm infants with bronchopulmonary dysplasia,"OBJECTIVE: To investigate factors associated with development of early and late pulmonary hypertension (E/LPH) in preterm infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: A retrospective case-control observational study of preterm infants with BPD admitted to a level IV referral neonatal intensive care unit over 5 years. We compared pre- and postnatal characteristics between infants with or without BPD-associated EPH and LPH. RESULTS: Fifty-nine out of 220 infants (26.8%) had LPH, while 85 out of 193 neonates (44%) had EPH. On multiple logistic regression, novel factors associated with development of BPD–LPH included presence of maternal diabetes, EPH, tracheostomy, tracheitis, intraventricular hemorrhage (IVH, grade ≥3) and systemic steroid use. For EPH, these were maternal diabetes, IVH grade ≥3, high frequency ventilator use, and absence of maternal antibiotics use. CONCLUSION: We identified novel factors and confirmed previously established factors with development of LPH and EPH, which can help develop a screening strategy in BPD patients."
1199,Effectiveness and Safety of High Dose Tigecycline for the Treatment of Severe Infections: A Systematic Review and Meta-Analysis,"BACKGROUND: Studies assessing the effect of high dose tigecycline on severe infections are limited and remain controversial. OBJECTIVES: To assess systematically the effectiveness and safety of high dose tigecycline in the treatment of severe infections. METHODS: Pubmed, Web of Science, Embase, MEDLINE, Cochrane Library and ClinicalTrials were searched up to February 20, 2019 for studies that compared the effectiveness and safety of high dose tigecycline with standard dose tigecycline or other non-tigecycline-containing regimens in the treatment of severe infections. Rates for all-cause mortality, clinical cure, microbiological eradication and adverse events were analysed. RESULTS: Ten studies with 593 patients were included. The results indicated that using high dose tigecycline resulted in better outcomes compared with controls with lower all-cause mortality (OR 0.44, 95% CI 0.30–0.66, p < 0.0001), higher clinical cure (OR 3.43, 95% CI 2.09–5.63, p < 0.00001), higher microbiological eradication (OR 2.25, 95% CI 1.44–3.50, p = 0.0003), and without increasing adverse events rates. Subgroup analysis showed that high dose tigecycline reduced all-cause mortality in nosocomial acquired pneumonia (OR 0.39, 95% CI 0.22–0.70, p = 0.002), bloodstream infections (OR 0.19, 95% CI 0.06–0.58, p = 0.004) and mixed infections (OR 0.20, 95% CI 0.07–0.59, p = 0.003), with no statistical differences in complicated intra-abdominal infections (OR 2.04, 95% CI 0.80–5.23, p = 0.14). In carbapenem-resistant pathogens, the microbiological eradication rate in those given high dose tigecycline did not differ from controls (OR 1.07, 95% CI 0.44–2.60, p = 0.87), although mortality was reduced (OR 0.20, 95% CI 0.09–0.45, p = 0.0001). The main limitation of the review is that most of the included studies are observational studies with small sample sizes and high risks of bias. CONCLUSIONS: High dose tigecycline treatment is effective and safe for severe infections owing to its lower all-cause mortality, higher clinical cure, microbiological eradication and comparable adverse events. However, as a result of the high risks of bias of the included studies, well-designed randomised clinical trials are warranted to establish the effectiveness and safety of high dose tigecycline compared with standard dose tigecycline and other commonly used antibiotics."
1200,Clinical Profile of Critical Pertussis in Children at a Pediatric Intensive Care Unit in Northern India,"OBJECTIVE: To delineate the clinical profile, complications, intensive care needs, and predictors of mortality in children with critical pertussis. METHODS: Retrospective analysis of case records of children in the pediatric intensive care unit of a tertiary-care hospital, with a diagnosis of critical pertussis over 3 years. Diagnostic criteria included CDC case definition and confirmation by polymerase chain reaction (PCR), when available. Survivors and nonsurvivors were compared to identify predictors of mortality. RESULTS: 36 records were analysed, most cases were infants (31, 86.1%). 10 (27.7%) were (below 6 weeks of age). In the rest, 16 (61.5%) were partially immunized or unimmunized against pertussis. Rapid breathing (88.9%), paroxysmal cough (86.1%) and apnea (41.7%) were common presenting complaints. Hypoxemia (97.2%), hyperleukocytosis (61.1%) and encephalopathy (52.8%) were common complications. Intensive care needs were mechanical ventilation in 11 (30.6%), vasoactive support in 7 (19.4%) and exchange transfusion in 3 (8.3%). Female gender, apnea, hyperleukocytosis, encephalopathy, need for vasoactive support, and mechanical ventilation predicted mortality. CONCLUSION: Pertussis demands attention due to its varied presentation, increased complications and higher mortality."
1201,"Synthesis, Type II diabetes inhibitory activity, antimicrobial evaluation and docking studies of indeno[1,2-c]pyrazol-4(1H)-ones","We report a convenient and efficient synthesis of indeno[1,2-c]pyrazol-4(1H)-ones (4a‒o) by the reaction of a variety of 2-acyl-(1H)-indene-1,3(2H)-diones (1) and 2-hydrazinylbenzo[d]thiazole/2-hydrazinyl-6-substitutedbenzo[d]thiazoles (2) in the presence of glacial acetic acid in good yields. The structure of the compounds thus prepared were confirmed by analytical and spectral (FT-IR, (1)H NMR, (13)C NMR, and HRMS) techniques. All the synthesized indeno[1,2-c]pyrazol-4(1H)-ones (4a‒o) were assayed for their in vitro Type II diabetes inhibitory activity by using Acarbose as standard drug and in vitro antimicrobial activity utilizing Streptomycin and Fluconazole as reference drugs. Among the synthesized derivatives, 4e (IC(50) = 6.71 μg/mL) was found to be more potent against α-glucosidase enzyme as compared with the standard Acarbose (IC(50) = 9.35 μg/mL) and 4i (IC(50) = 11.90 μg/mL) exhibited good inhibitory activity against α-amylase enzyme as compared with the standard Acarbose (IC(50) = 22.87 μg/mL). Also, all the titled compounds showed good antimicrobial activity. In addition, in vitro α-glucosidase and α-amylase inhibition were supported by docking studies performed on the derivatives 4e and 4o, respectively. [Image: see text]"
1202,Strongyloides stercoralis Hyper infection Syndrome,"Strongyloides stercoralis is a helminth, widely distributed in tropical and subtropical countries. Its infestation in humans usually does not produce symptoms. However, in some patients, severe and life-threatening forms of this infection can occur, especially in immunocompromised individuals. Severe parasitic infection is triggered by any imbalance in the host’s immunity favouring the auto-infective cycle. This results in an increase in the intraluminal parasitic burden. In addition, tissue infestation is also very common. Clinical presentation is variable, and it is very difficult to diagnose clinically. Diagnosis requires a high index of suspicion. In some cases, the diagnosis is established only on histopathological examination of the excised tissue by the pathologist. Here, the authors report a case of an elderly male diabetic patient, who presented to the emergency department with the features of acute abdomen. On exploratory laparotomy, he was found to have the features suggestive of gangrene of small bowel. Resection of the gangrenous bowel was done, and end-to-end anastomosis was done as the rest of the bowel appeared to be normal. However, the patient died of multi-organ failure and septicaemia on the second postoperative day. The resected intestine showed tissue infestation of Strongyloides stercoralis on histopathological examination. In this review article, the authors summarize a case of hyper infection syndrome of strongyloidiasis and discuss the various aspects of Strongyloides stercoralis infection with emphasis on life cycle of the parasite and different clinical features of the disease."
1203,"Self-compassion as a Stress Moderator: A Cross-sectional Study of 1700 Doctors, Nurses, and Medical Students","OBJECTIVES: Work stress is common in healthcare and reliably predicts negative outcomes, including burnout and lower quality of life (QOL). However, few studies have investigated factors that might attenuate the impact of stress on these negative outcomes. We investigated whether the tendency to be kind to the self during times of difficulty—self-compassion—might buffer the effect of work stress on outcomes. METHODS: Registered nurses (n = 801), physicians (n = 516), and medical students (n = 383) were recruited using convenience sampling in New Zealand. Following consent, participants (N = 1700) completed a survey including the Copenhagen Burnout Inventory, Satisfaction with Life Scale, and Self-Compassion Scale–Short Form. RESULTS: Across groups, greater work stress consistently predicted greater burnout and lower QOL, while greater self-compassion predicted lower burnout and better QOL. Self-compassion moderated the relationship between stress and burnout in nurses (albeit in the opposite direction to what had been predicted), but not in doctors or medical students. CONCLUSIONS: While self-compassion predicted better outcomes (and may thus represent a target to enhance wellbeing), it strengthened the association between stress and burnout in nurses. How self-compassion impacts the experience of stress and its correlates and why it does so differently in different groups of professionals remains unclear."
1204,Measuring the Quality of Palliative Care for Patients with End-Stage Liver Disease,"BACKGROUND/AIMS: We examined the quality of palliative care received by patients with decompensated cirrhosis using an explicit set of palliative care quality indicators (QIs) for patients with end-stage liver disease (PC-ESLD). METHODS: We identified patients newly diagnosed with decompensated cirrhosis at a single veterans health center and followed up them for 2 years or until death. We piloted measurement of PC-ESLD QIs in all patients confirmed to have ESLD using a chart abstraction tool. RESULTS: Out of 167 patients identified using at least one sampling strategy, 62 were confirmed to meet ESLD criteria with chart abstraction. Ninety-eight percent of veterans in the cohort were male, mean age at diagnosis was 61 years, and 74% were White. The overall QI pass rate was 68% (64% for information care planning QIs and 76% for supportive care QIs). Patients receiving specialty palliative care consultation were more likely to receive information care planning QIs (67% vs. 37%, p = 0.02). The best performing sampling strategy had a sensitivity of 62% and specificity of 60%. CONCLUSION: Measuring the quality of palliative care for patients with ESLD is feasible in the veteran population. Our single-center data suggest that the quality of palliative care is inadequate in the veteran population with ESLD, though patients offered specialty palliative care consultation and those affected by homelessness, drug, and alcohol abuse may receive better care. Our combination of ICD-9 codes can be used to identify a cohort of patients with ESLD, though better sensitivity and specificity may be needed."
1205,Left ventricular overloading identified by critical care echocardiography is key in weaning-induced pulmonary edema,"PURPOSE: To assess the role of left ventricular overload and cumulated fluid balance in the development weaning-induced pulmonary edema (WIPO). METHODS: Ventilated patients in sinus rhythm with COPD and/or heart failure (ejection fraction ≤ 40%) were studied. Echocardiography was performed immediately before and during a 30-min spontaneous breathing trial (SBT) using a T-tube. Patients who failed were treated according to echocardiography results before undergoing a second SBT. RESULTS: Twelve of 59 patients failed SBT, all of them developing WIPO. Patients who succeeded SBT had lower body weight (− 2.5 kg [− 4.8; − 1] vs. + 0.75 kg [− 2.95; + 5.57]: p = 0.02) and cumulative fluid balance (− 2326 ml [− 3715; + 863] vs. + 143 ml [− 2654; + 4434]: p = 0.007) than those who developed WIPO. SBT-induced central hemodynamic changes were more pronounced in patients who developed WIPO, with higher E wave velocity (122 cm/s [92; 159] vs. 93 cm/s [74; 109]: p = 0.017) and E/A ratio (2.1 [1.2; 3.6] vs. 0.9 [0.8; 1.4]: p = 0.001), and shorter E wave deceleration time (85 ms [72; 125] vs. 147 ms [103; 175]: p = 0.004). After echocardiography-guided treatment, all patients who failed the first SBT were successfully extubated. Fluid balance was then negative (− 2224 ml [− 7056; + 100] vs. + 146 ml [− 2654; + 4434]: p = 0.005). Left ventricular filling pressures were lower (E/E′: 7.3 [5; 10.4] vs. 8.9 [5.9; 13.1]: p = 0.028); SBT-induced increase in E wave velocity (+ 10.6% [− 2.7/ + 18] vs. + 25.6% [+ 12.7/ + 49]: p = 0.037) and of mitral regurgitation area were significantly smaller. CONCLUSION: In high-risk patients, WIPO appears related to overloaded left ventricle associated with excessive fluid balance. SBT-induced central hemodynamic changes monitored by CCE help in guiding therapy for successful weaning. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06061-y) contains supplementary material, which is available to authorized users."
1206,Effects of Mindfulness-Based Interventions on Self-compassion in Health Care Professionals: a Meta-analysis,"OBJECTIVES: Health care professionals have elevated rates of burnout and compassion fatigue which are correlated with poorer quality of life and patient care, and inversely correlated with self-compassion. Primary studies have evaluated the extent to which mindfulness-based interventions increase self-compassion with contradictory findings. A meta-analytic review of the literature was conducted to quantitatively synthesize the effects of mindfulness-based interventions on self-compassion among health care professionals. METHODS: Twenty-eight treatment outcome studies were identified eligible for inclusion. Five cumulative effect sizes were calculated using random-effects models to evaluate differences of changes in self-compassion for treatment and control groups. Within and between group comparisons were evaluated. Sub-group and moderator analyses were conducted to explore potential moderating variables. RESULTS: Twenty-seven articles (k = 29, N = 1020) were utilized in the pre-post-treatment meta-analysis. Fifteen samples (52%) included health care professionals and fourteen (48%) professional health care students. Results showed a moderate effect size between pre-post-treatment comparisons (g = .61, 95% CI = .47 to .76) for self-compassion and a strong effect size for pre-treatment to follow-up (g = .76, 95% CI = .41 to 1.12). The effect size comparing post-treatment versus post-control was moderate. One exploratory moderator analysis was significant, with stronger effects for interventions with a retreat component. CONCLUSIONS: Findings suggest mindfulness-based interventions improve self-compassion in health care professionals. Additionally, a variety of mindfulness-based programs may be useful for employees and trainees. Future studies with rigorous methodology evaluating effects on self-compassion and patient care from mindfulness-based interventions are warranted to extend findings and explore moderators. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12671-020-01342-5) contains supplementary material, which is available to authorized users."
1207,Generating Survival Times Using Cox Proportional Hazards Models with Cyclic and Piecewise Time-Varying Covariates,"Time-to-event outcomes with cyclic time-varying covariates are frequently encountered in biomedical studies that involve multiple or repeated administrations of an intervention. In this paper, we propose approaches to generating event times for Cox proportional hazards models with both time-invariant covariates and a continuous cyclic and piecewise time-varying covariate. Values of the latter covariate change over time through cycles of interventions and its relationship with hazard differs before and after a threshold within each cycle. The simulations of data are based on inverting the cumulative hazard function and a log link function for relating the hazard function to the covariates. We consider closed-form derivations with the baseline hazard following the exponential, Weibull, or Gompertz distribution. We propose two simulation approaches: one based on simulating survival data under a single-dose regimen first before data are aggregated over multiple-dosing cycles and another based on simulating survival data directly under a multiple-dose regimen. We consider both fixed intervals and varying intervals of the drug administration schedule. The method’s validity is assessed in simulation experiments. The results indicate that the proposed procedures perform well in generating data that conform to their cyclic nature and assumptions of the Cox proportional hazards model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12561-020-09266-3) contains supplementary material, which is available to authorized users."
1208,Designing intervention scheme for vaccine market: a bilevel programming approach,"Public-interest goods benefit consumers and also generate external benefits boosting societal welfare. Despite this characteristic of these goods, their level of consumption or production are generally well below the socially desirable levels without intervention. Motivated by influenza vaccine market, this paper examines the intervention design problem for a public-interest good facing yield uncertainty in production as well as inefficiencies in distribution and allocation. The proposed mechanism considers two intervention tools with the aim of resolving the inefficiencies in the system and allowing the actors to take socially desirable decisions. The first tool is to intervene so that demand level for the good is increased; we call it demand increasing strategy. The second tool aims to support the production, allocation, and distribution by investing in research and development and better planning and enhances the availability; we call this as availability increasing strategy. The intervention design problem is based on stylized demand and availability models that take into account investments made to improve them. The model suggested is experimented by a numerical study to analyze the impact of applying proposed joint mechanism in US influenza vaccine market. The results show that proposed strategy is very effectual in terms of vaccination percentages achieved and budget savings realized beyond the current practices, and the improvement in vaccination percentages is even greater when uncertainty in the system is higher. Besides, the results suggest that as long as the parameter calibration and decision problems are solved consistently, availability can be approximated by its average value when necessary."
1209,Secondary Trauma: Emotional Safety in Sensitive Research,
1210,Transfusion strategies in non-bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine,"OBJECTIVE: To develop evidence-based clinical practice recommendations regarding transfusion practices in non-bleeding, critically ill adults. DESIGN: A task force involving 13 international experts and three methodologists used the GRADE approach for guideline development. METHODS: The task force identified four main topics: red blood cell transfusion thresholds, red blood cell transfusion avoidance strategies, platelet transfusion, and plasma transfusion. The panel developed structured guideline questions using population, intervention, comparison, and outcomes (PICO) format. RESULTS: The task force generated 16 clinical practice recommendations (3 strong recommendations, 13 conditional recommendations), and identified five PICOs with insufficient evidence to make any recommendation. CONCLUSIONS: This clinical practice guideline provides evidence-based recommendations and identifies areas where further research is needed regarding transfusion practices and transfusion avoidance in non-bleeding, critically ill adults. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05884-8) contains supplementary material, which is available to authorized users."
1211,Immunity check should be performed for all patients with septic shock? Yes,
1212,An intervention to decrease time to parents’ first hold of infants in the Neonatal Intensive Care Unit requiring respiratory support,"BACKGROUND: There are many barriers to parental skin-to-skin contact for critically ill neonates. Our aims were to decrease median time to first parental hold of neonates requiring respiratory support from 6.4 to 3 days, and to increase the percentage of neonates held within the first 24 h after birth from 6 to 75%. METHODS: Lean Six Sigma methodology was used to identify barriers to holding and opportunities for improvement. INTERVENTION: A multifactorial improvement bundle was implemented to reduce the time to first parental hold of critically ill neonates. RESULTS: Median time to first parental hold was reduced from 6.4 to 1.2 days (p < 0.01). Infants held within the first 24 h after birth increased from 6 to 35%. There was no increase in adverse events associated with parental holding. CONCLUSIONS: Implementation of an improvement bundle resulted in a significant reduction in time to first parental hold of infants requiring respiratory support."
1213,The Role of Social Support in the Link Between Economic Abuse and Economic Hardship,"More data is needed about the pathways through which intimate partner violence (IPV) impacts the economic well-being of survivors. The current study assesses the moderating influence of social support on the association between economic abuse (EA) and economic hardship. Female participants (n = 435) were recruited to participate in a web-based survey which included standardized measures of EA, other forms of IPV, domains of social support, and economic hardship. Analysis included bivariate and multivariate regression with an investigation into interaction effects.Experiencing EA was significantly correlated with economic hardship, even with extent of physical and emotional IPV controlled. Both tangible and appraisal support had significant negative association with extent of material hardship. Significant interactions between forms of social support and economic abuse were observed. For those at high levels of economic abuse, support had less influence on economic hardship. A mix of direct economic aid, advocacy, education and support could provide a blueprint for addressing the economic hardship experiences of community-dwelling survivors of economic abuse. A comprehensive response to EA requires interventions aimed directly at economically controlling and exploitative tactics, including credit building, individual economic advocacy, and education. Interventions that seek to enhance survivors’ access to social support may be necessary but not sufficient to buffer the impacts of violence on survivors’ economic outcomes."
1214,External validation of a prognostic model for intensive care unit mortality: a retrospective study using the Ontario Critical Care Information System,"PURPOSE: To externally validate an intensive care unit (ICU) mortality prediction model that was created using the Ontario Critical Care Information System (CCIS), which includes the Multiple Organ Dysfunction Score (MODS). METHODS: We applied the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) recommendations to a prospective longitudinal cohort of patients discharged between 1 July 2015 and 31 December 31 2016 from 90 adult level-3 critical care units in Ontario. We used multivariable logistic regression with measures of discrimination, calibration-in-the-large, calibration slope, and flexible calibration plots to compare prediction model performance of the entire data set and for each ICU subtype. RESULTS: Among 121,201 CCIS records with ICU mortality of 11.3%, the C-statistic for the validation data set was 0.805. The C-statistic ranged from 0.775 to 0.846 among the ICU subtypes. After intercept recalibration to adjust the baseline risk, the mean predicted risk of death matched actual ICU mortality. The calibration slope was close to 1 with all CCIS data and ICU subtypes of cardiovascular and community hospitals with low ventilation rates. Calibration slopes significantly less than 1 were found for ICUs in teaching hospitals and community hospitals with high ventilation rates whereas coronary care units had a calibration slope significantly higher than 1. Calibration plots revealed over-prediction in high risk groups to a varying degree across all cohorts. CONCLUSIONS: A risk prediction model primarily based on the MODS shows reproducibility and transportability after intercept recalibration. Risk adjusting models that use existing and feasible data collection can support performance measurement at the individual ICU level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12630-020-01686-5) contains supplementary material, which is available to authorized users."
1215,Inducing Brain Cooling Without Core Temperature Reduction in Pigs Using a Novel Nasopharyngeal Method: An Effectiveness and Safety Study,"BACKGROUND: Acute brain lesions constitute an alarming public health concern. Neuroprotective therapies have been implemented to stabilize, prevent, or reduce brain lesions, thus improving neurological outcomes and survival rates. Hypothermia is the most effective approach, mainly attributed to the reduction in cellular metabolic activity. Whole-body cooling is currently implemented by healthcare professionals; however, adverse events are frequent, limiting the potential benefits of therapeutic hypothermia. Therefore, selective methods have been developed to reduce adverse events while delivering neuroprotection. Nasopharyngeal approaches are the safest and most effective methods currently considered. Our primary objective was to determine the effects of a novel nasopharyngeal catheter on the brain temperature of pigs. METHODS: In this prospective, non-randomized, interventional experimental trial, 10 crossbred pigs underwent nasopharyngeal cooling for 60 min followed by 15 min of rewarming. Nasopharyngeal catheters were inserted into the left nostril and properly positioned at the nasopharyngeal cavity. RESULTS: Nasopharyngeal cooling was associated with a decrease in brain temperature, which was more significant in the left cerebral hemisphere (p = 0.01). There was a reduction of 1.47 ± 0.86 °C in the first 5 min (p < 0.001), 2.45 ± 1.03 °C within 10 min (p < 0.001), and 4.45 ± 1.36 °C after 1 h (p < 0.001). The brain-core gradient was 4.57 ± 0.87 °C (p < 0.001). Rectal, esophageal, and pulmonary artery temperatures and brain and systemic hemodynamic parameters, remained stable during the procedure. Following brain cooling, values of oxygen partial pressure in brain tissue significantly decreased. No mucosal lesions were detected during nasal, pharyngeal, or oral inspection after nasopharyngeal catheter removal. CONCLUSIONS: In this study, a novel nasopharyngeal cooling catheter effectively induced and maintained exclusive brain cooling when combined with effective counter-warming methods. Exclusive brain cooling was safe with no device-related local or systemic complications and may be desired in selected patient populations."
1216,"The Mycobiome in Health and Disease: Emerging Concepts, Methodologies and Challenges","Fungal disease is an increasingly recognised global clinical challenge associated with high mortality. Early diagnosis of fungal infection remains problematic due to the poor sensitivity and specificity of current diagnostic modalities. Advances in sequencing technologies hold promise in addressing these shortcomings and for improved fungal detection and identification. To translate such emerging approaches into mainstream clinical care will require refinement of current sequencing and analytical platforms, ensuring standardisation and consistency through robust clinical benchmarking and its validation across a range of patient populations. In this state-of-the-art review, we discuss current diagnostic and therapeutic challenges associated with fungal disease and provide key examples where the application of sequencing technologies has potential diagnostic application in assessing the human ‘mycobiome’. We assess how ready access to fungal sequencing may be exploited in broadening our insight into host–fungal interaction, providing scope for clinical diagnostics and the translation of emerging mycobiome research into clinical practice."
1217,The influence of mindfulness and moral disengagement on the psychological health and willingness to work of civil servants experiencing compassion fatigue,"Both public administration scholars and practitioners believe that “good governance” relies on the involvement of compassionate officials. However, they overlook the fact that “compassion fatigue” often occurs when officials face the dual pressure arising from superiors’ orders and empathy for service receivers. This would inevitably not only affect their individual behaviors, but also influence the effectiveness of their service. A full-scale investigation of animal protection administrators in Taiwan was conducted so as to analyze compassion fatigue that civil servants would encounter and further establish a relationship between various variables and the hypotheses of this study by combining the studies of public administration and psychology. It should be noted that compassion fatigue may affect animal protection administrators’ mental health in spite of little influence on their willingness to work hard. However, both “mindfulness” and “moral disengagement” are coping strategies which were developed for helping tackle the dilemma of compassion fatigue. Although applying the strategy of mindfulness can generate more positive impacts on individuals and organizations than that of moral disengagement, animal protection administrators tended to adopt the latter. Accordingly, encouraging animal protection administrators to adopt mindfulness instead of moral disengagement as their coping strategy will be a priority of work for the authorities in the future."
1218,Prediction of Potential Epitopes for Peptide Vaccine Formulation Against Teschovirus A Using Immunoinformatics,"Teschovirus A belongs to the family Picornaviridae and is a causal agent of the disease Teschovirus encephalomyelitis and other infections that remain asymptomatic. The present study was performed to design epitope-based peptide vaccine against Teschovirus A by identifying the potential T cell and B-cell epitopes from capsid proteins (VP1, VP3 and VP2) of the virus using reverse vaccinology and immunoinformatics approaches. In the current study, hexapeptide T-cell and octapeptide B-cell epitopes were analyzed for immunogenicity, antigenicity and hydrophilicity scores of each epitope. Each potential epitope was further characterized using ExPASy-ProtParam and Antimicrobial Peptide Database (APD3) tools for determining various physical and chemical parameters of the epitope. One linear hexapeptide T-cell epitope, i.e., RPVNDE (epitope position 77–82) and one linear octapeptide B-cell epitope, i.e., AYSRSHPQ (236–243) were identified from the viral capsid protein as they possess the capability to raise effective immunogenic reaction in the host organism against the virus. Pharmaceutical industries could harness the results of this investigation to develop epitope-based peptide vaccines by loading the identified epitopes in combination with targeting signal peptides of T-cells and B-cells and then inserting the combination into virus like particle (vlp) or constructing subunit vaccines for further trial."
1219,"Design, synthesis, and screening of sulfonylurea-derived NLRP3 inflammasome inhibitors","Inflammasomes are multiprotein assemblies that produce robust inflammatory responses upon stimulation with pathogen- and/or danger-associated molecular patterns. Uncontrolled inflammasome activation has been linked to the pathophysiology of a wide array of disorders including life-threatening pathogenic infections, e.g., Francisella tularensis. There has been a great deal of interest in the development of small molecule inflammasome inhibitors. Using computational modeling based on chalcone derivatives, we have developed novel tertiary sulfonylurea compounds as inhibitors of the NLRP3 inflammasome. The polar enone functional alert of chalcone was replaced with a sulfonylurea scaffold while maintaining the relative positions of the two aromatic rings. These compounds were evaluated for their ability to inhibit NLRP3 and AIM2 inflammasome activation triggered by Francisella tularensis infection."
1220,Vaccine hesitancy: Report of a student study group,"In summer 2019 an extracurricular activity was started at the Medical University of Vienna (MUW) with the title: “Esoterism in Medicine”, where different chapters were evaluated by students. Here we present the subheading “Vaccine Hesitancy”. Three students formulated arguments from sceptic, hesitant or anti-vaccine groups and discussed the scientific literature to rebut it. Frequent objections were partly taken from the homepage of the German Robert-Koch-Institute, the home of the “Ständige Impfkommission”. Other objections were taken from blogs and social media. The students’ rebuttal was based on current scientific literature (preferentially pubmed), but also from other scientific sources like authorities."
1221,Exploring oncology nurses’ perception of the consequences of clinical empathy in patients and nurses: a qualitative study,"PURPOSE: Clinical empathy is the ability to understand the patient's situation, perspective, feelings, and actions, based on the patient’s perception, in a helping or therapeutic way. This study was conducted with the aim of exploring oncology nurses’ perception of the consequences of clinical empathy in patients and nurses and the factors influencing it. METHODS: A qualitative study was conducted by semi-structured face-to-face interviews. The participants were 6 male and 9 female oncology nurses who were selected by purposive sampling. Data were analyzed using conventional content analysis. RESULTS: The theme of “empathy as a double-sided mirror” was created, based on oncology nurses’ perception of the effects of clinical empathy in patients and nurses. Two themes of “organizational factors” and “contextual factors” were generated in response to influencing factors on clinical empathy. CONCLUSIONS: By awareness of the effects of clinical empathy, controlling the barriers and strengthening the facilitators, there is a possibility to design interventional programs to develop empathy as a clinical competency in oncology nurses."
1222,Transcending the Professional–Client Divide: Supporting Young People with Complex Support Needs Through Transitions,"Young people with complex support needs frequently experience multiple intersecting forms of disadvantage including experiences of violence, abuse and neglect, housing instability and homelessness, problematic substance use, exclusion from education, and contact with the criminal justice system. Many of these young people have mental health, cognitive disability and/or other health issues that also impact on their lives. These young people need to navigate multiple, diverse, and often difficult transitions between services, adding to the existing chaos in their lives. This article explores the experiences of young people with complex support needs in transition, specifically young people’s viewpoints and experiences of supports they receive from paid professionals. This qualitative study used body mapping research methods and in-depth interviews with 38 young people aged 16 to 26 years in three Australian states. Helpful and trusting paid relationships could serve as an anchor to young people during complex transitions and other highly turbulent life periods. These relationships were contingent on a deep and non-judgmental knowing of the young person, contributed constructive outcomes and stability in young people’s lives, and for some young people, had ‘life-saving’ effects. These findings present opportunities and challenges for policymakers and practitioners to balance the tensions between authentic relationship-based work with young people and risk-averse, economically-driven imperatives in contemporary youth service provision."
1223,Synthesis and Photocatalytic Sterilization Performance of SA/TiO(2),"The photocatalyst sorbic acid (SA)/titanium dioxide (TiO(2)) was successfully synthesized by sol–gel method and characterized. The composite exhibited regularly spherical particles with the size of 50 nm and the specific surface area of 90.3 m(2) g(−1), furthermore, it showed mesoporous structure and significantly improved dispersion. SA was grafted on TiO(2) surface by –COOTi and TiO(2) existed as pure anatase phase in the composite. The addition of SA made the band gap of TiO(2) increased from 3.03 to 3.35 eV, which indicting that the composite exhibited a strong response to the ultraviolet light. The optimum preparation parameters of the catalyst were as follows: n(Ti):n(SA) = 1:0.05, ethanol 60 mL, glacial acetic acid 40 mL, hydrothermal temperature 180 °C, hydrothermal time 12 h. The composite could reach the 4.31 log reduction of E. coli, with the optimum catalyst dosage of 0.7 g L(−1), irradiated by UV light for 60 min. SA/TiO(2) was an environmentally friendly, non-toxic and safe sterilized nanocomposite material appropriate for future bactericidal applications, providing a new way to effectively increase the dispersion of TiO(2) particles to achieve superior photocatalytic sterilization efficiency."
1224,HIV Prevalence and Factors Related to HIV Infection Among Transgender Women in Vietnam: A Respondent Driven Sampling Approach,"Transgender women are at higher risk of HIV infection, however, there is a lack of information about HIV infection and related factors among transgender women in Vietnam. From February 2018 to June 2018, 456 transgender women were recruited in the study using Respondent-Driven Sampling technique. Participants completed the computer-based questionnaire and were tested for HIV serostatus. Multivariable logistic regression was used to identify factors related to HIV infection. The prevalence of HIV infection was 77 (16.5%), of which 19 (24.7%) were not aware of their HIV-positive status prior to the study. Factors associated with HIV infection included popper use (aOR 2.01, p = 0.044) and having regular male partner(s) (aOR 0.42, p = 0.006). More efforts are needed to reduce the high prevalence of HIV infection, such as expanding the reach of HIV screening and prevention programs to the transgender women population, particularly for substance users. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10461-020-02867-5) contains supplementary material, which is available to authorized users."
1225,Poster,
1226,Oestrogen Receptor β Activation Protects Against Myocardial Infarction via Notch1 Signalling,"PURPOSE: Oestrogen receptor β is believed to exert a cardioprotective effect against ischaemic injury. Nonetheless, the mechanism underlying its protective action remains to be fully elucidated. Recently, increased attention has been focused on Notch1 signalling for ameliorating cardiac ischaemic injury. Here, we hypothesised that oestrogen receptor β activation attenuates myocardial infarction (MI)-induced cardiac damage by modulating the Notch1 signalling pathway. METHODS: Male C57BL/6 mice were used to establish an MI model through the ligation of the anterior descending branch of the left coronary artery. Two chemical drugs, 2,3-Bis(4-hydroxyphenyl)-propionitrile (DPN) and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-s-phenylglycine t-butyl ester (DAPT), a specific inhibitor of Notch1 signalling) were administered via intraperitoneal injection to change oestrogen receptor β and Notch1 activities. Immunohistochemistry, western blot analysis, enzyme-linked immunosorbent assay (Elisa) assessment and echocardiography were used in this study to analyse cardiac oxidative stress, apoptosis, infraction volume, fibrosis and cardiac function. RESULTS: DPN-mediated oestrogen receptor β activation effectively protected cardiomyocytes from MI-induced oxidative damage and apoptosis. Furthermore, oestrogen receptor β activation reduced the infarct size and lowered the levels of myocardial enzymes in the serum, thereby leading to greater overall cardiac function improvement. Ischaemic injury–induced myocardial fibrosis was attenuated by oestrogen receptor β activation. Nevertheless, all of these cardioprotective effects of oestrogen receptor β activation were almost abrogated by DAPT administration, i.e. DAPT attenuated the anti-oxidative and anti-apoptotic effects and the decrease in infarct and fibrotic areas and reversed cardiac functional recovery. The levels of phospho-phosphatidylinositol-3-kinase (PI3K) and phospho-protein kinase B (Akt) were increased after DPN administration, and this change was reversed after DAPT was administered. CONCLUSIONS: All of these new findings indicate that oestrogen receptor β activation is effective in ameliorating MI-induced cardiac dysfunction by enhancing Notch1 signalling and that PI3K/Akt signalling is the downstream mediator. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10557-020-06949-3) contains supplementary material, which is available to authorized users."
1227,Aberrant B cell repertoire selection associated with HIV neutralizing antibody breadth,"A goal of HIV vaccine development is to elicit antibodies with neutralizing breadth. Broadly neutralizing antibodies (bNAbs) to HIV often have unusual sequences with long heavy-chain complementarity-determining region loops, high somatic mutation rates and polyreactivity. A subset of HIV-infected individuals develops such antibodies, but it is unclear whether this reflects systematic differences in their antibody repertoires or is a consequence of rare stochastic events involving individual clones. We sequenced antibody heavy-chain repertoires in a large cohort of HIV-infected individuals with bNAb responses or no neutralization breadth and uninfected controls, identifying consistent features of bNAb repertoires, encompassing thousands of B cell clones per individual, with correlated T cell phenotypes. These repertoire features were not observed during chronic cytomegalovirus infection in an independent cohort. Our data indicate that the development of numerous B cell lineages with antibody features associated with autoreactivity may be a key aspect in the development of HIV neutralizing antibody breadth."
1228,Prediction of Postoperative Mortality in Patients with Organ Failure After Gastric Cancer Surgery,"BACKGROUND: Scarce data are available on the characteristics of postoperative organ failure (POF) and mortality after gastrectomy. We aimed to describe the causes of organ failure and mortality related to gastrectomy for gastric cancer and to identify patients with POF who are at a risk of failure to rescue (FTR). METHODS: The study examined patients with POF or in-hospital mortality in Seoul National University Hospital between 2005 and 2014. We identified patients at a high risk of FTR by analyzing laboratory findings, complication data, intensive care unit records, and risk scoring including Acute Physiology and Chronic Health Evaluation (APACHE) IV, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score (SAPS) 3 at ICU admission. RESULTS: Among the 7304 patients who underwent gastrectomy, 80 (1.1%) were identified with Clavien–Dindo classification (CDC) grade ≥ IVa. The numbers of patients with CDC grade IVa, IVb, and V were 48 (0.66%), 11 (0.15%), and 21 (0.29%), respectively. Pulmonary failure (43.8%), surgical site complication (27.5%), and cardiac failure (13.8%) were the most common causes of POF and mortality. Cancer progression (100%) and cardiac events (45.5%) showed high FTR rates. In univariate analysis, acidosis, hypoalbuminemia, SOFA, APACHE IV, and SAPS 3 were identified as risk factors for FTR (P < 0.05). Finally, SAPS 3 was identified as an independent predictive factor for FTR. CONCLUSIONS: Cancer progression and acute cardiac failure were the most lethal causes of FTR. SAPS 3 is an independent predictor of FTR among POF patients after gastrectomy."
1229,Effect of Early Tracheostomy on Mortality of Mechanically Ventilated Patients with Guillain–Barré Syndrome: A Nationwide Observational Study,"BACKGROUND: Patients with Guillain–Barré syndrome (GBS) who require mechanical ventilation (MV) are regarded as candidates for early tracheostomy because of the high risk of prolonged MV; however, the association between early tracheostomy and favorable outcomes in patients with GBS remains unclear. In this study, we evaluated the association between early tracheostomy and outcomes in mechanically ventilated patients with GBS. METHODS: This retrospective observational study included adult patients with GBS identified in the Japanese Diagnosis Procedure Combination national inpatient database from July 1, 2010, to March 31, 2018, who initiated MV within the first week of admission and who received MV for more than 1 week. Early tracheostomy was defined as tracheostomy performed within 7 days of MV. The primary outcome was in-hospital mortality, and the secondary outcomes were 28-day mortality, nosocomial pneumonia, length of hospital stay, length of intensive care unit (ICU) stay, duration of MV, duration of sedation, duration of analgesia, duration of delirium, and total hospitalization costs. Propensity scores for early tracheostomy were calculated using a logistic regression model on the following variables: age; sex; body mass index; Japan Coma Scale status at admission; Charlson comorbidity index score; comorbidity of chronic pulmonary disease; complication of pneumonia at admission; complication of hyponatremia at admission; neurological presentation at admission; ambulance use; referral from other hospitals; treatment year; days from hospital admission to MV initiation; ICU admission until the day of MV initiation; and treatments until the day of MV initiation. Stabilized inverse probability of treatment weighting analyses was performed to compare the outcomes between patients with and without early tracheostomy. RESULTS: Among 919 eligible patients, 654 patients (71%) underwent tracheostomy, with 136 patients (15%) receiving early tracheostomy. Overall, the median time from initiation of MV to tracheostomy was 12 days (interquartile range 8–15 days). After stabilized inverse probability of treatment weighting, early tracheostomy was not associated with lower in-hospital mortality (risk difference 0.4%; 95% confidence interval − 5.6 to 6.7%) compared with patients without early tracheostomy. There were no significant differences in 28-day mortality (risk difference − 1.3%; 95% confidence interval − 3.5 to 0.9%) and incidence of nosocomial pneumonia (risk difference − 2.6%; 95% confidence interval − 9.1 to 4.2%) between the two groups. None of the other secondary outcomes differed significantly between the groups. CONCLUSIONS: Early tracheostomy was not significantly associated with decreased mortality or morbidity in patients with GBS requiring MV for more than 1 week."
1230,Lung–kidney cross-talk in the critically ill: insights from the Lung Safe study,
1231,Self-Injury in Japanese Manga: A Content Analysis,"This study explored representations of self-injury in Japanese manga (graphic novels). A content analysis of fifteen slice-of-life manga published between 2000-2017 was conducted, focusing on forty scenes that depict eighteen characters engaging in self-injury. Most depictions of self-injury reflect a stereotypical perception of “self-injurer,” a young girl cutting herself to cope with negative emotion. Characters receive informal support from friends and partners, while parents are portrayed as unsupportive and even triggering. An emergent trend was observed among manga targeting male readers to label self-injuring women as “menhera” - mentally vulnerable damsels in distress - inviting a fetishistic gaze on the self-injuring female bodies."
1232,Trials on oxygen supplementation in sepsis: better late than never,
1233,Quality assessment and response to less invasive surfactant administration (LISA) without sedation,"BACKGROUND: Although sedative premedication for endotracheal intubation is considered standard of care, less invasive surfactant administration (LISA) is often performed without sedative premedication. The aim of this study was to assess success rates, technical quality and vital parameters in LISA without sedative premedication. METHODS: Prospective observational study in 86 neonates <32 weeks’ gestation. LISA was performed according to a standardized protocol without use of sedative premedication. Outcome measures were success rates of LISA attempts, reasons for failure and quality of technical conditions. In 37 neonates, heart rate and oxygen saturation levels from 20 min before until 30 min after start of LISA were collected. RESULTS: In 48% of LISAs the first attempt failed and in 34% quality of technical conditions was inadequate. The success rate was significantly correlated with quality of technical conditions and experience of the performer. Desaturations <80% occurred in 54% of patients while bradycardia <80/min did not occur. CONCLUSION: This study shows a relatively low success rate of the first attempt of LISA, frequent inadequacy of technical quality and frequent oxygen desaturations. These effects may be improved by the use of sedative premedication."
1234,"Minds, brains, and hearts: an empirical study on pluralism concerning death determination","Several authors in bioethics literature have expressed the view that a whole brain conception of death is philosophically indefensible. If they are right, what are the alternatives? Some authors have suggested that we should go back to the old cardiopulmonary criterion of death and abandon the so-called Dead Donor Rule. Others argue for a pluralist solution. For example, Robert Veatch has defended a view that competent persons should be free to decide which criterion of death should be used to determine their death. However, there is very little data on people’s preferences about death determination criteria. We conducted online vignette-based survey with Latvian participants (N = 1416). The data suggest that the pluralist solution fits best with the way our study participants think about death determination—widely differing preferences concerning death determination criteria were observed. Namely, most participants choose one of the three criteria discussed in the literature: whole brain, higher brain, and cardiopulmonary. Interestingly, our data also indicate that study participants tend to prefer less restrictive criteria for determination of their own deaths than for determination of deaths of their closest relatives. Finally, the preferences observed in our sample are largely in accord with the Dead Donor Rule for organ procurement for transplantation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40592-020-00114-0) contains supplementary material, which is available to authorized users."
1235,Tracheoesophageal fistula in the developing world: are we ready for thoracoscopic repair?,"PURPOSE: Tracheoesophageal fistula (TEF) is a bellwether for a country’s ability to care for sick newborns. We aim to review the existing literature from low- and middle-income countries in regard to management of those newborns and the possible approaches to improve their outcomes. METHODS: A review of the existing English literature was conducted with the aim of assessing challenges faced by providers in LMIC in terms of diagnostic, preoperative, operative and post-operative care for TEF patients. We also review the limited literature for performing thoracoscopic repair in the developing world context and suggest methods for introduction of advanced thoracoscopic procedures including techniques for providing anesthesia to these challenging babies. RESULTS: While outcomes related to technique from LMIC are comparable to the developed world, rates of secondary complications like sepsis and pneumonia are higher. In many areas, repairs are conducted in a staged fashion with minimal utilization of thoracoscopic approach. The paucity of resources creates strain on intraoperative and post-operative management. CONCLUSION: Clearly, not all developing world contexts are ready to attempt thoracoscopic repair but we outline suggestions for assessing the existing capabilities and a stepwise gradual implementation of advanced thoracoscopy when appropriate."
1236,"An appraisal of oriental theileriosis and the Theileria orientalis complex, with an emphasis on diagnosis and genetic characterisation","Oriental theileriosis, a tick-borne disease of bovids caused by members of the Theileria orientalis complex, has a worldwide distribution. Globally, at least 11 distinct genotypes of T. orientalis complex, including type 1 (chitose), type 2 (ikeda), type 3 (buffeli), types 4 to 8, and N1–N3, have been described based on the sequence of the major piroplasm surface protein (MPSP) gene. Of these 11 genotypes, mainly ikeda and chitose are known to be pathogenic and cause considerable morbidity (including high fever, anaemia, jaundice and abortion), production losses and/or mortality in cattle. Mixed infections with two or more genotypes of T. orientalis is common, but do not always lead to a clinical disease, posing challenges in the diagnosis of asymptomatic or subclinical forms of oriental theileriosis. The diagnosis of oriental theileriosis is usually based on clinical signs, the detection of piroplasms of T. orientalis in blood smears, and/or the use of serological or molecular techniques. This paper reviews current methods used for the diagnosis of T. orientalis infections and the genetic characterisation of members of the T. orientalis complex, and proposes that advanced genomic tools should be established for investigations of these and related haemoparasites."
1237,Measuring endotracheal tube intracuff pressure: no room for complacency,"Tracheal intubation constitutes a routine part in the care of critically ill and anaesthetised patients. Prolonged use of endotracheal with inflated cuff is one of the major multifactorial causes of complications. Both under-inflation and over-inflation of cuff are associated with complications. Despite known problems, regular measurement of cuff pressure is not routine, and it is performed on an ad hoc basis."
1238,Towards new TB vaccines,"Mycobacterium tuberculosis remains the leading cause of death attributed to a single infectious organism. Bacillus Calmette-Guerin (BCG), the standard vaccine against M. tuberculosis, is thought to prevent only 5% of all vaccine-preventable deaths due to tuberculosis, thus an alternative vaccine is required. One of the principal barriers to vaccine development against M. tuberculosis is the complexity of the immune response to infection, with uncertainty as to what constitutes an immunological correlate of protection. In this paper, we seek to give an overview of the immunology of M. tuberculosis infection, and by doing so, investigate possible targets of vaccine development. This encompasses the innate, adaptive, mucosal and humoral immune systems. Though MVA85A did not improve protection compared with BCG alone in a large-scale clinical trial, the correlates of protection this has revealed, in addition to promising results from candidate such as VPM1002, M72/ASO1E and H56:IC31 point to a brighter future in the field of TB vaccine development."
1239,Incidence of coagulase-negative staphylococcal bacteremia among ICU patients: decontamination studies as a natural experiment,"The epidemiology of coagulase-negative staphylococcal (CNS) bacteremia among adult ICU patients remains unclear. Decontamination studies among ICU patients provide a unique opportunity to study the impacts of different diagnostic criteria, exposure to various decontamination interventions, and various other factors, on its incidence over three decades. Decontamination studies among ICU patients reporting CNS bacteremia incidence data were obtained mostly from recent systematic reviews. The CNS bacteremia incidence within component (control and intervention) groups of decontamination studies was benchmarked versus studies without intervention (observational groups). The impacts of antibiotic versus chlorhexidine decontamination interventions, control group concurrency, publication year, and diagnostic criteria were examined in meta-regression models. Among non-intervention (observational) studies which did versus did not specify stringent (≥ 2 positive blood cultures) diagnostic criteria, the mean CNS bacteremia incidence per 100 patients (and 95% CI; n) is 1.3 (0.9–2.0; n = 23) versus 3.6 (1.8–6.9; n = 8), respectively, giving an overall benchmark of 1.8 (1.2–2.4; n = 31). Versus the benchmark incidence, the mean incidence is high among concurrent control (5.7; 3.6–9.1%) and intervention (5.2; 3.6–6.9%), but not non-concurrent control (1.0; 0.4–3.9%) groups of 21 antibiotic studies, nor among eleven component groups of chlorhexidine studies. This high incidence remained apparent (p < 0.01) in meta-regression models adjusting for group wide factors such as diagnostic criteria and publication year. The incidence of CNS bacteremia within both intervention and concurrent (but not non-concurrent) control groups of antibiotic-based decontamination studies are unusually high even accounting for variable diagnostic criteria and other factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-019-03763-0) contains supplementary material, which is available to authorized users."
1240,Evaluation of respiratory syncytial virus IgG antibody dynamics in mother-infant pairs cohort,"RSV is one of the most important agents of lower respiratory infections in childhood. In this study, anti-RSV antibody levels in mother-infant pairs and factors related to antibody transfer ratio were investigated. One hundred and twenty-seven women that had term babies and their babies and 84 mother-infant pairs of them who continued the study after 6 months were enrolled. Anti-RSV IgG antibodies of the mothers and infants were positive in 46.5% and 61.5%, respectively. At the sixth month, anti-RSV antibodies were negative in all infants. Median of the anti-RSV antibody levels of the mothers and infants at birth were 12.08 IU/ml (1.21–119.27) and 13.78 IU/ml (3.99–108.6), respectively. There was a significant correlation between anti-RSV antibody levels of mothers and infants at birth (p: 0.0001, r: 0.667) and anti-RSV antibody levels of infants at birth and at 6th month (p: 0.0001, r: 0.343). Median ratio of infant and mother antibody levels was 1.22 (0.14–6.05). Median ratio that was detected in appropriate for gestational age infants was significantly higher than in small for gestational age or large for gestational age infants. In this study, the significant positive correlation between maternal antibody levels and infants’ antibody levels at birth suggests that maternal vaccination strategies may be logical. We showed that antibody transfer rate was highest in appropriate for gestational age infants. It should be kept in mind that maternal vaccination strategies may be less effective in small for gestational age and large for gestational age infants."
1241,Distinction between good palliative care and intending death,
1242,Intracranial pressure monitoring associated with increased mortality in pediatric brain injuries,"BACKGROUND: Utilization of ICP monitors for pediatric patients is low and varies between centers. We hypothesized that in more severely injured patients (GCS 3–4), there would be a decreased mortality associated with invasive monitoring devices. METHODS: The pediatric Trauma Quality Improvement Program (TQIP) was queried for patients aged ≤ 16 years meeting criteria for invasive monitors. Our primary outcome was mortality. Patients with ICP monitoring were compared to those without. A logistic regression was used to examine the risk of mortality. RESULTS: Of 3,808 patients, 685 (18.0%) underwent ICP monitoring. ICP monitors were associated with increased risk of mortality (OR 1.82, CI 1.36–2.44, p < 0.001). A secondary analysis including type of invasive ICP monitor and dividing GCS into 3 categories revealed both intraventricular drain (OR 1.89, CI 1.3–2.7, p = 0.001) and intraparenchymal pressure monitor (OR 1.86, CI 1.32–2.6, p < 0.001) to be independently associated with an increased likelihood of mortality regardless of GCS, while intraparenchymal oxygen monitoring was not (OR 0.47, CI 0.11–2.05, p = 0.316). The strongest effect was seen in those patients with a GCS of 5–6. CONCLUSION: ICP monitors are an independent risk factor for mortality, particularly with intraventricular drains and intraparenchymal monitors in patients with a GCS 5–6."
1243,"Structural proteomics, electron cryo-microscopy and structural modeling approaches in bacteria–human protein interactions","A central challenge in infection medicine is to determine the structure and function of host–pathogen protein–protein interactions to understand how these interactions facilitate bacterial adhesion, dissemination and survival. In this review, we focus on proteomics, electron cryo-microscopy and structural modeling to showcase instances where affinity-purification (AP) and cross-linking (XL) mass spectrometry (MS) has advanced our understanding of host–pathogen interactions. We highlight cases where XL-MS in combination with structural modeling has provided insight into the quaternary structure of interspecies protein complexes. We further exemplify how electron cryo-tomography has been used to visualize bacterial–human interactions during attachment and infection. Lastly, we discuss how AP-MS, XL-MS and electron cryo-microscopy and -tomography together with structural modeling approaches can be used in future studies to broaden our knowledge regarding the function, dynamics and evolution of such interactions. This knowledge will be of relevance for future drug and vaccine development programs."
1244,The role of vacuum-assisted closure (VAC) therapy in the management of FOURNIER’S gangrene: a retrospective multi-institutional cohort study,"PURPOSE: To explore the role of vacuum assisted closure (VAC) therapy versus conventional dressings in the Fournier’s gangrene wound therapy. PATIENTS AND METHODS: This is a retrospective multi-institutional cohort study. Data of 92 patients from nine centers between 2007 and 2018 were retrospectively analyzed. After surgery, patient having a local or a disseminated FG were managed with VAC therapy or with conventional dressings. The 10-weeks wound closure cumulative rate and OS were analyzed. RESULTS: Of the 92 patients, 62 (67.4%) showed local and 30 (32.6%) a disseminated FG. After surgery, 19 patients (20.7%) with local and 14 (15.2%) with disseminated FG underwent to VAC therapy; 43 (46.7%) with local and 16 (17.4%) with disseminated FG were treated using conventional dressings. The multivariable logistic regression analysis demonstrated that the VAC in patients with disseminated FG led to a higher cumulative rate of wound closure than patients treated with no-VAC (OR = 6.5; 95% CI 1.1–37.4, p = 0.036). The Kaplan–Meier survival curves for the OS showed a significant difference between no-VAC patients with local and disseminated FG (OS rate at 90 days 0.90, 95% CI 0.71–0.97 vs 0.55, 95% CI 0.24–0.78, respectively; p = 0.039). Cox regression confirmed that no-VAC patients with disseminated FG showed the lowest OS (hazard ratio adjusted for sex and age HR = 3.4, 95% CI 1.1–10.4; p = 0.033). CONCLUSIONS: In this large cohort study, VAC therapy in patients with disseminated FG may offer an advantage in terms of 10-weeks wound closure cumulative rate and OS at 90 days after initial surgery."
1245,Authors’ Response to Drs. Ece Salihoglu and Ziya Salihoglu’s Letter to the Editor,
1246,"Evidence supporting recommendations from international guidelines on treatment, diagnosis, and prevention of HAP and VAP in adults","Clinical practice guidelines (CPGs) are intended to support clinical decisions and should be based on high-quality evidence. The objective of the study was to evaluate the quality of evidence supporting the recommendations issued in CPGs for therapy, diagnosis, and prevention of hospital-acquired and ventilator-associated pneumonia (HAP/VAP). CPGs released by international scientific societies after year 2000, using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, were analyzed. Number and strength of recommendations and quality of evidence (high, moderate, low, and very low) were extracted and indexed in the aforementioned sections. High-quality evidence was based on randomized control trials (RCT) without important limitations and exceptionally on rigorous observational studies. Eighty recommendations were assessed, with 7 (8.7%), 24 (30.0%), 29 (36.3%), and 20 (25.0%) being supported by high, moderate, low, and very low-quality evidence, respectively. Highest evidence degree was reported for 26 prevention recommendations, with 7 (26.9%) supported by high-quality evidence and no recommendation based on very low-quality evidence. In contrast, among 9 recommendations for diagnosis and 45 for therapy, none was supported by high-quality evidence, in spite of being recommended as strong in 33.3% and 46.7%, respectively. Among HAP/VAP diagnosis recommendations, the majority of evidence was rated as low or very low-quality (55.6% and 22.2%, respectively) whereas among HAP/VAP therapy recommendations, 4/5 were rated as low and very low-quality (40% each). In conclusion, among HAP/VAP international guidelines, most recommendations, particularly in therapy, remain supported by observational studies, case reports, and expert opinion. Well-designed RCTs are urgently needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-019-03748-z) contains supplementary material, which is available to authorized users."
1247,Influence of different PEEP levels on electrical impedance tomography findings in patients under general anesthesia ventilated in the lateral decubitus position,"To determine the effect of various PEEP levels on electrical impedance tomography (EIT) measured differences in regional ventilation, hemodynamics, lung mechanics and parameters of alveolar gas exchange. Thirty three patients scheduled for elective urologic surgery in general anesthesia in lateral decubitus position were randomized into three groups—PEEP 0, 5 and 10 mbar. EIT recording, arterial blood gas analysis and hemodynamic parameters were captured at three timepoints—before induction (T0), 5 min after lateral positioning (T1) and 90 min after positioning (T2). Dynamic compliance (Cdyn) was measured at T1 and T2. Offline EIT data analysis was performed to calculate EIT derived parameters of ventilation distribution. Patients ventilated with PEEP of 10 mbar had a significantly lower A-a (alveolo arterial) gradient over measurements and symmetrical distribution of ventilation measured by EIT. There was no significant difference in Cdyn, center of ventilation indices and inhomogeneity index between groups. There was no difference of mean arterial pressure, cardiac index and heart rate between groups. Patients with 5 mbar of PEEP had higher stroke volume index compared to 0 and 10 mbar at baseline and over measurements. Nondependent/dependent TV ratio as well as global inhomogeneity index were correlated with A-a gradient. Dynamic compliance showed no correlation to A-a gradient. In our study, a PEEP level of 10 mbar improved alveolar gas exchange without compromising hemodynamic stability in patients mechanically ventilated in the lateral decubitus position. EIT measured parameters may be used to determine optimal ventilation parameters in these patients with inhomogeneous lung mechanics. Further studies are needed in patients with various lung pathologies."
1248,Oropharyngeal colostrum therapy reduces the incidence of ventilator-associated pneumonia in very low birth weight infants: a systematic review and meta-analysis,"BACKGROUND: Oropharyngeal colostrum (OC) is a novel feeding strategy to prevent complications of prematurity. A meta-analysis was conducted to investigate whether very low birth weight infants (VLBWs) can benefit from OC. METHODS: Randomized controlled trials (RCTs) were searched from Embase, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials from the date of inception until May 2019. RCTs were eligible if they used OC therapy on VLBW infants. The primary outcomes included ventilator-associated pneumonia (VAP), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), late-onset sepsis, and death. The secondary outcomes included the time of full enteral feeding and the length of stay. RESULTS: Eight RCTs involving 682 patients (OC group: 332; non-OC group: 350) were included in the meta-analysis. The results suggested that OC was associated with a significantly reduced incidence of VAP [odds ratio (OR) = 0.39, 95% confidence interval (CI): 0.17–0.88, P = 0.02] and full enteral feeding days (mean difference = −2.66, 95% CI: −4.51 to −0.80, P = 0.005), a potential significance of NEC (OR = 0.51, 95% CI: 0.26–0.99, P = 0.05), a trend toward downregulating mortality (OR = 0.60, 95% CI: 0.34–1.08, P = 0.09) and proven sepsis (OR = 0.64, 95% CI: 0.40–1.01, P = 0.06). CONCLUSIONS: OC could significantly reduce the occurrence of VAP, and consequently, its routine use should be considered for VLBWs to prevent infectious diseases. IMPACT: OC significantly reduces the occurrence of VAP and NEC in VLBW infants. OC may reduce the incidence of VAP and NEC by increasing IgA levels. Early OC therapy for mechanical ventilation of low-weight infants may prevent the occurrence of VAP."
1249,Dynamic data in the ED predict requirement for ICU transfer following acute care admission,"Misidentification of illness severity may lead to patients being admitted to a ward bed then unexpectedly transferring to an ICU as their condition deteriorates. Our objective was to develop a predictive analytic tool to identify emergency department (ED) patients that required upgrade to an intensive or intermediate care unit (ICU or IMU) within 24 h after being admitted to an acute care floor. We conducted a single-center retrospective cohort study to identify ED patients that were admitted to an acute care unit and identified cases where the patient was upgraded to ICU or IMU within 24 h. We used data available at the time of admission to build a logistic regression model that predicts early ICU transfer. We found 42,332 patients admitted between January 2012 and December 2016. There were 496 cases (1.2%) of early ICU transfer. Case patients had 18.0-fold higher mortality (11.1% vs. 0.6%, p < 0.001) and 3.4 days longer hospital stays (5.9 vs. 2.5, p < 0.001) than those without an early transfer. Our predictive analytic model had a cross-validated area under the receiver operating characteristic of 0.70 (95% CI 0.67–0.72) and identified 10% of early ICU transfers with an alert rate of 1.6 per week (162.2 acute care admits per week, 1.9 early ICU transfers). Predictive analytic monitoring based on data available in the emergency department can identify patients that will require upgrade to ICU or IMU if admitted to acute care. Incorporating this tool into ED practice may draw attention to high-risk patients before acute care admit and allow early intervention."
1250,Melanocortin 4 receptor (MC4R) gene variants in children and adolescents having familial early-onset obesity: genetic and clinical characteristics,"Melanocortin 4 receptor gene plays an important role in food intake, energy balance, and weight control. The autosomal dominantly inherited MC4R variants cause obesity by causing hyperphagia and decreased sense of satiety. Homozygous variants are rarely reported, and they cause earlier/severe obesity. Our objective is to determine the MC4R gene variant frequency in children and adolescents with familial early-onset obesity. One hundred thirty-nine children and adolescents (57 girls/82 boys) whose weight increase started before the age of 5 years and who had early-onset obesity in at least one of their first-degree relatives were included in the study. Obesity is defined as body mass index (BMI) of ≥ 95th percentile, and as extreme obesity is defined if the BMI ≥ 120% of the 95th percentile or ≥ 35 kg/m(2). Children having genetic syndromes associated with obesity and mental retardation or taking drugs that promote changes in eating behavior or weight were excluded from the study. Coding region of the MC4R gene was sequenced by using the Illumina MiSeq Next Generation Sequencing System. The mean age of the patients was 7.3 ± 3.7 years, and the mean BMI SDS was 3.7 ± 0.7. While 118 patients (85%) were prepubertal, 21 patients (15%) were pubertal. Seven different variants were identified in 12 patients by giving a variant detection rate of 8.6%, of these five were previously identified missense variants p.N274S, p.S136F, p.V166I, p.R165W, and p.I291SfsX10. One homozygous variant p.I291SfsX10 (c.870delG) was detected in a severely obese 2-year-old boy, and other variants were heterozygous. Two novel variants were found: p.M200del and p.S188L. By using the in silico analysis software, these novel variants were predicted to be disease causing. Conclusion: MC4R gene variants are quite common in childhood obesity in Turkish population. Screening the variants in MC4R gene is necessary in patients with severe childhood-onset obesity. In such patients, comorbidities of obesity can be seen from early years."
1251,Correct Antemortem Diagnosis of Pneumonia in Children With Fatal Illnesses,"This retrospective study analyzed the level of concordance between clinical and autopsy diagnosis of pneumonia over a 3-year period. Utilizing the Goldman classification, the concordance rate was found to be 37.5%. Major discrepancies (Class I and II) were found in 25% cases, and minor discrepancies (Class III and IV) in 37.5% cases."
1252,Refeeding Syndrome with Hypoglycemia in a Severely Malnourished Infant,"A 5-mo-old severely malnourished 3.5 kg boy was brought to the emergency department with hypoglycemia, bradycardia, bradypnea, and hypothermia. His findings were likely due to severe malnutrition secondary to parental neglect. Resuscitation with dextrose containing intravenous fluids was promptly started. On day 2 of admission, refeeding was initiated. From that time, he had multiple hypoglycemic episodes along with hypophosphatemia, hypomagnesemia, and hypokalemia. Hypoglycemia was associated with the initiation of enteral feeding and an increase in calories and amounts of enteral feeding. Hypoglycemia associated with refeeding syndrome in infant has not been previously reported."
1253,Review of Cystic Echinococcosis in Nigeria: A Story of Neglect,"PURPOSE: Cystic echinococcosis (CE) caused by Echinococcus granulosus sensu lato is a widespread zoonotic disease of global concern. In Nigeria, the exact picture/status of CE is unclear, as most of the states are largely uninvestigated. Yet, as with every parasitic zoonosis, the first step towards planning a comprehensive management and control programme involves assessment of available national/regional prevalence data, host range, and risk factors at play in the transmission dynamics. METHODS: Published articles on echinococcosis were searched on PubMed and Africa Journal Online (AJOL) databases. Inclusion criteria were based on studies reporting prevalence of echinococcosis in animals and humans (including case reports) from 1970 to 2018. RESULTS: In this study, we evaluated and summarized cystic echinococcosis reports in Nigeria and found that post 1970–80s, studies on cystic echinococcosis have remained sparse regardless of the high prevalence recorded in the early years of CE investigation. In addition, information on the genetic population structure and the role of wildlife in CE transmission is still lacking. CONCLUSIONS: This study appraises the prevalence and distribution of CE in Nigeria and identified areas where surveillance and control efforts should be focused and intensified."
1254,Non-Amyloid Approaches to Disease Modification for Alzheimer’s Disease: An EU/US CTAD Task Force Report,"While amyloid-targeting therapies continue to predominate in the Alzheimer’s disease (AD) drug development pipeline, there is increasing recognition that to effectively treat the disease it may be necessary to target other mechanisms and pathways as well. In December 2019, The EU/US CTAD Task Force discussed these alternative approaches to disease modification in AD, focusing on tau-targeting therapies, neurotrophin receptor modulation, anti-microbial strategies, and the innate immune response; as well as vascular approaches, aging, and non-pharmacological approaches such as lifestyle intervention strategies, photobiomodulation and neurostimulation. The Task Force proposed a general strategy to accelerate the development of alternative treatment approaches, which would include increased partnerships and collaborations, improved trial designs, and further exploration of combination therapy strategies."
1255,The global preclinical antibacterial pipeline,"Antibacterial resistance is a great concern and requires global action. A critical question is whether enough new antibacterial drugs are being discovered and developed. A review of the clinical antibacterial drug pipeline was recently published, but comprehensive information about the global preclinical pipeline is unavailable. This Review focuses on discovery and preclinical development projects and has found, as of 1 May 2019, 407 antibacterial projects from 314 institutions. The focus is on Gram-negative pathogens, particularly bacteria on the WHO priority bacteria list. The preclinical pipeline is characterized by high levels of diversity and interesting scientific concepts, with 135 projects on direct-acting small molecules that represent new classes, new targets or new mechanisms of action. There is also a strong trend towards non-traditional approaches, including diverse antivirulence approaches, microbiome-modifying strategies, and engineered phages and probiotics. The high number of pathogen-specific and adjunctive approaches is unprecedented in antibiotic history. Translational hurdles are not adequately addressed yet, especially development pathways to show clinical impact of non-traditional approaches. The innovative potential of the preclinical pipeline compared with the clinical pipeline is encouraging but fragile. Much more work, focus and funding are needed for the novel approaches to result in effective antibacterial therapies to sustainably combat antibacterial resistance."
1256,How I Manage Natural Killer Cell Deficiency,"Natural killer (NK) cell deficiency (NKD) is a subset of primary immunodeficiency disorders (PID) in which an abnormality of NK cells represents a major immunological defect resulting in the patient’s clinical immunodeficiency. This is distinct from a much larger group of PIDs that include an NK cell abnormality as a minor component of the immunodeficiency. Patients with NKD most frequently have atypical consequences of herpesviral infections. There are now 6 genes that have been ascribed to causing NKD, some exclusively and others that also cause other known immunodeficiencies. This list has grown in recent years and as such the mechanistic and molecular clarity around what defines an NKD is an emerging and important field of research. Continued increased clarity will allow for more rational approaches to the patients themselves from a therapeutic standpoint. Having evaluated numerous individuals for NKD, I share my perspective on approaching the diagnosis and managing these patients."
1257,"Prostaglandin E(2) in a TLR3- and 7/8-agonist-based DC maturation cocktail generates mature, cytokine-producing, migratory DCs but impairs antigen cross-presentation to CD8(+) T cells","Mature dendritic cells (DCs) represent cellular adjuvants for optimal antigen presentation in cancer vaccines. Recently, a combination of prostaglandin E(2) (PGE(2)) with Toll-like receptor agonists (TLR-P) was proposed as a new standard to generate superior cytokine-producing DCs with high migratory capacity. Here, we compare TLR-P DCs with conventional DCs matured only with the proinflammatory cytokines TNFα and IL-1ß (CDCs), focussing on the interaction of resulting DCs with CD8(+) T-cells. TLR-P matured DCs showed elevated expression of activation markers such as CD80 and CD83 compared to CDCs, together with a significantly higher migration capacity. Secretion of IL-6, IL-8, IL-10, and IL-12 was highest after 16 h in TLR-P DCs, and only TLR-P DCs secreted active IL-12p70. TLR-P DCs as well as CDCs successfully primed multifunctional CD8(+) T-cells from naïve precursors specific for the peptide antigens Melan-A, NLGN4X, and PTP with comparable priming efficacy and T-cell receptor avidity. CD8(+) T-cells primed by TLR-P DCs showed significantly elevated expression of the integrin VLA-4 and a trend for higher T-cell numbers after expansion. In contrast, TLR-P DCs displayed a substantially reduced capability to cross-present CMVpp65 protein antigen to pp65-specific T cells, an effect that was dose-dependent on PGE(2) during DC maturation and reproducible with several responder T-cell lines. In conclusion, TLR-P matured DCs might be optimal presenters of antigens not requiring processing such as short peptides. However, PGE(2) seems less favorable for maturation of DCs intended to process and cross-present more complex vaccine antigens such as lysates, proteins or long peptides. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00262-019-02470-1) contains supplementary material, which is available to authorized users."
1258,Respiratory Virus Co-infection in Acute Respiratory Infections in Children,"PURPOSE OF REVIEW: This investigation aims to understand the role and burden of viral co-infections for acute respiratory illnesses in children. Co-infection can be either viral-viral or viral-bacterial and with new technology there is more information on the role they play on the health of children. RECENT FINDINGS: With the proliferation of multiplex PCR for rapid diagnosis of multiple viruses as well as innovations on identification of bacterial infections, research has been attempting to discover how these co-infections affect each other and the host. Studies are aiming to discern if the epidemiology of viruses seen at a population level is related to the interaction between different viruses on a host level. Studies are also attempting to discover the burden of morbidity and mortality of these viral-viral co-infections on the pediatric population. It is also becoming important to understand the interplay of certain viruses with specific bacteria and understanding the impact of viral-bacterial co-infections. SUMMARY: RSV continues to contribute to a large burden of disease for pediatric patients with acute respiratory illnesses. However, recent literature suggests that viral-viral co-infections do not add to this burden and might, in some cases, be protective of severe disease. Viral-bacterial co-infections, on the other hand, are most likely adding to the burden of morbidity in pediatric patients because of the synergistic way they can infect the nasopharyngeal space. Future research needs to focus on confirming these conclusions as it could affect hospital cohorting, role of molecular testing, and therapeutic interventions."
1259,Antibody-based therapeutic interventions: possible strategy to counter chikungunya viral infection,"Chikungunya virus (CHIKV), a mosquito-transmitted disease that belongs to the genus Alphaviruses, has been emerged as an epidemic threat over the last two decades, and the recent co-emergence of this virus along with other circulating arboviruses and comorbidities has influenced atypical mortality rate up to 10%. Genetic variation in the virus has resulted in its adaptability towards the new vector Aedes albopictus other than Aedes aegypti, which has widen the horizon of distribution towards non-tropical and non-endemic areas. As of now, no licensed vaccines or therapies are available against CHIKV; the treatment regimens for CHIKV are mostly symptomatic, based on the clinical manifestations. Development of small molecule drugs and neutralizing antibodies are potential alternatives of worth investigating until an efficient or safe vaccine is approved. Neutralizing antibodies play an important role in antiviral immunity, and their presence is a hallmark of viral infection. In this review, we describe prospects for effective vaccines and highlight importance of neutralizing antibody-based therapeutic and prophylactic applications to combat CHIKV infections. We further discuss about the progress made towards CHIKV therapeutic interventions as well as challenges and limitation associated with the vaccine development. Furthermore this review describes the lesson learned from chikungunya natural infection, which could help in better understanding for future development of antibody-based therapeutic measures."
1260,Positive end-expiratory pressure titration via esophageal balloon monitoring in a morbidly obese patient undergoing laparoscopic nephrectomy,
1261,"Closer and closer? Maternal immunization: current promise, future horizons","This state-of-the art manuscript highlights our current understanding of maternal immunization—the practice of vaccinating pregnant women to confer protection on them as well as on their young infants, and thereby reduce vaccine-preventable morbidity and mortality. Advances in our understanding of the immunologic processes that undergird a normal pregnancy, studies from vaccines currently available and recommended for pregnant women, and vaccines for administration in special situations are beginning to build the case for safe scale-up of maternal immunization. In addition to well-known diseases, new diseases are emerging which pose threats. Several new vaccines are currently under development and increasingly include pregnant women. In this manuscript, targeted at clinicians, vaccinologists, scientists, public health practitioners, and policymakers, we also outline key considerations around maternal immunization introduction and delivery, discuss noninfectious horizons for maternal immunization, and provide a framework for the clinician faced with immunizing a pregnant woman."
1262,Naloxone as an antidote for angiotensin converting enzyme inhibitor poisoning: a case report,
1263,Patterns of Inpatient Antibiotic Use Among Public Hospitals in Hong Kong from 2000 to 2015,"BACKGROUND: Studies have demonstrated that higher rates of antibiotic resistance are found in countries with higher antibiotic consumption. The global increase in antibiotic consumption is a major public health concern. OBJECTIVES: The objective of this study was to describe the antibiotic dispensing patterns in public hospitals in Hong Kong from 2000 to 2015. METHODS: We acquired data on all hospital admissions with any antibiotics dispensed from 2000 to 2015 from the Hong Kong public hospitals. The annual proportion of hospital admissions with antibiotics dispensed was estimated and stratified by age group. An interrupted time series analysis was conducted to examine any potential change in tetracycline dispensing after the release of the new clinical practice guideline. RESULTS: A total of 35,535,506 antibiotic prescriptions were dispensed among 2,161,360 unique hospitalized patients from 2000 to 2015. Antibiotics were dispensed in 29.2% of all hospital admissions in the public hospitals, the annual proportions of hospital admissions with antibiotics dispensed increased over the study period from 27.87% in 2000 to 31.39% in 2015, ranging from 27.17 to 31.39%. However, a significant increase was only observed in age groups of 5–19, 20–44, and 85 years or above when stratifying by age. In the interrupted time series analysis, a change in trend was detected for tetracycline dispensing that coincided with the time of publication of the new clinical practice guideline. CONCLUSIONS: We found that the overall volume of antibiotic use increased between 2000 and 2015. The rise in the dispensing of carbapenems in our study is concerning. The significant change in tetracycline use after being recommended as one of the preferred regimens demonstrated that the change in the clinical practice guideline had an immediate effect on the antibiotic prescribing practice in Hong Kong public hospitals."
1264,Breaking Down Myasthenic Crisis,
1265,Translation of the Frailty Paradigm from Older Adults to Children with Cardiac Disease,"Children and adolescents with cardiac disease (CCD) have significant morbidity and lower quality of life. However, there are no broadly applicable tools similar to the frailty score as described in the elderly, to define functional phenotype in terms of physical capability and psychosocial wellbeing in CCD. The purpose of this study is to investigate the domains of the frailty in CCD. We prospectively recruited CCD (8–17.5 years old, 70% single ventricle, 27% heart failure, 12% pulmonary hypertension; NYHA classes I, II and III) and age and gender matched healthy controls (total n = 56; CCD n = 34, controls n = 22; age 12.6 ± 2.6 years; 39.3% female). We measured the five domains of frailty: slowness, weakness, exhaustion, body composition and physical activity using developmentally appropriate methods. Age and gender-based population norms were used to obtain Z scores and percentiles for each measurement. Two-tailed t-tests were used to compare the two groups. The CCD group performed significantly worse in all five domains of frailty compared to healthy controls. Slowness: 6-min walk test with Z score −3.9 ± 1.3 vs −1.4 ± 1.3, p < 0.001; weakness: handgrip strength percentile 18.9 ± 20.9 vs 57.9 ± 26.0, p < 0.001; exhaustion: multidimensional fatigue scale percentile 63.7 ± 13.5 vs 83.3 ± 14.4, p < 0.001; body composition: height percentile 43.4 ± 29.5 vs 71.4 ± 25.2, p < 0.001, weight percentile 46.0 ± 36.0 vs 70.9 ± 24.3, p = 0.006, BMI percentile 48.4 ± 35.5 vs 66.9 ± 24.2, p = 0.04, triceps skinfold thickness 41.0 ± 24.0 vs 54.4 ± 22.1, p = 0.04; physical activity: pediatric activity questionnaire score 2 ± 0.6 vs 2.7 ± 0.6, p < 0.001. The domains of frailty can be quantified in children using developmentally appropriate methods. CCD differ significantly from controls in all five domains, supporting the concept of quantifying the domains of frailty. Larger longitudinal studies are needed to study frailty in CCD and examine if it predicts adverse health outcomes. Clinical Trial Registration: The ClinicalTrials.gov identification number is NCT02999438. https://clinicaltrials.gov/ct2/show/NCT02999438."
1266,Factors Predictive of Ventilator-associated Pneumonia in Critically Ill Trauma Patients,"BACKGROUND: Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation. We sought to investigate factors associated with the development of VAP in critically ill trauma patients. METHODS: We conducted a retrospective review of trauma patients admitted to our trauma intensive care unit between 2016 and 2018. Patients with ventilator-associated pneumonia were identified from the trauma database. Data collected from the trauma database included demographics (age, gender and race), mechanism of injury (blunt, penetrating), injury severity (injury severity score “ISS”), the presence of VAP, transfused blood products and presenting vital signs. RESULTS: A total of 1403 patients were admitted to the trauma intensive care unit (TICU) during the study period; of these, 45 had ventilator-associated pneumonia. Patients with VAP were older (p = 0.030), and they had a higher incidence of massive transfusion (p = 0.015) and received more packed cells in the first 24 h of admission (p = 0.028). They had a higher incidence of face injury (p = 0.001), injury to sternum (p = 0.011) and injury to spine (p = 0.024). Patients with VAP also had a higher incidence of acute kidney injury (AKI) (p < 0.001) and had a longer ICU (p < 0.001) and hospital length of stay (p < 0.001). Multiple logistic regression models controlling for age and injury severity (ISS) showed massive transfusion (p = 0.017), AKI (p < 0.001), injury to face (p < 0.001), injury to sternum (p = 0.007), injury to spine (p = 0.047) and ICU length of stay (p < 0.001) to be independent predictors of VAP. CONCLUSIONS: Among critically ill trauma patients, acute kidney injury, injury to the spine, face or sternum, massive transfusion and intensive care unit length of stay were associated with VAP."
1267,Andronov–Hopf and Neimark–Sacker bifurcations in time-delay differential equations and difference equations with applications to models for diseases and animal populations,"In many areas, researchers might think that a differential equation model is required, but one might be forced to use an approximate difference equation model if data is only available at discrete points in time. In this paper, a detailed comparison is given of the behavior of continuous and discrete models for two representative time-delay models, namely a model for HIV and an extended logistic growth model. For each model, there are seven different time-delay versions because there are seven different positions to include time delays. For the seven different time-delay versions of each model, proofs are given of necessary and sufficient conditions for the existence and stability of equilibrium points and for the existence of Andronov–Hopf bifurcations in the differential equations and Neimark–Sacker bifurcations in the difference equations. We show that only five of the seven time-delay versions have bifurcations and that all bifurcation versions have supercritical limit cycles with one having a repelling cycle and four having attracting cycles. Numerical simulations are used to illustrate the analytical results and to show that critical times for Neimark–Sacker bifurcations are less than critical times for Andronov–Hopf bifurcations but converge to them as the time step of the discretization tends to zero."
1268,"Full-genome sequences of GII.13[P21] recombinant norovirus strains from an outbreak in Changsha, China","On 31 March 2019, 68 school students suffered from vomiting, diarrhea, and abdominal pain after participating in a group activity at a commercial park. In this outbreak, multiple norovirus genotypes were observed, including GII.2[P16], GII.17[P17], and GII.13[P21]. Further, we determined the full-genome sequences of two strains of GII.13[P21] recombinant noroviruses, which were 7434 nt long. Phylogenetic analysis based on open reading frames (ORFs) 1 and 2 revealed that these recombinants were related to stains of different genotypes from different countries. The full genome nucleotide sequences of the two isolates were 97.0% and 98.0% identical to those of strains from London and Thailand, respectively. Simplot analysis revealed the presence of a break point at nt 5059 in the ORF1 region. The histo-blood group antigen binding sites were conserved in both recombinant viruses. Our findings not only provide valuable genetic information about a recombinant norovirus but also contribute to our general understanding of the evolution, genetic diversity, and distribution of noroviruses."
1269,Antiviral Activities of Hibiscus sabdariffa L. Tea Extract Against Human Influenza A Virus Rely Largely on Acidic pH but Partially on a Low-pH-Independent Mechanism,"Influenza A virus (IAV) infection is perennially one of the leading causes of death worldwide. Effective therapy and vaccination are needed to control viral expansion. However, current anti-IAV drugs risk inducing drug-resistant virus emergence. Although intranasal administration of whole inactivated virus vaccine can induce efficient protective immunity, formalin and β-propiolactone are the currently used and harmful inactivating agents. Here, we analyzed the antiviral activity of hibiscus (Hibiscus sabdariffa L.) tea extract against human IAV and evaluated its potential as a novel anti-IAV drug and a safe inactivating agent for whole inactivated vaccine. The in vitro study revealed that the pH of hibiscus tea extract is acidic, and its rapid and potent antiviral activity relied largely on the acidic pH. Furthermore, the mouse study showed that the acidic extract was not effective for either therapeutic or vaccination purposes. However, hibiscus tea extract and protocatechuic acid, one of the major components of the extract, showed not only potent acid-dependent antiviral activity but also weak low-pH-independent activity. The low-pH-independent activity did not affect the conformation of immunodominant hemagglutinin protein. Although this low-pH-independent activity is very limited, it may be suitable for the application to medication and vaccination because this activity is not affected by the neutral blood environment and does not lose antigenicity of hemagglutinin. Further study of the low-pH-independent antiviral mechanism and attempts to enhance the antiviral activity may establish a novel anti-IAV therapy and vaccination strategy."
1270,Uniportal Thoracoscopic McKeown Esophagectomy,We performed the technique of uniportal thoracoscopic McKeown esophagectomy. The incision was located in the fourth intercostal space on the right axillary midline. The right recurrent laryngeal nerve lymph nodes were dissected. Four hemlocks were applied to clamp the proximal and distal ends of the aortic arch. The esophagus was suspended with purse-string at the level of the azygos vein arch to assist the dissection of the left recurrent laryngeal nerve lymph nodes. A silk thread was drawn out from the incision in order to remove the subcarinal lymph nodes. A thoracic drainage tube was placed at the back of the incision at the end.
1271,Carbapenem-Resistant Enterobacterales: Considerations for Treatment in the Era of New Antimicrobials and Evolving Enzymology,"PURPOSE OF REVIEW: Gram-negative resistance is a growing concern globally. Enterobacterales, formerly Enterobacteriaceae, have developed resistance mechanisms to carbapenems that leave very few antimicrobial options in the clinician’s armamentarium. RECENT FINDINGS: New antimicrobials like ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and plazomicin have the potential to overcome resistance mechanisms in Enterobacterales including different classes of carbapenemases. SUMMARY: Novel β-lactam/β-lactamase inhibitors, plazomicin, and cefiderocol give the clinician options that were once not available. Utilizing these options is of the utmost importance when treating carbapenem-resistant Enterobacterales."
1272,Hypocapnia after traumatic brain injury: how does it affect the time constant of the cerebral circulation?,"The time constant of the cerebral arterial bed (“tau”) estimates how fast the blood entering the brain fills the arterial vascular sector. Analogous to an electrical resistor–capacitor circuit, it is expressed as the product of arterial compliance (Ca) and cerebrovascular resistance (CVR). Hypocapnia increases the time constant in healthy volunteers and decreases arterial compliance in head trauma. How the combination of hyocapnia and trauma affects this parameter has yet to be studied. We hypothesized that in TBI patients the intense vasoconstrictive action of hypocapnia would dominate over the decrease in compliance seen after hyperventilation. The predominant vasoconstrictive response would maintain an incoming blood volume in the arterial circulation, thereby lengthening tau. We retrospectively analyzed recordings of intracranial pressure (ICP), arterial blood pressure (ABP), and blood flow velocity (FV) obtained from a cohort of 27 severe TBI patients [(39/30 years (median/IQR), 5 women; admission GCS 6/5 (median/IQR)] studied during a standard clinical CO(2) reactivity test. The reactivity test was performed by means of a 50-min increase in ventilation (20% increase in respiratory minute volume). CVR and Ca were estimated from these recordings, and their product calculated to find the time constant. CVR significantly increased [median CVR pre-hypocapnia/during hypocapnia: 1.05/1.35 mmHg/(cm(3)/s)]. Ca decreased (median Ca pre-hypocapnia/during hypocapnia: 0.130/0.124 arbitrary units) to statistical significance (p = 0.005). The product of these two parameters resulted in a significant prolongation of the time constant (median tau pre-hypocapnia/during hypocapnia: 0.136 s/0.152 s, p ˂ .001). Overall, the increase in CVR dominated over the decrease in compliance, hence tau was longer. We demonstrate a significant increase in the time constant of the cerebral circulation during hypocapnia after severe TBI, and attribute this to an increase in cerebrovascular resistance which outweighs the decrease in cerebral arterial bed compliance."
1273,Poly-phosphate increases SMC differentiation of mesenchymal stem cells on PLGA–polyurethane nanofibrous scaffold,"The use of bioactive scaffolds in tissue engineering has a significant effect on the damaged tissue healing by an increase in speed and quality of the process. Herein, electrospinning was applied to fabricate composite nanofibrous scaffolds by Poly lactic-co-glycolic acid (PLGA) and Polyurethane (PU) with and without poly-phosphate (poly-P). Scaffolds were characterized morphologically by scanning electron microscope (SEM), and their biocompatibility was also investigated by SEM, protein adsorption, cell attachment and survival assays. The applicability of the scaffolds for bladder tissue engineering was also evaluated by culturing mesenchymal stem cells (MSCs) on the scaffolds and their differentiation into smooth muscle cell (SMC) was studied at the gene and protein levels. The results demonstrated that scaffold biocompatibility was increased significantly by loading poly-P. SMC related gene and protein expression level in MSCs cultured on poly-P-loaded scaffold was also increased significantly compared to those cells cultured on empty scaffold. It can be concluded that poly-P hasn’t also increased scaffold biocompatibility, but also SMC differentiation potential of MSCs was also increased while cultured on the poly-P containing scaffold compared to the empty scaffold. Taken together, our study showed that PLGA–PU–poly-P alone and in combination with MSCs has a promising potential for support urinary bladder smooth muscle tissue engineering."
1274,Evaluation of specific quality metrics to assess the performance of a specialised newborn transport programme,"There is a lack of consensus on quality indicators suitable for neonatal transport. The aim of this study is to make a proposal for specific quality indicators for newborn transport. A retrospective descriptive study was performed (2009 to 2015) where twenty-four indicators were selected, evaluated and classified according to the 6 dimensions of quality of the Institute of Medicine. Among the 24 evaluated quality metrics, there were 3 of them which needed a correction when evaluating neonatal transport performance, because they were significantly correlated with gestational age. They were (a) stabilisation time, (b) prevalence of newborn arterial hypotension (defined by gestational age) and (c) unnoticed hypothermia at referral hospital. Conclusion: Quality evaluation through the definition of specific metrics in newborn transport is feasible. These indicators should be defined or adjusted for newborn population to measure the actual performance of the transport service."
1275,Antioxidant molecular mechanism of adenosyl homocysteinase from cyanobacteria and its wound healing process in fibroblast cells,"An antioxidant molecule namely, adenosyl homocysteinase (AHc) was identified from the earlier constructed transcriptome database of Spirulina, where it was cultured in a sulphur deprived condition. From the AHc protein, a small peptide NL13 was identified using bioinformatics tools and was predicted to have antioxidant property. Further, the peptide was synthesised and its antioxidant mechanism was addressed at molecular level. NL13 was subjected to various antioxidant assays including DPPH assay, HARS assay, SARS Assay, NO assay and ABTS assay, where NL13 exhibited significant (P < 0.05) potential antioxidant activity compared to its antioxidant control, Trolox. Cytotoxicity was performed on Human whole blood and the cell viability was performed on VERO fibroblast cells. In both assays, it was found that NL13 did not exhibit any cytotoxic effect towards the cells. Further, the intracellular ROS was performed on Multimode reader followed by imaging on fluorescence microscope which showed scavenging activity even at lower concentration of NL13 (31.2 µM). An effective wound healing property of NL13 on VERO cells was confirmed by analysing the cell migration rate at two different time intervals (24 and 48 h). Overall, the study shows that NL13 peptide scavenges the intracellular oxidative stress. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11033-020-05276-y) contains supplementary material, which is available to authorized users."
1276,A seven-gene-deleted African swine fever virus is safe and effective as a live attenuated vaccine in pigs,"African swine fever (ASF) is a devastating infectious disease in swine that is severely threatening the global pig industry. An efficacious vaccine is urgently required. Here, we used the Chinese ASFV HLJ/18 as a backbone and generated a series of gene-deleted viruses. The virulence, immunogenicity, safety, and protective efficacy evaluation in specific-pathogen-free pigs, commercial pigs, and pregnant sows indicated that one virus, namely HLJ/18-7GD, which has seven genes deleted, is fully attenuated in pigs, cannot convert to the virulent strain, and provides complete protection of pigs against lethal ASFV challenge. Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV, and as such is expected to play an important role in controlling the spread of ASFV. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1657-9 and is accessible for authorized users."
1277,A Component Analysis of the Mindfulness-Based Positive Behavior Support (MBPBS) Program for Mindful Parenting by Mothers of Children with Autism Spectrum Disorder,"OBJECTIVES: Mindfulness-Based Positive Behavior Support (MBPBS) has been shown to be effective in reducing stress and burnout in parents and professional caregivers of children and adolescents with intellectual and developmental disabilities (IDD) and autism spectrum disorder (ASD). The aim of this study was to assess the comparative effects of the mindfulness (MB) and positive behavior support (PBS) components against the MBPBS program for mindful parenting. METHODS: The study utilized a three-arm randomized controlled trial design, with a 10-week pre-treatment control condition, 30 weeks of intervention, and 3 years of post-intervention follow-up. Mothers of children with ASD were randomly assigned to the MB, PBS, and MBPBS conditions and provided 3 days of training specific to each condition. The effects of these programs were assessed on the mothers (i.e., training attendance, meditation time, perceived psychological stress) and spillover effects were assessed on their children with ASD (i.e., aggression, disruptive behavior, compliance with mothers’ requests). RESULTS: Mothers in the MBPBS condition reported greater reductions in perceived psychological stress, followed by those in the MB condition, and with no significant changes reported by those in the PBS condition. Reduction in the children’s aggression and disruptive behavior followed a similar pattern, with most to least significant reductions being in MBPBS, MB, and PBS condition, respectively. Significant increases in compliance (i.e., responsiveness to mothers’ requests) were largest in the MBPBS condition, followed by MB, and then PBS. Changes across all variables for both mothers and their children were maintained for 3 years post-intervention. After time and training type were controlled for, meditation time was a significant predictor in reducing aggressive and disruptive behaviors, and in enhancing compliance of the children with mothers’ requests. CONCLUSIONS: Positive outcomes for mothers and their children with ASD were significantly greater in the MBPBS condition, followed by the MB condition, and least in the PBS condition. MBPBS appears to be an effective mindful parenting program on the assessed variables."
1278,Sense of coherence and burnout among school psychologists: The moderating role of loneliness,"School psychologist have been considered at a high risk for developing work burnout due to their multiple responsibilities, overload and engagement in caring for children, families and professionals. In line with the salutogenic approach, the aim of the current research was to investigate protective and risk factors to burnout. Research has indicated that sense of coherence (SOC) may act as a protective factor. Studies reported that loneliness has been found a risk factor that may advance burnout. The current study hypothesized that loneliness may moderate the link between SOC and burnout. In a sample of 104 Israeli school psychologists, demographic aspects such as the gender, years of experience, or type of school in which they work did not predict the burnout, focusing on the importance of emotional aspects. The analysis demonstrated that the SOC was negatively associated with burnout among low or mean levels of loneliness, but not among psychologists with high levels of loneliness. The current study provides a new insight into the burnout risk, through the focus on personal resources and social perceptions. Implications for theoretical and practices are further discussed."
1279,Perioperative Outcomes of Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in Patients with Diabetes Mellitus: an Analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Database,"BACKGROUND: The safety and efficacy of laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) to treat obesity and associated comorbidities, including diabetes mellitus, is well established. As diabetes may add risk to the perioperative period, we sought to characterize perioperative outcomes of these surgical procedures in diabetic patients. METHODS: Using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database, we identified patients who underwent LSG and LRYGB between 2015 and 2017, grouping by non-diabetics (NDM), non-insulin-dependent diabetics (NIDDM), and insulin-dependent diabetics (IDDM). Primary outcomes included serious adverse events, 30-day readmission, 30-day reoperation, and 30-day mortality. Univariate and multivariable analyses were used to evaluate the outcome in each diabetic cohort. RESULTS: Multivariable analysis of patients who underwent LSG (with NDM patients as reference) showed higher 30-day mortality (NIDDM AOR = 1.52, p = 0.043; IDDM AOR = 1.91, p = 0.007) and risk of serious adverse events (NIDDM AOR = 1.15, p < 0.001; IDDM AOR = 1.58, p < 0.001) in the diabetic versus NDM groups. Multivariable analysis of patients who underwent LRYGB (with NDM patients as reference) showed higher risk of serious adverse events (NIDDM AOR = 1.09, p = 0.014; IDDM AOR = 1.43, p < 0.001) in the diabetic versus NDM groups. CONCLUSIONS: Diabetics who underwent LSG and LRYGB had higher rates of several perioperative complications compared with non-diabetics. IDDM had a stronger association with several perioperative complications compared with NIDDM. This increase in morbidity and mortality is modest and should be weighed against the real benefits of bariatric surgery in patient with obesity and diabetes mellitus."
1280,"Heart Retransplantation: Candidacy, Outcomes, and Management","PURPOSE OF REVIEW: To describe the incidence and epidemiology of heart retransplantation in adults and children and to review the risk factors associated with adverse outcome following retransplantation to help guide recipient selection. RECENT FINDINGS: Heart retransplantation is associated with inferior short-term and long-term survival when compared with primary heart transplantation and its use remains controversial although less so in the pediatric heart transplant population. SUMMARY: In the most recent era of heart transplantation, patients retransplanted for CAV, greater than 1 year from their primary transplant, and who are not in critical condition have improved survival compared with other retransplant recipients. Survival with retransplantation can approach that of primary transplantation when patients are appropriately selected. More research is needed regarding the optimal timing for retransplantation and the optimal management for patients after retransplantation."
1281,Nasal continuous positive airway pressure versus noninvasive NAVA in preterm neonates with apnea of prematurity: a pilot study with a novel approach,"BACKGROUND: Neonates with apnea of prematurity often fail CPAP because it does not provide adequate support during apnea. NAVA provides proportional ventilator support based on electrical activity of the diaphragm. When the NAVA level is 0 cmH(2)0/mcV, the patient receives minimal support above PEEP when breathing and backup ventilation when apneic. This study compares number of clinically significant events on CPAP versus noninvasive NAVA level 0. METHODS: Retrospective study of preterm neonates having apnea of prematurity on nasal CPAP. Patients were then placed on NAVA level 0. The number of events on each mode was collected. Statistics were paired t-test. RESULTS: Seventeen subjects with gestational age 26.1 ± 1.7 weeks, study age 19.5 ± 12.5 days. Events decreased from 17.9 ± 7.8 on CPAP to 10.2 ± 8.1 events on NAVA level 0 (p = 0.00047). CONCLUSIONS: NAVA level 0 reduced the number of clinically significant events compared with CPAP in premature neonates with apnea of prematurity."
1282,Spine neurosurgeons facing the judicialization of their profession: disenchantment and alteration of daily practice—a qualitative study,"BACKGROUND: The judicialization of medicine can lead to professional disenchantment and defensive attitudes among surgeons. Some quantitative studies have investigated this topic in spine surgery, but none has provided direct thematic feedback from physicians. This qualitative study aimed to identify the impact of this phenomenon in the practice of spine neurosurgeons. METHODS: We proposed a qualitative study using grounded theory approach. Twenty-three purposively selected private neurosurgeons participated. Inclusion took place until data saturation was reached. Data were collected through individual interviews and analyzed thematically and independently by three researchers (an anthropologist, a psychiatrist, and a neurosurgeon). RESULTS: Data analysis identified five superordinate themes that were based on items that recurred in interviews: (1) private practice of spinal surgery (high-risk surgery based on frequent functional symptoms, in an unfavorable medicolegal context); (2) societal transformation of the doctor-patient relationship (new societal demands, impact of the internet and social network); (3) judicialization of spine surgery (surgeons’ feelings about the frequency and motivation of the complaints they receive, and their own management of them); (4) coping strategies (identification and solutions for “at risk” situations and patients); and (5) professional disenchantment (impact of these events on surgeons’ daily practice and career planning). Selected quotes of interviews were reported to support these findings. CONCLUSIONS: Our study highlights several elements that can alter the quality of care in a context of societal change and the judicialization of medicine. The alteration of the doctor-patient relationship and the permanent pressure of a possible complaint encourage surgeons to adopt defensive attitudes in order to minimize the risks of litigation and increased insurance premiums. These phenomena can affect the quality of care and the privacy of physicians to the extent that they may consider changing or interrupting their careers earlier. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00701-020-04302-z) contains supplementary material, which is available to authorized users."
1283,"Severe fever with thrombocytopenia syndrome (SFTS) treated with a novel antiviral medication, favipiravir (T-705)","BACKGROUND: Severe fever and thrombocytopenia syndrome (SFTS) is an acute illness with a high mortality (16.2–29.1%). Unfortunately, there is no specific cure or vaccine for SFTS. METHODS: In this open-label study, two patients with SFTS were treated with favipiravir, a new antiviral drug. RESULTS: Patients had a sustainable virologic, immunologic and symptomatic recovery. CONCLUSIONS: Favipiravir may be a prosiming drug for the treatment of SFTS. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s15010-019-01364-9) contains supplementary material, which is available to authorized users."
1284,The Role of Healthcare Robotics in Providing Support to Older Adults: a Socio-ecological Perspective,"PURPOSE OF REVIEW: In this review, we provide an overview of how healthcare robotics can facilitate healthy aging, with an emphasis on physical, cognitive, and social supports. We next provide a synthesis of future challenges and considerations in the development and application of healthcare robots. We organize these considerations using a socio-ecological perspective and discuss considerations at the individual, care partner, community healthcare, and healthcare policy levels. RECENT FINDINGS: Older adults are the fastest growing segment of the US population. Age-related changes and challenges can present difficulties, for older adults want to age healthily and maintain independence. Technology, specifically healthcare robots, has potential to provide health supports to older adults. These supports span widely across the physical, cognitive, and social aspects of healthy aging. SUMMARY: Our review suggests that while healthcare robotics has potential to revolutionize the way in which older adults manage their health, there are many challenges such as clinical effectiveness, technology acceptance, health informatics, and healthcare policy and ethics. Addressing these challenges at all levels of the healthcare system will help ensure that healthcare robotics promote healthy aging and are applied safely, effectively, and reliably."
1285,Non-invasive estimation of cerebral perfusion pressure using transcranial Doppler ultrasonography in children with severe traumatic brain injury,"OBJECTIVE: To identify if cerebral perfusion pressure (CPP) can be non-invasively estimated by either of two methods calculated using transcranial Doppler ultrasound (TCD) parameters. DESIGN: Retrospective review of previously prospectively gathered data. SETTING: Pediatric intensive care unit in a tertiary care referral hospital. PATIENTS: Twenty-three children with severe traumatic brain injury (TBI) and invasive intracranial pressure (ICP) monitoring in place. INTERVENTIONS: TCD evaluation of the middle cerebral arteries was performed daily. CPP at the time of the TCD examination was recorded. For method 1, estimated cerebral perfusion pressure (CPPe) was calculated as: CPPe = MAP × (diastolic flow (Vd)/mean flow (Vm)) + 14. For method 2, critical closing pressure (CrCP) was identified as the intercept point on the x-axis of the linear regression line of blood pressure and flow velocity parameters. CrCP/CPPe was then calculated as MAP-CrCP. MEASUREMENTS AND MAIN RESULTS: One hundred eight paired measurements were available. Using patient averaged data, correlation between CPP and CPPe was significant (r = 0.78, p = < 0.001). However, on Bland-Altman plots, bias was 3.7 mmHg with 95% limits of agreement of − 17 to + 25 for CPPe. Using patient averaged data, correlation between CPP and CrCP/CPPe was significant (r = 0.59, p = < 0.001), but again bias was high at 11 mmHg with wide 95% limits of agreement of − 15 to + 38 mmHg. CONCLUSIONS: CPPe and CrCP/CPPe do not have clinical value to estimate the absolute CPP in pediatric patients with TBI."
1286,Risk of Readmission and Mortality Following Hospitalization with Hypercapnic Respiratory Failure,"PURPOSE: Hypercapnic respiratory failure (HRF) is a frequent cause of hospitalization and a common comorbidity in hospitalized patients. There are few studies addressing what factors might predict poor outcomes in this patient population. The purpose of the current study was to investigate characteristics and outcomes of patients hospitalized with HRF. METHODS: A study of patients ≥ 18 years admitted with HRF in a 1-year period. Patients with limited life expectancy related to other conditions, and those with a non-respiratory cause of HRF, were excluded. RESULTS: 202 subjects met eligibility criteria: 24% had a diagnosis of obstructive sleep apnea, 6% obesity hypoventilation, 46% chronic obstructive pulmonary disease, and 10% asthma. Fifteen (7%) died during the index admission. Forty-one patients (23%) were readmitted within 30 days: peripheral vascular disease [adjusted odds ratio (aOR) 4.78, CI 1.45–15.74] and tachycardia (aOR 2.97, CI 1.22–7.26) were associated with an increased risk of readmission. Sixty-six patients (36%) died after discharge. Risk of death was increased in older patients (aOR 1.32, CI 1.13–1.54 per 5 years), those with peripheral vascular disease (aOR 12.56, CI 2.35–67.21), higher Charlson co-morbidity index (aOR 1.39, CI 1.09–1.76), use of home oxygen (aOR 4.03, CI 1.89–8.57), and those who had been readmitted (aOR 3.07, CI 1.46–6.43). CONCLUSIONS: Hospitalization for HRF is associated with a high morbidity and mortality. Our observation that home oxygen use was associated with increased mortality suggests that oxygen use could be a risk factor for death in patients with HRF."
1287,"Inhaled nitric oxide as an adjunct to neonatal resuscitation in premature infants: a pilot, double blind, randomized controlled trial","BACKGROUND: Nitric oxide (NO) plays an important role in normal postnatal transition. Our aims were to determine whether adding inhaled NO (iNO) decreases supplemental oxygen exposure in preterm infants requiring positive pressure ventilation (PPV) during resuscitation and to study iNO effects on heart rate (HR), oxygen saturation (SpO(2)), and need for intubation during the first 20 min of life. METHODS: This was a pilot, double-blind, randomized, placebo-controlled trial. Infants 25 0/7–31 6/7 weeks’ gestational age requiring PPV with supplemental oxygen during resuscitation were enrolled. PPV was initiated with either oxygen (FiO(2)–0.30) + iNO at 20 ppm (iNO group) or oxygen (FiO(2)–0.30) + nitrogen (placebo group). Oxygen was titrated targeting defined SpO(2) per current guidelines. After 10 min, iNO/nitrogen was weaned stepwise per protocol and terminated at 17 min. RESULTS: Twenty-eight infants were studied (14 per group). The mean gestational age in both groups was similar. Cumulative FiO(2) and rate of exposure to high FiO(2) (>0.60) were significantly lower in the iNO group. There were no differences in HR, SpO(2), and need for intubation. CONCLUSIONS: Administration of iNO as an adjunct during neonatal resuscitation is feasible without side effects. It diminishes exposure to high levels of supplemental oxygen."
1288,Plasmodium asexual growth and sexual development in the haematopoietic niche of the host,"Plasmodium spp. parasites are the causative agents of malaria in humans and animals, and they are exceptionally diverse in their morphology and life cycles. They grow and develop in a wide range of host environments, both within blood-feeding mosquitoes, their definitive hosts, and in vertebrates, which are intermediate hosts. This diversity is testament to their exceptional adaptability and poses a major challenge for developing effective strategies to reduce the disease burden and transmission. Following one asexual amplification cycle in the liver, parasites reach high burdens by rounds of asexual replication within red blood cells. A few of these blood-stage parasites make a developmental switch into the sexual stage (or gametocyte), which is essential for transmission. The bone marrow, in particular the haematopoietic niche (in rodents, also the spleen), is a major site of parasite growth and sexual development. This Review focuses on our current understanding of blood-stage parasite development and vascular and tissue sequestration, which is responsible for disease symptoms and complications, and when involving the bone marrow, provides a niche for asexual replication and gametocyte development. Understanding these processes provides an opportunity for novel therapies and interventions."
1289,"Microbial acetylcholinesterase inhibitors for Alzheimer’s therapy: recent trends on extraction, detection, irradiation-assisted production improvement and nano-structured drug delivery","ABSTRACT: Neurodegenerative disorders especially Alzheimer’s disease (AD) are significantly threatening the public health. Acetylcholinesterase (AChE) inhibitors are compounds of great interest which can be used as effective agents for the symptomatic treatment of AD. Although plants are considered the largest source for these types of inhibitors, the microbial production of AChE inhibitors represents an efficient, easily manipulated, eco-friendly, cost-effective, and alternative approach. This review highlights the recent advances on the microbial production of AChE inhibitors and summarizes all the previously reported successful studies on isolation, screening, extraction, and detecting methodologies of AChE inhibitors from the microbial fermentation, from the earliest trials to the most promising anti-AD drug, huperzine A (HupA). In addition, improvement strategies for maximizing the industrial production of AChE inhibitors by microbes will be discussed. Finally, the promising applications of nano-material-based drug delivery systems for natural AChE inhibitor (HupA) will also be summarized. KEY POINTS: • AChE inhibitors are potential therapies for Alzheimer’s disease. • Microorganisms as alternate sources for prospective production of such inhibitors. • Research advances on extraction, detection, and strategies for production improvement. • Nanotechnology-based approaches for an effective drug delivery for Alzheimer’s disease."
1290,"De novo transcriptomic analysis of light-induced flavonoid pathway, transcription factors in the flower buds of Lonicera japonica","KEY MESSAGE: Transcriptomic analysis of the relationship between gene expression patterns and flavonoid contents in the flower buds of Lonicera japonica under light-induced conditions, especially the flavonoid pathway genes and transcription factors. ABSTRACT: Flos Lonicerae Japonicae (FLJ), the flower buds of Lonicera japonica Thunb., has been used to treat some human diseases including severe respiratory syndromes and hand-foot-and-mouth diseases owing to its putative antibacterial, and antiviral effects. Luteoloside is a flavonoid that is used by the Chinese Pharmacopoeia to evaluate the quality of FLJ. Light is an important environmental factor that affects flavonoid biosynthesis in the flower buds of L. japonica. However, how light triggers increases in flavonoid production remains unclear. To enhance our understanding of the mechanism involved in light-regulated flavonoid biosynthesis, we sequenced the transcriptomes of L. japonica exposed to three different light conditions: 100% light intensity (CK), 50% light intensity (LI50), and 25% light intensity (LI25) using an Illumina HiSeq 4000 System. A total of 77,297 unigenes with an average length of 809 bp were obtained. Among them, 43,334 unigenes (56.06%) could be matched to at least one biomolecular database. Additionally, 4188, 1545 and 1023 differentially expressed genes (DEGs) were identified by comparative transcriptomics LI25-vs-CK, LI50-vs-CK, and LI25-vs-LI50, respectively. Of note, genes known to be involved in flavonoid biosynthesis, such as 4-coumarate coenzyme A ligase (4CL), and chalcone synthase (CHS) were up-regulated. In addition, a total of 1649 transcription factors (TFs) were identified and divided into 58 TF families; 98 TFs exhibited highly dynamic changes in response to light intensity. Quantitative real-time PCR (qRT-PCR) was used to test the expression profiles of the RNA sequencing (RNA-Seq) data. This study offers insight into how transcriptional expression pattern is influenced by light in the flower buds of L. japonica, and will enhance the understanding of molecular mechanisms of flavonoid biosynthesis in response to light in L. japonica. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00468-019-01916-4) contains supplementary material, which is available to authorized users."
1291,Assistive Robots for the Social Management of Health: A Framework for Robot Design and Human–Robot Interaction Research,"There is a close connection between health and the quality of one’s social life. Strong social bonds are essential for health and wellbeing, but often health conditions can detrimentally affect a person’s ability to interact with others. This can become a vicious cycle resulting in further decline in health. For this reason, the social management of health is an important aspect of healthcare. We propose that socially assistive robots (SARs) could help people with health conditions maintain positive social lives by supporting them in social interactions. This paper makes three contributions, as detailed below. We develop a framework of social mediation functions that robots could perform, motivated by the special social needs that people with health conditions have. In this framework we identify five types of functions that SARs could perform: (a) changing how the person is perceived, (b) enhancing the social behavior of the person, (c) modifying the social behavior of others, (d) providing structure for interactions, and (e) changing how the person feels. We thematically organize and review the existing literature on robots supporting human–human interactions, in both clinical and non-clinical settings, and explain how the findings and design ideas from these studies can be applied to the functions identified in the framework. Finally, we point out and discuss challenges in designing SARs for supporting social interactions, and highlight opportunities for future robot design and HRI research on the mediator role of robots."
1292,Viral genomics in Ebola virus research,"Filoviruses such as Ebola virus continue to pose a substantial health risk to humans. Advances in the sequencing and functional characterization of both pathogen and host genomes have provided a wealth of knowledge to clinicians, epidemiologists and public health responders during outbreaks of high-consequence viral disease. Here, we describe how genomics has been historically used to investigate Ebola virus disease outbreaks and how new technologies allow for rapid, large-scale data generation at the point of care. We highlight how genomics extends beyond consensus-level sequencing of the virus to include intra-host viral transcriptomics and the characterization of host responses in acute and persistently infected patients. Similar genomics techniques can also be applied to the characterization of non-human primate animal models and to known natural reservoirs of filoviruses, and metagenomic sequencing can be the key to the discovery of novel filoviruses. Finally, we outline the importance of reverse genetics systems that can swiftly characterize filoviruses as soon as their genome sequences are available."
1293,Influenza Vaccination and Healthcare Personnel Compliance,"PURPOSE OF REVIEW: We reviewed the benefit of influenza vaccination in healthcare personnel (HCP), rates of vaccine coverage, and practices used to try to boost vaccine coverage among HCP. RECENT FINDINGS: Influenza vaccination in HCP provides benefits to both HCP and patients, including reductions in patient morbidity and mortality and decreases in HCP absenteeism. Despite these benefits, influenza vaccine coverage among HCP still falls short of the Healthy People 2020 goal of 90%. As a result, healthcare institutions have used various practices to boost vaccination, including mandatory vaccine policies and requiring non-immunized HCP to wear masks during the influenza season. All of these efforts have been successful at increasing vaccination rates, and employer vaccination requirements have led to rates that meet the Healthy People 2020 goal. Rates of mandatory vaccine policies have increased over time, and several states now have influenza vaccine requirements. However, additional study into how these policies improve patient outcomes is needed. SUMMARY: Continued effort is needed to boost influenza vaccination rates among HCP, and mandatory vaccine policies may be used if other methods have not been effective in adequately raising vaccination rates. Future research should focus on how mandatory vaccine policies can improve patient outcomes."
1294,Choosing the best supraglottic airway for ophthalmic general anaesthesia: a manikin study,"General anaesthesia is sometimes favoured over regional anaesthesia in ophthalmic surgery. The use of supraglottic airway (SGA) or laryngeal mask airway (LMA) as the primary airway device is increasing due to numerous advantages over tracheal intubation. Compared with 1st generation SGAs, 2nd generation SGAs have an added benefit of isolating the airway from the alimentary tract. However, the vertical profile of SGAs may encroach into the surgical field and hence interfere with surgery. We investigated the vertical projections of 1st generation SGAs (LMA Classic, Ambu AuraFlex) and commonly used 2nd generation SGAs in our institution (LMA ProSeal, LMA Supreme, LMA Protector, Ambu AuraGain and I-gel) in a manikin model. Each device was connected to a corrugated catheter mount or angled connector following insertion as per usual clinical practice in our institutions. Vertical projections of all devices were measured from the chin using a centimetre ruler. Securing of airway device to the chin with an adhesive tape was possible for the LMA Classic and Ambu AuraFlex with straight corrugated connector, whereas the stiffer 2nd generations SGAs required the addition of an angled connector or straight corrugated tubing to direct the airway tube caudally, away from the surgical field. The LMA ProSeal had the lowest vertical projection amongst the 2nd generation SGAs and may be the suitable choice for ophthalmic surgery. We also describe a novel technique of utilising a 1st generation SGA with placement of an orogastric tube, although with some reservations. This study has several limitations and transferability of our findings into clinical practice is questionable as the use of a manikin may not fully imitate the real condition of the patient. Our study is the first study comparing vertical projected height of different SGAs in manikin, but future studies should investigate the use of SGA in the clinical setting during ophthalmic surgery."
1295,Early changes in diaphragmatic function evaluated using ultrasound in cardiac surgery patients: a cohort study,"Little is known about the evolution of diaphragmatic function in the early post-cardiac surgery period. The main purpose of this work is to describe its evolution using ultrasound measurements of muscular excursion and thickening fraction (TF). Single-center prospective study of 79 consecutive uncomplicated elective cardiac surgery patients, using motion-mode during quiet unassisted breathing. Excursion and TF were measured sequentially for each patient [pre-operative (D1), 1 day (D2) and 5 days (D3) after surgery]. Pre-operative median for right and left hemidiaphragmatic excursions were 1.8 (IQR 1.6 to 2.1) cm and 1.7 (1.4 to 2.0) cm, respectively. Pre-operative median right and left thickening fractions were 28 (19 to 36) % and 33 (22 to 51) %, respectively. At D2, there was a reduction in both excursion (right: 1.5 (1.1 to 1.8) cm, p < 0.001, left: 1.5 (1.1 to 1.8), p = 0.003) and thickening fractions (right: 20 (15 to 34) %, p = 0.021, left: 24 (17 to 39) %, p = 0.002), followed by a return to pre-operative values at D3. A positive moderate correlation was found between excursion and thickening fraction (Spearman’s rho 0.518 for right and 0.548 for left hemidiaphragm, p < 0.001). Interobserver reliability yielded a bias below 0.1 cm with limits of agreement (LOA) of ± 0.3 cm for excursion and − 2% with LOA of ± 21% for thickening fractions. After cardiac surgery, the evolution of diaphragmatic function is characterized by a transient impairment followed by a quick recovery. Although ultrasound diaphragmatic excursion and thickening fraction are correlated, excursion seems to be a more feasible and reproducible method in this population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-019-00350-8) contains supplementary material, which is available to authorized users."
1296,Neonatal transport in California: findings from a qualitative investigation,"OBJECTIVE: To identify characteristics of neonatal transport in California and which factors influence team performance. STUDY DESIGN: We led focus group discussions with 19 transport teams operating in California, interviewing 158 neonatal transport team members. Transcripts were analyzed using a thematic analysis approach. RESULT: The composition of transport teams varied widely. There was strong thematic resonance to suggest that the nature of emergent neonatal transports is unpredictable and poses several significant challenges including staffing, ambulance availability, and administrative support. Teams reported dealing with this unpredictability by engaging in teamwork, gathering experience with staff at referral hospitals, planning for a wide variety of circumstances, specialized training, debriefing after events, and implementing quality improvement strategies. CONCLUSION: Our findings suggest potential opportunities for improvement in neonatal transport. Future research can explore the cost and benefits of strategies such as dedicated transport services, transfer centers, and telemedicine."
1297,Diaphragm and Lung Ultrasound Indices in Prediction of Outcome of Weaning from Mechanical Ventilation in Pediatric Intensive Care Unit,"OBJECTIVE: To predict the added value of diaphragmatic and lung ultrasound indices (US) in anticipation of the outcome of mechanical ventilation of pediatric patients in the intensive care unit. METHODS: This prospective study was conducted in Zagazig University, Pediatric Hospitals, PICU; Egypt. One hundred six mechanically ventilated children aged between 1 mo to 170 mo were included in the study. All patients were candidates for weaning and have been given a chance for spontaneous breathing trial (SBT), during which diaphragmatic and lung US was performed for them. The diaphragm thickening fraction (DTF), the diaphragmatic excursion and the lung US score (LUS), that included 4 US aeration forms, were assessed. RESULTS: There were statistically significant differences between patients with failed weaning and those with successful weaning regarding DTF, diaphragmatic excursion and LUS (p < 0.001). The best cut-off value of DTF, diaphragmatic excursion, and LUS for predicting weaning failure was ≥23.175%, ≥ 6.2 mm, and ≥ 12 with an AUC (area under curve) of 0.932, 0.876, and 0.934, respectively. CONCLUSIONS: Diaphragmatic and lung US add a quick, accurate and non-invasive indices to the weaning readiness parameters compared to the other standard parameters alone. So, it is recommended to be added to the predictive parameters of weaning outcome."
1298,Clinical decision-making on spinal cord injury-associated pneumonia: a nationwide survey in Germany,"STUDY DESIGN: Survey study. OBJECTIVES: Spinal cord injury (SCI)-associated pneumonia (SCI-AP) is associated with poor functional recovery and a major cause of death after SCI. Better tackling SCI-AP requires a common understanding on how SCI-AP is defined. This survey examines clinical algorithms relevant for diagnosis and treatment of SCI-AP. SETTING: All departments for SCI-care in Germany. METHODS: The clinical decision-making on SCI-AP and the utility of the Centers for Disease Control and Prevention (CDC) criteria for diagnosis of ‘clinically defined pneumonia’ were assessed by means of a standardized questionnaire including eight case vignettes of suspected SCI-AP. The diagnostic decisions based on the case information were analysed using classification and regression trees (CART). RESULTS: The majority of responding departments were aware of the CDC-criteria (88%). In the clinical vignettes, 38–81% of the departments diagnosed SCI-AP in accordance with the CDC-criteria and 7–41% diagnosed SCI-AP in deviation from the CDC-criteria. The diagnostic agreement was not associated with the availability of standard operating procedures for SCI-AP management in the departments. CART analysis identified radiological findings, fever, and worsened gas exchange as most important for the decision on SCI-AP. Frequently requested supplementary diagnostics were microbiological analyses, C-reactive protein, and procalcitonin. For empirical antibiotic therapy, the departments used (acyl-)aminopenicillins/β-lactamase inhibitors, cephalosporins, or combinations of (acyl-)aminopenicillins/β-lactamase inhibitors with fluoroquinolones or carbapenems. CONCLUSIONS: This survey reveals a diagnostic ambiguity regarding SCI-AP despite the awareness of CDC-criteria and established SOPs. Heterogeneous clinical practice is encouraging the development of disease-specific guidelines for diagnosis and management of SCI-AP."
1299,Octogenarians with blunt splenic injury: not all geriatrics are the same,"Geriatric trauma patients (GTP) (age ≥ 65 years) with blunt splenic injury (BSI) have up to a 6% failure rate of non-operative management (NOM). GTPs failing NOM have a similar mortality rate compared to GTPs managed successfully with NOM. However, it is unclear if this remains true in octogenarians (aged 80–89 years). We hypothesized that the failure rate for NOM in octogenarians would be similar to their younger geriatric cohort, patients aged 65–79 years; however risk of mortality in octogenarians who fail NOM would be higher than that of octogenarians managed successfully with NOM. The Trauma Quality Improvement Program (2010–2016) was queried for patients with BSI. Those undergoing splenectomy within 6 h were excluded to select for patients undergoing NOM. Patients aged 65–79 years (young GTPs) were compared to octogenarians. A multivariable logistic regression model was used to determine the risk for failed NOM and mortality. From 43,041 BSI patients undergoing NOM, 3660 (8.5%) were aged 65–79 years and 1236 (2.9%) were octogenarians. Both groups had a similar median Injury Severity Score (ISS) (p = 0.10) and failure rate of NOM (6.6% young GTPs vs. 6.8% octogenarians p = 0.82). From those failing NOM, octogenarians had similar units of blood products transfused (p > 0.05) and a higher mortality rate (40.5% vs. 18.2%, p < 0.001), compared to young GTPs. Independent risk factors for failing NOM in octogenarians included ≥ 1 unit of packed red blood cells (PRBC) (p = 0.039) within 24 h of admission. Octogenarians who failed NOM had a higher mortality rate compared to octogenarians managed successfully with NOM (40.5% vs 23.6% p = 0.001), which persisted in a multivariable logistic regression analysis (OR 2.25, CI 1.37–3.70, p < 0.001). Late failure of NOM ≥ 24 h (vs. early failure) was not associated with increased risk of mortality (p = 0.88), but ≥ 1 unit of PRBC transfused had higher risk (OR 1.88, CI 1.20–2.95, p = 0.006). Compared to young GTPs with BSI, octogenarians have a similar rate of failed NOM. Octogenarians with BSI who fail NOM have over a twofold higher risk of mortality compared to those managed successfully with NOM. PRBC transfusion increases risk for mortality. Therefore, clinicians should consider failure of NOM earlier in the octogenarian population to mitigate the risk of increased mortality."
1300,Systemic lupus erythematosus presenting with status epilepticus and acute cardiomyopathy with acute heart failure: case report,"INTRODUCTION: Systemic lupus erythematosus is a connective tissue disorder, which causes complex multi organ involvement. Neurological and cardiac manifestations have been well noted but complications such as status epilepticus and acute myocarditis with heart failure at presentation remains uncommon. CASE DESCRIPTION: A 15-year-old, previously healthy, South Asian, Sri Lankan female presented with status epilepticus and the seizures only responded to intravenous midazolam and thiopentone sodium. On the fourth day, she developed tachycardia and shortness of breath and was found to have cardiomyopathy with heart failure with an ejection fraction 40%. Along with a positive urinary sediment, a positive ANA with a very high level of ds-DNA and low C3 and C4 levels confirmed our suspicion of systemic lupus erythematosus. DISCUSSION AND EVALUATION: Systemic lupus erythematosus presents in a variety of clinical presentations and the spectrum may range from unique to ubiquitous. Clinicians should have a high index of suspicion specially when encountering atypical presentations with multi-organ involvement, especially when patients tend to be young females. Status epilepticus and myocarditis are uncommon manifestations of systemic lupus erythematosus, and should be appreciated early, as if inappropriately managed would have a deleterious impact on mortality and morbidity."
1301,Questioning dogma: does a GCS of 8 require intubation?,"BACKGROUND: There is no evidence supporting intubation for a Glasgow Coma Scale (GCS) of 8. We investigated the effect of intubation in trauma patients with a GCS 6–8, with the hypothesis that intubation would increase mortality and length of stay. METHODS: We studied adult patients with GCS 6–8 from the 2016 National Trauma Data Bank. Intubated and non-intubated patients were compared using inverse probability weighted regression adjustment (IPWRA) to control for injury severity and patient characteristics. Outcomes were mortality, intensive care unit length of stay (ICU LOS), and total LOS. Stratified analysis was performed to investigate the effect in patients with and without head injuries. RESULTS: Among 6676 patients with a GCS between 6 and 84,078 were intubated within 1 h of arrival to the emergency department. The overall mortality rate was 15.1%. IPWRA revealed an increase in mortality associated with intubation (OR 1.05, 95% CI 1.03, 1.06). The results were similar in patients with head injuries (OR 1.04, 95% CI 1.02, 1.06) and without (OR 1.06, 95% CI 1.03, 1.10). Among the 5,742 patients admitted to the ICU, intubation was associated with a 14% increase in ICU LOS (95% CI 8–20%; 5.5 vs. 4.8 days; p < 0.001). The overall length of stay was 27% longer (95% CI 19.8–34.3%) among intubated patients (mean 7.7 vs 6.0 days; p < 0.001). CONCLUSION: Among patients with GCS of 6 to 8, intubation on arrival was associated with an increase in mortality and with longer ICU and overall length of stay. The use of a strict threshold GCS to mandate intubation should be revisited."
1302,Screening of compound libraries for inhibitors of Toxoplasma growth and invasion,"Toxoplasma gondii can infect virtually all warm-blooded animals, including humans. It can differentiate between rapidly replicating tachyzoites that cause acute infection and slowly growing bradyzoites in tissue cysts. Treatment options for toxoplasmosis are challenging because current therapies cannot eradicate the latent T. gondii infection that is mainly caused by the bradyzoite forms. Accordingly, recurrence of infection is a problem for immunocompromised patients and congenitally infected patients. Protein kinases have been widely studied in eukaryotic cells, and while little is known about signaling in Toxoplasma infection, it is likely that protein kinases play a key role in parasite proliferation, differentiation, and probably invasion. To identify optimized new kinase inhibitors for drug development against T. gondii, we screened a library of kinase inhibitor compounds for anti-Toxoplasma activity and host cell cytotoxicity. Pyrimethamine served as a positive control and 0.5% DMSO was used as a negative control. Among the 80 compounds screened, 6 compounds demonstrated ≥ 80% parasite growth inhibition at concentrations at which 5 compounds did not suppress host cell viability, while 3 kinase inhibitors (Bay 11-7082, Tyrphostin AG 1295 and PD-98059) had suppressive effects individually on parasite growth and host cell invasion, but did not strongly induce bradyzoite formation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00436-020-06673-9) contains supplementary material, which is available to authorized users."
1303,Vascular compression of the left bronchus in a patient with funnel chest,"We present a case of 5 year-old female with funnel chest, by which cardiovascular structures were displaced into the left chest cavity. This caused left bronchial compression by the pulmonary artery and the descending aorta, for which an external stenting was successfully performed. The patient had features suggestive of skeletal dysplasia with tracheobronchial malacia. One possible mechanism of vascular compression could be an association of fragility of the thoracic cavity and inspiratory dyspnea, causing thoracic deformity."
1304,"Influence of ZnO, SiO(2) and TiO(2) on the aging process of PLA fibers produced by electrospinning method","The aim of this work was to study the effect of ceramics particles addition (SiO(2), ZnO, TiO(2)) on the ultraviolet (UV) aging of poly(lactic acid) nonwovens fabricated using electrospinning method. The resistance to aging is a key factor for outdoor and medical applications (UV light sterilization). Nonwovens were placed in special chamber with UV light. Changes of physicochemical properties were recorded using differential scanning calorimetry and attenuated total reflection Fourier-transform infrared spectroscopy. The fibers’ morphology was studied by using scanning electron microscopy. Obtained results clearly showed that only PLA fibers with ZnO particles gained an increase in UV resistance. The paper presents a description of structural changes taking place under the influence of UV aging processes and describes the mechanisms of this process and the effect of ceramic addition on the lifetime of such materials."
1305,How to ventilate preterm infants with lung compliance close to circuit compliance: real-time simulations on an infant hybrid respiratory simulator,"Circuit compliance close to lung compliance can create serious problems in effective and safe mechanical ventilation of preterm infants. We considered what ventilation technique is the most beneficial in this case. A hybrid (numerical–physical) simulator of infant respiratory system mechanics, the Bennett Ventilator and NICO apparatus were used to simulate pressure-controlled ventilation (PC) and volume-controlled ventilation with constant flow (VCV(CF)) and descending flow (VCV(DF)), under permissive hypercapnia (PHC) (6 ml kg(−1)) and normocapnia (SV) (8 ml kg(−1)) conditions. Respiratory rate (RR) was 36 or 48 min(−1) and PEEP was 0.3 or 0.6 kPa. Peak inspiratory pressure (PIP), mean airway pressure (MAP), and work of breathing by the ventilator (WOB) were lower (P < 0.01, 1 − β = 0.9) using the PHC strategy compared to the SV strategy. The WOB increased (P < 0.01; 1 − β = 0.9) when the RR increased. The PC, VCV(CF), and VCV(DF) modes did not differ in minute ventilation produced by the ventilator (MV(V)), but the PC mode delivered the highest minute ventilation to the patient (MV(T)) (P < 0.01; 1 − β = 0.9) at the same PIP, MAP, and WOB. The most beneficial ventilation technique appeared to be PC ventilation with the PHC strategy, with lower RR (36 min(−1)). [Figure: see text]"
1306,Influence of cellular lipid content on influenza A virus replication,"Influenza A virus (IAV) depends on the metabolism of its cellular host to provide energy and essential factors, including lipids, for viral replication. Previous studies have shown that fatty acids (FAs) play an important role in IAV replication and that inhibition of FA biosynthesis can diminish viral replication. However, cellular lipids can either be synthesized intracellularly or be imported from the extracellular environment. Interfering with FA import mechanisms may reduce the cellular lipid content and inhibit IAV replication. To test this hypothesis, MDCK and Detroit 562 cells were infected with IAV followed by exposure to palmitic acid and inhibitors of FA import. Replication of IAV significantly increased when infected cells were supplied with palmitic acid. This enhancement could be reduced by adding an FA import inhibitor. The addition of palmitic acid significantly increased the cellular lipid content, and this increased level was reduced by treatment with an FA import inhibitor. These results show that reducing the cellular lipid level might be an approach for IAV therapy."
1307,Steering Efficacy of Nano Molybdenum Towards Cancer: Mechanism of Action,"Conventional cancer therapies possess a plethora of limitations which led to the awakening of nanotechnology and nanomedicine. However, technological success is widely dependent on complete understanding of the complexity and heterogeneity of tumor biology on one hand and nanobiointeractions associated with challenges of synthesis, translation, and commercialization on the other. The present study therefore deals with one such targeted approach aiming at synthesizing, characterizing, and understanding the efficacy of molybdenum oxide nanoparticles. The phase structure, morphology, and elemental composition of the synthesized nanoparticles were characterized using Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and scanning electron microscopy. The cytotoxicity studies revealed that the IC(50) vales of molybdenum trioxide (MoO(3)) particles against skin cancer cells (melanoma and non-melanoma) were around 200–300 μg. The nanoparticles were found to induce mitochondrial-mediated apoptosis driven by the apoptotic genes such as BAX and Bcl(2). Molybdenum being a cofactor for the majority of metabolic enzymes could have triggered the selective internalization of the nanoparticles which in turn could have modified the granularity of the cytoplasm and subsequently lead to mitochondrial-mediated apoptosis. Further, the anti-angiogenic property of MoO(3) nanoparticles was corroborated using Chick chorioallantoic membrane (CAM) assay and aortic ring assay. Taken together , unraveling the role of MoO(3) nanoparticles in cancer and angiogenesis opens up venues for nano biological intervention of selective cancer cell targeting with minimal damage to the normal cells using natural trace elements that are generally known to influence various metabolic enzymes."
1308,Conservative oxygen therapy for mechanically ventilated adults with sepsis: a post hoc analysis of data from the intensive care unit randomized trial comparing two approaches to oxygen therapy (ICU-ROX),"PURPOSE: Sepsis is a common reason for intensive care unit (ICU) admission and mortality in ICU patients. Despite increasing interest in treatment strategies limiting oxygen exposure in ICU patients, no trials have compared conservative vs. usual oxygen in patients with sepsis. METHODS: We undertook a post hoc analysis of the 251 patients with sepsis enrolled in a trial that compared conservative oxygen therapy with usual oxygen therapy in 1000 mechanically ventilated ICU patients. The primary end point for the current analysis was 90-day mortality. Key secondary outcomes were cause-specific mortality, ICU and hospital length of stay, ventilator-free days, vasopressor-free days, and the proportion of patients receiving renal replacement therapy in the ICU. RESULTS: Patients with sepsis allocated to conservative oxygen therapy spent less time in the ICU with an SpO(2) ≥ 97% (23.5 h [interquartile range (IQR) 8–70] vs. 47 h [IQR 11–93], absolute difference, 23 h; 95% CI 8–38), and more time receiving an FiO(2) of 0.21 than patients allocated to usual oxygen therapy (20.5 h [IQR 1–79] vs. 0 h [IQR 0–10], absolute difference, 20 h; 95% CI 14–26). At 90-days, 47 of 130 patients (36.2%) assigned to conservative oxygen and 35 of 120 patients (29.2%) assigned to usual oxygen had died (absolute difference, 7 percentage points; 95% CI − 4.6 to 18.6% points; P = 0.24; interaction P = 0.35 for sepsis vs. non-sepsis). There were no statistically significant differences between groups for secondary outcomes but point estimates of treatment effects consistently favored usual oxygen therapy. CONCLUSIONS: Point estimates for the treatment effect of conservative oxygen therapy on 90-day mortality raise the possibility of clinically important harm with this intervention in patients with sepsis; however, our post hoc analysis was not powered to detect the effects suggested and our data do not exclude clinically important benefit or harm from conservative oxygen therapy in this patient group. CLINICAL TRIALS REGISTRY: ICU-ROX Australian and New Zealand Clinical Trials Registry number ACTRN12615000957594. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05857-x) contains supplementary material, which is available to authorized users."
1309,Clinical deterioration during neonatal transport in California,"OBJECTIVE: Identify clinical factors, transport characteristics and transport time intervals associated with clinical deterioration during neonatal transport in California. STUDY DESIGN: Population-based database was used to evaluate 47,794 infants transported before 7 days after birth from 2007 to 2016. Log binomial regression was used to estimate relative risks. RESULTS: 30.8% of infants had clinical deterioration. Clinical deterioration was associated with prematurity, delivery room resuscitation, severe birth defects, emergent transports, transports by helicopter and requests for delivery room attendance. When evaluating transport time intervals, time required for evaluation by the transport team was associated with increased risk of clinical deterioration. Modifiable transport intervals were not associated with increased risk. CONCLUSION: Our results suggest that high-risk infants are more likely to be unstable during transport. Coordination and timing of neonatal transport in California appears to be effective and does not seem to contribute to clinical deterioration despite variation in the duration of these processes."
1310,Oral delivery of Bacillus subtilis spores expressing Clonorchis sinensis paramyosin protects grass carp from cercaria infection,"Clonorchis sinensis (C. sinensis), an important fishborne zoonotic parasite threatening public health, is of major socioeconomic importance in epidemic areas. Effective strategies are still urgently expected to prevent against C. sinensis infection. In the present study, paramyosin of C. sinensis (CsPmy) was stably and abundantly expressed on the surface of Bacillus subtilis spores. The recombinant spores (B.s-CotC-CsPmy) were incorporated in the basal pellets diet in three different dosages (1 × 10(5), 1 × 10(8), 1 × 10(11) CFU/g pellets) and orally administrated to grass carp (Ctenopharyngodon idella). The immune responses and intestinal microbiota in the treated grass carp were investigated. Results showed that specific anti-CsPmy IgM levels in sera, skin mucus, bile, and intestinal mucus, as well as mRNA levels of IgM and IgZ in the spleen and head kidney, were significantly increased in B.s-CotC-CsPmy-10(11) group. Besides, transcripts levels of IL-8 and TNF-αin the spleen and head kidney were also significantly elevated than the control groups. Moreover, mRNA levels of tight junction proteins in the intestines of B.s-CotC-CsPmy-10(11) group increased. Potential pathogenetic bacteria with lower abundance and higher abundances of candidate probiotics and bacteria associated with digestion in 1 × 10(11) CFU/g B.s-CotC-CsPmy spores administrated fishes could be detected compared with control group. The amount of metacercaria in per gram fish flesh was statistically decreased in 1 × 10(11) CFU/g B.s-CotC-CsPmy spores orally immunized group. Our work demonstrated that B. subtilis spores presenting CsPmy on the surface could be a promising effective, safe, and needle-free candidate vaccine against C. sinensis infection for grass carp. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-019-10316-0) contains supplementary material, which is available to authorized users."
1311,Mathematical analysis for a new nonlinear measles epidemiological system using real incidence data from Pakistan,"Modeling of infectious diseases is essential to comprehend dynamic behavior for the transmission of an epidemic. This research study consists of a newly proposed mathematical system for transmission dynamics of the measles epidemic. The measles system is based upon mass action principle wherein human population is divided into five mutually disjoint compartments: susceptible S(t)—vaccinated V(t)—exposed E(t)—infectious I(t)—recovered R(t). Using real measles cases reported from January 2019 to October 2019 in Pakistan, the system has been validated. Two unique equilibria called measles-free and endemic (measles-present) are shown to be locally asymptotically stable for basic reproductive number [Formula: see text] and [Formula: see text] , respectively. While using Lyapunov functions, the equilibria are found to be globally asymptotically stable under the former conditions on [Formula: see text] . However, backward bifurcation shows coexistence of stable endemic equilibrium with a stable measles-free equilibrium for [Formula: see text] . A strategy for measles control based on herd immunity is presented. The forward sensitivity indices for [Formula: see text] are also computed with respect to the estimated and fitted biological parameters. Finally, numerical simulations exhibit dynamical behavior of the measles system under influence of its parameters which further suggest improvement in both the vaccine efficacy and its coverage rate for substantial reduction in the measles epidemic."
1312,"Chest Trauma: Current Recommendations for Rib Fractures, Pneumothorax, and Other Injuries","PURPOSE OF REVIEW: This article provides an overview of the common and important chest injuries that the anesthesiologist may encounter in patients following trauma including blunt injury, pneumothorax, hemothorax, blunt aortic injury, and blunt cardiac injury. RECENT FINDINGS: Rib fractures are frequently associated with chest injury and are associated with significant pain and other complications. Regional anesthesia techniques combined with a multimodal analgesic strategy can improve patient outcomes and reduce complications. There is increasing evidence for paravertebral blocks for this indication, and the myofascial plane blocks are a popular emerging technique. Recent changes to recommended management of tension pneumothorax are also described. SUMMARY: Chest trauma is commonly encountered, and anesthesiologists have the potential to significantly improve morbidity and mortality in this group of patients."
1313,"Impact of multiple placental pathologies on neonatal death, bronchopulmonary dysplasia, and neurodevelopmental impairment in preterm infants","BACKGROUND: To determine the association of placental pathology, including multiple placental lesions, with the occurrence and severity of bronchopulmonary dysplasia (BPD), death, and neurodevelopmental impairment (NDI) in preterm infants. METHOD: A retrospective cohort study of neonates <29 weeks gestational age (GA) born at Parkland Hospital from 08/2009 to 08/2012. Infants were stratified as follows: Group 1: no significant placental pathology; Group 2: single significant placental lesion; and Group 3: ≥2 placental lesions (multiple lesions). Primary outcome was death and/or BPD. Two-year neurodevelopmental follow-up was compared. RESULTS: In all, 42% (100/241) of infants had one placental lesion, and 34% (82/241) ≥2 lesions. As the number of the pathologic lesions increased (no lesions vs. 1 vs. ≥2), the occurrence of death or BPD increased (25%, 37%, and 52%, respectively; P = 0.004). Moreover, infants with multiple pathologic lesions were more likely to have NDI (29%, 29%, and 46%, respectively; P = 0.03). After logistic regression, infants with multiple pathologic lesions were more likely to develop moderate-to-severe BPD [P < 0.01; OR 3.9 (1.5–10.1)] but not NDI. CONCLUSION(S): Neonates <29 weeks GA with multiple placental pathologic lesions have an increased risk for developing BPD, suggesting an interaction between placental inflammation and vascular pathology and the pathogenesis of BPD; however, the risk of NDI is not increased."
1314,Peanut Oral Immunotherapy: a Current Perspective,"PURPOSE OF THE REVIEW: Peanut oral immunotherapy (OIT) is one of the most studied experimental therapies for food allergy. With the recently FDA-approved peanut product, Palforzia, the goal of this article is to review the most recent data from clinical trials, discuss recent trends, and anticipate future developments. RECENT FINDINGS: The latest research suggests that peanut OIT could be a promising option for peanut-allergic patients, with the majority of participants in research studies achieving the primary efficacy endpoint of desensitization, as well as sustained unresponsiveness in select populations. Some studies also showed improvements in food allergy-related quality of life. However, peanut OIT is not without risk or side effects, including potentially serious allergic reactions. SUMMARY: Future research will need to evaluate the short- and long-term effectiveness of the therapy in the real-world setting, predictors of important treatment outcomes, and the use of adjunctive therapies that may mitigate some of these allergic reactions."
1315,Low-temperature laminar flow ward for the treatment of multidrug resistance Acinetobacter baumannii pneumonia,"This study was designed to investigate the effect of low-temperature laminar flow ward (LTLFW) on the Acinetobacter baumannii pneumonia (MDR-ABP) in neurosurgical intensive care unit (NICU) patients. We evaluated whether patients in a LTLFW had significantly improved clinical outcomes as compared to those in nonconstant-temperature NICU (room temperature). The association of temperature with the prevalence of ABP and A. baumannii isolates (ABI) found in NICU patients was specifically investigated. In vitro microbiological experiments were conducted to measure the proliferation, antibiotic sensitivity, and genomic profiles of A. baumannii (AB) that grew in variable temperatures. MDR-ABP patients in LTLFW had significantly improved outcomes than those in the room temperature NICU. In addition, the numbers of ABI were positively associated with mean ambient outdoor temperatures (P = 0.002), with the incidence of ABP and average numbers of ABI among NICU patients being substantially lower in the winter as compared to other seasons. However, there were no significant seasonal variations in the other strains of the top five bacteria. Consistent with these clinical observations, AB growing at 20°C and 25°C had significantly reduced viability and antibiotic resistance compared to those growing at 35°C. The expression of genes related to AB survival ability, drug resistance, and virulence also differed between AB growing at 20°C and those at 35°C. LTLFW is effective in promoting the recovery of MDR-ABP patients because low temperatures reduced the density and virulence of AB and enhanced the efficacy of antibiotics, likely at the genetic level. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-019-03790-x) contains supplementary material, which is available to authorized users."
1316,Effective Catheter Manoeuvre for the Removal of Phlegm by Suctioning: A Biomechanical Analysis of Experts and Novices,"PURPOSE: The aim of this study was to determine the effective biomechanical technique for suctioning phlegm. METHODS: A novel tracheal suctioning simulator combined with a motion capture system was used to calculate the amount of simulated phlegm suctioned and the biomechanical parameters of the associated suctioning manoeuvre. A laboratory study, including 12 nurses with > 3 years of suctioning experience and 12 nursing students without any clinical suctioning experience, was conducted. The amount of phlegm suctioned, the maximum length of catheter insertion, and the biomechanical parameters of hand movement were calculated. RESULTS: The mean amount of phlegm suctioned per second was significantly larger in the experienced group than in the non-experienced group. The amount of phlegm suctioned correlated positively with the length of the vertical path of motion of the wrist and forearm, and with the angular velocity of thumb rotation in both the groups. CONCLUSION: Greater vertical motion of the wrist and thumb rotation improved the effectiveness of phlegm suctioning and prevented the need for deep suctioning, which is unsafe."
1317,Long-Term Outcomes After Open Repair for Ruptured Abdominal Aortic Aneurysm,"BACKGROUND: Early mortality in ruptured abdominal aneurysm (rAAA) is high, but data on long-term outcome are scarce. The aim of this study was to investigate the long-term outcome in survivors after open surgery for rAAA in well-defined population. METHODS: This is a population-based, observational long-term follow-up (beyond 30-day mortality) study of patients surgically treated for rAAA from 2000 through 2014. Long-term survival was analysed using Kaplan–Meier estimates and compared to the general population by analyses of relative survival. RESULTS: Out of 178 patients operated for rAAA, 95 patients (55%) either died in the perioperative period, were referred from other hospitals or were lost to follow-up (two patients). Altogether 83 patients were eligible for long-term outcomes: 72 men and 11 women. Estimated median crude survival time was 6.5 years [95% confidence interval (CI) 4.8–8.2]. Men had a median survival of 7.3 years (95% CI 5.1–9.4) versus 5.4 years in females (95% CI 3.5–7.3) (P = 0.082). Reinterventions during follow-up occurred in 31 (37%). Relative survival demonstrated a slightly higher risk of death in the rAAA population compared to the general age- and gender-matched population. Age, but not comorbidities, had a significant influence on long-term survival. CONCLUSION: For survivors beyond 30 days after surgery for rAAA, long-term survival compares well to that of an age- and sex-matched population. A high frequency of cardiovascular comorbidities did not seem to affect long-term survival."
1318,Interventions to Improve Antiretroviral Therapy Adherence Among Adolescents and Youth in Low- and Middle-Income Countries: A Systematic Review 2015–2019,"Adolescents and youth living with HIV have poorer antiretroviral treatment (ART) adherence and viral suppression outcomes than all other age groups. Effective interventions promoting adherence are urgently needed. We reviewed and synthesized recent literature on interventions to improve ART adherence among this vulnerable population. We focus on studies conducted in low- and middle-income countries (LMIC) where the adolescent and youth HIV burden is greatest. Articles published between September 2015 and January 2019 were identified through PubMed. Inclusion criteria were: [1] included participants ages 10–24 years; [2] assessed the efficacy of an intervention to improve ART adherence; [3] reported an ART adherence measurement or viral load; [4] conducted in a LMIC. Articles were reviewed for study population characteristics, intervention type, study design, outcomes measured, and intervention effect. Strength of each study’s evidence was evaluated according to an adapted World Health Organization GRADE system. Articles meeting all inclusion criteria except being conducted in an LMIC were reviewed for results and potential transportability to a LMIC setting. Of 108 articles identified, 7 met criteria for inclusion. Three evaluated patient-level interventions and four evaluated health services interventions. Of the patient-level interventions, two were experimental designs and one was a retrospective cohort study. None of these interventions improved ART adherence or viral suppression. Of the four health services interventions, two targeted stable patients and reduced the amount of time spent in the clinic or grouped patients together for bi-monthly meetings, and two targeted patients newly diagnosed with HIV or not yet deemed clinically stable and augmented clinical care with home-based case-management. The two studies targeting stable patients used retrospective cohort designs and found that adolescents and youth were less likely to maintain viral suppression than children or adults. The two studies targeting patients not yet deemed clinically stable included one experimental and one retrospective cohort design and showed improved ART adherence and viral suppression outcomes. ART adherence and viral suppression outcomes remain a major challenge among adolescents and youth. Intensive home-based case management models of care hold promise for improving outcomes in this population and warrant further research."
1319,"The contribution of frailty, cognition, activity of daily life and comorbidities on outcome in acutely admitted patients over 80 years in European ICUs: the VIP2 study","PURPOSE: Premorbid conditions affect prognosis of acutely-ill aged patients. Several lines of evidence suggest geriatric syndromes need to be assessed but little is known on their relative effect on the 30-day survival after ICU admission. The primary aim of this study was to describe the prevalence of frailty, cognition decline and activity of daily life in addition to the presence of comorbidity and polypharmacy and to assess their influence on 30-day survival. METHODS: Prospective cohort study with 242 ICUs from 22 countries. Patients 80 years or above acutely admitted over a six months period to an ICU between May 2018 and May 2019 were included. In addition to common patients’ characteristics and disease severity, we collected information on specific geriatric syndromes as potential predictive factors for 30-day survival, frailty (Clinical Frailty scale) with a CFS > 4 defining frail patients, cognitive impairment (informant questionnaire on cognitive decline in the elderly (IQCODE) with IQCODE ≥ 3.5 defining cognitive decline, and disability (measured the activity of daily life with the Katz index) with ADL ≤ 4 defining disability. A Principal Component Analysis to identify co-linearity between geriatric syndromes was performed and from this a multivariable model was built with all geriatric information or only one: CFS, IQCODE or ADL. Akaike’s information criterion across imputations was used to evaluate the goodness of fit of our models. RESULTS: We included 3920 patients with a median age of 84 years (IQR: 81–87), 53.3% males). 80% received at least one organ support. The median ICU length of stay was 3.88 days (IQR: 1.83–8). The ICU and 30-day survival were 72.5% and 61.2% respectively. The geriatric conditions were median (IQR): CFS: 4 (3–6); IQCODE: 3.19 (3–3.69); ADL: 6 (4–6); Comorbidity and Polypharmacy score (CPS): 10 (7–14). CFS, ADL and IQCODE were closely correlated. The multivariable analysis identified predictors of 1-month mortality (HR; 95% CI): Age (per 1 year increase): 1.02 (1.–1.03, p = 0.01), ICU admission diagnosis, sequential organ failure assessment score (SOFA) (per point): 1.15 (1.14–1.17, p < 0.0001) and CFS (per point): 1.1 (1.05–1.15, p < 0.001). CFS remained an independent factor after inclusion of life-sustaining treatment limitation in the model. CONCLUSION: We confirm that frailty assessment using the CFS is able to predict short-term mortality in elderly patients admitted to ICU. Other geriatric syndromes do not add improvement to the prediction model. Since CFS is easy to measure, it should be routinely collected for all elderly ICU patients in particular in connection to advance care plans, and should be used in decision making. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05853-1) contains supplementary material, which is available to authorized users."
1320,Dietary supplementation with Withania somnifera root powder ameliorates experimentally induced Infectious Bursal Disease in chicken,"Infectious Bursal Disease (IBD) is an economically important, immunosuppressive viral disease of chicken. Withania somnifera, a well-known Indian medicinal plant and functional food, finds extensive ethnomedicinal and ethnoveterinary use in the subcontinent. Root extracts of Withania somnifera have been shown to inhibit IBD virus (IBDV) in vitro. The effect of dietary supplementation with whole root powder of Withania somnifera was studied in chicken experimentally infected with IBDV. Dietary supplementation with the root powder improved erythrocytic indices, biochemical parameters, bursal weight index, and lymphocyte stimulation indices, and reduced histopathological insult in the infected birds. Viral load decreased to less than one-fourth in the birds receiving dietary supplementation with Withania somnifera root powder. It could be concluded that continued supplementation of IBDV-infected chicken with Withania somnifera root powder alleviated virus-induced stress and histological and immunological alterations and reduced viral persistence in the host."
1321,Dual-targeting nanoparticle vaccine elicits a therapeutic antibody response against chronic hepatitis B,"Chronic hepatitis B is caused by prolonged infection with the hepatitis B virus (HBV), which can substantially increase the risk of developing liver disease. Despite the development of preventive vaccines against HBV, a therapeutic vaccine inducing an effective antibody response still remains elusive. The preS1 domain of the large HBV surface protein is the major viral attachment site on hepatocytes and thus offers a therapeutic target; however, its poor immunogenicity limits clinical translation. Here, we design a ferritin nanoparticle vaccine that can deliver preS1 to specific myeloid cells, including SIGNR1(+) dendritic cells (which activate T follicular helper cells) and lymphatic sinus-associated SIGNR1(+) macrophages (which can activate B cells). This nanoparticle vaccine induces a high-level and persistent anti-preS1 response that results in efficient viral clearance and partial serological conversion in a chronic HBV mouse model, offering a promising translatable vaccination strategy for the functional cure of chronic hepatitis B."
1322,"Benefit-to-risk balance of bronchoalveolar lavage in the critically ill. A prospective, multicenter cohort study","PURPOSE: To assess the benefit-to-risk balance of bronchoalveolar lavage (BAL) in intensive care unit (ICU) patients. METHODS: In 16 ICUs, we prospectively collected adverse events during or within 24 h after BAL and assessed the BAL input for decision making in consecutive adult patients. The occurrence of a clinical adverse event at least of grade 3, i.e., sufficiently severe to need therapeutic action(s), including modification(s) in respiratory support, defined poor BAL tolerance. The BAL input for decision making was declared satisfactory if it allowed to interrupt or initiate one or several treatments. RESULTS: We included 483 BAL in 483 patients [age 63 years (interquartile range (IQR) 53–72); female gender: 162 (33.5%); simplified acute physiology score II: 48 (IQR 37-61); immunosuppression 244 (50.5%)]. BAL was begun in non-intubated patients in 105 (21.7%) cases. Sixty-seven (13.9%) patients reached the grade 3 of adverse event or higher. Logistic regression showed that a BAL performed by a non-experienced physician (non-pulmonologist, or intensivist with less than 10 years in the specialty or less than 50 BAL performed) was the main predictor of poor BAL tolerance in non-intubated patients [OR: 3.57 (95% confidence interval 1.04–12.35); P = 0.04]. A satisfactory BAL input for decision making was observed in 227 (47.0%) cases and was not predictable using logistic regression. CONCLUSIONS: Adverse events related to BAL in ICU patients are not infrequent nor necessarily benign. Our findings call for an extreme caution, when envisaging a BAL in ICU patients and for a mandatory accompaniment of the less experienced physicians. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05896-4) contains supplementary material, which is available to authorized users."
1323,Lung-ultrasound objective structured assessment of technical skills (LUS-OSAUS): utility in the assessment of lung-ultrasound trained medical undergraduates,"PURPOSE: Recently, some attempts have been made to integrate lung ultrasound (LUS) teaching into medical curricula. However, current education studies of LUS are extremely heterogeneous due to the lack of evidence-based guidelines on LUS education. In particular, the assessment of competencies is poorly standardized and mostly relies on non-validated scales. A new validated tool, the objective structured assessment of lung ultrasound skills (LUS-OSAUS), has the potential to overcome these limitations. Therefore, we adopted the LUS-OSAUS tool to assess the competencies of a group of LUS-trained undergraduates. Existing no prior practical applications of the LUS-OSAUS, our aim was to investigate the practical utility of this tool and its applicability in the evaluation of US-trained medical students. METHODS: Eight undergraduates (two males, six females) were enrolled on a voluntary basis to receive a theoretical and practical training in LUS. Once completed their training, each student performed an LUS examination on a different patient hospitalized for respiratory symptoms. The same eight patients were also scanned by a senior resident in emergency medicine for a comparison with students’ results. Students and the senior resident were tested by an examiner using the LUS-OSAUS tool. We compared the scores obtained by operators in all areas of competence of the LUS-OSAUS, the total scores, and the time needed to complete the sonographic task. RESULTS: Median students’ score in the single items of the scale was significantly lower than the ones obtained by the senior resident (4.0 [3.3–5.0] vs. 5.0 [5.0–5.0]; p < 0.0001). Students scored significantly lower than the senior resident in each item, except for B-line identification, choice of the correct transducer, and suggested focused questions. Median total score was also lower for students compared to the senior resident (70.5 [61.0–74.8] vs. 84.0 [83.5–84.3] (p = 0.0116). Median time required to complete the examination was significantly higher for students (14.1 [12.8–16.1] vs. 4.7 [3.9–5.2] min, p = 0.0117). CONCLUSIONS: The LUS-OSAUS tool allowed for a standardized and comprehensive assessment of student’s competencies in lung ultrasound, and helped to discriminate their level of expertise from that of a more experienced operator. The scale also specifically tests the theoretical knowledge of trainees, thus making redundant the use of questionnaires designed for this purpose. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40477-020-00454-x) contains supplementary material, which is available to authorized users."
1324,"The CTA1-DD adjuvant strongly potentiates follicular dendritic cell function and germinal center formation, which results in improved neonatal immunization","Vaccination of neonates and young infants is hampered by the relative immaturity of their immune systems and the lack of safe and efficacious vaccine adjuvants. Immaturity of the follicular dendritic cells (FDCs), in particular, appears to play a critical role for the inability to stimulate immune responses. Using the CD21mT/mG mouse model we found that at 7 days of life, FDCs exhibited a mature phenotype only in the Peyer´s patches (PP), but our unique adjuvant, CTA1-DD, effectively matured FDCs also in peripheral lymph nodes following systemic, as well as mucosal immunizations. This was a direct effect of complement receptor 2-binding to the FDC and a CTA1-enzyme-dependent enhancing effect on gene transcription, among which CR2, IL-6, ICAM-1, IL-1β, and CXCL13 encoding genes were upregulated. This way we achieved FDC maturation, increased germinal center B-cell- and Tfh responses, and enhanced specific antibody levels close to adult magnitudes. Oral priming immunization of neonates against influenza infection with CTA1-3M2e-DD effectively promoted anti-M2e-immunity and significantly reduced morbidity against a live virus challenge infection. To the best of our knowledge, this is the first study to demonstrate direct effects of an adjuvant on FDC gene transcriptional functions and the subsequent enhancement of neonatal immune responses."
1325,Effect of corticosteroids on myocardial injury among patients hospitalized for community-acquired pneumonia: rationale and study design. The colosseum trial,"Community-acquired pneumonia (CAP) is often complicated by elevation of cardiac troponin, a marker of myocardial injury that can be isolated or associated with myocardial infarction (MI). A retrospective study showed that corticosteroid treatment lowers the incidence of MI during the hospital stay. No data exist so far on the effect of corticosteroids on myocardial injury in CAP patients. The primary objective of the study is to evaluate if methylprednisolone is able to reduce myocardial injury, as assessed by serum high-sensitivity cardiac T Troponin (hs-cTnT), in a cohort of patients hospitalized for CAP. Secondary aims are to evaluate the potential effect of methylprednisolone on cardiovascular events during hospitalization, at 30 days from hospital admission and during 2 years’ follow-up. The trial will also examine whether the potential protective effects of methylprednisolone might be due to platelet activation down-regulation. Double-blind randomized placebo-controlled trial. One hundred twenty-two eligible patients will be randomized to a week treatment with iv methylprednisolone (20 mg b.i.d) or placebo from hospital admission. Serum hs-cTnT will be measured at admission and every day until up 3 days from admission. ECG will be monitored every day until discharge. After discharge, all patients will be followed-up 2 years. This is the first clinical trial aimed at examining whether methylprednisolone treatment may reduce myocardial injury. The results of this trial may constitute the basis for conducting a larger multicenter trial aimed to evaluate the effect of corticosteroid on cardiovascular events in this setting."
1326,"The implications of Neoliberalism on African economies, health outcomes and wellbeing: a conceptual argument","Not only did the 2015 Ebola Outbreak in West African countries leave the whole of the sub-Saharan region with a sense of uncertainty and panic, it was also a stress test to Africa’s and the wider world’s capacity to respond to and mitigate humanitarian crises in the twenty-first century. One plausible conclusion drawn from the spread and impact of the pandemic is that the pace of health infrastructure development in sub-Saharan Africa has lagged behind its population and economic growth posted in the last decade (2003–2013). An exhaustive audit of health infrastructure and remedial measures is, therefore, critical in navigating Africa to sustainable growth and development in the next decade. For the next charge of growth and development to not only be robust but also more sustainable and resilient to major emergencies (such as Ebola), there is a need to edify the state of healthcare across the continent to ensure the optimisation of the human resource and to redress the gap aggravated by loss of human-hours due to poor health."
1327,Metal ions and graphene-based compounds as alternative treatment options for burn wounds infected by antibiotic-resistant Pseudomonas aeruginosa,"Burn infections caused by Pseudomonas aeruginosa pose a major complication in wound healing. This study aimed to determine the antimicrobial effect of metal ions, graphene (Gr), and graphene oxide (GO), individually and in combination, against the planktonic and biofilm states of two antimicrobially resistant clinical strains of P. aeruginosa each with different antibiotic resistance profiles. Minimum inhibitory, minimum bactericidal, and fractional inhibitory concentrations were performed to determine the efficacy of the metal ions and graphene composites individually and their synergy in combination. Crystal violet biofilm and XTT assays measured the biofilm inhibition and metabolic activity, respectively. Molybdenum, platinum, tin, gold, and palladium ions exhibited the greatest antimicrobial activity (MIC = 7.8–26.0 mg/L), whilst GO and Gr demonstrated moderate-to-no effect against the planktonic bacterial cells, irrespective of their antibiograms. Biofilms were inhibited by zinc, palladium, silver, and graphene. In combination, silver–graphene and molybdenum–graphene inhibited both the planktonic and biofilm forms of the bacteria making them potential candidates for development into topical antimicrobials for burns patients infected with antibiotic-resistant P. aeruginosa."
1328,Characteristics associated with spine injury on magnetic resonance imaging in children evaluated for abusive head trauma,"BACKGROUND: Spine injuries are increasingly common in the evaluation for abusive head trauma (AHT), but additional information is needed to explore the utility of spine MRI in AHT evaluations and to ensure an accurate understanding of injury mechanism. OBJECTIVE: To assess the incidence of spine injury on MRI in children evaluated for AHT, and to correlate spine MRI findings with clinical characteristics. MATERIALS AND METHODS: We identified children younger than 5 years who were evaluated for AHT with spine MRI. Abuse likelihood was determined a priori by expert consensus. We blindly reviewed spine MRIs and compared spinal injury, abuse likelihood, patient demographics, severity of brain injury, presence of retinal hemorrhages, and pattern of head injury between children with and without spine injury. RESULTS: Forty-five of 76 (59.2%) children had spine injury. Spine injury was associated with more severe injury (longer intensive care stays [P<0.001], lower initial mental status [P=0.01] and longer ventilation times [P=0.001]). Overall abuse likelihood and spine injury were not associated. Spinal subdural hemorrhage was the only finding associated with a combination of retinal hemorrhages (P=0.01), noncontact head injuries (P=0.008) and a diagnosis of AHT (P<0.05). Spinal subdural hemorrhage was associated with other spine injury (P=0.004) but not with intracranial hemorrhage (P=0.28). CONCLUSION: Spinal injury is seen in most children evaluated for AHT and might be clinically and forensically valuable. Spinal subdural hemorrhage might support a mechanism of severe acceleration/deceleration head injury and a diagnosis of AHT."
1329,Practical guide for safe central venous catheterization and management 2017,"Central venous catheterization is a basic skill applicable in various medical fields. However, because it may occasionally cause lethal complications, we developed this practical guide that will help a novice operator successfully perform central venous catheterization using ultrasound guidance. The focus of this practical guide is patient safety. It details the fundamental knowledge and techniques that are indispensable for performing ultrasound-guided internal jugular vein catheterization (other choices of indwelling catheters, subclavian, axillary, and femoral venous catheter, or peripherally inserted central venous catheter are also described in alternatives)."
1330,The pig as a model for immunology research,"The pig is an omnivorous, monogastric species with many advantages to serve as an animal model for human diseases. There are very high similarities to humans in anatomy and functions of the immune system, e g., the presence of tonsils, which are absent in rodents. The porcine immune system resembles man for more than 80% of analyzed parameters in contrast to the mouse with only about 10%. The pig can easily be bred, and there are less emotional problems to use them as experimental animals than dogs or monkeys. Indwelling cannulas in a vein or lymphatic vessel enable repetitive stress-free sampling. Meanwhile, there are many markers available to characterize immune cells. Lymphoid organs, their function, and their role in lymphocyte kinetics (proliferation and migration) are reviewed. For long-term experiments, minipigs (e.g., Göttingen minipig) are available. Pigs can be kept under gnotobiotic (germfree) conditions for some time after birth to study the effects of microbiota. The effects of probiotics can be tested on the gut immune system. The lung has been used for extracorporeal preservation and immune engineering. After genetic modifications are established, the pig is the best animal model for future xenotransplantation to reduce the problem of organ shortage for organ transplantation. Autotransplantation of particles of lymphnodes regenerates in the subcutaneous tissue. This is a model to treat secondary lymphedema patients. There are pigs with cystic fibrosis and severe combined immune deficiency available."
1331,Entwicklung von Impfstoffen gegen Malaria – aktueller Stand,"Globally, 3.1 billion people live in areas endemic for malaria (the tropics and subtropics). Annually, around 200 million fall ill, and around 500,000 persons die as a result of this infection. Mainly children are the victims. In order to control and eventually prevent any new infection, the development of effective vaccines is pivotal. In this review, background information about the history of vaccine development and malaria disease as well as possibilities for therapy and control is given. In the main part of the article, an update on the development of vaccines against Plasmodium falciparum is provided followed by an extensive discussion. Malaria is a parasitic infectious disease caused by the single cell organism Plasmodium. Five different Plasmodium species can induce disease in humans with P. falciparum being the origin for more than 99% of infections in Africa. The vector is the Anopheles mosquito. The life cycle of Plasmodium offers several approaches for vaccines to have an impact. Out of around 70 candidates, pre-erythrocytic vaccine candidates interfering with the liver phase of the parasite are the most developed. However, a vaccine with more than 75% efficacy, as required by the World Health Organization (WHO), is not yet in sight. Currently, for the first time, a moderately efficacious vaccine (RTS,S/AS01) is being applied in large-scale operations. But it is obvious that malaria can only be controlled in combination with concurring measures. For example, the use of impregnated mosquito nets, indoor residual spraying, elimination of vector breeding sites, rapid diagnosis, and therapy of the infection as well as a functioning health system are important elements, which can hardly be guaranteed in areas characterized by poverty."
1332,Evaluation of a Loop-Mediated Isothermal Amplification Technique for the Rapid Visual Detection of Hepatozoon canis Infection,"BACKGROUND: Laboratory diagnosis of Hepatozoon canis infection is tedious, especially in chronic and/or latent infections. PURPOSE: The study was planned to develop a simple read out loop mediated isothermal amplification (LAMP) assay targeting a partial 18S rRNA gene of H. canis with naked eye visualisation of LAMP products. METHODS: A LAMP assay was employed to assess the DNA amplification by adding SYBR Green I dye for naked eye inspection of DNA accumulating in reaction tubes. Positive amplification was read through observation of change in colour of reaction mixture following addition of dye. The visual results were further verified with those of agarose gel electrophoresis. Genomic DNA of other haemoparasites of dog viz. Babesia vogeli, B. gibsoni, Ehrlichia canis and Trypanosoma evansi along with no-template control were used to determine the specificity of assay. RESULTS: Among the 109 blood samples presented at Small Animal Clinics, Teaching Veterinary Clinical Complex, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana, Punjab (India) tested, 39 revealed colour change from orange to green indicating positive reaction while 70 were negative as revealed by no colour change. The results of visual inspection were comparable to those obtained by agarose gel electrophoresis. The LAMP primers specifically amplified H. canis DNA, whereas no amplification was detected in DNA samples of other haemoparasites and no-template control revealing specificity of the assay. The diagnostic sensitivity and specificity (95% CI) of visual LAMP assay with respect to microscopy in detection of H. canis varied from 100% (15.81–100.00%) and 65.42% (55.61–74.35%), respectively. CONCLUSION: The present investigation has developed a specific and rapid LAMP assay for the detection of H. canis, using SYBR Green I dye, which has practical applications for the screening of field samples."
1333,Rib fracture displacement worsens over time,"PURPOSE: Rib fractures (RF) occur in 10% of trauma patients; associated with significant morbidity and mortality. Despite advancing technology of surgical stabilization of rib fractures (SSRF), treatment and indications remain controversial. Lack of displacement is often cited as a reason for non-operative management. The purpose was to examine RF patterns hypothesizing RF become more displaced over time. METHODS: Retrospective review of all RF patients from 2016–2017 at our institution. Patients with initial chest CT (CT1) followed by repeat CT (CT2) within 84 days were included. Basic demographics were obtained. Primary outcomes included RF displacement in millimeters (mm) between CT1 and CT2 in three planes (AP = anterior/posterior, O = overlap/gap, and SI = superior/inferior). Displacement was calculated by subtracting CT1 fracture displacement from CT2 displacement for each rib. Given anatomic and clinical characteristics, ribs were grouped (1–2, 3–6, 7–10, 11–12), averaged, and analyzed for displacement. Secondary outcome included number of missed RF on CT1. Non-parametric sign test and paired t test were used for analysis. Significance was set at p < 0.002. RESULTS: 78 of 477 patients with RF on CT1 had CT2 during the study period: primarily male (76%) and age 55.8 ± 20.1 with blunt mechanism of injury (99%). Median Injury Severity Score was 21 (IQR, 13–27) with Chest Abbreviated Injury Score of 3 (IQR, 3–4). Median time between CT1 and CT2 was 6 days (IQR, 3–12). Missed RF rate for CT1 was 10.1% (p = 0.11). Average fracture displacement was significantly increased for all rib groupings except 11–12 in all planes (p < 0.002). CONCLUSION: RF become more displaced over time. Pain regimens and SSRF considerations should be adjusted accordingly."
1334,A model of respiratory syncytial virus (RSV) infection of infants in newborn lambs,"Many animal models have been established for respiratory syncytial virus (RSV) infection of infants with the purpose of studying the pathogenesis, immunological response, and pharmaceutical testing and the objective of finding novel therapies and preventive measures. This review centers on a neonatal lamb model of RSV infection that has similarities to RSV infection of infants. It includes a comprehensive description of anatomical and immunological similarities between ovine and human lungs along with comparison of pulmonary changes and immune responses with RSV infection. These features make the newborn lamb an effective model for investigating key aspects of RSV infection in infants. The importance of RSV lamb model application in preclinical therapeutic trials and current updates on new studies with the RSV-infected neonatal lamb are also highlighted."
1335,A pilot study exploring interventions for physician distress in pediatric subspecialists,"BACKGROUND: While institution-sponsored wellness programs may be effective, little is known about their availability and utilization in pediatric subspecialists, and about programs physicians wish were available. METHODS: A survey of perceptions about, and availability and utilization of institutional wellness activities, was distributed electronically to pediatric subspecialists nationally. Bivariate analyses were performed using χ(2) tests or independent t tests. Multivariable logistic regression models for categories of institution-sponsored programming as a function of potential predictors of program utilization were performed. Qualitative content analysis was performed for free-text survey answers. RESULTS: Approximately 60% of respondents participated in institution-sponsored wellness opportunities. Debriefs, Schwartz Center Rounds, mental health services, and team building events were the most available institution-sponsored wellness activities, whereas debriefs, team building, Schwartz Center Rounds, and pet therapy were most frequently utilized. Respondents desired greater social/emotional support, improved leadership, enhanced organizational support, and modifications to the physical work environment, with no significant differences across subspecialties for “wish list” items. CONCLUSIONS: Physician wellness requires more than a “one-size-fits-all” initiative. Our data highlight the importance of encouraging and normalizing self-care practices, and of listening to what physicians articulate about their needs. Pre-implementation needs assessment allows a “bottom-up” approach where physician voices can be heard."
1336,Improved MHC II epitope prediction — a step towards personalized medicine,"Numerous neoepitope-based vaccination strategies are in testing for clinical use in the treatment of cancer. Rapid identification of immunostimulatory neoantigen targets hastens neoantigen vaccine development. Papers recently published in Nature Biotechnology describe two independent machine-learning-based algorithms that demonstrate improved identification of MHC class II-binding peptides. Herein, we outline the benefits of these algorithms and their implications for future immunotherapies."
1337,A Real-World Analysis of Patient Characteristics and Predictors of Hospitalization Among US Medicare Beneficiaries with Respiratory Syncytial Virus Infection,"INTRODUCTION: Little has been published on respiratory syncytial virus (RSV) among Medicare patients at high risk (HR) of RSV complications due to age or comorbidity. METHODS: Adult patients (at least 18 years of age) with at least 1 diagnostic code for RSV were identified using the 5% US Medicare database from 2011 through 2015. Patients were required to have continuous health plan enrollment for 180 days pre- and 180 days post-RSV diagnosis (baseline and follow-up periods, respectively). HR was defined as diagnosis of chronic lung disease, congestive heart failure, or weakened immune system for 180 days during the baseline period. Patients were categorized as initially hospitalized if hospitalized within 1 day of RSV diagnosis. Logistic regression models were developed to determine predictors of initial hospitalization. Healthcare utilization and costs for 180 days pre- and post-RSV diagnosis were compared. RESULTS: The study included 756 HR patients who were initially hospitalized with RSV diagnoses. Among these, 61.7% were diagnosed in the emergency department vs 15.3% in a physician’s office, with hypertension (76.3%), chronic obstructive pulmonary disease (COPD) (53.7%), and high cholesterol (52.0%) observed as the most prevalent comorbidities. Of these, COPD, congestive heart failure, chronic kidney disease, and previous evidence of pneumonia were significant predictors of hospitalization. Other significant predictors of hospitalization included older age, hematological malignancies, stroke, and baseline healthcare resource use. Among both HR and non-HR hospitalized patients, there was a significant increase in healthcare resource utilization following hospitalization, including the number of inpatient admissions and longer hospital stays post-RSV diagnosis. The total mean all-cause healthcare costs among HR hospitalized patients increased by $9210 per patient (p < 0.0001) post-RSV diagnosis. CONCLUSION: Hospitalized Medicare beneficiaries with RSV infections pose a significant healthcare burden as compared with non-hospitalized patients, mainly driven by higher comorbidity, higher likelihood of multiple inpatient admissions, and costly medical interventions."
1338,Approaches to optimize therapeutic bacteriophage and bacteriophage-derived products to combat bacterial infections,"The emerging occurrence of antibiotic-resistant bacterial pathogens leads to a recollection of bacteriophage as antimicrobial therapeutics. This article presents a short overview of the clinical phage application including their use in military medicine and discusses the genotypic and phenotypic properties of a potential “ideal” therapeutic phage. We describe current efforts to engineer phage for their improved usability in pathogen treatment. In addition, phage can be applied for pathogen detection, selective drug delivery, vaccine development, or food and surface decontamination. Instead of viable phage, (engineered) phage-derived enzymes, such as polysaccharide depolymerases or peptidoglycan-degrading enzymes, are considered as promising therapeutic candidates. Finally, we briefly summarize the use of phage for the detection and treatment of “Category A priority pathogens”."
1339,The recurrent bleeding risk of a Forrest IIc lesion at the second-look endoscopy can be indicated by high Rockall scores ≥ 6,"BACKGROUND: The Forrest classification is widely applied to guide endoscopic hemostasis for peptic ulcer bleeding. Accordingly, practice guidelines suggest medical treatment only for ulcer with a Forrest IIc lesion because it has low rebleeding risk even without endoscopic therapy, ranging from 0 to 13%. However, the risk ranges widely and it is unclear who is at risk of rebleeding with such a lesion. This study assessed whether the Rockall score, which evaluates patients holistically, could indicate the risk of recurrent bleeding among patients with a Forrest IIc lesion at the second-look endoscopy. METHODS: Patients who had peptic ulcer bleeding with Ia-IIb lesions received endoscopic hemostasis at the primary endoscopy, and they were enrolled if their Ia-IIb lesions had been fading to IIc at the second-look endoscopy after 48- to 72-h intravenous proton pump inhibitor (PPI) infusion. Primary outcomes were rebleeding during the 4th–14th day and 4(th)–28th day after the first bleeding episode. RESULTS: The prospective cohort study enrolled 140 patients, who were divided into a Rockall scores ≥ 6 group or a Rockall scores < 6 group. The rebleeding rates in the Rockall scores ≥ 6 group and the Rockall scores < 6 group during the 4th–14th day and the 4th–28th day were 13/70 (18.6%) versus 2/70 (2.9%), p = 0.003 and 17/70 (24.3%) versus 3/70 (4.3%), p = 0.001, respectively, based on an intention-to-treat analysis and 5/62 (8.1%) versus 0/68 (0%), p = 0.023 and 6/59 (10.2%) versus 0/67 (0%), p = 0.009, respectively, based on a per-protocol analysis. The Kaplan–Meier curves showed that the Rockall scores ≥ 6 group had a significantly lower cumulative rebleeding-free proportion than the Rockall scores < 6 group (p = 0.01). CONCLUSIONS: Combined Rockall scores ≥ 6 on arrival with a Forrest IIc lesion at the second-look endoscopy can identify patients at risk of recurrent peptic ulcer bleeding following initial endoscopic and intravenous PPI treatment. Trial registration Trial registration identifier: NCT01591083"
1340,In Silico Modeling of Crimean Congo Hemorrhagic Fever Virus Glycoprotein-N and Screening of Anti Viral Hits by Virtual Screening,"Crimean-Congo hemorrhagic fever (CCHF) is a widespread zoonotic viral disease, caused by a tick-born virus Crimean-Congo hemorrhagic fever virus (CCHFV). This disease is endemic in Middle East, Asia, Africa and South-Eastern Europe with the mortality rate of 5–30%. CCHFV genome is composed of three segments: large, medium and small segments. M segment encodes a polyprotein (glycoprotein) so called glycoprotein N (Gn) which is considered as a potential druggable target for the effective therapy of CCHF. The complete structure of Gn is still not characterized. The aim of the current study is to predict the complete three-dimensional (3D-) structure of CCHFV Gn protein via threading-based modeling and investigate the residues crucial for binding with CCHFV envelop. The developed model displayed excellent stereo-chemical and geometrical properties. Subsequently structure based virtual screening (SBVS) was applied to discover novel inhibitors of Gn protein. A library of > 1300 anti-virals was selected from PubChem database and directed to the predicted binding site of Gn. The SBVS results led to the identification of thirty-seven compounds that inhibit the protein in computational analysis. Those 37 hits were subject to pharmacokinetic profiling which demonstrated that 30/37 compound possess safer pharmacokinetic properties. Thus, by specifically targeting Gn, less toxic and more potent inhibitors of CCHFV were identified in silico. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10989-020-10055-1) contains supplementary material, which is available to authorized users."
1341,"Outer Membrane Protein, Oma87 Prevents Acinetobacter baumannii Infection","Acinetobacter baumannii is one of the most problematic pathogens in clinical settings. Emerging of its antibiotic-resistant strains persuade researchers to find alternative treatment options such as immunization against the notorious nosocomial pathogen. Oma87 has been introduced as an immunogenic outer membrane protein via reverse vaccinology. However, protectivity of A. baumannii Oma87 is not well known. The current research undertakes a study on the immunogenicity of recombinant Oma87 in a murine model. Some physico-chemical properties were assessed via in silico analyses. The corresponding gene was amplified and cloned into pET28a plasmid. The recombinant protein was purified and then was administered to immunize mice. Sera obtained from the immunized mice were assessed with respect to the triggered antibodies. Challenges were performed on actively or passively immunized mice. In silico analyses revealed that this protein is the same as BamA. A high titer of specific antibody was raised against rOma87 even after the first injection. The specific antibody recognized the whole cell of A. baumannii. Both active and passive immunizations confer 100 and 50% protection, respectively against ~ 2 × lethal dose (LD) of A. baumannii in the murine sepsis model. Although none of mice received ~ 5 × LD of A. baumannii survived in passive immunization, 25% of mice challenged with ~ 7 × LD of the bacteria survived and the dead mice exhibited a delayed death. Based on these results, Oma87 is the same as BamA which could be considered as a promising vaccine candidate against A. baumannii in the sepsis model. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10989-020-10056-0) contains supplementary material, which is available to authorized users."
1342,Outcomes after pneumonectomy versus limited lung resection in adults with traumatic lung injury,"Pneumonectomy after traumatic lung injury (TLI) is associated with shock, increased pulmonary vascular resistance, and eventual right ventricular failure. Historically, trauma pneumonectomy (TP) mortality rates ranged between 53 and 100%. It is unclear if contemporary mortality rates have improved. Therefore, we evaluated outcomes associated with TP and limited lung resections (LLR) (i.e., lobectomy and segmentectomy) and aimed to identify predictors of mortality, hypothesizing that TP is associated with greater mortality versus LLR. We queried the Trauma Quality Improvement Program (2010–2016) and performed a multivariable logistic regression to determine the independent predictors of mortality in TLI patients undergoing TP versus LLR. TLI occurred in 287,276 patients. Of these, 889 required lung resection with 758 (85.3%) undergoing LLR and 131 (14.7%) undergoing TP. Patients undergoing TP had a higher median injury severity score (26.0 vs. 24.5, p = 0.03) but no difference in initial median systolic blood pressure (109 vs. 107 mmHg, p = 0.92) compared to LLR. Mortality was significantly higher for TP compared to LLR (64.9% vs 27.2%, p < 0.001). The strongest independent predictor for mortality was undergoing TP versus LLR (OR 4.89, CI 3.18–7.54, p < 0.001). TP continues to be associated with a higher mortality compared to LLR. Furthermore, TP is independently associated with a fivefold increased risk of mortality compared to LLR. Future investigations should focus on identifying parameters or treatment modalities that improve survivability after TP. We recommend that surgeons reserve TP as a last-resort management given the continued high morbidity and mortality associated with this procedure."
1343,"Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases","Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy–Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment."
1344,Epidemiological characteristics and early complications after spinal cord injury in Former Yugoslav Republic of Macedonia,"STUDY DESIGN: Prospective cohort study OBJECTIVES: To describe epidemiological data and complications after acute traumatic spinal cord injury (tSCI) in Former Yugoslav Republic of Macedonia (FYROM). SETTING: University Clinic for Traumatology, Orthopedics, Anesthesia and Intensive Care Unit and Emergency Center (TOARILUC), Mother Teresa, Skopje, FYROM. METHOD: During the inclusion period March 2015 to September 2016, 38 tSCI patients were included. MRI, CT scan, and clinical examinations including International Standards for Neurological Classification of SCI were performed at admission. The information included: demographic data, transport type, date of admission and discharge, past illnesses, addiction habits, cause and type of injury, injury level, associated injuries, injury-related complications, and mortality. RESULTS: Mean age was 43 years (median 41, range 17–83). Seventeen patients had a complete and 15 an incomplete SCI, six were unknown. Most frequent causes for tSCI were traffic accidents (42%) and falls (40%), 24% of the accidents were contracted at work. Sixteen patients were ventilator dependent at some point during the acute period. Common complications were pressure ulcers, gastrointestinal-related, and infections. Hospital length of stay (LOS) ranged from 1 to 73 days. The in-hospital mortality rate was 32%. CONCLUSION: The annual incidence of tSCI in FYROM was in 2015–16 13 persons/million inhabitants per year. The epidemiological profile of tSCI in FYROM implies that preventive measures should be taken to reduce incidence of accidents in traffic and at work places. The high mortality rate and complications underline further actions to improve the acute care of tSCI in FYROM."
1345,Bioinformatics Analysis of Domain 1 of HCV-Core Protein: Iran,"Hepatitis C virus (HCV) infection is a serious global health problem and a cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Bioinformatics software has been an effective tool to study the HCV genome as well as core domains. Our research was based on employing several bioinformatics software applications to find important mutations in domain 1 of core protein in Iranian HCV infected samples from 2006 to 2017, and an investigation of general properties, B-cell and T-cell epitopes, modification sites, and structure of domain 1. Domain 1 sequences of 188 HCV samples isolated from 2006 to 2017, Iran, were retrieved from NCBI gene bank. Using several tools, all sequences were analyzed for determination of mutations, physicochemical analysis, B-cell epitopes prediction, T-cell and CTL epitopes prediction, post modification, secondary and tertiary structure prediction. Our analysis determined several mutations in some special positions (70, 90, 91, and 110) that are associated with HCC and hepatocarcinogenesis, efficacy of triple therapy and sustained virological response, and interaction between core and CCR6. Several B-cell, T-cell, and CTL epitopes were recognized. Secondary and tertiary structures were mapped fordomain1 and core proteins. Our study, as a first report, offered inclusive data about frequent mutation in HCV-core gene domain 1 in Iranian sequences that can provide helpful analysis on structure and function of domain 1 of the core gene."
1346,Induction of Rabies Virus Infection in Mice Brain may Up and Down Regulate Type II Interferon gamma via epigenetic modifications,"As feared and deadly human diseases globally, Rabies virus contrived mechanisms to escape early immune recognition via suppression of the interferon response. This study, preliminarily investigated whether Rabies virus employs epigenetic mechanism for the suppression of the interferon using the Challenge virus standard (CVS) strain and Nigerian street Rabies virus (SRV) strain. Mice were challenged with Rabies virus (RABV) infection, and presence of RABV antigen was assessed by direct fluorescent antibody test (DFAT). A real time quantitative Polymerase chain reaction (qRT-PCR) was used to measure the expression of type II interferon gamma (IFNG) and methylation specific quantitative PCR for methylation analysis of 1FNG promoter region. Accordingly, DNA methyltransferase (DNMT) and histone acetyltransferase (HAT) enzymes activities were determined. RABV antigen was detected in all infected samples. A statistically significant increase (p < 0.05) in mRNA level of IFNG was observed at the onset of the disease and a decrease as the disease progressed. An increase in methylation in the test groups from the control group was observed, with a fluctuation in methylation as the disease progressed. DNMT and HAT activities also agree with methylation as there was an observed increase activity in test group compared with control group. Similar fluctuation pattern was observed in both CVS and SRV groups as the disease progressed with HAT, being the most active proportionally. This study suggests that epigenetic modification via DNA methylation and histone acetylation may have played a role in the expression of type II interferon gamma in Rabies virus infection. [Figure: see text]"
1347,Plant-Derived Bioactive Peptides: A Treatment to Cure Diabetes,"ABSTRACT: Recent advances in analytical techniques have opened new opportunities for plant-based drug discovery in the field of peptide and proteins. Enzymatic hydrolysis of plant parent proteins forms bioactive peptides which are explored in the treatment of various diseases. In this review, we will discuss the identified plant-based bioactive proteins and peptides and the in vitro, in vivo results for the treatment of diabetes. Extraction, isolation, characterization and commercial utilization of plant proteins is a challenge for the pharmaceutical industry as plants contain several interfering secondary metabolites. The market of peptide drugs for the treatment of diabetes is growing at a fast rate. Plant-based bioactive peptides might open up new opportunities to discover economic lead for the management of various diseases. GRAPHIC ABSTRACT: [Image: see text]"
1348,"The effect of balneotherapy on body mass index, adipokine levels, sleep disturbances, and quality of life of women with morbid obesity","To investigate the effect of balneotherapy on body mass index, adipokine levels, sleep disturbances, and quality of life in women with morbid obesity. Fifty-four women with morbid obesity were included in the study. The body mass indexes (BMI) and waist/hip ratios (WHR) of the women were calculated. Subcutaneous fat thickness was measured using a *skinfold meter, and the percentage of adipose tissue was calculated. The *Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, and the Nottingham Health Profile (NHP) was used to assess quality of life. In addition to routine biochemical tests, leptin, adipokine, visfatin from blood, and cortisol from saliva samples were studied. Participants were given 15 sessions of balneotherapy for 20 min each. After treatment, the laboratory and clinical parameters of the participants were *reevaluated. There was no statistically significant difference of BMI, WHR, and percentage of adipose tissue between before and after treatment measurements (p ˃ 0.05).There was a statistically significant improvement in PSQI and NSP scores (p ˂ 0.001). The levels of blood glucose, leptin, and visfatin were significantly decreased, and adiponectin was significantly increased after treatment (p = 0.047, p ˂ 0.001, p ˂ 0.001, and p ˂ 0.001, respectively).There was no statistically significant changes in salivary cortisol levels (p = 0.848). Patients with diabetes showed a statistically significant decrease in glucose levels after treatment (p = 0.017).There was a statistically significant decrease in low-density lipoprotein cholesterol levels in patients with dyslipidemia compared with pre-treatment (p = 0.018). Balneotherapy improves sleep and quality of life of women with morbid obesity. After balneotherapy, glucose, leptin, adiponectin, and visfatin levels may change positively."
1349,Successful implementation of a Fracture Liaison Service through effective change management: a qualitative study,"SUMMARY: We assessed the context in which a hip Fracture Liaison Service was implemented. We conducted semi-structured interviews with 21 key informants at two time points to understand organizational readiness, facilitators, and barriers to change. We identified strategies important to successful implementation, particularly in the context of change fatigue. PURPOSE: Fracture Liaison Service (FLS) is effective for secondary fracture prevention. Two hospital sites implemented FLS for hip fracture patients, 50 + years, in Alberta, Canada. We assessed organizational readiness, facilitators, and barriers to change to better understand the context in which the FLS was implemented to inform its potential spread provincially. METHODS: We recruited individuals involved in FLS implementation at provincial and site levels to participate in telephone interviews at baseline and 16 months post-implementation. Interviews were transcribed and analyzed using thematic content analysis. In addition, site-level participants were invited to complete the Organizational Readiness to Implement Change tool at baseline. RESULTS: We conducted 33 semi-structured interviews (20 at baseline; 13 at post-implementation) with 21 key informants. Participants included managers (24%), FLS physicians/clinical nurses (19%), operational/leadership roles (19%), physicians/surgeons (14%), pharmacists (10%), nurse practitioners (10%), and social work (5%). Seventeen site-level participants completed the ORIC tool at baseline; all participants scored high (71%) or neutral (29%). We found that the use of several strategies, including demonstrating value, providing resources, and selecting appropriate sites, were important to implementation, particularly in the context of change fatigue. Participants perceived the FLS as acceptable and there was evidence of facilitated learning rather than simply monitoring implementation as intended. CONCLUSIONS: An effective change management approach neutralized change fatigue. This approach, if maintained, bodes well for the potential spread of the FLS provincially if proven effective and cost effective. Change readiness assessment tools could be used strategically to inform the spread of the FLS to early adopter sites. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11657-020-0692-0) contains supplementary material, which is available to authorized users."
1350,An experience with a bubble CPAP bundle: is chronic lung disease preventable?,"BACKGROUND: Continuous positive airway pressure (CPAP) is associated with marginal decrease in chronic lung disease (CLD). This study aims to report outcomes, with focus on CLD, of preterm infants managed with a bubble CPAP (b-CPAP) bundle of care. METHODS: Infants <1500 g were stratified into four groups depending on intubation status through first 3 days of life. The incidence of mortality, CLD and other morbidities were compared over four chronological epochs. Outcomes of the most recent epoch were compared to contemporaneous benchmarks from Vermont Oxford Network (VON). RESULTS: Of 773 infants (median GA = 28 weeks, average BW = 995 g), 24.5% were intubated in DR and 11.7% in the first day of life. Mechanical ventilation, bCPAP and oxygen days in survivors were 1.5, 29 and 14, respectively. Overall incidence of CLD was 6.4% that remained consistent in the four epochs (7.6%, 7.5%, 5.8% and 5%), respectively. In comparison to VON, CLD was significantly less (p < 0.001). Initial DR intubation was not associated with increased CLD compared to initial management with CPAP that required subsequent intubation. CONCLUSION: It is feasible and sustainable to administer a b-CPAP bundle of care to decrease CLD. Cluster randomized trials are needed to validate the reproducibility of this approach."
1351,A Pot Ignored Boils On: Sustained Calls for Explicit Consent of Intimate Medical Exams,"Unconsented intimate exams (UIEs) on men and women are known to occur for training purposes and diagnostic reasons, mostly during gynecological surgeries but also during prostate examinations and abdominal surgeries. UIEs most often occur on anesthetized patients but have also been reported on conscious patients. Over the last 30 years, several parties—both within and external to medicine—have increasingly voiced opposition to these exams. Arguments from medical associations, legal scholars, ethicists, nurses, and some physicians have not compelled meaningful institutional change. Opposition is escalating in the form of legislative bans and whistleblower reports. Aspiring to professional and scientific detachment, institutional consent policies make no distinction between intimate exams and exams on any other body part, but patients do not think of their intimate regions in a detached or neutral way and believe intimate exams call for special protections. UIEs are found to contribute to moral erosion and moral distress of medical students and compromise the sacred trust between the medical community and the general public. This paper refutes the main arguments in favor of the status quo, identifies a series of harms related to continuing the current practice, and proposes an explicit consent policy for intimate exams along with specific changes to medical school curriculum and institutional culture. Because patients are the rights-holders of their bodies, consent practices should reflect and uphold patient values which call for explicit consent for intimate exams."
1352,Less empiric broad-spectrum antibiotics is more in the ICU,
1353,"Delphine Parrott, a pioneer of T cell biology","The first article in our Women in Immunology series pays tribute to Delphine Parrott, who conducted pioneering work in the fields of T cell biology, lymphoid tissue anatomy, lymphocyte trafficking and mucosal immunology."
1354,Immunogenicity and protective potency of Norovirus GII.17 virus-like particle-based vaccine,"OBJECTIVES: Noroviruses (NoVs) are major cause of acute viral gastroenteritis in worldwide, and the lack of a cell culture system that must be considered the virus like particles (VLPs) are used as an effective vaccine development. MATERIALS AND METHODS: In the present study, we investigated the expression of the major capsid protein (VP1) of the Genogroup II, genotype 17 (GII.17) NoV, using recombinant baculovirus system in insect cells, as well as a saliva binding blockade assay to detect their protective potency. RESULTS: Our results showed that GII.17 VLPs could be successfully generated in sf9 insect cells, and electron microscopic revealed that GII.17 VLPs appeared as spherical particles with a − 35 nm diameter. Immunized mice with purified VLPs produced GII.17 specific sera and could efficiently block GII.17 VLPs binding to the saliva histo-blood group antigens (HBGAs). CONCLUSIONS: Together, these results suggested that GII.17 VLPs represent a promising vaccine candidate against NoV GII.17 infection and strongly support further preclinical and clinical studies."
1355,Acute kidney injury in hospitalized children: consequences and outcomes,"Over the past decade, the nephrology and critical care communities have adopted a consensus approach to diagnosing acute kidney injury (AKI) and, as a result, we have seen transformative changes in our understanding of pediatric AKI epidemiology. The data regarding outcomes among neonates and children who develop AKI have become far more robust and AKI has been clearly linked with an increased need for mechanical ventilation, longer inpatient stays, and higher mortality. Though AKI was historically thought to be self-limited, we now know that renal recovery is far from universal, particularly when AKI is severe; the absence of recovery from AKI also carries longitudinal prognostic implications. AKI survivors, especially those without full recovery, are at risk for chronic renal sequelae including proteinuria, hypertension, and chronic kidney disease. This review comprehensively describes AKI-related outcomes across the entire pediatric age spectrum, using the most rigorous studies to identify the independent effects of AKI events."
1356,Comparative Effectiveness of Caregiver Training in Mindfulness-Based Positive Behavior Support (MBPBS) and Positive Behavior Support (PBS) in a Randomized Controlled Trial,"Caregivers of individuals with intellectual and developmental disabilities are often stressed due to the demands of the job, including the nature and severity of challenging behaviors of the clients, work conditions, degree of management support for the staff, and the demands of implementing some interventions under adverse conditions. Mindfulness-Based Positive Behavior Support (MBPBS) and PBS alone have been shown to be effective in assisting caregivers to better manage the challenging behaviors of clients with intellectual and developmental disabilities. The aim of the present study was to undertake a head-to-head assessment of the effectiveness of MBPBS and PBS alone in a 40-week randomized controlled trial. Of the 123 caregivers who met inclusion criteria, 60 were randomly assigned to MBPBS and 63 to PBS alone, with 59 completing the trial in the MBPBS condition and 57 in the PBS alone condition. Results showed both interventions to be effective, but the caregiver, client, and agency outcomes for MBPBS were uniformly superior to those of PBS alone condition. In addition, the MBPBS training was substantially more cost-effective than the PBS alone training. The present results add to the evidence base for the effectiveness of MBPBS and, if independently replicated, could provide an integrative health care approach in the field of intellectual and developmental disabilities."
1357,Molecular characteristics and predictors of mortality among Gram-positive bacteria isolated from bloodstream infections in critically ill patients during a 5-year period (2012–2016),"To identify the molecular characteristics of Gram-positive cocci isolated from blood cultures and clinical outcome among critically ill patients. This retrospective study was conducted in the general intensive care unit of the University General Hospital of Patras, Greece, during a 5-year period (2012–2016). All adult patients with a Gram-positive BSI were included. PCR was applied to identify mecA gene (staphylococci); vanA, vanB, and vanC genes (enterococci). Linezolid-resistant S. epidermidis, MRSA, and VRE were further typed by multilocus sequence typing. Mutations in region V of 23S rDNA and ribosomal protein L4were investigated by PCR and sequencing analysis. The presence of the cfr gene was tested by PCR. In total, 141 Gram-positive BSIs were included. Coagulase-negative staphylococci predominated (n = 69; 65 methicillin-resistant, 23 linezolid-resistant carrying both C2534T and T2504A mutations and belonging to the ST22 clone), followed by enterococci (n = 46; 11 vancomycin-resistant carrying vanA gene, classified into four clones), S. aureus (n = 22; 10 methicillin-resistant, classified into three clones) and streptococci (n = 4). The most common type of infection was catheter-related (66; 46.8%), followed by primary BSI (28; 19.9%). Overall 14-day fatality was 24.8%. Multivariate analysis revealed septic shock as independent predictor of fatality, while appropriate empiric antimicrobial treatment and catheter-related BSI were identified as a predictor of good prognosis. Even though most of Gram-positive cocci were multidrug-resistant, fatality rate was low, associated with catheter-related BSIs. Among CNS, LR isolates represented one-third of BSIs due to the dissemination of ST22 S. epidermidis propagated by utilization of linezolid."
1358,Evaluation of clinically asymptomatic high risk infants with congenital cytomegalovirus infection,"OBJECTIVE: To determine the frequency of abnormal findings on evaluation of neonates with congenital CMV infection who have a normal physical examination STUDY DESIGN: Retrospective, 2-center study (1996–2017) that reviewed results of complete blood cell count and platelets, serum alanine aminotransferase (ALT) and bilirubin concentrations, eye examination, cranial ultrasonography or other neuroimaging, and brainstem evoked responses performed on neonates with congenital CMV infection and a normal physical examination RESULTS: Of 34 infants with congenital CMV infection and a normal physical examination, 56% (19/34) had ≥1 abnormality: 39%, elevated ALT concentration; 45%, abnormal neuroimaging (five, lenticulostriate vasculopathy; six, intraventricular hemorrhage; four, calcifications); 12%, anemia; 16%, thrombocytopenia; and 3%, chorioretinitis. Seven (21%) infants had sensorineural hearing loss, and 18 infants received antiviral therapy. CONCLUSION: Some infants with congenital CMV infection and a normal physical examination had abnormalities on laboratory or neuroimaging evaluation, which in some cases prompted antiviral treatment."
1359,The effects of smoking on adolescent trauma patients: a propensity-score-matched analysis,"PURPOSE: Cigarettes have been demonstrated to be toxic to the pulmonary connective tissue by impairing the lung’s ability to clear debris, resulting in infection and acute respiratory distress syndrome (ARDS). Approximately 8% of adolescents are smokers. We hypothesized that adolescent trauma patients who smoke have a higher rate of ARDS and pneumonia when compared to non-smokers. METHODS: The Trauma Quality Improvement Program (2014–2016) was queried for adolescent trauma patients aged 13–17 years. Adolescent smokers were 1:2 propensity-score-matched to non-smokers based on age, comorbidities, and injury type. Data were analyzed using chi square for categorical data and Mann–Whitney U test for continuous data. RESULTS: From 32,610 adolescent patients, 997 (3.1%) were smokers. After matching, 459 smokers were compared to 918 non-smokers. There were no differences in matched characteristics. Compared to non-smokers, smokers had an increased rate of pneumonia (3.1% vs. 1.1%, p = 0.01) but not ARDS (0.2% vs. 0%, p = 0.16). Compared to the non-smoking group, the smokers had a longer median total hospital length-of-stay (3 vs. 2 days, p = 0.01) and no difference in overall mortality (1.5% vs. 2.4%, p = 0.29). CONCLUSION: Smoking is associated with an increased rate of pneumonia in adolescent trauma patients. Future research should target smoking cessation and/or interventions to mitigate the deleterious effects of smoking in this population."
1360,Airway Pressure Release Ventilation as a Rescue Therapy in Pediatric Acute Respiratory Distress Syndrome,"OBJECTIVES: To describe experience with airway pressure release ventilation (APRV) in children with severe acute respiratory distress syndrome (ARDS) refractory to conventional low tidal volume ventilation. METHODS: This retrospective observational study was performed in an 11-bed, level 3 pediatric intensive care unit. Evaluation was made of 30 pediatric patients receiving airway pressure release ventilation as rescue therapy for severe ARDS. RESULTS: Patients were switched to APRV on an average 3.2 ± 2.6 d following intubation. When changed from conventional mechanical ventilation (CMV) to APRV, there was an expected increase in the SpO(2)/FiO(2) ratio (165.1 ± 13.6 vs. 131.7 ± 10.2; p = 0.035). Mean peak inspiratory pressure was significantly lower during APRV (25.4 ± 1.26 vs. 29.8 ± 0.60, p < 0.001) compared to CMV prior to APRV but mean airway pressure (P(aw)) was significantly higher during APRV (19.1 ± 0.9 vs. 15.3 ± 1.3, p < 0.001). Hospital mortality in this study group was 16.6%. CONCLUSIONS: The results of this study support the hypothesis that APRV may offer potential clinical advantages for ventilatory management and may be considered as an alternative rescue mechanical ventilation mode in pediatric ARDS patients refractory to conventional ventilation."
1361,Putting African swine fever on ice,
1362,“Quality of life”: parent and neonatologist perspectives,"OBJECTIVE: To assess how physicians and families understand quality of life (QOL) for NICU patients, and to explore the feasibility of developing a standardized definition for QOL. STUDY DESIGN: Surveys were developed and administered to neonatologists and eligible families. Quantitative analysis was conducted using standard statistical methods. Qualitative analysis was conducted using NVivo software. Focus groups were conducted with the same groups, and audio recordings were obtained and analyzed for recurring themes. RESULTS: Both parents and physicians value QOL as a metric for guiding care in the NICU. Parents were more likely to accept higher levels of disability, while neonatologists were more likely to accept higher levels of dependence on medical equipment. In relation to infant QOL, predominant themes expressed in the parent focus groups were stress levels in the NICU, advocating as parents, and the way in which long-term outcomes were presented by the medical team; in the physician focus group, the ambiguity of predicting outcomes and thus QOL was the main theme. CONCLUSIONS: Both parents and physicians recognize the importance of QOL in the decision-making process for critically ill infants, but the two groups differ in their assessment of what QOL means in this context. These data suggest that QOL cannot be adequately defined for standardized use in a clinical context, and as such, should be used thoughtfully by neonatologists in discussions of end- of-life care."
1363,Mother’s own milk dose is associated with decreased time from initiation of feedings to discharge and length of stay in infants with gastroschisis,"OBJECTIVE: To determine if mother’s own milk (MOM) dose after gastroschisis repair is associated with time from feeding initiation to discharge. Secondary outcomes included parenteral nutrition (PN) duration and length of stay (LOS). STUDY DESIGN: Retrospective study of 44 infants with gastroschisis examined demographics, gastroschisis type, PN days, timing of nutrition milestones, feeding composition, and LOS. RESULTS: MOM dose was significantly associated with shorter time to discharge from feeding initiation (adjusted hazard ratio [HR] for discharge per 10% increase in MOM dose, 1.111; 95% CI, 1.011–1.220, p = 0.029). MOM dose was also significantly associated with shorter LOS (adjusted HR for discharge per 10% increase in MOM dose, 1.130; 95% CI, 1.028–1.242, p = 0.011). CONCLUSIONS: MOM dose was significantly associated with a decrease in time to discharge from feeding initiation and LOS in a dose-dependent manner. Mothers of gastroschisis patients should receive education and proactive lactation support to optimize MOM volume for feedings."
1364,Antibiotics in the clinical pipeline in October 2019,"The development of new and effective antibacterial drugs to treat multi-drug resistant (MDR) bacteria, especially Gram-negative (G−ve) pathogens, is acknowledged as one of the world’s most pressing health issues; however, the discovery and development of new, nontoxic antibacterials is not a straightforward scientific task, which is compounded by a challenging economic model. This review lists the antibacterials, β-lactamase/β-lactam inhibitor (BLI) combinations, and monoclonal antibodies (mAbs) first launched around the world since 2009 and details the seven new antibiotics and two new β-lactam/BLI combinations launched since 2016. The development status, mode of action, spectra of activity, lead source, and administration route for the 44 small molecule antibacterials, eight β-lactamase/BLI combinations, and one antibody drug conjugate (ADC) being evaluated in worldwide clinical trials at the end of October 2019 are described. Compounds discontinued from clinical development since 2016 and new antibacterial pharmacophores are also reviewed. There has been an increase in the number of early stage clinical candidates, which has been fueled by antibiotic-focused funding agencies; however, there is still a significant gap in the pipeline for the development of new antibacterials with activity against β-metallolactamases, orally administered with broad spectrum G−ve activity, and new treatments for MDR Acinetobacter and gonorrhea."
1365,A pilot survey of ventilated cancer patients’ perspectives and recollections of early mobility in the intensive care unit,"PURPOSE: To determine the level of recall, satisfaction, and perceived benefits of early mobility (EM) among ventilated cancer patients after extubation in the intensive care unit (ICU). METHODS: A survey of patients’ perceptions and recollections of EM was administered within 72 h of extubation. Data on recall of EM participation, activities achieved, adequacy of staffing and rest periods, strength to participate, activity level of difficulty, satisfaction with staff instructions, breathing management, and overall rating of the experience were analyzed. The Confusion Assessment Method for ICU (CAM-ICU) was used for delirium screening. RESULTS: Fifty-four patients comprised the study group. Nearly 90% reported satisfaction with instructions, staffing, rest periods, and breathing management during EM. Participants indicated that EM maintained their strength (67%) and gave them control over their recovery (61%); a minority felt optimistic (37%) and safe (22%). Patients who achieved more sessions and “out-of-bed” exercises had better recall of actual activities compared with those who exercised in bed. Overall, patients with CAM-ICU-positive results (33%) performed less physical and occupational therapy exercises. CONCLUSIONS: Ventilated cancer patients reported an overall positive EM experience, but factual memory impairment of EM activities was common. These findings highlight the needs and the importance of shaping strategies to deliver a more patient focused EM experience. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00520-019-04867-1) contains supplementary material, which is available to authorized users."
1366,"Epidemiology of long-stay patients in the pediatric intensive care unit: prevalence, characteristics, resource consumption and complications","BACKGROUND: The impact of pediatric intensive care unit (PICU) utilization and resource consumption among long-stay patients has not been characterized recently. This study aimed to describe the resource consumption and characteristics of long-stay patients in a PICU. METHODS: This was a single-center descriptive cohort study of 1309 patients admitted to a PICU in 2017. The main outcome was ICU length of stay (LOS). Patients were divided into prolonged LOS (PLS) and non-PLS groups if they had an LOS of ≥ 28 or < 28 days, respectively. Two groups were compared to characterize PLS. RESULTS: Thirty-two (2.4%) patients had a PLS and utilized 33% of PICU bed days. Factors associated with PLS with odds ratio [95% confidence interval (CI)] were being a neonate (7.8 [2.5–25.4], p = <0.001), being an infant (2.9 [1.0–9.0], p = 0.04), admission for a respiratory ailment (7.3 [1.6–44.2], p = 0.003), cardiovascular dysfunction (24.1 [4.8–152.1], p = <0.001), post-cardiac operation (8.0 [1.7–50.1], p = 0.003), post-cardiopulmonary arrest (22.8 [1.7–211.9], p = 0.01), and transfer from another facility (4.2 [1.8–10.7], p = 0.001). PLS patients developed more nosocomial infections and disproportionately received monitoring and therapeutic resources. CONCLUSIONS: A PLS was associated with substantial PICU utilization and complication rates. Future studies should aim to alleviate both institutional and patient-related issues in the affected population harboring possible risk factors for PLS."
1367,Insight into Evolution and Conservation Patterns of B1-Subfamily Members of GPCR,"The diverse, evolutionary architectures of proteins can be regarded as molecular fossils, tracing a historical path that marks important milestones across life. The B1-subfamily of GPCRs (G-protein-coupled receptors) are medically significant proteins that comprise 15 transmembrane receptor proteins in Homo sapiens. These proteins control the intracellular concentration of cyclic AMP as well as various vital processes in the body. However, little is known about the evolutionary correlation and conservational blueprint of this GPCR subfamily. We performed a comprehensive analysis to understand the evolutionary architecture among 13 members of the B1-subfamily. Multiple sequence alignment analysis exhibited six multiple sequence aligned blocks and five highly aligned blocks. Molecular phylogenetics indicated that CRHR1 and CRHR2 share a typical ancestral relationship and are siblings in 100% bootstrap replications with a total of 24 nodes observed in the cladogram. CRHR2 has the maximum number of extremely conserved amino acids followed by ADCYAP1R1. The longest continuous number sequence logos (74) were found between sequence location 349 and 423, and consequently, the maximum and minimum logo height recorded was 3.6 bits and 0.18 bits, respectively. Finally, to understand the model and pattern of evolutionary relatedness, the conservation blueprint, and the diversification among the members of a protein family, GPCR distribution from several species throughout the animal kingdom was analysed. Together, the study provides an evolutionary insight and offers a rapid method to explore the potential of depicting the evolutionary relationship, conservation blueprint, and diversification among the B1-subfamily of GPCRs using bioinformatics, algorithm analysis, and mathematical models. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10989-020-10043-5) contains supplementary material, which is available to authorized users."
1368,Utility of Pulmonary Artery Acceleration Time to Estimate Systolic Pulmonary Artery Pressure in Neonates and Young Infants,"Transthoracic echocardiogram (TTE) is commonly used to screen for pulmonary hypertension (PHTN) in neonates and young infants. However, in the absence of sufficient tricuspid regurgitation (TR), a ventricular septal defect (VSD), or a patent ductus arteriosus (PDA), the estimation of systolic pulmonary artery pressure (SPAP) becomes challenging. Pulmonary artery acceleration time (PAAT) is an alternate parameter that is easy to obtain in almost all patients and does not require the presence of tricuspid valvar regurgitation or an anatomical cardiac defect. We sought to examine the correlation of PAAT with estimated SPAP by TTE and create an equation to estimate the SPAP using PAAT. We performed a retrospective review of TTEs performed on neonates and young infants (4 months of age or younger) at our institution between April 2017 and December 2018, along with the corresponding medical records. We included TTEs that provided estimation for SPAP and at least one PAAT measurement. During the study period, 138 TTEs performed on 82 patients met the inclusion criteria. Strong correlation was delineated between PAAT and SPAP estimated by the maximum velocity of tricuspid valve regurgitation Doppler, correlation coefficient (r) = − 0.83. Moderate correlation was detected between PAAT and SPAP estimated by PDA Doppler, r = − 0.66. Utilizing the following equation “SPAP = 82.6 − 0.58 × PAAT + RA mean pressure”, PAAT can be used to estimate SPAP in neonates and young infants. PAAT can be used as an alternative to TR jet to assess SPAP when the latter is absent or insufficient. Further studies are needed to verify the accuracy of this equation."
1369,Occurrence of Atypical and New Genotypes of Toxoplasma Gondii in Free-Range Chickens Intended for Human Consumption in Brazil,"PURPOSE: The aim of the present study was to detect and genotype T. gondii in free-range chickens destined to human consumption in Alagoas state, Brazil. METHODS: Two hundred blood samples were collected from free-range chickens and submitted to indirect immunofluorescence antibody test (IFAT). Brain tissue from 14 animals randomly selected were subjected to mouse bioassay. Positive samples in mouse bioassay were submitted to PCR and genotyped by PCR–RFLP. RESULTS: Out of two hundred blood samples from chickens, 72 (36%) samples were considered positive by IFAT. Two T. gondii strains were isolated, both being characterized as atypical and classified as #146 and a new genotype, named #279 in ToxoDB database. CONCLUSIONS: Our results showed a sero-occurrence of T. gondii in free-range chickens intended for humans, and the genetic diversity of the parasite in Brazil, with a new genotype described."
1370,"Development of eco-friendly, self-cleaning, antibacterial membrane for the elimination of chromium (VI) from tannery wastewater","Hydrophobic polyvinylidene fluoride membrane was reformed to the hydrophilic membrane by incorporating synthesized titanium dioxide nanoparticles using Cajanus cajan seed extract. Spectroscopic and microscopic techniques characterized the composite membrane. The X-ray diffraction confirms the anatase phase of titanium dioxide nanoparticles of crystalline size 15.89 nm. The effect of titanium dioxide concentration on the thermodynamical and rheological properties on the polyvinylidene fluoride casting solution was investigated by the triangle phase diagram and viscosity measurement. It was concluded that titanium dioxide introduction caused thermodynamic enhancement, but the impact of rheological hinderance was higher at high concentrations. The polyvinylidene fluoride/titanium dioxide membranes were used as a bi-functional membrane to evaluate the rejection of chromium (VI) from wastewater; then, they were applied as sunlight-active catalyst membrane to reduce the concentrated chromium (VI) to chromium (III) by reduction. It was concluded that at 0.02 wt% of titanium dioxide, the maximum rejection of 85.59% and a% reduction of 92% was achieved with enhanced flux."
1371,Anti-inflammatory coating of hernia repair meshes: a 5-rabbit study,"PURPOSE: Polymeric mesh implantation has become the golden standard in hernia repair, which nowadays is one of the most frequently performed surgeries in the world. However, many biocompatibility issues remain to be a concern for hernioplasty, with chronic pain being the most notable post-operative complication. Oxidative stress appears to be a major factor in the development of those complications. Lack of material inertness in vivo and oxidative environment formed by inflammatory cells result in both mesh deterioration and slowed healing process. In a pilot in vivo study, we prepared and characterized polypropylene hernia meshes with vitamin E (α-tocopherol)-a potent antioxidant. The results of that study supported the use of vitamin E as potential coating to alleviate post-surgical inflammation, but the pilot nature of the study yielded limited statistical data. The purpose of this study was to verify the observed trend of the pilot study statistically. METHODS: In this work, we conducted a 5-animal experiment where we have implanted vitamin E-coated and uncoated control meshes into the abdominal walls of rabbits. Histology of the mesh-adjacent tissues and electron microscopy of the explanted mesh surface were conducted to characterize host tissue response to the implanted meshes. RESULTS: As expected, modified meshes exhibited reduced foreign body reaction, as evidenced by histological scores for fatty infiltrates, macrophages, neovascularization, and collagen organization, as well as by the surface deterioration of the meshes. CONCLUSION: In conclusion, results indicate that vitamin E coating reduces inflammatory response following hernioplasty and protects mesh material from oxidative deterioration."
1372,Maxillofacial injuries in severely injured patients after road traffic accidents—a retrospective evaluation of the TraumaRegister DGU® 1993–2014,"OBJECTIVES: It was the aim of the study to analyse the prevalence of maxillofacial trauma (MFT) in severely injured patients after road traffic accidence (RTA) and to investigate associated factors. MATERIALS AND METHODS: In a retrospective study, data from patients after RTA by the TraumaRegister DGU® from 1993 to 2014 were evaluated for demographical and injury characteristics. The predictor variable was mechanism of injury and the outcome variables were type of injury, severity and hospital resources utilization. RESULTS: During the investigation period, n = 62,196 patients were enclosed with a prevalence of maxillofacial injuries of 20.3% (MFT positive). The injury severity score of MFT-positive patients was higher than in the MTF-negative subgroup (27 ± 12.8 vs. 23.0 ± 12.7). If MFT positive, 39.8% show minor, 37.1% moderate, 21.5% serious and 1.6% severe maxillofacial injuries. Injuries of the midface occurred in 60.3% of MTF-positive patients. A relevant blood loss (> 20% of total blood volume) occurred in 1.9%. MFT-positive patients had a higher coincidence with cervical spine fractures (11.3% vs. 7.8%) and traumatic brain injuries (62.6% vs. 34.8%) than MFT-negative patients. There was a noticeable decrease in the incidence of facial injuries in car/truck drivers during the study period. CONCLUSIONS: Every 5th patient after RTA shows a MFT and the whole trauma team must be aware that this indicates a high prevalence of traumatic brain and cervical spine injuries. CLINICAL RELEVANCE: Even if sole injuries of the face are seldom life threatening, maxillofacial expertise in interdisciplinary trauma centres is strongly recommended."
1373,Automated pupillometry and the FOUR score — what is the diagnostic benefit in neurointensive care?,"INTRODUCTION: The Glasgow Coma Scale (GCS) and visual inspection of pupillary function are routine measures to monitor patients with impaired consciousness and predict their outcome in the neurointensive care unit (neuro-ICU). Our aim was to compare more recent measures, i.e. FOUR score and automated pupillometry, to standard monitoring with the GCS and visual inspection of pupils. METHODS: Supervised trained nursing staff examined a consecutive sample of patients admitted to the neuro-ICU of a tertiary referral centre using GCS and FOUR score and assessing pupillary function first by visual inspection and then by automated pupillometry. Clinical outcome was evaluated 6 months after admission using the Glasgow Outcome Scale-Extended. RESULTS: Fifty-six consecutive patients (median age 63 years) were assessed a total of 234 times. Of the 36 patients with at least one GCS score of 3, 13 had a favourable outcome. All seven patients with at least one FOUR score of ≤ 3 had an unfavourable outcome, which was best predicted by a low “brainstem” sub-score. Compared to automated pupillometry, visual assessment underestimated pupillary diameters (median difference, 0.4 mm; P = 0.006). Automated pupillometry detected a preserved pupillary light reflex in 10 patients, in whom visual inspection had missed pupillary constriction. DISCUSSION: Training of nursing staff to implement frequent monitoring of patients in the neuro-ICU with FOUR score and automated pupillometry is feasible. Both measures provide additional clinical information compared to the GCS and visual assessment of pupillary function, most importantly a more granular classification of patients with low levels of consciousness by the FOUR score."
1374,Tracheostomy practice and timing in traumatic brain-injured patients: a CENTER-TBI study,"PURPOSE: Indications and optimal timing for tracheostomy in traumatic brain-injured (TBI) patients are uncertain. This study aims to describe the patients’ characteristics, timing, and factors related to the decision to perform a tracheostomy and differences in strategies among different countries and assess the effect of the timing of tracheostomy on patients’ outcomes. METHODS: We selected TBI patients from CENTER-TBI, a prospective observational longitudinal cohort study, with an intensive care unit stay ≥ 72 h. Tracheostomy was defined as early (≤ 7 days from admission) or late (> 7 days). We used a Cox regression model to identify critical factors that affected the timing of tracheostomy. The outcome was assessed at 6 months using the extended Glasgow Outcome Score. RESULTS: Of the 1358 included patients, 433 (31.8%) had a tracheostomy. Age (hazard rate, HR = 1.04, 95% CI = 1.01–1.07, p = 0.003), Glasgow coma scale ≤ 8 (HR = 1.70, 95% CI = 1.22–2.36 at 7; p < 0.001), thoracic trauma (HR = 1.24, 95% CI = 1.01–1.52, p = 0.020), hypoxemia (HR = 1.37, 95% CI = 1.05–1.79, p = 0.048), unreactive pupil (HR = 1.76, 95% CI = 1.27–2.45 at 7; p < 0.001) were predictors for tracheostomy. Considerable heterogeneity among countries was found in tracheostomy frequency (7.9–50.2%) and timing (early 0–17.6%). Patients with a late tracheostomy were more likely to have a worse neurological outcome, i.e., mortality and poor neurological sequels (OR = 1.69, 95% CI = 1.07–2.67, p = 0.018), and longer length of stay (LOS) (38.5 vs. 49.4 days, p = 0.003). CONCLUSIONS: Tracheostomy after TBI is routinely performed in severe neurological damaged patients. Early tracheostomy is associated with a better neurological outcome and reduced LOS, but the causality of this relationship remains unproven. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-05935-5) contains supplementary material, which is available to authorized users."
1375,Development and application of a novel ELISA for detecting antibodies against group I fowl adenoviruses,"Since 2015, outbreaks of hepatitis-hydropericardium syndrome (HPS) caused by a novel genotype of fowl adenovirus 4 (FAdV-4) infection have created serious economic losses in China. Given that other serotypes of hypervirulent FAdVs have also been reported in poultry around the world, a common ELISA for all serotypes within the group I fowl adenoviruses (FAdV-I) is urgently needed, especially for clinical epidemic serotypes. In this study, we used high purity and concentration virions of FAdV-4 and developed a common ELISA for detecting antibodies against 12 FAdV-I serotypes. The developed ELISA was able to distinguish between antibodies against FAdV-I, FAdV-III, and other heterologous viruses without any cross-reaction. Furthermore, the ELISA showed higher sensitivity than the FAdV-1-based ELISA to the novel FAdV-4 found in China. Moreover, since there are no commercial vaccines against FAdVs in China, the ELISA was applied to detect sera samples from specific pathogen-free chickens inoculated with inactivated FAdV-1, FAdV-4, and FAdV-8a. The assay showed high sensitivities for all three detected serotypes within FAdV-I. In conclusion, a novel, common ELISA for FAdV-I was developed in this study and could be a powerful tool for seroepidemiological investigations and FAdVs vaccine development."
1376,The value of a superior vena cava collapsibility index measured with a miniaturized transoesophageal monoplane continuous echocardiography probe to predict fluid responsiveness compared to stroke volume variations in open major vascular surgery: a prospective cohort study,"Superior vena cava collapsibility index (SVC-CI) and stroke volume variation (SVV) have been shown to predict fluid responsiveness. SVC-CI has been validated only with conventional transoesophageal echocardiography (TEE) in the SVC long axis, on the basis of SVC diameter variations, but not in the SVC short axis or by SVC area variations. SVV was not previously tested in vascular surgery patients. Forty consecutive adult patients undergoing open major vascular surgical procedures received 266 intraoperative volume loading tests (VLTs), with 500 ml of gelatine over 10 min. The hSVC-CI was measured using a miniaturized transoesophageal echocardiography probe (hTEE). The SVV and cardiac index (CI) were measured using Vigileo-FloTrac technology. VLTs were considered ‘positive’ (≥ 11% increase in CI) or ‘negative’ (< 11% increase in CI). We compared SVV and hSVC-CI measurements in the SVC short axis to predict fluid responsiveness. Areas under the receiver operating characteristic curves for hSVC-CI and SVV were not significantly different (P = 0.56), and both showed good predictivity at values of 0.92 (P < 0.001) and 0.89 (P < 0.001), respectively. The cutoff values for hSVC-CI and SVV were 37% (sensitivity 90%, specificity of 83%) and 15% (sensitivity 78%, specificity of 100%), respectively. Our study validated the value of the SVC-CI measured as area variations in the SVC short axis to predict fluid responsiveness in anesthetized patients. An hTEE probe was used to monitor and measure the hSVC-CI but conventional TEE may also offer this new dynamic parameter. In our cohort of significant preoperative hypovolemic patients undergoing major open vascular surgery, hSVC-CI and SVV cutoff values of 37% and 15%, respectively, predicted fluid responsiveness with good accuracy."
1377,The FASILA Score: A Novel Bio-Clinical Score to Predict Massive Blood Transfusion in Patients with Abdominal Trauma,"BACKGROUND: Early identification of patients who may need massive blood transfusion remains a major challenge in trauma care. This study proposed a novel and easy-to-calculate prediction score using clinical and point of care laboratory findings in patients with abdominal trauma (AT). METHODS: Patients with AT admitted to a trauma center in Qatar between 2014 and 2017 were retrospectively analyzed. The FASILA score was proposed and calculated using focused assessment with sonography in trauma (0 = negative, 1 = positive), Shock Index (SI) (0 = 0.50–0.69, 1 = 0.70–0.79, 2 = 0.80–0.89, and 3 ≥ 0.90), and initial serum lactate (0 ≤ 2.0, 1 = 2.0–4.0, and 2 ≥ 4.0 mmol/l). Outcome variables included mortality, laparotomy, and massive blood transfusion (MT). FASILA was compared to other prediction scores using receiver operating characteristics and areas under the curves. Bootstrap procedure was employed for internal validation. RESULTS: In 1199 patients with a mean age of 31 ± 13.5 years, MT, MT protocol (MTP) activation, exploratory laparotomy (ExLap), and hospital mortality were related linearly with the FASILA score, Injury Severity Score, and total length of hospital stay. Initial hemoglobin, Revised Trauma Score (RTS), and Trauma Injury Severity Score (TRISS) were inversely proportional. FASILA scores correlated significantly with the Assessment of Blood Consumption (ABC) (r = 0.65), Revised Assessment of Bleeding and Transfusion (RABT) (r = 0.63), SI (r = 0.72), RTS (r = − 0.34), and Glasgow Coma Scale (r = − 0.32) and outperformed other predictive systems (RABT, ABC, and SI) in predicting MT, MTP, ExLap, and mortality. CONCLUSIONS: The novel FASILA score performs well in patients with abdominal trauma and offers advantages over other scores. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00268-019-05289-0) contains supplementary material, which is available to authorized users."
1378,Ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: understanding nebulization of aminoglycosides and colistin,
1379,"Compassion fatigue among oncologists: the role of grief, sense of failure, and exposure to suffering and death","PURPOSE: Oncologists cope with unique work characteristics that increase their risk of developing compassion fatigue—that is, burnout and secondary traumatic stress—and can result in reduced capacity and interest in being empathetic to the suffering of others (Stamm B. The concise ProQOL manual, 2010). At the same time, oncologists can experience compassion satisfaction—that is, the positive aspects of caring. This study explored the associations of compassion fatigue and compassion satisfaction with oncologists’ grief and sense of failure beyond their reported exposure to suffering and death. METHODS: Seventy-four oncologists completed self-administered questionnaires examining compassion fatigue, compassion satisfaction, grief, exposure to suffering and death, and sense of failure. RESULTS: The oncologists reported that they face the loss of approximately 50% of their patients, and that their patients suffer from profound emotional and physical pain. High levels of compassion fatigue and grief, and moderate levels of sense of failure, were reported. Findings showed a lack of association between exposure to suffering and death and compassion fatigue and satisfaction. However, grief and sense of failure were found to predict both aspects of compassion fatigue: secondary traumatic stress (p < 0.001, p < 0.003, respectively) and burnout (p < 0.002, p < 0.025, respectively). CONCLUSIONS: These results highlight the importance of the oncologists’ subjective experiences of grief and sense of failure, beyond their reports of exposure to suffering and death, in terms of their levels of compassion fatigue. Implications of these findings include the need to develop interventions for oncologists that will allow them to acknowledge, process, and overcome negative experiences of failure and grief."
1380,Does lack of thoracic trauma attenuate the severity of pulmonary failure? An 8-year analysis of critically injured patients,"PURPOSE: Patients with thoracic trauma are presumed to be at higher risk for pulmonary dysfunction, but adult respiratory distress syndrome (ARDS) may develop in any patient, regardless of associated chest injury. This study evaluated the impact of thoracic trauma and pulmonary failure on outcomes in trauma patients admitted to the intensive-care unit (ICU). METHODS: All trauma patients admitted to the ICU over an 8-year period were identified. Patients that died within 48 h of arrival were excluded. Patients were stratified by baseline characteristics, injury severity, development of ARDS, and infectious complications. Multiple logistic regression was used to determine variables significantly associated with the development of ARDS. RESULTS: 10,362 patients were identified. After exclusions, 4898 (50%) patients had chest injury and 4975 (50%) did not. 200 (2%) patients developed ARDS (3.6% of patients with chest injury and 0.5% of patients without chest injury). Patients with ARDS were more likely to have chest injury than those without ARDS (87% vs 49%, p < 0.001). However, of the patients without chest injury, the development of ARDS still led to a significant increase in mortality compared to those patients without ARDS (58% vs 5%, p < 0.001). Multiple logistic regression found ventilator-associated pneumonia (VAP) to be the only independent predictor for the development of ARDS in ICU patients without chest injury. CONCLUSIONS: ARDS development was more common in patients with thoracic trauma. Nevertheless, the development of ARDS in patients without chest injury was associated with a tenfold higher risk of death. The presence of VAP was found to be the only potentially preventable and treatable risk factor for the development of ARDS in ICU patients without chest injury."
1381,A multidisciplinary quality improvement effort to reduce bronchopulmonary dysplasia incidence,"BACKGROUND: Bronchopulmonary Dysplasia (BPD) is the most common prematurity complication. Although several practices have been proposed for BPD prevention, none of these in isolation prevent BPD. METHODS: Our initiative focused on two key drivers: oxygen management and noninvasive ventilation strategies. We created best practice guidelines and followed outcome measures using Shewhart control charts. RESULTS: PDSAs of protocols preceded a large-scale rollout of a “0.21 by 28” campaign in 2014 leading to a special cause reduction in the “any BPD” rate, and a decrease in severe BPD (from 57 to 29%). At the end of 2017, we reinvigorated the project, which led to dramatic decreases in the “any BPD” rate to 41% and the “severe BPD” rate to 21%. CONCLUSIONS: A multidisciplinary QI initiative focused on process improvement geared towards the pathophysiological contributors of BPD has successfully reduced the rate of BPD in an all referral level IV NICU."
1382,Climate change: an enduring challenge for vector-borne disease prevention and control,"Climate change is already affecting vector-borne disease transmission and spread, and its impacts are likely to worsen. In the face of ongoing climate change, we must intensify efforts to prevent and control vector-borne diseases."
1383,Identification and study of InV as an inverse autotransporter family representative in Edwardsiella piscicida,"Invasins and intimins, members of virulence-related adhesin family which is involved in attachment and adherence to epithelial cells during infection, are found in various pathogens. These pathogens can attach to enterocytes and lead to the formation of a pedestal-like structure. Invasins and intimins belong to type Ve secretion systems, and the N-terminal β-barrel domain acts as a translocation pore to secrete the C-terminal passenger domain. However, the relationship between invasins/intimins and type III secretion system (T3SS) has been poorly studied. Based on the transposon insertion mutant library of Edwardsiella piscicida, we got a transposon insertion mutant with significant T3SS defect and identified the mutated gene ETAE_0323 (named inV later). This gene encoded a protein with 2359 amino acid residues and was predicted to be an invasin. To study the relationship between InV and T3SS, strains with N-terminus or C-terminus deleted InV fragments were made. However, none of them was able to copy the phenotype of the transposon insertion mutant previously identified. The localization of InV in ΔT3SS strain was not significantly different from WT, suggesting that the T3SS defect in the transposon insertion mutant was likely to be caused by polar effect. Nevertheless, depletion of inV still showed dramatic internalization and virulence defect in HeLa cell and zebrafish model, respectively, suggesting InV as a virulence related protein."
1384,Obesity is Associated with Worse Outcomes Among Abdominal Trauma Patients Undergoing Laparotomy: A Propensity-Matched Nationwide Cohort Study,"INTRODUCTION: Obesity is associated with increased morbidity and mortality in abdominal trauma patients. The characteristics of abdominal trauma patients with poor outcomes related to obesity require evaluation. We hypothesize that obesity is related to increased mortality and length of stay (LOS) among abdominal trauma patients undergoing laparotomies. METHODS: Abdominal trauma patients were identified from the National Trauma Data Bank between 2013 and 2015. Patients who received laparotomies were analyzed using propensity score matching (PSM) to evaluate the mortality rate and LOS between obese and non-obese patients. Patients without laparotomies were analyzed as a control group using PSM cohort analysis. RESULTS: A total of 33,798 abdominal trauma patients were evaluated, 10,987 of them received laparotomies. Of these patients, the proportion of obesity in deceased patients was significantly higher when compared to the survivors (33.1% vs. 26.2%, p < 0.001). Elevation of one kg/m(2) of body mass index independently resulted in 2.5% increased odds of mortality. After a well-balanced PSM, obese patients undergoing laparotomies had significantly higher mortality rates [3.7% vs. 2.4%, standardized difference (SD) = 0.241], longer hospital LOS (11.1 vs. 9.6 days, SD = 0.135), and longer intensive care unit LOS (3.5 vs. 2.3 days, SD = 0.171) than non-obese patients undergoing laparotomies. CONCLUSIONS: Obesity is associated with increased mortality in abdominal trauma patients who received laparotomies versus those who did not. Obesity requires a careful evaluation of alternatives to laparotomy in injured patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00268-019-05268-5) contains supplementary material, which is available to authorized users."
1385,The application of non-invasive and invasive mechanical ventilation in the first episode of acute respiratory failure,"Acute respiratory failure (RF) is a life-threatening syndrome. This study investigated the application of two major clinical strategies, non-invasive mechanical ventilation (NIV) and invasive mechanical ventilation (IMV), in the first episode of acute RF. Data from the longitudinal health insurance database, which included 1,000,000 insured citizens, were used. The NIV group consisted of 1201 patients and the IMV group consisted of 16,072 patients. Chi-square test and t test were applied to determine the differences in categorical and continuous variables. Further analysis was performed by using univariate and multivariable logistic regression and Poisson regression. There was a significant increase of 733% in the number of NIV users from 2000 to 2012. NIV use was frequently observed in old-age persons (aOR 3.99, 95% CI 3.06–5.21 for those aged ≥ 80 years), women (aOR 1.33, 95% CI 1.18–1.50), patients admitted to a high-level hospital (aOR 1.95, 95% CI 1.63−2.34 for those admitted to a medical center), and patients with a higher Charlson comorbidity index (CCI, aOR 1.38−1.66 for those CCI ≥ 2). In addition, patients with chronic pulmonary disease, cancer, and congestive heart failure were predominant in NIV users and were significantly associated with NIV use. Overall, the use of NIV has markedly increased over the past few years. Persons of advanced age, women, patients admitted to a high-level hospital, and patients with multiple comorbidities were associated with more frequent NIV use. Chronic pulmonary disease, cancer, and congestive heart failure were most important comorbidities for NIV use. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11739-020-02315-1) contains supplementary material, which is available to authorized users."
1386,Safety and oncological efficacy of bilateral recurrent laryngeal nerve lymph-node dissection after neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma: a propensity-matched analysis,"BACKGROUND: We sought to evaluate the safety and oncological efficacy of bilateral recurrent laryngeal nerve (RLN) lymph-node dissection (LND) in patients with esophageal squamous cell carcinoma (ESCC) who had undergone neoadjuvant chemoradiotherapy (nCRT). METHODS: We retrospectively examined the records of ESCC patients who were judged to be ycN-RLN(-) following nCRT. Patients were divided into two groups according to the extent of LND [standard two-field LND (STL group) versus total two-field LND (TTL group)]. Only lower mediastinal and upper abdominal lymph nodes were removed in the STL group. In addition to the standard procedure, patients in the TTL group underwent resection of upper mediastinal lymph nodes located along the bilateral RLN. Using propensity score matching, 29 pairs were identified and compared with regard to perioperative complications, lymph-node metastases rates, overall survival (OS), and disease-specific survival (DSS). RESULTS: No significant intergroup differences were identified in terms of in-hospital mortality and morbidity. Metastases to the RLN lymph nodes were identified in 20.7% (6/29) of TTL patients, being the only site of lymph-node metastases in three of them. TTL was associated with lower upper mediastinal lymph-node recurrence rate (6.5%) compared with STL (21.5%, p = 0.134), although the overall recurrence rate was similar (STL, 44.8% versus TTL, 46.4%). No significant intergroup differences were also evident with regard to 3-year DSS and OS rates. CONCLUSIONS: RLN LND can be safely performed in ESCC patients who had undergone nCRT, ultimately resulting in an improved local control, and should be practiced as part of the surgical routine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10388-019-00688-7) contains supplementary material, which is available to authorized users."
1387,"The spontaneous breathing trial is of low predictive value regarding spontaneous breathing ability in subjects with prolonged, unsuccessful weaning","BACKGROUND: The spontaneous breathing trial (SBT) is a well-established diagnostic test for predicting extubation failure in intubated intensive care unit (ICU) patients. However, the SBT has not been evaluated in a specific cohort of tracheostomized patients in whom weaning is prolonged and ultimately unsuccessful. OBJECTIVE: The aim of the trial was to investigate the relevance of SBT failure criteria in chronic respiratory failure subjects undergoing long-term invasive home mechanical ventilation following tracheostomy and weaning failure. METHODS: Measurement of all established failure criteria including pneumotachygraphical assessment of the rapid shallow breathing index (RSBI) took place during an SBT. The decision to continue spontaneous breathing was based on failure criteria as well as the subjective willingness of the patient. RESULTS: Fifteen subjects with a median age of 58 years (interquartile range [IQR] 44–74) were studied; 10 with COPD, 4 with neuromuscular diseases and 1 with both. Twelve subjects met the SBT failure criteria within 30 min, but one third of these subjects were still able to continue with spontaneous breathing. In contrast, 3 subjects could not be weaned despite the SBT being successful. An increased RSBI was the most frequently observed SBT failure criterion (57% of all SBT). However, the SBT varied substantially in individual subjects who were able to sustain spontaneous breathing, despite having reached the cut-off for SBT failure. CONCLUSION: The SBT was of low predictive value regarding spontaneous breathing ability in chronic respiratory failure subjects with prolonged, unsuccessful weaning."
1388,Clinical Experience with Telavancin for the Treatment of Patients with Bacteremia and Endocarditis: Real-World Results from the Telavancin Observational Use Registry (TOUR™),"BACKGROUND: Bacteremia and endocarditis caused by Staphylococcus aureus (S. aureus), particularly methicillin-resistant S. aureus (MRSA), are challenging to treat and are associated with high morbidity and mortality. Telavancin is a lipoglycopeptide antibacterial active against susceptible Gram-positive pathogens, including MRSA. OBJECTIVE: This registry study assessed the real-world use and clinical outcomes of telavancin in patients with bacteremia or endocarditis enrolled in the Telavancin Observation Use Registry (TOUR™). METHODS: The subset of patients enrolled in TOUR who were diagnosed with endocarditis and/or bacteremia with a known or unknown primary source (N = 151) were analyzed. Data including demographics, infection type, baseline pathogens, prior or concomitant antimicrobial therapy, dosing regimen, clinical response, treatment-emergent adverse events (TEAEs) of interest, and mortality were collected by retrospective medical chart review. RESULTS: Telavancin was primarily used as a second-line or greater therapy (n = 132, 87.4%). MRSA was present in 87 (57.6%) patients. Median telavancin dose was 740.6 mg (interquartile range (IQR) 206.0 mg) and median duration of therapy was 9.0 days (IQR 24.0 days). Of the 132/151 (87.4%) patients with an available assessment at the end of telavancin therapy, a positive clinical response was achieved in 98/132 (74.2%), while 14/132 (10.6%) failed therapy and 20/132 (15.2%) had an indeterminant outcome. TEAEs occurred in 24 (15.9%) patients. The most frequent TEAE was renal failure (n = 12, 7.9%); seven of these patients were receiving concomitant nephrotoxic medications. There was no change in creatinine clearance for 67/89 (75.3%) patients with values recorded at the beginning and the end of telavancin therapy. CONCLUSIONS: In real-world clinical practice, overall positive clinical outcomes are observed in patients with bacteremia or endocarditis treated with telavancin, including in those patients infected with MRSA or another S. aureus pathogen. Telavancin may be an alternative treatment option for these patients. TRIAL REGISTRATION: This trial was registered with clinicaltrials.gov (NCT02288234) on 11 November 2014. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40801-020-00191-x) contains supplementary material, which is available to authorized users."
1389,"A comprehensive analysis to understand the mechanism of action of balneotherapy: why, how, and where they can be used? Evidence from in vitro studies performed on human and animal samples","Balneotherapy (BT) is one of the most commonly used complementary therapies for many pathological conditions. Its beneficial effects are related to physical and chemical factors, but the exact mechanism of action is not fully understood. Recently, there has been an increased interest in the use of preclinical models to investigate the influence of BT on inflammation, immunity, and cartilage and bone metabolism. The objective of this comprehensive analysis was to summarize the current knowledge about the in vitro studies in BT and to revise the obtained results on the biological effects of mineral waters. Special attention has been paid to the main rheumatological and dermatological conditions, and to the regulation of the immune response. The objective of this review was to summarize the in vitro studies, on human and animal samples, investigating the biological effects of BT. In particular, we analyzed the properties of a thermal water, as a whole, of an inorganic molecule, such as hydrogen sulfide in different cell cultures (keratinocytes, synoviocytes, chondrocytes, and peripheral blood cells), or of the organic component. The results corroborated the scientific value of in vitro studies in demonstrating the anti-inflammatory, antioxidant, chondroprotective, and immunosuppressive role of BT at the cellular level. However, the validity of the cell culture model is limited by several sources of bias, as the differences in experimental procedures, the high heterogeneity among the available researches, and the difficulties in considering all the chemical and physical factors of BT. We would like to stimulate the scientific community to standardize the experimental procedures and enhance in vitro research in the field of BT."
1390,Use of Noninvasive Ventilation in Respiratory Failure After Extubation During Postoperative Care in Pediatrics,"The purpose of this study was to determine the rate of failure of noninvasive ventilation (NIV) after cardiac surgery in pediatric patients with respiratory failure after extubation and to identify predictive success factors. This was a prospective cohort study of pediatric patients diagnosed with congenital heart disease who underwent heart surgery and used NIV. Data were collected from 170 patients with a median age of 2 months. No patient presented cardiorespiratory arrest nor any other complication during the use of NIV. The success rate for the use of NIV was 61.8%. Subjects were divided for analysis into successful and failed NIV groups. Statistical analysis used Chi-square, Mann–Whitney, and Student’s t tests, which were performed after univariate and multivariate logistic regression for p < 0.05. In the multivariate analysis, only the minimal pressure gradient (OR 1.45 with p = 0.007), maximum oxygen saturation (OR 0.88 with p = 0.011), and maximum fraction of inspired oxygen (FiO(2)) (OR 1.16 with p < 0.001) influenced NIV failure. The following variables did not present a statistical difference: extracorporeal circulation time (p = 0.669), pulmonary hypertension (p = 0.254), genetic syndrome (p = 0.342), RACHS-1 score (p = 0.097), age (p = 0.098), invasive mechanical ventilation duration (p = 0.186), and NIV duration (p = 0.804). In conclusion, NIV can be successfully used in children who, after cardiac surgery, develop respiratory failure in the 48 h following extubation. Although the use of higher pressure gradients and higher FiO(2) are associated with a greater failure rate for NIV use, it was found to be generally safe."
1391,Study protocol of a double-blind randomised placebo-controlled trial on the effect of a multispecies probiotic on the incidence of antibiotic-associated diarrhoea in persons with spinal cord injury,"STUDY DESIGN: Multi-centre, double-blind randomised placebo-controlled study. OBJECTIVE: To investigate whether the use of a multispecies probiotic can prevent antibiotic-associated diarrhoea in people with spinal cord injury (SCI). SETTING: Three Dutch SCI rehabilitation centres. METHODS: Fifty-six people aged 18–75 years with SCI during inpatient rehabilitation, who require antibiotics, will be given probiotics or placebo randomly assigned (T0). After cessation of the antibiotics (T1), the participants will use probiotics/placebo for 3 more weeks (T2). Defaecation, assessed by the Bristol Stool Scale, and bowel management will be monitored daily until 2 weeks after cessation of probiotics/placebo intake (T3). Also, the degree of nausea and information on quality of life will be collected at T0, T1, T2 and T3. MAIN OUTCOME MEASURES: The difference between the incidence of antibiotic-associated diarrhoea between people with SCI using probiotics compared to those using a placebo at the moment the antibiotics stops, the probiotics stops and two weeks thereafter. SECONDARY OUTCOME MEASURES: The time to reach effective bowel management, degree of nausea and quality of life. REGISTRATION: The Dutch Trial Register- NTR 5831."
1392,Alternative pathway of complement activation has a beneficial role against Chandipura virus infection,"The complement system is a critical component of both innate and adaptive immune responses. It has both protective and pathogenic roles in viral infections. There are no studies regarding the role of complement system in Chandipura virus (CHPV) infection. The current study has investigated the role of complement pathways in the in vitro neutralization of CHPV in Vero E6 cells. Using normal human serum (NHS), heat-inactivated serum (HIS), human serum deficient of complement factor, respective reconstituted serum, assays like in vitro neutralization, real-time PCR, and flow cytometry-based tissue culture-based limited dose assay (TC-LDA) were carried out for assessing the activation of different complement pathways. NHS from 9/10 donors showed complement dependent neutralization, reduction in viral load and decrease in percentage of CHPV-positive cells compared to their HIS counterparts. EGTA or EDTA pretreatment experiments indicated that CHPV neutralization proceeds through the alternative pathway of the complement activation. Our data showed a strong dependence on C3 for the in vitro neutralization of CHPV. Disparity in CHPV neutralization levels between factor B-deficient and reconstituted sera could be attributed to amplification loop/“tick-over” mechanism. Assays using C3, C5, and C8 deficient sera indicated that complement-mediated CHPV neutralization and suppression of CHPV infectivity are primarily through C3 and C5, and not dependent on downstream complement factor C8. With no specific anti-viral treatment/vaccine against Chandipura, the current data, elucidating role of human complement system in the neutralization of CHPV, may help in designing effective therapeutics."
1393,Coping Behaviors Mediate Associations between Occupational Factors and Compassion Satisfaction among the Intimate Partner Violence and Sexual Assault Workforce,"The intimate partner violence (IPV) and sexual assault (SA) workforce faces significant occupational stressors yet little is known about positive occupational outcomes associated with this work. Therefore, this study analyzed factors associated with compassion satisfaction among the IPV/SA workforce in one southwestern U.S. state (n = 623). Drawing from the Resilience Portfolio Model (Grych et al. 2015), researchers examined the possible role of coping behaviors in mediating associations between compassion satisfaction and workplace resources / assets, perceived job security, and resilience. Analyses revealed partial mediation in the models that included workload, values, and resilience as independent variables, suggesting that these factors both influence workers’ coping behaviors and have an independent association with compassion satisfaction. Models investigating control, rewards, community, fairness, and perceived job security indicated significant total effects of the independent variables on compassion satisfaction. Overall, IPV/SA workers who engaged more frequently in a range of coping behaviors reported higher levels of compassion satisfaction. The findings point to implications for organizational and employee practice, including building in worktime for key individual coping behaviors, balancing workloads among staff members, and enhancing organizational level coping strategies, such as team supervision and team care planning."
1394,NAD(+) homeostasis in renal health and disease,"The mammalian kidney relies on abundant mitochondria in the renal tubule to generate sufficient ATP to provide the energy required for constant reclamation of solutes from crude blood filtrate. The highly metabolically active cells of the renal tubule also pair their energetic needs to the regulation of diverse cellular processes, including energy generation, antioxidant responses, autophagy and mitochondrial quality control. Nicotinamide adenine dinucleotide (NAD(+)) is essential not only for the harvesting of energy from substrates but also for an array of regulatory reactions that determine cellular health. In acute kidney injury (AKI), substantial decreases in the levels of NAD(+) impair energy generation and, ultimately, the core kidney function of selective solute transport. Conversely, augmentation of NAD(+) may protect the kidney tubule against diverse acute stressors. For example, NAD(+) augmentation can ameliorate experimental AKI triggered by ischaemia–reperfusion, toxic injury and systemic inflammation. NAD(+)-dependent maintenance of renal tubular metabolic health may also attenuate long-term profibrotic responses that could lead to chronic kidney disease. Further understanding of the genetic, environmental and nutritional factors that influence NAD(+) biosynthesis and renal resilience may lead to novel approaches for the prevention and treatment of kidney disease."
1395,"Genetic characterization of a novel recombinant echovirus 30 strain causing a regional epidemic of aseptic meningitis in Hokkaido, Japan, 2017","A regional epidemic of aseptic meningitis caused by echovirus 30 (E30) occurred in Hokkaido, Japan, during the period of August-December 2017. To investigate their phylogenetic relationship to other human enteroviruses, we determined the complete genomic nucleotide sequences of isolates from this outbreak. Phylogenetic analysis of the viral capsid protein 1 gene showed that the strains were most closely related to E30 strains detected in Germany, France, and Russia in 2013. In contrast, the region encoding the viral protease and the RNA-dependent RNA polymerase had a close phylogenetic relationship to non-E30 enteroviruses detected in the United Kingdom and Switzerland in 2015-2017, suggesting that a recombination event had occurred. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04484-7) contains supplementary material, which is available to authorized users."
1396,Processing the Removal and Managing the Moves or Removals of Foster Children: A Qualitative Exploration of Foster Parents’ Experiences,"Foster parents are crucial to the function of the child welfare system. Despite developments in research related to the grief and loss of foster parents, more research would be helpful in building a stronger understanding and knowledge base for helping foster parents manage the removals of foster children in their home. This study included ten foster parents from the United States and explored their experience with loss and the stress associated with the expected or unexpected removal of a foster child from their home. The findings of the data analysis yielded three overarching themes: (1) managing or coping with ambiguous loss; (2) systemic impacts of a move or removal on a family; (3) need for helpful preparation or support for dealing with the loss of foster child. Implications include better preparation and support for foster parents dealing with moves and removals of foster children, as well as considering less abrupt removals of children from foster homes."
1397,"Outcomes in conventional laparoscopic versus robotic-assisted revisional bariatric surgery: a retrospective, case–controlled study of the MBSAQIP database","INTRODUCTION: Revisional bariatric surgery is being increasingly performed and is associated with higher operative risks. Optimal techniques to minimize complications remain controversial. Here, we report a retrospective review of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Participant User Files (PUF) database, comparing outcomes between revision RBS and LBS. METHODS: The 2015 and 2016 MBSAQIP PUF database was retrospectively reviewed. Revision cases were identified using the Revision/Conversion Flag. Selected cases were further stratified by surgical approach. Subgroup analysis of sleeve gastrectomy and gastric bypass cases was performed. Case–controlled matching (1:1) was performed of the RBS and LBS cohorts, including gastric bypass and sleeve gastrectomy cohorts separately. Cases and controls were match by demographics, ASA classification, and preoperative comorbidities. RESULTS: 26,404 revision cases were identified (93.3% LBS, 6.7% RBS). 85.6% were female and 67% white. Mean age and BMI were 48 years and 40.9 kg/m(2). 1144 matched RBS and LBS cases were identified. RBS was associated with longer operative duration (p < 0.0001), LOS (p = 0.0002) and a higher rate of ICU admissions (1.3% vs 0.5%, p = 0.05). Aggregate bleeding and leak rates were higher in the RBS cohort. In both gastric bypass and sleeve gastrectomy cohorts, the robotic-assisted surgery remain associated with longer operative duration (p < 0.0001). In gastric bypass, rates of aggregate leak and bleeding were higher with robotic surgery, while transfusion was higher with laparoscopy. For sleeve gastrectomy cases, reoperation, readmission, intervention, sepsis, organ space SSI, and transfusion were higher with robotic surgery. CONCLUSION: In this matched cohort analysis of revision bariatric surgery, both approaches were overall safe. RBS was associated with longer operative duration and higher rates of some complications. Complications were higher in the robotic sleeve cohort. Robotic is likely less cost-effective with no clear patient safety benefit, particularly for sleeve gastrectomy cases."
1398,Impact of vaccination during pregnancy and staphylococci concentration on the presence of Bacillus cereus in raw human milk,"OBJECTIVE: This study aimed to determine whether vaccination during pregnancy, prematurity, and staphylococci concentration influenced the presence of B. cereus or staphylococcal enterotoxins (SEs) in raw human milk from healthy mothers. STUDY DESIGN: Human milk samples were collected from 152 healthy women. B. cereus, S. aureus and coagulase-negative staphylococci (CNS) were enumerated using selective agar culture media. The detection of B. cereus spores and SEs were determined using ELISA. RESULTS: CNS and B. cereus concentrations in milk from non-vaccinated mothers were higher than that from mothers vaccinated during pregnancy, but S. aureus did not differ. Prematurity did not affect B. cereus or staphylococci in human milk. S. aureus and CNS concentrations in human milk with the presence of B. cereus were higher than that with the absence of B. cereus. Viable B. cereus was present in 9.2% of raw human milk samples whereas SEs were not detected in any samples. CONCLUSIONS: Vaccination during pregnancy and low concentration of staphylococci could reduce the risk of B. cereus in raw human milk. The screening of B. cereus in raw human milk must be performed before pasteurization to reduce the risk of B. cereus infection in preterm infants."
1399,"The influence of pain, agitation, and their management on the immature brain","Preterm infants are exposed to frequent painful procedures and agitating stimuli over the many weeks of their hospitalization in the neonatal intensive care unit (NICU). The adverse neurobiological impact of pain and stress in the preterm infant has been well documented, including neuroimaging and neurobehavioral outcomes. Although many tools have been validated to assess acute pain, few methods are available to assess chronic pain or agitation (a clinical manifestation of neonatal stress). Both nonpharmacologic and pharmacologic approaches are used to reduce the negative impact of pain and agitation in the preterm infant, with concerns emerging over the adverse effects of analgesia and sedatives. Considering benefits and risks of available treatments, units must develop a stepwise algorithm to prevent, assess, and treat pain. Nonpharmacologic interventions should be consistently utilized prior to mild to moderately painful procedures. Sucrose may be utilized judiciously as an adjunctive therapy for minor painful procedures. Rapidly acting opioids (fentanyl or remifentanil) form the backbone of analgesia for moderately painful procedures. Chronic sedation during invasive mechanical ventilation represents an ongoing challenge; appropriate containment and an optimal environment should be standard; when indicated, low-dose morphine infusion may be utilized cautiously and dexmedetomidine infusion may be considered as an emerging adjunct."
1400,Ebola virus disease,"Ebola virus disease (EVD) is a severe and frequently lethal disease caused by Ebola virus (EBOV). EVD outbreaks typically start from a single case of probable zoonotic transmission, followed by human-to-human transmission via direct contact or contact with infected bodily fluids or contaminated fomites. EVD has a high case–fatality rate; it is characterized by fever, gastrointestinal signs and multiple organ dysfunction syndrome. Diagnosis requires a combination of case definition and laboratory tests, typically real-time reverse transcription PCR to detect viral RNA or rapid diagnostic tests based on immunoassays to detect EBOV antigens. Recent advances in medical countermeasure research resulted in the recent approval of an EBOV-targeted vaccine by European and US regulatory agencies. The results of a randomized clinical trial of investigational therapeutics for EVD demonstrated survival benefits from two monoclonal antibody products targeting the EBOV membrane glycoprotein. New observations emerging from the unprecedented 2013–2016 Western African EVD outbreak (the largest in history) and the ongoing EVD outbreak in the Democratic Republic of the Congo have substantially improved the understanding of EVD and viral persistence in survivors of EVD, resulting in new strategies toward prevention of infection and optimization of clinical management, acute illness outcomes and attendance to the clinical care needs of patients."
1401,Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper(#),"PURPOSE: This Position Paper aims to review and discuss the available data on therapeutic drug monitoring (TDM) of antibacterials, antifungals and antivirals in critically ill adult patients in the intensive care unit (ICU). This Position Paper also provides a practical guide on how TDM can be applied in routine clinical practice to improve therapeutic outcomes in critically ill adult patients. METHODS: Literature review and analysis were performed by Panel Members nominated by the endorsing organisations, European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/Pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) and International Society of Antimicrobial Chemotherapy (ISAC). Panel members made recommendations for whether TDM should be applied clinically for different antimicrobials/classes. RESULTS: TDM-guided dosing has been shown to be clinically beneficial for aminoglycosides, voriconazole and ribavirin. For most common antibiotics and antifungals in the ICU, a clear therapeutic range has been established, and for these agents, routine TDM in critically ill patients appears meritorious. For the antivirals, research is needed to identify therapeutic targets and determine whether antiviral TDM is indeed meritorious in this patient population. The Panel Members recommend routine TDM to be performed for aminoglycosides, beta-lactam antibiotics, linezolid, teicoplanin, vancomycin and voriconazole in critically ill patients. CONCLUSION: Although TDM should be the standard of care for most antimicrobials in every ICU, important barriers need to be addressed before routine TDM can be widely employed worldwide. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06050-1) contains supplementary material, which is available to authorized users."
1402,Modeling the effect of information transmission on the drug dynamic,"In each community, there is a lot of information about the disadvantages and risks of drug use and its negative effects on health, work, honor, and other living funds of people. A group of individuals, who can be called responsive individuals, will be safe from the risk of drug abuse, by receiving and understanding such information. In this paper, by proposing mathematical models, we investigate the effect of the distribution of this kind of information on the transformation of susceptible individuals into responsive individuals as well as their effect in preventing the occurrence of substance abuse epidemics. In these models, we take into account the fact that the spirit of responsiveness of these individuals can be decayed with time, and these people can become susceptible people, and eventually to addicts. We analyze the dynamical properties of the models, such as local and global stability of equilibrium points and the occurrence of backward bifurcation. The results of this study show that the higher the rate of conversion of susceptible individuals to those responsive, the prevention of drug epidemy is easier."
1403,2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias,"Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. An expert writing group, after reviewing and discussing the literature, including a systematic review and meta-analysis published in conjunction with this document, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Each recommendation is presented in knowledge byte format and is accompanied by supportive text and references. Further sections provide a practical synopsis of the various techniques and of the specific ventricular arrhythmia sites and substrates encountered in the electrophysiology lab. The purpose of this document is to help electrophysiologists around the world to appropriately select patients for catheter ablation, to perform procedures in a safe and efficacious manner, and to provide follow-up and adjunctive care in order to obtain the best possible outcomes for patients with ventricular arrhythmias. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10840-019-00663-3) contains supplementary material, which is available to authorized users."
1404,Compassion Meditation for Veterans with Posttraumatic Stress Disorder (PTSD): a Nonrandomized Study,"Compassion meditation (CM) is a contemplative practice that is intended to cultivate the ability to extend and sustain compassion toward self and others. Although research documents the benefits of CM in healthy populations, its use in the context of psychopathology is largely unexamined. The purpose of this study was to refine and initially evaluate a CM protocol, Cognitively Based Compassion Training (CBCT®), for use with Veterans with PTSD. To this end, our research team developed and refined a manualized protocol, CBCT-Vet, over 4 sets of groups involving 36 Veterans. This protocol was delivered in 8–10 sessions, each lasting 90–120 min and led by a CBCT®-trained clinical psychologist. Quantitative and qualitative data were used to identify areas to be improved and to assess change that occurred during the treatment period. Based on pooled data from this series of groups, CM appears to be acceptable to Veterans with PTSD. Group participation was associated with reduced symptoms of PTSD (partial eta squared = .27) and depression (partial eta squared = .19), but causality should not be inferred given the nonrandomized design. No change was observed in additional outcomes, including positive emotion and social connectedness. The results of this open trial support additional exploration of CM as part of the recovery process for Veterans with PTSD."
1405,Renal outcomes of neonates with early presentation of posterior urethral valves: a 10-year single center experience,"OBJECTIVE: Evaluate renal outcomes and early predictive factors in infants with congenital posterior urethral valves who required catheter or surgical urinary tract decompression within the first 7 days of life. STUDY DESIGN: A 10-year retrospective study at a single hospital. Primary outcomes were estimated glomerular filtration rate (eGFR) and development of end stage renal disease (ESRD). RESULTS: Of 35 infants, 50% developed eGFR <90 mL/min/1.73 m(2) and 15% progressed to ESRD. Nadir creatinine, need for invasive ventilation in the newborn period, and need for surgical diversion after catheter diversion were associated with worse outcomes. 50% of infants requiring invasive ventilation as neonates developed eGFR <60 mL/min/1.73 m(2) in childhood. CONCLUSIONS: Half of infants with early presentation and intervention developed significant renal insufficiency in childhood, similar to children with later presentation or who had fetal intervention. Invasive ventilation in the newborn period and need for surgical urinary diversion are associated with worse outcomes."
1406,Missed vaccinations and critical care admission: all you may wish to know or rediscover—a narrative review,"Most vaccines are so effective that they could lead to the control/elimination of the diseases they target and directly impact on intensive care admissions or complications. This is best illustrated by the use of vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, zoster, yellow fever, Ebola virus, influenza or measles—but also by third party strategies such as maternal, toddler and care-giver immunization. However, each of these vaccine-induced protection is threatened by insufficient vaccine uptake. Here, we briefly discuss how vaccine hesitancy has led to the resurgence of diseases that were considered as controlled and explore the effect of vaccine-hesitant healthcare workers on nosocomial infections. As intensive care physicians are in charge of polymorbid patients, we briefly summarize the current recommendations for vaccinations in high-risk patients. We finally give some perspective on ongoing research, and discuss how institutional policies and intensive care physicians could play a role in increasing the impact of vaccination, overall and in intensive care units."
1407,A brief airway occlusion is sufficient to measure the patient’s inspiratory effort/electrical activity of the diaphragm index (PEI),"Pressure generated by patient’s inspiratory muscles (Pmus) during assisted mechanical ventilation is of significant relevance. However, Pmus is not commonly measured since an esophageal balloon catheter is required. We have previously shown that Pmus can be estimated by measuring the electrical activity of the diaphragm (EAdi) through the Pmus/EAdi index (PEI). We investigated whether PEI could be reliably measured by a brief end-expiratory occlusion maneuver to propose an automated PEI measurement performed by the ventilator. Pmus, EAdi, airway pressure (Paw), and flow waveforms of 12 critically ill patients undergoing assisted mechanical ventilation were recorded. Repeated end-expiratory occlusion maneuvers were performed. PEI was measured at 100 ms (PEI(0.1)) and 200 ms (PEI(0.2)) from the start of the occlusion and compared to the PEI measured at the maximum Paw deflection (PEI(occl), reference). PEI(0.1) and PEI(0.2) tightly correlated with PEI(occl), (p < 0.001, R(2) = 0.843 and 0.847). At a patient-level analysis, the highest percentage error was -64% and 50% for PEI(0.1) and PEI(0.2), respectively, suggesting that PEI(0.2) might be a more reliable measurement. After correcting the error bias, the PEI(0.2) percentage error was lower than ± 30% in all but one subjects (range − 39 to + 29%). It is possible to calculate PEI over a brief airway occlusion of 200 ms at inspiratory onset without the need for a full patient's inspiratory effort. Automated and repeated brief airway occlusions performed by the ventilator can provide a real time measurement of PEI; combining the automatically measured PEI with the EAdi trace could be used to continuously display the Pmus waveform at the bedside without the need of an esophageal balloon catheter. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-020-00459-1) contains supplementary material, which is available to authorized users."
1408,"Immune thrombocytopenic purpura risk by live, inactivated and simultaneous vaccinations among Japanese adults, children and infants: a matched case–control study","This case–control study investigated immune thrombocytopenic purpura (ITP) risk following live, inactivated, and simultaneous vaccination, with a focus on infants aged < 2 years. We matched case patients with ITP to one or two control patients with other diseases by institution, hospital visit timing, sex, and age. We calculated McNemar’s pairwise odds ratios (ORs [95% confidence interval]) with 114 case–control pairs. The case group had 27 (44%) males and 22 (35%) infants, and the control group included 49 (43%) males and 42 (37%) infants. For all age groups, the McNemar’s OR for ITP occurrence was 1.80 (0.54–6.84, p = 0.64) for all vaccines. Among infants, these were 1.50 (0.17–18.0, p = 0.50) for all vaccines, 2.00 (0.29–22.1, p = 0.67) for live vaccines, and 1.00 (0.01–78.5, p = 0.50) for inactivated vaccines. Sex-adjusted common ORs for simultaneous vaccination were 1.52 (0.45–5.21, p = 0.71) for all vaccines, 1.83 (0.44–7.59, p = 0.40) for inactivated vaccines only, and 1.36 (0.29–6.30, p = 0.69) for mixed live and inactivated vaccines. In infants, these were 1.95 (0.44–8.72, p = 0.38), 1.41 (0.29–6.94, p = 0.67) and 2.85 (0.43–18.9, p = 0.28), respectively. These limited data suggest no significant ITP risk following vaccinations or simultaneous vaccination in any age group, including infants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12185-020-02866-1) contains supplementary material, which is available to authorized users."
1409,Safety of Major Abdominal Operations in the Elderly: A Study of Geriatric-Specific Determinants of Health,"BACKGROUND: Preoperative assessment of geriatric-specific determinants of health may enhance perioperative risk stratification among elderly patients. This study examines effects of geriatric-specific variables on postoperative outcomes in patients undergoing elective major abdominal operations. METHODS: Patients included in the ACS NSQIP pilot Geriatric Surgery Research File program who underwent elective pancreatic, liver, and colorectal operations between 2014 and 2016 were examined. Multivariable analyses were performed to evaluate associations between patient-specific geriatric variables and risk of death, morbidity, readmission, and discharge destination. RESULTS: A total of 4165 patients were included. Patients ≥85 years were more likely to die, experience postoperative morbidity, and be discharged to a facility (all p ≤ 0.039) than younger patients. Preoperatively, patients ≥85 years were more likely to use a mobility aid, have a prior fall, have consent signed by a surrogate, and to live alone at home prior to operation (all p < 0.001). After adjustment for ACS NSQIP-estimated probabilities of morbidity or mortality, no geriatric-specific preoperative risk factors were significantly associated with increased risk of death or complications in any age group (all p > 0.055). Patients 75–84 and ≥85 years were more likely to be discharged to facility (OR 2.33 and 4.75, respectively, both p < 0.001) compared to patients 65–74 years. All geriatric-specific variables: use of mobility aid, living alone, consent signed by a surrogate, and fall history, were significantly associated with discharge to a facility (all p ≤ 0.001). CONCLUSIONS: After adjusting for comorbid conditions, geriatric-specific variables are not associated with postoperative mortality and morbidity among elderly patients; however, geriatric-specific variables are significantly associated with discharge to a facility."
1410,The Consent Form in the Chinese CRISPR Study: In Search of Ethical Gene Editing,"This editorial provides an ethical analysis of the consent materials and other documents relating to the recent creation and birth of twin girls who had their genes edited using CRISPR-cas9 in a controversial Chinese research study. It also examines the “draft ethical principles” published by the leader of the research study. The results of the analysis further intensify serious ethical concerns about the conduct of this study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11673-019-09953-x) contains supplementary material, which is available to authorized users."
1411,Two-site regional oxygen saturation and capnography monitoring during resuscitation after cardiac arrest in a swine pediatric ventricular fibrillatory arrest model,"To investigate the use of two-site regional oxygen saturations (rSO(2)) and end tidal carbon dioxide (EtCO(2)) to assess the effectiveness of resuscitation and return of spontaneous circulation (ROSC). Eight mechanically ventilated juvenile swine underwent 28 ventricular fibrillatory arrests with open cardiac massage. Cardiac massage was administered to achieve target pulmonary blood flow (PBF) as a percentage of pre-cardiac arrest baseline. Non-invasive data, including, EtCO(2), cerebral rSO(2) (C-rSO(2)) and renal rSO(2) (R-rSO(2)) were collected continuously. Our data demonstrate the ability to measure both rSO(2) and EtCO(2) during CPR and after ROSC. During resuscitation EtCO(2) had a strong correlation with goal CO with r = 0.83 (p < 0.001) 95% CI [0.67–0.92]. Both C-rSO(2) and R-rSO(2) had moderate and statistically significant correlation with CO with r = 0.52 (p = 0.003) 95% CI (0.19–0.74) and 0.50 (p = 0.004) 95% CI [0.16–0.73]. The AUCs for sudden increase of EtCO(2), C-rSO(2), and R-rSO(2) at ROSC were 0.86 [95% CI, 0.77–0.94], 0.87 [95% CI, 0.8–0.94], and 0.98 [95% CI, 0.96–1.00] respectively. Measurement of continuous EtCO(2) and rSO(2) may be used during CPR to ensure effective chest compressions. Moreover, both rSO(2) and EtCO(2) may be used to detect ROSC in a swine pediatric ventricular fibrillatory arrest model."
1412,Impact of Leadership of Trained Intensivist in Pediatric Intensive Care Unit in a Middle Income Country: An Uncontrolled Before-After Study,"OBJECTIVE: To evaluate the effects generated by an intensivist in pediatric intensive care unit (PICU) on the process of care and patient outcomes. METHODS: This study was a retrospective observational study conducted in the 16-bedded PICU of a tertiary referral center. Two years (2013–2015) period of the PICU without an intensivist and the following two years (2015–2017) when it was attended by an intensivist who was also the first ever graduate of the fellowship program in Turkey were compared. RESULTS: Number of patients followed in PICU increased more than 2-fold. Number of mechanically ventilated patients increased more than 2-folds and presence of intensivist reduced the mechanical ventilation duration by 59%. Presence of intensivist reduced the mortality rates by 2.18 times. It was shown that management of PICU beds by an intensivist resulted in increased number of patients per year per PICU bed, increased care of true critical care patients who are in need of more intensive therapies and invasive procedures including extracorporeal treatment options, decreased length of stay, decreased number and rate of nosocomial infections, and decreased mortality rate. CONCLUSIONS: What transforms a unit full of critically ill patients to an intensive care unit is a dedicated intensivist. The current study demonstrated that intensivist is the crucial component of the PICUs."
1413,"Influence of Inhalation Injury on Incidence, Clinical Profile and Recovery Pattern of Dysphagia Following Burn Injury","Inhalation injury is predictive of dysphagia post burns; however, the nature of dysphagia associated with inhalation burns is not well understood. This study describes the clinical profile and recovery pattern of swallowing following inhalation burn injury. All patients admitted 2008–2017 with confirmed inhalation burns on laryngoscopy and managed by speech-language pathology (SLP) were included. Initial dysphagia presentation and dysphagia recovery pattern were documented using the FOIS. Co-presence of dysphonia was determined clinically and rated present/absent. Persistent laryngeal/pharyngeal injury at 6 months was documented using laryngoscopy. Data were compared to published data from a large adult burn cohort. All patients with confirmed inhalation burns during the study period received SLP input, enabling review of 38 patients (68% male; m = 40.8 years). Percent Total Body Surface Area burn ranged 1–90%, 100% had head and neck burns, 97% required mechanical ventilation (mean 9.4 days), 18% required tracheostomy and 100% had dysphonia. Comparing to non-inhalation burn patients, the inhalation cohort had significantly (p < 0.01) higher dysphagia incidence (89.47% vs 5.6%); more with severe dysphagia at presentation (78.9% vs 1.7%); increased duration to initiate oral intake (m = 24.69 vs 0.089 days); longer duration of enteral feeding (m = 45.03 vs 1.96 days); and longer duration to resolution of dysphagia (m = 29.79 vs 1.67 days). Persistent laryngeal pathology was present in 47.37% at 6 months. This study shows dysphagia incidence in burn patients with inhalation injury is 16 times greater than for those without inhalation injury. Laryngeal pathology due to inhalation injury increases dysphagia severity and duration to dysphagia recovery."
1414,Single-stage synthesis of heterocyclic alkaloid-like compounds from (+)-camphoric acid and their antiviral activity,"ABSTRACT: An effective technique for one-stage synthesis of new polycyclic nitrogen-containing compounds has been developed. The procedure involves refluxing mixtures of camphoric acid with aliphatic or aromatic diamine without catalysts. In cases where the starting amine has a low boiling point (less than 200 °C), phenol is used as a solvent, as it is the most optimal one for obtaining products with good yields. It has been shown that the use of Lewis acids as catalysts reduces the yield of the reaction products. A set of compounds have been synthesized, which can be attributed to synthetic analogues of alkaloids. In vitro screening for activity influenza virus A was carried out for the obtained compounds. The synthesized quinazoline-like agent 14 has inhibitory activity against different strains of influenza viruses. GRAPHICAL ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11030-019-09932-9) contains supplementary material, which is available to authorized users."
1415,Vaccination against the Epstein–Barr virus,"Epstein–Barr virus (EBV) was the first human tumor virus being discovered and remains to date the only human pathogen that can transform cells in vitro. 55 years of EBV research have now brought us to the brink of an EBV vaccine. For this purpose, recombinant viral vectors and their heterologous prime-boost vaccinations, EBV-derived virus-like particles and viral envelope glycoprotein formulations are explored and are discussed in this review. Even so, cell-mediated immune control by cytotoxic lymphocytes protects healthy virus carriers from EBV-associated malignancies, antibodies might be able to prevent symptomatic primary infection, the most likely EBV-associated pathology against which EBV vaccines will be initially tested. Thus, the variety of EBV vaccines reflects the sophisticated life cycle of this human tumor virus and only vaccination in humans will finally be able to reveal the efficacy of these candidates. Nevertheless, the recently renewed efforts to develop an EBV vaccine and the long history of safe adoptive T cell transfer to treat EBV-associated malignancies suggest that this oncogenic γ-herpesvirus can be targeted by immunotherapies. Such vaccination should ideally implement the very same immune control that protects healthy EBV carriers."
1416,"Prevention of Pain During Screening for Retinopathy of Prematurity: A Randomized Control Trial Comparing Breast Milk, 10% Dextrose and Sterile Water","OBJECTIVES: To compare the efficacy of orally administered 10% dextrose, breast milk and sterile water on pain prevention during screening examination for Retinopathy of prematurity (ROP) in preterm neonates as measured by Premature infant pain profile (PIPP). METHODS: A three-limbed double-blinded randomized control trial was conducted in a Level 3 neonatal intensive care unit. Forty five preterm neonates undergoing ROP screening were included. Eligible babies were randomly assigned to one of the three groups that orally received either expressed breast milk (n = 14), 10% dextrose solution (n = 14) or sterile water (n = 17), one minute before eye examination. The outcome measure was PIPP score. RESULTS: All 3 groups were similar in baseline characteristics. The mean PIPP scores were comparable (p = 0.18) in the three groups (11.8 ± 2.8 vs. 9.8 ± 3.3 vs. 10.2 ± 2.9). The behavioral and physiological variables were also similar across all three groups. CONCLUSIONS: Expressed breast milk, 10% dextrose or sterile water administered orally before ROP screening in preterm neonates have similar analgesic effects and do not significantly alleviate pain during the procedure."
1417,Human unconventional T cells in Plasmodium falciparum infection,"Malaria is an old scourge of humankind and has a large negative impact on the economic development of affected communities. Recent success in malaria control and reduction of mortality seems to have stalled emphasizing that our current intervention tools need to be complemented by malaria vaccines. Different populations of unconventional T cells such as mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells and γδ T cells are gaining attention in the field of malaria immunology. Significant advances in our basic understanding of unconventional T cell biology in rodent malaria models have been made, however, their roles in humans during malaria are less clear. Unconventional T cells are abundant in skin, gut and liver tissues, and long-lasting expansions and functional alterations were observed upon malaria infection in malaria naïve and malaria pre-exposed volunteers. Here, we review the current understanding of involvement of unconventional T cells in anti-Plasmodium falciparum immunity and highlight potential future research avenues."
1418,Dual-room twin-CT scanner in multiple trauma care: first results after implementation in a level one trauma centre,"PURPOSE: The trauma centre of the Wuerzburg University Hospital has integrated a pioneering dual-room twin-CT scanner in a multiple trauma pathway. For concurrent treatment of two trauma patients, two carbon CT examination and intervention tables are positioned head to head with one sliding CT-Gantry in the middle. The focus of this study is the process of trauma care with the time to CT (tCT) and the time to operation (tOR) as quality indicator. METHODS: All patients with suspected multiple trauma, who required emergency surgery and who were initially diagnosed by the CT trauma protocol between 05/2018 and 12/2018 were included. Data relating to time spans (tCT and tOR), severity of injury and outcome was obtained. RESULTS: 110 of the 589 screened trauma patients had surgery immediately after finishing primary assessment in the ER. The ISS was 17 (9–34) (median and interquartile range, IQR). tCT was 15 (11–19) minutes (median and IQR) and tOR was 96.5 (75–119) minutes (median and IQR). In the first 30 days, seven patients died (6.4%) including two within the first 24 h (2%). There were two ICU days (1–6) (median and IQR) and one (0–1) (median and IQR) ventilator day. CONCLUSION: The twin-CT technology is a fascinating tool to organize high-quality trauma care for two multiple trauma patients simultaneously."
1419,Exploring Lassa Virus Proteome to Design a Multi-epitope Vaccine Through Immunoinformatics and Immune Simulation Analyses,"Lassa virus (LASV) is responsible for a type of acute viral haemorrhagic fever referred to as Lassa fever. Lack of adequate treatment and preventive measures against LASV resulted in a high mortality rate in its endemic regions. In this study, a multi-epitope vaccine was designed using immunoinformatics as a prophylactic agent against the virus. Following a rigorous assessment, the vaccine was built using T-cell (N(CTL) = 8 and N(HTL) = 6) and B-cell (N(LBL) = 4) epitopes from each LASV-derived protein in addition with suitable linkers and adjuvant. The physicochemistry, immunogenic potency and safeness of the designed vaccine (~ 68 kDa) were assessed. In addition, chosen CTL and HTL epitopes of our vaccine showed 97.37% worldwide population coverage. Besides, disulphide engineering also improved the stability of the chimeric vaccine. Molecular docking of our vaccine protein with toll-like receptor 2 (TLR2) showed binding efficiency followed by dynamics simulation for stable interaction. Furthermore, higher levels of cell-mediated immunity and rapid antigen clearance were suggested by immune simulation and repeated-exposure simulation, respectively. Finally, the optimized codons were used in in silico cloning to ensure higher expression within E. coli K12 bacterium. With further assessment both in vitro and in vivo, we believe that our proposed peptide-vaccine would be potential immunogen against Lassa fever. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10989-019-10003-8) contains supplementary material, which is available to authorized users."
1420,Dose-escalation trial of budesonide in surfactant for prevention of bronchopulmonary dysplasia in extremely low gestational age high-risk newborns (SASSIE),"BACKGROUND: Initial trials of lung-targeted budesonide (0.25 mg/kg) in surfactant to prevent bronchopulmonary dysplasia (BPD) in premature infants have shown benefit; however, the optimal safe dose is unknown. METHODS: Dose-escalation study of budesonide (0.025, 0.05, 0.10 mg/kg) in calfactatant in extremely low gestational age neonates (ELGANs) requiring intubation at 3−14 days. Tracheal aspirate (TA) cytokines, blood budesonide concentrations, and untargeted blood metabolomics were measured. Outcomes were compared with matched infants receiving surfactant in the Trial Of Late SURFactant (TOLSURF). RESULTS: Twenty-four infants with mean gestational age 25.0 weeks and 743 g birth weight requiring mechanical ventilation were enrolled at mean age 6 days. Budesonide was detected in the blood of all infants with a half-life of 3.4 h. Of 11 infants with elevated TA cytokine levels at baseline, treatment was associated with sustained decrease (mean 65%) at all three dosing levels. There were time- and dose-dependent decreases in blood cortisol concentrations and changes in total blood metabolites. Respiratory outcomes did not differ from the historic controls. CONCLUSIONS: Budesonide/surfactant had no clinical respiratory benefit at any dosing levels for intubated ELGANs. One-tenth the dose used in previous trials had minimal systemic metabolic effects and appeared effective for lung-targeted anti-inflammatory action."
1421,A conjugated mTOR/MEK bifunctional inhibitor as potential polypharmacological anticancer agent: the prototype compound discovery,"mTOR/MEK bifunctional inhibitors have the potential to surmount the drug resistance aroused from cross talk between PI3K/Akt/mTOR (PAM) and Ras/MEK/ERK pathways. Herein, we report the discovery of a conjugated dual-targeted molecule, compound 13, as the prototype mTOR/MEK bifunctional inhibitor. It exhibited moderately high inhibitory activity against mTOR and MEK1 with IC(50) values of 0.19 μM and 0.98 μM, respectively. In particular, it displayed attractive antiproliferative activity against both A549 (GI(50) = 4.66 μM) and HCT116 (GI(50) = 5.47 μM) cell lines. To our knowledge, it has been the first example of a conjugated mTOR/MEK bifunctional inhibitor. In addition, from this proof-of-principle study, it has become evident that the single-agent dual inhibition of mTOR and MEK can be fulfilled via covalently attaching mTOR kinase inhibitor to an allosteric MEK inhibitor."
1422,Focus on paediatrics,
1423,The possible regions to design Human Papilloma Viruses vaccine in Iranian L1 protein,"Human Papilloma Virus (HPV) genome encodes several proteins, as L1is major capsid protein and L2 is minor capsid protein. Among all HPV types HPV-16 and HPV-18 are the most common high-risk HPV (HR-HPV) types globally and the majority of cases are infected with these types. HPV entry and the initial interaction with the host cell are mainly related to the L1 protein which is the main component of HPV vaccines. The aim of this research was comparison analysis among all Iranian L1 protein sequences submitted in NCBI GenBank to find the major substitutions as well as structural and immune properties of this protein. All sequences HPV L1 protein from Iranian isolates from 2014 to 2016 were selected and obtained from NCBI data bank. “CLC Genomics Workbench” was used to translate alignment. To predict B cell epitopes, we employed several programs. Modification sites such as phosphorylation, glycosylation, and disulfide bonds were determined. Secondary and tertiary structures of all sequences were analyzed. Several mutations were found and major mutations were in amino acid residues 102, 202, 207, 292, 379, and 502. The mentioned mutations showed the minor effect on B cell and physicochemical properties of the L1 protein. Six disulfide bonds were determined in L1 protein and also in several N-link glycosylation and phosphorylation sites. Five L1 loops were determined, which had great potential to be B cell epitopes with high antigenic properties. All in all, this research as the first report from Iran described the tremendous potential of two L1 loops (BC and FG) to induce immune system which can be used as the descent candidate to design a new vaccine against HPV in the Iranian population. In addition, some differences between the reference sequence and Iranian patients’ sequences were determined. It is essential to consider these differences to monitor the effectiveness and efficacy of the vaccine for the Iranian population. Our results provide a vast understanding of L1 protein that can be useful for further studies on HPV infections and new vaccine generations."
1424,Pre-clinical Stress Management Workshops Increase Medical Students’ Knowledge and Self-awareness of Coping with Stress,"OBJECTIVES: To investigate the effects of a stress management workshop on medical students’ knowledge of stress and potential coping strategies. METHODS: A panel discussion with small group breakouts on stress in clinical medicine, learning challenges, competition with colleagues, handling stressful events, and recognizing burnout symptoms was conducted with medical students entering clerkships. A longitudinal survey design was utilized to measure pre-, post-, and long-term (3-month) changes in knowledge (impact of stress on personal health, learning, and patient care), confidence, perceived skills, and attitude (towards utilizing adaptive coping strategies) among participating students (N = 135). Paired t test and multivariate analyses were performed to assess the differences between survey responses on a 5-point Likert scale. RESULTS: Survey response rates were pre-90.4%, post-77%, and long-term post-71.1%. Compared to pre-workshop, students reported significant improvement in all four domains immediately post-workshop: knowledge (4.4 vs. 4.7, p < 0.05), confidence (3.6 vs. 3.9, p < 0.05), perceived skills (3.3 vs. 3.7, p < 0.05), and attitude (2.6 vs. 2.8, p < 0.05). Compared to immediate post-workshop, students’ scores slightly decreased at 3 months but were overall significantly higher than the pre-workshop scores. CONCLUSIONS: A stress management workshop can improve medical students’ knowledge of the impact of stress as well as the use of adaptive stress coping strategies."
1425,Methylnaltrexone for the treatment of opioid-induced constipation and gastrointestinal stasis in intensive care patients. Results from the MOTION trial,"PURPOSE: Constipation can be a significant problem in critically unwell patients, associated with detrimental outcomes. Opioids are thought to contribute to the mechanism of bowel dysfunction. We tested if methylnaltrexone, a pure peripheral mu-opioid receptor antagonist, could reverse opioid-induced constipation. METHODS: The MOTION trial is a multi-centre, double blind, randomised placebo-controlled trial to investigate whether methylnaltrexone alleviates opioid-induced constipation (OIC) in critical care patients. Eligibility criteria included adult ICU patients who were mechanically ventilated, receiving opioids and were constipated (had not opened bowels for a minimum 48 h) despite prior administration of regular laxatives as per local bowel management protocol. The primary outcome was time to significant rescue-free laxation. Secondary outcomes included gastric residual volume, tolerance of enteral feeds, requirement for rescue laxatives, requirement for prokinetics, average number of bowel movements per day, escalation of opioid dose due to antagonism/reversal of analgesia, incidence of ventilator-associated pneumonia, incidence of diarrhoea and Clostridium difficile infection and finally 28 day, ICU and hospital mortality. RESULTS: A total of 84 patients were enrolled and randomized (41 to methylnaltrexone and 43 to placebo). The baseline demographic characteristics of the two groups were generally well balanced. There was no significant difference in time to rescue-free laxation between the groups (Hazard ratio 1.42, 95% CI 0.82–2.46, p = 0.22). There were no significant differences in the majority of secondary outcomes, particularly days 1–3. However, during days 4–28, there were fewer median number of bowel movements per day in the methylnaltrexone group, (p = 0.01) and a greater incidence of diarrhoea in the placebo group (p = 0.02). There was a marked difference in mortality between the groups, with ten deaths in the methylnaltrexone group and two in the placebo group during days 4–28 (p = 0.007). CONCLUSION: We found no evidence to support the addition of methylnaltrexone to regular laxatives for the treatment of opioid-induced constipation in critically ill patients; however, the confidence interval was wide and a clinically important difference cannot be excluded. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05913-6) contains supplementary material, which is available to authorized users."
1426,Family reflections: our family’s journey with Wolfram syndrome,
1427,“She is Like a Sister to Me.” Gender-Affirming Services and Relationships are Key to the Implementation of HIV Care Engagement Interventions with Transgender Women of Color,"We present findings from qualitative interviews (N = 67) with 36 staff and 31 participants of nine distinct individual and/or group level interventions to engage transgender women of color (TWOC) in HIV care in the U.S. We examine the commonalities amongst the intervention services (addressing unmet basic needs, facilitating engagement in HIV care, health system navigation, improving health literacy, emotional support), and the relationships formed during implementation of the interventions (between interventionists and participants, among participants in intervention groups, between participants and peers in the community). Interventionists, often TWOC themselves, who provided these services developed caring relationships, promoted personal empowerment, and became role models for participants and the community. Intervention groups engaged participants to reinforce the importance of health and HIV care and provided mutual support. Gender affirming services and caring relationships may be two key characteristics of interventions that address individual and structural-level barriers to engage TWOC in HIV care."
1428,Immunogenicity of the inactivated influenza vaccine in children who have undergone allogeneic haematopoietic stem cell transplant,"Influenza vaccination is recommended for children following allogeneic haematopoietic stem cell transplant (HSCT), however there is limited evidence regarding its benefit. A prospective multicentre study was conducted to evaluate the immunogenicity of the inactivated influenza vaccine in children who have undergone HSCT compared with healthy age-matched controls. Participants were vaccinated between 2013 and 2016 according to Australian guidelines. Influenza-specific hemagglutinin inhibition antibody titres were performed prior to each vaccination and 4 weeks following the final vaccination. A nasopharyngeal aspirate for influenza was performed on participants that developed influenza-like illness. There were 86 children recruited; 43 who had undergone HSCT and 43 controls. For the HSCT group, seroprotection and seroconversion rates were 81.4% and 60.5% for H3N2, 41.9% and 32.6% for H1N1, and 44.2% and 39.5% for B strain respectively. There was a significant geometric mean fold increase to the H3N2 (GMFI 5.80, 95% CI 3.68–9.14, p < 0.001) and B (GMFI 3.44, 95% CI 2.36–5.00, p = 0.048) strains. Serological response was superior in age-matched controls to all vaccine strains. There were no serious adverse events following vaccination. For children who underwent HSCT, incidence of laboratory-proven influenza infection was 2.3%. Overall, this study provides evidence to support annual inactivated influenza vaccine administration to children following HSCT."
1429,"Incidence, Risk Factors, and Outcomes of Ventilator-Associated Pneumonia in Traumatic Brain Injury: A Meta-analysis","Ventilator-associated pneumonia (VAP) is one of the most severe complications in patients with traumatic brain injury (TBI) and is considered a risk factor for poor outcomes. However, the incidence of VAP among patients with TBI reported in studies varies widely. What is more, the risk factors and outcomes of VAP are controversial. This study estimates the incidence, risk factors, and outcomes of VAP in patients with TBI and provides evidence for prevention and treatment. PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched from the earliest records to May 2018. Data involving the incidence, risk factors, and outcomes were extracted for meta-analysis. The results showed that the incidence of VAP was 36% (95% confidence interval (CI) 31–41%); risk factors analyses showed that smoking [odds ratio (OR) 2.13; 95% CI 1.16–3.92], tracheostomy (OR 9.55; 95% CI 3.24–28.17), blood transfusion on admission (OR 2.54; 95% CI 1.24–5.18), barbiturate infusion (OR 3.52; 95% CI 1.68–7.40), injury severity score (OR 4.65; 95% CI 1.96–7.34), and head abbreviated injury scale (OR 2.99; 95% CI 1.66–5.37) were related to the occurrence of VAP. When patients developed VAP, mechanical ventilation time (OR 5.45; 95% CI 3.78–7.12), ICU length of stay (OR 6.85; 95% CI 4.90–8.79), and hospital length of stay (OR 10.92; 95% CI 9.12–12.72) were significantly increased. However, VAP was not associated with an increased risk of mortality (OR 1.28; 95% CI 0.74–2.21). VAP is common in patients with TBI. It is affected by a series of factors and has a poor prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-019-00773-w) contains supplementary material, which is available to authorized users."
1430,Non-immune Hydrops in Neonates: A Tertiary Care Center Experience,"OBJECTIVE: To evaluate the clinical profile and outcome of neonates with non-immune hydrops (NIH). METHODS: Data of all the NIH cases admitted to neonatal intensive care unit at our center, New Delhi from January, 2010 to October, 2017 were extracted from hospital records, which included clinical profile and outcomes. RESULTS: Of the 17,299 total births, 27 neonates were identified to have NIH. Antenatal interventions were undertaken in five (18.5%) cases. The most common etiology of NIH was cardiac (n=5; 18.5%). Two babies with chylothorax were successfully managed with octreotide infusions. Overall survival rate of NIH was 70.3% (n=19). All neonates with a suspected genetic syndrome died. CONCLUSION: Multidisciplinary team including obstetricians, pediatric surgeons, geneticists and neonatologists can improve outcome in neonates with NIH."
1431,The harm of high-frequency oscillatory ventilation (HFOV) in ARDS is not related to a high baseline risk of acute cor pulmonale or short-term changes in hemodynamics,
1432,Protocol for two-arm pragmatic cluster randomized hybrid implementation-effectiveness trial comparing two education strategies for improving the uptake of noninvasive ventilation in patients with severe COPD exacerbation,"BACKGROUND: COPD is the fourth leading cause of death in the US, and COPD exacerbations result in approximately 700,000 hospitalizations annually. Patients with acute respiratory failure due to severe COPD exacerbation are treated with invasive (IMV) or noninvasive mechanical ventilation (NIV). Although IMV reverses hypercapnia/hypoxia, it causes significant morbidity and mortality. There is strong evidence that patients treated with NIV have better outcomes, and NIV is recommended as first line therapy in these patients. Yet, several studies have demonstrated substantial variation in the use of NIV across hospitals, leading to preventable morbidity and mortality. Through a series of mixed-methods studies, we have found that successful implementation of NIV requires physicians, respiratory therapists (RTs), and nurses to communicate and collaborate effectively, suggesting that efforts to increase the use of NIV in COPD need to account for the complex and interdisciplinary nature of NIV delivery and the need for team coordination. Therefore, we propose to compare two educational strategies: online education (OLE) and interprofessional education (IPE) which targets complex team-based care in NIV delivery. METHODS AND DESIGN: Twenty hospitals with low baseline rates of NIV use will be randomized to either the OLE or IPE study arm. The primary outcome of the trial is change in the hospital rate of NIV use among patients with COPD requiring ventilatory support. In aim 1, we will compare the uptake change over time of NIV use among patients with COPD in hospitals enrolled in the two arms. In aim 2, we will explore mediators’ role (respiratory therapist autonomy and team functionality) on the relationship between the implementation strategies and implementation effectiveness. Finally, in aim 3, through interviews with providers, we will assess acceptability and feasibility of the educational training. DISCUSSIONS: This study will be among the first to carefully test the impact of IPE in the inpatient setting. This work promises to change practice by offering approaches to facilitate greater uptake of NIV and may generalize to other interventions directed to seriously-ill patients. TRIAL REGISTRATION: Name of registry: ClinicalTrials.gov Trial registration number: NCT04206735 Date of Registration: December 20, 2019"
1433,Progress in research and application development of surface display technology using Bacillus subtilis spores,"Bacillus subtilis is a widely distributed aerobic Gram-positive species of bacteria. As a tool in the lab, it has the advantages of nonpathogenicity and limited likelihood of becoming drug resistant. It is a probiotic strain that can be directly used in humans and animals. It can be induced to produce spores under nutrient deficiency or other adverse conditions. B. subtilis spores have unique physical, chemical, and biochemical characteristics. Expression of heterologous antigens or proteins on the surface of B. subtilis spores has been successfully performed for over a decade. As an update and supplement to previously published research, this paper reviews the latest research on spore surface display technology using B. subtilis. We have mainly focused on the regulation of spore coat protein expression, display and application of exogenous proteins, and identification of developing research areas of spore surface display technology."
1434,Effectiveness of adjunctive nebulized antibiotics in critically ill patients with respiratory tract infections,"The purpose of the study was to analyze the effectiveness of adding nebulized antibiotics to systemic antimicrobials in critically ill patients with respiratory tract infections (pneumonia or tracheobronchitis) and the effect on renal function. A retrospective observational cohort study including critically ill patients with respiratory tract infections during a 2-year period was conducted. Intervention group included patients that received nebulized and systemic antimicrobials. Patients in the control group received only systemic antimicrobials. Clinical resolution was the primary endpoint. Secondary outcomes included change in fever, inflammatory parameters, and creatinine clearance; length of hospital stay, systemic therapy, and mechanical ventilation; hospital readmission; and mortality. Regression models were performed to estimate the effect of nebulized antibiotics on outcome variables adjusted by potential confounders. A total of 136 patients were included (93 in control group and 43 in intervention group). The intervention group had higher odds of clinical resolution (adjusted odds ratio (OR): 7.1; 95% confidence interval (95% CI): 1.2, 43.3). Nebulized antibiotic therapy was independently associated with reduction in procalcitonin (adjusted OR: 12.4; 95% CI: 1.4, 109.7). There were no significant differences in the rest of the secondary outcomes or in creatinine clearance reduction. Adding nebulized antibiotics for the management of respiratory tract infections has a positive impact on clinical resolution without increasing the risk of renal toxicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-019-03733-6) contains supplementary material, which is available to authorized users."
1435,Ventilator-associated pneumonia diagnosis: a prioritization exercise based on multi-criteria decision analysis,"The aim was to provide global experts ranking on priorities in diagnostic tools for VAP in clinical practice. A multiple criteria decision analysis (MCDA) was performed to identify diagnosis tools for VAP diagnosis. Priority factors were identified after literature review. An international, multidisciplinary expert panel reviewed variables and ranked diagnostic tools. Experts from ten European hospitals participated. Regarding bedside clinical practices, seven required chest X-ray use in all patients, whereas six reported the use of blood cultures and endotracheal aspirate in all patients. Invasive techniques were routinely performed in seven sites. CRP, PCT, and Gram stains were performed in all patients by 5, 2, and 8, respectively. Impact on patient outcomes, safety, and impact on the decision to start antibiotic therapy were ranked as the top three relevant concerns (7.7/10, 7/10, and 6.9/10, respectively). Chest X-ray was ranked as the most important imaging technique to diagnose VAP (score 251.7). Apart from blood cultures, endotracheal aspirate culture was identified as the main collection method for the microbiological testing (scores of 274.8 and 246.8, respectively). Mini-BAL was the preferred invasive technique with a score of 208. Top three biomarkers were CRP (score 184.3), PCT (181.3), and WBC (166.4). Gram stain (192.5) was prioritized among laboratory diagnostic techniques. Using MCDA, it is recommended to perform a combination of diagnostic techniques including images (chest X-ray), culture of clinical specimens (blood cultures and endotracheal aspirate), and biomarkers (CRP or PCT) for VAP diagnosis at the bedside. Gram stain was ranked as the preferred laboratory technique. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-019-03720-x) contains supplementary material, which is available to authorized users."
1436,Acute normovolemic hemodilution reduced allogeneic blood transfusion without increasing perioperative complications in patients undergoing free-flap reconstruction of the head and neck,"PURPOSE: The present case–control study was conducted to evaluate whether acute normovolemic hemodilution (ANH) can reduce the need for perioperative allogeneic blood transfusion (ABT) and affect the incidence of perioperative complications in free-flap reconstruction of the head and neck. METHODS: This single-center, retrospective, observational study included the perioperative data of 123 patients who underwent free-flap reconstruction of the head and neck following oncological surgery. Patients were divided into the following two groups according to whether they received ANH: ANH group and non-ANH group. We investigated whether ANH can reduce the need for perioperative ABT using propensity score-adjusted logistic regression analysis. RESULTS: Of the 123 patients, 113 patients were assessed; 57 patients were in the ANH group and 56 patients were in the non-ANH group. The rate [ANH group vs. non-ANH group, n (%): 2 (3.5%) vs. 23 (41.1%), p < 0.0001] and amount [median (IQR): 0 mL (0, 0) vs. 0 mL (0, 280), p < 0.0001] of ABT were significantly lower in the ANH group than in the non-ANH group. Propensity score-adjusted multivariate logistic regression analysis indicated that ANH use [odds ratio (OR): 0.040; 95% confidence interval (CI) 0.005, 0.320; p = 0.0024)] was one of the independent predictors of perioperative ABT. There were no significant differences in the incidences of post-operative complications between the two groups. CONCLUSION: ANH use can reduce the need for perioperative ABT in patients undergoing free-flap reconstruction of the head and neck without increasing the incidence of post-operative complications."
1437,Involvement of fat mass and obesity gene (FTO) in the anti-obesity action of Annona muricata Annonaceae: in silico and in vivo studies,"BACKGROUND: Annona muricata (Annonaceae) known as soursop is a common tropical plant species known for its numerous medicinal properties including obesity. The underlying mechanism of anti-obesity effect of A. muricata was investigated. The fat mass and obesity associated protein (FTO) is a validated potential target for anti-obesity drugs. METHODS: The interaction of compounds previously characterized from A. muricata was investigated against FTO using Autodock Vina. Also, modulation of FTO and STAT-3 mRNA expression by A. muricata was investigated in high fat diet induced obese rats (HFDR) using RT-PCR. RESULTS: A significant up-regulation of FTO gene was observed in HFDR when compared to control rats, while administration of A. muricata (200 mg/kg) significantly (p < 0.05) down-regulated FTO gene expression when compared to HFDR group. The effect of obesity on STAT-3 gene expression was also reversed by A. muricata (200 mg/kg). In silico study revealed annonaine and annonioside (−9.2 kcal/mol) exhibited the highest binding affinity with FTO, followed by anonaine and isolaureline (−8.6 kcal/mol). Arg-96 is a critical amino acid enhancing anonaine, isolaureline-FTO binding. CONCLUSION: This study suggests the possible anti-obesity mechanism of A. muricata is via down-regulation of FTO with concomitant up-regulation of STAT-3 genes. This study confirmed the use of this plant in the management of obesity and the probable compounds responsible for its antiobesity effect are annonaine and annonioside."
1438,Do-not-intubate orders in patients with acute respiratory failure: a systematic review and meta-analysis,"PURPOSE: To assess the rates and variability of do-not-intubate orders in patients with acute respiratory failure. METHODS: We conducted a systematic review of observational studies that enrolled adult patients with acute respiratory failure requiring noninvasive ventilation or high-flow nasal cannula oxygen from inception to 2019. RESULTS: Twenty-six studies evaluating 10,755 patients were included. The overall pooled rate of do-not-intubate orders was 27%. The pooled rate of do-not-intubate orders in studies from North America was 14% (range 9–22%), from Europe was 28% (range 13–58%), and from Asia was 38% (range 9–83%), p = 0.001. Do-not-intubate rates were higher in studies with higher patient age and in studies where do-not-intubate decisions were made without reported patient/family input. There were no significant differences in do-not-intubate orders according to illness severity, observed mortality, malignancy comorbidity, or methodological quality. Rates of do-not-intubate orders increased over time from 9% in 2000–2004 to 32% in 2015–2019. Only 12 studies (46%) reported information about do-not-intubate decision-making processes. Only 4 studies (15%) also reported rates of do-not-resuscitate. CONCLUSIONS: One in four patients with acute respiratory failure (who receive noninvasive ventilation or high-flow nasal cannula oxygen) has a do-not-intubate order. The rate of do-not-intubate orders has increased over time. There is high inter-study variability in do-not-intubate rates—even when accounting for age and illness severity. There is high variability in patient/family involvement in do-not-intubate decision making processes. Few studies reported differences in rates of do-not-resuscitate and do-not-intubate—even though recovery is very different for acute respiratory failure and cardiac arrest. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05828-2) contains supplementary material, which is available to authorized users."
1439,Transient protein expression in tobacco BY-2 plant cell packs using single and multi-cassette replicating vectors,"KEY MESSAGE: This is the first evidence that replicating vectors can be successfully used for transient protein expression in BY-2 plant cell packs. ABSTRACT: Transient recombinant protein expression in plants and recently also plant cell cultures are of increasing interest due to the speed, safety and scalability of the process. Currently, studies are focussing on the design of plant virus-derived vectors to achieve higher amounts of transiently expressed proteins in these systems. Here we designed and tested replicating single and multi-cassette vectors that combine elements for enhanced replication and hypertranslation, and assessed their ability to express and particularly co-express proteins by Agrobacterium-mediated transient expression in tobacco BY-2 plant cell packs. Substantial yields of green and red fluorescent proteins of up to ~ 700 ng/g fresh mass were detected in the plant cells along with position-dependent expression. This is the first evidence of the ability of replicating vectors to transiently express proteins in BY-2 plant cell packs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00299-020-02544-w) contains supplementary material, which is available to authorized users."
1440,Next-generation influenza vaccines: opportunities and challenges,"Seasonal influenza vaccines lack efficacy against drifted or pandemic influenza strains. Developing improved vaccines that elicit broader immunity remains a public health priority. Immune responses to current vaccines focus on the haemagglutinin head domain, whereas next-generation vaccines target less variable virus structures, including the haemagglutinin stem. Strategies employed to improve vaccine efficacy involve using structure-based design and nanoparticle display to optimize the antigenicity and immunogenicity of target antigens; increasing the antigen dose; using novel adjuvants; stimulating cellular immunity; and targeting other viral proteins, including neuraminidase, matrix protein 2 or nucleoprotein. Improved understanding of influenza antigen structure and immunobiology is advancing novel vaccine candidates into human trials."
1441,Effects of a Single Head Exposure to GSM-1800 MHz Signals on the Transcriptome Profile in the Rat Cerebral Cortex: Enhanced Gene Responses Under Proinflammatory Conditions,"Mobile communications are propagated by electromagnetic fields (EMFs), and since the 1990s, they operate with pulse-modulated signals such as the GSM-1800 MHz. The biological effects of GSM-EMF in humans affected by neuropathological processes remain seldom investigated. In this study, a 2-h head-only exposure to GSM-1800 MHz was applied to (i) rats undergoing an acute neuroinflammation triggered by a lipopolysaccharide (LPS) treatment, (ii) age-matched healthy rats, or (iii) transgenic hSOD1(G93A) rats that modeled a presymptomatic phase of human amyotrophic lateral sclerosis (ALS). Gene responses were assessed 24 h after the GSM head-only exposure in a motor area of the cerebral cortex (mCx) where the mean specific absorption rate (SAR) was estimated to be 3.22 W/kg. In LPS-treated rats, a genome-wide mRNA profiling was performed by RNA-seq analysis and revealed significant (adjusted p value < 0.05) but moderate (fold changes < 2) upregulations or downregulations affecting 2.7% of the expressed genes, including genes expressed predominantly in neuronal or in glial cell types and groups of genes involved in protein ubiquitination or dephosphorylation. Reverse transcription-quantitative PCR analyses confirmed gene modulations uncovered by RNA-seq data and showed that in a set of 15 PCR-assessed genes, significant gene responses to GSM-1800 MHz depended upon the acute neuroinflammatory state triggered in LPS-treated rats, because they were not observed in healthy or in hSOD1(G93A) rats. Together, our data specify the extent of cortical gene modulations triggered by GSM-EMF in the course of an acute neuroinflammation and indicate that GSM-induced gene responses can differ according to pathologies affecting the CNS."
1442,Decreasing radiographs in neonates through targeted quality improvement interventions,"OBJECTIVE: Our aim was to decrease radiograph use for monitoring placement of peripherally inserted central catheters (PICC) and endotracheal tubes (ETT) in neonates admitted to the neonatal intensive care unit (NICU) by 20% from November 2017 to November 2018. STUDY DESIGN: We carried out three Plan-Do-Study-Act (PDSA) cycles: (1) implementation of a radiograph protocol emphasizing ideal patient positioning, standard radiograph views and frequency, (2) standardizing ETT depth using the NRP guidelines, and (3) implementation of an institution specific ETT depth guideline. RESULTS: The pre-intervention radiographs per PICC day was 0.86 versus a post-intervention value of 0.46 (P = 0.004). The pre-intervention radiographs per ETT day was 1.45 versus a post-intervention value of 1.07 (P = 0.002). CONCLUSIONS: Our multidisciplinary NICU team performed a QI project, which resulted in more than a 20% decrease in the number of radiographs used for monitoring placement of PICCs and ETTs."
1443,A review of approaches for resolving disputes between physicians and families on end-of-life care for newborns,
1444,Effect of edaravone therapy in Korean amyotrophic lateral sclerosis (ALS) patients,"Oxidative stress caused by free radicals has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Edaravone (also known as MCI-186), a free radical scavenger, was approved as an ALS treatment in 2015 in Japan. However, the therapeutic effects of edaravone on patients with ALS outside of Japan are not yet reported. This study aims to investigate effects of edaravone on ALS patients in the Korean population. The study included 22 patients with ALS who were treated with edaravone. Of the 16 patients who finished six cycles of treatment, a mean decline of ALSFRS-R after the treatments was 5.75 ± 6.07 points and the average change of FVC was − 8.7 ± 17.0%. Patients experienced only minor adverse events. This study reports on the open-label study of edaravone on patients in Korea for ALS patients, which showed a modest effect of edaravone in this population of ALS patients."
1445,Evidence-based impact by clinical engineers on global patients outcomes,"The intersection of technological changes and societal evolution has transformed every aspect of human life. Technological advancements are transforming how healthcare knowledge is expanding and accelerating the outreach of critical medical services delivery (Jamal et al. in Health Information Management Journal 38(3):26–37, 2009). While this transformation facilitates new opportunities simultaneously it also introduces challenges (Jacobzone and Oxley, 2001). Appropriate Health Technology (HT) is vital to new and existing global health care programs. Therefore, qualified professionals who can safely guide the development, evaluation, installation, integration, performance assurance, and risk mitigation of HT must be in position to lead. Trained Clinical Engineers (CE) and Biomedical Engineers (BE) have been recognized by the World Health Organization (WHO) as the essential practitioners to providing this critically needed guidance. Over the past four years, a senior professional group participated in an international project that seeks evidence for the hypothesis - that the engagement of CE and BE in guiding HT - impacts positively on patient outcomes, while the alternative is that there is no difference. The group collected published data that was subjected to peer review screening; additional data qualification conditions are described in this paper. The project was initiated at the Global CE Summit during the first International Clinical Engineering and Health Technology Management Congress (ICEHTMC) in Hangzhou, China in October 2015 (Global Clinical Engineering Summit at the First International Clinical Engineering and Health Technology Management Congress, 2015). Following the adoption of a resolution to investigate CE contributions to the improvement of world health status, an international survey and literature survey were initiated. During the first two years of this project 150 case studies from 90 countries were identified covering the previous ten years. The results of this survey were presented to health leaders at the World Health Organization (WHO) World Health Assembly in 2016. Last year, 250 case studies were added including 35 more countries covering the 2016–2017 period. The combined project contains 400 qualified submissions from 125 countries. The conclusion was that engagement of CE and BME is critical for successful investment in HT and for achieving intended patient outcomes. This paper describes the project’s plan, the results of the literature review performed, and the evidence identified during the process."
1446,The Janus faces of bicarbonate therapy in the ICU: not sure!,
1447,Addressing Diversity in PTSD Treatment: Clinical Considerations and Guidance for the Treatment of PTSD in LGBTQ Populations,"PURPOSE OF REVIEW: Trauma exposure is widespread but is especially common among lesbian, gay, bisexual, transgender, and queer (LGBTQ) individuals. LGBTQ individuals also experience higher rates of discrimination, victimization, and minority stress which can complicate posttraumatic stress disorder (PTSD) treatment but also represent independent intervention targets. In this review, we highlight existing evidence-based practices, current limitations, and provide recommendations for care in the absence of established guidelines for treatment PTSD among LGBTQ patients. RECENT FINDINGS: Trauma-focused therapies (e.g., CPT, PE) and medications (e.g., SSRIs, SNRIs) have shown benefit for people with PTSD. However, evaluations of these interventions have failed to examine the role of LGBTQ identities in recovery from trauma, and existing PTSD treatments do not account for ongoing threat to safety or the pervasive minority stress experienced by LGBTQ patients. In addition, many LGBTQ patients report negative experiences with healthcare, necessitating increased education and cultural awareness on the part of clinicians to provide patient-centered care and, potentially, corrective mental health treatment experiences. SUMMARY: Providers should routinely assess trauma exposure, PTSD, and minority stress among LGBTQ patients. We provide assessment and screening recommendations, outline current evidence-based treatments, and suggest strategies for integrating existing treatments to treat PTSD among LGBTQ patients."
1448,Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by Chlamydia psittaci,"PURPOSE: Chlamydia psittaci infection in humans can lead to serious clinical manifestations, including severe pneumonia, adult respiratory distress syndrome, and, rarely, death. Implementation of metagenomic next-generation sequencing (mNGS) gives a promising new tool for diagnosis. The clinical spectrum of severe psittacosis pneumonia is described to provide physicians with a better understanding and to highlight the rarity and severity of severe psittacosis pneumonia. METHODS: Nine cases of severe psittacosis pneumonia were diagnosed using mNGS. Retrospective analysis of the data on disease progression, new diagnosis tool, treatments, and outcomes, and the findings were summarised. RESULTS: Frequent symptoms included chills and remittent fever (100%), cough and hypodynamia (100%), and headache and myalgia (77.8%). All patients were severe psittacosis pneumonia developed respiratory failure, accompanied by sepsis in 6/9 patients. mNGS takes 48–72 h to provide the results, and help to identify diagnosis of psittacosis. Laboratory data showed normal or slightly increased leucocytes, neutrophils, and procalcitonin but high C-reactive protein levels. Computed tomography revealed air-space consolidation and ground-glass opacity, which began in the upper lobe of one lung, and spread to both lungs, along with miliary, nodular, or consolidated shadows. One patient died because of secondary infection with Klebsiella pneumoniae, while the other eight patients experienced complete recoveries. CONCLUSIONS: The use of mNGS can improve accuracy and reduce the delay in diagnosis of psittacosis. Severe psittacosis pneumonia responds well to the timely use of appropriate antibiotics."
1449,MiR-802 alleviates lipopolysaccharide-induced acute lung injury by targeting Peli2,"INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition. It is characterized by serious lung inflammation or injury. Characterizing novel miRNAs implicated in ARDS pathogenesis may provide new therapeutic strategy for managing ARDS. METHODS: We employed LPS-induced lung injury model to profile miRNAs associated with ARDS. We isolated one miRNA candidate and characterized its role in lipopolysaccharide (LPS)-induced proinflammatory cytokine production in lung macrophages. We further evaluated its functional role in ARDS model by assessing histological change, neutrophil activation, tissue permeability and tumor necrosis factor alpha (TNFα) production. We also characterized its downstream target using luciferase assay, Western blotting, enzyme-linked immunosorbent assay and cell inflammation assay. RESULTS: Microarray profiling revealed miR-802 was significantly downregulated in ARDS mouse model. LPS-induced miR-802 downregulation was confirmed in lung macrophages. Overexpression of miR-802 significantly suppressed LPS-induced inflammatory cytokine production in vitro and alleviates LPS-induced acute lung injury in vivo. Peli2 was identified as a downstream target of miR-802 and found upregulated in ARDS model. Overexpressing Peli2 abolished the antagonizing effect of miR-802 on LPS-mediated inflammatory response. CONCLUSION: MiR-802 carried a protective role against LPS-induced acute lung injury by downregulating Peli2. MiR-802/Peli2 axis may act as intervening targets to manage ARDS."
1450,Incidence and complications of cannula changes in long-term tracheotomized patients: a prospective observational study,"STUDY DESIGN: Prospective, monocentric observational study. OBJECTIVE: Investigation of incidence and complication rate of cannula changes in long-term tracheotomized patients suffering spinal cord injury. SETTING: University hospital in Bochum, Germany. METHODS: Prospective data collection of all cannula changes between September 2016 and September 2017. Physicians recorded mechanical complications and techniques to solve them, and/or complications resulting in patient-threatening condition. RESULTS: There were 149 cannula changes during 3191 observation days. Overall, urgent cannula changes occurred 2.1 times per 100 observation days. Within the first 8 weeks after tracheostomy, urgent cannula changes were necessary four times per 100 observation days, and were mandatory less than two times per 100 observation days thereafter. Overall, mechanical complications occurred in 12% of cannula changes, and 8% of cannula changes were accompanied by patient-threatening complications. Accidental decannulation (AD) occurred in 0.97 of 100 observation days. Recannulation after AD was accompanied by 29% of mechanical complications during reinsertion, and 16% led to patient-threatening complications. The major risk factors for mechanical complications were the time lag between cannula change and tracheostomy, and the urgency of the procedure while the thyroid cartilage–jugular distance was significantly associated with patient-threatening complications. CONCLUSION: AD and the requirement for urgent cannula changes are common and often related with mechanical and patient-threatening complications. Even weeks after tracheostomy, caregivers need to be aware of serious events, and therefore provide monitoring, knowledge, and appropriate resources to handle these events."
1451,Response Measures to Infection Outbreaks During the Second Year of Sustenance Phase of Infection Control Quality Improvement,"OBJECTIVE: To analyze the infection outbreaks, control measures and outcomes of the outbreak in the NICU of a tertiary care centre in the year 2018. METHODS: This study was conducted in a 30 bedded tertiary care NICU from January 2018 through December 2018. The study design was an Outbreak investigation, based on a program of prospective surveillance for nosocomial infection. All neonates admitted to the NICU formed part of the the study. An Infection Control Quality Improvement (QI) team was available to analyze the infection and initiate response action to outbreaks. RESULTS: Three outbreaks were reported in the year 2018. The first was in May 2018 and comprised of colonization with rectal Multi-drug resistant gram negative bacilli (MDR GNB). The outbreak was controlled by using Aseptic non-touch technique (ANTT) for fortification of milk and using distilled water for cleaning of diaper area. The second outbreak in August 2018 was Methicillin resistant Staphylococcus aureus (MRSA) whose source was a maternal Lower segment cesarean section (LSCS) wound. The third outbreak in October 2018 was MDR Acinetobacter. The source was from an outborn having the same organism. All infants were in close proximity to the index case. This outbreak was controlled with cohorting, hand hygiene and strengthening of bundle care. CONCLUSIONS: Surveillance aids in early detection and successful control of outbreaks. A systematic search for the source and meticulous containment of spread can successfully control an outbreak."
1452,Should MASP-2 Deficiency Be Considered a Primary Immunodeficiency? Relevance of the Lectin Pathway,"Mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) is an indispensable enzyme for the activation of the lectin pathway of complement. Its deficiency is classified as a primary immunodeficiency associated to pyogenic bacterial infections, inflammatory lung disease, and autoimmunity. In Europeans, MASP-2 deficiency, due to homozygosity for c.359A > G (p.D120G), occurs in 7 to 14/10,000 individuals. We analyzed the presence of the p.D120G mutation in adults (increasing the sample size of our previous studies) and children. Different groups of patients (1495 adults hospitalized with community-acquired pneumonia, 186 adults with systemic lupus erythematosus, 103 pediatric patients with invasive pneumococcal disease) and control individuals (1119 healthy adult volunteers, 520 adult patients without history of relevant infectious diseases, and a pediatric control group of 311 individuals) were studied. Besides our previously reported MASP-2-deficient healthy adults, we found a new p.D120G homozygous individual from the pediatric control group. We also reviewed p.D120G homozygous individuals reported so far: a total of eleven patients with a highly heterogeneous range of disorders and nine healthy controls (including our four MASP-2-deficient individuals) have been identified by chance in association studies. Individuals with complete deficiencies of several pattern recognition molecules of the lectin pathway (MBL, collectin-10 and collectin-11, and ficolin-3) as well as of MASP-1 and MASP-3 have also been reviewed. Cumulative evidence suggests that MASP-2, and even other components of the LP, are largely redundant in human defenses and that individuals with MASP-2 deficiency do not seem to be particularly prone to infectious or autoimmune diseases."
1453,Neurally adjusted ventilatory assist preserves cerebral blood flow velocity in patients recovering from acute brain injury,"Neurally adjusted ventilatory assist (NAVA) has never been applied in patients recovering from acute brain injury (ABI) because neural respiratory drive could be affected by intracranial disease with detrimental effects on cerebral blood flow (CBF) velocity. Our primary aim was to assess the impact of NAVA and pressure support ventilation (PSV) on CBF velocity. In fifteen adult patients recovering from ABI and undergoing invasive assisted ventilation, PSV and NAVA were applied over 30-min-lasting trials, in the following sequence: PSV(1), NAVA, and PSV(2). While PSV was set to deliver a tidal volume ranging between 6 and 8 ml kg(−1) of predicted body weight, in NAVA the level of assistance was chosen to achieve the same inspiratory peak airway pressure as PSV. At the end of each trial, a sonographic evaluation of CBF mean velocity was bilaterally obtained on the middle cerebral artery and an arterial blood gas sample was taken for analysis. CBF mean velocity was 51.8 [41.9,75.2] cm s(−1) at baseline, 51.9 [43.4,71.0] cm s(−1) in PSV(1), 53.6 [40.7,67.7] cm s(−1) in NAVA, and 49.5 [42.1,70.8] cm s(−1) in PSV(2) (p = 0.0514) on the left and 50.2 [38.0,77.7] cm s(−1) at baseline, 47.8 [41.7,68.2] cm s(−1) in PSV(1), 53.9 [40.1,78.5] cm s(−1) in NAVA, and 55.6 [35.9,74.1] cm s(−1) in PSV(2) (p = 0.8240) on the right side. No differences were detected for pH (p = 0.0551), arterial carbon dioxide tension (p = 0.8142), and oxygenation (p = 0.0928) over the entire study duration. NAVA and PSV preserved CBF velocity in patients recovering from ABI. Trial registration: The present trial was prospectively registered at www.clinicatrials.gov (NCT03721354) on October 18th, 2018. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-020-00523-w) contains supplementary material, which is available to authorized users."
1454,SAMD4 family members suppress human hepatitis B virus by directly binding to the Smaug recognition region of viral RNA,"HBV infection initiates hepatitis B and promotes liver cirrhosis and hepatocellular carcinoma. IFN-α is commonly used in hepatitis B therapy, but how it inhibits HBV is not fully understood. We screened 285 human interferon-stimulated genes (ISGs) for anti-HBV activity using a cell-based assay, which revealed several anti-HBV ISGs. Among these ISGs, SAMD4A was the strongest suppressor of HBV replication. We found the binding site of SAMD4A in HBV RNA, which was a previously unidentified Smaug recognition region (SRE) sequence conserved in HBV variants. SAMD4A binds to the SRE site in viral RNA to trigger its degradation. The SAM domain in SAMD4A is critical for RNA binding and the C-terminal domain of SAMD4A is required for SAMD4A anti-HBV function. Human SAMD4B is a homolog of human SAMD4A but is not an ISG, and the murine genome encodes SAMD4. All these SAMD4 proteins suppressed HBV replication when overexpressed in vitro and in vivo. We also showed that knocking out the Samd4 gene in hepatocytes led to a higher level of HBV replication in mice and AAV-delivered SAMD4A expression reduced the virus titer in HBV-producing transgenic mice. In addition, a database analysis revealed a negative correlation between the levels of SAMD4A/B and HBV in patients. Our data suggest that SAMD4A is an important anti-HBV ISG for use in IFN therapy of hepatitis B and that the levels of SAMD4A/B expression are related to HBV sensitivity in humans."
1455,Blood Component Transfusion in a Tertiary Care Hospital,"OBJECTIVES: To study the rational use of the blood components in pediatric and neonatal wards. METHODS: It was a retrospective study conducted by department of pediatrics of a tertiary care centre in western part of India. The patients were included from the pediatric ward, pediatric surgery ward, neonatal intensive care unit (NICU), pediatric intensive care unit (PICU) over a period of three months. All the patients below 12 y of age receiving blood components, admitted in general pediatric wards, pediatric intensive care unit, neonatal intensive care unit and pediatric surgery ward were included in the study. Each transfusion episode was assessed as per predetermined guidelines. RESULTS: Of the total 336 episodes of blood component transfusions, 244 episodes were appropriate and 92 episodes were inappropriate. Among these, platelets had highest inappropriate (36.84%) episodes followed by fresh frozen plasma (FFP) (28.95%) and packed red blood cell transfusions (PRBC) (21.21%). Majority inappropriate transfusions were seen in intensive care settings. CONCLUSIONS: Almost one-third of blood component transfusions (FFP, platelets and PRBC) were given without any definitive indication. Judicious use of various blood products by following recommended guidelines may help in decreasing the inappropriate use of blood components."
1456,2019: Archives of Virology celebrates its eightieth birthday with a scientific symposium,
1457,Worldwide Organization of Neurocritical Care: Results from the PRINCE Study Part 1,"INTRODUCTION: Neurocritical care focuses on the care of critically ill patients with an acute neurologic disorder and has grown significantly in the past few years. However, there is a lack of data that describe the scope of practice of neurointensivists and epidemiological data on the types of patients and treatments used in neurocritical care units worldwide. To address these issues, we designed a multicenter, international, point-prevalence, cross-sectional, prospective, observational, non-interventional study in the setting of neurocritical care (PRINCE Study). METHODS: In this manuscript, we analyzed data from the initial phase of the study that included registration, hospital, and intensive care unit (ICU) organizations. We present here descriptive statistics to summarize data from the registration case report form. We performed the Kruskal–Wallis test followed by the Dunn procedure to test for differences in practices among world regions. RESULTS: We analyzed information submitted by 257 participating sites from 47 countries. The majority of those sites, 119 (46.3%), were in North America, 44 (17.2%) in Europe, 34 (13.3%) in Asia, 9 (3.5%) in the Middle East, 34 (13.3%) in Latin America, and 14 (5.5%) in Oceania. Most ICUs are from academic institutions (73.4%) located in large urban centers (44% > 1 million inhabitants). We found significant differences in hospital and ICU organization, resource allocation, and use of patient management protocols. The highest nursing/patient ratio was in Oceania (100% 1:1). Dedicated Advanced Practiced Providers are mostly present in North America (73.7%) and are uncommon in Oceania (7.7%) and the Middle East (0%). The presence of dedicated respiratory therapist is common in North America (85%), Middle East (85%), and Latin America (84%) but less common in Europe (26%) and Oceania (7.7%). The presence of dedicated pharmacist is highest in North America (89%) and Oceania (85%) and least common in Latin America (38%). The majority of respondents reported having a dedicated neuro-ICU (67% overall; highest in North America: 82%; and lowest in Oceania: 14%). CONCLUSION: The PRINCE Study results suggest that there is significant variability in the delivery of neurocritical care. The study also shows it is feasible to undertake international collaborations to gather global data about the practice of neurocritical care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-019-00750-3) contains supplementary material, which is available to authorized users."
1458,Defining patient–ventilator asynchrony severity according to recurrence,
1459,"Prevalence, Clinical Characteristics, and Outcomes Related to Ventilator-Associated Events in Neurocritically Ill Patients","BACKGROUND: The prevalence, characteristics, and outcomes related to the ventilator-associated event(s) (VAE) in neurocritically ill patients are unknown and examined in this study. METHODS: A retrospective study was performed on neurocritically ill patients at a 413-bed level 1 trauma and stroke center who received three or more days of mechanical ventilation to describe rates of VAE, describe characteristics of patients with VAE, and examine the association of VAE on ventilator days, mortality, length of stay, and discharge to home. RESULTS: Over a 5-year period from 2014 through 2018, 855 neurocritically ill patients requiring mechanical ventilation were identified. A total of 147 VAEs occurred in 130 (15.2%) patients with an overall VAE rate of 13 per 1000 ventilator days and occurred across age, sex, BMI, and admission Glasgow Coma Scores. The average time from the start of ventilation to a VAE was 5 (range 3–48) days after initiation of mechanical ventilation. Using Centers for Disease Control and Prevention definitions, VAEs met criteria for a ventilator-associated condition in 58% of events (n = 85), infection-related VAE in 22% of events (n = 33), and possible ventilator-associated pneumonia in 20% of events (n = 29). A most common trigger for VAE was an increase in positive end-expiratory pressure (84%). Presence of a VAE was associated with an increase in duration of mechanical ventilation (17.4[IQR 20.5] vs. 7.9[8.9] days, p < 0.001, 95% CI 7.86–13.92), intensive care unit (ICU) length of stay (20.2[1.1] vs. 12.5[0.4] days, p < 0.001 95% CI 5.3–10.02), but not associated with in-patient mortality (34.1 vs. 31.3%. 95% CI 0.76–1.69) or discharge to home (12.7% vs. 16.3%, 95% 0.47–1.29). CONCLUSIONS: VAE are prevalent in the neurocritically ill. They result in an increased duration of mechanical ventilation and ICU length of stay, but may not be associated with in-hospital mortality or discharge to home. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-019-00910-5) contains supplementary material, which is available to authorized users."
1460,New-Onset Refractory Status Epilepticus with Underlying Autoimmune Etiology: a Case Report,"Management of new-onset refractory status epilepticus and the approach to burst suppression variable is often challenging. We present the unusual case of a previously healthy 18-year-old male with new-onset status epilepticus admitted to the neurologic intensive care unit for 70 days. Despite treatment with multiple anti-epileptic drugs in addition to IV anesthetics, burst suppression was initially unsustainable and the patient remained in super-refractory status epilepticus. Extensive evaluation revealed an underlying autoimmune-mediated etiology with positivity for glutamic acid decarboxylase-65 antibody. Clinical response with a goal of 1–2 bursts per screen on EEG monitor was eventually achieved after a course of rituximab and plasma exchange therapy as well as a 7-day barbiturate coma with a regimen of clobazam, lacosamide, Keppra, and oxcarbazepine followed by a slow taper of phenobarbital and the addition of fosphenytoin. Remarkably, the patient was subsequently discharged to a rehabilitation facility with complete neurologic recovery. We discuss treatment strategies for new-onset refractory status epilepticus and highlight the role of rapid initiation of burst suppression with high-dose IV anesthetics to ensure neuroprotection while the underlying etiology is addressed with immune-modulating therapy."
1461,Post-Marketing Pooled Safety Analysis for CT-P13 Treatment of Patients with Immune-Mediated Inflammatory Diseases in Observational Cohort Studies,"BACKGROUND: At EU marketing authorisation, safety data for CT-P13 (biosimilar infliximab) were limited, particularly in some indications, and uncommon adverse events (AEs) could not be evaluated among relatively small analysis populations. OBJECTIVES: Our objective was to investigate the overall safety profile and incidence rate of AEs of special interest (AESIs), including serious infections and tuberculosis, in CT-P13-treated patients. METHODS: Data were pooled from six observational studies representing authorised indications of CT-P13 (ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, adult and paediatric Crohn’s disease and ulcerative colitis). Patients were analysed by indication and treatment (patients who received CT-P13 or those who switched from reference infliximab to CT-P13 ≤ 6 months prior to enrolment or during the study). RESULTS: Overall, 4393 patients were included (n = 3677 CT-P13 group; n = 716 switched group); 64.03% of patients had inflammatory bowel disease and 6.31% of patients were antidrug antibody positive. Overall, 32.94% and 9.58% of patients experienced treatment-emergent AEs (TEAEs) and treatment-emergent serious AEs, respectively. Across indications, TEAEs were more frequent with CT-P13 than with the switched group. Infections including tuberculosis were the most frequent serious AESI overall (2.48%) and by treatment group or indication. In total, 14 patients (0.32%) reported active tuberculosis. Overall incidence rates per 100 patient-years (95% confidence interval) were 3.40 (2.788–4.096) for serious infections including tuberculosis and 0.44 (0.238–0.732) for active tuberculosis. Infusion-related reactions were the second most frequent AESI following infection including tuberculosis. CONCLUSION: The CT-P13 safety profile appears consistent with previous studies for CT-P13 and reference infliximab, supporting the favourable risk/benefit balance for CT-P13 treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40259-020-00421-2) contains supplementary material, which is available to authorized users."
1462,"Dear Mental Health Practitioners, Take Care of Yourselves: a Literature Review on Self-Care","Stress, burnout, and professional impairment are prevalent among mental health professionals and can have a negative impact on their clinical work, whilst engagement in self-care can help promote therapist well-being. This literature review examines the role of self-care in the promotion of well-being among mental health practitioners. Specifically, empirical research is presented in relation to specific domains of self-care practice, including awareness, balance, flexibility, physical health, social support, and spirituality. Findings from this review underscore the importance of taking a proactive approach to self-care and, in particular, integrating self-care directly into clinical training programs and into the quality assurance processes of professional organizations within the field of mental health."
1463,Bloodstream infections in critically ill patients: an expert statement,"Bloodstream infection (BSI) is defined by positive blood cultures in a patient with systemic signs of infection and may be either secondary to a documented source or primary—that is, without identified origin. Community-acquired BSIs in immunocompetent adults usually involve drug-susceptible bacteria, while healthcare-associated BSIs are frequently due to multidrug-resistant (MDR) strains. Early adequate antimicrobial therapy is a key to improve patient outcomes, especially in those with criteria for sepsis or septic shock, and should be based on guidelines and direct examination of available samples. Local epidemiology, suspected source, immune status, previous antimicrobial exposure, and documented colonization with MDR bacteria must be considered for the choice of first-line antimicrobials in healthcare-associated and hospital-acquired BSIs. Early genotypic or phenotypic tests are now available for bacterial identification and early detection of resistance mechanisms and may help, though their clinical impact warrants further investigations. Initial antimicrobial dosing should take into account the pharmacokinetic alterations commonly observed in ICU patients, with a loading dose in case of sepsis or septic shock. Initial antimicrobial combination attempting to increase the antimicrobial spectrum should be discussed when MDR bacteria are suspected and/or in the most severely ill patients. Source identification and control should be performed as soon as the hemodynamic status is stabilized. De-escalation from a broad-spectrum to a narrow-spectrum antimicrobial may reduce antibiotic selection pressure without negative impact on mortality. The duration of therapy is usually 5–8 days though longer durations may be discussed depending on the underlying illness and the source of infection. This narrative review covers the epidemiology, diagnostic workflow and therapeutic aspects of BSI in ICU patients and proposed up-to-date expert statements."
1464,Event-triggered averaging of electrical impedance tomography (EIT) respiratory waveforms as compared to low-pass filtering for removal of cardiac related impedance changes,"Electrical impedance tomography (EIT) is used for bedside ventilation monitoring; cardiac related impedance changes represent a source of noise superimposed on the ventilation signal, commonly removed by low-pass filtering (LPF). We investigated if an alternative approach, based on an event-triggered averaging (ETA) process, is more effective at preserving the actual ventilation waveform. Ten paralyzed patients undergoing volume-controlled ventilation were studied; 30 breaths for each patient were identified to compare LPF and ETA. For ETA the identified breaths were temporally aligned on the beginning of inspiration; the values of the thirty curves at each time point were averaged. The analysis was conducted on the global EIT signal and on four ventral-to-dorsal regions of interest. Global tidal variations by ETA resulted higher than LPF (average difference 139 ± 88 arbitrary units, p = 0.004). Both for global and regional waveforms, minimum and maximum EIT slopes were steeper by ETA as compared to LPF (average difference respectively − 57 ± 60 mL/s and 144 ± 96 mL/s for global signal, p < 0.05); ventilator inspiratory peak airflow correlated with maximum slope measured by ETA (r = 0.902, p < 0.001), but not LPF (p = 0.319). Beginning of inspiration identified on the ventilator waveform and on the global EIT signal by ETA occurred simultaneously, (+ 0.04 ± 0.07 s, p = 0.081), while occurred earlier by LPF (− 0.26 ± 0.1 s, p < 0.001). Removal of cardiac related impedance changes by ETA results in a ventilation signal more similar to the waveforms recorded by the ventilator, particularly regarding the slope of impedance changes and time at the minimum values as compared to LPF. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-019-00348-2) contains supplementary material, which is available to authorized users."
1465,The changing face of neurosurgery for the older person,"Increased life expectancy and illness prevention and treatment have led to a growing population of older patients. These changes in patient population are apparent in neurosurgery; however, relatively little is reported about specific outcomes and prognostication in this group. This review summarises the challenges and management changes occurring in the treatment of three common neurosurgical pathologies; aneurysmal subarachnoid haemorrhage, head injury, and haemorrhagic stroke. A move towards less invasive neurosurgical techniques has implications on the risk–benefit profile of interventions. This creates the opportunity to intervene in older patients with greater co-morbidity, as long as improved outcomes can be evidenced. A critical part of assessing appropriateness for surgical intervention in older patients may be to change from a mindset of age to one of frailty and growing interest in scales assessing this may aid treatment decisions in the future."
1466,Respiratory and Blood Stream Infections are Associated with Subsequent Venous Thromboembolism After Primary Intracerebral Hemorrhage,"BACKGROUND: Infection and venous thromboembolism (VTE) are associated with worse outcomes after intracerebral hemorrhage (ICH). The relationship between infection and VTE in ICH patients is unclear. We hypothesized that infection would be associated with subsequent VTE after ICH. METHODS: We retrospectively studied consecutively admitted spontaneous primary ICH patients from 2009 to 2018 surviving beyond 24 h. The primary predictor variable was infection, diagnosed prior to VTE. The primary outcome was VTE. We used multivariable logistic regression models to estimate the odds ratios and 95% confidence intervals (OR, 95% CI) for VTE risk after infection of any type, after adjusting for ICH score, length of stay and days to deep venous thrombosis (DVT) prophylaxis. Similar analysis was done to estimate the association of infection subtypes, including respiratory and urinary and blood stream infections (BSI) with VTE. RESULTS: There were 414 patients (mean age 65 years, 47% female) that met were analyzed. Infection was diagnosed in 181 (44%) patients. Incident VTE was diagnosed in 36 (9%) patients, largely comprised of DVT (n = 32; 89%). Infection overall was associated with increased risk of subsequent VTE (adjusted OR 4.5, 95% CI 1.6–12.6). Respiratory (adjusted OR 5.7, 95% CI 2.8–11.7) and BSI (adjusted OR 4.0, 95% CI 1.3–11.0) were associated with future VTE. Urinary and other infections were not associated with subsequent VTE. CONCLUSIONS: Infections are associated with subsequent risk of VTE among patients with ICH. Further investigation is required to elucidate mechanisms behind this association and to improve VTE prevention after ICH."
1467,Ultrasound-guided supraclavicular cannulation of the brachiocephalic vein may reduce central line–associated bloodstream infection in preterm infants,"The objective of this study was to assess the risk of central line–associated bloodstream infection (CLABSI) of ultrasound (US)-guided cannulation of the brachiocephalic vein (BCV) compared to standard epicutaneous cava catheters (ECCs) in preterm infants. This was a retrospective cohort study in preterm infants with a birth weight of less than 1500 g. Each BCV catheter was matched 1:3 with ECCs according to sex, birth weight, and year of insertion. The main outcome was the CLABSI density rate per 1000 days. Secondary outcomes included CLABSI episodes, CLABSI episodes per infant, and CLABSI/death. A multivariate Cox regression analysis was performed to assess whether the type of catheter (ECC vs. BCV) was associated with CLABSI risk. Ninety-six catheters (21 BCVs and 75 ECCs) in 79 infants were included (993 catheter days). BCV catheters were associated with a reduced CLABSI density rate compared to ECCs (3.05/1000 days vs 21.1/1000 days; p < 0.001). ECCs were associated with increased CLABSI risk compared to BCV catheters in multivariate analysis (hazard ratio 36; (95% CI, 2.5–511); p = 0.008). Conclusion: US-guided supraclavicular cannulation of the BCV was associated with a reduced risk of CLABSI compared to ECCs. This finding deserves further multicenter research."
1468,Lens-induced uveitis: an update,"Ocular inflammation resulting from a lens pathology is rare in the absence of a cataract or lens trauma because of the lens’ immune privilege. The lens can be a source of ocular inflammation when the capsule is broken or when lens proteins leak out through an intact capsule. These uveitides are termed lens-induced uveitis (LIU) and are often associated with advanced cataracts. Cataracts are part of the normal aging process, and in today’s world, cataract surgery is a safe and affordable means of vision restoration in the developed world. In patients with neglected cataracts and in the developing world where cataract surgery rates are lower, LIU rates are higher together with the associated complications. In this literature review, we intend to equip the armamentarium of the practicing ophthalmologist with an updated knowledge on the demographic features, clinical characteristics, treatment options, and outcomes of LIU. This is to highlight the need for timely management of cataracts before the development of advanced cataracts and LIU."
1469,Resilience in palliative healthcare professionals: a systematic review,"PURPOSE: Exposure to end-of-life and chronic illness on a daily basis may put palliative healthcare professionals’ well-being at risk. Resilience may represent a protective factor against stressful and demanding challenges. Therefore, the aim is to systematically review the quantitative studies on resilience in healthcare professionals providing palliative care to adult patients. METHODS: A literature search on PubMed, Scopus, Web of Science and PsycINFO databases was performed. The review process has followed the international PRISMA statement guidelines. RESULTS: At the initial search, a total of 381 records were identified. Twelve articles were assessed for eligibility and, finally, 6 studies met all the inclusion criteria. Of these, four researches were observational and two interventional pilot studies. From the systematic synthesis, palliative care providers’ resilience revealed to be related to other psychological constructs, including secondary traumatic stress, vicarious posttraumatic growth, death anxiety, burnout, compassion satisfaction, hope and perspective taking. CONCLUSIONS: The current systematic review reported informative data leading to consider resilience as a process modulator and facilitator among palliative care professionals. A model on palliative healthcare providers’ experience and the role of resilience was proposed. Further studies may lead to its validation and implementation in assessment and intervention contributing to foster palliative healthcare professionals’ well-being."
1470,Transcranial Doppler ultrasound findings in children with moderate-to-severe traumatic brain injury following abusive head trauma,"PURPOSE: Abusive head trauma (AHT) is the leading cause of fatal head injuries for children under 2 years. The objective was to evaluate, using transcranial Doppler ultrasound (TCD), whether children with AHT have a similar neurovascular response to injury compared with children without AHT. METHODS: Retrospective sub-analysis of previously prospectively acquired data in a pediatric intensive care unit in a level 1 trauma hospital. TCD was performed daily until hospital day 8, discharge, or death. Neurologic outcome was assessed using the Glasgow Outcome Scale Extended (GOS-E Peds) at 1 month from initial injury. RESULTS: Sixty-nine children aged 1 day to 17 years with moderate-to-severe traumatic brain injury were enrolled. Fifteen children suffered AHT and 54 had no suspicion for AHT. Fifteen children with AHT underwent 80 serial TCD examinations; 54 children without AHT underwent 308 exams. After standardization for age and gender normative values, there was no statistically significant difference in mean cerebral blood flow velocity of the middle cerebral artery (V(MCA)) between children with and without AHT. There was no difference in the incidence of extreme cerebral blood flow velocity (CBFV, greater or less than 2 standard deviations from normative value) between groups. Within the AHT group, there were no statistically significant differences in V(MCA) between children with a favorable (GOS-E Peds 1–4) versus unfavorable neurologic outcome (GOS-E Peds 5–8). CONCLUSION: Children with AHT have no significant differences in V(MCA) or percentage of extreme CBFV in the middle cerebral artery compared to with those without AHT."
1471,An index to prioritize the preventive maintenance of medical equipment,"We propose an index to prioritize preventive maintenance for medical equipment. Our index considers seven variables: type of equipment, equipment function, maintenance requirements, calibration, equipment age, equipment location, and equipment hazards. We developed a mathematical model using these variables, and its result is interpreted as an index of equipment maintenance priority. The numerical output of the index was classified into three categories: high, medium, and low priority. We proposed our index model to technical staff at the Department of Biomedical Engineering of the National Institute of Respiratory Diseases in Mexico as a protocol for scheduling appropriate preventive maintenance for medical equipment during the year. The index was tested in a sample of 16 different medical equipment. Our model provides a guide to define the priority and the number of preventive maintenance routines required for medical equipment per year."
1472,Clinical characteristics and risk factors of tigecycline-associated hypofibrinogenaemia in critically ill patients,"PURPOSE: To analyze the clinical features and risk factors of tigecycline-associated hypofibrinogenaemia and study whether cefoperazone/sulbactam combined with tigecycline aggravates coagulopathy or hypofibrinogenaemia. METHODS: A retrospective case–control study of patients with severe infection who were treated with tigecycline was conducted. Patients were assigned to the hypofibrinogenaemia group (< 2.0 g/L) and normal fibrinogen (normal) group (≥ 2.0 g/L) to assess the clinical features of patients with tigecycline-associated hypofibrinogenaemia. The traits of patients treated with cefoperazone/sulbactam in the hypofibrinogenaemia group were also analyzed. RESULTS: In total, 127 patients were enrolled in the study, including 71 patients with hypofibrinogenaemia and 56 patients with normal fibrinogen levels. Hypofibrinogenaemia developed at a median of 6 (4–8) days after tigecycline treatment, and the fibrinogen level returned to normal at a median of 3 (3–5) days after tigecycline discontinuation. In the multivariate analysis, intra-abdominal infection (p = 0.005), fibrinogen level at tigecycline initiation (p < 0.001), maintenance dose (p = 0.039), and treatment duration (p = 0.002) were found to be related to hypofibrinogenaemia. Treatment with cefoperazone/sulbactam was not associated with hypofibrinogenaemia (p = 0.681), but patients treated with cefoperazone/sulbactam had a higher incidence of coagulopathy (p = 0.009) and needed more blood products (p = 0.003) than those treated without cefoperazone/sulbactam. CONCLUSION: Tigecycline-associated hypofibrinogenaemia often developed on the 6th (4th–8th) day of tigecycline use and was associated with intra-abdominal infection, fibrinogen level at tigecycline initiation, maintenance dose, and treatment duration of tigecycline but not cefoperazone/sulbactam."
1473,What Would the Screen-and-Treat Strategy for Helicobacter pylori Mean in Terms of Antibiotic Consumption?,"Several guidelines recommend the screen-and-treat strategy, i.e. active search for the presence of Helicobacter pylori infection and its eradication to prevent the possibility of gastric cancer. It is thought that a relatively short duration antibiotic regimen given once in a lifetime would not significantly increase overall antibiotic consumption. However, this would mean offering antibiotic treatment to the majority of the population in countries with the biggest burden of gastric cancer who would, therefore, have the greatest benefit from such a strategy. So far, no country has implemented an eradication strategy. With an example based on the current situation in Latvia, we have estimated the increase in antibiotic consumption if the screen-and-treat strategy was applied. Depending on the scenario that might be chosen, clarithromycin consumption would increase up to sixfold, and amoxicillin consumption would double if the recommendations of the current guideline in the local circumstances was applied. It appears that an increase in commonly used antibiotic consumption cannot be justified from the viewpoint of antibiotic stewardship policies. Solutions to this problem could be the use of antibiotics that are not required for treating life-threatening diseases or more narrow selection of the target group, e.g. young people before family planning to avoid transmission to offspring. Additional costs related to the increase in resistome should be considered for future cost-effectiveness modelling of the screen-and-treat strategy."
1474,Train-Associated Injuries Pose a Significant Burden on Trauma Care Systems of Emerging Economies,"BACKGROUND: The Indian railway system is the fourth largest in the world and causes about 15 deaths every day, due to intentional or unintentional reasons. This study presents a 5-year retrospective analysis of patients injured due to train-associated events, managed at a level-1 trauma center in India. MATERIALS AND METHODS: Hospital-based trauma registry data of train-associated injuries presenting between 2012 and 2016 were analyzed. Data from 726 patients were analyzed for demographics, injury events, injury regions, their management and outcomes. ISS and NISS were used to quantify the injury severity. RESULTS: Mean age was 33 years, with male-to-female ratio 86 to 14%. The majority of patients (62%) were between 20–40 years. The median ISS was 9 (IQR 4–16), median hospital stays 11 days (IQR6-23), with in-hospital mortality of 17.4%. Presence of head injury; ISS > 9 and CPR in ED were independent risk factors of mortality. Trespassers on the rail track had significantly more severe injuries compared to passengers (Median ISS 13 vs. 9, p = 0.012; Median NISS 22 vs.17, p = 0.015); however, mortality and hospital length of stay were not significantly different. Location of injury event (on platform or tracks) showed no difference between the severity of injuries, mortality and hospital length of stay. CONCLUSIONS: Current study reports comprehensive injury patterns and outcomes of train-associated injuries from a low- and middle-income country (LMIC). Apart from the mortality, there is a high incidence of permanent disabilities from extremity amputations. No significant difference was noted in the severity and outcomes among patients injured on or off train platforms, emphasizing the need for comprehensive safety measures including enforcement and promoting safe behavior not only on locations like train tracks but equally at platforms."
1475,The effects of oral feeding while on nasal continuous positive airway pressure (NCPAP) in preterm infants,"OBJECTIVE: To determine whether delaying oral feeding until coming off NCPAP will alter feeding and respiratory-related morbidities in preterm infants. DESIGN: In this retrospective pre–post analysis, outcomes were compared in two preterm infant groups (≤32 weeks gestation). Infants in Group 1 were orally fed while on NCPAP, while infants in Group 2 were only allowed oral feedings after ceasing NCPAP. RESULTS: Although infants in Group 2 started feeds at a later postmenstrual age (PMA), they reached full oral feeding at a similar PMA compared with Group 1. Interestingly, there was a positive correlation between the duration of oral feeding while on NCPAP and the time spent on respiratory support in Group 1. CONCLUSIONS: Delayed oral feeding until ceasing NCPAP did not contribute to feeding-related morbidities. We recommend caution when initiating oral feedings in preterm infants on NCPAP without evaluating the safety of the infants and their readiness for oral feedings."
1476,An endotracheal tube providing “pressurized sealing” prevents fluid leakage in mechanically ventilated critically ill patients: a pilot study,"Microaspiration of bacteriologically contaminated oropharyngeal secretions alongside the cuff of an endotracheal tube (ETT) is a key mechanism for development of ventilator-associated pneumonia. We have constructed a prototype double-cuffed ETT equipped with a supplemental port in-between the cuffs through which continuous positive airway pressure (CPAP) is delivered. Pressure in the intercuff space propels secretions upwards and produces 100% tracheal sealing in an in vitro model. We conducted a 24 h study to investigate the sealing effect of this ETT in 12 critically ill mechanically ventilated patients. Methylene blue, instilled through a bronchoscope on top of the proximal cuff, was used as leakage tracer. Fiberoptic visualisation of the trachea was performed 1 h and 24 h thereafter. Leakage was confirmed if blue dye was detected on the tracheal mucosa beyond the tip of the ETT. In no patient, dye passed by the cuffs during the study period. Presence of the ETT did not interfere with ventilator settings, patient mobilization, physiotherapy, and technical acts. Overall, pressures in the intercuff space remained between 10 and 15 cmH(2)O. Excessive pressure swings were swiftly corrected by the CPAP system. A double-cuffed ETT, offering “pressurized sealing” of the trachea, safely and effectively prevented leakage during 24 h mechanical ventilation."
1477,Pre-admission air pollution exposure prolongs the duration of ventilation in intensive care patients,"PURPOSE: Air pollutant exposure constitutes a serious risk factor for the emergence or aggravation of (existing) pulmonary disease. The impact of pre-intensive care ambient air pollutant exposure on the duration of artificial ventilation was, however, not yet established. METHODS: The medical records of 2003 patients, admitted to the intensive care unit (ICU) of the Antwerp University Hospital (Flanders, Belgium), who were artificially ventilated on ICU admission or within 48 h after admission, for the duration of at least 48 h, were analyzed. For each patient’s home address, daily air pollutant exposure [particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM(2.5)) and ≤ 10 µm (PM(10)), nitrogen dioxide (NO(2)) and black carbon (BC)] up to 10 days prior to hospital admission was modeled using a high-resolution spatial–temporal model. The association between duration of artificial ventilation and air pollution exposure during the last 10 days before ICU admission was assessed using distributed lag models with a negative binomial regression fit. RESULTS: Controlling for pre-specified confounders, an IQR increment in BC (1.2 µg/m(3)) up to 10 days before admission was associated with an estimated cumulative increase of 12.4% in ventilation duration (95% CI 4.7–20.7). Significant associations were also observed for PM(2.5), PM(10) and NO(2), with cumulative estimates ranging from 7.8 to 8.0%. CONCLUSION: Short-term ambient air pollution exposure prior to ICU admission represents an unrecognized environmental risk factor for the duration of artificial ventilation in the ICU. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-05999-3) contains supplementary material, which is available to authorized users."
1478,Refractory and Super-refractory Status Epilepticus,"CONTEXT: Refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) are neurological emergencies with considerable mortality and morbidity. In this paper, we provide an overview of causes, evaluation, treatment, and consequences of RSE and SRSE, reflecting the lack of high-quality evidence to inform therapeutic approach. SOURCES: This is a narrative review based on personal practice and experience. Nevertheless, we searched MEDLINE (using PubMed and OvidSP vendors) and Cochrane central register of controlled trials, using appropriate keywords to incorporate recent evidence. RESULTS: Refractory status epilepticus is commonly defined as an acute convulsive seizure that fails to respond to two or more anti-seizure medications including at least one nonbenzodiazepine drug. Super-refractory status epilepticus is a status epilepticus that continues for ≥24 hours despite anesthetic treatment, or recurs on an attempted wean of the anesthetic regimen. Both can occur in patients known to have epilepsy or de novo, with increasing recognition of autoimmune and genetic causes. Electroencephalography monitoring is essential to monitor treatment response in refractory/super-refractory status epilepticus, and to diagnose non-convulsive status epilepticus. The mainstay of treatment for these disorders includes anesthetic infusions, primarily midazolam, ketamine, and pentobarbital. Dietary, immunological, and surgical treatments are viable in selected patients. Management is challenging due to multiple acute complications and long-term adverse consequences. CONCLUSIONS: We have provided a synopsis of best practices for diagnosis and management of refractory/superrefractory status epilepticus and highlighted the lack of sufficient high-quality evidence to drive decision making, ending with a brief foray into avenues for future research."
1479,A physiology-based mathematical model for the selection of appropriate ventilator controls for lung and diaphragm protection,"Mechanical ventilation is used to sustain respiratory function in patients with acute respiratory failure. To aid clinicians in consistently selecting lung- and diaphragm-protective ventilation settings, a physiology-based decision support system is needed. To form the foundation of such a system, a comprehensive physiological model which captures the dynamics of ventilation has been developed. The Lung and Diaphragm Protective Ventilation (LDPV) model centers around respiratory drive and incorporates respiratory system mechanics, ventilator mechanics, and blood acid–base balance. The model uses patient-specific parameters as inputs and outputs predictions of a patient’s transpulmonary and esophageal driving pressures (outputs most clinically relevant to lung and diaphragm safety), as well as their blood pH, under various ventilator and sedation conditions. Model simulations and global optimization techniques were used to evaluate and characterize the model. The LDPV model is demonstrated to describe a CO(2) respiratory response that is comparable to what is found in literature. Sensitivity analysis of the model indicate that the ventilator and sedation settings incorporated in the model have a significant impact on the target output parameters. Finally, the model is seen to be able to provide robust predictions of esophageal pressure, transpulmonary pressure and blood pH for patient parameters with realistic variability. The LDPV model is a robust physiological model which produces outputs which directly target and reflect the risk of ventilator-induced lung and diaphragm injury. Ventilation and sedation parameters are seen to modulate the model outputs in accordance with what is currently known in literature. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-020-00479-x) contains supplementary material, which is available to authorized users."
1480,Trends in 3D Printing Processes for Biomedical Field: Opportunities and Challenges,[Image: see text]
1481,Dendritic cells and Brucella spp. interaction: the sentinel host and the stealthy pathogen,"As dendritic cells (DCs) are among the first cells to encounter antigens, these cells trigger both innate and T cell responses, and are the most potent antigen-presenting cells. Brucella spp., which is an intracellular facultative and stealthy pathogen, is able to evade the bactericidal activities of professional phagocytes. Several studies have demonstrated that Brucella can survive and replicate intracellularly, thereby provoking impaired maturation of DCs. Therefore, the interaction between DCs and Brucella becomes an interesting model to study the immune response. In this review, we first will describe the most common techniques for DCs differentiation in vitro as well as general features of brucellosis. Then, the interaction of DCs and Brucella, including pathogen recognition, molecular mechanisms of bacterial pathogenesis, and intracellular trafficking of Brucella to subvert innate response, will be reviewed. Finally, we will debate diversity in immunological DC response and the controversial role of DC activation against Brucella infection."
1482,Epitope Prediction by Novel Immunoinformatics Approach: A State-of-the-art Review,"Immunoinformatics is a science that helps to create significant immunological information using bioinformatics softwares and applications. One of the most important applications of immunoinformatics is the prediction of a variety of specific epitopes for B cell recognition and T cell through MHC class I and II molecules. This method reduces costs and time compared to laboratory tests. In this state-of-the-art review, we review about 50 papers to find the latest and most used immunoinformatic tools as well as their applications for predicting the viral, bacterial and tumoral structural and linear epitopes of B and T cells. In the clinic, the main application of prediction of epitopes is for designing peptide-based vaccines. Peptide-based vaccines are a considerably potential alternative to low-cost vaccines that may reduce the risks related to the production of common vaccines."
1483,Integrating nanoparticle quantification and statistical design of experiments for efficient HIV-1 virus-like particle production in High Five cells,"The nature of enveloped virus-like particles (VLPs) has triggered high interest in their application to different research fields, including vaccine development. The baculovirus expression vector system (BEVS) has been used as an efficient platform for obtaining large amounts of these complex nanoparticles. To date, most of the studies dealing with VLP production by recombinant baculovirus infection utilize indirect detection or quantification techniques that hinder the appropriate characterization of the process and product. Here, we propose the application of cutting-edge quantification methodologies in combination with advanced statistical designs to exploit the full potential of the High Five/BEVS as a platform to produce HIV-1 Gag VLPs. The synergies between CCI, MOI, and TOH were studied using a response surface methodology approach on four different response functions: baculovirus infection, VLP production, VLP assembly, and VLP productivity. TOH and MOI proved to be the major influencing factors in contrast with previous reported data. Interestingly, a remarkable competition between Gag VLP production and non-assembled Gag was detected. Also, the use of nanoparticle tracking analysis and flow virometry revealed the existence of remarkable quantities of extracellular vesicles. The different responses of the study were combined to determine two global optimum conditions, one aiming to maximize the VLP titer (quantity) and the second aiming to find a compromise between VLP yield and the ratio of assembled VLPs (quality). This study provides a valuable approach to optimize VLP production and demonstrates that the High Five/BEVS can support mass production of Gag VLPs and potentially other complex nanoparticles. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-019-10319-x) contains supplementary material, which is available to authorized users."
1484,Synthetic cathelicidin LL-37 reduces Mycobacterium avium subsp. paratuberculosis internalization and pro-inflammatory cytokines in macrophages,"Mycobacterium avium subsp. paratuberculosis (MAP) causes chronic diarrheic intestinal infections in domestic and wild ruminants (paratuberculosis or Johne’s disease) for which there is no effective treatment. Critical in the pathogenesis of MAP infection is the invasion and survival into macrophages, immune cells with ability to carry on phagocytosis of microbes. In a search for effective therapeutics, our objective was to determine whether human cathelicidin LL-37, a small peptide secreted by leuckocytes and epithelial cells, enhances the macrophage ability to clear MAP infection. In murine (J774A.1) macrophages, MAP was quickly internalized, as determined by confocal microscopy using green fluorescence protein expressing MAPs. Macrophages infected with MAP had increased transcriptional gene expression of pro-inflammatory TNF-α, IFN-γ, and IL-1β cytokines and the leukocyte chemoattractant IL-8. Pretreatment of macrophages with synthetic LL-37 reduced MAP load and diminished the transcriptional expression of TNF-α and IFN-γ whereas increased IL-8. Synthetic LL-37 also reduced the gene expression of Toll-like receptor (TLR)-2, key for mycobacterial invasion into macrophages. We concluded that cathelicidin LL-37 enhances MAP clearance into macrophages and suppressed production of tissue-damaging inflammatory cytokines. This cathelicidin peptide could represent a foundational molecule to develop therapeutics for controlling MAP infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00441-019-03098-4) contains supplementary material, which is available to authorized users."
1485,Clinical and Environmental Surveillance of Rotavirus Common Genotypes Showed High Prevalence of Common P Genotypes in Egypt,"The objective of this study was to compare the prevalence of human rotavirus group A common G and P genotypes in human Egyptian stool specimens and raw sewage samples to determine the most common genotypes for future vaccine development. From 1026 stool specimens of children with acute diarrhea and using nested RT-PCR, 250 samples (24.37%) were positive for human rotavirus group A. Using multiplex RT-PCR, rotavirus common P and G genotypes were detected as 89.20% and 46.40% of the positive clinical specimens respectively. This low percentage of common G genotypes frequency may affect the efficiency of the available live attenuated oral rotavirus vaccines [Rotarix® (human rotavirus G1P[8]) and RotaTeq® (reassortant bovine–human rotavirus G1-4P[5] and G6P[8])], however the percentage of clinical specimens which were negative for common G genotypes but positive for P[8] genotype was 12.00%. From 24 positive raw sewage samples for rotavirus group A VP6 collected from Zenin and El-Gabal El-Asfar wastewater treatment plants (WWTPs), 21 samples (87.50%) were typeable for common P genotypes while 13 samples (54.17%) were typeable for common G genotypes. Phylogenetic analysis of a VP8 partial gene of 45 P-typeable clinical isolates and 20 P-typeable raw sewage samples showed high similarity to reference strains and the majority of mutations were silent and showed lower to non-significant similarity with the two vaccine strains. This finding is useful for determining the most common antigens required for future vaccine development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12560-020-09426-0) contains supplementary material, which is available to authorized users."
1486,Listening to the neurological teams for multiple sclerosis: the SMART project,"OBJECTIVE: Aim of the research was to define the quality of life of Italian neurologists and nurses’ professional caring for multiple sclerosis, to understand their living the clinical practice and identify possible signals of compassion fatigue. MATERIAL AND METHODS: One hundred five neurologists and nurses from 30 Italian multiple sclerosis centres were involved in an online quali-quantitative survey on the organization of care, combined with the Satisfaction and Compassion Fatigue Test and a collection of narratives. Descriptive statistics of the quantitative data were integrated with the results obtained by the narrative medicine methods of analysis. RESULTS: Most of the practitioners were neurologists, 46 average years old, 69% women, 43% part time dedicated to multiple sclerosis. An increased number of patients in the last 3 years were referred in 29 centres. Differences were found between neurologists and nurses. Physicians showed higher risks of burnout, reporting intensive working paces, lack of medical personnel, and anxiety caused by the precarious employment conditions. Nurses appeared more satisfied, although the reference to the lack of spaces, and the cross professional roles risk of compassion fatigue. Both positive and negative relationships of care were depicted as influencing the professional quality of life. CONCLUSION: The interviewed neurological teams need to limit the risk of compassion fatigue, which appeared from the first years of the career. The prevalence of the risk among neurologists suggests more awareness among scientific societies and health care managers on the risk for this category, as first step to prevent it. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10072-020-04301-z) contains supplementary material, which is available to authorized users."
1487,Enlightened Self-interest in Altruism (ESIA),"Altruism and the medical profession have been linked throughout the history of medicine. Students are drawn to the calling of medicine because of altruistic values, dedication to service, and the desire to alleviate suffering and promote healing. Despite a dedication to these values, altruism in medicine is threatened by empathy erosion that develops in the clinical years of medical school and an increasing rate of medical student burnout. Currently, there are two widespread movements in medicine aimed at addressing the dual loss of altruism and physician and student burnout—professionalism and wellness. Despite widespread recognition of the problems and programs aimed at improving them, there has been little headway, and even calls to abandon altruism in the modern marketplace of medicine. What is needed is not an abandonment of a fundamental, defining value of the profession, but a re-evaluation of the meaning of altruism in medicine and a framework that allows for students and physicians to provide altruistic care for a sustainable, rewarding career in the healing profession. This paper proposes the Enlightened Self-Interest in Altruism (ESIA) model as an ethical framework to allow medical students to synergize the interests of the self with those they serve in a mutually beneficial relationship to improve patient care and the healthcare system at large. The ESIA model acknowledges that egoism and altruism are intertwined, dynamic motivators of behavior. In the enlightened self-interest approach, the interests of the group are also the interests of the self. The physician–patient relationship is a dyad in which egoism and altruism may converge in an enlightened way that acknowledges that the interests of one are the interests of the whole. This is a paradigm shift from the historical view of egoism and altruism as opposing motivations. This paper will present the threats to altruism, explore the interface of egoism and altruism in a clinical vignette, and then present the ESIA framework as an educational approach to aligning the interests of providers and patients to prevent burnout and promote altruism."
1488,"Do Vaccines Trigger Neurological Diseases? Epidemiological Evaluation of Vaccination and Neurological Diseases Using Examples of Multiple Sclerosis, Guillain–Barré Syndrome and Narcolepsy","This article evaluates the epidemiological evidence for a relationship between vaccination and neurological disease, specifically multiple sclerosis, Guillain–Barré syndrome and narcolepsy. The statistical methods used to test vaccine safety hypotheses are described and the merits of different study designs evaluated; these include the cohort, case-control, case-coverage and the self-controlled case-series methods. For multiple sclerosis, the evidence does not support the hypothesized relationship with hepatitis B vaccine. For Guillain−Barré syndrome, the evidence suggests a small elevated risk after influenza vaccines, though considerably lower than after natural influenza infection, with no elevated risk after human papilloma virus vaccine. For narcolepsy, there is strong evidence of a causal association with one adjuvanted vaccine used in the 2009/10 influenza pandemic. Rapid investigation of vaccine safety concerns, however biologically implausible, is essential to maintain public and professional confidence in vaccination programmes."
1489,Understanding resistance in Pseudomonas,
1490,Antibiotic prophylaxis in the ICU: to be or not to be administered for patients undergoing procedures?,
1491,Peripheral perfusion index as a predictor of failed weaning from mechanical ventilation,"We hypothesized that impairment of peripheral perfusion index (PPI) during spontaneous breathing trial (SBT) might be predictive of weaning failure. We included 44 consecutive, adult, patients, who were scheduled for weaning after at least 48 h of invasive mechanical ventilation in this prospective observational study. Weaning failure was defined as failed SBT or reintubation within 48 h of extubation. PPI readings were obtained before initiation of the SBT, and every 5 min till the end of the SBT. PPI ratio was calculated at every time point as: PPI value/ baseline PPI. The primary outcome was the accuracy of PPI ratio at the end of the SBT in detecting failed weaning. Forty-three patients were available for the final analysis. Eighteen patients (42%) were considered failed weaning. PPI ratio was higher in patients with successful weaning compared to patients with failed weaning during the last 15 min of the SBT. PPI ratio at the end of SBT was higher in patients with successful weaning compared to patients with failed weaning. PPI ratio at the end of SBT had good predictive ability for weaning failure {area under receiver operating characteristic curve (95% confidence interval): 0.833(0.688–0.929), cutoff value ≤ 1.41}. The change in PPI during SBT is an independent predictor for re-intubation. PPI could be a useful tool for monitoring the patient response to SBT. Patients with successful weaning showed higher augmentation of PPI during the SBT compared to re-intubated patients. Failure of augmenting the PPI by 41% at the end of SBT could predict re-intubation with negative predictive value of 95%. Clinical trial identifier: NCT03974568. https://clinicaltrials.gov/ct2/show/NCT03974568?term=ahmed+hasanin&draw=3&rank=17"
1492,Hypercapnia Exacerbates the Blood–Brain Barrier Disruption Via Promoting HIF-1a Nuclear Translocation in the Astrocytes of the Hippocampus: Implication in Further Cognitive Impairment in Hypoxemic Adult Rats,"Hypercapnia in combination with hypoxemia is usually present in severe respiratory disease in the intensive care unit (ICU) and can lead to more severe cognitive dysfunction. Increasing evidence has indicated that the compromised blood–brain barrier (BBB) in the hippocampus in hypoxemia conditions can result in cognitive dysfunction. However, the role and underlying mechanism of hypercapnia in the BBB disruption remains poorly known. A rat model of hypercapnia was first established in this study by intubation and mechanical ventilation with a small-animal ventilator. After this, the cognitive function of the experimental rats was assessed by the Morris water maze test. The BBB permeability was evaluated by the Evans Blue (EB) test and brain water content (BWC). Western blot analysis was carried out to detect the protein expressions of total and nuclear hypoxia-inducible factor-1α (HIF-1α), matrixmetalloproteinase-9 (MMP-9) and Aquaporins-4 (AQP-4) in the hippocampus tissue. Double immunofluorescence further verified the protein expression of different biomarkers was localized in the astrocytes of the hippocampus. Hypercapnia alone did not disrupt the BBB, but it could further enhance the BBB permeability in hypoxemia. Concomitantly, up-regulation of nuclear HIF-1α, AQP-4, MMP-9 protein expression along with increased degradation of the occludin and claudin-5 proteins was found in the hypercapnia rat model, while the total HIF-1α remained unchanged. Interestingly, these changes were independent of the acidosis induced by hypercapnia. Of note, after premedication of 2-Methoxyestradiol (2ME2, an inhibitor of HIF-1α nuclear translocation), the disrupted BBB could be restored resulting in improvement of the cognitive impairment. Meanwhile, accumulation of nuclear HIF-1α, protein expression of AQP-4 and MMP-9 and protein degradation of the occludin and claudin-5 were decreased. Thus, our study demonstrated that hypercapnia can further disrupt the BBB through promoting HIF-1α nuclear translocation and up-regulation of AQP-4 and MMP-9 in hypoxemia. It is therefore suggested that the cascade of hypercapnia-induced nuclear HIF-1α protein translocation in hypoxia-activated astrocytes may be a potential target for ameliorating cognitive impairment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11064-020-03038-7) contains supplementary material, which is available to authorized users."
1493,Towards common ground in the biodiversity–disease debate,"The disease ecology community has struggled to come to consensus on whether biodiversity reduces or increases infectious disease risk, a question that directly affects policy decisions for biodiversity conservation and public health. Here, we summarize the primary points of contention regarding biodiversity–disease relationships and suggest that vector-borne, generalist wildlife and zoonotic pathogens are the types of parasites most likely to be affected by changes to biodiversity. One synthesis on this topic revealed a positive correlation between biodiversity and human disease burden across countries, but as biodiversity changed over time within these countries, this correlation became weaker and more variable. Another synthesis—a meta-analysis of generally smaller-scale experimental and field studies—revealed a negative correlation between biodiversity and infectious diseases (a dilution effect) in various host taxa. These results raise the question of whether biodiversity–disease relationships are more negative at smaller spatial scales. If so, biodiversity conservation at the appropriate scales might prevent wildlife and zoonotic diseases from increasing in prevalence or becoming problematic (general proactive approaches). Further, protecting natural areas from human incursion should reduce zoonotic disease spillover. By contrast, for some infectious diseases, managing particular species or habitats and targeted biomedical approaches (targeted reactive approaches) might outperform biodiversity conservation as a tool for disease control. Importantly, biodiversity conservation and management need to be considered alongside other disease management options. These suggested guiding principles should provide common ground that can enhance scientific and policy clarity for those interested in simultaneously improving wildlife and human health."
1494,Acute respiratory distress syndrome-attributable mortality in critically ill patients with sepsis,"PURPOSE: Previous studies assessing impact of acute respiratory distress syndrome (ARDS) on mortality have shown conflicting results. We sought to assess the independent association of ARDS with in-hospital mortality among intensive care unit (ICU) patients with sepsis. METHODS: We studied two prospective sepsis cohorts drawn from the Early Assessment of Renal and Lung Injury (EARLI; n = 474) and Validating Acute Lung Injury markers for Diagnosis (VALID; n = 337) cohorts. ARDS was defined by Berlin criteria. We used logistic regression to compare in-hospital mortality in patients with and without ARDS, controlling for baseline severity of illness. We also estimated attributable mortality, adjusted for illness severity by stratification. RESULTS: ARDS occurred in 195 EARLI patients (41%) and 99 VALID patients (29%). ARDS was independently associated with risk of hospital death in multivariate analysis, even after controlling for severity of illness, as measured by APACHE II (odds ratio [OR] 1.65 (95% confidence interval [CI] 1.02, 2.67), p = 0.04 in EARLI; OR 2.12 (CI 1.16, 3.92), p = 0.02 in VALID). Patients with severe ARDS (P/F < 100) primarily drove this relationship. The attributable mortality of ARDS was 27% (CI 14%, 37%) in EARLI and 37% (CI 10%, 51%) in VALID. ARDS was independently associated with ICU mortality, hospital length of stay (LOS), ICU LOS, and ventilator-free days. CONCLUSIONS: Development of ARDS among ICU patients with sepsis confers increased risk of ICU and in-hospital mortality in addition to other important outcomes. Clinical trials targeting patients with severe ARDS will be best poised to detect measurable differences in these outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06010-9) contains supplementary material, which is available to authorized users."
1495,Ventilator-associated pneumonia and bloodstream infections in intensive care unit cancer patients: a retrospective 12-year study on 3388 prospectively monitored patients,"PURPOSE: Some publications suggest high rates of healthcare-associated infections (HAIs) and of nosocomial pneumonia portending a poor prognosis in ICU cancer patients. A better understanding of the epidemiology of HAIs in these patients is needed. METHODS: A retrospective analysis of all the patients hospitalized for ≥ 48 h during a 12-year period in the 12-bed ICU of the Gustave Roussy hospital, monitored prospectively for ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) and for use of medical devices. RESULTS: During 3388 first stays in the ICU, 198 cases of VAP and 103 primary, 213 secondary, and 77 catheter-related BSIs were recorded. The VAP rate was 24.5/1000 ventilator days (95% confidence interval [CI] 21.2–28.0); the catheter-related BSI rate was 2.3/1000 catheter days (95% CI 1.8–2.8). The cumulative incidence during the first 25 days of exposure was 58.8% (95% CI 49.1–66.6%) for VAP, 8.9% (95% CI, 6.2–11.5%) for primary, 15.1% (95% CI 11.6–18.5%) for secondary and 5.0% (95% CI 3.2–6.8%) for catheter-related BSIs. VAP or BSIs were not associated with a higher risk of ICU mortality. CONCLUSIONS: This is the first study to report HAI rates in a large cohort of critically ill cancer patients. Although both the incidence of VAP and the rate of BSI are higher than in general ICU populations, this does not impact patient outcomes. The occurrence of device-associated infections is essentially due to severe medical conditions in patients and to the characteristics of malignancy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00520-019-04800-6) contains supplementary material, which is available to authorized users."
1496,"Childhood obesity, cardiovascular and liver health: a growing epidemic with age","BACKGROUND: The frequency of childhood obesity has increased over the last 3 decades, and the trend constitutes a worrisome epidemic worldwide. With the raising obesity risk, key aspects to consider are accurate body mass index classification, as well as metabolic and cardiovascular, and hepatic consequences. DATA SOURCES: The authors performed a systematic literature search in PubMed and EMBASE, using selected key words (obesity, childhood, cardiovascular, liver health). In particular, they focused their search on papers evaluating the impact of obesity on cardiovascular and liver health. RESULTS: We evaluated the current literature dealing with the impact of excessive body fat accumulation in childhood and across adulthood, as a predisposing factor to cardiovascular and hepatic alterations. We also evaluated the impact of physical and dietary behaviors starting from childhood on cardio-metabolic consequences. CONCLUSIONS: The epidemic of obesity and obesity-related comorbidities worldwide raises concerns about the impact of early abnormalities during childhood and adolescence. Two key abnormalities in this context include cardiovascular diseases, and nonalcoholic fatty liver disease. Appropriate metabolic screenings and associated comorbidities should start as early as possible in obese children and adolescents. Nevertheless, improving dietary intake and increasing physical activity performance are to date the best therapeutic tools in children to weaken the onset of obesity, cardiovascular diseases, and diabetes risk during adulthood."
1497,Anti-Sarcocystis Antibodies in Lambs Deprived of Colostrum,"INTRODUCTION: The objective of this study was to evaluate the presence of anti-Sarcocystis spp. specific IgG antibodies in serum samples from precolostral lambs to determine the occurrence of transplacental transmission of Sarcocystis spp. in sheep. METHODS: Blood samples were collected from 80 ewes and their respective lambs, immediately after lambing and before colostrum ingestion, respectively. The presence of anti-Sarcocystis spp. IgG was evaluated in serum samples using the indirect fluorescent antibody test (IFAT). Positive samples of the lambs were submitted to titration and IFAT to detect anti-T. gondii and anti-N. caninum specific IgG. RESULTS: Anti-Sarcocystis spp. IgG was detected in 62.5% of the ewes (50/80) and in 4% of the lambs of the seropositive ewes (2/50). None of the lambs from seronegative ewes were positive. The final titers of the positive lambs were 80. No cross reaction was detected among the positive samples to anti-Sarcocystis spp., anti-N. caninum, and anti-T. gondii IgG. The detection of anti-Sarcocystis spp. antibodies in serum samples of lambs deprived of colostrum suggests transplacental transmission of infection. Thus, the vertical transmission may be an alternative route of infection of Sarcocystis spp. also in sheep. Further studies are warranted to confirm transplacental transmission in sheep and to explain the importance of this infection pathway."
1498,Cerebral venous volume changes and pressure autoregulation in critically ill infants,"OBJECTIVE: To determine whether ventilator-related fluctuations in cerebral blood volume (CBV) are associated with cerebral pressure passivity. STUDY DESIGN: In a prospective study of newborns undergoing positive-pressure ventilation, we calculated coherence between continuous mean arterial pressure (MAP) and cerebral near-infrared spectroscopy hemoglobin difference (HbD). Significant HbD–MAP coherence indicated cerebral pressure passivity. CBV changes were measured as the spectral power of total hemoglobin (S(HbT)) at the ventilator frequency. A regression model tested whether S(HbT) predicts cerebral pressure passivity and/or death/brain injury, controlling for birth gestational age and other factors. RESULTS: We studied 68 subjects with prematurity (n = 19), congenital heart disease (n = 11), and hypoxic–ischemic encephalopathy (n = 38). S(HbT), sedative use, and pCO(2) were positively associated, and circulating hemoglobin negatively associated, with cerebral pressure passivity (p < 0.001), which was positively associated with brain injury (p < 0.001). CONCLUSION: In sick newborns, ventilator-related CBV fluctuations may predispose to cerebral pressure passivity, which may predispose to an adverse neonatal outcome."
1499,Productive Aging in the Social Work Profession: A Comparison of Licensed Workers 60 Years and Older with Their Younger Counterparts,"This article reports the findings of an online survey in 13 U.S. states that compared the self-described demographics, wellness factors (mental health, physical health, and substance misuse), practice factors (fields of practice and work environment issues), and feelings about being a social worker (compassion satisfaction, workplace stress, being glad one chose social work and feeling valued as a professional in society) of 870 employed licensed social workers age 60 and older to 4076 licensed social workers under age 60. The results indicate that the older social workers were more likely to be male and white, less likely to report mental health problems, and more likely to work exclusively in private practice. Although older workers reported more serious physical health problems, they rated their physical health more favorably than their younger counterparts. In both bivariate and multivariate analyses, the older social workers scored significantly higher in compassion satisfaction, being glad they chose social work as a career, and feeling valued as a professional in society. The older social workers scored lower in workplace stress at levels that were statistically significant in a bivariate analysis, but not in a multivariate analysis."
1500,Locating stridor caused by tumor compression by using a multichannel electronic stethoscope: a case report,A 67-year-old male patient with chronic obstructive pulmonary disease was admitted to a hospital in northern Taiwan for progressive dyspnea and productive cough with an enlarged left upper lobe tumor (5.3 × 6.8 × 3.9 cm(3)). Previous chest auscultation on outpatient visits had yielded diffuse wheezes. A localized stridor (fundamental frequency of 125 Hz) was captured using a multichannel electronic stethoscope comprising four microelectromechanical system microphones. An energy-based localization algorithm was used to successfully locate the sound source of the stridor caused by tumor compression. The results of the algorithm were compatible with the findings obtained from computed tomography and bronchoscopy (mean radius = 9.40 mm and radial standard deviation = 14.97 mm). We demonstrated a potential diagnostic aid for pulmonary diseases through sound-source localization technology based on respiratory monitoring. The proposed technique can facilitate detection when advanced imaging tools are not immediately available. Continuing effort on the development of more precise estimation is warranted.
1501,Methods for Feature Selection in Down-Selection of Vaccine Regimens Based on Multivariate Immune Response Endpoints,"In clinical trials, it is often of interest to compare and order several candidate regimens based on multiple endpoints. For example, in HIV vaccine development, immune response profiles induced by vaccination are key for selecting vaccine regimens to advance to efficacy evaluation. Motivated by the need to rank and choose a few vaccine regimens based on their immunogenicity in phase I trials, Huang et al. (Biostatistics 18(2):230–243, 2017) proposed a ranking/filtering/selection algorithm that down-selects vaccine regimens to satisfy the superiority and non-redundancy criteria, based on multiple immune response endpoints. In practice, many candidate immune response endpoints can be correlated with each other. An important question that remains to be addressed is how to choose a parsimonious set of the available immune response endpoints to effectively compare regimens. In this paper, we propose novel algorithms for selecting immune response endpoints to be used in regimen down-selection, based on importance weights assigned to individual endpoints and their correlation structure. We show through extensive simulation studies that pre-selection of endpoints can substantially improve performance of the subsequent regimen down-selection process. The application of the proposed method is demonstrated using a real example in HIV vaccine research, although the methods are also applicable in general to clinical research for dimension reduction when comparing regimens based on multiple candidate endpoints. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12561-020-09275-2) contains supplementary material, which is available to authorized users."
1502,Elimination of Staphylococcus aureus nasal carriage in intensive care patients lowers infection rates,"This study surveys the clinical relevance of the nasal Staphylococcus aureus colonization status on intensive care unit (ICU)–acquired S. aureus infections and compares molecular characteristics of isolates from the nose and infectious sites. The 390 patients included comprised 278 non-carriers and 112 carriers. Among the carriers, 56 were decolonized with mupirocin. Decolonization was verified through a second (negative) culture. Spa typing and virulence gene profiling were performed for all isolates. Twenty six S. aureus infections were detected in the carriage group and 20 in the non-carriage group. Eighteen of these 26 (69.2%) infections were among carriers, and 8 of these 26 (30.8%) infections occurred among decolonized carriers (p = 0.02). Overall, 31/112 (27.7%) of the colonized patients and 25/46 (60.1%) of infection were due to methicillin-resistant S. aureus (MRSA). The highest frequency virulence genes were sea and hlg (both 100%) in nasal isolates and sea, hlg, fnb, and clf (100%) for infectious isolates. t030 was the most abundant spa type overall. S. aureus carriers were more likely to develop S. aureus infection compared with decolonized and non-carrying patients. The sources of ICU S. aureus infection appear to be exogenous mostly, and a predominant clone (spa type 030) plays an important role. We confirm that nasal mupirocin treatment prevents ICU infections even when there is an increased prevalence of nosocomial MRSA."
1503,The artificial kidney induces acute kidney injury: yes,
1504,"New Developments in Bacterial, Viral, and Fungal Cutaneous Infections","PURPOSE OF REVIEW: This review highlights clinically relevant updates to common and significant bacterial, viral, and fungal cutaneous infection within the past 5 years. Recent developments are presented so that the clinician may provide evidence-based, high-quality patient care. RECENT FINDINGS: New resistance patterns in cutaneous pathogens have recently emerged as a result of inappropriate antimicrobial use. Several new FDA-approved antimicrobials have been approved to treat such infections, including multi-drug resistant pathogens. Several organizational guidelines for cutaneous infection management have been updated with new recommendations for screening, diagnostic, and treatment strategies. SUMMARY: Clinicians should be aware of the most recent evidence and guidelines for the management of cutaneous infections in order to reduce the emergence of antimicrobial resistance and most effectively treat their patients."
1505,‘I’m sorry to hear that’—Empathy and Empathic Dissonance: the Perspectives of PA Students,"CONTEXT: Our understanding of clinical empathy could be enhanced through qualitative research—research currently under-represented in the field. Physician associates within the UK undergo an intensive 2-year postgraduate medical education. As a new group of health professionals, they represent a fresh pair of eyes through which to examine clinical empathy, its nature and teaching. METHODS: Working with a constructivist paradigm, utilising grounded theory methodology, researchers studied 19 purposively sampled physician associate students in two UK medical schools. One-to-one semi-structured interviews were transcribed verbatim. Data were analysed using a grounded theory approach. RESULTS: The global themes were the pathways to empathy, empathy modifiers and empathic dissonance a novel term to describe the discomfort students experience when pressurised into making empathic statements they don’t sincerely feel. Students preferred using non-verbal over verbal expressions of empathy. A conceptual model is proposed. The more substantial empathic pathway, affective empathy, involves input from the heart. An alternative empathy, more constrained, comes from the head: cognitive empathy was considered a solution to time pressure and emotional burden. Formal teaching establishes empathic dissonance, a problem which stems from over-reliance on the empathic statement as the means to deliver clinical empathy. CONCLUSIONS: This study furthers our understanding of the construct and teaching of empathy. It identifies empathic barriers, especially time pressure. It proposes a novel concept—empathic dissonance—a concept that challenges medical educationalists to reframe future empathy teaching."
1506,Melittin: a venom-derived peptide with promising anti-viral properties,"Despite tremendous advances in the development of anti-viral therapeutics, viral infections remain a chief culprit accounting for ongoing morbidity and mortality worldwide. Natural products, in particular animal venoms, embody a veritable cornucopia of exotic constituents, suggesting an immensurable source of anti-infective drugs. In this context, melittin, the principal constituent in the venom of the European honeybee Apis mellifera, has been demonstrated to exert anti-cancer, anti-inflammatory, anti-diabetic, anti-infective, and adjuvant properties. To our knowledge, there is no review appertaining to effects of melittin against viruses, prompting us to synopsize experimental investigations on its anti-viral activity throughout the past decades. Accumulating evidence indicates that melittin curbs infectivity of a diverse array of viruses including coxsackievirus, enterovirus, influenza A viruses, human immunodeficiency virus (HIV), herpes simplex virus (HSV), Junín virus (JV), respiratory syncytial virus (RSV), vesicular stomatitis virus (VSV), and tobacco mosaic virus (TMV). However, medication safety, different routes of administrations, and molecular mechanisms behind the anti-viral activity of melittin should be scrutinized in future studies."
1507,Effect of the “Recruitment” Maneuver on Respiratory Mechanics in Laparoscopic Sleeve Gastrectomy Surgery,"PURPOSE: LSG surgery is used for surgical treatment of morbid obesity. Obesity, anesthesia, and pneumoperitoneum cause reduced pulmoner functions and a tendency for atelectasis. The alveolar “recruitment” maneuver (RM) keeps airway pressure high, opening alveoli, and increasing arterial oxygenation. The aim of our study is to research the effect on respiratory mechanics and arterial blood gases of performing the RM in LSG surgery. MATERIALS AND METHODS: Sixty patients undergoing LSG surgery were divided into two groups (n = 30) Patients in group R had the RM performed 5 min after desufflation with 100% oxygen, 40 cmH(2)O pressure for 40 s. Group C had standard mechanical ventilation. Assessments of respiratory mechanics and arterial blood gases were made in the 10th min after induction (T1), 10th min after insufflation (T2), 5th min after desufflation (T3), and 15th min after desufflation (T4). Arterial blood gases were assessed in the 30th min (T5) in the postoperative recovery unit. RESULTS: In group R, values at T5, PaO(2) were significantly high, while PaCO(2) were significantly low compared with group C. Compliance in both groups reduced with pneumoperitoneum. At T4, the compliance in the recruitment group was higher. In both groups, there was an increase in PIP with pneumoperitoneum and after desufflation this was identified to reduce to levels before pneumoperitoneum. CONCLUSION: Adding the RM to PEEP administration for morbidly obese patients undergoing LSG surgery is considered to be effective in improving respiratory mechanics and arterial blood gas values and can be used safely."
1508,Measuring lung mechanics of expiratory tidal breathing with non-invasive breath occlusion,"BACKGROUND AND OBJECTIVE: Lung mechanics measurements provide clinically useful information about disease progression and lung health. Currently, there are no commonly practiced methods to non-invasively measure both resistive and elastic lung mechanics during tidal breathing, preventing the important information provided by lung mechanics from being utilised. This study presents a novel method to easily assess lung mechanics of spontaneously breathing subjects using a dynamic elastance, single-compartment lung model. METHODS: A spirometer with a built-in shutter was used to occlude expiration during tidal breathing, creating exponentially decaying flow when the shutter re-opened. The lung mechanics measured were respiratory system elastance and resistance, separated from the exponentially decaying flow, and interrupter resistance calculated at shutter closure. Progressively increasing resistance was added to the spirometer mouthpiece to simulate upper airway obstruction. The lung mechanics of 17 healthy subjects were successfully measured through spirometry. RESULTS: N = 17 (8 female, 9 male) healthy subjects were recruited. Measured decay rates ranged from 5 to 42/s, subjects with large variation of decay rates showed higher muscular breathing effort. Lung elastance measurements ranged from 3.9 to 21.2 cmH[Formula: see text] O/L, with no clear trend between change in elastance and added resistance. Resistance calculated from decay rate and elastance ranged from 0.15 to 1.95 cmH[Formula: see text] Os/L. These very small resistance values are due to the airflow measured originating from low-resistance areas in the centre of airways. Occlusion resistance measurements were as expected for healthy subjects, and increased as expected as resistance was added. CONCLUSIONS: This test was able to identify reasonable dynamic lung elastance and occlusion resistance values, providing new insight into expiratory breathing effort. Clinically, this lung function test could impact current practice. It does not require high levels of cooperation from the subject, allowing a wider cohort of patients to be assessed more easily. Additionally, this test can be simply implemented in a small standalone device, or with standard lung function testing equipment."
1509,A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease,"In chronic-phase chronic myeloid leukaemia (CP-CML), residual BCR-ABL1+ leukaemia stem cells are responsible for disease persistence despite TKI. Based on in vitro data, CHOICES (CHlorOquine and Imatinib Combination to Eliminate Stem cells) was an international, randomised phase II trial designed to study the safety and efficacy of imatinib (IM) and hydroxychloroquine (HCQ) compared with IM alone in CP-CML patients in major cytogenetic remission with residual disease detectable by qPCR. Sixty-two patients were randomly assigned to either arm. Treatment ‘successes’ was the primary end point, defined as ≥0.5 log reduction in 12-month qPCR level from trial entry. Selected secondary study end points were 24-month treatment ‘successes’, molecular response and progression at 12 and 24 months, comparison of IM levels, and achievement of blood HCQ levels >2000 ng/ml. At 12 months, there was no difference in ‘success’ rate (p = 0.58); MMR was achieved in 80% (IM) vs 92% (IM/HCQ) (p = 0.21). At 24 months, the ‘success’ rate was 20.8% higher with IM/HCQ (p = 0.059). No patients progressed. Seventeen serious adverse events, including four serious adverse reactions, were reported; diarrhoea occurred more frequently with combination. IM/HCQ is tolerable in CP-CML, with modest improvement in qPCR levels at 12 and 24 months, suggesting autophagy inhibition maybe of clinical value in CP-CML."
1510,Protective cellular immune response against hepatitis C virus elicited by chimeric protein formulations in BALB/c mice,"The eradication of hepatitis C virus (HCV) infection is a public health priority. Despite the efficiency of treatment with direct-acting antivirals, the high cost of the therapy and the lack of accurate data about the HCV-infected population worldwide constitute important factors hampering this task. Hence, an affordable preventive vaccine is still necessary for reducing transmission and the future disease burden globally. In this work, chimeric proteins (EnvCNS3 and NS3EnvCo) encompassing conserved and immunogenic epitopes from the HCV core, E1, E2 and NS3 proteins were produced in Escherichia coli, and their immunogenicity was evaluated in BALB/c mice. The impact of recombinant HCV E2.680 protein and oligodeoxynucleotide 39M (ODN39M) on the immune response to chimeric proteins was also assessed. Immunization with chimeric proteins mixed with E2.680 enhanced the antibody and cellular response against HCV antigens and chimeric proteins. Interestingly, the combination of NS3EnvCo with E2.680 and ODN39M as adjuvant elicited a potent antibody response characterized by an increase in antibodies of the IgG2a subclass against E2.680, NS3 and chimeric proteins, suggesting the induction of a Th1-type response. Moreover, a cytotoxic T lymphocyte response and a broad response of IFN-γ-secreting cells against HCV antigens were induced with this formulation as well. This T cell response was able to protect vaccinated mice against challenge with a surrogate model based on HCV recombinant vaccinia virus. Overall, the vaccine candidate NS3EnvCo/E2.680/ODN39M might constitute an effective immunogen against HCV with potential for reducing the likelihood of viral persistence."
1511,Medical Ethics in Extreme and Austere Environments,"American society has a history of turning to physicians during times of extreme need, from plagues in the past to recent outbreaks of communicable diseases. This public instinct comes from a deep seated trust in physician duty that has been earned over the centuries through dedicated and selfless care, often in the face of personal risks. As dangers facing our communities include terroristic events physicians must be adequately prepared to respond, both medically and ethically. While the ethical principles that govern physician behavior—beneficence, nonmaleficence, autonomy, and social justice—are unchanging, fundamental doctrines must change with the new risks inherent to terroristic events. Responding to mass casualty disasters caused by terrorists, natural calamities, and combat continue to be challenging frontiers in medicine. Preparing physicians to deal with the consequences of a terroristic disease must include understanding the ethical challenges that can occur."
1512,Megaprosthesis in distal femur nonunions in elderly patients—experience from twenty four cases,"PURPOSE OF THE STUDY: To evaluate the outcomes and complications using cemented megaprosthesis in elderly patients with distal femur nonunions (DFN). MATERIALS AND METHODS: Between 2012 and 2016, 24 patients of DFN with an average age of 71.8 years (66–83) and an average 1.9(1–3) prior surgery was managed with distal femur replacement using cemented modular endoprosthesis. Outcomes were analysed on the following criteria: implant status, complications, knee range of motion, Knee Society Score (KSS) and Musculoskeletal Tumor Society (MSTS) score. RESULTS: All patients were extremely satisfied with their outcomes. At an average 22.1 months (10–43) follow-up, patients had an average 69.5° (40°-110°) knee flexion, an average KSS of 75.7 (63–88) and an average MSTS score of 19.3 (17–25). Four patients died at an average 21.3 months after surgery due to causes unrelated to the fracture. One patient (4.1%) had implant-related complication; deep infection which required debridement and intravenous antibiotics. There were no late amputations or peri-operative deaths and no patient had aseptic loosening of components. CONCLUSION: By permitting immediate full weight-bearing ambulation and with most patients returning to an acceptable functional status, cemented megaprosthesis is a viable and useful single-stage management option in elderly patients with DFN."
1513,The Spectrophotometric Characteristic of Immunoglobulin Conjugates for Diagnostics of Causative Agents of Especially Dangerous Infections,The possibility of characterizing fluorescent immunoglobulins using spectrophotometric analysis as a testing method is considered. The comparative analysis of optical properties of fluorescent immunoglobulin preparations and their components—immunoglobulins and fluorochrome—is carried out. The obtained results testify that the proposed methodological approach of optical detection of labeled immunoglobulin molecules can be promising for tests on obtaining conjugates used in immunological tests on revealing specific antigens of causative agents of especially dangerous infections.
1514,Practical approach to respiratory emergencies in neurological diseases,"Many neurological diseases may cause acute respiratory failure (ARF) due to involvement of bulbar respiratory center, spinal cord, motoneurons, peripheral nerves, neuromuscular junction, or skeletal muscles. In this context, respiratory emergencies are often a challenge at home, in a neurology ward, or even in an intensive care unit, influencing morbidity and mortality. More commonly, patients develop primarily ventilatory impairment causing hypercapnia. Moreover, inadequate bulbar and expiratory muscle function may cause retained secretions, frequently complicated by pneumonia, atelectasis, and, ultimately, hypoxemic ARF. On the basis of the clinical onset, two main categories of ARF can be identified: (i) acute exacerbation of chronic respiratory failure, which is common in slowly progressive neurological diseases, such as movement disorders and most neuromuscular diseases, and (ii) sudden-onset respiratory failure which may develop in rapidly progressive neurological disorders including stroke, convulsive status epilepticus, traumatic brain injury, spinal cord injury, phrenic neuropathy, myasthenia gravis, and Guillain–Barré syndrome. A tailored assistance may include manual and mechanical cough assistance, noninvasive ventilation, endotracheal intubation, invasive mechanical ventilation, or tracheotomy. This review provides practical recommendations for prevention, recognition, management, and treatment of respiratory emergencies in neurological diseases, mostly in teenagers and adults, according to type and severity of baseline disease."
1515,Cyclosporine A prevents cardiac arrest-induced acute respiratory failure: a post-hoc analysis of the CYRUS trial,
1516,Contemporary strategies to improve clinical trial design for critical care research: insights from the First Critical Care Clinical Trialists Workshop,"BACKGROUND: Conducting research in critically-ill patient populations is challenging, and most randomized trials of critically-ill patients have not achieved pre-specified statistical thresholds to conclude that the intervention being investigated was beneficial. METHODS: In 2019, a diverse group of patient representatives, regulators from the USA and European Union, federal grant managers, industry representatives, clinical trialists, epidemiologists, and clinicians convened the First Critical Care Clinical Trialists (3CT) Workshop to discuss challenges and opportunities in conducting and assessing critical care trials. Herein, we present the advantages and disadvantages of available methodologies for clinical trial design, conduct, and analysis, and a series of recommendations to potentially improve future trials in critical care. CONCLUSION: The 3CT Workshop participants identified opportunities to improve critical care trials using strategies to optimize sample size calculations, account for patient and disease heterogeneity, increase the efficiency of trial conduct, maximize the use of trial data, and to refine and standardize the collection of patient-centered and patient-informed outcome measures beyond mortality. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-05934-6) contains supplementary material, which is available to authorized users."
1517,Burn injury,"Burn injuries are under-appreciated injuries that are associated with substantial morbidity and mortality. Burn injuries, particularly severe burns, are accompanied by an immune and inflammatory response, metabolic changes and distributive shock that can be challenging to manage and can lead to multiple organ failure. Of great importance is that the injury affects not only the physical health, but also the mental health and quality of life of the patient. Accordingly, patients with burn injury cannot be considered recovered when the wounds have healed; instead, burn injury leads to long-term profound alterations that must be addressed to optimize quality of life. Burn care providers are, therefore, faced with a plethora of challenges including acute and critical care management, long-term care and rehabilitation. The aim of this Primer is not only to give an overview and update about burn care, but also to raise awareness of the ongoing challenges and stigmata associated with burn injuries."
1518,Comparison of Conventional Intensive Care Scoring Systems and Prognostic Scores Specific for Intracerebral Hemorrhage in Predicting One-Year Mortality,"BACKGROUND: Specific prognostic models for intracerebral hemorrhage (ICH) have short and simple features, whereas intensive care unit (ICU) severity scales include more complicated parameters. Even though newly developed ICU severity scales have disease-specific properties, they still lack radiologic parameters, which is crucial for ICH. AIMS: To compare the performance of the Simplified Acute Physiology Score (SAPS) III, Acute Physiology and Chronic Health Evaluation (APACHE) IV, Logistic Organ Dysfunction Score (LODS), ICH, max-ICH, ICH functional outcome score (ICH-FOS), and Essen-ICH for prediction of in-hospital and one-year mortality of patients with ICH. METHODS: A single-center analysis of 137 patients with ICH was conducted over 5 years. The performance of scoring systems was evaluated with receiver operating characteristic analysis. The independent predictors of one-year mortality were investigated with a multivariate logistic regression analysis. The SAPS-III score was calculated both in the emergency department (ED) and ICU. RESULTS: Among the independent variables, the need for mechanical ventilation, hematoma volume, the presence of intraventricular hemorrhage, and hematoma originating from both lobar and nonlobar regions were found as the strongest predictor of one-year mortality. For in-hospital mortality, the discriminative power of SAPS-II, APACHE-IV, and LODS was excellent, and for SAPS-III-ICU and SAPS-III-ED, it was good. For one-year mortality, the discriminative power of SAPS-II, APACHE-IV, LODS, and SAPS-III-ICU was good, and for SAPS-III-ED, Essen-ICH, ICH, max-ICH, and ICH-FOS, it was fair. CONCLUSIONS: Although all three ICH-specific prognostic scales performed satisfactory results for predicting one-year mortality, the common intensive care severity scoring showed better performance. SAPS-III scores may be recommended for use in EDs after proper customization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-020-00987-3) contains supplementary material, which is available to authorized users."
1519,Male gender is an independent risk factor for patients undergoing laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass: an MBSAQIP® database analysis,"BACKGROUND: Male patients undergoing bariatric surgery have (historically) been considered higher risk than females. The aim of this study was to examine the disparity between genders undergoing laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) procedures and assess gender as an independent risk factor. METHODS: The MBSAQIP® Data Registry Participant User Files for 2015–2017 was reviewed for patients having primary SG and RYGB. Patients were divided into groups based on gender and procedure. Variables for major complications were grouped together, including but not limited to PE, stroke, and MI. Univariate and propensity matching analyses were performed. RESULTS: Of 429,664 cases, 20.58% were male. Univariate analysis demonstrated males were older (46.48 ± 11.96 vs. 43.71 ± 11.89 years, p < 0.0001), had higher BMI (46.58 ± 8.46 vs. 45.05 ± 7.75 kg/m(2), p < 0.0001), and had higher incidence of comorbidities. Males had higher rates of major complications (1.72 vs. 1.05%; p < 0.0001) and 30-day mortality (0.18 vs. 0.07%, p < 0.0001). Significance was maintained after subgroup analysis of SG and RYGB. Propensity matched analysis demonstrated male gender was an independent risk factor for RYGB and SG, major complications [2.21 vs. 1.7%, p < 0.0001 (RYGB), 1.12 vs. 0.89%, p < 0.0001 (SG)], and mortality [0.23 vs. 0.12%, p < 0.0001 (RYGB), 0.10 vs. 0.05%; p < 0.0001 (SG)]. CONCLUSION: Males continue to represent a disproportionately small percentage of bariatric surgery patients despite having no difference in obesity rates compared to females. Male gender is an independent risk factor for major post-operative complications and 30-day mortality, even after controlling for comorbidities."
1520,"Design, synthesis and evaluation of 3-hydroxypyridin-4-ones as inhibitors of catechol-O-methyltransferase","ABSTRACT: The most effective treatment of Parkinson’s disease is restoring central dopamine levels with levodopa, the metabolic precursor of dopamine. However, due to extensive peripheral metabolism by aromatic l-amino acid decarboxylase and catechol-O-methyltransferase (COMT), only a fraction of the levodopa dose reaches the brain unchanged. Thus, by preventing levodopa metabolism and increasing the availability of levodopa for uptake into the brain, the inhibition of COMT would be beneficial in Parkinson’s disease. Although nitrocatechol COMT inhibitors have been used in the treatment of Parkinson’s disease, efforts have been made to discover non-nitrocatechol inhibitors. In the present study, the 3-hydroxypyridin-4-one scaffold was selected for the design and synthesis of non-nitrocatechol COMT inhibitors since the COMT inhibitory potential of this class has been illustrated. Using COMT obtained from porcine liver, it was shown that a synthetic series of ten 3-hydroxypyridin-4-ones are in vitro inhibitors with IC(50) values ranging from 4.55 to 19.8 µM. Although these compounds are not highly potent inhibitors, they may act as leads for the development of non-nitrocatechol COMT inhibitors. Such compounds would be appropriate for the treatment of Parkinson’s disease. GRAPHIC ABSTRACT: 3-Hydroxypyridin-4-ones have been synthesised and evaluated as non-nitrocatechol COMT inhibitors. In vitro, the IC(50) values ranged from 4.55 to 19.8 μM. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11030-020-10053-x) contains supplementary material, which is available to authorized users."
1521,"The immunology of other mycobacteria: M. ulcerans, M. leprae","Mycobacterial pathogens can be categorized into three broad groups: Mycobacterium tuberculosis complex causing tuberculosis, M. leprae and M. lepromatosis causing leprosy, and atypical mycobacteria, or non-tuberculous mycobacteria (NTM), responsible for a wide range of diseases. Among the NTMs, M. ulcerans is responsible for the neglected tropical skin disease Buruli ulcer (BU). Most pathogenic mycobacteria, including M. leprae, evade effector mechanisms of the humoral immune system by hiding and replicating inside host cells and are furthermore excellent modulators of host immune responses. In contrast, M. ulcerans replicates predominantly extracellularly, sheltered from host immune responses through the cytotoxic and immunosuppressive effects of mycolactone, a macrolide produced by the bacteria. In the year 2018, 208,613 new cases of leprosy and 2713 new cases of BU were reported to WHO, figures which are notoriously skewed by vast underreporting of these diseases."
1522,Antimicrobial de-escalation as part of antimicrobial stewardship in intensive care: no simple answers to simple questions—a viewpoint of experts,"Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more components of combination empirical therapy, and/or the change from a broad-spectrum to a narrower spectrum antimicrobial. It is most commonly recommended in the intensive care unit (ICU) patient who is treated with broad-spectrum antibiotics as a strategy to reduce antimicrobial pressure of empirical broad-spectrum therapy and prevent antimicrobial resistance, yet this has not been convincingly demonstrated in a clinical setting. Even if it appears beneficial, ADE may have some unwanted side effects: it has been associated with prolongation of antimicrobial therapy and could inappropriately be used as a justification for unrestricted broadness of empirical therapy. Also, exposing a patient to multiple, sequential antimicrobials could have unwanted effects on the microbiome. For these reasons, ADE has important shortcomings to be promoted as a quality indicator for appropriate antimicrobial use in the ICU. Despite this, ADE clearly has a role in the management of infections in the ICU. The most appropriate use of ADE is in patients with microbiologically confirmed infections requiring longer antimicrobial therapy. ADE should be used as an integral part of an ICU antimicrobial stewardship approach in which it is guided by optimal specimen quality and relevance. Rapid diagnostics may further assist in avoiding unnecessary initiation of broad-spectrum therapy, which in turn will decrease the need for subsequent ADE."
1523,Preoperative miRNA-208a as a Predictor of Postoperative Complications in Children with Congenital Heart Disease Undergoing Heart Surgery,Major perioperative cardiovascular events are important causes of morbidity in pediatric patients with congenital heart disease who undergo reparative surgery. Current preoperative clinical risk assessment strategies have poor accuracy for identifying patients who will sustain adverse events following heart surgery. There is an ongoing need to integrate clinical variables with novel technology and biomarkers to accurately predict outcome following pediatric heart surgery. We tested whether preoperative levels of miRNAs-208a can serve as such a biomarker. Serum samples were obtained from pediatric patients immediately before heart surgery. MiRNA-208a was quantified by RQ-PCR. Correlations between the patient’s clinical variables and miRNA levels were tested. Lower levels of preoperative miRNA-208a correlated with and could predict the appearance of postoperative cardiac and inflammatory complications. MiRNA-208a may serve as a biomarker for the prediction of patients who are at risk to develop complications following surgery for the repair of congenital heart defects.
1524,Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model,"Acute lung injury is an inflammatory condition developed after severe sepsis in response to excessive secretion of pro-inflammatory cytokines. Doxycycline is widely reported to possess immunomodulatory activity through inhibition of various inflammatory pathways. Considering the broad spectrum of anti-inflammatory activity, protective effect of doxycycline was evaluated in clinically relevant murine polymicrobial sepsis model induced by caecal ligation and puncture (CLP). In this model, sepsis is accompanied with infection and therefore ceftriaxone at sub-protective dose was combined to retard the bacterial growth. Three hours after CLP challenge, mice were administered vehicle, ceftriaxone (100 mg/kg subcutaneously) alone and in combination with immunomodulatory dose of doxycycline (50 mg/kg, intraperitoneal) and survival were monitored for 5 days. Bacterial count in blood and peritoneal fluid along with cytokines [interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α] and myeloperoxidase (MPO) in plasma and lung homogenate were measured at 18 h post-CLP. Plasma glutathione (GSH) was also determined. Doxycycline in presence of ceftriaxone improved survival of septic mice by significantly reducing the plasma and lung pro-inflammatory cytokines and MPO levels. It also increased plasma GSH levels. Doxycycline did not improve antibacterial effect of ceftriaxone in combination, suggesting that the protective effect of doxycycline was due to its immunomodulatory activity. Doxycycline in the presence of ceftriaxone demonstrated improved survival of septic mice by modulating the immune response."
1525,Development of a measure of stigma towards occupational stress for mental health professionals,"PURPOSE: Stigma is a common barrier to mental health professionals (MHPs) seeking help for occupational stress and burnout, although there is a lack of psychometrically sound tools to measure this construct. The current study aimed to develop and validate a scale (the Mental Health Professional Stigma Scale; MHPSS) for this purpose. METHODS: The MHPSS and related measures were completed by 221 Australian MHPs via online survey, with a subsample completing the MHPSS again 2 weeks after initial completion. RESULTS: Exploratory factor analysis revealed a four-factor solution, comprising of 13 items and accounting for 50.16% of variance. Factors were Perceived Other Stigma, Perceived Structural Stigma, Personal Stigma, and Self stigma. The internal consistency, test–retest reliability, and validity of the scale were supported. CONCLUSIONS: The MHPSS has utility to capture stigmatising attitudes and beliefs related to occupational stress and burnout among MHPs. It may be used to assist in the development and evaluation of initiatives to reduce stigma and increase help-seeking among MHPs."
1526,"Tidal Volume Lowering by Instrumental Dead Space Reduction in Brain-Injured ARDS Patients: Effects on Respiratory Mechanics, Gas Exchange, and Cerebral Hemodynamics","BACKGROUND: Limiting tidal volume (V(T)), plateau pressure, and driving pressure is essential during the acute respiratory distress syndrome (ARDS), but may be challenging when brain injury coexists due to the risk of hypercapnia. Because lowering dead space enhances CO(2) clearance, we conducted a study to determine whether and to what extent replacing heat and moisture exchangers (HME) with heated humidifiers (HH) facilitate safe V(T) lowering in brain-injured patients with ARDS. METHODS: Brain-injured patients (head trauma or spontaneous cerebral hemorrhage with Glasgow Coma Scale at admission < 9) with mild and moderate ARDS received three ventilatory strategies in a sequential order during continuous paralysis: (1) HME with V(T) to obtain a PaCO(2) within 30–35 mmHg (HME1); (2) HH with V(T) titrated to obtain the same PaCO(2) (HH); and (3) HME1 settings resumed (HME2). Arterial blood gases, static and quasi-static respiratory mechanics, alveolar recruitment by multiple pressure–volume curves, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and mean flow velocity in the middle cerebral artery by transcranial Doppler were recorded. Dead space was measured and partitioned by volumetric capnography. RESULTS: Eighteen brain-injured patients were studied: 7 (39%) had mild and 11 (61%) had moderate ARDS. At inclusion, median [interquartile range] PaO(2)/FiO(2) was 173 [146–213] and median PEEP was 8 cmH(2)O [5–9]. HH allowed to reduce V(T) by 120 ml [95% CI: 98–144], V(T)/kg predicted body weight by 1.8 ml/kg [95% CI: 1.5–2.1], plateau pressure and driving pressure by 3.7 cmH(2)O [2.9–4.3], without affecting PaCO(2), alveolar recruitment, and oxygenation. This was permitted by lower airway (− 84 ml [95% CI: − 79 to − 89]) and total dead space (− 86 ml [95% CI: − 73 to − 98]). Sixteen patients (89%) showed driving pressure equal or lower than 14 cmH(2)O while on HH, as compared to 7 (39%) and 8 (44%) during HME1 and HME2 (p < 0.001). No changes in mean arterial pressure, cerebral perfusion pressure, intracranial pressure, and middle cerebral artery mean flow velocity were documented during HH. CONCLUSION: The dead space reduction provided by HH allows to safely reduce V(T) without modifying PaCO(2) nor cerebral perfusion. This permits to provide a wider proportion of brain-injured ARDS patients with less injurious ventilation."
1527,Small steps forward for HIV vaccine development,"A trial of a therapeutic vaccine against HIV induces cellular immunity and, although it provides hope, it highlights the hurdles for the development of such strategies."
1528,The role of physical exercise and rehabilitation in delirium,"PURPOSE: This article aims to analyze the intersections between delirium, physical exercise and rehabilitation, to better understand their interrelation and to visualize future lines of research. METHODS: In this narrative review, after an overview of brain neurophysiology and function, as common substrates to understand the relationship between delirium and physical function, we explore the scientific evidence in: (1) physical dysfunction as a risk factor for delirium; (2) physical dysfunction as a symptom of delirium and (3) functional consequences related to delirium. Later, we analyze the physical therapy as one of the main strategies in multicomponent interventions to prevent delirium, by examining intervention studies including rehabilitation, which have shown to be effective in managing delirium. Finally, we analyze how frailty, delirium and physical exercise interact with each other. RESULTS: This review confirms the close relationship between delirium and physical dysfunction; therefore, it is not surprising that physical exercise is widely used in delirium preventive strategies. Although delirium is catalogued as a neurocognitive disorder, scientific evidence shows that it is also a motor disorder, which is to be expected, since a vast body of literature already supports an interaction between motor and cognitive function. CONCLUSION: The motor component of delirium should be taken into account when designing interventions or strategies to address delirium. These interventions may have a special importance in frail older adults."
1529,Infektionsschutzrecht nach Inkrafttreten des Masernschutzgesetzes,
1530,ICU-acquired weakness,"Critically ill patients often acquire neuropathy and/or myopathy labeled ICU-acquired weakness. The current insights into incidence, pathophysiology, diagnostic tools, risk factors, short- and long-term consequences and management of ICU-acquired weakness are narratively reviewed. PubMed was searched for combinations of “neuropathy”, “myopathy”, “neuromyopathy”, or “weakness” with “critical illness”, “critically ill”, “ICU”, “PICU”, “sepsis” or “burn”. ICU-acquired weakness affects limb and respiratory muscles with a widely varying prevalence depending on the study population. Pathophysiology remains incompletely understood but comprises complex structural/functional alterations within myofibers and neurons. Clinical and electrophysiological tools are used for diagnosis, each with advantages and limitations. Risk factors include age, weight, comorbidities, illness severity, organ failure, exposure to drugs negatively affecting myofibers and neurons, immobility and other intensive care-related factors. ICU-acquired weakness increases risk of in-ICU, in-hospital and long-term mortality, duration of mechanical ventilation and of hospitalization and augments healthcare-related costs, increases likelihood of prolonged care in rehabilitation centers and reduces physical function and quality of life in the long term. RCTs have shown preventive impact of avoiding hyperglycemia, of omitting early parenteral nutrition use and of minimizing sedation. Results of studies investigating the impact of early mobilization, neuromuscular electrical stimulation and of pharmacological interventions were inconsistent, with recent systematic reviews/meta-analyses revealing no or only low-quality evidence for benefit. ICU-acquired weakness predisposes to adverse short- and long-term outcomes. Only a few preventive, but no therapeutic, strategies exist. Further mechanistic research is needed to identify new targets for interventions to be tested in adequately powered RCTs."
1531,Neuroprotective Role of Oral Vitamin D Supplementation on Consciousness and Inflammatory Biomarkers in Determining Severity Outcome in Acute Traumatic Brain Injury Patients: A Double-Blind Randomized Clinical Trial,"BACKGROUND AND OBJECTIVE: Early management of traumatic brain injury (TBI) is essential. We aimed to evaluate the efficacy of vitamin D over early clinical outcome and serum cytokine levels in patients with moderate to severe brain injury. METHODS: Thirty-five patients with moderate to severe traumatic brain injury who were admitted to the ICU unit were recruited into the study. Subjects were randomly allocated to a treatment regimen comprising either a one-time oral dose of 120,000 IU (two tablets of 60,000 IU each) of vitamin D (n = 20) or 8 mg of saccharide (two tablets of 4 g each) as placebo (n = 15). The main parameters evaluated included duration of mechanical ventilation and ICU stay, Glasgow Coma Scale (GCS) and cytokine levels (interleukin (IL)-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, IL-2). RESULTS: The results indicated an improvement in the level of consciousness after 7 days in the vitamin D-treated group compared with placebo. An elevation in GCS score by 3.86 units in the vitamin D-treated group with a 0.19-unit descent in the control group was recorded. Duration of mechanical ventilation was reduced in the vitamin D-treated group compared with the control group (4.7 days vs. 8.2 days, p value 0.0001). A noticeable reduction was recorded in inflammatory biomarkers (cytokines) in the vitamin D-treated group (IL-6 p = 0.08, TNF-α p = 0.02, IL-2 p = 0.36) with notable elevation in IFN-γ (p = 0.65) compared to the control group. CONCLUSION: In the acute phase of moderate to severe traumatic brain injury, vitamin D supplementation plays a vital role and has a favourable effect on the consciousness level of patients. Clinical trial Registry (CTRI) No. CTRI/2019/05/019259."
1532,"Respiratory drive in the acute respiratory distress syndrome: pathophysiology, monitoring, and therapeutic interventions","Neural respiratory drive, i.e., the activity of respiratory centres controlling breathing, is an overlooked physiologic variable which affects the pathophysiology and the clinical outcome of acute respiratory distress syndrome (ARDS). Spontaneous breathing may offer multiple physiologic benefits in these patients, including decreased need for sedation, preserved diaphragm activity and improved cardiovascular function. However, excessive effort to breathe due to high respiratory drive may lead to patient self-inflicted lung injury (P-SILI), even in the absence of mechanical ventilation. In the present review, we focus on the physiological and clinical implications of control of respiratory drive in ARDS patients. We summarize the main determinants of neural respiratory drive and the mechanisms involved in its potentiation, in health and ARDS. We also describe potential and pitfalls of the available bedside methods for drive assessment and explore classical and more “futuristic” interventions to control drive in ARDS patients."
1533,Dengue vaccine development: status and future,"Dengue, the most common arbovirus, represents an increasingly significant cause of morbidity worldwide, including in travelers. After decades of research, the first dengue vaccine was licensed in 2015: CYD-TDV, a tetravalent live attenuated vaccine with a yellow fever vaccine backbone. Recent analyses have shown that vaccine performance is dependent on serostatus. In those who have had a previous dengue infection, i.e., who are seropositive, the efficacy is high and the vaccine is safe. However, in seronegative vaccinees, approximately 3 years after vaccination the vaccine increases the risk of developing severe dengue when the individual experiences a natural dengue infection. The World Health Organization recommends that this vaccine be administered only to seropositive individuals. Current efforts are underway to develop rapid diagnostic tests to facilitate prevaccination screening. Two second-generation dengue vaccine candidates, both also live attenuated recombinant vaccines in late-stage development, may not present the same limitations because of differences in the backbone used, but results of phase 3 trials need to be available before firm conclusions can be drawn. Dengue is increasingly frequent in travelers, but the only licensed dengue vaccine to date can be used only in seropositive individuals. However, the vast majority of travelers are seronegative. Furthermore, the primary series of three doses given 6 months apart renders this vaccine difficult in the travel medicine context."
1534,Ethics as a Non-technical Skill for Surgical Education in Sub-Saharan Africa,"BACKGROUND: In recent years, surgical education has increased its focus on the non-technical skills such as communication and interpersonal relationships while continuing to strive for technical excellence of procedures and patient care. An awareness of the ethical aspects of surgical practice that involve non-technical skills and judgment is of vital concern to surgical educators and encompasses disparate issues ranging from adequate supervision of trainees to surgical care access. METHODS: This bibliographical research effort seeks to report on ethical challenges from a sub-Saharan Africa (SSA) perspective as found in the peer-reviewed literature employing African Journals Online, Bioline, and other sources with African information as well as PubMed and PubMed Central. The principles of autonomy, non-maleficence, beneficence, and justice offer a framework for a study of issues including: access to care (socioeconomic issues and distance from health facilities); resource utilization and decision making based on availability and cost of resources, including ICU and terminal extubation; informed consent (both communication about reasonable expectations post-procedure and research participation); research ethics, including local projects and international collaboration; quality and safety including supervision of less experienced professionals; and those religious and cultural issues that may affect any ethical decision making. The religious and cultural environment receives attention because beliefs and traditions affect medical choices ranging from acceptance of procedures, amputations, to end-of-life decisions. RESULTS AND CONCLUSIONS: Ethics awareness and ethics education should be a vital component of non-technical skills training in surgical education and medical practice in SSA for trainees. Continuing professional development of faculty should include an awareness of ethical issues."
1535,Neurally adjusted ventilatory assist versus pressure support ventilation: a randomized controlled feasibility trial performed in patients at risk of prolonged mechanical ventilation,"BACKGROUND: The clinical effectiveness of neurally adjusted ventilatory assist (NAVA) has yet to be demonstrated, and preliminary studies are required. The study aim was to assess the feasibility of a randomized controlled trial (RCT) of NAVA versus pressure support ventilation (PSV) in critically ill adults at risk of prolonged mechanical ventilation (MV). METHODS: An open-label, parallel, feasibility RCT (n = 78) in four ICUs of one university-affiliated hospital. The primary outcome was mode adherence (percentage of time adherent to assigned mode), and protocol compliance (binary—≥ 65% mode adherence). Secondary exploratory outcomes included ventilator-free days (VFDs), sedation, and mortality. RESULTS: In the 72 participants who commenced weaning, median (95% CI) mode adherence was 83.1% (64.0–97.1%) and 100% (100–100%), and protocol compliance was 66.7% (50.3–80.0%) and 100% (89.0–100.0%) in the NAVA and PSV groups respectively. Secondary outcomes indicated more VFDs to D28 (median difference 3.0 days, 95% CI 0.0–11.0; p = 0.04) and fewer in-hospital deaths (relative risk 0.5, 95% CI 0.2–0.9; p = 0.032) for NAVA. Although overall sedation was similar, Richmond Agitation and Sedation Scale (RASS) scores were closer to zero in NAVA compared to PSV (p = 0.020). No significant differences were observed in duration of MV, ICU or hospital stay, or ICU, D28, and D90 mortality. CONCLUSIONS: This feasibility trial demonstrated good adherence to assigned ventilation mode and the ability to meet a priori protocol compliance criteria. Exploratory outcomes suggest some clinical benefit for NAVA compared to PSV. Clinical effectiveness trials of NAVA are potentially feasible and warranted. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01826890. Registered 9 April 2013."
1536,Focus on infection,
1537,Exploring the Experiences of Child Welfare-Focused Therapeutic Service Providers,"The importance of mental and behavioral health for child welfare clients is well-documented; yet, little is known about the challenges therapeutic service providers (TSPs) experience working in child welfare practice. To explore this topic, five focus groups were conducted with 40 TSPs in a contracted mental and behavioral health agency and data were analyzed following an inductive thematic process. Eleven primary challenges were identified, including the difficulty of navigating numerous involved parties, an overwhelmed work environment, legal intersections common to child welfare cases, unrealistic agency expectations, and heighten case complexity when working with child welfare populations. Findings are organized across system, agency, and client levels and add to the understanding of TSP perspectives working with child welfare. Targeted interventions are discussed, such as efforts to promote realistic expectations and training strategies, as well as directions for future research to improve the intersection between child welfare and mental and behavioral health."
1538,Association between anemia and hematological indices with mortality among cardiac intensive care unit patients,"BACKGROUND: Anemia and elevated red cell distribution width (RDW) or mean corpuscular volume (MCV) are associated with an adverse prognosis in patients with cardiovascular disease and critical illness. Limited data exist regarding these associations in unselected cardiac intensive care unit (CICU) patients. METHODS: Retrospective cohort study of CICU patients between January 1, 2007, and December 31, 2015, with a hemoglobin (Hb) level measured at admission. Multivariable regression was performed to determine predictors of hospital mortality, and Kaplan–Meier analysis was used to determine post-discharge survival. RESULTS: We included 9644 patients with a mean age of 67.5 ± 15.1 years, including 3604 (37.4%) females. The median (IQR) values of Hb, MCV and RDW were 12.2 g/dL (10.6, 13.7), 90.7 fL (87.3, 94.2) fL, and 14.1% (13.3, 15.8), respectively. Anemia (admission Hb < 12 g/dL) was present in 4434 (46%) patients. A total of 845 (8.8%) patients died in the hospital. Patients with anemia had higher hospital mortality (11.3% vs. 6.6%, unadjusted OR 1.82, 95% CI 1.58–2.10, p < 0.001). After multivariable regression, admission Hb and MCV were not significantly associated with hospital mortality (both p > 0.1), while admission RDW (adjusted OR 1.12 per 1%, 95% CI 1.07–1.18, p < 0.001) was significantly associated with hospital mortality. Hospital survivors with lower Hb, higher MCV, or higher RDW had lower post-discharge survival. CONCLUSION: Elevated RDW on admission was independently associated with higher hospital mortality in CICU patients. These data emphasize the importance of hematologic abnormalities for mortality risk stratification in CICU populations. GRAPHIC ABSTRACT: [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00392-019-01549-0) contains supplementary material, which is available to authorized users."
1539,Does Partisanship Affect Compliance with Government Recommendations?,"This article studies the role of partisanship in American’s willingness to follow government recommendations. I combine survey and behavioral data to examine partisans’ vaccination rates during the Bush and Obama administrations. I find that presidential co-partisans are more likely to believe that vaccines are safe and more likely to vaccinate themselves and their children than presidential out-partisans. Depending on the vaccine, presidential co-partisans are 4–10 percentage points more likely to vaccinate than presidential out-partisans. Using causal mediation analysis, I find that this effect is the result of partisans’ differing levels of trust in government. This finding sheds light on the far-reaching role of partisanship in Americans’ interactions with the federal government. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11109-020-09613-6) contains supplementary material, which is available to authorized users."
1540,Atmospheric Plasma Supported by TiO(2) Catalyst for Decolourisation of Reactive Orange 16 Dye in Water,"PURPOSE: Every advanced oxidation process (AOP) has its limitations in water purification. Novel designs with simultaneous application of different AOPs can offer better solutions for cleaner water. METHODS: We have comparatively studied two advanced oxidation processes (AOPs) on decolourisation of Reactive Orange 16 (RO 16) azo dye pollutant from water: gas plasma treatment by low power atmospheric pressure plasma using novel plasma needle configuration, and semiconductor heterogeneous photocatalysis using titanium dioxide (TiO(2)) nanopowders. Additionally, simultaneous application of two advanced oxidation processes on azo dye decolourisation was studied. RESULTS: It was found that plasma treatment is very efficient system for the dye removal even for low flow rates (1 slm) of the Ar as feed gas. The presence of 10% of O(2) in Ar flow intensified dye oxidation process and shortened required time for total decolourisation. When plasma and catalyst were simultaneously applied, TiO(2) was activated with a few Watts plasma source as well as 300 W UV lamp source. The synergic effect of two AOPs was more pronounced for higher feed gas flow rates, resulting in improved decolourisation efficiency. CONCLUSION: Plasma needle can efficiently remove Reactive Orange 16 azo dye from water with a power consumption of only few Watts. With the addition of TiO(2) the removal efficiency is significantly improved. GRAPHIC ABSTRACT: [Image: see text]"
1541,The spread and control of rumors in a multilingual environment,"This paper studies the rumor propagation model with heterogeneous networks in a multilingual environment. Firstly, a rumor propagation model with two language spreaders, in which the immunologic mechanism is considered in the ignorant, is proposed on heterogeneous networks. Secondly, the basic reproduction number and the dynamic behaviors are analyzed by using the next-generation matrix method and Lyapunov stability theory, respectively. Moreover, two control strategies are designed to effectively suppress the spread of the rumor. The one is continuous control strategy. By applying real-time control to the spreaders, the rumor spreading time can be greatly reduced and the rumor can die out in a short time. The other is event-triggered impulsive control strategy, which can effectively reduce the consumption of resources and ensure the extinction of the rumor. Finally, the correctness of theoretical analysis and the feasibility of control methods are verified by numerical simulations."
1542,A summary of second systemic pulmonary shunt for congenital heart disease with pulmonary hypoxemia,"BACKGROUND: There has been an increasing number of children with congenital heart disease that undergo primary or second systemic-pulmonary shunt, while there are few reports on the second systemic-pulmonary shunt. Therefore, this study summarizes the experience of second systemic-pulmonary shunt for congenital heart disease in our hospital. METHODS AND RESULTS: Sixty-five children with congenital heart disease who underwent systemic-pulmonary shunt for the second time in our hospital were analyzed. At the early stage after the operation, cyanosis improved and SpO(2) significantly increased. One patient died in hospital (1.54%) and the causes of death were aggravated atrioventricular regurgitation, low cardiac output syndrome, and liver failure. Early complications occurred in 18 patients (27.7%). All the children were rechecked in our hospital every 3–6 months and the McGoon index significantly increased. CONCLUSION: Systemic-pulmonary artery shunt can promote pulmonary vascular development, improve cyanosis symptoms, and increase the chance of radical treatment in children with pulmonary vascular dysplasia."
1543,Tuning antiviral CD8 T-cell response via proline-altered peptide ligand vaccination,"Viral escape from CD8(+) cytotoxic T lymphocyte responses correlates with disease progression and represents a significant challenge for vaccination. Here, we demonstrate that CD8(+) T cell recognition of the naturally occurring MHC-I-restricted LCMV-associated immune escape variant Y4F is restored following vaccination with a proline-altered peptide ligand (APL). The APL increases MHC/peptide (pMHC) complex stability, rigidifies the peptide and facilitates T cell receptor (TCR) recognition through reduced entropy costs. Structural analyses of pMHC complexes before and after TCR binding, combined with biophysical analyses, revealed that although the TCR binds similarly to all complexes, the p3P modification alters the conformations of a very limited amount of specific MHC and peptide residues, facilitating efficient TCR recognition. This approach can be easily introduced in peptides restricted to other MHC alleles, and can be combined with currently available and future vaccination protocols in order to prevent viral immune escape."
1544,Digital exercise interventions for improving measures of central obesity: a systematic review,"OBJECTIVES: We aimed to systematically review the potential benefits of digital exercise interventions for improving measures of central obesity including visceral adipose tissue (VAT) and anthropometric surrogates for VAT in overweight or centrally obese adults aged 18 or over. METHODS: A systematic literature search was conducted in three databases up until March 2020 (PROSPERO registration nr CRD42019126764). RESULTS: N = 5 studies including 438 participants (age 48–80) with body mass index ≥ 25 kg/m(2) met the eligibility criteria and were included. The duration of the interventions ranged from 8 to 24 weeks. No study measured the primary outcome VAT, although in N = 4 studies, waist circumference (WC) decreased by between 1.3 and 5.6 cm in the intervention groups. CONCLUSIONS: This systematic review shows that there is no evidence for the effects of digital exercise on VAT, although digital exercise may decrease WC. These findings highlight the need for additional randomized controlled trials to confirm the findings with respect to WC, and to further investigate the effects of digital exercise on VAT. Together, this may have important implications for reducing the burden of physical inactivity and obesity."
1545,COVID 19,
1546,Transmission electron microscopy imaging of SARS-CoV-2,
1547,Trauma Does not Quarantine: Violence During the COVID-19 Pandemic,
1548,What’s Important: Hoping to Help: An Orthopaedic Perspective,
1549,Thoughts on Dermatology Residents who are New Parents,
1550,Parkin contributes to synaptic vesicle autophagy in Bassoon-deficient mice,"Mechanisms regulating the turnover of synaptic vesicle (SV) proteins are not well understood. They are thought to require poly-ubiquitination and degradation through proteasome, endo-lysosomal or autophagy-related pathways. Bassoon was shown to negatively regulate presynaptic autophagy in part by scaffolding Atg5. Here, we show that increased autophagy in Bassoon knockout neurons depends on poly-ubiquitination and that the loss of Bassoon leads to elevated levels of ubiquitinated synaptic proteins per se. Our data show that Bassoon knockout neurons have a smaller SV pool size and a higher turnover rate as indicated by a younger pool of SV2. The E3 ligase Parkin is required for increased autophagy in Bassoon-deficient neurons as the knockdown of Parkin normalized autophagy and SV protein levels and rescued impaired SV recycling. These data indicate that Bassoon is a key regulator of SV proteostasis and that Parkin is a key E3 ligase in the autophagy-mediated clearance of SV proteins."
1551,Combined ultrasound–CT approach to monitor acute exacerbation of interstitial lung disease,"BACKGROUND: Lung ultrasound is a bedside non-irradiating tool for assessment and monitoring of lung diseases. A lung ultrasound score based on visualized artefacts allows reliable quantification of lung aeration, and is useful to monitor mechanical ventilation setting, fluid resuscitation and antibiotic response in critical care. In the context of interstitial lung diseases associated to connective tissue disorders, lung ultrasound has been integrated to computed tomography for diagnosis and follow-up monitoring of chronic lung disease progression. CASE PRESENTATION: This case describes a severe acute exacerbation of interstitial lung disease associated to dermatomyositis–polymyositis requiring prolonged extra-corporeal life support. Lung ultrasound score was performed daily and allowed monitoring and guiding both the need of advanced imaging as computed tomography and immunosuppressive therapy. CONCLUSIONS: This case suggests lung ultrasound may be a useful monitoring tool for the response to immunosuppressive therapy in acute severe rheumatic interstitial lung disease, where chest X-ray is poorly informative, and transportation is at high risk."
1552,"Association of Burnout with Emotional Coping Strategies, Friendship, and Institutional Support Among Internal Medicine Physicians","Physician burnout influences physician mental health, staff stress, safety events, and patient outcomes. The association of burnout with compassion satisfaction, secondary stress, emotional coping strategies and many psychosocial variables, such as institutional support, friendship, and spirituality, have not been well studied. A convenience sample of internal medicine physicians was emailed a survey using validated instruments to explore these associations. The response rate was 337/1021 (33%), with a burnout prevalence of 175/337 (52%). Grit, acceptance, active coping, positive reframing, and strategy planning were associated with lower burnout domains and greater compassion satisfaction. Certain emotional coping strategies such as denial, disengagement, self-blame, substance abuse, and venting were associated with greater burnout and lower compassion satisfaction. Greater institutional support was associated with lower burnout (r = − .35, p < .001), secondary stress (r = − .14, p < .05), and compassion satisfaction (r = .28, p < .0001). Friendship was associated with lower burnout (r = − .25, p < .0001) and greater compassion satisfaction (r = .28, p < .0001). This study suggests that amelioration of burnout requires both intrinsic strategies that emphasize physician coping skills as well as extrinsic strategies that address institutional support."
1553,Multiple arboviral infections during a DENV-2 outbreak in Solomon Islands,"BACKGROUND: Solomon Islands, a country made up of tropical islands, has suffered cyclic dengue fever (DF) outbreaks in the past three decades. An outbreak of dengue-like illness (DLI) that occurred in April 2016 prompted this study, which aimed to determine the population’s immunity status and identify the arboviruses circulating in the country. METHODS: A household survey, involving 188 participants in two urban areas (Honiara and Gizo), and a parallel hospital-based clinical survey were conducted in April 2016. The latter was repeated in December after a surge in DLI cases. Arbovirus IgG ELISA were performed on the household blood samples to determine the prevalence of arboviruses in the community, while qPCR testing of the clinical samples was used to identify the circulating arboviruses. Dengue virus (DENV)-positive samples were further characterized by amplifying and sequencing the envelope gene. RESULTS: The overall prevalence rates of DENV, Zika virus, and chikungunya virus were 83.4%, 7.6%, and 0.9%, respectively. The qPCR positivity rates of the clinical samples collected in April 2016 were as follows: DENV 39.6%, Zika virus 16.7%, and chikungunya virus 6.3%, which increased to 74%, 48%, and 20% respectively in December 2016. The displacement of the circulating serotype-3, genotype-1, with DENV serotype 2, genotype cosmopolitan was responsible for the outbreak in 2016. CONCLUSIONS: A DENV outbreak in Solomon Islands was caused by the introduction of a single serotype. The high prevalence of DENV provided transient cross-protection, which prevented the introduction of a new serotype from the hyperendemic region for at least 3 years. The severe outcomes seen in the recent outbreak probably resulted from changes in the causative viruses and the effects of population immunity and changes in the outbreak pattern. Solomon Islands needs to step up surveillance to include molecular tools, increase regional communication, and perform timely interventions."
1554,P1′ Residue-Oriented Virtual Screening for Potent and Selective Phosphinic (Dehydro) Dipeptide Inhibitors of Metallo-Aminopeptidases,"Designing side chain substituents complementary to enzyme binding pockets is of great importance in the construction of potent and selective phosphinic dipeptide inhibitors of metallo-aminopeptidases. Proper structure selection makes inhibitor construction more economic, as the development process typically consists of multiple iterative preparation/bioassay steps. On the basis of these principles, using noncomplex computation and modeling methodologies, we comprehensively screened 900 commercial precursors of the P1′ residues of phosphinic dipeptide and dehydrodipeptide analogs to identify the most promising ligands of 52 metallo-dependent aminopeptidases with known crystal structures. The results revealed several nonproteinogenic residues with an improved energy of binding compared with the best known inhibitors. The data are discussed taking into account the selectivity and stereochemical implications of the enzymes. Using this approach, we were able to identify nontrivial structural elements substituting the recognized phosphinic peptidomimetic scaffold of metallo-aminopeptidase inhibitors."
1555,A High-Throughput Single-Clone Phage Fluorescence Microwell Immunoassay and Laser-Driven Clonal Retrieval System,"Phage display is one of the most frequently used platform technologies utilized to screen and select therapeutic antibodies, and has contributed to the development of more than 10 therapeutic antibodies used in the clinic. Despite advantages like efficiency and low cost, it has intrinsic technical limitations, such as the asymmetrical amplification of the library after each round of biopanning, which is regarded as a reason for it yielding a very limited number of antigen binders. In this study, we developed a high-throughput single-clonal screening system comprised of fluorescence immunoassays and a laser-driven clonal DNA retrieval system using microchip technology. Using this system, from a single-chain variable fragment (scFv) library displayed on phages with a complexity of 5.21 × 10(5) harboring random mutations at five amino acid residues, more than 70,000 clones—corresponding to ~14% of the library complexity—were screened, resulting in 78 antigen-reactive scFv sequences with mutations restricted to the randomized residues. Our results demonstrate that this system can significantly reduce the number of biopanning rounds, or even eliminate the need for this process for libraries with lower complexity, providing an opportunity to obtain more diverse clones from the library."
1556,Fully Human Antibodies for Malignant Pleural Mesothelioma Targeting,"Immunotherapy is the most promising therapeutic approach against malignant pleural mesothelioma (MPM). Despite technological progress, the number of targetable antigens or specific antibodies is limited, thus hindering the full potential of recent therapeutic interventions. All possibilities of finding new targeting molecules must be exploited. The specificity of targeting is guaranteed by the use of monoclonal antibodies, while fully human antibodies are preferred, as they are functional and generate no neutralizing antibodies. The aim of this review is to appraise the latest advances in screening methods dedicated to the identification and harnessing of fully human antibodies. The scope of identifying useful molecules proceeds along two avenues, i.e., through the antigen-first or binding-first approaches. The first relies on screening human antibody libraries or plasma from immunized transgenic mice or humans to isolate binders to specific antigens. The latter takes advantage of specific binding to tumor cells of antibodies present in phage display libraries or in responders’ plasma samples without prior knowledge of the antigens. Additionally, next-generation sequencing analysis of B-cell receptor repertoire pre- and post-therapy in memory B-cells from responders allows for the identification of clones expanded and matured upon treatment. Human antibodies identified can be subsequently reformatted to generate a plethora of therapeutics like antibody-drug conjugates, immunotoxins, and advanced cell-therapeutics such as chimeric antigen receptor-transduced T-cells."
1557,"Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine","BACKGROUND: Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. METHODS: This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. RESULTS: Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. CONCLUSIONS: Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects."
1558,Independent risk factors and the long-term outcomes for postoperative continuous renal replacement treatment in patients who underwent emergency surgery for type a acute aortic dissection,"OBJECTIVE: The study objective was to investigate the incidence and risk factors of continuous renal replacement therapy (CRRT) in patients undergoing emergency surgery for type A acute aortic dissection (TA-AAD) and evaluate the perioperative and long-term outcomes. METHODS: From January 2014 to December 2018, 712 consecutive patients were enrolled in the study. These patients were divided into two groups according to whether or not needed postoperative CRRT: the CRRT group vs the control group. Univariate analysis and binary logistic regression analysis were used to analyze the risk factors of CRRT. To avoid the selection bias and confounders, baseline characteristics were matched for propensity scores. Kaplan-Meier curves were generated to provide survival estimates at postoperative points in time. RESULTS: Before propensity score matching, univariate analysis showed that there were significant differences in age, preoperative hypertension, pericardial effusion, preoperative serum creatinine (sCr), intraoperative need for combined coronary artery bypass grafting (CABG) or mitral valve or tricuspid valve surgery, cardiopulmonary bypass (CPB) time, extracorporeal circulation assistant time, aortic cross-clamp time, drainage volume 24 h after surgery and ventilator time between two groups. All were higher in the CRRT group (P < 0.05). These risk factors were included in binary logistic regression. It showed that preoperative sCr and CPB time were independent risk factors for CRRT patients undergoing surgery for TA-AAD. And there were significant differences regarding 30-day mortality (P < 0.001) and long-term overall cumulative survival (P < 0.001) with up to a 6-year follow-up. After propensity scoring, 29 pairs (58 patients) were successfully matched. Among these patients, the analysis showed that CPB time was still significantly longer in the CRRT group (P = 0.004), and the 30-day mortality rate was also higher in this group (44.8% vs 10.3%; P = 0.003). CONCLUSION: CRRT after TA-AAD is common and worsened short- and long- term mortality. The preoperative sCr and CPB time are independent risk factors for postoperative CRRT patients. Shorten the CPB time as much as possible is recommended to reduce the risk of CRRT after the operation."
1559,Epidemiological analysis of the Kaohsiung city strategy for dengue fever quarantine and epidemic prevention,"BACKGROUND: Dengue is endemic in over 100 countries and is an important public health problem worldwide. Dengue fever is not endemic in Taiwan; the importation of dengue viruses from neighboring countries via close commercial links and air travel is considered to be the cause of local outbreaks. Therefore, efforts toward disease control have focused on preventing the importation of dengue into Taiwan. In this study, we investigated the relationships between the numbers of imported and indigenous dengue cases to test the validity of this strategy. METHODS: Data on cases of dengue fever that occurred between 2013 and 2018 were obtained from the surveillance systems of the Taiwan Center for Disease Control and Kaohsiung City Health Department. Standard epidemiological data, including the monthly numbers of indigenous and imported cases of dengue, were calculated. Potential associations between the numbers of indigenous and imported cases were investigated using correlation analyses. RESULTS: We identified a possible relationship between the period of disease concealment and the number of imported dengue cases, which resulted in epidemics of indigenous dengue fever within local communities. Further analysis of confirmed cases during previous epidemics in Kaohsiung City found that the risk of indigenous dengue fever may be related to the likelihood that patients with imported dengue fever will stay within local communities. CONCLUSION: Given the correlations found between imported and indigenous cases of dengue fever, as well as the relationship between the disease concealment period and the risk of indigenous dengue fever, prevention of disease importation and efficient identification of dengue cases within high-risk communities remain the major priorities for disease control."
1560,M1 macrophage features in severe Plasmodium falciparum malaria patients with pulmonary oedema,"BACKGROUND: Pulmonary oedema (PE) is a serious complication of Plasmodium falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarization is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarization of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients, with and without evidence of PE. METHODS: Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorized into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68+, all macrophages; CD40+, M1 macrophage; and CD163+, M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. RESULTS: Lung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE (63.44 ± 1.98%), compared to non-PE group (53.22 ± 3.85%, p < 0.05), whereas there was no difference observed for CD163 (M2 macrophage) between PE and non-PE groups. CONCLUSIONS: The study demonstrates M1 polarization in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterization in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria."
1561,Trauma complications and in-hospital mortality: failure-to-rescue,"BACKGROUND: Reducing medical errors and minimizing complications have become the focus of quality improvement in medicine. Failure-to-rescue (FTR) is defined as death after a surgical complication, which is an institution-level surgical safety and quality metric that is an important variable affecting mortality rates in hospitals. This study aims to examine whether complication and FTR are different across low- and high-mortality hospitals for trauma care. METHODS: This was a retrospective cohort study performed at trauma care hospitals registered at Japan Trauma Data Bank (JTDB) from 2004 to 2017. Trauma patients aged ≥ 15 years with injury severity score (ISS) of ≥ 3 and those who survived for > 48 h after hospital admission were included. The hospitals in JTDB were categorized into three groups by standardized mortality rate. We compared trauma complications, FTR, and in-hospital mortality by a standardized mortality rate (divided by the institute-level quartile). RESULTS: Among 184,214 patients that were enrolled, the rate of any complication was 12.7%. The overall mortality rate was 3.7%, and the mortality rate among trauma patients without complications was only 2.8% (non-precedented deaths). However, the mortality rate among trauma patients with any complications was 10.2% (FTR). Hospitals were categorized into high- (40 facilities with 44,773 patients), average- (72 facilities with 102,368 patients), and low- (39 facilities with 37,073 patients) mortality hospitals, using the hospital ranking of a standardized mortality rate. High-mortality hospitals showed lower ISS than low-mortality hospitals [10 (IQR, 9–18) vs. 11 (IQR, 9–20), P < 0.01]. Patients in high-mortality hospitals showed more complications (14.2% vs. 11.2%, P < 0.01), in-hospital mortality (5.1% vs. 2.5%, P < 0.01), FTR (13.6% vs. 7.4%, P < 0.01), and non-precedented deaths (3.6% vs. 1.9%, P < 0.01) than those in low-mortality hospitals. CONCLUSIONS: Unlike reports of elective surgery, complication rates and FTR are associated with in-hospital mortality rates at the center level in trauma care."
1562,Stochastic epidemic dynamics on extremely heterogeneous networks,"Networks of contacts capable of spreading infectious diseases are often observed to be highly heterogeneous, with the majority of individuals having fewer contacts than the mean, and a significant minority having relatively very many contacts. We derive a two-dimensional diffusion model for the full temporal behavior of the stochastic susceptible-infectious-recovered (SIR) model on such a network, by making use of a time-scale separation in the deterministic limit of the dynamics. This low-dimensional process is an accurate approximation to the full model in the limit of large populations, even for cases when the time-scale separation is not too pronounced, provided the maximum degree is not of the order of the population size."
1563,Network Reconstruction and Community Detection from Dynamics,"We present a scalable nonparametric Bayesian method to perform network reconstruction from observed functional behavior that at the same time infers the communities present in the network. We show that the joint reconstruction with community detection has a synergistic effect, where the edge correlations used to inform the existence of communities are also inherently used to improve the accuracy of the reconstruction which, in turn, can better inform the uncovering of communities. We illustrate the use of our method with observations arising from epidemic models and the Ising model, both on synthetic and empirical networks, as well as on data containing only functional information."
1564,De Profundis II,
1565,Restructuring the surgical service during the COVID-19 pandemic: Experience from a tertiary institution in Singapore,
1566,"À l’occasion de la journée mondiale 2020 de sensibilisation à l’autisme, message et recommandations de l’Académie nationale de médecine",
1567,Synthetic nucleic acid antibody prophylaxis confers rapid and durable protective immunity against Zika virus challenge,"Significant concerns have arisen over the past 3 y from the increased global spread of the mosquito-borne flavivirus, Zika. Accompanying this spread has been an increase in cases of the devastating birth defect microcephaly as well as of Guillain–Barré syndrome in adults in many affected countries. Currently there is no vaccine or therapy for this infection; however, we sought to develop a combination approach that provides more rapid and durable protection than traditional vaccination alone. A novel immune-based prophylaxis/therapy strategy entailing the facilitated delivery of a synthetic DNA consensus prME vaccine along with DNA-encoded anti-ZIKV envelope monoclonal antibodies (dMAb) were developed and evaluated for antiviral efficacy. This immediate and persistent protection strategy confers the ability to overcome shortcomings inherent with conventional active vaccination or passive immunotherapy. A collection of novel dMAbs were developed which were potent against ZIKV and could be expressed in serum within 24–48 h of in vivo administration. The DNA vaccine, from a previous development, was potent after adaptive immunity was developed, protecting against infection, brain and testes pathology in relevant mouse challenge models and in an NHP challenge. Delivery of potent dMAbs protected mice from the same murine viral challenge within days of delivery. Combined injection of dMAb and the DNA vaccine afforded rapid and long-lived protection in this challenge model, providing an important demonstration of the advantage of this synergistic approach to pandemic outbreaks."
1568,Science in the Time of Coronavirus,
1569,Antigenic drift of hemagglutinin and neuraminidase in seasonal H1N1 influenza viruses from Saudi Arabia in 2014 to 2015,"Antigenic drift of the hemagglutinin (HA) and neuraminidase (NA) proteins of the influenza virus cause a decrease in vaccine efficacy. Since the information about the evolution of these viruses in Saudi is deficient so we investigated the genetic diversity of circulating H1N1 viruses. Nasopharyngeal aspirates/swabs collected from 149 patients hospitalized with flu‐like symptoms during 2014 and 2015 were analyzed. Viral RNA extraction was followed by a reverse transcription‐polymerase chain reaction and genetic sequencing. We analyzed complete gene sequences of HA and NA from 80 positive isolates. Phylogenetic analysis of HA and NA genes of 80 isolates showed similar topologies and co‐circulation of clades 6b. Genetic diversity was observed among circulating viruses belonging to clade 6B.1A. The amino acid residues in the HA epitope domain were under purifying selection. Amino acid changes at key antigenic sites, such as position S101N, S179N (antigenic site‐Sa), I233T (antigenic site‐Sb) in the head domain might have resulted in antigenic drift and emergence of variant viruses. For NA protein, 36% isolates showed the presence of amino acid changes such as V13I (n = 29), I314M (n = 29) and 12% had I34V (n = 10). However, H257Y mutation responsible for resistance to neuraminidase inhibitors was missing. The presence of amino acid changes at key antigenic sites and their topologies with structural mapping of residues under purifying selection highlights the importance of antigenic drift and warrants further characterization of recently circulating viruses in view of vaccine effectiveness. The co‐circulation of several clades and the predominance of clade 6B.1 suggest multiple introductions in Saudi."
1570,"Defence in Depth Against Human Extinction: Prevention, Response, Resilience, and Why They All Matter","We look at classifying extinction risks in three different ways, which affect how we can intervene to reduce risk. First, how does it start causing damage? Second, how does it reach the scale of a global catastrophe? Third, how does it reach everyone? In all of these three phases there is a defence layer that blocks most risks: First, we can prevent catastrophes from occurring. Second, we can respond to catastrophes before they reach a global scale. Third, humanity is resilient against extinction even in the face of global catastrophes. The largest probability of extinction is posed when all of these defences are weak, that is, by risks we are unlikely to prevent, unlikely to successfully respond to, and unlikely to be resilient against. We find that it’s usually best to invest significantly into strengthening all three defence layers. We also suggest ways to do so tailored to the classes of risk we identify. Lastly, we discuss the importance of underlying risk factors – events or structural conditions that may weaken the defence layers even without posing a risk of immediate extinction themselves."
1571,Electronic cigarettes: Tumultuous times,See related https://onlinelibrary.wiley.com/doi/10.1111/resp.13696
1572,"Human papillomavirus E6: Host cell receptor, GRP78, binding site prediction","Human papillomavirus (HPV) is the main cervical cancer‐promoting element that is transmitted through sexual routes. Anal, head, and throat cancers are also reported to be accompanied by HPV infection. E6 is one of the HPV nonstructural proteins, which is responsible for cell differentiation by targeting tumor suppressor genes, p105Rb and p53. E6 was reported to be stabilized by two chaperone proteins; glucose‐regulated protein 78 (GRP78) and heat shock protein 90. GRP78 is responsible for the unfolded protein response of the cells, and it was reported to be upregulated in many cancers, including cervical cancer. It was reported that knocking out GRP78 destabilizes E6 leading to faster degradation of E6 in vivo. The current work predicts the possible binding mode between E6 and GRP78 based on sequence and structural similarities."
1573,MASS SPECTROMETRY IN VIROLOGICAL SCIENCES,"Virology, as a branch of the life sciences, discovered mass spectrometry (MS) to be the pivotal tool around two decades ago. The technique unveiled the complex network of interactions between the living world of pro‐ and eukaryotes and viruses, which delivered “a piece of bad news wrapped in protein” as defined by Peter Medawar, Nobel Prize Laureate, in 1960. However, MS is constantly evolving, and novel approaches allow for a better understanding of interactions in this micro‐ and nanoworld. Currently, we can investigate the interplay between the virus and the cell by analyzing proteomes, interactomes, virus‐cell interactions, and search for the compounds that build viral structures. In addition, by using MS, it is possible to look at the cell from the broader perspective and determine the role of viral infection on the scale of the organism, for example, monitoring the crosstalk between infected tissues and the immune system. In such a way, MS became one of the major tools for the modern virology, allowing us to see the infection in the context of the whole cell or the organism. © 2019 Wiley Periodicals, Inc. Mass Spec Rev"
1574,Mycoplasma bovis and viral agents associated with the development of bovine respiratory disease in adult dairy cows,"The etiology and pathologic findings of bovine respiratory disease (BRD) in adult dairy cows (n = 35) from a commercial dairy herd in Southern Brazil were investigated. Pulmonary samples were examined for histopathologic patterns and specific features within these patterns, while immunohistochemical (IHC) assays were designed to detect the intralesional antigens of viral infectious disease agents and Mycoplasma bovis. Pneumonia was diagnosed in 91.4% (32/35) of these cases; neither pneumonia nor any of the infectious disease pathogens evaluated occurred in three cows. The presence of multiple respiratory pathogens in 75% (24/32) of these cases indicated the complex origin of pneumonia in cattle. Interstitial pneumonia, necrosuppurative bronchopneumonia and suppurative bronchopneumonia were the principal patterns of pulmonary disease identified by histopathology. The most frequent pathogens identified by IHC were bovine viral diarrhea virus (BVDV; n = 18), M. bovis (n = 16) and bovine alphaherpesvirus type 1 (BoHV‐1; n = 14), followed by bovine respiratory syncytial virus (BRSV; n = 11) and bovine parainfluenza virus type 3 (BPIV‐3; n = 5). Obliterative bronchiolitis and peribronchial lymphocytic cuffings were the characteristic histopathologic features associated with M. bovis. Necrohemorrhagic bronchitis with bronchial angiogenesis was associated with BoHV‐1. Necrotizing bronchitis and bronchiolitis were associated with BVDV, BoHV‐1 and BRSV. Ballooning degeneration of the bronchial and bronchiolar epithelia was associated with BRSV and BoHV‐1. This is the first report from Brazil that correlated the histopathologic findings of BRD with the associated infectious disease agents by immunohistochemistry. M. bovis was frequently detected in the tissues of cows with fatal pulmonary disease during this study and may be a possible primary disease pathogen associated with the development of BRD in dairy cows. Additionally, the histopathologic features identified within patterns of pulmonary disease during this investigation may be an efficient diagnostic tool to associate histopathologic findings with specific agents of BRD in dairy cows."
1575,The effects of inequality on total factor productivity across districts in South Africa: a spatial econometric analysis,"This study builds on the fundamentals of the new economic geography and the skill-biased technological change argument, to empirically investigate whether increasing income/earning inequality enhances total factor productivity in South Africa. In so doing, panel data of district-municipalities and spatial econometric techniques are used for the period between 1995 and 2015, to gain a better understanding of the role of location and distance in the effects of income inequality on total factor productivity. The results from the analysis and empirical estimations indicate that: (1) there is strong support for the existence of positive spatial interactions in the effects of income inequality on total factor productivity; (2) the estimated direct effect of income inequality on TFP in local district-municipalities is negative and statistically significant, while the indirect effect is positive and statistically significant as well. These findings suggest that district-municipalities with moderate levels of inequality and high economic opportunities, attract more businesses, investments and important stocks of skilled labour from district-municipalities with high inequality. Furthermore, the finding of negative effects supports previous research suggesting that high levels of inequality set the stage for the adoption of distortionary policies which adversely influence the investment climate and produce political instability, thereby stifling the level of productivity and growth."
1576,Extracorporeal Life Support Organization Coronavirus Disease 2019 Interim Guidelines: A Consensus Document from an International Group of Interdisciplinary Extracorporeal Membrane Oxygenation Providers,"The Extracorporeal Life Support Organization (ELSO) Coronavirus Disease 2019 (COVID-19) Guidelines have been developed to assist existing extracorporeal membrane oxygenation (ECMO) centers to prepare and plan provision of ECMO during the ongoing pandemic. The recommendations have been put together by a team of interdisciplinary ECMO providers from around the world. Recommendations are based on available evidence, existing best practice guidelines, ethical principles, and expert opinion. This is a living document and will be regularly updated when new information becomes available. ELSO is not liable for the accuracy or completeness of the information in this document. These guidelines are not meant to replace sound clinical judgment or specialist consultation but rather to strengthen provision and clinical management of ECMO specifically, in the context of the COVID-19 pandemic."
1577,Inter-domain dynamics drive cholesterol transport by NPC1 and NPC1L1 proteins,"Transport of LDL-derived cholesterol from lysosomes into the cytoplasm requires NPC1 protein; NPC1L1 mediates uptake of dietary cholesterol. We introduced single disulfide bonds into NPC1 and NPC1L1 to explore the importance of inter-domain dynamics in cholesterol transport. Using a sensitive method to monitor lysosomal cholesterol efflux, we found that NPC1’s N-terminal domain need not release from the rest of the protein for efficient cholesterol export. Either introducing single disulfide bonds to constrain lumenal/extracellular domains or shortening a cytoplasmic loop abolishes transport activity by both NPC1 and NPC1L1. The widely prescribed cholesterol uptake inhibitor, ezetimibe, blocks NPC1L1; we show that residues that lie at the interface between NPC1L1's three extracellular domains comprise the drug’s binding site. These data support a model in which cholesterol passes through the cores of NPC1/NPC1L1 proteins; concerted movement of various domains is needed for transfer and ezetimibe blocks transport by binding to multiple domains simultaneously."
1578,Updates on Gene Therapy for Diabetic Retinopathy,"PURPOSE OF REVIEW: Diabetic retinopathy (DR), a leading cause of visual impairment in the developed country, is characterized by vascular lesions and neuronal damage of the retina. Treatment options for this condition are currently limited. The advent of therapy targeting vascular endothelial growth factor (VEGF) demonstrated significant benefits to patients with DR. However, this treatment is limited by its short half-life and requirement for frequent invasive intravitreal injections. In addition, many patients failed to achieve clinically significant improvement in visual function. Gene therapy has the potential to provide an alternative treatment for DR with distinct advantages, such as longer therapeutic effect, less injection frequency, ability to intervene at disease onset, and potentially fewer side effects. RECENT FINDINGS: Strategies for gene therapy in DR, stemming from the current understanding of the disease pathogenesis, focus on the inhibition of neovascularization and protection of neurovascular degeneration in the retina. Studies with promising results have mainly focussed on animal models due to efficacy and safety concerns, despite a number of successful preclinical studies using adeno-associated virus-mediated transduction to treat both vascular dysfunction and neuronal degeneration. With the optimization of delivery vectors, transgene regulation, and outcome measure, gene therapy will potentially become available for patients with DR. SUMMARY: This review provides an update on the current strategies utilized in DR gene therapy research. Several barriers to the clinical application of gene therapy for DR are highlighted, and future directions for this research are proposed."
1579,A modified live bat influenza A virus-based vaccine prototype provides full protection against HPAIV H5N1,"Highly pathogenic avian influenza viruses (HPAIVs) of subtype H5 are a major threat for poultry holdings worldwide, here especially the zoonotic Asian H5N1 viruses. These HPAIVs have caused more than 500 fatal spillover infections from poultry to humans, with a looming danger of a new pandemic by establishing human-to-human transmissions. Besides culling measures in infected farms in endemic areas, vaccination is the major tool against HPAIV. However, the mainly used inactivated preparations have several limitations, like application to the individual animal by injection and a reduced efficiency. Here we present a modified live influenza vaccine prototype, which is based on the H17N10 bat influenza virus. The new chimeric vaccine strain R65(mono)/H17N10 was able to provide full protection against a lethal challenge infection with HPAIV H5N1 of juvenile and subadult chickens, as well as ferrets after oronasal immunization. In addition, the H5 vaccine prototype cannot reassort with avian influenza viruses and therefore is a promising tool against HPAIV H5 infection, allowing new vaccination strategies for efficient disease control."
1580,The epidemiology of invasive meningococcal disease and the utility of vaccination in Malta,"Invasive meningococcal disease (IMD) is a vaccine-preventable devastating infection that mainly affects infants, children and adolescents. We describe the population epidemiology of IMD in Malta in order to assess the potential utility of a meningococcal vaccination programme. All cases of microbiologically confirmed IMD in the Maltese population from 2000 to 2017 were analysed to quantify the overall and capsular-specific disease burden. Mean overall crude and age-specific meningococcal incidence rates were calculated to identify the target age groups that would benefit from vaccination. Over the 18-year study period, 111 out of the 245 eligible notified cases were confirmed microbiologically of which 70.3% had septicaemia, 21.6% had meningitis, and 6.3% had both. The mean overall crude incidence rate was 1.49/100,000 population with an overall case fatality rate of 12.6%. Meningococcal capsular groups (Men) B followed by C were the most prevalent with W and Y appearing over the last 6 years. Infants had the highest meningococcal incidence rate of 18.9/100,000 followed by 6.1/100,000 in 1–5 year olds and 3.6/100,000 in 11–15 year old adolescents. The introduction of MenACWY and MenB vaccines on the national immunization schedule in Malta would be expected to reduce the disease burden of meningococcal disease in children and adolescents in Malta."
1581,The ICU Liberation Bundle and Strategies for Implementation in Pediatrics,"PURPOSE OF REVIEW: We briefly review post-intensive care syndrome (PICS) and the morbidities associated with critical illness that led to the intensive care unit (ICU) liberation movement. We review each element of the ICU liberation bundle, including pediatric support data, as well as tips and strategies for implementation in a pediatric ICU (PICU) setting. RECENT FINDINGS: Numerous studies have found children have cognitive, physical, and psychiatric deficits after a PICU stay. The effects of the full ICU liberation bundle in children have not been published, but in adults, bundle implementation (even partial) resulted in significant improvement in survival, mechanical ventilation use, coma, delirium, restraint-free care, ICU readmissions, and post-ICU discharge disposition. SUMMARY: Although initially described in adults, children also suffer from PICS. The ICU liberation bundle is feasible in children and may ameliorate the effects of a PICU stay. Further studies are needed to characterize the benefits of the ICU liberation bundle in children."
1582,"Effects of larval exposure to sublethal doses of Bacillus thuringiensis var. israelensis on body size, oviposition and survival of adult Anopheles coluzzii mosquitoes","BACKGROUND: Application of the larvicide Bacillus thuringiensis var. israelensis (Bti) is a viable complementary strategy for malaria control. Efficacy of Bti is dose-dependent. There is a knowledge gap on the effects of larval exposure to sublethal Bti doses on emerging adult mosquitoes. The present study examined the effect of larval exposure to sublethal doses of Bti on the survival, body size and oviposition rate in adult Anopheles coluzzii. METHODS: Third-instar An. coluzzii larvae were exposed to control and sublethal Bti concentrations at LC(20), LC(50) and LC(70) for 48 h. Surviving larvae were reared to adults under standard colony conditions. Thirty randomly selected females from each treatment were placed in separate cages and allowed to blood feed. Twenty-five gravid females from the blood-feeding cages were randomly selected and transferred into new cages where they were provided with oviposition cups. Numbers of eggs laid in each cage and mortality of all adult mosquitoes were recorded daily. Wing lengths were measured of 570 mosquitoes as a proxy for body size. RESULTS: Exposure to LC(70)Bti doses for 48 h as third-instar larvae reduced longevity of adult An. coluzzii mosquitoes. Time to death was 2.58 times shorter in females exposed to LC(70)Bti when compared to the control females. Estimated mortality hazard rates were also higher in females exposed to the LC(50) and LC(20) treatments, but these differences were not statistically significant. The females exposed to LC(70) concentrations had 12% longer wings than the control group (P < 0.01). No differences in oviposition rate of the gravid females were observed between the treatments. CONCLUSIONS: Exposure of An. coluzzii larvae to sublethal Bti doses reduces longevity of resultant adults and is associated with larger adult size and unclear effect on oviposition. These findings suggest that anopheline larval exposure to sublethal Bti doses, though not recommended, could reduce vectorial capacity for malaria vector populations by increasing mortality of resultant adults. [Image: see text]"
1583,The Time Sequences of Oral and Fecal Viral Shedding of Coronavirus Disease 2019 (COVID-19) Patients,
1584,Response to “Visualization of Putative Coronavirus in Kidney”,
1585,Análisis de la amenaza percibida por la COVID-19 en población española,
1586,Re: Al-Muharraqi MA. Testing recommendation for COVID-19 (SARS-CoV-2) in patients planned for surgery – continuing the service and ‘suppressing’ the pandemic. Br J Oral Maxillofac Surg. 2020 Apr 13 pii: S0266-4356(20)30164-9. doi: 10.1016/j.bjoms.2020.04.014. [Epub ahead of print],
1587,Impact of the Coronavirus Disease 2019 (COVID-19) Pandemic on Imaging Case Volumes,"OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has had significant economic impact on radiology with markedly decreased imaging case volumes. The purpose of this study was to quantify the imaging volumes during the COVID-19 pandemic across patient service locations and imaging modality types. METHODS: Imaging case volumes in a large health care system were retrospectively studied, analyzing weekly imaging volumes by patient service locations (emergency department, inpatient, outpatient) and modality types (x-ray, mammography, CT, MRI, ultrasound, interventional radiology, nuclear medicine) in years 2020 and 2019. The data set was split to compare pre-COVID-19 (weeks 1-9) and post-COVID-19 (weeks 10-16) periods. Independent-samples t tests compared the mean weekly volumes in 2020 and 2019. RESULTS: Total imaging volume in 2020 (weeks 1-16) declined by 12.29% (from 522,645 to 458,438) compared with 2019. Post-COVID-19 (weeks 10-16) revealed a greater decrease (28.10%) in imaging volumes across all patient service locations (range 13.60%-56.59%) and modality types (range 14.22%-58.42%). Total mean weekly volume in 2020 post-COVID-19 (24,383 [95% confidence interval 19,478-29,288]) was statistically reduced (P = .003) compared with 33,913 [95% confidence interval 33,429-34,396] in 2019, across all patient service locations and modality types. The greatest decline in 2020 was seen at week 16 specifically for outpatient imaging (88%) affecting all modality types: mammography (94%), nuclear medicine (85%), MRI (74%), ultrasound (64%), interventional (56%), CT (46%), and x-ray (22%). DISCUSSION: Since the duration of COVID-19 pandemic remains uncertain, these results may assist in guiding short-term and long-term practice decisions based on the magnitude of imaging volume decline across different patient service locations and specific imaging modality types."
1588,Mechanisms of neurological injury in COVID -19,
1589,"A Multicenter Study into Burnout, Perceived Stress, Job Satisfaction, Coping Strategies, and General Health among Emergency Department Nursing Staff","Burnout is a major problem among nurses working in emergency departments and is closely related to a high turnover of personnel, nursing errors, and patient dissatisfaction. The aims of this study were to estimate burnout, perceived stress, job satisfaction, coping and general health levels experienced by nurses working in emergency departments in Spain and to analyze the relationships between sociodemographic, occupational, and psychological variables and the occurrence of burnout syndrome among these professionals. A cross-sectional study was conducted in four emergency departments in Andalusia (Spain) from March to December 2016. The study sample was composed of n = 171 nurses. An ad hoc questionnaire was prepared to collect sociodemographic and work data, and the Maslach Burnout Inventory, the Perceived Stress Scale, the Font–Roja Questionnaire, the Brief Cope Orientation to Problem Experience and the General Health Questionnaire were used. The prevalence of high burnout was 8.19%. The levels of perceived stress and job satisfaction were moderate. The most frequent clinical manifestations were social dysfunction and somatic symptoms, and problem-focused coping was the strategy most used by nurses. Lack of physical exercise, gender, years worked at an emergency department, anxiety, social dysfunction, and avoidance coping were significant predictors of the dimensions of burnout."
1590,Oral-Health-Related Quality of Life in Adult Patients with Rheumatic Diseases—A Systematic Review,"Objectives: The aim of this systematic review was to assess the oral-health-related quality of life (OHRQoL) of adult patients with rheumatic diseases. Material and Methods: A systematic literature search was performed, including clinical studies on adults (aged at least 18 years) with a verified diagnosis of rheumatic disease. Results: 26 out of 41 clinical studies including rheumatoid arthritis (RA, seven studies), systemic sclerosis (SSc, five), Sjögren syndrome (SS, eight), Behcet disease (BD, four), systemic lupus erythematosus (SLE, one) and ankylosing spondylitis (AS, one) were found. In 15 studies, a healthy control group was recruited. The short form of the Oral Health Impact Profile (OHIP 14) was most frequently applied. The majority of studies (14/15) reported worse OHRQoL in patients with rheumatic disease compared to healthy individuals. In particular, patients with SS (salivary flow and composition) or BD (oral ulcers) showed a relation between OHRQoL and disease-specific oral manifestations. Most studies investigating subscales of OHRQoL (5/6) found the subscale physical disability to be predominantly affected in patients with rheumatic diseases. About half of the studies reported impaired psychosocial aspects. Conclusion: Patients with rheumatic diseases exhibit reduced OHRQoL, especially in diseases with oral manifestations like SS and BD. Physical affections due to oral diseases and psychosocial impairments caused by disease-related parameters must be recognized within patient-centered dental care."
1591,PLASTA National Webinar Series: A developing model for remote surgical education,
1592,Leveraging the social network for treatment of social anxiety: Pilot study of a youth-specific digital intervention with a focus on engagement of young men,"OBJECTIVE: The primary objective was to determine the acceptability, feasibility and safety of a novel digital intervention (Entourage) for young people with prominent social anxiety symptoms, with a particular focus on the engagement of young men. The secondary aim was to explore whether the intervention was associated with clinically significant improvements to clinical and social variables known to co-occur with social anxiety. METHOD: A multidisciplinary team comprising of mental health clinicians, researchers, young adult fiction writers, a comic artist and young people with a lived experience of social anxiety developed the Entourage platform in collaboration. Entourage combines evidence-based therapeutic techniques for social anxiety with an engaging, social-media-based interface that allows users to build social connections, while also receiving expert clinical moderation and support from peer workers. Acceptability, feasibility and safety outcomes of Entourage were tested in a 12-week pilot study with 89 young people (48.3% male; age M = 19.8 years, SD = 3.3 years). Eligible participants were recruited via liaison with four headspace early-intervention centres in north-western Melbourne. RESULTS: 56.8% of the sample reported social anxiety symptoms in the severe or very severe range at baseline. Results demonstrated the Entourage intervention was feasible, safe, and potentially acceptable, with 98.6% of participants reporting they would recommend Entourage to another young person experiencing social anxiety. Usage results were also comparable across male and non-male participants. Results showed that young people reliably and significantly improved on clinical and social variables. In particular, young males showed a clinically significant improvement on social anxiety symptoms (d = 0.79, p < .001), depression (d = 0.71, p < .001), belongingness (d = 0.58, p = .001), increased feelings of social connectedness (d = 0.46, p = .004) and decreased loneliness (d = 0.46, p = .006). Non-male participants also experienced a significant increase in social connectedness (d = 0.76, p < .001), alongside reduced social anxiety (d = 0.78, p < .001) and experiential avoidance (d = 0.81, p < .001). CONCLUSIONS: Entourage is a highly engaging and potentially effective intervention that represents a novel combination of features designed both to reduce social anxiety symptoms and improve social connection among young people. Entourage demonstrated some acceptability, feasibility and safety, with encouraging benefits to clinical and social variables. Entourage also showed favorable results for the engagement and support of young men with social anxiety symptoms."
1593,Next-Generation Sequencing Analysis of Cellular Response to Influenza B Virus Infection,"Influenza B virus (IBV) is a respiratory pathogen that infects humans and causes seasonal influenza epidemics. However, cellular response to IBV infection in humans and mechanisms of host-mediated restriction of IBV replication are not thoroughly understood. In this study, we used next-generation sequencing (NGS) to perform transcriptome profiling of IBV-infected human lung epithelial A549 cells at 0, 6, 12, and 24 h post infection (hpi) and characterized the cellular gene expression dynamics. We observed that more than 4000 host genes were differentially regulated during the study period, which included up regulation of genes encoding proteins, having a role in the innate antiviral immune responses, immune activation, cellular metabolism, autophagy, and apoptosis, as well as down regulation of genes involved in mitosis and cell proliferation. Further analysis of RNA-Seq data coupled with RT-qPCR validation collectively showed that double-strand RNA recognition pathways, including retinoic acid-inducible gene I (RIG-I) and Toll-like receptor 3 (TLR3), were substantially activated following IBV infection. Taken together, these results provide important initial insights into the intimate interaction between IBV and lung epithelial cells, which can be further explored towards elucidation of the cellular mechanisms in restriction or elimination of IBV infections in humans."
1594,Isolation and Characterisation of Alongshan Virus in Russia,"In recent decades, many new flavi-like viruses have been discovered predominantly in different invertebrates and, as was recently shown, some of them may cause disease in humans. The Jingmenvirus (JMV) group holds a special place among flaviviruses and flavi-like viruses because they have a segmented ssRNA(+) genome. We detected Alongshan virus (ALSV), which is a representative of the JMV group, in ten pools of adult Ixodes persulcatus ticks collected in two geographically-separated Russian regions. Three of the ten strains were isolated in the tick cell line IRE/CTVM19. One of the strains persisted in the IRE/CTVM19 cells without cytopathic effect for three years. Most ALSV virions purified from tick cells were spherical with a diameter of approximately 40.5 nm. In addition, we found smaller particles of approximately 13.1 nm in diameter. We obtained full genome sequences of all four segments of two of the isolated ALSV strains, and partial sequences of one segment from the third strain. Phylogenetic analysis on genome segment 2 of the JMV group clustered our novel strains with other ALSV strains. We found evidence for the existence of a novel upstream open reading frame in the glycoprotein-coding segment of ALSV and other members of the JMV group."
1595,"Broad Antiviral Activity of Ginkgolic Acid against Chikungunya, Mayaro, Una, and Zika Viruses","The alphaviruses Chikungunya (CHIKV), Mayaro (MAYV), Una (UNAV), and the flavivirus Zika (ZIKV) are emerging or re-emerging arboviruses which are responsible for frequent epidemic outbreaks. Despite the large impact of these arboviruses on health systems, there are no approved vaccines or treatments to fight these infections. As a consequence, there is an urgent need to discover new antiviral drugs. Natural products are a rich source of compounds with distinct biological activities, including antiviral properties. Thus, we aimed to explore the potential antiviral activity of Ginkgolic acid against the arboviruses CHIKV, MAYV, UNAV, and ZIKV. Viral progeny production in supernatants from cells treated or not treated with Ginkgolic acid was quantified by plaque-forming assay. Ginkgolic acid’s direct virucidal activity against these arboviruses was also determined. Additionally, viral protein expression was assessed using Western blot and immunofluorescence. Our results reveal that Ginkgolic acid promotes a dose-dependent decrease in viral titers in all tested viruses. Moreover, the compound demonstrated strong virucidal activity. Finally, we found that viral protein expression was affected by treatment with this drug. Collectively, these findings suggest that Ginkgolic acid could have broader antiviral activity."
1596,The In Silico Prediction of Hotspot Residues that Contribute to the Structural Stability of Subunit Interfaces of a Picornavirus Capsid,"The assembly of picornavirus capsids proceeds through the stepwise oligomerization of capsid protein subunits and depends on interactions between critical residues known as hotspots. Few studies have described the identification of hotspot residues at the protein subunit interfaces of the picornavirus capsid, some of which could represent novel drug targets. Using a combination of accessible web servers for hotspot prediction, we performed a comprehensive bioinformatic analysis of the hotspot residues at the intraprotomer, interprotomer and interpentamer interfaces of the Theiler’s murine encephalomyelitis virus (TMEV) capsid. Significantly, many of the predicted hotspot residues were found to be conserved in representative viruses from different genera, suggesting that the molecular determinants of capsid assembly are conserved across the family. The analysis presented here can be applied to any icosahedral structure and provides a platform for in vitro mutagenesis studies to further investigate the significance of these hotspots in critical stages of the virus life cycle with a view to identify potential targets for antiviral drug design."
1597,Metabolomic Analysis of Cricket paralysis virus Infection in Drosophila S2 Cells Reveals Divergent Effects on Central Carbon Metabolism as Compared with Silkworm Bm5 Cells,"High-throughput approaches have opened new opportunities for understanding biological processes such as persistent virus infections, which are widespread. However, the potential of persistent infections to develop towards pathogenesis remains to be investigated, particularly with respect to the role of host metabolism. To explore the interactions between cellular metabolism and persistent/pathogenic virus infection, we performed untargeted and targeted metabolomic analysis to examine the effects of Cricket paralysis virus (CrPV, Dicistroviridae) in persistently infected silkworm Bm5 cells and acutely infected Drosophila S2 cells. Our previous study (Viruses 2019, 11, 861) established that both glucose and glutamine levels significantly increased during the persistent period of CrPV infection of Bm5 cells, while they decreased steeply during the pathogenic stages. Strikingly, in this study, an almost opposite pattern in change of metabolites was observed during different stages of acute infection of S2 cells. More specifically, a significant decrease in amino acids and carbohydrates was observed prior to pathogenesis, while their abundance significantly increased again during pathogenesis. Our study illustrates the occurrence of diametrically opposite changes in central carbon mechanisms during CrPV infection of S2 and Bm5 cells that is possibly related to the type of infection (acute or persistent) that is triggered by the virus."
1598,High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication,"Interferon (IFN) regulatory factor 3 (IRF3) is the key transcription factor for the induction of IFN and antiviral genes. The absence of antiviral genes in IRF3 deficiency leads to susceptibility to a wide range of viral infections. Previously, we uncovered a function for nontranscriptional IRF3 (nt-IRF3), RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA), which triggers apoptotic killing of virus-infected cells. Using knock-in mice expressing a transcriptionally inactive, but RIPA-active, IRF3 mutant, we demonstrated the relative contribution of RIPA to host antiviral defense. Given that RIPA is a cellular antiviral pathway, we hypothesized that small molecules that promote RIPA in virus-infected cells would act as antiviral agents. To test this, we conducted a high throughput screen of a library of FDA-approved drugs to identify novel RIPA activators. Our screen identified doxorubicin as a potent RIPA-activating agent. In support of our hypothesis, doxorubicin inhibited the replication of vesicular stomatitis virus, a model rhabdovirus, and its antiviral activity depended on its ability to activate IRF3 in RIPA. Surprisingly, doxorubicin inhibited the transcriptional activity of IRF3. The antiviral activity of doxorubicin was expanded to flavivirus and herpesvirus that also activate IRF3. Mechanistically, doxorubicin promoted RIPA by activating the extracellular signal-regulated kinase (ERK) signaling pathway. Finally, we validated these results using another RIPA-activating compound, pyrvinium pamoate, which showed a similar antiviral effect without affecting the transcriptional activity of IRF3. Therefore, we demonstrate that the RIPA branch of IRF3 can be targeted therapeutically to prevent virus infection."
1599,Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation,"Rabies, caused by rabies virus (RABV), is a fatal neurological disease that still causes more than 59,000 human deaths each year. Type III interferon IFN-λs are cytokines with type I IFN-like antiviral activities. Although IFN-λ can restrict the infection for some viruses, especially intestinal viruses, the inhibitory effect against RABV infection remains undefined. In this study, the function of type III IFN against RABV infection was investigated. Initially, we found that IFN-λ2 and IFN-λ3 could inhibit RABV replication in cells. To characterize the role of IFN-λ in RABV infection in a mouse model, recombinant RABVs expressing murine IFN-λ2 or IFN-λ3, termed as rB2c-IFNλ2 or rB2c-IFNλ3, respectively, were constructed and rescued. It was found that expression of IFN-λ could reduce the pathogenicity of RABV and limit viral spread in the brains by different infection routes. Furthermore, expression of IFN-λ could induce the activation of the JAK-STAT pathway, resulting in the production of interferon-stimulated genes (ISGs). It was also found that rRABVs expressing IFN-λ could reduce the production of inflammatory cytokines in primary astrocytes and microgila cells, restrict the opening of the blood-brain barrier (BBB), and prevent excessive infiltration of inflammatory cells into the brain, which could be responsible for the neuronal damage caused by RABV. Consistently, IFN-λ was found to maintain the integrity of tight junction (TJ) protein ZO-1 of BBB to alleviate neuroinflammation in a transwell model. Our study underscores the role of IFN-λ in inhibiting RABV infection, which potentiates IFN-λ as a possible therapeutic agent for the treatment of RABV infection."
1600,Vero Cells as a Mammalian Cell Substrate for Human Norovirus,"Human norovirus (HuNoV) is a principal cause of acute gastroenteritis worldwide, particularly in developing countries. Its global prevalence is underscored by more serious morbidity and some mortality in the young (<5 years) and the elderly. To date, there are no licensed vaccines or approved therapeutics for HuNoV, mostly because there are limited cell culture systems and small animal models available. Recently described cell culture systems are not ideal substrates for HuNoV vaccine development because they are not clonal or only support a single strain. In this study, we show Vero cell-based replication of two pandemic GII.4 HuNoV strains and one GII.3 strain and confirm exosome-mediated HuNoV infection in Vero cells. Lastly, we show that trypsin addition to virus cultures or disruption of Vero cell host genes can modestly increase HuNoV replication. These data provide support for Vero cells as a cell culture model for HuNoV."
1601,Host–Virus Interaction: How Host Cells Defend against Influenza A Virus Infection,"Influenza A viruses (IAVs) are highly contagious pathogens infecting human and numerous animals. The viruses cause millions of infection cases and thousands of deaths every year, thus making IAVs a continual threat to global health. Upon IAV infection, host innate immune system is triggered and activated to restrict virus replication and clear pathogens. Subsequently, host adaptive immunity is involved in specific virus clearance. On the other hand, to achieve a successful infection, IAVs also apply multiple strategies to avoid be detected and eliminated by the host immunity. In the current review, we present a general description on recent work regarding different host cells and molecules facilitating antiviral defenses against IAV infection and how IAVs antagonize host immune responses."
1602,A Humanized Monoclonal Antibody Cocktail to Prevent Pulmonary Ricin Intoxication,"PB10 IgG(1), a monoclonal antibody (MAb) directed against an immunodominant epitope on the enzymatic subunit (RTA) of ricin toxin (RT), has been shown to passively protect mice and non-human primates from an aerosolized lethal-dose RT challenge. However, it was recently demonstrated that the therapeutic efficacy of PB10 IgG1 is significantly improved when co-administered with a second MAb, SylH3, targeting RT’s binding subunit (RTB). Here we report that the PB10/SylH3 cocktail is also superior to PB10 alone when used as a pre-exposure prophylactic (PrEP) in a mouse model of intranasal RT challenge. The benefit of the PB10/SylH3 cocktail prompted us to engineer a humanized IgG1 version of SylH3 (huSylH3). The huPB10/huSylH3 cocktail proved highly efficacious in the mouse model, thereby opening the door to future testing in non-human primates."
1603,Development of a real-time loop-mediated isothermal amplification method for the detection of severe fever with thrombocytopenia syndrome virus,"Severe fever with thrombocytopenia syndrome (SFTS) is being reported annually in South Korea since its first detection there in 2010. The causal agent is a negative-strand RNA virus 80–100 nm in diameter. It causes fever, thrombocytopenia, leukocytopenia, gastrointestinal symptoms, and neural symptoms. The mortality rate of SFTS was 32.6% among 172 cases reported from 2012 to 2015 in South Korea. Thus, is necessary to develop an effective diagnostic method that selectively identifies the isolates circulating in South Korea. The real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay is a simple, rapid, and sensitive approach for molecular diagnosis. Here, we designed novel primers for this assay and found that the technique had very high specificity, sensitivity, and efficiency. This real-time RT-LAMP approach using the novel primers developed herein can be applied for early diagnosis of SFTSV strains in South Korea to reduce the mortality rate of SFTS."
1604,Stages or phenotypes? A critical look at COVID-19 pathophysiology,
1605,Association of the bleeding time test with aspects of traumatic brain injury in patients with alcohol use disorder,"BACKGROUND—AIM: Traumatic brain injury (TBI) and alcohol use disorder (AUD) can occur concomitantly and be associated with coagulopathy that influences TBI outcome. The use of bleeding time tests in TBI management is controversial. We hypothesized that in TBI patients with AUD, a prolonged bleeding time is associated with more severe injury and poor outcome. MATERIAL AND METHODS: Moderate and severe TBI patients with evidence of AUD were examined with bleeding time according to IVY bleeding time on admission during neurointensive care. Baseline clinical and radiological characteristics were recorded. A standardized IVY bleeding time test was determined by staff trained in the procedure. Bleeding time test results were divided into normal (≤ 600 s), prolonged (> 600 s), and markedly prolonged (≥ 900 s). Normal platelet count (PLT) was defined as > 150,000/μL. This cohort was compared with another group of TBI patients without evidence of AUD. RESULTS: Fifty-two patients with TBI and AUD were identified, and 121 TBI patients without any history of AUD were used as controls. PLT was low in 44.2% and bleeding time was prolonged in 69.2% of patients. Bleeding time values negatively correlated with PLT (p < 0.05). TBI patients with markedly prolonged values (≥ 900 s) had significantly increased hematoma size, and more frequently required intracranial pressure measurement and mechanical ventilation compared with those with bleeding times < 900 s (p < 0.05). Most patients (88%) with low platelet count had prolonged bleeding time. No difference in 6-month outcome between the bleeding time groups was observed (p > 0.05). Subjects with TBI and no evidence for AUD had lower bleeding time values and higher platelet count compared with those with TBI and history of AUD (p < 0.05). CONCLUSIONS: Although differences in the bleeding time values between TBI cohorts exist and prolonged values may be seen even in patients with normal platelet count, the bleeding test is a marker of primary hemostasis and platelet function with low specificity. However, it may provide an additional assessment in the interpretation of the overall status of TBI patients with AUD. Therefore, the bleeding time test should only be used in combination with the patient’s bleeding history and careful assessment of other hematologic parameters."
1606,Contrast-enhanced ultrasound (CEUS) of the lung reveals multiple areas of microthrombi in a COVID-19 patient,
1607,Solving an ethical issue involved in experimentation with animals in a brazilian teaching laboratory,"Changes are occurring within Brazilian institutes of higher education; currently several universities are reviewing their course offerings and teaching approaches to determine if they meet the needs of today's undergraduate students. When changes are made to the curriculum of experimental courses, there should be an understood guarantee that all efforts to avoid ethical and biosafety issues have been diligently considered. Ethical considerations lead us to create an alternative experimental session to be conducted that eliminated the use of rats, the conventional in vivo model employed for learning metabolism of glycogen in our university. To avoid possible biosafety issues, we prepared an alternative sample to simulate human urine, which we called guarurine. Using our new method, it is possible to verify positive results imitating a diabetic and starving people samples for detection of glucose and ketone. The alternative tool described herein is not only particularly suited to bypass the ethics of using animals for teaching, but also permits the discussion of significant aspects of pathological and physiological situations such as diabetics and starvation in a simple, safe, and interesting way."
1608,Locked nucleic acid containing antisense oligonucleotides enhance inhibition of HIV‐1 genome dimerization and inhibit virus replication,"We have evaluated antisense design and efficacy of locked nucleic acid (LNA) and DNA oligonucleotide (ON) mix‐mers targeting the conserved HIV‐1 dimerization initiation site (DIS). LNA is a high affinity nucleotide analog, nuclease resistant and elicits minimal toxicity. We show that inclusion of LNA bases in antisense ONs augments the interference of HIV‐1 genome dimerization. We also demonstrate the concomitant RNase H activation by six consecutive DNA bases in an LNA/DNA mix‐mer. We show ON uptake via receptor‐mediated transfection of a human T‐cell line in which the mix‐mers subsequently inhibit replication of a clinical HIV‐1 isolate. Thus, the technique of LNA/DNA mix‐mer antisense ONs targeting the conserved HIV‐1 DIS region may provide a strategy to prevent HIV‐1 assembly in the clinic."
1609,Upcoming Events in Pediatric Cardiology Pediatric Cardiology 41–4,
1610,Optimal sleep health among frontline healthcare workers during the COVID-19 pandemic,
1611,Synthesis and biological evaluation of a new series of 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives as new anticancer agents,"The diaryl ureas are very important fragments in medicinal chemistry. By means of computer-aided design, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives were designed and synthesized, and evaluated for their antiproliferative activity against A549, HCT-116, PC-3 cancer cell lines, and HL7702 human normal liver cell lines in vitro by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Most of the target compounds demonstrate significant antiproliferative effects on all the selective cancer cell lines. The calculated IC(50) values were reported. The target compound 1-(4-chlorophenyl)-3-{4-{[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methoxy}phenyl}urea (7u) demonstrated the most potent inhibitory activity (IC(50) = 2.39 ± 0.10 μM for A549 and IC(50) = 3.90 ± 0.33 μM for HCT-116), comparable to the positive-control sorafenib (IC(50) = 2.12 ± 0.18 μM for A549 and IC(50) = 2.25 ± 0.71 μM for HCT-116). Conclusively, 1-aryl-3-[4-(pyridin-2-ylmethoxy)phenyl]urea derivatives as the new anticancer agents were discovered, and could be used as the potential BRAF inhibitors for further research."
1612,Vertical transmission of COVID-19: SARS-CoV-2 RNA on the fetal side of the placenta in pregnancies with COVID-19 positive mothers and neonates at birth,
1613,The synchronized gene expression of retrotransposons and type I interferon in dermatomyositis,
1614,“Considerable unreimbursed medical care is delivered through electronic patient portals: a retrospective review”,
1615,Editorial ECTES Abstracts 2020,
1616,Genetic and antigenic characterization of H5 and H7 avian influenza viruses isolated from migratory waterfowl in Mongolia from 2017 to 2019,"The circulation of highly pathogenic avian influenza viruses (HPAIVs) of various subtypes (e.g., H5N1, H5N6, H5N8, and H7N9) in poultry remains a global concern for animal and public health. Migratory waterfowls play important roles in the transmission of these viruses across countries. To monitor virus spread by wild birds, active surveillance for avian influenza in migratory waterfowl was conducted in Mongolia from 2015 to 2019. In total, 5000 fecal samples were collected from lakesides in central Mongolia, and 167 influenza A viruses were isolated. Two H5N3, four H7N3, and two H7N7 viruses were characterized in this study. The amino acid sequence at hemagglutinin (HA) cleavage site of those isolates suggested low pathogenicity in chickens. Phylogenetic analysis revealed that all H5 and H7 viruses were closely related to recent H5 and H7 low pathogenic avian influenza viruses (LPAIVs) isolated from wild birds in Asia and Europe. Antigenicity of H7Nx was similar to those of typical non-pathogenic avian influenza viruses (AIVs). While HPAIVs or A/Anhui/1/2013 (H7N9)-related LPAIVs were not detected in migratory waterfowl in Mongolia, sporadic introductions of AIVs including H5 and H7 viruses into Mongolia through the wild bird migration were identified. Thus, continued monitoring of H5 and H7 AIVs in both domestic and wild birds is needed for the early detection of HPAIVs spread into the country. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-020-01764-2) contains supplementary material, which is available to authorized users."
1617,Nursing in uncertain times,
1618,Arrigo Moglia (1947–2020),
1619,Transcriptome Landscape of Intracellular Brucella ovis Surviving in RAW264.7 Macrophage Immune System,"Brucella ovis infection results in genital damage and epididymitis in rams, placental inflammation and rare abortion in ewes, and neonatal mortality in lambs. However, the mechanism underlying B. ovis infection remains unclear. In the present study, we used prokaryotic transcriptome sequencing to identify the differentially expressed genes (DEGs) between wild-type B. ovis and intracellular B. ovis in RAW264.7 macrophages. Gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed, and quantitative reverse transcriptase PCR (qRT-PCR) was used to validate the top 10 upregulated and downregulated DEGs. The results showed that 212 genes were differentially expressed, including 68 upregulated and 144 downregulated genes, which were mainly enriched in 30 GO terms linked to biological process, cellular component, and molecular function. KEGG analysis showed that the DEGs were enriched in the hypoxia-inducible factor 1 (HIF-1) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, beta-alanine metabolism, and quorum sensing pathway. BME_RS01160, BME_RS04270, BME_RS08185, BME_RS12880, BME_RS25875, predicted_RNA865, and predicted_RNA953 were confirmed with the transcriptome sequencing data. Hence, our findings not only reveal the intracellular parasitism of B. ovis in the macrophage immune system, but also help to understand the mechanism of chronic B. ovis infection."
1620,Generation and validation of a highly sensitive bioluminescent HIV-1 reporter vector that simplifies measurement of virus release,"BACKGROUND: The continued persistence of HIV-1 as a public health concern due to the lack of a cure calls for the development of new tools for studying replication of the virus. Here, we used NanoLuc, a small and extremely bright luciferase protein, to develop an HIV-1 bioluminescent reporter virus that simplifies functional measurement of virus particle production. RESULTS: The reporter virus encodes a Gag protein containing NanoLuc inserted between the matrix (MA) and capsid (CA) domains of Gag, thereby generating virus particles that package high levels of the NanoLuc reporter. We observe that inserting the NanoLuc protein within HIV-1 Gag has minimal impact on Gag expression and virus particle release. We show that the reporter virus recapitulates inhibition of HIV-1 particle release by Gag mutations, the restriction factor tetherin, and the small-molecule inhibitor amphotericin-B methyl ester. CONCLUSION: These results demonstrate that this vector will provide a simple and rapid tool for functional studies of virus particle assembly and release and high-throughput screening for cellular factors and small molecules that promote or inhibit HIV-1 particle production."
1621,Genetic polymorphism of merozoite surface protein-3 in Myanmar Plasmodium falciparum field isolates,"BACKGROUND: Plasmodium falciparum merozoite surface protein-3 (PfMSP-3) is a target of naturally acquired immunity against P. falciparum infection and is a promising vaccine candidate because of its critical role in the erythrocyte invasion of the parasite. Understanding the genetic diversity of pfmsp-3 is important for recognizing genetic nature and evolutionary aspect of the gene in the natural P. falciparum population and for designing an effective vaccine based on the antigen. METHODS: Blood samples collected from P. falciparum-infected patients in Naung Cho and Pyin Oo Lwin, Myanmar, in 2015 were used in this study. The pfmsp-3 was amplified by polymerase chain reaction, cloned, and sequenced. Genetic polymorphism and natural selection of Myanmar pfmsp-3 were analysed using the programs DNASTAR, MEGA6, and DnaSP 5.10.00. Genetic diversity and natural selection of the global pfmsp-3 were also comparatively analysed. RESULTS: Myanmar pfmsp-3 displayed 2 different alleles, 3D7 and K1. The 3D7 allelic type was predominant in the population, but genetic polymorphism was less diverse than for the K1 allelic type. Polymorphic characters in both allelic types were caused by amino acid substitutions, insertions, and deletions. Amino acid substitutions were mainly occurred at the alanine heptad repeat domains, whereas most insertions and deletions were found at the glutamate rich domain. Overall patterns of amino acid polymorphisms detected in Myanmar pfmsp-3 were similar in the global pfmsp-3 population, but novel amino acid changes were observed in Myanmar pfmsp-3 with low frequencies. Complicated patterns of natural selection and recombination events were predicted in the global pfmsp-3, which may act as major driving forces to maintain and generate genetic diversity of the global pfmsp-3 population. CONCLUSION: Global pfmsp-3 revealed genetic polymorphisms, suggesting that the functional and structural consequences of the polymorphisms should be considered in designing a vaccine based on PfMSP-3. Further examination of genetic diversity of pfmsp-3 in the global P. falciparum population is necessary to gain in-depth insight for the population structure and evolutionary aspect of global pfmsp-3."
1622,Mental health: why it still matters in the midst of a pandemic,
1623,Corrigendum,
1624,Identification of 2-(4-(Phenylsulfonyl)piperazine-1-yl)pyrimidine Analogues as Novel Inhibitors of Chikungunya Virus,"[Image: see text] The chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus, and it is the causative agent of chikungunya fever (CHIKF). Although it has re-emerged as an epidemic threat, so far there are neither vaccines nor pharmacotherapy available to prevent or treat an infection. Herein, we describe the synthesis and structure–activity relationship studies of a class of novel small molecule inhibitors against CHIKV and the discovery of a new potent inhibitor (compound 6a). The starting point of the optimization process was N-ethyl-6-methyl-2-(4-(4-fluorophenylsulfonyl)piperazine-1-yl)pyrimidine-4-amine (1) with an EC(50) of 8.68 μM, a CC(50) of 122 μM, and therefore a resulting selectivity index (SI) of 14.2. The optimized compound 6a, however, displays a much lower micromolar antiviral activity (EC(50) value of 3.95 μM), considerably better cytotoxic liability (CC(50) value of 260 μM) and consequently an improved SI of greater than 61. Therefore, we report the identification of a promising novel compound class that has the potential for further development of antiviral drugs against the CHIKV."
1625,Supervised pulmonary hypertension exercise rehabilitation (SPHERe): study protocol for a multi-centre randomised controlled trial,"BACKGROUND: Supervised cardio-pulmonary rehabilitation may be safe and beneficial for people with pulmonary hypertension (PH) in groups 1 (pulmonary arterial hypertension) and 4 (chronic thromboembolic disease), particularly as a hospital in-patient. It has not been tested in the most common PH groups; 2 (left heart disease), 3 (lung disease), or 5 (other disorders). Further it has not been evaluated in the UK National Health Service (NHS) out-patient setting, or with long-term follow-up. The aim of this randomised controlled trial (RCT) is to test the clinical and cost-effectiveness of a supervised exercise rehabilitation intervention with psychosocial support compared to best practice usual care for people with PH in the community/outpatient setting. METHODS: This multi-centre, pragmatic, two-arm RCT with embedded process evaluation aims to recruit 352 clinically stable adults with PH (groups 1–5) and WHO functional class II-IV. Participants will be randomised to either the Supervised Pulmonary Hypertension Exercise Rehabilitation (SPHERe) intervention or control. The SPHERe intervention consists of 1) individual assessment and familiarisation sessions; 2) 8-week, twice-weekly, supervised out-patient exercise training; 3) psychosocial/motivational support and education; 4) guided home exercise plan. The control intervention consists of best practice usual care with a single one-to-one practitioner appointment, and general advice on physical activity. Outcomes will be measured at baseline, 4 months (post-intervention) and 12 months by researchers blinded to treatment allocation. The primary outcome is the incremental shuttle walk test at 4 months. Secondary outcomes include health-related quality of life (HRQoL), time to clinical worsening and health and social care use. A purposive sample of participants (n = 20 intervention and n = 20 control) and practitioners (n = 20) will be interviewed to explore experiences of the trial, outcomes and interventions. DISCUSSION: The SPHERe study is the first multi-centre clinical RCT to assess the clinical and cost effectiveness of a supervised exercise rehabilitation intervention compared to usual care, delivered in the UK NHS, for people in all PH groups. Results will inform clinicians and commissioners as to whether or not supervised exercise rehabilitation is effective and should be routinely provided for people with PH. TRIAL REGISTRATION: ISRCTN no. 10608766, prospectively registered on 18th March 2019."
1626,Morbidity and Mortality of Typhoid Intestinal Perforation Among Children in Sub-Saharan Africa 1995–2019: A Scoping Review,"BACKGROUND: Typhoid fever incidence and complications, including intestinal perforation, have declined significantly in high-income countries, with mortality rates <1%. However, an estimated 10.9 million cases still occur annually, most in low- and middle-income countries. With the availability of a new typhoid conjugate vaccine licensed for children and recommended by the World Health Organization, understanding severe complications, including associated mortality rates, is essential to inform country-level decisions on introduction of this vaccine. This scoping review summarizes over 20 years of the literature on typhoid intestinal perforation in sub-Saharan Africa. METHODS: We searched EMBASE, PubMed, Medline, and Cochrane databases for studies reporting mortality rates due to typhoid intestinal perforation in children, under 18 years old, in sub-Saharan Africa published from January 1995 through June 2019. RESULTS: Twenty-four papers from six countries were included. Reported mortality rates ranged from 4.6–75%, with 16 of the 24 studies between 11 and 30%. Thirteen papers included postoperative morbidity rates, ranging from 16–100%. The most documented complications included surgical site infections, intra-abdominal abscesses, and enterocutaneous fistulas. High mortality rates can be attributed to late presentation to tertiary centers, sepsis and electrolyte abnormalities requiring preoperative resuscitation, prolonged perforation-to-surgery interval, and lack of access to critical care or an intensive care unit postoperatively. CONCLUSIONS: Current estimates of mortality related to typhoid intestinal perforation among children in sub-Saharan Africa remain unacceptably high. Prevention of typhoid fever is essential to reduce mortality, with the ultimate goal of a comprehensive approach that utilizes vaccination, improvements in water, sanitation, and hygiene, and greater access to surgical care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00268-020-05567-2) contains supplementary material, which is available to authorized users."
1627,Medical Licensure: It is time to eliminate practice borders within the United States,
1628,2020 Letter from the Editor-in-Chief,
1629,Aktuelles Studienergebnis unterstreicht zurückhaltende Kommentierung,
1630,What can the world learn from New Zealand on climate?,
1631,When does a major outbreak become a Public Health Emergency of International Concern?,
1632,Obituary: Arnold Demain 1927–2020,
1633,"Abstracts from the International Science Symposium on HIV and Infectious Diseases (ISSHID 2019): Infectious diseases: Chennai, India. 12-14 October 2019",
1634,In vitro Studies on The Inhibition of Replication of Zika and Chikungunya Viruses by Dolastane Isolated from Seaweed Canistrocarpus cervicornis,"The lack of vaccines and antiviral treatment, along with the increasing number of cases of Zika virus (ZIKV) and Chikungunya virus (CHIKV) infections, emphasize the need for searching for new therapeutic strategies. In this context, the marine brown seaweed Canistrocarpus cervicornis has been proved to hold great antiviral potential. Hence, the aim of this work was to evaluate the anti-ZIKV and anti-CHIKV activity of a marine dolastane isolated from brown seaweed C. cervicornis and its crude extract. Vero cells were used in antiviral assays, submitted to ZIKV and CHIKV, and treated with different concentrations of C. cervicornis extract or dolastane. The crude extract of C. cervicornis showed inhibitory activities for both ZIKV and CHIKV, with EC(50) values of 3.3 μg/mL and 3.1 μg/mL, respectively. However, the isolated dolastane showed a more significant and promising inhibitory effect (EC(50) = 0.95 µM for ZIKV and 1.3 µM for CHIKV) when compared to both the crude extract and ribavirin, which was used as control. Also, the dolastane showed a very potent virucidal activity against CHIKV and was able to inhibit around 90% of the virus infectivity at 10 μM. For the ZIKV, the effects were somewhat lower, although interesting, at approximately 64% in this same concentration. Further, we observed that both the extract and the dolastane were able to inhibit the replication of ZIKV and CHIKV at different times of addition post-infection, remaining efficient even if added after 8 hours post-infection, but declining soon after. A synergistic effect using sub-doses of the extract and isolates was associated with ribavirin, inhibiting above 80% replication even at the lowest concentrations. Therefore, this work has unveiled the anti-ZIKV and CHIKV potential of C. cervicornis crude extract and an isolated dolastane, which, in turn, can be used as a preventive or therapeutic strategy in the future."
1635,Derivation and validation of a prognostic score for neonatal mortality in Ethiopia: a case-control study,"BACKGROUND: Early warning scores for neonatal mortality have not been designed for low income countries. We developed and validated a score to predict mortality upon admission to a NICU in Ethiopia. METHODS: We conducted a retrospective case-control study at the University of Gondar Hospital, Gondar, Ethiopia. Neonates hospitalized in the NICU between January 1, 2016 to June 31, 2017. Cases were neonates who died and controls were neonates who survived. RESULTS: Univariate logistic regression identified variables associated with mortality. The final model was developed with stepwise logistic regression. We created the Neonatal Mortality Score, which ranged from 0 to 52, from the model’s coefficients. Bootstrap analysis internally validated the model. The discrimination and calibration were calculated. In the derivation dataset, there were 207 cases and 605 controls. Variables associated with mortality were admission level of consciousness, admission respiratory distress, gestational age, and birthweight. The AUC for neonatal mortality using these variables in aggregate was 0.88 (95% CI 0.85–0.91). The model achieved excellent discrimination (bias-corrected AUC) under internal validation. Using a cut-off of 12, the sensitivity and specificity of the Neonatal Mortality Score was 81 and 80%, respectively. The AUC for the Neonatal Mortality Score was 0.88 (95% CI 0.85–0.91), with similar bias-corrected AUC. In the validation dataset, there were 124 cases and 122 controls, the final model and the Neonatal Mortality Score had similar discrimination and calibration. CONCLUSIONS: We developed, internally validated, and externally validated a score that predicts neonatal mortality upon NICU admission with excellent discrimination and calibration."
1636,Factors affecting tracheostomy in critically ill paediatric patients in Japan: a data-based analysis,"BACKGROUND: There has been an increasing number of children surviving with high medical needs, for whom tracheostomy and/or home ventilation is part of their chronic disease management. The purpose of this study was to describe the indications, epidemiology, frequency, and associated factors for tracheostomy in critically ill paediatric patients using the data available in the Japanese Registry of Paediatric Acute Care (JaRPAC). METHODS: This multicentre epidemiologic study collected data concerning paediatric tracheostomy from the JaRPAC database. Patients were divided into two groups: those with or without tracheostomies when they were discharged from the Intensive Care Unit (ICU) or Paediatric Intensive Care Unit (PICU). Consecutive patients aged ≤16 years who did not undergo tracheostomy when admitted to ICU or PICU between April 2014 and March 2017 were included. RESULTS: A total of 23 hospitals participated, involving 6199 paediatric patients registered in the JaRPAC database during the study period. Of the registered paediatric patients, 5769 (95%) patients were admitted to the ICUs or PICUs without tracheostomies. Among the patients, 181 patients (3.1%) had undergone tracheostomies. There were significant differences in chronic conditions (134, 74.0% versus 3096, 55.4%, p < 0.01), chromosomal anomalies (19, 10.5% versus 326, 5.8%, p < 0.01), urgent admission (151, 83.4% versus 3093, 55.4%, p < 0.01). More tracheostomies were performed on patients who were admitted for respiratory failure (61, 33.7% versus 926, 16.1%, p < 0.01) and for post-cardiac pulmonary arrest (CPA) resuscitation (40, 22.1% versus 71, 1.1%, p < 0.01). CONCLUSIONS: This is the first report to use a large-scale registry of critically ill paediatric patients in Japan to describe the interrelated factors of tracheostomies. Chronic conditions (especially for neuromuscular disease), chromosomal anomaly, admission due to respiratory failure, or treatment for post-CPA resuscitation all had the possibility to be risk factors for tracheostomy."
1637,Start Now,
1638,Cold Exposure-Induced Up-Regulation of Hsp70 Positively Regulates PEDV mRNA Synthesis and Protein Expression In Vitro,"Porcine epidemic diarrhea (PED) is a highly contagious, intestinal infectious disease caused by porcine epidemic diarrhea virus (PEDV). PEDV as an emerging and re-emerging epizootic virus of swine causes substantial economic losses to the pig industry in China and other countries. In China, the occurrence of PED shows significant seasonal variations, usually outbreak during the winter season. The epidemic characteristics of PED may be highly correlated with the changes of ambient temperature. However, molecular mechanism on the seasonal occurrence of PED still remains unclear. It has been widely observed that low ambient temperature up-regulates the expression of host heat shock protein 70 (Hsp70). Here, we showed that nucleotide and protein levels of Hsp70 were up-regulated in the intestinal of cold exposed pig and cold exposed Vero E6 cells. We found that overexpression of Hsp70 could increase PEDV mRNA synthesis and protein expression in Vero E6 and IPEC-J2 cells, while the siRNAs mediated knockdown of Hsp70 and VER155008 mediated inhibition of Hsp70 resulted in inhibition of viral mRNA synthesis and protein expression in Vero E6 cells. These data suggested that Hsp70 positively regulated PEDV mRNA synthesis and protein expression, which being helpful for understanding the seasonality of PED epidemics and development of novel antiviral therapies in the future."
1639,Novel Approaches Towards a Functional Cure of HIV/AIDS,"Therapeutic approaches towards a functional cure or eradication of HIV have gained renewed momentum upon encouraging data emerging from studies in SIV monkey models and recent results from human clinical studies. However, a multitude of questions remain to be addressed, including how to deal with the latent viral reservoir, how to boost the host immune response to the virus and what the hurdles are to reach relevant viral compartments in the body. Advances have been made especially with regard to identifying agents that can reactivate the latent virus in vivo and boost the cellular and humoral immunity, but it remains largely unclear whether any of these strategies can awaken a sufficiently large fraction of the viral reservoir and whether the boosted immunity can prevent rapid viral replication once antiretroviral treatments are stopped."
1640,Retrobulbar Sinus Injection of Doxorubicin is More Efficient Than Lateral Tail Vein Injection at Inducing Experimental Nephrotic Syndrome in Mice: A Pilot Study,"Doxorubicin-induced nephropathy in mice is a model for studying experimental nephrotic syndrome. It corresponds to puromycin aminonucleoside nephrosis in rats. In this model, susceptible 129 S1/SvImJ mice are administered a rapid intravenous injection that can be accomplished via either the lateral tail vein or the retrobulbar sinus. Because doxorubicin is a highly toxic substance, extravasation must be avoided during the administration of the intravenous injection to prevent the development of large necrotizing lesions and exacerbation of the animals’ stress. In the present study, we compared the safety and stress of these two injection routes by using histopathological analyses of the animals’ orbital cavities or tails, respectively. The injection of 14.5 µg/g body weight doxorubicin into the mice’s lateral tail veins (n = 9) or retrobulbar sinuses (n = 19) caused no clinically detectable stress or impairment. Histopathologies of the specimens five days after doxorubicin injection revealed inflammatory lesions at the injection sites in both groups. In the orbital sinus specimens from the retrobulbar-injected group, fibrosis was evident 25 days after injection. Moreover, while all of the retrobulbar-injected mice (100%) developed nephrotic syndrome, tail vein-injected mice had a significantly lower response rate (66%, p = 0.047, Fisher’s exact test) and exhibited only attenuated features of nephrotic syndrome. It was therefore concluded that doxorubicin administration via either lateral tail vein or retrobulbar sinus injections led to a similar induction of histopathological changes with no effects on the clinical well-being of the mice. However, retrobulbar sinus injections were more efficient for inducing experimental nephrotic syndrome."
1641,SPR 2020,
1642,Authors’ correction for Euro Surveill. 2020;25(17),
1643,A guide to cancer immunotherapy: from T cell basic science to clinical practice,"The T lymphocyte, especially its capacity for antigen-directed cytotoxicity, has become a central focus for engaging the immune system in the fight against cancer. Basic science discoveries elucidating the molecular and cellular biology of the T cell have led to new strategies in this fight, including checkpoint blockade, adoptive cellular therapy and cancer vaccinology. This area of immunological research has been highly active for the past 50 years and is now enjoying unprecedented bench-to-bedside clinical success. Here, we provide a comprehensive historical and biological perspective regarding the advent and clinical implementation of cancer immunotherapeutics, with an emphasis on the fundamental importance of T lymphocyte regulation. We highlight clinical trials that demonstrate therapeutic efficacy and toxicities associated with each class of drug. Finally, we summarize emerging therapies and emphasize the yet to be elucidated questions and future promise within the field of cancer immunotherapy."
1644,Balancing Expediency and Scientific Rigor in Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Development,
1645,Re: Reflections on the COVID-19 Pandemic,
1646,Amantadine and Modafinil as Neurostimulants Following Acute Stroke: A Retrospective Study of Intensive Care Unit Patients,"BACKGROUND/OBJECTIVE: Neurostimulants may improve or accelerate cognitive and functional recovery after intracerebral hemorrhage (ICH), ischemic stroke (IS), or subarachnoid hemorrhage (SAH), but few studies have described their safety and effectiveness in the intensive care unit (ICU). The objective of this study was to describe amantadine and modafinil administration practices during acute stroke care starting in the ICU and to evaluate safety and effectiveness. METHODS: Consecutive adult ICU patients treated with amantadine and/or modafinil following acute non-traumatic IS, ICH, or SAH were evaluated. Neurostimulant administration data were extracted from the electronic medication administration record, including medication (amantadine, modafinil, or both), starting dose, time from stroke to initiation, and whether the neurostimulant was continued at hospital discharge. Patients were considered responders if they met two of three criteria within 9 days of neurostimulant initiation: increase in Glasgow coma scale (GCS) score ≥ 3 points from pre-treatment baseline, improved wakefulness or participation documented in caregiver notes, or clinical improvement documented in physical or occupational therapy notes. Potential confounders of the effectiveness assessment and adverse drug effects were also recorded. RESULTS: A total of 87 patients were evaluable during the 3.7-year study period, including 41 (47%) with ICH, 29 (33%) with IS, and 17 (20%) with SAH. The initial neurostimulant administered was amantadine in 71 (82%) patients, modafinil in 13 (15%), or both in 3 (3%) patients. Neurostimulants were initiated a median of 7 (4.25, 12.75) days post-stroke (range 1–27 days) for somnolence (77%), not following commands (32%), lack of eye opening (28%), or low GCS (17%). The most common starting dose was 100 mg twice daily for both amantadine (86%) and modafinil (54%). Of the 79 patients included in the effectiveness evaluation, 42 (53%) were considered responders, including 34/62 (55%) receiving amantadine monotherapy and 8/24 (33%) receiving both amantadine and modafinil at the time they met the definition of a responder. No patient receiving modafinil monotherapy was considered a responder. The median time from initiation to response was 3 (2, 5) days. Responders were more frequently discharged home or to acute rehabilitation compared to non-responders (90% vs 62%, p = 0.006). Among survivors, 63/72 (88%) were prescribed a neurostimulant at hospital discharge. The most common potential adverse drug effect was sleep disruption (16%). CONCLUSIONS: Neurostimulant administration during acute stroke care may improve wakefulness. Future controlled studies with a neurostimulant administration protocol, prospective evaluation, and discretely defined response and safety criteria are needed to confirm these encouraging findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-020-00986-4) contains supplementary material, which is available to authorized users."
1647,Dynamical footprints enable detection of disease emergence,"Developing methods for anticipating the emergence or reemergence of infectious diseases is both important and timely; however, traditional model-based approaches are stymied by uncertainty surrounding the underlying drivers. Here, we demonstrate an operational, mechanism-agnostic detection algorithm for disease (re-)emergence based on early warning signals (EWSs) derived from the theory of critical slowing down. Specifically, we used computer simulations to train a supervised learning algorithm to detect the dynamical footprints of (re-)emergence present in epidemiological data. Our algorithm was then challenged to forecast the slowly manifesting, spatially replicated reemergence of mumps in England in the mid-2000s and pertussis post-1980 in the United States. Our method successfully anticipated mumps reemergence 4 years in advance, during which time mitigation efforts could have been implemented. From 1980 onwards, our model identified resurgent states with increasing accuracy, leading to reliable classification starting in 1992. Additionally, we successfully applied the detection algorithm to 2 vector-transmitted case studies, namely, outbreaks of dengue serotypes in Puerto Rico and a rapidly unfolding outbreak of plague in 2017 in Madagascar. Taken together, these findings illustrate the power of theoretically informed machine learning techniques to develop early warning systems for the (re-)emergence of infectious diseases."
1648,An immunoassay cassette with a handheld reader for HIV urine testing in point-of-care diagnostics,"Currently, most HIV tests are performed with blood samples, or alternatively saliva samples are used for HIV testing. Simple HIV tests need to be performed in hospitals or other medical agencies instead of more invasive HIV blood tests. To enable point-of-care (POC) HIV diagnostics, based on a recently developed lateral flow strip for HIV urine testing, a microfluidic immunoassay cassette with a handheld optical reader is developed. Based on lateral flow strip with gold colloid reporter, the integrated immunoassay cassette can perform sample introduction, metering, discharging, applying and detection which simplifies HIV testing. An indicator is incorporated into the cassette to guide sample introduction based on color change, and further, the excess test sample is stored inside the sealed cassette to avoid any contamination. The low-cost handheld optical reader can provide a test result within a few seconds, which is useful for simple, sensitive and affordable HIV onsite detection. Instead of using normal white LEDs, a customized back light module embedded with green LEDs is adopted to illuminate the lateral flow strip with an appropriate working current to achieve optimal performance. Compared to the standard lateral flow strips using a benchtop reader, with the disposable immunoassay cassette assisted by the handheld optical reader, more convenient, easier-to-operate, and more affordable HIV urine testing can be achieved in POC diagnostics."
1649,"Rotavirus infection in children in Southeast Asia 2008–2018: disease burden, genotype distribution, seasonality, and vaccination","BACKGROUND: Rotaviruses (RVs) are recognized as a major cause of acute gastroenteritis (AGE) in infants and young children worldwide. Here we summarize the virology, disease burden, prevalence, distribution of genotypes and seasonality of RVs, and the current status of RV vaccination in Southeast Asia (Cambodia, Indonesia, Lao People’s Democratic Republic, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam) from 2008 to 2018. METHODS: Rotavirus infection in Children in Southeast Asia countries was assessed using data from Pubmed and Google Scholars. Most countries in Southeast Asia have not yet introduced national RV vaccination programs. We exclude Brunei Darussalam, and Timor Leste because there were no eligible studies identified during that time. RESULTS: According to the 2008–2018 RV surveillance data for Southeast Asia, 40.78% of all diarrheal disease in children were caused by RV infection, which is still a major cause of morbidity and mortality in children under 5 years old in Southeast Asia. Mortality was inversely related to socioeconomic status. The most predominant genotype distribution of RV changed from G1P[8] and G2P[4] into the rare and unusual genotypes G3P[8], G8P[8], and G9P[8]. Although the predominat strain has changed, but the seasonality of RV infection remains unchanged. One of the best strategies for decreasing the global burden of the disease is the development and implementation of effective vaccines. CONCLUSIONS: The most predominant genotype distribution of RV was changed time by time. Rotavirus vaccine is highly cost effective in Southeast Asian countries because the ratio between cost per disability-adjusted life years (DALY) averted and gross domestic product (GDP) per capita is less than one. These data are important for healthcare practitioners and officials to make appropriate policies and recommendations about RV vaccination."
1650,Reply,
1651,Promoting best practice in nucleotide sequence data sharing,"Today, Scientific Data is refining its standards for new submissions describing nucleic acid sequence data."
1652,Prospective avenues for human population genomics and disease mapping in southern Africa,"Population substructure within human populations is globally evident and a well-known confounding factor in many genetic studies. In contrast, admixture mapping exploits population stratification to detect genotype–phenotype correlations in admixed populations. Southern Africa has untapped potential for disease mapping of ancestry-specific disease risk alleles due to the distinct genetic diversity in its populations compared to other populations worldwide. This diversity contributes to a number of phenotypes, including ancestry-specific disease risk and response to pathogens. Although the 1000 Genomes Project significantly improved our understanding of genetic variation globally, southern African populations are still severely underrepresented in biomedical and human genetic studies due to insufficient large-scale publicly available data. In addition to a lack of genetic data in public repositories, existing software, algorithms and resources used for imputation and phasing of genotypic data (amongst others) are largely ineffective for populations with a complex genetic architecture such as that seen in southern Africa. This review article, therefore, aims to summarise the current limitations of conducting genetic studies on populations with a complex genetic architecture to identify potential areas for further research and development."
1653,Pediatric Palliative Care: An Innovative Approach to Pediatric Care for Children With Life-Threatening Conditions,
1654,Comparative genomics of Streptococcus parauberis: new target for molecular identification of serotype III,"ABSTRACT: This paper describes the predicted structure for the cps loci involved in capsule biosynthesis for Streptococcus parauberis serotypes III, IV, and V. Based on the specific serotype regions I, II, and III, a multiplex PCR protocol (mPCR) was designed to differentiate the main serotypes causing fish diseases. A real-time PCR method (qPCR) is also described to identify S. parauberis of serotype III in bacterial cultures and fish tissues. In silico and in vitro analyses revealed that both methods have a 100% specificity. The mPCR assay was optimized for the detection of S. parauberis strains of subtypes Ia (amplicon size 213 bp), subtypes Ib and Ic (both amplicon size 303 bp), serotype II (amplicon size 403 bp), and serotype III (amplicon size 130 bp) from bacterial cultures. The qPCR assay was optimized for the identification and quantification of S. parauberis serotype III strains in bacterial cultures and fish tissues. This assay achieved a sensitivity of 2.67 × 10(2) gene copies (equivalent to 3.8 × 10(−9) ng/μl) using pure bacterial cultures of S. parauberis serotype III and 1.76 × 10(2) gene copies in fish tissues experimentally and naturally infected with S. parauberis of the serotype III. The specificity and sensitivity of the protocols described in this study suggest that these methods could be used for diagnostic and/or epidemiological purposes in clinical diagnostic laboratories. KEY POINTS: • Structure of loci cps for S. parauberis of serotypes III, IV and V was described. • mPCR to differentiate S. parauberis serotypes causing disease in fish was optimized. • qPCR assay to quantify strains of S. parauberis serotype III in fish tissues. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-020-10683-z) contains supplementary material, which is available to authorized users."
1655,Correspondence regarding recently published editorial: ‘Will children reveal their secret? The coronavirus dilemma’,"When individuals without prior immunity are considered, case fatality ratios are typically higher in adults than in children for most infectious diseases, with few exceptions."
1656,Continuous positive airway pressure in children with severe pneumonia: a meta-analysis,
1657,An overview of management of intracranial hypertension in the intensive care unit,"Intracranial hypertension (IH) is a clinical condition commonly encountered in the intensive care unit, which requires immediate treatment. The maintenance of normal intracranial pressure (ICP) and cerebral perfusion pressure in order to prevent secondary brain injury (SBI) is the central focus of management. SBI can be detected through clinical examination and invasive and non-invasive ICP monitoring. Progress in monitoring and understanding the pathophysiological mechanisms of IH allows the implementation of targeted interventions in order to improve the outcome of these patients. Initially, general prophylactic measures such as patient’s head elevation, fever control, adequate analgesia and sedation depth should be applied immediately to all patients with suspected IH. Based on specific indications and conditions, surgical resection of mass lesions and cerebrospinal fluid drainage should be considered as an initial treatment for lowering ICP. Hyperosmolar therapy (mannitol or hypertonic saline) represents the cornerstone of medical treatment of acute IH while hyperventilation should be limited to emergency management of life-threatening raised ICP. Therapeutic hypothermia could have a possible benefit on outcome. To control elevated ICP refractory to maximum standard medical and surgical treatment, at first, high-dose barbiturate administration and then decompressive craniectomy as a last step are recommended with unclear and probable benefit on outcomes, respectively. The therapeutic strategy should be based on a staircase approach and be individualized for each patient. Since most therapeutic interventions have an uncertain effect on neurological outcome and mortality, future research should focus on both studying the long-term benefits of current strategies and developing new ones."
1658,Corneal donation for research versus for transplantation: A-year prospective study of acceptance rates in a French University Hospital,"Fresh corneal donation is essential for basic and preclinical research, but more unknown to public and the medical teams than donation for transplantation: it may raise concerns. We prospectively compared the acceptance rates and the characteristics of targeted corneal donation for research versus donation for transplantation during one year. The Agence de la Biomédecine authorized us to procure fresh corneas targeted for research, only from the donors with medical contraindications for transplantation, in order not to increase grafts shortage. Three nurses from the hospital coordination team of Saint-Etienne University Hospital, obtained consent for research and transplantation in parallel, screening all intra-hospital deaths cases, following standard protocol to check no refusal from families, despite the French opt-out system. They contacted 127 families for research and 244 for transplantation, in 71% of cases by telephone. Consent was obtained in 62% of cases for research and 54% for transplantation (P = 0.135). The main contraindication for transplantation was the cognitive disorders (66%) followed by the blood cancers (8%). This new specific activity, providing new source of fresh corneas for research immediately usable without any eyebank storage steps, didn’t reduce the number of corneas procured for transplantation versus previous years (P = 0.998). Donors in the research group were 10 years older (P<0.001) without difference regarding endothelial cell quality (P = 0.071), allowing maximal clinical relevance for protocols using these fresh human scientific corneas provided by targeted donation."
1659,Development of a competency profile for professionals involved in infectious disease preparedness and response in the air transport public health sector,"BACKGROUND: Recent infectious disease outbreaks highlight the importance of competent professionals with expertise on public health preparedness and response at airports. The availability of a competency profile for this workforce supports efficient education and training. Although competency profiles for infectious disease control professionals are available, none addresses the complex airport environment. Therefore, the main aim of this study is to develop a competency profile for professionals involved in infectious disease preparedness and response at airports in order to stimulate and direct further education and training. METHODS: We developed the competency profile through the following steps: 1) extraction of competencies from relevant literature, 2) assessment of the profile in a national RAND modified Delphi study with an interdisciplinary expert group (n = 9) and 3) assessment of the profile in an international RAND modified Delphi study with an airport infectious disease management panel of ten European countries (n = 10). RESULTS: We systematically studied two competency profiles on infectious disease control and three air transport guidelines on event management, and extracted 61 relevant competencies for airports. The two RAND modified Delphi procedures further refined the profile, mainly by specifying a competency’s target group, the organizational level it should be present on, and the exact actions that should be mastered. The final profile, consisting of 59 competencies, covers the whole process from infectious disease preparedness, through the response phase and the recovery at airports. CONCLUSION: We designed a profile to support training and exercising the multidisciplinary group of professionals in infectious disease management in the airport setting, and which is ready for use in practice. The many adaptations and adjustments that were needed to develop this profile out of existing profiles and air transport guidelines suggest that other setting-specific profiles in infectious disease control are desirable."
1660,"Knowledge, Attitudes, and Interactions with Chaplains and Nursing Staff Outcomes: A Survey Study","We conducted a cross-sectional survey of nursing staff (n = 51) in an academic hospital finding a significant inverse relationship between the frequency of chaplaincy interaction and perceived stress (r = − 0.27, p = 0.05). We also found a significant positive relationship between rated importance of having a chaplain at the hospital and secondary trauma (r = 0.30, p = 0.03). There was a significant positive relationship between religiosity and rated importance for having a chaplain (r = 0.30, p = 0.03) and rated helpfulness of chaplains (r = 0.32, p = 0.02). Similarly, there was a significant positive relationship between spirituality and average length of conversations with a chaplain, rated importance for having a chaplain, and helpfulness of chaplains (r = 0.32, p = 0.03; r = 0.44, p = 0.001; and r = 0.52, p = 0.0001, respectively). Interaction with chaplains is associated with decreased employee perceived stress for nursing staff who provide care for severely ill patients."
1661,Association between racial discrimination and health-related quality of life and the impact of social relationships,"PURPOSE: Interpersonal racial discrimination is associated with poor health. Social relationships may moderate the impact of discrimination and represent modifiable behaviors that can be targeted by public health interventions. We described citywide associations between self-reported racial discrimination and health-related quality of life among the overall New York City (NYC) adult residential population and by four main race/ethnicity groups and explored whether social relationships moderated health effects of discrimination. METHODS: We analyzed cross-sectional survey data from 2335 adults weighted to be representative of the NYC population. We measured exposures to lifetime interpersonal racial discrimination in nine domains using a modified version of the Experiences of Discrimination scale. We performed unadjusted and adjusted regression analyses on four self-rated health-related quality of life outcomes including general health, physical health, mental health, and limitations from physical or mental health. RESULTS: Overall, 47% [95% CI 44.5, 50.3] of respondents reported having experienced racial discrimination in at least one domain. In the overall population, significant associations with racial discrimination were noted in adjusted models for poor physical health, poor mental health, and limitations by poor physical and mental health. Among those exposed to racial discrimination, the risk of experiencing poor mental health was lower among those who had contact with family or friends outside their household at least once a week, compared with those who had less frequent social contact. CONCLUSION: This study provides evidence that social relationships may moderate the impact of racial discrimination on mental health and should be integrated into health promotion efforts."
1662,Sodium–glucose cotransporter 2 inhibition suppresses HIF-1α-mediated metabolic switch from lipid oxidation to glycolysis in kidney tubule cells of diabetic mice,"Inhibition of sodium–glucose cotransporter 2 (SGLT2) in the proximal tubule of the kidney has emerged as an effective antihyperglycemic treatment. The potential protective role of SGLT2 inhibition on diabetic kidney disease (DKD) and underlying mechanism, however, remains unknown. In this study, metabolic switch was examined using kidney samples from human with diabetes and streptozocin (STZ)-induced experimental mouse model of diabetes treated with or without SGLT2 inhibitor dapagliflozin. Results were further validated using primarily cultured proximal tubule epithelial cells. We found that DKD development and progression to renal fibrosis entailed profound changes in proximal tubule metabolism, characterized by a switch from fatty acid utilization to glycolysis and lipid accumulation, which is associated with the increased expression of HIF-1α. Diabetes-induced tubulointerstitial damage, such as macrophage infiltration and fibrosis, was significantly improved by dapagliflozin. Consistent with the effects of these beneficial interventions, the metabolic disorder was almost completely eliminated by dapagliflozin. The increased level of HIF-1α in renal proximal tubule was nearly nullified by dapagliflozin. Moreover, dapagliflozin protects against glucose-induced metabolic shift in PTCs via inhibiting HIF-1α. It suggests that SGLT2 inhibition is efficient in rectifying the metabolic disorder and may be a novel prevention and treatment strategy for kidney tubule in DKD."
1663,The Negative Implications of Being Tolerated: Tolerance From the Target’s Perspective,"Intergroup toleration is a requirement for living with diversity and actively promoted by local, national, and international bodies. However, although psychological researchers have extensively considered the implications of being discriminated, little is known about the psychological consequences of being tolerated. In this article, we argue that beyond the freedoms implied by tolerance, being “merely” tolerated also implies social identity threats that compromise specific psychological needs (belongingness, esteem, control, certainty). We further consider the psychological consequences of being tolerated at the personal, interpersonal, and intergroup levels and consider factors that may moderate the impact of being tolerated for minority outcomes. Taken together, this work provides the first theoretical argument and overview of what it means to be tolerated by considering the negative implications of toleration in diverse nations."
1664,How short is too short? A randomised controlled trial evaluating short-term existential behavioural therapy for informal caregivers of palliative patients,"BACKGROUND: Informal caregivers of palliative patients show higher levels of depression and distress compared with the general population. Fegg’s (2013) existential behavioural therapy was shortened to two individual 1-h sessions (short-term existential behavioural therapy). AIM: Testing the effectiveness of sEBT on psychological symptoms of informal caregivers in comparison with active control. DESIGN: Randomised controlled trial. SETTING/PARTICIPANTS: Informal caregivers of palliative in-patients. METHODS: The primary outcome was depression; secondary outcomes were anxiety, subjective distress and minor mental disorders, positive and negative affect, satisfaction with life, quality of life and direct health care costs. General linear mixed models allow several measurements per participant and change over time. Reasons for declining the intervention were investigated by Rosenstock’s Health Belief Model. RESULTS: Overall inclusion rate was 41.0%. Data of 157 caregivers were available (63.1% females; mean age: 54.6 years, standard deviation (SD): 14.1); 127 participants were included in the main analysis. Participation in sEBT or active control was not significantly associated with post-treatment depression. Outcomes showed prevailingly significant association with time of investigation. Self-efficacy, scepticism of benefit of the intervention, belief of better coping alone and support by family and friends were significant factors in declining participation in the randomised controlled trial. CONCLUSION: Inclusion rate was tripled compared with a previously evaluated longer EBT group intervention. By shortening the intervention, inclusion rate was traded for effectiveness and the intervention could not impact caregivers’ psychological state. Early integration of sEBT and combination of individual and group setting and further study of the optimal length for caregiver interventions are suggested."
1665,Making Sense of the World: Infant Learning From a Predictive Processing Perspective,"For human infants, the first years after birth are a period of intense exploration—getting to understand their own competencies in interaction with a complex physical and social environment. In contemporary neuroscience, the predictive-processing framework has been proposed as a general working principle of the human brain, the optimization of predictions about the consequences of one’s own actions, and sensory inputs from the environment. However, the predictive-processing framework has rarely been applied to infancy research. We argue that a predictive-processing framework may provide a unifying perspective on several phenomena of infant development and learning that may seem unrelated at first sight. These phenomena include statistical learning principles, infants’ motor and proprioceptive learning, and infants’ basic understanding of their physical and social environment. We discuss how a predictive-processing perspective can advance the understanding of infants’ early learning processes in theory, research, and application."
1666,"The Association Between Adverse Child Health, Psychological, Educational and Social Outcomes, and Nondependent Parental Substance: A Rapid Evidence Assessment","BACKGROUND: Between 5% and 30% of children in high-income countries live with a substance misusing parent, the majority of which is below dependent levels. However, little is understood about the impact of nondependent parental substance misuse upon children. METHODS: We searched the international literature using rigorous systematic methods to identify studies examining parental substance misuse and adverse outcomes in children. The inclusion criteria were cross-sectional, longitudinal, case-control, and cohort studies; of children aged 0–18 years whose parents are high-risk substance misusers; reporting on their health, psychological, substance use, educational, and social outcomes. RESULTS: We identified 36 papers (from 33 unique studies), most of which were assessed as being of medium to high methodological quality (N= 28). Parental nondependent substance misuse was found to be associated with adversity in children, with strong evidence of an association with externalizing difficulties (N = 7 papers, all finding an association) and substance use (N = 23 papers, all finding an association) in adolescents and some evidence of adverse health outcomes in early childhood (N = 6/8 papers finding an association). There is less evidence of an association between parental substance misuse and adverse educational and social outcomes. The body of evidence was largest for parental alcohol misuse, with research examining the impact of parental illicit drug use being limited. CONCLUSION: Methodological limitations restrict our ability to make causal inference. Nonetheless, the prevalence of adverse outcomes in children whose parents are nondependent substance misusers highlights the need for practitioners to intervene with this population before a parent has developed substance dependency."
1667,"Image-Based Marker-Free Screening of GABA(A) Agonists, Antagonists, and Modulators","The ionotropic GABA(A) receptors represent the main target for different groups of widely used drugs having hypnotic and anxiolytic effects. So far, most approaches used to assess GABA activity involve invasive low -throughput electrophysiological techniques or rely on fluorescent dyes, preventing the ability to conduct noninvasive and thus nonperturbing screens. To address this limitation, we have developed an automated marker-free cell imaging method, based on digital holographic microscopy (DHM). This technology allows the automatically screening of compounds in multiple plates without having to label the cells or use special plates. This methodological approach was first validated by screening the GABA(A) receptor expressed in HEK cells using a selection of active compounds in agonist, antagonist, and modulator modes. Then, in a second blind screen of a library of 3041 compounds (mostly composed of natural products), 5 compounds having a specific agonist action on the GABA(A) receptor were identified. The hits validated from this unbiased screen were the natural products muscimol, neurosteroid alphaxalone, and three compounds belonging to the avermectin family, all known for having an agonistic effect on the GABA(A) receptor. The results obtained were exempt from false negatives (structurally similar unassigned hits), and false-positive hits were detected and discarded without the need for performing electrophysiological measurements. The outcome of the screen demonstrates the applicability of our screening by imaging method for the discovery of new chemical structures, particularly regarding chemicals interacting with the ionotropic GABA(A) receptor and more generally with any ligand-gated ion channels and transporters."
1668,Transitioning from dental school,
1669,A lifesaving update for the dental team,
1670,The BDA; together,
1671,More than science,
1672,Oral healthcare workforce planning in post-Brexit Britain,"The terms of the United Kingdom's (UK's) departure from the European Union (EU) are currently being negotiated. It is therefore uncertain exactly what effect they will have on planning the UK's oral healthcare workforce. Nevertheless, as 16% of dentists currently registered with the Genral Dental Council (GDC) have migrated to the UK from EU countries, this factor must be taken into consideration by workforce planners. However, it is far from being the only factor. This opinion piece therefore describes the current numbers of non-UK EU dentists and DCPs registered with the GDC and poses the question 'will they remain in the UK in the future'? It then comments on the current legislation on recognition of non-UK dental qualifications. It goes on to consider the Migration Advisory Committee's recommendation for dental practitioners, the oral healthcare needs of the population of the UK, who could address them and the implications for the Advancing Dental Care project"
1673,A plausible transmission mode,
1674,Redeployment to research?,
1675,A simple pleasure,
1676,Working group publishes rapid review for re-opening dental services,
1677,Progression of specialist trainees,
1678,Adopting an organised and cohesive team-based approach,
1679,'I am excited to start my career as a qualified dentist',
1680,Another way for fractured jaws,
1681,Oral cancer patients,
1682,What will be viable for FDs?,
1683,Prescribing antibiotics for urgent dental care during the pandemic,
1684,DIY ultrasonic scaling,
1685,Webinar popularity,
1686,Orthodontic adjustments,
1687,Structural and molecular analyses of functional epitopes and escape mutants in Japanese encephalitis virus envelope protein domain III,"The Japanese encephalitis virus (JEV) is one of the vector borne causes of encephalitis found in southeastern Asia. This positive single-stranded RNA virus is a member of the Flaviviridae family, which notably includes dengue, tick-borne, West Nile, Zika as well as yellow fever, and transmits to humans by infected mosquitos. The main site of interactions for antibodies against this virus is the envelope protein domain III (ED3). The present report investigates the time-dependent structural and conformational changes of JEV ED3 functional epitopes and escape mutants by computer simulations. The results indicate the presence of significant structural differences between the functional epitopes and the escape mutants. Mutation-induced structural/conformational instabilities of this type can decrease the antibody neutralization activity. Among the different escape mutants studied here, Ser40Lys/Asp41Arg appear to be most unstable, while Ser40Glu/Asp41Leu exhibit the lowest structural variations. The highest level of escape mutation observed in Ser40Lys is linked to the relatively higher values of root mean square deviation/fluctuation found in the molecular dynamics simulation of this protein. Secondary-structure deviations and depletion of H bonding are other contributing factors to the protein’s increased instability. Overall, the proteins with residue 41 mutations are found to be structurally more ordered than those with residue 40 mutations. The detailed time-based structural assessment of the mutant epitopes described here may contribute to the development of novel vaccines and antiviral drugs necessary to defend against future outbreaks of JEV escape mutants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12026-020-09130-y) contains supplementary material, which is available to authorized users."
1688,Successful respiratory management of a Marshall-Smith syndrome patient with a tracheo-innominate artery fistula,"BACKGROUND: Tracheo-innominate artery fistula (TIF) is a life-threatening complication of tracheostomy. We describe perioperative management for innominate artery transection in a case with TIF. CASE PRESENTATION: A 4-year-old Japanese female with Marshal-Smith syndrome presented for management of TIF. She underwent tracheostomy at the age of 3 months and an uncuffed tracheostomy tube was inserted. One month before admission to our hospital, intermittent tracheal bleeding, suggesting TIF, occurred. Although we considered to change to a cuffed endotracheal tube, craniofacial abnormality suggested difficult oral intubation, and there was a possibility of rebleeding. Finally, innominate artery transection was performed under total intravenous anesthesia without changing the tracheostomy tube. Surgery completed uneventfully and she received mechanical ventilation under sedation for a day, followed by weaning without complications. CONCLUSIONS: A cuffed tracheostomy tube should have been inserted before surgery for effective hemostasis against sudden bleeding from TIF even though conversion to oral intubation was difficult."
1689,Assessing the intestinal carriage rates of vancomycin-resistant enterococci (VRE) at a tertiary care hospital in Hungary,"Excessive use of antibiotics contributes to the selection of resistant bacteria and intestinal colonization with multiresistant pathogens poses a risk factor for subsequent infections. The present study assessed vancomycin-resistant enterococci (VRE) carriage rates in patients admitted to our tertiary care hospital. Stool samples sent for routine culturing were screened with vancomycin containing solid or broth enrichment media. VRE isolates were identified with matrix-assisted laser desorption/ionization-time of flight mass spectrometry and antibiotic susceptibilities were tested by E-test. Vancomycin resistance genes were detected by polymerase chain reaction. Medical records of carriers were examined for suspected risk factors for colonization. Altogether 3025 stool specimens were analyzed. Solid media identified a VRE carriage rate of 2.2% while broth enrichment detected 5.8%. Seventy percent of the isolates were Enterococcus faecium. VanB genotype was detected in 38.2%, VanA in 37.3%, VanC1 in 22.6%, and VanC2 in 1.9%. All VRE were sensitive to linezolid, daptomycin, and tigecycline. Collective risk factors for carriage were diabetes, normal flora absence, Clostridioides difficile positivity, longer hospital stay, and advanced age. 78.5% of the carriers received antibiotic therapy which was metronidazole in most cases (47.3%). We recommend regular screening of risk groups such as patients with diabetes, history of recent hospitalization, or former C. difficile infection as an imperative step for preventing VRE dissemination."
1690,Pandemie-Panik: Sollen sich die Patienten einmauern?: Etwas Realismus tut Not,
1691,In Bewegung bleiben …: Editorial,Bei aller Dringlichkeit der Corona-Pandemie und der erforderlichen Fokussierung unserer aktuellen Arbeit leiden Patienten weiterhin an den sog. großen „Volkskrankheiten“ wie koronare Herzerkrankung oder chronische Herzinsuffizienz. Sie müssen von uns weiterhin gut versorgt werden.
1692,Inhaltsverzeichnis,
1693,HZV: Engmaschige Kontrolle von COVID-19-Patienten: Neues Software-Modul,
1694,Pneumonie: CRB-65-Score mit neuem „Plus“,
1695,Nephritis signalisiert schweren Verlauf,
1696,Thinking Beyond HLH: Clinical Features of Patients with Concurrent Presentation of Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy,"Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of excessive immune system activation driven mainly by high levels of interferon gamma. The clinical presentation of HLH can have considerable overlap with other inflammatory conditions. We present a cohort of patients with therapy refractory HLH referred to our center who were found to have a simultaneous presentation of complement-mediated thrombotic microangiopathy (TMA). Twenty-three patients had therapy refractory HLH (13 primary, 4 EVB-HLH, 6 HLH without known trigger). Sixteen (69.6%) met high-risk TMA criteria. Renal failure requiring renal replacement therapy, severe hypertension, serositis, and gastrointestinal bleeding were documented only in patients with HLH who had concomitant complement-mediated TMA. Patients with HLH and without TMA required ventilator support mainly due to CNS symptoms, while those with HLH and TMA had respiratory failure predominantly associated with pulmonary hypertension, a known presentation of pulmonary TMA. Ten patients received eculizumab for complement-mediated TMA management while being treated for HLH. All patients who received the complement blocker eculizumab in addition to the interferon gamma blocker emapalumab had complete resolution of their TMA and survived. Our observations suggest co-activation of both interferon and complement pathways as a potential culprit in the evolution of thrombotic microangiopathy in patients with inflammatory disorders like refractory HLH and may offer novel therapeutic approaches for these critically ill patients. TMA should be considered in children with HLH and multi-organ failure, as an early institution of a brief course of complement blocking therapy in addition to HLH-targeted therapy may improve clinical outcomes in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-020-00789-4) contains supplementary material, which is available to authorized users."
1697,Schwerer Verlauf bei Adipösen,
1698,Universal access to essential health information: accelerating progress towards universal health coverage and other SDG health targets,"The information that people need to protect and manage their own health and the health of those for whom they are responsible is a fundamental element of an effective people-centred healthcare system. Achieving universal health coverage (UHC) requires universal access to essential health information. While it was recently recognised by the World Medical Association, universal access to essential health information is not yet reflected in official monitoring of progress on UHC for the sustainable development goals (SDGs). In this paper, we outline key features that characterise universal access to essential health information and indicate how it is increasingly achievable. We highlight the growing evidence of the impact of wider access to practical and actionable information on health for the public, carers and frontline health workers and provide illustrative, evidence-based, examples of how increasing access to essential health information can accelerate the achievement of UHC and other health targets of the SDGs. The paper ends with an assessment of reasons why universal access to essential health information has not yet been achieved, and an associated call to action to key stakeholders—such as governments, multilaterals, funding bodies, policy-makers, health professionals and knowledge intermediaries—to explicitly recognise the foundational role of universal access to essential health information for achieving UHC and the rest of the health SDGs, to include it in the relevant SDG target and associated monitoring indicators, and to incorporate actions in their own policies and programmes to promote and enable this access."
1699,Could Environment Affect the Mutation of H1N1 Influenza Virus?,"H1N1 subtype influenza A viruses are the most common type of influenza A virus to infect humans. The two major outbreaks of the virus in 1918 and 2009 had a great impact both on human health and social development. Though data on their complete genome sequences have recently been obtained, the evolution and mutation of A/H1N1 viruses remain unknown to this day. Among many drivers, the impact of environmental factors on mutation is a novel hypothesis worth studying. Here, a geographically disaggregated method was used to explore the relationship between environmental factors and mutation of A/H1N1 viruses from 2000–2019. All of the 11,721 geo-located cases were examined and the data was analysed of six environmental elements according to the time and location (latitude and longitude) of those cases. The main mutation value was obtained by comparing the sequence of the influenza virus strain with the earliest reported sequence. It was found that environmental factors systematically affect the mutation of A/H1N1 viruses. Minimum temperature displayed a nonlinear, rising association with mutation, with a maximum ~15 °C. The effects of precipitation and social development index (nighttime light) were more complex, while population density was linearly and positively correlated with mutation of A/H1N1 viruses. Our results provide novel insight into understanding the complex relationships between mutation of A/H1N1 viruses and environmental factors."
1700,Perfectionism Profiles and Motivation to Exercise Based on Self-Determination Theory,"This study complements extant variable-centered research that focus on the relationship between perfectionism and the autonomous and controlled motivation to exercise. A person-centered approach is used for identifying perfectionism profiles as well as analyzing inter-profile differences in terms of the six regulatory styles located on the autonomy-control continuum. A sample of 597 (M(age) = 22.08, SD = 3.33) Ecuadorian undergraduates enrolled in a sport science degree program was employed. Latent Profile Analysis based on two higher-order perfectionism dimensions, Perfectionistic Strivings (PS) and Perfectionistic Concerns (PC), supported a four-class solution: Non-Perfectionists (low PS and PC), Adaptive Perfectionists (high PS and low PC), Maladaptive Perfectionists (high PS and PC), and Moderate Perfectionists (moderate PS and PC). Adaptive Perfectionists obtained the highest means on Intrinsic, Integrated, and Identified regulations. However, these differences where only significant when compared with Moderate Perfectionists, and only in the case of Integrated regulation, in comparison with Non-Perfectionists. In contrast, Maladaptive Perfectionists obtained significantly higher scores on Introjected and External regulations as well as on Amotivation than the other three classes. Results are discussed in light of Self-Determination Theory."
1701,Evolution of the Output–Workforce Relationship in Primary Care Facilities in China from 2009 to 2017,"This study evaluates trends in workforce supply compared with those in the volume of service delivery (output) for basic clinical care (CC) and public health (PH) services from 2009 to 2017 in China. A cross-sectional survey (2018) was combined with retrospective data (2009–2017) from 785 primary care (PC) facilities in six provinces. Measures for the output of clinical care and of public health services were aggregated into a single (weighted) index for both service profiles. The output–workforce relationship was measured by its ratio. Latent class growth analysis and logistic regression analysis were applied to classify trajectories and determine associations with facility-level, geographic, and economic characteristics. From 2009 to 2017, the proportion of PC to overall healthcare workforce decreased from 24.25% to 18.57%; the proportion of PH to PC providers at PC facilities increased from 23.6% to 29.5%, while the proportion of PH output increased from 44.3% to 65.9%. Four trajectories of the output–workforce relationship were identified for CC, and five trajectories for PH services of which 85.3% of the facilities showed initially increasing and then slightly decreasing trends. Geographic characteristics impacted different trajectories. The PC workforce falls behind hospital workforce. The expansion in workload of PH services is unbalanced with that of workforce."
1702,Digital Undergraduate Education in Dentistry: A Systematic Review,"The aim of this systematic review was to investigate current penetration and educational quality enhancements from digitalization in the dental curriculum. Using a modified PICO strategy, the literature was searched using PubMed supplemented with a manual search to identify English-language articles published between 1994 and 2020 that reported the use of digital techniques in dental education. A total of 211 articles were identified by electronic search, of which 55 articles were selected for inclusion and supplemented with 27 additional publications retrieved by manual search, resulting in 82 studies that were included in the review. Publications were categorized into five areas of digital dental education: Web-based knowledge transfer and e-learning, digital surface mapping, dental simulator motor skills (including intraoral optical scanning), digital radiography, and surveys related to the penetration and acceptance of digital education. This review demonstrates that digitalization offers great potential to revolutionize dental education to help prepare future dentists for their daily practice. More interactive and intuitive e-learning possibilities will arise to stimulate an enjoyable and meaningful educational experience with 24/7 facilities. Augmented and virtual reality technology will likely play a dominant role in the future of dental education."
1703,"Kaizen–Kata, a Problem-Solving Approach to Public Service Health Care in Mexico. A Multiple-Case Study","Purpose: Mexico’s public hospitals are experiencing major operational problems which seriously affect the care of Mexican citizens. Some hospitals have initiated efforts to apply the Kaizen philosophy to improve this situation. Therefore, the purpose of this article is to analyze the methodological impact of Kaizen–Kata implementation in Mexican public hospitals that have tried to solve operational problems using this improvement approach. Design/Methodology/Approach: The service organization implemented Kaizen–Kata methodology in order to improve one operational problem-process in health care. A case-study approach was used in this research in order to understand the effects of the Kaizen–Kata methodology in solving problems in their operational procedures. Findings: Six specific drivers were identified when applying the Kaizen–Kata methodology. Furthermore, the impact on the levels of implementation of the Kaizen–Kata methodology in each of the improvement teams studied was also identified. Research Limitations: The main limitation of the research is that only three case-studies are presented thus it is not possible to generalize its results. Practical Implications (Where Possible): Other public hospitals can use this specific example as a working guide to solve the operational problems of health systems. Originality/Value: A methodology of continuous improvement in manufacturing was imported from the industry sector for application in an operational health care process. The Kaizen–Kata methodology contributed significantly to improving issues involving delays, customer complaints, process reworks and extra-cost, among other effects of operational problems."
1704,Developments of Riboswitches and Toehold Switches for Molecular Detection—Biosensing and Molecular Diagnostics,"Riboswitches and toehold switches are considered to have potential for implementation in various fields, i.e., biosensing, metabolic engineering, and molecular diagnostics. The specific binding, programmability, and manipulability of these RNA-based molecules enable their intensive deployments in molecular detection as biosensors for regulating gene expressions, tracking metabolites, or detecting RNA sequences of pathogenic microorganisms. In this review, we will focus on the development of riboswitches and toehold switches in biosensing and molecular diagnostics. This review introduces the operating principles and the notable design features of riboswitches as well as toehold switches. Moreover, we will describe the advances and future directions of riboswitches and toehold switches in biosensing and molecular diagnostics."
1705,Recent advances in the understanding of trimeric autotransporter adhesins,"Adhesion is the initial step in the infection process of gram-negative bacteria. It is usually followed by the formation of biofilms that serve as a hub for further spread of the infection. Type V secretion systems engage in this process by binding to components of the extracellular matrix, which is the first step in the infection process. At the same time they provide protection from the immune system by either binding components of the innate immune system or by establishing a physical layer against aggressors. Trimeric autotransporter adhesins (TAAs) are of particular interest in this family of proteins as they possess a unique structural composition which arises from constraints during translocation. The sequence of individual domains can vary dramatically while the overall structure can be very similar to one another. This patchwork approach allows researchers to draw conclusions of the underlying function of a specific domain in a structure-based approach which underscores the importance of solving structures of yet uncharacterized TAAs and their individual domains to estimate the full extent of functions of the protein a priori. Here, we describe recent advances in understanding the translocation process of TAAs and give an overview of structural motifs that are unique to this class of proteins. The role of BpaC in the infection process of Burkholderia pseudomallei is highlighted as an exceptional example of a TAA being at the centre of infection initiation."
1706,Immunogenicity of trimeric autotransporter adhesins and their potential as vaccine targets,"The current problem of increasing antibiotic resistance and the resurgence of numerous infections indicate the need for novel vaccination strategies more than ever. In vaccine development, the search for and the selection of adequate vaccine antigens is the first important step. In recent years, bacterial outer membrane proteins have become of major interest, as they are the main proteins interacting with the extracellular environment. Trimeric autotransporter adhesins (TAAs) are important virulence factors in many Gram-negative bacteria, are localised on the bacterial surface, and mediate the first adherence to host cells in the course of infection. One example is the Neisseria adhesin A (NadA), which is currently used as a subunit in a licensed vaccine against Neisseria meningitidis. Other TAAs that seem promising vaccine candidates are the Acinetobacter trimeric autotransporter (Ata), the Haemophilus influenzae adhesin (Hia), and TAAs of the genus Bartonella. Here, we review the suitability of various TAAs as vaccine candidates."
1707,Recent Advances in the Chemical Synthesis and Evaluation of Anticancer Nucleoside Analogues,"Nucleoside analogues have proven to be highly successful chemotherapeutic agents in the treatment of a wide variety of cancers. Several such compounds, including gemcitabine and cytarabine, are the go-to option in first-line treatments. However, these materials do have limitations and the development of next generation compounds remains a topic of significant interest and necessity. Herein, we discuss recent advances in the chemical synthesis and biological evaluation of nucleoside analogues as potential anticancer agents. Focus is paid to 4′-heteroatom substitution of the furanose oxygen, 2′-, 3′-, 4′- and 5′-position ring modifications and the development of new prodrug strategies for these materials."
1708,"Phenylpyrazalopyrimidines as Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, and Molecular Simulations","N1-(α,β-Alkene)-substituted phenylpyrazolopyrimidine derivatives with acetyl and functionalized phenyl groups at α- and β-positions, respectively, were synthesized by the reaction of 3-phenylpyrazolopyrimidine (PhPP) with bromoacetone, followed by a chalcone reaction with differently substituted aromatic aldehydes. The Src kinase enzyme assay revealed modest inhibitory activity (half maximal inhibitory concentration, IC(50) = 21.7–192.1 µM) by a number of PhPP derivatives. Antiproliferative activity of the compounds was evaluated on human leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), breast carcinoma (MDA-MB-231), and colon adenocarcinoma (HT-29) cells in vitro. 4-Chlorophenyl carbo-enyl substituted 3-phenylpyrazolopyrimidine (10) inhibited the cell proliferation of HT-29 and SK-OV-3 by 90% and 79%, respectively, at a concentration of 50 µM after 96 h incubation. The compound showed modest inhibitory activity against c-Src (IC(50) = 60.4 µM), Btk (IC(50) = 90.5 µM), and Lck (IC(50) = 110 µM), while it showed no activity against Abl1, Akt1, Alk, Braf, Cdk2, and PKCa. In combination with target selection and kinase profiling assay, extensive theoretical studies were carried out to explore the selectivity behavior of compound 10. Specific interactions were also explored by examining the changing trends of interactions of tyrosine kinases with the phenylpyrazolopyrimidine derivative. The results showed good agreement with the experimental selectivity pattern among c-Src, Btk, and Lck."
1709,COVID-19 in Brazil: “So what?”,
1710,COVID-19: remaking the social contract,
1711,Index of biochemical reviews,
1712,Factors Influencing Atypical Clinical Presentations during the 2017 Madagascar Pneumonic Plague Outbreak: A Prospective Cohort Study,"In late 2017, Madagascar experienced a large urban outbreak of pneumonic plague, the largest outbreak to date this century. During the outbreak, there were widespread reports of plague patients presenting with atypical symptoms, such as prolonged duration of illness and upper respiratory tract symptoms. Reported mortality among plague cases was also substantially lower than that reported in the literature (25% versus 50% in treated patients). A prospective multicenter observational study was carried out to investigate potential reasons for these atypical presentations. Few subjects among our cohort had confirmed or probable plague, suggesting that, in part, there was overdiagnosis of plague cases by clinicians. However, 35% subjects reported using an antibiotic with anti-plague activity before hospital admission, whereas 55% had antibiotics with anti-plague activity detected in their serum at admission. Although there may have been overdiagnosis of plague by clinicians during the outbreak, the high frequency of community antibiotic may partly explain the relatively few culture-positive sputum samples during the outbreak. Community antibiotic use may have also altered the clinical presentation of plague patients. These issues make accurate detection of patients and the development of clinical case definitions and triage algorithms in urban pneumonic plague outbreaks difficult."
1713,Caveolar communication with xenobiotic-stalled ribosomes compromises gut barrier integrity,"In response to internal and external insults, the intestinal lining undergoes various types of epithelial adaptation or pathologic distress via stress-responsive eIF2α kinase signaling and subsequent cellular reprogramming. As a vital platform for growth factor-linked adaptive signaling, caveolae were evaluated for epithelial modulation of the insulted gut. Patients under ulcerative insult displayed enhanced expression of caveolin-1, the main structural component of caveolae, which was positively associated with expression of protein kinase R (PKR), the ribosomal stress-responsive eIF2α kinase. PKR-linked biological responses were simulated in experimental gut models of ribosome-inactivating stress using mice and Caenorhabditis elegans. Caveolar activation counteracted the expression of wound-protective epidermal growth factor receptor (EGFR) and its target genes, such as chemokines that were pivotal for epithelial integrity in the ribosome-inactivated gut. Mechanistic findings regarding ribosomal inactivation-associated disorders in the gut barrier provide crucial molecular evidence for detrimental caveolar actions against EGFR-mediated epithelial protection in patients with IBD."
1714,Worldwide Experiences in Disaster Medicine Education,
1715,La mascarilla (que tanto necesitamos es la que hubiéramos necesitado)(),
1716,"Eliminating HCV: a marathon, not a sprint",
1717,Remembering Stephen Schwartz,
1718,Reviving the US CDC,
1719,Operational Considerations in Emergency Radiology,
1720,Coronavirus disease 2019: achieving good mental health during social isolation,"The coronavirus disease 2019 pandemic has led to unprecedented disruption to the normal way of life for people around the globe. Social distancing, self-isolation or shielding have been strongly advised or mandated in most countries. We suggest evidence-based ways that people can maintain or even strengthen their mental health during this crisis."
1721,An Asymptomatic Patient with COVID-19,
1722,Supporting your team during a global pandemic,
1723,COVID-19 and changing social norms,
1724,Humor and sympathy in medical practice,"Medical professionals seem to interpret their uses of humor very differently from those outside the medical profession. Nurses and physicians argue that humor is necessary for them to do their jobs well. Many (potential) patients are horrified that they could one day be the butt of their physician’s jokes. The purpose of this paper is to encourage the respectful use of humor in clinical prac-tice, so as to support its importance in medical practice, while simultaneously protecting against its potential abuse. I begin by examining two extremes of supporting or chastising the use of medical humor. I look at these views through the lenses of popular theories of humor to help explain their theoretical bases. In this second section, I explain the emotional aspect of humor as an embodied and embedded transformation of the world. This clarifies the role that humor plays in our daily lives, as well as why the ethical or unethical nature of its use is dependent on context. Third, I address the potential problems in the relationship between humor and clinical sympathy, and how this further affects the relationship between medical professionals and their patients. I conclude by arguing that humor can conflict with clinical sympathy, but this need not be the case. If medical professionals actively engage with clinical sympathy and focus on using humor in a way that is respectful towards their patients, then humor can continue to be a positive force in their lives while still providing the best care for their patients."
1725,Viral delivery of tissue nonspecific alkaline phosphatase diminishes craniosynostosis in one of two FGFR2(C342Y/+) mouse models of Crouzon syndrome,"Craniosynostosis is the premature fusion of cranial bones. The goal of this study was to determine if delivery of recombinant tissue nonspecific alkaline phosphatase (TNAP) could prevent or diminish the severity of craniosynostosis in a C57BL/6 FGFR2(C342Y/+) model of neonatal onset craniosynostosis or a BALB/c FGFR2(C342Y/+) model of postnatal onset craniosynostosis. Mice were injected with a lentivirus encoding a mineral targeted form of TNAP immediately after birth. Cranial bone fusion as well as cranial bone volume, mineral content and density were assessed by micro CT. Craniofacial shape was measured with calipers. Alkaline phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST) activity levels were measured in serum. Neonatal delivery of TNAP diminished craniosynostosis severity from 94% suture obliteration in vehicle treated mice to 67% suture obliteration in treated mice, p<0.02) and the incidence of malocclusion from 82.4% to 34.7% (p<0.03), with no effect on cranial bone in C57BL/6 FGFR2(C342Y/+) mice. In contrast, treatment with TNAP increased cranial bone volume (p< 0.01), density (p< 0.01) and mineral content (p< 0.01) as compared to vehicle treated controls, but had no effect on craniosynostosis or malocclusion in BALB/c FGFR2(C342Y/+) mice. These results indicate that postnatal recombinant TNAP enzyme therapy diminishes craniosynostosis severity in the C57BL/6 FGFR2(C342Y/+) neonatal onset mouse model of Crouzon syndrome, and that effects of exogenous TNAP are genetic background dependent."
1726,Harnessing the potential of blood donation archives for influenza surveillance and control,"Many blood donation services around the globe maintain large archives of serum and/or plasma specimens of blood donations which could potentially be used for serologic surveillance and risk assessment of influenza. Harnessing this potential requires robust evidence that the outcomes of influenza serology in plasma, which is rarely used, is consistent with that in serum, which is the conventional choice of specimens for influenza serology. We harvested EDTA-plasma specimens from the blood donation archives of Hong Kong Red Cross Transfusion Services, where EDTA is the type of anticoagulant used for plasma collection, compared their antibody titers and responses to that in serum. Influenza A/H1N1/California/7/2009 and A/H3N2/Victoria/208/2009 were the test strains. Our results showed that antibody titers in 609 matched serum/EDTA-plasma specimens (i.e. obtained from the same donor at the same time) had good agreement inferred by Intraclass Correlation Coefficient, the value of which was 0.82 (95% CI: 0.77–0.86) for hemagglutination inhibition assay and 0.95 (95% CI: 0.93–0.96) for microneutralization assay; seroconversion rates (based on hemagglutination inhibition titers) during the 2010 and 2011 influenza seasons in Hong Kong inferred from paired EDTA-plasma were similar to that inferred from paired sera. Our study provided the proof-of-concept that blood donation archives could be leveraged as a valuable source of longitudinal blood specimens for the surveillance, control and risk assessment of both pandemic and seasonal influenza."
1727,Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma,"BACKGROUND: A pilot study of stereotactic body radiation therapy (SBRT) followed by high-dose interleukin-2 (IL-2) showed a higher than anticipated objective response rate (ORR) among patients with metastatic melanoma (MM). We performed a prospective randomized study to determine if the ORR of SBRT + IL-2 was greater than IL-2 monotherapy in patients with advanced melanoma. METHODS: Patients with MM who had adequate physiological reserve for IL-2 and at least one site suitable for SBRT were eligible. There was a 1:1 randomization to SBRT + IL-2 or IL-2 monotherapy. Patients received one or two doses of SBRT (20 Gy per fraction) with the last dose administered 3 days before starting the first cycle of IL-2. IL-2 (600,000 IU per kg via intravenous bolus infusion) was given every 8 hours for a maximum of 14 doses with a second cycle after a 2-week rest. Responding patients received up to six IL-2 cycles. Patients assigned to IL-2 monotherapy who exhibited progression of melanoma after cycle 2 were allowed to crossover and receive SBRT and additional IL-2. Response Evaluation Criteria in Solid Tumors 1.1 criteria were applied to non-irradiated lesions for response assessment. RESULTS: 44 patients were included in the analysis. The ORR in the SBRT + IL-2 group was 54%: 21% complete response (CR), 33% partial response (PR), 21% stable disease (SD) and 25% progressive disease (PD). The ORR in patients receiving IL-2 monotherapy was 35%: 15% CR, 20% PR, 25% SD and 40% PD. Seven patients assigned to IL-2 subsequently received SBRT + IL-2. One CR and two PRs were observed in the crossover group. There was no difference in progression-free or overall survival (OS). At 5 years the OS was 26% in the SBRT + IL-2 group and 25% in the IL-2 monotherapy group. The disease control rate (DCR) was higher in the SBRT + IL-2 group (75% vs 60%, p=0.34). CONCLUSIONS: SBRT + IL-2 induced more objective responses with a higher DCR compared to IL-2 monotherapy in MM. IL-2 monotherapy resulted in a significantly higher ORR than anticipated. Some patients in the crossover group also achieved objective responses. TRIAL REGISTRATION NUMBER: NCT01416831."
1728,To Petabytes and beyond: recent advances in probabilistic and signal processing algorithms and their application to metagenomics,"As computational biologists continue to be inundated by ever increasing amounts of metagenomic data, the need for data analysis approaches that keep up with the pace of sequence archives has remained a challenge. In recent years, the accelerated pace of genomic data availability has been accompanied by the application of a wide array of highly efficient approaches from other fields to the field of metagenomics. For instance, sketching algorithms such as MinHash have seen a rapid and widespread adoption. These techniques handle increasingly large datasets with minimal sacrifices in quality for tasks such as sequence similarity calculations. Here, we briefly review the fundamentals of the most impactful probabilistic and signal processing algorithms. We also highlight more recent advances to augment previous reviews in these areas that have taken a broader approach. We then explore the application of these techniques to metagenomics, discuss their pros and cons, and speculate on their future directions."
1729,"Remdesivir, la esperanza antiviral frente al SARS-CoV-2","On December 31, 2019 a pneumonia outbreak caused by a new coronavirus (SARS-CoV-2) was detected in the city of Wuhan (China). Due to the high capacity of diffusion and human infection it has become a new zoonotic pandemic. The absence of a vaccine has determined the search for antiviral drugs with the capacity to inhibit the replication of the new virus. Among them, remdesivir, an analogue of adenosine, is what seems to have a more promising future. This drug has shown in vitro and in animals a high capacity to block infection and viral replication with attainable concentrations in human plasma. Although all studies have been carried out with SARS-CoV and MERS-CoV, it seems that by virological and functional analogy, remdesivir is one of the few antiviral drugs with proven efficacy. However, studies and clinical trials in humans are required to know the result of their application in them."
1730,Porcine parvovirus nonstructural protein NS1 activates NF-κB and it involves TLR2 signaling pathway,"BACKGROUND: Porcine parvovirus (PPV) is a single-stranded DNA virus that causes porcine reproductive failure. It is of critical importance to study PPV pathogenesis for the prevention and control of the disease. NS1, a PPV non-structural protein, is participated in viral DNA replication, transcriptional regulation, and cytotoxicity. Our previous research showed that PPV can activate nuclear factor kappa B (NF-κB) signaling pathway and then up-regulate the expression of interleukin (IL)-6. OBJECTIVES: Herein, the purpose of this study is to determine whether the non-structural protein NS1 of PPV also has the same function. METHODS: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay, western blot, immunofluorescence assay and small interfering RNA (siRNA) were used. RESULTS: Our findings demonstrated that PPV NS1 protein can up-regulate the expression levels of IL-6 and tumor necrosis factor-alpha in a dose-dependent manner. Moreover, PPV NS1 protein was found to induce the phosphorylation of IκBα, then leading to the phosphorylation and nuclear translocation of NF-κB. In addition, the NS1 protein activated the upstream pathways of NF-κB. Meanwhile, TLR2-siRNA assay showed TLR2 plays an important role in the activation of NF-κB signaling pathway induced by PPV-NS1. CONCLUSIONS: These findings indicated that PPV NS1 protein induced the up-regulated of IL-6 expression through activating the TLR2 and NF-κB signaling pathways. In conclusion, these findings provide a new avenue to study the innate immune mechanism of PPV infection."
1731,A safe distance between doctor and patient,
1732,Error in Methods,
1733,The year of the nurse and midwife 2020: activating the potential and power of nursing,
1734,Protecting the psychological well‐being of healthcare providers affected by the COVID‐19 outbreak: Implications for the psychological rescue work of international community,
1735,Does my personal protective equipment really work? A simulation‐based approach,
1736,COVID-19 & the Residency Match: The Added Importance of Mentoring,
1737,Wearing an N95 Respiratory Mask: An Unintended Exercise Benefit?,
1738,Potential Cost Savings With Low-Dose Abiraterone in the United States,
1739,Department of Error,
1740,Radiotherapy in the time of the Coronavirus pandemic: when less is better,
1741,COVID-19 will not leave behind refugees and migrants,
1742,2020 year of the nurse and midwife: Meeting new challenges,
1743,Uneventful course in IBD patients during SARS-CoV-2 outbreak in northern Italy,
1744,Authors' reply,
1745,Ebola virus disease in DR Congo,
1746,Redefining vulnerability in the era of COVID-19,
1747,A tale of two emergencies,
1748,Building bridges in Yemen,
1749,The conference of the future today?,
1750,Editor's perspectives – April 2020,
1751,Feline Leukemia/Sarcoma Viruses and Immunodeficiency,"This chapter discusses the structure feline leukemia virus (FeLV) and pathogenesis of lymphomas and leukemias BY FeLV. FeLV is quite similar to the better-studied murine leukemia viruses in structure and genetic map. The virus particles bud from cytoplasmic membranes into either extracellular spaces or into vacuoles. FeLV has long been considered a typical noncytopathogenic, longlatency leukemia virus based on its behavior in fibroblasts in vitro. Recent evidence suggests that its in vivo behavior in critical target hemolymphatic tissues is as likely to be cytopathic as transforming. The type of FeLV-related disease that occurs and the disease-free interval probably are influenced by viral envelope proteins and glycoproteins and the consequences of proviral integration. FeLV subgroup specificity apparently determines when and what type of disease will occur. The ecotropic FeLV-A is the most frequent subgroup found in pet cats and is transmitted contagiously. Immunosuppression is the most frequent and the most devastating manifestation of FeLV viremia in clinical and experimental studies. It seems that multiple cell types and multiple processes are involved in the development of feline retrovirus-induced immunosuppression. Although no solid evidence is available for the malfunctioning of cat T helper cells because of the paucity of T-cell specific markers, the circumstantial evidence provided thus far indicates an impaired T helper function in FeLV-infected cats similar to that observed in humans infected with HIV. Studies on the pathogenesis of FeLV-induced immunosuppression might provide a valuable mode for a better understanding and means of control of human AIDS."
1752,The evolving landscape around genome editing in agriculture: Many countries have exempted or move to exempt forms of genome editing from GMO regulation of crop plants,The EU and New Zealand are the only legislations where genome‐edited plants are considered and regulated as GMOs while many other countries move to exempt genome‐edited crops.[Image: see text]
1753,Use of Bronchoalveolar Lavage in Humans—Past Necessity and Future Imperative,"Limited bronchoalveolar lavage (BAL) as an extension of fiberoptic bronchoscopy has permitted the recovery of airway-alveolar space cells and soluble substances in the extracellular lining fluid that have been used diagnostically and as research specimens in patients with a variety of lung diseases and in normal subjects for the study of lung host defenses. During the past three decades, use of BAL specimens has stimulated immunologic and cellular research of pulmonary diseases, which has provided significant insight into local host immunity, inflammation, fibrogenesis, asthma mechanisms, and infections. From this research new methods of antifibrotic therapy of interstitial pulmonary fibrosis, for example, have followed. Moreover, BAL applications have greatly enhanced professional interest in the field of pulmonary medicine. This review attempts to analyze the history and impact of BAL, appraise its current status, and assess its future usefulness. Understanding the immunopathogenesis of many lung diseases is predicated on obtaining in situ specimens from affected lung tissue and airways. BAL provides a direct sample that can be compared with an endobronchial or transbronchial biopsy tissue specimen and with cellular and immunologic components in the vascular circulation. Thus, the recovery of BAL fluid and its components involved directly with a disease process or continguous with interstitial tissue permits a much more detailed assessment of new cellular mediators and cytokines participating in the pathologic process. Furthermore, subjecting BAL cells to microarrays of DNA to discern what genes are activated will be one step closer to identifying intracellular processes involved or deranged. Identification of causative factors may solve questions of causation, so that preventive strategies or definitive therapy can be used."
1754,In reply to the Letter to the Editor “Leadership to improve consistency in echocardiography date”,
1755,"Immunolocalization of Disorganized Muscle Protein-1 in Different Life Stages of Human Lymphatic Filariid, Brugia malayi","PURPOSE: We recently identified disorganized muscle protein-1 of Brugia malayi (DIM-1bm) as a vaccine candidate for human lymphatic filariasis. The present study was aimed at investigating the localization of DIM-1bm in the life-stages of B. malayi to identify the tissue target of vaccine action. METHODS: Recombinant DIM-1bm (rDIM-1bm) was prepared and antibodies were raised in BALB/c mice. Immunoblots of SDS-PAGE resolved B. malayi infective 3rd stage larvae (L(3)) and adult worm antigens and rDIM-1bm were prepared and reacted with anti-rDIM-1bm sera. Sections of adult female worms and whole-mount preparations of L(3) and microfilariae (mf) were stained by immunofluorescence using rDIM-1bm antibodies and Alexa Fluor 488 labeled secondary antibodies, and examined under a confocal microscope. RESULTS: Immunofluorescence staining showed that DIM-1bm is localized mainly in the subcuticular muscle layer in the L(3) and the adult worms; no fluorescent signal could be detected in mf. CONCLUSION: The localization of DIM-1bm in the parasites’ muscle layer suggests that the immunoprophylactic efficacy of DIM-1 is evidently due to immobilization of the parasite and its subsequent immune elimination."
1756,Human genetics and malaria resistance,"Malaria has been the pre-eminent cause of early mortality in many parts of the world throughout much of the last five thousand years and, as a result, it is the strongest force for selective pressure on the human genome yet described. Around one third of the variability in the risk of severe and complicated malaria is now explained by additive host genetic effects. Many individual variants have been identified that are associated with malaria protection, but the most important all relate to the structure or function of red blood cells. They include the classical polymorphisms that cause sickle cell trait, α-thalassaemia, G6PD deficiency, and the major red cell blood group variants. More recently however, with improving technology and experimental design, others have been identified that include the Dantu blood group variant, polymorphisms in the red cell membrane protein ATP2B4, and several variants related to the immune response. Characterising how these genes confer their effects could eventually inform novel therapeutic approaches to combat malaria. Nevertheless, all together, only a small proportion of the heritable component of malaria resistance can be explained by the variants described so far, underscoring its complex genetic architecture and the need for continued research."
1757,The role of diagnostic laparoscopy for trauma at a high-volume level one center,"BACKGROUND: The role of minimally invasive surgery in trauma has continued to evolve over the past 20 years. Diagnostic laparoscopy (DL) has become increasingly utilized for the diagnosis and management of both blunt and penetrating injuries. OBJECTIVE: While the safety and feasibility of laparoscopy has been established for penetrating thoracoabdominal trauma, it remains a controversial tool for other injury patterns due to the concern for complications and missed injuries. We sought to examine the role of laparoscopy for the initial management of traumatic injuries at our urban Level 1 trauma center. METHODS: All trauma patients who underwent DL for blunt or penetrating trauma between 2009 and 2018 were retrospectively reviewed. Demographic data, indications for DL, injuries identified, rate of conversion to open surgery, and outcomes were evaluated. RESULTS: A total of 316 patients were included in the cohort. The mean age was 34.9 years old (± 13.7), mean GCS 14 (± 3), and median ISS 10 (4–18). A total of 110/316 patients (35%) sustained blunt injury and 206/316 patients (65%) sustained penetrating injury. Indications for DL included evaluation for peritoneal violation (152/316, 48%), free fluid without evidence of solid organ injury (52/316, 16%), evaluation of bowel injury (42/316, 13%), and evaluation for diaphragmatic injury (35/316, 11%). Of all DLs, 178/316 (56%) were negative for injury requiring intervention, which was 58% of blunt cases and 55% of penetrating cases. There were no missed injuries noted. Average hospital length of stay was significantly shorter for patients that underwent DL vs conversion to open exploration (2.2 days vs. 4.5 days, p < 0.05). CONCLUSION: In this single institution, retrospective study, the high volume of cases appears to show that DL is a reliable tool for detecting injury and avoiding potential negative or non-therapeutic laparotomies. However, when injuries were present, the high rate of conversion to open exploration suggests that its utility for therapeutic intervention warrants further study."
1758,Accuracy of a multiparametric score based on pulse wave analysis for prediction of fluid responsiveness: ancillary analysis of an observational study,"PURPOSE: The pressure recording analytical method (PRAM) monitor is a non-invasive pulse contour cardiac output (CO) device that cannot be considered interchangeable with the gold standard for CO estimation. It, however, generates additional hemodynamic indices that need to be evaluated. Our objective was to investigate the performance of a multiparametric predictive score based on a combination of several parameters generated by the PRAM monitor to predict fluid responsiveness. METHODS: Secondary analysis of a prospective observational study from April 2016 to December 2017 in two French teaching hospitals. We included critically ill patients who were monitored by esophageal Doppler monitoring and an invasive arterial line, and received a 250–500 mL crystalloid fluid challenge. The main outcome measure was the predictive score discrimination evaluated by the area under the receiver operating characteristics curve. RESULTS: The three baseline PRAM-derived parameters associated with fluid responsiveness in univariate analysis were pulse pressure variation, cardiac cycle efficiency, and arterial elastance (P < 0.01, P = 0.03, and P < 0.01, respectively). The median [interquartile range] predictive score, calculated after discretization of these parameters according to their optimal threshold value was 3 [2–3] in fluid responders and 1 [1–2] in fluid non-responders, respectively (P < 0.001). The area under the curve of the predictive score was 0.807 (95% confidence interval, 0.662 to 0.909; P < 0.001). CONCLUSION: A multiparametric score combining three parameters generated by the PRAM monitor can predict fluid responsiveness with good positive and negative predictive values in intensive care unit patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12630-020-01736-y) contains supplementary material, which is available to authorized users."
1759,Outcomes of Paraesophageal Hernia Repair: Analysis of the Veterans Affairs Surgical Quality Improvement Program Database,"BACKGROUND: While there have been many outcome studies on paraesophageal hernia repair in the civilian population, there is sparse recent data on the veteran population. This study analyzes the mortality and morbidities of veterans who underwent paraesophageal hernia repair in the Veterans Affairs Surgical Quality Improvement Program database. METHODS: Veterans who underwent paraesophageal hernia repair from 2010 to 2017 were identified using Current Procedural Terminology codes. Multivariable analysis was used to compare laparoscopic and open, including abdominal and thoracic approaches, groups. The outcomes were postoperative complications and mortality. RESULTS: There were 1607 patients in the laparoscopic group and 366 in the open group, with 84.1% men and mean age of 61 years. Gender and body mass index did not influence the type of surgical approach. The mortality rates at 30 and 180 days were 0.5% and 0.7%, respectively. Postoperative complications, including reintubation (2.2%), pneumonia (2.0%), intubation > 48 h (2.0%), and sepsis (2.0%) were higher in the open group (15.9% versus 7.2%, p < 0.001). The laparoscopic group had a significantly shorter length of stay (4.3 versus 9.6 days, p < 0.001) and a lower percentage of return to surgery within 30 days (3.9% versus 8.2%, p < 0.001) than the open group. The ratio of open versus laparoscopic paraesophageal hernia repairs varied significantly by different Veterans Integrated Services Network regions. CONCLUSIONS: Veterans undergoing laparoscopic paraesophageal hernia repair experience similar outcomes as patients in the private sector. Veterans who underwent laparoscopic paraesophageal hernia repair had significantly less complications compared to an open approach even after adjusting for patient comorbidities and demographics. The difference in open versus laparoscopic practices between various regions requires further investigation."
1760,Transformation of medical education in uncertainty,
1761,Our new feature: Narrative Medicine,
1762,Addendum to: Risk Stratification and Personal Protective Equipment Use in Pediatric Endoscopy During the COVID-19 Outbreak: A Single-center Protocol,
1763,Long-range movements coupled with heterogeneous incubation period sustain dog rabies at the national scale in Africa,"Dog-transmitted rabies is responsible for more than 98% of human cases worldwide, remaining a persistent problem in developing countries. Mass vaccination targets predominantly major cities, often compromising disease control due to re-introductions. Previous work suggested that areas neighboring cities may behave as the source of these re-introductions. To evaluate this hypothesis, we introduce a spatially explicit metapopulation model for rabies diffusion in Central African Republic. Calibrated on epidemiological data for the capital city, Bangui, the model predicts that long-range movements are essential for continuous re-introductions of rabies-exposed dogs across settlements, eased by the large fluctuations of the incubation period. Bangui’s neighborhood, instead, would not be enough to self-sustain the epidemic, contrary to previous expectations. Our findings suggest that restricting long-range travels may be very efficient in limiting rabies persistence in a large and fragmented dog population. Our framework can be applied to other geographical contexts where dog rabies is endemic."
1764,"Measles outbreak amplified in a pediatric ward: Lyantonde District, Uganda, August 2017","BACKGROUND: Measles is a highly infectious viral disease. In August 2017, Lyantonde District, Uganda reported a measles outbreak to Uganda Ministry of Health. We investigated the outbreak to assess the scope, factors facilitating transmission, and recommend control measures. METHODS: We defined a probable case as sudden onset of fever and generalized rash in a resident of Lyantonde, Lwengo, or Rakai Districts from 1 June-30 September 2017, plus ≥1 of the following: coryza, conjunctivitis, or cough. A confirmed case was a probable case with serum positivity of measles-specific IgM. We conducted a neighborhood- and age-matched case-control study to identified exposure factors, and used conditional logistic regression to analyze the data. We estimated vaccine effectiveness and vaccination coverage. RESULTS: We identified 81 cases (75 probable, 6 confirmed); 4 patients (4.9%) died. In the case-control study, 47% of case-patients and 2.3% of controls were hospitalized at Lyantonde Hospital pediatric department for non-measles conditions 7–21 days before case-patient’s onset (OR(adj) = 34, 95%CI: 5.1–225). Estimated vaccine effectiveness was 95% (95%CI: 75–99%) and vaccination coverage was 76% (95%CI: 68–82%). During the outbreak, an “isolation” ward was established inside the general pediatric ward where there was mixing of both measles and non-measles patients. CONCLUSIONS: This outbreak was amplified by nosocomial transmission and facilitated by low vaccination coverage. We recommended moving the isolation ward outside of the building, supplemental vaccination, and vaccinating pediatric patients during measles outbreaks."
1765,Targeting Intrinsically Disordered Proteins through Dynamic Interactions,"Intrinsically disordered proteins (IDPs) are over-represented in major disease pathways and have attracted significant interest in understanding if and how they may be targeted using small molecules for therapeutic purposes. While most existing studies have focused on extending the traditional structure-centric drug design strategies and emphasized exploring pre-existing structure features of IDPs for specific binding, several examples have also emerged to suggest that small molecules could achieve specificity in binding IDPs and affect their function through dynamic and transient interactions. These dynamic interactions can modulate the disordered conformational ensemble and often lead to modest compaction to shield functionally important interaction sites. Much work remains to be done on further elucidation of the molecular basis of the dynamic small molecule–IDP interaction and determining how it can be exploited for targeting IDPs in practice. These efforts will rely critically on an integrated experimental and computational framework for disordered protein ensemble characterization. In particular, exciting advances have been made in recent years in enhanced sampling techniques, Graphic Processing Unit (GPU)-computing, and protein force field optimization, which have now allowed rigorous physics-based atomistic simulations to generate reliable structure ensembles for nontrivial IDPs of modest sizes. Such de novo atomistic simulations will play crucial roles in exploring the exciting opportunity of targeting IDPs through dynamic interactions."
1766,Serum Metabolomics Revealed the Differential Metabolic Pathway in Calves with Severe Clinical Diarrhea Symptoms,"SIMPLE SUMMARY: The present study focuses on the metabolic changes in the diarrhea of calves, which are manifested with the following symptoms: a thin water-like stool, cold ears and nose, throbbing bowels, oliguria, a pale or yellowish complexion, a smooth mouth, and a slow pulse. The differential metabolic pathways in calves with diarrhea were screened by metabolomics. There were nine biomarkers in the serum of healthy calves and calves with diarrhea. On the basis of these biomarkers, their associated mineral absorption, protein digestion and absorption, and other metabolic pathways, the targeted regulation of the metabolic differences of calves with diarrhea may contribute to the diagnosis, treatment, and discussion of the mechanism of calf diarrhea. ABSTRACT: The complex etiology, higher morbidity and mortality, poor prognosis, and expensive cost of calf diarrhea have made it a catastrophic disease in the dairy industry. This study aims to assess the biomarkers in calves with diarrhea and to predict the biomarkers related to the pathway. As subjects, nine calves with diarrhea and nine healthy calves were enrolled, according to strict enrollment criteria. The serum metabolites were detected by a liquid chromatographic tandem mass spectrometry (LC-MS/MS), and then analyzed by online multivariate statistical analysis software to further screen the biomarkers. In addition, the biomarkers involved in the metabolic pathways of calves with diarrhea and healthy calves were analyzed. In the serum of calves with diarrhea, nine biomarkers were found to which several biomarkers exhibited a certain relation. Moreover, these biomarkers were involved in important metabolic pathways, including protein digestion and absorption, ABC transporters, aminoacyl-tRNA biosynthesis, mineral absorption, and fatty acid biosynthesis. All these findings suggested that the imbalance of these markers was closely related to the occurrence and development of calf diarrhea. The targeted regulation of metabolic pathways involved in these biomarkers may facilitate the diagnosis, treatment, and discussion of the mechanism of calf diarrhea."
1767,Study of the Metabolomics of Equine Preovulatory Follicular Fluid: A Way to Improve Current In Vitro Maturation Media,"SIMPLE SUMMARY: Commercial in vitro embryo production in horses by ICSI (intracytoplasmic sperm injection) is currently used to produce embryos clinically. However, the successful pregnancy and foaling rates obtained after ICSI are only 10% of the oocytes matured in vitro. Conditions used for oocyte in vitro maturation are not optimized for equine oocytes. Hence, in the present work, we aimed to elucidate the major metabolites present in equine preovulatory follicular fluid obtained from postmortem mares using proton nuclear magnetic resonance spectroscopy ((1)H-NMR). Twenty-two metabolites were identified; among these, nine of them are not included in the composition of in vitro maturation media. Hence, our data suggest that the currently used media for equine oocyte maturation can be further improved. ABSTRACT: Production of equine embryos in vitro is currently a commercial technique and a reliable way of obtaining offspring. In order to produce those embryos, immature oocytes are retrieved from postmortem ovaries or live mares by ovum pick-up (OPU), matured in vitro (IVM), fertilized by intracytoplasmic sperm injection (ICSI), and cultured until day 8–10 of development. However, at best, roughly 10% of the oocytes matured in vitro and followed by ICSI end up in successful pregnancy and foaling, and this could be due to suboptimal IVM conditions. Hence, in the present work, we aimed to elucidate the major metabolites present in equine preovulatory follicular fluid (FF) obtained from postmortem mares using proton nuclear magnetic resonance spectroscopy ((1)H-NMR). The results were contrasted against the composition of the most commonly used media for equine oocyte IVM: tissue culture medium 199 (TCM-199) and Dulbecco’s modified eagle medium/nutrient mixture F-12 Ham (DMEM/F-12). Twenty-two metabolites were identified in equine FF; among these, nine of them are not included in the composition of DMEM/F-12 or TCM-199 media, including (mean ± SEM): acetylcarnitine (0.37 ± 0.2 mM), carnitine (0.09 ± 0.01 mM), citrate (0.4 ± 0.04 mM), creatine (0.36 ± 0.14 mM), creatine phosphate (0.36 ± 0.05 mM), fumarate (0.05 ± 0.007 mM), glucose-1-phosphate (6.9 ± 0.4 mM), histamine (0.25 ± 0.01 mM), or lactate (27.3 ± 2.2 mM). Besides, the mean concentration of core metabolites such as glucose varied (4.3 mM in FF vs. 5.55 mM in TCM-199 vs. 17.5 mM in DMEM/F-12). Hence, our data suggest that the currently used media for equine oocyte IVM can be further improved."
1768,Epidemiology of firearm injuries in a Scandinavian trauma center,"BACKGROUND: There is a concern that civilian gunshot injuries in Europe are increasing but there is a lack of contemporary studies. The purpose of this study was to investigate the current epidemiology and outcome of firearm injuries. METHODS: Retrospective cohort study of all patients (n = 235) treated for firearm injuries admitted to a Scandinavian trauma center between 2005 and 2016. Local and national trauma registries were used for data collection. RESULTS: Mean age was 31.3 years (SD ± 12.9; range 16–88 years); 93.6% males; mean ISS was 14.3 (SD ± 15.9); 31.9% (75/235) had ISS > 15. There was a significant increase in penetrating trauma (P < 0.001) and firearm injuries (P < 0.001) over the years. The most common anatomical location of firearm injury was the lower extremity, (n = 138/235; 38%), followed by the abdomen (n = 69;19%), upper extremity (n = 53;15%), chest (n = 50; 14%), and head and neck (n = 50; 14%). Ninety patients (38.3%) had more than one anatomic injury location. There were in total 360 firearm injuries and 168 major surgical procedures were performed. 53% (n = 125) of patients underwent at least one surgical procedure. The most common procedures were fracture surgery 42% (n = 70/168), followed by laparotomy 30%% (n = 51), chest tube 17% (n = 29), and thoracotomy 11% (n = 18). Forty-one patients (17%) had at least one major vascular injury (n = 54). The most common vascular injury was lower extremity vessel injuries, 26/54 (48%), followed by vessels in chest and abdomen. There was a significant increase in vascular injuries during the study period (P < 0.006). The 30-day mortality was 12.8% (n = 30); 24 patients died within 24 h mainly due to injuries to the chest and the head and neck region. CONCLUSIONS: Firearm injuries cause significant morbidity and mortality and are an important medical and public health problem. In a Scandinavian trauma center there has been an increase of firearm injuries in recent years. The lower extremities followed by the abdomen are the dominating injured regions and there has been an increase in associated vascular injuries."
1769,Antiedematogenic and Anti-Inflammatory Activity of the Monoterpene Isopulegol and Its β-Cyclodextrin (β-CD) Inclusion Complex in Animal Inflammation Models,"Isopulegol (ISO) is an alcoholic monoterpene widely found in different plant species, such as Melissa officinalis, and has already been reported to have a number of pharmacological properties. Like other terpenes, ISO is a highly volatile compound that is slightly soluble in water, so its inclusion into cyclodextrins (CDs) is an interesting approach to increase its solubility and bioavailability. Thus, our aim was to evaluate the antiedematogenic and anti-inflammatory activity of isopulegol and a β-cyclodextrin–isopulegol inclusion complex (ISO/β-CD) in rodent models. For the anti-inflammatory activity evaluation, antiedematogenic plethysmometry and acute (peritonitis and pleurisy), as well as chronic (cotton pellet-induced granuloma) anti-inflammatory models, were used. The docking procedure is used to evaluate, analyze, and predict their binding mode of interaction with H1 and Cox-2 receptors. The animals (n = 6) were divided into groups: ISO and ISO/β-CD, negative control (saline), and positive control (indomethacin and promethazine). ISO and ISO/β-CD were able to reduce acute inflammatory activity by decreasing albumin extravasation, leukocyte migration, and MPO concentration, and reducing exudate levels of IL-1β and TNF-α. ISO and ISO/β-CD significantly inhibited edematogenic activity in carrageenan- and dextran-induced paw edema. Moreover, both significantly reduced chronic inflammatory processes, given the lower weight and protein concentration of granulomas in the foreign body granulomatous inflammation model. The results suggest that the inclusion of ISO in β-cyclodextrins improves its pharmacological properties, with the histamine and prostaglandin pathways as probable mechanisms of inhibition, and also reinforces the anti-inflammatory profile of this terpene."
1770,EDEM1 Drives Misfolded Protein Degradation via ERAD and Exploits ER-Phagy as Back-Up Mechanism When ERAD Is Impaired,"Endoplasmic reticulum (ER)-associated degradation (ERAD) is the main mechanism of targeting ER proteins for degradation to maintain homeostasis, and perturbations of ERAD lead to pathological conditions. ER-degradation enhancing α-mannosidase-like (EDEM1) was proposed to extract terminally misfolded proteins from the calnexin folding cycle and target them for degradation by ERAD. Here, using mass-spectrometry and biochemical methods, we show that EDEM1 is found in auto-regulatory complexes with ERAD components. Moreover, the N-terminal disordered region of EDEM1 mediates protein–protein interaction with misfolded proteins, whilst the absence of this domain significantly impairs their degradation. We also determined that overexpression of EDEM1 can induce degradation, even when proteasomal activity is severely impaired, by promoting the formation of aggregates, which can be further degraded by autophagy. Therefore, we propose that EDEM1 maintains ER homeostasis and mediates ERAD client degradation via autophagy when either dislocation or proteasomal degradation are impaired."
1771,Ophthalmology of clinically normal alpacas (Vicugna pacos) in the United Kingdom: a cross-sectional study,"BACKGROUND: Alpacas are being more frequently presented to veterinarians in the UK. It is important to validate whether published normal ocular parameters are consistent with the alpaca population in the UK. METHODS: Ophthalmic examinations were performed on healthy alpacas (Vicugna pacos) from three farms in East Anglia, UK. RESULTS: On direct ophthalmoscopy of 35 alpacas, there was a 50 per cent prevalence of opacities within the lens in alpacas older than two years old (n=8/16). There was a 36.8 per cent prevalence of persistent hyaloid arteries in alpacas under two years old (n=7/19). The mean Schirmer tear test-1 value was 20.0 ±6 mm/minute (n=40). The mean intraocular pressure measured by rebound tonometry was 17.2 ±5.5 mmHg (n=46), and applanation tonometry resulted in statistically similar values (P=0.30; n=25). There was a significant variation in intraocular pressure throughout a 24-hour period (n=8). Fluorescein dye was not detected at the nostrils of any of the alpacas which underwent a Jones test to assess nasolacrimal duct patency (n=8). CONCLUSION: The ophthalmic findings appear largely consistent with previously published values from North America and continental Europe. Variations include the large range of measurements obtained and evidence of diurnal variation in intraocular pressure."
1772,Characterising keratometry in different dog breeds using an automatic handheld keratometer,"BACKGROUND: Keratometry is clinically important and is routinely performed as part of human ophthalmic examination. In veterinary ophthalmology, little is known about keratometry in dogs, and its practical application has been limited. The present study aimed to describe keratometry in some dog breeds popular in Japan using a handheld keratometer. METHODS: Client-owned dogs of various signalment were enrolled prospectively in the keratometry examination. Interbreed variations in mean corneal curvatures (R1R2avg) and corneal astigmatism (Δ(R1−R2)) were evaluated statistically with respect to their bodyweight based on the data which fulfilled the predetermined inclusion criteria. P<0.05 was considered statistically significant. RESULTS: On examination of 237 dogs from 16 different breeds, R1R2avg (mean±sd) ranged from 7.54±0.30 mm in Pomeranians to 9.28±0.19 mm in golden retrievers. Δ(R1−R2) (mean±sd) ranged from 0.22±0.11 mm in miniature schnauzers to 0.57±0.30 mm in French bulldogs. CONCLUSION: The present study successfully described keratometry in 16 dog breeds. The study revealed considerable interbreed variations in both R1R2avg and Δ(R1−R2), which did not necessarily correlate with bodyweight. These results are useful both clinically in fitting contact lenses in the management of corneal diseases and non-clinically in optometric studies in dogs."
1773,Identification of the MAPK Cascade and its Relationship with Nitrogen Metabolism in the Green Alga Chlamydomonas reinhardtii,"The mitogen activated protein kinases (MAPKs) form part of a signaling cascade through phosphorylation reactions conserved in all eukaryotic organisms. The MAPK cascades are mainly composed by three proteins, MAPKKKs, MAPKKs and MAPKs. Some signals induce MAPKKK-mediated phosphorylation and activation of MAPKK that phosphorylate and activate MAPK. Afterward, MAPKs can act either in the cytoplasm or be imported into the nucleus to activate other proteins or transcription factors. In the green microalga Chlamydomonas reinhardtii the pathway for nitrogen (N) assimilation is well characterized, yet its regulation still has many unknown features. Nitric oxide (NO) is a fundamental signal molecule for N regulation, where nitrate reductase (NR) plays a central role in its synthesis. The MAPK cascades could be regulating N assimilation, since it has been described that the phosphorylation of NR by MAPK6 promotes NO production in Arabidopsis thaliana. We have identified the proteins involved in the MAPK cascades in Chlamydomonas reinhardtii, finding 17 MAPKs, 2 MAPKKs and 108 MAPKKKs (11 MEKK-, 94 RAF- and 3 ZIK-type) that have been structurally and phylogenetically characterized. The genetic expressions of MAPKs and the MAPKK were slightly regulated by N. However, the genetic expressions of MAPKKKs RAF14 and RAF79 showed a very strong repression by ammonium, which suggests that they may have a key role in the regulation of N assimilation, encouraging to further analyze in detail the role of MAPK cascades in the regulation of N metabolism."
1774,The KOMPACT-P study: Knee Osteoarthritis Management with Physiotherapy informed by Acceptance and Commitment Therapy—Pilot study protocol,"INTRODUCTION: Incidence of total knee arthroplasty (TKA) is projected to rise 276% in 2030, and psychological distress affects up to 42% of people with knee osteoarthritis undergoing TKA, with demonstrated detrimental effects on postoperative outcomes. Few studies have assessed psychological treatment in people awaiting TKA, and these have been psychologist-delivered treatments. No evidence exists regarding psychologically-informed interventions delivered by health professionals currently embedded in TKA clinical pathways. The primary aim of this pilot study is to explore the safety, acceptability and feasibility of the Knee Osteoarthritis Management with Physiotherapy informed by Acceptance and Commitment Therapy (KOMPACT) approach in people awaiting TKA. METHODS AND ANALYSIS: 51 community-dwelling adults scheduled for a primary TKA at two hospitals will be recruited to this pilot, mixed-methods, prospective randomised controlled trial with assessor blinding. Participants will be randomised in a 1:2 ratio to either usual care (education class) or usual care plus KOMPACT (2 hours 20 min of preoperative physiotherapy informed by Acceptance and Commitment Therapy). Our primary outcome measures are safety (length of stay, complications and psychological health after KOMPACT), acceptability (treatment credibility and qualitative data) and feasibility (recruitment, retention and intervention fidelity) of the KOMPACT approach. Secondary outcomes include health service outcomes, patient-reported physical and psychological outcomes, and physical performance measures. Quantitative data collection was conducted at baseline, 1–2 weeks before TKA, 6 weeks after TKA and 6 months after TKA. Qualitative data collection is 1–2 weeks before TKA. Data analysis will take a quantitative-led approach with triangulation after thematic analysis of the qualitative data. ETHICS AND DISSEMINATION: This study has full ethics approval (HREC/18/WMEAD/440). Results from this study will be published in peer-reviewed journals and presented at local and international conferences. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trials Registry (ACTRN12618001867280p)."
1775,Targeting the C-Terminal Domain Small Phosphatase 1,"The human C-terminal domain small phosphatase 1 (CTDSP1/SCP1) is a protein phosphatase with a conserved catalytic site of DXDXT/V. CTDSP1’s major activity has been identified as dephosphorylation of the 5th Ser residue of the tandem heptad repeat of the RNA polymerase II C-terminal domain (RNAP II CTD). It is also implicated in various pivotal biological activities, such as acting as a driving factor in repressor element 1 (RE-1)-silencing transcription factor (REST) complex, which silences the neuronal genes in non-neuronal cells, G1/S phase transition, and osteoblast differentiation. Recent findings have denoted that negative regulation of CTDSP1 results in suppression of cancer invasion in neuroglioma cells. Several researchers have focused on the development of regulating materials of CTDSP1, due to the significant roles it has in various biological activities. In this review, we focused on this emerging target and explored the biological significance, challenges, and opportunities in targeting CTDSP1 from a drug designing perspective."
1776,Development of a Portable SPR Sensor for Nucleic Acid Detection,"Nucleic acid detection is of great significance in clinical diagnosis, environmental monitoring and food safety. Compared with the traditional nucleic acid amplification detection method, surface plasmon resonance (SPR) sensing technology has the advantages of being label-free, having simple operation, and providing real-time detection. However, the angle scanning system in many SPR angle modulation detection applications usually requires a high-resolution stepper motor and complex mechanical structure to adjust the angle. In this paper, a portable multi-angle scanning SPR sensor was designed. The sensor only uses one stepping motor to rotate a belt, and the belt pulls the mechanical linkages of incident light and reflected light to move in opposite directions for achieving the SPR angle scanning mode that keeps the incident angle and reflected angle equal. The sensor has an angle scanning accuracy of 0.002°, response sensitivity of 3.72 × 10(−6) RIU (refractive index unit), and an angle scanning range of 30°–74°. The overall size of the system is only 480 mm × 150 mm × 180 mm. The portable SPR sensor was used to detect nucleic acid hybridization on a gold film chip modified with bovine serum albumin (BSA). The result revealed that the sensor had high sensitivity and fast response, and could successfully accomplish the hybridization detection of target DNA solution of 0.01 μmol/mL."
1777,Impact and Diagnostic Gaps of Comprehensive Genomic Profiling in Real-World Clinical Practice,"Purpose: next-generation sequencing based comprehensive genomic profiling (CGP) is becoming common practice. Although numerous studies have shown its feasibility to identify actionable genomic alterations in most patients, its clinical impact as part of routine management across all cancers in the community remains unknown. Methods: we conducted a retrospective study of all patients that underwent CGP as part of routine cancer management from January 2013 to June 2017 at an academic community-based NCI-designated cancer center. CGP was done in addition to established first tier reflex molecular testing as per national guidelines (e.g., EGFR/ALK for non-small cell lung cancer (NSCLC) and extended-RAS for colorectal cancer). Results: 349 tests were sent for CGP from 333 patients and 95% had at least one actionable genomic alteration reported. According to the reported results, 23.2% had a Food and Drug Administration (FDA) approved therapy available, 61.3% had an off-label therapy available and 77.9% were potentially eligible for a clinical trial. Treatment recommendations were also reviewed within the OncoKB database and 47% of them were not clinically validated therapies. The CGP results led to treatment change in only 35 patients (10%), most commonly in NSCLC. Nineteen of these patients (54% of those treated and 5% of total) had documented clinical benefit with targeted therapy. Conclusion: we demonstrate that routine use of CGP in the community across all cancer types detects potentially actionable genomic alterations in a majority of patients, however has modest clinical impact enriched in the NSCLC subset."
1778,mRNA stem-loops can pause the ribosome by hindering A-site tRNA binding,"Although the elongating ribosome is an efficient helicase, certain mRNA stem-loop structures are known to impede ribosome movement along mRNA and stimulate programmed ribosome frameshifting via mechanisms that are not well understood. Using biochemical and single-molecule Förster resonance energy transfer (smFRET) experiments, we studied how frameshift-inducing stem-loops from E. coli dnaX mRNA and the gag-pol transcript of Human Immunodeficiency Virus (HIV) perturb translation elongation. We find that upon encountering the ribosome, the stem-loops strongly inhibit A-site tRNA binding and ribosome intersubunit rotation that accompanies translation elongation. Electron cryo-microscopy (cryo-EM) reveals that the HIV stem-loop docks into the A site of the ribosome. Our results suggest that mRNA stem-loops can transiently escape the ribosome helicase by binding to the A site. Thus, the stem-loops can modulate gene expression by sterically hindering tRNA binding and inhibiting translation elongation."
1779,"It’s not you versus us, it’s us versus the virus",
1780,"The case for national standards for the development, management and delivery of interprofessional education",
1781,Mycobacterium bovis: From Genotyping to Genome Sequencing,"Mycobacterium bovis is the main pathogen of bovine, zoonotic, and wildlife tuberculosis. Despite the existence of programs for bovine tuberculosis (bTB) control in many regions, the disease remains a challenge for the veterinary and public health sectors, especially in developing countries and in high-income nations with wildlife reservoirs. Current bTB control programs are mostly based on test-and-slaughter, movement restrictions, and post-mortem inspection measures. In certain settings, contact tracing and surveillance has benefited from M. bovis genotyping techniques. More recently, whole-genome sequencing (WGS) has become the preferential technique to inform outbreak response through contact tracing and source identification for many infectious diseases. As the cost per genome decreases, the application of WGS to bTB control programs is inevitable moving forward. However, there are technical challenges in data analyses and interpretation that hinder the implementation of M. bovis WGS as a molecular epidemiology tool. Therefore, the aim of this review is to describe M. bovis genotyping techniques and discuss current standards and challenges of the use of M. bovis WGS for transmission investigation, surveillance, and global lineages distribution. We compiled a series of associated research gaps to be explored with the ultimate goal of implementing M. bovis WGS in a standardized manner in bTB control programs."
1782,Joint Statement of the Korean Society for Preventive Medicine and the Korean Society of Epidemiology on the response to the COVID-19 outbreak,
1783,Medical Education in Turkey in Time of COVID-19,
1784,Asymptomatic Patients with Novel Coronavirus Disease (COVID-19),
1785,Easy and Accessible Protection against Aerosol Contagion during Airway Management,
1786,The “Uncurated Exposure” of Videoconferencing,
1787,Thinking Outside the Box: A Low-cost and Pragmatic Alternative to Aerosol Boxes for Endotracheal Intubation of COVID-19 Patients,Supplemental Digital Content is available in the text.
1788,Master manipulators: how herpesviruses alter immune responses to RSV,"In this commentary on “A gammaherpesvirus licenses CD8 T cells to protect the host from pneumovirus-induced immunopathologies”, the authors highlight the growing literature suggesting that herpesvirus infections shape subsequent immune responses to other pathogens, especially by broadening CD8+T-cell responses. These observations have implications for vaccine development against other important pathogens, such as Respiratory Syncytial Virus."
1789,Less invasive surfactant administration versus endotracheal surfactant instillation followed by limited peak pressure ventilation in preterm infants with respiratory distress syndrome in China: study protocol for a randomized controlled trial,"BACKGROUND: Less invasive surfactant administration (LISA) is a way of giving surfactant without endotracheal intubation and has shown to be promising in reducing the incidence of bronchopulmonary dysplasia (BPD) in preterm infants. However, the mechanism underlying its beneficial effect and variations in the technique of administration may prevent its widespread use. This trial aims to evaluate the effects of two methods of surfactant administration, LISA or endotracheal surfactant administration followed by low peak pressure (LPPSA) ventilation, in preterm infants with respiratory distress syndrome (RDS). METHODS: The LISA Or Low Peak Pressure trial is to be conducted in 14 tertiary neonatal intensive care units in China. A total of 600 preterm infants born with gestational age between 25(0/7) and 31(6/7) weeks and with a primary diagnosis of RDS will be involved in the study. Infants will be randomized to the LISA or LPPSA group when surfactant therapy is indicated. Primary outcomes include mortality, severity of bronchopulmonary dysplasia at 36 weeks of postmenstrual age (PMA), and mechanical ventilation (MV) in the first 72 h of life. Secondary outcomes include the days of MV, duration of all sorts of non-invasive respiratory support, fraction of inspired oxygen, oxygen saturation before and after surfactant administration, and time required to perform the procedure for surfactant administration. The incidence of comorbidities, including retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), hemodynamically significant patent ductus arteriosus (hsPDA), pneumothorax, and massive pulmonary hemorrhage within 48 h of surfactant administration, and the failure rates of each technique will be determined. DISCUSSION: Data from recent systematic review and meta-analysis have suggested a possible improvement in outcomes of preterm infants with RDS by the LISA technique. However, robust evidence is lacking. Why LISA plays a potential role in reducing respiratory morbidity, mainly BPD in preterm infants, remains unclear. The possible explanations are the active and uninterrupted delivery of continuous positive airway pressure during the LISA procedure and the avoidance of complications caused by intubation and relatively high pressure/volume ventilation following surfactant administration. We hypothesized that LISA’s effectiveness lies mainly in avoiding relatively high-pressure positive ventilation immediately following surfactant administration. Thus, this multicenter randomized controlled trial will focus on issues of endotracheal intubation and the pressure/volume used during conventional surfactant administration. The effectiveness, safety and comorbidities of preterm infants following LISA or LPPSA will be evaluated. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900020970. Registered on 23 January 2019."
1790,Procalcitonin and C-reactive protein perform better than the neutrophil/lymphocyte count ratio in evaluating hospital acquired pneumonia,"BACKGROUND: The relationship between biomarkers and hospital-acquired pneumonia (HAP) is understudied, especially in severe cases admitted to the intensive care unit (ICU). Compared with community-acquired pneumonia (CAP), HAP might have different traits regarding biomarkers due to the previous history in hospitals. METHODS: A total of 593 adult patients were enrolled in this retrospective cohort study to determine the neutrophil/lymphocyte count ratio (NLCR), procalcitonin (PCT), C-reactive protein (CRP) and serum lactate level upon admission to the ICU. According to diagnosis, patients were divided into two groups: non-infection and HAP. Discriminant analysis was performed based on better outcomes of diagnostic performance and severity evaluation. The diagnostic performance of each individual biomarker was assessed by constructing receiver operating characteristic (ROC) curves and calculating the area under each ROC curve (AUROC). Multivariable analysis was also applied to determine the most appropriate prognostic factors. RESULTS: NLCR, PCT and CRP were markedly different between the non-infection and HAP groups. NLCR had a worse ability to discriminate severe infection (AUROC 0.626; 95% CI 0.581–0.671) than conventional markers such as CRP (0.685, 95% CI 0.641–0.730) and PCT (0.661, 95% CI 0.615–0.707). In addition, the AUROC of composite biomarkers, especially the combination of NLCR, CRP and WBC, was significantly greater than that of any single biomarker. CONCLUSIONS: NLCR was not comparable to conventional single biomarkers, such as CRP and PCT, for diagnosing or evaluating the severity of HAP. Composite biomarkers that have good accessibility, especially the combination of NLCR, CRP and WBC, could help with early diagnosis and severity evaluation."
1791,Secretive and close? How sharing secrets may impact perceptions of distance,"Having secrets is incredibly common. However, secrecy has only recently started to receive more attention in research. What has largely been neglected so far are the consequences of secret-sharing for the relationship between sharer and receiver. In this project, we aim to fill this gap. Previous research has shown that closeness can make secret-sharing more likely. Building on research from the self-disclosure and relationship literature, we experimentally investigate whether secret-sharing might in turn increase perceptions of closeness. In addition, we test the valence of the secrets shared as potential driver of the hypothesized effect, as negative secrets might signal a high level of trust, but might also present a burden to the receiver. To provide a holistic picture, we build on a variety of methods to investigate three perspectives: Study 1 focuses on the receiver and tests whether another person sharing secrets (vs. nonconfidential information) decreases distance in the eyes of the receiver. Study 2 investigates lay theories and tests how an observer perceives the relationship between two people who share secrets (vs. nonconfidential information). Study 3 tests whether these lay theories about sharing secrets are predictive of behavior, and how a sharer might choose secrets of negative or positive valence to decrease perceived distance on the receiver’s side. Our results will contribute to the understanding of how sharing secrets affects the way individuals think about each other, how close they feel to each other, and how they interact with each other."
1792,The effectiveness of internal control and innovation performance: An intermediary effect based on corporate social responsibility,"From the perspective of the effectiveness of internal control, this study analyzes the influence of internal control on innovation performance and internal control on corporate social responsibility (CSR), and then analyzes the intermediary effect of CSR between internal control and innovation performance. The results show that the improvement of the effectiveness of internal control has a significant promoting effect on innovation performance, and promotes enterprises to strengthen CSR performance. Meanwhile, CSR activities take a significant intermediary effect in the process of improving innovation performance through internal control. Finally, it is suggested that state-owned enterprises and non-state-owned enterprises should communicate and cooperate, strengthen the construction of internal control system, and improve innovation performance and CSR practices. Furthermore, the intermediary effect of CSR activities in the process of improving innovation performance through internal control should be brought into play, so as to return the expectations and demands of stakeholders."
1793,Epigenetic inheritance of circadian period in clonal cells,"Circadian oscillations are generated via transcriptional-translational negative feedback loops. However, individual cells from fibroblast cell lines have heterogeneous rhythms, oscillating independently and with different period lengths. Here we showed that heterogeneity in circadian period is heritable and used a multi-omics approach to investigate underlying mechanisms. By examining large-scale phenotype-associated gene expression profiles in hundreds of mouse clonal cell lines, we identified and validated multiple novel candidate genes involved in circadian period determination in the absence of significant genomic variants. We also discovered differentially co-expressed gene networks that were functionally associated with period length. We further demonstrated that global differential DNA methylation bidirectionally regulated these same gene networks. Interestingly, we found that depletion of DNMT1 and DNMT3A had opposite effects on circadian period, suggesting non-redundant roles in circadian gene regulation. Together, our findings identify novel gene candidates involved in periodicity, and reveal DNA methylation as an important regulator of circadian periodicity."
1794,Identification of interferon-stimulated genes that attenuate Ebola virus infection,"The West Africa Ebola outbreak was the largest outbreak ever recorded, with over 28,000 reported infections; this devastating epidemic emphasized the need to understand the mechanisms to counteract virus infection. Here, we screen a library of nearly 400 interferon-stimulated genes (ISGs) against a biologically contained Ebola virus and identify several ISGs not previously known to affect Ebola virus infection. Overexpression of the top ten ISGs attenuates virus titers by up to 1000-fold. Mechanistic studies demonstrate that three ISGs interfere with virus entry, six affect viral transcription/replication, and two inhibit virion formation and budding. A comprehensive study of one ISG (CCDC92) that shows anti-Ebola activity in our screen reveals that CCDC92 can inhibit viral transcription and the formation of complete virions via an interaction with the viral protein NP. Our findings provide insights into Ebola virus infection that could be exploited for the development of therapeutics against this virus."
1795,Transcriptome Analysis of Gene Expression Profiles of Tomato Yellow Leaf Curl Virus-Infected Whiteflies over Different Viral Acquisition Access Periods,"Tomato yellow leaf curl virus (TYLCV), which is transmitted by Bemisia tabaci in a persistent-circulative manner, threatens tomato production worldwide. Little is known about the complicated interaction during this process at the molecular level. In this study, viral AAPs at 0 h, 2 h, 6 h, 12 h and 48 h were investigated using a comparative transcriptome analysis to uncover the transcriptional responses of whiteflies to virus infection. Our results have shown that 755, 587, 1140 and 1347 differentially expressed genes (DEGs) were identified in the comparisons of the data of 0 h vs. 2 h, 0 h vs. 6 h, 0 h vs. 12 h and 0 h vs. 48 h, respectively. KEGG analysis showed that DEGs associated with metabolisms and signal transduction were down-regulated in virus-infected whiteflies. Additionally, 16 up-regulated putative transporter genes and 10 down-regulated genes associated with IL-17 signaling pathway were identified by time-associated gene cluster analysis. These data boost our comprehensions on whitefly-TYLCV interactions associated with different viral AAPs."
1796,Drug Resistance Prediction Using Deep Learning Techniques on HIV-1 Sequence Data,"The fast replication rate and lack of repair mechanisms of human immunodeficiency virus (HIV) contribute to its high mutation frequency, with some mutations resulting in the evolution of resistance to antiretroviral therapies (ART). As such, studying HIV drug resistance allows for real-time evaluation of evolutionary mechanisms. Characterizing the biological process of drug resistance is also critically important for sustained effectiveness of ART. Investigating the link between “black box” deep learning methods applied to this problem and evolutionary principles governing drug resistance has been overlooked to date. Here, we utilized publicly available HIV-1 sequence data and drug resistance assay results for 18 ART drugs to evaluate the performance of three architectures (multilayer perceptron, bidirectional recurrent neural network, and convolutional neural network) for drug resistance prediction, jointly with biological analysis. We identified convolutional neural networks as the best performing architecture and displayed a correspondence between the importance of biologically relevant features in the classifier and overall performance. Our results suggest that the high classification performance of deep learning models is indeed dependent on drug resistance mutations (DRMs). These models heavily weighted several features that are not known DRM locations, indicating the utility of model interpretability to address causal relationships in viral genotype-phenotype data."
1797,"Scope, quality, and inclusivity of clinical guidelines produced early in the covid-19 pandemic: rapid review",
1798,Innate Type 2 Responses to Respiratory Syncytial Virus Infection,"Respiratory syncytial virus (RSV) is a common and contagious virus that results in acute respiratory tract infections in infants. In many cases, the symptoms of RSV remain mild, however, a subset of individuals develop severe RSV-associated bronchiolitis. As such, RSV is the chief cause of infant hospitalization within the United States. Typically, the immune response to RSV is a type 1 response that involves both the innate and adaptive immune systems. However, type 2 cytokines may also be produced as a result of infection of RSV and there is increasing evidence that children who develop severe RSV-associated bronchiolitis are at a greater risk of developing asthma later in life. This review summarizes the contribution of a newly described cell type, group 2 innate lymphoid cells (ILC2), and epithelial-derived alarmin proteins that activate ILC2, including IL-33, IL-25, thymic stromal lymphopoietin (TSLP), and high mobility group box 1 (HMGB1). ILC2 activation leads to the production of type 2 cytokines and the induction of a type 2 response during RSV infection. Intervening in this innate type 2 inflammatory pathway may have therapeutic implications for severe RSV-induced disease."
1799,Evaluation of Viral RNA Recovery Methods in Vectors by Metagenomic Sequencing,"Identification and characterization of viral genomes in vectors including ticks and mosquitoes positive for pathogens of great public health concern using metagenomic next generation sequencing (mNGS) has challenges. One such challenge is the ability to efficiently recover viral RNA which is typically dependent on sample processing. We evaluated the quantitative effect of six different extraction methods in recovering viral RNA in vectors using negative tick homogenates spiked with serial dilutions of tick-borne encephalitis virus (TBEV) and surrogate Langat virus (LGTV). Evaluation was performed using qPCR and mNGS. Sensitivity and proof of concept of optimal method was tested using naturally positive TBEV tick homogenates and positive dengue, chikungunya, and Zika virus mosquito homogenates. The amount of observed viral genome copies, percentage of mapped reads, and genome coverage varied among different extractions methods. The developed Method 5 gave a 120.8-, 46-, 2.5-, 22.4-, and 9.9-fold increase in the number of viral reads mapping to the expected pathogen in comparison to Method 1, 2, 3, 4, and 6, respectively. Our developed Method 5 termed ROVIV (Recovery of Viruses in Vectors) greatly improved viral RNA recovery and identification in vectors using mNGS. Therefore, it may be a more sensitive method for use in arbovirus surveillance."
1800,The Obstacle Course of Reperfusion for ST-Segment–Elevation Myocardial Infarction in the COVID-19 Pandemic,
1801,HER2-LAMP vaccines effectively traffic to endolysosomal compartments and generate enhanced polyfunctional T cell responses that induce complete tumor regression,"BACKGROUND: The advent of immune checkpoint blockade antibodies has demonstrated that effective mobilization of T cell responses can cause tumor regression of metastatic cancers, although these responses are heterogeneous and restricted to certain histologic types of cancer. To enhance these responses, there has been renewed emphasis in developing effective cancer-specific vaccines to stimulate and direct T cell immunity to important oncologic targets, such as the oncogene human epidermal growth factor receptor 2 (HER2), expressed in ~20% of breast cancers (BCs). METHODS: In our study, we explored the use of alternative antigen trafficking through use of a lysosome-associated membrane protein 1 (LAMP) domain to enhance vaccine efficacy against HER2 and other model antigens in both in vitro and in vivo studies. RESULTS: We found that inclusion of this domain in plasmid vaccines effectively trafficked antigens to endolysosomal compartments, resulting in enhanced major histocompatibility complex (MHC) class I and II presentation. Additionally, this augmented the expansion/activation of antigen-specific CD4+ and CD8+ T cells and also led to elevated levels of antigen-specific polyfunctional CD8+ T cells. Significantly, vaccination with HER2-LAMP produced tumor regression in ~30% of vaccinated mice with established tumors in an endogenous model of metastatic HER2+ BC, compared with 0% of HER2-WT vaccinated mice. This therapeutic benefit is associated with enhanced tumor infiltration of activated CD4+ and CD8+ T cells. CONCLUSIONS: These data demonstrate the potential of using LAMP-based endolysosomal trafficking as a means to augment the generation of polyfunctional, antigen-specific T cells in order to improve antitumor therapeutic responses using cancer antigen vaccines."
1802,Shear stress activates ADAM10 sheddase to regulate Notch1 via the Piezo1 force sensor in endothelial cells,"Mechanical force is a determinant of Notch signalling but the mechanism of force detection and its coupling to Notch are unclear. We propose a role for Piezo1 channels, which are mechanically-activated non-selective cation channels. In cultured microvascular endothelial cells, Piezo1 channel activation by either shear stress or a chemical agonist Yoda1 activated a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), a Ca(2+)-regulated transmembrane sheddase that mediates S2 Notch1 cleavage. Consistent with this observation, we found Piezo1-dependent increase in the abundance of Notch1 intracellular domain (NICD) that depended on ADAM10 and the downstream S3 cleavage enzyme, γ-secretase. Conditional endothelial-specific disruption of Piezo1 in adult mice suppressed the expression of multiple Notch1 target genes in hepatic vasculature, suggesting constitutive functional importance in vivo. The data suggest that Piezo1 is a mechanism conferring force sensitivity on ADAM10 and Notch1 with downstream consequences for sustained activation of Notch1 target genes and potentially other processes."
1803,Abrogation of PRRSV infectivity by CRISPR-Cas13b-mediated viral RNA cleavage in mammalian cells,"CRISPR/Cas9 enables dsDNA viral genome engineering. However, the lack of RNA targeting activities limits the ability of CRISPR/Cas9 to combat RNA viruses. The recently identified class II type VI CRISPR/Cas effectors (Cas13) are RNA-targeting CRISPR enzymes that enable RNA cleavage in mammalian and plant cells. We sought to knockdown the viral RNA of porcine reproductive and respiratory syndrome virus (PRRSV) directly by exploiting the CRISPR/Cas13b system. Effective mRNA cleavage by CRISPR/Cas13b-mediated CRISPR RNA (crRNA) targeting the ORF5 and ORF7 genes of PRRSV was observed. To address the need for uniform delivery of the Cas13b protein and crRNAs, an all-in-one system expressing Cas13b and duplexed crRNA cassettes was developed. Delivery of a single vector carrying double crRNAs enabled the simultaneous knockdown of two PRRSV genes. Transgenic MARC-145 cells stably expressing the Cas13b effector and crRNA mediated by lentiviral-based transduction showed a robust ability to splice the PRRSV genomic RNA and subgenomic RNAs; viral infection was almost completely abrogated by the combination of double crRNAs simultaneously targeting the ORF5 and ORF7 genes. Our study indicated that the CRISPR/Cas13b system can effectively knockdown the PRRSV genome in vitro and can potentially be used as a potent therapeutic antiviral strategy."
1804,Time series analysis of temporal trends in hemorrhagic fever with renal syndrome morbidity rate in China from 2005 to 2019,"Hemorrhagic fever with renal syndrome (HFRS) is seriously endemic in China with 70%~90% of the notified cases worldwide and showing an epidemic tendency of upturn in recent years. Early detection for its future epidemic trends plays a pivotal role in combating this threat. In this scenario, our study investigates the suitability for application in analyzing and forecasting the epidemic tendencies based on the monthly HFRS morbidity data from 2005 through 2019 using the nonlinear model-based self-exciting threshold autoregressive (SETAR) and logistic smooth transition autoregressive (LSTAR) methods. The experimental results manifested that the SETAR and LSTAR approaches presented smaller values among the performance measures in both two forecasting subsamples, when compared with the most extensively used seasonal autoregressive integrated moving average (SARIMA) method, and the former slightly outperformed the latter. Descriptive statistics showed an epidemic tendency of downturn with average annual percent change (AAPC) of −5.640% in overall HFRS, however, an upward trend with an AAPC = 1.213% was observed since 2016 and according to the forecasts using the SETAR, it would seemingly experience an outbreak of HFRS in China in December 2019. Remarkably, there were dual-peak patterns in HFRS incidence with a strong one occurring in November until January of the following year, additionally, a weak one in May and June annually. Therefore, the SETAR and LSTAR approaches may be a potential useful tool in analyzing the temporal behaviors of HFRS in China."
1805,Antimicrobial resistance and over the counter use of drugs in Nepal,
1806,"Effects of Sterilization With Hydrogen Peroxide and Chlorine Dioxide on the Filtration Efficiency of N95, KN95, and Surgical Face Masks","This quality improvement study examines the effects of sterilization with hydrogen peroxide and chlorine dioxide on the filtration efficiency of N95, KN95, and surgical face masks."
1807,Integrative computational epigenomics to build data-driven gene regulation hypotheses,"BACKGROUND: Diseases are complex phenotypes often arising as an emergent property of a non-linear network of genetic and epigenetic interactions. To translate this resulting state into a causal relationship with a subset of regulatory features, many experiments deploy an array of laboratory assays from multiple modalities. Often, each of these resulting datasets is large, heterogeneous, and noisy. Thus, it is non-trivial to unify these complex datasets into an interpretable phenotype. Although recent methods address this problem with varying degrees of success, they are constrained by their scopes or limitations. Therefore, an important gap in the field is the lack of a universal data harmonizer with the capability to arbitrarily integrate multi-modal datasets. RESULTS: In this review, we perform a critical analysis of methods with the explicit aim of harmonizing data, as opposed to case-specific integration. This revealed that matrix factorization, latent variable analysis, and deep learning are potent strategies. Finally, we describe the properties of an ideal universal data harmonization framework. CONCLUSIONS: A sufficiently advanced universal harmonizer has major medical implications, such as (i) identifying dysregulated biological pathways responsible for a disease is a powerful diagnostic tool; (2) investigating these pathways further allows the biological community to better understand a disease’s mechanisms; and (3) precision medicine also benefits from developments in this area, particularly in the context of the growing field of selective epigenome editing, which can suppress or induce a desired phenotype."
1808,FOMO in the time of coronavirus disease,
1809,"2019 Coronavirus Disease, Beware of Psychogenic Issue",
1810,An easy protective measure in ophthalmology against medical supply shortage,
1811,"Cost–utility analysis of antibiotic treatment in patients with chronic low back pain and Modic changes: results from a randomised, placebo-controlled trial in Norway (the AIM study)","OBJECTIVE: To evaluate the cost–utility of 100 days of antibiotics in patients with chronic low back pain (LBP) and type I or II Modic changes included in the Antibiotic treatment In patients with chronic low back pain and Modic changes (AIM) study. DESIGN: A cost–utility analysis from a societal and healthcare perspective alongside a double-blinded, parallel group, placebo, multicentre trial. SETTING: Hospital outpatient clinics at six hospitals in Norway. The main results from the AIM study showed a small effect in back-related disability in favour of the antibiotics group, and slightly larger in those with type I Modic changes, but this effect was below the pre-defined threshold for clinically relevant effect. PARTICIPANTS: 180 patients with chronic LBP, previous disc herniation and Modic changes type I (n=118) or type II (n=62) were randomised to antibiotic treatment (n=89) or placebo-control (n=91). INTERVENTIONS: Oral treatment with either 750 mg amoxicillin or placebo three times daily for 100 days. MAIN OUTCOME MEASURES: Quality-adjusted life years (QALYs) by EuroQoL-5D over 12 months and costs for healthcare and productivity loss measured in Euro (€1=NOK 10), in the intention-to-treat population. Cost–utility was expressed in incremental cost-effectiveness ratio (ICER). RESULTS: Mean (SD) total cost was €21 046 (20 105) in the amoxicillin group and €19 076 (19 356) in the placebo group, mean difference €1970 (95% CI; −3835 to 7774). Cost per QALY gained was €24 625. In those with type I Modic changes, the amoxicillin group had higher healthcare consumption than the placebo group, resulting in €39 425 per QALY gained. Given these ICERs and a willingness-to-pay threshold of €27 500 (NOK 275 000), the probability of amoxicillin being cost-effective was 51%. Even when the willingness-to-pay threshold increased to €55 000, the probability of amoxicillin being cost-effective was never higher than 53%. CONCLUSIONS: Amoxicillin treatment showed no evidence of being cost-effective for people with chronic LBP and Modic changes during 1-year follow-up. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02323412."
1812,General Anesthesia Recommendations for Electroconvulsive Therapy During the Coronavirus Disease 2019 Pandemic,"Coronavirus disease 2019 is an infectious viral disease first identified in December 2019 in Wuhan, China, and very rapidly spread globally resulting in a pandemic. Common symptoms include fever, cough, and shortness of breath. Although the majority of patients recover, there are still a significant number of patients who progress to respiratory failure, multiorgan failure, and death. The virus is mainly spread during close contact and by small droplets produced by coughing, sneezing, or talking. Because of the highly contagious element and easy spread in a communal living arrangement that exists within an inpatient psychiatric hospitals, the following guidelines were established to improve patient and staff safety while still maintaining efficiency and capability to provide this needed treatment to a subgroup of patients. OBJECTIVE: The objective of this study was to devise a safe and efficient methodology to deliver potential lifesaving electroconvulsive therapy to inpatients during the coronavirus disease 2019 pandemic."
1813,Pulchritudo in Brevitate (Beauty in Brevity): Introducing the Research Letter to Spine,
1814,"In response to a Letter to the Editor of the American Journal of Physical Medicine & Rehabilitation, ID: AJPMR-D-20-00284",
1815,Genomic and phenotypic evolution of Escherichia coli in a novel citrate-only resource environment,"Evolutionary innovations allow populations to colonize new ecological niches. We previously reported that aerobic growth on citrate (Cit(+)) evolved in an Escherichia coli population during adaptation to a minimal glucose medium containing citrate (DM25). Cit(+) variants can also grow in citrate-only medium (DM0), a novel environment for E. coli. To study adaptation to this niche, we founded two sets of Cit(+) populations and evolved them for 2500 generations in DM0 or DM25. The evolved lineages acquired numerous parallel mutations, many mediated by transposable elements. Several also evolved amplifications of regions containing the maeA gene. Unexpectedly, some evolved populations and clones show apparent declines in fitness. We also found evidence of substantial cell death in Cit(+) clones. Our results thus demonstrate rapid trait refinement and adaptation to the new citrate niche, while also suggesting a recalcitrant mismatch between E. coli physiology and growth on citrate."
1816,Spider‐Web‐Inspired PM(0.3) Filters Based on Self‐Sustained Electrostatic Nanostructured Networks,"Particulate matter (PM) pollution has become a serious public health issue, especially with outbreaks of emerging infectious diseases. However, most present filters are bulky, opaque, and show low‐efficiency PM(0.3)/pathogen interception and inevitable trade‐off between PM removal and air permeability. Here, a unique electrospraying–netting technique is used to create spider‐web‐inspired network generator (SWING) air filters. Manipulation of the dynamic of the Taylor cone and phase separation of its ejected droplets enable the generation of 2D self‐charging nanostructured networks on a large scale. The resultant SWING filters show exceptional long‐range electrostatic property driven by aeolian vibration, enabling self‐sustained PM adhesion. Combined with their Steiner‐tree‐structured pores (size 200–300 nm) consisting of nanowires (diameter 12 nm), the SWING filters exhibit high efficiency (>99.995% PM(0.3) removal), low air resistance (<0.09% atmosphere pressure), high transparency (>82%), and remarkable bioprotective activity for biohazard pathogens. This work may shed light on designing new fibrous materials for environmental and energy applications."
1817,Reverse quarantine: Management of COVID‐19 by Kerala with its higher number of aged population,
1818,In Response,
1819,Medical Ethics Versus Healthcare Workers’ Rights: Fight-or-Flee Response,
1820,"Detection of Ciprofloxacin-Resistant, β-Lactamase–Producing Neisseria meningitidis Serogroup Y Isolates — United States, 2019–2020",
1821,Optimizing classical risk scores to predict complications in head and neck surgery: a new approach,"PURPOSE: To validate tools to identify patients at risk for perioperative complications to implement prehabilitation programmes in head and neck surgery (H&N). METHODS: Retrospective cohort including 128 patients submitted to H&N, with postoperative Intermediate Care Unit admittance. The accuracy of the risk calculators ASA, P-POSSUM, ACS-NSQIP and ARISCAT to predict postoperative complications and mortality was assessed. A multivariable analysis was subsequently performed to create a new risk prediction model for serious postoperative complications in our institution. RESULTS: Our 30-day morbidity and mortality were 45.3% and 0.8%, respectively. The ACS-NSQIP failed to predict complications and had an acceptable discrimination ability for predicting death. The discrimination ability of ARISCAT for predicting respiratory complications was acceptable. ASA and P-POSSUM were poor predictors for mortality and morbidity. Our new prediction model included ACS-NSQIP and ARISCAT (area under the curve 0.750, 95% confidence intervals: 0.63–0.87). CONCLUSION: Despite the insufficient value of these risk calculators when analysed individually, we designed a risk tool combining them which better predicts the risk of serious complications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00405-020-06133-1) contains supplementary material, which is available to authorized users."
1822,Department of Error,
1823,Research round-up,
1824,Global governance for COVID-19 vaccines,
1825,ASGCT Meeting Showcases Fast-Paced Development of Gene and Cell Therapy Technologies,
1826,Response to ‘Evaluation of modelling study shows limits of COVID-19 importing risk simulations in sub-Saharan Africa’ (Epidemiology and Infection – HYG-LE-10513-May-20),
1827,Implementing sequence-based antigenic distance calculation into immunological shape space model,"BACKGROUND: In 2009, a novel influenza vaccine was distributed worldwide to combat the H1N1 influenza “swine flu” pandemic. However, antibodies induced by the vaccine display differences in their specificity and cross-reactivity dependent on pre-existing immunity. Here, we present a computational model that can capture the effect of pre-existing immunity on influenza vaccine responses. The model predicts the region of the virus hemagglutinin (HA) protein targeted by antibodies after vaccination as well as the level of cross-reactivity induced by the vaccine. We tested our model by simulating a scenario similar to the 2009 pandemic vaccine and compared the results to antibody binding data obtained from human subjects vaccinated with the monovalent 2009 H1N1 influenza vaccine. RESULTS: We found that both specificity and cross-reactivity of the antibodies induced by the 2009 H1N1 influenza HA protein were affected by the viral strain the individual was originally exposed. Specifically, the level of antigenic relatedness between the original exposure HA antigen and the 2009 HA protein affected antigenic-site immunodominance. Moreover, antibody cross-reactivity was increased when the individual’s pre-existing immunity was specific to an HA protein antigenically distinct from the 2009 pandemic strain. Comparison of simulation data with antibody binding data from human serum samples demonstrated qualitative and quantitative similarities between the model and real-life immune responses to the 2009 vaccine. CONCLUSION: We provide a novel method to evaluate expected outcomes in antibody specificity and cross-reactivity after influenza vaccination in individuals with different influenza HA antigen exposure histories. The model produced similar outcomes as what has been previously reported in humans after receiving the 2009 influenza pandemic vaccine. Our results suggest that differences in cross-reactivity after influenza vaccination should be expected in individuals with different exposure histories."
1828,Walk with a Doc—a Call to Action for Physician-Led Walking Programs,"PURPOSE OF REVIEW: An abundance of data supports the health benefits of physical activity, social connectedness, and spending time outdoors. Yet, a majority of Americans are living lives that are sedentary, lonely, and not connected with nature. We have three primary goals in writing this paper. First, we will review the well-documented health challenges arising from a sedentary, isolated lifestyle. Second, we will discuss the benefits of walking as a primary means of increasing physical activity. Finally, we will shine a light on the exponential success of Walk with a Doc, a national non-profit organization. Walk with a Doc focuses on bringing physician-led enthusiasm into our communities by organizing regular doctor-led walks in the outdoors; as well as Walk with a Future Doc, which encourages medical students to start their own Walk with a Doc programs. RECENT FINDINGS: The Physical Activity Guidelines for Americans share that physical activity is an important action that people of all ages can take to improve their health. These guidelines recommend that adults partake in at least 150 min of moderate aerobic physical activity. Currently, only 23% of Americans are achieving this amount of aerobic activity. In addition, recent data suggest that 3 in 4 people are lonely, a significant social determinant of health. Finally, over half of all Americans spend fewer than 5 h outside each week. Walk with a Doc and Walk with a Future Doc are having an enormous impact on combating the negative effects of these health challenges. An evaluability assessment was completed in 2018 showing Walk with a Doc attendees felt the program increased their physical activity and their social connections, with a majority of Walk with a Doc gatherings occurring in nature. Physicians and other Walk with a Doc program leaders also reported high levels of satisfaction with their participation in Walk with a Doc. SUMMARY: As teammates in this healthcare fight, we are all painfully aware of the crisis on our hands. Of our patients, 70% are overweight or obese, nearly 80% of us are not getting enough physical activity, with all of this leading to billions of dollars in healthcare costs. Adding fuel to the fire, our doctors are burning out because of it. Today, we want to share what we have learned to be an extremely viable solution. The solution has the capacity to save 5 million lives and $68 billion dollars per year. Additionally, it is bolstering the job satisfaction and happiness of our providers. Personally, it turned my life around in 2005, and since then, it is now greater than 560 communities around the USA (and 34 other countries). We call it, simply, Walk with a Doc."
1829,Performance and impact of a multiplex PCR in ICU patients with ventilator-associated pneumonia or ventilated hospital-acquired pneumonia,"BACKGROUND: Early appropriate antibiotic therapy reduces morbidity and mortality of severe pneumonia. However, the emergence of bacterial resistance requires the earliest use of antibiotics with the narrowest possible spectrum. The Unyvero Hospitalized Pneumonia (HPN, Curetis) test is a multiplex PCR (M-PCR) system detecting 21 bacteria and 19 resistance genes on respiratory samples within 5 h. We assessed the performance and the potential impact of the M-PCR on the antibiotic therapy of ICU patients. METHODS: In this prospective study, we performed a M-PCR on bronchoalveolar lavage (BAL) or plugged telescoping catheter (PTC) samples of patients with ventilated HAP or VAP with Gram-negative bacilli or clustered Gram-positive cocci. This study was conducted in 3 ICUs in a French academic hospital: the medical and infectious diseases ICU, the surgical ICU, and the cardio-surgical ICU. A multidisciplinary expert panel simulated the antibiotic changes they would have made if the M-PCR results had been available. RESULTS: We analyzed 95 clinical samples of ventilated HAP or VAP (72 BAL and 23 PTC) from 85 patients (62 males, median age 64 years). The median turnaround time of the M-PCR was 4.6 h (IQR 4.4–5). A total of 90/112 bacteria were detected by the M-PCR system with a global sensitivity of 80% (95% CI, 73–88%) and specificity of 99% (95% CI 99–100). The sensitivity was better for Gram-negative bacteria (90%) than for Gram-positive cocci (62%) (p = 0.005). Moreover, 5/8 extended-spectrum beta-lactamases (CTX-M gene) and 4/4 carbapenemases genes (3 NDM, one oxa-48) were detected. The M-PCR could have led to the earlier initiation of an effective antibiotic in 20/95 patients (21%) and to early de-escalation in 37 patients (39%) but could also have led to one (1%) inadequate antimicrobial therapy. Among 17 empiric antibiotic treatments with carbapenems, 10 could have been de-escalated in the following hours according to the M-PCR results. The M-PCR also led to 2 unexpected diagnosis of severe legionellosis confirmed by culture methods. CONCLUSIONS: Our results suggest that the use of a M-PCR system for respiratory samples of patients with VAP and ventilated HAP could improve empirical antimicrobial therapy and reduce the use of broad-spectrum antibiotics."
1830,A proof of concept phase I/II pilot trial of LSD1 inhibition by tranylcypromine combined with ATRA in refractory/relapsed AML patients not eligible for intensive therapy,"All-trans-retinoic acid (ATRA) is highly active in acute promyelocytic leukemia but not in other types of acute myeloid leukemia (AML). Previously, we showed that ATRA in combination with Lysine-specific demethylase 1 (LSD1) inhibition by tranylcypromine (TCP) can induce myeloid differentiation in AML blasts. This phase I/II clinical trial investigated the safety and efficacy of TCP/ATRA treatment as salvage therapy for relapsed/refractory (r/r) AML. The combination was evaluated in 18 patients, ineligible for intensive treatment. The overall response rate was 20%, including two complete remissions without hematological recovery and one partial response. We also observed myeloid differentiation upon TCP/ATRA treatment in patients who did not reach clinical remission. Median overall survival (OS) was 3.3 months, and one-year OS 22%. One patient developed an ATRA-induced differentiation syndrome. The most frequently reported adverse events were vertigo and hypotension. TCP plasma levels correlated with intracellular TCP concentration. Increased H3K4me1 and H3k4me2 levels were observed in AML blasts and white blood cells from some TCP/ATRA treated patients. Combined TCP/ATRA treatment can induce differentiation of AML blasts and lead to clinical response in heavily pretreated patients with r/r AML with acceptable toxicity. These findings emphasize the potential of LSD1 inhibition combined with ATRA for AML treatment."
1831,Using indirect calorimetry in place of fixed energy prescription was feasible and energy targets were more closely met: do not forget an important limitation,
1832,Lissencephaly in Shih Tzu dogs,"BACKGROUND: Lissencephaly is a brain malformation characterized by smooth and thickened cerebral surface, which may result in structural epilepsy. Lissencephaly is not common in veterinary medicine. Here, we characterize the first cases of lissencephaly in four Shih Tzu dogs, including clinical presentations and findings of magnetic resonance imaging of lissencephaly and several concomitant brain malformations. CASE PRESENTATION: Early-onset acute signs of forebrain abnormalities were observed in all dogs, which were mainly cluster seizures and behavioral alterations. Based on neurological examination, the findings were consistent with symmetrical and bilateral forebrain lesions. Metabolic disorders and inflammatory diseases were excluded. Magnetic resonance imaging for three dogs showed diffuse neocortical agyria and thickened gray matter while one dog had mixed agyria and pachygyria. Other features, such as internal hydrocephalus, supracollicular fluid accumulation, and corpus callosum hypoplasia, were detected concomitantly. Antiepileptic drugs effectively controlled cluster seizures, however, sporadic isolated seizures and signs of forebrain abnormalities, such as behavioral alterations, central blindness, and strabismus persisted. CONCLUSIONS: Lissencephaly should be considered an important differential diagnosis in Shih Tzu dogs presenting with early-onset signs of forebrain abnormalities, including cluster seizures and behavioral alterations. Magnetic resonance imaging was appropriate for ante-mortem diagnosis of lissencephaly and associated cerebral anomalies."
1833,Choosing and Doing wisely: triage level I resuscitation a possible new field for starting palliative care and avoiding low-value care – a nationwide matched-pair retrospective cohort study in Taiwan,"BACKGROUND: The association between palliative care and life-sustaining treatment following emergency department (ED) resuscitation is unclear. This study aims to analyze the usage of palliative care and life-sustaining treatments among ED triage level I resuscitation patients based on a nationally representative sample of patients in Taiwan. METHODS: A matched-pair retrospective cohort study was conducted to examine the association between palliative care and outcome variables using multivariate logistic regression and Kaplan–Meier survival analyses. Between 2009 and 2013, 336 ED triage level I resuscitation patients received palliative care services (palliative care group) under a universal health insurance scheme. Retrospective cohort matching was performed with those who received standard care at a ratio of 1:4 (usual care group). Outcome variables included the number of visits to emergency and outpatient departments, hospitalization duration, total medical expenses, utilization of life-sustaining treatments, and duration of survival following ED triage level I resuscitation. RESULTS: The mean survival duration following level I resuscitation was less than 1 year. Palliative care was administered to 15% of the resuscitation cohort. The palliative care group received significantly less life-sustaining treatment than did the usual care group. CONCLUSION: Among patients who underwent level I resuscitation, palliative care was inversely correlated with the scope of life-sustaining treatments. Furthermore, triage level I resuscitation status may present a possible new field for starting palliative care intervention and reducing low-value care."
1834,Comparing clinical outcomes of piperacillin-tazobactam administration and dosage strategies in critically ill adult patients: a systematic review and meta-analysis,"BACKGROUND: Recently, continuous administration of piperacillin-tazobactam has been proposed as a valuable alternative to traditional intermittent administration especially in critically ill patients. However, antibiotic dosing remains a challenge for clinicians as antibiotic dosing regimens are usually determined in non-critically ill hospitalized adult patients. The aim was to conduct a systematic review to identify and highlight studies comparing clinical outcomes of piperacillin tazobactam dosing regimens, continuous/prolonged infusion vs intermittent infusion in critically ill patients. Meta-analyses were performed to assess the overall effect of dosing regimen on clinical efficacy. METHODS: Studies were identified systematically through searches of PubMed and Science Direct, in compliance with PRISMA guidelines. Following the systematic literature review, meta-analyses were performed using Review Manager. RESULTS: Twenty-three studies were included in the analysis involving 3828 critically ill adult participants in total (continuous/prolonged infusion = 2197 and intermittent infusion = 1631) from geographically diverse regions. Continuous/prolonged resulted in significantly: higher clinical cure rates (Odds Ratio 1.56, 95% Confidence Interval 1.28–1.90, P = 0 .0001), lower mortality rates (Odds Ratio 0.68, 95% Confidence Interval 0.55–0.84, P = 0 .0003), higher microbiological success rates (Odds Ratio 1.52, 95% Confidence Interval 1.10–2.11, P = 0.01) and decreasing the length of hospital stay (Mean Difference − 1.27, 95% Confidence Interval − 2.45—0.08, P = 0.04) in critically ill patients. CONCLUSION: Results from this study show that there is a significant level of evidence that clinical outcome in critically ill patients is improved in patients receiving piperacillin-tazobactam via continuous/prolonged infusion. However, more rigorous scientific studies in critically ill patients are warranted to reach a sufficient level of evidence and promote further implementation of C/PI as a dosing strategy."
1835,Pandemic flu: from the front lines,Researchers describe the scientific and public-health challenges they face in battling the H1N1 virus.
1836,Wearable Technology for “Real-World Research”: Realistic or Not?,
1837,Protecting Participants in Genomic Research: Understanding the “Web of Protections” Afforded by Federal and State Law,"Researchers now commonly collect biospecimens for genomic analysis together with information from mobile devices and electronic health records. This rich combination of data creates new opportunities for understanding and addressing important health issues, but also intensifies challenges to privacy and confidentiality. Here, we elucidate the “web” of legal protections for precision medicine research by integrating findings from qualitative interviews with structured legal research and applying them to realistic research scenarios involving various privacy threats."
1838,People With Advanced Cancer: The Process of Living Well With Awareness of Dying,"Literature suggests that it is possible to live well with advanced cancer but little is known about the process. In this article, we present a secondary analysis of experiences of living with advanced cancer (n = 22) that refines the theory of “Living Well with Chronic Illness” for a different context and population. The refined theory explains the experience of living well with advanced cancer illuminating a five-phase iterative process: struggling, accepting, living with advanced cancer, sharing the illness experience, and reconstructing life. These five phases revolve around the core concept of Awareness of Dying, which varied from awareness of the possibility of dying, to accepting the possibility of dying, to acceptance that “I am dying.” Awareness of Dying led to a focus on living well with advanced cancer and movement towards living a life rather than living an illness."
1839,UK consensus on pre-clinical vascular cognitive impairment functional outcomes assessment: Questionnaire and workshop proceedings,"Assessment of outcome in preclinical studies of vascular cognitive impairment (VCI) is heterogenous. Through an ARUK Scottish Network supported questionnaire and workshop (mostly UK-based researchers), we aimed to determine underlying variability and what could be implemented to overcome identified challenges. Twelve UK VCI research centres were identified and invited to complete a questionnaire and attend a one-day workshop. Questionnaire responses demonstrated agreement that outcome assessments in VCI preclinical research vary by group and even those common across groups, may be performed differently. From the workshop, six themes were discussed: issues with preclinical models, reasons for choosing functional assessments, issues in interpretation of functional assessments, describing and reporting functional outcome assessments, sharing resources and expertise, and standardization of outcomes. Eight consensus points emerged demonstrating broadly that the chosen assessment should reflect the deficit being measured, and therefore that one assessment does not suit all models; guidance/standardisation on recording VCI outcome reporting is needed and that uniformity would be aided by a platform to share expertise, material, protocols and procedures thus reducing heterogeneity and so increasing potential for collaboration, comparison and replication. As a result of the workshop, UK wide consensus statements were agreed and future priorities for preclinical research identified."
1840,A Critical Perspective on Mental Health News in Six European Countries: How Are “Mental Health/Illness” and “Mental Health Literacy” Rhetorically Constructed?,"In this study, we aim to contribute to the field of critical health communication research by examining how notions of mental health and illness are discursively constructed in newspapers and magazines in six European countries and how these constructions relate to specific understandings of mental health literacy. Using the method of cluster-agon analysis, we identified four terminological clusters in our data, in which mental health/illness is conceptualized as “dangerous,” “a matter of lifestyle,” “a unique story and experience,” and “socially situated.” We furthermore found that we cannot unambiguously assume that biopsychiatric discourses or discourses aimed at empathy and understanding are either exclusively stigmatizing or exclusively empowering and normalizing. We consequently call for a critical conception of mental health literacy arguing that all mental health news socializes its audience in specific understandings of and attitudes toward mental health (knowledge) and that discourses on mental health/illness can work differently in varying contexts."
1841,"Optogenetic assessment of VIP, PV, SOM and NOS inhibitory neuron activity and cerebral blood flow regulation in mouse somato-sensory cortex","The impact of different neuronal populations on local cerebral blood flow (CBF) regulation is not well known and insight into these relationships could enhance the interpretation of brain function and dysfunction from brain imaging data. We investigated the role of sub-types of inhibitory neuron activity on the regulation of CBF using optogenetics, laser Doppler flowmetry and different transgenic mouse models (parvalbumin (PV), vasoactive intestinal peptide (VIP), somatostatin (SOM) and nitric oxide synthase (NOS)). Whisker stimulation was used to verify that typical CBF responses were obtained in all mice. Photo-stimulation of SOM-cre and NOS-cre mice produced significant increases in CBF that were similar to whisker responses. In NOS-cre mice, CBF responses scaled with the photo-stimulus pulse duration and frequency. In SOM-cre mice, CBF increases were followed by decreases. In VIP-cre mice, photo-stimulation did not consistently produce significant changes in CBF, while slower increases in CBF that peaked 14–18 s after stimulation onset were observed in PV-cre mice. Control experiments performed in non-expressing regions showed no changes in CBF. These findings suggest that dysfunction in NOS or SOM neurons can have a significant impact on vascular responses that are detected by brain imaging methods like functional magnetic resonance imaging (fMRI)."
1842,Distinct Region- and Time-Dependent Functional Cortical Adaptations in C57BL/6J Mice after Short and Prolonged Alcohol Drinking,"Alcohol (ethanol) use disorder is associated with changes in frontal cortical areas including the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) that contribute to cognitive deficits, uncontrolled drinking, and relapse. Acute ethanol exposure reduces intrinsic excitability of lateral OFC (lOFC) neurons, while chronic exposure and long-term drinking influence plasticity of intrinsic excitability and function of glutamatergic synapses. However, the time course that these adaptations occur across a history of ethanol drinking is unknown. The current study examined whether short-term and long-term voluntary ethanol consumption using an intermittent access paradigm would alter the biophysical properties of deep-layer pyramidal neurons in the ACC and lOFC. Neuronal spiking varied in the ACC with an initial increase in evoked firing after 1 d of drinking followed by a decrease in firing in mice that consumed ethanol for one week. No difference in lOFC spike number was observed between water controls and 1-d ethanol drinking mice, but mice that consumed ethanol for one week or more showed a significant increase in evoked firing. Voluntary ethanol drinking for 4 weeks also produced a total loss of ethanol inhibition of lOFC neurons. There was no effect of drinking on excitatory or inhibitory synaptic events in ACC or lOFC neurons across all time points in this model. Overall, these results demonstrate that voluntary drinking alters neuronal excitability in the ACC and lOFC in distinct ways and on a different time scale that may contribute to the impairment of prefrontal cortex-dependent behaviors observed in individuals with alcohol use disorder (AUD)."
1843,Detailed balance for diffusion in a potential with trapping and forward–backward symmetry of trapping time distributions,"For particles diffusing in a potential, detailed balance guarantees the absence of net fluxes at equilibrium. Here, we show that the conventional detailed balance condition is a special case of a more general relation that works when the diffusion occurs in the presence of a distributed sink that eventually traps the particle. We use this relation to study the lifetime distribution of particles that start and are trapped at specified initial and final points. It turns out that when the sink strength at the initial point is nonzero, the initial and final points are interchangeable, i.e., the distribution is independent of which of the two points is initial and which is final. In other words, this conditional trapping time distribution possesses forward–backward symmetry."
1844,Estimation of Heart Rate and Respiratory Rate from PPG Signal Using Complementary Ensemble Empirical Mode Decomposition with both Independent Component Analysis and Non-Negative Matrix Factorization,"This paper proposes a framework combining the complementary ensemble empirical mode decomposition with both the independent component analysis and the non-negative matrix factorization for estimating both the heart rate and the respiratory rate from the photoplethysmography (PPG) signal. After performing the complementary ensemble empirical mode decomposition on the PPG signal, a finite number of intrinsic mode functions are obtained. Then, these intrinsic mode functions are divided into two groups to perform the further analysis via both the independent component analysis and the non-negative matrix factorization. The surrogate cardiac signal related to the heart activity and another surrogate respiratory signal related to the respiratory activity are reconstructed to estimate the heart rate and the respiratory rate, respectively. Finally, different records of signals acquired from the Medical Information Mart for Intensive Care database downloaded from the Physionet Automated Teller Machine (ATM) data bank are employed for demonstrating the outperformance of our proposed method. The results show that our proposed method outperforms both the digital filtering approach and the conventional empirical mode decomposition based methods in terms of reconstructing both the surrogate cardiac signal and the respiratory signal from the PPG signal as well as both achieving the higher accuracy and the higher reliability for estimating both the heart rate and the respiratory rate."
1845,Fiber Optic Particle Plasmon Resonance Biosensor for Label-Free Detection of Nucleic Acids and Its Application to HLA-B27 mRNA Detection in Patients with Ankylosing Spondylitis,"We developed a label-free, real-time, and highly sensitive nucleic acid biosensor based on fiber optic particle plasmon resonance (FOPPR). The biosensor employs a single-strand deoxyoligonucleotides (ssDNA) probe, conjugated to immobilized gold nanoparticles on the core surface of an optical fiber. We explore the steric effects on hybridization affinity and limit of detection (LOD), by using different ssDNA probe designs and surface chemistries, including diluent molecules of different lengths in mixed self-assembled monolayers, ssDNA probes of different oligonucleotide lengths, ssDNA probes in different orientations to accommodate target oligonucleotides with a hybridization region located unevenly in the strand. Based on the optimized ssDNA probe design and surface chemistry, we achieved LOD at sub-nM level, which makes detection of target oligonucleotides as low as 1 fmol possible in the 10-μL sensor chip. Additionally, the FOPPR biosensor shows a good correlation in determining HLA-B27 mRNA, in extracted blood samples from patients with ankylosing spondylitis (AS), with the clinically accepted real-time reverse transcription-polymerase chain reaction (RT-PCR) method. The results from this fundamental study should guide the design of ssDNA probe for anti-sense sensing. Further results through application to HLA-B27 mRNA detection illustrate the feasibility in detecting various nucleic acids of chemical and biological relevance."
1846,Level-Set Segmentation-Based Respiratory Volume Estimation Using a Depth Camera,"In this paper, a method is proposed to measure human respiratory volume using a depth camera. The level-set segmentation method, combined with spatial and temporal information, was used to measure respiratory volume accurately. The shape of the human chest wall was used as spatial information. As temporal information, the segmentation result from the previous frame in the time-aligned depth image was used. The results of the proposed method were verified using a ventilator. The proposed method was also compared with other level-set methods. The result showed that the mean tidal volume error of the proposed method was 8.41% compared to the actual tidal volume. This was calculated to have less error than with two other methods: the level-set method with spatial information (14.34%) and the level-set method with temporal information (10.93%). The difference between these methods of tidal volume error was statistically significant [Formula: see text]. The intra-class correlation coefficient (ICC) of the respiratory volume waveform measured by a ventilator and by the proposed method was 0.893 on an average, while the ICC between the ventilator and the other methods were 0.837 and 0.879 on an average."
1847,Evaluating Physiological Dynamics via Synchrosqueezing: Prediction of Ventilator Weaning,"Oscillatory phenomena abound in many types of signals. Identifying the individual oscillatory components that constitute an observed biological signal leads to profound understanding about the biological system. The instantaneous frequency (IF), the amplitude modulation (AM), and their temporal variability are widely used to describe these oscillatory phenomena. In addition, the shape of the oscillatory pattern, repeated in time for an oscillatory component, is also an important characteristic that can be parametrized appropriately. These parameters can be viewed as phenomenological surrogates for the hidden dynamics of the biological system. To estimate jointly the IF, AM, and shape, this paper applies a novel and robust time-frequency analysis tool, referred to as the synchrosqueezing transform (SST). The usefulness of the model and SST are shown directly in predicting the clinical outcome of ventilator weaning. Compared with traditional respiration parameters, the breath-to-breath variability has been reported to be a better predictor of the outcome of the weaning procedure. So far, however, all these indices normally require at least [Formula: see text] min of data acquisition to ensure predictive power. Moreover, the robustness of these indices to the inevitable noise is rarely discussed. We find that based on the proposed model, SST and only [Formula: see text] min of respiration data, the ROC area under curve of the prediction accuracy is [Formula: see text]. The high predictive power that is achieved in the weaning problem, despite a shorter evaluation period, and the stability to noise suggest that other similar kinds of signal may likewise benefit from the proposed model and SST."
1848,Multiple Vital-Sign-Based Infection Screening Outperforms Thermography Independent of the Classification Algorithm,"Goal: Thermography-based infection screening at international airports plays an important role in the prevention of pandemics. However, studies show that thermography suffers from low sensitivity and specificity. To achieve higher screening accuracy, we developed a screening system based on the acquisition of multiple vital-signs. This multimodal approach increases accuracy, but introduces the need for sophisticated classification methods. This paper presents a comprehensive analysis of the multimodal approach to infection screening from a machine learning perspective. Methods: We conduct an empirical study applying six classification algorithms to measurements from the multimodal screening system and comparing their performance among each other, as well as to the performance of thermography. In addition, we provide an information theoretic view on the use of multiple vital-signs for infection screening. The classification methods are tested using the same clinical data, which has been analyzed in our previous study using linear discriminant analysis. A total of 92 subjects were recruited for influenza screening using the system, consisting of 57 inpatients diagnosed to have seasonal influenza and 35 healthy controls. Results: Our study revealed that the multimodal screening system reduces the misclassification rate by more than 50% compared to thermography. At the same time, none of the multimodal classifiers needed more than 6 ms for classification, which is negligible for practical purposes. Conclusion: Among the tested classifiers k-nearest neighbors, support vector machine and quadratic discriminant analysis achieved the highest cross-validated sensitivity score of 93%. Significance: Multimodal infection screening might be able to address the shortcomings of thermography."
1849,The Association between Utilization of Media Information and Current Health Anxiety Among the Fukushima Daiichi Nuclear Disaster Evacuees,"The 2011 nuclear disaster in Fukushima was not only a health disaster, but also an information disaster. Although media can promote health communication following disasters, studies have revealed associations between media information and negative psychological reactions. To clarify the relationship between media utilization and current health anxiety due to radiation exposure, a cross-sectional questionnaire survey was conducted in Fukushima. We selected 2000 subjects from evacuation (i.e., 500) and non-evacuation (i.e., 1500) areas by two-stage stratified random sampling. As the independent variable, participants were asked about current health anxiety due to radiation exposure at the time of answering the questionnaire. For utilization of media about radiation exposure, local media, national media, Internet media, public broadcasts, and public relations information from local government were set as the dependent variables. Questionnaire data were analyzed by evacuation type (i.e., forced/voluntary). In a multivariate logistic regression analysis, the use of public relations information was significantly associated with lower anxiety for the forced evacuees (odds ratio: 0.72; 95% confidence interval: 0.56–0.93). Our findings highlight the importance of public relations information from local government in terms of it being associated with lower current health anxiety, and this could potentially aid in preparing for future disasters."
1850,Perinatal risk factors for pulmonary hemorrhage in extremely low-birth-weight infants,"BACKGROUND: Pulmonary hemorrhage (PH) is a life-threatening respiratory complication of extremely low-birth-weight infants (ELBWIs). However, the risk factors for PH are controversial. Therefore, the purpose of this study was to analyze the perinatal risk factors and short-term outcomes of PH in ELBWIs. METHODS: This was a retrospective cohort study of live born infants who had birth weights that were less than 1000 g, lived for at least 12 hours, and did not have major congenital anomalies. A logistic regression model was established to analyze the risk factors associated with PH. RESULTS: There were 168 ELBWIs born during this period. A total of 160 infants were included, and 30 infants were diagnosed with PH. Risk factors including gestational age, small for gestational age, intubation in the delivery room, surfactant in the delivery room, repeated use of surfactant, higher FiO(2) during the first day, invasive ventilation during the first day and early onset sepsis (EOS) were associated with the occurrence of PH by univariate analysis. In the logistic regression model, EOS was found to be an independent risk factor for PH. The mortality and intraventricular hemorrhage rate of the group of ELBWIs with PH were significantly higher than those of the group of ELBWIs without PH. The rates of periventricular leukomalacia, moderate-to-severe bronchopulmonary dysplasia and severe retinopathy of prematurity, and the duration of the hospital stay were not significantly different between the PH and no-PH groups. CONCLUSIONS: Although PH did not extend hospital stay or increase the risk of bronchopulmonary dysplasia, it increased the mortality and intraventricular hemorrhage rate in ELBWIs. EOS was the independent risk factor for PH in ELBWIs."
1851,Identification of cardiovascular and molecular prognostic factors for the medium-term and long-term outcomes of sepsis (ICROS): protocol for a prospective monocentric cohort study,"INTRODUCTION: Sepsis is one of the most prevalent life-threatening conditions in the intensive care unit. Patients suffer from impaired organ function, reduced physical functional capacity and decreased quality of life even after surviving sepsis. The identification of prognostic factors for the medium-term and long-term outcomes of this condition is necessary to develop personalised theragnostic approaches. Sepsis can cause cardiac impairment. The impact of this septic cardiomyopathy on patient’s long-term outcome remains unclear. This study aims to evaluate cardiovascular risk factors, particularly the occurrence of septic cardiomyopathy, regarding their suitability as prognostic factors for the short-term and long-term outcomes of septic patients. Additionally, the study seeks to validate preclinical pathophysiological findings of septic cardiomyopathy in the clinical setting. METHODS AND ANALYSIS: In this prospective monocentric cohort study, patients will be clinically assessed during the acute and postacute phase of sepsis and two follow-ups after 6 and 12 months. To determine the effect of septic cardiomyopathy and concomitant cellular and molecular changes on patient mortality and morbidity, a comprehensive cardiovascular and molecular deep phenotyping of patients will be performed. This includes an echocardiographic and electrocardiographic assessment, and the evaluation of heart rate variability, body composition, mitochondrial oxygen metabolism, macrocirculation and microcirculation, and endothelial barrier function. These analyses are complemented by routine immunological, haematological and biochemical laboratory tests and analyses of the serum metabolome and lipidome, microbiome and epigenetic modifications of immune cells. The reversibility of patients’ organ dysfunction, their quality of life and physical functional capacity will be investigated in the follow-ups. Patients with cardiomyopathy without infection and healthy subjects will serve as control groups. ETHICS AND DISSEMINATION: Approval was obtained from the Ethics Committee of the Friedrich Schiller University Jena (5276-09/17). The results will be published in peer-reviewed journals and presented at appropriate conferences. TRIAL REGISTRATION NUMBERS: DRKS00013347; NCT03620409."
1852,The MNK1/2-eIF4E Axis as a Potential Therapeutic Target in Melanoma,"Melanoma is a type of skin cancer that originates in the pigment-producing cells of the body known as melanocytes. Most genetic aberrations in melanoma result in hyperactivation of the mitogen activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways. We and others have shown that a specific protein synthesis pathway known as the MNK1/2-eIF4E axis is often dysregulated in cancer. The MNK1/2-eIF4E axis is a point of convergence for these signaling pathways that are commonly constitutively activated in melanoma. In this review we consider the functional implications of aberrant mRNA translation in melanoma and other malignancies. Moreover, we discuss the consequences of inhibiting the MNK1/2-eIF4E axis on the tumor and tumor-associated cells, and we provide important avenues for the utilization of this treatment modality in combination with other targeted and immune-based therapies. The past decade has seen the increased development of selective inhibitors to block the action of the MNK1/2-eIF4E pathway, which are predicted to be an effective therapy regardless of the melanoma subtype (e.g., cutaneous, acral, and mucosal)."
1853,A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research,"Isatin (indole-2,3-dione) is an endogenous regulator, exhibiting a wide range of biological and pharmacological activities. At doses of 100 mg/kg and above, isatin is neuroprotective in different experimental models of neurodegeneration. Good evidence exists that its effects are realized via interaction with numerous isatin-binding proteins identified in the brain and peripheral tissues studied. In this study, we investigated the effect of a single dose administration of isatin to mice (100 mg/kg, 24 h) on differentially expressed proteins and a profile of the isatin-binding proteins in brain hemispheres. Isatin administration to mice caused downregulation of 31 proteins. However, these changes cannot be attributed to altered expression of corresponding genes. Although at this time point isatin influenced the expression of more than 850 genes in brain hemispheres (including 433 upregulated and 418 downregulated genes), none of them could account for the changes in the differentially expressed proteins. Comparative proteomic analysis of brain isatin-binding proteins of control and isatin-treated mice revealed representative groups of proteins sensitive to isatin administration. Control-specific proteins (n = 55) represent specific targets that interact directly with isatin. Appearance of brain isatin-binding proteins specific to isatin-treated mice (n = 94) may be attributed to the formation of new clusters of protein–protein interactions and/or novel binding sites induced by a high concentration of this regulator (ligand-induced binding sites). Thus, isatin administration produces multiple effects in the brain, which include changes in gene expression and also profiles of isatin-binding proteins and their interactomes. Further studies are needed for deeper insight into the mechanisms of the multilevel changes in the brain proteome induced by isatin. In the context of the neuroprotective action, these changes may be aimed at interruption of pathological links that begin to form after initiation of pathological processes."
1854,A Clinical Study of Hospitalized H1N1 Infected Children in Western Rajasthan,"Objective: To study the cases of H1N1 influenza admitted in our hospital. Method: Hospital records of all the admitted patients diagnosed as H1N1 positive by throat swab rt-PCR (real time polymerase chain reaction) were retrospectively studied. Results: Between November 2009 and February 2010 total 62 children were hospitalized with 2009 H1N1 influenza virus infection. Of the admitted children, 19 (30.6%) were admitted in ICU and 4 (6.4%) expired. Consolidation was observed in 25 (40%) cases while 4 (6%) patients had pleural effusion and 1 patient each developed pneumothorax and pulmonary edema. Conclusions: Pandemic 2009 H1N1 influenza caused serious respiratory complications in children not usually seen with seasonal influenza."
1855,"Clinical and Epidemiological Characteristics of Pandemic Influenza A/(H1N1) in Hospitalized Pediatric Patients at a University Hospital, Istanbul, Turkey","Background: The aim of this study was to describe the clinical and epidemiological characteristics of pandemic influenza in hospitalized children. Methods: A total of 114 patients with suspected H1N1 virus infection were hospitalized, and nasal swabs were sent to National Influenza Reference Laboratory for confirmation of pandemic influenza A (H1N1) virus infection by rRT–PCR assay. Results: Forty-six female and 68 male patients were included in the study. Age of the patients ranged from 40 days to 16 years. Clinical and/or radiological pneumonia were detected in 96% of all. Sixteen patients required mechanical ventilation due to hypoxemia. Previously healthy children required mechanical ventilation and oxygen therapy more than patients with chronic diseases. Elevated levels of CRP and LDH in patients with respiratory distress and patients who required mechanical ventilation were statistically significant. Conclusion: Our study showed that progress of pandemic influenza infection in previously healthy children is as severe as their counterparts with chronic underlying diseases."
1856,The Influenza Pandemic of 1918–1919 in the British Caribbean,"The influenza pandemic swept through the Caribbean during the period October 1918 to March 1919 and resulted in c. 100 000 deaths. This article focuses on the British possessions and is based principally on official reports and the local press. It looks at how the virus entered and spread through the region, the possible reasons for variations in levels of morbidity and mortality between islands, popular responses to the infection, and the mainly fruitless official attempts to arrest and deal with the disease. Jamaica was the first island to be affected, and along with Belize and Guyana, suffered most severely. A number of islands, particularly those in the eastern Caribbean, appear to have escaped relatively lightly. Although all sections of the population were vulnerable, the heaviest mortality rates were among the very poor, East Indian immigrant labourers, and native Americans. There was also a high toll among males aged 15–40. Altogether the death rate from influenza in the British Caribbean was c. 30 000. In London influenza was added to the official list of British ‘imperial diseases’, and although it was recognized that poverty provided the conditions for the spread of disease, the resources in the Caribbean were barely used to improve standards of living and nutrition."
1857,Pandemic non-adjuvanted influenza A H1N1 vaccine in a cohort of patients with systemic sclerosis,"OBJECTIVE: To assess the possible effect of therapy, disease subtype and severity on H1N1 immunogenicity in patients with SSc. METHODS: Ninety-two patients and 92 age- and gender-matched healthy controls received adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Blood samples were collected immediately before and 3 weeks after vaccination to evaluate antibody responses to the H1N1 virus. Efficacy was assessed by seroprotection (SP) and seroconversion (SC) rates and the factor increase in geometric mean antibody titre. Participants received a 21-day symptom diary card and were instructed to report local and systemic adverse events. RESULTS: SSc patients were predominantly females (91%) and 61% had limited SSc, 12% had severe skin involvement and 57.6% were on immunosuppressive (IS) therapy. SSc patients and controls presented comparable overall SP (P = 0.20) and SC (P = 0.61) rates. Further evaluation of the possible effect of disease and therapy revealed similar rates of SP and SC in patients with dcSSc vs lcSSc (SP P = 0.62 and SC P = 0.66), severe vs mild/moderate skin involvement (SP P = 1 and SC P = 0.45) and with vs without IS (SP P = 0.26 and SC P = 0.10). The frequency of mild local and minor systemic reactions was similar in patients with dcSSC vs lcSSc (P = 0.70 vs 0.32) and in those with and without severe skin involvement (P = 0.59 vs 0.28). CONCLUSION: The non-adjuvanted influenza H1N1 virus vaccine proved to be safe and effective, independent of SSc clinical subtype, disease severity or therapy. These latter factors do not seem to contribute to mild adverse events observed in SSc. Our data support the annual influenza vaccination recommendation for these patients. TRIAL REGISTRATION: ClinicalTrials.gov (http://clinicaltrials.gov), NCT01151644"
1858,Preparedness of Residential and Nursing Homes for Pandemic Flu,"BACKGROUND: Work is being undertaken across a wide range of agencies to ensure a high level of preparedness for pandemic influenza. In England, the Department of Health has published a range of guidance to support this. The impact of pandemic flu on care homes, especially if unprepared may have a major knock on effect on the rest of the health and social care system. OBJECTIVE AND METHODS: A rapid survey was undertaken of a small number of care homes in West Yorkshire to assess preparedness. The homes were both local authority and privately owned. RESULTS: It was apparent that little preparation had been done at the time of the survey. A range of readily implementable ideas that may help this sector prepare was identified. CONCLUSION: Planning for pandemic flu in this sector will require effort and coordination across a range of sectors; it might best be coordinated through Local Resilience Forums."
1859,TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients,"Objective. To evaluate the immunogenicity of the anti-influenza A H1N1/2009 vaccine in RA and spondyloarthritis (SpA) patients receiving distinct classes of anti-TNF agents compared with patients receiving DMARDs and healthy controls. Methods. One hundred and twenty patients (RA, n = 41; AS, n = 57; PsA, n = 22) on anti-TNF agents (monoclonal, n = 94; soluble receptor, n = 26) were compared with 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection, seroconversion (SC), geometric mean titre, factor increase in geometric mean titre and adverse events were evaluated 21 days after vaccination. Results. After immunization, SC rates (58.2% vs 74.3%, P = 0.017) were significantly lower in SpA patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared with healthy controls (P = 0.067). SpA patients receiving mAbs (infliximab/adalimumab) had a significantly lower SC rate compared with healthy controls (51.6% vs 74.3%, P = 0.002) or those on DMARDs (51.6% vs 74.7%, P = 0.005), whereas no difference was observed for patients on etanercept (86.7% vs 74.3%, P = 0.091). Further analysis of non-seroconverting and seroconverting SpA patients revealed that the former group had a higher mean age (P = 0.003), a higher frequency of anti-TNF (P = 0.031) and mAbs (P = 0.001) and a lower frequency of MTX (P = 0.028). In multivariate logistic regression, only older age (P = 0.015) and mAb treatment (P = 0.023) remained significant factors for non-SC in SpA patients. Conclusion. This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in SpA patients using mAbs. Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01151644."
1860,Immunogenicity of an adjuvanted 2009 pandemic influenza A (H1N1) vaccine in haemodialysed patients,"Background. The 2009 pandemic of influenza A (H1N1) prompted an urgent worldwide vaccination campaign, especially of high-risk subjects, such as maintenance haemodialysis (HD) patients. Still the immunogenicity of the pandemic A (H1N1) vaccine in HD patients is unknown. Methods. We prospectively studied the immunogenicity of a monovalent adjuvanted influenza A/California/2009 (H1N1) vaccine (Pandemrix®, GSK Biologicals, Rixensart, Belgium) in HD patients and controls. Antibody level was measured using a seroneutralization assay before (D(0)) and 30 days after (D(30)) a single 3.75 μg vaccine dose. Specimens were tested in quadruplicates. Geometric mean (GM) antibody titers were determined in each subject at D(0) and D(30). Seroconversion was defined as an increase in GM titers by a factor 4 or more. Results. Fifty-three adult HD patients [aged 71 ± 10, 58.5% males, on HD for a median of 38 (3 − 146) months] and 32 control subjects (aged 47.3 ± 14, 31.3% males) were analyzed. Baseline GM titers were similar in HD patients and controls [7.9 (6.6 − 9.6) vs 10 (6 − 17); p = 0.69]. Seroconversion was observed in 30 (93.8%) controls and 34 (64.2%) HD patients (p = 0.002). In addition, GM titers at D(30) were significantly higher in controls than in HD patients [373 (217 − 640) vs 75.5 (42.5 − 134); p = 0.001]. HD patients were significantly older than controls (p < 0.001) and more likely to be males (p = 0.02). However, by multivariate analysis, HD status [OR 0.13 (0.02-0.78), p = 0.03], but neither age [OR 0.99 (0.96 − 1.03); p = 0.7] nor male gender [OR 1.31 (0.45 − 3.85); p = 0.63] was independently associated with seroconversion. The vaccine was generally well tolerated by HD patients. Conclusions. Only 64% of chronic HD patients developed seroconversion after a single dose of adjuvanted influenza A (H1N1) vaccine, a much lower rate than in controls (94%). These results underscore the substantial immunodeficiency associated with End-Stage Renal Disease. The persistence of protective antibodies as well as the effect of a booster dose remain to be investigated in HD patients."
1861,The epidemiology of influenza,"Influenza remains a globally important cause of febrile respiratory illness. Influenza virus activity in the community results in significant mortality, morbidity and economic disruption, particularly in those at high risk of developing complications, such as the elderly and those with underlying chronic medical conditions, including pulmonary disease and diabetes mellitus. The occurrence in Hong Kong in 1997 of avian influenza H5N1 in man, which resulted in six deaths, served to remind us of the importance of continuing surveillance and preparation for the next pandemic."
1862,Picture of a pandemic: visual aids in the COVID-19 crisis,"As a global crisis, COVID-19 has underscored the challenge of disseminating evidence-based public health recommendations amidst a rapidly evolving, often uncensored information ecosystem—one fueled in part by an unprecedented degree of connected afforded through social media. In this piece, we explore an underdiscussed intersection between the visual arts and public health, focusing on the use of validated infographics and other forms of visual communication to rapidly disseminate accurate public health information during the COVID-19 pandemic. We illustrate our arguments through our own experience in creating a validated infographic for patients, now disseminated through social media and other outlets across the world in nearly 20 translations. Visual communication offers a creative and practical medium to bridge critical health literacy gaps, empower diverse patient communities through evidence-based information and facilitate public health advocacy during this pandemic and the ‘new normal’ that lies ahead."
1863,Antiviral treatment for outpatient use during an influenza pandemic: a decision tree model of outcomes averted and cost-effectiveness,"BACKGROUND: Many countries have acquired antiviral stockpiles for pandemic influenza mitigation and a significant part of the stockpile may be focussed towards community-based treatment. METHODS: We developed a spreadsheet-based, decision tree model to assess outcomes averted and cost-effectiveness of antiviral treatment for outpatient use from the perspective of the healthcare payer in the UK. We defined five pandemic scenarios—one based on the 2009 A(H1N1) pandemic and four hypothetical scenarios varying in measures of transmissibility and severity. RESULTS: Community-based antiviral treatment was estimated to avert 14–23% of hospitalizations in an overall population of 62.28 million. Higher proportions of averted outcomes were seen in patients with high-risk conditions, when compared to non-high-risk patients. We found that antiviral treatment was cost-saving across pandemic scenarios for high-risk population groups, and cost-saving for the overall population in higher severity influenza pandemics. Antiviral effectiveness had the greatest influence on both the number of hospitalizations averted and on cost-effectiveness. CONCLUSIONS: This analysis shows that across pandemic scenarios, antiviral treatment can be cost-saving for population groups at high risk of influenza-related complications."
1864,Is there really good news about pandemic diabetic nephropathy?,
1865,The determinants of health-seeking behaviour during the A/H1N1 influenza pandemic: an ecological study,"BACKGROUND: This is an ecological study that examines the relationship between antiviral drug collection during the 2009/2010 A/H1N1 influenza pandemic, and area-level ethnicity, socioeconomic deprivation and distance from an antiviral collection point (ACP). METHODS: Age-standardized antiviral collection rates (ACR) were calculated for each super output area (geographic areas representing a population of ∼1500) in Sandwell, UK for all residents who received an antiviral drug for influenza-like illness between 23 July 2009 and 7 February 2010. Multivariable regression was used to examine the relationship between ACR and ethnicity (percentage population non-white), socioeconomic deprivation (index of multiple deprivation, IMD) and distance from an ACP. RESULTS: Socioeconomic deprivation, ethnicity and distance from an ACP were independently associated with a reduction in ACR. Each one-point increase in the IMD score was associated with a drop in the ACR of 15.7 prescriptions per 100 000 population (P= 0.013). CONCLUSIONS: Socioeconomic deprivation, ethnicity and distance from an ACP may have influenced health-seeking behaviour during the 2009/2010 influenza pandemic. This suggests possible inequalities in access to antivirals during the most recent influenza pandemic. Qualitative research is needed to examine the reasons for this. Individual-level data on ethnicity should be routinely collected in the event of a future pandemic."
1866,"An open-label, randomized clinical trial assessing immunogenicity, safety and tolerability of pandemic influenza A/H1N1 MF59-adjuvanted vaccine administered sequentially or simultaneously with seasonal virosomal-adjuvanted influenza vaccine to paediatric kidney transplant recipients","Background. The aim of this study was to investigate the immunogenicity, safety and tolerability of the 2009 A/H1N1 MF59-adjuvanted influenza vaccine, administered sequentially or simultaneously with the seasonal 2009–10 virosomal-adjuvanted influenza vaccine, to paediatric kidney transplant recipients. Methods. Thirty-two children and adolescents with transplanted kidneys and 32 age- and gender-matched healthy controls were randomized 1:1 to receive the pandemic vaccine upon enrolment and the seasonal vaccine 1 month later (16 transplant recipients and 16 healthy controls), or to receive the two vaccines simultaneously upon enrolment (16 transplant recipients and 16 healthy controls). Results. When the pandemic vaccine was administered sequentially to the seasonal vaccine, it was significantly less immunogenic in the patients than in the controls (P < 0.05); when it was administered together with the seasonal vaccine, the immune response of both patients (P < 0.05) and controls (P < 0.05) was significantly greater than when it was administered sequentially. Seroconversion rates and the geometric mean titres of all of the seasonal antigens were significantly lower in the patients, regardless of the type of vaccine administration (P < 0.05). Simultaneous administration was associated with a better immune response against A/H1N1 and A/H3N2 antigens in both patients and controls, and did not increase the mild local and systemic reactions. No impact on renal function was observed. Conclusions. Paediatric kidney transplant recipients have a lower immune response to the pandemic influenza A/H1N1 MF59-adjuvanted and seasonal virosomal-adjuvanted influenza vaccines than healthy controls. The simultaneous administration of the two vaccines seems to increase immune response to both pandemic and seasonal A/H1N1 and A/H3N2 antigens, and has the same safety profile as that of the pandemic vaccine administered sequentially to the seasonal vaccine."
1867,"Influenza Virus Research and Eu Export Regulations: Publication, Proliferation, and Pandemic Risks","An influenza pandemic would be a global health emergency, and laboratory-based research on influenza viruses is an important component of worldwide efforts to prevent and prepare for this. There are concerns, however, that publishing the findings of such research might sometimes increase the risk of a pandemic caused by a laboratory accident or the deliberate release of a deadly virus. This article addresses the challenge of governing scientific information sharing, with regard to public health benefits and risks, from an export-control perspective. The discussion focuses on research findings produced in 2011 by a team of influenza virologists in the Netherlands, and on the Dutch Government’s unprecedented decision to regard the intended publication of these findings as being subject to European Union regulations on the export of ‘dual-use’ items. I argue that, when a government is uncertain about whether the benefits of publishing particular research findings in a scientific journal outweigh the risks, a process of selectively disseminating those findings should be available as an alternative to official censorship."
1868,The Global Threat of Animal Influenza Viruses of Zoonotic Concern: Then and Now,"Animal influenza viruses can reassort or mutate to infect and spread sustainably among people and cause a devastating worldwide pandemic. Since the first evidence of human infection with an animal influenza virus, in 1958, 16 different novel, zoonotic influenza A virus subtype groups in 29 countries, Taiwan, and Hong Kong have caused human infections, with differing severity and frequency. The frequency of novel influenza virus detection is increasing, and human infections with influenza A(H5N1) and A(H7N9) viruses are now annual seasonal occurrences in Asia. The study of the epidemiology and virology of animal influenza viruses is key to understanding pandemic risk and informing preparedness. This supplement brings together select recent articles that look at the risk of emergence and transmission of and approaches to prevent novel influenza virus infections."
1869,Serum Samples From Middle-aged Adults Vaccinated Annually with Seasonal Influenza Vaccines Cross-neutralize Some Potential Pandemic Influenza Viruses,"We examined serum samples from adults ages 48–64 who received multiple seasonal influenza vaccines from 2004 to 2009 for cross-neutralizing antibodies to potential pandemic strains. Using pseudoviruses bearing various hemagglutinins (HA-pseudoviruses), we found serum neutralization titers (≥160) in 100% against A/Japan/305/1957 (H2N2), 53% against A/Hong Kong/1073/99 (H9N2), 56% against the H3N2 variant A/Indiana/08/11 (H3N2v), 11% against A/Hong Kong/G9/97 (H9N2), and 36% A/chicken/Hong Kong/SF4/01 (H6N1). None had titers >160 to A/Shanghai/2/13 (H7N9) or A/Netherlands/219/03 (H7N7). Thirty-six percent to 0% had neutralization titers to various H5N1 strains. Titers to H9, H6, and H5 HA-pseudoviruses correlated with each other, but not with H3N2v, suggesting group-specific cross-neutralization."
1870,Infectious Diseases Society of America and Gain-of-Function Experiments With Pathogens Having Pandemic Potential,
1871,Response to Malkovsky,
1872,The Beneficial Effects of Neuraminidase Inhibitor Drug Therapy on Severe Patient Outcomes During the 2009–2010 Influenza A Virus Subtype H1N1 Pandemic,
1873,A Case Report of Neonatal Acute Respiratory Failure Due to Severe Acute Respiratory Syndrome Coronavirus-2,
1874,Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection,"BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78–.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment."
1875,Waiting for the Flu: Cognitive Inertia and the Spanish Influenza Pandemic of 1918–19,"This study looks at public awareness and understanding of the Spanish flu in the United States between June 1918, when the flu became “Spanish,” and the end of September when the deadly second wave reached the majority of the country. Based on an extensive reading of local newspapers, it finds a near universal lack of preparation or panic or other signs of personal concern among those in the unaffected areas, despite extensive and potentially worrying coverage of the flu's progress. The normal reaction to news of the inexorable approach of a pandemic of uncertain virulence is anxiety and action. The Spanish flu produced neither in the uninfected areas for a month. The most likely reason appears to be cognitive inertia—the tendency of existing beliefs or habits of thought to blind people to changed realities. This inertia grew out of the widespread understanding of flu as a seasonal visitor that while frequently unpleasant almost never killed the strong and otherwise healthy. This view of the flu was powerful enough that it blinded many in the unaffected regions to the threat for weeks even in the face of daily or near daily coverage of the pandemic's spread."
1876,Priming for Pandemic Influenza: Thanks for the Memories,
1877,WHO Knows Best? National and International Responses to Pandemic Threats and the “Lessons” of 1976,"The discovery of a novel influenza strain at Fort Dix, New Jersey, in 1976—dubbed Swine Flu—prompted differing responses from national and international health organizations. The United States crafted a vaccination campaign to inoculate every citizen; conversely, the World Health Organization (WHO) recommended a ‘wait and see’ policy. An examination of the WHO conference that issued the influenza policy reveals the decision was driven by the limits of its member states' ability to produce inactivated vaccine and concern over the premature use of unstable live-virus vaccines. The WHO recommendation's reliance upon an uneven surveillance system would have replicated the 1957 and 1968 vaccination failures if a pandemic had appeared."
1878,Survey of Human Antibody Responses to Influenza Virus Matrix Protein 2 by Use of a Sensitive Flow Cytometric Method,
1879,Perceived usefulness of syndromic surveillance in Ontario during the H1N1 pandemic,"BACKGROUND: Despite the growing popularity of syndromic surveillance, little is known about if or how these systems are accepted, utilized and valued by end users. This study seeks to describe the use of syndromic surveillance systems in Ontario and users' perceptions of the value of these systems within the context of other surveillance systems. METHODS: Ontario's 36 public health units, the provincial ministry of health and federal public health agency completed a web survey to identify traditional and syndromic surveillance systems used routinely and during the pandemic and to describe system attributes and utility in monitoring pandemic activity and informing decision-making. RESULTS: Syndromic surveillance systems are used by 20/38 (53%) organizations. For routine surveillance, laboratory, integrated Public Health Information System and school absenteeism data are the most frequently used sources. Laboratory data received the highest ratings for reliability, timeliness and accuracy (‘very acceptable’ by 92, 51 and 89%). Hospital/clinic screening data were rated as the most reliable and timely syndromic data source (50 and 43%) and ED visit data the most accurate (48%). During the pandemic, laboratory data were considered the most useful for monitoring the epidemiology and informing decision-making while ED screening and visit data were considered the most useful syndromic sources. CONCLUSIONS: End user perceptions are valuable for identifying opportunities for improvement and guiding further investments in public health surveillance."
1880,Antibody Response to Influenza A(H1N1)pdm09 Among Healthcare Personnel Receiving Trivalent Inactivated Vaccine: Effect of Prior Monovalent Inactivated Vaccine,"Background. Few data are available on the immunogenicity of repeated annual doses of influenza A(H1N1)pdm09-containing vaccines. Methods. We enrolled healthcare personnel (HCP) in direct patient care during the autumn of 2010 at 2 centers with voluntary immunization. We verified the receipt of A(H1N1)pdm09-containing monovalent inactivated influenza vaccine (MIIV) and 2010–2011 trivalent inactivated vaccine (TIV). We performed hemagglutination inhibition antibody (HI) assays on preseason, post-TIV, and end-of-season serum samples. We compared the proportion of HCPs with HI titer ≥40 against A(H1N1)pdm09 per receipt of prior-season MIIV, current-season TIV, both, or neither. Results. At preseason (n = 1417), HI ≥ 40 was significantly higher among those who received MIIV (34%) vs those who did not (14%) (adjusted relative risk [ARR], 3.26; 95% confidence interval [CI], 2.72–3.81). At post-TIV (n = 865), HI ≥ 40 was lower among HCP who received MIIV and TIV (66%) than among those receiving only TIV (85%) (ARR, 0.93 [95% CI, .84–.997]). At end-of-season (n = 1254), HI ≥ 40 was 40% among those who received both MIIV and TIV and 67% among those receiving only TIV (ARR, 0.76 [95% CI, .65–.88]), 52% among those who received MIIV only, and 12% among those receiving neither. Conclusions. HCP immunization programs should consider effects of host immune response and vaccine antigenic distance on immunogenicity of repeated annual doses of influenza vaccines."
1881,Pandemic controllability: a concept to guide a proportionate and flexible operational response to future influenza pandemics,"The 2009 H1N1 influenza pandemic posed challenges for governments worldwide. Strategies designed to limit community transmission, such as antiviral deployment, were largely ineffective due to both feasibility constraints and the generally mild nature of disease, resulting in incomplete case ascertainment. Reviews of national pandemic plans have identified pandemic impact, primarily linked to measures of transmissibility and severity, as a key concept to incorporate into the next generation of plans. While an assessment of impact provides the rationale under which interventions may be warranted, it does not directly provide an assessment on whether particular interventions may be effective. Such considerations motivate our introduction of the concept of pandemic controllability. For case-targeted interventions, such as antiviral treatment and post-exposure prophylaxis, we identify the visibility and transmissibility of a pandemic as the key drivers of controllability. Taking a case-study approach, we suggest that high-impact pandemics, for which control is most desirable, are likely uncontrollable with case-targeted interventions. Strategies that do not rely on the identification of cases may prove relatively more effective. By introducing a pragmatic framework for relating the assessment of impact to the ability to mitigate an epidemic (controllability), we hope to address a present omission identified in pandemic response plans."
1882,Pediatric Coronavirus Disease-2019–Associated Multisystem Inflammatory Syndrome,
1883,How Live Attenuated Vaccines Can Inform the Development of Broadly Cross-Protective Influenza Vaccines,
1884,Influenza A(H5N1) Vaccines: Are We Better Prepared for the Next Pandemic?,
1885,Virological self-sampling to monitor influenza antiviral susceptibility in a community cohort,"OBJECTIVE: To perform antiviral susceptibility monitoring of treated individuals in the community during the 2009 influenza A(H1N1) pandemic in England. PATIENTS AND METHODS: Between 200 and 400 patients were enrolled daily through the National Pandemic Flu Service (NPFS) and issued with a self-sampling kit. Initially, only persons aged 16 and over were eligible, but from 12 November (week 45), self-sampling was extended to include school-age children (5 years and older). All samples received were screened for influenza A(H1N1)pdm09 as well as seasonal influenza [A(H1N1), A(H3N2) and influenza B] by a combination of RT–PCR and virus isolation methods. Influenza A(H1N1)pdm09 RT–PCR-positive samples were screened for the oseltamivir resistance-inducing H275Y substitution, and a subset of samples also underwent phenotypic antiviral susceptibility testing by enzyme inhibition assay. RESULTS: We were able to detect virus by RT–PCR in self-taken samples and recovered infectious virus enabling further virological characterization. The majority of influenza A(H1N1)pdm09 RT–PCR-positive NPFS samples (n = 1273) were taken after oseltamivir treatment had begun. No reduction in phenotypic susceptibility to neuraminidase inhibitors was detected, but five cases with minority quasi-species of oseltamivir-resistant virus (an H275Y amino acid substitution in neuraminidase) were detected. CONCLUSIONS: Self-sampling is a useful tool for community surveillance, particularly for the follow-up of drug-treated patients. The virological study of self-taken samples from the NPFS provided a unique opportunity to evaluate the emergence of oseltamivir resistance in treated individuals with mild illness in the community, a target population that may not be captured by traditional sentinel surveillance schemes."
1886,Pandemic influenza preparedness in Latin America: analysis of national strategic plans,"The threat of a human pandemic of influenza has prompted the development of national influenza pandemic preparedness plans over the last 4 years. Analyses have been carried out to assess preparedness in Europe, Asia and Africa. We assessed plans to evaluate the national strategic pandemic influenza preparedness in the countries of Latin America. Published national pandemic influenza preparedness plans from Latin American countries were evaluated against criteria drawn from the World Health Organization checklist. Plans were eligible for inclusion if formally published before 16 November 2007. Fifteen national plans were identified and retrieved from the 17 Latin American countries surveyed. Latin American countries demonstrated different degrees of preparedness, and that a high level of completeness of plans was correlated to a country's wealth to a certain extent. Plans were judged strong in addressing surveillance requirements, and provided appropriate communication strategies directed to the general public and health care personnel. However, gaps remained, including the organization of health care services’ response; planning and maintenance of essential services; and the provision of containment measures such as the stockpiling of necessary medical supplies including vaccines and antiviral medications. In addition, some inconsistencies and variations which may be important, such as in border control measures and the capacity to contain outbreaks, exist between country plans—issues that could result in confusion in the event of a pandemic. A number of plans remain developmental in nature and, as elsewhere, more emphasis should be placed on strengthening the operability of plans, and in testing them. Whilst taking account of resources constraints, plans should be further developed in a coherent manner with both regional and international imperatives."
1887,HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic,
1888,Encephalitis after influenza and vaccination: a nationwide population-based registry study from Norway,"BACKGROUND: Influenza is known to be associated with various neurological complications, including encephalitis. We conducted a registry-based study to assess the risk of encephalitis after influenza and A(H1N1)pdm09 vaccine. METHODS: Data from Norwegian national health registries during 2008–14 were linked using the unique personal identifiers given to all Norwegian residents (N = 5 210 519). Cox proportional-hazard models with time-varying variables were fitted to estimate hazard ratios (HRs) of encephalitis after influenza and A(H1N1)pdm09 vaccine, using the risk windows 0–7, 0–14, 0–30, 0–60, 0–90 and 0–180 days. RESULTS: In Norway, 684 172 individuals received an influenza diagnosis and 2793 patients were hospitalized with encephalitis during 2008–14. The risk of encephalitis increased after influenza: HR, 7-day risk window: 47.8 (95% confidence interval (CI): 35.8–63.8), and the HR decreased for longer risk windows; HR, 180-day risk window: 3.8 (95% CI: 3.1–4.7). HR of encephalitis after influenza during the 2009 main pandemic wave using a 7-day risk window was 30.0 (95% CI: 10.8–83.2). We found no differences in the risk of encephalitis after the seasonal influenza compared with influenza during the 2009 main pandemic wave; HR, 7-day risk window: 1.3 (95% CI: 0.4–4.3). A(H1N1)pdm09 vaccine was not associated with the risk of encephalitis: HR, 14-day risk window: 0.6 (95% CI: 0.2–2.1). CONCLUSIONS: There was an increased risk of encephalitis following influenza but not after A(H1N1)pdm09 vaccine. The risk of encephalitis was highest in the first few weeks after influenza."
1889,Pandemic influenza preparedness in Africa is a profound challenge for an already distressed region: analysis of national preparedness plans,"A new highly pathogenic strain of influenza virus, H5N1, has emerged causing severe outbreaks in poultry and high mortality rates when humans are infected. The threat of a new influenza pandemic has prompted countries to draft national strategic preparedness plans to prevent, contain and mitigate the next human influenza pandemic. To evaluate preparedness for an influenza pandemic in the African region we analysed African national preparedness plans available in the public domain. A data extraction tool, based on a World Health Organization checklist for influenza epidemic preparedness, was designed in consultation with pandemic influenza planning experts and experts on the region's public health challenges. Thirty-five plans were identified and available from 53 African countries. Most plans are relatively robust in addressing detection and containment of influenza in animals but strategic preparedness to respond to pandemic human influenza is weak. In most plans communication strategies have been developed with the aim to raise awareness of transmission factors and promote hygiene measures. By contrast, the human health care sector is ill-prepared. Case management, triage procedures, identification of health care facilities for patient treatment (including home care and provisions for the distribution and administration of pharmaceuticals) are poorly addressed by most plans. The maintenance of essential services in the event of a pandemic is absent from most plans. Whilst many African countries have strategic pandemic influenza preparedness plans, most are developmental in nature and lack operational clarity, or focus principally on the containment of avian influenza rather than pandemic human influenza. Clear strategies, that are operational, need to be developed that reflect the realities of national context and resource constraints and that meet national objectives. These objectives need also to be coherent with international imperatives such that the global threat of pandemic influenza can be met effectively and efficiently."
1890,Avian and pandemic human influenza policy in South-East Asia: the interface between economic and public health imperatives,"The aim of this study was to analyse the contemporary policies regarding avian and human pandemic influenza control in three South-East Asia countries: Thailand, Indonesia and Vietnam. An analysis of poultry vaccination policy was used to explore the broader policy of influenza A H5N1 control in the region. The policy of antiviral stockpiling with oseltamivir, a scarce regional resource, was used to explore human pandemic influenza preparedness policy. Several policy analysis theories were applied to analyse the debate on the use of vaccination for poultry and stockpiling of antiviral drugs in each country case study. We conducted a comparative analysis across emergent themes. The study found that whilst Indonesia and Vietnam introduced poultry vaccination programmes, Thailand rejected this policy approach. By contrast, all three countries adopted similar strategic policies for antiviral stockpiling in preparation. In relation to highly pathogenic avian influenza, economic imperatives are of critical importance. Whilst Thailand's poultry industry is large and principally an export economy, Vietnam's and Indonesia's are for domestic consumption. The introduction of a poultry vaccination policy in Thailand would have threatened its potential to trade and had a major impact on its economy. Powerful domestic stakeholders in Vietnam and Indonesia, by contrast, were concerned less about international trade and more about maintaining a healthy domestic poultry population. Evidence on vaccination was drawn upon differently depending upon strategic economic positioning either to support or oppose the policy. With influenza A H5N1 endemic in some countries of the region, these policy differences raise questions around regional coherence of policies and the pursuit of an agreed overarching goal, be that eradication or mitigation. Moreover, whilst economic imperatives have been critically important in guiding policy formulation in the agriculture sector, questions arise regarding whether agriculture sectoral policy is coherent with public health sectoral policy across the region."
1891,Influenza: interspecies transmission and emergence of new pandemics,
1892,"Detection of VIM-34, a novel VIM-1 variant identified in the intercontinental ST15 Klebsiella pneumoniae clone",
1893,Bacteriophage Therapy of a Vibrio parahaemolyticus Infection Caused by a Multiple-Antibiotic–Resistant O3:K6 Pandemic Clinical Strain,"Background. Recently isolated Vibrio parahaemolyticus strains have displayed multiple antibiotic resistance. Alternatives to conventional antibiotics are needed, especially for the multiple-antibiotic–resistant V. parahaemolyticus pandemic strain. Methods. A bacteriophage, designated pVp-1, showed effective infectivity for multiple-antibiotic–resistant V. parahaemolyticus and V. vulnificus, including V. parahaemolyticus pandemic strains. The therapeutic potential of the phage was studied in a mouse model of experimental infection using a multiple-antibiotic–resistant V. parahaemolyticus pandemic strain. We monitored the survivability and histopathological changes, quantified the bacterial and phage titers during phage therapy, and observed the immune response induced by phage induction. Results. Phage-treated mice displayed protection from a V. parahaemolyticus infection and survived lethal oral and intraperitoneal bacterial challenges. Conclusions. To the best of our knowledge, this is the first report of phage therapy in a mouse model against a multiple-antibiotic–resistant V. parahaemolyticus pandemic strain infection."
1894,"Influenza-like illness in Norway: clinical course, attitudes towards vaccination and preventive measures during the 2009 pandemic","Objectives. To document clinical characteristics of influenza-like illness, reported use of health preventive measures and attitudes towards vaccination among patients with influenza-like illness in general practice during the influenza pandemic in 2009. Methods. Cross-sectional survey in general practice. Patients, who were identified as having influenza-like illness during the peak of the influenza pandemic activity in Norway, were eligible for inclusion in the study. A questionnaire was sent 2–4 weeks after the patients visit to the GP with influenza-like illness diagnosis during October to December 2009, from general practices in Norway. A sample of responders >18 years also had a blood test to check for serological response to the pandemic H1N1 virus. Results. Questionnaires were sent to 1324 patients, and 357 (27%) were returned. Fever (91% versus 49%, P < 0.01), cough (85% versus 73%, P = 0.016) and gastrointestinal symptoms (58% versus 38%, P < 0.01) were more frequent in the age group <18 years compared to older patients. Serological H1N1 responses were analysed in 72 patients; 34 (47%) were positive (haemagglutination inhibition assay titres ≥40). There were no statistically significant differences in symptoms between seropositive and seronegative patients. Women reported better adherence to personal protective measures, such as hand washing and cough etiquette than men. Women were also more concerned about possible adverse effects of the pandemic influenza vaccine than men. Conclusions. Discrimination between influenza and other viral upper respiratory tract infections is difficult in daily clinical practice, even during an influenza pandemic. A gender difference was found in reported precautions to prevent influenza."
1895,"Lessons from Pandemic H1N1 2009 to Improve Prevention, Detection, and Response to Influenza Pandemics from a One Health Perspective","In April 2009, a novel influenza A subtype H1N1 triple reassortant virus (novel H1N1 2009), composed of genes from swine, avian, and human influenza A viruses, emerged in humans in the United States and Mexico and spread person-to-person around the world to become the first influenza pandemic of the 21(st) century. The virus is believed to have emerged from a reassortment event involving a swine virus some time in the past 10 to 20 years, but pigs, pork, and pork products have not been involved with infection or spread of the virus to or among people. Because countries quickly implemented recently developed pandemic influenza plans, the disease was detected and reported and public health authorities instituted control measures in a timely fashion. But the news media's unfortunate and inappropriate naming of the disease as the “swine flu” led to a drop in the demand for pork and several countries banned pork imports from affected countries, resulting in serious negative economic impacts on the pork industry. With the continual circulation and interspecies transmission of human, swine, and avian influenza viruses in countries around the world, there are calls for strengthening influenza surveillance in pigs, birds, and other animals to aid in monitoring and assessing the risk of future pandemic virus emergence involving different species. We identify and discuss several lessons to be learned from pandemic H1N1 2009 from a One Health perspective, as stronger collaboration among human, animal, and environmental health sectors is necessary to more effectively prevent or detect and respond to influenza pandemics and thus improve human, animal, and environmental health and well-being."
1896,Why did many more diamond miners than gold miners die in South Africa during the 1918 influenza pandemic?,"The very large difference in mortality rates between Kimberley diamond miners and Witwatersrand gold miners during the 1918 influenza pandemic has never been explained. We examined extant epidemiological records from South African mining operations and other related activities to determine if mortality risk factors could be measured. During October 1918 when pandemic influenza struck in South Africa, the mortality rates in Kimberley diamond miners (22.4%, n = 11 445) were >35 times that of Rand gold miners (0.6%, n = 200 000). There were no differences discernable between diamond and gold miners regarding their recruitment, working conditions, housing or medical care that would explain the great variance in mortality rates. Reports of influenza-like illness in Natal Province some weeks prior to the main pandemic suggest infection from a mild version of influenza and thus protection of the gold miners from mortality whereas the more isolated diamond miners only experienced the second, more lethal, wave. The huge mortality difference between South African diamond and gold miners in 1918 is most likely explained by the circulation of a related but not identical virus to the A/H1N1 pandemic strain which reached Johannesburg prior to October 1918 because of its better transportation connections."
1897,"Five years of non-prescription oseltamivir: effects on resistance, immunization and stockpiling","OBJECTIVES: In 2007 New Zealand (NZ) became the first country to make oseltamivir (Tamiflu®) available off-prescription. This study investigated the extent of pharmacist supply of oseltamivir over 5 years, including during the influenza A(H1N1) pandemic, and the impact of pharmacist supply of oseltamivir on influenza virus oseltamivir susceptibility, personal stockpiling and influenza vaccine uptake. METHODS: Randomly selected community pharmacies in NZ reported oseltamivir provision by prescription and through pharmacist supply from 1 January 2007 to 15 September 2011. Oseltamivir resistance data on influenza viruses isolated during influenza surveillance from 2008 to 2011 were obtained, along with influenza vaccine uptake data from 2005 to 2011 and influenza detection data. RESULTS: Seventy of 85 eligible pharmacies completed the study (82% response rate). Most supplies of oseltamivir throughout the 5 years were dispensed against a prescription rather than pharmacist supplied, with pharmacist supply responsible for 11% of supplies during the pandemic years (2009–10) versus 27% and 31% during 2007 and 2008, respectively. Pharmacist-supplied oseltamivir did not appear to be associated with the development of resistance, with identified likely stockpiling or with a decline in influenza immunization. Pharmacist supplies largely matched the timing of influenza in the community and peaked in June 2009, as did prescription supplies. CONCLUSIONS: Five years of non-prescription oseltamivir in NZ has resulted in no significant change in the development of resistance or rates of influenza immunization. Supplies remained modest and significant consumer stockpiling through pharmacist supply has not occurred, even during the influenza A(H1N1)pdm09 pandemic in 2009 and 2010. Pharmacists could be better utilized in ensuring fast distribution of antivirals to influenza sufferers during a pandemic."
1898,Factors in vaccination intention against the pandemic influenza A/H1N1,"Background: Vaccination against pandemic influenza A/H1N1 is an effective strategy to mitigate the spread of the disease. While the vaccine is now available, social acceptance remains relatively uncertain in many societies. The purpose of this study was to examine the beliefs, attitudes and practices associated with the intention to get vaccinated against the A/H1N1 virus among the general population in France. Methods: A representative sample of 1001 individuals (stratified random recruitment procedure, ages 16–90 years) was interviewed by telephone. The questionnaire included a variety of items associated with socio-demographic characteristics, risk perceptions, illness perceptions, political attitudes and worldviews as well as intention to get vaccinated. Results: More than 6 out of 10 of the respondents indicated that they planned to get vaccinated when the vaccine becomes available. The same proportion of parents also reported the intention to vaccinate their children against the disease. In multiple regression analyses, socio-cognitive factors consistently predicting influenza A/H1N1 vaccination were: level of worry, risk perception and previous experience of vaccine against seasonal flu. Conclusions: The factors found to predict vaccination intention and their distribution are assumed to be a consequence of the fact that people perceive the risk of swine flu to be similar to that of seasonal flu. As a result, in the absence of an increase of the risk perception of pandemic influenza A/H1N1, a very low level of actual vaccination is forecasted. Behavioural change would require that the risks and consequences of pandemic influenza A/H1N1 be perceived as highly different from seasonal flu."
1899,Evaluating the effectiveness of antiviral treatment in models for influenza pandemic,"We study the effectiveness of antiviral treatment in simple susceptible–exposed–infectious–removed models that are at the base of models used for influenza pandemic. The strategy is assessed in terms of the value of the reproductive ratio R(0). We consider a general framework and analyse six different specific cases. The same antiviral strategy is simulated in all models, but they slightly differ in the compartmental structure. These differences correspond to different underlying assumptions concerning the timing of the intervention and the selection of individuals who receive treatment. It is shown that these details can have a strong influence on the predicted effectiveness of the strategy: for instance, with R(0) = 1.8 in absence of treatment, different models predict that with treatment R(0) can become as low as 0.4 or as high as 1.3; still, in all models 70% of infected individuals are treated and the infectiousness of treated individuals is reduced by 80%. A particular assumption that can be included when modelling influenza is time-varying infectivity. We consider a specific model to verify if the predicted effectiveness of antiviral treatment is influenced by the inclusion of this assumption. We compare the results obtained with constant and variable infectivity, in relation also to the time of intervention. It is likely that existing differences in the predictions of the effect of control measures depend on such modelling details. This finding stresses the need for carefully defining the structure of models in order to obtain results useful for policymakers in pandemic planning."
1900,Thoracic surgeons’ insights: Improving thoracic surgery outcomes during the Coronavirus Disease 2019 pandemic,
1901,Hospitalized Patients With COVID-19 and Human Immunodeficiency Virus: A Case Series,
1902,Editorial Commentary: Flying Under the Radar: The Stealth Pandemic of Escherichia coli Sequence Type 131,
1903,Using Results From Infectious Disease Modeling to Improve the Response to a Potential H7N9 Influenza Pandemic,"As the Centers for Disease Control and Prevention (CDC) and other government agencies prepared for a possible H7N9 pandemic, many questions arose about the virus's expected burden and the effectiveness of key interventions. Public health decision makers need information to compare interventions so that efforts can be focused on interventions most likely to have the greatest impact on morbidity and mortality. To guide decision making, CDC's pandemic response leadership turned to experts in modeling for assistance. H7N9 modeling results provided a quantitative estimate of the impact of different interventions and emphasized the importance of key assumptions. In addition, these H7N9 modeling efforts highlighted the need for modelers to work closely with investigators collecting data so that model assumptions can be adjusted as new information becomes available and with decision makers to ensure that the results of modeling impact policy decisions."
1904,Seasonal Influenza Vaccine Impact on Pandemic H1N1 Vaccine Efficacy,"BACKGROUND: In 2009, a novel influenza A (pH1N1) was identified, resulting in a pandemic with significant morbidity and mortality. A monovalent pH1N1 vaccine was separately produced in addition to the seasonal trivalent influenza vaccine. Formulation of the seasonal influenza vaccine (injectable trivalent inactivated influenza vaccine [TIV] vs. intranasal live, attenuated influenza vaccine [LAIV]) was postulated to have impacted the efficacy of the pH1N1 vaccination. METHODS: We reviewed electronic health and databases, which included vaccination records, and healthcare encounters for influenza-like illness (ILI), influenza, and pneumonia among US military members. We examined rates by vaccination type to identify factors associated with the risk for study outcomes. RESULTS: Compared with those receiving the seasonal influenza vaccine alone, subjects receiving the pH1N1 vaccine, either alone (RR, 0.49) or in addition to the seasonal vaccine (RR, 0.51), had an approximately 50% reduction in ILI, 88% reduction in influenza (RR, 0.11 and 0.12, respectively), and 63% reduction in pneumonia (RR, 0.37 and 0.35, respectively). There was no clinically significant difference in ILI, influenza, or pneumonia attack rates among those receiving the pH1N1 vaccine with or without presence of the seasonal vaccine. Similarly, there was no clinically relevant difference in pH1N1 effectiveness between seasonal TIV and LAIV recipients. CONCLUSIONS: During the 2009–2010 pandemic, the pH1N1 vaccination was effective in reducing rates of ILI, influenza, and pneumonia. Administration of the seasonal vaccine should continue without concern of potential interference with a novel pandemic vaccine, though more studies are needed to determine if this is applicable to other influenza seasons."
1905,How Will Physicians Respond to the Next Influenza Pandemic?,"The emergence of the H7N9 virus in China is another reminder of the threat of a global influenza pandemic. Many believe we could confront a pandemic by expanding our capacity to provide timely supplies of affordable pandemic vaccines and antiviral agents. Experience in 2009 demonstrated that this cannot and will not be done. Consequently, physicians may have little more to offer their patients than they had in the 1918 pandemic. Fortunately, several modern drugs (eg, statins, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors) can modify the host response to inflammatory illness, and laboratory and clinical studies suggest they might be used to treat pandemic patients. Unfortunately, little attention has been given to the research needed to support their use in patient care. There is no guarantee these drugs will work, but physicians will never know unless those responsible for pandemic preparedness recognize and act on the extraordinary possibility that they might save lives."
1906,Ebola in Antiquity?,"This article addresses whether Ebola may have been present in an urban setting in Athens in 430 bce and explores the historical importance of the ancient outbreak. New knowledge from today's West African epidemic allows a more accurate assessment of whether Ebola may have caused the Athenian outbreak than was once possible. The Athenian disease, whose etiology remains unknown, developed abruptly with fevers, abdominal pain, vomiting, diarrhea, dehydration, and hemorrhage. It originated in sub-Saharan Africa and was especially contagious to doctors and caregivers. No remedies were effective. But the few survivors who were reexposed to diseased patients were not attacked a second time, suggesting protective immunity. What lessons can we learn from the ancient outbreak that bears a clinical and epidemiologic resemblance to Ebola? The historian Thucydides, an eyewitness and disease sufferer, described how the unsuspecting city panicked as it struggled to handle the rapidly spreading, devastating disease. Moreover, he stressed a theme that has relevance today—namely, that fear and panic intensified the disruption of society and damage to the individual that was directly caused by the disease. Moreover, fear amplified the spread of disease. The destructive nature of fear has remained a signature feature of pestilences that have subsequently caught ill-prepared societies off-guard—Bubonic plague in medieval times, AIDS in the 1980s, and Ebola today. The ancient Athenian epidemic is relevant for today's West African Ebola outbreak because it shows how fear and panic can endanger the individual, our society, and our efforts to handle the disease."
1907,Effectiveness of Nonadjuvanted Monovalent Influenza A(H1N1)pdm09 Vaccines for Preventing Reverse Transcription Polymerase Chain Reaction–Confirmed Pandemic Influenza Hospitalizations: Case-Control Study of Children and Adults at 10 US Influenza Surveillance Network Sites,"During 2009–2010, we examined 217 patients hospitalized with laboratory-confirmed pandemic influenza in 9 Influenza Hospitalization Surveillance Network sites and 413 age- and community-matched controls and found that a single dose of monovalent nonadjuvanted influenza A(H1N1)pdm09 vaccine was 50% (95% confidence interval, 13%–71%) effective in preventing hospitalization associated with A(H1N1)pdm09 virus infection."
1908,Readiness for Responding to a Severe Pandemic 100 Years After 1918,"The 1918 H1N1 pandemic caused an unprecedented number of deaths worldwide. The tools to deal with the global emergency were limited; there were insufficient surveillance systems and a dearth of diagnostic, treatment, and prevention options. With continuing focus on pandemic planning, technologic advances in surveillance, vaccine capabilities, and 21st century medical care and countermeasures, we are more prepared for a severe pandemic than people were 100 years ago; however, notable gaps remain."
1909,Editorial Commentary: Is Prepandemic Vaccination a Wise Investment?,
1910,Investing in Immunity: Prepandemic Immunization to Combat Future Influenza Pandemics,"We are unlikely, with current technologies, to have sufficient pandemic influenza vaccine ready in time to impact the first wave of the next pandemic. Emerging data show that prior immunization with an immunologically distinct hemagglutinin of the same subtype offers the potential to “prime” recipients for rapid protection with a booster dose, years later, of a vaccine then manufactured to match the pandemic strain. This article proposes making prepandemic priming vaccine(s) available for voluntary use, particularly to those at high risk of early occupational exposure, such as first responders and healthcare workers, and to others maintaining critical infrastructure. In addition to providing faster protection and potentially reducing social disruption, being able, early in a pandemic, to immunize those who had received prepandemic vaccine with one dose of the pandemic vaccine, rather than the 2 doses typically required, would reduce the total doses of pandemic vaccine then needed, extending vaccine supplies."
1911,Reassessing the Global Mortality Burden of the 1918 Influenza Pandemic,"Mortality estimates of the 1918 influenza pandemic vary considerably, and recent estimates have suggested that there were 50 million to 100 million deaths worldwide. We investigated the global mortality burden using an indirect estimation approach and 2 publicly available data sets: the Human Mortality Database (13 countries) and data extracted from the records of the Statistical Abstract for British India. The all-cause Human Mortality Database was used to estimate mortality annually for 1916–1921 for detailed age groups. Three different calculation methods were applied to the data (low, medium, and high scenarios), and we used a multilevel regression model to control for distorting factors (e.g., war and the underlying time trend in mortality). Total pandemic mortality was an estimated 15 million deaths worldwide in 1918 (n = 2.5 million in 1919) after including the rates for British India and controlling for wars and the underlying mortality trend. According to our validity analysis, simulations of total number of deaths being greater than 25 million are not realistic based on the underlying mortality rates included in Human Mortality Database and in British India. Our results suggest the global death impact of the 1918 pandemic was important (n = 17.4 million) but not as severe as most frequently cited estimates."
1912,Potential Demand for Respirators and Surgical Masks During a Hypothetical Influenza Pandemic in the United States,"Background. To inform planning for an influenza pandemic, we estimated US demand for N95 filtering facepiece respirators (respirators) by healthcare and emergency services personnel and need for surgical masks by pandemic patients seeking care. Methods. We used a spreadsheet-based model to estimate demand for 3 scenarios of respirator use: base case (usage approximately follows epidemic curve), intermediate demand (usage rises to epidemic peak and then remains constant), and maximum demand (all healthcare workers use respirators from pandemic onset). We assumed that in the base case scenario, up to 16 respirators would be required per day per intensive care unit patient and 8 per day per general ward patient. Outpatient healthcare workers and emergency services personnel would require 4 respirators per day. Patients would require 1.2 surgical masks per day. Results and Conclusions. Assuming that 20% to 30% of the population would become ill, 1.7 to 3.5 billion respirators would be needed in the base case scenario, 2.6 to 4.3 billion in the intermediate demand scenario, and up to 7.3 billion in the maximum demand scenario (for all scenarios, between 0.1 and 0.4 billion surgical masks would be required for patients). For pandemics with a lower attack rate and fewer cases (eg, 2009-like pandemic), the number of respirators needed would be higher because the pandemic would have longer duration. Providing these numbers of respirators and surgical masks represents a logistic challenge for US public health agencies. Public health officials must urgently consider alternative use strategies for respirators and surgical masks during a pandemic that may vary from current practices."
1913,Short-Term Birth Sequelae of the 1918–1920 Influenza Pandemic in the United States: State-Level Analysis,"This paper examines short-term birth sequelae of the influenza pandemic of 1918–1920 in the United States using monthly data on births and all-cause deaths for 19 US states in conjunction with data on maternal deaths, stillbirths, and premature births. The data on births and all-cause deaths are adjusted for seasonal and trend effects, and the residual components of the 2 time series coinciding with the timing of peak influenza mortality are examined for these sequelae. Notable findings include: 1) a drop in births in the 3 months following peak mortality; 2) a reversion in births to normal levels occurring 5–7 months after peak mortality; and 3) a steep drop in births occurring 9–10 months after peak mortality. Interpreted in the context of parallel data showing elevated premature births, stillbirths, and maternal mortality during times of peak influenza mortality, these findings suggest that the main impacts of the 1918–1920 influenza on reproduction occurred through: 1) impaired conceptions, possibly due to effects on fertility and behavioral changes; 2) an increase in the preterm delivery rate during the peak of the pandemic; and 3) elevated maternal and fetal mortality, resulting in late-term losses in pregnancy."
1914,Complications Among Adults Hospitalized With Influenza: A Comparison of Seasonal Influenza and the 2009 H1N1 Pandemic,"Background. Persons with influenza can develop complications that result in hospitalization and death. These are most commonly respiratory related, but cardiovascular or neurologic complications or exacerbations of underlying chronic medical conditions may also occur. Patterns of complications observed during pandemics may differ from typical influenza seasons, and characterizing variations in influenza-related complications can provide a better understanding of the impact of pandemics and guide appropriate clinical management and planning for the future. Methods. Using a population-based surveillance system, we compared clinical complications using International Classification of Diseases, Ninth Revision (ICD-9) discharge diagnosis codes in adults hospitalized with seasonal influenza (n = 5270) or 2009 pandemic influenza A(H1N1) (H1N1pdm09; n = 4962). Results. Adults hospitalized with H1N1pdm09 were younger (median age, 47 years) than those with seasonal influenza (median age, 68 years; P < .01), and differed in the frequency of certain underlying medical conditions. Whereas there was similar risk for many influenza-associated complications, after controlling for age and type of underlying medical condition, adults hospitalized with H1N1pdm09 were more likely to have lower respiratory tract complications, shock/sepsis, and organ failure than those with seasonal influenza. They were also more likely to be admitted to the intensive care unit, require mechanical ventilation, or die. Young adults, in particular, had 2–4 times the risk of severe outcomes from H1N1pdm09 than persons of the same ages with seasonal influenza. Conclusions. Although H1N1pdm09 was thought of as a relatively mild pandemic, these data highlight the impact of the 2009 pandemic on the risk of severe influenza, especially among younger adults, and the impact this virus may continue to have."
1915,"The Rise of the Current Mortality Pattern of the United States, 1890–1930","This article examines how the epidemiologic transition and the reduction of the urban mortality penalty gave rise to the current mortality regime of the United States and demonstrates how the 1918 influenza pandemic signaled its advent. This article approaches those issues through the analysis of urban-rural mortality differentials from 1890 to 1930. Until 1910, infectious diseases dwarfed degenerative diseases in leading causes of death, and generally, the more urban the location was, the higher infectious disease and overall death rates were—a direct relationship. But by 1930, degenerative diseases had eclipsed infectious diseases, and infectious disease mortality had ceased to differ between cities and rural areas. The 1918 influenza pandemic broke out toward the end of these changes, and the larger the city was, the lower influenza and overall death rates were in that year—an inverse relationship. Such gradations characterized a new mortality regime emerging in the late 1910s and foreshadowed urban-rural mortality differentials in 1930 among persons aged 45 years or older, the group whose high rates of degenerative disease death would symbolize that regime. Thus, intertwined changes in the late 19th and early 20th centuries—a shift in leading causes of death from infectious diseases to degenerative diseases and a concomitant shift from a direct relationship to an inverse relationship between urban environment and mortality—produced the current mortality regime of the United States."
1916,Further Evidence for Bias in Observational Studies of Influenza Vaccine Effectiveness: The 2009 Influenza A(H1N1) Pandemic,"Preinfluenza periods have been used to test for uncontrolled confounding in studies of influenza vaccine effectiveness, but some authors have claimed that confounding differs in preinfluenza and influenza periods. We tested this claim by comparing estimates of the vaccine-mortality association during the 2009/2010 influenza year, when there was essentially no circulation of seasonal influenza in the United States, and 2007/2008, a typical influenza year. We pooled data on seniors (adults aged ≥65 years) from 7 US managed care organizations that participated in the Vaccine Safety Datalink Project. We defined influenza vaccination, all-cause mortality, and potential confounders from administrative databases. We quantified the vaccine-mortality association using Cox regression. During 2007/2008, the adjusted hazard ratio was 0.44 prior to influenza season, 0.62 during influenza season, and 0.71 after influenza season. A similar pattern was observed during 2009/2010, when any effect of seasonal influenza vaccine observed during all time periods must have resulted from confounding: 0.65 during the autumn, 0.80 during the winter, and 0.84 during the summer. In a year with minimal seasonal influenza, we found no evidence that confounding in autumn preinfluenza periods is qualitatively different from confounding in winter. This supports the use of preinfluenza periods as control time periods in studies of influenza vaccine effectiveness."
1917,The 1918–1919 Influenza Pandemic in Portugal: A Regional Analysis of Death Impact,"Although the impact of deaths occurring during the 1918–1919 influenza pandemic has been assessed in many archeo-epidemiologic studies, detailed estimates are not available for Portugal. We applied negative binomial models to monthly data on respiratory-related and all-cause deaths at the national and district levels from Portugal for 1916–1922. Influenza-related excess mortality was computed as the difference between observed and expected deaths. Poisson regression was used to estimate the association of geographic and sociodemographic factors with excess mortality. Two waves of pandemic influenza—July 1918 to January 1919 and April to May 1919—were identified, for which the excess all-cause death rate was 195.7 per 10,000 persons. All districts of Portugal were affected. The pandemic hit earlier in southeastern districts and the main cities, but excess mortality was highest in the northeast, in line with the high death burden experienced by northern Spanish provinces. During the period of intense excess mortality (fall/winter 1918–1919), population density was negatively associated with pandemic impact. This pattern changed during the March 1919 to June 1920 wave, when excess mortality increased with population density and in northern and western directions. Portuguese islands were less and later affected. Given the geographic heterogeneity evidenced in our study, subnational sociodemographic characteristics and connectivity should be integrated in pandemic preparedness plans."
1918,Social Class and Excess Mortality in Sweden During the 1918 Influenza Pandemic,"Consensus is lacking in the literature about the role of socioeconomic factors on influenza-associated deaths during the 1918 pandemic. Although some scholars have found that social factors were important, others have not. In this study, we analyzed differences in excess mortality by social class in Sweden during the 1918 pandemic. We analyzed individual-level mortality of the entire population aged 30–59 years by combining information from death records with census data on occupation. Social class was measured by an occupation-based class scheme. Excess mortality during the pandemic was measured as the number of deaths relative to the number occurring in the same month the year before. Social class differences in numbers of deaths were modeled using a complementary log-log model that was adjusted for potential confounding at the family, the residential (urban/rural), and the county levels. We found notable class differences in excess mortality but no perfect class gradient. Class differences were somewhat larger for men than for women."
1919,Loose Ends in the Epidemiology of the 1918 Pandemic: Explaining the Extreme Mortality Risk in Young Adults,"In the century since the 1918 influenza pandemic, insights have been sought to explain the pandemic’s signature pattern of high death rates in young adults and low death rates in the elderly and infants. Our understanding of the origin and evolution of the pandemic has shifted considerably. We review evidence of the characteristic age-related pattern of death during the 1918 pandemic relative to the “original antigenic sin” hypothesis. We analyze age-stratified mortality data from Copenhagen around 1918 to identify break points associated with unusual death risk. Whereas infants had no meaningful risk elevation, death risk gradually increased, peaking for young adults 20–34 years of age before dropping sharply for adults ages 35–44 years, suggesting break points for birth cohorts around 1908 and 1878. Taken together with data from previous studies, there is strong evidence that those born before 1878 or after 1908 were not at increased risk of dying of 1918 pandemic influenza. Although the peak death risk coincided with the 1889–1892 pandemic, the 1908 and 1878 break points do not correspond with known pandemics. An increasing number of interdisciplinary studies covering fields such as virology, phylogenetics, death, and serology offer exciting insights into patterns and reasons for the unusual extreme 1918 pandemic mortality risk in young adults."
1920,Simulation: Keeping Pace With Pandemics,
1921,COVID-KOP: Integrating Emerging COVID-19 Data with the ROBOKOP Database,"In response to the COVID-19 pandemic, we established COVID-KOP, a new knowledgebase integrating the existing ROBOKOP biomedical knowledge graph with information from recent biomedical literature on COVID-19 annotated in the CORD-19 collection. COVID-KOP can be used effectively to test new hypotheses concerning repurposing of known drugs and clinical drug candidates against COVID-19. COVID-KOP is freely accessible at https://covidkop.renci.org/. For code and instructions for the original ROBOKOP, see: https://github.com/NCATS-Gamma/robokop."
1922,Comparing the estimates of effect obtained from statistical causal inference methods: An example using bovine respiratory disease in feedlot cattle,"The causal effect of an exposure on an outcome of interest in an observational study cannot be estimated directly if the confounding variables are not controlled. Many approaches are available for estimating the causal effect of an exposure. In this manuscript, we demonstrate the advantages associated with using inverse probability weighting (IPW) and doubly robust estimation of the odds ratio in terms of reduced bias. IPW approach can be used to adjust for confounding variables and provide unbiased estimates of the exposure’s causal effect. For cluster-structured data, as is common in animal populations, inverse conditional probability weighting (ICPW) approach can provide a robust estimation of the causal effect. Doubly robust estimation can provide a robust method even when the specification of the model form is uncertain. In this paper, the usage of IPW, ICPW, and doubly robust approaches are illustrated with a subset of data with complete covariates from the Australian-based National Bovine Respiratory Disease Initiative as well as simulated data. We evaluate the causal effect of prior bovine viral diarrhea exposure on bovine respiratory disease in feedlot cattle. The results show that the IPW, ICPW and doubly robust approaches would provide a more accurate estimation of the exposure effect than the traditional outcome regression model, and doubly robust approaches are the most preferable overall."
1923,"Outbreaks Associated with Untreated Recreational Water — California, Maine, and Minnesota, 2018–2019",
1924,On some factors determining the pressure drop across tracheal tubes during high-frequency percussive ventilation: a flow-independent model,"To provide an in vitro estimation of the pressure drop across tracheal tubes (ΔP(TT)) in the face of given pulsatile frequencies and peak pressures (P(work)) delivered by a high-frequency percussive ventilator (HFPV) applied to a lung model. Tracheal tubes (TT) 6.5, 7.5 and 8.0 were connected to a test lung simulating the respiratory system resistive (R = 5, 20, 50 cmH(2)O/L/s) and elastic (C = 10, 20, and 50 mL/cmH(2)O) loads. The model was ventilated by HFPV with a pulse inspiratory peak pressure (work pressure P(work)) augmented in 5-cmH(2)O steps from 20 to 45 cmH(2)O, yielding 6 diverse airflows. The percussive frequency (f) was set to 300, 500 and 700 cycles/min, respectively. Pressure (Paw and Ptr) and flow (V’) measurements were performed for all 162 possible combinations of loads, frequencies, and work pressures for each TT size, thus yielding 486 determinations. For each respiratory cycle ΔP(TT) was calculated by subtracting each peak Ptr from its corresponding peak Paw. A non-linear model was constructed to assess the relationships between single parameters. Performance of the produced model was measured in terms of root mean square error (RMSE) and the coefficient of determination (r(2)). ΔP(TT) was predicted by P(work) (exponential Gaussian relationship), resistance (quadratic and linear terms), frequency (quadratic and linear terms) and tube diameter (linear term), but not by compliance. RMSE of the model on the testing dataset was 1.17 cmH(2)O, r(2) was 0.79 and estimation error was lower than 1 cmH(2)O in 68% of cases. As a result, even without a flow value, the physician would be able to evaluate ΔP(TT) pressure. If the present results of our bench study could be clinically confirmed, the use of a nonconventional ventilatory strategy as HFPV, would be safer and easier."
1925,Specific labeling of synaptic schwann cells reveals unique cellular and molecular features,"Perisynaptic Schwann cells (PSCs) are specialized, non-myelinating, synaptic glia of the neuromuscular junction (NMJ), that participate in synapse development, function, maintenance, and repair. The study of PSCs has relied on an anatomy-based approach, as the identities of cell-specific PSC molecular markers have remained elusive. This limited approach has precluded our ability to isolate and genetically manipulate PSCs in a cell specific manner. We have identified neuron-glia antigen 2 (NG2) as a unique molecular marker of S100β+ PSCs in skeletal muscle. NG2 is expressed in Schwann cells already associated with the NMJ, indicating that it is a marker of differentiated PSCs. Using a newly generated transgenic mouse in which PSCs are specifically labeled, we show that PSCs have a unique molecular signature that includes genes known to play critical roles in PSCs and synapses. These findings will serve as a springboard for revealing drivers of PSC differentiation and function."
1926,Development of a TB vaccine trial site in Africa and lessons from the Ebola experience,"Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination."
1927,Usefulness of point-of-care multiplex PCR to rapidly identify pathogens responsible for ventilator-associated pneumonia and their resistance to antibiotics: an observational study,"BACKGROUND: The use of multiplex PCR to shorten time to identification of pathogens and their resistance mechanisms for patients with ventilator-associated pneumonia (VAP) is attractive, but poorly studied. The multiplex PCR–based Unyvero pneumonia cartridge assay can directly identify 20 bacteria and one fungus, amongst the most frequently causing VAP, and 19 of their resistance markers in clinical specimens (bronchoalveolar lavage or tracheal aspirate), with a turnaround time of 4–5 h. We performed this study to evaluate the concordance between the multiplex PCR–based Unyvero pneumonia cartridge assay and conventional microbiological techniques to identify pathogens and their resistance mechanisms in patients with VAP. METHODS: All patients suspected of having VAP (January 2016 to January 2019), who underwent fiberoptic bronchoscopy with bronchoalveolar lavage fluid (BALF) and whose BALF microscopy examination revealed intracellular bacteria, were included. BALF conventional cultures (gold standard), antimicrobial susceptibility testing and processing for the Unyvero pneumonia cartridge were done. Culture and Unyvero results were compared. RESULTS: Compared to cultures of the 93 samples processed for both techniques, Unyvero correctly identified pathogens in 68 (73%) proven VAP episodes, was discordant for 25 (27%), detected no pathogen in 11 and overdetected a not otherwise found pathogen in six. For the eight remaining discordant results, the pathogen responsible for VAP was not included in the Unyvero cartridge panel or it grew at a non-significant level in culture. Amongst the 31 (33%) resistance mechanism discordances observed, 22 were resistance detection failures and 24 concerned Pseudomonas aeruginosa. CONCLUSIONS: Compared to conventional microbiological cultures, the Unyvero pneumonia cartridge had poor diagnostic performance: it correctly identified pathogens and their resistance mechanisms in 73% and 67% of VAP cases, respectively. The lack of performance on the resistance mechanism was more pronounced when the pathogen detected was a Pseudomonas aeruginosa."
1928,Oncology patient support,
1929,UDC highs and lows in Cornwall,
1930,Back to work,
1931,New video will promote silver diamine fluoride to children,
1932,Paediatric emergencies,
1933,A new era for dental education,
1934,Coronamolars?,
1935,Working through it,
1936,BDA updates its returning to work toolkit for members,
1937,Chlorhexidine has an antiviral effect against viruses,
1938,Virucidal activity,
1939,"Comparison of reduced-toxicity conditioning protocols using fludarabine, melphalan combined with thiotepa or carmustine in allogeneic hematopoietic cell transplantation","The age of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) has increased during the last decades, mainly due to improved reduced-intensity/toxicity conditioning protocols. A reduced-intensity conditioning based on fludarabin, carmustin/BCNU and melphalan (FBM) has been previously developed at our institution. Since we observed detrimental effects in individual patients with compromised lung function, efforts have been made in order to replace BCNU by thiotepa (FTM) to reduce toxicity. In this study, we retrospectively analyzed the outcome, GvHD incidence, lung function and organ toxicity of patients with a median age of 62 years (range 21–79) transplanted for malignant disease (96.7%, 62.3% in intermediate/advanced disease stage) at our institution after conditioning with FBM (n = 136) or FTM (n = 105) between 2013 and 2017. Median follow-up was 868 days (range 0–2615). In multivariate analysis for overall survival, no difference was detected between both conditioning protocols in the presence of impaired lung function, age, lower performance, and liver disease previous allo-HCT. In the subgroup analysis, FTM was not inferior to FBM in patients with pulmonary disease prior allo-HCT, lymphoid malignancies, and higher comorbidity index. In conclusion, the reduced-intensity FBM and FTM conditioning protocols show adequate antineoplastic efficacy and are suitable for patients with impaired lung function."
1940,' My training prepared me for far more than just clinical dentistry',
1941,"Cobalt-catalyzed highly enantioselective hydrogenation of α,β-unsaturated carboxylic acids","Asymmetric hydrogenation of α,β-unsaturated acids catalyzed by noble metals has been well established, whereas, the asymmetric hydrogenation with earth-abundant-metal was rarely reported. Here, we describe a cobalt-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic acids. By using chiral cobalt catalyst bearing electron-donating diphosphine ligand, high activity (up to 1860 TON) and excellent enantioselectivity (up to >99% ee) are observed. Furthermore, the cobalt-catalyzed asymmetric hydrogenation is successfully applied to a broad spectrum of α,β-unsaturated carboxylic acids, such as various α-aryl and α-alkyl cinnamic acid derivatives, α-oxy-functionalized α,β-unsaturated acids, α-substituted acrylic acids and heterocyclic α,β-unsaturated acids (30 examples). The synthetic utility of the protocol is highlighted by the synthesis of key intermediates for chiral drugs (6 cases). Preliminary mechanistic studies reveal that the carboxy group may be involved in the control of the reactivity and enantioselectivity through an interaction with the metal centre."
1942,Changes in pulmonary oxygen content are detectable with laser absorption spectroscopy: proof of concept in newborn piglets,"BACKGROUND: Using an optical method based on tunable diode laser absorption spectroscopy, we previously assessed oxygen (O(2)) and water vapor (H(2)O) content in a tissue phantom of the preterm infant lung. Here we applied this method on newborn piglets with induced lung complications. METHODS: Five mechanically ventilated piglets were subjected to stepwise increased and decreased fraction of inspired oxygen (FiO(2)), to atelectasis using a balloon catheter in the right bronchus, and to pneumothorax by injecting air in the pleural cavity. Two diode lasers (764 nm for O(2) gas absorption and 820 nm for H(2)O absorption) were combined in a probe delivering light either externally, on the skin, or internally, through the esophagus. The detector probe was placed dermally. RESULTS: Calculated O(2) concentrations increased from 20% (IQR 17−23%) when ventilated with room air to 97% (88−108%) at FiO(2) 1.0. H(2)O was only detectable with the internal light source. Specific light absorption and transmission patterns were identified in response to atelectasis and pneumothorax, respectively. CONCLUSIONS: The optical method detected FiO(2) variations and discriminated the two induced lung pathologies, providing a rationale for further development into a minimally invasive device for real-time monitoring gas changes in the lungs of sick newborn infants. IMPACT: Optical spectroscopy can detect pulmonary complications in an animal model. Oxygen concentrations can be evaluated in the lungs. Presents a novel minimally invasive method to detect lung oxygenation and complications. Potential to be developed into a lung monitoring method in newborn infants. Potential for bed-side detection of pulmonary complications in newborn infants."
1943,Status of Editing and Publishing of Scholarly Journals by Academic Societies of Science and Technology in Korea,"BACKGROUND: The present study analyzed publishing data of scholarly journals which were published in 2018 by academic societies of science and technology in Korea to observe journal editing and publishing status. METHODS: A total of 346 regional journals (59 natural science, 118 engineering, 44 agriculture, fisheries, and oceanography, and 125 medical and pharmacy) and 141 international journals (32 natural science, 43 engineering, 12 agriculture, fisheries, and oceanography, 54 medical and pharmacy) were included in this analysis, which applied the journal review by the Korea Federation of Science and Technology. Websites of the journals and the submitted publication data in 2019 were reviewed. RESULTS: Except for a few journals, all of the journals were published by academic societies. Basic information of journals was well displayed by both offline and online. Most of the 346 regional journals were published in Korean language or mixed with English but 77 (22.3%), mostly medical, were in English. One-third (n = 104) journals published less than 40 articles while 9 published over 200, and 261 journals (75.4%) received less than 100 submissions in 2018. Most (n = 298, 86.1%) of them were enlisted in the Korean Citation Index (KCI). Editorial board members performed manuscript editing in 171 (49.4%) journals, and most of the journals paid < 50,000,000 won for publishing costs. Of 141 international journals, 138 (97.9%) were published in English and all of them published overseas submissions. Forty-one (29.1%) journals accepted < 20% of submissions but 58 (41.1%) accepted 100%. Of them, 124 (87.9%) were indexed in the KCI, 93 (66.0%) in the Web of Science, 120 in Scopus, and 62 in PubMed. Editorial board members in 38 (27.0%) journals took responsibility of manuscript editing. Publishing cost of 79 (56.0%) journals was < 50,000,000 won. Only 157 (32.2%) of total 487 journals, mostly medical, documented gendered innovation in their instruction to authors. CONCLUSION: Most of the Korean science and technology journals keep global standard of editing and publishing. Their offline and online visibility is acceptable but most regional journals are small and of low academic impact while international journals are globally indexed and acknowledged. Korean scholarly journals should invite more and better articles to keep quality publication."
1944,Evaluating Safety and Efficacy of Follow-up for Patients With Abdominal Pain Using Video Consultation (SAVED Study): Randomized Controlled Trial,"BACKGROUND: The benefits of telemedicine include cost savings and decentralized care. Video consultation is one form that enables early detection of deteriorating patients and promotion of self-efficacy in patients who are well but anxious. Abdominal pain is a common symptom presented by patients in emergency departments. These patients could benefit from video consultation, as it enables remote follow-up of patients who do not require admission and facilitates early discharge of patients from overcrowded hospitals. OBJECTIVE: The study aimed to evaluate the safety and efficacy of the use of digital telereview in patients presenting with undifferentiated acute abdominal pain. METHODS: The SAVED study was a prospective randomized controlled trial in which follow-up using existing telephone-based telereview (control) was compared with digital telereview (intervention). Patients with undifferentiated acute abdominal pain discharged from the emergency department observation ward were studied based on intention-to-treat. The control arm received routine, provider-scheduled telereview with missed reviews actively coordinated and rescheduled by emergency department staff. The intervention arm received access to a platform for digital telereview (asynchronous and synchronous format) that enabled patient-led appointment rescheduling. Patients were followed-up for 2 weeks for outcomes of service utilization, efficacy (compliance with their disposition plan), and safety (re-presentation for the same condition). RESULTS: A total of 70 patients participated, with patients randomly assigned to each arm (1:1 ratio). Patients were a mean age of 40.0 (SD 13.8; range 22-71) years, predominantly female (47/70, 67%), and predominantly of Chinese ethnicity (39/70, 56%). The telereview service was used by 32 patients in the control arm (32/35, 91%) and 18 patients in the intervention arm (18/35, 51%). Most patients in control (33/35, 94%; 95% CI 79.5%-99.0%) and intervention (34/35, 97%; 95% CI 83.4%-99.9%) arms were compliant with their final disposition. There was a low rate of re-presentation at 72 hours and 2 weeks for both control (72 hours: 2/35, 6%; 95% CI 1.0%-20.5%; 2 weeks: 2/35, 6%, 95% CI 1.0%-20.5%) and intervention (72 hours: 2/35, 6%; 95% CI 1.0%-20.5%; 2 weeks: 3/35, 9%, 95% CI 2.2%-24.2%) arms. There were no significant differences in safety (P>.99) and efficacy (P>.99) between the two groups. CONCLUSIONS: The application of digital telereview for the follow-up of patients with abdominal pain may be safe and effective. Future studies are needed to evaluate its cost-effectiveness and usefulness for broader clinical application. TRIAL REGISTRATION: ISRCTN Registry ISRCTN28468556; http://www.isrctn.com/ISRCTN28468556."
1945,Generation of inner ear hair cells by direct lineage conversion of primary somatic cells,"The mechanoreceptive sensory hair cells in the inner ear are selectively vulnerable to numerous genetic and environmental insults. In mammals, hair cells lack regenerative capacity, and their death leads to permanent hearing loss and vestibular dysfunction. Their paucity and inaccessibility has limited the search for otoprotective and regenerative strategies. Growing hair cells in vitro would provide a route to overcome this experimental bottleneck. We report a combination of four transcription factors (Six1, Atoh1, Pou4f3, and Gfi1) that can convert mouse embryonic fibroblasts, adult tail-tip fibroblasts and postnatal supporting cells into induced hair cell-like cells (iHCs). iHCs exhibit hair cell-like morphology, transcriptomic and epigenetic profiles, electrophysiological properties, mechanosensory channel expression, and vulnerability to ototoxin in a high-content phenotypic screening system. Thus, direct reprogramming provides a platform to identify causes and treatments for hair cell loss, and may help identify future gene therapy approaches for restoring hearing."
1946,Case Studies in Neuroscience: The electrophysiology of a human obsession in nucleus accumbens,"Microelectrode recordings were performed during awake deep brain stimulation surgery for obsessive-compulsive disorder, revealing robust brain oscillations that were plainly visible throughout the ventral striatum. There was an elegant topological correspondence between each oscillation and the underlying brain anatomy, most prominently a ~35-Hz gamma-oscillation specific to the nucleus accumbens. Direct provocation of the patient’s contamination obsession modulated both firing rate and gamma-oscillation amplitude within the nucleus accumbens. NEW & NOTEWORTHY Surgical implantation of deep brain stimulating electrodes (DBS) to treat obsessive-compulsive disorder (OCD) is an option for patients who have not fully responded to medical intervention or cognitive behavioral therapy. We measured the electrophysiology of a collection of deep brain structures during awake DBS surgery for an OCD patient with an obsession about cleanliness and contamination. The anatomic delineation of these deep brain structures was revealed by distinct brain rhythms, most notably a ~35 Hz oscillation specific to the nucleus accumbens. In the first ever measurement of a human obsessive thought, we found that this ~35-Hz biomarker, as well as the local neuronal action potential rate, were modulated by handing the patient a toothbrush to bring to his face and instructing him to “imagine brushing your teeth with this dirty toothbrush.”"
1947,Implementing the chick embryo model to study vestibular developmental disorders,"Children with congenital vestibular disorders show delayed motor development and challenges in maintaining posture and balance. Computed tomography images reveal that these children have abnormal inner ears in the form of a sac, with the semicircular canals missing or truncated. Little is known about how this inner ear abnormality affects central vestibular development. At present, mice with the chromodomain helicase DNA-binding protein 7 mutation are the most common model for studying congenital vestibular disorders, despite forming multiple diverse inner ear phenotypes and inducing abnormal cerebellar and visual system development. To identify the effects of a sac-like inner ear on central vestibular development, we have designed and implemented a new model, the anterior-posterior axis rotated otocyst (ARO) chick, which forms a sac-like inner ear in 85% of cases. The ARO chick is produced by anterior-posterior rotation of the otocyst at embryonic day 2. Here, we describe for the first time the 15% of ARO chicks that form three small semicircular canals and rename the ARO chicks forming sacs (ARO/s chicks). The basic features of the vestibular sensory organs in ARO/s chicks are similar to those found in patients’ sacs, and ARO/s hatchlings experience balance and walking problems like patients. Thus, ARO/s chicks have a reproducible inner ear phenotype without abnormalities in vestibular-related structures, making the model a relatively simple one to evaluate the relationship between the sac-like inner ear pathology and formation of the central vestibular neural circuitry. Here, we describe unpublished details on the surgical approaches to produce ARO chicks, including pitfalls and difficulties to avoid. NEW & NOTEWORTHY This paper describes simple techniques for chick otocyst rotation resulting in a sac-like inner ear (85%), the common phenotype in congenital vestibular disorders. We now describe anterior-posterior axis rotated otocyst chicks, which form three small canals (15%), and rename chicks forming a sac (ARO/s chicks). Basic protocols and potential complications of otocyst rotation are described. With the use of ARO/s chicks, it will be possible to determine how the vestibular neural circuit is modified by sac-like inner ear formation."
1948,Differences in pulmonary arterial flow hemodynamics between children and adults with pulmonary arterial hypertension as assessed by 4D-flow CMR studies,"Despite different developmental and pathological processes affecting lung vascular remodeling in both patient populations, differences in 4D MRI findings between children and adults with PAH have not been studied. The purpose of this study was to compare flow hemodynamic state, including flow-mediated shear forces, between pediatric and adult patients with PAH matched by severity of pulmonary vascular resistance index (PVRi). Adults (n = 10) and children (n = 10) with PAH matched by pulmonary vascular resistance index (PVRi) and healthy adult (n = 10) and pediatric (n = 10) subjects underwent comprehensive 4D-flow MRI to assess peak systolic wall shear stress (WSS(max)) measured in the main (MPA), right (RPA), and left pulmonary arteries (LPA), viscous energy loss (E(L)) along the MPA-RPA and MPA-LPA tract, and qualitative analysis of secondary flow hemodynamics. WSS(max) was decreased in all pulmonary vessels in children with PAH when compared with the same age group (all P < 0.05). Similarly, WSS(max) was decreased in all pulmonary vessels in adult PAH patients when compared with healthy adult subjects (all P < 0.01). Average E(L) was increased in adult patients with PAH when compared with the same age group along both MPA-RPA (P = 0.020) and MPA-LPA (P = 0.025) tracts. There were no differences in E(L) indices between adults and pediatric patients. Children and adult patients with PAH have decreased shear hemodynamic forces. However, pathological flow hemodynamic formations appear to be more consistent in adult patients, whereas flow hemodynamic abnormalities appear to be more variable in children with PAH for comparable severity of PVRi. NEW & NOTEWORTHY Both children and adult patients with PAH have decreased shear hemodynamic forces inside the pulmonary arteries associated with the degree of vessel dilation and stiffness. These differences also exist between healthy normotensive children and adults. However, pathological flow hemodynamic formations appear to more uniform in adult patients, whereas in children with PAH flow, hemodynamic abnormalities appear to be more variable. Pathological flow formations appear not to have a major effect on viscous energy loss associated with the flow conduction through proximal pulmonary arteries."
1949,CORRIGENDUM,
1950,The Physiology of the Gastric Parietal Cell,"Parietal cells are responsible for gastric acid secretion, which aids in the digestion of food, absorption of minerals, and control of harmful bacteria. However, a fine balance of activators and inhibitors of parietal cell-mediated acid secretion is required to ensure proper digestion of food, while preventing damage to the gastric and duodenal mucosa. As a result, parietal cell secretion is highly regulated through numerous mechanisms including the vagus nerve, gastrin, histamine, ghrelin, somatostatin, glucagon-like peptide 1, and other agonists and antagonists. The tight regulation of parietal cells ensures the proper secretion of HCl. The H(+)-K(+)-ATPase enzyme expressed in parietal cells regulates the exchange of cytoplasmic H(+) for extracellular K(+). The H(+) secreted into the gastric lumen by the H(+)-K(+)-ATPase combines with luminal Cl(−) to form gastric acid, HCl. Inhibition of the H(+)-K(+)-ATPase is the most efficacious method of preventing harmful gastric acid secretion. Proton pump inhibitors and potassium competitive acid blockers are widely used therapeutically to inhibit acid secretion. Stimulated delivery of the H(+)-K(+)-ATPase to the parietal cell apical surface requires the fusion of intracellular tubulovesicles with the overlying secretory canaliculus, a process that represents the most prominent example of apical membrane recycling. In addition to their unique ability to secrete gastric acid, parietal cells also play an important role in gastric mucosal homeostasis through the secretion of multiple growth factor molecules. The gastric parietal cell therefore plays multiple roles in gastric secretion and protection as well as coordination of physiological repair."
1951,mRNA Metabolism in Cardiac Development and Disease: Life After Transcription,"The central dogma of molecular biology illustrates the importance of mRNAs as critical mediators between genetic information encoded at the DNA level and proteomes/metabolomes that determine the diverse functional outcome at the cellular and organ levels. Although the total number of protein-producing (coding) genes in the mammalian genome is ~20,000, it is evident that the intricate processes of cardiac development and the highly regulated physiological regulation in the normal heart, as well as the complex manifestation of pathological remodeling in a diseased heart, would require a much higher degree of complexity at the transcriptome level and beyond. Indeed, in addition to an extensive regulatory scheme implemented at the level of transcription, the complexity of transcript processing following transcription is dramatically increased. RNA processing includes post-transcriptional modification, alternative splicing, editing and transportation, ribosomal loading, and degradation. While transcriptional control of cardiac genes has been a major focus of investigation in recent decades, a great deal of progress has recently been made in our understanding of how post-transcriptional regulation of mRNA contributes to transcriptome complexity. In this review, we highlight some of the key molecular processes and major players in RNA maturation and post-transcriptional regulation. In addition, we provide an update to the recent progress made in the discovery of RNA processing regulators implicated in cardiac development and disease. While post-transcriptional modulation is a complex and challenging problem to study, recent technological advancements are paving the way for a new era of exciting discoveries and potential clinical translation in the context of cardiac biology and heart disease."
1952,CORRIGENDUM,
1953,Extracorporeal Membrane Oxygenation Resource Planning in the Setting of Pandemic Respiratory Illness,
1954,In Defense of Evidence-based Medicine for the Treatment of COVID-19 Acute Respiratory Distress Syndrome,
1955,Isolation and characterization of new Puumala orthohantavirus strains from Germany,"Orthohantaviruses are re-emerging rodent-borne pathogens distributed all over the world. Here, we report the isolation of a Puumala orthohantavirus (PUUV) strain from bank voles caught in a highly endemic region around the city Osnabrück, north-west Germany. Coding and non-coding sequences of all three segments (S, M, and L) were determined from original lung tissue, after isolation and after additional passaging in VeroE6 cells and a bank vole-derived kidney cell line. Different single amino acid substitutions were observed in the RNA-dependent RNA polymerase (RdRP) of the two stable PUUV isolates. The PUUV strain from VeroE6 cells showed a lower titer when propagated on bank vole cells compared to VeroE6 cells. Additionally, glycoprotein precursor (GPC)-derived virus-like particles of a German PUUV sequence allowed the generation of monoclonal antibodies that allowed the reliable detection of the isolated PUUV strain in the immunofluorescence assay. In conclusion, this is the first isolation of a PUUV strain from Central Europe and the generation of glycoprotein-specific monoclonal antibodies for this PUUV isolate. The obtained virus isolate and GPC-specific antibodies are instrumental tools for future reservoir host studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-020-01755-3) contains supplementary material, which is available to authorized users."
1956,Outbreak of KPC-2 Carbapenem-resistant Klebsiella pneumoniae ST76 and Carbapenem-resistant K2 Hypervirulent Klebsiella pneumoniae ST375 strains in Northeast China: molecular and virulent characteristics,"BACKGROUND: Carbapenem-resistant hypervirulent Klebsiella pneumoniae strains have recently come into existence worldwide; however, researchers in northeast China are not aware of their clinical features and molecular characteristics. METHODS: Here, the molecular and virulent characteristics of 44 carbapenem-resistant K. pneumoniae (CRKP) isolates collected from January 2015 to December 2017 were studied. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were carried out to define the clonal relatedness among the isolates. PCR and capsular serotyping of the virulence-associated genes, as well as biofilm formation and serum complement-mediated killing assays, were employed to determine the virulent potential. The genomic features and associated mobile genetic elements of JmsCRE57 were detected by whole genome sequencing. RESULTS: The only positive isolate was JmsCRE57, which belonged to the ST375 serotype K2 that expressed uge, mrkD, fimH, kpn, aerobactin and rmpA virulence-associated genes and showed strong biofilm formation and serum sensitivity. Sequencing results showed that the JmsCRE57 genome mainly consisted of a circular chromosome, three antimicrobial resistant plasmids and a virulent plasmid. The antimicrobial resistant plasmid expressing bla(KPC-2), bla(CTX-M-15), aph(3″)-Ib, aph(6)-Id, qnrB1, aac(3)-IIa, aac(6′)-Ib-cr, bla(OXA-1), bla(TEM-1B), catB4, sul2, dfrA14 and bla(SHV-99). The virulent plasmid belonged to the IncHI1B group, which is mainly composed of mucoid phenotype genes and siderophore-associated genes. The remaining CRKP strains that expressed uge, fimH, mrkD and kpn virulence-associated genes were not successfully typed. CONCLUSION: Our results provide new insights on the epidemiology of carbapenem-resistant K2 hypervirulent K. pneumoniae ST375 and CRKP ST76 strains in northeast China, which may help control their future outbreaks."
1957,Bariatric Surgery in Prior Solid Organ Transplantation Patients: Is Race a Predictor of Adverse Outcomes?,"PURPOSE: Metabolic and bariatric surgery (MBS) is increasingly performed in patients with previous solid organ transplantation (PSOT). In addition, controversy remains about whether racial disparity in outcomes following MBS exists. Therefore, the aim of this analysis was to determine if race independently predicts outcomes in MBS patients with PSOT. MATERIALS AND METHODS: Patients with PSOT undergoing sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) were identified in the 2017 Metabolic and Bariatric Surgery Accreditation Quality and Improvement Project (MBSAQIP) database. Patients were stratified by race (Black and White). Propensity score matching was utilized to adjust for multiple demographic variables. Multivariable logistic regression analyses were performed for overall and bariatric-related morbidity. RESULTS: Of 335 MBS patients with PSOT, 250 (75%) were white and 85 (25%) were black patents. Procedure-type and surgical approach (p > 0.1) were similarly distributed. Black patients were more likely (p < 0.05) to have hypertension dialysis-dependent chronic kidney disease, and be on chronic steroids). Mortality and morbidity were similar. Black patients had significantly (p < 0.05) higher rates of renal failure, pulmonary complications, and emergency department visits in unmatched analysis. After propensity score matching, 82 patients in each cohort were identified and were similar at baseline (p > 0.5). In the matched analysis, black patients had higher overall (17% vs. 10%, p = 0.12) and bariatric-related morbidity (14% vs. 7.2%, p = 0.05). In addition, black patients had significantly (p < 0.05) higher rates of postoperative pneumonias, progressive renal insufficiency, and emergency department visits. On multivariable regression analysis, black race did not independently predict overall or bariatric-related morbidity. CONCLUSION: MBS in racial cohorts with PSOT is safe, with very low rates of overall morbidity and mortality. Black race trended toward increased postoperative morbidity. Larger cohort studies are needed to validate our findings. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11695-020-04813-9) contains supplementary material, which is available to authorized users."
1958,How systems engineering can improve care in the ICU,
1959,Intellectual capital and the efficiency of SMEs in the transition economy China; Do financial resources strengthen the routes?,"Intellectual capital has been grabbed the attention of researchers due to its momentous role in sustainable competitive advantage and organizational success. There is a growing catalog of related assessments, publications and reviews that display the direct and indirect role of intellectual capital in business success and profitability. Despite the bourgeoning literature, studies have not yet unleashed the influence of each dimension of intellectual capital; human capital, structural capital and customer capital on SMEs' efficiency with financial resources as a moderator. The present study fills the gap and assesses if financial resources strengthen the paths between the dimensions of intellectual capital and SMEs' efficiency. A survey method was used and collected evidence from 264 Chinese SMEs. The findings exhibit that human capital directly enhances SMEs' efficiency but the presence of financial resources as a moderator weakens the influence. However, social capital and customer capital do not directly improve SMEs' efficiency but financial resources reinforce the paths social and customer capital and SMEs efficiency. This research recommends that owners and managers of SMEs need to use their financial resources complementary with structural and customer capital while human capital should be used exclusively."
1960,Does relational mobility vary across national regions? A within-country examination,"Relational mobility is a socio-ecological construct quantifying how much freedom and opportunity a society affords individuals to choose and dispose of interpersonal relationships. Past research has confirmed that relational mobility varies across nations, but no large-scale study has examined the degree to which relational mobility may vary within a single nation. We report two studies (Study 1, N = 647; Study 2, N = 7343) exploring within-country similarity or variability in relational mobility across all 27 states and five geo-socio-political regions in the continent-size country of Brazil. Results confirmed the measurement equivalence of the Relational Mobility Scale across respondents from all Brazilian states. Notably, relational mobility scores were uniform across Brazilian regions and states, indicating a common national culture regarding the amount of opportunities Brazilians have in selecting new relationship partners within their social context. Replicating existing findings, relational mobility was positively associated with pro-active tendencies that help people retain relationships—levels of intimacy and self-disclosure toward a close friend—indicating that friends tend to feel closer intimacy to their close friends, and reveal serious personal information to a larger degree in social contexts where opportunities to find and retain relationships with like-minded others are greater."
1961,"Giants in Chest Medicine: Professor Nan-shan Zhong, MD",
1962,Policies Should be Based on Data Not Dogma in Medicine and Government,
1963,Tip of the Iceberg,
1964,The RNA quality control pathway nonsense-mediated mRNA decay targets cellular and viral RNAs to restrict KSHV,"Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved RNA decay mechanism that has emerged as a potent cell-intrinsic restriction mechanism of retroviruses and positive-strand RNA viruses. However, whether NMD is capable of restricting DNA viruses is not known. The DNA virus Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma and primary effusion lymphoma (PEL). Here, we demonstrate that NMD restricts KSHV lytic reactivation. Leveraging high-throughput transcriptomics we identify NMD targets transcriptome-wide in PEL cells and identify host and viral RNAs as substrates. Moreover, we identified an NMD-regulated link between activation of the unfolded protein response and transcriptional activation of the main KSHV transcription factor RTA, itself an NMD target. Collectively, our study describes an intricate relationship between cellular targets of an RNA quality control pathway and KSHV lytic gene expression, and demonstrates that NMD can function as a cell intrinsic restriction mechanism acting upon DNA viruses."
1965,The power of cooperation,
1966,Reply: Vitamin C as a Possible Therapy for COVID-19,
1967,ApoE e4e4 genotype and mortality with COVID-19 in UK Biobank,
1968,Increased Burn Center Admissions During COVID 19 Pandemic,
1969,"Frontline workers sound the alarm: be always sure you’re right, then go ahead","Amid personal protective equipment shortage, clinicians, nurses, and other frontline workers across the world have faced threatening and/or firing for self-protection during this coronavirus disease 2019 (COVID-19) pandemic. This perspective describes the different challenges that the stressed and overworked frontline workers encounter when they raise concerns despite being right. It also highlights the importance of communication and appropriate execution upon hearing those concerns."
1970,ARTP statement on pulmonary function testing,
1971,Google Trends-based non-English language query data and epidemic diseases: a cross-sectional study of the popular search behaviour in Taiwan,"OBJECTIVE: This study developed a surveillance system suitable for monitoring epidemic outbreaks and assessing public opinion in non-English-speaking countries. We evaluated whether social media reflects social uneasiness and fear during epidemic outbreaks and natural catastrophes. DESIGN: Cross-sectional study. SETTING: Freely available epidemic data in Taiwan. MAIN OUTCOME MEASURE: We used weekly epidemic incidence data obtained from the Taiwan Centers for Disease Control and online search query data obtained from Google Trends between 4 October 2015 and 2 April 2016. To validate whether non-English query keywords were useful surveillance tools, we estimated the correlation between online query data and epidemic incidence in Taiwan. RESULTS: With our approach, we noted that keywords 感冒 (‘common cold’), 發燒 (‘fever’) and 咳嗽 (‘cough’) exhibited good to excellent correlation between Google Trends query data and influenza incidence (r=0.898, p<0.001; r=0.773, p<0.001; r=0.796, p<0.001, respectively). They also displayed high correlation with influenza-like illness emergencies (r=0.900, p<0.001; r=0.802, p<0.001; r=0.886, p<0.001, respectively) and outpatient visits (r=0.889, p<0.001; r=0.791, p<0.001; r=0.870, p<0.001, respectively). We noted that the query 腸病毒 (‘enterovirus’) exhibited excellent correlation with the number of enterovirus-infected patients in emergency departments (r=0.914, p<0.001). CONCLUSIONS: These results suggested that Google Trends can be a good surveillance tool for epidemic outbreaks, even in Taiwan, the non-English-speaking country. Online search activity indicates that people are concerned about epidemic diseases, even if they do not visit hospitals. This prompted us to develop useful tools to monitor social media during an epidemic because such media usage reflects infectious disease trends more quickly than does traditional reporting."
1972,A Champion of Host Defense: A Generic Large-Scale Cause for Platelet Dysfunction and Depletion in Infection,"Thrombocytopenia is commonly associated with sepsis and infections, which in turn are characterized by a profound immune reaction to the invading pathogen. Platelets are one of the cellular entities that exert considerable immune, antibacterial, and antiviral actions, and are therefore active participants in the host response. Platelets are sensitive to surrounding inflammatory stimuli and contribute to the immune response by multiple mechanisms, including endowing the endothelium with a proinflammatory phenotype, enhancing and amplifying leukocyte recruitment and inflammation, promoting the effector functions of immune cells, and ensuring an optimal adaptive immune response. During infection, pathogens and their products influence the platelet response and can even be toxic. However, platelets are able to sense and engage bacteria and viruses to assist in their removal and destruction. Platelets greatly contribute to host defense by multiple mechanisms, including forming immune complexes and aggregates, shedding their granular content, and internalizing pathogens and subsequently being marked for removal. These processes, and the nature of platelet function in general, cause the platelet to be irreversibly consumed in the execution of its duty. An exaggerated systemic inflammatory response to infection can drive platelet dysfunction, where platelets are inappropriately activated and face immunological destruction. While thrombocytopenia may arise by condition-specific mechanisms that cause an imbalance between platelet production and removal, this review evaluates a generic large-scale mechanism for platelet depletion as a repercussion of its involvement at the nexus of responses to infection."
1973,There Is No Place Like Home: Rethinking Away Rotations,
1974,Recurring Themes,
1975,"Perioperative Bluttransfusion: Nutzen, Risiken und Richtlinien","Surgical blood loss and trauma are the major causes of allogeneic blood transfusions, which still bear considerable risks. After the correction of hypovolemia, the anesthesiologist often has to deal with normovolemic anemia. The clinical relevance of this isolated decrease in hemoglobin concentration consists in an eventually compromised global or regional oxygen supply with the development of tissue hypoxia below a critical threshold. This is an individual threshold for each patient and depends on his or her capacity to compensate the decrease in blood oxygen content. Therefore, physiologic transfusion triggers should primarily be applied and not rigid numeric transfusion triggers, such as hemoglobin concentration, which do not take into account each patient’s individual reserve."
1976,"Benefits of Physical Activity and Its Associations with Resilience, Emotional Intelligence, and Psychological Distress in University Students from Southern Spain","This is a descriptive and cross-sectional study in a sample of 1095 university students from southern Spain. The aim was to identify the frequency of health-fulfilling physical activity engagement reported by participants. Sufficient physical activity was categorized according to whether participants ‘achieved minimum recommendations’ (≥150 min of moderate physical activity) or ‘did not achieve minimum recommendations’ (≤150 min of moderate physical activity). Participants were further categorized as: inactive (does not engage in physical activity or sport), engaging in physical activity that is not beneficial to health (≤300 min of moderate physical activity per week) and engaging in physical activity that is beneficial to health (≥300 min of moderate physical activity per week). Possible relationships with psychosocial factors and perceived psychological distress were explored. An ad hoc questionnaire was used to record the time in minutes of physical activity engagement per week. The Connor–Davidson Resilience Scale, the Trait Meta-mood Scale, and Kessler Psychological Distress Scale were also administered. Statically significant differences are shown between the three examined groups: physical inactivity and non-beneficial physical activity; physical inactivity and beneficial physical activity, and; non-beneficial physical activity and beneficial physical activity. Positive and direct correlations were seen with respect to resilience and understanding, and emotional regulation, in addition to negative associations with respect to psychological distress. In conclusion, the more individuals engage in beneficial physical activity, the greater their resilience and emotional management, and the lower their rates of psychological distress."
1977,"The 14th of April, Past and Present",
1978,3D Printed Monolithic Microreactors for Real-Time Detection of Klebsiella pneumoniae and the Resistance Gene bla(NDM-1) by Recombinase Polymerase Amplification,"We investigate the compatibility of three 3D printing materials towards real-time recombinase polymerase amplification (rtRPA). Both the general ability of the rtRPA reaction to occur while in contact with the cured 3D printing materials as well as the residual autofluorescence and fluorescence drift in dependence on post curing of the materials is characterized. We 3D printed monolithic rtRPA microreactors and subjected the devices to different post curing protocols. Residual autofluorescence and drift, as well as rtRPA kinetics, were then measured in a custom-made mobile temperature-controlled fluorescence reader (mTFR). Furthermore, we investigated the effects of storage on the devices over a 30-day period. Finally, we present the single- and duplex rtRPA detection of both the organism-specific Klebsiella haemolysin (khe) gene and the New Delhi metallo-β-lactamase 1 (bla(NDM-1)) gene from Klebsiella pneumoniae. Results: No combination of 3D printing resin and post curing protocol completely inhibited the rtRPA reaction. The autofluorescence and fluorescence drift measured were found to be highly dependent on printing material and wavelength. Storage had the effect of decreasing the autofluorescence of the investigated materials. Both khe and bla(NDM-1) were successfully detected by single- and duplex-rtRPA inside monolithic rtRPA microreactors printed from NextDent Ortho Clear (NXOC). The reaction kinetics were found to be close to those observed for rtRPA performed in a microcentrifuge tube without the need for mixing during amplification. Singleplex assays for both khe and bla(NDM-1) achieved a limit of detection of 2.5 × 10(1) DNA copies while the duplex assay achieved 2.5 × 10(1) DNA copies for khe and 2.5 × 10(2) DNA copies for bla(NDM-1). Impact: We expand on the state of the art by demonstrating a technology that can manufacture monolithic microfluidic devices that are readily suitable for rtRPA. The devices exhibit very low autofluorescence and fluorescence drift and are compatible with RPA chemistry without the need for any surface pre-treatment such as blocking with, e.g., BSA or PEG."
1979,Association between Health Problems and Turnover Intention in Shift Work Nurses: Health Problem Clustering,"Shift work nurses experience multiple health problems due to irregular shifts and heavy job demands. However, the comorbidity patterns of nurses’ health problems and the association between health problems and turnover intention have rarely been studied. This study aimed to identify and cluster shift work nurses’ health problems and to reveal the associations between health problems and turnover intention. In this cross-sectional study, we analyzed data from 500 nurses who worked at two tertiary hospitals in Seoul, South Korea. Data, including turnover intention and nine types of health issues, were collected between March 2018 and April 2019. Hierarchical clustering and multiple ordinal logistic regressions were used for the data analysis. Among the participants, 22.2% expressed turnover intention and the mean number of health problems was 4.5 (range 0–9). Using multiple ordinal logistic regressions analysis, it was shown that sleep disturbance, depression, fatigue, a gastrointestinal disorder, and leg or foot discomfort as a single health problem significantly increased turnover intention. After clustering the health problems, four clusters were identified and only the neuropsychological cluster—sleep disturbance, fatigue, and depression—significantly increased turnover intention. We propose that health problems within the neuropsychological cluster must receive close attention and be addressed simultaneously to decrease nurse’s turnover intentions."
1980,Molecular detection of Rickettsia species and host associations of Laelaps mites (Acari: Laelapidae) in Taiwan,"Various rickettsiae have recently been detected in Laelaps mites (Acari: Laelapidae), which are common ectoparasites of rodents; however, investigations on this topic remain very scarce, particularly in Asia. In the present study, shrews and rodents were trapped from 2006 to 2010 in eight lowland regions of Taiwan (< 500 m in elevation) to collect associated Laelaps mites, from which Rickettsia—a group of emerging pathogens—were detected and identified by assaying the gltA and ompB genes. A total of 853 Laelaps mites of at least four species were collected from a sample of 1004 small mammals that included one shrew and 10 rodent species. Rattus losea was the most common species (44.9% of total hosts) and hosted the highest percentage of mites (76.6% of total mites). Laelaps nuttalli was the most abundant mite species (51.7% of total mites), followed by Laelaps echidninus (24.2%), Laelaps sedlaceki (23.1%), and Laelaps myonyssognathus (0.2%). Notably, Rickettsia species with the highest similarity to spotted fever group (SFG) rickettsiae were identified from seven of the 72 pools of Laelaps mites. The presence of SFG rickettsiae in hematophagous Laelaps mites, particularly including species that are closely associated with commensal rodents in frequent contact with humans, calls for further investigation on the competence of Laelaps mites in transmitting rickettsiae."
1981,Implications of CRISPR/Cas9 system in Hypertension and its related diseases,
1982,Whole-organism behavioral profiling reveals a role for dopamine in state-dependent motor program coupling in C. elegans,"Animal behaviors are commonly organized into long-lasting states that coordinately impact the generation of diverse motor outputs such as feeding, locomotion, and grooming. However, the neural mechanisms that coordinate these distinct motor programs remain poorly understood. Here, we examine how the distinct motor programs of the nematode C. elegans are coupled together across behavioral states. We describe a new imaging platform that permits automated, simultaneous quantification of each of the main C. elegans motor programs over hours or days. Analysis of these whole-organism behavioral profiles shows that the motor programs coordinately change as animals switch behavioral states. Utilizing genetics, optogenetics, and calcium imaging, we identify a new role for dopamine in coupling locomotion and egg-laying together across states. These results provide new insights into how the diverse motor programs throughout an organism are coordinated and suggest that neuromodulators like dopamine can couple motor circuits together in a state-dependent manner."
1983,Quantifying the annual incidence and underestimation of seasonal influenza: A modelling approach,"BACKGROUND: Seasonal influenza poses a significant public health and economic burden, associated with the outcome of infection and resulting complications. The true burden of the disease is difficult to capture due to the wide range of presentation, from asymptomatic cases to non-respiratory complications such as cardiovascular events, and its seasonal variability. An understanding of the magnitude of the true annual incidence of influenza is important to support prevention and control policy development and to evaluate the impact of preventative measures such as vaccination. METHODS: We use a dynamic disease transmission model, laboratory-confirmed influenza surveillance data, and randomized-controlled trial (RCT) data to quantify the underestimation factor, expansion factor, and symptomatic influenza illnesses in the US and Canada during the 2011-2012 and 2012-2013 influenza seasons. RESULTS: Based on 2 case definitions, we estimate between 0.42−3.2% and 0.33−1.2% of symptomatic influenza illnesses were laboratory-confirmed in Canada during the 2011-2012 and 2012-2013 seasons, respectively. In the US, we estimate between 0.08−0.61% and 0.07−0.33% of symptomatic influenza illnesses were laboratory-confirmed in the 2011-2012 and 2012-2013 seasons, respectively. We estimated the symptomatic influenza illnesses in Canada to be 0.32−2.4 million in 2011-2012 and 1.8−8.2 million in 2012-2013. In the US, we estimate the number of symptomatic influenza illnesses to be 4.4−34 million in 2011-2012 and 23−102 million in 2012-2013. CONCLUSIONS: We illustrate that monitoring a representative group within a population may aid in effectively modelling the transmission of infectious diseases such as influenza. In particular, the utilization of RCTs in models may enhance the accuracy of epidemiological parameter estimation."
1984,Macrophage polarization and its role in the pathogenesis of acute lung injury/acute respiratory distress syndrome,"PURPOSE: Macrophages are highly plastic cells. Under different stimuli, macrophages can be polarized into several different subsets. Two main macrophage subsets have been suggested: classically activated or inflammatory (M1) macrophages and alternatively activated or anti-inflammatory (M2) macrophages. Macrophage polarization is governed by a highly complex set of regulatory networks. Many recent studies have shown that macrophages are key orchestrators in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and that regulation of macrophage polarization may improve the prognosis of ALI/ARDS. A further understanding of the mechanisms of macrophage polarization is expected to be helpful in the development of novel therapeutic targets to treat ALI/ARDS. Therefore, we performed a literature review to summarize the regulatory mechanisms of macrophage polarization and its role in the pathogenesis of ALI/ARDS. METHODS: A computer-based online search was performed using the PubMed database and Web of Science database for published articles concerning macrophages, macrophage polarization, and ALI/ARDS. RESULTS: In this review, we discuss the origin, polarization, and polarization regulation of macrophages as well as the role of macrophage polarization in various stages of ARDS. According to the current literature, regulating the polarized state of macrophages might be a potential therapeutic strategy against ALI/ARDS."
1985,Amplified Concern for Social Risk in Adolescence: Development and Validation of a New Measure,"In adolescence, there is a heightened propensity to take health risks such as smoking, drinking or driving too fast. Another facet of risk taking, social risk, has largely been neglected. A social risk can be defined as any decision or action that could lead to an individual being excluded by their peers, such as appearing different to one’s friends. In the current study, we developed and validated a measure of concern for health and social risk for use in individuals of 11 years and over (N = 1399). Concerns for both health and social risk declined with age, challenging the commonly held stereotype that adolescents are less worried about engaging in risk behaviours, compared with adults. The rate of decline was steeper for social versus health risk behaviours, suggesting that adolescence is a period of heightened concern for social risk. We validated our measure against measures of rejection sensitivity, depression and risk-taking behaviour. Greater concern for social risk was associated with increased sensitivity to rejection and greater depressed mood, and this association was stronger for adolescents compared with adults. We conclude that social risks should be incorporated into future models of risk-taking behaviour, especially when they are pitted against health risks."
1986,Human Parvoviruses May Affect the Development and Clinical Course of Meningitis and Meningoencephalitis,"Meningitis and meningoencephalitis are neurological inflammatory diseases, and although routine diagnostics include testing of a wide range of pathogens, still in many cases, no causative agent is detected. Human parvovirus B19 (B19V), human bocaviruses 1–4 (HBoV1–4), and human parvovirus 4 (hPARV4) are members of the Parvoviridae family and are associated with a wide range of clinical manifestations including neurological disorders. The main aim of this study was to determine whether human parvoviruses infection markers are present among patients with meningitis/meningoencephalitis in Latvia as well as to clarify the role of these viruses on the clinical course of the mentioned diseases. Our study revealed HBoV1–4 and B19V genomic sequences in 52.38% and 16.67% of patients, respectively. Furthermore, symptoms such as the presence of a headache and its severity, fatigue, disorientation, and difficulties to concentrate were significantly frequently present in patients with active parvovirus infection in comparison with parvoviruses negative patients, therefore we suggest that HBoV1–4 and B19V infection should be included in the diagnostics to reduce the number of meningitis/meningoencephalitis with unknown/unexplained etiology."
1987,Preclinical Efficacy of a Trivalent Human FcγRI-Targeted Adjuvant-Free Subunit Mucosal Vaccine against Pulmonary Pneumococcal Infection,"Lack of safe and effective mucosal adjuvants has severely hampered the development of mucosal subunit vaccines. In this regard, we have previously shown that immunogenicity of vaccine antigens can be improved by targeting the antigens to the antigen-presenting cells. Specifically, groups of mice immunized intranasally with a fusion protein (Bivalent-FP) containing a fragment of pneumococcal-surface-protein-A (PspA) as antigen and a single-chain bivalent antibody raised against the anti-human Fc-gamma-receptor-I (hFcγRI) elicited protective immunity to pulmonary Streptococcus pneumoniae infection. In order to further enhance the immunogenicity, an additional hFcγRI-binding moiety of the single chain antibody was incorporated. The modified vaccine (Trivalent-FP) induced significantly improved protection against lethal pulmonary S. pneumoniae challenge compared to Bivalent-FP. In addition, the modified vaccine exhibited over 85% protection with only two immunizations. Trivalent-FP also induced S. pneumoniae-specific systemic and mucosal antibodies. Moreover, Trivalent-FP also induced IL-17- and IL-22-producing CD4(+) T cells. Furthermore, it was found that the hFcγRI facilitated uptake and presentation of Trivalent-FP. In addition, Trivalent-FP also induced IL-1α, MIP-1α, and TNF-α; modulated recruitment of dendritic cells and macrophages; and induced CD80/86 and MHC-II expression on antigen presenting cells."
1988,Herpes Simplex Viruses Whose Replication Can Be Deliberately Controlled as Candidate Vaccines,"Over the last few years, we have been evaluating a novel paradigm for immunization using viruses or virus-based vectors. Safety is provided not by attenuation or inactivation of vaccine viruses, but by the introduction into the viral genomes of genetic mechanisms that allow for stringent, deliberate spatial and temporal control of virus replication. The resulting replication-competent controlled viruses (RCCVs) can be activated to undergo one or, if desired, several rounds of efficient replication at the inoculation site, but are nonreplicating in the absence of activation. Extrapolating from observations that attenuated replicating viruses are better immunogens than replication-defective or inactivated viruses, it was hypothesized that RCCVs that replicate with wild-type-like efficiency when activated will be even better immunogens. The vigorous replication of the RCCVs should also render heterologous antigens expressed from them highly immunogenic. RCCVs for administration to skin sites or mucosal membranes were constructed using a virulent wild-type HSV-1 strain as the backbone. The recombinants are activated by a localized heat treatment to the inoculation site in the presence of a small-molecule regulator (SMR). Derivatives expressing influenza virus antigens were also prepared. Immunization/challenge experiments in mouse models revealed that the activated RCCVs induced far better protective immune responses against themselves as well as against the heterologous antigens they express than unactivated RCCVs or a replication-defective HSV-1 strain. Neutralizing antibody and proliferation responses mirrored these findings. We believe that the data obtained so far warrant further research to explore the possibility of developing effective RCCV-based vaccines directed to herpetic diseases and/or diseases caused by other pathogens."
1989,Serodynamic Analysis of the Piglets Born from Sows Vaccinated with Modified Live Vaccine or E2 Subunit Vaccine for Classical Swine Fever,"Classical swine fever (CSF) caused by the CSF virus (CSFV) is one of the most important swine diseases, resulting in huge economic losses to the pig industry worldwide. Systematic vaccination is one of the most effective strategies for the prevention and control of this disease. Two main CSFV vaccines, the modified live vaccine (MLV) and the subunit E2 vaccine, are recommended. In Taiwan, CSF cases have not been reported since 2006, although systemic vaccination has been practiced for 70 years. Here, we examined the sero-dynamics of the piglets born from sows that received either the CSFV MLV or the E2 vaccine and investigated in the field the correlation between the porcine reproductive and respiratory syndrome virus (PRRSV) loads and levels of CSFV antibody. A total of 1398 serum samples from 42 PRRSV-positive farms were evaluated to determine the PRRSV loads by real-time PCR and to detect CSFV antibody levels by commercial ELISA. Upon comparing the two sow vaccination protocols (CSFV MLV vaccination at 4 weeks post-farrowing versus E2 vaccination at 4–5 weeks pre-farrowing), the lowest levels of CSFV antibody were found in piglets at 5–8 and 9–12 weeks of age for the MLV and E2 groups, respectively. Meanwhile, the appropriate time window for CSFV vaccination of offspring was at 5–8 and 9–12 weeks of age in the MLV and E2 groups, respectively. There was a very highly significant negative correlation between the PRRSV load and the level of CSFV antibody in the CSFV MLV vaccination group (P < 0.0001). The PRRSV detection rate in the pigs from the MLV group (27.78%) was significantly higher than that in pigs from the E2 group (21.32%) (P = 0.011). In addition, there was a significant difference (P = 0.019) in the PRRSV detection rate at 5–8 weeks of age between the MLV (42.15%) and E2 groups (29.79%). Our findings indicate that the vaccination of CSFV MLV in piglets during the PRRSV susceptibility period at 5–8 weeks of age may be overloading the piglet’s immune system and should be a critical concern for industrial pork production in the field."
1990,Prospects of and Barriers to the Development of Epitope-Based Vaccines against Human Metapneumovirus,"Human metapneumovirus (HMPV) is a major cause of respiratory illnesses in children, the elderly and immunocompromised patients. Although this pathogen was only discovered in 2001, an enormous amount of research has been conducted in order to develop safe and effective vaccines to prevent people from contracting the disease. In this review, we summarize current knowledge about the most promising experimental B- and T-cell epitopes of human metapneumovirus for the rational design of HMPV vaccines using vector delivery systems, paying special attention to the conservation of these epitopes among different lineages/genotypes of HMPV. The prospects of the successful development of an epitope-based HMPV vaccine are discussed in the context of recent findings regarding HMPV’s ability to modulate host immunity. In particular, we discuss the lack of data on experimental human CD4 T-cell epitopes for HMPV despite the role of CD4 lymphocytes in both the induction of higher neutralizing antibody titers and the establishment of CD8 memory T-cell responses. We conclude that current research should be focused on searching for human CD4 T-cell epitopes of HMPV that can help us to design a safe and cross-protective epitope-based HMPV vaccine."
1991,Development and Challenges in Animal Tuberculosis Vaccination,"Vaccination with Bacillus Calmette–Guérin (BCG) constituted a major advance in the prevention of human tuberculosis (TB) in the beginning of the past century. BCG has also a clear potential for use in animals and, in particular, in the main domestic species subjected to TB control programs, cattle. Nowadays, the use of BCG vaccination against TB in cattle is not permitted by European Union legislation because BCG can induce a cellular immune response producing diagnostic interference in the eradication programs based on tuberculin single and comparative intradermal tests imposed worldwide. In this review, we recall the history of TB vaccination as well as different vaccine trials and the response to vaccination in both domestic and wild animals. Promising potential inactivated vaccines are also reviewed. Research studies are mainly focused to improve vaccine efficacy, and at the same time to ensure its easy administration, safety and stability in the environment. Great challenges remain, particularly in terms of vaccine candidates and also in the acceptance of vaccination. Vaccination should be included in a strategic plan for integrated control of TB under a “one health” perspective, which also includes other measures such as improved biosafety on farms to avoid or decrease contact between domestic and wild animals or control of wildlife reservoirs to avoid overabundance that may favor infection maintenance."
1992,miRNA nanotherapeutics: potential and challenges in respiratory disorders,
1993,Droplet-based high-throughput cultivation for accurate screening of antibiotic resistant gut microbes,"Traditional cultivation approaches in microbiology are labor-intensive, low-throughput, and yield biased sampling of environmental microbes due to ecological and evolutionary factors. New strategies are needed for ample representation of rare taxa and slow-growers that are often outcompeted by fast-growers in cultivation experiments. Here we describe a microfluidic platform that anaerobically isolates and cultivates microbial cells in millions of picoliter droplets and automatically sorts them based on colony density to enhance slow-growing organisms. We applied our strategy to a fecal microbiota transplant (FMT) donor stool using multiple growth media, and found significant increase in taxonomic richness and larger representation of rare and clinically relevant taxa among droplet-grown cells compared to conventional plates. Furthermore, screening the FMT donor stool for antibiotic resistance revealed 21 populations that evaded detection in plate-based assessment of antibiotic resistance. Our method improves cultivation-based surveys of diverse microbiomes to gain deeper insights into microbial functioning and lifestyles."
1994,Interactions between Borrelia burgdorferi and ticks,"Borrelia burgdorferi is the causative agent of Lyme disease and is transmitted to vertebrate hosts by Ixodes spp. ticks. The spirochaete relies heavily on its arthropod host for basic metabolic functions and has developed complex interactions with ticks to successfully colonize, persist and, at the optimal time, exit the tick. For example, proteins shield spirochaetes from immune factors in the bloodmeal and facilitate the transition between vertebrate and arthropod environments. On infection, B. burgdorferi induces selected tick proteins that modulate the vector gut microbiota towards an environment that favours colonization by the spirochaete. Additionally, the recent sequencing of the Ixodes scapularis genome and characterization of tick immune defence pathways, such as the JAK–STAT, immune deficiency and cross-species interferon-γ pathways, have advanced our understanding of factors that are important for B. burgdorferi persistence in the tick. In this Review, we summarize interactions between B. burgdorferi and I. scapularis during infection, as well as interactions with tick gut and salivary gland proteins important for establishing infection and transmission to the vertebrate host."
1995,Renin-Angiotensin System in Lung Tumor and Microenvironment Interactions,"The mechanistic involvement of the renin-angiotensin system (RAS) reaches beyond cardiovascular physiopathology. Recent knowledge pinpoints a pleiotropic role for this system, particularly in the lung, and mainly through locally regulated alternative molecules and secondary pathways. Angiotensin peptides play a role in cell proliferation, immunoinflammatory response, hypoxia and angiogenesis, which are critical biological processes in lung cancer. This manuscript reviews the literature supporting a role for the renin-angiotensin system in the lung tumor microenvironment and discusses whether blockade of this pathway in clinical settings may serve as an adjuvant therapy in lung cancer."
1996,Assessing Advantages and Drawbacks of Rapidly Generated Ultra-Large 3D Breast Cancer Spheroids: Studies with Chemotherapeutics and Nanoparticles,"Traditionally, two-dimensional (2D) monolayer cell culture models have been used to study in vitro conditions for their ease of use, simplicity and low cost. However, recently, three-dimensional (3D) cell culture models have been heavily investigated as they provide better physiological relevance for studying various disease behaviors, cellular activity and pharmaceutical interactions. Typically, small-sized tumor spheroid models (100–500 μm) are used to study various biological and physicochemical activities. Larger, millimetric spheroid models are becoming more desirable for simulating native tumor microenvironments (TMEs). Here, we assess the use of ultra-large spheroid models (~2000 μm) generated from scaffolds made from a nozzle-free, ultra-high resolution printer; these models are explored for assessing chemotherapeutic responses with molecular doxorubicin (DOX) and two analogues of Doxil(Ⓡ) (Dox-NP(Ⓡ), Doxoves(TM)) on MDA-MB-231 and MCF-7 breast cancer cell lines. To provide a comparative baseline, small spheroid models (~500 μm) were developed using a self-aggregation method of MCF-7 breast cancer cell lines, and underwent similar drug treatments. Analysis of both large and small MCF-7 spheroids revealed that Dox-NP tends to have the highest level of inhibition, followed by molecular doxorubicin and then Doxoves. The experimental advantages and drawbacks of using these types of ultra-large spheroids for cancer research are discussed."
1997,Pilot Multi-Omic Analysis of Human Bile from Benign and Malignant Biliary Strictures: A Machine-Learning Approach,"Cholangiocarcinoma (CCA) and pancreatic adenocarcinoma (PDAC) may lead to the development of extrahepatic obstructive cholestasis. However, biliary stenoses can also be caused by benign conditions, and the identification of their etiology still remains a clinical challenge. We performed metabolomic and proteomic analyses of bile from patients with benign (n = 36) and malignant conditions, CCA (n = 36) or PDAC (n = 57), undergoing endoscopic retrograde cholangiopancreatography with the aim of characterizing bile composition in biliopancreatic disease and identifying biomarkers for the differential diagnosis of biliary strictures. Comprehensive analyses of lipids, bile acids and small molecules were carried out using mass spectrometry (MS) and nuclear magnetic resonance spectroscopy ((1)H-NMR) in all patients. MS analysis of bile proteome was performed in five patients per group. We implemented artificial intelligence tools for the selection of biomarkers and algorithms with predictive capacity. Our machine-learning pipeline included the generation of synthetic data with properties of real data, the selection of potential biomarkers (metabolites or proteins) and their analysis with neural networks (NN). Selected biomarkers were then validated with real data. We identified panels of lipids (n = 10) and proteins (n = 5) that when analyzed with NN algorithms discriminated between patients with and without cancer with an unprecedented accuracy."
1998,Strategies to Improve Health Communication: Can Health Professionals Be Heroes?,"Communicating evidence-based nutrition messages to the public is challenging and is often in conflict with popular opinions, particularly from social media influencers (SMIs). In order to increase engagement with nutrition professionals (NPs) on social media, we aimed to explore young adults’ perceptions of the authenticity and trustworthiness of SMIs and NPs Instagram posts. A cross-sectional questionnaire was administered to students (n = 149) from an Australian University. Participants viewed a real-life Instagram profile and one post from both a NP and a SMI. Main outcomes were post authenticity and trustworthiness, and emotional message appeals measured on five-point Likert scales. Regression models were developed to assess whose post (the NP or SMI) was perceived to be more authentic and trustworthy. Participants were young adults (median age (25th, 75th percentiles): 20 (19,21)), with approximately half identifying as female. A high heroic message appeal (+1SD above mean) significantly increased the perceived authenticity of the NPs post only (p = 0.01). Post authenticity enhanced post trustworthiness, but only when a heroic message appeal was used by the NP. When appropriate, NPs should convey positive emotions such as bravery and success to enhance the authenticity and trustworthiness of their posts."
1999,The Central Role of Iron in Human Nutrition: From Folk to Contemporary Medicine,"Iron is a fundamental element in human history, from the dawn of civilization to contemporary days. The ancients used the metal to shape tools, to forge weapons, and even as a dietary supplement. This last indication has been handed down until today, when martial therapy is considered fundamental to correct deficiency states of anemia. The improvement of the martial status is mainly targeted with dietary supplements that often couple diverse co-factors, but other methods are available, such as parenteral preparations, dietary interventions, or real-world approaches. The oral absorption of this metal occurs in the duodenum and is highly dependent upon its oxidation state, with many absorption influencers possibly interfering with the intestinal uptake. Bone marrow and spleen represent the initial and ultimate step of iron metabolism, respectively, and the most part of body iron circulates bound to specific proteins and mainly serves to synthesize hemoglobin for new red blood cells. Whatever the martial status is, today’s knowledge about iron biochemistry allows us to embrace exceedingly personalized interventions, which however owe their success to the mythical and historical events that always accompanied this metal."
2000,Modeling the Effect of the Oxidation Status of the Ingredient Oil on Stability and Shelf Life of Low-Moisture Bakery Products: The Case Study of Crackers,"In packed low-moisture foods such as crackers, oxidation is generally the main cause of quality depletion during storage. It is commonly believed, but scarcely investigated, that product shelf life depends on the oxidative status of the lipid ingredients. In this study, the influence of oxidation degree of the ingredient sunflower oil on cracker oxidative stability and hence shelf life was investigated. To this aim, oil with increasing peroxide values (PVs) (5, 11, and 25 mEqO(2)/kg(oil)) was used to prepare crackers. Just after production, crackers presented similar peroxide and rancid odor intensity, probably due to the interactive pathways of oxidative and Maillard reactions. Crackers were packed and analyzed for PV and rancid odor during storage at 20, 40, and 60 °C. Rancid odor well discriminated cracker oxidative status. Relevant oxidation rates were used to develop a shelf life predictive model based on the peroxide value of the ingredient oil. It was estimated that an oil PV from 5 to 15 mEqO(2)/kg(oil) shortens cracker Shelf Life (SL) by 50%, independently of storage temperature. These results demonstrate the critical impact of ingredient quality on product performance on the market."
2001,Development of a sensitive monoclonal antibody-based sandwich ELISA to detect Vip3Aa in genetically modified crops,"OBJECTIVES: To develop a sensitive monoclonal antibody-based sandwich enzyme-linked immunosorbent assay (ELISA) to detect Vip3Aa in genetically modified (GM) crops and their products. RESULTS: Vegetative insecticidal proteins (Vips) are secreted by Bacillus thuringiensis (Bt) and are known to be toxic to Lepidoptera species. Vip3Aa family proteins, Vip3Aa19 and Vip3Aa20, were successfully applied in GM crops to confer an effective and persistent insecticidal resistance. A sensitive monoclonal antibody-based sandwich ELISA was developed to detect Vip3Aa in GM crops and their products. Two monoclonal antibodies were raised against the overexpressed and purified His-Vip3Aa20, were purified from mouse ascites and characterized. A sandwich ELISA method was developed using the 2G3-1D7 monoclonal antibody for capture and the biotin-labeled 1F9-1F5 monoclonal antibody for detection of Vip3Aa20. The linear detection range of the method was found to be approximately 31.25–500 pg/ml, with a sensitivity of 10.24 pg/ml. CONCLUSIONS: The established ELISA was effective for detecting Vip3Aa family proteins other than Vip3Aa8, and was successfully applied in the detection of Vip3Aa20 and Vip3Aa19 expressed in transgenic maize and cotton."
2002,Assigning mitochondrial localization of dual localized proteins using a yeast Bi-Genomic Mitochondrial-Split-GFP,"A single nuclear gene can be translated into a dual localized protein that distributes between the cytosol and mitochondria. Accumulating evidences show that mitoproteomes contain lots of these dual localized proteins termed echoforms. Unraveling the existence of mitochondrial echoforms using current GFP (Green Fluorescent Protein) fusion microscopy approaches is extremely difficult because the GFP signal of the cytosolic echoform will almost inevitably mask that of the mitochondrial echoform. We therefore engineered a yeast strain expressing a new type of Split-GFP that we termed Bi-Genomic Mitochondrial-Split-GFP (BiG Mito-Split-GFP). Because one moiety of the GFP is translated from the mitochondrial machinery while the other is fused to the nuclear-encoded protein of interest translated in the cytosol, the self-reassembly of this Bi-Genomic-encoded Split-GFP is confined to mitochondria. We could authenticate the mitochondrial importability of any protein or echoform from yeast, but also from other organisms such as the human Argonaute 2 mitochondrial echoform."
2003,The Respiratory Specimen Collection Trial (ReSpeCT): A Randomized Controlled Trial to Compare Quality and Timeliness of Respiratory Sample Collection in the Home by Parents and Healthcare Workers From Children Aged <2 Years,"BACKGROUND: Most acute respiratory infection (ARI) research focuses on severe disease and overlooks the burden of community-managed illness. For community-based studies, home-based specimen collection by parents could be a resource-saving alternative to collection by healthcare workers (HCWs). In this study, we compared parent and HCW groups for their likelihood to collect specimens and the timeliness and quality of such collection. METHODS: In this unblinded randomized controlled trial, parents from Brisbane, Australia, were taught to identify new ARI episodes in their children aged <2 years. When their child had a new ARI, parents either collected a nasal swab from the child (P group) or contacted an HCW who visited to obtain a nasopharyngeal swab (HCW group). We compared the likelihood and timeliness of specimen collection and respiratory pathogen detection. A nested diagnostic study compared paired specimen collections from children in the HCW group. RESULTS: Included were 76 incident ARI episodes from 31 children and 102 episodes from 33 children in the P and HCW groups, respectively. The proportions of ARIs for which a specimen was collected were similar (P group, 69.7%; HCW group, 72.5%; P = .77), and pathogens were detected in 93.8% and 77.5% of the specimens, respectively (P = .03). The period between ARI onset and specimen collection was shorter in the P group than in the HCW group (mean difference, 1.9 days [95% confidence interval, 0.7–3.0 days]; P < .001). For the 69 paired specimens, viral loads were lower in the parent-collected swabs (mean cycle threshold difference, 4.5 [95% confidence interval, 3.1–5.9]; P < .001). CONCLUSIONS: Parents and HCWs obtained samples in similar proportions of ARI episodes, but the parents collected the samples fewer days after ARI onset and with a resulting higher likelihood of pathogen identification. This method can be used in population-based epidemiological studies of ARI as a resource-saving alternative. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00966069."
2004,Golgi compartments enable controlled biomolecular assembly using promiscuous enzymes,"The synthesis of eukaryotic glycans – branched sugar oligomers attached to cell-surface proteins and lipids – is organized like a factory assembly line. Specific enzymes within successive compartments of the Golgi apparatus determine where new monomer building blocks are linked to the growing oligomer. These enzymes act promiscuously and stochastically, causing microheterogeneity (molecule-to-molecule variability) in the final oligomer products. However, this variability is tightly controlled: a given eukaryotic protein type is typically associated with a narrow, specific glycan oligomer profile. Here, we use ideas from the mathematical theory of self-assembly to enumerate the enzymatic causes of oligomer variability and show how to eliminate each cause. We rigorously demonstrate that cells can specifically synthesize a larger repertoire of glycan oligomers by partitioning promiscuous enzymes across multiple Golgi compartments. This places limits on biomolecular assembly: glycan microheterogeneity becomes unavoidable when the number of compartments is limited, or enzymes are excessively promiscuous."
2005,The Case Is Much More Baffling than We Think,
2006,Letter to the Editor regarding the Article “Impact of Anterior Kidney Calyx Involvement of Complex Stones on Outcomes for Patients Undergoing Percutaneous Nephrolithotomy”,
2007,Reshaping neonatal intensive care units (NICUs) to avoid the spread of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to high-risk infants,
2008,"Skin manifestations in COVID‐19: A case series of five patients from Elazığ, Turkey",
2009,How do we reopen our motility laboratory safely and efficiently?,
2010,An Urgent Need for “Common Cold Units” to Study COVID-19,
2011,Predicting functional family of novel enzymes irrespective of sequence similarity: a statistical learning approach,"The function of a protein that has no sequence homolog of known function is difficult to assign on the basis of sequence similarity. The same problem may arise for homologous proteins of different functions if one is newly discovered and the other is the only known protein of similar sequence. It is desirable to explore methods that are not based on sequence similarity. One approach is to assign functional family of a protein to provide useful hint about its function. Several groups have employed a statistical learning method, support vector machines (SVMs), for predicting protein functional family directly from sequence irrespective of sequence similarity. These studies showed that SVM prediction accuracy is at a level useful for functional family assignment. But its capability for assignment of distantly related proteins and homologous proteins of different functions has not been critically and adequately assessed. Here SVM is tested for functional family assignment of two groups of enzymes. One consists of 50 enzymes that have no homolog of known function from PSI-BLAST search of protein databases. The other contains eight pairs of homologous enzymes of different families. SVM correctly assigns 72% of the enzymes in the first group and 62% of the enzyme pairs in the second group, suggesting that it is potentially useful for facilitating functional study of novel proteins. A web version of our software, SVMProt, is accessible at http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi."
2012,Improving gene annotation of complete viral genomes,"Gene annotation in viruses often relies upon similarity search methods. These methods possess high specificity but some genes may be missed, either those unique to a particular genome or those highly divergent from known homologs. To identify potentially missing viral genes we have analyzed all complete viral genomes currently available in GenBank with a specialized and augmented version of the gene finding program GeneMarkS. In particular, by implementing genome-specific self-training protocols we have better adjusted the GeneMarkS statistical models to sequences of viral genomes. Hundreds of new genes were identified, some in well studied viral genomes. For example, a new gene predicted in the genome of the Epstein–Barr virus was shown to encode a protein similar to α-herpesvirus minor tegument protein UL14 with heat shock functions. Convincing evidence of this similarity was obtained after only 12 PSI-BLAST iterations. In another example, several iterations of PSI-BLAST were required to demonstrate that a gene predicted in the genome of Alcelaphine herpesvirus 1 encodes a BALF1-like protein which is thought to be involved in apoptosis regulation and, potentially, carcinogenesis. New predictions were used to refine annotations of viral genomes in the RefSeq collection curated by the National Center for Biotechnology Information. Importantly, even in those cases where no sequence similarities were detected, GeneMarkS significantly reduced the number of primary targets for experimental characterization by identifying the most probable candidate genes. The new genome annotations were stored in VIOLIN, an interactive database which provides access to similarity search tools for up-to-date analysis of predicted viral proteins."
2013,Predicting genes expressed via −1 and +1 frameshifts,"Computational identification of ribosomal frameshift sites in genomic sequences is difficult due to their diverse nature, yet it provides useful information for understanding the underlying mechanisms and discovering new genes. We have developed an algorithm that searches entire genomic or mRNA sequences for frameshifting sites, and implements the algorithm as a web-based program called FSFinder (Frameshift Signal Finder). The current version of FSFinder is capable of finding −1 frameshift sites on heptamer sequences X XXY YYZ, and +1 frameshift sites for two genes: protein chain release factor B (prfB) and ornithine decarboxylase antizyme (oaz). We tested FSFinder on ∼190 genomic and partial DNA sequences from a number of organisms and found that it predicted frameshift sites efficiently and with greater sensitivity and specificity than existing approaches. It has improved sensitivity because it considers many known components of a frameshifting cassette and searches these components on both + and − strands, and its specificity is increased because it focuses on overlapping regions of open reading frames and prioritizes candidate frameshift sites. FSFinder is useful for discovering unknown genes that utilize alternative decoding, as well as for analyzing frameshift sites. It is freely accessible at http://wilab.inha.ac.kr/FSFinder/."
2014,Infertility management in primary care,"Infertility is a growing issue for couples. Primary care NPs can manage initial treatment as well as address the emotional and financial burdens of patients experiencing infertility. NPs can provide timely access to investigations and treatment, helping patients achieve their goal of pregnancy sooner."
2015,Astrocytes influence medulloblastoma phenotypes and CD133 surface expression,"The medulloblastoma (MB) microenvironment is diverse, and cell-cell interactions within this milieu is of prime importance. Astrocytes, a major component of the microenvironment, have been shown to impact primary tumor cell phenotypes and metastasis. Based on proximity of MB cells and astrocytes in the brain microenvironment, we investigated whether astrocytes may influence MB cell phenotypes directly. Astrocyte conditioned media (ACM) increased Daoy MB cell invasion, adhesion, and in vivo cellular protrusion formation. ACM conditioning of MB cells also increased CD133 surface expression, a key cancer stem cell marker of MB. Additional neural stem cell markers, Nestin and Oct-4A, were also increased by ACM conditioning, as well as neurosphere formation. By knocking down CD133 using short interfering RNA (siRNA), we showed that ACM upregulated CD133 expression in MB plays an important role in invasion, adhesion and neurosphere formation. Collectively, our data suggests that astrocytes influence MB cell phenotypes by regulating CD133 expression, a key protein with defined roles in MB tumorgenicity and survival."
2016,Ethical issues in intervention studies on the prevention and management of diabetes and hypertension in sub-Saharan Africa,
2017,"Actions, indicators, and outputs in urban biodiversity plans: A multinational analysis of city practice","Urban biodiversity offers important benefits to residents and may be crucial to reaching global biodiversity conservation targets, but little research has been conducted on how cities actually plan for biodiversity. In this study, we conducted a mixed methods content analysis of biodiversity plans by 39 cities around the world to determine whether they measured their actions, how they did so (via quantitative indicators and qualitative outputs), and what topics these actions and measures covered. We based our analytical framework on the Singapore Index on Cities’ Biodiversity (also known as the City Biodiversity Index), a widely applied 23-indicator index that helps cities track their progress in biodiversity planning. The Singapore Index groups its indicators into the following three core components: native biodiversity, ecosystem services, and governance and management. For actions and measures not classifiable by the Singapore Index, we inductively derived additional categories. Across all plans, we identified 2,231 actions, 346 indicators, and 444 outputs. We found that all of the plans included actions, while 82% included measures (67% included indicators and 72% included outputs). Only 29% of actions were associated with a measure. Overall, the plans covered all of the categories in the Singapore Index, particularly within the core components of native biodiversity and governance and management, though some plans had a narrower focus. The 20 additional urban biodiversity topics that were not covered by the Singapore Index framework included socioeconomic considerations, data collection, genetic diversity, urban agriculture and forestry, green infrastructure, human-wildlife conflicts, indigenous concerns, and citizen science. Indicators were the most common measures for native biodiversity and ecosystem service topics, while outputs were the most common measures for governance and management. Our results may inform the revision and development of urban biodiversity indicators in the post-2020 framework and of other initiatives that guide cities in contributing to local and global biodiversity goals."
2018,An Angelman syndrome substitution in the HECT E3 ubiquitin ligase C-terminal Lobe of E6AP affects protein stability and activity,"Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by speech impairment, intellectual disability, ataxia, and epilepsy. AS is caused by mutations in the maternal copy of UBE3A located on chromosome 15q11-13. UBE3A codes for E6AP (E6 Associated Protein), a prominent member of the HECT (Homologous to E6AP C-Terminus) E3 ubiquitin ligase family. E6AP catalyzes the posttranslational attachment of ubiquitin via its HECT domain onto various intracellular target proteins to regulate DNA repair and cell cycle progression. The HECT domain consists of an N-lobe, required for E2~ubiquitin recruitment, while the C-lobe contains the conserved catalytic cysteine required for ubiquitin transfer. Previous genetic studies of AS patients have identified point mutations in UBE3A that result in amino acid substitutions or premature termination during translation. An AS transversion mutation (codon change from ATA to AAA) within the region of the gene that codes for the catalytic HECT domain of E6AP has been annotated (I827K), but the molecular basis for this loss of function substitution remained elusive. Here, we demonstrate that the I827K substitution destabilizes the 3D fold causing protein aggregation of the C-terminal lobe of E6AP using a combination of spectropolarimetry and nuclear magnetic resonance (NMR) spectroscopy. Our fluorescent ubiquitin activity assays with E6AP-I827K show decreased ubiquitin thiolester formation and ubiquitin discharge. Using 3D models in combination with our biochemical and biophysical results, we rationalize why the I827K disrupts E6AP-dependent ubiquitylation. This work provides new insight into the E6AP mechanism and how its malfunction can be linked to the AS phenotype."
2019,The Crisis in Male Mental Health: A Call to Action,
2020,Improvisation – a new strategy in medical education?,
2021,ISMB 2020 proceedings,
2022,"Assisted reproduction and COVID-19: a joint statement of ASRM, ESHRE and IFFS",
2023,"Rotavirus group A genotype circulation patterns across Kenya before and after nationwide vaccine introduction, 2010–2018","BACKGROUND: Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010–June 2014) and post- (July 2014–December 2018) RVA vaccine introduction. METHODS: Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes. RESULTS: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters. CONCLUSION: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity."
2024,"NAADP‐regulated two‐pore channels drive phagocytosis through endo‐lysosomal Ca(2+) nanodomains, calcineurin and dynamin","Macrophages clear pathogens by phagocytosis and lysosomes that fuse with phagosomes are traditionally regarded as to a source of membranes and luminal degradative enzymes. Here, we reveal that endo‐lysosomes act as platforms for a new phagocytic signalling pathway in which FcγR activation recruits the second messenger NAADP and thereby promotes the opening of Ca(2+)‐permeable two‐pore channels (TPCs). Remarkably, phagocytosis is driven by these local endo‐lysosomal Ca(2+) nanodomains rather than global cytoplasmic or ER Ca(2+) signals. Motile endolysosomes contact nascent phagosomes to promote phagocytosis, whereas endo‐lysosome immobilization prevents it. We show that TPC‐released Ca(2+) rapidly activates calcineurin, which in turn dephosphorylates and activates the GTPase dynamin‐2. Finally, we find that different endo‐lysosomal Ca(2+) channels play diverse roles, with TPCs providing a universal phagocytic signal for a wide range of particles and TRPML1 being only required for phagocytosis of large targets."
2025,Hair arsenic level in rice-based diet-fed Staffordshire bull terriers,"BACKGROUND: There have been concerns related to inorganic arsenic (iAs) in rice and the risk of chronic toxicity in human beings, especially children. Rice is a common constituent of pet food, and dogs often eat the same food on a continual daily basis for long periods of time. Therefore, the purpose of this study was to assess the risk of chronic iAs exposure in rice-based diet-fed dogs. METHODS: Hair iAs level was measured in seven rice-based diet-fed dogs (mean age 3.8 years) and in nine dogs that did not consume any rice (mean age 4.4 years), using inductively coupled plasma mass spectrometry. RESULTS: The hair iAs level was significantly higher (P=0.005) in dogs fed a rice-based diet (mean 0.143 µg/g) than in dogs that did not consume any rice (mean 0.086 µg/g), while age and sex did not show associations with hair iAs level. CONCLUSION: The results suggest that eating a rice-based diet for long periods of time represents a risk for chronic iAs exposure in dogs."
2026,Thoughts of a Premedical Student on the Current State of the Medical School Application Process,
2027,The Cost of 1 Residency Position: A Studio Apartment of Sea Ice,
2028,Strands of injustice,
2029,A HIF1a-Dependent Pro-Oxidant State Disrupts Synaptic Plasticity and Impairs Spatial Memory in Response to Intermittent Hypoxia,"Sleep apnea causes cognitive deficits and is associated with several neurologic diseases. Intermittent hypoxia (IH) is recognized as a principal mediator of pathophysiology associated with sleep apnea, yet the basis by which IH contributes to impaired cognition remains poorly defined. Using a mouse model exposed to IH, this study examines how the transcription factor, hypoxia inducible factor 1a (HIF1a), contributes to disrupted synaptic physiology and spatial memory. In wild-type mice, impaired performance in the Barnes maze caused by IH coincided with a loss of NMDA receptor (NMDAr)-dependent long-term potentiation (LTP) in area CA1 and increased nuclear HIF1a within the hippocampus. IH-dependent HIF1a signaling caused a two-fold increase in expression of the reactive oxygen species (ROS) generating enzyme NADPH oxidase 4 (NOX4). These changes promoted a pro-oxidant state and the downregulation of GluN1 within the hippocampus. The IH-dependent effects were not present in either mice heterozygous for Hif1a (HIF1a(+/−)) or wild-type mice treated with the antioxidant manganese (III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP). Our findings indicate that HIF1a-dependent changes in redox state are central to the mechanism by which IH disrupts hippocampal synaptic plasticity and impairs spatial memory. This mechanism may enhance the vulnerability for cognitive deficit and lower the threshold for neurologic diseases associated untreated sleep apnea."
2030,Chest physiotherapy improves regional lung volume in ventilated children,
2031,"Terrorist incidents: strategic treatment objectives, tactical diagnostic procedures and the estimated need of blood and clotting products","BACKGROUND: Terrorism-related incidents that are associated with mass casualties (mass-casualty terrorist incidents) are a medical and organisational challenge for every hospital because of the special injury patterns involved, the time of the incident, the development of the situation, the initial lack of information, the number of injured, and the number of uninjured survivors who self-refer to a hospital. METHODS: The Terror and Disaster Surgical Care (TDSC®) - Course was developed in order to address mass-casualty terrorist incidents and to provide surgeons with the specialist medical and surgical knowledge and skills required for these special situations. The focus of the TDSC® course is on how to provide surgical care and how to deploy scarce resources in a particular tactical situation in such a way that the number of survivors is maximised. RESULTS: The effective management of such a tactical situation must be based on priorities and first and foremost requires the standardised sorting and categorisation of the injured at the hospital. The aim of triage, or the sorting of the injured, is to immediately identify patients with life-threatening injuries in environments with strained resources. The medical management of mass-casualty terrorist incidents requires tactical abbreviated surgical care (TASC) teams that have the skills needed to perform a primary survey and to provide care for casualties who need immediate surgery (triage category 1—T1). Initial fluid therapy should be restrictive (permissive hypotension) unless contraindicated. Clotting products are replaced in a standardised manner on the basis of patient requirements, which are calculated using rapidly available surrogates (blood gas analysis). Blood products can be administered or kept available depending on risks and triage categories. The highest priority should be given to the identification and management of haemodynamically unstable patients who require immediate surgery for injuries associated with bleeding into body cavities (T1 + +). CONCLUSION: The recommendations and approaches described here should be considered as proposals for hospitals to develop standards or modify well-established standards that enable them to prepare themselves successfully for situations (e.g. mass-casualty terrorist or shooter incidents) in which their resources are temporarily overwhelmed."
2032,Willingness to pay for an early warning system for infectious diseases,"Early warning systems for infectious diseases and foodborne outbreaks are designed with the aim of increasing the health safety of citizens. As a first step to determine whether investing in such a system offers value for money, this study used contingent valuation to estimate people’s willingness to pay for such an early warning system in six European countries. The contingent valuation experiment was conducted through online questionnaires administered in February to March 2018 to cross-sectional, representative samples in the UK, Denmark, Germany, Hungary, Italy, and The Netherlands, yielding a total sample size of 3140. Mean willingness to pay for an early warning system was €21.80 (median €10.00) per household per month. Pooled regression results indicate that willingness to pay increased with household income and risk aversion, while they decreased with age. Overall, our results indicate that approximately 80–90% of people would be willing to pay for an increase in health safety in the form of an early warning system for infectious diseases and food-borne outbreaks. However, our results have to be interpreted in light of the usual drawbacks of willingness to pay experiments. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10198-020-01171-2) contains supplementary material, which is available to authorized users."
2033,"Perinatal Vertical Transmission of Chikungunya Virus in Ruili, a Town on the Border between China and Burma",
2034,合并肢端缺血表现的危重型新型冠状病毒肺炎七例临床分析,"OBJECTIVE: To investigate the clinical and coagulation characteristics in patients with critical Coronavirus disease 2019 (COVID-19) and acro-ischemia. METHODS: The retrospective study included 7 critical COVID-19 patients with acro-ischemia in an intensive care unit (ICU) in Wuhan, from Feb 4 to Feb 15, 2020. The clinical and laboratory data before and during the ICU stay were analyzed. RESULTS: The median age of 7 patients was 59 years and 4 of them were men. Three patients were associated with underlying comorbidities. Fever, cough, dyspnea and diarrhea were common clinical symptoms. All patients had acro-ischemia presentations including finger/toe cyanosis, skin bulla and dry gangrene. D-dimer, fibrinogen and fibrinogen degradation product (FDP) were significantly elevated in most patients. Prothrombin time was prolonged in 4 patients. D-dimer and FDP levels progressively elevated consistent with COVID-2019 exacerbation. Four patients were diagnosed with disseminated intravascular coagulation (DIC). Low molecular weight heparin (LMWH) was administrated in 6 patients, which reduced D-dimer and FDP rather than improved clinical symptoms. Five patients died finally and the median time from acro-ischemia to death was 12 days. CONCLUSION: Coagulation parameters should be monitored closely in critical COVID-2019 patients. The timing and protocol of anticoagulation therapy are still under investigation based on more clinical data."
2035,Reply to Modesto-Alapont et al.: Breaking Circular Thinking about the Value of Oxygenation,
2036,Are Patients with COVID-19 Dying of or with Cardiac Injury?,
2037,Reply to Tsolaki and Zakynthinos: Are Patients with COVID-19 Dying of or with Cardiac Injury?,
2038,The surviving sepsis campaign: basic/translational science research priorities,"OBJECTIVES: Expound upon priorities for basic/translational science identified in a recent paper by a group of experts assigned by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. DATA SOURCES: Original paper, search of the literature. STUDY SELECTION: This study is selected by several members of the original task force with specific expertise in basic/translational science. Data extraction and data synthesis are not available. CONCLUSIONS: In the first of a series of follow-up reports to the original paper, several members of the original task force with specific expertise provided a more in-depth analysis of the five identified priorities directly related to basic/translational science. This analysis expounds on what is known about the question and what was identified as priorities for ongoing research. It is hoped that this analysis will aid the development of future research initiatives."
2039,The Recent Advances of Fluorescent Sensors Based on Molecularly Imprinted Fluorescent Nanoparticles for Pharmaceutical Analysis,"Fluorescent nanoparticles have good chemical stability and photostability, controllable optical properties and larger stokes shift. In light of their designability and functionability, the fluorescent nanoparticles are widely used as the fluorescent probes for diverse applications. To enhance the sensitivity and selectivity, the combination of the fluorescent nanoparticles with the molecularly imprinted polymer, i.e. molecularly imprinted fluorescent nanoparticles (MIFN), was an effective way. The sensor based on MIFN (the MIFN sensor) could be more compatible with the complex sample matrix, which was especially widely adopted in medical and biological analysis. In this mini-review, the construction method, detective mechanism and types of MIFN sensors are elaborated. The current applications of MIFN sensors in pharmaceutical analysis, including pesticides/herbicide, veterinary drugs/drugs residues and human related proteins, are highlighted based on the literature in the recent three years. Finally, the research prospect and development trend of the MIFN sensor are forecasted."
2040,Influence of ventilatory strategies on outcomes and length of hospital stay: assist-control and synchronized intermittent mandatory ventilation modes,"The use of synchronized intermittent mandatory ventilation with pressure support ventilation (SIMV + PSV) mode has been discontinued. This study analyzed the association between medical outcomes related to the use of assist-control (A/C) and SIMV + PSV in an intensive care unit. In this observational and retrospective study, modes of ventilation and medical data were collected from electronic medical records for three consecutive years and were related to medical outcomes (mortality), duration of mechanical ventilation, length of hospital stay and the need for tracheostomy. Participants were divided into groups according to the modes of ventilation: A/C and SIMV + PSV. Statistical analyses were performed in the R environment. Alpha = 0.05. The using chi-square, Fisher’s exact, Mann–Whitney and Kruskal–Wallis tests were used. 345 adult participants were included; 211/345 (61.16%) were males. Of the participants, 151/345 (43.77%) were on SIMV + PSV and 194/345 (56.23%) were on A/C. The comparative analysis between the modes of ventilation showed no significant differences in length of hospital stay (p = 0.675), duration of mechanical ventilation (p = 0.952), mortality (p = 0.241), failed extubation (p = 0.411) and the need for tracheostomy (p = 0.301). SIMV + PSV as a mode of ventilation showed similar statistical results to the A/C mode, when compared to analyzed medical outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11739-020-02444-7) contains supplementary material, which is available to authorized users."
2041,Full-length genome sequences of the first H9N2 avian influenza viruses isolated in the Northeast of Algeria,"BACKGROUND: H9N2 avian influenza viruses (AIV) has a worldwide geographic distribution and affects poultry of different types of production. H9N2 AIV was first reported in the Northeast of Algeria in April 2017, following an outbreak associated with high mortality, in broiler flocks. In the present study, we report full-length genome sequences of AIV H9N2, and the detailed phylogeny and molecular genetic analyses. METHODS: Ten AIV H9N2 strains, collected in broiler flocks, were amplified in 9-day-old embryonated specific pathogen free (SPF) chicken eggs. Their full-length genomes were successfully sequenced and phylogenetic and molecular characterizations were conducted. RESULTS: Phylogenetic analysis showed that the isolates were monophyletic, grouped within the G-1 lineage and were very close to Moroccan and Algerian strains identified in 2016 and 2017, respectively. The low pathogenicity of the strains was confirmed by the sequence motif (335RSSR/GLF341) at the hemagglutinin (HA) cleavage site. An exclusive substitution (T197A) that had not been previously reported for H9N2 viruses; but, conserved in some pandemic H1N1 viruses, was observed. When compared to the G1-like H9N2 prototype, the studied strains showed one less glycosylation site in HA, but 2–3 additional ones in the stalk of the neuraminidase (NA). The HA protein harbored the substitution 234 L, suggesting binding preference to human-like receptors. The NA protein harbored S372A and R403W substitutions, previously detected in H9N2 from Asia and the Middle East, and especially in H2N2 and H3N2 strains that caused human pandemics. Different molecular markers associated with virulence and mammalian infections have been detected in the viral internal proteins. The matrix M2 protein possessed the S31N substitution associated with drug resistance. The non-structural 1 (NS1) protein showed the “GSEV” PDZ ligand (PL) C-terminal motif and no 80–84 deletion. CONCLUSION: Characterized Algerian AIV isolates showed mutations that suggest increased zoonotic potential. Additional studies in animal models are required to investigate the pathogenicity of these H9N2 AIV strains. Monitoring their evolution in both migratory and domestic birds is crucial to prevent transmission to humans. Implementation of adequate biosecurity measures that limit the introduction and the propagation of AIV H9N2 in Algerian poultry farm is crucial."
2042,COVID-19 and the Role of Spine Surgeons,
2043,Epidemics Over the Centuries,
2044,Two Switchable Plasmonically Induced Transparency Effects in a System with Distinct Graphene Resonators,"General plasmonic systems to realize plasmonically induced transparency (PIT) effect only exist one single PIT mainly because they only allow one single coupling pathway. In this study, we propose a distinct graphene resonator-based system, which is composed of graphene nanoribbons (GNRs) coupled with dielectric grating-loaded graphene layer resonators, to achieve two switchable PIT effects. By designing crossed directions of the resonators, the proposed system exists two different PIT effects characterized by different resonant positions and linewidths. These two PIT effects result from two separate and polarization-selective coupling pathways, allowing us to switch the PIT from one to the other by simply changing the polarization direction. Parametric studies are carried to demonstrate the coupling effects whereas the two-particle model is applied to explain the physical mechanism, finding excellent agreements between the numerical and theoretical results. Our proposal can be used to design switchable PIT-based plasmonic devices, such as tunable dual-band sensors and perfect absorbers."
2045,A Shortage in the Number of Nurses—A Case Study from a Selected Region in the Czech Republic and International Context,"A lack of nurses in the Czech Republic is an issue that has been under discussion for several years. The aim of this paper is to analyze the lack and need of general nurses and midwives in the Hradec Kralove region where the shortage is higher than the national average. The used methods are quantitative research and structured interviews, to determine the number of nurses in healthcare institutions. The study uses data obtained from publicly available sources, i.e., Czech Statistical Office (CSO) and the National Institute of Education (NIE). The shortage of nurses in the Hradec Kralove region can be expected by 2030 to be in the range between 647.6 and 667.1 nurses while maintaining the existing conditions, that is, five times more than at present. In addition to the commonly considered measures that appear in the country’s strategies—such as improving the quality of conditions during studies and during employment, specifying or adjusting the role and competency of nurses and midwives in the healthcare system, or unifying employment standards— a focus on promoting the nursing profession can be recommended. Schools and ministries should be encouraged to focus on and invest in the promotion of this profession, so as to play a key role in recruiting new students for the nursing field of study at a time when the nursing profession is perceived positively, as an embodiment of solidarity and selflessness."
2046,"Identification of drought tolerant mechanisms in a drought-tolerant maize mutant based on physiological, biochemical and transcriptomic analyses","BACKGROUND: Frequently occurring drought stress negatively affects the production of maize worldwide. Numerous efforts have been made to develop drought-tolerant maize lines and to explore drought tolerant mechanisms in maize. However, there is a lack of comparative studies on transcriptomic changes between drought-tolerant and control maize lines. RESULTS: In the present study, we have developed a drought-tolerant maize mutant (C7–2t) by irradiating the seeds of maize inbred line ChangC7–2 (C7–2) with (60)Co-γ. Compared to its wild type C7–2, C7–2t exhibited a significantly delayed wilting and higher drought tolerance under both the controlled and field conditions, indicating its high water-holding ability. Transcriptomic profiling was performed to identify differentially expressed genes (DEGs) between C7–2 and C7–2t during drought. As a result, a total of 4552 DEGs were implied in drought tolerance of C7-2 and C7-2t. In particular, the expression of photosynthesis-related genes in C7–2 was inhibited, whereas these genes in C7–2t were almost unaffected under drought. Moreover, a specific set of the DEGs were involved in phenylpropanoid biosynthesis and taurine (hypotaurine) metabolism in C7–2t; these DEGs were enriched in cell components associated with membrane systems and cell wall biosynthesis. CONCLUSIONS: The drought tolerance of C7–2t was largely due to its high water-holding ability, stable photosynthesis (for supporting osmoregulation) and strengthened biosynthesis of cell walls under drought conditions."
2047,A Multidisciplinary Review of the Roles of Cripto in the Scientific Literature Through a Bibliometric Analysis of its Biological Roles,"Cripto is a small glycosylphosphatidylinisitol (GPI)-anchored and secreted oncofetal protein that plays important roles in regulating normal physiological processes, including stem cell differentiation, embryonal development, and tissue growth and remodeling, as well as pathological processes such as tumor initiation and progression. Cripto functions as a co-receptor for TGF-β ligands such as Nodal, GDF1, and GDF3. Soluble and secreted forms of Cripto also exhibit growth factor-like activity and activate SRC/MAPK/PI3K/AKT pathways. Glucose-Regulated Protein 78 kDa (GRP78) binds Cripto at the cell surface and has been shown to be required for Cripto signaling via both TGF-β and SRC/MAPK/PI3K/AKT pathways. To provide a comprehensive overview of the scientific literature related to Cripto, we performed, for the first time, a bibliometric analysis of the biological roles of Cripto as reported in the scientific literature covering the last 10 years. We present different fields of knowledge in comprehensive areas of research on Cripto, ranging from basic to translational research, using a keyword-driven approach. Our ultimate aim is to aid the scientific community in conducting targeted research by identifying areas where research has been conducted so far and, perhaps more importantly, where critical knowledge is still missing."
2048,Acute Disseminated Encephalomyelitis with Seizures and Myocarditis: A Fatal Triad,"Autoimmune pathology of acute disseminated encephalomyelitis (ADEM) is generally restricted to the brain. Our objective is to expand the phenotype of ADEM. A four-year-old girl was admitted to the pediatric emergency room of a university medical center five days after a common upper respiratory tract infection. Acute symptoms were fever, leg pain, and headaches. She developed meningeal signs, and her level of consciousness dropped rapidly. Epileptic seizure activity started, and she became comatose, requiring intubation and mechanical ventilation. Serial brain magnetic resonance imaging (MRI) illustrated the fulminant development of ADEM. Treatment escalation with high-dose corticosteroids, immunoglobulins, and plasma exchange did not lead to clinical improvement. On day ten, the patient developed treatment-refractory cardiogenic shock and passed away. The postmortem assessment confirmed ADEM and revealed acute lymphocytic myocarditis, likely explaining the acute cardiac failure. Human metapneumovirus and picornavirus were detected in the tracheal secrete by PCR. Data sources–medical chart of the patient. This case is consistent with evidence from experimental findings of an association of ADEM with myocarditis as a postinfectious systemic autoimmune response, with life-threatening involvement of the brain and heart."
2049,Oxone(®)-Mediated TEMPO-Oxidized Cellulose Nanomaterial Ultrafiltration and Dialysis Mixed-Matrix Hollow Fiber Membranes,"Recent exploration of cellulose nanomaterials has resulted in the creation of Oxone(®)-Mediated TEMPO-Oxidized Cellulose Nanomaterials (OTO-CNMs). These materials, when incorporated into a polymer matrix, have properties showing increased flux, decreased membrane resistance, and improved clearance, making them an ideal material for dialysis. This study is the first to focus on the implementation of OTO-CNMs into hollow fiber membranes and a comparison of these membranes for ultrafiltration and dialysis. Ultrafiltration and dialysis were performed using bovine serum albumin (BSA), lysozyme, and urea to analyze various properties of each hollow fiber membrane type. The results presented in this study provide the first quantitative evaluation of the clearance and sieving characteristics of Oxone(®)-Mediated TEMPO-Oxidized Cellulose-Nanomaterial-doped cellulose triacetate mixed-matrix hemodialyzers. While the cellulose nanomaterials increased flux (10–30%) in ultrafiltration mode, this was offset by increased removal of albumin. However, in dialysis mode, these materials drastically increased the mass transfer of components (50–100%), which could lead to significantly lower dialysis times for patients. This change in the performance between the two different modes is most likely due to the increased porosity of the cellulose nanomaterials."
2050,Differences in Results and Related Factors between Hospital-At-Home Modalities in Catalonia: A Cross-Sectional Study,"Hospital-at-home (HaH) is a healthcare modality that provides active treatment by healthcare staff in the patient’s home for a condition that would otherwise require hospitalization. The aims were to describe the characteristics of different types of hospital-at-home (HaH), assess their results, and examine which factors could be related to these results. A cross-sectional study based on data from all 2014 HaH contacts from Catalonia was designed. The following HaH modalities were considered—admission avoidance (n = 7214; 75.1%) and early assisted discharge (n = 2387; 24.9%). The main outcome indicators were readmission, mortality, and length of stay (days). Multivariable models were fitted to assess the association between explanatory factors and outcomes. Hospital admission avoidance is a scheme in which, instead of being admitted to acute care hospitals, patients are directly treated in their own homes. Early assisted discharge is a scheme in which hospital in-care patients continue their treatment at home. In the hospital avoidance modality, there were 8.3% readmissions, 0.9% mortality, and a mean length of stay (SD) of 9.6 (10.6) days. In the early assisted discharge modality, these figures were 7.9%, 0.5%, and 9.8 (11.1), respectively. In both modalities, readmission and mean length of stay were related to comorbidity and type of hospital, and mortality with age. The results of HaH in Catalonia are similar to those observed in other contexts. The factors related to these results identified might help to improve the effectiveness and efficiency of the different HaH modalities."
2051,"Positionspapier: Empfehlungen zur Behandlung der chronischen Rhinosinusitis während der COVID-19-Pandemie im deutschen Gesundheitssystem – Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNO-KHC) – Diese Empfehlungen basieren auf dem EAACI Positionspapier „Treatment of chronic RhinoSinusitis with nasal polyps (CRSwNP) in the COVID-19 pandemics – An EAACI Position Paper”, Allergy, 2020 und wurden auf die Situation im deutschen Gesundheitswesen angepasst","Hintergrund Von der chronischen Rhinosinusitis (CRS) sind weltweit etwa 5–12 % der Allgemeinbevölkerung betroffen. Die CRS gilt als chronische Atemwegserkrankung, die nach den Empfehlungen der WHO ein Risikofaktor für COVID-19-Patienten sein kann. Die entzündlichen Veränderungen der Nasenschleimhäute bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) sind in den meisten Fällen vom Entzündungsendotyp 2 (T2). Methoden Der aktuelle Wissensstand sowohl zu COVID-19 als auch zu den Behandlungsmöglichkeiten von CRSwNP wurde durch eine Literaturrecherche in Medline, Pubmed, internationalen Leitlinien, der Cochrane Library und im Internet analysiert. Ergebnisse Auf Grundlage der internationalen Literatur, der aktuellen Empfehlungen der WHO und anderer internationaler Organisationen sowie der bisherigen Erfahrungen gab ein Expertengremium von EAACI und ARIA Empfehlungen für die Behandlung von CRSwNP während der COVID-19-Pandemien. Schlussfolgerung Intranasale Kortikosteroide stellen die Standardbehandlung für CRS bei Patienten mit einer SARS-CoV-2-Infektion dar. Chirurgische Behandlungen sollten auf ein Minimum reduziert werden und nur bei Patienten mit lokalen Komplikationen und solchen, für die keine anderen Behandlungsmöglichkeiten bestehen, durchgeführt werden. Systemische Kortikosteroide sollten bei COVID-19-Patienten vermieden werden. Die Behandlung mit Biologika kann bei nicht infizierten Patienten unter sorgfältiger Überwachung fortgesetzt werden und sollte während einer SARS-CoV-2-Infektion vorübergehend unterbrochen werden."
2052,Stellungnahme der DGP zur Auswirkung von Mund-Nasenmasken auf den Eigen- und Fremdschutz bei aerogen übertragbaren Infektionen in der Bevölkerung,
2053,Quiescent stem cell marker genes in glioma gene networks are sufficient to distinguish between normal and glioblastoma (GBM) samples,"Grade 4 glioma or GBM has poor prognosis and is the most aggressive grade of glioma. Accurate diagnosis and classification of tumor grade is a critical determinant for development of treatment pathway. Extensive genomic sequencing of gliomas, different cell types, brain tissue regions and advances in bioinformatics algorithms, have presented an opportunity to identify molecular markers that can complement existing histology and imaging methods used to diagnose and classify gliomas. ‘Cancer stem cell theory’ purports that a minor population of stem cells among the heterogeneous population of different cell types in the tumor, drive tumor growth and resistance to therapies. However, characterization of stem cell states in GBM and ability of stem cell state signature genes to serve as diagnostic or prognostic molecular markers are unknown. In this work, two different network construction algorithms, Weighted correlation network analysis (WGCNA) and Multiscale Clustering of Geometric Network (MEGENA), were applied on publicly available glioma, control brain and stem cell gene expression RNA-seq datasets, to identify gene network regulatory modules associated with GBM. Both gene network algorithms identified consensus or equivalent modules, HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA), significantly associated with GBM. Characterization of HuAgeGBsplit_18 (WGCNA) and c1_HuAgeGBsplit_32/193 (MEGENA) modules showed significant enrichment of rodent quiescent stem cell marker genes (GSE70696_QNPbyTAP). A logistic regression model built with eight of these quiescent stem cell marker genes (GSE70696_QNPbyTAP) was sufficient to distinguish between control and GBM samples. This study demonstrates that GBM associated gene regulatory modules are characterized by diagnostic quiescent stem cell marker genes, which may potentially be used clinically as diagnostic markers and therapeutic targets in GBM."
2054,Assessment of Perceptions of the Public Charge Rule Among Low-Income Adults in Texas,This survey study investigates perceptions of the Trump administration’s new public charge rule among low-income Texan adults.
2055,The Finnish Canine Stifle Index: responsiveness to change and intertester reliability,"BACKGROUND: The responsiveness and the intertester reliability of the Finnish Canine Stifle Index (FCSI) were tested, and a cut-off between compromised and severely compromised performance level was set. METHODS: Three groups of dogs were used, 29 with any stifle dysfunction (STIF), 17 with other musculoskeletal disease except stifle (OTHER) and 11 controls (CTRL). All dogs were tested with the FCSI by the same physiotherapist at three occasions, at baseline, at six weeks and 10 weeks, and once also by another physiotherapist. RESULTS: Dogs in the STIF group demonstrated significantly higher (P<0.001) FCSI scores than in OTHER or CTRL groups at baseline. Only the STIF group showed a significant (P<0.001) change in FCSI score at all time points, indicating responsiveness to change. There were no significant differences between the evaluators (P=0.736), showing good intertester reliability, supported by moderate to good (0.78) intraclass correlation coefficient (ICC). The evaluator performing the FCSI did not have a significant effect when comparing the groups of dogs (P=0.214). The 95 per cent confidence intervals of the ICC per group were 0.79 (0.60, 0.91) for STIF, 0.83 (0.53, 0.96) for OTHER 0.78 (0.64, 0.88) for all dogs. A cut-off differentiating a severely compromised from a compromised performance was set at 120, having sensitivity of 83 per cent and specificity of 89 per cent. CONCLUSION: The FCSI is a recommendable measure of dogs’ stifle functionality."
2056,Canine behaviour problems in Brazil: a review of 180 referral cases,"BACKGROUND: Behavioural case loads may vary due to cultural differences, and so it is important to know how these differ with geography. METHODS: One hundred and eighty dog cases referred to a veterinary behaviourist in São Paulo (Brazil) during the period of 2008–2014 are described. RESULTS: Aggression against people was the most common behavioural complaint (22.2 per cent of the cases), followed by apparent fears and phobias (13.3 per cent). Forms of aggression against other dogs (12.2 per cent) and repetitive behaviours (11.1 per cent) were third and fourth most frequent, respectively. Female and male patients were equally reported (47.6 and 52.4 per cent, respectively). These results differ slightly from the findings of other international studies, in which aggression was the main behavioural complaint with fears and phobias less common. CONCLUSION: Regional demographic reviews of the case loads of veterinary behaviour specialists help the profession recognise the problems of most concern to pet owners in a given area and thus local priorities, as well as opening up the potential to generate new hypotheses relating to the reasons for regional differences."
2057,Possible origin of Mesocestoides litteratus,
2058,Prednisolone therapy for chronic hepatitis in English springer spaniels: a prospective study of 12 cases,"BACKGROUND: English springer spaniels (ESS) show an increased risk of chronic hepatitis (CH). In a previous study of 68 ESS with CH, in which only one dog received corticosteroids, a median survival time of 189 days was noted. Some ESS with CH appear to improve with prednisolone treatment; therefore, we aimed to investigate the response to prednisolone in this breed. PARTICIPANTS: ESS with histologically confirmed idiopathic CH were treated with prednisolone 1–2 mg/kg/day. Nine female and three male ESS were enrolled (median age at diagnosis of five years). Patients were monitored clinically and had biochemistry samples taken to assess markers of hepatocellular damage and function. RESULTS: The mean starting dose of prednisolone was 1.1 mg/kg/day. All symptomatic patients showed an initial clinical improvement. Two cases were euthanased while receiving prednisolone. The median time since diagnosis is 1715 days (range: 672–2105 days) and the remaining patients are clinically well, with seven patients still receiving a mean dose of 0.4 mg/kg prednisolone every other day. Statistical analysis demonstrated significant (P<0.05) reductions in serum alkaline phosphatase, alanine aminotransferase and bilirubin following 2–4 weeks of prednisolone treatment. CONCLUSION: This study demonstrates improved clinical and biochemical parameters when some ESS with CH are managed with prednisolone and standard supportive treatments."
2059,Confidence of veterinary surgeons in the United Kingdom in treating and diagnosing exotic pet species,"BACKGROUND: With exotic pet species commonplace in the UK, owners are increasingly seeking veterinary advice regarding the health and welfare of their small mammals and reptiles. This study aimed to assess the confidence of veterinarians in the UK in treating and diagnosing rabbits, guinea pigs, small mammals and reptiles. METHODS: A 41-question survey was promoted via social media, including on interest groups focused specifically at veterinary professionals. A total of 131 practising veterinarians in the UK completed the questionnaire. RESULTS: Frequency of presentation of exotic pets to a practice had a significant effect (P<0.01) on the confidence of veterinarians in treating them. Veterinarians who were presented with exotics more frequently had increased self-reported knowledge of their health and disease and were more confident in treating, diagnosing and anaesthetising them. Knowledge of and confidence in diagnosing and treating exotic pets were significantly less than for dogs and cats (P<0.001). There was a significant effect of length of time qualified on confidence in treating exotic pet species (P<0.01). CONCLUSIONS: Increased provision and engagement with continuing professional development may increase veterinary confidence in diagnosing, treating and anaesthetising exotic pet species that are less commonly encountered in practice."
2060,Suspected adverse reaction to erysipelas vaccine in sheep,
2061,Suspected collision trauma deaths in pied wagtails,
2062,Awake Prone Positioning for Non-intubated Oxygen Dependent COVID-19 Pneumonia Patients,"We share preliminary evidence that awake prone positioning can be a low-risk, low-cost manoeuvre which can help patients with COVID-19 pneumonia delay or reduce the need for intensive care."
2063,Facing SpO(2) and SaO(2) discrepancies in ICU patients: is the perfusion index helpful?,"Peripheral oxygen saturation (SpO(2)) measured by pulse oximetry is an unreliable surrogate marker for arterial oxygenation (SaO(2)) in critically ill patients. We hypothesized that a higher perfusion index (PFI) would be associated with better accuracy of SpO(2) measurement. We retrospectively collected SaO(2), SpO(2), and PFI data for each arterial blood gas (ABG) analysis in a cohort of intensive care unit patients. PFI was categorised as low (PFI < 1.0), intermediate (1.0 ≤ PFI ≤ 2.5), or high (PFI > 2.5). The correlation between SpO(2) and SaO(2) was studied using Pearson’s correlation. The Bland–Altman plot was used to analyse the agreement between SpO(2) and SaO(2). Furthermore, the correlation between the (SpO(2)–SaO(2)) difference and PFI was assessed. The level of (dis)agreement was calculated for the three PFI categories separately. Overall, 281 patients and 1281 data points were analysed. There was a significant correlation between SaO(2) and SpO(2) (r = 0.69, p < 0.01). The Bland–Altman analysis revealed a mean difference between SaO(2) and SpO(2) of 0.2% with limits of agreement of ± 6% (SD ± 2%). The correlation between the PFI and the (SpO(2)–SaO(2)) difference was low; the (SpO(2)–SaO(2)) difference improved only marginally with higher PFI values. The accuracy of pulse oximetry for estimating arterial oxygenation was moderate and improved little with increasing PFI values. Thus, the additive value of PFI in clinical decision making is limited. Therefore, we advise performing an ABG before adjusting fraction of inspired oxygen (FiO(2)) settings."
2064,“As a Young Pregnant Girl… The Challenges You Face”: Exploring the Intersection Between Mental Health and Sexual and Reproductive Health Amongst Adolescent Girls and Young Women in South Africa,"In South Africa, adolescent girls and young women (AGYW) are at risk of poor mental health, HIV infection and early pregnancy. Poor mental health in AGYW is associated with increased sexual risk behaviours, and impeded HIV testing and care. Using in-depth interviews and focus group discussions, we explored subjective experiences of mental health and sexual and reproductive health (SRH) amongst 237 AGYW aged 15–24 years in five South African districts. Respondents shared narratives of stress, emotional isolation, feelings of depression, and suicidal ideation, interconnected with HIV, pregnancy and violence in relationships. Findings show that AGYW in South Africa face a range of mental health stressors and lack sufficient support, which intersect with SRH challenges to heighten their vulnerability. Framed within the syndemic theory, our findings suggest that South African AGYW’s vulnerability towards early pregnancy, HIV infection and poor mental health are bidirectional and interconnected. Considering the overlaps and interactions between mental health and SRH amongst AGYW, it is critical that mental health components are integrated into SRH interventions."
2065,Earlier re-initiation of enteral feeding after necrotizing enterocolitis decreases recurrence or stricture: a systematic review and meta-analysis,"OBJECTIVE: To assess the effects of earlier vs. later re-initiation of enteral feeds after necrotizing enterocolitis (NEC). STUDY DESIGN: We reviewed the literature to assess timing of enteral feeding after NEC using fixed effects models. RESULTS: Three studies met inclusion criteria; no randomized trials. After removal of Bell’s Stage I infants, the earlier refeeding group (<5–7 or median 4 days) included 79 infants and later refeeding group (≥5–7 or median 10 days) included 119 infants. Pooled analysis revealed earlier re-initiation reduced the incidence in the composite outcome of recurrent NEC and/or post-NEC stricture (OR = 0.27; 95% Cl = 0.10–0.75; p = 0.012). Individually, NEC recurrence (pooled OR = 0.34; 95% Cl = 0.09–1.29; p = 0.112) or stricture (OR = 0.34; 95% Cl = 0.09–1.26; p = 1.06) did not differ between groups. CONCLUSIONS: There was no increase in negative outcomes with earlier refeeding after NEC. Earlier initiation of enteral feeds resulted in a significantly lower risk for the combined outcome of recurrent NEC and/or post-NEC stricture."
2066,Exploring the Roles of Green Food Consumption and Social Trust in the Relationship between Perceived Consumer Effectiveness and Psychological Wellbeing,"Green food consumption is a core issue that contributes to solving environmental pollution and achieving sustainable development. This study aims to investigate the mediating role of green food consumption and social trust in the relationship between perceived consumer effectiveness and psychological wellbeing to provide new insights into green food consumption, based on social ideal theory and social trust theory. Using a sample data of 514 consumers in China, the results of structural equation modeling showed that perceived consumer effectiveness was positively related to psychological wellbeing. Furthermore, green food consumption mediated the relationship between perceived consumer effectiveness and psychological wellbeing. In addition, social trust moderated the relationship between perceived consumer effectiveness and green food consumption. Social trust also moderated the indirect effect of perceived consumer effectiveness on psychological wellbeing through green food consumption. The findings of this study enrich the extant literature relating to green food consumption and have practical implications for business managers and policymakers."
2067,Mind over Matter: Testing the Efficacy of an Online Randomized Controlled Trial to Reduce Distraction from Smartphone Use,"Evidence suggests a growing call for the prevention of excessive smartphone and social media use and the ensuing distraction that arises affecting academic achievement and productivity. A ten-day online randomized controlled trial with the use of smartphone apps, engaging participants in mindfulness exercises, self-monitoring and mood tracking, was implemented amongst UK university students (n = 143). Participants were asked to complete online pre- and post-intervention assessments. Results indicated high effect sizes in reduction of smartphone distraction and improvement scores on a number of self-reported secondary psychological outcomes. The intervention was not effective in reducing habitual behaviours, nomophobia, or time spent on social media. Mediation analyses demonstrated that: (i) emotional self-awareness but not mindful attention mediated the relationship between intervention effects and smartphone distraction, and (ii) online vigilance mediated the relationship between smartphone distraction and problematic social media use. The present study provides preliminary evidence of the efficacy of an intervention for decreased smartphone distraction and highlights psychological processes involved in this emergent phenomenon in the smartphone literature. Online interventions may serve as complementary strategies to reduce distraction levels and promote insight into online engagement. More research is required to elucidate the mechanisms of digital distraction and assess its implications in problematic use."
2068,Lymphocystis Disease Virus (Iridoviridae) Enters Flounder (Paralichthys olivaceus) Gill Cells via a Caveolae-Mediated Endocytosis Mechanism Facilitated by Viral Receptors,"In previous research, voltage-dependent anion channel protein 2 (VDAC2) and the receptor of activated protein C kinase 1 (RACK1) in flounder (Paralichthys olivaceus) were confirmed as functional receptors for lymphocystis disease virus (LCDV) entry; however, the underlying mechanism of VDAC2- and RACK1-mediated LCDV entry remains unclear. In this study, we elucidated the endocytosis pathway of LCDV entry into flounder gill (FG) cells by treatment with specific inhibitory agents, siRNAs, and co-localization analysis. LCDV entry was significantly inhibited by the disruption of caveolae-mediated endocytosis, dynamin, and microtubules, and the knockdown of caveoline-1 and dynamin expression, but was not inhibited by the disruption of clathrin-mediated endocytosis, micropinocytosis, or low-pH conditions. The disruption of caveolae-mediated and clathrin-mediated endocytosis was verified by the internalization of cholera toxin subunit B (CTB) and transferrin, respectively. Confocal immunofluorescence assay demonstrated that LCDV was co-localized with VDAC2 and RACK1, CTB was co-localized with VDAC2 and RACK1 and partially with LCDV, but transferrin was not co-localized with LCDV, VDAC2, or RACK1, indicating that LCDV utilized the same pathway as CTB, i.e., caveolae-mediated endocytosis. This was different from the pathway of transferrin, which used clathrin-mediated endocytosis. Furthermore, caveolin-1 was co-localized with LCDV, VDAC2, and RACK1, suggesting that caveolin-1 was involved in LCDV entry. These results revealed for the first time that LCDV entered into FG cells via caveolae-mediated endocytosis facilitated by VDAC2 and RACK1 receptors, relying on dynamin and microtubules in a pH-independent manner, which provided new insight into the molecular mechanisms of LCDV entry and potential for the development of antiviral agents, expanding our understanding of iridovirus infection."
2069,Eckol Alleviates Intestinal Dysfunction during Suckling-to-Weaning Transition via Modulation of PDX1 and HBEGF,"Maintaining intestinal health in livestock is critical during the weaning period. The precise mechanisms of intestinal dysfunction during this period are not fully understood, although these can be alleviated by phlorotannins, including eckol. This question was addressed by evaluating the changes in gene expression and intestinal function after eckol treatment during suckling-to-weaning transition. The biological roles of differentially expressed genes (DEGs) in intestinal development were investigated by assessing intestinal wound healing and barrier functions, as well as the associated signaling pathways and oxidative stress levels. We identified 890 DEGs in the intestine, whose expression was altered by eckol treatment, including pancreatic and duodenal homeobox (PDX)1, which directly regulate heparin-binding epidermal growth factor-like growth factor (HBEGF) expression in order to preserve intestinal barrier functions and promote wound healing through phosphoinositide 3-kinase (PI3K)/AKT and P38 signaling. Additionally, eckol alleviated H(2)O(2)-induced oxidative stress through PI3K/AKT, P38, and 5’-AMP-activated protein kinase (AMPK) signaling, improved growth, and reduced oxidative stress and intestinal permeability in pigs during the weaning period. Eckol modulates intestinal barrier functions, wound healing, and oxidative stress through PDX/HBEGF, and improves growth during the suckling-to-weaning transition. These findings suggest that eckol can be used as a feed supplement in order to preserve the intestinal functions in pigs and other livestock during this process."
2070,A retrospective review of 10-year trends in general anesthesia for cesarean delivery at a university hospital: the impact of a newly launched team on obstetric anesthesia practice,"BACKGROUND: The indications for general anesthesia (GA) in obstetric settings, which are determined in consideration of maternal and fetal outcome, could be affected by local patterns of clinical practice grounded in unique situations and circumstances that vary among medical institutions. Although the use of GA for cesarean delivery has become less common with more frequent adoption of neuraxial anesthesia, GA was previously chosen for pregnancy with placenta previa at our institution in case of unexpected massive hemorrhage. However, the situation has been gradually changing since formation of a team dedicated to obstetric anesthesia practice. Here, we report the results of a review of all cesarean deliveries performed under GA, and assess the impact of our newly launched team on trends in clinical obstetric anesthesia practice at our institution. METHODS: Our original database for obstetric GA during the period of 2010 to 2019 was analyzed. The medical records of all parturients who received GA for cesarean delivery were reviewed to collect detailed information. Interrupted time series analysis was used to evaluate the impact of the launch of our obstetric anesthesia team. RESULTS: As recently as 2014, more than 10% of cesarean deliveries were performed under GA, with placenta previa accounting for the main indication in elective and emergent cases. Our obstetric anesthesia team was formed in 2015 to serve as a communication bridge between the department of anesthesiology and the department of obstetrics. Since then, there has been a steady decline in the percentage of cesarean deliveries performed under GA, decreasing to a low of less than 5% in the latest 2 years. Interrupted time series analysis revealed a significant reduction in obstetric GA after 2015 (P = 0.04), which was associated with decreased use of GA for pregnancy with placenta previa. On the other hand, every year has seen a number of urgent cesarean deliveries requiring GA. CONCLUSIONS: There has been a trend towards fewer obstetric GA since 2015. The optimized use of GA for cesarean delivery was made possible mainly through strengthened partnerships between anesthesiologists and obstetricians with the support of our obstetric anesthesia team."
2071,The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through the suppression of MMP-3,"BACKGROUND AND AIM: The pathophysiology of rheumatoid arthritis (RA) is characterized by excess production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by neutrophils and macrophages in synovium. Additionally, these cytokines promote the production of reactive oxygen species (ROS), and increased production of matrix metalloproteinases (MMPs), including MMP-3, in synoviocytes that result in joint destruction. There is limited information on how proteolytic enzymes such as MMP-3 can be regulated. We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on RA and identified the relationship between the c-Jun N terminal kinase (JNK) pathway and MMP-3. We hypothesized that elucidating this relationship would lead to novel therapeutic approaches to RA treatment and management. METHODS: We investigated the effect of administering a low dose (1000 μM or less) of an antioxidant (NAC) to human rheumatoid fibroblast-like synoviocytes (MH7A cells). We also investigated the response of antioxidant genes such as nuclear factor erythroid -derived 2-related factor 2 (Nrf2) and Sequestosome 1 (p62). The influence of MMP-3 expression on the JNK pathway leading to joint destruction and the mechanisms underlying this relationship were investigated through primary dispersion culture cells collected from the synovial membranes of RA patients, consisting of rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS). RESULTS: Low-dose NAC (1000 μM) increased the expression of Nrf2 and phospho-p62 in MH7A cells, activating antioxidant genes, suppressing the expression of MMP-3, and inhibiting the phosphorylation of JNK. ROS, MMP-3 expression, and IL-6 was suppressed by administering 30 μM of SP600125 (a JNK inhibitor) in MH7A cells. Furthermore, the administration of SP600125 (30 μM) to RA-FLS suppressed MMP-3. CONCLUSIONS: We demonstrated the existence of an MMP-3 suppression mechanism that utilizes the JNK pathway in RA-FLS. We consider that the JNK pathway could be a target for future RA therapies."
2072,"Real-world adherence to, and persistence with, once- and twice-daily oral disease-modifying drugs in patients with multiple sclerosis: a systematic review and meta-analysis","BACKGROUND: Nonadherence to disease-modifying drugs (DMDs) for multiple sclerosis (MS) is associated with poorer clinical outcomes, including higher rates of relapse and disease progression, and higher medical resource use. A systematic review and quantification of adherence and persistence with oral DMDs would help clarify the extent of nonadherence and nonpersistence in patients with MS to help prescribers make informed treatment plans and optimize patient care. The objectives were to: 1) conduct a systematic literature review to assess the availability and variability of oral DMD adherence and/or persistence rates across ‘real-world’ data sources; and 2) conduct meta-analyses of the rates of adherence and persistence for once- and twice-daily oral DMDs in patients with MS using real-world data. METHODS: A systematic review of studies published between January 2010 and April 2018 in the PubMed database was performed. Only studies assessing once- and twice-daily oral DMDs were available for inclusion in the analysis. Study quality was evaluated using a modified version of the Newcastle-Ottawa Scale, a tool for assessing quality of observational studies. The random effects model evaluated pooled summary estimates of nonadherence. RESULTS: From 510 abstracts, 31 studies comprising 16,398 patients with MS treated with daily oral DMDs were included. Overall 1-year mean medication possession ratio (MPR; n = 4 studies) was 83.3% (95% confidence interval [CI] 74.5–92.1%) and proportion of days covered (PDC; n = 4 studies) was 76.5% (95% CI 72.0–81.1%). Pooled 1-year MPR ≥80% adherence (n = 6) was 78.5% (95% CI 63.5–88.5%) and PDC ≥80% (n = 5 studies) was 71.8% (95% CI 59.1–81.9%). Pooled 1-year discontinuation (n = 20) was 25.4% (95% CI 21.6–29.7%). CONCLUSIONS: Approximately one in five patients with MS do not adhere to, and one in four discontinue, daily oral DMDs before 1 year. Opportunities to improve adherence and ultimately patient outcomes, such as patient education, medication support/reminders, simplified dosing regimens, and reducing administration or monitoring requirements, remain. Implementation of efforts to improve adherence are essential to improving care of patients with MS."
2073,Identifying essential proteins in dynamic protein networks based on an improved h-index algorithm,"BACKGROUND: The essential proteins in protein networks play an important role in complex cellular functions and in protein evolution. Therefore, the identification of essential proteins in a network can help to explain the structure, function, and dynamics of basic cellular networks. The existing dynamic protein networks regard the protein components as the same at all time points; however, the role of proteins can vary over time. METHODS: To improve the accuracy of identifying essential proteins, an improved h-index algorithm based on the attenuation coefficient method is proposed in this paper. This method incorporates previously neglected node information to improve the accuracy of the essential protein search. Based on choosing the appropriate attenuation coefficient, the values, such as monotonicity, SN, SP, PPV and NPV of different essential protein search algorithms are tested. RESULTS: The experimental results show that, the algorithm proposed in this paper can ensure the accuracy of the found proteins while identifying more essential proteins. CONCLUSIONS: The described experiments show that this method is more effective than other similar methods in identifying essential proteins in dynamic protein networks. This study can better explain the mechanism of life activities and provide theoretical basis for the research and development of targeted drugs."
2074,Online adaptive radiotherapy compared to plan selection for rectal cancer: quantifying the benefit,"BACKGROUND: To compare online adaptive radiation therapy (ART) to a clinically implemented plan selection strategy (PS) with respect to dose to the organs at risk (OAR) for rectal cancer. METHODS: The first 20 patients treated with PS between May–September 2016 were included. This resulted in 10 short (SCRT) and 10 long (LCRT) course radiotherapy treatment schedules with a total of 300 Conebeam CT scans (CBCT). New dual arc VMAT plans were generated using auto-planning for both the online ART and PS strategy. For each fraction bowel bag, bladder and mesorectum were delineated on daily Conebeam CTs. The dose distribution planned was used to calculate daily DVHs. Coverage of the CTV was calculated, as defined by the dose received by 99% of the CTV volume (D99%). The volume of normal tissue irradiated with 95% of the prescribed fraction dose was calculated by calculating the volume receiving 95% of the prescribed fraction or more dose minus the volume of the CTV. For each fraction the difference between the plan selection and online adaptive strategy of each DVH parameter was calculated, as well as the average difference per patient. RESULTS: Target coverage remained the same for online ART. The median volume of the normal tissue irradiated with 95% of the prescribed dose dropped from 642 cm3 (PS) to 237 cm3 (online-ART)(p < 0.001). Online ART reduced dose to the OARs for all tested dose levels for SCRT and LCRT (p < 0.001). For V15Gy of the bowel bag the median difference over all fractions of all patients was − 126 cm(3) in LCRT, while the average difference per patient ranged from − 206 cm(3) to − 40 cm(3). For SCRT the median difference was − 62 cm(3), while the range of the average difference per patient was − 105 cm3 to − 51 cm(3). For V15Gy of the bladder the median difference over all fractions of all patients was 26% in LCRT, while the average difference per patient ranged from − 34 to 12%. For SCRT the median difference of V95% was − 8%, while the range of the average difference per patient was − 29 to 0%. CONCLUSIONS: Online ART for rectal cancer reduces dose the OARs significantly compared to a clinically implemented plan selection strategy, without compromising target coverage. TRIAL REGISTRATION: Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center (W19_357 # 19.420; Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands)."
2075,Antipsychotic treatment experiences of people with bipolar I disorder: patient perspectives from an online survey,"BACKGROUND: Oral antipsychotic (AP) medications are frequently prescribed to people with bipolar I disorder (BD-I). A cross-sectional online survey examined the experiences of people living with BD-I with a history of recent AP use. METHODS: Adults with self-reported physician-diagnosed BD-I (N = 200) who received oral APs during the prior year completed a survey on AP-related experiences, including side effects and their perceived burden on social functioning, adherence, and work. Items also assessed preferences for trade-offs (balancing symptom management and side effects) when considering a hypothetical new AP. The perceived impact of specific, prevalent side effects on adherence, work, and preferences for a hypothetical AP were also examined. Analyses were descriptive. RESULTS: The survey sample had a mean age of 43.2 (SD = 12.4) years, was 60% female, and 31% nonwhite. Almost all participants (98%) had experienced AP side effects. Common self-reported side effects were feeling drowsy or tired (83%), lack of emotion (79%), anxiety (79%), dry mouth (76%), and weight gain (76%). Weight gain was cited as the most bothersome side effect, rated by most participants (68%) as “very” or “extremely bothersome.” Nearly half of participants (49%) reported that AP side effects negatively impacted their job performance; almost all (92%) reported that side effects – most commonly anxiety and lack of emotion – negatively impacted social relationships (e.g., family or romantic partners). The most commonly-reported reason for stopping AP use was dislike of side effects (48%). Side effects most likely to lead to stopping or taking less of AP treatment included “feeling like a ‘zombie’” (29%), feeling drowsy or tired (25%), and weight gain (24%). When considering a hypothetical new AP, the most common side effects participants wanted to avoid included AP-induced anxiety (50%), weight gain (48%), and “feeling like a ‘zombie’” (47%). CONCLUSIONS: Side effects of APs were both common and bothersome, and impacted social functioning, adherence, and work. Findings highlight the prevailing unmet need for new APs with more favorable benefit-risk profiles."
2076,Protonic solid-state electrochemical synapse for physical neural networks,"Physical neural networks made of analog resistive switching processors are promising platforms for analog computing. State-of-the-art resistive switches rely on either conductive filament formation or phase change. These processes suffer from poor reproducibility or high energy consumption, respectively. Herein, we demonstrate the behavior of an alternative synapse design that relies on a deterministic charge-controlled mechanism, modulated electrochemically in solid-state. The device operates by shuffling the smallest cation, the proton, in a three-terminal configuration. It has a channel of active material, WO(3). A solid proton reservoir layer, PdH(x), also serves as the gate terminal. A proton conducting solid electrolyte separates the channel and the reservoir. By protonation/deprotonation, we modulate the electronic conductivity of the channel over seven orders of magnitude, obtaining a continuum of resistance states. Proton intercalation increases the electronic conductivity of WO(3) by increasing both the carrier density and mobility. This switching mechanism offers low energy dissipation, good reversibility, and high symmetry in programming."
2077,The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV,"Chronic hepatitis B virus (HBV) infection affects 257 million people globally. Current therapies suppress HBV but viral rebound occurs on cessation of therapy; novel therapeutic strategies are urgently required. To develop a therapeutic HBV vaccine that can induce high magnitude T cells to all major HBV antigens, we have developed a novel HBV vaccine using chimpanzee adenovirus (ChAd) and modified vaccinia Ankara (MVA) viral vectors encoding multiple HBV antigens. ChAd vaccine alone generated very high magnitude HBV specific T cell responses to all HBV major antigens. The inclusion of a shark Invariant (SIi) chain genetic adjuvant significantly enhanced the magnitude of T-cells against HBV antigens. Compared to ChAd alone vaccination, ChAd-prime followed by MVA-boost vaccination further enhanced the magnitude and breadth of the vaccine induced T cell response. Intra-cellular cytokine staining study showed that HBV specific CD8+ and CD4+ T cells were polyfunctional, producing combinations of IFNγ, TNF-α, and IL-2. In summary, we have generated genetically adjuvanted ChAd and MVA vectored HBV vaccines with the potential to induce high-magnitude T cell responses through a prime-boost therapeutic vaccination approach. These pre-clinical studies pave the way for new studies of HBV therapeutic vaccination in humans with chronic hepatitis B infection."
2078,Immune Imprinting in the Influenza Ferret Model,The initial exposure to influenza virus usually occurs during childhood. This imprinting has long-lasting effects on the immune responses to subsequent infections and vaccinations. Animal models that are used to investigate influenza pathogenesis and vaccination do recapitulate the pre-immune history in the human population. The establishment of influenza pre-immune ferret models is necessary for understanding infection and transmission and for designing efficacious vaccines.
2079,Deletion of the Gene for the Type I Interferon Inhibitor I329L from the Attenuated African Swine Fever Virus OURT88/3 Strain Reduces Protection Induced in Pigs,"Live attenuated vaccines are considered to be the fastest route to the development of a safe and efficacious African swine fever (ASF) vaccine. Infection with the naturally attenuated OURT88/3 strain induces protection against challenge with virulent isolates from the same or closely related genotypes. However, adverse clinical signs following immunisation have been observed. Here, we attempted to increase the OURT88/3 safety profile by deleting I329L, a gene previously shown to inhibit the host innate immune response. The resulting virus, OURT88/3ΔI329L, was tested in vitro to evaluate the replication and expression of type I interferon (IFN) and in vivo by immunisation and lethal challenge experiments in pigs. No differences were observed regarding replication; however, increased amounts of both IFN-β and IFN-α were observed in macrophages infected with the deletion mutant virus. Unexpectedly, the deletion of I329L markedly reduced protection against challenge with the virulent OURT88/1 isolate. This was associated with a decrease in both antibody levels against VP72 and the number of IFN-γ-producing cells in the blood of non-protected animals. Furthermore, a significant increase in IL-10 levels in serum was observed in pigs immunised with OURT88/3ΔI329L following challenge. Interestingly, the deletion of the I329L gene failed to attenuate the virulent Georgia/2007 isolate."
2080,"Digital technology adoption scale in the blended learning context in higher education: Development, validation and testing of a specific tool","The main aim of the present study was to develop, validate and test an extended Technology Acceptance Model (TAM) that contributes to the overall understanding of students' intention to use digital tools in a blended learning context of higher education. The external bidimensional factor of familiarity with digital tools, which is not usually explained by the TAM, was included, and evaluated. Following a four-stage scale development technique, a seven-dimensional 25-item survey was developed, which includes two external correlated variables: familiarity with high-tech digital tools and familiarity with traditional digital tools, two mediator variables—computer anxiety, and perceived barriers, and three response variables, perceived usefulness, perceived ease of use and intention to use. The initial version of the survey was administered on 250 undergraduate students. Next, for another sample of 206 students, latent dimensions of the survey were tested using exploratory factor analysis. The structure of the survey was validated in two other subsequent stages with one sample of 262 responses of undergraduates and one of 310 responses of master's students from two different universities. All students who agreed to participate in research attended blended learning. The validity, reliability and invariance of the instrument were established by psychometric analyses. Collected data indicated that the survey has an adequate multifactorial structure that is reliable and invariant across degree levels. The scale is recommended for use in higher education studies targeting the promotion of blended learning and reduction of negative attitudes of learners toward digital instruments, supporting university professors to select their own efficient way to teach."
2081,N-Glycosylation Alteration of Serum and Salivary Immunoglobulin A Is a Possible Biomarker in Oral Mucositis,"Background: Oral and enteral mucositis due to high-dose cytostatic treatment administered during autologous and allogeneic stem-cell transplantation increases mortality. Salivary secretory immunoglobulin A (sIgA) is a basic pillar of local immunity in the first line of defense. Altered salivary sialoglycoprotein carbohydrates are important in the pathologies in the oral cavity including inflammation, infection and neoplasia. Therefore, we assessed whether changes in the salivary and serum IgA glycosylation correlated with development and severity of oral mucositis. Methods: Using capillary electrophoresis, comparative analysis of serum and salivary IgA total N-glycans was conducted in 8 patients with autologous peripheral stem-cell transplantation (APSCT) at four different stages of transplantation (day −3/−7, 0, +7, +14) and in 10 healthy controls. Results: Fourteen out of the 31 structures identified in serum and 6 out of 38 in saliva showed significant changes upon transplantation compared with the control group. Only serum core fucosylated, sialylated bisecting biantennary glycan (FA2BG2S2) showed significant differences between any two stages of transplantation (day −3/−7 and day +14; p = 0.0279). Conclusion: Our results suggest that changes in the serum IgA total N-glycan profile could serve as a disease-specific biomarker in patients undergoing APSCT, while analysis of salivary IgA N-glycan reflects the effect of APSCT on local immunity."
2082,Sperm Antioxidant Biomarkers and Their Correlation with Clinical Condition and Lifestyle with Regard to Male Reproductive Potential,"Measurement of sperm oxidative-antioxidant indicators is widely used in the assessment and detection of biochemical causes of male infertility. The main purpose of this study was to identify biomarkers that assist in diagnostics and monitoring of male reproductive potential. We performed the assessment of oxidative-antioxidant malondialdehyde (MDA), glutathione (GSH), and total redox antioxidant potential (TRAP) indicators in seminal plasma, seminogram, clinical condition, and lifestyle of people with reproductive problems. The combined assessment of GSH and TRAP as potential biomarkers of male infertility in semen plasma was characterized by the highest total sensitivity and specificity. Furthermore, we provide evidence that male reproductive potential is significantly correlated with basic sperm parameters, sperm cell membrane integrity, their morphology, lifestyle, eating habits, occupation, and mental health. Our results provide evidence on the importance of oxidative stress and defense against free radicals in diagnosing and monitoring men with infertility that are consistent with previously conducted research. We provide an alternative approach on the possibility of interpreting the combination of the biomarkers that can bring benefits to a multi-threaded approach to the diagnosis and treatment of male infertility."
2083,Identification and characterization of adipose surface epitopes,"Adipose tissue is a central regulator of metabolism and an important pharmacological target to treat the metabolic consequences of obesity, such as insulin resistance and dyslipidemia. Among the various cellular compartments, the adipocyte cell surface is especially appealing as a drug target as it contains various proteins that when activated or inhibited promote adipocyte health, change its endocrine function and eventually maintain or restore whole-body insulin sensitivity. In addition, cell surface proteins are readily accessible by various drug classes. However, targeting individual cell surface proteins in adipocytes has been difficult due to important functions of these proteins outside adipose tissue, raising various safety concerns. Thus, one of the biggest challenges is the lack of adipose selective surface proteins and/or targeting reagents. Here, we discuss several receptor families with an important function in adipogenesis and mature adipocytes to highlight the complexity at the cell surface and illustrate the problems with identifying adipose selective proteins. We then discuss that, while no unique adipocyte surface protein might exist, how splicing, posttranslational modifications as well as protein/protein interactions can create enormous diversity at the cell surface that vastly expands the space of potentially unique epitopes and how these selective epitopes can be identified and targeted."
2084,Freeze-Drying Formulations Increased the Adenovirus and Poxvirus Vaccine Storage Times and Antigen Stabilities,"Successful vaccines induce specific immune responses and protect against various viral and bacterial infections. Noninactivated vaccines, especially viral vector vaccines such as adenovirus and poxvirus vaccines, dominate the vaccine market because their viral particles are able to replicate and proliferate in vivo and produce lasting immunity in a manner similar to natural infection. One challenge of human and livestock vaccination is vaccine stability related to the antigenicity and infectivity. Freeze-drying is the typical method to maintain virus vaccine stability, while cold chain transportation is required for temperatures about 2 °C–8 °C. The financial and technological resource requirements hinder vaccine distribution in underdeveloped areas. In this study, we developed a freeze-drying formula consisting of bovine serum albumin (BSA), l-glutamic acid (L-Glu), polyethylene glycol (PEG), and dextran (DEX) to improve the thermal stability and activity of viral vaccines, including vaccinia recombinant vaccine (rTTV-OVA) and adenovirus vaccine (Ad5-ENV). We compared a panel of five different formulations (PEG: DEX: BSA: L-GLU = 50:9:0:0(#1), 50:5:4:0(#2), 50:10:9:0(#3), 50:0:0:9(#4), and 50:1:0:8(#5), respectively) and optimized the freeze-drying formula for rTTV-OVA and Ad5-ENV. We found that the freeze-drying formulations #2 and #3 could maintain rTTV-OVA infectivity at temperatures of 4 °C and 25 °C and that rTTV-OVA immunogenicity was retained during lyophilization. However, formulations #4 and #5 maintained Ad5-ENV infectivity under the same conditions, and Ad5-ENV immunogenicity had maximum retention with freeze-drying formulation #4. In summary, we developed new freeze-drying formulations that increased virus vaccine storage times and retained immunogenicity at an ambient temperature."
2085,Socio-religious Prognosticators of Psychosocial Burden of Beta Thalassemia Major,"The study investigates the socio-religious factors in the propagation of genetically inherited disease of Beta thalassemia. The disorder which reportedly has a significant protraction through repeated cousin marriages results in the social maladjustment of the parents of the sick children due to constant depression, anxiety, and weak social interaction and may lead to social isolation as well. This research aims to find out the significant effect of socio-religious trends on psychosocial burden of beta thalassemia major among cousin and non-cousin couples in the province of Punjab in Pakistan. It takes a sample of 932 parents of sick children, among whom 735 were married with cousins and 197 with non-cousins, for data collection. The findings reveal that inadequate knowledge of the disease, insufficient or misdirected social support, stigmatization, and marriage breakups caused by the disease, superstitions, and misinterpretations of religion and the subsequent practices accordingly as significant predictors of psychosocial burden of beta thalassemia major among non-cousins and cousin couples. Additionally, it also finds patriarchy as only significant predictors of outcome variable among cousin couples."
2086,Enhancement of skin permeability with thermal ablation techniques: concept to commercial products,"Traditionally, the skin is considered as a protective barrier which acts as a highly impermeable region of the human body. But in recent times, it is recognized as a specialized organ that aids in the delivery of a wide range of drug molecules into the skin (intradermal drug delivery) and across the skin into systemic circulation (transdermal drug delivery, TDD). The bioavailability of a drug administered transdermally can be improved by several penetration enhancement techniques, which are broadly classified into chemical and physical techniques. Application of mentioned techniques together with efforts of various scientific and innovative companies had made TDD a multibillion dollar market and an average of 2.6 new transdermal drugs are being approved each year. Out of various techniques, the thermal ablation techniques involving chemicals, heating elements, lasers, and radiofrequency (RF) are proved to be more effective in terms of delivering the drug across the skin by disrupting the stratum corneum (SC). The reason behind it is that the thermal ablation technique resulted in improved bioavailability, quick treatment and fast recovery of the SC, and more importantly it does not cause any damage to underlying dermis layer. This review article mainly discussed about various thermal ablation techniques with commercial products and patents in each classes, and their safety aspects. This review also briefly presented anatomy of the skin, penetration pathways across the skin, and different generations of TDD. [Figure: see text]"
2087,Bioengineering Approaches for Corneal Regenerative Medicine,"BACKGROUND: Since the cornea is responsible for transmitting and focusing light into the eye, injury or pathology affecting any layer of the cornea can cause a detrimental effect on visual acuity. Aging is also a reason for corneal degeneration. Depending on the level of the injury, conservative therapies and donor tissue transplantation are the most common treatments for corneal diseases. Not only is there a lack of donor tissue and risk of infection/rejection, but the inherent ability of corneal cells and layers to regenerate has led to research in regenerative approaches and treatments. METHODS: In this review, we first discussed the anatomy of the cornea and the required properties for reconstructing layers of the cornea. Regenerative approaches are divided into two main categories; using direct cell/growth factor delivery or using scaffold-based cell delivery. It is expected delivered cells migrate and integrate into the host tissue and restore its structure and function to restore vision. Growth factor delivery also has shown promising results for corneal surface regeneration. Scaffold-based approaches are categorized based on the type of scaffold, since it has a significant impact on the efficiency of regeneration, into the hydrogel and non-hydrogel based scaffolds. Various types of cells, biomaterials, and techniques are well covered. RESULTS: The most important characteristics to be considered for biomaterials in corneal regeneration are suitable mechanical properties, biocompatibility, biodegradability, and transparency. Moreover, a curved shape structure and spatial arrangement of the fibrils have been shown to mimic the corneal extracellular matrix for cells and enhance cell differentiation. CONCLUSION: Tissue engineering and regenerative medicine approaches showed to have promising outcomes for corneal regeneration. However, besides proper mechanical and optical properties, other factors such as appropriate sterilization method, storage, shelf life and etc. should be taken into account in order to develop an engineered cornea for clinical trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13770-020-00262-8) contains supplementary material, which is available to authorized users."
2088,Predictors of complications from stoma closure in elective colorectal surgery: an assessment from the American College of Surgeons National Surgical Quality Improvement Program (ACSNSQIP),"BACKGROUND: There is significant morbidity after diverting ileostomy closure, so identifying predictors of complications could be of great benefit. The aim of our study was to evaluate the incidence and risk factors for postoperative morbidity after elective ileostomy closure. METHODS: The ACS-NSQIP dataset was evaluated for elective ileostomy closures from 1/1/2015 to 12/31/2016. Demographic characteristics, operative, and postoperative outcomes were evaluated. The primary outcome was 30-day major morbidity (Clavien class III and greater). Secondary outcomes were rates and predictors of major morbidity, superficial site infection (SSI), reoperation, and readmission from multivariate logistic regression modeling. RESULTS: We retrospectively evaluated 1885 patients. The median operative time was 65 (IQR 50–90) minutes and median length of stay was 3 (IQR 2–5) days. Major morbidity was recorded in 6.7%, including mortality (1.0%), deep/organ space SSI (2.6%), dehiscence (0.8%), reintubation (0.5%), sepsis (1.7%), septic shock (0.8%), and reoperation (3.7%). Readmission was recorded in 9.7% and 6.2% had SSI. Multivariate logistic regression showed male sex (OR 1.584; 95% CI 1.068–2.347; p = 0.022) and longer operative time (OR 1.004; 95% CI 1.001–1.007; p = 0.009) were among those variables associated with increased odds of major morbidity. Dyspnea (OR 2.431; 95% CI 1.139–5.094; p = 0.021) and longer operative time (OR 1.003; 95% CI 1.001–1.007; p = 0.034) were among the independent risk factors for SSI. Male sex (OR 2.246; 95% CI 1.297–3.892; p = 0.004, chronic obstructive pulmonary disease (OR 2.959; 95% CI 1.153–7.591; p = 0.024), and longer operative time (OR 1.005; 95% CI 1.001–1.009; p = 0.011) were associated with increased odds of reoperation. Chronic obstructive pulmonary disease (OR 2.578; 95% CI 1.338–4.968; p = 0.005), wound infection (OR 2.680; 95% CI 1.043–6.890; p = 0.041), and inflammatory bowel disease (OR 2.565; 95% CI 1.203–5.463; p = 0.015) were associated with increased odds of readmission. CONCLUSIONS: Elective stoma closure has significant risk of morbidity. Patients with longer operative times were at increased risk for major morbidity, overall SSI, and reoperation. From the analysis, factors specifically associated with major morbidity, overall infectious complications, readmissions, and reoperations were identified. This information can be used to prospectively prepare for these high-risk patients, potentially improving postoperative outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10151-020-02307-5) contains supplementary material, which is available to authorized users."
2089,"The Evolution, Spread and Global Threat of H6Nx Avian Influenza Viruses","Avian influenza viruses of the subtype H6Nx are being detected globally with increasing frequency. Some H6Nx lineages are becoming enzootic in Asian poultry and sporadic incursions into European poultry are occurring more frequently. H6Nx viruses that contain mammalian adaptation motifs pose a zoonotic threat and have caused human cases. Although currently understudied globally, H6Nx avian influenza viruses pose a substantial threat to both poultry and human health. In this review we examine the current state of knowledge of H6Nx viruses including their global distribution, tropism, transmission routes and human health risk."
2090,Resveratrol Enhances mRNA and siRNA Lipid Nanoparticles Primary CLL Cell Transfection,"Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western populations. Therapies such as mRNA and siRNA encapsulated in lipid nanoparticles (LNPs) represent a clinically advanced platform and are utilized for a wide variety of applications. Unfortunately, transfection of RNA into CLL cells remains a formidable challenge and a bottleneck for developing targeted therapies for this disease. Therefore, we aimed to elucidate the barriers to efficient transfection of RNA-encapsulated LNPs into primary CLL cells to advance therapies in the future. To this end, we transfected primary CLL patient samples with mRNA and siRNA payloads encapsulated in an FDA-approved LNP formulation and characterized the transfection. Additionally, we tested the potential of repurposing caffeic acid, curcumin and resveratrol to enhance the transfection of nucleic acids into CLL cells. The results demonstrate that the rapid uptake of LNPs is required for successful transfection. Furthermore, we demonstrate that resveratrol enhances the delivery of both mRNA and siRNA encapsulated in LNPs into primary CLL patient samples, overcoming inter-patient heterogeneity. This study points out the important challenges to consider for efficient RNA therapeutics for CLL patients and advocates the use of resveratrol in combination with RNA lipid nanoparticles to enhance delivery into CLL cells."
2091,Antisense Oligonucleotides: An Emerging Area in Drug Discovery and Development,"Antisense oligonucleotides (ASOs) bind sequence specifically to the target RNA and modulate protein expression through several different mechanisms. The ASO field is an emerging area of drug development that targets the disease source at the RNA level and offers a promising alternative to therapies targeting downstream processes. To translate ASO-based therapies into a clinical success, it is crucial to overcome the challenges associated with off-target side effects and insufficient biological activity. In this regard, several chemical modifications and diverse delivery strategies have been explored. In this review, we systematically discuss the chemical modifications, mechanism of action, and optimized delivery strategies of several different classes of ASOs. Further, we highlight the recent advances made in development of ASO-based drugs with a focus on drugs that are approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for clinical applications. We also discuss various promising ASO-based drug candidates in the clinical trials, and the outstanding opportunity of emerging microRNA as a viable therapeutic target for future ASO-based therapies."
2092,Effects of Renin-Angiotensin Inhibition on ACE2 (Angiotensin-Converting Enzyme 2) and TMPRSS2 (Transmembrane Protease Serine 2) Expression: Insights Into COVID-19,
2093,Congruence of Transcription Programs in Adult Stem Cell-Derived Jejunum Organoids and Original Tissue During Long-Term Culture,"The emergence of intestinal organoids, as a stem cell-based self-renewable model system, has led to many studies on intestinal development and cell-cell signaling. However, potential issues regarding the phenotypic stability and reproducibility of the methodology during culture still needs to be addressed for different organoids. Here we investigated the transcriptomes of jejunum organoids derived from the same pig as well as batch-to-batch variation of organoids derived from different pigs over long-term passage. The set of genes expressed in organoids closely resembled that of the tissue of origin, including small intestine specific genes, for at least 17 passages. Minor differences in gene expression were observed between individual organoid cultures. In contrast, most small intestine-specific genes were not expressed in the jejunum cell line IPEC-J2, which also showed gene expression consistent with cancer phenotypes. We conclude that intestinal organoids provide a robust and stable model for translational research with clear advantages over transformed cells."
2094,Anticancer Activity of Tetrandrine by Inducing Apoptosis in Human Breast Cancer Cell Line MDA-MB-231 In Vivo,"Tetrandrine (TET) is an alkaloid extracted from a traditional Chinese medicinal plant. It exerts remarkable anticancer activity and induces apoptotic cell death in various human cancer cells. The present study aimed to investigate the effects of TET on the inhibition of tumor growth and the induction of apoptosis in MDA-MB-231 breast cancer in xenograft mice. Tumor weight and volume were measured. The histopathological changes in the tumor tissue were observed. Immunohistochemistry analysis of Bcl-2-associated X protein (Bax) and B-cell lymphoma/leukemia-2 (Bcl-2) was carried out. The expression of apoptosis-associated genes and proteins, such as cysteine aspartic acid-specific protease-3 (Caspase-3), Survivin, Bax, Bcl-2, BH3-interacting domain death agonist (Bid), and poly ADP-ribose polymerase (PARP), was measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, respectively. TET inhibited tumor growth and induced apoptosis in TNBC cell line MDA-MB-231. The mechanism underlying this effect might be mediated by TET-upregulated Caspase-3, Bax, and Bid and downregulated by Bcl-2, Survivin, and PARP. Taken together, this study supported the fact that TET is a promising therapeutic agent for the treatment of TNBC, thereby providing experimental evidence for its use in the treatment of breast cancer."
2095,Forecasting seasonal influenza-like illness in South Korea after 2 and 30 weeks using Google Trends and influenza data from Argentina,"We aimed to identify variables for forecasting seasonal and short-term targets for influenza-like illness (ILI) in South Korea, and other input variables through weekly time-series of the variables. We also aimed to suggest prediction models for ILI activity using a seasonal autoregressive integrated moving average, including exogenous variables (SARIMAX) models. We collected ILI, FluNet surveillance data, Google Trends (GT), weather, and air-pollution data from 2010 to 2019, applying cross-correlation analysis to identify the time lag between the two respective time-series. The relationship between ILI in South Korea and the input variables were evaluated with Linear regression models. To validate selected input variables, the autoregressive moving average, including exogenous variables (ARMAX) models were used to forecast seasonal ILI after 2 and 30 weeks with a three-year window for the training set used in the fixed rolling window analysis. Moreover, a final SARIMAX model was constructed. Influenza A virus activity peaks in South Korea were roughly divided between the 51(st) and the 7(th) week, while those of influenza B were divided between the 3(rd) and 14(th) week. GT showed the highest correlation coefficient with forecasts from a week ahead, and seasonal influenza outbreak patterns in Argentina showed a high correlation with those 30 weeks ahead in South Korea. The prediction models after 2 and 30 weeks using ARMAX models had R(2) values of 0.789 and 0.621, respectively, indicating that reference models using only the previous seasonal ILI could be improved. The currently eligible input variables selected by the cross-correlation analysis helped propose short-term and long-term predictions for ILI in Korea. Our findings indicate that influenza surveillance in Argentina can help predict seasonal ILI patterns after 30 weeks in South Korea, and these can help the Korea Centers for Disease Control and Prevention determine vaccine strategies for the next ILI season."
2096,The opportunities and challenges of an Ebola modeling research coordination group,
2097,Homecare for sick family members while waiting for medical help during the 2014-2015 Ebola outbreak in Sierra Leone: a mixed methods study,"INTRODUCTION: Caring for an Ebola patient is a known risk factor for disease transmission. In Sierra Leone during the outbreak in 2014/2015, isolation of patients in specialised facilities was not always immediately available and caring for a relative at home was sometimes the only alternative. This study sought to assess population-level protective caregiving intentions, to understand how families cared for their sick and to explore perceived barriers and facilitators influencing caregiving behaviours. METHODS: Data from a nationwide household survey conducted in December 2014 were used to assess intended protective behaviours if caring for a family member with suspected Ebola. Their association with socio-demographic variables, Ebola-specific knowledge and risk perception was analysed using multilevel logistic regression. To put the results into context, semi-structured interviews with caregivers were conducted in Freetown. RESULTS: Ebola-specific knowledge was positively associated with the intention to avoid touching a sick person and their bodily fluids (adjusted OR (AOR) 1.29; 95% CI 1.01 to 1.54) and the intention to take multiple protective measures (AOR 1.38; 95% CI 1.16 to 1.63). Compared with residing in the mostly urban Western Area, respondents from the initial epicentre of the outbreak (Eastern Province) had increased odds to avoid touching a sick person or their body fluids (AOR 4.74; 95% CI 2.55 to 8.81) and to take more than one protective measure (AOR 2.94; 95% CI 1.37 to 6.34). However, interviews revealed that caregivers, who were mostly aware of the risk of transmission and general protective measures, felt constrained by different contextual factors. Withholding care was not seen as an option and there was a perceived lack of practical advice. CONCLUSIONS: Ebola outbreak responses need to take the sociocultural reality of caregiving and the availability of resources into account, offering adapted and acceptable practical advice. The necessity to care for a loved one when no alternatives exist should not be underestimated."
2098,Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE): protocol for a multisite prospective observational study of the causes of fever in Africa and Asia,"INTRODUCTION: Fever commonly leads to healthcare seeking and hospital admission in sub-Saharan Africa and Asia. There is only limited guidance for clinicians managing non-malarial fevers, which often results in inappropriate treatment for patients. Furthermore, there is little evidence for estimates of disease burden, or to guide empirical therapy, control measures, resource allocation, prioritisation of clinical diagnostics or antimicrobial stewardship. The Febrile Illness Evaluation in a Broad Range of Endemicities (FIEBRE) study seeks to address these information gaps. METHODS AND ANALYSIS: FIEBRE investigates febrile illness in paediatric and adult outpatients and inpatients using standardised clinical, laboratory and social science protocols over a minimum 12-month period at five sites in sub-Saharan Africa and Southeastern and Southern Asia. Patients presenting with fever are enrolled and provide clinical data, pharyngeal swabs and a venous blood sample; selected participants also provide a urine sample. Laboratory assessments target infections that are treatable and/or preventable. Selected point-of-care tests, as well as blood and urine cultures and antimicrobial susceptibility testing, are performed on site. On day 28, patients provide a second venous blood sample for serology and information on clinical outcome. Further diagnostic assays are performed at international reference laboratories. Blood and pharyngeal samples from matched community controls enable calculation of AFs, and surveys of treatment seeking allow estimation of the incidence of common infections. Additional assays detect markers that may differentiate bacterial from non-bacterial causes of illness and/or prognosticate illness severity. Social science research on antimicrobial use will inform future recommendations for fever case management. Residual samples from participants are stored for future use. ETHICS AND DISSEMINATION: Ethics approval was obtained from all relevant institutional and national committees; written informed consent is obtained from all participants or parents/guardians. Final results will be shared with participating communities, and in open-access journals and other scientific fora. Study documents are available online (https://doi.org/10.17037/PUBS.04652739)."
2099,Diversification in causes of death in low-mortality countries: emerging patterns and implications,"INTRODUCTION: An important role of public health organisations is to monitor indicators of variation, so as to disclose underlying inequality in health improvement. In industrialised societies, more individuals than ever are reaching older ages and have become more homogeneous in their age at death. This has led to a decrease in lifespan variation, with substantial implications for the reduction of health inequalities. We focus on a new form of variation to shed further light on our understanding of population health and ageing: variation in causes of death. METHODS: Data from the WHO Mortality Database and the Human Mortality Database are used to estimate cause-of-death distributions and life tables in 15 low-mortality countries. Cause-of-death variation, using 19 groups of causes, is quantified using entropy measures and analysed from 1994 to 2017. RESULTS: The last two decades have seen increasing diversity in causes of death in low-mortality countries. There have been important reductions in the share of deaths from diseases of the circulatory system, while the share of a range of other causes, such as diseases of the genitourinary system, mental and behavioural disorders, and diseases of the nervous system, has been increasing, leading to a more complex cause-of-death distribution. CONCLUSIONS: The diversification in causes of death witnessed in recent decades is most likely a result of the increase in life expectancy, together with better diagnoses and awareness of certain diseases. Such emerging patterns bring additional challenges to healthcare systems, such as the need to research, monitor and treat a wider range of diseases. It also raises new questions concerning the distribution of health resources."
2100,A data driven clinical algorithm for differential diagnosis of pertussis and other respiratory infections in infants,"BACKGROUND: Clinical criteria for pertussis diagnosis and clinical case definitions for surveillance are based on a cough lasting two or more weeks. As several pertussis cases seek care earlier, a clinical tool independent of cough duration may support earlier recognition. We developed a data-driven algorithm aimed at predicting a laboratory confirmed pertussis. METHODS: We enrolled children <12 months of age presenting with apnoea, paroxistic cough, whooping, or post-tussive vomiting, irrespective of the duration of cough. Patients underwent a RT-PCR test for pertussis and other viruses. Through a logistic regression model, we identified symptoms associated with laboratory confirmed pertussis. We then developed a predictive decision tree through Quinlan's C4.5 algorithm to predict laboratory confirmed pertussis. RESULTS: We enrolled 543 children, of which 160 had a positive RT-PCR for pertussis. A suspicion of pertussis by a physician (aOR 5.44) or a blood count showing leukocytosis and lymphocytosis (aOR 4.48) were highly predictive of lab confirmed pertussis. An algorithm including a suspicion of pertussis by a physician, whooping, cyanosis and absence of fever was accurate (79.9%) and specific (94.0%) and had high positive and negative predictive values (PPV 76.3% NPV 80.7%). CONCLUSIONS: An algorithm based on clinical symptoms, not including the duration of cough, is accurate and has high predictive values for lab confirmed pertussis. Such a tool may be useful in low resource settings where lab confirmation is unavailable, to guide differential diagnosis and clinical decisions. Algorithms may also be useful to improve surveillance for pertussis and anticipating classification of cases."
2101,Going Back One Car in the Train: Evaluation of the Relative Afferent Pupillary Defect in the Era of Tele–Neuro-Ophthalmology,
2102,"Evaluation of the certificate in emerging infectious disease research and the certificate in one health training programs, University of Florida","In developing countries, public health professionals and scientists need targeted training and practical skills to respond to global emerging infectious disease threats. The Certificate in Emerging Infectious Disease Research was developed in 2008 to aid such professionals to respond to complex emerging disease problems. The short-course was modified slightly in 2013 and renamed the Certificate in One Health. To evaluate the immediate impact of the short-course, an online survey of 176 past participants from both the courses was conducted. The survey tool assessed the program’s process, impact, and outcome measures respectively via assessing the courses’ perceived strengths and weaknesses, perceived skills gained, and the participants’ current position, publication status, funding status, and educational attainment; 85 (48.3%) participants completed the survey. Reported program strengths included the curriculum, expertise of lecturers, and diversity of the training cohort. The principal reported weakness was the compressed academic schedule. The most frequently reported benefits included: epidemiological and biostatistical skills, followed by One-Health knowledge, and research skills. Twenty-eight percent of the survey respondents reported publishing one or more manuscripts since completing the course and 21% reported receiving research funding. The course appears to have had a positive, immediate impact on the students’ self-perceived knowledge and capabilities."
2103,Foot ailments during Hajj: A short report,"A study of ailments of the feet in pilgrims of Hajj revealed that 31% of them suffered from blisters, and the prevalence was five times higher in females. The presence of comorbidity (diabetes, obesity and advanced age) warrants immediate attention to them to avoid serious complications."
2104,Dissecting the mechanism of signaling-triggered nuclear export of newly synthesized influenza virus ribonucleoprotein complexes,"Influenza viruses (IV) exploit a variety of signaling pathways. Previous studies showed that the rapidly accelerated fibrosarcoma/mitogen-activated protein kinase/extracellular signal-regulated kinase (Raf/MEK/ERK) pathway is functionally linked to nuclear export of viral ribonucleoprotein (vRNP) complexes, suggesting that vRNP export is a signaling-induced event. However, the underlying mechanism remained completely enigmatic. Here we have dissected the unknown molecular steps of signaling-driven vRNP export. We identified kinases RSK1/2 as downstream targets of virus-activated ERK signaling. While RSK2 displays an antiviral role, we demonstrate a virus-supportive function of RSK1, migrating to the nucleus to phosphorylate nucleoprotein (NP), the major constituent of vRNPs. This drives association with viral matrix protein 1 (M1) at the chromatin, important for vRNP export. Inhibition or knockdown of MEK, ERK or RSK1 caused impaired vRNP export and reduced progeny virus titers. This work not only expedites the development of anti-influenza strategies, but in addition demonstrates converse actions of different RSK isoforms."
2105,Using surgical wrapping material for the fabrication of respirator masks,"Given the current shortage of respirator masks and the resulting lack of personal protective equipment for use by clinical staff, we examined bottom-up solutions that would allow hospitals to fabricate respirator masks that: (i) meet requirements in terms of filtering capacities, (ii) are easy to produce rapidly and locally, and (iii) can be constructed using materials commonly available in hospitals worldwide. We found that Halyard H300 material used for wrapping of surgical instruments and routinely available in hospitals, met these criteria. Specifically, three layers of material achieved a filter efficiency of 94%, 99%, and 100% for 0.3 μm, 0.5 μm, and 3.0 μm particles, respectively; importantly, these values are close to the efficiency provided by FFP2 and N95 masks. After re-sterilization up to 5 times, the filter’s efficiency remains sufficiently high for use as an FFP1 respirator mask. Finally, using only one layer of the material satisfies the criteria for use as a ‘surgical mask’. This material can therefore be used to help protect hospital staff and other healthcare professionals who require access to high quality masks but lack commercially available solutions."
2106,Trends in prevalence of allergic diseases in Korean children: how and why?,
2107,The E2 Marie Kondo and the CTLH E3 ligase clear deposited RNA binding proteins during the maternal-to-zygotic transition,"The maternal-to-zygotic transition (MZT) is a conserved step in animal development, where control is passed from the maternal to the zygotic genome. Although the MZT is typically considered from its impact on the transcriptome, we previously found that three maternally deposited Drosophila RNA-binding proteins (ME31B, Trailer Hitch [TRAL], and Cup) are also cleared during the MZT by unknown mechanisms. Here, we show that these proteins are degraded by the ubiquitin-proteasome system. Marie Kondo, an E2 conjugating enzyme, and the E3 CTLH ligase are required for the destruction of ME31B, TRAL, and Cup. Structure modeling of the Drosophila CTLH complex suggests that substrate recognition is different than orthologous complexes. Despite occurring hours earlier, egg activation mediates clearance of these proteins through the Pan Gu kinase, which stimulates translation of Kdo mRNA. Clearance of the maternal protein dowry thus appears to be a coordinated, but as-yet underappreciated, aspect of the MZT."
2108,Protective role of neuronal and lymphoid cannabinoid CB(2) receptors in neuropathic pain,"Cannabinoid CB(2) receptor (CB(2)) agonists are potential analgesics void of psychotropic effects. Peripheral immune cells, neurons and glia express CB(2); however, the involvement of CB(2) from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB(2) agonist JWH133 in wild-type and knockout mice lacking CB(2) in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB(2) disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB(2) knockouts and was increased in mice defective in neuronal CB(2) knockouts suggestive of increased spontaneous pain. Interestingly, CB(2)-positive lymphocytes infiltrated the injured nerve and possible CB(2)transfer from immune cells to neurons was found. Lymphocyte CB(2)depletion also exacerbated JWH133 self-administration and inhibited antinociception. This work identifies a simultaneous activity of neuronal and lymphoid CB(2)that protects against spontaneous and evoked neuropathic pain."
2109,Diagnosis and treatment of acute appendicitis: 2020 update of the WSES Jerusalem guidelines,"BACKGROUND AND AIMS: Acute appendicitis (AA) is among the most common causes of acute abdominal pain. Diagnosis of AA is still challenging and some controversies on its management are still present among different settings and practice patterns worldwide. In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines. An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been updated in order to provide evidence-based statements and recommendations in keeping with varying clinical practice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of non-operative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and peri-operative antibiotic therapy. METHODS: This executive manuscript summarizes the WSES guidelines for the diagnosis and treatment of AA. Literature search has been updated up to 2019 and statements and recommendations have been developed according to the GRADE methodology. The statements were voted, eventually modified, and finally approved by the participants to the consensus conference and by the board of co-authors, using a Delphi methodology for voting whenever there was controversy on a statement or a recommendation. Several tables highlighting the research topics and questions, search syntaxes, and the statements and the WSES evidence-based recommendations are provided. Finally, two different practical clinical algorithms are provided in the form of a flow chart for both adults and pediatric (< 16 years old) patients. CONCLUSIONS: The 2020 WSES guidelines on AA aim to provide updated evidence-based statements and recommendations on each of the following topics: (1) diagnosis, (2) non-operative management for uncomplicated AA, (3) timing of appendectomy and in-hospital delay, (4) surgical treatment, (5) intra-operative grading of AA, (6) ,management of perforated AA with phlegmon or abscess, and (7) peri-operative antibiotic therapy."
2110,Thyroid dysfunction in Iranian pregnant women: a systematic review and meta-analysis,"BACKGROUND: Thyroid dysfunction during pregnancy is associated with adverse outcomes for both mother and fetus. The present meta-analysis was conducted to evaluate thyroid dysfunction in Iranian pregnant women. METHODS: We registered this review at PROSPERO (registration number: CRD42020166655). The research steps in this systematic review and meta-analysis were performed according to the MOOSE protocol, and finally, reports were provided based on the PRISMA guidelines. The literature search was performed in October 2019 using the international online databases, including Web of Science, Ovid, Science Direct, Scopus, EMBASE, PubMed/Medline, Cochrane Library, EBSCO, CINAHL, Google Scholar as well as national databases were reviewed. Data were extracted after applying the inclusion and exclusion criteria and qualitative evaluation of the studies. I(2) index and Q test were used to assess differences in studies. All analyses were performed using Comprehensive Meta-Analysis Software. P-value less than 0.05 was considered statistically significant. We identified 1261 potential articles from the databases, and 426 articles remained after removing the duplicate and unrelated studies. After evaluating the full text, 52 articles were removed. RESULTS: Finally, 19 eligible studies including 17,670 pregnant women included for meta-analysis. The prevalence of thyroid dysfunction in Iranian pregnant women was 18.10% (95%CI: 13.89–23.25). The prevalence of hypothyroidism, clinical hypothyroidism, and subclinical hypothyroidism in Iranian pregnant women was respectively estimated to be 13.01% (95%CI: 9.15–18.17), 1.35% (95%CI: 0.97–1.86) and 11.90% (95%CI: 7.40–18.57). The prevalence of hyperthyroidism, clinical hyperthyroidism, and subclinical hyperthyroidism in Iranian pregnant women was respectively estimated to be 3.31% (95%CI: 1.62–6.61), 1.06% (95%CI: 0.61–1.84) and 2.56% (95%CI: 0.90–7.05). The prevalence of anti-thyroperoxidase antibody was estimated to be 11.68% (95%CI: 7.92–16.89). CONCLUSION: The results of this meta-analysis showed a high prevalence of thyroid disorders, especially hypothyroidism. The decision to recommend thyroid screening during pregnancy for all women is still under debate, because the positive effects of treatment on pregnancy outcomes must be ensured. On the other hand, evidence about the effect of thyroid screening and treatment of thyroid disorders on pregnancy outcomes is still insufficient. Nevertheless, a large percentage of general practitioners, obstetricians and gynecologists perform screening procedures in Iran."
2111,"Overexpression of an apple LysM-containing protein gene, MdCERK1–2, confers improved resistance to the pathogenic fungus, Alternaria alternata, in Nicotiana benthamiana","BACKGROUND: Lysin motif (LysM)-containing proteins are involved in the recognition of fungal and bacterial pathogens. However, few studies have reported on their roles in the defense responses of woody plants against pathogens. A previous study reported that the apple MdCERK1 gene was induced by chitin and Rhizoctonia solani, and its protein can bind to chitin. However, its effect on defense responses has not been investigated. RESULTS: In this study, a new apple CERK gene, designated as MdCERK1–2, was identified. It encodes a protein that shares high sequence identity with the previously reported MdCERK1 and AtCERK1. Its chitin binding ability and subcellular location are similar to MdCERK1 and AtCERK1, suggesting that MdCERK1–2 may play a role in apple immune defense responses as a pattern recognition receptor (PRR). MdCERK1–2 expression in apple was induced by 2 fungal pathogens, Botryosphaeria dothidea and Glomerella cingulate, but not by the bacterial pathogen, Erwinia amylovora, indicating that MdCERK1–2 is involved in apple anti-fungal defense responses. Further functional analysis by heterologous overexpression (OE) in Nicotiana benthamiana (Nb) demonstrated that MdCERK1–2 OE improved Nb resistance to the pathogenic fungus, Alternaria alternata. H(2)O(2) accumulation and callose deposition increased after A. alternata infection in MdCERK1–2 OE plants compared to wild type (WT) and empty vector (EV)-transformed plants. The induced expression of NbPAL4 by A. alternata significantly (p < 0.01, n = 4) increased in MdCERK1–2 OE plants. Other tested genes, including NbNPR1, NbPR1a, NbERF1, and NbLOX1, did not exhibit significant changes after A. alternata infection in OE plants compared to EV or WT plants. OE plants also accumulated more polyphenols after A. alternata infection. CONCLUSIONS: Heterologous MdCERK1–2 OE affects multiple defense responses in Nb plants and increased their resistance to fungal pathogens. This result also suggests that MdCERK1–2 is involved in apple defense responses against pathogenic fungi."
2112,The statistical importance of a study for a network meta-analysis estimate,"BACKGROUND: In pairwise meta-analysis, the contribution of each study to the pooled estimate is given by its weight, which is based on the inverse variance of the estimate from that study. For network meta-analysis (NMA), the contribution of direct (and indirect) evidence is easily obtained from the diagonal elements of a hat matrix. It is, however, not fully clear how to generalize this to the percentage contribution of each study to a NMA estimate. METHODS: We define the importance of each study for a NMA estimate by the reduction of the estimate’s variance when adding the given study to the others. An equivalent interpretation is the relative loss in precision when the study is left out. Importances are values between 0 and 1. An importance of 1 means that the study is an essential link of the pathway in the network connecting one of the treatments with another. RESULTS: Importances can be defined for two-stage and one-stage NMA. These numbers in general do not add to one and thus cannot be interpreted as ‘percentage contributions’. After briefly discussing other available approaches, we question whether it is possible to obtain unique percentage contributions for NMA. CONCLUSIONS: Importances generalize the concept of weights in pairwise meta-analysis in a natural way. Moreover, they are uniquely defined, easily calculated, and have an intuitive interpretation. We give some real examples for illustration."
2113,PWAS: proteome-wide association study—linking genes and phenotypes by functional variation in proteins,"We introduce Proteome-Wide Association Study (PWAS), a new method for detecting gene-phenotype associations mediated by protein function alterations. PWAS aggregates the signal of all variants jointly affecting a protein-coding gene and assesses their overall impact on the protein’s function using machine learning and probabilistic models. Subsequently, it tests whether the gene exhibits functional variability between individuals that correlates with the phenotype of interest. PWAS can capture complex modes of heritability, including recessive inheritance. A comparison with GWAS and other existing methods proves its capacity to recover causal protein-coding genes and highlight new associations. PWAS is available as a command-line tool."
2114,High-resolution temporal profiling of the human gut microbiome reveals consistent and cascading alterations in response to dietary glycans,"BACKGROUND: Dietary glycans, widely used as food ingredients and not directly digested by humans, are of intense interest for their beneficial roles in human health through shaping the microbiome. Characterizing the consistency and temporal responses of the gut microbiome to glycans is critical for rationally developing and deploying these compounds as therapeutics. METHODS: We investigated the effect of two chemically distinct glycans (fructooligosaccharides and polydextrose) through three clinical studies conducted with 80 healthy volunteers. Stool samples, collected at dense temporal resolution (~ 4 times per week over 10 weeks) and analyzed using shotgun metagenomic sequencing, enabled detailed characterization of participants’ microbiomes. For analyzing the microbiome time-series data, we developed MC-TIMME2 (Microbial Counts Trajectories Infinite Mixture Model Engine 2.0), a purpose-built computational tool based on nonparametric Bayesian methods that infer temporal patterns induced by perturbations and groups of microbes sharing these patterns. RESULTS: Overall microbiome structure as well as individual taxa showed rapid, consistent, and durable alterations across participants, regardless of compound dose or the order in which glycans were consumed. Significant changes also occurred in the abundances of microbial carbohydrate utilization genes in response to polydextrose, but not in response to fructooligosaccharides. Using MC-TIMME2, we produced detailed, high-resolution temporal maps of the microbiota in response to glycans within and across microbiomes. CONCLUSIONS: Our findings indicate that dietary glycans cause reproducible, dynamic, and differential alterations to the community structure of the human microbiome."
2115,Seamless integration of image and molecular analysis for spatial transcriptomics workflows,"BACKGROUND: Recent advancements in in situ gene expression technologies constitute a new and rapidly evolving field of transcriptomics. With the recent launch of the 10x Genomics Visium platform, such methods have started to become widely adopted. The experimental protocol is conducted on individual tissue sections collected from a larger tissue sample. The two-dimensional nature of this data requires multiple consecutive sections to be collected from the sample in order to construct a comprehensive three-dimensional map of the tissue. However, there is currently no software available that lets the user process the images, align stacked experiments, and finally visualize them together in 3D to create a holistic view of the tissue. RESULTS: We have developed an R package named STUtility that takes 10x Genomics Visium data as input and provides features to perform standardized data transformations, alignment of multiple tissue sections, regional annotation, and visualizations of the combined data in a 3D model framework. CONCLUSIONS: STUtility lets the user process, analyze and visualize multiple samples of spatially resolved RNA sequencing and image data from the 10x Genomics Visium platform. The package builds on the Seurat framework and uses familiar APIs and well-proven analysis methods. An introduction to the software package is available at https://ludvigla.github.io/STUtility_web_site/."
2116,KAML: improving genomic prediction accuracy of complex traits using machine learning determined parameters,"Advances in high-throughput sequencing technologies have reduced the cost of genotyping dramatically and led to genomic prediction being widely used in animal and plant breeding, and increasingly in human genetics. Inspired by the efficient computing of linear mixed model and the accurate prediction of Bayesian methods, we propose a machine learning-based method incorporating cross-validation, multiple regression, grid search, and bisection algorithms named KAML that aims to combine the advantages of prediction accuracy with computing efficiency. KAML exhibits higher prediction accuracy than existing methods, and it is available at https://github.com/YinLiLin/KAML."
2117,instaGRAAL: chromosome-level quality scaffolding of genomes using a proximity ligation-based scaffolder,"Hi-C exploits contact frequencies between pairs of loci to bridge and order contigs during genome assembly, resulting in chromosome-level assemblies. Because few robust programs are available for this type of data, we developed instaGRAAL, a complete overhaul of the GRAAL program, which has adapted the latter to allow efficient assembly of large genomes. instaGRAAL features a number of improvements over GRAAL, including a modular correction approach that optionally integrates independent data. We validate the program using data for two brown algae, and human, to generate near-complete assemblies with minimal human intervention."
2118,Computational inference of cancer-specific vulnerabilities in clinical samples,"BACKGROUND: Systematic in vitro loss-of-function screens provide valuable resources that can facilitate the discovery of drugs targeting cancer vulnerabilities. RESULTS: We develop a deep learning-based method to predict tumor-specific vulnerabilities in patient samples by leveraging a wealth of in vitro screening data. Acquired dependencies of tumors are inferred in cases in which one allele is disrupted by inactivating mutations or in association with oncogenic mutations. Nucleocytoplasmic transport by Ran GTPase is identified as a common vulnerability in Her2-positive breast cancers. Vulnerability to loss of Ku70/80 is predicted for tumors that are defective in homologous recombination and rely on nonhomologous end joining for DNA repair. Our experimental validation for Ran, Ku70/80, and a proteasome subunit using patient-derived cells shows that they can be targeted specifically in particular tumors that are predicted to be dependent on them. CONCLUSION: This approach can be applied to facilitate the development of precision therapeutic targets for different tumors."
2119,In Response,
2120,Administering Cardiopulmonary Resuscitation to Personal Protective Equipment–Protected Health Care Worker During COVID-19,Supplemental Digital Content is available in the text.
2121,Computer tomographic assessment of gastric volume in major trauma patients: impact of pre-hospital airway management on gastric air,"BACKGROUND: Gastric dilation is frequently observed in trauma patients. However, little is known about average gastric volumes comprising food, fluids and air. Although literature suggests a relevant risk of gastric insufflation when endotracheal intubation (ETI) is required in the pre-hospital setting, this assumption is still unproven. METHODS: Primary whole body computed tomographic (CT) studies of 315 major trauma patients admitted to our Level 1 Trauma Centre Salzburg during a 7-year period were retrospectively assessed. Gastric volumes were calculated employing a CT volume rendering software. Patients intubated in the pre-hospital setting by emergency physicians (PHI, N = 245) were compared with spontaneously breathing patients requiring ETI immediately after arrival in the emergency room (ERI, N = 70). RESULTS: The median (range) total gastric content and air volume was 402 (26–2401) and 94 (0–1902) mL in PHI vs. 466 (59–1915) and 120 (1–997) mL in ERI patients (p = .59 and p = .35). PHI patients were more severely injured when compared with the ERI group (injury severity score (ISS) 33 (9–75) vs. 25 (9–75); p = .004). Mortality was higher in the PHI vs. ERI group (26.8% vs. 8.6%, p = .001). When PHI and ERI patients were matched for sex, age, body mass index and ISS (N = 50 per group), total gastric content and air volume was 496 (59–1915) and 119 (0–997) mL in the PHI vs. 429 (36–1726) and 121 (4–1191) mL in the ERI group (p = .85 and p = .98). Radiologic findings indicative for aspiration were observed in 8.1% of PHI vs. 4.3% of ERI patients (p = .31). Gastric air volume in patients who showed signs of aspiration was 194 (0–1355) mL vs. 98 (1–1902) mL in those without pulmonary CT findings (p = .08). CONCLUSION: In major trauma patients, overall stomach volume deriving from food, fluids and air must be expected to be around 400–500 mL. Gastric dilation caused by air is common but not typically associated with pre-hospital airway management. The amount of air in the stomach seems to be associated with the risk of aspiration. Further studies, specifically addressing patients after difficult airway management situations are warranted."
2122,"Ethical, Legal, and Social Challenges in the Development and Implementation of Disaster Telemedicine","In recent years, advances in communications technology and market factors have led to a substantial expansion of telemedicine practice. One potential use of telemedicine is in disaster response, both as a resource for responders as well as a direct link to patients. The advantages of using telehealth to assist in disaster response are accompanied by important questions related to social impact, ethical implications, and regulatory oversight. A narrative review of several of these issues is presented here. The next steps in the development of a robust disaster telemedicine system will include the development of best practices and ethical guidelines agreed upon by all stakeholders, as well as the development of public-private partnerships geared at providing the highest quality disaster telemedicine to the greatest possible number of patients."
2123,Global Pediatric Research Investigator: Mohammod Jobayer Chisti,
2124,N(6)-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I,"Internal N(6)-methyladenosine (m(6)A) modification is one of the most common and abundant modifications of RNA. However, the biological role(s) of viral RNA m(6)A remains elusive. Using human metapneumovirus (hMPV) as a model, we demonstrate that m(6)A serves as a molecular marker for innate immune discrimination of self from nonself RNAs. We show that hMPV RNAs are m(6)A methylated and that viral m(6)A methylation promotes hMPV replication and gene expression. Inactivating m(6)A addition sites with synonymous mutations or demethylase resulted in m(6)A deficient recombinant hMPVs and virion RNAs that induced significantly higher expression of type I interferon (IFN) which was dependent on the cytoplasmic RNA sensor RIG-I, not MDA5. Mechanistically, m(6)A-deficient virion RNA induces higher expression of RIG-I, binds more efficiently to RIG-I, and facilitates the conformational change of RIG-I, leading to enhanced IFN expression. Furthermore, m(6)A-deficient rhMPVs triggered higher IFN in vivo and were significantly attenuated in cotton rats yet retained high immunogenicity. Collectively, our results highlight that (i) virus acquires m(6)A in their RNAs as a means of mimicking cellular RNA to avoid detection by innate immunity; and (ii) viral RNA m(6)A can serve as a target to attenuate hMPV for vaccine purposes."
2125,Fecal Microbiota Transplantation: Screening and Selection to Choose the Optimal Donor,"In the past decade, fecal microbiota transplantation (FMT) has rapidly spread worldwide in clinical practice as a highly effective treatment option against recurrent Clostridioides difficile infection. Moreover, new evidence also supports a role for FMT in other conditions, such as inflammatory bowel disease, functional gastrointestinal disorders, or metabolic disorders. Recently, some studies have identified specific microbial characteristics associated with clinical improvement after FMT, in different disorders, paving the way for a microbiota-based precision medicine approach. Moreover, donor screening has become increasingly more complex over years, along with standardization of FMT and the increasing number of stool banks. In this narrative review, we discuss most recent evidence on the screening and selection of the stool donor, with reference to recent studies that have identified specific microbiological features for clinical conditions such as Clostridioides difficile infection, irritable bowel syndrome, inflammatory bowel disease, and metabolic disorders."
2126,The Epidemiological Characteristics of the Korean Bat Paramyxovirus between 2016 and 2019,"Bats are considered reservoirs of severe emerging human pathogens. Notably, bats host major mammalian paramyxoviruses from the family Paramyxoviridae, order Mononegavirales. In this study, paramyxoviruses were investigated by reverse transcription semi-nested polymerase chain reaction (RT-semi-nested PCR) and reverse transcription polymerase chain reaction (RT-PCR), based on the RT-semi-nested PCR using the consensus paramyxovirus primers targeting the RNA dependent-RNA-polymerase (RdRp) region. In addition, RT-PCR was performed using newly designed primers targeting regions of the fusion protein (F) and hemagglutinin-neuraminidase (HN). The dominant bat species in the collection site of paramyxoviruses were Miniopterus schreibersii, Myotis macrodactylus, Myotis petax, and Rhinolophus ferrumequinum. Paramyxoviruses were detected in four samples in 2016 and six in 2019. Meanwhile, in samples collected in 2017 and 2018, no paramyxoviruses were detected. Phylogenetic analysis based on the partial nucleotide sequences of RdRp, F, and HN proteins suggested that the viruses belonged to the proposed genus Shaanvirus. In conclusion, this study revealed that bat paramyxoviruses in Korea belonged to a single genus and circulated sporadically in several provinces, including Chungbuk, Gangwon, Jeju, and Jeonnam."
2127,Antimicrobial Peptides as Anticancer Agents: Functional Properties and Biological Activities,"Antimicrobial peptides (AMPs), or host defense peptides, are small cationic or amphipathic molecules produced by prokaryotic and eukaryotic organisms that play a key role in the innate immune defense against viruses, bacteria and fungi. AMPs have either antimicrobial or anticancer activities. Indeed, cationic AMPs are able to disrupt microbial cell membranes by interacting with negatively charged phospholipids. Moreover, several peptides are capable to trigger cytotoxicity of human cancer cells by binding to negatively charged phosphatidylserine moieties which are selectively exposed on the outer surface of cancer cell plasma membranes. In addition, some AMPs, such as LTX-315, have shown to induce release of tumor antigens and potent damage associated molecular patterns by causing alterations in the intracellular organelles of cancer cells. Given the recognized medical need of novel anticancer drugs, AMPs could represent a potential source of effective therapeutic agents, either alone or in combination with other small molecules, in oncology. In this review we summarize and describe the properties and the mode of action of AMPs as well as the strategies to increase their selectivity toward specific cancer cells."
2128,Roles of Macrophage Migration Inhibitory Factor in Dengue Pathogenesis: From Pathogenic Factor to Therapeutic Target,"Dengue virus (DENV) infection is the most prevalent mosquito-borne viral infection and can lead to severe dengue hemorrhagic fever (DHF) and even life-threatening dengue shock syndrome (DSS). Although the cytokine storm has been revealed as a critical factor in dengue disease, the limited understanding of dengue immunopathogenesis hinders the development of effective treatments. Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine that mediates diverse immune responses, and the serum level of MIF positively correlates with disease severity in patients with dengue. MIF is involved in DENV replication and many pathological changes, such as vascular leakage, during DENV infection. In this paper, the pathogenic roles of MIF and the regulation of MIF secretion during DENV infection are reviewed. Furthermore, whether MIF is a potential therapeutic target against DENV infection is also discussed."
2129,Hybrid Quinoline-Sulfonamide Complexes (M(2+)) Derivatives with Antimicrobial Activity,"Two new series of hybrid quinoline-sulfonamide complexes (M(2+): Zn(2+), Cu(2+), Co(2+) and Cd(2+)) derivatives (QSC) were designed, synthesized and tested for their antimicrobial activity. The synthesis is straightforward and efficient, involving two steps: acylation of aminoquinoline followed by complexation with metal acetate (Cu(2+), Co(2+) and Cd(2+)) or chloride (Zn(2+)). The synthesized QSC compounds were characterized by FTIR and NMR spectroscopy and by X-ray diffraction on single crystal. The QSC compounds were preliminary screened for their antibacterial and antifungal activity and the obtained results are very promising. In this respect, the hybrid N-(quinolin-8-yl)-4-chloro-benzenesulfonamide cadmium (II), considered as leading structure for further studies, has an excellent antibacterial activity against Staphylococcus aureus ATCC25923 (with a diameters of inhibition zones of 21 mm and a minimum inhibitory concentration (MIC) of 19.04 × 10(−5) mg/mL), a very good antibacterial activity against Escherichia coli ATCC25922 (with a diameters of inhibition zones of 19 mm and a MIC of 609 × 10(−5) mg/mL), and again an excellent antifungal activity against Candida albicans ATCC10231 (with a diameters of inhibition zones of 25 mm and a MIC of 19.04 × 10(−5) mg/mL)."
2130,Photo Quiz: Sudden Death,
2131,Conference Didactic Planning and Structure: An Evidence-based Guide to Best Practices from the Council of Emergency Medicine Residency Directors,"Emergency medicine residency programs around the country develop didactic conferences to prepare residents for board exams and independent practice. To our knowledge, there is not currently an evidence-based set of guidelines for programs to follow to ensure maximal benefit of didactics for learners. This paper offers expert guidelines for didactic instruction from members of the Council of Emergency Medicine Residency Directors Best Practices Subcommittee, based on best available evidence. Programs can use these recommendations to further optimize their resident conference structure and content. Recommendations in this manuscript include best practices in formatting didactics, selection of facilitators and instructors, and duration of individual sessions. Authors also recommend following the Model of Clinical Practice of Emergency Medicine when developing content, while incorporating sessions dedicated to morbidity and mortality, research methodology, journal article review, administration, wellness, and professionalism."
2132,Transfusion-Related Hypocalcemia After Trauma,"BACKGROUND: Hypocalcemia is cited as a complication of massive transfusion. However, this is not well studied as a primary outcome in trauma patients. Our primary outcome was to determine if transfusion of packed red blood cells (pRBC) was an independent predictor of severe hypocalcemia (ionized calcium ≤ 3.6 mg/dL). METHODS: Retrospective, single-center study (01/2004–12/2014) including all trauma patients ≥ 18 yo presenting to the ED with an ionized calcium (iCa) level drawn. Variables extracted included demographics, interventions, outcomes, and iCa. Regression models identified independent risk factors for severe hypocalcemia (SH). RESULTS: Seven thousand four hundred and thirty-one included subjects, 716 (9.8%) developed SH within 48 h of admission. Median age: 39 (Range: 18–102), systolic blood pressure: 131 (IQR: 114–150), median Glasgow Coma Scale (GCS): 15 (IQR: 10–15), Injury Severity Score (ISS): 14 (IQR: 9–24). SH patients were more likely to have depressed GCS (13 vs 15, p < 0.0001), hypotension (23.2% vs 5.1%, p < 0.0001) and tachycardia (57.0% vs 41.9%, p < 0.0001) compared to non-SH patients. They also had higher emergency operative rate (71.8% vs 29%, p < 0.0001) and higher blood administration prior to minimum iCa [pRBC: (8 vs 0, p < 0.0001), FFP: (4 vs 0, p < 0.0001), platelet: (1 vs 0, p < 0.0001)]. Multivariable analysis revealed penetrating mechanism (AOR: 1.706), increased ISS (AOR: 1.029), and higher pRBC (AOR: 1.343) or FFP administered (AOR: 1.097) were independent predictors of SH. SH was an independent predictor of mortality (AOR: 2.658). Regression analysis identified a significantly higher risk of SH at pRBC + FFP administration of 4 units (AOR: 18.706, AUC:. 897 (0.884–0.909). CONCLUSION: Transfusion of pRBC is an independent predictor of SH and is associated with increased mortality. The predicted probability of SH increases as pRBC + FFP administration increases."
2133,Der Sommer wird aktiv – die GeSRU stellt sich vor,
2134,America’s Unrecognized Health Workforce: Postal Workers,
2135,Risk Factors for Dysphagia and the Impact on Outcome After Spontaneous Subarachnoid Hemorrhage,"BACKGROUND: Despite the tremendous impact of swallowing disorders on outcome following ischemic stroke, little is known about the incidence of dysphagia after subarachnoid hemorrhage (SAH) and its contribution to hospital complications, length of intensive care unit stay, and functional outcome. METHODS: This is a retrospective analysis of an ongoing prospective cohort study. Swallowing ability was assessed in consecutive non-traumatic SAH patients admitted to our neurological intensive care unit using the Bogenhausen Dysphagia Score (BODS). A BODS > 2 points indicated dysphagia. Functional outcome was assessed 3 months after the SAH using the modified Rankin Scale with a score > 2 defined as poor functional outcome. RESULTS: Two-hundred and fifty consecutive SAH patients comprising all clinical severity grades with a median age of 57 years (interquartile range 47–67) were eligible for analysis. Dysphagia was diagnosed in 86 patients (34.4%). Factors independently associated with the development of dysphagia were poor clinical grade on admission (Hunt & Hess grades 4–5), SAH-associated parenchymal hematoma, hydrocephalus, detection of an aneurysm, and prolonged mechanical ventilation (> 48 h). Dysphagia was independently associated with a higher rate of pneumonia (OR = 4.32, 95% CI = 2.35–7.93), blood stream infection (OR = 4.3, 95% CI = 2.0–9.4), longer ICU stay [14 (8–21) days versus 29.5 (23–45) days, p < 0.001], and poor functional outcome after 3 months (OR = 3.10, 95% CI = 1.49–6.39). CONCLUSIONS: Dysphagia is a frequent complication of non-traumatic SAH and associated with poor functional outcome, infectious complications, and prolonged stay in the intensive care unit. Early identification of high-risk patients is needed to timely stratify individual patients for dysphagia treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12028-019-00874-6) contains supplementary material, which is available to authorized users."
2136,Antibiotic fidaxomicin is an RdRp inhibitor as a potential new therapeutic agent against Zika virus,"BACKGROUND: Zika virus (ZIKV) infection is a global health problem, and its complications, including congenital Zika syndrome and Guillain-Barré syndrome, constitute a continued threat to humans. Unfortunately, effective therapeutics against ZIKV infection are not available thus far. METHODS: We screened the compounds collection consisting of 1789 FDA-approved drugs by a computational docking method to obtain anti-ZIKV candidate compounds targeting ZIKV RNA-dependent RNA polymerase (RdRp). SPR (BIAcore) assay was employed to demonstrate the candidate compounds’ direct binding to ZIKV RdRp, and polymerase activity assay was used to determine the inhibitory effect on ZIKV RdRp-catalyzed RNA synthesis. The antiviral effects on ZIKV in vitro and in vivo were detected in infected cultured cells and in Ifnar1(−/−) mice infected by ZIKV virus using plaque assay, western blotting, tissue immunofluorescence, and immunohistochemistry. RESULTS: Here, we report that a first-in-class macrocyclic antibiotic, which has been clinically used to treat Clostridium difficile infection, fidaxomicin, potently inhibits ZIKV replication in vitro and in vivo. Our data showed that fidaxomicin was effective against African and Asian lineage ZIKV in a wide variety of cell lines of various tissue origins, and prominently suppressed ZIKV infection and significantly improved survival of infected mice. In addition, fidaxomicin treatment reduced the virus load in the brains and testes, and alleviated ZIKV-associated pathological damages, such as paralysis, hunching, and neuronal necrosis in the cerebra. Furthermore, our mechanistic study showed that fidaxomicin directly bound ZIKV NS5 protein and inhibited the RNA synthesis-catalyzing activity of ZIKV RdRp. CONCLUSIONS: Our data suggest that fidaxomicin may represent an effective anti-ZIKV agent. In the light that fidaxomicin is already a clinically used drug, there might be a promising prospect in the development of fidaxomicin to be an antiviral therapeutic."
2137,Vaccines Targeting PSCK9 for the Treatment of Hyperlipidemia,"Despite progress in both primary and secondary prevention, cardiovascular diseases (CVD) are still the largest group of ailments contributing to morbidity and mortality worldwide. Atherosclerotic changes, the primary pathological substrate for CVD, are closely related to hypercholesterolemia. Therefore, the treatment of hypercholesterolemia is a key therapeutic strategy for CVD management. Statins, as the gold standard in the treatment of hypercholesterolemia, have shown enhanced cardiac outcomes in many randomized clinical trials. However, often despite the maximum allowed and tolerated dosage of statins, we are not able to reach the target cholesterol levels, and thus patients persist at an increased cardiovascular risk. Recently, most of the large clinical studies in the field of preventive cardiology have focused on proprotein convertase subtilisin kexin type 9 (PCSK9) and its activity regulation. PCSK9 plays an essential role in the metabolism of LDL particles by inhibiting LDL receptor recirculation to the cell surface. Recent studies have shown that inhibition of PCSK9 by the administration of monoclonal antibodies is capable of significantly reducing LDL levels (up to an additional 60%) as well as reducing the incidence of CVD. However, this treatment procedure of administering the anti-PCSK9 antibodies, most frequently two times a month, has its limitations in terms of time, patient adherence, and nevertheless cost. Administration of active vaccination instead of passive immunization with anti-PCSK9 antibodies may be an effective way of controlling blood cholesterol levels. However, clinical data, as well as human testing, are still inadequate. This work aims to provide an overview of PCSK9 vaccines and their potential clinical benefit."
2138,Big Data for Clinical Trials: Automated Collection of SpO(2) for a Trial of Oxygen Targets during Mechanical Ventilation,
2139,Role of FTO and MC4R Polymorphisms in Escalating Obesity and Their Indirect Association With Risk of T2D in Indian Population,"INTRODUCTION: Obesity plays a pivotal role in the development of metabolic syndrome—excessive body fat, spikes in blood glucose levels and hypertension—and ultimately leads to cardiovascular diseases and type 2 diabetes (T2D), if left unattended. The present study aimed to investigate the associated risk of T2D with obesity risk alleles of fat mass and obesity-associated (FTO) and melanocortin 4 receptor (MC4R) genes. METHODS: The study includes 400 subjects (300 T2D diabetic cases and 100 healthy controls). Genetic analysis was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: The findings of the study show no significant increase in odds of diabetes associated with the prevalence of FTO and MC4R minor alleles. Rare allele frequencies for “A” of FTO rs9939609 were 0.34 and 0.30 in cases and controls, respectively. Rare allele frequencies for A of MC4R rs12970134 were found to be more common in controls (0.45) than cases (0.41), but the difference was insignificant (p 0.246); however, an increase in body weight with the presence of allele “A” of the FTO gene (p value < 0.001) was found, indicating indirect involvement in the development of T2D. In addition, these were also correlated with the demographic/lifestyle and clinico-pathological parameters between T2D cases and controls. We found that T2D patients with a history of smoking and high consumption of alcohol, fast foods and sweetened beverages are at high risk of T2D compared to healthy controls (p < 0.01*). CONCLUSION: The present study concludes that there is no direct association of rs9939609 of the FTO gene with the occurrence of diabetes in the Indian population, but its role in T2D development cannot be overlooked altogether. Furthermore, we conclude that the rs9939609 of FTO carries a potential risk of obesity and because of this FTO rs9939609 T > A is widely considered an obesity-associated allele/single-nucleotide polymorphism (SNP)."
2140,Supine versus semi-Fowler’s positions for tracheal extubation in abdominal surgery-a randomized clinical trial,"BACKGROUND: Tracheal extubation is commonly performed in the supine position. However, in patients undergoing abdominal surgery, the supine position increases abdominal wall tension, especially during coughing and deep breathing, which may aggravate pain and lead to abdominal wound dehiscence. The semi-Fowler’s position may reduce abdominal wall tension, but its safety and comfort in tracheal extubation have not been reported. We aimed to evaluate the safety and comfort of different extubation positions in patients undergoing abdominal surgery. METHODS: We enrolled 141 patients with an American Society of Anesthesiologists grade of I-III who underwent abdominal surgery. All patients were anesthetized with propofol, fentanyl, cisatracurium, and sevoflurane. After surgery, all patients were transferred to the post-anesthesia care unit (PACU). Patients were then randomly put into the semi-Fowler’s (n = 70) or supine (n = 71) position while 100% oxygen was administered. The endotracheal tube was removed after the patients opened their eyes and regained consciousness. Vital signs, coughing, and pain and comfort scores before and/or after extubation were recorded until the patients left the PACU. RESULTS: In comparison with the supine position, the semi-Fowler’s position significantly decreased the wound pain scores at all intervals after extubation (3.51 ± 2.50 vs. 4.58 ± 2.26, 2.23 ± 1.68 vs. 3.11 ± 2.00, 1.81 ± 1.32 vs. 2.59 ± 1.88, P = 0.009, 0.005 and 0.005, respectively), reduced severe coughing (8[11.43%] vs. 21[29.58%], P = 0.008) and bucking after extubation (3[4.29%] vs. 18[25.35%], P < 0.001), and improved the comfort scores 5 min after extubation (6.11 ± 2.30 vs. 5.17 ± 1.78, P = 0.007) and when leaving from post-anesthesia care unit (7.17 ± 2.27 vs. 6.44 ± 1.79, P = 0.034). The incidences of vomiting, emergence agitation, and respiratory complications were of no significant difference. CONCLUSION: Tracheal extubation in the semi-Fowler’s position is associated with less coughing, sputum suction, and pain, and more comfort, without specific adverse effects when compared to the conventional supine position. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900025566. Registered on 1st September 2019."
2141,Molecular epidemiology of Aleutian mink disease virus from fecal swab of mink in northeast China,"BACKGROUND: Aleutian mink disease parvovirus (AMDV) causes Aleutian mink disease (AMD), which is a serious infectious disease of mink. The aim of this study was to get a better understanding of the molecular epidemiology of AMDV in northeast China to control and prevent AMD from further spreading. This study for the first time isolated AMDV from fecal swab samples of mink in China. RESULTS: A total of 157/291 (54.0%) of the fecal swab samples were positive for AMDV. Of these, 23 AMDV positive samples were randomly selected for sequence alignment and phylogenetic analysis based on the acquired partial fragments of VP2 gene with the hypervariable region. Comparative DNA sequence analysis of 23 AMDV isolates with a reference nonpathogenic (AMDV-G) strain revealed 8.3% difference in partial VP2 nucleotide sequences. Amino acid alignment indicated the presence of several genetic variants, as well as one single amino acid residue deletion. The most concentrated area of variation was located in the hypervariable region of VP2 protein. According to phylogenetic analysis, the Chinese AMDV strains and the other reference AMDV strains from different countries clustered into three groups (clades A, B and C). Most of the newly sequenced strains were found to form a Chinese-specific group, which solely consisted of Chinese AMDV strains. CONCLUSION: These findings indicated that a high genetic diversity was found in Chinese AMDV strains and the virus distribution were not dependent on geographical origin. Both local and imported AMDV positive species were prevalent in the Chinese mink farming population. The genetic evidence of AMDV variety and epidemic isolates have importance in mink farming practice."
2142,"Conjugative plasmidic AmpC detected in Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae human clinical isolates from Portugal","AmpC is a type of β-lactamase enzyme produced by bacteria; these enzymes are classified in Class C and Group 1, and these confer resistance to cephamycin. Enterobacterales producing AmpC are reported worldwide and have great clinical importance due to therapeutic restriction and epidemiological importance once the easy dissemination by plasmidic genes to other bacteria is a real threat. These genes are naturally found in some enterobacteria as Enterobacter cloacae, Morganella morganii, and Citrobacter freundii, but other species have demonstrated similar resistance phenotype of AmpC production. Genes carried in plasmids have been described in these species conferring resistance to cefoxitin and causing therapeutic failure in some bacterial infections. This work detected and described five clinical strains of Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae that presented plasmid ampC (pAmpC) isolated from the north of Portugal collected in 2009. AmpC production was confirmed by inhibition of the enzyme by cloxacillin and boronic acid in agar diffusion tests. Also, PCR (polymerase chain reaction) was performed for the detection of gene universal to AmpC, bla(ampC), and others to AmpC group: bla(ACC), bla(CIT), bla(CMY), bla(DHA), and bla(EBC). The conjugation in liquid medium for 24 h was realized to determine if gene is localized in chromosome or plasmid. The isolates and their conjugants showed phenotypic characteristics and bla(CMY) and bla(CIT) were detected by PCR corroborating the AmpC characteristics observed in these bacteria. Confirmation of transfer of plasmid containing genes encoding AmpC is of high epidemiological relevance to the hospital studied and demonstrated the importance of AmpC surveillance and studies in hospital and community environments in order to choose the appropriate therapy for bacterial infections."
2143,Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome Supported with Extracorporeal Membrane Oxygenation. Lost in Translational Research?,
2144,Deep Convolutional Neural Network–Based Diagnosis of Anterior Cruciate Ligament Tears: Performance Comparison of Homogenous Versus Heterogeneous Knee MRI Cohorts With Different Pulse Sequence Protocols and 1.5-T and 3-T Magnetic Field Strengths,"OBJECTIVES: The aim of this study was to clinically validate a Deep Convolutional Neural Network (DCNN) for the detection of surgically proven anterior cruciate ligament (ACL) tears in a large patient cohort and to analyze the effect of magnetic resonance examinations from different institutions, varying protocols, and field strengths. MATERIALS AND METHODS: After ethics committee approval, this retrospective analysis of prospectively collected data was performed on 512 consecutive subjects, who underwent knee magnetic resonance imaging (MRI) in a total of 59 different institutions followed by arthroscopic knee surgery at our institution. The DCNN and 3 fellowship-trained full-time academic musculoskeletal radiologists evaluated the MRI examinations for full-thickness ACL tears independently. Surgical reports served as the reference standard. Statistics included diagnostic performance metrics, including sensitivity, specificity, area under the receiver operating curve (“AUC ROC”), and kappa statistics. P values less than 0.05 were considered to represent statistical significance. RESULTS: Anterior cruciate ligament tears were present in 45.7% (234/512) and absent in 54.3% (278/512) of the subjects. The DCNN had a sensitivity of 96.1%, which was not significantly different from the readers (97.5%–97.9%; all P ≥ 0.118), but significantly lower specificity of 93.1% (readers, 99.6%–100%; all P < 0.001) and “AUC ROC” of 0.935 (readers, 0.989–0.991; all P < 0.001) for the entire cohort. Subgroup analysis showed a significantly lower sensitivity, specificity, and “AUC ROC” of the DCNN for outside MRI (92.5%, 87.1%, and 0.898, respectively) than in-house MRI (99.0%, 94.4%, and 0.967, respectively) examinations (P = 0.026, P = 0.043, and P < 0.05, respectively). There were no significant differences in DCNN performance for 1.5-T and 3-T MRI examinations (all P ≥ 0.753, respectively). CONCLUSIONS: Deep Convolutional Neural Network performance of ACL tear diagnosis can approach performance levels similar to fellowship-trained full-time academic musculoskeletal radiologists at 1.5 T and 3 T; however, the performance may decrease with increasing MRI examination heterogeneity."
2145,Effects of Transcutaneous Neuromuscular Electrical Stimulation on Swallowing Disorders: A Systematic Review and Meta-Analysis,"OBJECTIVE: The aim of the study was to evaluate the efficacy of transcutaneous neuromuscular electrical stimulation on swallowing disorders. DESIGN: MEDLINE/PubMed, Embase, CENTRAL, Web of science, and PEDro were searched from their earliest record to August 1, 2019. All randomized controlled trials and quasi-randomized controlled trial were identified, which compared the efficacy of neuromuscular electrical stimulation plus traditional therapy with traditional therapy in swallowing function. The Grading of Recommendations Assessment, Development and Evaluation approach was applied to evaluate the quality of evidence. RESULTS: Eight randomized controlled trials and three quasi-randomized controlled trials were included. These studies demonstrated a significant, moderate pooled effect size (standard mean difference = 0.62; 95% confidence interval = 0.06 to 1.17). Studies stimulating suprahyoid muscle groups revealed a negative standard mean difference of 0.17 (95% confidence interval = −0.42, 0.08), whereas large effect size was observed in studies stimulating the infrahyoid muscle groups (standard mean difference = 0.89; 95% confidence interval = 0.47 to 1.30) and stimulating the suprahyoid and infrahyoid muscle groups (standard mean difference = 1.4; 95% confidence interval = 1.07 to 1.74). Stimulation lasting 45 mins or less showed a large, significant pooled effect size (standard mean difference = 0.89; 95% confidence interval = 0.58 to 1.20). The quality of evidences was rated as low to very low. CONCLUSIONS: There is no firm evidence to conclude on the efficacy of neuromuscular electrical stimulation on swallowing disorders. Larger-scale and well-designed randomized controlled trials are needed to reach robust conclusions."
2146,RNAseq Analysis of Rhizomania-Infected Sugar Beet Provides the First Genome Sequence of Beet Necrotic Yellow Vein Virus from the USA and Identifies a Novel Alphanecrovirus and Putative Satellite Viruses,"“Rhizomania” of sugar beet is a soilborne disease complex comprised of beet necrotic yellow vein virus (BNYVV) and its plasmodiophorid vector, Polymyxa betae. Although BNYVV is considered the causal agent of rhizomania, additional viruses frequently accompany BNYVV in diseased roots. In an effort to better understand the virus cohort present in sugar beet roots exhibiting rhizomania disease symptoms, five independent RNA samples prepared from diseased beet seedlings reared in a greenhouse or from field-grown adult sugar beet plants and enriched for virus particles were subjected to RNAseq. In all but a healthy control sample, the technique was successful at identifying BNYVV and provided sequence reads of sufficient quantity and overlap to assemble > 98% of the published genome of the virus. Utilizing the derived consensus sequence of BNYVV, infectious RNA was produced from cDNA clones of RNAs 1 and 2. The approach also enabled the detection of beet soilborne mosaic virus (BSBMV), beet soilborne virus (BSBV), beet black scorch virus (BBSV), and beet virus Q (BVQ), with near-complete genome assembly afforded to BSBMV and BBSV. In one field sample, a novel virus sequence of 3682 nt was assembled with significant sequence similarity and open reading frame (ORF) organization to members within the subgenus Alphanecrovirus (genus Necrovirus; family Tombusviridae). Construction of a DNA clone based on this sequence led to the production of the novel RNA genome in vitro that was capable of inducing local lesion formation on leaves of Chenopodium quinoa. Additionally, two previously unreported satellite viruses were revealed in the study; one possessing weak similarity to satellite maize white line mosaic virus and a second possessing moderate similarity to satellite tobacco necrosis virus C. Taken together, the approach provides an efficient pipeline to characterize variation in the BNYVV genome and to document the presence of other viruses potentially associated with disease severity or the ability to overcome resistance genes used for sugar beet rhizomania disease management."
2147,Histopathological Study of a Broad Spectrum of Skin Dermatoses in Patients Affected or Highly Suspected of Infection by COVID-19 in the Northern Part of Italy: Analysis of the Many Faces of the Viral-Induced Skin Diseases in Previous and New Reported Cases,"Skin manifestations of COVID-19 infections are diverse and are new to the dermatology community. We had the opportunity to examine the clinical and histopathological features of several patients who were divided into 3 groups. The first group included 8 COVID-19–positive patients who were hospitalized and quarantined at home. The second group included children and young adults who presented with chilblain erythema, erythema multiforme, and urticaria-like lesions. This group of patients was negative for the COVID-19 gene sequences by polymerase chain reaction but had a high risk of COVID-19 infection. The third group included clinically heterogeneous and challenging lesions. These patients were not subject to either polymerase chain reaction tests or serological analyses because they sought dermatological attention only for a dermatosis. The histopathological analysis of these cases showed a wide spectrum of histopathological patterns. What appears to be constant in all skin biopsies was the presence of prominent dilated blood vessels with a swollen endothelial layer, vessels engulfed with red blood cells, and perivascular infiltrates, consisting mainly of cytotoxic CD8+ lymphocytes and eosinophils. In 2 cases, there was diffuse coagulopathy in the cutaneous vascular plexus. In the early phases of the disease, there were numerous collections of Langerhans cells in the epidermis after being activated by the virus. The presence of urticarial lesions, chilblains, targetoid lesions (erythema multiforme–like lesions), exanthema, maculohemorrhagic rash, or chickenpox-like lesions associated with the histopathological features mentioned previously should cause clinical dermatologists to suspect the possibility of COVID-19 infection, especially in patients with fever and cough."
2148,"Antimicrobial Activity of Hybrid Nanomaterials Based on Star and Linear Polymers of N,N′-Dimethylaminoethyl Methacrylate with In Situ Produced Silver Nanoparticles","Well-defined linear and multi-arm star polymer structures were used as the templates for in situ synthesis and stabilization of silver nanoparticles (AgNPs). This approach led to hybrid nanomaterials with high stability and antibacterial activity to both Gram-positive and Gram-negative bacterial strains. The ecologically friendly so called “green” synthesis of nanomaterials was performed through AgNPs preparation in the aqueous solutions of star and linear poly(N,N′-dimethylaminoethyl methacrylate)s (PDMAEMAs); the process was followed with time. The size, shape, and zeta potential of the obtained hybrids were determined. To our knowledge, this is the first time that the antibacterial activity of PDMAEMA hybrid nanomaterial against Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa was investigated and assessed by minimum inhibitory concentration (MIC) and minimum biocidal concentration (MBC). Completely quaternized with ethyl bromide, star and linear PDMAEMAs were used in comparative biological tests. The modification of the polymers with in situ-formed AgNPs increased the antibacterial properties against all studied strains of bacteria by several times in comparison to non-modified polymers and quaternized polymers. These results yield novel nanohybrid materials that can be useful for applications in medicine and biology."
2149,Morphological and Mechanical Characterization of DNA SAMs Combining Nanolithography with AFM and Optical Methods,"The morphological and mechanical properties of thiolated ssDNA films self-assembled at different ionic strength on flat gold surfaces have been investigated using Atomic Force Microscopy (AFM). AFM nanoshaving experiments, performed in hard tapping mode, allowed selectively removing molecules from micro-sized regions. To image the shaved areas, in addition to the soft contact mode, we explored the use of the Quantitative Imaging (QI) mode. QI is a less perturbative imaging mode that allows obtaining quantitative information on both sample topography and mechanical properties. AFM analysis showed that DNA SAMs assembled at high ionic strength are thicker and less deformable than films prepared at low ionic strength. In the case of thicker films, the difference between film and substrate Young’s moduli could be assessed from the analysis of QI data. The AFM finding of thicker and denser films was confirmed by X-Ray Photoelectron Spectroscopy (XPS) and Spectroscopic Ellipsometry (SE) analysis. SE data allowed detecting the DNA UV absorption on dense monomolecular films. Moreover, feeding the SE analysis with the thickness data obtained by AFM, we could estimate the refractive index of dense DNA films."
2150,Challenges for Microelectronics in Non-Invasive Medical Diagnostics,"Microelectronics is emerging, sometimes with changing fortunes, as a key enabling technology in diagnostics. This paper reviews some recent results and technical challenges which still need to be addressed in terms of the design of CMOS analog application specific integrated circuits (ASICs) and their integration in the surrounding systems, in order to consolidate this technological paradigm. Open issues are discussed from two, apparently distant but complementary, points of view: micro-analytical devices, combining microfluidics with affinity bio-sensing, and gamma cameras for simultaneous multi-modal imaging, namely scintigraphy and magnetic resonance imaging (MRI). The role of integrated circuits is central in both application domains. In portable analytical platforms, ASICs offer miniaturization and tackle the noise/power dissipation trade-off. The integration of CMOS chips with microfluidics poses multiple open technological issues. In multi-modal imaging, now that the compatibility of the acquisition chains (thousands of Silicon Photo-Multipliers channels) of gamma detectors with Tesla-level magnetic fields has been demonstrated, other development directions, enabled by microelectronics, can be envisioned in particular for single-photon emission tomography (SPECT): a faster and simplified operation, for instance, to allow transportable applications (bed-side) and hardware pre-processing that reduces the number of output signals and the image reconstruction time."
2151,Avian Influenza A Virus Infects Swine Airway Epithelial Cells without Prior Adaptation,"Pigs play an important role in the interspecies transmission of influenza A viruses (IAV). The porcine airway epithelium contains binding sites for both swine/human IAV (α2,6-linked sialic acids) and avian IAV (α2,3-linked sialic acids) and therefore is suited for adaptation of viruses from other species as suggested by the “mixing vessel theory”. Here, we applied well-differentiated swine airway epithelial cells to find out whether efficient infection by avian IAV requires prior adaption. Furthermore, we analyzed the influence of the sialic acid-binding activity and the virus-induced detrimental effects. Surprisingly, an avian IAV H1N1 strain circulating in European poultry and waterfowl shows increased and prolonged viral replication without inducing a strong innate immune response. This virus could infect the lower respiratory tract in our precision cut-lung slice model. Pretreating the cells with poly (I:C) and/or JAK/STAT pathway inhibitors revealed that the interferon-stimulated innate immune response influences the replication of avian IAV in swine airway epitheliums but not that of swine IAV. Further studies indicated that in the infection by IAVs, the binding affinity of sialic acid is not the sole factor affecting the virus infectivity for swine or human airway epithelial cells, whereas it may be crucial in well-differentiated ferret tracheal epithelial cells. Taken together, our results suggest that the role of pigs being the vessel of interspecies transmission should be reconsidered, and the potential of avian H1N1 viruses to infect mammals needs to be characterized in more detail."
2152,“Together we move a mountain”: celebrating a decade of the Emerging Voices for Global Health network,
2153,Lung-resident mesenchymal stromal cells are tissue-specific regulators of lung homeostasis,"Until recently, data supporting the tissue-resident status of mesenchymal stromal cells (MSC) has been ambiguous since their discovery in the 1950–60s. These progenitor cells were first discovered as bone marrow-derived adult multipotent cells and believed to migrate to sites of injury, opposing the notion that they are residents of all tissue types. In recent years, however, it has been demonstrated that MSC can be found in all tissues and MSC from different tissues represent distinct populations with differential protein expression unique to each tissue type. Importantly, these cells are efficient mediators of tissue repair, regeneration, and prove to be targets for therapeutics, demonstrated by clinical trials (phase 1–4) for MSC-derived therapies for diseases like graft-versus-host-disease, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. The tissue-resident status of MSC found in the lung is a key feature of their importance in the context of disease and injuries of the respiratory system, since these cells could be instrumental to providing more specific and targeted therapies. Currently, bone marrow-derived MSC have been established in the treatment of disease, including diseases of the lung. However, with lung-resident MSC representing a unique population with a different phenotypic and gene expression pattern than MSC derived from other tissues, their role in remediating lung inflammation and injury could provide enhanced efficacy over bone marrow-derived MSC methods. Through this review, lung-resident MSC will be characterized, using previously published data, by surface markers, gene expression patterns, and compared with bone-marrow MSC to highlight similarities and, importantly, differences in these cell types."
2154,On the challenges associated with the study of police use of deadly force in the United States: A response to Schwartz & Jahn,"In response to Gabriel Schwartz and Jaquelyn Jahn’s descriptive study, “Mapping fatal police violence across U.S. metropolitan areas: Overall rates and racial/ethnic inequalities, 2013–2017,” I provide three reflections. First, the framing of this issue is vitally important. Second, police-involved fatalities represent a nonrandom sample of all incidents involving police use of deadly force (i.e., physical force that causes or is likely to cause death), and unfortunately, we lack comprehensive data on use of deadly force that does not result in fatalities. Finally, to make sense of who is killed by the police, researchers must also identify who was exposed to the risk of being killed by the police."
2155,Presence of Segmented Flavivirus Infections in North America,"Identifying viruses in synanthropic animals is necessary for understanding the origin of many viruses that can infect human hosts and developing strategies to prevent new zoonotic infections. The white-footed mouse, Peromyscus leucopus, is one of the most abundant rodent species in the northeastern United States. We characterized the serum virome of 978 free-ranging P. leucopus mice caught in Pennsylvania. We identified many new viruses belonging to 26 different virus families. Among these viruses was a highly divergent segmented flavivirus whose genetic relatives were recently identified in ticks, mosquitoes, and vertebrates, including febrile humans. This novel flavi-like segmented virus was found in rodents and shares ˂70% aa identity with known viruses in the highly conserved region of the viral polymerase. Our data will enable researchers to develop molecular reagents to further characterize this virus and its relatives infecting other hosts and to curtail their spread, if necessary."
2156,Porcine circovirus type 2 upregulates endothelial-derived IL-8 production in porcine iliac artery endothelial cells via the RIG-I/MDA-5/MAVS/JNK signaling pathway,"BACKGROUND: Dysfunction of endothelial cells and vascular system is one of the most important pathological changes of porcine circovirus disease (PCVD) caused by porcine circovirus type 2 (PCV2). PCV2-infected endothelial cells can upregulate the production of endothelial-derived IL-8, which can inhibit the maturation of dendritic cells. Endothelial-derived IL-8 has different structural and biological characteristics compared with monocyte-derived IL-8. However, the mechanism of endothelial-derived IL-8 production is still unclear. RESULTS: Key molecules of RIG-I-like signaling pathway RIG-I, MDA-5, MAVS and a key molecule of JNK signaling pathway c-Jun in PCV2-infected porcine iliac artery endothelial cells (PIECs) were upregulated significantly detected with quantitative PCR, Western blot and fluorescence confocal microscopy, while no significant changes were found in NF-κB signaling pathway. Meanwhile, the expression of endothelial-derived IL-8 was downregulated after RIG-I, MDA-5, or MAVS genes in PIECs were knocked down and PIECs were treated by JNK inhibitor. CONCLUSIONS: PCV2 can activate RIG-I/MDA-5/MAVS/JNK signaling pathway to induce the production of endothelial-derived IL-8 in PIECs, which provides an insight into the further study of endothelial dysfunction and vascular system disorder caused by PCV2."
2157,"Effektivität, Effizienz und Sicherheit der Schlaganfall-Telemedizin in Zeiten der Corona-Pandemie: Der „Fall“ Thüringen",
2158,Reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates with respiratory distress,"Hypercapnia occurs in ventilated infants even if tidal volume (V(T)) and minute ventilation (V(E)) are maintained. We hypothesised that increased physiological dead space (V(d,phys)) caused decreased minute alveolar ventilation (V(A); alveolar ventilation (V(A)) × respiratory rate) in well-ventilated infants with hypercapnia. We investigated the relationship between dead space and partial pressure of carbon dioxide (PaCO(2)) and assessed V(A). Intubated infants (n = 33; mean birth weight, 2257 ± 641 g; mean gestational age, 35.0 ± 3.3 weeks) were enrolled. We performed volumetric capnography (V(cap)), and calculated V(d,phys) and V(A) when arterial blood sampling was necessary. PaCO(2) was positively correlated with alveolar dead space (V(d,alv)) (r = 0.54, p < 0.001) and V(d,phys) (r = 0.48, p < 0.001), but not Fowler dead space (r = 0.14, p = 0.12). Normocapnia (82 measurements; 35 mmHg ≤ PaCO(2) < 45 mmHg) and hypercapnia groups (57 measurements; 45 mmHg ≤ PaCO(2)) were classified. The hypercapnia group had higher V(d,phys) (median 0.57 (IQR, 0.44–0.67)) than the normocapnia group (median V(d,phys)/V(T) = 0.46 (IQR, 0.37–0.58)], with no difference in V(T). The hypercapnia group had lower V(A) (123 (IQR, 87–166) ml/kg/min) than the normocapnia group (151 (IQR, 115–180) ml/kg/min), with no difference in V(E). Conclusion: Reduction of V(A) in well-ventilated neonates induces hypercapnia, caused by an increase in V(d,phys)."
2159,Novel imaging and clinical phenotypes of CONDSIAS disorder caused by a homozygous frameshift variant of ADPRHL2: a case report,"BACKGROUND: Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an autosomal recessive disorder caused by defects in the ADP-Ribosylhydrolase Like 2 (ADPRHL2; OMIM: 618170) gene. This gene encodes the ADP-ribosylhydrolase enzyme (ARH3) that eliminates the addition of poly-ADP ribose (PAR) in the cellular stress onto proteins in the ADP-ribosylation process in which adding one or more ADP-ribose moieties onto the target proteins in the post-translational modification have occurred. In this study, we report a new case of CONDSIAS in the Iranian population. A literature review of CONDSIAS is also included. CASE PRESENTATION: A four-year-old female patient, born to a consanguineous Iranian family, was referred with various clinical symptoms including impaired speech, variable ataxia, infrequent seizures, and gradual onset of truncal hypotonia. Over time, she developed complete motor and speech regression, bilateral sensorineural hearing loss, infrequent seizures, abdominal distension and gastrointestinal (GI) intolerance, and loss of consciousness. To better molecularly diagnose, trio-whole-exome sequencing (WES) was performed on the proband and her parents. Sanger sequencing was also applied to investigate co-segregation analysis. Using in silico predictive tools, the possible impacts of the variant on the structure and function of ADPRHL2 protein were predicted. All basic metabolic tests were normal, while serial coronal magnetic resonance imaging (MRI) showed progressive cerebral and cerebellar atrophy in addition to cerebral white matter signal changes as a novel neuroimaging finding. GI intolerance was another novelty of clinical scenarios in the patient. An auditory brainstem response test showed a severe bilateral sensorineural hearing loss. An electroencephalogram also confirmed focal seizures. From the molecular perspective, a novel homozygous frameshift variant in the ADPRHL2 gene (NM_017825.2; c.636_639del, p.(Leu212fs)) was identified by WES. CONCLUSIONS: CONDSIAS is an ultra-rare neurodegenerative disorder. In the present study, we introduced extra-neurological and neuroimaging findings of this disorder in a female child caused by a novel frameshift variation in the ADPRHL2 gene."
2160,"Soon after the previous issue of the International Journal on Dental Hygiene, the world has changed",
2161,Options for moving dental clinical education to a virtual learning experience,
2162,Virtual caries management competency,
2163,Case‐based competency assessments,
2164,Implementation of Procedure-Specific Opioid Guidelines: A Readily Employable Strategy to Improve Consistency and Decrease Excessive Prescribing Following Orthopaedic Surgery,"BACKGROUND: Evidence-based, procedure-specific guidelines for prescribing opioids are urgently needed to optimize pain relief while minimizing excessive opioid prescribing and potential opioid diversion in our communities. A multidisciplinary panel at our institution recently developed procedure-specific guidelines for discharge opioid prescriptions for common orthopaedic surgical procedures. The purpose of this study was to evaluate postoperative opioid prescription quantities, variability, and 30-day refill rates before and after implementation of the guidelines. METHODS: This retrospective cohort study was conducted at a single academic institution from December 2016 to March 2018. Guidelines were implemented on August 1, 2017, with a recommended maximum opioid prescription quantity for 14 common orthopaedic procedures. Patients who underwent these 14 procedures during the period of December 2016 to May 2017 made up the pre-guideline cohort (n = 2,223), and patients who underwent these procedures from October 2017 to March 2018 made up the post-guideline cohort (n = 2,300). Opioid prescription quantities were reported as oral morphine equivalents (OME), with medians and interquartile ranges (IQRs). Four levels were established for recommended prescription maximums, ranging from 100 to 400 OME. RESULTS: In the pre-guideline cohort, the median amount of prescribed opioids across all procedures was 600 OME (IQR, 390 to 863 OME), which decreased by 38% in the post-guideline period, to a median of 375 OME (IQR, 239 to 400 OME) in the post-guideline cohort (p < 0.001). The 30-day refill rate did not change significantly, from a rate of 24% in the pre-guideline cohort to 25% in the post-guideline cohort (p = 0.43). Multivariable analysis demonstrated that guideline implementation was the factor most strongly associated with prescriptions exceeding guideline maximums (odds ratio [OR] = 9.9; p < 0.001). Age groups of <80 years (OR = 2.0 to 2.4; p < 0.001) and males (OR = 1.2; p = 0.025) were also shown to have higher odds of exceeding guideline maximums. CONCLUSIONS: Procedure-specific guidelines are capable of substantially decreasing opioid prescription amounts and variability. Furthermore, the absence of change in refill rates suggests that pain control remains similar to pre-guideline prescribing practices. Evidence-based guidelines are a readily employable solution that can drive rapid change in practice and enhance the ability of orthopaedic surgeons to provide responsible pain management."
2165,Understanding Smartwatch Battery Utilization in the Wild,"Smartwatch battery limitations are one of the biggest hurdles to their acceptability in the consumer market. To our knowledge, despite promising studies analyzing smartwatch battery data, there has been little research that has analyzed the battery usage of a diverse set of smartwatches in a real-world setting. To address this challenge, this paper utilizes a smartwatch dataset collected from 832 real-world users, including different smartwatch brands and geographic locations. First, we employ clustering to identify common patterns of smartwatch battery utilization; second, we introduce a transparent low-parameter convolutional neural network model, which allows us to identify the latent patterns of smartwatch battery utilization. Our model converts the battery consumption rate into a binary classification problem; i.e., low and high consumption. Our model has 85.3% accuracy in predicting high battery discharge events, outperforming other machine learning algorithms that have been used in state-of-the-art research. Besides this, it can be used to extract information from filters of our deep learning model, based on learned filters of the feature extractor, which is impossible for other models. Third, we introduce an indexing method that includes a longitudinal study to quantify smartwatch battery quality changes over time. Our novel findings can assist device manufacturers, vendors and application developers, as well as end-users, to improve smartwatch battery utilization."
2166,Brain-Computer Interface-Based Humanoid Control: A Review,"A Brain-Computer Interface (BCI) acts as a communication mechanism using brain signals to control external devices. The generation of such signals is sometimes independent of the nervous system, such as in Passive BCI. This is majorly beneficial for those who have severe motor disabilities. Traditional BCI systems have been dependent only on brain signals recorded using Electroencephalography (EEG) and have used a rule-based translation algorithm to generate control commands. However, the recent use of multi-sensor data fusion and machine learning-based translation algorithms has improved the accuracy of such systems. This paper discusses various BCI applications such as tele-presence, grasping of objects, navigation, etc. that use multi-sensor fusion and machine learning to control a humanoid robot to perform a desired task. The paper also includes a review of the methods and system design used in the discussed applications."
2167,Drivers of Mobile Health Acceptance and Use From the Patient Perspective: Survey Study and Quantitative Model Development,"BACKGROUND: Mobile health (mHealth) has potential to play a significant role in realizing a reversal of the current paradigm in health care toward a more patient-centric and more collaborative system to improve the outcomes obtained along with the quality and sustainability of health care systems. OBJECTIVE: The aim of this study was to explore and understand individual mHealth acceptance drivers between two groups of users: those with chronic health conditions and those without. METHODS: The extended unified theory of acceptance and usage of technology (UTAUT2) was enhanced with a new health-related framework: behavior intention to recommend and new mediation effects. We applied partial least squares (PLS) causal modeling to test the research model. RESULTS: We obtained 322 valid responses through an online questionnaire. The drivers of behavior intention with statistical significance were performance expectancy (β=.29, P<.001), habit (β=.39, P<.001), and personal empowerment (β=.18, P=.01). The precursors of use behavior were habit (β= .47, P<.001) and personal empowerment (β=.17, P=.01). Behavior intention to recommend was significantly influenced by behavior intention (β=.58, P<.001) and personal empowerment (β=.26, P<.001). The model explained 66% of the total variance in behavior intention, 54% of the variance in use behavior, and 70% of the variance in behavior intention to recommend. CONCLUSIONS: Our study demonstrates a significant role of personal empowerment, as a second-order construct, in the mHealth acceptance context. The presence of a chronic health condition predicates an impact on acceptance of this technology."
2168,Correction: Considerations for an Individual-Level Population Notification System for Pandemic Response: A Review and Prototype,
2169,A novel poxvirus isolated from an Egyptian fruit bat in Israel,"An Egyptian fruit bat (Rousettus aegyptiacus) from the Zoological Gardens, at Tel Aviv, Israel, showed pox‐like clinical signs including vesicular and nodular skin lesions on the wings. Cell culture isolation, histopathology, electron microscopy and molecular analysis, revealed the presence of a novel bat poxvirus. Future research is needed to determine whether this virus can affect human health."
2170,Response to “COVID-19 conundrum: Clinical phenotyping based on pathophysiology as a promising approach to guide therapy in a novel illness” and “Strengthening the foundation of the house of CARDS by phenotyping on the fly” and “COVID-19 phenotypes: leading or misleading?”,"We argue that phenotyping of COVID-19 related ARDS should be done using careful, data-driven approaches."
2171,Tmprss12 is required for sperm motility and uterotubal junction migration in mice(†),"Spermatozoa are produced in the testis but gain their fertilizing ability during epididymal migration. This necessary step in sperm maturation includes posttranslational modification of sperm membrane proteins that includes protein processing by proteases. However, the molecular mechanism underpinning this epididymal sperm maturation remains unknown. In this study, we focused on transmembrane serine protease 12 (Tmprss12). Based on multi-tissue expression analysis by PCR, Tmprss12 was specifically expressed in the testis, and its expression started on day 10 postpartum, corresponding to the stage of zygotene spermatocytes. TMPRSS12 was detected in the acrosomal region of spermatozoa by immunostaining. To reveal the physiological function of TMPRSS12, we generated two knockout (KO) mouse lines using the CRISPR/Cas9 system. Both indel and large deletion lines were male sterile showing that TMPRSS12 is essential for male fertility. Although KO males exhibited normal spermatogenesis and sperm morphology, ejaculated spermatozoa failed to migrate from the uterus to the oviduct. Further analysis revealed that a disintegrin and metalloprotease 3 (ADAM3), an essential protein on the sperm membrane surface that is required for sperm migration, was disrupted in KO spermatozoa. Moreover, we found that KO spermatozoa showed reduced sperm motility via computer-assisted sperm analysis, resulting in a low fertilization rate in vitro. Taken together, these data indicate that TMPRSS12 has dual functions in regulating sperm motility and ADAM3-related sperm migration to the oviduct. Because Tmprss12 is conserved among mammals, including humans, our results may explain some genetic cases of idiopathic male infertility, and TMPRSS12 and its downstream cascade may be novel targets for contraception."
2172,Pandemic Pause: Lessons in Unscrambling My Daily Life,
2173,"Uncertainty Is the New Norm, Adaptability Is Essential",
2174,Excessive dietary salt promotes aortic stiffness in murine renovascular hypertension,"Renovascular hypertension is characterized by activation of the renin-angiotensin-aldosterone system, blunted natriuretic responses, and elevated sympathetic nerve activity. Excess dietary salt intake exaggerates arterial blood pressure (ABP) in multiple models of experimental hypertension. The present study tested whether a high-salt diet exaggerated ABP and vascular dysfunction in a 2-kidney, 1-clip (2K1C) murine model. Male C57BL/6J mice (8–12 wk) were randomly assigned, and fed a 0.1% or 4.0% NaCl diet, and instrumented with telemetry units to measure ABP. Then, the 2K1C model was produced by placing a cuff around the right renal artery. Systolic, diastolic, and mean ABP were significantly higher in mice fed 4.0% vs. 0.1% NaCl at 1 wk but not after 3 wk. Interestingly, 2K1C hypertension progressively increased arterial pulse pressure in both groups; however, the magnitude was significantly greater in mice fed 4.0% vs. 0.1% NaCl at 3 wk. Moreover, pulse wave velocity was significantly greater in 2K1C mice fed 4.0% vs. 0.1% NaCl diet or sham-operated mice fed either diet. Histological assessment of aortas indicated no structural differences among groups. Finally, endothelium-dependent vasodilation was significantly and selectively attenuated in the aorta but not mesenteric arteries of 2K1C mice fed 4.0% NaCl vs. 0.1% NaCl or sham-operated control mice. The findings suggest that dietary salt loading transiently exaggerates 2K1C renovascular hypertension but promotes chronic aortic stiffness and selective aortic vascular dysfunction. NEW & NOTEWORTHY High dietary salt exaggerates hypertension in multiple experimental models. Here we demonstrate that a high-salt diet produces a greater increase in arterial blood pressure at 1 wk after induction of 2-kidney, 1-clip (2K1C) hypertension but not at 3 wk. Interestingly, 2K1C mice fed a high-salt diet displayed an exaggerated pulse pressure, elevated pulse wave velocity, and reduced endothelium-dependent vasodilation of the aorta but not mesenteric arteries. These findings suggest that dietary salt may interact with underlying cardiovascular disease to promote selective vascular dysfunction and aortic stiffness."
2175,Functional knockout of ASIC3 attenuates the exercise pressor reflex in decerebrated rats with ligated femoral arteries,"The exercise pressor reflex arises from contracting muscle and is manifested by increases in arterial pressure, heart rate, and cardiac contractility. In patients with peripheral artery disease, the exercise pressor reflex is exaggerated. This effect is believed to be caused by a metabolite whose concentration is increased when the working muscles are inadequately perfused. Previous work in rats with simulated peripheral artery disease has shown that pharmacological blockade of acid-sensing ion channel 3 (ASIC3), which is found on group III and IV afferents, prevented the exaggeration of the exercise pressor reflex. Blockade of ASIC3, however, may have off-target effects that preclude a conclusion that ASIC3 plays a role in evoking the reflex in rats with simulated peripheral artery disease. In the present experiments performed in decerebrated rats with simulated peripheral artery disease, we compared the exercise pressor reflex in rats with a functional knockout of the ASIC3 (KO) with the reflex in their wild-type counterparts (WT). We found that the exercise pressor reflex in ASIC3 KO rats was significantly lower than the exercise pressor reflex in their WT counterparts (P < 0.05). ASIC 3 KO rats demonstrated lower pressor responses to intra‐arterial injection of diprotonated phosphate (86 mM; pH 6.0), lactic acid (12 mM; pH 2.85), and capsaicin (0.2 μg; pH 7.2) (P < 0.05). In contrast, both ligated WT and ASIC3 KO rats displayed similar pressor responses to tendon stretch (P > 0.05). We conclude that ASIC3 play an important role in evoking the exaggerated exercise pressor reflex in rats with peripheral artery disease. NEW & NOTEWORTHY We used a genetic approach to test the hypothesis that the magnitude of the exercise pressor reflex evoked in ligated ASIC3 KO rats was significantly lower than the magnitude of the exercise pressor reflex evoked in their ligated wild-type (WT) counterparts. The pressor response to contraction in ligated ASIC3 KO rats was significantly smaller than was the pressor response to contraction in ligated WT rats."
2176,Fast in vivo detection of myocardial norepinephrine levels in the beating porcine heart,"The sympathetic nervous system modulates cardiac function by controlling key parameters such as chronotropy and inotropy. Sympathetic control of ventricular function occurs through extrinsic innervation arising from the stellate ganglia and thoracic sympathetic chain. In the healthy heart, sympathetic release of norepinephrine (NE) results in positive modulation of chronotropy, inotropy, and dromotropy, significantly increasing cardiac output. However, in the setting of myocardial infarction or injury, sympathetic activation persists, contributing to heart failure and increasing the risk of arrhythmias, including sudden cardiac death. Methodologies for detection of norepinephrine in cardiac tissue are limited. Present techniques rely on microdialysis for analysis by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ED), radioimmunoassay, or other immunoassays, such as enzyme-linked immunosorbent assay (ELISA). Although significant information about the release and action of norepinephrine has been obtained with these methodologies, they are limited in temporal resolution, require large sample volumes, and provide results with a significant delay after sample collection (hours to weeks). In this study, we report a novel approach for measurement of interstitial cardiac norepinephrine, using minimally invasive, electrode-based, fast-scanning cyclic voltammetry (FSCV) applied in a beating porcine heart. The first multispatial and high temporal resolution, multichannel measurements of NE release in vivo are provided. Our data demonstrate rapid changes in interstitial NE profiles with regional differences in response to coronary ischemia, sympathetic nerve stimulation, and alterations in preload/afterload. NEW & NOTEWORTHY Pharmacological, electrical, or surgical regulation of sympathetic neuronal control can be used to modulate cardiac function and treat arrhythmias. However, present methods for monitoring sympathetic release of norepinephrine in the heart are limited in spatial and temporal resolution. Here, we provide for the first time a methodology and demonstration of practice and rapid measures of individualized regional autonomic neurotransmitter levels in a beating heart. We show dynamic, spatially resolved release profiles under normal and pathological conditions."
2177,"Acceptability and Utility of an Open-Access, Online Single-Session Intervention Platform for Adolescent Mental Health","BACKGROUND: Many youths with mental health needs are unable to access care. Single-session interventions (SSIs) have helped reduce youth psychopathology across multiple trials, promising to broaden access to effective, low-intensity supports. Online, self-guided SSIs may be uniquely scalable, particularly if they are freely available for as-needed use. However, the acceptability of online SSI and their efficacy have remained unexamined outside of controlled trials, and their practical utility is poorly understood. OBJECTIVE: We evaluated the perceived acceptability and proximal effects of Project YES (Youth Empowerment & Support), an open-access platform offering three online SSIs for youth internalizing distress. METHODS: After selecting one of three SSIs to complete, participants (ages 11-17 years) reported pre- and post-SSI levels of clinically relevant outcomes that SSIs may target (eg, hopelessness, self-hate) and perceived SSI acceptability. User-pattern variables, demographics, and depressive symptoms were collected to characterize youths engaging with YES. RESULTS: From September 2019 through March 2020, 694 youths accessed YES, 539 began, and 187 completed a 30-minute, self-guided SSI. SSI completers reported clinically elevated depressive symptoms, on average, and were diverse on several dimensions (53.75% non-white; 78.10% female; 43.23% sexual minorities). Regardless of SSI selection, completers reported pre- to post-program reductions in hopelessness (d(av)=0.53; d(z)=0.71), self-hate (d(av)=0.32; d(z)=0.61), perceived control (d(av)=0.60; d(z)=0.72) and agency (d(av)=0.39; d(z)=0.50). Youths rated all SSIs as acceptable (eg, enjoyable, likely to help peers). CONCLUSIONS: Results support the perceived acceptability and utility of open-access, free-of-charge SSIs for youth experiencing internalizing distress. TRIAL REGISTRATION: Open Science Framework; osf.io/e52p3"
2178,The effect of antenatal magnesium sulfate on intraventricular hemorrhage in premature infants: a systematic review and meta-analysis,"OBJECTIVE: The aim of this systematic review and meta-analysis study was to determine the pooled estimate of the effect of antenatal magnesium sulfate (MgSO(4)) on intraventricular hemorrhage (IVH) in premature infants. METHODS: Two review authors independently searched all randomized clinical trials from international databases, including Medline (PubMed), Web of Sciences, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Research Registers of ongoing trials (ClinicalTrials.gov), from January 1989 to August 2017. Two independent review authors were responsible for data collection. After extracting the necessary information from the evaluated articles, metaanalysis of the data was performed using Stata version 14. Also, sources of heterogeneity among studies were determined by Meta regression. RESULTS: In this study, among 126 articles that were extracted from primary studies, 7 papers that evaluated the effect of MgSO(4) on IVH were eligible for inclusion in the meta-analysis. The results of the meta-analysis showed that pooled relative risk (95% confidence interval [CI]) was 0.80 (95% CI, 0.63 to 1.03) for the effect of MgSO(4) on IVH. CONCLUSION: Results of this study showed that although MgSO(4) had a protective effect on IVH in premature infants, this effect was not statistically significant. Further studies are needed to determine the best dosage, timing, and gestational age to achieve the optimum effect of MgSO(4) on IVH. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) Identifier: CRD42019119610"
2179,Dipeptidyl peptidase like 6 promoter methylation is a potential prognostic biomarker for pancreatic ductal adenocarcinoma,"Background: Hypermethylation of gene promoters plays an important role in tumorigenesis. The present study aimed to identify and validate promoter methylation-driven genes (PMDGs) for pancreatic ductal adenocarcinoma (PDAC). Methods: Based on GSE49149 and the PDAC cohort of The Cancer Genome Atlas (TCGA), differential analyses of promoter methylation, correlation analysis, and Cox regression analysis were performed to identify PMDGs. The promoter methylation level was assessed by bisulfite sequencing polymerase chain reaction (BSP) in paired tumor and normal tissues of 72 PDAC patients. Kaplan−Meier survival analyses were performed to evaluate the clinical value of PMDGs. Results: In GSE49149, the β-value of the dipeptidyl peptidase like 6 (DPP6) promoter was significantly higher in tumor compared with normal samples (0.50 vs. 0.24, P<0.001). In the PDAC cohort of TCGA, the methylation level of the DPP6 promoter was negatively correlated with mRNA expression (r = −0.54, P<0.001). In a multivariate Cox regression analysis, hypermethylation of the DPP6 promoter was an independent risk factor for PDAC (hazard ratio (HR) = 543.91, P=0.002). The results of BSP revealed that the number of methylated CG sites in the DPP6 promoter was greater in tumor samples than in normal samples (7.43 vs. 2.78, P<0.001). The methylation level of the DPP6 promoter was moderately effective at distinguishing tumor from normal samples (area under ROC curve (AUC) = 0.74, P<0.001). Hypermethylation of the DPP6 promoter was associated with poor overall (HR = 3.61, P<0.001) and disease-free (HR = 2.01, P=0.016) survivals for PDAC patients. Conclusion: These results indicate that DPP6 promoter methylation is a potential prognostic biomarker for PDAC."
2180,Optimization of Vehicle Routing for Waste Collection and Transportation,"For the sake of solving the optimization problem of urban waste collection and transportation in China, a priority considered green vehicle routing problem (PCGVRP) model in a waste management system is constructed in this paper, and specific algorithms are designed to solve the model. We pay particular concern to the possibility of immediate waste collection services for high-priority waste bins, e.g., those containing hospital or medical waste, because the harmful waste needs to be collected immediately. Otherwise, these may cause dangerous or negative effects. From the perspective of environmental protection, the proposed PCGVRP model considers both greenhouse gas (GHG) emission costs and conventional waste management costs. Waste filling level (WFL) is considered with the deployment of sensors on waste bins to realize dynamic routes instead of fixed routes, so that the economy and efficiency of waste collection and transportation can be improved. The optimal solution is obtained by a local search hybrid algorithm (LSHA), that is, the initial optimal solution is obtained by particle swarm optimization (PSO) and then a local search is performed on the initial optimal solution, which will be optimized by a simulated annealing (SA) algorithm by virtue of the global search capability. Several instances are selected from the database of capacitated vehicle routing problem (CVRP) so as to test and verify the effectiveness of the proposed LSHA algorithm. In addition, to obtain credible results and conclusions, a case using data about waste collection and transportation is employed to verify the PCGVRP model, and the effectiveness and practicability of the model was tested by setting a series of values of bins’ number with high priority and WFLs. The results show that (1) the proposed model can achieve a 42.3% reduction of negative effect compared with the traditional one; (2) a certain value of WFL between 60% and 80% can realize high efficiency of the waste collection and transportation; and (3) the best specific value of WFL is determined by the number of waste bins with high priority. Finally, some constructive propositions are put forward for the Environmental Protection Administration and waste management institutions based on these conclusions."
2181,The Effects of Tai Chi and Qigong on Immune Responses: A Systematic Review and Meta-Analysis,"Background: Effective preventative health interventions are essential to maintain well-being among healthcare professionals and the public, especially during times of health crises. Several studies have suggested that Tai Chi and Qigong (TQ) have positive impacts on the immune system and its response to inflammation. The aim of this review is to evaluate the current evidence of the effects of TQ on these parameters. Methods: Electronic searches were conducted on databases (Medline, PubMed, Embase and ScienceDirect). Searches were performed using the following keywords: “Tai Chi or Qigong” and “immune system, immune function, immunity, Immun*, inflammation and cytokines”. Studies published as full-text randomized controlled trials (RCTs) in English were included. Estimates of change in the levels of immune cells and inflammatory biomarkers were pooled using a random-effects meta-analysis where randomised comparisons were available for TQ versus active controls and TQ versus non-active controls. Results: Nineteen RCTs were selected for review with a total of 1686 participants and a range of 32 to 252 participants within the studies. Overall, a random-effects meta-analysis found that, compared with control conditions, TQ has a significant small effect of increasing the levels of immune cells (SMD, 0.28; 95% CI, 0.13 to 0.43, p = 0.00), I(2) = 45%, but not a significant effect on reducing the levels of inflammation (SMD, −0.15; 95% CI, −0.39 to 0.09, p = 0.21), I(2) = 85%, as measured by the systemic inflammation biomarker C-reactive protein (CRP) and cell mediated biomarker cytokines. This difference in results is due to the bidirectional regulation of cytokines. An overall risk of bias assessment found three RCTs with a low risk of bias, six RCTs with some concerns of bias, and ten RCTs with a high risk of bias. Conclusions: Current evidence indicates that practising TQ has a physiologic impact on immune system functioning and inflammatory responses. Rigorous studies are needed to guide clinical guidelines and harness the power of TQ to promote health and wellbeing."
2182,"Use of Online Food Delivery Services to Order Food Prepared Away-From-Home and Associated Sociodemographic Characteristics: A Cross-Sectional, Multi-Country Analysis","Online food delivery services like Just Eat and Grubhub facilitate online ordering and home delivery of food prepared away-from-home. It is poorly understood how these services are used and by whom. This study investigated the prevalence of online food delivery service use and sociodemographic characteristics of customers, in and across Australia, Canada, Mexico, the UK, and the USA. We analyzed online survey data (n = 19,378) from the International Food Policy Study, conducted in 2018. We identified respondents who reported any online food delivery service use in the past 7 days and calculated the frequency of use and number of meals ordered. We investigated whether odds of any online food delivery service use in the past 7 days differed by sociodemographic characteristics using adjusted logistic regression. Overall, 15% of respondents (n = 2929) reported online food delivery service use, with the greatest prevalence amongst respondents in Mexico (n = 839 (26%)). Online food delivery services had most frequently been used once and the median number of meals purchased through this mode of order was two. Odds of any online food delivery service use were lower per additional year of age (OR: 0.95; 95% CI: 0.94, 0.95) and greater for respondents who were male (OR: 1.50; 95% CI: 1.35, 1.66), that identified with an ethnic minority (OR: 1.57; 95% CI: 1.38, 1.78), were highly educated (OR: 1.66; 95% CI: 1.46, 1.90), or living with children (OR: 2.71; 95% CI: 2.44, 3.01). Further research is required to explore how online food delivery services may influence diet and health."
2183,The Effect of Dynamic Food Labels with Real-Time Feedback on Diet Quality: Results from a Randomized Controlled Trial,"The rising prevalence of non-communicable diseases has brought attention to the importance of consuming a healthy diet. One strategy to improve diet quality is through front-of-pack (FOP) nutrition labels. Taking advantage of an online grocery store, we allowed consumers to choose the FOP labels they preferred, and combined this information with real-time feedback on the overall nutritional quality of the shopping basket. We hypothesized that these dynamic food labels with real-time feedback (DFLF) would improve nutritional quality of food purchases. This trial followed a two-arm (no-label control and DFLF) crossover design with 125 participants exposed to each condition once in random order via an online grocery store. A first difference regression model allowed for estimating the unbiased effect of the DFLF on diet quality, measured by the weighted average Nutri-Score (ranging 1 to 5) per serving (primary) and changes in select nutrients and calories. The mean weighted Nutri-Score was 0.4 (12.6%) higher in the DFLF arm (CI: [0.2, 0.6]) relative to the control. The DFLF also decreased the amount of sugar per serving by 0.9 g (CI: [−1.7, −0.0]) and total sugar per shop by 169.5 g (CI: [−284.5, −54.5]). The DFLF features significantly improved nutrition quality relative to no labelling, as measured by average Nutri-Score values. These results shed light on the considerable potential of the online shopping environment to improve diet quality through customization and real time feedback."
2184,"Pathological, Bacteriological and Virological Findings in Sudden and Unexpected Deaths in Young Dogs","SIMPLE SUMMARY: “Sudden death” has been defined by the World Health Organization as a non-violent, unexpected death occurring less than 24 h from the onset of symptoms. The causes of sudden death have been widely investigated in human forensic medicine. In contrast, few studies have been reported in the veterinary literature. This study aimed to investigate the frequency of sudden deaths in young dogs in different age ranges. A secondary aim was to collect information regarding clinical symptoms, and pathological and microbiological findings related to sudden death in young dogs. The results of the present study demonstrate that the highest frequency of sudden death occurs in animals in an age range from 10 days to 1 month and from 6 to 12 months. The most frequently observed clinical symptoms in cases of sudden death were acute respiratory symptoms. Furthermore, Canine parvovirus type 2, E. coli, Canine Distemper Virus, Clostridium perfringens type A, and Pasteurella spp. were the main causes of death observed in the present study. The results reported in the present study could provide a reference basis to better investigate sudden death in veterinary clinical practice. ABSTRACT: In human medicine, “sudden death” has been defined by the World Health Organization (WHO) as a non-violent, unexpected death occurring less than 24 h from the onset of symptoms. The aims of this study were: (1) to estimate the proportional mortality ratio for “sudden and unexpected death” (SUD) in young dogs; (2) to investigate the pathological and microbiological findings in SUD cases in young dogs. For these purposes, a retrospective study of a total of 145 cases of young dead dogs was performed. For each case, we collected information about the age, medical history and the gross and microbiological findings of the animals. The results of this study found 21 cases of SUD. The most frequently observed clinical symptoms in the cases of sudden death were acute respiratory symptoms, followed by acute gastroenteric symptoms, non-specific symptoms and neurological symptoms. The evaluation of necropsy reports allowed us to observe enteritis in 18 out of 21 cases and pneumonia in seven out of 21 cases. Viral infection with Canine parvovirus type 2 was the most common cause of SUD observed. These results could provide a valuable tool for the investigation of sudden death in young dogs."
2185,Coagulation profile in severe COVID-19 patients: what do we know so far?,
2186,MicroRNA22-5p targets ten-eleven translocation and regulates estrogen receptor 2 expression in infertile women with minimal/mild endometriosis during implantation window,"Based on microRNA (miR) microarray analysis, we previously found that miR22-5p expression is decreased in the mid-luteal endometrium of women with minimal/mild endometriosis. Bioinformatics analysis predicted that miR22-5p targets ten-eleven translocation (TET2) 3′-untranslated region. This study aimed to determine the regulation and roles of miR22-5p in the pathogenesis of minimal/mild endometriosis-associated infertility. MiR22-5p and TET2 expression in the mid-luteal endometrium from women with or without minimal/mild endometriosis was analyzed. After transfection with miR22-5p mimics or inhibitor, TET2 expression was analyzed by quantitative reverse transcription (RT-q) PCR, western blotting and immunohistochemistry. 5-Hydroxymethylcytosine was determined by immunofluorescence and dot blotting. Expression and promoter methylation of estrogen receptor 2 (ESR2) was measured by RT-qPCR and western blotting, and by bisulfite sequencing, respectively. We first established that miR22-5p expression decreased and TET2 expression increased in minimal/mild endometriosis during implantation window. TET2 was found to be a direct target of miR22-5p. MiR22-5p regulated the expression of ESR2, but did not directly affect methylation of its promoter region (–197/+359). Our results suggest that an imbalance in miR22-5p expression in the mid-luteal endometrium may be involved in minimal/mild endometriosis-associated infertility."
2187,Assessment of Preprint Policies of Top-Ranked Clinical Journals,This cross-sectional study examines the preprint publication policies of 100 clinical journals with the highest impact factor.
2188,Fostering Transnational Research Partnerships to Advance Men’s Health,
2189,Editorial note: possible undisclosed conflict of interest,
2190,Addendum for Euro Surveill. 2020;25(3),
2191,"Koala retrovirus epidemiology, transmission mode, pathogenesis, and host immune response in koalas (Phascolarctos cinereus): a review","Koala retrovirus (KoRV) is a major threat to koala health and conservation. It also represents a series of challenges across the fields of virology, immunology, and epidemiology that are of great potential interest to any researcher in the field of retroviral diseases. KoRV is a gammaretrovirus that is present in both endogenous and exogenous forms in koala populations, with a still-active endogenization process. KoRV may induce immunosuppression and neoplastic conditions such as lymphoma and leukemia and play a role in chlamydiosis and other diseases in koalas. KoRV transmission modes, pathogenesis, and host immune response still remain unclear, and a clear understanding of these areas is critical for devising effective preventative and therapeutic strategies. Research on KoRV is clearly critical for koala conservation. In this review, we provide an overview of the current understanding and future challenges related to KoRV epidemiology, transmission mode, pathogenesis, and host immune response and discuss prospects for therapeutic and preventive vaccines."
2192,"2’-Fluoro-2’-deoxycytidine inhibits murine norovirus replication and synergizes MPA, ribavirin and T705","Noroviruses are the main causative agents of acute viral gastroenteritis worldwide. However, no vaccine or specific antiviral treatment is available, imposing a heavy global health burden. The nucleoside analogue 2’-fluoro-2’-deoxycytidine (2’-FdC) has been reported to have broad antiviral activity. Here, we report that 2’-FdC significantly inhibits murine norovirus replication in macrophages. This effect was partially reversed by exogenous supplementation of cytidine triphosphate. The combination of 2’-FdC with mycophenolic acid, ribavirin or favipiravir (T705) exerts synergistic antiviral effects. These results indicate that 2’-FdC is a potential candidate for antiviral drug development against norovirus infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04759-4) contains supplementary material, which is available to authorized users."
2193,Molecular epidemiology of astrovirus in children with gastroenteritis in southwestern Nigeria,"Human astrovirus (HAstV) is recognized as one of the major causative agents of acute gastroenteritis in children worldwide. Data on the genetic diversity of HAstV in Nigeria are limited. The aim of this study was to determine the prevalence and molecular epidemiology of classical HAstV in children under 5 years of age with acute gastroenteritis in Ogun State, Nigeria. Fecal samples (331) as well as socio-demographic and clinical data were collected across the three senatorial districts of the state from February 2015 to April 2017. One hundred seventy-five samples were randomly selected and analyzed for the presence of HAstV using RT-PCR. PCR amplicons from positive samples were sequenced, and phylogenetic analysis was done to determine genotypes and lineages. The overall prevalence rate was 19.4% (34), with the highest occurrence observed in 2015 (41.4%). Viral coinfections were detected in 13 cases (38.2%). HAstV infection occurred throughout the year and in all age groups, mainly in the age group of 0-12 months. There was significant association between prevalence rate and collection year; however, no association was observed with gender, age, symptoms or risk factors. HAstV-5 was the predominant genotype (76.5%) circulating throughout the study period, followed by HAstV-1 (23.5%), which circulated only in the first 2 years of the study. Phylogenetic analysis showed that all HAstV-5 strains detected belonged to the 5a lineage, while HAstV-1 strains were grouped into lineage 1b. This study, to the best of our knowledge, is the first comprehensive report on molecular characterization of classical HAstV among children with gastroenteritis in the country, and this will serve as baseline information for implementing appropriate infection control practices."
2194,Lymphopenia and lymphocytosis in practical healthy people born and living in the North,"INTRODUCTION: The purpose of this study was to elucidate the mechanisms of the formation of lymphopenia and lymphocytosis in healthy people, who are living and working in the Arctic region. MATERIALS AND METHODS: A total of 88 practically healthy people living and working in the Arctic region were examined. An analysis of the results was carried out, depending on the concentration of lymphocytes in the peripheral venous blood: group 1—with lymphopenia, the content of lymphocytes below 1.5 × 10(9)cl/L (21 people); group 2—with a normal lymphocyte content from 1.5 to 3.5 × 10(9)cl/L (47 people); and group 3—with lymphocytosis, lymphocytes in the peripheral blood of more than 3.5 × 10(9)cl/L (20 people). RESULTS: It has been established that the main mechanism for the formation of lymphopenia in a person living in the Arctic is the activation of the migration of functionally active lymphocytes in the tissue. The decrease in the number of circulating lymphocytes is a consequence of their redistribution from the circulating pool to the marginal one and an increase in the activity of adhesive molecules, in particular, the selectin ligand. It was revealed that an increase in the content of lymphocytes in the blood occurs upon the activation of the intracellular energy‐intensive mechanisms of lymphoproliferation with an increase in the consumption of intracellular ATP and the participation of the nuclear factor of activated T cells 1. It was shown that the restoration of the circulating pool of mature neutrophils is ensured by the principle of reverse regulation in response to neutropenia by stimulating granulocyte‐colony stimulating factor granulopoiesis. CONCLUSIONS: The main mechanism for the formation of lymphopenia and lymphocytosis in healthy people was established."
2195,TRAIL-based gene delivery and therapeutic strategies,"TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), also known as APO2L, belongs to the tumor necrosis factor family. By binding to the death receptor 4 (DR4) or DR5, TRAIL induces apoptosis of tumor cells without causing side toxicity in normal tissues. In recent years TRAIL-based therapy has attracted great attention for its promise of serving as a cancer drug candidate. However, the treatment efficacy of TRAIL protein was under expectation in the clinical trials because of the short half-life and the resistance of cancer cells. TRAIL gene transfection can produce a “bystander effect” of tumor cell killing and provide a potential solution to TRAIL-based cancer therapy. In this review we focus on TRAIL gene therapy and various design strategies of TRAIL DNA delivery including non-viral vectors and cell-based TRAIL therapy. In order to sensitize the tumor cells to TRAIL-induced apoptosis, combination therapy of TRAIL DNA with other drugs by the codelivery methods for yielding a synergistic antitumor efficacy is summarized. The opportunities and challenges of TRAIL-based gene delivery and therapy are discussed."
2196,Will the new decade bring home remote monitoring of heart failure patients?,
2197,Remote monitoring of chronic heart failure patients: invasive versus non-invasive tools for optimising patient management,"Exacerbations of chronic heart failure (HF) with the necessity for hospitalisation impact hospital resources significantly. Despite all of the achievements in medical management and non-pharmacological therapy that improve the outcome in HF, new strategies are needed to prevent HF-related hospitalisations by keeping stable HF patients out of the hospital and focusing resources on unstable HF patients. Remote monitoring of these patients could provide the physicians with an additional tool to intervene adequately and promptly. Results of telemonitoring to date are inconsistent, especially those of telemonitoring with traditional non-haemodynamic parameters. Recently, the CardioMEMS device (Abbott Inc., Atlanta, GA, USA), an implantable haemodynamic remote monitoring sensor, has shown promising results in preventing HF-related hospitalisations in chronic HF patients hospitalised in the previous year and in New York Heart Association functional class III in the United States. This review provides an overview of the available evidence on remote monitoring in chronic HF patients and future perspectives for the efficacy and cost-effectiveness of these strategies."
2198,Decreasing the Duration of Discharge Antibiotic Treatment Following Inpatient Skin and Soft Tissue Abscess Drainage,"INTRODUCTION: Skin and soft tissue abscesses do not require prolonged systemic antimicrobial treatment following drainage. We aimed to decrease the duration of discharge antibiotic treatment to less than 5 days following inpatient incision and drainage of uncomplicated abscesses. METHODS: A new treatment protocol that defined uncomplicated abscesses, as well as inclusion and exclusion criteria, was created to monitor the accurate duration of prescribed therapy at discharge. We implemented a treatment algorithm that takes into account the epidemiologic changes in microbial etiologies and the presence of systemic findings for patients after surgical incision and drainage. We used control charts to assess the impact of the interventions. RESULTS: Four hundred and eighteen patients were discharged following abscess drainage from our inpatient infectious diseases unit in 2016. The patients were 3 months to 21 years of age. Only 72 (17%) patients had prescribed discharge antibiotic treatment courses that were less than 5 days [range 0–31 days, median 8 days (IQR 6, 9)], and the average prescribed course at discharge was 8.6 days. During the study period, we significantly decreased the average duration of discharge antibiotics to 7.3 days in all patients (P = 0.0016, 95% CI: −2.1036 to −0.4964, difference of means −1.3). The discharge treatment duration of patients with uncomplicated abscess was shorter at 4.7 days [range 0–9 days, median 5 days, (IQR 3, 5)]. Prescription compliance to less than 5 days treatment course at discharge increased from the baseline of 17% to 42% overall. CONCLUSIONS: Standardizing definitions of uncomplicated skin and soft tissue abscesses was critical to the success of this project. In addition to possible improved treatment adherence and decreased side effects, our protocol led to decreased patient care costs with no documented changes in readmission rates."
2199,Time to apply a social determinants of health lens to addressing sickle cell disorders in sub-Saharan Africa,
2200,Impact of a free care policy on the utilisation of health services during an Ebola outbreak in the Democratic Republic of Congo: an interrupted time-series analysis,"BACKGROUND: During past outbreaks of Ebola virus disease (EVD) and other infectious diseases, health service utilisation declined among the general public, delaying health seeking behaviour and affecting population health. From May to July 2018, the Democratic Republic of Congo experienced an outbreak of EVD in Equateur province. The Ministry of Public Health introduced a free care policy (FCP) in both affected and neighbouring health zones. We evaluated the impact of this policy on health service utilisation. METHODS: Using monthly data from the national Health Management Information System from January 2017 to January 2019, we examined rates of the use of nine health services at primary health facilities: total visits; first and fourth antenatal care visits; institutional deliveries; postnatal care visits; diphtheria, pertussis and tetanus (DTP) vaccinations and visits for uncomplicated malaria, pneumonia and diarrhoea. We used controlled interrupted time series analysis with a mixed effects model to estimate changes in the rates of services use during the policy (June–September 2018) and afterwards. FINDINGS: Overall, use of most services increased compared to control health zones, including EVD affected areas. Total visits and visits for pneumonia and diarrhoea initially increased more than two-fold relative to the control areas (p<0.001), while institutional deliveries and first antenatal care increased between 20% and 50% (p<0.01). Visits for DTP, fourth antenatal care visits and postnatal care visits were not significantly affected. During the FCP period, visit rates followed a downward trend. Most increases did not persist after the policy ended. INTERPRETATION: The FCP was effective at rapidly increasing the use of some health services both EVD affected and not affected health zones, but this effect was not sustained post FCP. Such policies may mitigate the adverse impact of infectious disease outbreaks on population health."
2201,WHO recommendations on antenatal nutrition: an update on multiple micronutrient supplements,
2202,Filoviruses Use the HOPS Complex and UVRAG To Traffic to Niemann-Pick C1 Compartments during Viral Entry,"Ebola virus (EBOV) entry requires internalization into host cells and extensive trafficking through the endolysosomal network in order to reach late endosomal/lysosomal compartments that contain triggering factors for viral membrane fusion. These triggering factors include low-pH-activated cellular cathepsin proteases, which cleave the EBOV glycoprotein (GP), exposing a domain which binds to the filoviral receptor, the cholesterol transporter Niemann-Pick C1 (NPC1). Here, we report that trafficking of EBOV to NPC1 requires expression of the homotypic fusion and protein sorting (HOPS) tethering complex as well as its regulator, UV radiation resistance-associated gene (UVRAG). Using an inducible clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, we demonstrated that depletion of HOPS subunits as well as UVRAG impairs entry by all pathogenic filoviruses. UVRAG depletion resulted in reduced delivery of EBOV virions to NPC1(+) cellular compartments. Furthermore, we show that deletion of a domain on UVRAG known to be required for interaction with the HOPS complex results in impaired EBOV entry. Taken together, our studies demonstrate that EBOV requires both expression of and coordination between the HOPS complex and UVRAG in order to mediate efficient viral entry. IMPORTANCE Ebola viruses (EBOV) and other filoviruses cause sporadic and unpredictable outbreaks of highly lethal diseases. The lack of FDA-approved therapeutics, particularly ones with panfiloviral specificity, highlights the need for continued research efforts to understand aspects of the viral life cycle that are common to all filoviruses. As such, viral entry is of particular interest, as all filoviruses must reach cellular compartments containing the viral receptor Niemann-Pick C1 to enter cells. Here, we present an inducible CRISPR/Cas9 method to rapidly and efficiently generate knockout cells in order to interrogate the roles of a broad range of host factors in viral entry. Using this approach, we showed that EBOV entry depends on both the homotypic fusion and protein sorting (HOPS) tethering complex in coordination with UV radiation resistance-associated gene (UVRAG). Importantly, we demonstrate that the HOPS complex and UVRAG are required by all pathogenic filoviruses, representing potential targets for panfiloviral therapeutics."
2203,Exocytosis of Progeny Infectious Varicella-Zoster Virus Particles via a Mannose-6-Phosphate Receptor Pathway without Xenophagy following Secondary Envelopment,"The literature on the egress of different herpesviruses after secondary envelopment is contradictory. In this report, we investigated varicella-zoster virus (VZV) egress in a cell line from a child with Pompe disease, a glycogen storage disease caused by a defect in the enzyme required for glycogen digestion. In Pompe cells, both the late autophagy pathway and the mannose-6-phosphate receptor (M6PR) pathway are interrupted. We have postulated that intact autophagic flux is required for higher recoveries of VZV infectivity. To test that hypothesis, we infected Pompe cells and then assessed the VZV infectious cycle. We discovered that the infectious cycle in Pompe cells was remarkably different from that of either fibroblasts or melanoma cells. No large late endosomes filled with VZV particles were observed in Pompe cells; only individual viral particles in small vacuoles were seen. The distribution of the M6PR pathway (trans-Golgi network to late endosomes) was constrained in infected Pompe cells. When cells were analyzed with two different anti-M6PR antibodies, extensive colocalization of the major VZV glycoprotein gE (known to contain M6P residues) and the M6P receptor (M6PR) was documented in the viral highways at the surfaces of non-Pompe cells after maximum-intensity projection of confocal z-stacks, but neither gE nor the M6PR was seen in abundance at the surfaces of infected Pompe cells. Taken together, our results suggested that (i) Pompe cells lack a VZV trafficking pathway within M6PR-positive large endosomes and (ii) most infectious VZV particles in conventional cell substrates are transported via large M6PR-positive vacuoles without degradative xenophagy to the plasma membrane. IMPORTANCE The long-term goal of this research has been to determine why VZV, when grown in cultured cells, invariably is more cell associated and has a lower titer than other alphaherpesviruses, such as herpes simplex virus 1 (HSV1) or pseudorabies virus (PRV). Data from both HSV1 and PRV laboratories have identified a Rab6 secretory pathway for the transport of single enveloped viral particles from the trans-Golgi network within small vacuoles to the plasma membrane. In contrast, after secondary envelopment in fibroblasts or melanoma cells, multiple infectious VZV particles accumulated within large M6PR-positive late endosomes that were not degraded en route to the plasma membrane. We propose that this M6PR pathway is most utilized in VZV infection and least utilized in HSV1 infection, with PRV’s usage being closer to HSV1’s usage. Supportive data from other VZV, PRV, and HSV1 laboratories about evidence for two egress pathways are included."
2204,The ASM Journals Committee Values the Contributions of Black Microbiologists,
2205,The Role of Deubiquitinating Enzymes in Acute Lung Injury and Acute Respiratory Distress Syndrome,"Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are characterized by an inflammatory response, alveolar edema, and hypoxemia. ARDS occurs most often in the settings of pneumonia, sepsis, aspiration of gastric contents, or severe trauma. The prevalence of ARDS is approximately 10% in patients of intensive care. There is no effective remedy with mortality high at 30–40%. Most functional proteins are dynamic and stringently governed by ubiquitin proteasomal degradation. Protein ubiquitination is reversible, the covalently attached monoubiquitin or polyubiquitin moieties within the targeted protein can be removed by a group of enzymes called deubiquitinating enzymes (DUBs). Deubiquitination plays an important role in the pathobiology of ALI/ARDS as it regulates proteins critical in engagement of the alveolo-capillary barrier and in the inflammatory response. In this review, we provide an overview of how DUBs emerge in pathogen-induced pulmonary inflammation and related aspects in ALI/ARDS. Better understanding of deubiquitination-relatedsignaling may lead to novel therapeutic approaches by targeting specific elements of the deubiquitination pathways."
2206,Small Molecule NF-κB Pathway Inhibitors in Clinic,"Nuclear factor kappa B (NF-κB) signaling is implicated in all major human chronic diseases, with its role in transcription of hundreds of gene well established in the literature. This has propelled research into targeting the NF-κB pathways for modulating expression of those genes and the diseases mediated by them. In-spite of the critical, but often promiscuous role played by this pathway and the inhibition causing adverse drug reaction, currently many biologics, macromolecules, and small molecules that modulate this pathway are in the market or in clinical trials. Furthermore, many marketed drugs that were later found to also have NF-κB targeting activity were repurposed for new therapeutic interventions. Despite the rising importance of biologics in drug discovery, small molecules got around 76% of US-FDA (Food and Drug Administration-US) approval in the last decade. This encouraged us to review information regarding clinically relevant small molecule inhibitors of the NF-κB pathway from cell surface receptor stimulation to nuclear signaling. We have also highlighted the underexplored targets in this pathway that have potential to succeed in clinic."
2207,Gradient Chitosan Hydrogels Modified with Graphene Derivatives and Hydroxyapatite: Physiochemical Properties and Initial Cytocompatibility Evaluation,"In this study, we investigated preparation of gradient chitosan-matrix hydrogels through a novel freezing–gelling–thawing method. The influence of three types of graphene family materials (GFM), i.e., graphene oxide (GO), reduced graphene oxide (rGO), and poly(ethylene glycol) grafted graphene oxide (GO-PEG), as well as hydroxyapatite (HAp) on the physicochemical and biological properties of the composite hydrogels was examined in view of their potential applicability as tissue engineering scaffolds. The substrates and the hydrogel samples were thoroughly characterized by X-ray photoelectron spectroscopy, X-ray diffractometry, infrared spectroscopy, digital and scanning electron microscopy, rheological and mechanical analysis, in vitro chemical stability and bioactivity assays, as well as initial cytocompatibility evaluation with human umbilical cord Wharton’s jelly mesenchymal stem cells (hUC-MSCs). We followed the green-chemistry approach and avoided toxic cross-linking agents, using instead specific interactions of our polymer matrix with tannic acid, non-toxic physical cross-linker, and graphene derivatives. It was shown that the most promising are the gradient hydrogels modified with GO-PEG and HAp."
2208,Quantifying the Transmission of Foot-and-Mouth Disease Virus in Cattle via a Contaminated Environment,"Indirect transmission via a contaminated environment can occur for a number of pathogens, even those typically thought of as being directly transmitted, such as influenza virus, norovirus, bovine tuberculosis, or foot-and-mouth disease virus (FMDV). Indirect transmission facilitates spread from multiple sources beyond the infectious host, complicating the epidemiology and control of these diseases. This study carried out a series of transmission experiments to determine the dose-response relationship between environmental contamination and transmission of FMDV in cattle from measurements of viral shedding and rates of environmental contamination and survival. Seven out of ten indirect exposures resulted in successful transmission. The basic reproduction number for environmental transmission of FMDV in this experimental setting was estimated at 1.65, indicating that environmental transmission alone could sustain an outbreak. Importantly, detection of virus in the environment prior to the appearance of clinical signs in infected cattle and successful transmission from these environments highlights there is a risk of environmental transmission even before foot-and-mouth disease (FMD) is clinically apparent in cattle. Estimated viral decay rates suggest that FMDV remained viable in this environment for up to 14 days, emphasizing the requirement for stringent biosecurity procedures following outbreaks of FMD and the design of control measures that reflect the biology of a pathogen."
2209,Surface Active Agents and Their Health-Promoting Properties: Molecules of Multifunctional Significance,"Surface active agents (SAAs) are molecules with the capacity to adsorb to solid surfaces and/or fluid interfaces, a property that allows them to act as multifunctional ingredients (e.g., wetting and dispersion agents, emulsifiers, foaming and anti-foaming agents, lubricants, etc.) in a widerange of the consumer products of various industrial sectors (e.g., pharmaceuticals, cosmetics, personal care, detergents, food, etc.). Given their widespread utilization, there is a continuously growing interest to explore their role in consumer products (relevant to promoting human health) and how such information can be utilized in order to synthesize better chemical derivatives. In this review article, weaimed to provide updated information on synthetic and biological (biosurfactants) SAAs and their health-promoting properties (e.g., anti-microbial, anti-oxidant, anti-viral, anti-inflammatory, anti-cancer and anti-aging) in an attempt to better define some of the underlying mechanism(s) by which they exert such properties."
2210,Extraction of Carotenoids from Tomato Pomace via Water-Induced Hydrocolloidal Complexation,"Agro-industrial waste is a largely untapped natural resource of bioactive compounds including carotenoids and pectin. However, conventional solvent extraction involves the excessive use of organic solvents, costly equipment, and tedious operation. These limitations of conventional extraction methods could be prospectively overcome by the carotenoid–pectin hydrocolloidal complexation. The complexation of lycopene and pectin was efficiently promoted in an aqueous environment, resulting in the colloidal complexes that can be subsequently recovered by sedimentation or centrifugation. In this study, the potential of carotenoid–pectin complexation on tomato pomace containing carotenoids and pectin was evaluated. Tomato pomace is a rich source of lycopene, β-carotene as well as pectin, making it suitable as the raw material for the carotenoid extraction. The extraction of carotenoid and pectin from tomato pomace was optimized using response surface methodology. The maximum recovery was 9.43 mg carotenoid fractions/100 g tomato pomace, while the purity of carotenoid-rich fractions was 92%. The antioxidant capacity of carotenoids extracted from the complexation method was found to be higher than that from the solvent extraction method. Moreover, extraction yield and antioxidant capacity of carotenoid obtained from the carotenoid–pectin complexation were comparable to that from solvent extraction. The carotenoid–pectin complexation is a promising green approach to valorize agro by-products for the extraction of valuable carotenoids."
2211,miR-7 Regulates GLP-1-Mediated Insulin Release by Targeting β-Arrestin 1,"Glucagon-like peptide-1 (GLP-1) has been shown to potentiate glucose-stimulated insulin secretion binding GLP-1 receptor on pancreatic β cells. β-arrestin 1 (βARR1) is known to regulate the desensitization of GLP-1 receptor. Mounting evidence indicates that microRNAs (miRNAs, miRs) are fundamental in the regulation of β cell function and insulin release. However, the regulation of GLP-1/βARR1 pathways by miRs has never been explored. Our hypothesis is that specific miRs can modulate the GLP-1/βARR1 axis in β cells. To test this hypothesis, we applied a bioinformatic approach to detect miRs that could target βARR1; we identified hsa-miR-7-5p (miR-7) and we validated the specific interaction of this miR with βARR1. Then, we verified that GLP-1 was indeed able to regulate the transcription of miR-7 and βARR1, and that miR-7 significantly regulated GLP-1-induced insulin release and cyclic AMP (cAMP) production in β cells. Taken together, our findings indicate, for the first time, that miR-7 plays a functional role in the regulation of GLP-1-mediated insulin release by targeting βARR1. These results have a decisive clinical impact given the importance of drugs modulating GLP-1 signaling in the treatment of patients with type 2 diabetes mellitus."
2212,Fumaric acid production by fermentation,"The potential of fumaric acid as a raw material in the polymer industry and the increment of cost of petroleum-based fumaric acid raises interest in fermentation processes for production of this compound from renewable resources. Although the chemical process yields 112% w/w fumaric acid from maleic anhydride and the fermentation process yields only 85% w/w from glucose, the latter raw material is three times cheaper. Besides, the fermentation fixes CO(2). Production of fumaric acid by Rhizopus species and the involved metabolic pathways are reviewed. Submerged fermentation systems coupled with product recovery techniques seem to have achieved economically attractive yields and productivities. Future prospects for improvement of fumaric acid production include metabolic engineering approaches to achieve low pH fermentations."
2213,Discovery and characterization of a putrescine oxidase from Rhodococcus erythropolis NCIMB 11540,"A gene encoding a putrescine oxidase (PuO(Rh), EC 1.4.3.10) was identified from the genome of Rhodococcus erythropolis NCIMB 11540. The gene was cloned in the pBAD vector and overexpressed at high levels in Escherichia coli. The purified enzyme was shown to be a soluble dimeric flavoprotein consisting of subunits of 50 kDa and contains non-covalently bound flavin adenine dinucleotide as a cofactor. From all substrates, the highest catalytic efficiency was found with putrescine (K (M) = 8.2 μM, k (cat) = 26 s(−1)). PuO(Rh) accepts longer polyamines, while short diamines and monoamines strongly inhibit activity. PuO(Rh) is a reasonably thermostable enzyme with t (1/2) at 50°C of 2 h. Based on the crystal structure of human monoamine oxidase B, we constructed a model structure of PuO(Rh), which hinted to a crucial role of Glu324 for substrate binding. Mutation of this residue resulted in a drastic drop (five orders of magnitude) in catalytic efficiency. Interestingly, the mutant enzyme showed activity with monoamines, which are not accepted by wt-PuO(Rh). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-007-1310-4) contains supplementary material, which is available to authorized users."
2214,Degradation of 4-fluorophenol by Arthrobacter sp. strain IF1,"A Gram-positive bacterial strain capable of aerobic biodegradation of 4-fluorophenol (4-FP) as the sole source of carbon and energy was isolated by selective enrichment from soil samples collected near an industrial site. The organism, designated strain IF1, was identified as a member of the genus Arthrobacter on the basis of 16S ribosomal RNA gene sequence analysis. Arthrobacter strain IF1 was able to mineralize 4-FP up to concentrations of 5 mM in batch culture. Stoichiometric release of fluoride ions was observed, suggesting that there is no formation of halogenated dead-end products during 4-FP metabolism. The degradative pathway of 4-FP was investigated using enzyme assays and identification of intermediates by gas chromatography (GC), GC–mass spectrometry (MS), high-performance liquid chromatography, and liquid chromatography–MS. Cell-free extracts of 4-FP-grown cells contained no activity for catechol 1,2-dioxygenase or catechol 2,3-dioxygenase, which indicates that the pathway does not proceed through a catechol intermediate. Cells grown on 4-FP oxidized 4-FP, hydroquinone, and hydroxyquinol but not 4-fluorocatechol. During 4-FP metabolism, hydroquinone accumulated as a product. Hydroquinone could be converted to hydroxyquinol, which was further transformed into maleylacetic acid and β-ketoadipic acid. These results indicate that the biodegradation of 4-FP starts with a 4-FP monooxygenase reaction that yields benzoquinone, which is reduced to hydroquinone and further metabolized via the β-ketoadipic acid pathway."
2215,Secretion of Streptomyces mobaraensis pro-transglutaminase by coryneform bacteria,"We previously reported on the secretion of Streptomyces mobaraensis transglutaminase by Corynebacterium glutamicum ATCC13869 (formerly classified as Brevibacterium lactofermentum). In the present work, we investigated whether any other coryneform bacteria showed higher productivity than C. glutamicum ATCC13869. We found that most coryneform species secreted pro-transglutaminase efficiently. Moreover, we confirmed that Corynebacterium ammoniagenes ATCC6872 produced about 2.5 g/l pro-transglutaminase over a 71-h period in a jar fermentor. Our findings suggest that some other coryneform bacteria, especially C. ammoniagenes ATCC6872, are potential hosts for industrial scale protein production."
2216,Lactic acid production from lime-treated wheat straw by Bacillus coagulans: neutralization of acid by fed-batch addition of alkaline substrate,"Conventional processes for lignocellulose-to-organic acid conversion requires pretreatment, enzymatic hydrolysis, and microbial fermentation. In this study, lime-treated wheat straw was hydrolyzed and fermented simultaneously to lactic acid by an enzyme preparation and Bacillus coagulans DSM 2314. Decrease in pH because of lactic acid formation was partially adjusted by automatic addition of the alkaline substrate. After 55 h of incubation, the polymeric glucan, xylan, and arabinan present in the lime-treated straw were hydrolyzed for 55%, 75%, and 80%, respectively. Lactic acid (40.7 g/l) indicated a fermentation efficiency of 81% and a chiral l(+)-lactic acid purity of 97.2%. In total, 711 g lactic acid was produced out of 2,706 g lime-treated straw, representing 43% of the overall theoretical maximum yield. Approximately half of the lactic acid produced was neutralized by fed-batch feeding of lime-treated straw, whereas the remaining half was neutralized during the batch phase with a Ca(OH)(2) suspension. Of the lime added during the pretreatment of straw, 61% was used for the neutralization of lactic acid. This is the first demonstration of a process having a combined alkaline pretreatment of lignocellulosic biomass and pH control in fermentation resulting in a significant saving of lime consumption and avoiding the necessity to recycle lime."
2217,"Competition and coexistence of sulfate-reducing bacteria, acetogens and methanogens in a lab-scale anaerobic bioreactor as affected by changing substrate to sulfate ratio","The microbial population structure and function of natural anaerobic communities maintained in lab-scale continuously stirred tank reactors at different lactate to sulfate ratios and in the absence of sulfate were analyzed using an integrated approach of molecular techniques and chemical analysis. The population structure, determined by denaturing gradient gel electrophoresis and by the use of oligonucleotide probes, was linked to the functional changes in the reactors. At the influent lactate to sulfate molar ratio of 0.35 mol mol(−1), i.e., electron donor limitation, lactate oxidation was mainly carried out by incompletely oxidizing sulfate-reducing bacteria, which formed 80–85% of the total bacterial population. Desulfomicrobium- and Desulfovibrio-like species were the most abundant sulfate-reducing bacteria. Acetogens and methanogenic Archaea were mostly outcompeted, although less than 2% of an acetogenic population could still be observed at this limiting concentration of lactate. In the near absence of sulfate (i.e., at very high lactate/sulfate ratio), acetogens and methanogenic Archaea were the dominant microbial communities. Acetogenic bacteria represented by Dendrosporobacter quercicolus-like species formed more than 70% of the population, while methanogenic bacteria related to uncultured Archaea comprising about 10–15% of the microbial community. At an influent lactate to sulfate molar ratio of 2 mol mol(−1), i.e., under sulfate-limiting conditions, a different metabolic route was followed by the mixed anaerobic community. Apparently, lactate was fermented to acetate and propionate, while the majority of sulfidogenesis and methanogenesis were dependent on these fermentation products. This was consistent with the presence of significant levels (40–45% of total bacteria) of D. quercicolus-like heteroacetogens and a corresponding increase of propionate-oxidizing Desulfobulbus-like sulfate-reducing bacteria (20% of the total bacteria). Methanogenic Archaea accounted for 10% of the total microbial community."
2218,Determination of fungal activity in modified wood by means of micro-calorimetry and determination of total esterase activity,"Beech and pine wood blocks were treated with 1,3-dimethylol-4,5-dihydroxyethylen urea (DMDHEU) to increasing weight percent gains (WPG). The resistance of the treated specimens against Trametes versicolor and Coniophora puteana, determined as mass loss, increased with increasing WPG of DMDHEU. Metabolic activity of the fungi in the wood blocks was assessed as total esterase activity (TEA) based on the hydrolysis of fluorescein diacetate and as heat or energy production determined by isothermal micro-calorimetry. Both methods revealed that the fungal activity was related with the WPG and the mass loss caused by the fungi. Still, fungal activity was detected even in wood blocks of the highest WPG and showed that the treatment was not toxic to the fungi. Energy production showed a higher consistency with the mass loss after decay than TEA; higher mass loss was more stringently reflected by higher heat production rate. Heat production did not proceed linearly, possibly due to the inhibition of fungal activity by an excess of carbon dioxide."
2219,Breeding of wastewater treatment yeasts that accumulate high concentrations of phosphorus,"Inorganic phosphate is an essential nutrient. In general, microorganisms take up phosphorus when the extracellular phosphorus concentration is low, but not when it is high. In Saccharomyces cerevisiae, the major phosphate transporters, such as Pho84p, and acid phosphatases (APases), such as Pho5p, are regulated in parallel by the phosphate signal transduction pathway (PHO pathway). We found that PHO mutants expressing PHO84 and PHO5, even under high-P conditions, could take up phosphorus at twice the rate of the wild-type strain. The regulatory pathway for phosphorus accumulation in two wastewater treatment yeasts, Hansenula fabianii J640 and Hansenula anomala J224-1, was found to be similar to that in S. cerevisiae. We screened for mutants of these yeasts that constitutively expressed APase. Such mutants formed blue colonies on high phosphorus concentration agar plates containing 5-bromo-4-chloro-3-indolylphosphate (X-phosphate). We found four mutants of H. fabianii J640 and one mutant of H. anomala J224-1 that accumulated from 2.2 to 3.5 times more phosphorus than the parent strains. The growth rates and abilities to remove dissolved total nitrogen and dissolved organic carbon of the mutants were similar to those of the parent strains. In addition, the mutants removed 95% of dissolved total phosphorus from shochu wastewater, while the parent strain removed only 50%."
2220,Regioselective synthesis of plant (iso)flavone glycosides in Escherichia coli,"The flavonoids genistein, biochanin A, luteolin, quercetin, and kaempferol are plant natural products with potentially useful pharmacological and nutraceutical activities. These natural products usually exist in plants as glycosides, and their glycosylation has a remarkable influence on their pharmacokinetic properties. The glycosyltransferases UGT71G1 and UGT73C8 from Medicago truncatula are excellent reagents for the regioselective glycosylation of (iso)flavonoids in Escherichia coli grown in Terrific broth. Ten to 20 mg/L of either genistein or biochanin A 7-O-glucoside was produced after feeding genistein or biochanin A to E. coli expressing UGT71G1, and similar levels of luteolin 4’-O- and 7-O-glucosides were produced after feeding luteolin to cultures expressing UGT73C8. For the production of kaempferol 3-O-glucoside or quercetin 3-O-glucoside, the Phe148Val or Tyr202Ala mutants of UGT71G1 were employed. Ten to 16 mg/L of either kaempferol 3-O- or quercetin 3-O-glucosides were produced on feeding kaempferol or quercetin to E. coli expressing these enzymes. More than 90% of the glucoside products were released to the medium, facilitating their isolation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-008-1554-7) contains supplementary material, which is available to authorized users."
2221,Glycoprotein gene truncation in avian metapneumovirus subtype C isolates from the United States,"The length of the published glycoprotein (G) gene sequences of avian metapneumovirus subtype-C (aMPV-C) isolated from domestic turkeys and wild birds in the United States (1996–2003) remains controversial. To explore the G gene size variation in aMPV-C by the year of isolation and cell culture passage levels, we examined 21 turkey isolates of aMPV-C at different cell culture passages. The early domestic turkey isolates of aMPV-C (aMPV/CO/1996, aMPV/MN/1a-b, and 2a-b/97) had a G gene of 1,798 nucleotides (nt) that coded for a predicted protein of 585 amino acids (aa) and showed >97% nt similarity with that of aMPV-C isolated from Canada geese. This large G gene got truncated upon serial passages in Vero cell cultures by deletion of 1,015 nt near the end of the open reading frame. The recent domestic turkey isolates of aMPV-C lacked the large G gene but instead had a small G gene of 783 nt, irrespective of cell culture passage levels. In some cultures, both large and small genes were detected, indicating the existence of a mixed population of the virus. Apparently, serial passage of aMPV-C in cell cultures and natural passage in turkeys in the field led to truncation of the G gene, which may be a mechanism of virus evolution for survival in a new host or environment."
2222,"Characterization of a modular enzyme of exo-1,5-α-l-arabinofuranosidase and arabinan binding module from Streptomyces avermitilis NBRC14893","A gene encoding an α-l-arabinofuranosidase, designated SaAraf43A, was cloned from Streptomyces avermitilis. The deduced amino acid sequence implies a modular structure consisting of an N-terminal glycoside hydrolase family 43 module and a C-terminal family 42 carbohydrate-binding module (CBM42). The recombinant enzyme showed optimal activity at pH 6.0 and 45°C and was stable over the pH range of 5.0–6.5 at 30°C. The enzyme hydrolyzed p-nitrophenol (PNP)-α-l-arabinofuranoside but did not hydrolyze PNP-α-l-arabinopyranoside, PNP-β-d-xylopyranoside, or PNP-β-d-galactopyranoside. Debranched 1,5-arabinan was hydrolyzed by the enzyme but arabinoxylan, arabinogalactan, gum arabic, and arabinan were not. Among the synthetic regioisomers of arabinofuranobiosides, only methyl 5-O-α-l-arabinofuranosyl-α-l-arabinofuranoside was hydrolyzed by the enzyme, while methyl 2-O-α-l-arabinofuranosyl-α-l-arabinofuranoside and methyl 3-O-α-l-arabinofuranosyl-α-l-arabinofuranoside were not. These data suggested that the enzyme only cleaves α-1,5-linked arabinofuranosyl linkages. The analysis of the hydrolysis product of arabinofuranopentaose suggested that the enzyme releases arabinose in exo-acting manner. These results indicate that the enzyme is definitely an exo-1,5-α-l-arabinofuranosidase. The C-terminal CBM42 did not show any affinity for arabinogalactan and debranched arabinan, although it bound arabinan and arabinoxylan, suggesting that the CBM42 bound to branched arabinofuranosyl residues. Removal of the module decreased the activity of the enzyme with regard to debranched arabinan. The CBM42 plays a role in enhancing the debranched arabinan hydrolytic action of the catalytic module in spite of its preference for binding arabinofuranosyl side chains."
2223,Growth of Pseudomonas chloritidismutans AW-1(T) on n-alkanes with chlorate as electron acceptor,"Microbial (per)chlorate reduction is a unique process in which molecular oxygen is formed during the dismutation of chlorite. The oxygen thus formed may be used to degrade hydrocarbons by means of oxygenases under seemingly anoxic conditions. Up to now, no bacterium has been described that grows on aliphatic hydrocarbons with chlorate. Here, we report that Pseudomonas chloritidismutans AW-1(T) grows on n-alkanes (ranging from C7 until C12) with chlorate as electron acceptor. Strain AW-1(T) also grows on the intermediates of the presumed n-alkane degradation pathway. The specific growth rates on n-decane and chlorate and n-decane and oxygen were 0.5 ± 0.1 and 0.4 ± 0.02 day(−1), respectively. The key enzymes chlorate reductase and chlorite dismutase were assayed and found to be present. The oxygen-dependent alkane oxidation was demonstrated in whole-cell suspensions. The strain degrades n-alkanes with oxygen and chlorate but not with nitrate, thus suggesting that the strain employs oxygenase-dependent pathways for the breakdown of n-alkanes."
2224,C(1) compounds as auxiliary substrate for engineered Pseudomonas putida S12,"The solvent-tolerant bacterium Pseudomonas putida S12 was engineered to efficiently utilize the C(1) compounds methanol and formaldehyde as auxiliary substrate. The hps and phi genes of Bacillus brevis, encoding two key steps of the ribulose monophosphate (RuMP) pathway, were introduced to construct a pathway for the metabolism of the toxic methanol oxidation intermediate formaldehyde. This approach resulted in a remarkably increased biomass yield on the primary substrate glucose when cultured in C-limited chemostats fed with a mixture of glucose and formaldehyde. With increasing relative formaldehyde feed concentrations, the biomass yield increased from 35% (C-mol biomass/C-mol glucose) without formaldehyde to 91% at 60% relative formaldehyde concentration. The RuMP-pathway expressing strain was also capable of growing to higher relative formaldehyde concentrations than the control strain. The presence of an endogenous methanol oxidizing enzyme activity in P. putida S12 allowed the replacement of formaldehyde with the less toxic methanol, resulting in an 84% (C-mol/C-mol) biomass yield. Thus, by introducing two enzymes of the RuMP pathway, co-utilization of the cheap and renewable substrate methanol was achieved, making an important contribution to the efficient use of P. putida S12 as a bioconversion platform host."
2225,Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis,"Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes."
2226,Citric acid wastewater as electron donor for biological sulfate reduction,"Citrate-containing wastewater is used as electron donor for sulfate reduction in a biological treatment plant for the removal of sulfate. The pathway of citrate conversion coupled to sulfate reduction and the microorganisms involved were investigated. Citrate was not a direct electron donor for the sulfate-reducing bacteria. Instead, citrate was fermented to mainly acetate and formate. These fermentation products served as electron donors for the sulfate-reducing bacteria. Sulfate reduction activities of the reactor biomass with acetate and formate were sufficiently high to explain the sulfate reduction rates that are required for the process. Two citrate-fermenting bacteria were isolated. Strain R210 was closest related to Trichococcus pasteurii (99.5% ribosomal RNA (rRNA) gene sequence similarity). The closest relative of strain S101 was Veillonella montepellierensis with an rRNA gene sequence similarity of 96.7%. Both strains had a complementary substrate range."
2227,Comparative study of imaging at 3.0 T versus 1.5 T of the knee,"PURPOSE: The objectives of the study were to compare MR imaging at 1.5 and 3.0 T in the same patients concerning image quality and visualization of cartilage pathology and to assess diagnostic performance using arthroscopy as a standard of reference. MATERIALS AND METHODS: Twenty-six patients were identified retrospectively as having comparative 1.5 and 3.0 T MR studies of the knee within an average of 102 days. Standard protocols included T1-weighted and fat-saturated intermediate-weighted fast spin-echo sequences in three planes; sequence parameters had been adjusted to account for differences in relaxation at 3.0 T. Arthroscopy was performed in 19 patients. Four radiologists reviewed each study independently, scored image quality, and analyzed pathological findings. Sensitivities, specificities, and accuracies in diagnosing cartilage lesions were calculated in the 19 patients with arthroscopy, and differences between 1.5 and 3.0 T exams were compared using paired Student’s t tests with a significance threshold of p < 0.05. RESULTS: Each radiologist scored the 3.0 T studies higher than those obtained at 1.5 T in visualizing anatomical structures and abnormalities (p < 0.05). Using arthroscopy as a standard of reference, diagnosis of cartilage abnormalities was improved at 3.0 T with higher sensitivity (75.7% versus 70.6%), accuracy (88.2% versus 86.4%), and correct grading of cartilage lesions (51.3% versus 42.9%). Diagnostic confidence scores were higher at 3.0 than 1.5 T (p < 0.05) and signal-to-noise ratio at 3.0 T was approximately twofold higher than at 1.5 T. CONCLUSION: MRI at 3.0 T improved visualization of anatomical structures and improved diagnostic confidence compared to 1.5 T. This resulted in significantly better sensitivity and grading of cartilage lesions at the knee."
2228,Assessment of cartilage-dedicated sequences at ultra-high-field MRI: comparison of imaging performance and diagnostic confidence between 3.0 and 7.0 T with respect to osteoarthritis-induced changes at the knee joint,"OBJECTIVE: The objectives of the study were to optimize three cartilage-dedicated sequences for in vivo knee imaging at 7.0 T ultra-high-field (UHF) magnetic resonance imaging (MRI) and to compare imaging performance and diagnostic confidence concerning osteoarthritis (OA)-induced changes at 7.0 and 3.0 T MRI. MATERIALS AND METHODS: Optimized MRI sequences for cartilage imaging at 3.0 T were tailored for 7.0 T: an intermediate-weighted fast spin-echo (IM-w FSE), a fast imaging employing steady-state acquisition (FIESTA) and a T1-weighted 3D high-spatial-resolution volumetric fat-suppressed spoiled gradient-echo (SPGR) sequence. Three healthy subjects and seven patients with mild OA were examined. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), diagnostic confidence in assessing cartilage abnormalities, and image quality were determined. Abnormalities were assessed with the whole organ magnetic resonance imaging score (WORMS). Focal cartilage lesions and bone marrow edema pattern (BMEP) were also quantified. RESULTS: At 7.0 T, SNR was increased (p < 0.05) for all sequences. For the IM-w FSE sequence, limitations with the specific absorption rate (SAR) required modifications of the scan parameters yielding an incomplete coverage of the knee joint, extensive artifacts, and a less effective fat saturation. CNR and image quality were increased (p < 0.05) for SPGR and FIESTA and decreased for IM-w FSE. Diagnostic confidence for cartilage lesions was highest (p < 0.05) for FIESTA at 7.0 T. Evaluation of BMEP was decreased (p < 0.05) at 7.0 T due to limited performance of IM-w FSE. CONCLUSION: Gradient echo-based pulse sequences like SPGR and FIESTA are well suited for imaging at UHF which may improve early detection of cartilage lesions. However, UHF IM-w FSE sequences are less feasible for clinical use."
2229,The evolution of cyclodextrin glucanotransferase product specificity,"Cyclodextrin glucanotransferases (CGTases) have attracted major interest from industry due to their unique capacity of forming large quantities of cyclic α-(1,4)-linked oligosaccharides (cyclodextrins) from starch. CGTases produce a mixture of cyclodextrins from starch consisting of 6 (α), 7 (β) and 8 (γ) glucose units. In an effort to identify the structural factors contributing to the evolutionary diversification of product specificity amongst this group of enzymes, we selected nine CGTases from both mesophilic, thermophilic and hyperthermophilic organisms for comparative product analysis. These enzymes displayed considerable variation regarding thermostability, initial rates, percentage of substrate conversion and ratio of α-, β- and γ-cyclodextrins formed from starch. Sequence comparison of these CGTases revealed that specific incorporation and/or substitution of amino acids at the substrate binding sites, during the evolutionary progression of these enzymes, resulted in diversification of cyclodextrin product specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-009-1988-6) contains supplementary material, which is available to authorized users."
2230,Successful Medical Management of Status Post-Roux-en-Y-Gastric-Bypass Hyperinsulinemic Hypoglycemia,"Roux-en-Y gastric bypass (RYGBP) is the most commonly performed type of bariatric surgery, which is used in the treatment of obesity and type 2 diabetes. Recent case reports and case series have described a rare complication of RYGBP, status post-gastric-bypass hyperinsulinemic hypoglycemia, which was mainly managed successfully with pancreatectomy. In this letter, we describe the first successful management of status post-gastric-bypass hyperinsulinemic hypoglycemia with diazoxide."
2231,Long-term performance and microbial community analysis of a full-scale synthesis gas fed reactor treating sulfate- and zinc-rich wastewater,"The performance of a full-scale (500 m(3)) sulfidogenic synthesis gas fed gas-lift reactor treating metal- and sulfate-rich wastewater was investigated over a period of 128 weeks. After startup, the reactor had a high methanogenic activity of 46 Nm(3)·h(−1). Lowering the carbon dioxide feed rate during the first 6 weeks gradually lowered the methane production rate. Between weeks 8 and 93, less than 1% of the hydrogen supplied was used for methanogenesis. Denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified 16S rRNA gene fragments showed that the archaeal community decreased in diversity but did not disappear completely. After the carbon dioxide feed rate increased in week 88, the methane production rate also increased, confirming that methane production was carbon dioxide limited. Even though lowering the carbon dioxide feed appeared to affect part of the sulfate-reducing community, it did not prevent achieving the desired rates of sulfate reduction. The average sulfate conversion rate was 181 kg∙h(−1) for the first 92 weeks. After 92 weeks, the sulfate input rate was increased and from week 94 to 128, the average weekly sulfate conversion rate was 295 kg·h(−1) (SD ± 87). Even higher sulfate conversion rates of up to 400 kg·h(−1) could be sustained for weeks 120–128. The long-term performance and stability together with the ability to control methanogenesis demonstrates that synthesis gas fed reactor can be used successfully at full scale to treat metal and sulfate-rich wastewater."
2232,Behavioral response of dissimilatory perchlorate-reducing bacteria to different electron acceptors,"The response behavior of three dissimilatory perchlorate-reducing bacteria to different electron acceptors (nitrate, chlorate, and perchlorate) was investigated with two different assays. The observed response was species-specific, dependent on the prior growth conditions, and was inhibited by oxygen. We observed attraction toward nitrate when Dechloromonas aromatica strain RCB and Azospira suillum strain PS were grown with nitrate. When D. aromatica and Dechloromonas agitata strain CKB were grown with perchlorate, both responded to nitrate, chlorate, and perchlorate. When A. suillum was grown with perchlorate, the organism responded to chlorate and perchlorate but not nitrate. A gene replacement mutant in the perchlorate reductase subunit (pcrA) of D. aromatica resulted in a loss of the attraction response toward perchlorate but had no impact on the nitrate response. Washed-cell suspension studies revealed that the perchlorate grown cells of D. aromatica reduced both perchlorate and nitrate, while A. suillum cells reduced perchlorate only. Based on these observations, energy taxis was proposed as the underlying mechanism for the responses to (per)chlorate by D. aromatica. To the best of our knowledge, this study represents the first investigation of the response behavior of perchlorate-reducing bacteria to environmental stimuli. It clearly demonstrates attraction toward chlorine oxyanions and the unique ability of these organisms to distinguish structurally analogous compounds, nitrate, chlorate, and perchlorate and respond accordingly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-009-2051-3) contains supplementary material, which is available to authorized users."
2233,Six-minute walking test in children with ESRD: discrimination validity and construct validity,"The six-minute walking test (6MWT) may be a practical test for the evaluation functional exercise capacity in children with end-stage renal disease (ESRD). The aim of this study was to investigate the 6MWT performance in children with ESRD compared to reference values obtained in healthy children and, secondly, to study the relationship between 6MWT performance with anthropometric variables, clinical parameters, aerobic capacity and muscle strength. Twenty patients (13 boys and seven girls; mean age 14.1 ± 3.4 years) on dialysis participated in this study. Anthropometrics were taken in a standardized manner. The 6MWT was performed in a 20-m-long track in a straight hallway. Aerobic fitness was measured using a cycle ergometer test to determine peak oxygen uptake [Formula: see text], peak rate (W(peak)) and ventilatory threshold (VT). Muscle strength was measured using hand-held myometry. Children with ESRD showed a reduced 6MWT performance (83% of predicted, p < 0.0001), irrespective of the reference values used. The strongest predictors of 6MWT performance were haematocrit and height. Regression models explained 59% (haematocrit and height) to 60% (haematocrit) of the variance in 6MWT performance. 6MWT performance was not associated with [Formula: see text], strength, or other anthropometric variables, but it was significantly associated with haematocrit and height. Children with ESRD scored lower on the 6MWT than healthy children. Based on these results, the 6MWT may be a useful instrument for monitoring clinical status in children with ESRD, however it cannot substitute for other fitness tests, such as a progressive exercise test to measure [Formula: see text] or muscle strength tests."
2234,Enhancement of toxin- and virus-neutralizing capacity of single-domain antibody fragments by N-glycosylation,"Single-domain antibody fragments (VHHs) have several beneficial properties as compared to conventional antibody fragments. However, their small size complicates their toxin- and virus-neutralizing capacity. We isolated 27 VHHs binding Escherichia coli heat-labile toxin and expressed these in Saccharomyces cerevisiae. The most potent neutralizing VHH (LT109) was N-glycosylated, resulting in a large increase in molecular mass. This suggests that N-glycosylation of LT109 improves its neutralizing capacity. Indeed, deglycosylation of LT109 decreased its neutralizing capacity three- to fivefold. We also studied the effect of glycosylation of two previously isolated VHHs on their ability to neutralize foot-and-mouth disease virus. For this purpose, these VHHs that lacked potential N-glycosylation sites were genetically fused to another VHH that was known to be glycosylated. The resulting fusion proteins were also N-glycosylated. They neutralized the virus at at least fourfold-lower VHH concentrations as compared to the single, non-glycosylated VHHs and at at least 50-fold-lower VHH concentrations as compared to their deglycosylated counterparts. Thus, we have shown that N-glycosylation of VHHs contributes to toxin- and virus-neutralizing capacity."
2235,Applications of thiol-disulfide oxidoreductases for optimized in vivo production of functionally active proteins in Bacillus,"Bacillus subtilis is a well-established cellular factory for proteins and fine chemicals. In particular, the direct secretion of proteinaceous products into the growth medium greatly facilitates their downstream processing, which is an important advantage of B. subtilis over other biotechnological production hosts, such as Escherichia coli. The application spectrum of B. subtilis is, however, often confined to proteins from Bacillus or closely related species. One of the major reasons for this (current) limitation is the inefficient formation of disulfide bonds, which are found in many, especially eukaryotic, proteins. Future exploitation of B. subtilis to fulfill the ever-growing demand for pharmaceutical and other high-value proteins will therefore depend on overcoming this particular hurdle. Recently, promising advances in this area have been achieved, which focus attention on the need to modulate the cellular levels and activity of thiol-disulfide oxidoreductases (TDORs). These TDORs are enzymes that control the cleavage or formation of disulfide bonds. This review will discuss readily applicable approaches for TDOR modulation and aims to provide leads for further improvement of the Bacillus cell factory for production of disulfide bond-containing proteins."
2236,Influence of trace erythromycin and erythromycin-H(2)O on carbon and nutrients removal and on resistance selection in sequencing batch reactors (SBRs),"Three sequencing batch reactors (SBRs) were operated in parallel to study the effects of trace erythromycin (ERY) and ERY-H(2)O on the treatment of a synthetic wastewater. Through monitoring (1) daily effluents and (2) concentrations of nitrogen (N) and phosphorous (P) in certain batch cycles of the three reactors operated from transient to steady states, the removal of carbon, N, and P was affected negligibly by ERY (100 µg/L) or ERY-H(2)O (50 µg/L) when compared with the control reactor. However, through analyzing microbial communities of the three steady state SBRs on high-density microarrays (PhyloChip), ERY, and ERY-H(2)O had pronounced effects on the community composition of bacteria related to N and P removal, leading to diversity loss and abundance change. The above observations indicated that resistant bacteria were selected upon exposure to ERY or ERY-H(2)O. Short-term batch experiments further proved the resistance and demonstrated that ammonium oxidation (56–95%) was inhibited more significantly than nitrite oxidation (18–61%) in the presence of ERY (100, 400, or 800 µg/L). Therefore, the presence of ERY or ERY-H(2)O (at µg/L levels) shifted the microbial community and selected resistant bacteria, which may account for the negligible influence of the antibiotic ERY or its derivative ERY-H(2)O (at µg/L levels) on carbon, N, and P removal in the SBRs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-009-2201-7) contains supplementary material, which is available to authorized users."
2237,Time before isolating cystinotic leukocytes affects reliability of cystine determination,
2238,"Heterologous expression and characterization of CpI, OcpA, and novel serine-type carboxypeptidase OcpB from Aspergillus oryzae","In the genome of Aspergillus oryzae, 12 genes have been predicted to encode serine-type carboxypeptidases. However, the carboxypeptidase activities of the proteins encoded by these genes have not yet been confirmed experimentally. In this study, we have constructed three of these 12 genes overexpressing strains using Aspergillus nidulans and characterized their overproduced recombinant proteins. Of these three genes, one was previously named cpI; the other two have not been reported yet, and hence, we named them ocpA and ocpB. The recombinant proteins released amino acid residues from the C terminus of peptides, and the activity of the enzymes was inhibited by phenylmethylsulfonyl fluoride, indicating the enzymes to be serine-type carboxypeptidases. Recombinant OcpA, OcpB, and CpI were stable at 45°C, 55°C, and 55°C, respectively, at a low pH. The enzymatic properties of recombinant OcpB were different from those of any reported serine-type carboxypeptidase. On the other hand, recombinant OcpA had similar enzymatic properties to A. oryzae carboxypeptidases O1 and O2. The DNA and N-terminal amino acid sequences of carboxypeptidases O1 and O2 from A. oryzae IAM2640 were similar to those of OcpA. Result of transcriptional analysis of ocpA, ocpB, and cpI suggest differences in transcriptional regulation between these genes."
2239,Secreted production of an elastin-like polypeptide by Pichia pastoris,"Elastin-like polypeptides (ELPs) are biocompatible designer polypeptides with inverse temperature transition behavior in solution. They have a wide variety of possible applications and a potential medical importance. Currently, production of ELPs is done at lab scale in Escherichia coli shake flask cultures. With a view to future large scale production, we demonstrate secreted production of ELPs in methanol-induced fed-batch cultures of Pichia pastoris and purification directly from the culture medium. The production of ELPs by P. pastoris proved to be pH dependent within the experimental pH range of pH 3 to 7, as an increasing yield was found in cultures grown at higher pH. Because ELP produced at pH 7 was partly degraded, a pH optimum for production of ELP was found at pH 6 with a yield of 255 mg of purified intact ELP per liter of cell-free medium."
2240,Achievements and new knowledge unraveled by metagenomic approaches,"Metagenomics has paved the way for cultivation-independent assessment and exploitation of microbial communities present in complex ecosystems. In recent years, significant progress has been made in this research area. A major breakthrough was the improvement and development of high-throughput next-generation sequencing technologies. The application of these technologies resulted in the generation of large datasets derived from various environments such as soil and ocean water. The analyses of these datasets opened a window into the enormous phylogenetic and metabolic diversity of microbial communities living in a variety of ecosystems. In this way, structure, functions, and interactions of microbial communities were elucidated. Metagenomics has proven to be a powerful tool for the recovery of novel biomolecules. In most cases, functional metagenomics comprising construction and screening of complex metagenomic DNA libraries has been applied to isolate new enzymes and drugs of industrial importance. For this purpose, several novel and improved screening strategies that allow efficient screening of large collections of clones harboring metagenomes have been introduced."
2241,Positive association between increased popliteal artery vessel wall thickness and generalized osteoarthritis: is OA also part of the metabolic syndrome?,"PURPOSE: The purpose of the study was to determine if a positive association exists between arterial vessel wall thickness and generalized osteoarthritis (OA). Our hypothesis is that generalized OA is another facet of the metabolic syndrome. MATERIALS AND METHODS: The medical ethical review board of our institution approved the study. Written informed consent was obtained from each patient prior to the study. Magnetic resonance (MR) images of the knee were obtained in 42 patients who had been diagnosed with generalized OA at multiple joint sites. Another 27 MR images of the knee were obtained from a matched normal (non-OA) reference population. Vessel wall thickness of the popliteal artery was quantitatively measured by dedicated software. Linear regression models were used to investigate the association between vessel wall thickness and generalized OA. Adjustments were made for age, sex, and body mass index (BMI). Confidence intervals (CI) were computed at the 95% level and a significance level of α = 0.05 was used. RESULTS: Patients in the generalized OA population had a significant higher average vessel wall thickness than persons from the normal reference population (p ≤ α), even when correction was made for sex, age, and BMI. The average vessel wall thickness of the popliteal artery was 1.09 mm in patients with generalized OA, and 0.96 mm in the matched normal reference population. CONCLUSION: The association found between increased popliteal artery vessel wall thickness and generalized osteoarthritis suggests that generalized OA might be another facet of the metabolic syndrome."
2242,Cam-type FAI: is the alpha angle the best MR arthrography has to offer? (Skeletal Radiol. 2009;38(9):855–62),
2243,Optimizing protein intake in preterm infants,
2244,Patent ductus arteriosus and effects of low oxygen saturation limits,
2245,"Diversity and quantity of ammonia-oxidizing Archaea and Bacteria in sediment of the Pearl River Estuary, China","The diversity and abundance of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in the sediment of the Pearl River Estuary were investigated by cloning and quantitative real-time polymerase chain reaction (qPCR). From one sediment sample S16, 36 AOA OTUs (3% cutoff) were obtained from three clone libraries constructed using three primer sets for amoA gene. Among the 36 OTUs, six were shared by all three clone libraries, two appeared in two clone libraries, and the other 28 were only recovered in one of the libraries. For AOB, only seven OTUs (based on 16S rRNA gene) and eight OTUs (based on amoA gene) were obtained, showing lower diversity than AOA. The qPCR results revealed that AOA amoA gene copy numbers ranged from 9.6 × 10(6) to 5.1 × 10(7) copies per gram of sediment and AOB amoA gene ranged from 9.5 × 10(4) to 6.2 × 10(5) copies per gram of sediment, indicating that the dominant ammonia-oxidizing microorganisms in the sediment of the Pearl River Estuary were AOA. The terminal restriction fragment length polymorphism results showed that the relative abundance of AOB species in the sediment samples of different salinity were significantly different, indicating that salinity might be a key factor shaping the AOB community composition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-011-3107-8) contains supplementary material, which is available to authorized users."
2246,Improved p-hydroxybenzoate production by engineered Pseudomonas putida S12 by using a mixed-substrate feeding strategy,"The key precursors for p-hydroxybenzoate production by engineered Pseudomonas putida S12 are phosphoenolpyruvate (PEP) and erythrose-4-phosphate (E4P), for which the pentose phosphate (PP) pathway is an important source. Since PP pathway fluxes are typically low in pseudomonads, E4P and PEP availability is a likely bottleneck for aromatics production which may be alleviated by stimulating PP pathway fluxes via co-feeding of pentoses in addition to glucose or glycerol. As P. putida S12 lacks the natural ability to utilize xylose, the xylose isomerase pathway from E. coli was introduced into the p-hydroxybenzoate producing strain P. putida S12palB2. The initially inefficient xylose utilization was improved by evolutionary selection after which the p-hydroxybenzoate production was evaluated. Even without xylose-co-feeding, p-hydroxybenzoate production was improved in the evolved xylose-utilizing strain, which may indicate an intrinsically elevated PP pathway activity. Xylose co-feeding further improved the p-hydroxybenzoate yield when co-fed with either glucose or glycerol, up to 16.3 Cmol% (0.1 g p-hydroxybenzoate/g substrate). The yield improvements were most pronounced with glycerol, which probably related to the availability of the PEP precursor glyceraldehyde-3-phosphate (GAP). Thus, it was demonstrated that the production of aromatics such as p-hydroxybenzoate can be improved by co-feeding different carbon sources via different and partially artificial pathways. Moreover, this approach opens new perspectives for the efficient production of (fine) chemicals from renewable feedstocks such as lignocellulose that typically has a high content of both glucose and xylose and (crude) glycerol."
2247,Advances in methods for detection of anaerobic ammonium oxidizing (anammox) bacteria,"Anaerobic ammonium oxidation (anammox), the biochemical process oxidizing ammonium into dinitrogen gas using nitrite as an electron acceptor, has only been recognized for its significant role in the global nitrogen cycle not long ago, and its ubiquitous distribution in a wide range of environments has changed our knowledge about the contributors to the global nitrogen cycle. Currently, several groups of methods are used in detection of anammox bacteria based on their physiological and biochemical characteristics, cellular chemical composition, and both 16S rRNA gene and selective functional genes as biomarkers, including hydrazine oxidoreductase and nitrite reductase encoding genes hzo and nirS, respectively. Results from these methods coupling with advances in quantitative PCR, reverse transcription of mRNA genes and stable isotope labeling have improved our understanding on the distribution, diversity, and activity of anammox bacteria in different environments both natural and engineered ones. In this review, we summarize these methods used in detection of anammox bacteria from various environments, highlight the strengths and weakness of these methods, and also discuss the new development potentials on the existing and new techniques in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-011-3230-6) contains supplementary material, which is available to authorized users."
2248,Isolation and characterisation of KP34—a novel φKMV-like bacteriophage for Klebsiella pneumoniae,"Bacteriophage KP34 is a novel virus belonging to the subfamily Autographivirinae lytic for extended-spectrum β-lactamase-producing Klebsiella pneumoniae strains. Its biological features, morphology, susceptibility to chemical and physical agents, burst size, host specificity and activity spectrum were determined. As a potential antibacterial agent used in therapy, KP34 molecular features including genome sequence and protein composition were examined. Phylogenetic analyses and clustering of KP34 phage genome sequences revealed its clear relationships with “phiKMV-like viruses”. Simultaneously, whole-genome analyses permitted clustering and classification of all phages, with completely sequenced genomes, belonging to the Podoviridae. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-011-3149-y) contains supplementary material, which is available to authorized users."
2249,High-flux isobutanol production using engineered Escherichia coli: a bioreactor study with in situ product removal,"Promising approaches to produce higher alcohols, e.g., isobutanol, using Escherichia coli have been developed with successful results. Here, we translated the isobutanol process from shake flasks to a 1-L bioreactor in order to characterize three E. coli strains. With in situ isobutanol removal from the bioreactor using gas stripping, the engineered E. coli strain (JCL260) produced more than 50 g/L in 72 h. In addition, the isobutanol production by the parental strain (JCL16) and the high isobutanol-tolerant mutant (SA481) were compared with JCL260. Interestingly, we found that the isobutanol-tolerant strain in fact produced worse than either JCL16 or JCL260. This result suggests that in situ product removal can properly overcome isobutanol toxicity in E. coli cultures. The isobutanol productivity was approximately twofold and the titer was 9% higher than n-butanol produced by Clostridium in a similar integrated system."
2250,Enhancing Jatropha oil extraction yield from the kernels assisted by a xylan-degrading bacterium to preserve protein structure,"We investigated the use of bacterial cells isolated from paddy crab for the extraction of oil from Jatropha seed kernels in aqueous media while simultaneously preserving the protein structures of this protein-rich endosperm. A bacterial strain—which was marked as MB4 and identified by means of 16S rDNA sequencing and physiological characterization as either Bacillus pumilus or Bacillus altitudinis—enhanced the extraction yield of Jatropha oil. The incubation of an MB4 starter culture with preheated kernel slurry in aqueous media with the initial pH of 5.5 at 37 °C for 6 h liberated 73% w/w of the Jatropha oil. Since MB4 produces xylanases, it is suggested that strain MB4 facilitates oil liberation via degradation of hemicelluloses which form the oil-containing cell wall structure of the kernel. After MB4 assisted oil extraction, SDS-PAGE analysis showed that the majority of Jatropha proteins were preserved in the solid phase of the extraction residues. The advantages offered by this process are: protein in the residue can be further processed for other applications, no purified enzyme preparation is needed, and the resulting oil can be used for biodiesel production."
2251,Host-specific genetic variation of highly pathogenic avian influenza viruses (H5N1),"The complete genome sequences of two isolates A/chicken/Egypt/CL6/07 (CL6/07) and A/duck/Egypt/D2br10/07 (D2br10/07) of highly pathogenic avian influenza virus (HPAI) H5N1 isolated at the beginning of 2007 outbreak in Egypt were determined and compared with all Egyptian HPAI H5N1 sequences available in the GenBank. Sequence analysis utilizing the RNA from the original tissue homogenate showed amino acid substitutions in seven of the viral segments in both samples. Interestingly, these changes were different between the CL6/07 and D2br10/07 when compared to other Egyptian isolates. Moreover, phylogenetic analysis showed independent sub-clustering of the two viruses within the Egyptian sequences signifying a possible differential adaptation in the two hosts. Further, pre-amplification analysis of H5N1 might be necessary for accurate data interpretation and identification of distinct factor(s) influencing the evolution of the virus in different poultry species."
2252,"Best practices in heterotrophic high-cell-density microalgal processes: achievements, potential and possible limitations","Microalgae of numerous heterotrophic genera (obligate or facultative) exhibit considerable metabolic versatility and flexibility but are currently underexploited in the biotechnological manufacturing of known plant-derived compounds, novel high-value biomolecules or enriched biomass. Highly efficient production of microalgal biomass without the need for light is now feasible in inexpensive, well-defined mineral medium, typically supplemented with glucose. Cell densities of more than 100 g l(−1) cell dry weight have been achieved with Chlorella, Crypthecodinium and Galdieria species while controlling the addition of organic sources of carbon and energy in fedbatch mode. The ability of microalgae to adapt their metabolism to varying culture conditions provides opportunities to modify, control and thereby maximise the formation of targeted compounds with non-recombinant microalgae. This review outlines the critical aspects of cultivation technology and current best practices in the heterotrophic high-cell-density cultivation of microalgae. The primary topics include (1) the characteristics of microalgae that make them suitable for heterotrophic cultivation, (2) the appropriate chemical composition of mineral growth media, (3) the different strategies for fedbatch cultivations and (4) the principles behind the customisation of biomass composition. The review confirms that, although fundamental knowledge is now available, the development of efficient, economically feasible large-scale bioprocesses remains an obstacle to the commercialisation of this promising technology."
2253,Application of the bacteriophage Mu-driven system for the integration/amplification of target genes in the chromosomes of engineered Gram-negative bacteria—mini review,"The advantages of phage Mu transposition-based systems for the chromosomal editing of plasmid-less strains are reviewed. The cis and trans requirements for Mu phage-mediated transposition, which include the L/R ends of the Mu DNA, the transposition factors MuA and MuB, and the cis/trans functioning of the E element as an enhancer, are presented. Mini-Mu(LR)/(LER) units are Mu derivatives that lack most of the Mu genes but contain the L/R ends or a properly arranged E element in cis to the L/R ends. The dual-component system, which consists of an integrative plasmid with a mini-Mu and an easily eliminated helper plasmid encoding inducible transposition factors, is described in detail as a tool for the integration/amplification of recombinant DNAs. This chromosomal editing method is based on replicative transposition through the formation of a cointegrate that can be resolved in a recombination-dependent manner. (E-plus)- or (E-minus)-helpers that differ in the presence of the trans-acting E element are used to achieve the proper mini-Mu transposition intensity. The systems that have been developed for the construction of stably maintained mini-Mu multi-integrant strains of Escherichia coli and Methylophilus methylotrophus are described. A novel integration/amplification/fixation strategy is proposed for consecutive independent replicative transpositions of different mini-Mu(LER) units with “excisable” E elements in methylotrophic cells."
2254,"Biochemical characterization of the carotenoid 1,2-hydratases (CrtC) from Rubrivivax gelatinosus and Thiocapsa roseopersicina","Two carotenoid 1,2-hydratase (CrtC) genes from the photosynthetic bacteria Rubrivivax gelatinosus and Thiocapsa roseopersicina were cloned and expressed in Escherichia coli in an active form and purified by affinity chromatography. The biochemical properties of the recombinant enzymes and their substrate specificities were studied. The purified CrtCs catalyze cofactor independently the conversion of lycopene to 1-HO- and 1,1′-(HO)(2)-lycopene. The optimal pH and temperature for hydratase activity was 8.0 and 30°C, respectively. The apparent K (m) and V (max) values obtained for the hydration of lycopene were 24 μM and 0.31 nmol h(−1) mg(−1) for RgCrtC and 9.5 μM and 0.15 nmol h(−1) mg(−1) for TrCrtC, respectively. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis revealed two protein bands of 44 and 38 kDa for TrCrtC, which indicate protein processing. Both hydratases are also able to convert the unnatural substrate geranylgeraniol (C20 substrate), which functionally resembles the natural substrate lycopene. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-011-3324-1) contains supplementary material, which is available to authorized users."
2255,Review of mass transfer aspects for biological gas treatment,"This contribution reviews the mass transfer aspects of biotechnological processes for gas treatment, with an emphasis on the underlying principles and technical feasible methods for mass transfer enhancements. Understanding of the mass transfer behavior in bioreactors for gas treatment will result in improved reactor designs, reactor operation, and modeling tools, which are important to maximize efficiency and minimize costs. Various methods are discussed that show the potential for a more effective treatment of compounds with poor water solubility."
2256,Ammonia-oxidizing archaea and ammonia-oxidizing bacteria in six full-scale wastewater treatment bioreactors,"In this study, dideoxy sequencing and 454 high-throughput sequencing were used to analyze diversities of the ammonia monooxygenase (amoA) genes and the 16S rRNA genes of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in six municipal wastewater treatment plants. The results showed that AOB amoA genes were quite diverse in different wastewater treatment plants while the 16S rRNA genes were relatively conserved. Based on the observed complexity of amoA and 16S rRNA genes, most of the AOB can be assigned to the Nitrosomonas genus, with Nitrosomonas ureae, Nitrosomonas oligotropha, Nitrosomonas marina, and Nitrosomonas aestuarii being the four most dominant species. From the sequences of the AOA amoA genes, most AOA observed in this study belong to the CGI.1b group, i.e., the soil lineage. The AOB amoA and 16S rRNA genes were quantified by quantitative PCR and 454 high-throughput pyrosequencing, respectively. Although the results from the two approaches show some disconcordance, they both indicated that the abundance of AOB in activated sludge was very low. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-011-3408-y) contains supplementary material, which is available to authorized users."
2257,Post-mortem volatiles of vertebrate tissue,"Volatile emission during vertebrate decay is a complex process that is understood incompletely. It depends on many factors. The main factor is the metabolism of the microbial species present inside and on the vertebrate. In this review, we combine the results from studies on volatile organic compounds (VOCs) detected during this decay process and those on the biochemical formation of VOCs in order to improve our understanding of the decay process. Micro-organisms are the main producers of VOCs, which are by- or end-products of microbial metabolism. Many microbes are already present inside and on a vertebrate, and these can initiate microbial decay. In addition, micro-organisms from the environment colonize the cadaver. The composition of microbial communities is complex, and communities of different species interact with each other in succession. In comparison to the complexity of the decay process, the resulting volatile pattern does show some consistency. Therefore, the possibility of an existence of a time-dependent core volatile pattern, which could be used for applications in areas such as forensics or food science, is discussed. Possible microbial interactions that might alter the process of decay are highlighted."
2258,Fungal enzyme sets for plant polysaccharide degradation,"Enzymatic degradation of plant polysaccharides has many industrial applications, such as within the paper, food, and feed industry and for sustainable production of fuels and chemicals. Cellulose, hemicelluloses, and pectins are the main components of plant cell wall polysaccharides. These polysaccharides are often tightly packed, contain many different sugar residues, and are branched with a diversity of structures. To enable efficient degradation of these polysaccharides, fungi produce an extensive set of carbohydrate-active enzymes. The variety of the enzyme set differs between fungi and often corresponds to the requirements of its habitat. Carbohydrate-active enzymes can be organized in different families based on the amino acid sequence of the structurally related catalytic modules. Fungal enzymes involved in plant polysaccharide degradation are assigned to at least 35 glycoside hydrolase families, three carbohydrate esterase families and six polysaccharide lyase families. This mini-review will discuss the enzymes needed for complete degradation of plant polysaccharides and will give an overview of the latest developments concerning fungal carbohydrate-active enzymes and their corresponding families."
2259,Optimization of fixation methods for observation of bacterial cell morphology and surface ultrastructures by atomic force microscopy,"Fixation ability of five common fixation solutions, including 2.5% glutaraldehyde, 10% formalin, 4% paraformaldehyde, methanol/acetone (1:1), and ethanol/acetic acid (3:1) were evaluated by using atomic force microscopy in the present study. Three model bacteria, i.e., Escherichia coli, Pseudomonas putida, and Bacillus subtilis were applied to observe the above fixation methods for the morphology preservation of bacterial cells and surface ultrastructures. All the fixation methods could effectively preserve cell morphology. However, for preserving bacterial surface ultrastructures, the methods applying aldehyde fixations performed much better than those using alcohols, since the alcohols could detach the surface filaments (i.e., flagella and pili) significantly. Based on the quantitative and qualitative assessments, the 2.5% glutaraldehyde was proposed as a promising fixation solution both for observing morphology of both bacterial cell and surface ultrastructures, while the methonal/acetone mixture was the worst fixation solution which may obtain unreliable results. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-011-3551-5) contains supplementary material, which is available to authorized users."
2260,Long-term in-vitro precision of direct digital X-ray radiogrammetry,"OBJECTIVE: Digital X-ray radiogrammetry (DXR) calculates peripheral bone mineral density (BMD) from hand radiographs. The short-term precision for direct DXR has been reported to be highly satisfactory. However, long-term precision for this method has not been examined. Thus, the aim of this study was to examine the long-term in-vitro precision for the new direct digital version of DXR. MATERIALS AND METHODS: The in-vitro precision for direct DXR was tested with cadaver phantoms on four different X-ray systems at baseline, 3 months, 6 months, and in one machine also at 12 months. At each time point, 31 measurements were performed. RESULTS: The in-vitro longitudinal precision for the four radiographic systems ranged from 0.22 to 0.43% expressed as coefficient of variation (CV%). The smallest detectable difference (SDD) ranged from 0.0034 to 0.0054 g/cm(2). CONCLUSIONS: The in vitro long-term precision for direct DXR was comparable to the previous reported short-term in-vitro precision for all tested X-ray systems. These data show that DXR is a stable method for detecting small changes in bone density during 6–12 months of follow-up."
2261,Diversity and enrichment of nitrite-dependent anaerobic methane oxidizing bacteria from wastewater sludge,"Recently discovered microorganisms affiliated to the bacterial phylum NC10, named “Candidatus Methylomirabilis oxyfera”, perform nitrite-dependent anaerobic methane oxidation. These microorganisms could be important players in a novel way of anaerobic wastewater treatment where ammonium and residual dissolved methane might be removed at the expense of nitrate or nitrite. To find suitable inocula for reactor startup, ten selected wastewater treatment plants (WWTPs) located in The Netherlands were screened for the endogenous presence of M. oxyfera using molecular diagnostic methods. We could identify NC10 bacteria with 98% similarity to M. oxyfera in nine out of ten WWTPs tested. Sludge from one selected WWTP was used to start a new enrichment culture of NC10 bacteria. This enrichment was monitored using specific pmoA primers and M. oxyfera cells were visualized with fluorescence oligonucleotide probes. After 112 days, the enrichment consumed up to 0.4 mM NO(2)(−) per day. The results of this study show that appropriate sources of biomass, enrichment strategies, and diagnostic tools existed to start and monitor pilot scale tests for the implementation of nitrite-dependent methane oxidation in wastewater treatment at ambient temperature. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-011-3361-9) contains supplementary material, which is available to authorized users."
2262,Translational Psychiatry: leading the transition from the cesspool of devastation to a place where the grass is really greener,
2263,Immunological aspects in chronic lymphocytic leukemia (CLL) development,"Chronic lymphocytic leukemia (CLL) is unique among B cell malignancies in that the malignant clones can be featured either somatically mutated or unmutated IGVH genes. CLL cells that express unmutated immunoglobulin variable domains likely underwent final development prior to their entry into the germinal center, whereas those that express mutated variable domains likely transited through the germinal center and then underwent final development. Regardless, the cellular origin of CLL remains unknown. The aim of this review is to summarize immunological aspects involved in this process and to provide insights about the complex biology and pathogenesis of this disease. We propose a mechanistic hypothesis to explain the origin of B-CLL clones into our current picture of normal B cell development. In particular, we suggest that unmutated CLL arises from normal B cells with self-reactivity for apoptotic bodies that have undergone receptor editing, CD5 expression, and anergic processes in the bone marrow. Similarly, mutated CLL would arise from cells that, while acquiring self-reactivity for autoantigens—including apoptotic bodies—in germinal centers, are also still subject to tolerization mechanisms, including receptor editing and anergy. We believe that CLL is a proliferation of B lymphocytes selected during clonal expansion through multiple encounters with (auto)antigens, despite the fact that they differ in their state of activation and maturation. Autoantigens and microbial pathogens activate BCR signaling and promote tolerogenic mechanisms such as receptor editing/revision, anergy, CD5+ expression, and somatic hypermutation in CLL B cells. The result of these tolerogenic mechanisms is the survival of CLL B cell clones with similar surface markers and homogeneous gene expression signatures. We suggest that both immunophenotypic surface markers and homogenous gene expression might represent the evidence of several attempts to re-educate self-reactive B cells."
2264,N-acetylcysteine reduces oxidative stress in sickle cell patients,"Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSβ(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress."
2265,Welcome to Oncogenesis,
2266,EuroFlow: Resetting leukemia and lymphoma immunophenotyping. Basis for companion diagnostics and personalized medicine,
2267,Crossing the boundary between research and health care: P3G policy statement on return of results from population studies,
2268,Dual copy number variants involving 16p11 and 6q22 in a case of childhood apraxia of speech and pervasive developmental disorder,
2269,"Native atretic coarctation of the aorta in a 37-year-old hypertensive woman, treated with a low-profile covered stent",
2270,Quadricuspid pulmonary valve and left pulmonary artery aneurysm in an asymptomatic patient assessed by cardiovascular MRI,"We present a coincidental finding of quadricuspid pulmonary valve and left pulmonary artery aneurysm. As both the pulmonary valve and the pulmonary trunk with its main branches are hard to visualise with cardiac ultrasound, most abnormalities described so far are from autopsy series. With the increasing use of CMR and its excellent potential for visualising both pulmonary valve and pulmonary arteries, we believe more cases will be discovered in the near future. Although pulmonary artery aneurysm are rare, timely detection may prevent lethal bleeding. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12471-011-0115-3) contains supplementary material, which is available to authorized users."
2271,Humoral autoimmune response heterogeneity in the spectrum of primary biliary cirrhosis,"OBJECTIVE: To compare autoantibody features in patients with primary biliary cirrhosis (PBC) and individuals presenting antimitochondria antibodies (AMAs) but no clinical or biochemical evidence of disease. METHODS: A total of 212 AMA-positive serum samples were classified into four groups: PBC (definite PBC, n = 93); PBC/autoimmune disease (AID; PBC plus other AID, n = 37); biochemically normal (BN) individuals (n = 61); and BN/AID (BN plus other AID, n = 21). Samples were tested by indirect immunofluorescence (IIF) on rat kidney (IIF-AMA) and ELISA [antibodies to pyruvate dehydrogenase E2-complex (PDC-E2), gp-210, Sp-100, and CENP-A/B]. AMA isotype was determined by IIF-AMA. Affinity of anti-PDC-E2 IgG was determined by 8 M urea-modified ELISA. RESULTS: High-titer IIF-AMA was more frequent in PBC and PBC/AID (57 and 70 %) than in BN and BN/AID samples (23 and 19 %) (p < 0.001). Triple isotype IIF-AMA (IgA/IgM/IgG) was more frequent in PBC and PBC/AID samples (35 and 43 %) than in BN sample (18 %; p = 0.008; p = 0.013, respectively). Anti-PDC-E2 levels were higher in PBC (mean 3.82; 95 % CI 3.36–4.29) and PBC/AID samples (3.89; 3.15–4.63) than in BN (2.43; 1.92–2.94) and BN/AID samples (2.52; 1.54–3.50) (p < 0.001). Anti-PDC-E2 avidity was higher in PBC (mean 64.5 %; 95 % CI 57.5–71.5 %) and PBC/AID samples (66.1 %; 54.4–77.8 %) than in BN samples (39.2 %; 30.9–37.5 %) (p < 0.001). PBC and PBC/AID recognized more cell domains (mitochondria, nuclear envelope, PML/sp-100 bodies, centromere) than BN (p = 0.008) and BN/AID samples (p = 0.002). Three variables were independently associated with established PBC: high-avidity anti-PDC-E2 (OR 4.121; 95 % CI 2.118–8.019); high-titer IIF-AMA (OR 4.890; 2.319–10.314); antibodies to three or more antigenic cell domains (OR 9.414; 1.924–46.060). CONCLUSION: The autoantibody profile was quantitatively and qualitatively more robust in definite PBC as compared with AMA-positive biochemically normal individuals."
2272,Perspective: the late preterm infant,
2273,Insights into Chinese perspectives on do-not-resuscitate (DNR) orders from an examination of DNR order form completeness for cancer patients,"PURPOSE: Discussing end-of-life care with patients is often considered taboo, and signing a do-not-resuscitate (DNR) order is difficult for most patients, especially in Chinese culture. This study investigated distributions and details related to the signing of DNR orders, as well as the completeness of various DNR order forms. METHODS: Retrospective chart reviews were performed. We screened all charts from a teaching hospital in Taiwan for patients who died of cancer during the period from January 2010 to December 2011. A total of 829 patient records were included in the analysis. The details of the DNR order forms were recorded. RESULTS: The DNR order signing rate was 99.8 %. The percentage of DNR orders signed by patients themselves (DNR-P) was 22.6 %, while the percentage of orders signed by surrogates (DNR-S) was 77.2 %. The percentage of signed DNR forms that were completely filled out was 78.4 %. The percentage of DNR-S forms that were completed was 81.7 %, while the percentage of DNR-P forms that were completely filled out was only 67.6 %. CONCLUSION: Almost all the cancer patients had a signed DNR order, but for the majority of them, the order was signed by a surrogate. Negative attitudes of discussing death from medical professionals and/or the family members of patients may account for the higher number of signed DNR-S orders than DNR-P orders. Moreover, early obtainment of signed DNR orders should be sought, as getting the orders earlier could promote the quality of end-of-life care, especially in non-oncology wards."
2274,"Effect of ghrelin and anamorelin (ONO-7643), a selective ghrelin receptor agonist, on tumor growth in a lung cancer mouse xenograft model","PURPOSE: Anamorelin (ONO-7643) is an orally active ghrelin receptor agonist in development for non-small cell lung cancer (NSCLC)-related anorexia/cachexia. It displays both orexigenic and anabolic properties via ghrelin mimetic activity and transient increases in growth hormone (GH). However, increasing GH and insulin-like growth factor-1 in cancer patients raises concerns of potentially stimulating tumor growth. Therefore, we investigated the effect of ghrelin and anamorelin on tumor growth in a murine NSCLC xenograft model. METHODS: Female nude mice (15–21/group) with established A549 tumors were administered ghrelin (2 mg/kg i.p.), anamorelin (3, 10, or 30 mg/kg p.o.), or vehicle controls daily for 28 days. Tumor growth, food consumption, and body weight were monitored. Murine growth hormone (mGH) and murine insulin-like growth factor-1 (mIGF-1) were measured in plasma. RESULTS: Tumor growth progressed throughout the study, with no significant differences between treatment groups. Daily food consumption was also relatively unchanged, while the percentage of mean body weight gain at the end of treatment was significantly increased in animals administered 10 and 30 mg/kg compared with controls (p < 0.01). Peak mGH levels were significantly higher in ghrelin- and anamorelin-treated animals than in controls, while peak mIGF-1 levels were slightly elevated but not statistically significant. All regimens were well tolerated. CONCLUSIONS: These findings demonstrate that neither anamorelin nor ghrelin promoted tumor growth in this model, despite increased levels of mGH and a trend of increased mIGF-1. Together with anamorelin’s ability to increase body weight, these results support the clinical development of ghrelin receptor agonist treatments for managing NSCLC-related anorexia/cachexia."
2275,Music-based interventions in palliative cancer care: a review of quantitative studies and neurobiological literature,"PURPOSE: This study aimed to review quantitative literature pertaining to studies of music-based interventions in palliative cancer care and to review the neurobiological literature that may bare relevance to the findings from these studies. METHODS: A narrative review was performed, with particular emphasis on RCTs, meta-analyses, and systematic reviews. The Cochrane Library, Ovid, PubMed, CINAHL Plus, PsycINFO, and ProQuest were searched for the subject headings music, music therapy, cancer, oncology, palliative care, pain, anxiety, depression, mood, quality of life, prevalence, neuroscience, functional imaging, endogenous opioids, GABA, 5HT, dopamine, and permutations of these same search terms. Data for the review were comprised of articles published between 1970 and 2012. References of all the cited articles were also reviewed. RESULTS: Available evidence suggests that music-based interventions may have a positive impact on pain, anxiety, mood disturbance, and quality of life in cancer patients. Advances in neurobiology may provide insight into the potential mechanisms by which music impacts these outcomes. CONCLUSIONS: More research is needed to determine what subpopulation of cancer patients is most likely to respond to music-based interventions, what interventions are most effective for individual outcomes, and what measurement parameters best gauge their effectiveness."
2276,Atrial fibrillation after coronary artery bypass grafting,
2277,"A phase Ib combination study of RO4929097, a gamma-secretase inhibitor, and temsirolimus in patients with advanced solid tumors","Background To determine the recommended phase II dose (RP2D) and assess the safety, pharmacokinetics (PKs) and pharmacodynamics of RO4929097in combination with temsirolimus. Methods Escalating doses of RO4929097 and temsirolimus were administered at three dose levels. Patients received once daily oral RO4929097 on a 3 days on/4 days off schedule every week, and weekly intravenous temsirolimus. Blood samples were collected for PK analysis. Archival tissue specimens were collected for Notch pathway biomarker analysis and genotyping of frequent oncogenic mutations. Results Seventeen patients with refractory advanced solid tumors were enrolled in three dose levels (DLs): DL1 (RO4929097 10 mg; Temsirolimus 25 mg), DL2 (RO4929097 20 mg; Temsirolimus 25 mg), and DL3 (RO4929097 20 mg; Temsirolimus 37.5 mg). The most common toxicities related to the study drug combination included: fatigue (82 %; grade 3 6 %), mucositis, (71 %; grade 3 6 %), neutropenia (59 %; grade 3 12 %), anemia (59 %; grade 3 0 %), and hypertriglyceridemia (59 %; grade 3 0 %). Two dose-limiting toxicities, grade 3 rash and grade 3 mucositis, were observed in the same patient in the first dose level prompting dose expansion. Eleven patients (73 %) had stable disease as their best response. Co-administration of RO4929097 was associated with increased clearance and reduced exposure to temsirolimus, suggestive of drug-drug interaction via CYP3A4 induction. No correlation between the expression of Notch pathway biomarkers or genotype and time to progression was noted. Conclusions RO4929097 can be safely combined with temsirolimus in patients with advanced solid tumors. The RP2D was established at 20 mg of RO4929097 combined with 37.5 mg of temsirolimus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10637-013-0001-5) contains supplementary material, which is available to authorized users."
2278,A phase II study of combined VEGF inhibitor (bevacizumab+sorafenib) in patients with metastatic breast cancer: Hoosier Oncology Group Study BRE06-109,"Purpose: Angiogenesis plays an essential role in tumor development, invasion and metastasis. We evaluated the efficacy and safety of dual angiogenesis blockade with bevacizumab and sorafenib in patients with metastatic breast cancer. Patients and Methods: Patients who had received no more than 2 prior chemotherapy regimens in any setting were treated with sorafenib 200 mg as a single oral dose daily plus bevacizumab intravenously 5 mg/kg every other week. Response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST). The primary endpoint was progression free survival (PFS). Results: Eighteen patients were enrolled. Median age was 56 yo, all had good performance status KPS of 0 or 1, and 17 patients had received 1 or 2 prior chemotherapy regimens. Median PFS was 2.8 months. There were no complete or partial responses; 3 patients had stable disease for >6 months. Toxicity was substantial with 9 (50 %) patients reporting Grade 3 toxicity. Seven (39 %) patients discontinued therapy due to adverse events including hypertension (N = 2), GI toxicity (N = 1), sensory neuropathy (N = 1), rash (N = 1), pain (N = 1) and wound complication (N = 1). Given the lack of clear efficacy and increased toxicity, accrual was terminated. Conclusion: The combination of sorafenib and bevacizumab has substantial toxicity and minimal efficacy in patients with previously treated metastatic breast cancer. Further study of this combination is not recommended."
2279,Phase II clinical study of modified FOLFOX7 (intermittent oxaliplatin administration) plus bevacizumab in patients with unresectable metastatic colorectal cancer—CRAFT study,"Purpose Continuous treatment with FOLFOX therapy is associated with peripheral nerve toxicity, and to improve this inconvenient side effect various methods of administration are being investigated. A regimen of intermittent oxaliplatin administration by continuous infusion therapy, i.e., modified FOLFOX7 (mFOLFOX7) + bevacizumab, was designed with the goal of alleviating severe peripheral nerve disorders and hematological toxicity. A phase II clinical study was conducted to evaluate the efficacy and safety of this regimen. Methods Previously untreated patients were assigned to mFOLFOX7 (oxaliplatin 85 mg/m(2), levofolinate [l-LV] 200 mg/m(2), 5-fluorouracil [5-FU] 2400 mg/m(2)) + bevacizumab (5 mg/kg) administered every 2 weeks for 8 cycles, maintenance without oxaliplatin for 8 cycles, and reintroduction of mFOLFOX7 + bevacizumab for 8 cycles or until disease progression. Progression free survival (PFS) following the first dose (PFS 1) and following reintroduction of oxaliplatin (PFS 2) were used as indices for assessing the efficacy of intermittent administration. Results Fifty-two patients were enrolled, with median age of 64 years (range, 36–74). Median PFS 1 was 11.8 months (95 % confidence interval [CI], 9.5 to 13.7), median time to treatment failure was 10.3 months (95 % CI, 5.6 to 12.1), percentage of patients with neutropenia of grade 3 or higher was 7.8 %, and percentage with peripheral nerve disorders was 3.9 %. Response rate was 50 %, and 84.4 % of patients who started modified simplified LV5FU2 + bevacizumab were reintroduced to oxaliplatin. Conclusion By excluding 5-FU bolus administration and administering bevacizumab continuously the mFOLFOX7 + bevacizumab regimen with preplanned withdrawal of oxaliplatin showed high tolerability and prevented severe peripheral neuropathy and neutropenia without reducing efficacy."
2280,"Phase II study of sunitinib in Japanese patients with unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumor","Background. Pancreatic neuroendocrine tumors (NETs) are rare but are frequently diagnosed at advanced stages and require systemic therapy. Patients and methods. This multicenter, open-label, phase II study evaluated sunitinib in Japanese patients with well-differentiated pancreatic NET. Patients received sunitinib 37.5 mg/day on a continuous daily dosing (CDD) schedule. The primary endpoint was clinical benefit rate (CBR; percentage of complete responses [CRs] plus partial responses [PRs] plus stable disease [SD] ≥24 weeks). Secondary endpoints included objective response rate (ORR), tumor shrinkage, progression-free survival (PFS) probability, safety, pharmacokinetics, and biomarkers. Results. Twelve patients received treatment. The CBR was 75 % (95 % confidence interval [CI], 43–94) and included 6 patients with a PR and 3 with SD. The ORR was 50 % (95 % CI, 21–79). PFS probability was 91 % (95 % CI, 54–99) at 6 months and 71 % (95 % CI, 34–90) at 12 months. Commonly reported treatment-emergent (all-causality), any-grade adverse events included diarrhea (n = 10), hand–foot syndrome and hypertension (both n = 8), fatigue and headache (both n = 7), and neutropenia (n = 6). No deaths on study were reported; one death due to disease progression occurred >28 days after end of treatment. Sunitinib on a CDD schedule resulted in sustained drug concentrations without accumulation across cycles. Tumor responses in all 12 patients did not appear to correlate with decreases in chromogranin A levels. Conclusions. Sunitinib 37.5 mg/day on a CDD schedule demonstrated antitumor activity in Japanese patients with unresectable, well-differentiated pancreatic NET. Commonly reported adverse events were consistent with the known safety profile of sunitinib. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10637-012-9910-y) contains supplementary material, which is available to authorized users."
2281,Risk factors for increased left ventricular hypertrophy in patients with chronic kidney disease,"BACKGROUND: Although left ventricular hypertrophy (LVH) has been established as a predictor of cardiovascular events in chronic kidney disease (CKD), the relationship between the prevalence of LVH and CKD stage during the predialysis period has not been fully examined. METHODS: We measured left ventricular mass index (LVMI) in a cross-sectional cohort of participants in the Chronic Kidney Disease Japan Cohort (CKD-JAC) study in order to identify factors that are associated with increased LVMI in patients with stage 3–5 CKD. LVH was defined as LVMI > 125 g/m(2) in male patients and >110 g/m(2) in female patients. RESULTS: We analyzed baseline characteristics in 1185 participants (male 63.7 %, female 36.3 %). Diabetes mellitus was the underlying disease in 41.3 % of patients, and mean age was 61.8 ± 11.1 years. LVH was detected in 21.7 % of patients at baseline. By multivariate logistic analysis, independent risk factors for LVH were past history of cardiovascular disease (odds ratio [OR] 0.574; 95 % confidence interval [CI] 0.360–0.916; P = 0.020), systolic blood pressure (OR 1.179; 95 % CI 1.021–1.360; P = 0.025), body mass index (OR 1.135; 95 % CI 1.074–1.200; P < 0.001), and serum calcium level (OR 0.589; 95 % CI 0.396–0.876; P = 0.009). CONCLUSION: Cross-sectional baseline data from the CKD-JAC study shed light on the association between LVH and risk factors in patients with decreased renal function. Further longitudinal analyses of the CKD-JAC cohort are needed to evaluate the prognostic value of LVH in CKD patients."
2282,Response to Stoll and Resta,
2283,Strain-related physiological and behavioral effects of Skeletonema marinoi on three common planktonic copepods,"Three strains of the chain-forming diatom Skeletonema marinoi, differing in their production of polyunsaturated aldehydes (PUA) and nutritional food components, were used in experiments on feeding, egg production, hatching success, pellet production, and behavior of three common planktonic copepods: Acartia tonsa, Pseudocalanus elongatus, and Temora longicornis. The three different diatom strains (9B, 1G, and 7J) induced widely different effects on Acartia tonsa physiology, and the 9B strain induced different effects for the three copepods. In contrast, different strains induced no or small alterations in the distribution, swimming behavior, and turning frequency of the copepods. 22:6(n-3) fatty acid (DHA) and sterol content of the diet typically showed a positive effect on either egg production (A. tonsa) or hatching success (P. elongatus), while other measured compounds (PUA, other long-chain polyunsaturated fatty acids) of the algae had no obvious effects. Our results demonstrate that differences between strains of a given diatom species can generate effects on copepod physiology, which are as large as those induced by different algae species or groups. This emphasizes the need to identify the specific characteristics of local diatoms together with the interacting effects of different mineral, biochemical, and toxic compounds and their potential implications on different copepod species."
2284,Phylogeography of the diamond turbot (Hypsopsetta guttulata) across the Baja California Peninsula,"We compared morphology and sequenced nuclear and mitochondrial genes from 11 populations of a previously genetically unstudied “Baja California disjunct” species, the diamond turbot (Hypsopsetta guttulata). This species exhibits very limited adult movement and restriction to soft-bottom habitats but has a moderately long pelagic larval duration. Therefore, if pelagic larval duration is correlated with gene flow between Gulf of California and Pacific populations, we expect a reduced level of genetic and morphological differentiation. However, if adult habitat and ecology have more effect on gene flow, we expect the populations in the two bodies of water to be more highly differentiated. We used logistic regression to compare morphological features and phylogenetic and population genetic analyses to compare nucleotide sequence data. Gulf of California H. guttulata are different from Pacific populations in morphology and both mitochondrial and nuclear gene sequences. MtDNA shows reciprocal monophyly, and nuclear sequences from the Gulf of California formed a monophyletic group. Population genetic analyses also suggest further population subdivision within the Pacific and within the Gulf of California. We argue that adult ecology has a significant effect on migration rates among populations in the Pacific Ocean and the Gulf of California."
2285,"Long-term individual identification and site fidelity of white sharks, Carcharodon carcharias, off California using dorsal fins","Mark-recapture techniques can be used to estimate white shark (Carcharodon carcharias) population abundance. These frameworks are based on assumptions that marks are conserved and animals are present at the sampling location over the entire duration of the study. Though these assumptions have been validated across short-time scales for white sharks, long-term studies of population trends are dependent on these assumptions being valid across longer periods. We use 22 years of photographic data from aggregation sites in central California to support the use of dorsal fin morphology as long-term individual identifiers. We identified five individuals over 16–22 years, which support the use of dorsal fins as long-time individual identifiers, illustrate strong yearly site fidelity to coastal aggregation sites across extended time periods (decades), and provide the first empirical validation of white shark longevity >22 years. These findings support the use of fin morphology in mark-recapture frameworks for white sharks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00227-011-1643-5) contains supplementary material, which is available to authorized users."
2286,Beyond newborn survival: the world you are born into determines your risk of disability-free survival,
2287,AT(2) Receptor and Tissue Injury: Therapeutic Implications,"The renin-angiotensin system (RAS) plays an important role in the initiation and progression of tissue injuries in the cardiovascular and nervous systems. The detrimental actions of the AT(1) receptor (AT(1)R) in hypertension and vascular injury, myocardial infarction and brain ischemia are well established. In the past twenty years, protective actions of the RAS, not only in the cardiovascular, but also in the nervous system, have been demonstrated. The so-called protective arm of the RAS includes AT(2)-receptors and Mas receptors (AT(2)R and MasR) and is characterized by effects different from and often opposing those of the AT(1)R. These include anti-inflammation, anti-fibrosis, anti-apoptosis and neuroregeneration that can counterbalance pathological processes and enable recovery from disease. The recent development of novel, small-molecule AT(2)R agonists offers a therapeutic potential in humans with a variety of clinical indications."
2288,"Waterborne cues from crabs induce thicker skeletons, smaller gonads and size-specific changes in growth rate in sea urchins","Indirect predator-induced effects on growth, morphology and reproduction have been extensively studied in marine invertebrates but usually without consideration of size-specific effects and not at all in post-metamorphic echinoids. Urchins are an unusually good system, in which, to study size effects because individuals of various ages within one species span four orders of magnitude in weight while retaining a nearly isometric morphology. We tracked growth of urchins, Strongylocentrotus droebachiensis (0.013–161.385 g), in the presence or absence of waterborne cues from predatory Jonah crabs, Cancer borealis. We ran experiments at ambient temperatures, once for 4 weeks during summer and again, with a second set of urchins, for 22 weeks over winter. We used a scaled, cube-root transformation of weight for measuring size more precisely and for equalizing variance across sizes. Growth rate of the smallest urchins (summer: <17 mm diameter; winter: <7 mm diameter) decreased by 40–42% in response to crab cues. In contrast, growth rate of larger urchins was unaffected in the summer and increased in response to crab scent by 7% in the winter. At the end of the 22-week experiment, additional gonadal and skeletal variables were measured. Cue-exposed urchins developed heavier, thicker skeletons and smaller gonads, but no differences in spine length or jaw size. The differences depended on urchin size, suggesting that there are size-specific shifts in gonadal and somatic investment in urchins."
2289,"The use of Instanyl® in the treatment of breakthrough pain in cancer patients: a 3-month observational, prospective, cohort study","PURPOSE: Instanyl® (intranasal fentanyl spray) is a novel treatment for breakthrough pain (BTP) in cancer patients. It has shown a rapid onset of pain relief in clinical trials. This study examines the use of Instanyl® in real-life settings. METHODS: A 3-month observational, prospective, cohort study of cancer patients with BTP receiving Instanyl® (50, 100, or 200 μg) under routine clinical practice. Data were collected at three time points corresponding with routine clinic visits – baseline, Week 4, and Week 13. Primary outcomes: success of titration and maintenance dose after titration. Secondary outcomes: change in maintenance dose of Instanyl® and level of background pain medication; Brief Pain Inventory—Short Form (BPI-SF) and Patient Treatment Satisfaction Scale (PTSS) scores; adverse drug reactions (ADRs). RESULTS: Titration with Instanyl® was successful in 84.5 % of 309 patients; most patients were titrated at the lowest dose (50 μg). The majority showed no change in maintenance dose, with little change in the level of background pain medication. BPI-SF and PTSS scores significantly improved from baseline to Week 4. The main reason for terminating Instanyl® was death, as expected due to the underlying disease; incidence of ADRs was low and no fatal ADRs were reported. CONCLUSIONS: In a real-life group of cancer patients with disease progression, Instanyl® was titrated successfully at doses <200 μg in the majority of patients, requiring only one dose, with no further change in maintenance dose. Pain severity, impact of pain on daily life, and treatment satisfaction significantly improved with Instanyl® treatment. No unexpected ADRs occurred."
2290,Genetic counseling for women referred for advanced maternal age: a telegenetic approach,
2291,Welcome to the next step for Oncogenesis,
2292,Hypothalamic Signaling Mechanisms in Hypertension,"The etiology of hypertension, a critical public health issue affecting one in three US adults, involves the integration of the actions of multiple organ systems, including the central nervous system. Increased activation of the central nervous system, driving enhanced sympathetic outflow and increased blood pressure, has emerged as a major contributor to the pathogenesis of hypertension. The hypothalamus is a key brain site acting to integrate central and peripheral inputs to ultimately impact blood pressure in multiple disease states that evoke hypertension. This review highlights recent advances that have identified novel signal transduction mechanisms within multiple hypothalamic nuclei (e.g., paraventricular nucleus, arcuate nucleus) acting to drive the pathophysiology of hypertension in neurogenic hypertension, angiotensin II hypertension, salt-sensitive hypertension, chronic intermittent hypoxia, and obesity-induced hypertension. Increased understanding of hypothalamic activity in hypertension has the potential to identify novel targets for future therapeutic interventions designed to treat hypertension."
2293,On the Development of Implicit and Control Processes in Relation to Substance Use in Adolescence,"Adolescence is a period in which brain structures involved in motivation and cognitive control continue to develop and also a period in which many youth begin substance use. Dual-process models propose that, among substance users, implicit or automatically activated neurocognitive processes gain in relative influence on substance use behavior, while the influence of cognitive control or reflective processes weakens. There is evidence that a variety of implicit cognitive processes, such as attentional bias, biased action tendencies (approach bias), memory bias and at a neural level, cue reactivity, are associated with adolescent substance use. The impact of these implicit processes on the further development of addictive behaviors appears to depend on moderating factors, such as (premorbid) executive control functions. Clear negative effects of adolescent substance use on executive control functions generally have not been found using behavioral tasks, although some studies have identified subtle and specific effects on cognitive functioning."
2294,Berardinelli-Seip syndrome and achalasia: a shared pathomechanism?,"Berardinelli-Seip congenital lipodystrophy (BSCL) is an uncommon autosomal recessive disorder. Patients with BSCL present with a distinct phenotype since subcutaneous fat is largely lacking and musculature has become more prominent. During childhood, diabetes and acanthosis nigricans evolve and female patients may develop hirsutism. Different genes encoding this entity have been described. Achalasia is a rare esophageal motility disorder, characterized by its distinct motility pattern with absent or incomplete lower esophageal sphincter (LES) relaxations. The exact cause of achalasia is yet unknown. Here, we describe a patient with achalasia in the context of BSCL, which might be linked by a shared pathophysiologic background, as evaluated in this case report. Conclusion: In a BSCL patient presenting with gastrointestinal symptoms, a motility disorder of the gastrointestinal tract should be considered."
2295,Towards an unbiased view of science,Authors at Nature Communications now have the option to choose double-blind peer review
2296,Are we overlooking the qualitative ‘look' of obesity?,
2297,Brain Imaging in Gambling Disorder,"Gambling disorder recently was reclassified under the category “substance-related and addictive disorders.” With regard to the diagnostic criteria, it overlaps a great deal with substance use disorder, i.e., loss of control, craving/withdrawal, and neglect of other areas of life. However, the gambling disorder symptom “chasing one’s losses” is the only criterion absent from substance use disorder. Therefore, special forms of reward (i.e., gain/loss) processing, such as the processing of loss avoidance and loss aversion, have just recently attracted attention among gambling disorder researchers. Because gambling disorder might be considered an addiction in its “pure” form, i.e., without the influence of a drug of abuse, investigating brain volume changes in people with this behavioral addiction is an important task for neuroimaging researchers in exploring the neural signatures of addiction. Because the brain is a complex network, investigation of alterations in functional connectivity has gained interest among gambling disorder researchers in order to get a more complete picture of functional brain changes in people with gambling disorder. However, only a few studies on brain structure and functional connectivity in gambling disorder have been performed so far. This review focuses on brain imaging studies of reward and loss processing, with an emphasis on loss avoidance and aversion as well as brain volume and functional connectivity in gambling disorder."
2298,Corrigendum: Circadian control of bile acid synthesis by a KLF15-Fgf15 axis,
2299,Corrigendum: Revealing the planar chemistry of two-dimensional heterostructures at the atomic level,
2300,Corrigendum: miR-218 is essential to establish motor neuron fate as a downstream effector of Isl1–Lhx3,
2301,Corrigendum: Programmed cell death 5 mediates HDAC3 decay to promote genotoxic stress response,
2302,Corrigendum: GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters,
2303,Corrigendum: Processing of visually evoked innate fear by a non-canonical thalamic pathway,
2304,Erratum: Steady-state cross-correlations for live two-colour super-resolution localization data sets,
2305,Erratum: A phosphorylation switch controls the spatiotemporal activation of Rho GTPases in directional cell migration,
2306,"A Novel Targeted Screening Tool for Hypogammaglobulinemia: Measurement of Serum Immunoglobulin (IgG, IgM, IgA) Levels from Dried Blood Spots (Ig-DBS Assay)","PURPOSE: To develop an assay to quantify serum immunoglobulin (IgG, IgM, IgA) levels using dried blood spots (DBS) obtained on collection cards to be used as a tool for targeted screening for hypogammaglobulinemia. METHODS: DBS samples, along with simultaneous serum samples, were collected from 107 healthy individuals (11 months to 57 years of age). After eluting proteins from DBS, IgG, IgM, and IgA were quantified by an enzyme-linked immunosorbent assay (ELISA). The Ig-DBS assay was validated through calibration curve performance, intra- and inter-assay precision, accuracy, specificity, selectivity, and linearity. The ELISA measurements were compared with serum Ig levels obtained using a standard nephelometry assay on serum samples collected simultaneously with the DBS samples and the results of the two assays were correlated. The stability of IgG, IgM, and IgA in the DBS was tested at room temperature, 36° to 38 °C, 2 to 8 °C, and −25 to −40 °C, from 4 to 14 days. RESULTS: The Ig-DBS assay demonstrated precision, accuracy, specificity, selectivity, and linearity. Using the identified correlation coefficients of 0.834 for IgG, 0.789 for IgM, and 0.918 for IgA, the standard nephelometry-based normal reference ranges for all 3 serum Ig isotypes could be used with the Ig-DBS assay in individuals ≥16 years of age. The DBS samples were stable for 14 days at room temperature in a closed polyethylene bag. CONCLUSIONS: The Ig-DBS assay is both sensitive and accurate for quantification of serum immunoglobulins. Samples are sufficiently stable at ambient temperature to allow for convenient shipping and analysis at a centralized laboratory. This assay therefore presents a new option for screening patients ≥16 years of age for hypogammaglobulinemia in any setting."
2307,Subcutaneous Immunoglobulin Replacement Therapy with Hizentra® is Safe and Effective in Children Less Than 5 Years of Age,"BACKGROUND: Hizentra® (IGSC 20 %) is a 20 % liquid IgG product approved for subcutaneous administration in adults and children 2 years of age and older who have primary immunodeficiency disease (PIDD). There is limited information about the use of IGSC 20 % in very young children including those less than 5 years of age. METHODS: A retrospective chart review involved 88 PIDD infants and children less than 5 years of age who received Hizentra®. RESULTS: The mean age at the start of Hizentra® was 34 months (range 2 to 59 months). IGSC 20 % was administered weekly to 86 infants (two additional infants received twice weekly and three times weekly infusions, respectively) and included an average of 63 infusions (range 6–182) for an observation period up to 45.5 months. Infusion by manual delivery occurred in 15 patients. The mean dose was 674 mg/kg/4 weeks. The mean IgG level was 942 mg/dL while on IGSC 20 %, compared to a mean trough IgG level of 794 mg/dL (p < 0.0001) during intravenous or subcutaneous IgG administration prior to IGSC 20 %. Average infusion time was 47 (range 5–120) minutes, and the median number of infusion sites was 2 (range 1–4). Local reactions were mostly mild and observed in 36/88 (41 %) children. No serious adverse events were reported. A significant increase in weight percentile (7 % ± 19.2, p = 0.0012) among subjects was observed during IGSC 20 % administration. The rate of serious bacterial infections was 0.067 per patient-year while receiving IGSC 20 %, similar to previously reported efficacy studies. CONCLUSIONS: Hizentra® is effective in preventing infections, and is well tolerated in children less than age 5 years."
2308,Erratum: A molecular propeller effect for chiral separation and analysis,
2309,Corrigendum: NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma,
2310,Erratum: Nanometre-scale probing of spin waves using single electron spins,
2311,Erratum: Low-threshold amplified spontaneous emission and lasing from colloidal nanocrystals of caesium lead halide perovskites,
2312,Corrigendum: Rh D blood group conversion using transcription activator-like effector nucleases,
2313,Erratum: Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity,
2314,Erratum: RTN1 mediates progression of kidney disease by inducing ER stress,
2315,Corrigendum: Tonic endocannabinoid-mediated modulation of GABA release is independent of the CB(1) content of axon terminals,
2316,Erratum: Exposure to a youthful circulation rejuvenates bone repair through modulation of β-catenin,
2317,Erratum: Structural isomerism in gold nanoparticles revealed by X-ray crystallography,
2318,Erratum: Autophagy and endosomal trafficking inhibition by Vibrio cholerae MARTX toxin phosphatidylinositol-3-phosphate-specific phospholipase A1 activity,
2319,Erratum: Coherence in the presence of absorption and heating in a molecule interferometer,
2320,Erratum: Cooper pair splitting in parallel quantum dot Josephson junctions,
2321,Erratum: The genomics of ecological vicariance in threespine stickleback fish,
2322,Erratum: Lateral forces on circularly polarizable particles near a surface,
2323,Transparent peer review at Nature Communications,Authors of papers submitted from January 2016 will be given the option to publish the peer review history of their paper
2324,Corrigendum: ChEC-seq kinetics discriminates transcription factor binding sites by DNA sequence and shape in vivo,
2325,Corrigendum: Rare coding variants and X-linked loci associated with age at menarche,
2326,Genetic screening in sudden cardiac death in the young can save future lives,"BACKGROUND: Autopsy of sudden cardiac death (SCD) in the young shows a structurally and histologically normal heart in about one third of cases. Sudden death in these cases is believed to be attributed in a high percentage to inherited arrhythmogenic diseases. The purpose of this study was to investigate the value of performing post-mortem genetic analysis for autopsy-negative sudden unexplained death (SUD) in 1 to 35 year olds. METHODS AND RESULTS: From January 2009 to December 2011, samples from 15 cases suffering SUD were referred to the Department of Clinical Genetics, Umeå University Hospital, Sweden, for molecular genetic evaluation. PCR and bidirectional Sanger sequencing of genes important for long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome type 1 (BrS1), and catecholaminergic polymorphic ventricular tachycardia (CPVT) (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and RYR2) was performed. Multiplex ligation-dependent probe amplification (MLPA) was used to detect large deletions or duplications in the LQTS genes. Six pathogenic sequence variants (four LQTS and two CPVT) were discovered in 15 SUD cases (40 %). Ten first-degree family members were found to be mutation carriers (seven LQTS and three CPVT). CONCLUSION: Cardiac ion channel genetic testing in autopsy-negative sudden death victims has a high diagnostic yield, with identification of the disease in 40 % of families. First-degree family members should be offered predictive testing, clinical evaluation, and treatment with the ultimate goal to prevent sudden death."
2327,Effect of body mass and clothing on carrion entomofauna,"Carcass mass largely affects pattern and rate of carrion decomposition. Supposedly, it is similarly important for carrion entomofauna; however, most of its likely effects have not been tested experimentally. Here, simultaneous effects of carcass mass and clothing are analyzed. A factorial block experiment with four levels of carcass mass (small carcasses 5–15 kg, medium carcasses 15.1–30 kg, medium/large carcasses 35–50 kg, large carcasses 55–70 kg) and two levels of carcass clothing (clothed and unclothed) was made in a grassland habitat of Western Poland. Pig carcasses (N = 24) were grouped into spring, early summer, and late summer blocks. Insects were sampled manually and with pitfall traps. Results demonstrate that insect assemblages are more complex, abundant, and long-lasting on larger carcasses, whereas clothing is of minor importance in this respect. Only large or medium/large carcasses were colonized by all guilds of carrion insects, while small or medium carcasses revealed high underrepresentation of late-colonizing insects (e.g., Cleridae or Nitidulidae). This finding indicates that carcasses weighing about 23 kg—a standard in forensic decomposition studies—give an incomplete picture of carrion entomofauna. Residencies of all forensically relevant insects were distinctly prolonged on larger carcasses, indicating that cadaver mass is a factor of great importance in this respect. The pre-appearance interval of most taxa was found to be unrelated to mass or clothing of a carcass. Moreover, current results suggest that rate of larval development is higher on smaller carcasses. In conclusion, this study demonstrates that carcass mass is a factor of crucial importance for carrion entomofauna, whereas the importance of clothing is small."
2328,Erratum: A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of theranostic agents,
2329,Corrigendum: Characterizing noise structure in single-cell RNA-seq distinguishes genuine from technical stochastic allelic expression,
2330,Corrigendum: Artemisinin-resistant Plasmodium falciparum clinical isolates can infect diverse mosquito vectors of Southeast Asia and Africa,
2331,Corrigendum: Impaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases,
2332,Erratum: Ankyrin-mediated self-protection during cell invasion by the bacterial predator Bdellovibrio bacteriovorus,
2333,Corrigendum: High-performance n-type black phosphorus transistors with type control via thickness and contact-metal engineering,
2334,Corrigendum: Optically initialized robust valley-polarized holes in monolayer WSe(2),
2335,Corrigendum: Photon number statistics uncover the fluctuations in non-equilibrium lattice dynamics,
2336,Erratum: The assembly dynamics of the cytolytic pore toxin ClyA,
2337,"Chronic antiplatelet therapy is not associated with alterations in the presentation, outcome, or host response biomarkers during sepsis: a propensity-matched analysis","PURPOSE: Sepsis is a major health burden worldwide. Preclinical investigations in animals and retrospective studies in patients have suggested that inhibition of platelets may improve the outcome of sepsis. In this study we investigated whether chronic antiplatelet therapy impacts on the presentation and outcome of sepsis, and the host response. METHODS: We performed a prospective observational study in 972 patients admitted with sepsis to the mixed intensive care units (ICUs) of two hospitals in the Netherlands between January 2011 and July 2013. Of them, 267 patients (27.5 %) were on antiplatelet therapy (95.9 % acetylsalicylic acid) before admission. To account for differential likelihoods of receiving antiplatelet therapy, a propensity score was constructed, including variables associated with use of antiplatelet therapy. Cox proportional hazards regression was used to estimate the association of antiplatelet therapy with mortality. RESULTS: Antiplatelet therapy was not associated with sepsis severity at presentation, the primary source of infection, causative pathogens, the development of organ failure or shock during ICU stay, or mortality up to 90 days after admission, in either unmatched or propensity-matched analyses. Antiplatelet therapy did not modify the values of 19 biomarkers providing insight into hallmark host responses to sepsis, including activation of the coagulation system, the vascular endothelium, the cytokine network, and renal function, during the first 4 days after ICU admission. CONCLUSIONS: Pre-existing antiplatelet therapy is not associated with alterations in the presentation or outcome of sepsis, or the host response. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-015-4171-9) contains supplementary material, which is available to authorized users."
2338,What’s new in bacterial meningitis,
2339,Corrigendum: Systematic pan-cancer analysis of tumour purity,
2340,Corrigendum: An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer,
2341,Corrigendum: Glycan complexity dictates microbial resource allocation in the large intestine,
2342,Corrigendum: A draft network of ligand-receptor-mediated multicellular signalling in human,
2343,Corrigendum: A fluorescent hormone biosensor reveals the dynamics of jasmonate signalling in plants,
2344,Corrigendum: Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations,
2345,Erratum: Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection,
2346,Corrigendum: Modulating protein activity using tethered ligands with mutually exclusive binding sites,
2347,Corrigendum: EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-β oligomers and plaques,
2348,Erratum: Inhibition of stationary phase respiration impairs persister formation in E. coli,
2349,Corrigendum: Delivery of crop pollination services is an insufficient argument for wild pollinator conservation,
2350,Corrigendum: Loess Plateau storage of Northeastern Tibetan Plateau-derived Yellow River sediment,
2351,Erratum: Nanoscale visualization of functional adhesion/excitability nodes at the intercalated disc,
2352,Corrigendum: Polaronic metal state at the LaAlO(3)/SrTiO(3) interface,
2353,New drug approvals in acute myeloid leukemia: what's the best end point?,
2354,Corrigendum: Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake,
2355,Corrigendum: DICER1 and microRNA regulation in post-traumatic stress disorder with comorbid depression,
2356,Corrigendum: Notch signal strength controls cell fate in the haemogenic endothelium,
2357,Erratum: RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection,
2358,Corrigendum: Elucidating the role of disorder and free-carrier recombination kinetics in CH(3)NH(3)PbI(3) perovskite films,
2359,Erratum: Multimodal stimulus coding by a gustatory sensory neuron in Drosophila larvae,
2360,Erratum: Graphene oxide/metal nanocrystal multilaminates as the atomic limit for safe and selective hydrogen storage,
2361,Corrigendum: An interactive web-based application for Comprehensive Analysis of RNAi-screen Data,
2362,Rethinking regeneration: empowerment of stem cells by inflammation,
2363,Corrigendum: CCR7-dependent trafficking of RORγ(+) ILCs creates a unique microenvironment within mucosal draining lymph nodes,
2364,Corrigendum: TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport,
2365,Estimating the age of Calliphora vicina eggs (Diptera: Calliphoridae): determination of embryonic morphological landmarks and preservation of egg samples,"Blow fly eggs may sometimes be the only entomological evidence recovered in a forensic case, especially in cooler weather when hatching might take several days: hence, a method for estimating their age is greatly needed. However, developmental data on blow fly eggs are mainly limited to records of the time to larval hatching. The current paper describes the morphological changes occurring during embryogenesis of the blow fly Calliphora vicina Robineau-Desvoidy and their timing in relation to temperature, in order to determine those characters which can be used for simple egg age estimation using light microscopy. At 7.3 and 25 °C, 15 easily visualised morphological landmarks were determined in C. vicina living embryos, allowing for their age estimation with a resolution of 10–20 % of total egg developmental time. The observed age intervals were compared to the embryonic stages described for the fruit fly Drosophila melanogaster Meigen, which are used as reference data in multiple developmental studies. Moreover, current guidelines for preservation of egg samples, which recommend the placement of living eggs directly into 80 % ethanol, were tested against the hot water killing (HWK) method prior to preservation in 80 % ethanol, recommended for larval and pupal specimens. Direct placement of eggs into 80 % ethanol caused marked decomposition of samples, and no morphological landmarks were discernible. On the other hand, HWK fixation prior to preservation in 80 % ethanol enabled visualisation of 11 of the 15 age-specific morphological landmarks that were discernible in living embryos. Therefore, HWK fixation prior to preservation in 80 % ethanol is recommended for egg samples, thus unifying the protocols for collecting entomological evidence."
2366,Erratum: Layer-dependent quantum cooperation of electron and hole states in the anomalous semimetal WTe(2),
2367,Amplicon-based semiconductor sequencing of human exomes: performance evaluation and optimization strategies,"The Ion Proton platform allows to perform whole exome sequencing (WES) at low cost, providing rapid turnaround time and great flexibility. Products for WES on Ion Proton system include the AmpliSeq Exome kit and the recently introduced HiQ sequencing chemistry. Here, we used gold standard variants from GIAB consortium to assess the performances in variants identification, characterize the erroneous calls and develop a filtering strategy to reduce false positives. The AmpliSeq Exome kit captures a large fraction of bases (>94 %) in human CDS, ClinVar genes and ACMG genes, but with 2,041 (7 %), 449 (13 %) and 11 (19 %) genes not fully represented, respectively. Overall, 515 protein coding genes contain hard-to-sequence regions, including 90 genes from ClinVar. Performance in variants detection was maximum at mean coverage >120×, while at 90× and 70× we measured a loss of variants of 3.2 and 4.5 %, respectively. WES using HiQ chemistry showed ~71/97.5 % sensitivity, ~37/2 % FDR and ~0.66/0.98 F1 score for indels and SNPs, respectively. The proposed low, medium or high-stringency filters reduced the amount of false positives by 10.2, 21.2 and 40.4 % for indels and 21.2, 41.9 and 68.2 % for SNP, respectively. Amplicon-based WES on Ion Proton platform using HiQ chemistry emerged as a competitive approach, with improved accuracy in variants identification. False-positive variants remain an issue for the Ion Torrent technology, but our filtering strategy can be applied to reduce erroneous variants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-016-1656-8) contains supplementary material, which is available to authorized users."
2368,Refining the Y chromosome phylogeny with southern African sequences,"The recent availability of large-scale sequence data for the human Y chromosome has revolutionized analyses of and insights gained from this non-recombining, paternally inherited chromosome. However, the studies to date focus on Eurasian variation, and hence the diversity of early-diverging branches found in Africa has not been adequately documented. Here, we analyze over 900 kb of Y chromosome sequence obtained from 547 individuals from southern African Khoisan- and Bantu-speaking populations, identifying 232 new sequences from basal haplogroups A and B. We identify new clades in the phylogeny, an older age for the root, and substantially older ages for some individual haplogroups. Furthermore, while haplogroup B2a is traditionally associated with the spread of Bantu speakers, we find that it probably also existed in Khoisan groups before the arrival of Bantu speakers. Finally, there is pronounced variation in branch length between major haplogroups; in particular, haplogroups associated with Bantu speakers have significantly longer branches. Technical artifacts cannot explain this branch length variation, which instead likely reflects aspects of the demographic history of Bantu speakers, such as recent population expansion and an older average paternal age. The influence of demographic factors on branch length variation has broader implications both for the human Y phylogeny and for similar analyses of other species. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-016-1651-0) contains supplementary material, which is available to authorized users."
2369,Allele-specific transcription factor binding to common and rare variants associated with disease and gene expression,"Genome-wide association studies (GWAS) have identified a large number of disease-associated SNPs, but in few cases the functional variant and the gene it controls have been identified. To systematically identify candidate regulatory variants, we sequenced ENCODE cell lines and used public ChIP-seq data to look for transcription factors binding preferentially to one allele. We found 9962 candidate regulatory SNPs, of which 16 % were rare and showed evidence of larger functional effect than common ones. Functionally rare variants may explain divergent GWAS results between populations and are candidates for a partial explanation of the missing heritability. The majority of allele-specific variants (96 %) were specific to a cell type. Furthermore, by examining GWAS loci we found >400 allele-specific candidate SNPs, 141 of which were highly relevant in our cell types. Functionally validated SNPs support identification of an SNP in SYNGR1 which may expose to the risk of rheumatoid arthritis and primary biliary cirrhosis, as well as an SNP in the last intron of COG6 exposing to the risk of psoriasis. We propose that by repeating the ChIP-seq experiments of 20 selected transcription factors in three to ten people, the most common polymorphisms can be interrogated for allele-specific binding. Our strategy may help to remove the current bottleneck in functional annotation of the genome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-016-1654-x) contains supplementary material, which is available to authorized users."
2370,Harnessing publicly available genetic data to prioritize lipid modifying therapeutic targets for prevention of coronary heart disease based on dysglycemic risk,"Therapeutic interventions that lower LDL-cholesterol effectively reduce the risk of coronary artery disease (CAD). However, statins, the most widely prescribed LDL-cholesterol lowering drugs, increase diabetes risk. We used genome-wide association study (GWAS) data in the public domain to investigate the relationship of LDL-C and diabetes and identify loci encoding potential drug targets for LDL-cholesterol modification without causing dysglycemia. We obtained summary-level GWAS data for LDL-C from GLGC, glycemic traits from MAGIC, diabetes from DIAGRAM and CAD from CARDIoGRAMplusC4D consortia. Mendelian randomization analyses identified a one standard deviation (SD) increase in LDL-C caused an increased risk of CAD (odds ratio [OR] 1.63 (95 % confidence interval [CI] 1.55, 1.71), which was not influenced by removing SNPs associated with diabetes. LDL-C/CAD-associated SNPs showed consistent effect directions (binomial P = 6.85 × 10(−5)). Conversely, a 1-SD increase in LDL-C was causally protective of diabetes (OR 0.86; 95 % CI 0.81, 0.91), however LDL-cholesterol/diabetes-associated SNPs did not show consistent effect directions (binomial P = 0.15). HMGCR, our positive control, associated with LDL-C, CAD and a glycemic composite (derived from GWAS meta-analysis of four glycemic traits and diabetes). In contrast, PCSK9, APOB, LPA, CETP, PLG, NPC1L1 and ALDH2 were identified as “druggable” loci that alter LDL-C and risk of CAD without displaying associations with dysglycemia. In conclusion, LDL-C increases the risk of CAD and the relationship is independent of any association of LDL-C with diabetes. Loci that encode targets of emerging LDL-C lowering drugs do not associate with dysglycemia, and this provides provisional evidence that new LDL-C lowering drugs (such as PCSK9 inhibitors) may not influence risk of diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00439-016-1647-9) contains supplementary material, which is available to authorized users."
2371,Corrigendum: Delivery of therapeutic agents by nanoparticles made of grapefruit-derived lipids,
2372,Corrigendum: Open access resources for genome-wide association mapping in rice,
2373,Corrigendum: Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders,
2374,Corrigendum: LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice,
2375,Corrigendum: Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis,
2376,Erratum: Oxygen depletion recorded in upper waters of the glacial Southern Ocean,
2377,Corrigendum: Growth of semiconducting single-wall carbon nanotubes with a narrow band-gap distribution,
2378,Erratum: Damage-free vibrational spectroscopy of biological materials in the electron microscope,
2379,Corrigendum: T-cell activation is an immune correlate of risk in BCG vaccinated infants,
2380,Corrigendum: A coral-on-a-chip microfluidic platform enabling live-imaging microscopy of reef-building corals,
2381,Corrigendum: High yield and ultrafast sources of electrically triggered entangled-photon pairs based on strain-tunable quantum dots,
2382,Corrigendum: Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan,
2383,Corrigendum: HSP90 regulates temperature-dependent seedling growth in Arabidopsis by stabilizing the auxin co-receptor F-box protein TIR1,
2384,Erratum: Magnetic droplet nucleation boundary in orthogonal spin-torque nano-oscillators,
2385,Erratum: Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression,
2386,Erratum: Myoscape controls cardiac calcium cycling and contractility via regulation of L-type calcium channel surface expression,
2387,Erratum: Transcriptomes of parents identify parenting strategies and sexual conflict in a subsocial beetle,
2388,Erratum: Nanoelectronic primary thermometry below 4 mK,
2389,Corrigendum: Radiocarbon constraints on the extent and evolution of the South Pacific glacial carbon pool,
2390,Corrigendum: Diverse human extracellular RNAs are widely detected in human plasma,
2391,Erratum: Induction of IL-25 secretion from tumour-associated fibroblasts suppresses mammary tumour metastasis,
2392,Corrigendum: The solvation of electrons by an atmospheric-pressure plasma,
2393,Corrigendum: Analysing black phosphorus transistors using an analytic Schottky barrier MOSFET model,
2394,"Erratum: The somatic mutation profiles of 2,433 breast cancers refine their genomic and transcriptomic landscapes",
2395,Erratum: Correspondence: Reply to ‘Enhancing a phase measurement by sequentially probing a solid-state system',
2396,Erratum: Correspondence: Enhancing a phase measurement by sequentially probing a solid-state system,
2397,Corrigendum: Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway,
2398,Corrigendum: Endothelial Dicer promotes atherosclerosis and vascular inflammation by miRNA-103-mediated suppression of KLF4,
2399,Erratum: Genetic link between renal birth defects and congenital heart disease,
2400,Erratum: Elastic spheres can walk on water,
2401,Corrigendum: Nuclear RNA-seq of single neurons reveals molecular signatures of activation,
2402,Corrigendum: Alternative futures for Borneo show the value of integrating economic and conservation targets across borders,
2403,Corrigendum: Iron-catalysed cross-coupling of organolithium compounds with organic halides,
2404,Corrigendum: Optogenetic dissection of ictal propagation in the hippocampal–entorhinal cortex structures,
2405,Corrigendum: Both respiration and photosynthesis determine the scaling of plankton metabolism in the oligotrophic ocean,
2406,Corrigendum: Intensification of the meridional temperature gradient in the Great Barrier Reef following the Last Glacial Maximum,
2407,Corrigendum: The seasonal sea-ice zone in the glacial Southern Ocean as a carbon sink,
2408,Further evidence for population specific differences in the effect of DNA markers and gender on eye colour prediction in forensics,"The genetics of eye colour has been extensively studied over the past few years, and the identified polymorphisms have been applied with marked success in the field of Forensic DNA Phenotyping. A picture that arises from evaluation of the currently available eye colour prediction markers shows that only the analysis of HERC2-OCA2 complex has similar effectiveness in different populations, while the predictive potential of other loci may vary significantly. Moreover, the role of gender in the explanation of human eye colour variation should not be neglected in some populations. In the present study, we re-investigated the data for 1020 Polish individuals and using neural networks and logistic regression methods explored predictive capacity of IrisPlex SNPs and gender in this population sample. In general, neural networks provided higher prediction accuracy comparing to logistic regression (AUC increase by 0.02–0.06). Four out of six IrisPlex SNPs were associated with eye colour in the studied population. HERC2 rs12913832, OCA2 rs1800407 and SLC24A4 rs12896399 were found to be the most important eye colour predictors (p < 0.007) while the effect of rs16891982 in SLC45A2 was less significant. Gender was found to be significantly associated with eye colour with males having ~1.5 higher odds for blue eye colour comparing to females (p = 0.002) and was ranked as the third most important factor in blue/non-blue eye colour determination. However, the implementation of gender into the developed prediction models had marginal and ambiguous impact on the overall accuracy of prediction confirming that the effect of gender on eye colour in this population is small. Our study indicated the advantage of neural networks in prediction modeling in forensics and provided additional evidence for population specific differences in the predictive importance of the IrisPlex SNPs and gender."
2409,Corrigendum: Mutations in CDCA7 and HELLS cause immunodeficiency–centromeric instability–facial anomalies syndrome,
2410,Corrigendum: Mechanical slowing-down of cytoplasmic diffusion allows in vivo counting of proteins in individual cells,
2411,Corrigendum: The child brain computes and utilizes internalized maternal choices,
2412,Corrigendum: Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3,
2413,Erratum: Embryonic transcription is controlled by maternally defined chromatin state,
2414,Chewing the fat about death with the neighbours,
2415,Corrigendum: Selectively enhanced photocurrent generation in twisted bilayer graphene with van Hove singularity,
2416,Erratum: Pathological lymphangiogenesis is modulated by galectin-8-dependent crosstalk between podoplanin and integrin-associated VEGFR-3,
2417,Corrigendum: Endothelin-1 supports clonal derivation and expansion of cardiovascular progenitors derived from human embryonic stem cells,
2418,Corrigendum: Beta 1-integrin–c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes,
2419,Predictors of Spasticity After Stroke,"PURPOSE OF REVIEW: Spasticity is a part of the upper motor neuron syndrome and can result in reduced function. Reduction of the complications may be facilitated by early intervention, making identification of stroke patients at high risk for developing spasticity essential. RECENT FINDING: Different predictors of poststroke spasticity (PSS) have been suggested in different studies, including development of increased muscle tone, greater severity of paresis, sensory impairment, and low Barthel Index score. The results also indicate that early identification of factors predictive of PSS is beneficial. SUMMARY: In this review article, the results of five studies are discussed and they all support the notion that early identification of factors predictive of PSS is beneficial and could help to identify individuals who would benefit most from intervention and thereby provide better outcome."
2420,Corrigendum: NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells,
2421,A novel method for pair-matching using three-dimensional digital models of bone: mesh-to-mesh value comparison,"The commingling of human remains often hinders forensic/physical anthropologists during the identification process, as there are limited methods to accurately sort these remains. This study investigates a new method for pair-matching, a common individualization technique, which uses digital three-dimensional models of bone: mesh-to-mesh value comparison (MVC). The MVC method digitally compares the entire three-dimensional geometry of two bones at once to produce a single value to indicate their similarity. Two different versions of this method, one manual and the other automated, were created and then tested for how well they accurately pair-matched humeri. Each version was assessed using sensitivity and specificity. The manual mesh-to-mesh value comparison method was 100 % sensitive and 100 % specific. The automated mesh-to-mesh value comparison method was 95 % sensitive and 60 % specific. Our results indicate that the mesh-to-mesh value comparison method overall is a powerful new tool for accurately pair-matching commingled skeletal elements, although the automated version still needs improvement. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00414-016-1334-3) contains supplementary material, which is available to authorized users."
2422,"Human cranial vault thickness in a contemporary sample of 1097 autopsy cases: relation to body weight, stature, age, sex and ancestry","The relation between human cranial vault thickness (CVT) and various elements of the physical anthropological biological profile is subject of ongoing discussion. Some results seem to indicate no correlation between CVT and the biological profile of the individual, whereas other results suggest that CVT measurements might be useful for identification purposes. This study assesses the correlation between CVT and body weight, stature, age, sex, and ancestry by reviewing data of 1097 forensic autopsies performed at the Netherlands Forensic Institute (NFI). In subadults (younger than 19 years of age at the time of death), all frontal, temporal, and occipital CVT measurements correlated moderately to strongly with indicators of growth (body weight, stature, and age). Neither sex nor ancestry correlated significantly with cranial thickness. In adults, body weight correlated with all CVT measurements. No meaningful correlation was found between CVT and stature or age. Females showed to have thicker frontal bones, and the occipital region was thicker in the Negroid subsample. All correlation in the adult group was weak, with the distribution of cranial thickness overlapping for a great deal between the groups. Based on these results, it was concluded that CVT generally cannot be used as an indicator for any part of the biological profile."
2423,Comparison of porcine thorax to gelatine blocks for wound ballistics studies,"Tissue simulants are typically used in ballistic testing as substitutes for biological tissues. Many simulants have been used, with gelatine amongst the most common. While two concentrations of gelatine (10 and 20 %) have been used extensively, no agreed standard exists for the preparation of either. Comparison of ballistic damage produced in both concentrations is lacking. The damage produced in gelatine is also questioned, with regards to what it would mean for specific areas of living tissue. The aim of the work discussed in this paper was to consider how damage caused by selected pistol and rifle ammunition varied in different simulants. Damage to gelatine blocks 10 and 20 % in concentration were tested with 9 mm Luger (9 × 19 full metal jacket; FMJ) rounds, while damage produced by .223 Remington (5.56 × 45 Federal Premium® Tactical® Bonded®) rounds to porcine thorax sections (skin, underlying tissue, ribs, lungs, ribs, underlying tissue, skin; backed by a block of 10 % gelatine) were compared to 10 and 20 % gelatine blocks. Results from the .223 Remington rifle round, which is one that typically expands on impact, revealed depths of penetration in the thorax arrangement were significantly different to 20 % gelatine, but not 10 % gelatine. The level of damage produced in the simulated thoraxes was smaller in scale to that witnessed in both gelatine concentrations, though greater debris was produced in the thoraxes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00414-015-1309-9) contains supplementary material, which is available to authorized users."
2424,Evaluation of post-mortem lateral cerebral ventricle changes using sequential scans during post-mortem computed tomography,"In the present study, we evaluated post-mortem lateral cerebral ventricle (LCV) changes using computed tomography (CT). Subsequent periodical CT scans termed “sequential scans” were obtained for three cadavers. The first scan was performed immediately after the body was transferred from the emergency room to the institute of legal medicine. Sequential scans were obtained and evaluated for 24 h at maximum. The time of death had been determined in the emergency room. The sequential scans enabled us to observe periodical post-mortem changes in CT images. The series of continuous LCV images obtained up to 24 h (two cases)/16 h (1 case) after death was evaluated. The average Hounsfield units (HU) within the LCVs progressively increased, and LCV volume progressively decreased over time. The HU in the cerebrospinal fluid (CSF) increased at an individual rate proportional to the post-mortem interval (PMI). Thus, an early longitudinal radiodensity change in the CSF could be potential indicator of post-mortem interval (PMI). Sequential imaging scans reveal post-mortem changes in the CSF space which may reflect post-mortem brain alterations. Further studies are needed to evaluate the proposed CSF change markers in correlation with other validated PMI indicators. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00414-016-1327-2) contains supplementary material, which is available to authorized users."
2425,Corrigendum: Generation of stem cell-derived β-cells from patients with type 1 diabetes,
2426,Erratum: Finite particle size drives defect-mediated domain structures in strongly confined colloidal liquid crystals,
2427,Corrigendum: Comprehensive multi-modality assessment of regional and global arterial structure and function in adults born preterm,
2428,Erratum: Revealing the mechanism of passive transport in lipid bilayers via phonon-mediated nanometre-scale density fluctuations,
2429,Corrigendum: Conformational heterogeneity of the calmodulin binding interface,
2430,Corrigendum: Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection,
2431,Gene amplification-associated overexpression of the RNA editing enzyme ADAR1 enhances human lung tumorigenesis,
2432,Erratum: Iridates from the molecular side,
2433,Corrigendum: A global reanalysis of storm surges and extreme sea levels,
2434,Erratum: Three-dimensional spatiotemporal focusing of holographic patterns,
2435,Corrigendum: Structural and compositional dependence of the CdTe(x)Se(1−x) alloy layer photoactivity in CdTe-based solar cells,
2436,Corrigendum: Highly selective plasma-activated copper catalysts for carbon dioxide reduction to ethylene,
2437,Erratum: A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis,
2438,Erratum: Stromal Hedgehog signalling is downregulated in colon cancer and its restoration restrains tumour growth,
2439,"A Phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients",
2440,Corrigendum: Hydrogel microphones for stealthy underwater listening,
2441,Erratum: Synergistic effects of ion transporter and MAP kinase pathway inhibitors in melanoma,
2442,Erratum: Survival trade-offs in plant roots during colonization by closely related beneficial and pathogenic fungi,
2443,Percentile reference values for anthropometric body composition indices in European children from the IDEFICS study,
2444,Deep data science to prevent and treat growth faltering in Maya children,
2445,Erratum: Magnetic measurements with atomic-plane resolution,
2446,Corrigendum: Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety,
2447,Erratum: Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis,
2448,"Attention-deficit hyperactivity disorder in adults: a systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies",
2449,Genome-wide analysis of over 106 000 individuals identifies 9 neuroticism-associated loci,
2450,Corrigendum: Determining crystal structures through crowdsourcing and coursework,
2451,Corrigendum: Geographic population structure analysis of worldwide human populations infers their biogeographical origins,
2452,Corrigendum: Cortical dynamics during cell motility are regulated by CRL3(KLHL21) E3 ubiquitin ligase,
2453,Retraction: Capturing carbon dioxide as a polymer from natural gas,
2454,Corrigendum: A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect,
2455,Erratum: Comparative genomics reveals adaptive evolution of Asian tapeworm in switching to a new intermediate host,
2456,Corrigendum: Ubiquitin ligase RNF20/40 facilitates spindle assembly and promotes breast carcinogenesis through stabilizing motor protein Eg5,
2457,Erratum: Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma,
2458,Ranibizumab for the treatment of wet AMD: a summary of real-world studies,
2459,Paving the way toward better peer review,We are committed to support our reviewers with all relevant information needed to draft their reports
2460,Transparent peer review one year on,The majority of our authors are opting in to publish reviewer reports of their papers
2461,Corrigendum: Circulating tumour DNA profiling reveals heterogeneity of EGFR inhibitor resistance mechanisms in lung cancer patients,
2462,Corrigendum: IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses,
2463,"STIM1, a direct target of microRNA-185, promotes tumor metastasis and is associated with poor prognosis in colorectal cancer",
2464,Corrigendum: Recent increases in Arctic freshwater flux affects Labrador Sea convection and Atlantic overturning circulation,
2465,Corrigendum: Regulation of PERK–eIF2α signalling by tuberous sclerosis complex-1 controls homoeostasis and survival of myelinating oligodendrocytes,
2466,Corrigendum: Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity,
2467,Special Considerations for the Treatment of Pain from Torture and War,"Pain care for survivors of torture and of war shows similarities and marked differences. For both, pain can be complex with unfamiliar presentations and the pains hard to assign to known disorders. For many survivors, pain and associated disability are overshadowed by psychological distress, often by post-traumatic stress symptoms that can be frightening and isolating. Pain medicine in war can exemplify best techniques and organisation, reducing suffering, but many military veterans have persistent pain that undermines their readjustment. By contrast, survivors of torture rarely have any acute health care; their risk for developing chronic pain is high. Even when settled as refugees in a well-resourced country, their access to healthcare may be restricted. Recent evidence is reviewed that informs assessment and treatment of pain in both groups, with the broader context of psychological distress addressed at the end. Clinical and research implications are briefly outlined."
2468,Aberrant Mer receptor tyrosine kinase expression contributes to leukemogenesis in acute myeloid leukemia,
2469,Erratum: Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides,
2470,"The nutritional quality of foods carrying health-related claims in Germany, The Netherlands, Spain, Slovenia and the United Kingdom",
2471,Corrigendum: Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues,
2472,Corrigendum: Chemotaxis towards autoinducer 2 mediates autoaggregation in Escherichia coli,
2473,Erratum: N-type organic electrochemical transistors with stability in water,
2474,Erratum: Molecular basis of cooperativity in pH-triggered supramolecular self-assembly,
2475,What causes mating system shifts in plants? Arabidopsis lyrata as a case study,
2476,Erratum: Suspension survival mediated by PP2A-STAT3-Col XVII determines tumour initiation and metastasis in cancer stem cells,
2477,Erratum: Coding and decoding libraries of sequence-defined functional copolymers synthesized via photoligation,
2478,Genetic differentiation and admixture between sibling allopolyploids in the Dactylorhiza majalis complex,
2479,A functional AT/G polymorphism in the 5′-untranslated region of SETDB2 in the IgE locus on human chromosome 13q14,
2480,The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response,
2481,"Prostate cancer risk related to foods, food groups, macronutrients and micronutrients derived from the UK Dietary Cohort Consortium food diaries",
2482,The Intersection of Oncology Prognosis and Cancer Rehabilitation,"PURPOSE OF REVIEW: This review examines the delivery of rehabilitation care to cancer patients with relation to disease prognosis. This includes the evaluation when patients are referred for rehabilitation services and the effectiveness of rehabilitation interventions across the cancer continuum. RECENT FINDINGS: Although prognosticating life expectancy is difficult, referrals for rehabilitation interventions appear to be affected by physician attitudes towards patients with advanced disease, in part because of misconceptions about the nature of rehabilitation for oncology patients. Rehabilitation may also be underutilized in long-term survivors with no evidence of disease. Despite this, our review found that rehabilitation in advanced disease, end-of-life, geriatric cancer patients, and in long-term survivors can be beneficial. There is a relative dearth in studies on rehabilitation interventions specifically at the end-of-life. SUMMARY: Cancer rehabilitation can be helpful to patients along the spectrum of cancer prognoses. Examining more accurate ways to prognosticate life expectancy, improving communication and education between oncologists and rehabilitation team members, and modifying survivorship plans to include patient education on functional changes over time may improve the delivery of rehabilitation care."
2483,Beneficial effects of early hemostasis on spinal cord injury in the rat,
2484,The concordance between the volume hotspot and the grade hotspot: a 3-D reconstructive model using the pathology outputs from the PROMIS trial,
2485,Erratum: Pure-quartic solitons,
2486,"RGS2 expression predicts amyloid-β sensitivity, MCI and Alzheimer's disease: genome-wide transcriptomic profiling and bioinformatics data mining",
2487,Neuroprotection after a first episode of mania: a randomized controlled maintenance trial comparing the effects of lithium and quetiapine on grey and white matter volume,
2488,A Critical Use of Foucault’s Art of Living,"Foucault’s vocabulary of arts of existence might be helpful to problematize the entwinement of humans and technology and to search for new types of hybrid selves. However, to be a serious new ethical vocabulary for technology, this art of existence should be supplemented with an ongoing critical discourse of technologies, including a critical analysis of the subjectivities imposed by technologies, and should be supplemented with new medical and philosophical regimens for an appropriate use of technologies."
2489,Social Autonomy and Heteronomy in the Age of ICT: The Digital Pharmakon and the (Dis)Empowerment of the General Intellect,"‘The art of living with ICTs (information and communication technologies)’ today not only means finding new ways to cope, interact and create new lifestyles on the basis of the new digital (network) technologies individually, as ‘consumer-citizens’. It also means inventing new modes of living, producing and, not in the least place, struggling collectively, as workers and producers. As the so-called digital revolution unfolds in the context of a neoliberal cognitive and consumerist capitalism, its ‘innovations’ are predominantly employed to modulate and control both production processes and consumer behavior in view of the overall goal of extracting surplus value. Today, the digital networks overwhelmingly destroy social autonomy, instead engendering increasing social heteronomy and proletarianization. Yet it is these very networks themselves, as technical pharmaka in the sense of French ‘technophilosopher’ Bernard Stiegler, that can be employed as no other to struggle against this tendency. This paper briefly explores this possibility by reflecting upon current diagnoses of our ‘technological situation’ by some exemplary post-operaist Marxists from a Stieglerian, pharmacological perspective."
2490,Whose Art Are We Talking About?,"Jeannette Pols and Tamar Sharon kindly reviewed my case study of the art of living with technology as an engagement with technomoral change. I am indebted to them for their careful reading and critical suggestions to further elaborate the project. In my response I focus on the question whose art we are talking about, while further elucidating the reflexivity addressed in my essay. I conclude with some remarks on what we can learn from micro studies like the one presented for macro level thinking on the ‘art of becoming’ with technology in a surveillance society."
2491,Love and Realism,"In this reply I try to show that, contrary to Milberry’s apparent assertion, the general intellect of the multitude does not have the explanatory robustness she accredits to it (following both Virno and the Hardt and Negri of the Empire trilogy). Digital network technologies are currently overwhelmingly effective in proletarianizing and disempowering the cognitariat and only an active technopolitics of deproletarianization could reverse this hegemonic situation. In my response to Verbeek, I attempt to correct his misinterpretation (shared by Milberry) of the Stieglerian approach as being dialectical in nature and show that, far from reinstating the humanist dichotomy between human beings and technologies, my analysis assumes their original, albeit fundamentally ambiguous and even ‘uncanny’ [unheimlich] interconnection. I conclude with pointing out some implications of this view for a ‘really realistic’ political theory of technology."
2492,How to Make Your Relationship Work? Aesthetic Relations with Technology,"Discussing the workings of technology in care as aesthetic rather than as ethical or epistemological interventions focusses on how technologies engage in and change relations between those involved. Such an aesthetic study opens up a repertoire to address values that are abundant in care, but are as yet hardly theorized. Kamphof studies the problem that sensor technology reveals things about the elderly patients without the patients being aware of this. I suggest improvement of these relations may be considered in aesthetic terms, for instance by developing the affective quality of people’s technological relationships."
2493,The Uses of Reason in Times of Technical Mediation,The art of living idiom suits well a practice-oriented approach in ethics of technology. But what remains or becomes of the functioning and use of reason in ethics? In reaction to the comments by Huijer this reply elaborates in more detail how Foucault’s art of living can be adapted for a critical contemporary ethics of technology. And the aesthetic-political rationality in Foucault’s ethics is compared with Wellner’s suggestions of holding on to the notion of code but with a new meaning. Foucault’s fourfold scheme of subjectivation and a distinction of “below and above reason” structure the argument.
2494,The Care of Our Hybrid Selves: Ethics in Times of Technical Mediation,"What can the art of living after Foucault contribute to ethics in relation to the mediation of human existence by technology? To develop the relation between technical mediation and ethics, firstly the theme of technical mediation is elaborated in line with Foucault’s notion of ethical problematization. Every view of what technology does to us at the same time expresses an ethical concern about technology. The contemporary conception of technical mediation tends towards the acknowledgement of ongoing hybridization, not ultimately good or bad but ambivalent, which means for us the challenge of taking care of ourselves as hybrid beings. Secondly, the work of Foucault provides elements for imagining this care for our hybrid selves, notably his notions of freedom as a practice and of the care of the self. A conclusions about technical mediation and ethics is that whereas the approaches of the delegation of morality to technology by Latour and mediated morality by Verbeek see technical mediation of behavior and moral outlook as an answer in ethics, this should rather be considered the problem that ethics is about."
2495,The Art of Living with NZT and ICT: Dialectics of an Artistic Case Study,"I wholeheartedly sympathize conceptually with Coeckelbergh’s paper. The dialectical relationship between vulnerability and technology constitutes the core of Hegel’s Master and Slave (the primal scene of contemporary philosophy). Yet, the empirical dimension is underdeveloped and Coeckelbergh’s ideas could profit from exposure to case studies. Building on a movie/novel (Limitless) devoted to vulnerability coping and living with ICT, I challenge the claim that modern heroism entails overcoming vulnerability with the help of enhancement and computers."
2496,"Towards a Phenomenology of Technologically Mediated Moral Change: Or, What Could Mark Zuckerberg Learn from Caregivers in the Southern Netherlands?","Kamphof offers an illuminating depiction of the technological mediation of morality. Her case serves as the basis for a plea for modesty up and against the somewhat heroic conceptualizations of techno-moral change to date—less logos, less autos, more practice, more relationality. Rather than a displacement of these conceptualizations, I question whether Kamphof’s art of living offers only a different perspective: in scale (as a micro-event of techno-moral change), and in unit of analysis (as an art of living oriented to relations with others rather than the relation to the self). As a supplement and not an alternative, this modest art has nonetheless audacious implications for the ethics of surveillance."
2497,A Modest Art: Securing Privacy in Technologically Mediated Homecare,"This article addresses the art of living in a technological culture as the active engagement with technomoral change. It argues that this engagement does not just take the form of overt deliberation. It shows in more modest ways as reflection-in-action, an experimental process in which new technology is fitted into existing practices. In this process challenged values are re-articulated in pragmatic solutions to the problem of working with new technology. This art of working with technology is also modest in the sense that it is not oriented to shaping one’s own subjectivity in relation to technology. It emanates from human existence as relational and aims at securing good relationships. The argument will be developed in relation to a case study of the ways in which homecare workers engaged with the value of privacy, challenged by tele-monitoring technology that was newly introduced into their work."
2498,The Struggle for Technology: Towards a Realistic Political Theory of Technology,"Pieter Lemmens’ neo-Marxist approach to technology urges us to rethink how to do political philosophy of technology. First, Lemmens’ high level of abstraction raises the question of how empirically informed a political theory of technology needs to be. Second, his dialectical focus on a “struggle” between humans and technologies reveals the limits of neo-Marxism. Political philosophy of technology needs to return “to the things themselves”. The political significance of technologies cannot be reduced to its origins in systems of production or social organization, but requires study at the micro-level, where technologies help to shape engagement, interaction, power, and social awareness."
2499,Does an Old Art Suffice for New Problems?,"In this review I argue that Puech draws on two important currents in modern thought: the criticism of the ontological and social priority of conflict, and the rehabilitation of praxis vis-à-vis theoria. Still, his plea for a non-confrontational art of living leaves important questions unanswered. What is the problem exactly? What does exactly count as (non)confrontational? What is non-confrontation exactly meant to solve? What is the antiposition here? And: how does this new (or rather: old) art of living relate to the political and ethical varieties of Technology Assessment?"
2500,Corrigendum: Flux of signalling endosomes undergoing axonal retrograde transport is encoded by presynaptic activity and TrkB,
2501,Atypical role of sprouty in colorectal cancer: sprouty repression inhibits epithelial–mesenchymal transition,
2502,Editorial Expression of Concern: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats,
2503,A natural food sweetener with anti-pancreatic cancer properties,
2504,MiR-186 inhibited aerobic glycolysis in gastric cancer via HIF-1α regulation,
2505,DNMT3A mutations mediate the epigenetic reactivation of the leukemogenic factor MEIS1 in acute myeloid leukemia,
2506,"Oncoprotein ZNF322A transcriptionally deregulates alpha-adducin, cyclin D1 and p53 to promote tumor growth and metastasis in lung cancer",
2507,Channeling in the Use of Nonprescription Paracetamol and Ibuprofen in an Electronic Medical Records Database: Evidence and Implications,"INTRODUCTION: Over-the-counter analgesics such as paracetamol and ibuprofen are among the most widely used, and having a good understanding of their safety profile is important to public health. Prior observational studies estimating the risks associated with paracetamol use acknowledge the inherent limitations of these studies. One threat to the validity of observational studies is channeling bias, i.e. the notion that patients are systematically exposed to one drug or the other, based on current and past comorbidities, in a manner that affects estimated relative risk. OBJECTIVES: The aim of this study was to examine whether evidence of channeling bias exists in observational studies that compare paracetamol with ibuprofen, and, if so, the extent to which confounding adjustment can mitigate this bias. STUDY DESIGN AND SETTING: In a cohort of 140,770 patients, we examined whether those who received any paracetamol (including concomitant users) were more likely to have prior diagnoses of gastrointestinal (GI) bleeding, myocardial infarction (MI), stroke, or renal disease than those who received ibuprofen alone. We compared propensity score distributions between drugs, and examined the degree to which channeling bias could be controlled using a combination of negative control disease outcome models and large-scale propensity score matching. Analyses were conducted using the Clinical Practice Research Datalink. RESULTS: The proportions of prior MI, GI bleeding, renal disease, and stroke were significantly higher in those prescribed any paracetamol versus ibuprofen alone, after adjusting for sex and age. We were not able to adequately remove selection bias using a selected set of covariates for propensity score adjustment; however, when we fit the propensity score model using a substantially larger number of covariates, evidence of residual bias was attenuated. CONCLUSIONS: Although using selected covariates for propensity score adjustment may not sufficiently reduce bias, large-scale propensity score matching offers a novel approach to consider to mitigate the effects of channeling bias. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40264-017-0581-7) contains supplementary material, which is available to authorized users."
2508,"Forces generated in stabbing attacks: an evaluation of the utility of the mild, moderate and severe scale","The commonest way of killing in the UK is by a sharp instrument. Knight reported in 1975 that it is impossible to discern with any degree of certainty the degree of force used to create a stab wound. Despite this, expert witnesses continue to approximate the degree of force used for their reports and evidence in court. It is usually subjectively categorized as mild, moderate or severe, based solely on the examination of the wound. We undertook a study considering forces generated in a range of blunt trauma actions, using a novel force plate dynamometer to measure the peak forces obtained by adult male and female volunteers. We then studied forces generated by stabbing skin simulants and porcine samples with knives and screwdrivers. Men generated more force than women during stabbings which was found to be equivalent to somewhere between the blunt trauma actions of pushing a button to a single-handed push. When asked to stab using what they thought was mild, moderate and severe force, although volunteers were able to actively decide the force used, the actual force was found to be influenced by the weapon, sex of the individual, hand used and biological/anatomical site penetrated. This study shows that the forces generated by volunteers in mild, moderate and severe stabbing tests in almost all cases were significantly greater than the forces required for skin penetration. We suggest that the use of subjective force scales is inappropriate. Rather than use of a subjective scale, we suggest that the force required in any stabbing requires investigation in four areas: the tip radius of the weapon, minimal force required for penetration, the sex of the assailant and whether the force required for penetration is greater than that that can be generated by a person stabbing. This allows for the use of an evidence-based two-tier scale to suggest the force required. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00414-017-1702-7) contains supplementary material, which is available to authorized users."
2509,Investigation of metabolites for estimating blood deposition time,"Trace deposition timing reflects a novel concept in forensic molecular biology involving the use of rhythmic biomarkers for estimating the time within a 24-h day/night cycle a human biological sample was left at the crime scene, which in principle allows verifying a sample donor’s alibi. Previously, we introduced two circadian hormones for trace deposition timing and recently demonstrated that messenger RNA (mRNA) biomarkers significantly improve time prediction accuracy. Here, we investigate the suitability of metabolites measured using a targeted metabolomics approach, for trace deposition timing. Analysis of 171 plasma metabolites collected around the clock at 2-h intervals for 36 h from 12 male participants under controlled laboratory conditions identified 56 metabolites showing statistically significant oscillations, with peak times falling into three day/night time categories: morning/noon, afternoon/evening and night/early morning. Time prediction modelling identified 10 independently contributing metabolite biomarkers, which together achieved prediction accuracies expressed as AUC of 0.81, 0.86 and 0.90 for these three time categories respectively. Combining metabolites with previously established hormone and mRNA biomarkers in time prediction modelling resulted in an improved prediction accuracy reaching AUCs of 0.85, 0.89 and 0.96 respectively. The additional impact of metabolite biomarkers, however, was rather minor as the previously established model with melatonin, cortisol and three mRNA biomarkers achieved AUC values of 0.88, 0.88 and 0.95 for the same three time categories respectively. Nevertheless, the selected metabolites could become practically useful in scenarios where RNA marker information is unavailable such as due to RNA degradation. This is the first metabolomics study investigating circulating metabolites for trace deposition timing, and more work is needed to fully establish their usefulness for this forensic purpose."
2510,DNA methylation in ELOVL2 and C1orf132 correctly predicted chronological age of individuals from three disease groups,"Improving accuracy of the available predictive DNA methods is important for their wider use in routine forensic work. Information on age in the process of identification of an unknown individual may provide important hints that can speed up the process of investigation. DNA methylation markers have been demonstrated to provide accurate age estimation in forensics, but there is growing evidence that DNA methylation can be modified by various factors including diseases. We analyzed DNA methylation profile in five markers from five different genes (ELOVL2, C1orf132, KLF14, FHL2, and TRIM59) used for forensic age prediction in three groups of individuals with diagnosed medical conditions. The obtained results showed that the selected age-related CpG sites have unchanged age prediction capacity in the group of late onset Alzheimer’s disease patients. Aberrant hypermethylation and decreased prediction accuracy were found for TRIM59 and KLF14 markers in the group of early onset Alzheimer’s disease suggesting accelerated aging of patients. In the Graves’ disease patients, altered DNA methylation profile and modified age prediction accuracy were noted for TRIM59 and FHL2 with aberrant hypermethylation observed for the former and aberrant hypomethylation for the latter. Our work emphasizes high utility of the ELOVL2 and C1orf132 markers for prediction of chronological age in forensics by showing unchanged prediction accuracy in individuals affected by three diseases. The study also demonstrates that artificial neural networks could be a convenient alternative for the forensic predictive DNA analyses."
2511,Sex-specific developmental models for Creophilus maxillosus (L.) (Coleoptera: Staphylinidae): searching for larger accuracy of insect age estimates,"Differences in size between males and females, called the sexual size dimorphism, are common in insects. These differences may be followed by differences in the duration of development. Accordingly, it is believed that insect sex may be used to increase the accuracy of insect age estimates in forensic entomology. Here, the sex-specific differences in the development of Creophilus maxillosus were studied at seven constant temperatures. We have also created separate developmental models for males and females of C. maxillosus and tested them in a validation study to answer a question whether sex-specific developmental models improve the accuracy of insect age estimates. Results demonstrate that males of C. maxillosus developed significantly longer than females. The sex-specific and general models for the total immature development had the same optimal temperature range and similar developmental threshold but different thermal constant K, which was the largest in the case of the male-specific model and the smallest in the case of the female-specific model. Despite these differences, validation study revealed just minimal and statistically insignificant differences in the accuracy of age estimates using sex-specific and general thermal summation models. This finding indicates that in spite of statistically significant differences in the duration of immature development between females and males of C. maxillosus, there is no increase in the accuracy of insect age estimates while using the sex-specific thermal summation models compared to the general model. Accordingly, this study does not support the use of sex-specific developmental data for the estimation of insect age in forensic entomology. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00414-017-1713-4) contains supplementary material, which is available to authorized users."
2512,Nose profile morphology and accuracy study of nose profile estimation method in Scottish subadult and Indonesian adult populations,"This study investigated nose profile morphology and its relationship to the skull in Scottish subadult and Indonesian adult populations, with the aim of improving the accuracy of forensic craniofacial reconstruction. Samples of 86 lateral head cephalograms from Dundee Dental School (mean age, 11.8 years) and 335 lateral head cephalograms from the Universitas Padjadjaran Dental Hospital, Bandung, Indonesia (mean age 24.2 years), were measured. The method of nose profile estimation based on skull morphology previously proposed by Rynn and colleagues in 2010 (FSMP 6:20–34) was tested in this study. Following this method, three nasal aperture-related craniometrics and six nose profile dimensions were measured from the cephalograms. To assess the accuracy of the method, six nose profile dimensions were estimated from the three craniometric parameters using the published method and then compared to the actual nose profile dimensions. In the Scottish subadult population, no sexual dimorphism was evident in the measured dimensions. In contrast, sexual dimorphism of the Indonesian adult population was evident in all craniometric and nose profile dimensions; notably, males exhibited statistically significant larger values than females. The published method by Rynn and colleagues (FSMP 6:20–34, 2010) performed better in the Scottish subadult population (mean difference of maximum, 2.35 mm) compared to the Indonesian adult population (mean difference of maximum, 5.42 mm in males and 4.89 mm in females). In addition, regression formulae were derived to estimate nose profile dimensions based on the craniometric measurements for the Indonesian adult population. The published method is not sufficiently accurate for use on the Indonesian population, so the derived method should be used. The accuracy of the published method by Rynn and colleagues (FSMP 6:20–34, 2010) was sufficiently reliable to be applied in Scottish subadult population."
2513,Ethical aspects of medical age assessment in the asylum process: a Swedish perspective,"According to European regulations and the legislations of individual member states, children who seek asylum have a different set of rights than adults in a similar position. To protect these rights and ensure rule of law, migration authorities are commonly required to assess the age of asylum seekers who lack reliable documentation, including through various medical methods. However, many healthcare professionals and other commentators consider medical age assessment to be ethically problematic. This paper presents a simplified and amended account of the main findings of a recent ethical analysis of medical age assessment in the asylum process commissioned by the Swedish National Board of Health and Welfare. A number of ethical challenges related to conflicting goals, equality and fairness, autonomy and informed consent, privacy and integrity, and professional values and roles are identified and analysed. It is concluded that most of these challenges can be met, but that this requires a system where the assessment is sufficiently accurate and where adequate safeguards are in place. Two important ethical questions are found to warrant further analysis. The first is whether asylum seekers’ consent to the procedure can be considered genuinely voluntary. The second is whether and how medical age assessments could affect negative public attitudes towards asylum seekers or discriminatory societal views more generally."
2514,Forensic differentiation between peripheral and menstrual blood in cases of alleged sexual assault—validating an immunochromatographic multiplex assay for simultaneous detection of human hemoglobin and D-dimer,"Sexual assault is a serious offense and identification of body fluids originating from sexual activity has been a crucial aspect of forensic investigations for a long time. While reliable tests for the detection of semen and saliva have been successfully implemented into forensic laboratories, the detection of other body fluids, such as vaginal or menstrual fluid, is more challenging. Especially, the discrimination between peripheral and menstrual blood can be highly relevant for police investigations because it provides potential evidence regarding the issue of consent. We report the forensic validation of an immunochromatographic test that allows for such discrimination in forensic stains, the SERATEC PMB test, and its performance on real casework samples. The PMB test is a duplex test combining human hemoglobin and D-dimer detection and was developed for the identification of blood and menstrual fluid, both at the crime scene and in the laboratory. The results of this study showed that the duplex D-dimer/hemoglobin assay reliably detects the presence of human hemoglobin and identifies samples containing menstrual fluid by detecting the presence of D-dimers. The method distinguished between menstrual and peripheral blood in a swab from a historical artifact and in real casework samples of alleged sexual assaults. Results show that the development of the new duplex test is a substantial progress towards analyzing and interpreting evidence from sexual assault cases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00414-017-1719-y) contains supplementary material, which is available to authorized users."
2515,Species identification of adult African blowflies (Diptera: Calliphoridae) of forensic importance,"Necrophagous blowflies can provide an excellent source of evidence for forensic entomologists and are also relevant to problems in public health, medicine, and animal health. However, access to useful information about these blowflies is constrained by the need to correctly identify the flies, and the poor availability of reliable, accessible identification tools is a serious obstacle to the development of forensic entomology in the majority of African countries. In response to this need, a high-quality key to the adults of all species of forensically relevant blowflies of Africa has been prepared, drawing on high-quality entomological materials and modern focus-stacking photomicroscopy. This new key can be easily applied by investigators inexperienced in the taxonomy of blowflies and is made available through a highly accessible online platform. Problematic diagnostic characters used in previous keys are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00414-017-1654-y) contains supplementary material, which is available to authorized users."
2516,Ancestry inference of 96 population samples using microhaplotypes,"Microhaplotypes have become a new type of forensic marker with a great ability to identify and deconvolute mixtures because massively parallel sequencing (MPS) allows the alleles (haplotypes) of the multi-SNP loci to be determined directly for an individual. As originally defined, a microhaplotype locus is a short segment of DNA with two or more SNPs defining three or more haplotypes. The length is short enough, less than about 300 bp, that the read length of current MPS technology can produce a phase-known sequence of each chromosome of an individual. As part of the discovery phase of our studies, data on 130 microhaplotype loci with estimates of haplotype frequency data on 83 populations have been published. To provide a better picture of global allele frequency variation, we have now tested 13 more populations for 65 of the microhaplotype loci from among those with higher levels of inter-population gene frequency variation, including 8 loci not previously published. These loci provide clear distinctions among 6 biogeographic regions and provide some information distinguishing up to 10 clusters of populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00414-017-1748-6) contains supplementary material, which is available to authorized users."
2517,The development of a post-mortem interval estimation for human remains found on land in the Netherlands,"The decomposition process of human remains can be used to estimate the post-mortem interval (PMI), but decomposition varies due to many factors. Temperature is believed to be the most important and can be connected to decomposition by using the accumulated degree days (ADD). The aim of this research was to develop a decomposition scoring method and to develop a formula to estimate the PMI by using the developed decomposition scoring method and ADD. A decomposition scoring method and a Book of Reference (visual resource) were made. Ninety-one cases were used to develop a method to estimate the PMI. The photographs were scored using the decomposition scoring method. The temperature data was provided by the Royal Netherlands Meteorological Institute. The PMI was estimated using the total decomposition score (TDS) and using the TDS and ADD. The latter required an additional step, namely to calculate the ADD from the finding date back until the predicted day of death. The developed decomposition scoring method had a high interrater reliability. The TDS significantly estimates the PMI (R (2) = 0.67 and 0.80 for indoor and outdoor bodies, respectively). When using the ADD, the R (2) decreased to 0.66 and 0.56. The developed decomposition scoring method is a practical method to measure decomposition for human remains found on land. The PMI can be estimated using this method, but caution is advised in cases with a long PMI. The ADD does not account for all the heat present in a decomposing remain and is therefore a possible bias. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00414-017-1700-9) contains supplementary material, which is available to authorized users."
2518,Elapsed time of light: science & applications,
2519,Overseas offices: a new attempt to disseminate Light,
2520,Enzyme-modified non-oxidized LDL (ELDL) induces human coronary artery smooth muscle cell transformation to a migratory and osteoblast-like phenotype,"Enzyme modified non-oxidative LDL (ELDL) is effectively taken up by vascular smooth muscle cells (SMC) and mediates transition into foam cells and produces phenotypic changes in SMC function. Our data show that incubation of human coronary artery SMC (HCASMC) with low concentration of ELDL (10 μg/ml) results in significantly enhanced foam cell formation compared to oxidized LDL (200 μg/ml; p < 0.01) or native LDL (200 μg/ml; p < 0.01). Bioinformatic network analysis identified activation of p38 MAPK, NFkB, ERK as top canonical pathways relevant for biological processes linked to cell migration and osteoblastic differentiation in ELDL-treated cells. Functional studies confirmed increased migration of HCASMC upon stimulation with ELDL (10 μg/ml) or Angiopoietin like protein 4, (ANGPTL4, 5 μg/ml), and gain in osteoblastic gene profile with significant increase in mRNA levels for DMP-1, ALPL, RUNX2, OPN/SPP1, osterix/SP7, BMP and reduction in mRNA for MGP and ENPP1. Enhanced calcification of HCASMC by ELDL was demonstrated by Alizarin Red staining. In summary, ELDL is highly potent in inducing foam cells in HCASMC and mediates a phenotypic switch with enhanced migration and osteoblastic gene profile. These results point to the potential of ELDL to induce migratory and osteoblastic effects in human smooth muscle cells with potential implications for migration and calcification of SMCs in human atherosclerosis."
2521,Guide to Enhancing Swallowing Initiation: Insights from Findings in Healthy Subjects and Dysphagic Patients,"PURPOSE OF REVIEW: Difficulty in initiating swallowing is one of the main symptoms of oropharyngeal dysphagia. Therefore, enhancing swallowing initiation is an important approach for the treatment of oropharyngeal dysphagia. This review aims to introduce recent approaches to enhancing swallowing and to discuss their therapeutic potential. RECENT FINDINGS: Both central interventions such as non-invasive brain stimulation and peripheral interventions such as electrical stimulation to peripheral tissues are conducted to enhance swallowing. Recent studies have paid more attention to generating neuroplasticity to produce long-lasting facilitative effect on swallowing. SUMMARY: Transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), pharyngeal electrical stimulation (PES), transcutaneous electrical stimulation, and somatic and chemical stimulation were introduced. Considerable evidence supports the therapeutic potential of TMS and PES. Other approaches need further studies to verify their efficacy (e.g., duration of the effect and a limit of effectiveness) and/or possible risk of adverse effects."
2522,Polycomb protein family member CBX7 regulates intrinsic axon growth and regeneration,"Neurons in the central nervous system (CNS) lose their intrinsic ability and fail to regenerate, but the underlying mechanisms are largely unknown. Polycomb group (PcG) proteins, which include PRC1 and PRC2 complexes function as gene repressors and are involved in many biological processes. Here we report that PRC1 components (polycomb chromobox (CBX) 2, 7, and 8) are novel regulators of axon growth and regeneration. Especially, knockdown of CBX7 in either embryonic cortical neurons or adult dorsal root ganglion (DRG) neurons enhances their axon growth ability. Two important transcription factors GATA4 and SOX11 are functional downstream targets of CBX7 in controlling axon regeneration. Moreover, knockdown of GATA4 or SOX11 in cultured DRG neurons inhibits axon regeneration response from CBX7 downregulation in DRG neurons. These findings suggest that targeting CBX signaling pathway may be a novel approach for promoting the intrinsic regenerative capacity of damaged CNS neurons."
2523,The use of gelatine in wound ballistics research,"Blocks of gelatine are used in both lethality and survivability studies for broadly the same reason, i.e. comparison of ammunition effects using a material that it is assumed represents (some part of) the human body. The gelatine is used to visualise the temporary and permanent wound profiles; elements of which are recognised as providing a reasonable approximation to wounding in humans. One set of researchers aim to improve the lethality of the projectile, and the other to understand the effects of the projectile on the body to improve survivability. Research areas that use gelatine blocks are diverse and include ammunition designers, the medical and forensics communities and designers of ballistic protective equipment (including body armour). This paper aims to provide an overarching review of the use of gelatine for wound ballistics studies; it is not intended to provide an extensive review of wound ballistics as that already exists, e.g. Legal Med 23:21–29, 2016. Key messages are that test variables, projectile type (bullet, fragmentation), impact site on the body and intermediate layers (e.g. clothing, personal protective equipment (PPE)) can affect the resulting wound profiles."
2524,The use of whole body diffusion-weighted post-mortem magnetic resonance imaging in timing of perinatal deaths,"OBJECTIVES: Diffusion-weighted MRI provides information regarding body water movement following death, which may be an imaging marker of post-mortem interval (time since death; PMI) or maceration (degree of tissue degradation during intra-uterine retention) in perinatal deaths. Our aim was to evaluate the relationship between maceration, PMI and body organ apparent diffusion coefficient (ADC) values in a cohort of subjects across a wide gestational range. MATERIALS: Whole body post-mortem MRI with diffusion-weighted imaging (DWI) sequences were performed at 1.5 T, with b values of 0, 500 and 1000 mm(2)/s. Mean ADC values were calculated from regions of interest (ROIs) placed in the lungs, myocardium, spleen, renal cortex, liver and psoas muscle by two independent readers. Multivariable regression analysis was performed against PMI, gestational age, post-mortem weight, maceration score and gender. RESULTS: Eighty perinatal deaths were imaged with mean gestational age of 32 weeks (18–41 weeks), of which 49 (61.3%) were male. The mean PMI was 8 days (1–18 days). Maceration scores were statistically significant predictive factors for ADC values in all included body organs except the lungs, but PMI was not a predictor for ADC values in any body organ. In the absence of maceration (n = 14), PMI was not statistically associated with ADC values in any of the body areas. The ratio of agreement in the majority of body areas was close to 1 (range between 0.95 and 1.10). CONCLUSION: Maceration, not PMI, is significantly associated with ADC values in perinatal deaths. Further research is needed to understand organ-specific changes in the post-mortem period."
2525,Developmental validation of GlobalFiler™ PCR amplification kit: a 6-dye multiplex assay designed for amplification of casework samples,"The GlobalFiler™ PCR Amplification Kit is a single multiplex assay that amplifies a set of 24 markers, which encompass the European Standard Set and CODIS (Combined DNA Index System) recommended composite set of loci. In addition to more loci and a 6-dye chemistry format, the Master Mix has been formulated to allow higher sample loading volume for trace DNA samples. The GlobalFiler™ Kit has been optimized to deliver high performance on casework samples, while also delivering fast thermal cycling, with an amplification time of approximately 80 min. Here, we report the results of the developmental validation study which followed the SWGDAM (Scientific Working Group on DNA Analysis Methods) guidelines and includes data for PCR-based studies, sensitivity, species specificity, stability, precision, reproducibility and repeatability, concordance, stutter, DNA mixtures, and performance on mock casework samples. The results validate the multiplex design as well as demonstrate the kit’s robustness, reliability, and suitability as an assay for human identification with casework DNA samples. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00414-018-1817-5) contains supplementary material, which is available to authorized users."
2526,Gout In Extremis: Massive Soft Tissue Tophaceous Deposits,
2527,Guideline Approaches for Cardioendocrine Disease Surveillance and Treatment Following Spinal Cord Injury,"PURPOSE OF REVIEW: Persons with spinal cord injuries (SCI) commonly experience individual risks and coalesced health hazards of the cardiometabolic syndrome (CMS). This review will examinethe role of exercise and nutritional intervention as countermeasures to these disease risks. RECENT FINDINGS: The CMS hazards of overweight/obesity, insulin resistance, hypertension, and dyslipidemia are strongly associated with physical deconditioning and are common after SCI. Both the CMS diagnosis and physical deconditioning worsen the prognosis for all-cause cardiovascular disease occurring early after SCI. Evidence supports a therapeutic role for physical activity after SCI as an effective countermeasure to these risks and often represents the first-line approach to CMS abatement. This evidence is supported by authoritative systematic reviews and associated guidelines that recommend specific activities, frequencies, and activities of work. In many cases, the most effective exercise programming uses more intense periods of work with limited rest. As SCI is also associated with poor dietary habits, including excessive energy intake and saturated fat consumption, more comprehensive lifestyle management incorporating both exercise and nutrition represents a preferred approach for overall health management. SUMMARY: Irrespective of the interventional strategy, improved surveillance of the population for CMS risks and encouraged incorporation of exercise and nutritional management according to recent population-specific guidelines will most likely play an important role in the preservation of activity, optimal health, and independence throughout the lifespan."
2528,Error rates for unvalidated medical age assessment procedures,"During 2014–2015, Sweden received asylum applications from more than 240,000 people, of which more than 40,000 were termed unaccompanied minors. In a large number of cases, claims by asylum seekers of being below 18 years were not trusted by Swedish authorities. To handle the situation, the Swedish national board of forensic medicine (Rättsmedicinalverket, RMV) was assigned by the government to create a centralized system for medical age assessments. RMV introduced a procedure including two biological age indicators; x-ray of the third molars and magnetic resonance imaging of the distal femoral epiphysis. In 2017, a total of 9617 males and 337 females were subjected to this procedure. No validation study for the procedure was however published, and the observed number of cases with different maturity combinations in teeth and femur were unexpected given the claims originally made by RMV. We present a general stochastic model enabling us to study which combinations of age indicator model parameters and age population profiles are consistent with the observed 2017 data for males. We find that, contrary to some RMV claims, maturity of the femur, as observed by RMV, appears on average well before maturity of teeth. According to our estimates, approximately 15% of the tested males were children. These children had an approximate 33% risk of being classified as adults. The corresponding risk for an adult to be misclassified as a child was approximately 7%. We determine uncertainties and ranges of estimates under reasonable perturbations of the prior."
2529,Analysis of male specific region of the human Y chromosome sheds light on historical events in Nazi occupied eastern Poland,"In Poland, during the World War II, almost 3 million people were killed during the Nazi occupation, and about 570,000 during the Soviet occupation. Furthermore, historians have estimated that after the World War II at least 30,000 people were killed during the Stalinist regime in Poland (1944–1956). The exact number is unknown, because both executions and burials were kept secret. Thousands of people just vanished. As a response to those events, forensic scientists from the Pomeranian Medical University in Szczecin in cooperation with historians from the Institute of National Remembrance started the project of the Polish Genetic Database of Victims of Totalitarianism, which aim is to identify victims killed in the years 1939–1956. Several exhumations were done under the project, with the biggest one done in Białystok. According to the information gathered by local historians, a detention centre in Białystok was the place of the secret burials in late 1940s and 1950s. Surprisingly, except few graves from the post-war period, most of the burials found in Białystok indicated that majority the victims were probably local civilians who died during the Nazi occupation. Unfortunately, data concerning what happened in the detention ward during that period of time is not very detailed. What was known is that people who got incarcerated were “political prisoners” what, according to Nazi politics, was based on their nationality, religion and activity against the Third Reich. The aim of this research was to test genetically the remains found in Białystok to determine their possible ethnic background, in order to shed new light on the victims and what happened in the Białystok detention centre during the Nazi occupation. The analysis of male specific region of the human Y chromosome shows that including phylogenetic analysis into the complex process led by the Polish Genetic Database of Victims of Totalitarianism may help with the final identification of hundreds of anonymous victims."
2530,Forensic genetic analysis of population of Madhya Pradesh with PowerPlex Fusion 6C(™) Multiplex System,"Performance of PowerPlex Fusion 6C kit (PP F6C) was assessed in 374 unrelated individuals belonging to Madhya Pradesh, an Indian state. The study evaluated the forensic parameters for the loci included in PP F6C Multiplex System. The combined discrimination power (CPD) and combined exclusion power (CPE) were 1 and 0.999999995, respectively, for all 23 autosomal STR loci. SE33 showed the greatest power of discrimination (0.990) in the studied population, whereas TPOX showed the lowest (0.843). The availability of three Y-STR loci in the Multiplex System is suitable for assessing male contribution and amelogenin deletion in a single Multiplex PCR simultaneously. The study also presents the first global report on polymorphism in the Indian population on SE 33 autosomal STR loci and PP Fusion 6C Multiplex System. The results revealed that the studied STR Multiplex System is highly polymorphic and suitable for forensic purposes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00414-019-02017-0) contains supplementary material, which is available to authorized users."
2531,Postmortem proteomics to discover biomarkers for forensic PMI estimation,"The assessment of postmortem degradation of skeletal muscle proteins has emerged as a novel approach to estimate the time since death in the early to mid-postmortem phase (approximately 24 h postmortem (hpm) to 120 hpm). Current protein-based methods are limited to a small number of skeletal muscle proteins, shown to undergo proteolysis after death. In this study, we investigated the usability of a target-based and unbiased system-wide protein analysis to gain further insights into systemic postmortem protein alterations and to identify additional markers for postmortem interval (PMI) delimitation. We performed proteomic profiling to globally analyze postmortem alterations of the rat and mouse skeletal muscle proteome at defined time points (0, 24, 48, 72, and 96 hpm), harnessing a mass spectrometry-based quantitative proteomics approach. Hierarchical clustering analysis for a total of 579 (rat) and 896 (mouse) quantified proteins revealed differentially expressed proteins during the investigated postmortem period. We further focused on two selected proteins (eEF1A2 and GAPDH), which were shown to consistently degrade postmortem in both rat and mouse, suggesting conserved intra- and interspecies degradation behavior, and thus preserved association with the PMI and possible transferability to humans. In turn, we validated the usefulness of these new markers by classical Western blot experiments in a rat model and in human autopsy cases. Our results demonstrate the feasibility of mass spectrometry–based analysis to discover novel protein markers for PMI estimation and show that the proteins eEF1A2 and GAPDH appear to be valuable markers for PMI estimation in humans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00414-019-02011-6) contains supplementary material, which is available to authorized users."
2532,Infant skull fracture risk for low height falls,"Skull fractures are common injuries in young children, typically caused by accidental falls and child abuse. The paucity of detailed biomechanical data from real-world trauma in children has hampered development of biomechanical thresholds for skull fracture in infants. The objectives of this study were to identify biomechanical metrics to predict skull fracture, determine threshold values associated with fracture, and develop skull fracture risk curves for low-height falls in infants. To achieve these objectives, we utilized an integrated approach consisting of case evaluation, anthropomorphic reconstruction, and finite element simulation. Four biomechanical candidates for predicting skull fracture were identified (first principal stress, first principal strain, shear stress, and von Mises stress) and evaluated against well-witnessed falls in infants (0–6 months). Among the predictor candidates, first principal stress and strain correlated best with the occurrence of parietal skull fracture. The principal stress and strain thresholds associated with 50 and 95% probability of parietal skull fracture were 25.229 and 36.015 MPa and 0.0464 and 0.0699, respectively. Risk curves using these predictors determined that infant falls from 0.3 m had a low probability (0–54%) to result in parietal skull fracture, particularly with carpet impact (0–1%). Head-first falls from 0.9 m had a high probability of fracture (86–100%) for concrete impact and a moderate probability (34–81%) for carpet impact. Probabilities of fracture in 0.6 m falls were dependent on impact surface. Occipital impacts from 0.9 m onto the concrete also had the potential (27–90% probability) to generate parietal skull fracture. These data represent a multi-faceted biomechanical assessment of infant skull fracture risk and can assist in the differential diagnosis for head trauma in children. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00414-018-1918-1) contains supplementary material, which is available to authorized users."
2533,Botulinum Toxin in the Management of Children with Cerebral Palsy,"During the past 25 years, botulinum toxin type A (BoNT-A) has become the most widely used medical intervention in children with cerebral palsy. In this review we consider the gaps in our knowledge in the use of BoNT-A and reasons why muscle morphology and function in children with cerebral palsy are impaired. We review limitations in our knowledge regarding the mechanisms underlying the development of contractures and the difficulty in preventing them. It is clear from this review that injection of BoNT-A in the large muscles of both the upper and lower limbs of children with cerebral palsy will result in a predictable decrease in muscle activity, which is usually reported as a reduction in spasticity, for between 3 and 6 months. These changes are noted by the use of clinical tools such as the Modified Ashworth Scale and the Modified Tardieu Scale. Decreased muscle over-activity usually results in improved range of motion in distal joints. Injection of the gastrocnemius muscle for toe-walking in a child with hemiplegia or diplegia usually has the effect of increasing the passive range of dorsiflexion at the ankle. In our review, we found that this may result in a measurable improvement in gait by the use of observational gait scales or gait analysis, in some children. However, improvements in gait function are not always achieved and are small in magnitude and short lived. We found that some of the differences in outcomes in clinical trials may relate to the use of adjunctive interventions such as serial casting, orthoses, night splints and intensive therapy. We note that the majority of clinical trials of the use of BoNT-A in children with cerebral palsy have focussed on a single injection cycle and this is insufficient to understand the balance between benefit and harm. Most outcomes were reported in terms of changes in muscle tone and there were fewer studies with robust methodology that reported improvements in function. Changes in the domains of activities and participation have rarely been reported in studies to date. There were no clinical reviews to date that consider the findings of studies in human volunteers and in experimental animals and their relevance to clinical protocols. In this review we found that studies in human volunteers and in experimental animals show muscle atrophy after an injection of BoNT-A for at least 12 months. Muscle atrophy was accompanied by loss of contractile elements in muscle and replacement with fat and connective tissue. It is not currently known if these changes, mediated at a molecular level, are reversible. We conclude that there is a need to revise clinical protocols by using BoNT-A more thoughtfully, less frequently and with greatly enhanced monitoring of the effects on injected muscle for both short-term and long-term benefits and harms."
2534,CXCR2 expression on granulocyte and macrophage progenitors under tumor conditions contributes to mo-MDSC generation via SAP18/ERK/STAT3,"Myeloid-derived suppressor cells (MDSCs) comprise a critical component of the tumor environment and CXCR2 reportedly plays a key role in the pathophysiology of various inflammatory diseases. Here, CXCR2 expression on granulocyte and macrophage progenitor cells (GMPs) was found to participate in myeloid cell differentiation within the tumor environment. In CXCR2-deficient tumor-bearing mice, GMPs exhibited fewer macrophage and dendritic cell progenitor cells than wild-type tumor-bearing mice, thereby decreasing monocytic MDSCs (mo-MDSCs) expansion. CXCR2 deficiency increased SAP18 expression in tumor-bearing mice, which reduced STAT3 phosphorylation through restraining ERK1/2 activation. Our findings reveal a critical role for CXCR2 in regulating hematopoietic progenitor cell differentiation under tumor conditions, and SAP18 is a key negative regulator in this process. Thus, inhibiting CXCR2 expression may alter the tumor microenvironment and attenuate tumor progression."
2535,A new method for estimating time since death by analysis of substances deposited on the surface of dental enamel in a body immersed in seawater,"The present investigation was performed with the objective of developing a method to estimate how long a corpse had been immersed in water after death (the time since death). Accurate determination of the time elapsed since death may lead to identification of the place of drowning, and therefore, serves not only as a piece of information useful for determination of the cause of death but also leads to prompt identification of the body. The results showed that diatoms attached to the surface of dental enamel increased with prolongation of immersion time in water. Further, as the immersion time increased, the quantity of O, Si, Mg, K, Al, and S detected on the surface of dental enamel increased, while the quantity of the main dental components (Ca and P) that were detected gradually decreased. Based on these results, we calculated a regression formula to estimate the immersion time. Our method is considered to be a breakthrough technique for evaluating the time since death more objectively, compared to the conventional method of determination based on the degree of decomposition of the corpse."
2536,Transgenic Aedes aegypti Mosquitoes Transfer Genes into a Natural Population,"In an attempt to control the mosquito-borne diseases yellow fever, dengue, chikungunya, and Zika fevers, a strain of transgenically modified Aedes aegypti mosquitoes containing a dominant lethal gene has been developed by a commercial company, Oxitec Ltd. If lethality is complete, releasing this strain should only reduce population size and not affect the genetics of the target populations. Approximately 450 thousand males of this strain were released each week for 27 months in Jacobina, Bahia, Brazil. We genotyped the release strain and the target Jacobina population before releases began for >21,000 single nucleotide polymorphisms (SNPs). Genetic sampling from the target population six, 12, and 27–30 months after releases commenced provides clear evidence that portions of the transgenic strain genome have been incorporated into the target population. Evidently, rare viable hybrid offspring between the release strain and the Jacobina population are sufficiently robust to be able to reproduce in nature. The release strain was developed using a strain originally from Cuba, then outcrossed to a Mexican population. Thus, Jacobina Ae. aegypti are now a mix of three populations. It is unclear how this may affect disease transmission or affect other efforts to control these dangerous vectors. These results highlight the importance of having in place a genetic monitoring program during such releases to detect un-anticipated outcomes."
2537,Study of the Transformations of Micro/Nano-crystalline Acetaminophen Polymorphs in Drug-Polymer Binary Mixtures,"This study elucidates the physical properties of sono-crystallised micro/nano-sized acetaminophen/paracetamol (PMOL) and monitors its possible transformation from polymorphic form I (monoclinic) to form II (orthorhombic). Hydrophilic Plasdone® S630 copovidone (S630), N-vinyl-2-pyrrolidone and vinyl acetate copolymer, and methacrylate-based cationic copolymer, Eudragit® EPO (EPO), were used as polymeric carriers to prepare drug/polymer binary mixtures. Commercially available PMOL was crystallised under ultra sound sonication to produce micro/nano-sized (0.2–10 microns) crystals in monoclinic form. Homogeneous binary blends of drug-polymer mixtures at various drug concentrations were obtained via a thorough mixing. The analysis conducted via the single X-ray crystallography determined the detailed structure of the crystallised PMOL in its monoclinic form. The solid state and the morphology analyses of the PMOL in the binary blends evaluated via differential scanning calorimetry (DSC), modulated temperature DSC (MTDSC), scanning electron microscopy (SEM) and hot stage microscopy (HSM) revealed the crystalline existence of the drug within the amorphous polymeric matrices. The application of temperature controlled X-ray diffraction (VTXRPD) to study the polymorphism of PMOL showed that the most stable form I (monoclinic) was altered to its less stable form II (orthorhombic) at high temperature (>112°C) in the binary blends regardless of the drug amount. Thus, VTXRD was used as a useful tool to monitor polymorphic transformations of crystalline drug (e.g. PMOL) to assess their thermal stability in terms of pharmaceutical product development and research."
2538,Correction: Corrigendum: Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1,
2539,Correction: Corrigendum: BMP signalling differentially regulates distinct haematopoietic stem cell types,
2540,Erratum: STAT3 regulated ARF expression suppresses prostate cancer metastasis,
2541,Correction: Corrigendum: Macroscopic ordering of helical pores for arraying guest molecules noncentrosymmetrically,
2542,Erratum: Structural diversity of supercoiled DNA,
2543,Erratum: A deuterostome origin of the Spemann organiser suggested by Nodal and ADMPs functions in Echinoderms,
2544,Correction: Corrigendum: IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel,
2545,Correction: Corrigendum: Resistive switching and its suppression in Pt/Nb:SrTiO(3) junctions,
2546,The Impact of Receiving Pretravel Health Advice on the Prevention of Hajj-Related Illnesses Among Australian Pilgrims: Cohort Study,"BACKGROUND: Pretravel health advice can play a crucial role in improving both travelers’ awareness about disease risk and compliance with preventive measures. General practitioners (GPs) and the internet have been reported internationally to be the main sources of health advice for travelers to non–mass gathering (MG) destinations. However, few studies have attempted to investigate the sources of health advice among travelers to MGs including the Hajj pilgrimage, and none of these studies further investigated the impact of pretravel advice on pilgrims’ health behaviors. OBJECTIVE: The objective of this study was to investigate the impact of the source of pretravel health advice (from GPs and specialized Hajj travel agents) on Hajj pilgrims’ awareness of and compliance with health recommendations, and the incidence of Hajj-associated illnesses. METHODS: A prospective cohort study (before and during Hajj) was conducted among Australian pilgrims aged ≥18 years in 2015. RESULTS: A total of 421 pilgrims participated prior to Hajj, and 391 (93%) provided follow-up data during Hajj. All participants obtained pretravel health advice from one or more sources, with Hajj travel agents (46%) and general practitioners (GPs; 40%) the most commonly reported sources. In total, 288 (74%) participants reported Hajj-related symptoms, of which 86% (248/288) were respiratory symptoms. Participants who obtained pretravel health advice from travel agents were more likely to be aware of the official Saudi recommendations (adjusted odds ratio [aOR] 2.1, 95% CI 1.2-3.8; P=.01), receive recommended vaccines before travel (aOR 2.4, 95% CI 1.4-3.9; P=.01), use hand sanitizers including soap (aOR 2.5, 95% CI 1.1-6.1; P=.03), and wash their hands after touching an ill person during Hajj (aOR 2.9, 95% CI 1.1-7.1; P=.01), compared to those who sought advice from GPs. However, neither advice from travel agents nor GPs was associated with a lower incidence of Hajj-related illnesses. CONCLUSIONS: Advice from travel agents appeared to be accessed by more travelers than that from GPs, and was associated with an increased likelihood of positive travel health behaviors."
2547,The political consequences of opioid overdoses,"The United States suffered a dramatic and well-documented increase in drug-related deaths from 2000 to 2018, primarily driven by prescription and non-prescription opioids, and concentrated in white and working-class areas. A growing body of research focuses on the causes, both medical and social, of this opioid crisis, but little work as yet on its larger ramifications. Using novel public records of accidental opioid deaths linked to behavioral political outcomes, we present causal analyses showing that opioid overdoses have significant political ramifications. Those close to opioid victims vote at lower rates than those less affected by the crisis, even compared to demographically-similar friends and family of other unexpected deaths. Moreover, among those friends and family affected by opioids, Republicans are 25% more likely to defect from the party than the statewide average Republican, while Democrats are no more likely to defect; Independents are moderately more likely to register as Democrats. These results illustrate an important research design for inferring the effects of tragic events and speak to the broad social and political consequences of what is becoming the largest public health crisis in modern United States history."
2548,Which sample type is better for Xpert MTB/RIF to diagnose adult and pediatric pulmonary tuberculosis?,"Objective: This review aimed to identify proper respiratory-related sample types for adult and pediatric pulmonary tuberculosis (PTB), respectively, by comparing performance of Xpert MTB/RIF when using bronchoalveolar lavage (BAL), induced sputum (IS), expectorated sputum (ES), nasopharyngeal aspirates (NPAs), and gastric aspiration (GA) as sample. Methods: Articles were searched in Web of Science, PubMed, and Ovid from inception up to 29 June 2020. Pooled sensitivity and specificity were calculated, each with a 95% confidence interval (CI). Quality assessment and heterogeneity evaluation across included studies were performed. Results: A total of 50 articles were included. The respective sensitivity and specificity were 87% (95% CI: 0.84–0.89), 91% (95% CI: 0.90–0.92) and 95% (95% CI: 0.93–0.97) in the adult BAL group; 90% (95% CI: 0.88–0.91), 98% (95% CI: 0.97–0.98) and 97% (95% CI: 0.95–0.99) in the adult ES group; 86% (95% CI: 0.84–0.89) and 97% (95% CI: 0.96–0.98) in the adult IS group. Xpert MTB/RIF showed the sensitivity and specificity of 14% (95% CI: 0.10–0.19) and 99% (95% CI: 0.97–1.00) in the pediatric ES group; 80% (95% CI: 0.72–0.87) and 94% (95% CI: 0.92–0.95) in the pediatric GA group; 67% (95% CI: 0.62–0.72) and 99% (95% CI: 0.98–0.99) in the pediatric IS group; and 54% (95% CI: 0.43–0.64) and 99% (95% CI: 0.97–0.99) in the pediatric NPA group. The heterogeneity across included studies was deemed acceptable. Conclusion: Considering diagnostic accuracy, cost and sampling process, ES was a better choice than other sample types for diagnosing adult PTB, especially HIV-associated PTB. GA might be more suitable than other sample types for diagnosing pediatric PTB. The actual choice of sample types should also consider the needs of specific situations."
2549,Polymeric Nanoparticles for Drug Delivery: Recent Developments and Future Prospects,"The complexity of some diseases—as well as the inherent toxicity of certain drugs—has led to an increasing interest in the development and optimization of drug-delivery systems. Polymeric nanoparticles stand out as a key tool to improve drug bioavailability or specific delivery at the site of action. The versatility of polymers makes them potentially ideal for fulfilling the requirements of each particular drug-delivery system. In this review, a summary of the state-of-the-art panorama of polymeric nanoparticles as drug-delivery systems has been conducted, focusing mainly on those applications in which the corresponding disease involves an important morbidity, a considerable reduction in the life quality of patients—or even a high mortality. A revision of the use of polymeric nanoparticles for ocular drug delivery, for cancer diagnosis and treatment, as well as nutraceutical delivery, was carried out, and a short discussion about future prospects of these systems is included."
2550,Simple Is Better for Local Beverage Tax Policy Diffusion,
2551,Anti-Acne Action of Peptides Isolated from Burdock Root—Preliminary Studies and Pilot Testing,"This work aimed to study the anti-bacterial, anti-biofilm and anti-oxidant potential effects of low molecular weight (LMW) peptides (Br-p) isolated from burdock (Arctium lappa L.) roots. We conducted a preliminary study to exclude or confirm the antibiotic activity of the LMW peptides fraction of this plant. Br-p were isolated using gel filtration and a 10 kDa cut-off membrane. The obtained peptides were identified by MALDI TOF/TOF. Antibacterial activity was tested against acne strains using diffusion tests, MIC and MBC. The fibroblast cytotoxicity of Br-p was tested, and the selectivity index (SI) value was determined. The fraction of 46 Br-p peptides isolated from burdock root with a molecular weight below 5000 Da and theoretic pI (isoelectric point) of 3.67–11.83 showed a narrow spectrum of activity against Gram-positive acne bacterial strains. One of the Br-p peptides assessed on MALDI RapidDeNovo was LRCDYGRFFASKSLYDPLKKRR cationic peptide. It was analogous to that contained in A. lappa protein, and theoretically it was matched as a peptide with antibiotic nature. Br-p did not show toxicity to fibroblasts in the tested concentration up to 10 mg/mL, obtaining CC(50) 10 mg/mL. The SI value for the tested Propionibacterium strains ranged from 160 to 320. Finally, an active dressing based on chitosan/alginate/genipin was prepared using freeze-drying. The formed dressing was evaluated for its anti-acne activity. To sum up: preliminary biological studies confirmed the anti-acne properties of the isolated peptide fraction from burdock root and pointed to the possibility of using it to create an active dressing on the skin."
2552,Patients with Community Acquired Pneumonia Exhibit Depleted Vitamin C Status and Elevated Oxidative Stress,"Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the Intensive Care Unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and hematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, an established marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs. 56 ± 24 µmol/L, p < 0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs. 24 ± 14 µmol/L, p = 0.02). The pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (p < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples from 28% of the cohort (mean 2.7 ± 1.7 days; range 1–7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (p = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease excessive oxidative stress and aid in their recovery."
2553,"Systematic Review of the Respiratory Syncytial Virus (RSV) Prevalence, Genotype Distribution, and Seasonality in Children from the Middle East and North Africa (MENA) Region","Respiratory syncytial virus (RSV) is one of the most common viruses to infect children worldwide and is the leading cause of lower respiratory tract illness (LRI) in infants. This study aimed to conduct a systematic review by collecting and reviewing all the published knowledge about the epidemiology of RSV in the Middle East and North Africa (MENA) region. Therefore, we systematically searched four databases; Embase, Medline, Scopus, and Cochrane databases from 2001 to 2019 to collect all the information related to the RSV prevalence, genotype distribution, and seasonality in children in MENA region. Our search strategy identified 598 studies, of which 83 met our inclusion criteria, which cover the past 19 years (2000–2019). Odds ratio (OR) and confidence interval (CI) were calculated to measure the association between RSV prevalence, gender, and age distribution. An overall prevalence of 24.4% (n = 17,106/69,981) of respiratory infections was recorded for RSV. The highest RSV prevalence was reported in Jordan (64%, during 2006–2007) and Israel (56%, 2005–2006). RSV A subgroup was more prevalent (62.9%; OR = 2.9, 95%CI = 2.64–3.13) than RSV B. RSV was most prevalent in children who were less than 12 months old (68.6%; OR = 4.7, 95%CI = 2.6–8.6) and was higher in males (59.6%; OR = 2.17, 95%CI = 1.2–3.8) than in female infants. Finally, the highest prevalence was recorded during winter seasons in all countries, except for Pakistan. RSV prevalence in the MENA region is comparable with the global one (24.4% vs. 22%). This first comprehensive report about RSV prevalence in the MENA region and our data should be important to guide vaccine introduction decisions and future evaluation."
2554,Environmental and economic effectiveness of the Kyoto Protocol,"This study investigates the environmental and economic impacts of the Kyoto Protocol on Annex I parties through an impact assessment by combining the propensity score matching and the difference-in-difference methods. We establish a country-level panel data set including CO(2) emissions, gross domestic product (GDP), and other socioeconomic data for 1997–2008 and 2005–2008. Based on the impact evaluation, we conduct the simulation predicting the impacts of the Protocol to capture the differences of marginal damage cost of carbon emissions between the actual and counterfactual situations. The results suggest that participating as an Annex I party has a significant positive impact on CO(2) emission reductions, but a negative impact on the GDP of the participants in the long run. The predicted marginal benefit of the Protocol based on the marginal damage cost of carbon emissions shows that the marginal benefit of emission reductions mitigates a limited portion of the GDP loss. Future global climate change frameworks should focus on balancing the impact on economic and environmental performance in order to ensure sustainable development, especially for developing countries that have low capacity to mitigate emissions."
2555,Error in Funding/Support,
2556,Biofunctional Polymer Coated Au Nanoparticles Prepared via RAFT-Assisted Encapsulating Emulsion Polymerization and Click Chemistry,"The use of reversible addition-fragmentation chain transfer (RAFT)-assisted encapsulating emulsion polymerization (REEP) has been explored to prepare diverse types of colloidal stable core–shell nanostructures. A major field of application of such nanoparticles is in emergent nanomedicines, which require effective biofunctionalization strategies, in which their response to bioanalytes needs to be firstly assessed. Herein, functional core–shell nanostructures were prepared via REEP and click chemistry. Thus, following the REEP strategy, colloidal gold nanoparticles (Au NPs, d = 15 nm) were coated with a poly(ethylene glycol) methyl ether acrylate (PEGA) macroRAFT agent containing an azide (N3) group to afford N3–macroRAFT@Au NPs. Then, chain extension was carried out from the NPs surface via REEP, at 44 °C under monomer-starved conditions, to yield N3–copolymer@Au NPs–core–shell type structures. Biotin was anchored to N3–copolymer@Au NPs via click chemistry using an alkynated biotin to yield biofunctionalized Au nanostructures. The response of the ensuing biotin–copolymer@Au NPs to avidin was followed by visible spectroscopy, and the copolymer–biotin–avidin interaction was further studied using the Langmuir–Blodgett technique. This research demonstrates that REEP is a promising strategy to prepare robust functional core–shell plasmonic nanostructures for bioapplications. Although the presence of azide moieties requires the use of low polymerization temperature, the overall strategy allows the preparation of tailor-made plasmonic nanostructures for applications of biosensors based on responsive polymer shells, such as pH, temperature, and photoluminescence quenching. Moreover, the interaction of biotin with avidin proved to be time dependent."
2557,CD38: T Cell Immuno-Metabolic Modulator,"Activation and subsequent differentiation of T cells following antigenic stimulation are triggered by highly coordinated signaling events that lead to instilling cells with a discrete metabolic and transcriptional feature. Compelling studies indicate that intracellular nicotinamide adenine dinucleotide (NAD(+)) levels have profound influence on diverse signaling and metabolic pathways of T cells, and hence dictate their functional fate. CD38, a major mammalian NAD(+) glycohydrolase (NADase), expresses on T cells following activation and appears to be an essential modulator of intracellular NAD(+) levels. The enzymatic activity of CD38 in the process of generating the second messenger cADPR utilizes intracellular NAD(+,) and thus limits its availability to different NAD(+) consuming enzymes (PARP, ART, and sirtuins) inside the cells. The present review discusses how the CD38-NAD(+) axis affects T cell activation and differentiation through interfering with their signaling and metabolic processes. We also describe the pivotal role of the CD38-NAD(+) axis in influencing the chromatin remodeling and rewiring T cell response. Overall, this review emphasizes the crucial contribution of the CD38(−)NAD(+) axis in altering T cell response in various pathophysiological conditions."
2558,Unveiling the Mechanism of Action of 7α-acetoxy-6β-hydroxyroyleanone on an MRSA/VISA Strain: Membrane and Cell Wall Interactions,"The number of cases of failure in the treatment of infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, 7α-Acetoxy-6β-hydroxyroyleanone (AHR), a diterpene isolated from different Plectranthus species, showed antibacterial activity, namely against Methicillin-resistant Staphylococcus aureus (MRSA) strains. The high antibacterial activity and low cytotoxicity render this natural compound an interesting alternative against resistant bacteria. The aim of this study is to understand the mechanism of action of AHR on MRSA, using the MRSA/Vancomycin-intermediate S. aureus (VISA) strain CIP 106760, and to study the AHR effect on lipid bilayers and on the cell wall. Although AHR interacted with lipid bilayers, it did not have a significant effect on membrane passive permeability. Alternatively, bacteria treated with this royleanone displayed cell wall disruption, without revealing cell lysis. In conclusion, the results gathered so far point to a yet undescribed mode of action that needs further investigation."
2559,Neutrophils as Main Players of Immune Response towards Nondegradable Nanoparticles,"Many nano/microparticles (n/µP), to which our body is exposed, have no physiological way of removal. Our immune system sense these “small particulate objects”, and tries to decrease their harmfulness. Since oxidation, phagocytosis and other methods of degradation do not work with small, chemically resistant, and hydrophobic nanoparticles (nP). This applies to soot from air pollution, nano-diamonds from cosmic impact, polishing and related machines, synthetic polymers, and dietary n/µP. Our body tries to separate these from the surrounding tissue using aggregates from neutrophil extracellular traps (NETs). This effectively works in soft tissues where n/µP are entrapped into granuloma-like structures and isolated. The interactions of hydrophobic nanocrystals with circulating or ductal patrolling neutrophils and the consequent formation of occlusive aggregated NETs (aggNETs) are prone to obstruct capillaries, bile ducts in gallbladder and liver, and many more tubular structures. This may cause serious health problems and often fatality. Here we describe how specific size and surface properties of n/µP can activate neutrophils and lead to aggregation-related pathologies. We discuss “natural” sources of n/µP and those tightly connected to unhealthy diets."
2560,miR-615 Fine-Tunes Growth and Development and Has a Role in Cancer and in Neural Repair,"MicroRNAs (miRNAs) are small noncoding RNAs that function as epigenetic modulators regulating almost any gene expression. Similarly, other noncoding RNAs, as well as epigenetic modifications, can regulate miRNAs. This reciprocal interaction forms a miRNA-epigenetic feedback loop, the deregulation of which affects physiological processes and contributes to a great diversity of diseases. In the present review, we focus on miR-615, a miRNA highly conserved across eutherian mammals. It is involved not only during embryogenesis in the regulation of growth and development, for instance during osteogenesis and angiogenesis, but also in the regulation of cell growth and the proliferation and migration of cells, acting as a tumor suppressor or tumor promoter. It therefore serves as a biomarker for several types of cancer, and recently has also been found to be involved in reparative processes and neural repair. In addition, we present the pleiad of functions in which miR-615 is involved, as well as their multiple target genes and the multiple regulatory molecules involved in its own expression. We do this by introducing in a comprehensible way the reported knowledge of their actions and interactions and proposing an integral view of its regulatory mechanisms."
2561,"Methylation regulation of Antiviral host factors, Interferon Stimulated Genes (ISGs) and T-cell responses associated with natural HIV control","GWAS, immune analyses and biomarker screenings have identified host factors associated with in vivo HIV-1 control. However, there is a gap in the knowledge about the mechanisms that regulate the expression of such host factors. Here, we aimed to assess DNA methylation impact on host genome in natural HIV-1 control. To this end, whole DNA methylome in 70 untreated HIV-1 infected individuals with either high (>50,000 HIV-1-RNA copies/ml, n = 29) or low (<10,000 HIV-1-RNA copies/ml, n = 41) plasma viral load (pVL) levels were compared and identified 2,649 differentially methylated positions (DMPs). Of these, a classification random forest model selected 55 DMPs that correlated with virologic (pVL and proviral levels) and HIV-1 specific adaptive immunity parameters (IFNg-T cell responses and neutralizing antibodies capacity). Then, cluster and functional analyses identified two DMP clusters: cluster 1 contained hypo-methylated genes involved in antiviral and interferon response (e.g. PARP9, MX1, and USP18) in individuals with high viral loads while in cluster 2, genes related to T follicular helper cell (Tfh) commitment (e.g. CXCR5 and TCF7) were hyper-methylated in the same group of individuals with uncontrolled infection. For selected genes, mRNA levels negatively correlated with DNA methylation, confirming an epigenetic regulation of gene expression. Further, these gene expression signatures were also confirmed in early and chronic stages of infection, including untreated, cART treated and elite controllers HIV-1 infected individuals (n = 37). These data provide the first evidence that host genes critically involved in immune control of the virus are under methylation regulation in HIV-1 infection. These insights may offer new opportunities to identify novel mechanisms of in vivo virus control and may prove crucial for the development of future therapeutic interventions aimed at HIV-1 cure."
2562,Exploring collective emotion transmission in face-to-face interactions,"Collective emotion is the synchronous convergence of an effective response across individuals toward a specific event or object. Previous studies have focused on the transmission of cyber collective emotion; however, little attention has been paid to the transmission of collective emotion in face-to-face interactions. Using an experimental design, we examined how emotions are transmitted from some members to the whole group in face-to-face situations. We used a news report of a social event as an emotion stimulus to induce anger and disgust in 158 middle school students aged 12 to 15, with an average age of 13.20 years (SD = 0.651) We randomly assigned one-third of the participants to be “transmitters,” while the others were “receivers.” Transmitters shared their feelings with receivers; then, receivers communicated with other group members. The results indicated that negative collective emotions were transmitted from high- to low-intensity members, which converged through the effect of emotional contagion. It accumulated through the effect of an emotional circle, during which the feedback reinforced emotion intensity. The collective emotion transmission model comprised emotion diffusion, contagion, and accumulation. This model elucidates the intrinsic features of collective emotion transmission, enriches the research on collective emotion, and provides theoretical references for monitoring and managing future public events."
2563,"Clinical evaluation of fully automated molecular diagnostic system “Simprova” for influenza virus, respiratory syncytial virus, and human metapneumovirus","Influenza virus, respiratory syncytial virus, and human metapneumovirus commonly cause acute upper and lower respiratory tract infections, especially in children and the elderly. Although rapid antigen detection tests for detecting these infections have been introduced recently, these are less sensitive than nucleic acid amplification tests. More recently, highly sensitive point-of-care testings (POCTs) have been developed based on nucleic acid amplification tests, which are easy to use in clinical settings. In this study, loop-mediated isothermal amplification (LAMP)-based POCT “Simprova” to detect influenza A and B viruses, respiratory syncytial virus, and human metapneumovirus was developed. Simprova system is fully automated and does not require skilled personnel. In addition, positive results can be achieved faster than with PCR. In this study, the accuracy of the POCT was retrospectively analyzed using 241 frozen stocked specimens. Additionally, the usability of the Simprova at clinical sites was assessed in a prospective clinical study using 380 clinical specimens and compared to those of real-time PCR and rapid antigen detection test. The novel LAMP-based POCT demonstrated high sensitivity and specificity in characterizing clinical specimens from patients with influenza-like illnesses. The Simprova is a powerful tool for early diagnosis of respiratory viral infections in point-of-care settings."
2564,Multidrug resistant and extensively drug resistant Acinetobacter baumannii hospital infection associated with high mortality: a retrospective study in the pediatric intensive care unit,"BACKGROUND: Multidrug resistant (MDR) and extensively drug resistant (XDR) Acinetobacter baumannii presents challenges for clinical treatment and causes high mortality in children. We aimed to assess the risk factors and overall mortality for MDR/XDR Acinetobacter baumannii infected pediatric patients. METHODS: This retrospective study included 102 pediatric patients who developed MDR/XDR Acinetobacter baumannii infection in the pediatric intensive care unit (PICU) of Shanghai Children’s Hospital in China from December 2014 to May 2018. Acinetobacter baumannii clinical isolates were recovered from different specimens including blood, sputum, bronchoalveolar lavage fluid, cerebrospinal fluid, ascites, hydrothorax, and urine. Antibiotic susceptibility test was determined according to the Clinical and Laboratory Standards Institute interpretive criteria. Clinical and biological data were obtained from the patients’ medical records. RESULTS: 102 patients with Acinetobacter baumannii infection were enrolled. The median age was 36 (9.6, 98.8) months, and there were 63 male in the case group. The overall mortality rate was 29.4%, while the Acinetobacter baumannii-associated mortality rate was 16.7% (17/102, 12 bloodstream infections, 4 meningitis and 1 intra-abdominal infection). Bloodstream infections occurred in 28 patients (27.5%), and 10 patients (9.8%) among them had central line-associated bloodstream infections (6 central venous catheters, 2 PICCs, 1 venous infusion port and 1 arterial catheter). Cerebrospinal fluid (CSF) cultures were positive in 4(3.9%) patients. 14(13.7%) patients got positive cultures in ascites and hydrothorax. Lower respiratory isolates (56/102) accounted for 54.9% of all patients. Non-survival patients appeared to have a lower NK cell activity (6.2% ± 3.61% vs. 9.15% ± 6.21%, P = 0.029), higher CD4+ T cell ratio (39.67% ± 12.18% vs. 32.66% ± 11.44%, P = 0.039),and a higher serum level of interlukin-8 (IL-8, 15.25 (1.62, 47.22)pg/mL vs. 0.1 (0.1, 22.99)pg/mL, P = 0.01) when Acinetobacter baumannii infection developed. Multivariate logistic analysis indicated that high serum level of Cr (RR, 0.934, 95%CI, 0.890–0.981; P = 0.007) and high BUN/ALB level (RR, 107.893, 95%CI, 1.425–870.574; p = 0.005) were associated with high risk of mortality in MDR/XDR Acinetobacter baumannii infected patients. CONCLUSION: MDR/XDR Acinetobacter baumannii infection is a serious concern in pediatric patients with high mortality. Bloodstream and central nervous system infection accounted for high risk of death. Acute kidney injury is associated with high risk of mortality."
2565,Effect of vaporized hydrogen peroxide reprocessing on N95 respirators,
2566,Spatiotemporal DNA methylome dynamics of the developing mouse fetus,"Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited(1,2). Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at 9 developmental stages from embryogenesis to adulthood. We identified 1,808,810 genomic regions that showed variations in CG methylation by comparing the methylomes of different tissues or organs from different developmental stages. These DNA elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. During late stages of fetal development, non-CG methylation accumulated within the bodies of key developmental transcription factor genes, coinciding with their transcriptional repression. Integration of genome-wide DNA methylation, histone modification and chromatin accessibility data enabled us to predict 461,141 putative developmental tissue-specific enhancers, the human orthologues of which were enriched for disease-associated genetic variants. These spatiotemporal epigenome maps provide a resource for studies of gene regulation during tissue or organ progression, and a starting point for investigating regulatory elements that are involved in human developmental disorders."
2567,Occupancy maps of 208 chromatin-associated proteins in one human cell type,"Transcription factors are DNA-binding proteins that have key roles in gene regulation(1,2). Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes(3–6). However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–seq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP–seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium."
2568,An atlas of dynamic chromatin landscapes in mouse fetal development,"The Encyclopedia of DNA Elements (ENCODE) project has established a genomic resource for mammalian development, profiling a diverse panel of mouse tissues at 8 developmental stages from 10.5 days after conception until birth, including transcriptomes, methylomes and chromatin states. Here we systematically examined the state and accessibility of chromatin in the developing mouse fetus. In total we performed 1,128 chromatin immunoprecipitation with sequencing (ChIP–seq) assays for histone modifications and 132 assay for transposase-accessible chromatin using sequencing (ATAC–seq) assays for chromatin accessibility across 72 distinct tissue-stages. We used integrative analysis to develop a unified set of chromatin state annotations, infer the identities of dynamic enhancers and key transcriptional regulators, and characterize the relationship between chromatin state and accessibility during developmental gene regulation. We also leveraged these data to link enhancers to putative target genes and demonstrate tissue-specific enrichments of sequence variants associated with disease in humans. The mouse ENCODE data sets provide a compendium of resources for biomedical researchers and achieve, to our knowledge, the most comprehensive view of chromatin dynamics during mammalian fetal development to date."
2569,"Male Nursing Practitioners and Nursing Educators: The Relationship between Childhood Experience, Social Stigma, and Social Bias","The population of nurses and nursing educators is facing significant human resource shortages. One of the pathways to combat this shortage is to recruit male individuals. However, due to social bias and social stigma, the social context may prevent male individuals from joining. There are two purposes of this study. First, this study aims to explore how the childhood experiences of these male nursing practitioners and nursing educators influence their educational decision. Second, from the perspectives of male nursing practitioners and nursing educators, the study aims to explore how the participants describe the relationships between their childhood experiences and lived stories. Based on Interpretative Phenomenological Analysis, the researcher collected data from 10 experienced male nursing practitioners and nursing educators in the United States. The general inductive approach was employed to categorize the themes. The results indicated that early life experiences, positive working experiences, and sense of belonging in the field of nursing always allowed the participants to overcome the social bias and stigma regarding the occupational bias of the nursing profession. The outcomes of this study provide clear recommendations to educators, policymakers, school leaders, and human resource planners to encourage gender social justice and improve their current curriculum for potential nursing professionals."
2570,Current Concepts in Community and Ventilator Associated Lower Respiratory Tract Infections in ICU Patients,"It is widely known that pneumonia (either community acquired or hospital acquired, as like ventilator associated pneumonia (VAP)), is the most frequent type of severe infection and continues to pose a significant burden on healthcare services worldwide. Despite new diagnostic developments, most pneumonia cases continue to be difficult to diagnose clinically, partly due to acquired antibiotic resistance and the lack of a ‘gold standard’ method of diagnosis. In other words, the lack of a rapid, accurate diagnostic test, as well as the uncertainty of the initial etiologic diagnosis and the risk stratification, results in empirical antibiotic treatments. There are significant changes in the aetiology of patients with ventilator associated lower respiratory tract infections (VA-LRTI), which are characterised by a higher incidence of multi drug resistant organisms. Evidence suggests that when patients with VA-LRTI develop organ failure, the associated mortality can be exceptionally high with frequent complications, including acute respiratory distress syndrome, acute kidney injury, and septic shock. Appropriate antibiotic treatments must consider that the present cardiovascular failure seen in patients has a different association with the patient’s mortality. Unlike patients with less severe clinical presentations, who have a higher chance of survival when the appropriate antibiotics are administered promptly, for patients with a severe subtype of the disease, the appropriateness of antibiotic treatment will impact the patient’s outcome to a lesser extent. The present review highlights certain factors detectable at the time of admission that could indicate patients who are at a high risk of bacteraemia and who, therefore, merit more intense therapy and stratified care."
2571,"The Current State of Research, Challenges, and Future Research Directions of Blockchain Technology in Patient Care: Systematic Review","BACKGROUND: Blockchain offers a promising new distributed technology to address the challenges of data standardization, system interoperability, security, privacy, and accessibility of medical records. OBJECTIVE: The purpose of this review is to assess the research on the use of blockchain technology for patient care and the associated challenges and to provide a research agenda for future research. METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We queried the Cumulative Index of Nursing and Allied Health Literature (CINAHL), PubMed, Excerpta Medica dataBASE (EMBASE), and Web of Science databases for peer-reviewed research articles published up to December 2019 that examined the implementation of blockchain technology in health care settings. We identified 800 articles from which we selected 70 empirical research articles for a detailed review. RESULTS: Blockchain-based patient care applications include medical information systems, personal health records, mobile health and telemedicine, data preservation systems and social networks, health information exchanges and remote monitoring systems, and medical research systems. These blockchain-based health care applications may improve patient engagement and empowerment, improve health care provider access to information, and enhance the use of health care information for medical research. CONCLUSIONS: Blockchain health information technology (HIT) provides benefits such as ensuring data privacy and security of health data, facilitating interoperability of heterogeneous HIT systems, and improving the quality of health care outcomes. However, barriers to using blockchain technology to build HIT include security and privacy vulnerabilities, user resistance, high computing power requirements and implementation costs, inefficient consensus algorithms, and challenges of integrating blockchain with existing HIT. With 51% of the research focused on medical information systems such as electronic health record and electronic medical record, and 53% of the research focused on data security and privacy issues, this review shows that HIT research is primarily focused on the use of blockchain technologies to address the current challenges HIT faces. Although Blockchain presents significant potential for disrupting health care, most ideas are in their infancy."
2572,"Small Animal Models for Human Immunodeficiency Virus (HIV), Hepatitis B, and Tuberculosis: Proceedings of an NIAID Workshop","The main advantage of animal models of infectious diseases over in vitro studies is the gain in the understanding of the complex dynamics between the immune system and the pathogen. While small animal models have practical advantages over large animal models, it is crucial to be aware of their limitations. Although the small animal model at least needs to be susceptible to the pathogen under study to obtain meaningful data, key elements of pathogenesis should also be reflected when compared to humans. Well‐designed small animal models for HIV, hepatitis viruses and tuberculosis require, additionally, a thorough understanding of the similarities and differences in the immune responses between humans and small animals and should incorporate that knowledge into the goals of the study. To discuss these considerations, the NIAID hosted a workshop on ‘Small Animal Models for HIV, Hepatitis B, and Tuberculosis’ on May 30, 2019. Highlights of the workshop are outlined below."
2573,Perspectives on ENCODE,"The Encylopedia of DNA Elements (ENCODE) Project launched in 2003 with the long-term goal of developing a comprehensive map of functional elements in the human genome. These included genes, biochemical regions associated with gene regulation (for example, transcription factor binding sites, open chromatin, and histone marks) and transcript isoforms. The marks serve as sites for candidate cis-regulatory elements (cCREs) that may serve functional roles in regulating gene expression(1). The project has been extended to model organisms, particularly the mouse. In the third phase of ENCODE, nearly a million and more than 300,000 cCRE annotations have been generated for human and mouse, respectively, and these have provided a valuable resource for the scientific community."
2574,Global reference mapping of human transcription factor footprints,"Combinatorial binding of transcription factors to regulatory DNA underpins gene regulation in all organisms. Genetic variation in regulatory regions has been connected with diseases and diverse phenotypic traits(1), but it remains challenging to distinguish variants that affect regulatory function(2). Genomic DNase I footprinting enables the quantitative, nucleotide-resolution delineation of sites of transcription factor occupancy within native chromatin(3–6). However, only a small fraction of such sites have been precisely resolved on the human genome sequence(6). Here, to enable comprehensive mapping of transcription factor footprints, we produced high-density DNase I cleavage maps from 243 human cell and tissue types and states and integrated these data to delineate about 4.5 million compact genomic elements that encode transcription factor occupancy at nucleotide resolution. We map the fine-scale structure within about 1.6 million DNase I-hypersensitive sites and show that the overwhelming majority are populated by well-spaced sites of single transcription factor–DNA interaction. Cell-context-dependent cis-regulation is chiefly executed by wholesale modulation of accessibility at regulatory DNA rather than by differential transcription factor occupancy within accessible elements. We also show that the enrichment of genetic variants associated with diseases or phenotypic traits in regulatory regions(1,7) is almost entirely attributable to variants within footprints, and that functional variants that affect transcription factor occupancy are nearly evenly partitioned between loss- and gain-of-function alleles. Unexpectedly, we find increased density of human genetic variation within transcription factor footprints, revealing an unappreciated driver of cis-regulatory evolution. Our results provide a framework for both global and nucleotide-precision analyses of gene regulatory mechanisms and functional genetic variation."
2575,The changing mouse embryo transcriptome at whole tissue and single-cell resolution,"During mammalian embryogenesis, differential gene expression gradually builds the identity and complexity of each tissue and organ system(1). Here we systematically quantified mouse polyA-RNA from day 10.5 of embryonic development to birth, sampling 17 tissues and organs. The resulting developmental transcriptome is globally structured by dynamic cytodifferentiation, body-axis and cell-proliferation gene sets that were further characterized by the transcription factor motif codes of their promoters. We decomposed the tissue-level transcriptome using single-cell RNA-seq (sequencing of RNA reverse transcribed into cDNA) and found that neurogenesis and haematopoiesis dominate at both the gene and cellular levels, jointly accounting for one-third of differential gene expression and more than 40% of identified cell types. By integrating promoter sequence motifs with companion ENCODE epigenomic profiles, we identified a prominent promoter de-repression mechanism in neuronal expression clusters that was attributable to known and novel repressors. Focusing on the developing limb, single-cell RNA data identified 25 candidate cell types that included progenitor and differentiating states with computationally inferred lineage relationships. We extracted cell-type transcription factor networks and complementary sets of candidate enhancer elements by using single-cell RNA-seq to decompose integrative cis-element (IDEAS) models that were derived from whole-tissue epigenome chromatin data. These ENCODE reference data, computed network components and IDEAS chromatin segmentations are companion resources to the matching epigenomic developmental matrix, and are available for researchers to further mine and integrate."
2576,Landscape of cohesin-mediated chromatin loops in the human genome,"Physical interactions between distal regulatory elements have a key role in regulating gene expression, but the extent to which these interactions vary between cell types and contribute to cell-type-specific gene expression remains unclear. Here, to address these questions as part of phase III of the Encyclopedia of DNA Elements (ENCODE), we mapped cohesin-mediated chromatin loops, using chromatin interaction analysis by paired-end tag sequencing (ChIA-PET), and analysed gene expression in 24 diverse human cell types, including core ENCODE cell lines. Twenty-eight per cent of all chromatin loops vary across cell types; these variations modestly correlate with changes in gene expression and are effective at grouping cell types according to their tissue of origin. The connectivity of genes corresponds to different functional classes, with housekeeping genes having few contacts, and dosage-sensitive genes being more connected to enhancer elements. This atlas of chromatin loops complements the diverse maps of regulatory architecture that comprise the ENCODE Encyclopedia, and will help to support emerging analyses of genome structure and function."
2577,A large-scale binding and functional map of human RNA-binding proteins,"Many proteins regulate the expression of genes by binding to specific regions encoded in the genome(1). Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs. We describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. Integrative analyses using five assays identify RBP binding sites on RNA and chromatin in vivo, the in vitro binding preferences of RBPs, the function of RBP binding sites and the subcellular localization of RBPs, producing 1,223 replicated data sets for 356 RBPs. We describe the spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization. These data expand the catalogue of functional elements encoded in the human genome by the addition of a large set of elements that function at the RNA level by interacting with RBPs."
2578,Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression,"The type I interferon (IFN) response is a principal component of our immune system that allows to counter a viral attack immediately upon viral entry into host cells. Upon engagement of aberrantly localised nucleic acids, germline-encoded pattern recognition receptors convey their find via a signalling cascade to prompt kinase-mediated activation of a specific set of five transcription factors. Within the nucleus, the coordinated interaction of these dimeric transcription factors with coactivators and the basal RNA transcription machinery is required to access the gene encoding the type I IFN IFNβ (IFNB1). Virus-induced release of IFNβ then induces the antiviral state of the system and mediates further mechanisms for defence. Due to its key role during the induction of the initial IFN response, the activity of the transcription factor interferon regulatory factor 3 (IRF3) is tightly regulated by the host and fiercely targeted by viral proteins at all conceivable levels. In this review, we will revisit the steps enabling the trans-activating potential of IRF3 after its activation and the subsequent assembly of the multi-protein complex at the IFNβ enhancer that controls gene expression. Further, we will inspect the regulatory mechanisms of these steps imposed by the host cell and present the manifold strategies viruses have evolved to intervene with IFNβ transcription downstream of IRF3 activation in order to secure establishment of a productive infection."
2579,Concentrated Bioshell Calcium Oxide (BiSCaO) Water Kills Pathogenic Microbes: Characterization and Activity,"Bioshell calcium oxide (BiSCaO) exhibits deodorizing properties and broad microbicidal activity. In this study, we examined possible utility of BiSCaO Water for that purpose. BiSCaO Water was prepared by adding 10 wt% BiSCaO to clean water and gently collecting the supernatant in a bottle. The same volume of clean water was gently poured onto the BiSCaO precipitate and the supernatant was gently collected in a bottle; this process was repeated fifty times. The produced BiSCaO Water contained nanoparticles (about 400–800 nm) composed of smaller nanoparticles (100–200 nm), and was colorless and transparent, with a pH > 12.7. In vitro assays demonstrated that BiSCaO Water eliminated more than 99.9% of influenza A (H1N1) and Feline calicivirus, Escherichia coli such as NBRC 3972 and O-157:H7, Pseudomonas aeruginosa, Salmonella, and Staphylococcus aureus within 15 min. We compared BiSCaO Water with the other microbicidal reagents such as ethanol, BiSCaO, BiSCa(OH)(2) suspensions, povidone iodine, NaClO, BiSCaO dispersion and colloidal dispersion with respect to deodorization activity and microbicidal efficacy. The results showed that BiSCaO Water was a potent reagent with excellent deodorization and disinfection activities against pathogenic bacteria and viruses (including both enveloped and nonenveloped viruses)."
2580,Distinct Molecular Mechanisms of Host Immune Response Modulation by Arenavirus NP and Z Proteins,"Endemic to West Africa and South America, mammalian arenaviruses can cross the species barrier from their natural rodent hosts to humans, resulting in illnesses ranging from mild flu-like syndromes to severe and fatal haemorrhagic zoonoses. The increased frequency of outbreaks and associated high fatality rates of the most prevalent arenavirus, Lassa, in West African countries, highlights the significant risk to public health and to the socio-economic development of affected countries. The devastating impact of these viruses is further exacerbated by the lack of approved vaccines and effective treatments. Differential immune responses to arenavirus infections that can lead to either clearance or rapid, widespread and uncontrolled viral dissemination are modulated by the arenavirus multifunctional proteins, NP and Z. These two proteins control the antiviral response to infection by targeting multiple cellular pathways; and thus, represent attractive targets for antiviral development to counteract infection. The interplay between the host immune responses and viral replication is a key determinant of virus pathogenicity and disease outcome. In this review, we examine the current understanding of host immune defenses against arenavirus infections and summarise the host protein interactions of NP and Z and the mechanisms that govern immune evasion strategies."
2581,Psychological distress among mountainous farmers in Vietnam: a cross-sectional study of prevalence and associated factors,"BACKGROUND: Psychological distress has been known as a major health problem among farmers across the world. In Vietnam, approximately 50% of farmers have lived in rural and mountainous areas. Yet, little has been known about how psychological distress impacts mountainous farmers’ health. OBJECTIVES: This study aimed to examine the prevalence and risk factors related to psychological distress among mountainous farmers in Vietnam. DESIGN AND SETTING: A cross-sectional study was performed from August to September 2018 in Moc Chau district, Vietnam. A structured questionnaire and face-to-face interviews were used for data collection. PARTICIPANTS: A random sample of 197 farmers aged at least 18 years, spoke Vietnamese, was not suffering from severe diseases and residing in Moc Chau at the time of the survey were recruited. PRIMARY AND SECONDARY OUTCOME MEASURES: The Kessler Psychological Distress Scale (K6) was employed to measure psychological distress. The tobit and logistic regressions were applied to indicate associated factors. RESULTS: The prevalence of psychological distress was 38.2% (95% CI 31.3% to 45.5%). Having a greater comorbidities (OR=6.17; 95% CI 1.44 to 26.43), drinking alcohol (OR=3.86; 95% CI 1.02 to 14.59) and obtaining health information from health workers (OR=3.77; 95% CI 1.22 to 11.66) were positively associated with the prevalence of psychological distress. By contrast, being overweight (OR=0.29; 95% CI 0.09 to 0.93), adopting books as the primary source of health information (OR=0.11; 95% CI 0.01 to 0.8), and receiving a higher number of home visits by community health workers (CHWs) (OR=0.38; 95% CI 0.14 to 0.99) were negatively associated with the prevalence of psychological distress. CONCLUSION: This study highlighted a high prevalence of psychological distress among mountainous farmers. Providing routine psychological and physical health screening, developing CHWs to provide clinical support and raising health awareness are critical implications for reducing psychological distress in this population."
2582,Branched chain aldehydes: production and breakdown pathways and relevance for flavour in foods,"Branched aldehydes, such as 2-methyl propanal and 2- and 3-methyl butanal, are important flavour compounds in many food products, both fermented and non-fermented (heat-treated) products. The production and degradation of these aldehydes from amino acids is described and reviewed extensively in literature. This paper reviews aspects influencing the formation of these aldehydes at the level of metabolic conversions, microbial and food composition. Special emphasis was on 3-methyl butanal and its presence in various food products. Knowledge gained about the generation pathways of these flavour compounds is essential for being able to control the formation of desired levels of these aldehydes."
2583,Cinacalcet and primary hyperparathyroidism: systematic review and meta regression,"PURPOSE: Primary hyperparathyroidism (PHPT) is a common condition affecting people of all ages and is mainly treated with parathyroidectomy. Cinacalcet has been widely used in secondary or tertiary hyperparathyroidism, but the use of cinacalcet in PHPT is less clear. METHODS: Searches were conducted in Medline and Embase for cinacalcet use in PHPT from induction to 10 April 2020. Articles and conferences abstracts describing the use of cinacalcet for PHPT in prospective or retrospective cohorts and randomized controlled trials restricted to English language only. We initially identified 1301 abstracts. Each article went extraction by two blinded authors on a structured proforma. Continuous outcomes were pooled with weight mean difference (WMD). Quality of included articles was assessed with Newcastle Ottwa Scale and Cochrane Risk of Bias 2.0. RESULTS: Twenty-eight articles were included. Normalization rate of serum Ca levels was reported at 90% (CI: 0.82 to 0.96). Serum levels of Ca and PTH levels were significantly reduced (Ca, WMD: 1.647, CI: −1.922 to −1.371; PTH, WMD: −31.218, CI: −41.671 to −20.765) and phosphate levels significantly increased (WMD: 0.498, CI: 0.400 to 0.596) after cinacalcet therapy. The higher the baseline Ca levels, the greater Ca reduction with cinacalcet treatment. Age and gender did not modify the effect of cinacalcet on serum Ca levels. CONCLUSION: The results from the meta-analysis support the use of cinacalcet as an alternative or bridging therapy to treat hypercalcemia in people with PHPT."
2584,Clinical Course of a Patient with Radiographically Described Acute Necrotizing Encephalopathy (ANE),
2585,"Lung Mechanics in COVID-19 Resemble Respiratory Distress Syndrome, Not Acute Respiratory Distress Syndrome: Could Surfactant Be a Treatment?",
2586,Morbidity and mortality of Hispanic trauma patients with diabetes mellitus,"PURPOSE: DM and trauma are leading causes of death in Hispanic patients, yet the interaction between them remains obscure. We aimed to assess the complications and in-hospital mortality rate of Hispanic diabetic trauma patients. METHODS: A retrospective cohort study was carried out using data from the Puerto Rico Trauma Hospital databank. Patients were matched based on gender, age, mechanism of injury, Glasgow Coma Scale, and Injury Severity Score using propensity-score matching. From 2000 to 2014, a total of 1134 patients with DM were compared to 1134 patients who did not have DM. The outcomes measured were hospital and TICU lengths of stay, days on mechanical ventilation, complications, and in-hospital mortality rate. A logistic regression model was carried out to evaluate the relationship of DM with complications and mortality after trauma. RESULTS: Hispanic patients with DM had longer hospital and TICU stays and required mechanical ventilation for extended periods. Complications, predominantly of an infectious nature, were more common among DM patients than they were among non-DM patients: 31.3% in the DM group vs. 11.6% in the non-DM group (OR 3.46; 95% CI 2.77–4.31). Despite an increase in the number of complications, DM was not associated with higher in-hospital mortality rates. CONCLUSIONS: DM is associated with a twofold increase in complications in Hispanic diabetic trauma patients, which may account for their longer hospital and TICU stays. This indicates that diabetic Hispanic trauma patients may need earlier and more aggressive intervention to reduce their risk of developing complications."
2587,Damage-associated molecular patterns in trauma,"In 1994, the “danger model” argued that adaptive immune responses are driven rather by molecules released upon tissue damage than by the recognition of “strange” molecules. Thus, an alternative to the “self versus non-self recognition model” has been provided. The model, which suggests that the immune system discriminates dangerous from safe molecules, has established the basis for the future designation of damage-associated molecular patterns (DAMPs), a term that was coined by Walter G. Land, Seong, and Matzinger. The pathological importance of DAMPs is barely somewhere else evident as in the posttraumatic or post-surgical inflammation and regeneration. Since DAMPs have been identified to trigger specific immune responses and inflammation, which is not necessarily detrimental but also regenerative, it still remains difficult to describe their “friend or foe” role in the posttraumatic immunogenicity and healing process. DAMPs can be used as biomarkers to indicate and/or to monitor a disease or injury severity, but they also may serve as clinically applicable parameters for optimized indication of the timing for, i.e., secondary surgeries. While experimental studies allow the detection of these biomarkers on different levels including cellular, tissue, and circulatory milieu, this is not always easily transferable to the human situation. Thus, in this review, we focus on the recent literature dealing with the pathophysiological importance of DAMPs after traumatic injury. Since dysregulated inflammation in traumatized patients always implies disturbed resolution of inflammation, so-called model of suppressing/inhibiting inducible DAMPs (SAMPs) will be very briefly introduced. Thus, an update on this topic in the field of trauma will be provided."
2588,Cyclin G2 inhibits epithelial-to-mesenchymal transition by disrupting Wnt/β-catenin signalling,
2589,Retraction: Carbon enters silica forming a cristobalite-type CO(2)–SiO(2) solid solution,
2590,Improved PCR method for the creation of saturation mutagenesis libraries in directed evolution: application to difficult-to-amplify templates,"Saturation mutagenesis constitutes a powerful method in the directed evolution of enzymes. Traditional protocols of whole plasmid amplification such as Stratagene’s QuikChange™ sometimes fail when the templates are difficult to amplify. In order to overcome such restrictions, we have devised a simple two-primer, two-stage polymerase chain reaction (PCR) method which constitutes an improvement over existing protocols. In the first stage of the PCR, both the mutagenic primer and the antiprimer that are not complementary anneal to the template. In the second stage, the amplified sequence is used as a megaprimer. Sites composed of one or more residues can be randomized in a single PCR reaction, irrespective of their location in the gene sequence.The method has been applied to several enzymes successfully, including P450-BM3 from Bacillus megaterium, the lipases from Pseudomonas aeruginosa and Candida antarctica and the epoxide hydrolase from Aspergillus niger. Here, we show that megaprimer size as well as the direction and design of the antiprimer are determining factors in the amplification of the plasmid. Comparison of the results with the performances of previous protocols reveals the efficiency of the improved method."
2591,Microbiological analysis of the population of extremely haloalkaliphilic sulfur-oxidizing bacteria dominating in lab-scale sulfide-removing bioreactors,"Thiopaq biotechnology for partial sulfide oxidation to elemental sulfur is an efficient way to remove H(2)S from biogases. However, its application for high-pressure natural gas desulfurization needs upgrading. Particularly, an increase in alkalinity of the scrubbing liquid is required. Therefore, the feasibility of sulfide oxidation into elemental sulfur under oxygen limitation was tested at extremely haloalkaline conditions in lab-scale bioreactors using mix sediments from hypersaline soda lakes as inoculum. The microbiological analysis, both culture dependent and independent, of the successfully operating bioreactors revealed a domination of obligately chemolithoautotrophic and extremely haloalkaliphilic sulfur-oxidizing bacteria belonging to the genus Thioalkalivibrio. Two subgroups were recognized among the isolates. The subgroup enriched from the reactors operating at pH 10 clustered with Thioalkalivibrio jannaschii–Thioalkalivibrio versutus core group of the genus Thioalkalivibrio. Another subgroup, obtained mostly with sulfide as substrate and at lower pH, belonged to the cluster of facultatively alkaliphilic Thioalkalivibrio halophilus. Overall, the results clearly indicate a large potential of the genus Thiolalkalivibrio to efficiently oxidize sulfide at extremely haloalkaline conditions, which makes it suitable for application in the natural gas desulfurization. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-008-1598-8) contains supplementary material, which is available to authorized users."
2592,Utilization of arylaliphatic nitriles by haloalkaliphilic Halomonas nitrilicus sp. nov. isolated from soda soils,"An enrichment culture from saline soda soils, using acetate as carbon and energy source and 2-phenylpropionitrile as nitrogen source (PPN) at pH 10, resulted in the isolation of strain ANL-αCH3. The strain was identified as a representative of the genus Halomonas in the Gammaproteobacteria. The bacterium was capable of PPN utilization as a nitrogen source only, while phenylacetonitrile (PAN) served both as carbon, energy and nitrogen source. This capacity was not described previously for any other haloalkaliphilic bacteria. Apart from the nitriles mentioned above, resting cells of ANL-αCH3 also hydrolyzed mandelonitrile, benzonitrile, acrylonitrile, and phenylglycinonitrile, presumably using nitrilase pathway. Neither nitrile hydratase nor amidase activity was detected. The isolate showed a capacity to grow with benzoate and salicylate as carbon and energy source and demonstrated the ability to completely mineralize PAN. These clearly indicated a potential to catabolize aromatic compounds. On the basis of unique phenotype and distinct phylogeny, strain ANL-αCH3 is proposed as a novel species of the genus Halomonas—Halomonas nitrilicus sp. nov. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-008-1685-x) contains supplementary material, which is available to authorized users."
2593,"Physiological and taxonomic description of the novel autotrophic, metal oxidizing bacterium, Pseudogulbenkiania sp. strain 2002","A lithoautotrophic, Fe(II) oxidizing, nitrate-reducing bacterium, strain 2002 (ATCC BAA-1479; =DSM 18807), was isolated as part of a study on nitrate-dependent Fe(II) oxidation in freshwater lake sediments. Here we provide an in-depth phenotypic and phylogenetic description of the isolate. Strain 2002 is a gram-negative, non-spore forming, motile, rod-shaped bacterium which tested positive for oxidase, catalase, and urease. Analysis of the complete 16S rRNA gene sequence placed strain 2002 in a clade within the family Neisseriaceae in the order Nessieriales of the Betaproteobacteria 99.3% similar to Pseudogulbenkiania subflava. Similar to P. sublfava, predominant whole cell fatty acids were identified as 16:17c, 42.4%, and 16:0, 34.1%. Whole cell difference spectra of the Fe(II) reduced minus nitrate oxidized cyctochrome content revealed a possible role of c-type cytochromes in nitrate-dependent Fe(II) oxidation. Strain 2002 was unable to oxidize aqueous or solid-phase Mn(II) with nitrate as the electron acceptor. In addition to lithotrophic growth with Fe(II), strain 2002 could alternatively grow heterotrophically with long-chain fatty acids, simple organic acids, carbohydrates, yeast extract, or casamino acids. Nitrate, nitrite, nitrous oxide, and oxygen also served as terminal electron acceptors with acetate as the electron donor."
2594,Inhibition of microbiological sulfide oxidation by methanethiol and dimethyl polysulfides at natron-alkaline conditions,"To avoid problems related to the discharge of sulfidic spent caustics, a biotechnological process is developed for the treatment of gases containing both hydrogen sulfide and methanethiol. The process operates at natron-alkaline conditions (>1 mol L(−1) of sodium- and potassium carbonates and a pH of 8.5–10) to enable the treatment of gases with a high partial CO(2) pressure. In the process, methanethiol reacts with biologically produced sulfur particles to form a complex mixture predominantly consisting of inorganic polysulfides, dimethyl disulfide (DMDS), and dimethyl trisulfide (DMTS). The effect of these organic sulfur compounds on the biological oxidation of sulfide to elemental sulfur was studied with natron-alkaliphilic bacteria belonging to the genus Thioalkalivibrio. Biological oxidation rates were reduced by 50% at 0.05 mM methanethiol, while for DMDS and DMTS, this was estimated to occur at 1.5 and 1.0 mM, respectively. The inhibiting effect of methanethiol on biological sulfide oxidation diminished due to its reaction with biologically produced sulfur particles. This reaction increases the feasibility of biotechnological treatment of gases containing both hydrogen sulfide and methanethiol at natron-alkaline conditions."
2595,Diversity of microbial communities in open mixed culture fermentations: impact of the pH and carbon source,"Anaerobic fermentation by an open mixed culture was investigated at different pH values (4–8.5) and with three substrates (glucose, glycerol and xylose). The populations established in each condition were assessed by denaturing gradient gel electrophoresis analysis of the 16S ribosomal RNA gene fragments. The fermentation pattern and the composition of the microbial population were also evaluated when operational variations were imposed (increase of substrate concentration or introduction of a second substrate). The experimental results demonstrated that at low and high pH values, a clearly different fermentation pattern was associated with the dominance of a specialised group of clostridiae. At intermediate pH values, the product spectrum was rather variable and seemed to be sensitive to variations in the microbial community. Different substrates resulted in the establishment of different microbial communities. When fed with a mixture of two substrates, mixotrophic microorganisms (capable of degrading both substrates) were found to overgrow the originally dominant specialists. Overall, the experiments have shown that some operational variables have a clear impact on the fermentation pattern and on the population established. However, a uniform relationship between the process characteristics (associated to a metabolic response) and the microbial population present is not always possible. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-008-1669-x) contains supplementary material, which is available to authorized users."
2596,Is a single direct MR arthrography series in ABER position as accurate in detecting anteroinferior labroligamentous lesions as conventional MR arthography?,"PURPOSE: The purpose of this study is to retrospectively compare accuracy of single magnetic resonance (MR) arthrography series in Abduction External Rotation (ABER) with conventional MR arthrography for detection and characterisation of anteroinferior labroligamentous lesions, with arthroscopy as reference standard. Inter-observer variability of both protocols was determined. METHODS AND MATERIALS: Institutional review board approval was obtained; informed consent was waived. MR arthrograms, including oblique axial fat suppressed T1-weighted images in ABER position and conventional imaging directions of 250 patients (170 men, 80 women; mean age, 36 years), were retrospectively and independently evaluated by three reviewers. Reviewers were blinded to clinical information and arthroscopic results. Labroligamentous lesions were registered in both ABER and MRa. The lesions were sub-classified (Bankart, Perthes, anterior labrum periosteal sleeve avulsion (ALPSA) or lesions not otherwise specified). Inter-observer agreement was assessed by Kappa statistics for all 250 patients. Ninety-two of 250 patients underwent arthroscopy. Sensitivity, specificity and accuracy of ABER versus conventional MR arthrography were calculated and compared using paired McNemar test. RESULTS: Kappa values of the ABER and conventional MR arthrography ranged from 0.44 to 0.56 and 0.44 to 0.62, respectively. According to arthroscopy, 45 of 92 patients had an intact anteroinferior labrum, and in 44 patients, a labroligamentous lesion (eight Bankart, seven Perthes, 29 ALPSA and three lesions not otherwise specified) was diagnosed. There were no statistically significant differences between ABER and conventional MR arthrography regarding sensitivity (85–89%, 89–96%), specificity (82–91%, 84–89%) and overall accuracy (50–62%, 53–63%). CONCLUSION: The results of a single MR arthrography series in ABER position are comparable with those of conventional MR arthrography for detecting anteroinferior labroligamentous lesions."
2597,Bioaugmentation of UASB reactors with immobilized Sulfurospirillum barnesii for simultaneous selenate and nitrate removal,"Whole-cell immobilization of selenate-respiring Sulfurospirillum barnesii in polyacrylamide gels was investigated to allow the treatment of selenate contaminated (790 µg Se × L(−1)) synthetic wastewater with a high molar excess of nitrate (1,500 times) and sulfate (200 times). Gel-immobilized S. barnesii cells were used to inoculate a mesophilic (30°C) bioreactor fed with lactate as electron donor at an organic loading rate of 5 g chemical oxygen demand (COD) × L(−1) day(−1). Selenate was reduced efficiently (>97%) in the nitrate and sulfate fed bioreactor, and a minimal effluent concentration of 39 µg Se × L(−1) was obtained. Scanning electron microscopy with energy dispersive X-ray (SEM–EDX) analysis revealed spherical bioprecipitates of ≤2 µm diameter mostly on the gel surface, consisting of selenium with a minor contribution of sulfur. To validate the bioaugmentation success under microbial competition, gel cubes with immobilized S. barnesii cells were added to an Upflow Anaerobic Sludge Bed (UASB) reactor, resulting in earlier selenate (24 hydraulic retention times (HRTs)) and sulfate (44 HRTs) removal and higher nitrate/nitrite removal efficiencies compared to a non-bioaugmented control reactor. S. barnesii was efficiently immobilized inside the UASB bioreactors as the selenate-reducing activity was maintained during long-term operation (58 days), and molecular analysis showed that S. barnesii was present in both the sludge bed and the effluent. This demonstrates that gel immobilization of specialized bacterial strains can supersede wash-out and out-competition of newly introduced strains in continuous bioaugmented systems. Eventually, proliferation of a selenium-respiring specialist occurred in the non-bioaugmented control reactor, resulting in simultaneous nitrate and selenate removal during a later phase of operation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-009-1915-x) contains supplementary material, which is available to authorized users."
2598,Xylose anaerobic conversion by open-mixed cultures,"Xylose is, after glucose, the dominant sugar in agricultural wastes. In anaerobic environments, carbohydrates are converted into volatile fatty acids and alcohols. These can be used as building blocks in biotechnological or chemical processes, e.g., to produce bioplastics. In this study, xylose fermentation by mixed microbial cultures was investigated and compared with glucose under the same conditions. The product spectrum obtained with both substrates was comparable. It was observed that, in the case of xylose, a higher fraction of the carbon was converted into catabolic products (butyrate, acetate, and ethanol) and the biomass yield was approximately 20% lower than on glucose, 0.16 versus 0.21 Cmol X/Cmol S. This lower yield is likely related to the need of an extra ATP during xylose uptake. When submitted to a pulse of glucose, the population cultivated on xylose could instantaneously convert the glucose. No substrate preference was observed when glucose and xylose were fed simultaneously to the continuously operated bioreactor."
2599,Phage Mu-driven two-plasmid system for integration of recombinant DNA in the Methylophilus methylotrophus genome,"A phage Mu-driven two-plasmid system for DNA integration in Escherichia coli genome has been adjusted for Methylophilus methylotrophus. Constructed helper plasmids with broad-host-range replicons carry thermo-inducible genes for transposition factors MuA and MuB. Integrative plasmids that are only replicated in E. coli could be mobilized to M. methylotrophus and contained mini-Mu unit with a short terminus of Mu DNA, Mu-attL/R. Mini-Mu unit was integrated in the M. methylotrophus genome via mobilization of the integrative plasmid to the cells carrying the helper in conditions of thermo-induced expression of MuA and MuB. In this system, mini-Mu unit was mainly integrated due to replicative transposition, and the integrated copy could be amplified in the M. methylotrophus chromosome in the presence of helper plasmid. A kan-gene flanked by FRT sites was inserted in one of the mini-Mu units, and it could be readily excised by yeast FLP recombinase that is encoded by the designed plasmid. The multiple Mu-driven gene insertion was carried out by integration of the Bacillus amyloliquefaciens α-amylase gene followed by curing the Km(R) marker before integration of the second mini-Mu unit with Pseudomonas putida xylE gene encoding catechol 2,3-dioxygenase (C23O)."
2600,Development of a quantitative PCR method to differentiate between viable and nonviable bacteria in environmental water samples,"Ethidium monoazide bromide (EMA) treatment of pure culture and environmental waters at low concentrations (1.0–7.5 µg/ml) indicated effective enumeration of viable and viable but nonculturable Escherichia coli in pure cultures, creek waters, and secondary activated sludge effluent samples by quantitative polymerase chain reaction (qPCR) amplification of the uidA and fliC gene targets at turbidity values <10 NTU. However, EMA treatment was not effective in primary clarifier and secondary trickling filter effluents where turbidities were ≥10 NTU. In viable pure cultures, rapidly dividing and senescent cells were most affected by increasing EMA concentrations. Amplification of heat-killed pure bacterial cultures decreased 4 to 6 logs depending on EMA concentration and culture age. The greatest difference was observed in 5-h cultures using 7.5 μg/ml EMA. Turbidity (≥100 NTU) in environmental samples inhibited EMA effectiveness on viability discrimination. Enumeration of E. coli in certain wastewaters using EMA-qPCR was similar to culture suggesting that EMA treatment could be incorporated into qPCR assays for the quantification of viable bacteria increasing assay time no more than 30 min. Our results indicate that EMA can be used in routine qPCR assays, but optimum conditions for exposure must be identified for each sample type due to sample matrix effects such as turbidity."
2601,Comparative metabolomic analysis of Sinorhizobium sp. C4 during the degradation of phenanthrene,"Comparative metabolic responses of Sinorhizobium sp. C4 were investigated. Comprehensive metabolites profiles, including polar metabolites, fatty acids, and polyhydroxyalkanoates were evaluated through untargeted metabolome analyses. Intracellular metabolomes during the degradation of phenanthrene were compared with those from natural carbon sources. Principal component analysis showed a clear separation of metabolomes of phenanthrene degradation from other carbon sources. Shift to more hydrophobic fatty acid was observed from the analysis of fatty acid methyl ester. Polyhydroxyalkanoate from strain C4 was composed mainly with 3-hydroxybutyric acid and small amount of 3-hydroxypentanoic acid, while the monomeric composition was independent on carbon sources. However, the amount of polyhydroxyalkanoates during degradation of phenanthrene was 50–210% less than those from other carbon sources. Among 207 gas chromatography–mass spectrometry peaks from the polar metabolite fraction, 60% of the peaks were identified and compared. Several intermediates in tricarboxylic acid cycles and glycolysis were increased during phenanthrene degradation. Accumulation of trehalose was also evident in the phenanthrene-treated bacterium. Some amino acid, including branched amino acids, glycine, homoserine, and valine, were also increased, while more than 70% of identified metabolites were decreased during the phenanthrene metabolism. Accumulation of sulfur amino acids and nicotinic acid suggested the possible oxidative stress conditions during phenanthrene metabolism."
2602,In situ removal and purification of biosurfactants by automated surface enrichment,"A new method is described to remove and separate biosurfactants from complex mixtures by compressing and harvesting the liquid surface layer. This method was applied to Bacillus subtilis cultures, in which the lipopeptide antibiotic fengycin as well as the polyketide antibiotic bacillaene were produced. The automated harvesting and collection in a custom-built glass body called ‘flounder’ was repeated several hundred times. The fengycin concentration in the fractions was found to be four times higher than in the culture centrifugate. Of the overall fengycin, 50% (w/w) were recovered after 300 cycles, 95% (w/w) after 800 harvesting cycles. A separation of fengycin from the less surface-active bacillaene could be achieved due to stronger surface activity of fengycin. The ratio of partition coefficients of fengycin and bacillaene was nine times higher compared to foam fractionation. A stepwise increase of the equilibrium surface tension in the centrifugate from 29 to 33 mN/m indicated a fractionated separation of different surface-active substances. The utilization of cell containing culture broth instead of centrifugate had only slight effects on separation efficiency. These results demonstrate the possibility to separate biosurfactants directly from cultivation without the use of extraction solvents or foam formation."
2603,A Rare Complication After Laparoscopic Gastric Banding: Connecting-Tube Penetration into the Hilus of the Kidney,"Laparoscopic adjustable gastric banding is a common operation for morbid obesity. Late complications mainly originate from either the injection port (dislocation, infection, leakage) or the gastric band (pouch dilatation, slippage, leakage, gastric erosion). Complications from the tube, connecting the port with the band, are rarely described. We report the penetration of a loose connecting tube into the kidney 8 months after removal of an infected injection port."
2604,An Improved Intragastric Balloon Procedure Using a New Balloon: Preliminary Analysis of Safety and Efficiency,"BACKGROUND: The authors developed a new intragastric balloon procedure with the objective of making it safer, faster, and less expensive than the established ones. The proposed procedure uses a new gastric balloon with technical improvements in the placement and removal procedures. METHODS: From June 2006 to July 2007, 52 patients were submitted to the new treatment with the Silimed Gastric Balloon (SGB), as part of a multidisciplinary program involving clinical, psychological, and behavioral approaches. RESULTS: The new placement and removal procedures of the SGB were effective and safe in all the cases. Due to simplicity and shortened duration of the procedures, all the patients left the outpatient clinic in less than 1 h after the placement or removal of the SGB. For the 14 patients who had completed the 6-month treatment, the initial mean weight, mean body mass index (BMI), and mean excess of weight (EW) were, respectively, 100.7 kg, 35.7 kg/m(2), and 30.0 kg. After the 6-month treatment, these values decreased significantly: 89.4 kg, 31.8 kg/m(2), and 19.6 kg. CONCLUSIONS: Preliminary data suggest that the procedure with the new balloon comes forth as a safe and effective alternative to the treatment of weight loss in patients with appropriate indication of use."
2605,Production of 2-methyl-1-butanol in engineered Escherichia coli,"Recent progress has been made in the production of higher alcohols by harnessing the power of natural amino acid biosynthetic pathways. Here, we describe the first strain of Escherichia coli developed to produce the higher alcohol and potential new biofuel 2-methyl-1-butanol (2MB). To accomplish this, we explored the biodiversity of enzymes catalyzing key parts of the isoleucine biosynthetic pathway, finding that AHAS II (ilvGM) from Salmonella typhimurium and threonine deaminase (ilvA) from Corynebacterium glutamicum improve 2MB production the most. Overexpression of the native threonine biosynthetic operon (thrABC) on plasmid without the native transcription regulation also improved 2MB production in E. coli. Finally, we knocked out competing pathways upstream of threonine production (ΔmetA, Δtdh) to increase its availability for further improvement of 2MB production. This work led to a strain of E. coli that produces 1.25 g/L 2MB in 24 h, a total alcohol content of 3 g/L, and with yields of up to 0.17 g 2MB/g glucose."
2606,MR-plastination-arthrography: a new technique used to study the distal tibiofibular syndesmosis,"PURPOSE: The purpose of this study was to describe a new technique called MR plastination arthrography to study both intra- and extra-articular anatomy. MATERIALS AND METHODS: In six human cadaveric lower legs MR arthrography was performed in either a one-step or two-step procedure. In the former a mixture of diluted Gadolinium and dyed polymer was injected. In the latter the dyed polymer was injected after arthrography wih diluted Gadolinium. Three-millimeter slices of these legs, obtained in a plane identical to that of the MR images, were plastinated according to the E12 technique of von Hagens. The plastination slices were subsequently compared with the MR images. RESULTS: The one-step procedure resulted in an inhomogeneous arthrogram. The two-step procedure resulted in a good correlation between the high-resolution MR images and plastination slices, as expressed by a good comparison of anatomic detail of the small syndesmotic recess. CONCLUSIONS: Images of the distal tibiofibular syndesmosis obtained with plastination arthrography correlated well with images acquired by MR arthrography when performed in a two-step procedure."
2607,Initiation and Maintenance of Weight Loss after Laparoscopic Adjustable Gastric Banding. The role of Outcome Expectation and Satisfaction with the Psychosocial Outcome,"BACKGROUND: A premise of this study was that different psychological processes would predict the initiation and maintenance of weight loss after surgery for morbid obesity. Our aim was to examine whether more favorable preoperative expectations of psychosocial outcomes predict weight loss in the first year after laparoscopic adjustable gastric banding (LAGB) and whether postoperative satisfaction with these outcomes predicts weight maintenance in the second year after the operation. METHODS: Six months before and 1 year after surgery, the “Obesity Psychosocial State Questionnaire” was filled out by 91 patients (77 female, 14 male, mean age 45 ± 9 years, mean preoperative body mass index 47 ± 6 kg/m(2)). We evaluated the preoperative outcome expectations and the postoperative satisfaction for the seven domains of psychosocial and physical functioning of this questionnaire, as well as the correlations between these scores and both weight loss and weight maintenance. RESULTS: Patients showed high satisfaction with psychosocial outcomes after LAGB in all seven domains (p < 0.001), even though the improvement was less than expected in five of the domains (p ≤ 0.01). While weight loss 1 year after the operation was related to satisfaction with psychosocial outcomes (p ≤ 0.05), preoperative expectations were not related to weight loss in the first year after surgery, and satisfaction with the outcomes was not related to weight maintenance in the second year after surgery. CONCLUSION: Our study suggests that surgically induced effects of weight loss and weight maintenance are achieved independently of the patient’s preoperative expectations of and postoperative satisfaction with the psychosocial outcomes."
2608,Ionic liquids in biotechnology: applications and perspectives for biotransformations,"Ionic liquids are considered as an alternative to organic solvents for catalysis. The literature in this field is reviewed with focus on advantageous use of ionic liquids in biocatalysis and biotransformations. The overview reveals that the exploration and mapping of ionic liquids with respect to biocatalysis is still sketchy. It is apparent that advantages can be gained in view of activity, stability and selectivity. Furthermore, integration of reaction and separation has a high potential in the field. The review presents quantitative data on the productivities, space–time yields, as well as stability as far as they can be extracted from the literature. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-008-1730-9) contains supplementary material, which is available to authorized users."
2609,A dormancy state in nonspore-forming bacteria,"While cultivation is a convenient way of proliferating and understanding bacteria, studies have shown the formation of nonculturable cells in nonspore-forming bacteria in response to environmental stress and thus in turn have generated immense interest. Whether these cells are in a state of dormancy or in a stage preceding cell death has been considered of paramount importance for the past couple of decades. In this study, osmotic-stress-induced dormant bacterial cells were separated by cell sorting and revived by osmotic down-shift in the absence of nutrients, source(s) that potentially could supply nutrients, and/or the external addition of resuscitation factor(s). Reversal of dormancy followed a definite pattern akin to population asynchrony of dormant cells, and the phenomenon was observed across three species, namely, Enterobacter sp. strain mcp11b, Klebsiella pneumonia strain mcp11d and Escherichia coli. In addition, our study precisely forecasted the presence of multiple subpopulations in dormant cells, which is explained by an emerging theory of survival mechanisms in stressful environments. These observations reveal that the state of dormancy induced by environmental stress in these nonspore-forming bacteria is “reversible” and also implies that it is an orderly and spontaneous adaptation to circumvent adverse conditions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-008-1712-y) contains supplementary material, which is available to authorized users."
2610,Molecular characterization of grapevine yellow speckle viroid-2 (GYSVd-2),"Grapevine yellow speckle viroid-2 (GYSVd-2) is a viroid found only in grapevines in China and Australia. Here, we report the molecular characterization of GYSVd-2 isolated from three grapevine varieties in China. A total of 90 cDNA clones were sequenced including 30 cDNA clones obtained from each of the Black Olympia, Zaoyu, and Thomson Seedless isolates. Sequencing analysis identified 20, 18, and 12 different sequence variants from the 3 isolates, respectively. Furthermore, each of the isolates included one predominant sequence variant. Compared to the Australian variant of GYSVd-2 (Accession number: NC_003612), the Black Olympia variant was identical and the Zaoyu variant contained one substitution. In contrast, the Thomson Seedless isolate significantly varied from the Australian variant with three substitutions, two insertions, and four deletions. In silico structure analysis predicted that the variations were clustered in the terminal left, the pathogenicity, and the variable region of the predicted secondary structure of GYSVd-2."
2611,Autophagy regulates fatty acid availability for oxidative phosphorylation through mitochondria-endoplasmic reticulum contact sites,"Autophagy has been associated with oncogenesis with one of its emerging key functions being its contribution to the metabolism of tumors. Therefore, deciphering the mechanisms of how autophagy supports tumor cell metabolism is essential. Here, we demonstrate that the inhibition of autophagy induces an accumulation of lipid droplets (LD) due to a decrease in fatty acid β-oxidation, that leads to a reduction of oxidative phosphorylation (OxPHOS) in acute myeloid leukemia (AML), but not in normal cells. Thus, the autophagic process participates in lipid catabolism that supports OxPHOS in AML cells. Interestingly, the inhibition of OxPHOS leads to LD accumulation with the concomitant inhibition of autophagy. Mechanistically, we show that the disruption of mitochondria–endoplasmic reticulum (ER) contact sites (MERCs) phenocopies OxPHOS inhibition. Altogether, our data establish that mitochondria, through the regulation of MERCs, controls autophagy that, in turn finely tunes lipid degradation to fuel OxPHOS supporting proliferation and growth in leukemia."
2612,Ground glass opacity on chest CT scans from screening to treatment: A literature review,"Lung cancer is the most common cause of cancer death in the world. However, recent studies have found that patients with pulmonary ground-glass opacity (GGO) have a better prognosis. Considering its low invasiveness, sublobar resection may be an appropriate treatment of choice. Low-dose computed tomography (CT) is recommended for the high-risk groups of lung cancer. Patients with nonsolid nodule are suggested to take annual low dose CT following-up. For part-solid or solid nodules, the solid component size less or more than 8 mm is the watershed of surgical treatment. Increasing tumor size is a hint of malignancy. Biopsy can be performed for clinically highly suspected malignant nodules. The endobronchial ultrasound biopsy, CT-guide biopsy, or surgical excision are the mainstream for the diagnosis of lung nodules. But for treatment, the sublobar resection is the mainstream of pulmonary GGO. A precise localization technique makes surgeons get enough resection margin and preserve more pulmonary function of the patients. The different localization technique is suitable for different kind nodular position. For patients with pure pulmonary GGO, annual low dose CT checkup is suitable. If the tumor size or solid part of the tumors increased gradually, adequate sublobar resection after tumor localization technique may provide good prognosis and preserve more pulmonary function of the patients."
2613,Compartment syndrome of the hand as a complication of prolonged mechanical cardiopulmonary resuscitation,"A 45‐year‐old man suffered compartment syndrome of the hands as a complication of prolonged cardiopulmonary resuscitation. He was admitted following a hypothermic out‐of‐hospital cardiac arrest due to cold‐water submersion. The patient was in cardiac arrest for 4 h with mechanical cardiopulmonary resuscitation delivered using the Lund University Cardiac Arrest System (Jolife AB, Lund, Sweden). Cardiopulmonary resuscitation along with aggressive rewarming achieved return of spontaneous circulation. He developed compartment syndrome in his left hand which was likely exacerbated by having his arm strapped to the Lund University Cardiac Arrest System device throughout the resuscitation. The compartment syndrome was managed conservatively. Despite preservation of neurological function the patient died of complications from the cardiac arrest after an extended intensive care unit stay. We recommend healthcare providers unstrap patient's hands during prolonged mechanical cardiopulmonary resuscitation."
2614,Education and Training to Build Capacity in Total Worker Health(®): Proposed Competencies for an Emerging Field,"OBJECTIVE: Establishment of core competencies for education and training of professionals entering the emerging field of Total Worker Health®. METHODS: Compilation and distillation of information obtained over a 5-year period from Total Worker Health symposia, workshops, and academic offerings, plus contributions from key stakeholders regarding education and training needs. RESULTS: A proposed set of Total Worker Health competencies aligns under six broad domains: Subject Matter Expertize; Advocacy and Engagement; Program Planning, Implementation and Evaluation; Communications and Dissemination; Leadership and Management; and Partnership Building and Coordination. CONCLUSIONS: Proposed set of core competencies will help standardize education and training for professionals being trained in Total Worker Health. It serves as an invitation for further input from stakeholders in academia, business, labor, and government."
2615,Microblog topic identification using Linked Open Data,"Much valuable information is embedded in social media posts (microposts) which are contributed by a great variety of persons about subjects that of interest to others. The automated utilization of this information is challenging due to the overwhelming quantity of posts and the distributed nature of the information related to subjects across several posts. Numerous approaches have been proposed to detect topics from collections of microposts, where the topics are represented by lists of terms such as words, phrases, or word embeddings. Such topics are used in tasks like classification and recommendations. The interpretation of topics is considered a separate task in such methods, albeit they are becoming increasingly human-interpretable. This work proposes an approach for identifying machine-interpretable topics of collective interest. We define topics as a set of related elements that are associated by having posted in the same contexts. To represent topics, we introduce an ontology specified according to the W3C recommended standards. The elements of the topics are identified via linking entities to resources published on Linked Open Data (LOD). Such representation enables processing topics to provide insights that go beyond what is explicitly expressed in the microposts. The feasibility of the proposed approach is examined by generating topics from more than one million tweets collected from Twitter during various events. The utility of these topics is demonstrated with a variety of topic-related tasks along with a comparison of the effort required to perform the same tasks with words-list-based representations. Manual evaluation of randomly selected 36 sets of topics yielded 81.0% and 93.3% for the precision and F1 scores respectively."
2616,Efficient cloning system for construction of gene silencing vectors in Aspergillus niger,"An approach based on Gateway recombination technology to efficiently construct silencing vectors was developed for use in the biotechnologically important fungus Aspergillus niger. The transcription activator of xylanolytic and cellulolytic genes XlnR of A. niger was chosen as target for gene silencing. Silencing was based on the expression vector pXLNRir that was constructed and used in co-transformation. From all the strains isolated (N = 77), nine showed poor xylan-degrading activities in two semi-quantitative plate assays testing different activities for xylan degradation. Upon induction on d-xylose, transcript levels of xlnR were decreased in the xlnR-silenced strains, compared to a wild-type background. Under these conditions, the transcript levels of xyrA and xynB (two genes regulated by XlnR) were also decreased for these xlnR-silenced strains. These results indicate that the newly developed system for rapid generation of silencing vectors is an effective tool for A. niger, and this can be used to generate strains with a tailored spectrum of enzyme activities or product formation by silencing specific genes encoding, e.g., regulators such as XlnR."
2617,"Caenorhabditis elegans nuclear RNAi factor SET-32 deposits the transgenerational histone modification, H3K23me3","Nuclear RNAi provides a highly tractable system to study RNA-mediated chromatin changes and epigenetic inheritance. Recent studies have indicated that the regulation and function of nuclear RNAi-mediated heterochromatin are highly complex. Our knowledge of histone modifications and the corresponding histonemodifying enzymes involved in the system remains limited. In this study, we show that the heterochromatin mark, H3K23me3, is induced by nuclear RNAi at both exogenous and endogenous targets in C. elegans. In addition, dsRNA-induced H3K23me3 can persist for multiple generations after the dsRNA exposure has stopped. We demonstrate that the histone methyltransferase SET-32, methylates H3K23 in vitro. Both set-32 and the germline nuclear RNAi Argonaute, hrde-1, are required for nuclear RNAi-induced H3K23me3 in vivo. Our data poise H3K23me3 as an additional chromatin modification in the nuclear RNAi pathway and provides the field with a new target for uncovering the role of heterochromatin in transgenerational epigenetic silencing."
2618,In Response,
2619,Airway Alert Bracelets: Enhancing Safety in the Coronavirus Disease 2019 Era,
2620,Scenario-Based Verification of Uncertain MDPs,"We consider Markov decision processes (MDPs) in which the transition probabilities and rewards belong to an uncertainty set parametrized by a collection of random variables. The probability distributions for these random parameters are unknown. The problem is to compute the probability to satisfy a temporal logic specification within any MDP that corresponds to a sample from these unknown distributions. In general, this problem is undecidable, and we resort to techniques from so-called scenario optimization. Based on a finite number of samples of the uncertain parameters, each of which induces an MDP, the proposed method estimates the probability of satisfying the specification by solving a finite-dimensional convex optimization problem. The number of samples required to obtain a high confidence on this estimate is independent from the number of states and the number of random parameters. Experiments on a large set of benchmarks show that a few thousand samples suffice to obtain high-quality confidence bounds with a high probability."
2621,Generation of ssDNA aptamers as diagnostic tool for Newcastle avian virus,"Aptamers are short single-stranded DNA (ssDNA), RNA or synthetic XNA molecules, which are used as a class of affinity binders recognizing target molecules with a very high affinity and specificity. The aim of this study was to generate and characterize ssDNA aptamers for the detection of Newcastle disease virus (NDV). These aptamers were selected using systematic evolution of ligands by exponential enrichment (SELEX) in combination with quantitative high-throughput DNA sequencing. After three rounds of selections, a highly enriched ssDNA pool was sequenced, and the results were analyzed using FASTAptamer Toolkit. Sequencing reads were sorted by copy numbers and clustered into groups, according to their sequence homology. Top aptameric sequences were used to develop a sandwich enzymatic linked aptamer assay (ELAA) for rapid and sensitive detection of NDV in farm samples. The selected aptamers have an affinity within the nanomolar range, and a high specificity with no cross-reactivity towards other avian viruses. Following optimization of the sandwich ELAA method, the results demonstrated that both selected aptamers Apt_NDV01 and Apt_NDV03 with dissociation constant values of 31 nM and 78.1 nM, respectively, showed the highest specificity and affinity for NDV detection. The ELAA results were verified by quantitative real-time PCR, demonstrating strong concordance, and showing outstanding accuracy for detection of NDV in field sample. In summary, combination of SELEX with high-throughput DNA sequencing allowed rapid screening and selection of aptamers. The selected aptamers allowed recognition of NDV with high affinities. This is the first report that uses a validated sandwich ELAA for rapid and specific detection of NDV in poultry samples."
2622,Time Series Analysis and Forecasting with Automated Machine Learning on a National ICD-10 Database,"The application of machine learning (ML) for use in generating insights and making predictions on new records continues to expand within the medical community. Despite this progress to date, the application of time series analysis has remained underexplored due to complexity of the underlying techniques. In this study, we have deployed a novel ML, called automated time series (AutoTS) machine learning, to automate data processing and the application of a multitude of models to assess which best forecasts future values. This rapid experimentation allows for and enables the selection of the most accurate model in order to perform time series predictions. By using the nation-wide ICD-10 (International Classification of Diseases, Tenth Revision) dataset of hospitalized patients of Romania, we have generated time series datasets over the period of 2008–2018 and performed highly accurate AutoTS predictions for the ten deadliest diseases. Forecast results for the years 2019 and 2020 were generated on a NUTS 2 (Nomenclature of Territorial Units for Statistics) regional level. This is the first study to our knowledge to perform time series forecasting of multiple diseases at a regional level using automated time series machine learning on a national ICD-10 dataset. The deployment of AutoTS technology can help decision makers in implementing targeted national health policies more efficiently."
2623,Oral Supplementation of the Vitamin D Metabolite 25(OH)D(3) Against Influenza Virus Infection in Mice,"Vitamin D is a fat-soluble vitamin that is metabolized by the liver into 25-hydroxyvitamin D [25(OH)D] and then by the kidney into 1,25-dihydroxyvitamin D [1,25(OH)(2)D], which activates the vitamin D receptor expressed in various cells, including immune cells, for an overall immunostimulatory effect. Here, to investigate whether oral supplementation of 25-hydroxyvitamin D(3) [25(OH)D(3)], a major form of vitamin D metabolite 25(OH)D, has a prophylactic effect on influenza A virus infection, mice were fed a diet containing a high dose of 25(OH)D(3) and were challenged with the influenza virus. In the lungs of 25(OH)D(3)-fed mice, the viral titers were significantly lower than in the lungs of standardly fed mice. Additionally, the proinflammatory cytokines IL-5 and IFN-γ were significantly downregulated after viral infection in 25(OH)D(3)-fed mice, while anti-inflammatory cytokines were not significantly upregulated. These results indicate that 25(OH)D(3) suppresses the production of inflammatory cytokines and reduces virus replication and clinical manifestations of influenza virus infection in a mouse model."
2624,The Hidden Curriculum and Integrating Cure- and Care-Based Approaches to Medicine,"Although current literature about the “cure versus care” issue tends to promote a patient-centered approach, the disease-centered approach remains the prevailing model in practice. The perceived dichotomy between the two approaches has created a barrier that could make it difficult for medical students and physicians to integrate psychosocial aspects of patient care into the prevailing disease-based model. This article examines the influence of the formal and hidden curricula on the perception of these two approaches and finds that the hidden curriculum perpetuates the notion that “cure” and “care” based approaches are dichotomous despite significant changes in formal curricula that promote a more integrated approach. The authors argue that it is detrimental for clinicians to view the two approaches as oppositional rather than complementary and attempt to give recommendations on how the influence of the hidden curriculum can be reduced to get a both-cure-and-care-approach, rather than an either-cure-or-care-approach."
2625,Identifying disease trajectories with predicate information from a knowledge graph,"BACKGROUND: Knowledge graphs can represent the contents of biomedical literature and databases as subject-predicate-object triples, thereby enabling comprehensive analyses that identify e.g. relationships between diseases. Some diseases are often diagnosed in patients in specific temporal sequences, which are referred to as disease trajectories. Here, we determine whether a sequence of two diseases forms a trajectory by leveraging the predicate information from paths between (disease) proteins in a knowledge graph. Furthermore, we determine the added value of directional information of predicates for this task. To do so, we create four feature sets, based on two methods for representing indirect paths, and both with and without directional information of predicates (i.e., which protein is considered subject and which object). The added value of the directional information of predicates is quantified by comparing the classification performance of the feature sets that include or exclude it. RESULTS: Our method achieved a maximum area under the ROC curve of 89.8% and 74.5% when evaluated with two different reference sets. Use of directional information of predicates significantly improved performance by 6.5 and 2.0 percentage points respectively. CONCLUSIONS: Our work demonstrates that predicates between proteins can be used to identify disease trajectories. Using the directional information of predicates significantly improved performance over not using this information."
2626,Physiological effects of two driving pressure-based methods to set positive end-expiratory pressure during one lung ventilation,"During one-lung ventilation (OLV), titrating the positive end-expiratory pressure (PEEP) to target a low driving pressure (∆P) could reduce postoperative pulmonary complications. However, it is unclear how to conduct PEEP titration: by stepwise increase starting from zero PEEP (PEEP(INCREMENTAL)) or by stepwise decrease after a lung recruiting manoeuvre (PEEP(DECREMENTAL)). In this randomized trial, we compared the physiological effects of these two PEEP titration strategies on respiratory mechanics, ventilation/perfusion mismatch and gas exchange. Patients undergoing video-assisted thoracoscopic surgery in OLV were randomly assigned to a PEEP(INCREMENTAL) or PEEP(DECREMENTAL) strategy to match the lowest ∆P. In the PEEP(INCREMENTAL) group, PEEP was stepwise titrated from ZEEP up to 16 cm H(2)O, whereas in the PEEP(DECREMENTAL) group PEEP was decrementally titrated, starting from 16 cm H(2)O, immediately after a lung recruiting manoeuvre. Respiratory mechanics, ventilation/perfusion mismatch and blood gas analyses were recorded at baseline, after PEEP titration and at the end of surgery. Sixty patients were included in the study. After PEEP titration, shunt decreased similarly in both groups, from 50 [39–55]% to 35 [28–42]% in the PEEP(INCREMENTAL) and from 45 [37–58]% to 33 [25–45]% in the PEEP(DECREMENTAL) group (both p < 0.001 vs baseline). The resulting ∆P, however, was lower in the PEEP(DECREMENTAL) than in the PEEP(INCREMENTAL) group (8 [7–11] vs 10 [9–11] cm H(2)O; p = 0.03). In the PEEP(DECREMENTAL) group the PaO(2)/ FIO(2) ratio increased significantly after intervention (from 140 [99–176] to 186 [152–243], p < 0.001). Both the PEEP(INCREMENTAL) and the PEEP(DECREMENTAL) strategies were able to decrease intraoperative shunt, but only PEEP(DECREMENTAL) improved oxygenation and lowered intraoperative ΔP. Clinical trial number NCT03635281; August 2018; “retrospectively registered” ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-020-00582-z) contains supplementary material, which is available to authorized users."
2627,Incidence and outcomes of acute respiratory distress syndrome in intensive care units of mainland China: a multicentre prospective longitudinal study,"OBJECTIVES: To evaluate the incidence and mortality of acute respiratory distress syndrome (ARDS) in medical/respiratory intensive care units (MICUs/RICUs) to assess ventilation management and the use of adjunct therapy in routine clinical practice for patients fulfilling the Berlin definition of ARDS in mainland China. METHODS: This was a multicentre prospective longitudinal study. Patients who met the Berlin definition of ARDS were included. Baseline data and data on ventilator management and the use of adjunct therapy were collected. RESULTS: Of the 18,793 patients admitted to participating ICUs during the study timeframe, 672 patients fulfilled the Berlin ARDS criteria and 527 patients were included in the analysis. The most common predisposing factor for ARDS in 402 (77.0) patients was pneumonia. The prevalence rates were 9.7% (51/527) for mild ARDS, 47.4% (250/527) for moderate ARDS, and 42.9% (226/527) for severe ARDS. In total, 400 (75.9%) patients were managed with invasive mechanical ventilation during their ICU stays. All ARDS patients received a tidal volume of 6.8 (5.8–7.9) mL/kg of their predicted body weight and a positive end-expository pressure (PEEP) of 8 (6–12) cmH(2)O. Recruitment manoeuvres (RMs) and prone positioning were used in 61 (15.3%) and 85 (16.1%) ventilated patients, respectively. Life-sustaining care was withdrawn from 92 (17.5%) patients. When these patients were included in the mortality analysis, 244 (46.3%) ARDS patients (16 (31.4%) with mild ARDS, 101 (40.4%) with moderate ARDS, and 127 (56.2%) with severe ARDS) died in the hospital. CONCLUSIONS: Among the 18 ICUs in mainland China, the incidence of ARDS was low. The rates of mortality and withdrawal of life-sustaining care were high. The recommended lung protective strategy was followed with a high degree of compliance, but the implementation of adjunct treatment was lacking. These findings indicate the potential for improvement in the management of patients with ARDS in China. TRIAL REGISTRATION: Clinicaltrials.gov NCT02975908. Registered on 29 November 2016—retrospectively registered."
2628,Chemical Tools in Biological Discovery,
2629,Speaking with Frankenstein,"This collaborative essay experimentally applies the insights of Mary Shelley's 1818 gothic fantasy Frankenstein to clinical interactions between present-day physicians and the patients they, akin to Shelley's human protagonist, so often seem to bring (back) to life. Because that process is frequently fraught with unspoken elements of ambivalence, disappointment, frustration, and failure, we find in Shelley's speculative fiction less a cautionary tale of overreach than a dynamic parable of the role that the unspoken, the invisible, and the unknown might play in contemporary physician/patient relationships. Playing with that parable, we consider its relevance to four often unacknowledged dynamics that shape physician/patient interaction: commitment to a false binary of life and death; the tyranny of normative aesthetics; shared negative affect; and the ethics of care and care-denial. To ""speak with Frankenstein"" is, we show, to make space for the otherwise unspeakable. The result is a more complete model of narrative medicine that accommodates to its ideal of open communication and full attention the persistence of what cannot be said, seen, or known--only imagined and approximated."
2630,Modified mRNA as a Therapeutic Tool for the Heart,"Despite various clinical modalities available for patients, heart disease remains among the leading causes of mortality and morbidity worldwide. Genetic medicine, particularly mRNA, has broad potential as a therapeutic. More specifically, mRNA-based protein delivery has been used in the fields of cancer and vaccination, but recent changes to the structural composition of mRNA have led the scientific community to swiftly embrace it as a new drug to deliver missing genes to injured myocardium and many other organs. Modified mRNA (modRNA)–based gene delivery features transient but potent protein translation and low immunogenicity, with minimal risk of insertional mutagenesis. In this review, we compared and listed the advantages of modRNA over traditional vectors for cardiac therapy, with particular focus on using modRNA therapy in cardiac repair. We present a comprehensive overview of modRNA’s role in cardiomyocyte (CM) proliferation, cardiac vascularization, and prevention of cardiac apoptosis. We also emphasize recent advances in modRNA delivery strategies and discuss the challenges for its clinical translation."
2631,Hand hygiene improvement or antibiotic restriction to control the household transmission of extended-spectrum β-lactamase-producing Escherichia coli: a mathematical modelling study,"BACKGROUND: The best strategy to control ESBL-producing Escherichia coli (ESBL-EC) spread in the community is lacking. METHODS: We developed an individual-based transmission model to evaluate the impact of hand hygiene (HH) improvement and reduction in antibiotic use on the within-household transmission of ESBL-EC. We used data from the literature and incorporated key elements of ESBL-EC transmission such as the frequency and nature of contacts among household members, antibiotic use in the community and hand hygiene behaviour. We introduced in a household a single ESBL-EC colonised person and simulated the transmission dynamics of ESBL-EC over a one-year time horizon. RESULTS: The probability of ESBL-EC transmission depended on the household composition and the profile of the initial carrier. In the two-person household, the probability of ESBL-EC transmission was 5.3% (95% CI 5.0–5.6) or 6.6% (6.3–6.9) when the index person was a woman or a man, respectively. In a four-person household, the probability of transmission varied from 61.4% (60.9–62.0) to 68.8% (68.3–69.3) and was the highest when the index patient was the baby. Improving HH by 50% reduced the probability of transmission by 33–62%. Antibiotic restriction by 50% reduced the transmission by 2–6%. CONCLUSIONS: The transmission of ESBL-EC is frequent in households and especially those with a baby. Antibiotic reduction had little impact on ESBL-EC. Improvement of hygiene in the community could help prevent transmission of ESBL-EC."
2632,Retained bullet in the cervical spinal canal and the associated surgical management conundrum: case report and review of the literature,"INTRODUCTION: Gunshot wounds (GSW) to the cervical spine remain uncommon. Surgery often does not yield significant neurological improvement and the decision to utilize surgery depends on a number of factors. We describe the case of a 28 year-old male suffering a complete spinal cord injury (SCI) secondary to a bullet lodged in the cervical spinal canal. We present the unique radiological findings and review the indications for and utility of spine surgery for cervical GSW. CASE PRESENTATION: The patient was a 28 year-old male involved in a motor vehicle accident immediately after sustaining a gunshot wound to the cervical spine. Neurologic exam revealed a complete SCI at the C4 level. CT scan revealed a retained bullet in the spinal canal at the C4/5 level without vascular injury or unstable vertebral fracture. He was managed nonoperatively, however, he remained ventilator dependent and ultimately expired secondary to cardiac arrest from a suspected pulmonary embolism. DISCUSSION: We present a case of complete SCI secondary to a retained bullet in the cervical spine. These cases can be managed both operatively and nonoperatively. Given the high risk of morbidity and overall poor neurological recovery after surgical intervention for SCI secondary to GSW, physicians must understand the appropriate indications for surgical intervention. These indications include, but are not limited to, progressive neurological deficit, cerebrospinal fluid leak, spinal instability, and acute lead toxicity."
2633,Unlocking the secrets of the genome,"Despite the successes of genomics, little is known about how genetic information produces complex organisms. A look at the crucial functional elements of fly and worm genomes could change that. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/459927a) contains supplementary material, which is available to authorized users."
2634,Expanded encyclopaedias of DNA elements in the human and mouse genomes,"The human and mouse genomes contain instructions that specify RNAs and proteins and govern the timing, magnitude, and cellular context of their production. To better delineate these elements, phase III of the Encyclopedia of DNA Elements (ENCODE) Project has expanded analysis of the cell and tissue repertoires of RNA transcription, chromatin structure and modification, DNA methylation, chromatin looping, and occupancy by transcription factors and RNA-binding proteins. Here we summarize these efforts, which have produced 5,992 new experimental datasets, including systematic determinations across mouse fetal development. All data are available through the ENCODE data portal (https://www.encodeproject.org), including phase II ENCODE(1) and Roadmap Epigenomics(2) data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes."
2635,Response to Trevisson et al.,
2636,Branching out,"The chimp was a great start. But the genomes of our other primate relatives will help to reveal a whole lot more, says Carina Dennis."
2637,De novo mutations in autosomal recessive congenital malformations,
2638,"Developing Effective Methods for Electronic Health Personalization: Protocol for Health Telescope, a Prospective Interventional Study","BACKGROUND: Existing evaluations of the effects of mobile apps to encourage physical activity have been criticized owing to their common lack of external validity, their short duration, and their inability to explain the drivers of the observed effects. This protocol describes the setup of Health Telescope, a longitudinal panel study in which the long-term effects of mobile electronic health (eHealth) apps are investigated. By setting up Health Telescope, we aim to (1) understand more about the long-term use of eHealth apps in an externally valid setting, (2) understand the relationships between short-term and long-term outcomes of the usage of eHealth apps, and (3) test different ways in which eHealth app allocation can be personalized. OBJECTIVE: The objectives of this paper are to (1) demonstrate and motivate the validity of the many choices that we made in setting up an intensive longitudinal study, (2) provide a resource for researchers interested in using data generated by our study, and (3) act as a guideline for researchers interested in setting up their own longitudinal data collection using wearable devices. For the third objective, we explicitly discuss the General Data Protection Regulation and ethical requirements that need to be addressed. METHODS: In this 4-month study, a group of approximately 450 participants will have their daily step count measured and will be asked daily about their mood using experience sampling. Once per month, participants will receive an intervention containing a recommendation to download an app that focuses on increasing physical activity. The mechanism for assigning recommendations to participants will be personalized over time, using contextual data obtained from previous interventions. RESULTS: The data collection software has been developed, and all the legal and ethical checks are in place. Recruitment will start in Q4 of 2020. The initial results will be published in 2021. CONCLUSIONS: The aim of Health Telescope is to investigate how different individuals respond to different ways of being encouraged to increase their physical activity. In this paper, we detail the setup, methods, and analysis plan that will enable us to reach this aim. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/16471"
2639,The civil registration system is a potentially viable data source for reliable subnational mortality measurement in India,"INTRODUCTION: The Indian national Civil Registration System (CRS) is the optimal data source for subnational mortality measurement, but is yet under development. As an alternative, data from the Sample Registration System (SRS), which covers less than 1% of the national population, is used. This article presents a comparison of mortality measures from the SRS and CRS in 2017, and explores the potential of the CRS to meet these subnational data needs. METHODS: Data on population and deaths by age and sex for 2017 from each source were used to compute national-level and state-level life tables. Sex-specific ratios of death probabilities in five age categories (0–4, 5–14, 15–29, 30–69, 70–84) were used to evaluate CRS data completeness using SRS probabilities as reference values. The quality of medically certified causes of death was assessed through hospital reporting coverage and proportions of deaths registered with ill-defined causes from each state. RESULTS: The CRS operates through an extensive infrastructure with high reporting coverage, but child deaths are uniformly under-reported, as are female deaths in many states. However, at ages 30–69 years, CRS death probabilities are higher than the SRS values in 15 states for males and 10 states for females. SRS death probabilities are of limited precision for measuring mortality trends and differentials. Data on medically certified causes of death are of limited use due to low hospital reporting coverage. CONCLUSIONS: The Indian CRS is more reliable than the SRS for measuring adult mortality in several states. Targeted initiatives to improve the recording of child and female deaths, to strengthen the reporting and quality of medically certified causes of death, and to promote use of verbal autopsy methods can establish the CRS as a reliable source of subnational mortality statistics in the near future."
2640,Hazara Nairovirus Requires COPI Components in both Arf1-Dependent and Arf1-Independent Stages of Its Replication Cycle,"Hazara nairovirus (HAZV) is an enveloped trisegmented negative-strand RNA virus classified within the Nairoviridae family of the Bunyavirales order and a member of the same subtype as Crimean-Congo hemorrhagic fever virus, responsible for fatal human disease. Nairoviral subversion of cellular trafficking pathways to permit viral entry, gene expression, assembly, and egress is poorly understood. Here, we generated a recombinant HAZV expressing enhanced green fluorescent protein and used live-cell fluorescent imaging to screen an siRNA library targeting genes involved in cellular trafficking networks, the first such screen for a nairovirus. The screen revealed prominent roles for subunits of the coat protein 1 (COPI)-vesicle coatomer, which regulates retrograde trafficking of cargo between the Golgi apparatus and the endoplasmic reticulum, as well as intra-Golgi transport. We show the requirement of COPI-coatomer subunits impacted at least two stages of the HAZV replication cycle: an early stage prior to and including gene expression and also a later stage during assembly and egress of infectious virus, with COPI-knockdown reducing titers by approximately 1,000-fold. Treatment of HAZV-infected cells with brefeldin A (BFA), an inhibitor of Arf1 activation required for COPI coatomer formation, revealed that this late COPI-dependent stage was Arf1 dependent, consistent with the established role of Arf1 in COPI vesicle formation. In contrast, the early COPI-dependent stage was Arf1 independent, with neither BFA treatment nor siRNA-mediated ARF1 knockdown affecting HAZV gene expression. HAZV exploitation of COPI components in a noncanonical Arf1-independent process suggests that COPI coatomer components may perform roles unrelated to vesicle formation, adding further complexity to our understanding of cargo-mediated transport. IMPORTANCE Nairoviruses are tick-borne enveloped RNA viruses that include several pathogens responsible for fatal disease in humans and animals. Here, we analyzed host genes involved in trafficking networks to examine their involvement in nairovirus replication. We revealed important roles for genes that express multiple components of the COPI complex, which regulates transport of Golgi apparatus-resident cargos. COPI components influenced at least two stages of the nairovirus replication cycle: an early stage prior to and including gene expression and also a later stage during assembly of infectious virus, with COPI knockdown reducing titers by approximately 1,000-fold. Importantly, while the late stage was Arf1 dependent, as expected for canonical COPI vesicle formation, the early stage was found to be Arf1 independent, suggestive of a previously unreported function of COPI unrelated to vesicle formation. Collectively, these data improve our understanding of nairovirus host-pathogen interactions and suggest a new Arf1-independent role for components of the COPI coatomer complex."
2641,Hematopoietic Stem Cell Transplantation in Neuromyelitis Optica-Spectrum Disorders (NMO-SD): State-of-the-Art and Future Perspectives,"Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune inflammatory disorders of the central nervous system (CNS). Understanding of the molecular basis of these diseases in the last decades has led to an important improvement in the treatment of this disease, in particular, to the use of immunotherapeutic approaches, such as monoclonal antibodies and Hematopoietic Stem Cell Transplantation (HSCT). The aim of this review is to summarize the pathogenesis, biological basis and new treatment options of these disorders, with a particular focus on HSCT applications. Different HSCT strategies are being explored in NMOSD, both autologous and allogeneic HSCT, with the new emergence of therapeutic effects such as an induction of tolerance to auto-antigens and graft versus autoimmunity effects that can be exploited to hopefully treat a disease that still has prognosis."
2642,TRPM8 Channel Activation Reduces the Spontaneous Contractions in Human Distal Colon,"The transient receptor potential-melastatin 8 (TRPM8) is a non-selective Ca(2+)-permeable channel, activated by cold, membrane depolarization, and different cooling compounds. TRPM8 expression has been found in gut mucosal, submucosal, and muscular nerve endings. Although TRPM8 plays a role in pathological conditions, being involved in visceral pain and inflammation, the physiological functions in the digestive system remain unclear as yet. The aims of the present study were: (i) to verify the TRPM8 expression in human distal colon; (ii) to examine the effects of TRPM8 activation on colonic contractility; (iii) to characterize the mechanism of action. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting were used to analyze TRPM8 expression. The responses of human colon circular strips to different TRPM8 agonists [1-[Dialkyl-phosphinoyl]-alkane (DAPA) 2–5, 1-[Diisopropyl-phosphinoyl]-alkane (DIPA) 1–7, DIPA 1–8, DIPA 1–9, DIPA 1–10, and DIPA 1–12) were recorded using a vertical organ bath. The biomolecular analysis revealed gene and protein expression of TRPM8 in both mucosal and smooth muscle layers. All the agonists tested, except-DIPA 1–12, produced a concentration-dependent decrease in spontaneous contraction amplitude. The effect was significantly antagonized by 5-benzyloxytryptamine, a TRPM8 antagonist. The DIPA 1–8 agonist resulted in the most efficacious and potent activation among the tested molecules. The DIPA 1–8 effects were not affected by tetrodotoxin, a neural blocker, but they were significantly reduced by tetraethylammonium chloride, a non-selective blocker of K(+) channels. Moreover, iberiotoxin, a blocker of the large-conductance Ca(2+)-dependent K(+)-channels, but not apamin, a blocker of small-conductance Ca(2+)-dependent K(+) channels, significantly reduced the inhibitory DIPA 1–8 actions. The results of the present study demonstrated that TRPM8 receptors are also expressed in human distal colon in healthy conditions and that ligand-dependent TRPM8 activation is able to reduce the colonic spontaneous motility, probably by the opening of the large-conductance Ca(2+)-dependent K(+)-channels."
2643,Anti-Angiogenic and Anti-Proliferative Graphene Oxide Nanosheets for Tumor Cell Therapy,"Graphene oxide (GO) is a bidimensional novel material that exhibits high biocompatibility and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS). In this work, we set up an experimental methodology for the fabrication of GO@peptide hybrids by the immobilization, via irreversible physical adsorption, of the Ac-(GHHPH)(4)-NH(2) peptide sequence, known to mimic the anti-angiogenic domain of the histidine-proline-rich glycoprotein (HPRG). The anti-proliferative capability of the graphene-peptide hybrids were tested in vitro by viability assays on prostate cancer cells (PC-3 line), human neuroblastoma (SH-SY5Y), and human retinal endothelial cells (primary HREC). The anti-angiogenic response of the two cellular models of angiogenesis, namely endothelial and prostate cancer cells, was scrutinized by prostaglandin E2 (PGE(2)) release and wound scratch assays, to correlate the activation of inflammatory response upon the cell treatments with the GO@peptide nanocomposites to the cell migration processes. Results showed that the GO@peptide nanoassemblies not only effectively induced toxicity in the prostate cancer cells, but also strongly blocked the cell migration and inhibited the prostaglandin-mediated inflammatory process both in PC-3 and in HRECs. Moreover, the cytotoxic mechanism and the internalization efficiency of the theranostic nanoplatforms, investigated by mitochondrial ROS production analyses and confocal microscopy imaging, unraveled a dose-dependent manifold mechanism of action performed by the hybrid nanoassemblies against the PC-3 cells, with the detection of the GO-characteristic cell wrapping and mitochondrial perturbation. The obtained results pointed out to the very promising potential of the synthetized graphene-based hybrids for cancer therapy."
2644,The Feasibility of Host Transcriptome Profiling as a Diagnostic Tool for Microbial Etiology in Childhood Cancer Patients with Febrile Neutropenia,"Infection is a common and serious complication of cancer treatment in children that often presents as febrile neutropenia (FN). Gene-expression profiling techniques can reveal transcriptional signatures that discriminate between viral, bacterial and asymptomatic infections in otherwise healthy children. Here, we examined whether gene-expression profiling was feasible in children with FN who were undergoing cancer treatment. The blood transcriptome of the children (n = 63) was investigated at time of FN diagnosed as viral, bacterial, co-infection or unknown etiology, respectively, and compared to control samples derived from 12 of the patients following the FN episode. RNA sequencing was successful in 43 (68%) of the FN episodes. Only two genes were significantly differentially expressed in the bacterial versus the control group. Significantly up-regulated genes in patients with the other three etiologies versus the control group were enriched with cellular processes related to proliferation and cellular stress response, with no clear enrichment with innate responses to pathogens. Among the significantly down-regulated genes, a few clustered into pathways connected to responses to infection. In the present study of children during cancer treatment, the blood transcriptome was not suitable for determining the etiology of FN because of too few circulating immune cells for reliable gene expression analysis."
2645,Cold Press Pomegranate Seed Oil Attenuates Dietary-Obesity Induced Hepatic Steatosis and Fibrosis through Antioxidant and Mitochondrial Pathways in Obese Mice,"Aim: Obesity is associated with metabolic syndrome, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. In this study, we investigated whether the dietary supplementation of pomegranate seed oil (PSO) exerted a protective effect on liver lipid uptake, fibrosis, and mitochondrial function in a mouse model of obesity and insulin resistance. Method: In this in vivo study, eight-week-old C57BL/6J male mice were fed with a high fat diet (HFD) for 24 weeks and then were divided into three groups as follows: group (1) Lean; group (n = 6) (2) HF diet; group (n = 6) (3) HF diet treated with PSO (40 mL/kg food) (n = 6) for eight additional weeks starting at 24 weeks. Physiological parameters, lipid droplet accumulation, inflammatory biomarkers, antioxidant biomarkers, mitochondrial biogenesis, insulin sensitivity, and hepatic fibrosis were determined to examine whether PSO intervention prevents obesity-associated metabolic syndrome. Results: The PSO group displayed an increase in oxygen consumption, as well as a decrease in fasting glucose and blood pressure (p < 0.05) when compared to the HFD-fed mice group. PSO increased both the activity and expression of hepatic HO-1, downregulated inflammatory adipokines, and decreased hepatic fibrosis. PSO increased the levels of thermogenic genes, mitochondrial signaling, and lipid metabolism through increases in Mfn2, OPA-1, PRDM 16, and PGC1α. Furthermore, PSO upregulated obesity-mediated hepatic insulin receptor phosphorylation Tyr-(972), p-IRB tyr(1146), and pAMPK, thereby decreasing insulin resistance. Conclusions: These results indicated that PSO decreased obesity-mediated insulin resistance and the progression of hepatic fibrosis through an improved liver signaling, as manifested by increased insulin receptor phosphorylation and thermogenic genes. Furthermore, our findings indicate a potential therapeutic role for PSO in the prevention of obesity-associated NAFLD, NASH, and other metabolic disorders."
2646,Effect of Graphene Family Materials on Multiple Myeloma and Non-Hodgkin’s Lymphoma Cell Lines,"The interest around the graphene family of materials is constantly growing due to their potential application in biomedical fields. The effect of graphene and its derivatives on cells varies amongst studies depending on the cell and tissue type. Since the toxicity against non-adherent cell lines has barely been studied, we investigated the effect of graphene and two different graphene oxides against four multiple myeloma cell lines, namely KMS-12-BM, H929, U226, and MM.1S, as well as two non-Hodgkin lymphoma cells lines, namely KARPAS299 and DOHH-2. We performed two types of viability assays, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide conversion) and ATP (adenosine triphosphate detection), flow cytometry analysis of apoptosis induction and cell cycle, cell morphology, and direct interaction analysis using two approaches—visualization of living cells by two different systems, and visualization of fixed and dyed cells. Our results revealed that graphene and graphene oxides exhibit low to moderate cytotoxicity against cells, despite visible interaction between the cells and graphene oxide. This creates possibilities for the application of the selected graphene materials for drug delivery systems or theragnostics in hematological malignancies; however, further detailed studies are necessary to explain the nature of interactions between the cells and the materials."
2647,Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in Escherichia coli,"Every cell must produce enough membrane to contain itself. However, the mechanisms by which the rate of membrane synthesis is coupled with the rate of cell growth remain unresolved. By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. Due to feedback regulation of the fatty acid pathway, PlsB activity also indirectly controls synthesis of lipopolysaccharide, a major component of the outer membrane synthesized from a fatty acid synthesis intermediate. Surprisingly, concentrations of the enzyme that catalyzes the committed step of lipopolysaccharide synthesis (LpxC) do not differ across steady-state growth conditions, suggesting that steady-state lipopolysaccharide synthesis is modulated primarily via indirect control by PlsB. In contrast to steady-state regulation, we found that responses to environmental perturbations are triggered directly via changes in acetyl coenzyme A (acetyl-CoA) concentrations, which enable rapid adaptation. Adaptations are further modulated by ppGpp, which regulates PlsB activity during slow growth and growth arrest. The strong reliance of the membrane synthesis pathway upon posttranslational regulation ensures both the reliability and the responsiveness of membrane synthesis."
2648,ACNP efforts toward reducing climate change,
2649,Mitteilungen der DGKFO,
2650,Offline World: the Internet as Social Infrastructure among the Unconnected in Quasi-Rural Illinois,"The United States continues to experience a persistent rural-urban digital divide. However, in this area of research, less attention has been paid to the divide in regions between these two demographic and geographic extremes. In this paper, we examine the perceived effects of internet inaccessibility in this in-between space, which we term “quasi-rural.” Using quasi-rural Illinois as a case study, semi-structured interview data is used to highlight the experiences of those who are directly affected by the digital divide, as well as those who provide service alternatives and advocate for internet connectivity. With this data, we describe the personal experience of at-home internet inaccessibility. We then focus on how limited, or a lack of access shapes the perceptions of community connectedness and disadvantage among those affected by the divide. Our findings demonstrate the internet’s function as social infrastructure; differences in access are then conceptualized as a form of socioeconomic inequality."
2651,Informatics in the Times of Change,
2652,Characterization of Neoschoengastia gallinarum from subtropical China by rDNA and identification of two genotypes based on mitochondrial cox1,"Genetic variations in the 18S ribosomal DNA (18S), 28S ribosomal DNA (28S), second internal transcribed spacer of ribosomal DNA (ITS2), and mitochondrial cytochrome c oxidase subunit 1 (cox1) of Neoschoengastia gallinarum collected from subtropical China were examined. First, a portion of the 18S (p18S), a portion of the 28S (p28S), and the complete ITS2 were separately amplified from individual mites and sequenced. The lengths of the sequences of p18S, p28S, and ITS2 were found to be 1379 bp, 3465~3468 bp, and 200 bp, respectively. The intraspecific sequence variation was 0~0.1% for p28S and 0~1.6% for ITS2, though no variation was observed for p18S, suggesting conservation of rDNA sequences. Second, a portion of the mitochondrial cox1 gene (pcox1) of N. gallinarum was analyzed. The length of the pcox1 sequence is 460 bp, and two distinct groups were observed in N. gallinarum. All pcox1 sequences in group I were identical, and there was only one nucleotide transition observed in group II; however, 7.0~7.2% variations between the two groups were observed, suggesting that two genotypes of N. gallinarum: genotype I and genotype II. Phylogenetic analyses based on pcox1 sequences indicated that N. gallinarum isolates (genotype I or genotype II) clustered into one branch; according to cox1 sequence analysis of Trombiculidae, Walchia hayashii is the closest species. The present study shows that ITS2 rDNA sequence can act as marker for the identification of N. gallinarum samples. Furthermore, analysis of the mitochondrial pcox1 sequence suggests the existence of two genotypes, which has implications for further studies of the ecology and population genetic structures of N. gallinarum."
2653,"OBEDIS Core Variables Project: European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions","Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing − focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity − ultimately leading to better patient care and improved obesity outcomes."
2654,RNA Recognition and Immunity—Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms,"RNA acts as an immunostimulatory molecule in the innate immune system to activate nucleic acid sensors. It functions as an intermediate, conveying genetic information to control inflammatory responses. A key mechanism for RNA sensing is discriminating self from non-self nucleic acids to initiate antiviral responses reliably, including the expression of type I interferon (IFN) and IFN-stimulated genes. Another important aspect of the RNA-mediated inflammatory response is posttranscriptional regulation of gene expression, where RNA-binding proteins (RBPs) have essential roles in various RNA metabolisms, including splicing, nuclear export, modification, and translation and mRNA degradation. Recent evidence suggests that the control of mRNA stability is closely involved in signal transduction and orchestrates immune responses. In this study, we review the current understanding of how RNA is sensed by host RNA sensing machinery and discuss self/non-self-discrimination in innate immunity focusing on mammalian species. Finally, we discuss how posttranscriptional regulation by RBPs shape immune reactions."
2655,Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology,"Mitochondrial permeability transition (MPT) is the sudden loss in the permeability of the inner mitochondrial membrane (IMM) to low-molecular-weight solutes. Due to osmotic forces, MPT is paralleled by a massive influx of water into the mitochondrial matrix, eventually leading to the structural collapse of the organelle. Thus, MPT can initiate outer-mitochondrial-membrane permeabilization (MOMP), promoting the activation of the apoptotic caspase cascade and caspase-independent cell-death mechanisms. The induction of MPT is mostly dependent on mitochondrial reactive oxygen species (ROS) and Ca(2+), but is also dependent on the metabolic stage of the affected cell and signaling events. Therefore, since its discovery in the late 1970s, the role of MPT in human pathology has been heavily investigated. Here, we summarize the most significant findings corroborating a role for MPT in the etiology of a spectrum of human diseases, including diseases characterized by acute or chronic loss of adult cells and those characterized by neoplastic initiation."
2656,A Practical Perspective on the Roles of Solution NMR Spectroscopy in Drug Discovery,"Solution nuclear magnetic resonance (NMR) spectroscopy is a powerful tool to study structures and dynamics of biomolecules under physiological conditions. As there are numerous NMR-derived methods applicable to probe protein–ligand interactions, NMR has been widely utilized in drug discovery, especially in such steps as hit identification and lead optimization. NMR is frequently used to locate ligand-binding sites on a target protein and to determine ligand binding modes. NMR spectroscopy is also a unique tool in fragment-based drug design (FBDD), as it is able to investigate target-ligand interactions with diverse binding affinities. NMR spectroscopy is able to identify fragments that bind weakly to a target, making it valuable for identifying hits targeting undruggable sites. In this review, we summarize the roles of solution NMR spectroscopy in drug discovery. We describe some methods that are used in identifying fragments, understanding the mechanism of action for a ligand, and monitoring the conformational changes of a target induced by ligand binding. A number of studies have proven that (19)F-NMR is very powerful in screening fragments and detecting protein conformational changes. In-cell NMR will also play important roles in drug discovery by elucidating protein-ligand interactions in living cells."
2657,STAT2 Limits Host Species Specificity of Human Metapneumovirus,"The host tropism of viral infection is determined by a variety of factors, from cell surface receptors to innate immune signaling. Many viruses encode proteins that interfere with host innate immune recognition in order to promote infection. STAT2 is divergent between species and therefore has a role in species restriction of some viruses. To understand the role of STAT2 in human metapneumovirus (HMPV) infection of human and murine tissues, we first infected STAT2(−/−) mice and found that HMPV could be serially passaged in STAT2(−/−), but not WT, mice. We then used in vitro methods to show that HMPV inhibits expression of both STAT1 and STAT2 in human and primate cells, but not in mouse cells. Transfection of the murine form of STAT2 into STAT2-deficient human cells conferred resistance to STAT2 inhibition. Finally, we sought to understand the in vivo role of STAT2 by infecting hSTAT2 knock-in mice with HMPV, and found that mice had increased weight loss, inhibition of type I interferon signaling, and a Th2-polarized cytokine profile compared to WT mice. These results indicate that STAT2 is a target of HMPV in human infection, while the murine version of STAT2 restricts tropism of HMPV for murine cells and tissue."
2658,Dendropanax Morbifera Extract-Mediated ZnO Nanoparticles Loaded with Indole-3-Carbinol for Enhancement of Anticancer Efficacy in the A549 Human Lung Carcinoma Cell Line,"Dendropanax morbifera is a versatile plant that has been used as a herbal medicine due to its various useful medicinal effects. To protect its active component from biological stress and increase its drug efficacy as well as drug bioavailability, nanoemulsion was prepared. Dendropanax morbifera zinc oxide nanoparticles (DM-ZnO NPs) were synthesized using the plant extract via the co-precipitation method and loaded with active indole-3-carbinol for nanoemulsion formulation using the ultrasonication process. Field emission transmission electron microscope revealed the flower shape of the Dendropanax morbifera indole-3-carbinol zinc oxide nanoemulsion (DM-ZnO-I3C-NE). In contrast, DM-ZnO NPs showed a spheroid shape that coincides agreeably with field emission electron scanning microscope. The hydrodynamic sizes by dynamic light scattering are about 65 ± 3 nm and 239.6 ± 6 nm and the crystallite sizes from X-ray diffraction are 11.52 nm and 16.07 nm for DM-ZnO NPs and DM-ZnO-I3C-NE, respectively. In vitro analysis revealed the cytotoxicity of DM-ZnO-I3C-NE against a human lung cancer cell line (A549) at 12.5 µg/mL as well as reactive oxygen species (ROS) production. The DM-ZnO-I3C-NE-induced ROS generation level was higher than that of DM-ZnO NPs and free indole-3-carbinol. The synergistic effect of DM-ZnO and indole-3-carbinol indicates DM-ZnO-I3C-NE as a potential candidate for future lung cancer drug and could be scope for functional food."
2659,Correction,
2660,From subordination to complementarity?,
2661,Research Progress of Oxidative Stress and MicroRNAs in the Prevention of Catheter-Related Thrombus Under Resistance Exercise,"Central venous access devices (CVADs) have completely changed the care for patients who require long-term venous access. With the widespread use of CVADs, the incidence of catheter-related thrombus (CRT) has increased. Catheter-related thrombus is a common complication in patients who use CVADs and is mainly caused by endothelial injury, blood stasis, and hypercoagulability. In recent years, the correlations between oxidative stress (OS) and microRNA (miRNA) and CRT have become a hot topic in clinical research. When a catheter punctures the vessel wall, it causes OS damage to the vascular endothelial cells, leading to a series of CRT diseases. MicroRNAs can regulate the mechanism of thrombus and play an important role in the formation of anti-thrombus. Numerous studies have shown that resistance exercise can reduce the level of OS in vascular endothelial cells, inhibit vascular endothelial cell dysfunction, and maintain the stability of hemodynamics and biochemical state. In the current work, the recent studies on the effects of resistance exercise on OS and miRNA in vascular endothelial cells were reviewed."
2662,Problematic Facebook use and problematic video gaming as mediators of relationship between impulsivity and life satisfaction among female and male gamers,"Over the past few decades, many new technologies have emerged, such as portable computers, the internet and smartphones, which have contributed to improving the lives of individuals. While the benefits of these new technologies are overwhelmingly positive, negative consequences are experienced by a minority of individuals. One possible negative aspect of new technologies is their problematic use due to impulsive use which may lead to lower life satisfaction. The present study investigated the mediating role of problematic video gaming (PVG) and problematic Facebook use (PFU) in the relationship between impulsivity dimensions and life satisfaction as well as the relationship between impulsivity dimensions and problematic behaviors. Additionally, the potential impact of gender differences was also examined. The study comprised 673 gamers (391 females) aged 17–38 years (M = 21.25 years, SD = 2.67) selected from 1365 individuals who completed an offline survey. PFU was assessed using the Facebook Intrusion Scale, and PVG was assessed using the nine-item Internet Gaming Disorder Scale–Short-Form (IGDS9-SF). Impulsivity dimensions such as attention, cognitive instability, motor, perseverance, self-control, and cognitive complexity were assessed using the Barratt Impulsiveness Scale (BIS-11), and life satisfaction was assessed using the Satisfaction With Life Scale (SWLS). Depending on the specific impulsivity dimension, findings showed both positive and negative relationships between impulsivity and life satisfaction. Attention and perseverance subtypes of impulsivity were primarily associated with problematic behaviors. Additionally, cognitive complexity was associated with PFU among female gamers, whereas cognitive instability was associated with PVG among male gamers. Additionally, PVG was primarily associated with lower life satisfaction. However, there was no mediation effects between impulsivity dimensions and life satisfaction via PFU or PVG. These findings provide a better understanding of the relationship between problematic behaviors, life satisfaction, and impulsivity among gamers and the differences between male and female gamers."
2663,Estimating the Effect of Depression on HIV Transmission Risk Behaviors Among People Who Inject Drugs in Vietnam: A Causal Approach,"The burden of depression and HIV is high among people who inject drugs (PWID), yet the effect of depression on transmission risk behaviors is not well understood in this population. Using causal inference methods, we analyzed data from 455 PWID living with HIV in Vietnam 2009–2013. Study visits every 6 months over 2 years measured depressive symptoms in the past week and injecting and sexual behaviors in the prior 3 months. Severe depressive symptoms (vs. mild/no symptoms) increased injection equipment sharing (risk difference [RD] = 3.9 percentage points, 95% CI −1.7, 9.6) but not condomless sex (RD = −1.8, 95% CI −6.4, 2.8) as reported 6 months later. The cross-sectional association with injection equipment sharing at the same visit (RD = 6.2, 95% CI 1.4, 11.0) was stronger than the longitudinal effect. Interventions on depression among PWID may decrease sharing of injection equipment and the corresponding risk of HIV transmission. Clinical trial registration ClinicalTrials.gov NCT01689545. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10461-020-03007-9) contains supplementary material, which is available to authorized users."
2664,Immunological status and virological suppression among HIV-infected adults on highly active antiretroviral therapy,"BACKGROUND: World Health Organization (WHO) recommends that viral load ([VL) is a primary tool that clinicians and researchers have used to monitor patients on antiretroviral therapy (ART), an antiviral drug against retroviruses. Whereas, CD4 cell counts can only be used to monitor clinical response to ART in the absence of VL testing service. Therefore, this study is aimed to assess the level of immunological status and virological suppression, and identify associated factors among human immunodeficiency virus ([HIV)-infected adults who were taking antiretroviral drugs of combination regimen know as highly active antiretroviral therapy (HAART). METHODS: A hospital-based cross-sectional study was conducted at the University of Gondar comprehensive specialized referral hospital from February to April 2018. A total of 323 adult participants on HAART were selected using a systematic random sampling technique and enrolled into the study. Blood samples for viral load determination and CD4 cell count were collected. Binary logistic regression analysis was used to determine factors associated with immunologic status and virological suppression in HIV patients on HAART. Odds ratio with 95% CI was used to measure the strength of association. RESULTS: Virological suppression (VL level < 1000 copies/ml) was found in 82% (95% CI 77.7, 86.1) of study participants, and it has been associated with CD4 cell count between 350 and 499 cells/mm(3) (adjusted odds ratio (AOR) = 2.56; 95% CI 1.14, 5.75) and > 499 cells/mm(3) (AOR = 7.71; 95% CI 3.48, 17.09) at VL testing and current age > 45 years old (AOR = 5.99; 95% CI 2.12, 16.91). Similarly, favorable immunological status (≥ 400 cells/mm(3) for male and ≥ 466 cells/mm(3) for female) was observed in 52.9% (95% CI 47.4, 58.8) of the study participants. Baseline CD4 cell count of > 200 cells/mm(3), age at enrollment of 26 through 40 years old, and urban residence were significantly associated with favorable immunological status. CONCLUSION: Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery."
2665,Normal modes analysis and surface electrostatics of haemagglutinin proteins as fingerprints for high pathogenic type A influenza viruses,"BACKGROUND: Type A influenza viruses circulate and spread among wild birds and mostly consist of low pathogenic strains. However, fast genome variation timely results in the insurgence of high pathogenic strains, which when infecting poultry birds may cause a million deaths and strong commercial damage. More importantly, the host shift may concern these viruses and sustained human-to-human transmission may result in a dangerous pandemic outbreak. Therefore, fingerprints specific to either low or high pathogenic strains may represent a very important tool for global surveillance. RESULTS: We combined Normal Modes Analysis and surface electrostatic analysis of a mixed strain dataset of influenza A virus haemagglutinins from high and low pathogenic strains in order to infer specific fingerprints. Normal Modes Analysis sorted the strains in two different, homogeneous clusters; sorting was independent of clades and specific instead to high vs low pathogenicity. A deeper analysis of fluctuations and flexibility regions unveiled a special role for the 110-helix region. Specific sorting was confirmed by surface electrostatics analysis, which further allowed to focus on regions and mechanisms possibly crucial to the low-to-high transition. CONCLUSIONS: Evidence from previous work demonstrated that changes in surface electrostatics are associated with the evolution and spreading of avian influenza A virus clades, and seemingly involved also in the avian to mammalian host shift. This work shows that a combination of electrostatics and Normal Modes Analysis can also identify fingerprints specific to high and low pathogenicity. The possibility to predict which specific mutations may result in a shift to high pathogenicity may help in surveillance and vaccine development."
2666,Hazards of ophthalmic patients wearing face masks,
2667,Durable Suppression and Low Rate of Virologic Failure 3 Years After Switch to Dolutegravir + Rilpivirine 2-Drug Regimen: 148-Week Results From the SWORD-1 and SWORD-2 Randomized Clinical Trials,"The SWORD trials showed that in participants who achieved virologic suppression taking 3-drug or 4-drug regimens, switching to the 2-drug regimen dolutegravir plus rilpivirine was noninferior in maintaining HIV-1 RNA <50 copies/mL at the week 48 primary endpoint. We present pooled week 148 analysis results from both studies. SETTING: SWORD-1: 65 centers, 13 countries; SWORD-2: 60 centers, 11 countries. METHODS: SWORD-1 and SWORD-2 are identical, open-label, phase III studies. Participants with screening HIV-1 RNA <50 copies/mL for ≥6 months; no prior virologic failure; and no documented resistance-associated major protease inhibitor, integrase inhibitor, nucleoside reverse transcriptase inhibitor (NRTI), or non-NRTI mutations or integrase resistance-associated substitution R263K were randomly assigned 1:1 to switch to once-daily dolutegravir 50 mg plus rilpivirine 25 mg on day 1 (early-switch group) or to continue their current antiretroviral regimen and, if virologically suppressed at week 48, switch to dolutegravir plus rilpivirine at week 52 (late-switch group) until week 148. RESULTS: Using snapshot algorithm at week 148, 432 of 513 (84%) early-switch participants (148 weeks of exposure) and 428 of 477 (90%) late-switch participants (96 weeks of exposure) maintained HIV-1 RNA <50 copies/mL. Eleven participants (1%) on dolutegravir plus rilpivirine met the confirmed virologic withdrawal criterion through week 148 (early-switch group, n = 8; late-switch group, n = 3) with no integrase resistance identified. Non-NRTI resistance-associated mutations were identified in 6 participants (<1%). Drug-related adverse events (grades 2–4) were observed in 31 (6%) early-switch and 16 (3%) late-switch participants. Significant improvements in bone biomarkers were observed. Significant improvements were observed in renal biomarkers in participants taking tenofovir disoproxil fumarate pre‐switch. CONCLUSION: Switching to the 2-drug regimen dolutegravir plus rilpivirine maintained virologic suppression for a high proportion of participants through 3 years, with low rates of virologic failure and a well-tolerated safety profile."
2668,Detecting Patches of Protein Sites of Influenza A Viruses under Positive Selection,"Influenza A viruses are single-stranded RNA viruses capable of evolving rapidly to adapt to environmental conditions. Examples include the establishment of a virus in a novel host or an adaptation to increasing immunity within the host population due to prior infection or vaccination against a circulating strain. Knowledge of the viral protein regions under positive selection is therefore crucial for surveillance. We have developed a method for detecting positively selected patches of sites on the surface of viral proteins, which we assume to be relevant for adaptive evolution. We measure positive selection based on dN/dS ratios of genetic changes inferred by considering the phylogenetic structure of the data and suggest a graph-cut algorithm to identify such regions. Our algorithm searches for dense and spatially distinct clusters of sites under positive selection on the protein surface. For the hemagglutinin protein of human influenza A viruses of the subtypes H3N2 and H1N1, our predicted sites significantly overlap with known antigenic and receptor-binding sites. From the structure and sequence data of the 2009 swine-origin influenza A/H1N1 hemagglutinin and PB2 protein, we identified regions that provide evidence of evolution under positive selection since introduction of the virus into the human population. The changes in PB2 overlap with sites reported to be associated with mammalian adaptation of the influenza A virus. Application of our technique to the protein structures of viruses of yet unknown adaptive behavior could identify further candidate regions that are important for host–virus interaction."
2669,"Responses to A(H1N1)pdm09 Influenza Vaccines in Participants Previously Vaccinated With Seasonal Influenza Vaccine: A Randomized, Observer-Blind, Controlled Study","Background. Prior receipt of a trivalent seasonal influenza vaccine (TIV) can affect hemagglutination inhibition (HI) antibody responses to pandemic influenza vaccines. We investigated the effect of TIV priming on humoral responses to AS03-adjuvanted and nonadjuvanted A(H1N1)pdm09 vaccines, the role of AS03 on cell-mediated immune (CMI) responses, and vaccine safety. Methods. Healthy adults (aged 19–40 years) were randomized 1:1:1:1 to receive TIV or saline followed 4 months later by 2 doses, 3 weeks apart, of adjuvanted or nonadjuvanted A(H1N1)pdm09 vaccine and followed up to study end (day 507). Pre- and postvaccination responses of HI and neutralizing antibody, CD4(+)/CD8(+) T cells, memory B cells, and plasmablasts were assessed. Results. Ninety-nine of the 133 participants enrolled completed the study. No vaccine-related serious adverse events were recorded. In TIV-primed participants, A(H1N1)pdm09-specific antibody and CD4(+) T-cell and memory B-cell responses to the pandemic vaccine tended to be diminished. Vaccine adjuvantation led to increased responses of vaccine-homologous and -heterologous HI and neutralizing antibodies and CD4(+) T cells, homologous memory B cells, and plasmablasts. Conclusions. In healthy adults, prior TIV administration decreased humoral and CMI responses to A(H1N1)pdm09 vaccine. Adjuvantation of A(H1N1)pdm09 antigen helped to overcome immune interference between the influenza vaccines. No safety concerns were observed. Registration. Clinical Trials.gov identifier NCT00707967."
2670,Heterologous Prime-Boost Vaccination Using an AS03(B)-Adjuvanted Influenza A(H5N1) Vaccine in Infants and Children <3 Years of Age,"Background. Protecting young children from pandemic influenza should also reduce transmission to susceptible adults, including pregnant women. Methods. An open study assessed immunogenicity and reactogenicity of a heterologous booster dose of A/turkey/Turkey/1/2005(H5N1)-AS03(B) (AS03(B) is an Adjuvant System containing α-tocopherol and squalene in an oil-in-water emulsion [5.93 mg tocopherol]) in infants and children aged 6 to < 36 months that was given 6 months following 2-dose primary vaccination with A/Indonesia/05/2005(H5N1)-AS03(B). Vaccines contained 1.9 µg of hemagglutinin antigen and AS03(B). Hemagglutinin inhibition (HI) responses, microneutralization titers, and antineuraminidase antibody levels were assessed for 6 months following the booster vaccination. Results. For each age stratum (defined on the basis of the subject's age at first vaccination as 6 to < 12 months, 12 to < 24 months, and 24 to < 36 months) and overall (n = 113), European influenza vaccine licensure criteria were fulfilled for responses to A/turkey/Turkey/1/2005(H5N1) 10 days following the booster vaccination. Local pain and fever increased with consecutive doses. Anamnestic immune responses were demonstrated for HI, neutralizing, and antineuraminidase antibodies against vaccine-homologous/heterologous strains. Antibody responses to vaccine-homologous/heterologous strains persisted in all children 6 months following the booster vaccination. Conclusions. Prevaccination of young children with a clade 2 strain influenza A(H5N1) AS03-adjuvanted vaccine followed by heterologous booster vaccination boosted immune responses to the homologous strain and a related clade, with persistence for at least 6 months. The results support a prime-boost vaccination approach in young children for pandemic influenza preparedness. Clinical Trials Registration. NCT01323946."
2671,Standardizing Scenarios to Assess the Need to Respond to an Influenza Pandemic,
2672,Multiple Herpes Simplex Virus-1 (HSV-1) Reactivations Induce Protein Oxidative Damage in Mouse Brain: Novel Mechanisms for Alzheimer’s Disease Progression,"Compelling evidence supports the role of oxidative stress in Alzheimer’s disease (AD) pathophysiology. Interestingly, Herpes simplex virus-1 (HSV-1), a neurotropic virus that establishes a lifelong latent infection in the trigeminal ganglion followed by periodic reactivations, has been reportedly linked both to AD and to oxidative stress conditions. Herein, we analyzed, through biochemical and redox proteomic approaches, the mouse model of recurrent HSV-1 infection we previously set up, to investigate whether multiple virus reactivations induced oxidative stress in the mouse brain and affected protein function and related intracellular pathways. Following multiple HSV-1 reactivations, we found in mouse brains increased levels of oxidative stress hallmarks, including 4-hydroxynonenal (HNE), and 13 HNE-modified proteins whose levels were found significantly altered in the cortex of HSV-1-infected mice compared to controls. We focused on two proteins previously linked to AD pathogenesis, i.e., glucose-regulated protein 78 (GRP78) and collapsin response-mediated protein 2 (CRMP2), which are involved in the unfolded protein response (UPR) and in microtubule stabilization, respectively. We found that recurrent HSV-1 infection disables GRP78 function and activates the UPR, whereas it prevents CRMP2 function in mouse brains. Overall, these data suggest that repeated HSV-1 reactivation into the brain may contribute to neurodegeneration also through oxidative damage."
2673,Cellular Virotherapy Increases Tumor-Infiltrating Lymphocytes (TIL) and Decreases their PD-1(+) Subsets in Mouse Immunocompetent Models,"Oncolytic virotherapy uses viruses designed to selectively replicate in cancer cells. An alternative to intratumoral administration is to use mesenchymal stem cells (MSCs) to transport the oncolytic viruses to the tumor site. Following this strategy, our group has already applied this treatment to children and adults in a human clinical trial and a veterinary trial, with good clinical responses and excellent safety profiles. However, the development of immunocompetent cancer mouse models is still necessary for the study and improvement of oncolytic viroimmunotherapies. Here we have studied the antitumor efficacy, immune response, and mechanism of action of a complete murine version of our cellular virotherapy in mouse models of renal adenocarcinoma and melanoma. We used mouse MSCs infected with the mouse oncolytic adenovirus dlE102 (OAd-MSCs). In both models, treatment with OAd-MSCs significantly reduced tumor volumes by 50% and induced a pro-inflammatory tumor microenvironment. Furthermore, treated mice harboring renal adenocarcinoma and melanoma tumors presented increased infiltration of tumor-associated macrophages (TAMs), natural killer cells, and tumor-infiltrating lymphocytes (TILs). Treated mice also presented lower percentage of TILs expressing programmed cell death protein 1 (PD-1)—the major regulator of T cell exhaustion. In conclusion, treatment with OAd-MSCs significantly reduced tumor volume and induced changes in tumor-infiltrating populations of melanoma and renal cancer."
2674,Pteropine Orthoreovirus in an Angolan Soft-Furred Fruit Bat (Lissonycteris angolensis) in Uganda Dramatically Expands the Global Distribution of an Emerging Bat-Borne Respiratory Virus,"Pteropine orthoreovirus (PRV; Reoviridae: Spinareovirinae) is an emerging bat-borne zoonotic virus that causes influenza-like illness (ILI). PRV has thus far been found only in Australia and Asia, where diverse old-world fruit bats (Pteropodidae) serve as hosts. In this study, we report the discovery of PRV in Africa, in an Angolan soft-furred fruit bat (Lissonycteris angolensis ruwenzorii) from Bundibugyo District, Uganda. Metagenomic characterization of a rectal swab yielded 10 dsRNA genome segments, revealing this virus to cluster within the known diversity of PRV variants detected in bats and humans in Southeast Asia. Phylogeographic analyses revealed a correlation between geographic distance and genetic divergence of PRVs globally, which suggests a geographic continuum of PRV diversity spanning Southeast Asia to sub-Saharan Africa. The discovery of PRV in an African bat dramatically expands the geographic range of this zoonotic virus and warrants further surveillance for PRVs outside of Southeast Asia."
2675,Prioritizing Training Needs of School Health Staff: The Example of Vietnam,"Competencies of school health staff (SHS) members, including school nurses, are crucial to improving child and adolescent health. In Vietnam, although SHS members are dispatched to schools, they have limited training opportunities. This study identified SHS members’ training needs in a province of Vietnam. A cross-sectional, online survey was conducted with 204 SHS members. The performance and importance of SHS members’ competencies were measured using 59-items and rated by a 5-point Likert scale. SHS members’ training priorities were analyzed using the Borich Needs Assessment and the Locus for Focus model. Controlling infectious disease was the highest training priority while implementing health promotion programs was of relatively low priority. The high-priority training needs identified could be rendered mandatory in policy for continuing education of SHS members. Awareness of the importance of health promotion, which has been emphasized globally, should also be promoted via school health policy. These findings could guide development of future training programs for SHS members."
2676,Error in Results Section,
2677,Abstractband DOG 2020,
2678,Pain management during the withholding and withdrawal of life support in critically ill patients at the end-of-life: a systematic review and meta-analysis,"PURPOSE: To review and summarize the most frequent medications and dosages used during withholding and withdrawal of life-prolonging measures in critically ill patients in the intensive care unit. METHODS: We searched PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Virtual Health Library from inception through March 2019. We considered any study evaluating pharmaceutical interventions for pain management during the withholding or withdrawing of life support in adult critically ill patients at the end-of-life. Two independent investigators performed the screening and data extraction. We pooled data on utilization rate of analgesic and sedative drugs and summarized the dosing between the moment prior to withholding or withdrawal of life support and the moment before death. RESULTS: Thirteen studies met inclusion criteria. Studies were conducted in the United States (38%), Canada (31%), and the Netherlands (31%). Eleven studies were single-cohort and twelve had a Newcastle–Ottawa Scale score of less than 7. The mean age of the patients ranged from 59 to 71 years, 59–100% were mechanically ventilated, and 47–100% of the patients underwent life support withdrawal. The most commonly used opioid and sedative were morphine [utilization rate 60% (95% CI 48–71%)] and midazolam [utilization rate 28% (95% CI 23–32%)], respectively. Doses increased during the end-of-life process (pooled mean increase in the dose of morphine: 2.6 mg/h, 95% CI 1.2–4). CONCLUSIONS: Pain control is centered on opioids and adjunctive benzodiazepines, with dosages exceeding those recommended by guidelines. Despite consistency among guidelines, there is significant heterogeneity among practices in end-of-life care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06139-7) contains supplementary material, which is available to authorized users."
2679,HLA-associated protection of lymphocytes during influenza virus infection,"BACKGROUND: Heterozygosity at HLA class I loci is generally considered beneficial for host defense. We report here an element of HLA class I homozygosity that may or may not help preserve its existence in populations but which could indicate a new avenue for antiviral research. METHODS: Lymphocytes from serologically HLA-homozygous or -heterozygous donors were examined for synthesis of influenza virus proteins and RNA after exposure to virus as peripheral blood mononuclear cells. The virus-exposed lymphocytes were also examined for internalization of the virus after exposure, and for susceptibility to virus-specific cytotoxic T lymphocytes in comparison with virus-exposed monocytes/macrophages and unseparated peripheral blood mononuclear cells. Results were compared using two-tailed Fisher’s exact test. RESULTS: Serologically-defined HLA-A2-homozygous lymphocytes, in contrast to heterozygous lymphocytes, did not synthesize detectable influenza virus RNA or protein after exposure to the virus. HLA-A2-homozygous lymphocytes, including both homozygous and heterozygous donors by genetic sequence subtyping, did internalize infectious virus but were not susceptible to lysis by autologous virus-specific cytotoxic T lymphocytes (“fratricide”). Similar intrinsic resistance to influenza virus infection was observed with HLA-A1- and HLA-A11-homozygous lymphocytes and with HLA-B-homozygous lymphocytes. CONCLUSIONS: A significant proportion of individuals within a population that is characterized by common expression of HLA class I alleles may possess lymphocytes that are not susceptible to influenza virus infection and thus to mutual virus-specific lysis. Further study may identify new approaches to limit influenza virus infection."
2680,The autophagy adaptor NDP52 and the FIP200 coiled-coil allosterically activate ULK1 complex membrane recruitment,The selective autophagy pathways of xenophagy and mitophagy are initiated when the adaptor NDP52 recruits the ULK1 complex to autophagic cargo. Hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) was used to map the membrane and NDP52 binding sites of the ULK1 complex to unique regions of the coiled coil of the FIP200 subunit. Electron microscopy of the full-length ULK1 complex shows that the FIP200 coiled coil projects away from the crescent-shaped FIP200 N-terminal domain dimer. NDP52 allosterically stimulates membrane-binding by FIP200 and the ULK1 complex by promoting a more dynamic conformation of the membrane-binding portion of the FIP200 coiled coil. Giant unilamellar vesicle (GUV) reconstitution confirmed that membrane recruitment by the ULK1 complex is triggered by NDP52 engagement. These data reveal how the allosteric linkage between NDP52 and the ULK1 complex could drive the first membrane recruitment event of phagophore biogenesis in xenophagy and mitophagy.
2681,Polyploidy in the adult Drosophila brain,"Long-lived cells such as terminally differentiated postmitotic neurons and glia must cope with the accumulation of damage over the course of an animal’s lifespan. How long-lived cells deal with ageing-related damage is poorly understood. Here we show that polyploid cells accumulate in the adult fly brain and that polyploidy protects against DNA damage-induced cell death. Multiple types of neurons and glia that are diploid at eclosion, become polyploid in the adult Drosophila brain. The optic lobes exhibit the highest levels of polyploidy, associated with an elevated DNA damage response in this brain region. Inducing oxidative stress or exogenous DNA damage leads to an earlier onset of polyploidy, and polyploid cells in the adult brain are more resistant to DNA damage-induced cell death than diploid cells. Our results suggest polyploidy may serve a protective role for neurons and glia in adult Drosophila melanogaster brains."
2682,No Visitors Allowed,
2683,Material Suitability Testing for Nonmedical Grade Community Face Masks to Decrease Viral Transmission During a Pandemic,"OBJECTIVES: Cloth face covering has been recommended by the Centers for Disease Control and Prevention to decrease community viral transmission. This study aims to determine the filtration efficiency and airflow resistance of common household materials available for homemade mask production by comparing numbers of fabrics, various layers, and manipulation. METHODS: Common household woven, knitted, and nonwoven fabrics were tested for filtration efficiency using a fit testing setup and airflow resistance with pressure gauge setup. Three different levels of layering (1, 2, and 4) were tested. Some fabric material was further tested after washing and drying. Filtration performance, the area under the fitted curve comparing airflow resistance and filtration efficiency, was calculated for each fabric material and compared. RESULTS: Layering increased filtration efficiency and airflow resistance (P < 0.0001 and P < 0.01, respectively). Polyester felt demonstrated the highest filtration performance index (P < 0.0001), higher than all tested 100% cotton materials (all P < 0.05) as well as surgical masks (P < 0.05). Washing plus drying did not alter filtration performance significantly (P > 0.05). CONCLUSIONS: A filtration performance of common household fabrics were compared. Homemade mask designers and producers will have improved data to better balance effectiveness, availability, and comfort with the goal of decreasing community viral transmission."
2684,Animal Galectins and Plant Lectins as Tools for Studies in Neurosciences,"Lectins are proteins or glycoproteins of non-immunological origin capable of reversibly and specifically binding to glycoconjugates. They exist in free form or associated with cells and are widely distributed in nature, being found in plants, microorganisms, and animals. Due to their characteristics and mainly due to the possibility of reversible binding to glycoconjugates, lectins have stood out as important tools in research involving Neurobiology. These proteins have the ability to modulate molecular targets in the central nervous system (CNS) which may be involved with neuroplasticity, neurobehavioral effects, and neuroprotection. The present report integrates existing information on the activity of animal and plant lectins in different areas of Neuroscience, presenting perspectives to direct new research on lectin function in the CNS, providing alternatives for understanding neurological diseases such as mental disorders, neurodegenerative, and neuro-oncological diseases, and for the development of new drugs, diagnoses and therapies in the field of Neuroscience."
2685,Assessing the Impact of Lean Healthcare on Inpatient Care: A Systematic Review,"Healthcare services are facing challenges in increasing their efficiency, quality of care, and coping with surges in demand. To this end, some hospitals have implemented lean healthcare. The aim of this systematic review is to evaluate the effects of lean healthcare (LH) interventions on inpatient care and determine whether patient flow and efficiency outcomes improve. The review was performed according to PRISMA. We used six databases to search for studies published from 2002 to 2019. Out of 5732 studies, 39 measuring one or more defined outcomes were included. Hospital length of stay (LOS) was measured in 23 studies, 16 of which reported a reduction, turnover time (TOT) decreased in six out of eight studies, while the turnaround time (TAT) and on-time starts (OTS) improved in all five and seven studies, respectively. Moreover, eight out of nine studies reported an earlier discharge time, and the boarding time decreased in all four cases. Meanwhile, the readmission rate did not increase in all nine studies. Lastly, staff and patient satisfaction improved in all eight studies. Our findings show that by focusing on reducing non-value-added activities, LH contributed to improving patient flow and efficiency within inpatient care."
2686,Accurate Spirometry with Integrated Barometric Sensors in Face-Worn Garments,"Cardiorespiratory (CR) signals are crucial vital signs for fitness condition tracking, medical diagnosis, and athlete performance evaluation. Monitoring such signals in real-life settings is among the most widespread applications of wearable computing. We investigate how miniaturized barometers can be used to perform accurate spirometry in a wearable system that is built on off-the-shelf training masks often used by athletes as a training aid. We perform an evaluation where differential barometric pressure sensors are compared concurrently with a digital spirometer, during an experimental setting of clinical forced vital capacity (FVC) test procedures with 20 participants. The relationship between the two instruments is derived by mathematical modeling first, then by various regression methods from experiment data. The results show that the error of FVC vital values between the two instruments can be as low as 2∼3%. Beyond clinical tests, the method can also measure continuous tidal breathing air volumes with a 1∼3% error margin. Overall, we conclude that barometers with millimeter footprints embedded in face mask apparel can perform similarly to a digital spirometer to monitor breathing airflow and volume in pulmonary function tests."
2687,Authors’ correction for Euro Surveill. 2020;25(32),
2688,"Study protocol for a double-blind, randomised placebo-controlled trial evaluating clinical effects of platelet-rich plasma injection for acute grade-2 hamstring tear among high performance athletes","INTRODUCTION: Hamstring injury among athletes often results in significant morbidity. Currently, there are controversies regarding the clinical use of platelet-rich plasma (PRP) for the treatment of acute hamstring injury. METHODS AND ANALYSIS: This study is a single-centre double-blind randomised placebo-controlled trial. Sixty-eight patients will be randomised to receive under ultrasound guidance either a single injection of leucocyte-rich PRP (LR-PRP) or normal saline. All patients will undergo a standardised hamstring rehabilitation programme under the supervision of a sports physiotherapist. Outcome data will be collected before intervention (baseline), and thereafter on a weekly basis. The primary outcome measure is the duration to return-to-play. It is defined as the duration (in days) from the date on which the injury occurred until the patients were pain-free, able to perform the active knee extension test and have regained hamstring muscle strength. Secondary outcome measures include assessment of pain intensity and the effect of pain on to day-to-day functions using the self-reported Brief Pain Inventory—Short Form questionnaire. Both the primary and secondary outcomes were assessed at baseline and thereafter once a week until return to play. Also, hamstring injury recurrence within the first 6 months after recovery will be monitored via telephone. The results of this study will provide insights into the effect of LR-PRP in muscle and may help to identify the best PRP application protocol for muscle injuries. ETHICS AND DISSEMINATION: Ethics approval were obtained from the Medical Research Ethics Committee of the University of Malaya Medical Centre. Results of this trial will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN76844299."
2689,Integrated analysis of whole genome and transcriptome sequencing in a young patient with gastric cancer provides insights for precision therapy,"Gastric cancer is a leading cause of cancer-associated deaths worldwide and is considered to be an age-related disease. In younger patients, gastric cancer is biologically more aggressive, and prognosis is worse compared with that in elderly patients. In the present case report, the whole genome and transcriptome was sequenced in a 26-year-old patient with gastric cancer who presented with gastric cancer-related symptoms and was admitted to the First Affiliated Anhui Medical Hospital (Hefei, China) in December 2016. In total, 9 germline and 4 somatic mutations were identified in the patient, and there were more deleterious sites in the germline mutated genes. Genes with somatic mutations, such as MUC2, MUC4, SLC8A2, and with structural variations, including CCND3, FGFR2 and FGFR3, were found to be differentially expressed. Cancer-associated pathways, such as the ‘calcium signaling pathway’, ‘cGMP-PKG signaling pathway’ and ‘transcriptional mis-regulation’ were also enriched at both the genomic and transcriptomic levels. The genes found to have germline (SFRP4), somatic (MUC2, MUC4, SLC8A2) mutations, or structural variations (CCND3, FGFR2 and FGFR3) were differentially expressed in the patient and could be promising precision therapy targets."
2690,Evaluating the predictive performance of malaria antibodies and FCGR3B gene polymorphisms on Plasmodium falciparum infection outcome: a prospective cohort study,"BACKGROUND: Malaria antigen-specific antibodies and polymorphisms in host receptors involved in antibody functionality have been associated with different outcomes of Plasmodium falciparum infections. Thus, to identify key prospective malaria antigens for vaccine development, there is the need to evaluate the associations between malaria antibodies and antibody dependent host factors with more rigorous statistical methods. In this study, different statistical models were used to evaluate the predictive performance of malaria-specific antibodies and host gene polymorphisms on P. falciparum infection in a longitudinal cohort study involving Ghanaian children. METHODS: Models with different functional forms were built using known predictors (age, sickle cell status, blood group status, parasite density, and mosquito bed net use) and malaria antigen-specific immunoglobulin (Ig) G and IgG subclasses and FCGR3B polymorphisms shown to mediate antibody-dependent cellular functions. Malaria antigens studied were Merozoite surface proteins (MSP-1 and MSP-3), Glutamate Rich Protein (GLURP)-R0, R2, and the Apical Membrane Antigen (AMA-1). The models were evaluated through visualization and assessment of differences between the Area Under the Receiver Operating Characteristic Curve and Brier Score estimated by suitable internal cross-validation designs. RESULTS: This study found that the FCGR3B-c.233C>A genotype and IgG against AMA1 were relatively better compared to the other antibodies and FCGR3B genotypes studied in classifying or predicting malaria risk among children. CONCLUSIONS: The data supports the P. falciparum, AMA1 as an important malaria vaccine antigen, while FCGR3B-c.233C>A under the additive and dominant models of inheritance could be an important modifier of the effect of malaria protective antibodies."
2691,The top 100 most cited articles on bronchoscopy: a bibliometric analysis,"BACKGROUND: Bronchoscopy is applied broadly in the diagnosis and treatment of pulmonary diseases. Over the past few decades, an increasing number of studies about bronchoscopy have been published. However, little is known about their qualities and characteristics. METHODS: All of the databases in Web of Science (including the Web of Science Core Collection, BIOSIS Citation Index, KCI-Korean Journal Database, MEDLINE, Russian Science Citation Index, and SciELO Citation Index) were utilized to identify articles published from 1990 to 2020. The top 100 most cited articles about bronchoscopy were selected for degree centrality analysis and analyses regarding publication time, total citation number, the citation density, time-related flux, first author, published journal, geographic origin, and research theme. RESULTS: The selected articles were published mainly in the 2000s and 1990s. Citations per article ranged from 731 to 196. The leading country was the USA, followed by the United Kingdom. The most frequently studied themes were bronchoalveolar lavage (BAL) fluid and biopsy. The degree centrality analysis connoted that “BAL, inflammation, diagnosis” had a high degree of centrality in the 1990s, while “diagnosis, BAL, biopsy, prospective” took centre stage in the 2000s. CONCLUSIONS: The time, area, and theme distribution of the 100 most cited articles on bronchoscopy have been thoroughly analyzed. It is noticeable that researches based on BAL and endobronchial or transbronchial biopsies currently plays a major role."
2692,Celebrating Molecular Medicine,
2693,Exploring dentists' professional behaviours reported in United Kingdom newspaper media,"Aim Stories of dentists and their professional behaviours can be communicated around the world through news media. This may influence people's perceptions of dentistry and their trust in professionals. The aim of this study was to explore reports of dentists and their professional behaviours in newspaper media. Method All articles which included the term 'dentist' alongside 'professional' or 'misconduct' or 'behaviour' between 1 January 2016 and 31 October 2019 were retrieved from the ten most commonly read newspaper print media in the United Kingdom. Thematic analysis was undertaken following the application of inclusion and exclusion criteria. Results A total of 122 articles were identified. Key themes included poor practice, dishonesty and fraud, the killing of Cecil the lion, sexual misconduct, racism and crime. Many articles focused on a small number of extreme cases, labelling the dentists involved and sensationalising the stories. Reports did not reflect the majority of fitness to practise cases seen by the General Dental Council. Conclusion The sensationalist approach to the reporting of dental professional behaviours in the news may cause patients to have less trust in their dentist, and it is recommended that dentists and journalists work constructively together in the best interests of the public."
2694,Herausforderungen der Digitalisierung in der Traumaversorgung,"The increasing digitalization of social life opens up new possibilities for modern health care. This article describes innovative application possibilities that could help to sustainably improve the treatment of severe injuries in the future with the help of methods such as big data, artificial intelligence, intelligence augmentation, and machine learning. For the successful application of these methods, suitable data sources must be available. The TraumaRegister DGU® (TR-DGU) currently represents the largest database in Germany in the field of care for severely injured patients that could potentially be used for digital innovations. In this context, it is a good example of the problem areas such as data transfer, interoperability, standardization of data sets, parameter definitions, and ensuring data protection, which still represent major challenges for the digitization of trauma care. In addition to the further development of new analysis methods, solutions must also continue to be sought to the question of how best to intelligently link the relevant data from the various data sources."
2695,Experience with Temporary Centrifugal Pump Bi-ventricular Assist Device for Pediatric Acute Heart Failure: Comparison with ECMO,"Though ventricular assist devices (VADs) are an important treatment option for acute heart failure, an extracorporeal membrane oxygenator (ECMO) is usually used in pediatric patients for several reasons. However, a temporary centrifugal pump-based Bi-VAD might have clinical advantages versus ECMO or implantable VADs. From January 2000 to July 2018, we retrospectively reviewed 36 pediatric patients who required mechanical circulatory support (MCS) for acute heart failure. Cases with postoperative MCS were excluded. Since 2016, we have tried to immediately add a right VAD rather than ECMO, when the patients begin to present features of right heart failure after left VAD support started in cases that the patients’ respiratory function did not require an oxygenator. Original diagnoses included dilated cardiomyopathy (n = 18), myocarditis (n = 11), and others (n = 7). Eleven patients were supported by Bi-VAD, and 25 patients were supported by ECMO; of these. Four patients were successfully weaned from VAD, and 10 patients were weaned from ECMO. Eleven patients underwent heart transplantation. Overall, we have 15 (41.7%) early mortalities. There were no significant differences in early mortality, morbidity, and weaning rate between the Bi-VAD group and the ECMO group. During the support, patients with Bi-VADs significantly required fewer platelets and showed less hemolysis than ECMO patients. Patients with myocarditis were successfully weaned from Bi-VAD support and bridged to transplantation thereafter. A temporary centrifugal pump-based Bi-VAD was clinically comparable to ECMO for pediatric patients with acceptable pulmonary function."
2696,"Efficacy of Milrinone Plus Sildenafil in the Treatment of Neonates with Persistent Pulmonary Hypertension in Resource-Limited Settings: Results of a Randomized, Double-Blind Trial","BACKGROUND: The management of severe persistent pulmonary hypertension (PPHN) can be very challenging in many resource-limited centers without access to inhaled nitric oxide or extracorporeal membrane oxygenation. OBJECTIVES: The current study aimed to investigate the efficacy of oral sildenafil and intravenous milrinone infusion and compare the effects of these drugs in combination versus as monotherapy in neonates with PPHN. METHODS: A double-blind randomized controlled trial was conducted in which neonates with PPHN were divided into three groups of 20 patients each: group 1 received oral sildenafil starting at 0.5 mg/kg every 6 h to a target maintenance dose of 2 mg/kg every 6 h; group 2 received intravenous milrinone 0.5 μg/kg/min as a continuous infusion; and group 3 received both oral sildenafil and intravenous milrinone. RESULTS: Post-treatment pulmonary artery systolic pressure was significantly lower in group 3 than in groups 1 and 2, which both received monotherapy (p = 0.031). The oxygenation index also decreased significantly in the dual-therapy group (p = 0.002) compared with the monotherapy groups. Combined use of both drugs demonstrated a beneficial synergistic effect with better outcomes and reduced mortality. CONCLUSION: Dual therapy using sildenafil and milrinone was superior to monotherapy with either drug in neonates with severe PPHN and is recommended for use in resource-constrained settings. REGISTRATION: Pan African Clinical Trial Registry identifier number PACTR201902691230243."
2697,Understanding long-term HIV survivorship among African American/Black and Latinx persons living with HIV in the United States: a qualitative exploration through the lens of symbolic violence,"BACKGROUND: Persons living with HIV (PLWH) are living longer, although racial/ethnic and socioeconomic status (SES) disparities persist. Yet, little is known about the experience of living with and managing HIV over decades. The present study took a qualitative approach and used the lens of symbolic violence, a type of internalized, non-physical violence manifested in the power differential between social groups. We focused on adult African American/Black and Latinx (AABL) PLWH from low-SES backgrounds. METHODS: Data were drawn from two studies with AABL PLWH in New York City (N = 59). After providing signed informed consent, participants engaged in in-depth semi-structured interviews on aspects of HIV management. Interviews were audio-recorded and professionally transcribed verbatim, and data were analyzed using directed qualitative content analysis. RESULTS: Participants in the two studies were comparable on sociodemographic and background characteristics. They had lived with HIV for 20 years, on average (range 3–33 years). All were from low-SES backgrounds and most were African American/Black and men. Participants experienced a convergence of multiple social exclusions, harms, and stigmas, consistent with symbolic violence, which contributed to disengagement from HIV care and discontinuation of HIV medications. We organized results into five sub-themes: (1) participants were “ground down” over time by material, social, and emotional challenges and this diminished self-worth and, at times, the will to live; (2) social isolation and self-isolation, based in part on feeling devalued and dehumanized, served as stigma-avoidance strategies and mechanisms of social exclusion; (3) stigmatizing aspects of patient-provider interactions, both experienced and anticipated, along with (4) restricted autonomy in HIV care and other settings (e.g., parole) reduced engagement; and (5) poor HIV management was internalized as a personal failure. Importantly, resilience was evident throughout the five sub-themes. CONCLUSIONS: Symbolic violence is a useful framework for understanding long-term HIV management and survivorship among AABL PLWH from low-SES backgrounds. Indeed, forms of symbolic violence are internalized over time (e.g., experiencing devaluation, dehumanization, loss of self-worth, and anticipated stigma), thereby impeding successful HIV management, in part because avoiding HIV care and discontinuing HIV medications are primary coping strategies. Results have implications for interventions in community and health care settings."
2698,"Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose","BACKGROUND: The Plasmodium falciparum sexual-stage surface proteins Pfs25 and Pfs230 are antigen candidates for a malaria transmission-blocking vaccine (TBV), and have been widely investigated as such. It is not clear whether simultaneously presenting these two antigens in a particulate vaccine would enhance the transmission reducing activity (TRA) of induced antibodies. To assess this, immunization was carried out with liposomes containing synthetic lipid adjuvant monophosphoryl lipid A (MPLA), and cobalt-porphyrin-phospholipid (CoPoP), which rapidly converts recombinant, his-tagged antigens into particles. METHODS: His-tagged, recombinant Pfs25 and Pfs230C1 were mixed with CoPoP liposomes to form a bivalent vaccine. Antigens were fluorescently labelled to infer duplex particleization serum-stability and binding kinetics using fluorescence resonance energy transfer. Mice and rabbits were immunized with individual or duplexed particleized Pfs25 and Pfs230C1, at fixed total antigen doses. The resulting antibody responses were assessed for magnitude and TRA. RESULTS: Pfs230C1 and Pfs25 rapidly bound CoPoP liposomes to form a serum-stable, bivalent particle vaccine. In mice, immunization with 5 ng of total antigen (individual antigen or duplexed) elicited functional antibodies against Pfs25 and Pfs230. Compared to immunization with the individual antigen, Pfs25 antibody production was moderately lower for the bivalent CoPoP vaccine, whereas Pfs230C1 antibody production was not impacted. All antibodies demonstrated at least 92% inhibition in oocyst density at 750 μg/mL purified mouse IgG in the standard membrane feeding assay (SMFA). At lower IgG concentrations, the bivalent vaccine did not improve TRA; antibodies induced by particleized Pfs25 alone showed stronger function in these conditions. In rabbits, immunization with a 20 µg total antigen dose with the duplexed antigens yielded similar antibody production against Pfs25 and Pfs230 compared to immunization with a 20 µg dose of individual antigens. However, no enhanced TRA was observed with duplexing. CONCLUSIONS: Pfs25, Pfs230 or the duplexed combination can readily be prepared as particulate vaccines by mixing CoPoP liposomes with soluble, recombinant antigens. This approach induces potent transmission-reducing antibodies following immunization in mice and rabbits. Immunization with bivalent, particleized, Pfs230 and Pfs25 did not yield antibodies with superior TRA compared to immunization with particleized Pfs25 as a single antigen. Altogether, duplexing antigens is straightforward and effective using CoPoP liposomes, but is likely to be more useful for targeting distinct parasite life stages."
2699,Comparative analysis of ankyrin (ANK) genes of five capripoxviruses isolate strains from Xinjiang province in China,"BACKGROUND: Sheeppox and goatpox are both economically important animal diseases in which pathogens are goatpox virus (GTPV) and sheeppox virus (SPPV). They can’t cause cross-species infection between sheep and goats in general. But in recent decades, the infection of sheep by goatpox or goats by sheeppox has been reported. The literature has indicated that the occurrence of these cases has a significant and direct relationship with mutations of ankyrin genes families (ANK genes 010,138,140,141.2,145) located in two-terminal regions of capripoxvirus genomes. So it is very important to decipher these nucleotides and their coding amino acid sequences of the five genes regarded as host range and virulence factors for effective prevention and control of capripoxvirus diseases. METHODS: In this study, all the ankyrin genes of three goatpox virus, two sheeppox virus, and one GTPV vaccine strains from Nanjiang areas of Xinjiang province of China during 2010–2011 were collected, amplified, cloned and sequenced. The sequence of every ankyrin genes has been compared with not only sequences from six viruses but also all sequences from three species of capripoxvirus genus from Gene bank, and every ANK gene’s mutated nucleotides and amino acids have been screened, and the relationship of genetic evolution among different virus strains has been analyzed, as well as the domain architecture of these genes was forecasted and analyzed. RESULTS: The six capripoxvirus strains can be well-distinguished GTPV and SPPV based on five ANK genes’ sequence identicalness except for GTPV-SS strain, which showed higher identicalness with SPPV. The ANK gene sequence of the GTPV-SS strain was 100% identical with SPPV-M1 (ANK138,140,145) and SPPV-M2 (ANK138,145), respectively. Phylogenetically, these six capripoxvirus strains were also grouped into the same cluster of India reference strains in lineages and showed extreme identical conservative or variable regions with India capripoxvirus isolates by sequence alignment. Moreover, for the functional domains, these ANK genes of capripoxvirus except for ANK gene 145, are identical in size, and ANK genes 145 of SPPV are usually 100 bp (approximately 30 aa) longer than those of GTPV and eventually form a PRANC domain at C-terminus. CONCLUSIONS: The isolated strain of GTPV-SS may be a cross-species infection or the collected material was contaminated, and the inferred Capripox outbreak in Xinjiang in 2010 can be introduced from India. ANK genes 138,140,141.2 and 145 of capripoxvirus can be used as the target genes to identify GTPV and SPPV. Moreover, the four ANK genes determining the host range are more significant than the ANK gene 010. These ANK genes play combining roles for their function."
2700,Geografische Ansätze in der Gesundheitsberichterstattung,"The interest in using geographic methods for health monitoring has grown strongly over the last two decades. Through these methods, analysis and visualization of health data can be more focused and target-group specific. The application in health monitoring is possible mostly due to broader technical possibilities and more available datasets. In this article, we show which geographic aspects are adapted in health monitoring at different levels (federal, state, municipality). For example, at the federal level, surveillance methods are used; at the state level health atlases are created; and on the municipality level geographic analyses are performed for possible public health interventions. Methods range from simple maps on different levels of aggregation to more complex methods like space-temporal visualization or spatial-smoothing methods. While the technical possibilities are in place, a broader implementation of geographic methods is mostly hindered by missing data access to small-area information and data protection policies. Better access to data could especially improve the possibility for geographic methods in health monitoring and could inform the population and decision makers to inform and improve population health or healthcare."
2701,Machine learning based refined differential gene expression analysis of pediatric sepsis,"BACKGROUND: Differential expression (DE) analysis of transcriptomic data enables genome-wide analysis of gene expression changes associated with biological conditions of interest. Such analysis often provides a wide list of genes that are differentially expressed between two or more groups. In general, identified differentially expressed genes (DEGs) can be subject to further downstream analysis for obtaining more biological insights such as determining enriched functional pathways or gene ontologies. Furthermore, DEGs are treated as candidate biomarkers and a small set of DEGs might be identified as biomarkers using either biological knowledge or data-driven approaches. METHODS: In this work, we present a novel approach for identifying biomarkers from a list of DEGs by re-ranking them according to the Minimum Redundancy Maximum Relevance (MRMR) criteria using repeated cross-validation feature selection procedure. RESULTS: Using gene expression profiles for 199 children with sepsis and septic shock, we identify 108 DEGs and propose a 10-gene signature for reliably predicting pediatric sepsis mortality with an estimated Area Under ROC Curve (AUC) score of 0.89. CONCLUSIONS: Machine learning based refinement of DE analysis is a promising tool for prioritizing DEGs and discovering biomarkers from gene expression profiles. Moreover, our reported 10-gene signature for pediatric sepsis mortality may facilitate the development of reliable diagnosis and prognosis biomarkers for sepsis."
2702,Crushing pancreatic enzymes with enteral feeds in an extremely premature infant with cystic fibrosis—a novel and effective technique,
2703,Qualitative analysis of latent safety threats uncovered by in situ simulation-based operations testing before moving into a single-family-room neonatal intensive care unit,"OBJECTIVES: We aimed to identify: (a) latent safety threats (LSTs) in a new neonatal intensive care unit (NICU) through simulation-based pre-occupancy operations testing, and (b) LSTs that remained unresolved 1-year post-occupancy. STUDY DESIGN: In this qualitative study, 111 healthcare professionals participated in patient care simulations and debriefings in a new NICU. Debriefing transcripts were inductively analyzed to characterize LSTs. Unresolved LSTs were identified 1 year after NICU occupancy. RESULTS: Thematic saturation was attained after analysis of nine debriefings. Four major themes affecting staff function and patient safety emerged from 305 threats: relay of information, workplace design, patient care processes, and patient family and staff focus. One-year post occupancy, 29 (9%) LSTs remained unresolved. CONCLUSION: Team debriefings of simulated patient events uncover LSTs that can largely be resolved before transitioning patient care into a new NICU. Understanding how LSTs interact provides a platform to develop viable strategies to mitigate patient safety risks."
2704,Influence of Corticosteroid Dose on Viral Shedding Duration in Patients With COVID-19,
2705,Blindness: behaviour in an epidemic(†),"In ‘Blindness’ José Saramago transports us into a society in which an unexpected epidemic of blindness spreads quickly, disseminating chaos between citizens and institutions. This new reality acts as a magnifying glass highlighting the weaknesses and (few) forces of individuals and community. From this masterpiece we can learn many insights useful to understand the SARS-CoV-2 pandemic."
2706,Assessment of workers’ personal vulnerability to covid-19 using ‘covid-age’,
2707,Social marketing interventions to promote physical activity among 60 years and older: a systematic review of the literature,"BACKGROUND: Falls are a significant source of morbidity in people aged 65 and over, affecting one in three people in this age group. The scientific evidence indicates that physical activity is the most effective method for preventing falls among seniors. Although public health professionals often use social marketing to design and plan successful interventions, its use to promote physical activity and prevent falls among older people remains low. This article aims to provide a new systematic literature review of social marketing interventions promoting physical activity and targeting people aged 60 and over. METHODS: Following CRD’s guidance and PRISMA guidelines, we searched between January 2008 and July 2019 for relevant articles in five primary databases using predefined search and inclusion criteria. Two independent reviewers analysed the selected articles to identify evidence of the seven social marketing benchmark criteria, defined by experts in the field as the common elements that contribute to social marketing success. RESULTS: The final review included nine studies. Of the studies selected, three specifically targeted over 60-year-olds, whereas the others segmented the population into several age-based subcategories, including over 60-year-olds. Eight studies highlighted positive results for the participants with an increase in participation or an increase in physical activity level. None of the nine studies selected for this systematic review implemented the entire social marketing approach. CONCLUSION: Few published interventions use the seven social marketing criteria. Further research is required to encourage uptake and inclusion in successful social marketing interventions to increase program effectiveness in this target population."
2708,Die wissenschaftlichen Beiträge und deren Auswahlverfahren für den 72. Kongress der Deutschen Gesellschaft für Urologie e. V. 2020,
2709,Visual Interpretability in Computer-Assisted Diagnosis of Thyroid Nodules Using Ultrasound Images,"BACKGROUND: The number of studies on deep learning in artificial intelligence (AI)-assisted diagnosis of thyroid nodules is increasing. However, it is difficult to explain what the models actually learn in artificial intelligence-assisted medical research. Our aim is to investigate the visual interpretability of the computer-assisted diagnosis of malignant and benign thyroid nodules using ultrasound images. MATERIAL/METHODS: We designed and implemented 2 experiments to test whether our proposed model learned to interpret the ultrasound features used by ultrasound experts to diagnose thyroid nodules. First, in an anteroposterior/transverse (A/T) ratio experiment, multiple models were trained by changing the A/T ratio of the original nodules, and their classification, accuracy, sensitivity, and specificity were tested. Second, in a visualization experiment, class activation mapping used global average pooling and a fully connected layer to visualize the neural network to show the most important features. We also examined the importance of data preprocessing. RESULTS: The A/T ratio experiment showed that after changing the A/T ratio of the nodules, the accuracy of the neural network model was reduced by 9.24–30.45%, indicating that our neural network model learned the A/T ratio information of the nodules. The visual experiment results showed that the nodule margins had a strong influence on the prediction of the neural network. CONCLUSIONS: This study was an active exploration of interpretability in the deep learning classification of thyroid nodules. It demonstrated the neural network-visualized model focused on irregular nodule margins and the A/T ratio to classify thyroid nodules."
2710,Cell type- and replication stage-specific influenza virus responses in vivo,"Influenza A viruses (IAVs) remain a significant global health burden. Activation of the innate immune response is important for controlling early virus replication and spread. It is unclear how early IAV replication events contribute to immune detection. Additionally, while many cell types in the lung can be infected, it is not known if all cell types contribute equally to establish the antiviral state in the host. Here, we use single-cycle influenza A viruses (scIAVs) to characterize the early immune response to IAV in vitro and in vivo. We found that the magnitude of virus replication contributes to antiviral gene expression within infected cells prior to the induction of a global response. We also developed a scIAV that is only capable of undergoing primary transcription, the earliest stage of virus replication. Using this tool, we uncovered replication stage-specific responses in vitro and in vivo. Using several innate immune receptor knockout cell lines, we identify RIG-I as the predominant antiviral detector of primary virus transcription and amplified replication in vitro. Through a Cre-inducible reporter mouse, we used scIAVs expressing Cre-recombinase to characterize cell type-specific responses in vivo. Individual cell types upregulate unique sets of antiviral genes in response to both primary virus transcription and amplified replication. We also identified antiviral genes that are only upregulated in response to direct infection. Altogether, these data offer insight into the early mechanisms of antiviral gene activation during influenza A infection."
2711,The role of the NMD factor UPF3B in olfactory sensory neurons,"The UPF3B-dependent branch of the nonsense-mediated RNA decay (NMD) pathway is critical for human cognition. Here, we examined the role of UPF3B in the olfactory system. Single-cell RNA-sequencing (scRNA-seq) analysis demonstrated considerable heterogeneity of olfactory sensory neuron (OSN) cell populations in wild-type (WT) mice, and revealed that UPF3B loss influences specific subsets of these cell populations. UPF3B also regulates the expression of a large cadre of antimicrobial genes in OSNs, and promotes the selection of specific olfactory receptor (Olfr) genes for expression in mature OSNs (mOSNs). RNA-seq and Ribotag analyses identified classes of mRNAs expressed and translated at different levels in WT and Upf3b-null mOSNs. Integrating multiple computational approaches, UPF3B-dependent NMD target transcripts that are candidates to mediate the functions of NMD in mOSNs were identified in vivo. Together, our data provides a valuable resource for the olfactory field and insights into the roles of NMD in vivo."
2712,Electronic Mental Health as an Option for Egyptian Psychiatry: Cross-Sectional Study,"BACKGROUND: Egypt is a country of nearly 100 million citizens, and there are less than 1000 registered psychiatrists. The mental health care system is under resourced and nearly inaccessible for the majority of the population. In addition, youth under the age of 25 years represent 50% of Egyptian citizens; however, there are no specific services addressing their unique needs. How can the needs of the largest population in the Middle East be effectively addressed? Is a web-based framework an option for Egyptian psychiatrists to serve the population? OBJECTIVE: The aims of this study were to better understand the opinions of psychiatrists on the current state of mental health care services in Egypt and their current knowledge on electronic mental health (EMH); assess the attitudes of Egyptian psychiatrists toward web-based interventions and telemedicine for mental health; and identify perceived advantages and barriers of EMH development in Egypt. METHODS: A cross-sectional survey was conducted online among 640 Egyptian psychiatrists. It included a total of 36 items within a set of 16 questions asking about EMH literacy, integrating EMH into the mental health care system, and the perceived priorities and barriers of EMH. The sampling was supported by Tanta University, a large academic institution close to Cairo. Statistical analysis was performed using SPSS 25 (IBM Corp). Descriptive statistics, the chi-square test, the independent sample t test, and analysis of variance were applied. RESULTS: A total of 188 participants responded (response rate of 29.4%), of which 54.2% (102/188) were female and 54.3% (102/188) were between 30 and 45 years old. Less than half of the participants thought that the current health care system was efficient for adults (69/155, 44.4%), and even less thought it was efficient for youth (44/155, 28.3%). Almost all participants agreed that EMH would be beneficial for patient care (147/155, 94.8%) and that integrating EMH into the current health care system would be a good idea (118/155, 76.2%). The highest rated utility of web-based solutions was documentation, followed by psychoeducation and communication with professionals. The main advantages were to improve access to care in rural areas of the country and its convenience. CONCLUSIONS: There is scarcity of mental health resources in Egypt. Egyptian psychiatrists are interested in EMH and believe web-based platforms can become part of the solution for the Egyptian mental health care system."
2713,Letter to the editor: importance of a careful investigation to avoid attributing Legionnaires’ disease cases to an incorrect source of infection,
2714,The Impact of Accidental Hypothermia on Mortality in Trauma Patients Overall and Patients with Traumatic Brain Injury Specifically: A Systematic Review and Meta-Analysis,"BACKGROUND: Accidental hypothermia is a known predictor for worse outcomes in trauma patients, but has not been comprehensively assessed in a meta-analysis so far. The aim of this systematic review and meta-analysis was to investigate the impact of accidental hypothermia on mortality in trauma patients overall and patients with traumatic brain injury (TBI) specifically. METHODS: This is a systematic review and meta-analysis using the Ovid Medline/PubMed database. Scientific articles reporting accidental hypothermia and its impact on outcomes in trauma patients were included in qualitative synthesis. Studies that compared the effect of hypothermia vs. normothermia at hospital admission on in-hospital mortality were included in two meta-analyses on (1) trauma patients overall and (2) patients with TBI specifically. Meta-analysis was performed using a Mantel–Haenszel random-effects model. RESULTS: Literature search revealed 264 articles. Of these, 14 studies published 1987–2018 were included in the qualitative synthesis. Seven studies qualified for meta-analysis on trauma patients overall and three studies for meta-analysis on patients with TBI specifically. Accidental hypothermia at admission was associated with significantly higher mortality both in trauma patients overall (OR 5.18 [95% CI 2.61–10.28]) and patients with TBI specifically (OR 2.38 [95% CI 1.53–3.69]). CONCLUSIONS: In the current meta-analysis, accidental hypothermia was strongly associated with higher in-hospital mortality both in trauma patients overall and patients with TBI specifically. These findings underscore the importance of measures to avoid accidental hypothermia in the prehospital care of trauma patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00268-020-05750-5) contains supplementary material, which is available to authorized users."
2715,Clinical Trials for Inflammatory Bowel Disease: Global Guidance During the COVID-19 Pandemic,
2716,A special collection of reviews on frontiers in immunology,
2717,Thank you for sharing,"The pandemic has highlighted long-standing, deep-rooted challenges to the sharing of biological samples. Greater attention is needed to mechanisms for incentivizing materials transfer."
2718,"On “Translating COVID-19 Evidence to Maximize Physical Therapists’ Impact and Public Health Response.” Dean E, Jones A, Yu H.P-M., Gosselink R, Skinner M. [Published Online Ahead of Print June 26, 2020] Phys Ther. 2020. DOI: https://doi.org/10.1093/ptj/pzaa115. Implications for Advancing Therapy Education, Practice and Public health in China",
2719,One-year survival of patients with high-grade glioma discharged alive from the intensive care unit,"INTRODUCTION: Only limited data are available regarding the long-term prognosis of patients with high-grade glioma discharged alive from the intensive care unit. We sought to quantify 1-year mortality and evaluate the association between mortality and (1) functional status, and (2) management of anticancer therapy in patients with high-grade glioma discharged alive from the intensive care unit. PATIENTS AND METHODS: Retrospective observational cohort study of patients with high-grade glioma admitted to two intensive care units between January 2009 and June 2018. Functional status was assessed by the Karnofsky Performance Status. Anticancer therapy after discharge was classified as (1) continued (unchanged), (2) modified (changed or stopped), or (3) initiated (for newly diagnosed disease). RESULTS: Ninety-one high-grade glioma patients (73% of whom had glioblastoma) were included and 78 (86%) of these patients were discharged alive from the intensive care unit. Anticancer therapy was continued, modified, and initiated in 41%, 42%, and 17% of patients, respectively. Corticosteroid therapy at the time of ICU admission [odds ratio (OR) 0.07] and cancer progression (OR 0.09) was independently associated with continuation of anticancer therapy. The mortality rate 1 year after ICU admission was 73%. On multivariate analysis, continuation of anticancer therapy (OR 0.18) and Karnofsky performance status on admission (OR 0.90) were independently associated with lower 1-year mortality. CONCLUSION: The presence of high-grade glioma is not sufficient to justify refusal of intensive care unit admission. Performance status and continuation of anticancer therapy are associated with higher survival after intensive care unit discharge. PREVIOUS PRESENTATION: Preliminary results were presented at the most recent congress of the French Intensive Care Society, Paris, 2019. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00415-020-10191-0) contains supplementary material, which is available to authorized users."
2720,First in the Nation: Washington State's Long‐Term Care Trust Act,
2721,Determining the ideal prevention strategy for multidrug-resistance organisms in resource-limited countries: a cost-effectiveness analysis study,"The aim of this study was to determine the most cost-effective strategy for the prevention and control of multidrug-resistant organisms (MDROs) in intensive care units (ICUs) in areas with limited health resources. The study was conducted in 12 ICUs of four hospitals. The total cost for the prevention of MDROs and the secondary attack rate (SAR) of MDROs for each strategy were collected retrospectively from 2046 subjects from January to December 2017. The average cost-effectiveness ratio (CER), incremental cost-effectiveness ratio (ICER) and cost-effectiveness acceptability curve were calculated. Hand hygiene (HH) had the lowest total cost (2149.6 RMB) and SAR of MDROs (8.8%) while single-room isolation showed the highest cost (33 700.2 RMB) and contact isolation had the highest SAR of MDROs (31.8%). The average cost per unit infection prevention was 24 427.8 RMB, with the HH strategy followed by the environment disinfection strategy (CER = 21 314.67). HH had the highest iterative cost effect under willingness to pay less than 2000 RMB. Due to the low cost for repeatability and obvious effectiveness, we conclude that HH is the optimal strategy for MDROs infections in ICUs in developing countries. The cost-effectiveness of the four prevention strategies provides some reference for developing countries but multiple strategies remain to be examined."
2722,Error in Figure,
2723,Error in Author Affiliation,
2724,A multilevel analysis of short birth interval and its determinants among reproductive age women in developing regions of Ethiopia,"BACKGROUND: Short Birth Interval negatively affects the health of both mothers and children in developing nations, like, Ethiopia. However, studies conducted to date in Ethiopia upon short birth interval were inconclusive and they did not show the extent and determinants of short birth interval in developing (Afar, Somali, Gambella, and Benishangul-Gumuz) regions of the country. Thus, this study was intended to assess the short birth interval and its determinants in the four developing regions of the country. METHODS: Data were retrieved from the Demographic and Health Survey program official database website (http://dhsprogram.com). A sample of 2683 women of childbearing age group (15–49) who had at least two alive consecutive children in the four developing regions of Ethiopia was included in this study. A multilevel multivariable logistic regression model was fitted to identify the independent predictors of short birth interval and Akaike’s Information Criterion (AIC) was used during the model selection procedure. RESULTS: In this study, the prevalence of short birth interval was 46% [95% CI; 43.7%, 47.9%]. The multilevel multivariable logistic regression model showed women living in rural area [AOR = 1.52, CI: 1.12, 2.05], women attended secondary education and above level [AOR = 0.27, CI: 0.05, 0.54], have no media exposure [AOR = 1.35, CI: 1.18, 1.56], female sex of the index child [AOR = 1.13, CI:1.07,1.20], breastfeeding duration [AOR = 0.79, CI: 0.77, 0.82], having six and more ideal number of children [AOR = 1.14, CI: 1.09, 1.20] and having preferred waiting time to birth two years and above [AOR = 0.86, CI: 0.78, 0.95] were the predictors of short birth interval. CONCLUSIONS: The prevalence of short birth intervals in the developing regions of Ethiopia is still high. Therefore, the government of Ethiopia should work on the access of family planning and education in rural parts of the developing regions where more than 90% of the population in these regions is pastoral."
2725,Mathematically modeling spillovers of an emerging infectious zoonosis with an intermediate host,"Modeling the behavior of zoonotic pandemic threats is a key component of their control. Many emerging zoonoses, such as SARS, Nipah, and Hendra, mutated from their wild type while circulating in an intermediate host population, usually a domestic species, to become more transmissible among humans, and this transmission route will only become more likely as agriculture and trade intensifies around the world. Passage through an intermediate host enables many otherwise rare diseases to become better adapted to humans, and so understanding this process with accurate mathematical models is necessary to prevent epidemics of emerging zoonoses, guide policy interventions in public health, and predict the behavior of an epidemic. In this paper, we account for a zoonotic disease mutating in an intermediate host by introducing a new mathematical model for disease transmission among three species. We present a model of these disease dynamics, including the equilibria of the system and the basic reproductive number of the pathogen, finding that in the presence of biologically realistic interspecies transmission parameters, a zoonotic disease with the capacity to mutate in an intermediate host population can establish itself in humans even if its R(0) in humans is less than 1. This result and model can be used to predict the behavior of any zoonosis with an intermediate host and assist efforts to protect public health."
2726,Past world economic production constrains current energy demands: Persistent scaling with implications for economic growth and climate change mitigation,"Climate change has become intertwined with the global economy. Here, we describe the contribution of inertia to future trends. Drawing from thermodynamic principles, and using 38 years of available statistics between 1980 to 2017, we find a constant scaling between current rates of world primary energy consumption [Image: see text] and the historical time integral W of past world inflation-adjusted economic production Y, or [Image: see text] . In each year, over a period during which both [Image: see text] and W more than doubled, the ratio of the two remained nearly unchanged, that is [Image: see text] Gigawatts per trillion 2010 US dollars. What this near constant implies is that current growth trends in energy consumption, population, and standard of living, perhaps counterintuitively, are determined by past innovations that have improved the economic production efficiency, or enabled use of less energy to transform raw materials into the makeup of civilization. Current observed growth rates agree well with predictions derived from available historical data. Future efforts to stabilize carbon dioxide emissions are likely also to be constrained by the contributions of past innovation to growth. Assuming no further efficiency gains, options look limited to rapid decarbonization of energy consumption through sustained implementation of at least one Gigawatt of renewable or nuclear power capacity per day. Alternatively, with continued reliance on fossil fuels, civilization could shift to a steady-state economy, one that devotes economic production exclusively to maintining ongoing metabolic needs rather than to material expansion. Even if such actions could be achieved immediately, energy consumption would continue at its current level, and atmospheric carbon dioxide concentrations would only begin to balance natural sinks at concentrations exceeding 500 ppmv."
2727,Canine vaccination in Germany: A survey of owner attitudes and compliance,"BACKGROUND: Vaccination is the most important preventive measure for protection against infectious diseases in humans and companion animals. Nevertheless, scepticism about the safety and importance of vaccines is increasing in human and in veterinary medicine. Although owner attitudes towards vaccination have been investigated in cats, there are no similar studies in dogs. The goals of this study were therefore to investigate the vaccination status of dogs in Germany, to determine owner compliance with vaccination and to identify factors that play a role in owners’ decisions to have their dogs vaccinated. METHODS: Data were collected from August 2018 to February 2019 using an online survey targeting dog owners in Germany. A total of 3,881 questionnaires were evaluated, and factors associated with the vaccination status of dogs were determined by a linear logistic regression model using Akaike information criterion. Cohen's kappa statistic was used to evaluate agreement between questionnaire and 340 vaccination passports submitted voluntarily by owners. RESULTS: A total of 46.8% (n = 1,818/3,881) of dogs were vaccinated with core vaccines according to current guidelines with the lowest vaccination rate for leptospirosis (50.1%; n = 1,941/3,874). Dog’s age (16 weeks to 15 months) (odds ratio (OR): 3.08; 95% CI: 2.05–4.68), type (working dog) (OR: 2.06; 95% CI: 1.22–3.53) and travelling abroad within previous 36 months (OR: 1.82; 95% CI: 1.12–2.96) had the strongest ‘positive’ association with the vaccination status. Recommendation from a veterinarian not to vaccinate against leptospirosis had the strongest ‘negative’ association (OR: 0.08; 95% CI: 0.04–0.18). CONCLUSION: The study revealed a need for improvement in vaccination compliance because of inadequate vaccination coverage, especially for leptospirosis, in dogs. Factors influencing owner compliance were numerous. Vaccination recommendations made by the veterinarian had a strong association with the vaccination status and should be used to increase canine vaccination rates."
2728,"Notes from the Field: CDC Polio Surge Response to Expanding Outbreaks of Type 2 Circulating Vaccine-Derived Poliovirus — Africa and Philippines, September 2019–March 2020",
2729,Assessing 3 Outbreak Detection Algorithms in an Electronic Syndromic Surveillance System in a Resource-Limited Setting,"We evaluated the performance of X-bar chart, exponentially weighted moving average, and C3 cumulative sums aberration detection algorithms for acute diarrheal disease syndromic surveillance at naval sites in Peru during 2007–2011. The 3 algorithms’ detection sensitivity was 100%, specificity was 97%–99%, and positive predictive value was 27%–46%."
2730,"Hepatitis E Virus Genotype 7 RNA and Antibody Kinetics in Naturally Infected Dromedary Calves, United Arab Emirates","Orthohepevirus A genotype 7 is a novel zoonotic variant of hepatitis E virus. To clarify infection in the animal reservoir, we virologically monitored 11 dromedary dam–calf pairs. All calves became infected during the first 6 months of life and cleared the virus after an average of 2 months. Dams did not become infected."
2731,Nonpharmaceutical Measures for Pandemic Influenza in Nonhealthcare Settings—International Travel-Related Measures,
2732,"Identification of Streptococcus suis Meningitis by Direct Triplex Real-Time PCR, Burkina Faso","Meningitis confirmation in Burkina Faso uses PCR for detecting Streptococcus pneumoniae, Neisseria meningitidis, or Hemophilus influenzae. We identified 38 cases of meningitis among 590 that were PCR-positive for 3 nonpneumococcal streptococcal pathogens, including 21 cases of Streptococcus suis. Among the country’s 13 regions, 10 had S. suis–positive cases."
2733,"Vital Signs: Clinical Characteristics of Patients with Confirmed Acute Flaccid Myelitis, United States, 2018","BACKGROUND: Acute flaccid myelitis (AFM) is a serious neurologic syndrome that affects mostly children and is characterized by the acute onset of limb weakness or paralysis. Since U.S. surveillance for AFM began in 2014, reported cases have peaked biennially. This report describes the clinical characteristics of AFM patients during 2018, the most recent peak year. METHODS: Medical records from persons meeting AFM clinical criterion (acute onset of flaccid limb weakness) were submitted to CDC. Patients with confirmed AFM met the clinical criterion and had magnetic resonance imaging indicating spinal cord lesions largely restricted to gray matter and spanning one or more vertebral segments. Symptoms, physical findings, test and imaging results, and hospitalization data were abstracted and described. RESULTS: Among 238 patients with confirmed AFM during 2018, median age was 5.3 years. Among the 238 patients, 205 (86%) had onset during August–November. Most (92%) had prodromal fever, respiratory illness, or both beginning a median of 6 days before weakness onset. In addition to weakness, common symptoms at clinical evaluation were gait difficulty (52%), neck or back pain (47%), fever (35%), and limb pain (34%). Among 211 who were outpatients when weakness began, most (76%) sought medical care within 1 day, and 64% first sought treatment at an emergency department. Overall, 98% of patients were hospitalized, 54% were admitted to an intensive care unit, and 23% required endotracheal intubation and mechanical ventilation. CONCLUSION: Clinicians should suspect AFM in children with acute flaccid limb weakness, especially during August–November and when accompanied by neck or back pain and a recent history of febrile respiratory illness. Increasing awareness in frontline settings such as emergency departments should aid rapid recognition and hospitalization for AFM."
2734,"Is Exercise the Best Medicine during a COVID-19 Pandemic? Comment on Constandt, B.; Thibaut, E.; De Bosscher, V.; Scheerder, J.; Ricour, M.; Willem, A. Exercising in Times of Lockdown: An Analysis of the Impact of COVID-19 on Levels and Patterns of Exercise among Adults in Belgium. Int. J. Environ. Res. Public Health 2020, 17, 4144","From Constandt et al.’s survey of 13,515 Belgium respondents, regular physical activity can be successfully initiated and sustained during a lockdown, with appropriate social distancing measures. Documentation that 77% of highly active people and 58% of low active people exercised as much or more following the institution of a nationwide lockdown was impressive, given that the cases of COVID-19 were accelerating at that time. The Belgian government’s central promotion of exercise, to boost both the mental and physical health of the population, likely contributed to the health, tolerance, and ultimate success of lockdown. In this commentary, we wish to pose a follow-up query which highlights the potential detrimental effects of intense exercise (competition) performed without social distancing measures. The proposed graphical abstract elucidates these possible risks, in contrast to the favorable results outlined in Constandt et al.’s study."
2735,“NO LOAD” Resistance Training Promotes High Levels of Knee Extensor Muscles Activation—A Pilot Study,"The present article aims to compare electromyographic (EMG) activity of the knee extensors during traditional resistance training (TRT) and no load resistance training with or without visual feedback (NL-VF and NL-NF). Sixteen healthy men (age: 25.2 ± 3.6) volunteered to participate in the study. Participants visited the laboratory on three occasions involving: (1) a 10 repetition maximum test (10 RM test), (2) familiarization and (3) performance of knee extensions using TRT, NL-VF and NL-NF in a random order, with 10 min of rest between them. TRT involved the performance of a set to momentary muscle failure using the 10 RM load. NL-NF involved the performance of 10 repetitions with no external load, but with the intention to maximally contract the muscles during the whole set. NL-VF involved the same procedure as NL-NF, but a monitor was positioned in front of the participants to provide visual feedback on the EMG activity. Peak and mean EMG activity were evaluated on the vastus medialis (VM), vastus lateralis (VL) and rectus femoris (RF). Results: there were no significant differences in VM and VL peak EMG activity among different situations. There was a significant difference for peak EMG activity for RF, where TRT resulted in higher values than NL-VF and NL-NF (p < 0.05). Higher values of mean EMG activity were found for VM, VL and RF during TRT in comparison with both NL-VF and NL-NF. Conclusions: resistance training with no external load produced high levels of peak muscle activation, independent of visual feedback, but mean activation was higher during TRT. These results suggest that training with no external load might be used as a strategy for stimulating the knee extensors when there is limited access to specialized equipment. Although the clinical applications of no load resistance training are promising, it is important to perform long-term studies to test if these acute results will reflect in muscle morphological and functional changes."
2736,MCMV Dissemination from Latently-Infected Allografts Following Transplantation into Pre-Tolerized Recipients,"Transplantation tolerance is achieved when recipients are unresponsive to donor alloantigen yet mobilize against third-party antigens, including virus. After transplantation, cytomegalovirus (CMV) reactivation in latently-infected transplants reduces allograft viability. To determine if pre-tolerized recipients are resistant to viral dissemination in this setting, we transfused chemically-fixed donor splenocytes (1-ethyl-3- (3′-dimethyl-aminopropyl)-carbo-diimide (ECDI)-treated splenocytes (ECDIsp)) to induce donor antigen tolerance without immunosuppression. In parallel, we implanted donor islet cells to validate operational tolerance. These pre-tolerized recipients were implanted with murine CMV (MCMV) latently-infected donor kidneys (a validated model of CMV latency) to monitor graft inflammation and viral dissemination. Our results indicate that tolerance to donor islets was sustained in recipients after implantation of donor kidneys. In addition, kidney allografts implanted after ECDIsp and islet implantation exhibited low levels of fibrosis and tubulitis. In contrast, kidney cellular and innate immune infiltrates trended higher in the CMV group and exhibited increased markers of CD8(+) T cell activation. Tolerance induction was unable to prevent increases in MCMV-specific CD8(+) T cells or dissemination of viral IE-1 DNA. Our data suggest that latently-infected allografts are inherently more susceptible to inflammation that is associated with viral dissemination in pre-tolerized recipients. Thus, CMV latently-infected allografts require enhanced strategies to protect allograft integrity and viral spread."
2737,Unique Polyhalogenated Peptides from the Marine Sponge Ircinia sp.,"Two new bromopyrrole peptides, haloirciniamide A (1) and seribunamide A (2), have been isolated from an Indonesian marine sponge of the genus Ircinia collected in the Thousand Islands (Indonesia). The planar structure of both compounds was assigned on the basis of extensive 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration of the amino acid residues in 1 and 2 was determined by the application of Marfey’s method. Compound 1 is the first dibromopyrrole cyclopeptide having a chlorohistidine ring, while compound 2 is a rare peptide possessing a tribromopyrrole ring. Both compounds failed to show significant cytotoxicity against four human tumor cell lines, and neither compound was able to inhibit the enzyme topoisomerase I or impair the interaction between programmed cell death protein PD1 and its ligand, PDL1."
2738,A System Dynamics Simulation Applied to Healthcare: A Systematic Review,"In recent years, there has been significant interest in developing system dynamics simulation models to analyze complex healthcare problems. However, there is a lack of studies seeking to summarize the available papers in healthcare and present evidence on the effectiveness of system dynamics simulation in this area. The present paper draws on a systematic selection of published literature from 2000 to 2019, in order to form a comprehensive view of current applications of system dynamics methodology that address complex healthcare issues. The results indicate that the application of system dynamics has attracted significant attention from healthcare researchers since 2013. To date, articles on system dynamics have focused on a variety of healthcare topics. The most popular research areas among the reviewed papers included the topics of patient flow, obesity, workforce demand, and HIV/AIDS. Finally, the quality of the included papers was assessed based on a proposed ranking system, and ways to improve the system dynamics models’ quality were discussed."
2739,Response to the Letter: How do we reopen our motility laboratory safely and efficiently?,
2740,"COVID‐19, Black Lives Matter and making a difference",
2741,Stronger Together: Multivalent Phage Capsids Inhibit Virus Entry,"Antivirals are now more important than ever. To efficiently inhibit virus replication, antiviral multivalent strategies need sufficient affinity to overcome the excellent matching between the virus and its receptor. This report highlights a phage capsid scaffold strategy that can be used to precisely position sialic acid moieties to inhibit influenza A virus replication"
2742,"Telehealth—Improving access for rural, regional and remote communities",
2743,Taking Perioperative Nursing Skills Back to the Bedside in Response to the Pandemic,
2744,Preparing for the next infectious disease pandemic,
2745,"The plural of anecdote is not data, please mind the gap between virtual and real life",
2746,Subphenotyping Acute Respiratory Distress Syndrome in Patients with COVID-19: Consequences for Ventilator Management,
2747,COVID-19 Lung Injury and “Typical” Acute Respiratory Distress Syndrome: The Danger of Presumed Equivalency,
2748,Identifying mutations in Tunisian families with retinal dystrophy,"Retinal dystrophies (RD) are a rare genetic disorder with high genetic heterogeneity. This study aimed at identifying disease-causing variants in fifteen consanguineous Tunisian families. Full ophthalmic examination was performed. Index patients were subjected to IROme analysis or whole exome sequencing followed by homozygosity mapping. All detected variations were confirmed by direct Sanger sequencing. Mutation analysis in our patients revealed two compound heterozygous mutations p.(R91W);(V172D) in RPE65, and five novel homozygous mutations: p.R765C in CNGB1, p.H337R in PDE6B, splice site variant c.1129-2A > G and c.678_681delGAAG in FAM161A and c.1133 + 3_1133 + 6delAAGT in CERKL. The latter mutation impacts pre-mRNA splicing of CERKL. The other changes detected were six previously reported mutations in CNGB3 (p.R203*), ABCA4 (p.W782*), NR2E3 (p.R311Q), RPE65 (p.H182Y), PROM1 (c.1354dupT) and EYS (c.5928-2A > G). Segregation analysis in each family showed that all affected individuals were homozygotes and unaffected individuals were either heterozygote carriers or homozygous wild type allele. These results confirm the involvement of a large number of genes in RD in the Tunisian population."
2749,Corrigendum: Investigating starch gelatinization through Stokes vector resolved second harmonic generation microscopy,
2750,Author Correction: Biodiversity estimates and ecological interpretations of meiofaunal communities are biased by the taxonomic approach,
2751,Non-locality and the misdiagnosis of Spinal Cord Injury Without Radiographic Abnormality: proof of concept,"STUDY DESIGN: This is a retrospective review. OBJECTIVES: To validate the concept of “non-locality” to explain cases of Spinal Cord Injury Without Radiographic Abnormality (SCIWORA) previously deemed inexplicable. To investigate and challenge the source data for the SCIWORA hypothesis which has the built-in assumption that a traumatic spinal cord injury (SCI) can only be caused by a local or adjacent spinal column injury and which, therefore, postulates that the pediatric spinal column is inherently more flexible than the spinal cord to explain SCI whenever a local spinal column injury is not detected. SETTING: A National Rehabilitation Center, one of fourteen which reports to the Spinal Cord Injury Model System. METHODS: We examined all residual SCIWORA cases over a 5-year period. In addition, we performed an extensive literature search to trace the evidence supporting the SCIWORA hypothesis that children’s spinal columns are inherently lax and may stretch more than the spinal cord prior to disruption. RESULTS: Six SCI patients with a residual diagnosis of SCIWORA were identified, 3 pediatric and 3 adult. All had injuries fitting non-locality. None were an actual SCIWORA. Source data do not appear to support the SCIWORA hypothesis. CONCLUSION: Borrowing from quantum mechanics, we reveal non-locality as a real entity in the spine. The assumption of locality-only is invalid and likely contributed to the SCIWORA hypothesis for the pediatric spine. Misdiagnosis and misunderstanding of SCIWORA may lead to improper treatment and increased cost. Awareness may facilitate search for adequate explanations for difficult cases rather than mere assignment as SCIWORA."
2752,Correction: Traumatic spinal cord injury due to human tower accident in Catalonia,
2753,Correction: Severe chronic pain following spinal cord damage: a pragmatic perspective for prescribing opioids,
2754,Proximal femoral resection and Tensor Fascia Lata flap for recalcitrant trochanteric pressure ulcers,"INTRODUCTION: Trochanteric pressure ulcers (PrUs) are difficult to treat and are often complicated by infection spreading to the hip joint. We review three cases from India where proximal femoral resection and pedicled Tensor Fascia Lata (TFL) flapping was used in the management of infected deep trochanteric ulcers communicating to the hip joint. CASE PRESENTATION: Three patients had a total of four trochanteric PrUs communicating to the hip joint. Proximal femoral resection along with radical debridement of the pressure ulcer (PrU) was the first step in our surgical protocol. Serial debridements were performed to make the resulting cavity healthier and ready for the subsequent flap surgery. TFL flapping was done to cover the raw area of the PrU and the donor site was closed either primarily or with a split skin graft. All patients were males with AIS A spinal cord injury (SCI) and stage 4 PrUs in the trochanteric region. One patient had bilateral trochanteric ulcers. There was complete healing of all PrUs with improvement in wheelchair mobility, and general health. DISCUSSION: PrUs are a common complication of patients with SCI and are often considered one of the most neglected issues of health care delivery in India. Proximal femoral resection with pedicled TFL muscle flap is a versatile and reliable procedure for the coverage of recalcitrant trochanteric PrU with hip joint involvement. Minimal donor site morbidity occurs."
2755,Survey on current treatments for pain after spinal cord damage,"STUDY DESIGN: An online questionnaire. OBJECTIVES: To assess the international spinal cord medicine and rehabilitation community’s utilization of pharmacological and non-pharmacological treatments for spinal cord damage (SCD)-related pain and to determine whether approaches to SCD-related pain differ between developed and less developed nations. SETTING: An international collaboration of authors. METHODS: An on-line survey querying availability and utilization of a number of approaches to SCD-related pain was developed, distributed, and made available for 6 months. Responses were analyzed for the entire cohort and according to participants’ descriptions of their home nations’ economies. RESULTS: A total of 153 responses were submitted, mostly from developed nations. Nearly three quarters of subjects reported offering their patients with SCD narcotics; only 13% reported offering their patients with SCD medical cannabis. Subjects from developing countries were more likely than those from developed countries to prescribe buprenorphine (20.0% vs 15.6%; p = 0.001) and less likely to prescribe medical cannabis (0% vs 15.6%; p = 0.001) and acupuncture (4.0% vs 23.4%; p = 0.02). CONCLUSIONS: Most spinal cord medicine clinicians employ a multimodal approach to pain. There are significant differences in utilization of pharmacologic and non-pharmacologic approach to SCD-related pain between clinicians from more and less developed countries."
2756,Citrullination mediated by PPAD constrains biofilm formation in P. gingivalis strain 381,"Porphyromonas gingivalis is the only known human-associated prokaryote that produces a peptidylarginine deiminase (PPAD), a protein-modifying enzyme that is secreted along with a number of virulence factors via a type IX secretion system (T9SS). While the function of PPAD in P. gingivalis physiology is not clear, human peptidylarginine deiminases are known to convert positively charged arginine residues within proteins to neutral citrulline and, thereby, impact protein conformation and function. Here, we report that the lack of citrullination in a PPAD deletion mutant (Δ8820) enhances biofilm formation. More Δ8820 cells attached to the surface than the parent strain during the early stages of biofilm development and, ultimately, mature Δ8820 biofilms were comprised of significantly more cell–cell aggregates and extracellular matrix. Imaging by electron microscopy discovered that Δ8820 biofilm cells secrete copious amounts of protein aggregates. Furthermore, gingipain-derived adhesin proteins, which are also secreted by the T9SS were predicted by mass spectrometry to be citrullinated and citrullination of these targets by wild-type strain 381 in vitro was confirmed. Lastly, Δ8820 biofilms contained more gingipain-derived adhesin proteins and more gingipain activity than 381 biofilms. Overall, our findings support the model that citrullination of T9SS cargo proteins known to play a key role in colonization, such as gingipain-derived adhesin proteins, is an underlying mechanism that modulates P. gingivalis biofilm development."
2757,Polymicrobial synergy within oral biofilm promotes invasion of dendritic cells and survival of consortia members,"Years of human microbiome research have confirmed that microbes rarely live or function alone, favoring diverse communities. Yet most experimental host-pathogen studies employ single species models of infection. Here, the influence of three-species oral microbial consortium on growth, virulence, invasion and persistence in dendritic cells (DCs) was examined experimentally in human monocyte-derived dendritic cells (DCs) and in patients with periodontitis (PD). Cooperative biofilm formation by Streptococcus gordonii, Fusobacterium nucleatum and Porphyromonas gingivalis was documented in vitro using growth models and scanning electron microscopy. Analysis of growth rates by species-specific 16s rRNA probes revealed distinct, early advantages to consortium growth for S. gordonii and F. nucleatum with P. gingivalis, while P. gingivalis upregulated its short mfa1 fimbriae, leading to increased invasion of DCs. F. nucleatum was only taken up by DCs when in consortium with P. gingivalis. Mature consortium regressed DC maturation upon uptake, as determined by flow cytometry. Analysis of dental plaques of PD and healthy subjects by 16s rRNA confirmed oral colonization with consortium members, but DC hematogenous spread was limited to P. gingivalis and F. nucleatum. Expression of P. gingivalis mfa1 fimbriae was increased in dental plaques and hematogenous DCs of PD patients. P. gingivalis in the consortium correlated with an adverse clinical response in the gingiva of PD subjects. In conclusion, we have identified polymicrobial synergy in a three-species oral consortium that may have negative consequences for the host, including microbial dissemination and adverse peripheral inflammatory responses."
2758,"On the nature of “skeletal” biofilm patterns, “hidden” heterogeneity and the role of bubbles to reveal them",A short communication on the recent paper by Jang et al. discusses the role of “mushroom” structures and effects of nearly static bubbles on nascent biofilms.
2759,A metabolomic study of the effect of Candida albicans glutamate dehydrogenase deletion on growth and morphogenesis,"There are two glutamate dehydrogenases in the pathogenic fungus Candida albicans. One is an NAD(+)-dependent glutamate dehydrogenase (GDH2) and the other is an NADPH-dependent glutamate dehydrogenase (GDH3). These two enzymes are part of the nitrogen and nicotinate/nicotinamide metabolic pathways, which have been identified in our previous studies as potentially playing an important role in C. albicans morphogenesis. In this study, we created single gene knockout mutants of both dehydrogenases in order to investigate whether or not they affect the morphogenesis of C. albicans. The GDH genes were deleted and the phenotypes of the knockout mutants were studied by growth characterisation, metabolomics, isotope labelling experiments, and by quantifying cofactors under various hyphae-inducing conditions. We found that the gdh2/gdh2 mutant was unable to grow on either arginine or proline as a sole carbon and nitrogen source. While the gdh3/gdh3 mutant could grow on these carbon and nitrogen sources, the strain was locked in the yeast morphology in proline-containing medium. We detected different concentrations of ATP, NAD(+), NADH, NAPD(+), NADPH, as well as 62 other metabolites, and 19 isotopically labelled metabolites between the mutant and the wild-type strains. These differences were associated with 44 known metabolic pathways. It appears that the disequilibrium of cofactors in the gdh3/gdh3 mutant leads to characteristic proline degradation in the central carbon metabolism. The analysis of the gdh2/gdh2 and the gdh3/gdh3 mutants confirmed our hypothesis that redox potential and nitrogen metabolism are related to filament formation and identified these metabolic pathways as potential drug targets to inhibit morphogenesis."
2760,"Author Correction: Human motor cortex relies on sparse and action-specific activation during laughing, smiling and speech production",
2761,Tenosynovial giant cell tumor of the cervical spine: a case report,"INTRODUCTION: Tenosynovial giant cell tumors (TSGCTs) generally occur in the limb joints, and only rarely in the spine. This case report describes a patient with TSGCT of the spine at C1–C2, which was treated surgically and diagnosed as TSGCT. CASE PRESENTATION: A 32-year-old woman with a 4-month history of neck pain and numbness in both upper extremities was referred to our department. Magnetic resonance imaging (MRI) revealed a neoplastic lesion extending from the left epidural space to the erector spinae muscles at the C1–C2 vertebral level, which was isointense on T1-weighted images, heterogeneously hypointense on T2-weighted images, and showed heterogeneous enhancement on gadopentetate dimeglumine (Gd-DTPA)-enhanced T1-weighted images. Computed tomography showed no findings suggestive of bone destruction of the vertebral body. Because the neurological symptoms were progressive, total macroscopic resection of the tumor was performed via a posterior approach. Histopathological examination of the resected specimen revealed the diagnosis of TSGCT. Improvement of the both the neck pain and upper-extremity numbness was noted postoperatively. An MRI obtained 6 months after the surgery revealed no evidence of tumor recurrence and the postoperative course was uneventful. DISCUSSION: TSGCT of the upper cervical spine (C1–C2) is rare, and this is the tenth reported case. If a tumor is heterogeneously hypointense on T2-weighted MRI, which reflects hemosiderosis, the possibility of this tumor should be considered in the differential diagnosis."
2762,Late-onset “white cord syndrome” in an elderly patient after posterior cervical decompression and fusion: a case report,"INTRODUCTION: In 2013, a rare early complication following cervical decompression the so-called “white cord syndrome” (WCS) was described for first time. This designation was given on the basis of the postoperative appearance of intramedullary hypertense areas in T2-MRI, resulting in devastating neurological damage. To our knowledge, only three cases of WCS have been published; we hereby present the fourth case, but the first one with late-onset presentation of this syndrome. CASE PRESENTATION: A 79-year-old male patient with Nurick grade 3 CSM was referred to our institution. He had already had a double-level C4–C6 anterior cervical decompression and fusion (ACDF) 2 years ago in another institution. The patient underwent posterior decompression from C3 to C6 plus C2–C7 lateral mass screw fusion. Within the first 24 h following surgery, he gradually developed C6 incomplete paraplegia (ASIA B). Cervical MRI disclosed a hypertensive signal in T2-weighted sequences at C6–C7 levels and the diagnosis of WCS was suspected. Revision surgery was made 30 h following our first surgery, with wider posterior decompression accompanied by intravenous methylprednisolone. The patient’s neurologic status was improved, but the final neurologic outcome was worse (Nurick 4) than the preoperative status and subsequently did not change at all. DISCUSSION: To the best of our knowledge, this is the first report of a late-onset WCS and the fourth case of WCS per se. Spine surgeons should be aware of this rare but serious complication. We highlight possible risk factors and review the literature on the hypotheses about the pathophysiology of WCS."
2763,Lack of adequate care post spinal cord injury - a case report,"INTRODUCTION: Health needs of individuals with spinal cord injury (SCI) are unmet in developing countries. Quality of life of these individuals is not on par with global standards. The decline in quality of life can be attributed to lack of a specialised rehabilitation centres, lack of expertise in local hospitals and lack of access to dedicated SCI wards/centres in India. The present case report depicts many such challenges in India. CASE PRESENTATION: As part of an online focus group, A 21-year-old male was identified who sustained SCI in motor vehicle. His care was inappropriate at the accident site. He was not taught basic skills such as bed mobility, transfers, and wheel-chair mobility and was not educated about long-term complications before discharged to home. Lack of training made him functionally dependent on others for his basic needs. There were few job opportunities for him in his state. He strongly emphasises the need to create an awareness regarding SCI among the general public in India. DISCUSSION: This case report depicts many challenges faced by a person with paraplegia in India. These include mishandling at the accident site, lack of adequate care post injury and lack of follow-up post discharge. In addition, lack of knowledge of SCI among the general public and lack of education regarding SCI for the patient and his care givers post injury are reported."
2764,Establishing the inter-rater reliability of spinal cord damage manual measurement using magnetic resonance imaging,"STUDY DESIGN: Retrospective study. OBJECTIVES: To establish the inter-rater reliability in the quantitative evaluation of spinal cord damage following cervical incomplete spinal cord injury (SCI) utilizing magnetic resonance imaging (MRI). MRI was used to perform manual measurements of the cranial and caudal boundaries of edema, edema length, midsagittal tissue bridge ratio, axial damage ratio, and edema volume in 10 participants with cervical incomplete SCI. SETTING: Academic university setting. METHODS: Structural MRIs of 10 participants with SCI were collected from Northwestern University’s Neuromuscular Imaging and Research Lab. All manual measures were performed using OsiriX (Pixmeo Sarl, Geneva, Switzerland). Intraclass correlation coefficients (ICC) were used to determine inter-rater reliability across seven raters of varying experience. RESULTS: High-to-excellent inter-rater reliability was found for all measures. ICC values for cranial/caudal levels of involvement, edema length, midsagittal tissue bridge ratio, axial damage ratio, and edema volume were 0.99, 0.98, 0.90, 0.84, and 0.93, respectively. CONCLUSIONS: Manual MRI measures of spinal cord damage are reliable between raters. Researchers and clinicians may confidently utilize manual MRI measures to quantify cord damage. Future research to predict functional recovery following SCI and better inform clinical management is warranted."
2765,Osteoporosis prophylaxis in acute SCI,"Osteoporosis is a serious complication of spinal cord injury that is associated with increased fracture rates. Diagnosis and management of osteoporosis is limited by the lack of rigorous, well powered clinical trials with fracture as a primary outcome. Due to a lack of evidence-based guidelines, clinical practice varies greatly. This Point-counterpoint series address prophylaxis of osteoporosis in acute SCI."
2766,Progression to ambulation following lower limb fractures in an individual with a spinal cord injury: a case report,"INTRODUCTION: Patients with spinal cord injury (SCI) and concomitant lower limb fractures are a challenge to rehabilitate. Conventionally, postural orientation is an important milestone in the rehabilitative process. We propose an alternative strategy in achieving goals in individuals with an SCI with concomitant injuries that preclude weight bearing below the knee. CASE PRESENTATION: A 16-year-old girl sustained a burst fracture of L1 in conjunction with bilateral ankle fractures. During rehabilitation, the calcaneal fracture on the left and tibial plafond fracture on the right prevented her progression in conventional rehabilitation. An alternative strategy “K-ing” (Kneel Standing/Kneel Walking) was adopted to facilitate truncal activation without loading the ankle joints. This was found to be helpful in obtaining upright posture stability without hampering her recovery of associated ankle injuries. DISCUSSION: “K-ing” strategy can be useful and presents a simple alternative in the presence of associated ankle injuries. It also avoids complications associated with bedrest when there is delay in initiation of ambulation."
2767,Treatment and cost of pressure injury stage III or IV in four patients with spinal cord injury: the Basel Decubitus Concept,"STUDY DESIGN: Retrospective chart analyses as part of a quality improvement project. OBJECTIVES: To demonstrate treatment of pressure injury (PI) in patients with spinal cord injuries (SCI) and analyse costs using the “modified Basel Decubitus Concept”. SETTING: Inpatient setting of a specialised acute care and rehabilitation clinic for SCI. METHODS: Complex treatment courses of four patients with chronic SCI and PI stage III or IV were described and costs were recorded. The total healthcare services’ costs per patient and different profession’s involvement were analysed in relation to patient characteristics, treatment phases and milestones demonstrated. RESULTS: The treatment of PI stage III and IV in patients with SCI included input from plastic surgery, rehabilitation medicine, nursing and other involved professions. Recommended interventions were chosen according to the “modified Basel Decubitus Concept”. The cost course of PI treatment in patients with SCI depicted the multimodal treatment concept, including three clinically and financially relevant milestones (debridement, flap surgery and mobilisation to wheelchair) as well as the highest costs in the functionally highly dependent patient. Acute care and rehabilitation overlapped with different intensities during the whole treatment process. CONCLUSION: Multimodal treatment concepts connecting acute and rehabilitation care were applied in these complex health conditions. Cost-explication models including treatment phases and milestones helped to understand resources more easily and integrate aspects of process-based management and quality of care. Scientific evidence is needed to create a recommended quality standard in line with adequate financing of this health condition."
2768,A single-subject study of robotic upper limb training in the subacute phase for four persons with cervical spinal cord injury,"STUDY DESIGN: Single-subject design, standard training (“B”) compared with Robotic training (“C”). OBJECTIVES: To explore the impact of robotic training on upper limb function, activities of daily living (ADL) and training experience in subacute tetraplegic inpatients. SETTING: Inpatient subacute Norwegian spinal cord injury (SCI) unit. METHODS: Four participants (C4–7, AIS A-C) completed 11 sessions of robotic training using a passive robotic exoskeleton (Armeo Spring®). Descriptive statistics and visual analyses were used for comparing standard occupational therapy and robotic training. Outcome measures included the Spinal Cord Independence Measure (SCIM-III), the Graded Redefined Assessment of Strength Sensibility and Prehension (GRASSP), and a questionnaire. RESULTS: All of the participants exhibited an increase in assessments of upper limb function (GRASSP-total) right side (0.4%–61.2%), and all except for one participant (−8%) showed an increase on their left side (20.9%–106.2%). Three out of four participants had improvements in ADL function SCIM-III (ranging from 5.6% to 46.7%). Results demonstrated improvements during the robotic intervention period in five out of 28 measurements. The participants enjoyed the exercise, and found it motivating and relevant to their injury (median ranged from 3.5 to 6.5 on a 0–7 scale). CONCLUSIONS: Three out of four participants improved upper limb function and ADL independence, but the study could not confirm that improvements were due to the robotic intervention. The participants enjoyed the robotic training and found it relevant to their injury."
2769,Normalization cancer immunotherapy: blocking Siglec-15!,
2770,Comparison of abdominal compression devices in persons with abdominal paralysis due to spinal cord injury,"STUDY DESIGN: Single subject design with five subjects. OBJECTIVES: The objetive of this study is to compare the effectiveness and usability of alternative commercial abdominal compression garments with participants’ usual medical binders. SETTING: Private residences in Pierce and King Counties, WA, USA. METHODS: Participants wore each garment for 5 days followed by a 2-day washout in personal binder. Week 1: Personal binder. Weeks 2 and 3: Randomly ordered test garments (tank, bodysuit). Physiologic measurements: blood pressure (SBP, DBP), blood oxygen saturation (SaO(2)), forced expiratory volume in one second (FEV(1)), and heart rate (HR). Participants completed logs twice daily for 5 days per garment regarding ease of use, comfort, respiration, and appearance. We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research. RESULTS: The use of a personal binder results in significant increases in SBP and FEV(1). Personal binders support FEV(1) significantly better than test garments. There is no difference in SBP between test garments and personal binders. There are no significant differences between DBP, SaO(2), or HR between participants’ personal binders and no binder. Participants reported that neither tank nor bodysuit felt adequately supportive or easy to use. CONCLUSIONS: Abdominal compression improves respiratory function and supports SBP in individuals with chronic SCI. Further research is needed to guide the development of an easy-to-use and physiologically supportive abdominal compression garment."
2771,Cauda equina syndrome in an obese pregnant patient secondary to double level lumbar disc herniation – A case report and review of literature,"INTRODUCTION: Lumbar disc herniation during pregnancy poses a significant challenge to the spine surgeon towards achieving good clinical, maternal, and fetal outcomes. Surgical intervention is warranted in patients with significant neural deficits, and cauda equina syndrome and needs to be performed at the earliest in order to avoid irreversible neurological sequelae. CASE PRESENTATION: We report a 29-year-old primigravida in her 21st week of gestational period, who was diagnosed with cauda equina syndrome secondary to two level lumbar disc herniations. The lengthier surgical duration in performing double level disc herniations in an obese patient raises concerns in anesthetic dosing of drugs and surgical positioning which may result in fetal distress. A double level decompression and discectomy in prone position was done under general anesthesia. Despite the surgical challenges, the postoperative period was uneventful resulting in immediate pain relief and complete neurological recovery, followed by the delivery of a 2.7-kg healthy male child. DISCUSSION: Surgical intervention can be performed in pregnancy, to avoid irreversible neurological deficits, even in an obese individual with double level lumbar pathology. However, it is essential that the surgeon appraises the situation and involves an integrated multidisciplinary team comprising anesthetist, spine surgeon, obstetrician, and psychologist, and inculcates certain precautions in the perioperative management to achieve good surgical and fetal outcomes."
2772,Oropharyngeal dysphagia management in cervical spinal cord injury patients: an exploratory survey of variations to care across specialised and non-specialised units,"STUDY DESIGN: A multi-centre online survey to staff working in specialised and non-specialised acute units. OBJECTIVES: To identify clinical decisions and practices made for acute cervical spinal cord injury (CSCI) patients with respiratory impairments and oropharyngeal dysphagia. SETTINGS: All hospital intensive care units in the UK that admit acute cervical spinal cord injury patients. METHODS: Online distribution of a 35-question multiple-choice survey on the clinical management of ventilation, swallowing, nutrition, oral hygiene and communication for CSCI patients, to multi-disciplinary staff based in specialised and non-specialised intensive care units across UK. RESULTS: Responses were received from 219 staff members based in 92 hospitals. Of the 77 units that admitted CSCI patients, 152 participants worked in non-specialised and 30 in specialised units. Non-specialised unit staff showed variations in clinical decisions for respiratory management compared to specialised units with limited use of vital capacity measures and graduated weaning programme, reliance on coughing to indicate aspiration, inconsistent manipulation of tracheostomy cuffs for speech and swallowing and limited use of instrumental assessments of swallowing. Those in specialised units employed a multi-discplinary approach to clinical management of nutritional needs. CONCLUSIONS: Variation in the clinical management of respiratory impairments and oropharyngeal dysphagia between specialised and non-specialised units have implications for patient outcomes and increase the risk of respiratory complications that impact mortality. The future development of clinical guidance is required to ensure best practice and consistent care across all units."
2773,Case report – Gluteal hematoma in two spinal cord patients on enoxaparin for venous thromboembolism prophylaxis: evidence needed for a wiser choice,"INTRODUCTION: Acute spinal cord injury is associated with an increased risk of thromboembolic events. Low-molecular-weight heparins are first-line medications for both the treatment and prevention of venous thromboembolism. Pharmacological prophylaxis may be indicated for high-risk patients and low-risk patients may be managed with non-pharmacological measures. CASE PRESENTATION: We report two cases of gluteal hematomas that occurred in patients with chronic spinal cord injury who were under prophylactic doses of enoxaparin at a tertiary rehabilitation hospital. There was no local trauma. The patients needed multiple surgical interventions and rehabilitation treatment was delayed. DISCUSSION: There is a lack of evidence to correctly estimate the thromboembolic risk in chronic spinal cord injury and the duration of prophylaxis. Over-prescription of pharmacological prophylaxis may expose patients to unnecessary risks. These patients frequently present with polypharmacy and reducing the amount of prescribed medication may begin with reducing prophylactic treatments for venous thromboembolism, which may be an overtreatment based on risk overestimation."
2774,Malignancies of suprapubic catheter (SPC) tracts in spinal cord injury patients: a case series and review of literature,"INTRODUCTION: Spinal cord injury (SCI) patients are at increased risk of bladder cancer. A rare variation of this is a malignancy arising or including the suprapubic catheter (SPC) tract. CASE SERIES: We present the first case series of malignancy of the SPC tract in SCI patients, including a case of mucinous adenocarcinoma, squamous cell carcinoma and sarcoma. Presentation of patients ranged from bleeding at the site of the SPC to a rapidly growing mass. All three patients were thoroughly investigated, and management was bespoke to the extent of disease and their physiological state at the time of diagnosis. This ranged from extensive surgical intervention including cystectomy, partial sigmoidectomy, excision of the abdominal wall with reconstruction and ileal conduit formation to palliation. DISCUSSION: SCI patients represent 50% of all known published cases of malignancy of the SPC tract. Presentation and diagnosis can be challenging; however, prompt investigation and intervention are essential given the high degree of morbidity and mortality. Routine check of the SPC site may be indicated in those patients in whom the SPC has been present for more than 5 years."
2775,Assessment of pain symptoms and quality of life using the International Spinal Cord Injury Data Sets in persons with chronic spinal cord injury,"INTRODUCTION: Traumatic spinal cord injury (SCI) triggers complex changes that can negatively impact health and quality of life. The International SCI Data Sets were developed to enable more comparable data collection on the complex sequelae of SCI across studies. This should facilitate progress in mechanistic understanding and improving treatments of SCI. STUDY DESIGN: Prospective observational pilot study. OBJECTIVES: To collect data on pain symptoms and quality of life (QoL) in adults living with chronic SCI. SETTING: Academic medical center, New York, USA. METHODS: The International SCI Basic Pain and Qol Data Sets were used to collect data from participants with chronic SCI (N = 31) at 2 study visits held 6 months apart. The QoL Data Set was also used to collect data from able-bodied persons of similar age and gender distribution (N = 28). RESULTS: Most participants with SCI had multiple types and locations of pain problems at both study visits, despite reported being treated for pain. At both visits, the worst pain problem type was nociceptive, followed by neuropathic, which was typically rated of higher intensity. QoL scores were significantly lower across all domains of the data set in persons with SCI than able-bodied persons. Persons with pain tended to have lower QoL scores, although this trend was not significant. CONCLUSIONS: This study demonstrates the presence, complexity and stability of pain symptoms refractory to treatment and lower quality of life ratings in persons with chronic SCI. SPONSORSHIP: Grants from the Craig H. Neilsen Foundation, New York Empire Clinical Research Program, New York State Spinal Cord Injury Research Board."
2776,Epigenetic drug library screening identified an LSD1 inhibitor to target UTX-deficient cells for differentiation therapy,"UTX (also known as KDM6A), a histone 3 lysine 27 demethylase, is among the most frequently mutated epigenetic regulators in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Recent studies have suggested that UTX mutations promote MDS and AML by blocking the differentiation of hematopoietic stem and progenitor cells (HSPCs). Here, we performed an epigenetic drug library screening for small molecules able to release the differentiation block on HSPCs induced by UTX deficiency. We found that SP2509, a selective inhibitor of LSD1, specifically promoted the differentiation of Utx-null HSPCs while sparing wild-type HSPCs. Transcriptome profiling showed that Utx loss reduced the expression of differentiation-related and tumor suppressor genes, correlating with their potential roles in HSPC self-renewal and leukemogenesis. In contrast, SP2509 treatment reversed these changes in gene expression in Utx-null HSPCs. Accordingly, Utx loss decreased H3K4 methylation level probably through the COMPASS-like complex, while LSD1 inhibition by SP2509 partially reversed the reduction of H3K4 methylation in Utx-deficient HSPCs. Further, SP2509 promoted the differentiation of Utx-null AML cells in vitro and in vivo and, therefore, extended the survival of these leukemic mice. Thus, our study identified a novel strategy to specifically target both premalignant and malignant cells with Utx deficiency for differentiation therapy and provided insights into the molecular mechanisms underlying the role of Utx in regulating HSPCs and related diseases."
2777,The expanding vulnerabilities of being UTXless,
2778,Publisher Correction: A c-di-AMP riboswitch controlling kdpFABC operon transcription regulates the potassium transporter system in Bacillus thuringiensis,
2779,A microbiota-generated bile salt induces biofilm formation in Clostridium difficile,"Clostridium difficile is a major cause of nosocomial infections. Bacterial persistence in the gut is responsible for infection relapse; sporulation and other unidentified mechanisms contribute to this process. Intestinal bile salts cholate and deoxycholate stimulate spore germination, while deoxycholate kills vegetative cells. Here, we report that sub-lethal concentrations of deoxycholate stimulate biofilm formation, which protects C. difficile from antimicrobial compounds. The biofilm matrix is composed of extracellular DNA and proteinaceous factors that promote biofilm stability. Transcriptomic analysis indicates that deoxycholate induces metabolic pathways and cell envelope reorganization, and represses toxin and spore production. In support of the transcriptomic analysis, we show that global metabolic regulators and an uncharacterized lipoprotein contribute to deoxycholate-induced biofilm formation. Finally, Clostridium scindens enhances biofilm formation of C. difficile by converting cholate into deoxycholate. Together, our results suggest that deoxycholate is an intestinal signal that induces C. difficile persistence and may increase the risk of relapse."
2780,Publisher Correction: Calaxin is required for cilia-driven determination of vertebrate laterality,
2781,Utilization of medicinal cannabis for pain by individuals with spinal cord injury,"STUDY DESIGN: A cross-sectional multi-center study using an on-line survey addressing utilization, knowledge, and perceptions of medicinal cannabis (MC) by people with spinal cord injury (SCI). OBJECTIVE: To characterize differences between current (CU), past (PU), and never users (NU) of MC with SCI; to determine why people with SCI use MC; to examine reports of MCs’ efficacy and tolerability by individuals with SCI. SETTING: Three academic medical centers in the United States. METHODS: Comparison of demographic and attitudinal differences between CU, PU, and NU and differences in the groups’ reports of pain, health, and quality of life (QOL). Evaluation of utilization patterns and perceived efficacy of MC among CU and PU and reports of side effects of MC versus prescription medications. Data were analyzed using either Chi Square, distribution-free exact statistics, or t-tests for continuous data. RESULTS: Among a nationwide sample (n = 353) of individuals with SCI, NU were less likely than CU and PU to believe that cannabis ought to be legalized and more likely to endorse risks of use. Current users and PU reported greater pain interference in daily life than did NU, but there were no between group differences in QOL or physical or emotional health. Current users and PU took MC to address pain (65.30%), spasms (63.30%), sleeplessness (32.70%), and anxiety (24.00%), and 63.30% reported it offered “great relief” from symptoms. Participants reported that MC is more effective and carries fewer side effects than prescription medications. CONCLUSIONS: Medicinal cannabis is an effective and well-tolerated treatment for a number of SCI-related symptoms."
2782,Participant-reported priorities and preferences for developing a home-based physical activity telemonitoring program for persons with tetraplegia: a qualitative analysis,"STUDY DESIGN: Focus group. OBJECTIVES: The purpose of this qualitative study was to explore perceptions and priorities of persons with spinal cord injury (SCI) for physical activity and to incorporate their feedback to inform future development of a physical activity program delivered via a telemonitoring platform. SETTING: New York. METHODS: Qualitative data were collected from a purposive sample of adults with tetraplegia (N = 7). Two investigators led an audio-recorded focus group using a moderator’s guide. Data were analyzed using a six-phase thematic analysis approach. RESULTS: The discussion focused on two major areas, which resulted in multiple derived themes and subthemes. The first theme centered on the daily life of persons with tetraplegia, including changes after SCI, gain of function prioritization, and identification of psychosocial support systems that facilitate community reintegration after injury. The second theme centered on participant perceptions and recommendations for a physical activity program delivered via a telemonitoring platform. Desired design features included variations in schedule, diverse activities, or exercises included in each class, and optional two-way video to enable social interactions with classmates. CONCLUSIONS: Participants favorably viewed the concept of a physical activity program delivered via a telemonitoring platform and contributed program design ideas. Although this was a small sample size, challenges to obtaining physical activity expressed by participants were consistent with those identified previously in larger studies of persons with tetraplegia. Therefore, we expect these concepts and their recommendations to be relevant to the greater SCI community."
2783,Intradural extramedullary metastasis: a review of literature and case report,"INTRODUCTION: Intradural extramedullary (IDEM) metastatic disease is infrequently encountered by spine surgeons and consequently poorly understood. Discovery often corresponds with the onset of neurologic symptoms and no consensus exists regarding the importance of complete resection or anticipated postoperative outcome. We aim to elucidate treatment methodologies that exist in the literature. CASE PRESENTATION: We present a unique case of a 57-year-old male with a known history of esophageal adenocarcinoma, including brain and visceral metastases, who presented with cauda equina syndrome. An IDEM metastatic esophageal adenocarcinoma lesion was identified on advanced imaging and biopsy. This was treated operatively without return of neurologic function. DISCUSSION: We reviewed and summarized the existing literature. Trends are highlighted to further guide surgeons treating this unusual metastatic phenomenon. CONCLUSION: Intradural metastasis is a harbinger of advanced disease with a poor prognosis regardless of the etiology of the primary lesion. There are a number of proposed mechanisms for metastatic spread with little available literature for surgeon guidance. Most authors are advocates of a palliative, decompressive approach."
2784,"Correlation between thyroid function, testosterone levels, and depressive symptoms in females with spinal cord injury","STUDY DESIGN: Prospective case series. OBJECTIVE: Investigate the association of testosterone and thyroid-stimulating hormone (TSH) levels with depressive symptoms in women after spinal cord injury (SCI). SETTING: Community SCI clinic. METHODS: Twenty-seven participants were enrolled in this study. Total testosterone (Total T) and TSH levels as well as the Center for Epidemiological Studies Depression Scale (CES-D) survey and monthly sexual activity were obtained from only 20 participants. Pearson’s correlations were used to assess the relationship between age, time from injury, Total T level, TSH level, and CES-D total score. Follow-up analyses investigating the role of monthly sexual activity was also explored. RESULTS: Participants’ average age and time from injury was 44.4 ± 12.7 years old and 11.7 ± 8.89 years, respectively. Low Total T was observed in four participants and one of those participant’s presented with low TSH as well. Nine women were classified as “at risk for clinical depression” on the CES-D (total score >15). Pearson’s correlations revealed a significant association between time from injury and TSH (r = .536, p = .015), as well as CES-D total score (r = −.547, p = .013). Total T was associated with CES-D total score (ρ = −.541, p = .02). CONCLUSIONS: This study provides preliminary results on abnormal hormone levels and depressive symptoms in women after SCI. Twenty percent of this sample presented with low Total T, which was associated with increased depressive symptoms after accounting for time from injury. Further research is needed to investigate the impact of SCI on hormone function and mental health in women post SCI. SPONSORSHIP: Sally Rynne National Association of Women’s Health Quality Award 2002."
2785,"On when guidelines conflict: Patient safety, quality of life and CAUTI reduction in patients with spinal cord injury",
2786,Mycobacteriumabscessus-associated vertebral osteomyelitis in an immunocompetent patient: a rare case report and literature review,"INTRODUCTION: Vertebral osteomyelitis (VO) is an uncommon infection with Staphylococcus aureus as the most commonly implicated organism. VO caused by nontuberculous mycobacteria (NTM) such as Mycobacterium abscessus (M. abscesscus) is exceedingly rare with only eight cases reported in literature. CASE PRESENTATION: We report a rare case of an 82-year-old male with a remote history of trauma who was diagnosed with NTM vertebral osteomyelitis. The patient initially underwent a vertebroplasty of T12 and kyphoplasty of L1 for pathologic compression fractures. Subsequent cultures revealed M. abscessus. The patient further underwent an anterior T12-L2 corpectomy and debridement with instrumented fusion, as well as a posterior T9-L4 instrumentation and fusion. He received multi-agent antibiotic therapy; however, was ultimately unable to tolerate the aggressive treatment regimen and his prolonged postoperative course. DISCUSSION: Nontuberculous mycobacteria vertebral osteomyelitis is exceedingly rare. NTM vertebral osteomyelitis is challenging to treat. Surgical management plays a limited role in early VO, but is the mainstay treatment in chronic VO. Early recognition of the condition and shared patient management with multidisciplinary teams is key to successfully treating cases of NTM VO."
2787,"Autologous, micro-fragmented adipose tissue as a treatment for chronic shoulder pain in a wheelchair using individual with spinal cord injury: a case report","INTRODUCTION: Shoulder pain is common in persons with chronic spinal cord injury (SCI), with a prevalence reported as high as 70%. Current treatment of shoulder pain includes conservative measures such as physical therapy, pain medications, patient education, injections, and assistive devices. When conservative treatments fail, shoulder surgery is often the next option. Unfortunately, outcomes after shoulder surgery in persons with SCI are limited and conflicting. CASE PRESENTATION: This is a case of a 54-year-old right-handed male with T10 complete SCI (duration of injury = 10 years) who had a complaint of right-sided shoulder pain for 3 years. The individual used a manual wheelchair as his primary means of mobility and was an avid weight-lifter. Physical examination and MRI demonstrated a rotator cuff tear and degenerative changes of the acromioclavicular joint. He was previously managed conservatively with physical therapy and intermittent corticosteroid injections but failed to improve. He was enrolled in an IRB approved study and underwent an ultrasound-guided injection with autologous, micro-fragmented adipose tissue (MFAT) and ultimately received improvements in pain and function that were maintained a year after treatment. DISCUSSION: To our knowledge, this is the first reported case of treatment of chronic refractory shoulder pain in a person with SCI using MFAT. Complete relief from pain was maintained at the 1-year follow-up. Injection of MFAT under ultrasound guidance is an effective and promising treatment for chronic refractory shoulder pain in upper limb-dependent persons with SCI and warrants further research."
2788,Communication with general practitioners: a survey of spinal cord injury physicians’ perspectives,"STUDY DESIGN: An online questionnaire. OBJECTIVES: To gauge spinal cord injury (SCI) specialists’ assessment of their communications with general practitioners (GPs). To determine whether economic or health-care system-related factors enhance or inhibit such communication. SETTING: A collaboration of co-authors from a health-care system. METHODS: An online survey interrogating a number of aspects of communication between SCI specialists and GPs was developed, distributed, and made available for 4 months. Responses were analyzed for the entire cohort then according to descriptions of participants’ home nations’ economies and the type of health-care delivery systems in which they work. RESULTS: A total of 88 responses were submitted. The majority (64%) were from nations with developed economies, a plurality (47.1%) were from countries that offer universal health coverage, and half used a combination of paper and electronic health records. A majority of respondents (61.8%) reported routinely communicating with their patients’ GPs, but most (53.4%) rated those communications as only “fair”. The most commonly listed barriers to communication with GPs were lack of time (46.3%) and a perceived lack of receptivity by GPs (26.9%). Nearly all respondents (91.6%) believed that the care they provide would be enhanced by improved communication with GPs. Participants who used electronic means of communication were more likely to communicate with GPs and to describe those interactions as “positive”. CONCLUSIONS: Although there are a number of barriers to communication between SCI specialists and GPs, most SCI specialists are eager for such inter-physician communication and believe it would enhance their care they deliver."
2789,Progressive hemiparesis due to spino-laminar anomaly of the axis—a case report and literature review,"INTRODUCTION: Some of the most common developmental malformations of the axis include anomalies of the odontoid, for example, hypoplasia or aplasia. Isolated anomalies of the posterior arch of the axis rarely occur. This study reports a unique case of congenital anomaly of the neural arch of the axis vertebra, which manifested clinically as progressive hemiparesis. CASE PRESENTATION: A 33-year-old man presented with progressive weakness of the right upper and lower limbs that had lasted 18 months. The patient reported loss of right-hand dexterity in the 6 months period before he consulted us. Plain radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) revealed C5–C6 block vertebra, primary canal stenosis and spino-laminar anomaly of the axis, along with invagination of the lamina into the canal causing severe cord compression. DISCUSSION: The anomalous posterior element of the axis was excised, and the cord was decompressed. The presence of congenital stenosis and block vertebrae at the C5–C6 level necessitated decompression and instrumentation between C2–C6. Simultaneous occurrence of a posterior arch anomaly, primary canal stenosis, and block vertebra has not been previously described. A cervical spine anomaly presenting as hemiparesis is uncommon in clinical practice. Information enabling clinicians to identify causative anomaly and determine the appropriate surgical intervention is useful, and can facilitate a good clinical outcome."
2790,"When guidelines conflict: patient safety, quality of life, and CAUTI reduction in patients with spinal cord injury","The current Medicare payment structure and some of the recent guidelines aimed at reducing catheter-associated urinary tract infections may be generating a financial incentive for the protocolized, systematic removal of indwelling catheters in hospitalized patients—including those with spinal cord injury. This creates a tension with the Consortium for Spinal Cord Medicine’s clinical practice guidelines for the management of neurogenic bladder. This article presents a series of cases and a discussion of the implications with regard to patient safety and quality of life."
2791,Intercostal artery hemorrhage with hemothorax following combined lateral and posterior lumbar interbody fusion: a case report,"INTRODUCTION: Lateral lumbar interbody fusion (LLIF) is a safe treatment for degenerative spine conditions. However, risk of complications such as vascular injuries remains. We report a unique case of an intercostal artery (ICA) hemorrhage with hemothorax following LLIF. CASE PRESENTATION: One hour after a right-sided LLIF L3-4 with posterior decompression L2-4 and L3-5 instrumentation, the patient became hypotensive, anemic and required vasopressor support. Evaluation revealed a right-sided hemothorax, which was caused by a bleeding intercostal artery, laterally at the 10th intercostal space. A lateral thoracotomy was performed to stop the bleeding. After vessel ligation and placement of two chest tubes, the patients’ hemodynamics improved. The patient remained intubated overnight and was extubated on the first postoperative day. DISCUSSION: Vascular injury is a rare complication of LLIF procedures. Most vascular injuries are segmental vessel lacerations, which resolve postoperatively. This is the first case description of ICA bleeding associated with LLIF surgery. Spontaneous ICA bleeding exists, but surgeons should be aware of careful handling in patients with vascular risk factors, especially with regard to patient positioning required in certain spinal surgical approaches. Timely vascular injury identification is critical for hemostasis and clinical management."
2792,"Satisfaction with life, health and well-being: comparison between non-traumatic spinal cord dysfunction, traumatic spinal cord injury and Australian norms","STUDY DESIGN: Cross-sectional survey. OBJECTIVES: The objective of this study is to compare self-reported satisfaction with life, and self-reported health and well-being of people with NTSCD, to that of people with TSCI, and with Australian population. SETTING: Victoria, Australia. METHODS: Participants completed surveys by post or email. The Satisfaction with Life Scale (SWLS) and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were used to assess self-reported satisfaction with life, and health and well-being. Descriptive statistics are reported including median and interquartile range (IQR). The Mann–Whitney U-test was used to investigate differences between groups. RESULTS: There were 41 participants: NTSCD (n = 14) and TSCI (n = 27). There were no significant differences in the median scores on the SWLS for NTSCD and TSCI, but both groups scored lower than the Australian non-disabled sample mean. There were significant differences between NTSCD and TSCI for SF-36 domains physical functioning, role limitations physical and vitality (p < 0.05). Median scores for both groups in all eight domains were lower than the means of the comparative Australian sample, except for role limitations emotional. CONCLUSIONS: There were more apparent difficulties for people with NTSCD in completing desired functional tasks than those with TSCI. Both groups had lower self-reported satisfaction with life, and lower reported health and well-being in comparison to samples of non-disabled Australians."
2793,Abdominal compartment syndrome following posterior lumbar fusion in a patient with previous abdominal surgery,"INTRODUCTION: Perioperative complications associated with spinal fusion have been investigated steadily to reduce morbidity and mortality. Although there are several reports reviewing abdominal complications occurring with anterior spinal fusion, complications related to posterior spinal fusion (PSF) are rare. However, abdominal compartment syndrome (ACS) after PSF could be the most fatal and unpredictable complication in spinal surgery. CASE PRESENTATION: This 73-year-old man with body mass index (BMI) of 23.02, and surgical history of appendectomy 10 years prior complained of severe nausea and vomiting on the second postoperative day of L4–5 transforaminal lumbar interbody fusion (TLIF). By postoperative day 4, he presented with dyspnea and fever, and the first diagnostic impression suggested aspiration pneumonia due to vomiting. Physical examination revealed severe abdominal distention and tenderness to palpation at most of the abdomen. Computed tomography (CT) scan of abdomen and chest revealed left inguinal hernia of the small bowel with incarceration suggesting intra-abdominal hypertension (IAH), and multifocal peri-bronchial consolidation in both lungs, respectively. His respiratory symptoms progressed to respiratory failure, and he was finally mechanically ventilated in conjunction with antibiotics. After 2 weeks of intensive care, the patient’s symptom had improved, and finally he was transferred to a nursing facility. DISCUSSION: IAH and ACS rarely occur as abdominal complications of PSF. We suggest several risk factors including body mass index, abdominal surgical history, and long segment fusion for development of abdominal complications."
2794,Muscle belly in the tunnel: an unusual cause of carpal tunnel syndrome in a patient with spinal cord injury,"INTRODUCTION: Carpal tunnel syndrome, entrapment of median nerve at the wrist, is one of the most commonly encountered peripheral neuropathies in the upper extremity. It is also common in individuals with spinal cord injury due to repetitive movements during wheelchair use. Although it is well known that prevalence of carpal tunnel syndrome is high in individuals with spinal cord injury, no previous study identified aberrant muscle as the cause. CASE PRESENTATION: A 43-year-old man with T10 incomplete, ASIA Impairment Scale (AIS) C, patient with paraplegia who is a wheelchair basketball player presented to our electrodiagnostic laboratory with complaints of bilateral hand numbness after intensive training for a local veteran wheelchair basketball tournament. Nerve conduction studies showed carpal tunnel syndrome. Ultrasonographic assessment of carpal tunnel revealed the presence of abnormal muscle in the carpal tunnel encroaching the median nerve dynamically. DISCUSSION: It is important to identify the underlying cause of carpal tunnel syndrome, which is a common cause of upper extremity impairment in individuals with spinal cord injury because individuals with spinal cord injury who use wheelchair depend on their arms for mobility, transfers, and most activities of daily life."
2795,"Construct validity, test-retest reliability, and the ability to detect change of the Canadian Occupational Performance Measure in a spinal cord injury population","STUDY DESIGN: Cross-sectional study. OBJECTIVES: To examine the construct validity and the ability to detect change, of the Italian version of the Canadian Occupational Performance Measure (COPM) in a spinal cord injury (SCI) population. SETTINGS: Rehabilitation service of the Paraplegic Center of Ostia, Italy. METHODS: Thirty-nine spinal cord injury participants were recruited. The clinimetric properties of the measure were assessed following international guidelines. Cronbach’s alpha and the intraclass correlation coefficient were assessed for internal consistency and test-retest reliability, respectively. Construct validity was evaluated, by calculating correlation between COPM and the Spinal Cord Independence Measure (SCIM) through Pearson’s correlation coefficient and Spearman’s Rho. The ability to detect change was evaluated on the overall sample. RESULTS: The COPM was shown to be reliable in a spinal cord injury sample with positive and statistically significant results for Cronbach’s alpha (0.89) and ICC (0.99 for the performance subtest and 0.98 for the satisfaction subtest). Correlation coefficients did not show a correlation between the COPM total score and the SCIM. The COPM scores improved significantly during in-patient rehabilitation, moreover the mean change between the start of treatment and the end of the therapy as evaluated with the Wilcoxon signed-rank test was −4.25 points for the performance score and −2.96 points for the satisfaction score. CONCLUSIONS: This study showed that the COPM is a reliable tool for assessing SCI clients’ perceived performance of daily activities and their satisfaction with their performance."
2796,Efficacy of water spray for evaporative cooling in athletes with spinal cord injury,"STUDY DESIGN: Interventional crossover study. OBJECTIVE: Spinal cord injury (SCI) disrupts afferent input to the hypothalamus and impairs efferent vaso- and sudomotor output, especially in lesions above the sympathetic chain (T1-L2). In consequence, persons with SCI under heat stress experience impairment in the ability to dissipate heat proportional to the lesion level. Thermoregulatory dysfunction places an individual at high risk of hyperthermia, which can be life threatening, especially for athletes with SCI during exercise. Current evidence on therapeutic cooling techniques in athletes with SCI is limited, but basic physiologic and research data suggest water spray (WS) might be efficacious, particularly in athletes with tetraplegia (TP), who are most impaired in thermoregulation. The aim of this study was to evaluate the effect of WS on core temperature (Tc) during exercise in athletes with SCI. SETTING: Texas, USA. METHODS: Eleven individuals with SCI: seven with TP, four with paraplegia (PP); and sixteen able-bodied (AB) controls underwent a wheelchair intermittent sprint exercise for 90 min under two conditions: (1) WS application every 15 min and (2) control (C), without WS. Tc was measured every 15 min and was analyzed for the effect of group (TP, PP, and AB) and time. Change in Tc (ΔTc) was also compared between groups. RESULTS: ΔTc was significantly higher in TP vs. PP (p < 0.0001) and TP vs. AB (p < 0.0001) groups under C treatment. WS significantly attenuated ΔTc in TP (p = 0.001), but did not change ΔTc in PP or AB. CONCLUSION: WS effectively attenuated Tc elevation during exercise in athletes with TP. SPONSORSHIP: Texas chapter of the Paralyzed Veterans of America."
2797,Early use of an implantable diaphragm pacing stimulator for a child with severe acute flaccid myelitis—a case report,"INTRODUCTION: Acute Flaccid Myelitis (AFM) is a recently recognized, polio-like illness of children that can be functionally devastating. Severe cases can lead to ventilatory failure. Incomplete phrenic nerve injuries in other populations has been shown to respond to diaphragmatic stimulation. We therefore proposed an early assessment for incomplete denervation by laparoscopic direct stimulation of the diaphragm and placement of a diaphragmatic pacing system to enhance diaphragm function. CASE PRESENTATION: A 3 year-old girl presented with AFM with clinically and electrodiagnostically severe involvement of all four limbs and muscles of respiration. Direct stimulation of the diaphragm demonstrated contraction and a diaphragmatic stimulator was placed at 3 weeks post presentation. The patient was immediately able to tolerate short bouts of reduced ventilation settings. Electromyography via the pacing wires demonstrated intact motor units consistent with partial denervation/reinnervation in the left hemidiaphragm, and no motor units in the right hemidiaphragm. At three months, she tolerated 6 h of pacing on pressure support setting. At 5 months she demonstrated larger tidal volumes with active pacing than without. DISCUSSION: In our experience, AFM patients who require chronic ventilator support are rarely able to be weaned. Despite clinical and surface electrodiagnostic evidence of complete phrenic nerve involvement, the patient’s diaphragm responded to direct stimulation. The patient preferred pacing over non-pacing times and showed improved ventilatory ability with pacing as opposed to without, though remains ventilator-dependent. These findings support augmentation of diaphragm function and possible enhanced recovery of spontaneous function."
2798,The history of the use of intrathecal prostigmine to achieve fertility in men with spinal cord injuries,
2799,Acquired Chiari malformation following spinal cord injury—a case series,"INTRODUCTION: Chiari malformation is characterized by caudal descent of the cerebellar tonsils through the foramen magnum. Acquired Chiari malformations (ACM) have previously been described after a variety of pathologies including lumbar puncture, cerebrospinal fluid (CSF) drainage, lumboperitoneal shunts, and conditions causing craniocephalic disproportion. CASE PRESENTATION: We present four cases of ACM following spinal cord injury (SCI), which has not previously been described in the literature. DISCUSSION: ACM is rare and typically associated with abnormalities in CSF pressure or space-occupying lesions. This case series describes the potential association of SCI with ACM. We discuss the imaging findings and clinical management of these patients. Early recognition and intervention may be important to prevent progressive neurology in this vulnerable patient group."
2800,"#spinalcordinjury, #life, #climate, #sustainability",
2801,Fluoroscopy-guided percutaneous needle aspiration of posterior epidural abscesses: a report of two cases,"INTRODUCTION: Spinal epidural abscesses are most commonly treated with surgical decompression and antibiotics or in specific instances managed medically with antibiotic therapy alone. Image-guided percutaneous aspiration as an alternative to surgery has only rarely been reported in the literature. CASE PRESENTATION: We report two cases of successful fluoroscopy-guided needle aspiration of posterior epidural abscesses. Case 1 is a 48-year-old man who presented with several days of escalating back pain and constitutional symptoms with MRI showing a posterior epidural abscess at L2–L3 causing spinal stenosis. The patient remained neurologically intact. Percutaneous needle aspiration of the collection provided dramatic pain relief with the aspirate growing methicillin sensitive Staphylococcus aureus. The patient made a full recovery on antibiotic therapy. Case 2 is an 81-year-old man who presented with worsening upper back pain and was found to have osteomyelitis/discitis with a large posterior epidural abscess in the thoracic spine. Needle drainage was performed with the sample growing Bacteroides fragilis. This patient also responded successfully to nonsurgical management with full recovery after appropriate antibiotic therapy. DISCUSSION: In carefully selected patients, image-guided needle aspiration of posterior epidural abscesses may be a viable and less invasive alternative to surgery."
2802,Risk-benefit value of upper extremity function by an implanted electrical stimulation device targeting chronic cervical spinal cord injury,"STUDY DESIGN: A cross-sectional stated-preference survey using direct-assessment questions. OBJECTIVE: To determine the relative value placed on different outcomes to be used in a pivotal trial for the upper extremity configuration of the Networked Neuroprosthesis (NNP) as well as the tolerance of the expected adverse event profile. SETTING: Academic medical center in the United States. METHODS: Distribution of an online survey to adults living with tetraplegia; extent of agreement with each question/statement was obtaining using a 1–7 Likert scale. RESULTS: There were 8 statements about potential benefits in arm/hand function; for all statements, more than 70% of participants rated the functions as “1-very important” to regain. There were variable degrees of concern related to risks that could occur during the 30-day post-surgical period and increasing degrees of concern related to risks that could occur in the first 5 years, potentially due to the device, based on the increasing degree of invasiveness of the intervention required to address the event. When analysing the results based on all degrees of interest, more than 64% of responders were interested in getting the NNP with a success rate threshold as low as 50% regardless of time post-injury. Chi-squared analyses revealed some associations between responses and sex, injury level, and injury duration; however, none of these were statistically significant upon post-hoc analysis. CONCLUSION: Data here indicate that people with tetraplegia are highly interested in a range of arm/hand functions and are tolerant of expected risks that may be associated with implanted neuroprosthetics. SPONSORSHIP: The Institute for Functional Restoration funded this project through a sub-contract to K.D. Anderson from a larger Special Projects Award (grant number FP0020773) from the Craig H. Neilsen Foundation."
2803,Cross-sectional and prospective data-collection in North Macedonia—methodological considerations,"STUDY DESIGN: Cross-sectional and prospective cohort-study. OBJECTIVES: To describe methodological issues, experienced challenges related to data collection in North Macedonia and to discuss possible improvements of epidemiological data collection in future studies. SETTING: Clinic for Traumatology, Orthopedics, Anesthesia, Reanimation, Intensive Care Unit and Emergency Center, Mother Teresa Skopje University Hospital, Skopje and community settings, North Macedonia. METHOD: A description of methodological challenges experienced in collecting data from 78 persons with acute and chronic traumatic spinal cord injury (SCI) examined and interviewed in 2015–2017 using a semiquantitative questionnaire and standard assessments tools. RESULTS: This study identified three major challenges with data collection in this setting: (1) research logistics and procedures, such as recruitment, infrastructure, and compensation, (2) ethical issues and the initial lack of mutual trust and understanding between researchers and participants, and (3) scientific quality and interpretation, including representativeness. CONCLUSIONS: Methodological issues influenced by settings, are important to consider when interpreting study results. Healthcare systems vary between (and sometimes in) countries, language and culture may introduce barriers to understanding, and epidemiological research also rely on infrastructure and surroundings. For this study, making time for and listening to the participants without being intruding was of special importance in building trust and a good relationship with the participants during recruiting participants and collecting data. We here provide suggestions regarding how to facilitate future epidemiological data collections in North Macedonia."
2804,Persistent knee pain after uncomplicated total knee arthroplasty secondary to undiagnosed spondylotic myelopathy: a case report,"INTRODUCTION: Knee osteoarthritis and cervical spondylotic myelopathy are both frequent disorders in the aging patient. Total knee arthroplasty is an increasingly common surgical procedure, with approximately 20% of patients describing persistent knee pain after the procedure, for which it is often difficult to find a cause. We review known reasons for pain after total knee arthroplasty and present a new clinically challenging case of persistent knee pain due to previously undiagnosed cervical spondylotic myelopathy. CASE PRESENTATION: Our patient presented with painful knee spasms after an uncomplicated total knee arthroplasty. Her workup revealed cervical spondylotic myelopathy with isolated changes in tone in the affected extremity as well as weakness and atrophy in non-painful limbs. Her clinical status improved after cervical decompression and fusion. We perform a literature review for prior reports of isolated knee pain due to cervical spondylotic myelopathy and find no previous reported association with total knee arthroplasty. DISCUSSION: Cervical spondylotic myelopathy is the most common spinal cord disorder in older adults. Incidence increases with age and the clinical manifestations may present with a variety of neurological findings. Careful musculoskeletal and neurologic examination is critical to an accurate and timely diagnosis."
2805,International survey responses from an interdisciplinary cohort of spinal cord injury clinicians assessing professional burnout and meaning in work,"STUDY DESIGN: While clinicians who care for patients with spinal cord injury may experience heightened levels of workplace stress related to secondary trauma, little is known about the characteristics of burnout and potential protective factors among interdisciplinary professionals who care for this distinct clinical population. An online survey of self-reported burnout symptoms and meaning in work was conducted to assess the prevalence of burnout and characteristics of meaning in work among spinal cord injury professionals. OBJECTIVES: To assess symptoms of professional burnout and meaning in work among a broad-ranging cohort of spinal cord injury clinicians and researchers. SETTING: A group of international spinal cord injury professionals. METHODS: An online survey was developed using commonly assessed metrics of burnout and meaning in work based upon prior literature. RESULTS: A majority of survey respondents reported feeling exhaustion (60.1%), while fewer reported feelings of burnout (41.1%) or work-life imbalance (31.9%). Many respondents found support in personal relationship from friends and family and reported using various strategies to deal with work stress, including exercise, meditation, and engaging in personally meaningful activities outside of work. CONCLUSIONS: Exhaustion is a prevalent issue for many spinal cord injury professionals and burnout appears to be a significant issue for a subset of responders, yet despite potential workplace stressors, spinal cord injury professionals reported high meaningfulness of work, positive impact from colleagues, and satisfaction with intellectual stimulation at work."
2806,Spinal holocord epidural abscess evacuated with double thoracic interval laminectomy: a rare case report with literature review,"INTRODUCTION: Holocord spinal cord epidural abscess is an uncommon condition that may result in serious neurological complications. Prompt diagnosis and early treatment is of paramount importance for an optimum clinical outcome. This case report describes a novel technique of interval laminectomy at two sites in the thoracic spine and surgical decompression with the help of infant feeding tubes in a case of holocord spinal epidural abscess (HSEA). CASE PRESENTATION: An 18-year-old male presented to the emergency department with high-grade fever and low back ache of 2 weeks duration and loss of bowel and bladder control for 4 days. Neurological examination revealed intact motor power and sensation in all four limbs at presentation; however, there was a rapid deterioration to complete quadriplegia within 24 h. A diagnosis of holocord epidural abscess was made. Emergent decompression via interval thoracic laminectomy was done and appropriate antimicrobial therapy was instituted. At 10 months of follow-up, the individual showed complete neurological recovery. DISCUSSION: The technique used in this case is unique with respect to the level of laminectomy and the manoeuvre employed for pus evacuation. Complete neurological and functional recovery was achieved despite complete paralysis pre-operatively. The outcome indicates that there may be good prognosis for individuals with HSEA accompanied with neurological deficit and emergent surgical decompression."
2807,Penetrating spinal cord injury causing paraplegia in a bird hunter in rural Tanzania,"INTRODUCTION: Cultural and socioeconomic factors influence the risk of sustaining a Traumatic Spinal Cord Injury (TSCI). The standard of management and rehabilitation available to TSCI patients differs greatly between high-income and low-income countries. CASE PRESENTATION: We report a 17-year-old male bird hunter, with no prior medical history, presenting with paraplegia and sensory loss from the xiphoid process down after being struck by an arrow in the left lateral side of the neck. DISCUSSION: Penetrating neck injuries are potentially life threatening because of the complex arrangement of vital structures in the neck. Management of spinal cord trauma resulting from such injuries in low-resource settings is challenging."
2808,Version 2.1 of the International Spinal Cord Injury Bowel Function Basic Data Set,
2809,Spinal extradural arachnoid cyst in cervicothoracic junction,"INTRODUCTION: Spinal extradural arachnoid cysts (SEACs) are rare expansive lesions that account for ~1% of all spinal tumors. They develop as the result of arachnoid membrane herniation through a small dural defect and are mostly reported to be located at lower thoracic region and thoracolumbar junction. CASE PRESENTATION: We report a rare case of SEAC located in the cervicothoracic junction causing neurologic compression. DISCUSSION: Only 3% of all SEACs are observed in the cervical spine. They are the most common in young men and present with compressive symptoms. SEACs have potential to enlarge. As they are surgically removable lesions, early and definite diagnosis is important in preventing clinical deterioration. MRI is recommended for the diagnosis and preoperative planning."
2810,A rare cause of neurological deterioration to complete paraplegia after surgery for thoracic myelopathy: a case report,"INTRODUCTION: Progressive deterioration of neurological status post-thoracic myelopathy surgery after a clinically stable period is rare and can pose a diagnostic dilemma. We present our experience with such a case where all known etiologies were ruled out and the cause of deterioration could not be conclusively identified. The course was found to be similar to sub-acute post-traumatic ascending myelopathy (SPAM). However, the condition has only been described for traumatic injuries so far. CASE PRESENTATION: Our patient presented a history of back pain and associated gait instability for one and a half months. There was no history of trauma. Investigations suggested an Anderson-like lesion at T11–T12 with cord edema at the same level suggestive of instability. She underwent posterior stabilization T9 to L2 and laminectomy of T11 as well as T12 under neuromonitoring. The postoperative sequence of events included an episode of pyrexia on the fifth day of surgery, neurological deterioration from the seventh day of surgery proceeding to complete paraplegia by the fourteenth day, no response to steroid treatment and no signs of recovery till two years post surgery. MRI findings were suggestive of SPAM, and there was no evidence of infection. DISCUSSION: Ascending myelopathy is a potential but rare cause of delayed deterioration in neurological status after surgical intervention. MRI findings of cord edema extending more than four levels above the involved segments is a characteristic finding of the condition. Ascending myelopathy may lead to complete cord injury. The precise cause of the condition is unknown and prognosis remains poor."
2811,"Pulse article: opioid prescription for pain after spinal cord damage (SCD), differences from recommended guidelines, and a proposed algorithm for the use of opioids for pain after SCD","STUDY DESIGN: Online questionnaire of spinal cord injury (SCI) physicians. OBJECTIVES: The objective of this study is to characterize the approach to opioid prescription for persons with spinal cord damage (SCD). SETTING: An international online questionnaire. METHODS: A survey was posted online and circulated among international societies within the field of SCI medicine from August to November 2018. RESULTS: One hundred and twenty-three physicians responded to the survey. Of these, 107 (92%) managed pain for persons with SCD. Most (82%) felt that opioid prescription was appropriate for uncontrolled acute pain, but fewer (67%) felt it was appropriate for chronic pain. Of those who felt opioids had a role in the treatment of neuropathic pain, 46% did not think there should be a specific upper limit of opioid dose. The majority (85%) would continue prescribing high doses (250 morphine milligram equivalent (MME) doses/day) if that dose were effective. Tramadol was the most common opioid prescribed first line. CONCLUSION: Most physicians who responded to this survey prescribe opioids for intractable pain after SCD. A significant proportion of respondents believed that there should not be a specific upper limit of opioid dose prescribed if the drug is tolerated; this does not align with current recommendations. Most physicians do not feel influenced in their prescribing habits by regulatory bodies. If physicians decide to taper an opioid that is being tolerated well, it is most commonly related to a fear of the patient developing an opioid-use disorder. The authors propose an algorithm that may help align practice patterns with current recommended practice guidelines."
2812,Medullary involvement in neurosyphilis: a report of 12 cases and a review of the literature,"STUDY DESIGN: Retrospective case series. OBJECTIVES: To describe the epidemiological, clinical, MRI and therapeutic features and the outcomes of patients with syphilitic myelitis in a third-level hospital in Marrakesh in southern Morocco. SETTING: The Neurology Department, University Hospital Mohamed VI Marrakesh, Morocco. METHODS: Twelve charts of persons with syphilitic myelitis over a period of 17 years were reviewed to determine demographics, presenting symptoms, clinical and radiological findings, biological features, treatment received and outcomes. RESULTS: There were 120 reports of neurosyphilis. Twelve patients (10%) had syphilitic myelitis. Eleven patients (92%) were male with mean age of 44 at presentation. Tabes dorsalis was the most common clinical form. Cerebrospinal fluid analysis showed lymphocytic meningitis in nine patients (75%). Spine MRI was abnormal in four patients (33%). All patients were treated with 30 million units of aqueous penicillin G IV per day for 10 days, every 3 months. In follow-up, two patients (17%) with clinical syphilitic meningomyelitis improved significantly, eight patients (66%) with tabes dorsalis and subacute transverse myelitis showed partial improvement but clinical status was stationary for two patients (17%) with Erb paraplegia. CONCLUSIONS: All patients with myelopathy should undergo syphilitic serology because of nonspecific manifestations and curability of this disease."
2813,Genome-wide identification of DNA-PKcs-associated RNAs by RIP-Seq,
2814,Jumonji domain-containing 6 (JMJD6) identified as a potential therapeutic target in ovarian cancer,"Jumonji domain-containing 6 (JMJD6) is a candidate gene associated with tumorigenesis, and JMJD6 overexpression predicts poor differentiation and unfavorable survival in some cancers. However, there are no studies reporting the expression of JMJD6 in ovarian cancer, and no JMJD6 inhibitors have been developed and applied to targeted cancer therapy research. In the present study, we found that the high expression of JMJD6 in ovarian cancer was correlated with poor prognosis in ovarian cancer. A potential inhibitor (SKLB325) was designed based on the crystal structure of the jmjC domain of JMJD6. This molecule significantly suppressed proliferation and induced apoptosis in a dose-dependent manner in SKOV3 cell lines as detected by CCK-8 cell proliferation assays and flow cytometry. A Matrigel endothelial tube formation assay showed that SKLB325 inhibited capillary tube organization and migration in HUVECs in vitro. We also observed that JMJD6 colocalized with p53 protein in the nucleus, with mRNA and protein expression of p53 as well as its downstream effectors significantly increasing both in vitro and in intraperitoneal tumor tissues treated with SKLB325. In addition, SKLB325 significantly reduced the intraperitoneal tumor weight and markedly prolonged the survival of tumor-bearing mice. Taken together, our findings suggest that JMJD6 may be a marker of poor prognosis in ovarian cancer and that SKLB325 may be a potential candidate drug for the treatment of ovarian cancer."
2815,EGFR TKIs impair lysosome-dependent degradation of SQSTM1 to compromise the effectiveness in lung cancer,"Tyrosine kinase inhibitors for epidermal growth factor receptor (EGFR TKIs) greatly improved clinical outcomes of patients with non-small cell lung cancer (NSCLC). Unfortunately, primary and acquired resistance limits their clinical benefits. To overcome such resistance, new generations of EGFR TKIs have been developed by targeting newly identified mutations in EGFR. However, much less effort has been put into alternative strategies, such as targeting the intrinsic protective responses to EGFR TKIs. In this study, we found that EGFR TKIs, including gefitinib and AZD9291, impaired lysosome-dependent degradation of SQSTM1, thus compromising their anti-cancer efficiency. By accumulating in the lysosome lumen, gefitinib and AZD9291 attenuated lysosomal acidification and impaired autolysosomal degradation of SQSTM1 owing to their intrinsic alkalinity. As a result, SQSTM1 protein was stabilized in response to gefitinib and AZD9291 treatment and conferred EGFR TKI resistance. Depleting SQSTM1 significantly increased the sensitivity of NSCLC cells to gefitinib and AZD9291 both in vitro and in vivo. Furthermore, a chemically modified gefitinib analog lacking alkalinity displayed stronger inhibitory effects on NSCLC cells. Therefore, targeting accumulated SQSTM1 or chemically modified EGFR TKIs may represent new strategies to increase the effectiveness of EGFR targeted therapy."
2816,"The proatherosclerotic function of indoleamine 2, 3-dioxygenase 1 in the developmental stage of atherosclerosis","The discrepancy of indoleamine 2, 3-dioxygenase 1 (IDO1) function in atherosclerosis has been noted. Compared to the protective effect of IDO1 against established atherogenesis, the role of IDO1 in the developmental process of atherosclerosis is still unclear. Here, the expression patterns and activities of IDO1 and its isoenzyme tryptophan 2,3-dioxygenase (TDO) in aortas and blood samples of patients with atherosclerosis were investigated. IDO1 and TDO were colocalized with CD3-positive lymphocytes and CD68-positive macrophages in atherosclerotic lesions. The expression and activity of IDO1 and TDO increased with the grade of the histological classification in early atherosclerosis (grade I, II), but the increase did not continue in advanced atherosclerosis (grade III). Treatment of THP-1 macrophages (THP-M) with oxidized low-density lipoprotein (oxLDL) induced the expression of IDO1 via the PI3K/Akt/NF-κB pathway, indicating the potential function of IDO1 in foam cells. Before and after treatment with oxLDL on THP-M, IFN-γ-induced IDO1 exhibited different degrees of promotion on foaming, inflammatory factor production and cell apoptosis. Finally, we found that the IDO1 inhibitor 1-methyl-tryptophan could elevate the high-density lipoprotein cholesterol level in serum and reduce the area of the aortic atherosclerotic lesions in high-fat diet-fed ApoE(−/−) mice. Our study indicated that IDO1 played a complicated and unfixed role in the entire process of atherogenesis, despite the atheroprotective role in established atherosclerosis. IDO1 also had proatherosclerotic functions in the developmental stages of atherosclerosis. Modulation of IDO1 could be a good method for alleviating atherosclerosis."
2817,Tumor-suppressive function and mechanism of HOXB13 in right-sided colon cancer,"Right-sided colon cancer (RCC) and left-sided colon cancer (LCC) differ in their clinical and molecular features. An investigation of differentially expressed genes (DEGs) between RCC and LCC could contribute to targeted therapy for colon cancer, especially RCC, which has a poor prognosis. Here, we identified HOXB13, which was significantly less expressed in RCC than in LCC and associated with prognosis in RCC, by using 5 datasets from the Gene Expression Omnibus (GEO). Tissue sample analysis showed that HOXB13 was differentially expressed between normal and only RCC tumor tissues. HOXB13 inhibited colon cancer cell proliferation and induced apoptosis both in vitro and in vivo. Furthermore, we found that HOXB13 might be regulated by DNMT3B and suppress C-myc expression to exert antitumor effects via β-catenin/TCF4 signals in RCC. In conclusion, the current study is the first to demonstrate that HOXB13 has a tumor-suppressive effect in RCC. High expression levels of HOXB13 are associated with prolonged overall survival in patients with RCC. The DNMT3B-HOXB13-C-myc signaling axis might be a molecular target for the treatment of RCC."
2818,Publisher Correction: Endogenous formaldehyde is a memory-related molecule in mice and humans,
2819,Perceptions of Digital Health Education Among European Medical Students: Mixed Methods Survey,"BACKGROUND: Digital health technologies hold promise to enhance patient-related outcomes, to support health care staff by reducing their workload, and to improve the coordination of care. As key users of digital health technologies, health care workers are crucial to enable a meaningful digital transformation of health care. Digital health literacy and digital skills should become prerequisite competencies for health professionals to facilitate the implementation and leverage the potential of digital technologies to improve health. OBJECTIVE: We aimed to assess European medical students’ perceived knowledge and opinions toward digital health, the status of digital health implementation in medical education, and the students’ most pressing needs. METHODS: The explanatory design of our mixed methods study was based on an online, anonymous, self-administered survey targeted toward European medical students. A linear regression analysis was used to identify the influence of the year of medical studies on the responses. Additional analysis was performed by grouping the responses by the self-evaluated frequency of eHealth technology use. Written responses to four qualitative questions in the survey were analyzed using an inductive approach. RESULTS: The survey received a total of 451 responses from 39 European countries, and there were respondents for every year of medical studies. The majority of respondents saw advantages in the use of digital health. While 40.6% (183/451) felt prepared to work in a digitized health care system, more than half (240/451, 53.2%) evaluated their eHealth skills as poor or very poor. Medical students considered lack of education to be the reason for this, with 84.9% (383/451) agreeing or strongly agreeing that more digital health education should be implemented in the medical curriculum. Students demanded introductory and specific eHealth courses covering data management, ethical aspects, legal frameworks, research and entrepreneurial opportunities, role in public health and health systems, communication skills, and practical training. The emphasis lay on tailoring learning to future job requirements and interprofessional education. CONCLUSIONS: This study shows a lack of digital health-related formats in medical education and a perceived lack of digital health literacy among European medical students. Our findings indicate a gap between the willingness of medical students to take an active role by becoming key players in the digital transformation of health care and the education that they receive through their faculties."
2820,"Development of an International, Multicenter, Hyperbaric Oxygen Treatment Registry and Research Consortium: Protocol for Outcome Data Collection and Analysis","BACKGROUND: Hyperbaric oxygen (HBO(2))—oxygen at pressures higher than atmospheric—is approved for 14 indications by the Undersea and Hyperbaric Medical Society. HBO(2)’s main effect is to increase oxygen content in plasma and body tissues, which can counteract hypoxia or ischemia. Laboratory studies show that HBO(2) has effects beyond relieving hypoxia (eg, promoting angiogenesis in irradiated tissue, anti-inflammatory effects, radiosensitization of tumors, hypoxia preconditioning, and fungal growth inhibition) and has potential to treat conditions such as inflammatory bowel disease and pyoderma gangrenosum. Lack of consistently collected outcome data on a large cohort of individuals receiving HBO(2) therapy limits its use for both established and new indications. A course of therapy often involves 30-40 visits to a hyperbaric chamber, so the number of patients seen at any given center is constrained by chamber capacity. As a result, published HBO(2) outcome data tend to be from small case series because few patients with a particular condition are treated at a given center. To solve this problem, a registry that collects and pools data systematically from multiple institutions has been established. OBJECTIVE: The aim of this study is to collect consistent outcome data across multiple hyperbaric centers to assess treatment effectiveness and establish a research consortium. METHODS: A consortium of hyperbaric centers who have agreed to collect consistent outcome data on all patients seen has been assembled. Data are collected at each participating center using Research Electronic Data Capture (REDCap), a web-based, data collection system used frequently for research. Standard outcome measures have been defined for each condition, which are programmed into the REDCap data collection templates. Governance is through a consortium agreement that defines data security, data sharing, publications, liability, and other issues. Centers obtain Institutional Review Board (IRB) and ethics approval to participate, either from their own institutions or by relying on the IRB at the coordinating center at Dartmouth College. Dissemination will occur through a yearly report and by publications based on the data in the registry. RESULTS: Early results from some common indications show significant pretreatment to posttreatment changes. Additional indications and outcome measures are being added using the procedures outlined in the consortium agreement. CONCLUSIONS: The registry collects consistent outcome information for a therapy that needs further study and a stronger evidence base. It also overcomes the challenge of collecting data from an adequate number of patients for both established and emerging indications by combining data collection from multiple centers. The data entry requirements should be within the capabilities of existing staff at any given hyperbaric center. By using REDCap, the registry can be expanded to include detailed information on particular indications and long-term follow-up on selected patients without significantly increasing the basic data entry requirements. Through the registry, a network of enrolled hyperbaric centers has been established that provides the basis for a clinical trial network. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18857"
2821,Right Knee—The Weakest Point of the Best Ultramarathon Runners of the World? A Case Study,"The impact of ultramarathons (UM) on the organs, especially in professional athletes, is poorly understood. We tested a 36-year-old UM male runner before and after winning a 24-h marathon. The primary goal of the study was cardiovascular assessment. The athlete experienced right knee pain for the first time after 12 h of running (approximately 130 km), which intensified, affecting his performance. The competitors ran on a 1984 m rectangle-loop (950 × 42 m) in an atypical clockwise fashion. The winner completed 516 rectangular corners. Right knee Magnetic Resonance Imaging (MRI) one day after the run showed general overload in addition to degenerative as well as specific features associated with “turning to the right”. Re-examination after three years revealed none of these findings. Different kinds of overloading of the right lower limb, including right knee pain, were indicated in 6 of 10 competitors from the top 20, including a woman who set the world record. The affected competitors suggested as cause for discomfort the shape of the loop and running direction. They believed that changing the direction of the run during the competition and an athletics stadium loop shape on a 2000–2500 m length is better for 24-h UM runners. In the absence of technical alternatives, the “necessary evil” is a counterclockwise run (also Association of Athletics Federations IAAF recommendation). Results suggest that a one-way, clockwise, 24-h UM run had an adverse effect on the athlete’s right knee, as a result of unsymmetrical load. Organizers of 24-h UM runs should consider the shape of the competition loop and apply the principle of uniform load on the musculoskeletal system (alternate directions run). In case of technical impossibility, it would be better to run counterclockwise, which is more common, preferred by runners, and recommended by the IAAF."
2822,Suicidal Presentations to Emergency Departments in a Large Australian Public Health Service over 10 Years,"This paper presents trends and characteristics for 32,094 suicidal presentations to two Emergency Departments (EDs) in a large health service in Australia across a 10-year period (2009–2018). Prevalence of annual suicidal presentations and for selected groups of consumers (by sex, age groups, and ethnicity) was determined from a machine learning diagnostic algorithm developed for this purpose and a Bayesian estimation approach. A linear increase in the number of suicidal presentations over 10 years was observed, which was 2.8-times higher than the increase noted in all ED presentations and 6.1-times higher than the increase in the population size. Females had higher presentation rates than males, particularly among younger age groups. The highest rates of presentations were by persons aged 15–24. Overseas-born persons had around half the rates of suicidal presentations than Australian-born persons, and Indigenous persons had 2.9-times higher rates than non-Indigenous persons. Of all presenters, 70.6% presented once, but 5.7% had five or more presentations. Seasonal distribution of presentations showed a peak at the end of spring and a decline in winter months. These findings can inform the allocation of health resources and guide the development of suicide prevention strategies for people presenting to hospitals in suicidal crisis."
2823,Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation,"Molecular-glue degraders mediate interactions between target proteins and components of the ubiquitin-proteasome system to cause selective protein degradation. Here, we report a new molecular glue HQ461 discovered by high-throughput screening. Using loss-of-function and gain-of-function genetic screening in human cancer cells followed by biochemical reconstitution, we show that HQ461 acts by promoting an interaction between CDK12 and DDB1-CUL4-RBX1 E3 ubiquitin ligase, leading to polyubiquitination and degradation of CDK12-interacting protein Cyclin K (CCNK). Degradation of CCNK mediated by HQ461 compromised CDK12 function, leading to reduced phosphorylation of a CDK12 substrate, downregulation of DNA damage response genes, and cell death. Structure-activity relationship analysis of HQ461 revealed the importance of a 5-methylthiazol-2-amine pharmacophore and resulted in an HQ461 derivate with improved potency. Our studies reveal a new molecular glue that recruits its target protein directly to DDB1 to bypass the requirement of a substrate-specific receptor, presenting a new strategy for targeted protein degradation."
2824,Statistical issues regarding the article by Liu et al.,
2825,Consistent apparent Young’s modulus of human embryonic stem cells and derived cell types stabilized by substrate stiffness regulation promotes lineage specificity maintenance,"BACKGROUND: Apparent Young’s modulus (AYM), which reflects the fundamental mechanical property of live cells measured by atomic force microscopy and is determined by substrate stiffness regulated cytoskeletal organization, has been investigated as potential indicators of cell fate in specific cell types. However, applying biophysical cues, such as modulating the substrate stiffness, to regulate AYM and thereby reflect and/or control stem cell lineage specificity for downstream applications, remains a primary challenge during in vitro stem cell expansion. Moreover, substrate stiffness could modulate cell heterogeneity in the single-cell stage and contribute to cell fate regulation, yet the indicative link between AYM and cell fate determination during in vitro dynamic cell expansion (from single-cell stage to multi-cell stage) has not been established. RESULTS: Here, we show that the AYM of cells changed dynamically during passaging and proliferation on substrates with different stiffness. Moreover, the same change in substrate stiffness caused different patterns of AYM change in epithelial and mesenchymal cell types. Embryonic stem cells and their derived progenitor cells exhibited distinguishing AYM changes in response to different substrate stiffness that had significant effects on their maintenance of pluripotency and/or lineage-specific characteristics. On substrates that were too rigid or too soft, fluctuations in AYM occurred during cell passaging and proliferation that led to a loss in lineage specificity. On a substrate with ‘optimal’ stiffness (i.e., 3.5 kPa), the AYM was maintained at a constant level that was consistent with the parental cells during passaging and proliferation and led to preservation of lineage specificity. The effects of substrate stiffness on AYM and downstream cell fate were correlated with intracellular cytoskeletal organization and nuclear/cytoplasmic localization of YAP. CONCLUSIONS: In summary, this study suggests that optimal substrate stiffness regulated consistent AYM during passaging and proliferation reflects and contributes to hESCs and their derived progenitor cells lineage specificity maintenance, through the underlying mechanistic pathways of stiffness-induced cytoskeletal organization and the downstream YAP signaling. These findings highlighted the potential of AYM as an indicator to select suitable substrate stiffness for stem cell specificity maintenance during in vitro expansion for regenerative applications."
2826,Endoscopic dacryocystorhinostomy with and without mucosal flap—is there any difference?,"BACKGROUND: The nasal mucosa is sacrificed in conventional endoscopic dacryocystorhinostomies (EDCRs). Some surgeons, however, modify the technique by elevating a mucosal flap prior to creating the osteotomy with the aim of preserving the mucosa. To our knowledge, no clear-cut benefit of a mucosal flap has been established. The aim of this study is to examine the differences in surgical techniques and success rates of EDCRs with and without mucosal flap preservation. METHODS: We carried out a medical record review of all patients who underwent primary EDCR at the Goldschleger Eye Institute from October 2009 to October 2017. The following data were retrieved from the medical database and analyzed: patient demographics (age at diagnosis and gender), medical history, examination findings, surgical details, postoperative success, complications, and follow-up. RESULTS: A total of 107 patients who underwent 117 EDCRs participated in the study. Fifty-one patients comprised the group without a mucosal flap and 56 patients comprised the group with mucosal flap preservation. The medical history, presenting complaints, and preoperative examination findings were similar for both groups. The surgical success rate was not significantly different between the groups (82.1% without flap vs. 86.8% with flap, P = 0.478, Chi-square). CONCLUSION: The findings of this comparison of EDCRs with and without mucosal flap preservation in a large patient population revealed no differences in surgical success or complications rates between the two procedures and, therefore, no benefit for adding flap preservation to conventional EDCRs."
2827,Berberine derivatives with a long alkyl chain branched by hydroxyl group and methoxycarbonyl group at 9-position show improved anti-proliferation activity and membrane permeability in A549 cells,"Berberine (BBR) exhibits diverse bioactivities, including anticancer activity; but its poor druggability limits its applications. In this study, we designed and synthesized a series of 9-O position modified BBR derivatives aiming to improve its cell permeability and anticancer activity, utilizing a long alkyl chain branched by hydroxyl group and methoxycarbonyl group. Among these compounds, B10 showed 3.6-fold higher intracellular concentration than BBR, as well as 60-fold increased anti-proliferation activity against human lung cancer A549 cells compared with BBR. Treatment with B10 (1, 2 μM) induced apoptosis of A549 cells. Further investigations showed that B10 treatment dose-dependently affected mitochondrial functions, including oxygen consumption rate (OCR), mitochondrial membrane potential (MMP) and the morphology of mitochondria in A549 cells. Therefore, this work offers a new way for BBR structural modification through improving cell membrane permeability to affect mitochondrial functions and potential anti-tumor therapy in the future."
2828,Targeting the cholinergic system in Parkinson’s disease,"Motor control in the striatum is an orchestra played by various neuronal populations. Loss of harmony due to dopamine deficiency is considered the primary pathological cause of the symptoms of Parkinson’s disease (PD). Recent progress in experimental approaches has enabled us to examine the striatal circuitry in a much more comprehensive manner, not only reshaping our understanding of striatal functions in movement regulation but also leading to new opportunities for the development of therapeutic strategies for treating PD. In addition to dopaminergic innervation, giant aspiny cholinergic interneurons (ChIs) within the striatum have long been recognized as a critical node for balancing dopamine signaling and regulating movement. With the roles of ChIs in motor control further uncovered and more specific manipulations available, striatal ChIs and their corresponding receptors are emerging as new promising therapeutic targets for PD. This review summarizes recent progress in functional studies of striatal circuitry and discusses the translational implications of these new findings for the treatment of PD."
2829,PEITC triggers multiple forms of cell death by GSH-iron-ROS regulation in K7M2 murine osteosarcoma cells,"Phenethyl isothiocyanate (PEITC) is an isothiocyanate that largely exists in cruciferous vegetables and exhibits chemopreventive and chemotherapeutic potential against various cancers. However, it is little known about the molecular mechanisms of its antitumor action against osteosarcoma, which is the second highest cause of cancer-related death in children and adolescents. In this study, we investigated the effects of PEITC on K7M2 murine osteosarcoma both in vitro and in vivo. We found that treatment with PEITC dose-dependently inhibited the viability of K7M2 murine osteosarcoma cells with an IC(50) value of 33.49 μM at 24 h. PEITC (1, 15, 30 μM) dose-dependently inhibited the cell proliferation, caused G(2)/M cell cycle arrest, depleted glutathione (GSH), generated reactive oxygen species (ROS), altered iron metabolism, and triggered multiple forms of cell death, namely ferroptosis, apoptosis, and autophagy in K7M2 cells. We further revealed that PEITC treatment activated MAPK signaling pathway, and ROS generation was a major cause of PEITC-induced cell death. In a syngeneic orthotopic osteosarcoma mouse model, administration of PEITC (30, 60 mg/kg every day, ig, for 24 days) significantly inhibited the tumor growth, but higher dose of PEITC (90 mg/kg every day) compromised its anti-osteosarcoma effect. Histological examination showed that multiple cell death processes were initiated, iron metabolism was altered and MAPK signaling pathway was activated in the tumor tissues. In conclusion, we demonstrate that PEITC induces ferroptosis, autophagy, and apoptosis in K7M2 osteosarcoma cells by activating the ROS-related MAPK signaling pathway. PEITC has promising anti-osteosarcoma activity. This study sheds light on the redox signaling-based chemotherapeutics for cancers."
2830,Inactivation of TSC1 promotes epithelial-mesenchymal transition of renal tubular epithelial cells in mouse diabetic nephropathy,"Epithelial–mesenchymal transition (EMT) of renal tubular epithelial cells is one of the potential mechanisms of renal fibrosis, which promotes the development of diabetic nephropathy (DN). However, the molecular mechanisms of EMT remain largely unknown. Tuberous sclerosis proteins TSC1 and TSC2 are key integrators of growth factor signaling, and the loss of TSC1 or TSC2 function leads to a spectrum of diseases that underlie abnormalities in cell growth, proliferation, differentiation, and migration. In this study, we investigated the effects of TSC1 on high glucose (HG)-induced EMT of human proximal tubular epithelial HK-2 cells in vitro and renal fibrosis in TSC1(−/−) and db/db mice. We found that the exposure of HK-2 cells to HG (30 mM) time-dependently decreased TSC1 expression, increased the phosphorylation of mTORC1, P70S6K, and 4E-BP-1, and promoted cell migration, resulting in EMT. Transfection of the cells with TSC1 mimic significantly ameliorated HG-induced EMT of HK-2 cells. The tubules-specific TSC1 knockout mice (TSC1(−/−)) displayed a significant decline in renal function. TSC1(−/−) mice, similar to db/db mice, showed greatly activated mTORC1 signaling and EMT process in the renal cortex and exacerbated renal fibrosis. Overexpression of TSC1 through LV-TSC1 transfection significantly alleviated the progression of EMT and renal fibrosis in the renal cortex of db/db mice. Taken together, our results suggest that TSC1 plays a key role in mediating HG-induced EMT, and inhibition of TSC1-regulated mTORC1 signaling may be a potential approach to prevent renal fibrosis in DN."
2831,Mechanisms and pharmacokinetic/pharmacodynamic profiles underlying the low nephrotoxicity and ototoxicity of etimicin,"Etimicin (ETM), a fourth-generation aminoglycosides (AGs), is now widely clinically used in China due to its high efficacy and low toxicity. However, the mechanisms underlying its low nephrotoxicity and ototoxicity remain unclear. In the present study we compared the antibacterial and toxicity profiles of etimicin, gentamicin (GM, a second-generation AG), and amikacin (AMK, a third-generation AG), and investigated their pharmacokinetic properties in the toxicity target organs (kidney and inner ear) and subcellular compartments. We first demonstrated that ETM exhibited superior antibacterial activities against clinical isolates to GM and AMK, and it exerted minimal nephrotoxicity and ototoxicity in rats following multi-dose administration. Then, we conducted pharmacokinetic studies in rats, showed that the three AGs accumulated in the kidney and inner ear with ETM being distributed to a lesser degree in the two toxicity target organs as compared with GM and AMK high-dose groups. Furthermore, we conducted in vitro experiments in NRK-52E rat renal tubular epithelial cells and HEI-OC1 cochlear hair cells, and revealed that all the three AGs were distributed predominantly in the mitochondria with ETM showing minimal accumulation; they not only directly inhibited the activity of mitochondrial complexes IV and V but also inhibited mitochondrial function and its related PGC-1α-NRF1-TFAM pathway; ETM caused minimal damage to the mitochondrial complex and mitochondrial biogenesis. Our results demonstrate that the minimal otonephrotoxicity of ETM results from its lesser accumulation in mitochondria of target cells and subsequently lesser inhibition of mitochondrial function. These results provide a new strategy for discovering novel AGs with high efficacy and low toxicity."
2832,Response to Comment on: Quantification of anterior chamber reaction after intravitreal injections of conbercept and ranibizumab: a pilot study,
2833,Discovery of novel CBP bromodomain inhibitors through TR-FRET-based high-throughput screening,"The cAMP-responsive element binding protein (CREB) binding protein (CBP) and adenoviral E1A-binding protein (P300) are two closely related multifunctional transcriptional coactivators. Both proteins contain a bromodomain (BrD) adjacent to the histone acetyl transferase (HAT) catalytic domain, which serves as a promising drug target for cancers and immune system disorders. Several potent and selective small-molecule inhibitors targeting CBP BrD have been reported, but thus far small-molecule inhibitors targeting BrD outside of the BrD and extraterminal domain (BET) family are especially lacking. Here, we established and optimized a TR-FRET-based high-throughput screening platform for the CBP BrD and acetylated H4 peptide. Through an HTS assay against an in-house chemical library containing 20 000 compounds, compound DC_CP20 was discovered as a novel CBP BrD inhibitor with an IC(50) value of 744.3 nM. This compound bound to CBP BrD with a K(D) value of 4.01 μM in the surface plasmon resonance assay. Molecular modeling revealed that DC_CP20 occupied the Kac-binding region firmly through hydrogen bonding with the conserved residue N1168. At the celluslar level, DC_CP20 dose-dependently inhibited the proliferation of human leukemia MV4-11 cells with an IC(50) value of 19.2 μM and markedly downregulated the expression of the c-Myc in the cells. Taken together, the discovery of CBP BrD inhibitor DC_CP20 provides a novel chemical scaffold for further medicinal chemistry optimization and a potential chemical probe for CBP-related biological function research. In addition, this inhibitor may serve as a promising therapeutic strategy for MLL leukemia by targeting CBP BrD protein."
2834,Shikonin attenuates hyperhomocysteinemia-induced CD4(+) T cell inflammatory activation and atherosclerosis in ApoE(−/−) mice by metabolic suppression,"T cell metabolic activation plays a crucial role in inflammation of atherosclerosis. Shikonin (SKN), a natural naphthoquinone with anti-inflammatory activity, has shown to exert cardioprotective effects, but the effect of SKN on atherosclerosis is unclear. In addition, SKN was found to inhibit glycolysis via targeting pyruvate kinase muscle isozyme 2 (PKM2). In the present study, we investigated the effects of SKN on hyperhomocysteinemia (HHcy)-accelerated atherosclerosis and T cell inflammatory activation in ApoE(−/−) mice and the metabolic mechanisms in this process. Drinking water supplemented with Hcy (1.8 g/L) was administered to ApoE(−/−) mice for 2 weeks and the mice were injected with SKN (1.2 mg/kg, i.p.) or vehicle every 3 days. We showed that SKN treatment markedly attenuated HHcy-accelerated atherosclerosis in ApoE(−/−) mice and significantly decreased inflammatory activated CD4(+) T cells and proinflammatory macrophages in plaques. In splenic CD4(+) T cells isolated from HHcy-ApoE(−/−) mice, SKN treatment significantly inhibited HHcy-stimulated PKM2 activity, interferon-γ secretion and the capacity of these T cells to promote macrophage proinflammatory polarization. SKN treatment significantly inhibited HHcy-stimulated CD4(+) T cell glycolysis and oxidative phosphorylation. Metabolic profiling analysis of CD4(+) T cells revealed that Hcy administration significantly increased various glucose metabolites as well as lipids and acetyl-CoA carboxylase 1, which were reversed by SKN treatment. In conclusion, our results suggest that SKN is effective to ameliorate atherosclerosis in HHcy-ApoE(−/−) mice and this is at least partly associated with the inhibition of SKN on CD4(+) T cell inflammatory activation via PKM2-dependent metabolic suppression."
2835,"A thienopyridine, CB-20, exerts diuretic activity by inhibiting urea transporters","Urea transporters (UTs) are transmembrane proteins selectively permeable to urea and play an important role in urine concentration. UT-knockout mice exhibit the urea-selective urine-concentrating defect, without affecting electrolyte balance, suggesting that UT-B inhibitors have the potential to be developed as novel diuretics. In this study, we characterized a novel compound 5-ethyl-2-methyl-3-amino-6-methylthieno[2,3-b]pyridine-2,5-dicarboxylate (CB-20) with UT inhibitory activity as novel diuretics with excellent pharmacological properties. This compound was discovered based on high-throughput virtual screening combined with the erythrocyte osmotic lysis assay. Selectivity of UT inhibitors was assayed using transwell chambers. Diuretic activity of the compound was examined in rats and mice using metabolic cages. Pharmacokinetic parameters were detected in rats using LC–MS/MS. Molecular docking was employed to predict the potential binding modes for the CB-20 with human UT-B. This compound dose-dependently inhibited UT-facilitated urea transport with IC(50) values at low micromolar levels. It exhibited nearly equal inhibitory activity on both UT-A1 and UT-B. After subcutaneous administration of CB-20, the animals showed polyuria, without electrolyte imbalance and abnormal metabolism. CB-20 possessed a good absorption and rapid clearance in rat plasma. Administration of CB-20 for 5 days did not cause significant morphological abnormality in kidney or liver tissues of rats. Molecular docking showed that CB-20 was positioned near several residues in human UT-B, including Leu364, Val367, and so on. This study provides proof of evidence for the prominent diuretic activity of CB-20 by specifically inhibiting UTs. CB-20 or thienopyridine analogs may be developed as novel diuretics."
2836,AZD9291 inactivates the PRC2 complex to mediate tumor growth inhibition,"Deregulated Polycomb repressive complex 2 (PRC2) is intimately involved in tumorigenesis and progression, making it an invaluable target for epigenetic cancer therapy. Disrupting the EZH2–EED interaction, which is required for PRC2 enzymatic activity, is a promising strategy for cancer treatment. However, this kind of inhibitors are still limited. The in-cell protein–protein interaction screening was conducted for approximately 1300 compounds by NanoBRET technology. Co-immunoprecipitation (Co-IP), protein thermal shift assay (PTSA), and cellular thermal shift assay (CETSA) were performed to investigate the regulation of PRC2 by AZD9291. The anti-tumor effects of AZD9291 on breast cancer (BC) cells and diffuse large B-cell lymphoma (DLBCL) cells were detected. MicroRNA array assay, luciferase reporter assay, and qRT-PCR were conducted to identify the interaction and regulation among AZD9291, EZH2, and miR-34a. We discovered that, AZD9291, a potent and selective EGFR inhibitor, disrupted the interaction of EZH2–EED, leading to impairment of PRC2 activity and downregulation of EZH2 protein. In addition, AZD9291 declined EZH2 mRNA expression via upregulating the expression of a tumor suppressor, miR-34a. Our results suggest that AZD9291 can serve as a lead compound for further development of antagonist of PRC2 protein–protein interactions and EZH2 mRNA may be a direct target of miR-34a through non-canonical base pairing."
2837,Editorial on the consensus statement on diabetic retinopathy care pathway,
2838,Adipose-derived mesenchymal stem cells protect against CMS-induced depression-like behaviors in mice via regulating the Nrf2/HO-1 and TLR4/NF-κB signaling pathways,"Increasing studies show that inflammatory processes may be involved in depressive disorders. Nuclear factor erythroid-2 related factor 2 (Nrf2) modulates tissue microglial M1 phenotypic changes to the M2 phenotype, which is implicated in protection against inflammatory diseases. We have reported that the adipose-derived mesenchymal stem cells (ADSCs) display anti-inflammatory activity. In this study we explored whether the mechanism of anti-inflammatory activity of ADSCs was related to Nrf2. ADSCs were isolated from mouse fat pads and intravenously administered to chronic mild stress (CMS)-exposed C57BL/6 mice at the dose of 1 × 10(6) once a week for 3 weeks. We showed that ADSC administration significantly remedied CMS-induced depressive-like behaviors in sucrose preference test, tail suspension test, and forced swim test accompanied by suppressing microglial activation and the expression of inflammatory factors including MCP-1, TNF-α, IL-1β, and IL-6. Furthermore, ADSC administration promoted both the expression of BDNF and TrkB, and promoted Nrf2/HO-1 signaling but suppressed TLR4/NF-κB signaling in brain tissue. In order to elucidate the role of Nrf2/HO-1 signaling in ADSC-caused neuroprotection, Nrf2-modified ADSCs were cocultured with BV2 microglial cells, then exposed to lipopolysaccharide (LPS). Downregulation of Nrf2 in ADSCs decreased the protective effects of ADSCs against LPS-induced microglial activation and M1 polarization. Nrf2 overexpression in ADSCs markedly suppressed LPS-induced TLR4 and NF-κB expression in microglial cells. These results suggest a possible antidepressive mechanism correlated with microglial polarization for anti-inflammatory agents, which may provide a new microglia-targeted strategy for depression therapy."
2839,Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol,"Kaempferol is a natural flavonol that possesses various pharmacological activities, including anti-arthritis effects, yet the underlying mechanisms remain controversial. To evaluate the anti-arthritis efficacy and the underlying mechanisms of kaempferol, collagen-induced arthritis (CIA) mice were treated with kaempferol intragastrically (200 mg · kg(−1) · d(−1)) and intraperitoneally (20 mg · kg(−1) · d(−1)). Pharmacodynamic and pharmacokinetic studies showed that the oral administration of kaempferol produced distinct anti-arthritis effects in model mice with arthritis in terms of the spleen index, arthritis index, paw thickness, and inflammatory factors; the bioavailability (1.5%, relative to that of the intraperitoneal injection) and circulatory exposure of kaempferol (C(max) = 0.23 ± 0.06 ng/mL) and its primary metabolite kaempferol-3-O-glucuronide (C(max) = 233.29 ± 89.64 ng/mL) were rather low. In contrast, the intraperitoneal injection of kaempferol caused marginal anti-arthritis effects, although it achieved a much higher in vivo exposure. The much higher kaempferol content in the gut implicated a potential mechanism involved in the gut. Analysis of 16S ribosomal RNA revealed that CIA caused imbalance of 14 types of bacteria at the family level, whereas kaempferol largely rebalanced the intestinal microbiota in CIA mice. A metabolomics study showed that kaempferol treatment significantly reversed the perturbation of metabolites involved in energy production and the tryptophan, fatty acid and secondary bile acid metabolisms in the gut contents of the CIA mice. In conclusion, we demonstrate for the first time that the high level of kaempferol in the gut regulates the intestinal flora and microbiotic metabolism, which are potentially responsible for the anti-arthritis activities of kaempferol."
2840,RGD-hirudin-based low molecular weight peptide prevents blood coagulation via subcutaneous injection,"Thromboembolic disease is a common cardio-cerebral vascular disease that threatens human life and health. Thrombin not only affects the exogenous coagulation pathway, but also the endogenous pathway. Thus, it becomes one of the most important targets of anticoagulant drugs. RGD-hirudin is an anticoagulant drug targeting thrombin, but it can only be administered intravenously. We designed a low molecular weight peptide based on RGD-hirudin that could prevent blood clots. We first used NMR to identify the key amino acid residues of RGD-hirudin that interacted with thrombin. Then, we designed a novel direct thrombin inhibitor peptide (DTIP) based on the structure and function of RGD-hirudin using homology modeling. Molecular docking showed that the targeting and binding of DTIP with thrombin were similar to those of RGD-hirudin, suggesting DTIP interacted directly with thrombin. The active amino acids of DTIP were identified by alanine scanning, and mutants were successfully constructed. In blood clotting time tests in vitro, we found that aPTT, PT, and TT in the rat plasma added with DTIP were greatly prolonged than in that added with the mutants. Subcutaneous injection of DTIP in rats also could significantly prolong the clotting time. Thrombelastography analysis revealed that DTIP significantly delayed blood coagulation. Bio-layer interferometry study showed that there were no significant differences between DTIP and the mutants in thrombin affinity constants, suggesting that it might bind to other sites of thrombin rather than to its active center. Our results demonstrate that DTIP with low molecular weight can prevent thrombosis via subcutaneous injection."
2841,N-myristoylation: from cell biology to translational medicine,"Various lipids and lipid metabolites are bound to and modify the proteins in eukaryotic cells, which are known as ‘protein lipidation’. There are four major types of the protein lipidation, i.e. myristoylation, palmitoylation, prenylation, and glycosylphosphatidylinositol anchor. N-myristoylation refers to the attachment of 14-carbon fatty acid myristates to the N-terminal glycine of proteins by N-myristoyltransferases (NMT) and affects their physiology such as plasma targeting, subcellular tracking and localization, thereby influencing the function of proteins. With more novel pathogenic N-myristoylated proteins are identified, the N-myristoylation will attract great attentions in various human diseases including infectious diseases, parasitic diseases, and cancers. In this review, we summarize the current understanding of N-myristoylation in physiological processes and discuss the hitherto implication of crosstalk between N-myristoylation and other protein modification. Furthermore, we mention several well-studied NMT inhibitors mainly in infectious diseases and cancers and generalize the relation of NMT and cancer progression by browsing the clinic database. This review also aims to highlight the further investigation into the dynamic crosstalk of N-myristoylation in physiological processes as well as the potential application of protein N-myristoylation in translational medicine."
2842,"Discovery and biological evaluation of N-(3-(7-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-4-methyl-2-oxo-2H-pyrimido[4,5-d][1,3]oxazin-1(4H)-yl)phenyl)acrylamide as potent Bruton’s tyrosine kinase inhibitors","Bruton’s tyrosine kinase (BTK) is a key component of the B cell receptor (BCR) signaling pathway and plays a crucial role in B cell malignancies and autoimmune disorders; thus, it is an attractive target for the treatment of B cell related diseases. Here, we evaluated the BTK inhibitory activity of a series of pyrimido[4,5-d][1,3]oxazin-2-one derivatives. Combining this evaluation with structure-activity relationship (SAR) analysis, we found that compound 2 exhibited potent BTK kinase inhibitory activity, with an IC(50) of 7 nM. This derivative markedly inhibited BTK activation in TMD8 B cell lymphoma cells and thus inhibited the in vitro growth of the cells. Further studies revealed that compound 2 dose dependently arrested TMD8 cells at G(1) phase, accompanied by decreased levels of Rb, phosphorylated Rb, and cyclin D1. Moreover, following treatment with compound 2, TMD8 cells underwent apoptosis associated with PARP and caspase 3 cleavage. Interestingly, the results of the kinase activity assay on a small panel of 35 kinases showed that the kinase selectivity of compound 2 was superior to that of the first-generation inhibitor ibrutinib, suggesting that compound 2 could be a second-generation inhibitor of BTK. In conclusion, we identified a potent and highly selective BTK inhibitor worthy of further development."
2843,"ZYZ-803, a novel hydrogen sulfide-nitric oxide conjugated donor, promotes angiogenesis via cross-talk between STAT3 and CaMKII","Endothelial angiogenesis plays a vital role in recovery from chronic ischemic injuries. ZYZ-803 is a hybrid donor of hydrogen sulfide (H(2)S) and nitric oxide (NO). Previous studies showed that ZYZ-803 stimulated endothelial cell angiogenesis both in vitro and in vivo. In this study, we investigated whether the signal transducer and activator of transcription 3 (STAT3) and Ca(2+)/CaM-dependent protein kinase II (CaMKII) signaling was involved in ZYZ-803-induced angiogenesis. Treatment with ZYZ-803 (1 μM) significantly increased the phosphorylation of STAT3 (Tyr705) and CaMKII (Thr286) in human umbilical vein endothelial cells (HUVECs), these two effects had a similar time course. Pretreatment with WP1066 (STAT3 inhibitor) or KN93 (CAMKII inhibitor) blocked ZYZ-803-induced STAT3/CAMKII activation and significantly suppressed the proliferation and migration of HUVECs. In addition, pretreatment with the inhibitors significantly decreased ZYZ-803-induced tube formations along with the outgrowths of branch-like microvessels in aortic rings. In the mice with femoral artery ligation, administration of ZYZ-803 significantly increased the blood perfusion and vascular density in the hind limb, whereas co-administration of WP1066 or KN93 abrogated ZYZ-803-induced angiogenesis. By using STAT3 siRNA, we further explored the cross-talk between STAT3 and CaMKII in ZYZ-803-induced angiogenesis. We found that STAT3 knockdown suppressed ZYZ-803-induced HUVEC angiogenesis and affected CaMKII expression. ZYZ-803 treatment markedly enhanced the interaction between CaMKII and STAT3. ZYZ-803 treatment induced the nuclear translocation of STAT3. We demonstrated that both STAT3 and CaMKII functioned as positive regulators in ZYZ-803-induced endothelial angiogenesis and STAT3 was important in ZYZ-803-induced CaMKII activation, which highlights the beneficial role of ZYZ-803 in STAT3/CaMKII-related cardiovascular diseases."
2844,CRISPR-cas9: a powerful tool towards precision medicine in cancer treatment,"Cancer is a highly heterogeneous disease in term of molecular signature even though it is originated from the same tissue type. Cancer heterogeneity may occur during its development or treatment, which is the main cause resulting in drug resistance and recurrence. Precision medicine refers to matching the right medicine to the right patients based on their molecular signatures. Therefore, a thorough understanding of the mechanism of tumorigenesis and drug resistance is essential to precision medicine. CRISPR-cas9 system is a powerful tool for gene editing and CRISPR-based high-throughput screening has been widely applied especially in searching for tumor-driven or synergistic lethal genes aiming to overcome drug resistance. In this review, we describe the progress of CRISPR-cas9-based unbiased screening in precision medicine including identification of new drug targets, biomarkers and elucidation of mechanisms leading to drug resistance. The existing challenges as well as the future directions are also discussed."
2845,Ganoderic acid A protects neural cells against NO stress injury in vitro via stimulating β adrenergic receptors,"Excessive nitric oxide (NO) causes extensive damage to the nervous system, and the adrenergic system is disordered in many neuropsychiatric diseases. However, the role of the adrenergic system in protection of the nervous system against sodium nitroprusside (SNP) injury remains unclear. In this study, we investigated the effect of ganoderic acid A (GA A) against SNP injury in neural cells and the role of adrenergic receptors in GA A neuroprotection. We found that SNP (0.125−2 mM) dose-dependently decreased the viability of both SH-SY5Y and PC12 cells and markedly increased NO contents. Pretreatment with GA A (10 μM) significantly attenuated SNP-induced cytotoxicity and NO increase in SH-SY5Y cells, but not in PC12 cells. Furthermore, pretreatment with GA A caused significantly higher adrenaline content in SH-SY5Y cells than in PC12 cells. In order to elucidate the mechanism of GA A-protecting SH-SY5Y cells, we added adrenaline, phentolamine, metoprolol, or ICI 118551 1 h before GA A was added to the culture medium. We found that addition of adrenaline (10 μM) significantly improved GA A protection in PC12 cells. The addition of β1-adrenergic receptor antagonist metoprolol (10 μM) or β2-adrenergic receptor antagonist ICI 118551 (0.1 μM) blocked the protective effect of GA A, whereas the addition of α-adrenergic receptor antagonist phentolamine (0.1 μM) did not affect GA A protection in SH-SY5Y cells. These results suggest that β-adrenergic receptors play an important role in the protection of GA A in SH-SY5Y cells against SNP injuries, and excessive adrenaline system activation caused great damage to the nervous system."
2846,ERK1/2-HNF4α axis is involved in epigallocatechin-3-gallate inhibition of HBV replication,"Epigallocatechin gallate (EGCG), a major polyphenol in green tea, exhibits diverse biological activities. Previous studies show that EGCG could effectively suppress HBV gene expression and replication, but the role of EGCG in HBV replication and its underlying mechanisms, especially the signaling pathways involved, remain unclear. In this study we investigated the mechanisms underlying EGCG inhibition on HBV replication with a focus on the signaling pathways. We showed that EGCG (12.5−50 μM) dose-dependently inhibited HBV gene expression and replication in HepG2.2.15 cells. Similar results were observed in HBV mice receiving EGCG (25 mg· kg(−1)· d(−1), ip) for 5 days. In HepG2.2.15 cells, we showed that EGCG (12.5−50 μM) significantly activate ERK1/2 MAPK signaling, slightly activate p38 MAPK and JAK2/STAT3 signaling, while had no significant effect on the activation of JNK MAPK, PI3K/AKT/mTOR and NF-κB signaling. By using specific inhibitors of these signaling pathways, we demonstrated that ERK1/2 signaling pathway, but not other signaling pathways, was involved in EGCG-mediated inhibition of HBV transcription and replication. Furthermore, we showed that EGCG treatment dose-dependently decreased the expression of hepatocyte nuclear factor 4α (HNF4α) both at the mRNA and protein levels, which could be reversed by pretreatment with the ERK1/2 inhibitor PD98059 (20 μM). Moreover, we revealed that EGCG treatment dose-dependently inhibited the activity of HBV core promoter and the following HBV replication. In summary, our results demonstrate that EGCG inhibits HBV gene expression and replication, which involves ERK1/2-mediated downregulation of HNF4α.These data reveal a novel mechanism for EGCG to inhibit HBV gene expression and replication."
2847,"Compound LM9, a novel MyD88 inhibitor, efficiently mitigates inflammatory responses and fibrosis in obesity-induced cardiomyopathy","Mechanisms of cardiomyopathy caused by obesity/hyperlipidemia are complicated. Obesity is usually associated with chronic low-grade inflammation and may lead to the onset and progression of myocardial fibrosis and remodeling. TLR4/MyD88 signaling pathway, as a key regulator of inflammation, plays an important role in the pathogenesis of obesity-induced cardiomyopathy. We previously demonstrated that LM9, a novel MyD88 inhibitor, attenuated inflammatory responses and fibrosis in obesity-induced cardiomyopathy by inhibiting the formation of TLR4/MyD88 complex. In this study, we investigated the protective effects of LM9 on obesity-induced cardiomyopathy in vitro and in vivo. We showed that LM9 (5, 10 μM) significantly attenuates palmitic acid (PA)-induced inflammation in mouse peritoneal macrophages, evidenced by decreased expression of proinflammatory genes including TNF-α, IL-6, IL-1β, and ICAM-1. In cardiac-derived H9C2 cells, LM9 treatment suppressed PA-induced inflammation, lipid accumulation, and fibrotic responses. In addition, LM9 treatment also inhibited PA-activated TLR4/MyD88/NF-κB signaling pathway. We further revealed in HEK293 cells that LM9 treatment blocked the TLR4/MyD88 binding and MyD88 homodimer formation. In HFD-fed mice, administration of LM9 (5, 10 mg/kg, ig, every other days for 8 weeks) dose-dependently alleviated inflammation and fibrosis in heart tissues and decreased serum lipid concentration. In conclusion, this study demonstrates that MyD88 inhibitor LM9 exerts protective effects against obesity-induced cardiomyopathy, suggesting LM9 to be a promising therapeutic candidate drug for the obesity-related cardiac complications."
2848,Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence,"Midbrain dopaminergic (DA) neurons are governed by an endogenous cholinergic system, originated in the mesopontine nuclei. Nicotine hijacks nicotinic acetylcholine receptors (nAChRs) and interferes with physiological function of the cholinergic system. In this review, we describe the anatomical organization of the cholinergic system and the key nAChR subtypes mediating cholinergic regulation of DA transmission and nicotine reward and dependence, in an effort to identify potential targets for smoking intervention. Cholinergic modulation of midbrain DA systems relies on topographic organization of mesopontine cholinergic projections, and activation of nAChRs in midbrain DA neurons. Previous studies have revealed that α4, α6, and β2 subunit-containing nAChRs expressed in midbrain DA neurons and their terminals in the striatum regulate firings of midbrain DA neurons and activity-dependent dopamine release in the striatum. These nAChRs undergo modification upon chronic nicotine exposure. Clinical investigation has demonstrated that partial agonists of these receptors elevate the success rate of smoking cessation relative to placebo. However, further investigations are required to refine the drug targets to mitigate unpleasant side-effects."
2849,"WZ66, a novel acetyl-CoA carboxylase inhibitor, alleviates nonalcoholic steatohepatitis (NASH) in mice","The global prevalence of nonalcoholic steatohepatitis (NASH) increases incredibly. NASH ends up to advanced liver disease, which is highly threatening to human health. Currently, treatment of NASH is very limited. Acetyl-CoA carboxylases (ACC1/ACC2) are proved as effective drug targets for NASH. We aimed to develop novel ACC inhibitors and evaluate their therapeutic value for NASH prevention. ACC inhibitors were obtained through structure-based drug design, synthesized, screened from ACC enzymatic measurement platform and elucidated in cell culture-based assays and animal models. The lipidome and microbiome analysis were integrated to assess the effects of WZ66 on lipids profiles in liver and plasma as well as gut microbiota in the intestine. WZ66 was identified as a novel ACC1/2 inhibitor. It entered systemic circulation rapidly and could accumulate in liver. WZ66 alleviated NASH-related liver features including steatosis, Kupffer cells and hepatic stellate cells activation in diet-induced obese mice. The triglycerides (TGs) and other lipids including diglycerides (DGs), phosphatidylcholine (PC) and sphingomyelin (SM) were decreased in WZ66-treated mice as evidenced by lipidome analysis in livers. The lipids profiles in plasma were also altered with WZ66 treatment. Plasma TG were moderately increased, while the activation of SREBP1c was not detected. WZ66 also downregulated the abundance of Allobaculum, Mucispirillum and Prevotella genera as well as Mucispirillum schaedleri species in gut microbiota. WZ66 is an ideal lead compound and a potential drug candidate deserving further investigation in the therapeutics of NASH."
2850,Rg1 improves LPS-induced Parkinsonian symptoms in mice via inhibition of NF-κB signaling and modulation of M1/M2 polarization,"Ginsenoside Rg1 is one of the most active ingredients in ginseng, which has been reported to protect dopaminergic neurons and improve behavioral defects in MPTP model, 6-OHDA model and rotenone model. However, it is unclear whether Rg1 exerted neuroprotection in LPS-induced sub-acute PD model. In this study, we investigated the neuroprotective effect of Rg1 in the sub-acute PD mouse model and explored the related mechanisms. Rg1 (10, 20, 40 mg·kg(−1)·d(−1)) was orally administered to mice for 18 days. A sub-acute PD model was established in the mice through LPS microinjection into the substantia nigra (SN) from D8 to D13. We found that Rg1 administration dose-dependently inhibited LPS-induced damage of dopaminergic neurons and activation of glial cells in the substantia nigra pars compacta (SNpc). The neuroprotective effects of Rg1 were associated with the reduction of pro-inflammatory cytokines and the improvement of anti-inflammatory cytokines and neurotrophin in the midbrain. Rg1 shifted the polarization of microglia towards the M2 phenotype from M1, evidenced by decreased M1 markers (inducible NO synthase, CD16, etc.) and increased M2 markers (arginase 1 (Arg1), CD206, etc) in the midbrain. Furthermore, Rg1 administration markedly inhibited nuclear translocation of NF-κB in midbrain microglia. In conclusion, Rg1 protects PD mice induced by continuous LPS injection by inhibiting the nuclear entry of NF-κB and regulating the polarization balance of microglia, shedding new light on a disease-modifying therapy of PD."
2851,Neuroprotective effects of olanzapine against rotenone-induced toxicity in PC12 cells,"Olanzapine is an antipsychotic drug used to treat patients with schizophrenia due to its lower incidence of extrapyramidal symptoms. Previous studies have shown that olanzapine activates AMP-activated protein kinase (AMPK), and induce autophagy in SH-SY5Y cell line. In this study, we investigated whether olanzapine protected against rotenone-induced neurotoxicity in PC12 cells. We showed that treatment with olanzapine increased the phosphorylation of AMPK in both dose- and time-dependent manners in PC12 cells. In addition, olanzapine activated autophagy and increased autophagic vacuoles. Furthermore, olanzapine pretreatment could protect PC12 cells from rotenone-induced apoptosis. Besides, olanzapine pretreatment could suppress the rotenone-induced depolarization of mitochondrial potential and thus protect the cells. Moreover, pretreatment with specific AMPK inhibitor compound C or with autophagy inhibitor 3-methyladenine impaired the protective effect of olanzapine on rotenone-treated PC12 cells. In summary, our results show for the first time that olanzapine ameliorates rotenone-induced injury by activating autophagy through AMPK pathway."
2852,Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway,"Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L., which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms. In both rat glioma C6 and human glioma U251 cell lines, xanthatin (1–15 μM) dose-dependently inhibited cell viability without apparent effect on the cell cycle. Furthermore, xanthatin treatment dose-dependently induced glioma cell apoptosis. In nude mice bearing C6 glioma tumor xenografts, administration of xanthatin (10, 20, 40 mg·kg(−1)·d(−1), ip, for 2 weeks) dose-dependently inhibited the tumor growth, but did not affect the body weight. More importantly, xanthatin treatment markedly increased the expression levels of the endoplasmic reticulum (ER) stress-related markers in both the glioma cell lines as well as in C6 xenografts, including glucose-regulated protein 78, C/EBP-homologous protein (CHOP), activating factor 4, activating transcription factor 6, spliced X-box binding protein-1, phosphorylated protein kinase R-like endoplasmic reticulum kinase, and phosphorylated eukaryotic initiation factor 2a. Pretreatment of C6 glioma cells with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 7 mM) or knockdown of CHOP using small interfering RNA significantly attenuated xanthatin-induced cell apoptosis and increase of proapoptotic caspase-3. These results demonstrate that xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating the ER stress-related unfolded protein response pathway involving CHOP induction. Xanthatin may serve as a promising agent in the treatment of human glioma."
2853,Author Correction: AZD9291 inactivates the PRC2 complex to mediate tumor growth inhibition,
2854,Future-proofing biobanks’ governance,"Good biobank governance implies—at a minimum—transparency and accountability and the implementation of oversight mechanisms. While the biobanking community is in general committed to such principles, little is known about precisely which governance strategies biobanks adopt to meet those objectives. We conducted an exploratory analysis of governance mechanisms adopted by research biobanks, including genetic biobanks, located in Europe and Canada. We reviewed information available on the websites of 69 biobanks, and directly contacted them for additional information. Our study identified six types of commonly adopted governance strategies: communication, compliance, expert advice, external review, internal procedures, and partnerships. Each strategy is implemented through different mechanisms including, independent ethics assessment, informed consent processes, quality management, data access control, legal compliance, standard operating procedures and external certification. Such mechanisms rely on a wide range of bodies, committees and actors from both within and outside the biobanks themselves. We found that most biobanks aim to be transparent about their governance mechanisms, but could do more to provide more complete and detailed information about them. In particular, the retrievable information, while showing efforts to ensure biobanks operate in a legitimate way, does not specify in sufficient detail how governance mechanisms support accountability, nor how they ensure oversight of research operations. This state of affairs can potentially undermine biobanks’ trustworthiness to stakeholders and the public in a long-term perspective. Given the ever-increasing reliance of biomedical research on large biological repositories and their associated databases, we recommend that biobanks increase their efforts to future-proof their governance."
2855,Differential cytokine network profile in polycythemia vera and secondary polycythemia,"Polycythemia vera (PV) is a clonal disorder resulting from neoplastic transformation of hematopoietic stem cells, while secondary polycythemia (SP) is a disease characterized by increased absolute red blood cell mass caused by stimulation of red blood cell production. Although the physiopathology of SP and PV is distinct, patients with these diseases share similar symptoms. The early differential diagnosis may improve the quality of life and decrease the disease burden in PV patients, as well as enable curative treatment for SP patients. PV is considered an oncoinflammatory disease because PV patients exhibit augmented levels of several pro-inflammatory cytokines. In this sense, we examined whether analysis of the cytokine production profile of SP and PV patients would help to distinguish them, despite their clinical similarities. Here we reported that SP patients exhibited decreased plasma levels of, IL-17A, IFN-γ, IL-12p70 and TNF-α when compared with PV patients, suggesting that analysis of the cytokine production profile may be an useful diagnostic biomarker to distinguish PV from SP patients."
2856,Stressing the potential of guanfacine as a treatment for cocaine use disorder,
2857,Brolucizumab and fluid in neovascular age-related macular degeneration (n-AMD),
2858,A comparative study of outcomes of idarubicin- and etoposide-intensified conditioning regimens for allogeneic peripheral blood stem cell transplantation in patients with high-risk acute leukemia,"AIM: To analyze the results of idarubicin (IDA)- versus etoposide (VP16)-intensified myeloablative conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-SCT) for high-risk acute leukemia. METHODS: From January 2005 to June 2008, 48 consecutive patients (male: n=29; median age: 30 years, range 14–51 years) with high-risk acute leukemia underwent allo-SCT following an IDA- or VP16-intensified conditioning regimen. The conditioning regimens were modified BUCY2 (busulfan+cyclophosphamide) consisting of IDA (15 mg/m(2) per day, days -12 to -10) or VP16 (25 mg/kg per day, days -3 to -2) and CY/TBI (cyclophosphamide/total body irradiation) intensified with IDA (15 mg/m(2) per day, days -6 to -5) or VP16 (25 mg/kg per day, days -3 to -2) for acute myeloid leukemia and acute lymphoblastic leukemia, respectively. RESULTS: Between the two groups, no significant differences in terms of baseline characteristics, incidence of acute or chronic graft-versus-host disease (GVHD) or transplant-related mortality (TRM) (P=0.50) were observed. However, the IDA group demonstrated higher incidences of mucositis and Aspergillus pneumonia (P<0.01 and P=0.03, respectively). For the IDA and VP16 groups, relapse rates were 28% and 50%, respectively (P=0.13). For the same groups, the 2-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 72% versus 51% (P=0.04) and 74% versus 53% (P=0.04), respectively. CONCLUSION: This retrospective analysis suggests that conditioning regimens intensified with IDA can achieve better outcomes than conditioning regimens with VP16 in patients preparing to undergo allo-SCT for high-risk acute leukemia."
2859,Ganoderic acid A is the effective ingredient of Ganoderma triterpenes in retarding renal cyst development in polycystic kidney disease,"Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life-threatening monogenetic diseases characterized by progressive enlargement of fluid-filled renal cysts. Our previous study has shown that Ganoderma triterpenes (GT) retards PKD renal cyst development. In the present study we identified the effective ingredient of GT in suppression of kidney cyst development. Using an in vitro MDCK cystogenesis model, we identified ganoderic acid A (GA-A) as the most promising candidate among the 12 ganoderic acid (GA) monomers. We further showed that GA-A (6.25−100 μM) significantly inhibited cyst growth in MDCK cyst model and embryonic kidney cyst model in vitro, and the inhibitory effect was reversible. In kidney-specific Pkd1 knockout (kPKD) mice displaying severe cystic kidney disease, administration of GA-A (50 mg· kg(−1) ·d(−1), sc) significantly attenuated renal cyst development. In both MDCK cells and kidney of kPKD mice, we revealed that GA-A dose-dependently downregulated the Ras/MAPK signaling pathway. The expression of proliferating cell nuclear antigen (PCNA) was also suppressed, suggesting a possible effect of GA-A on cell proliferation. These experimental data suggest that GA-A may be the main ingredient of GT as a potential therapeutic reagent for treating ADPKD."
2860,Ouabain impairs cancer metabolism and activates AMPK-Src signaling pathway in human cancer cell lines,"In addition to the well-known cardiotonic effects, cardiac glycosides (CGs) produce potent anticancer effects with various molecular mechanisms. We previously show that ouabain induces autophagic cell death in human lung cancer cells by regulating AMPK-mediated mTOR and Src-mediated ERK1/2 signaling pathways. However, whether and how AMPK and Src signaling interacts in ouabain-treated cancer cells remains unclear. Given the pivotal role of AMPK in metabolism, whether ouabain affects cancer cell metabolism remains elusive. In this study we showed that treatment with ouabain (25 nM) caused simultaneous activation of AMPK and Src signaling pathways in human lung cancer A549 cells and human breast cancer MCF7 cells. Cotreatment with AMPK inhibitor compound C or siRNA greatly abrogates ouabain-induced Src activation, whereas cotreatment with Src inhibitor PP2 has little effect on ouabain-induced AMPK activity, suggesting that AMPK served as an upstream regulator of the Src signaling pathway. On the other hand, ouabain treatment greatly depletes ATP production in A549 and MCF7 cells, and supplement of ATP (100 μM) blocked ouabain-induced AMPK activation. We further demonstrated that ouabain greatly inhibited the mitochondrial oxidative phosphorylation (OXPHOS) in the cancer cells, and exerted differential metabolic effects on glycolysis depending on cancer cell type. Taken together, this study reveals that the altered cancer cell metabolism caused by ouabain may contribute to AMPK activation, as well as its cytotoxicity towards cancer cells."
2861,Correction: Use of biomaterials for sustained delivery for anti-VEGF to treat retinal diseases,
2862,Fecal microbiota transplantation improves metabolism and gut microbiome composition in db/db mice,"Fecal microbiota transplantation (FMT) has become an effective strategy to treat metabolic diseases, including type 2 diabetes mellitus (T2DM). We previously reported that the intestinal microbiome had significant difference between individuals with normal glucose tolerance and T2DM in Chinese Kazak ethnic group. In this study, we investigated the effects of transplanted fecal bacteria from Kazaks with normal glucose tolerance (KNGT) in db/db mice. The mice were treated with 0.2 mL of fecal bacteria solution from KNGT daily for 10 weeks. We showed that the fecal bacteria from KNGT successfully colonized in the intestinal tract of db/db mice detected on day 14. In the FMT-treated db/db mice, the levels of fasting blood glucose, postprandial glucose, total cholesterol, triglyceride, and low-density lipoprotein–cholesterol were significantly downregulated, whereas high-density lipoprotein–cholesterol levels were upregulated. In the FMT-treated db/db mice, Desulfovibrio and Clostridium coccoides levels in gut were significantly decreased, but the fecal levels of Akkermansia muciniphila and colon histone deacetylase-3 (HDAC3) protein expression were increased. At 8 weeks, both intestinal target bacteria and HDAC3 were correlated with glycolipid levels; Akkermansia muciniphila level was positively correlated with HDAC3 protein expression (r = +0.620, P = 0.037). Our results suggest that fecal bacteria from KNGT could potentially be used to treat diabetic patients."
2863,α(1)-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation,"Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries, which are mainly mediated by β-adrenergic receptors (β-ARs). However, α(1)-adrenergic receptors (α(1)-ARs) are also expressed in the heart and are activated upon acute sympathetic stress. In the present study, we investigated whether α(1)-AR activation induced cardiac inflammation and the underlying mechanisms. Male C57BL/6 mice were injected with a single dose of α(1)-AR agonist phenylephrine (PE, 5 or 10 mg/kg, s.c.) with or without pretreatment with α-AR antagonist prazosin (5 mg/kg, s.c.). PE injection caused cardiac dysfunction and cardiac inflammation, evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5, as well as macrophage infiltration in myocardium. These effects were blocked by prazosin pretreatment. Furthermore, PE injection significantly increased the expression of NOD-like receptor protein 3 (NLRP3) and the cleavage of caspase-1 (p20) and interleukin-18 in the heart; similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE (10 μM). Moreover, PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3(-/-) mice compared with wild-type mice. In conclusion, α(1)-AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes."
2864,A new recombinant MS-superoxide dismutase alleviates 5-fluorouracil-induced intestinal mucositis in mice,"Intestinal mucositis is a common side effect of anticancer regimens that exerts a negative impact on chemotherapy. Superoxide dismutase (SOD) is a potential therapy for mucositis but efficient product is not available because the enzyme is degraded following oral administration or induces an immune reaction after intravascular infusion. Multi-modified Stable Anti-Oxidant Enzymes(®) (MS-AOE(®)) is a new recombinant SOD with better resistance to pepsin and trypsin. We referred it as MS-SOD to distinguish from other SODs. In this study we investigated its potential to alleviate 5-FU-induced intestinal injury and the mechanisms. An intestinal mucositis model was established in C57/BL6 mice by 5-day administration of 5-FU (50 mg/kg every day, ip). MS-SOD (800 IU/10 g, ig) was given once daily for 9 days. 5-FU caused severe mucositis with intestinal morphological damage, bodyweight loss and diarrhea; MS-SOD significantly decreased the severity. 5-FU markedly increased reactive oxygen species (ROS) and inflammatory cytokines in the intestine which were ameliorated by MS-SOD. Furthermore, MS-SOD modified intestinal microbes, particularly reduced Verrucomicrobia, compared with the 5-FU group. In Caco2 cells, MS-SOD (250–1000 U/mL) dose-dependently decreased tBHP-induced ROS generation. In RAW264.7 cells, MS-SOD (500 U/mL) had no effect on LPS-induced inflammatory cytokines, but inhibited iNOS expression. These results demonstrate that MS-SOD can scavenge ROS at the initial stage of injury, thus play an indirect role in anti-inflammatory and barrier protein protection. In conclusion, MS-SOD attenuates 5-FU-induced intestinal mucositis by suppressing oxidative stress and inflammation, and influencing microbes. MS-SOD may exert beneficial effect in prevention of intestinal mucositis during chemotherapy in clinic."
2865,"Physiologically based pharmacokinetic–pharmacodynamic modeling for prediction of vonoprazan pharmacokinetics and its inhibition on gastric acid secretion following intravenous/oral administration to rats, dogs and humans","Vonoprazan is characterized as having a long-lasting antisecretory effect on gastric acid. In this study we developed a physiologically based pharmacokinetic (PBPK)-pharmacodynamic (PD) model linking to stomach to simultaneously predict vonoprazan pharmacokinetics and its antisecretory effects following administration to rats, dogs, and humans based on in vitro parameters. The vonoprazan disposition in the stomach was illustrated using a limited-membrane model. In vitro metabolic and transport parameters were derived from hepatic microsomes and Caco-2 cells, respectively. We found the most predicted plasma concentrations and pharmacokinetic parameters of vonoprazan in rats, dogs and humans were within twofold errors of the observed data. Free vonoprazan concentrations (f(u) × C(2)) in the stomach were simulated and linked to the antisecretory effects of the drug (I) (increases in pH or acid output) using the fomula dI/dt = k × f(u) × C(2) × (I(max) − I) − k(d) × I. The vonoprazan dissociation rate constant k(d) (0.00246 min(−1)) and inhibition index K(I) (35 nM) for H(+)/K(+)-ATPase were obtained from literatures. The vonoprazan-H(+)/K(+)-ATPase binding rate constant k was 0.07028 min(−1)· μM(−1) using ratio of k(d) to K(I). The predicted antisecretory effects were consistent with the observations following intravenous administration to rats (0.7 and 1.0 mg/kg), oral administration to dogs (0.3 and 1.0 mg/kg) and oral single dose or multidose to humans (20, 30, and 40 mg). Simulations showed that vonoprazan concentrations in stomach were 1000-fold higher than those in the plasma at 24 h following administration to human. Vonoprazan pharmacokinetics and its antisecretory effects may be predicted from in vitro data using the PBPK-PD model of the stomach. These findings may highlight 24-h antisecretory effects of vonoprazan in humans following single-dose or the sustained inhibition throughout each 24-h dosing interval during multidose administration."
2866,FSHR ablation induces depression-like behaviors,"Alteration in reproductive hormones profile is associated with the increasing risk of menopausal depression in women. Serum follicle-stimulating hormone (FSH) level is changed during the menopause transition, while the effect of FSH on menopausal depression has remained undefined. In this study we investigated whether or how FSH affected menopausal depression in postmenopausal (ovariectomized) FSHR knockout mice (Fshr(−/−)). We found that Fshr(−/−) mice displayed aggravated depression-like behaviors, accompanied by severe oxidative stress in the whole brain, resulted from significantly reduced glutamate cysteine ligase modifier subunit (GCLm) in glutathione synthesis and glucose-6-phosphate dehydrogenase (G6PD) in NADP/NADPH transition. Importantly, administration of ROS scavenger N-acetyl cysteine (NAC, 150 mg · kg(−1) · d(−1), i.p. for 12 weeks) attenuated the depression-like behaviors of Fshr(−/−) mice. Consistent with these in vivo experiment results, we found that pretreatment with FSH (50, 100 ng/mL) dose-dependently increased protein levels of GCLm and G6PD, and decreased the ROS production in N2a mouse neuroblastoma cells. These findings demonstrate that FSH signaling is involved in pathogenesis of menopausal depression, and likely to maintain the redox-optimized ROS balance in neurons."
2867,Urotensin II and urantide exert opposite effects on the cellular components of atherosclerotic plaque in hypercholesterolemic rabbits,"Increasing levels of plasma urotensin II (UII) are positively associated with atherosclerosis. In this study we investigated the role of macrophage-secreted UII in atherosclerosis progression, and evaluated the therapeutic value of urantide, a potent competitive UII receptor antagonist, in atherosclerosis treatment. Macrophage-specific human UII-transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet for 16 weeks to induce atherosclerosis. Immunohistochemical staining of the cellular components (macrophages and smooth muscle cells) of aortic atherosclerotic lesions revealed a significant increase (52%) in the macrophage-positive area in only male transgenic rabbits compared with that in the nontransgenic littermates. However, both male and female transgenic rabbits showed a significant decrease (45% in males and 31% in females) in the smooth muscle cell-positive area compared with that of their control littermates. The effects of macrophage-secreted UII on the plaque cellular components were independent of plasma lipid level. Meanwhile the wild-type rabbits were continuously subcutaneously infused with urantide (5.4 µg· kg(−1)· h(−1)) using osmotic mini-pumps. Infusion of urantide exerted effects opposite to those caused by UII, as it significantly decreased the macrophage-positive area in male wild-type rabbits compared with that of control rabbits. In cultured human umbilical vein endothelial cells, treatment with UII dose-dependently increased the expression of the adhesion molecules VCAM-1 and ICAM-1, and this effect was partially reversed by urantide. The current study provides direct evidence that macrophage-secreted UII plays a key role in atherogenesis. Targeting UII with urantide may promote plaque stability by decreasing macrophage-derived foam cell formation, which is an indicator of unstable plaque."
2868,"LW-213, a newly synthesized flavonoid, induces G2/M phase arrest and apoptosis in chronic myeloid leukemia","Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell neoplasm characterized by an uncontrolled proliferation of moderately and well differentiated cells of the granulocytic lineage. LW-213, a newly synthesized flavonoid compound, was found to exert antitumor effects against breast cancer through inducing G2/M phase arrest. We investigated whether LW-213 exerted anti-CML effects and the underlying mechanisms. We showed that LW-213 inhibited the growth of human CML cell lines K562 and imatinid-resistant K562 (K562r) in dose- and time-dependent manners with IC(50) values at the low μmol/L levels. LW-213 (5, 10, 15 μM) caused G(2)/M phase arrest of K562 and K562r cells via reducing the activity of G2/M phase transition-related proteins Cyclin B1/CDC2 complex. LW-213 treatment induced apoptosis of K562 and K562r cells via inhibiting the expression of CDK9 through lysosome degradation, thus leading to the suppression of RNAPII phosphorylation, down-regulation of a short-lived anti-apoptic protein MCL-1. The lysosome inhibitor, NH(4)Cl, could reverse the anti-CML effects of LW-213 including CDK9 degradation and apoptosis. LW-213 treatment also degraded the downstream proteins of BCR-ABL1, such as oncoproteins AKT, STAT3/5 in CML cells, which was blocked by NH(4)Cl. In primary CML cells and CD34(+) stem cells, LW-213 maintained its pro-apoptotic activity. In a K562 cells-bearing mice model, administration of LW-213 (2.5, 5.0 mg/kg, ip, every other day for 4 weeks) dose-dependently prolonged the survival duration, and significantly suppressed huCD45(+) cell infiltration and expression of MCL-1 in spleens. Taken together, our results demonstrate that LW-213 may be an efficient agent for CML treatment."
2869,Erratum: Thymic DCs derived IL-27 regulates the final maturation of CD4(+) SP thymocytes,
2870,Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCγ1-Ca(2+)-NFATc1 signaling pathway,"In chronic infectious diseases caused by gram-negative bacteria, such as osteomyelitis, septic arthritis, and periodontitis, osteoclastic activity is enhanced with elevated inflammation, which disturbs the bone homeostasis and results in osteolysis. Lipopolysaccharide (LPS), as a bacteria product, plays an important role in this process. Recent evidence shows that an antimalarial drug artesunate attenuates LPS-induced osteolysis independent of RANKL. In this study we evaluated the effects of artesunate on LPS-induced osteoclastogenesis in vitro and femur osteolysis in vivo, and explored the mechanisms underlying the effects of artesunate on LPS-induced osteoclast differentiation independent of RANKL. In preosteoclastic RAW264.7 cells, we found that artesunate (1.56−12.5 μM) dose dependently inhibited LPS-induced osteoclast formation accompanied by suppressing LPS-stimulated osteoclast-related gene expression (Fra-2, TRAP, Cathepsin K, β3-integrin, DC-STAMP, and Atp6v0d2). We showed that artesunate (3.125−12.5 µM) inhibited LPS-stimulated nuclear factor of activated T cells c1 (NFATc1) but not NF-κB transcriptional activity; artesunate (6.25, 12.5 μM) significantly inhibited LPS-stimulated NFATc1 protein expression. Furthermore, artesunate treatment markedly suppressed LPS-induced Ca(2+) influx, and decreased the expression of PP2B-Aα (calcineurin) and pPLCγ1 in the cells. In addition, artesunate treatment significantly decreased the expression of upstream signals TLR4 and TRAF6 during LPS-induced osteoclastogenesis. Administration of artesunate (10 mg/kg, ip) for 8 days effectively inhibited serum TNF-α levels and ameliorated LPS (5 mg/kg, ip)-induced inflammatory bone loss in vivo. Taken together, artesunate attenuates LPS-induced inflammatory osteoclastogenesis by inhibiting the expression of TLR4/TRAF6 and the downstream PLCγ1-Ca(2+)-NFATc1 signaling pathway. Artesunate is a valuable choice to treat bone loss induced by gram-negative bacteria infection or inflammation in RANKL-independent pathway."
2871,Advanced biomaterials for cancer immunotherapy,"Immunotherapy, as a powerful strategy for cancer treatment, has achieved tremendous efficacy in clinical trials. Despite these advancements, there is much to do in terms of enhancing therapeutic benefits and decreasing the side effects of cancer immunotherapy. Advanced nanobiomaterials, including liposomes, polymers, and silica, play a vital role in the codelivery of drugs and immunomodulators. These nanobiomaterial-based delivery systems could effectively promote antitumor immune responses and simultaneously reduce toxic adverse effects. Furthermore, nanobiomaterials may also combine with each other or with traditional drugs via different mechanisms, thus giving rise to more accurate and efficient tumor treatment. Here, an overview of the latest advancement in these nanobiomaterials used for cancer immunotherapy is given, describing outstanding systems, including lipid-based nanoparticles, polymer-based scaffolds or micelles, inorganic nanosystems, and others."
2872,Nanomedicine-based immunotherapy for central nervous system disorders,"Central nervous system (CNS) disorders represent a broad spectrum of brain ailments with short- and long-term disabilities, and nanomedicine-based approaches provide a new therapeutic approach to treating CNS disorders. A variety of potential drugs have been discovered to treat several neuronal disorders; however, their therapeutic success can be limited by the presence of the blood-brain barrier (BBB). Furthermore, unique immune functions within the CNS provide novel target mechanisms for the amelioration of CNS diseases. Recently, various therapeutic approaches have been applied to fight brain-related disorders, with moderate outcomes. Among the various therapeutic strategies, nanomedicine-based immunotherapeutic systems represent a new era that can deliver useful cargo with promising pharmacokinetics. These approaches exploit the molecular and cellular targeting of CNS disorders for enhanced safety, efficacy, and specificity. In this review, we focus on the efficacy of nanomedicines that utilize immunotherapy to combat CNS disorders. Furthermore, we detailed summarize nanomedicine-based pathways for CNS ailments that aim to deliver drugs across the BBB by mimicking innate immune actions. [Figure: see text]"
2873,Medicus curat: sungazing versus spectacles?,
2874,Rifampicin induces clathrin-dependent endocytosis and ubiquitin–proteasome degradation of MRP2 via oxidative stress-activated PKC-ERK/JNK/p38 and PI3K signaling pathways in HepG2 cells,"It was reported that antituberculosis medicines could induce liver damage via oxidative stress. In this study, we investigated the effects of rifampicin (RFP) on the membrane expression of multidrug resistance-associated protein 2 (MRP2) and the relationship between oxidative stress and RFP-induced endocytosis of MRP2 in HepG2 cells. We found that RFP (12.5–50 μM) dose-dependently decreased the expression and membrane localization of MRP2 in HepG2 cells without changing the messenger RNA level. RFP (50 μM) induced oxidative stress responses that further activated the PKC-ERK/JNK/p38 (protein kinase C-extracellular signal-regulated kinase/c-JUN N-terminal kinase/p38) and PI3K (phosphoinositide 3-kinase) signaling pathways in HepG2 cells. Pretreatment with glutathione reduced ethyl ester (2 mM) not only reversed the changes in oxidative stress indicators and signaling molecules but also diminished RFP-induced reduction in green fluorescence intensity of MRP2. We conducted co-immunoprecipitation assays and revealed that a direct interaction existed among MRP2, clathrin, and adaptor protein 2 (AP2) in HepG2 cells, and their expression was clearly affected by the changes in intracellular redox levels. Knockdown of clathrin or AP2 with small interfering RNA attenuated RFP-induced decreases of membrane and total MRP2. We further demonstrated that RFP markedly increased the ubiquitin–proteasome degradation of MRP2 in HepG2 cells, which was mediated by the E3 ubiquitin ligase GP78, but not HRD1 or TEB4. In conclusion, this study demonstrates that RFP-induced oxidative stress activates the PKC-ERK/JNK/p38 and PI3K signaling pathways that leads to clathrin-dependent endocytosis and ubiquitination of MRP2 in HepG2 cells, which provides new insight into the mechanism of RFP-induced cholestasis."
2875,Development and characterization of an inducible Dicer conditional knockout mouse model of Parkinson’s disease: validation of the antiparkinsonian effects of a sigma-1 receptor agonist and dihydromyricetin,"Parkinson’s disease (PD) is a common neurodegenerative disease characterized by motor impairment and progressive loss of dopamine (DA) neurons. At present, the acute application of neurotoxic drugs such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) are commonly used to simulate the pathology of PD; however, it is difficult to induce the progressive pathogenesis of PD with these models. In this study, we employed DAT promoter-mediated Cre transgenic mice to establish tamoxifen-inducible Dicer conditional knockout (cKO) mice in an effort to mimic the progressive loss of DA neurons and the development of PD-like behavioral phenotypes. The results showed that Dicer cKO mice exhibited progressive loss of DA neurons in the substantia nigra (SN) following tamoxifen administration. Significant DA loss was observed 6 weeks after tamoxifen administration; accordingly, progressive motor function impairment was also observed. We also found that a significant neuroinflammatory response, as evidenced by microglial proliferation, another hallmark of PD pathogenesis, accompanied the loss of DA neurons. The acute application of levo-DOPA (l-DOPA) relieved the PD-like motor impairments in Dicer cKO mice to exert its antiparkinsonian action, indicating that the model can be used to evaluate the antiparkinsonian efficacy of PD drugs. To further elucidate the potential application of this novel PD animal model for PD drug development, we employed the powerful neuroprotective agent dihydromyricetin (DHM) (10 mg/kg) and the selective sigma-1 receptor agonist PRE-084 (1 mg/kg), both of which were previously shown to produce antiparkinsonian effects. The results indicated that the chronic administration of either DHM or PRE-084 attenuated the Dicer cKO-induced loss of DA neurons and motor impairments, although the two drugs acted through different mechanisms. These data indicate that the Dicer cKO mouse model may be a useful model for investigating the pathological development of PD and intervention-mediated changes. In conclusion, this transgenic mouse model appears to simulate the progressive pathogenesis of PD and may be a potentially useful model for PD drug discovery."
2876,Cardioprotective mechanisms of salvianic acid A sodium in rats with myocardial infarction based on proteome and transcriptome analysis,"Ischemic heart diseases (IHDs) cause great morbidity and mortality worldwide, necessitating effective treatment. Salvianic acid A sodium (SAAS) is an active compound derived from the well-known herbal medicine Danshen, which has been widely used for clinical treatment of cardiovascular diseases in China. This study aimed to confirm the cardioprotective effects of SAAS in rats with myocardial infarction and to investigate the underlying molecular mechanisms based on proteome and transcriptome profiling of myocardial tissue. The results showed that SAAS effectively protected against myocardial injury and improved cardiac function. The differentially expressed proteins and genes included important structural molecules, receptors, transcription factors, and cofactors. Functional enrichment analysis indicated that SAAS participated in the regulation of actin cytoskeleton, phagosome, focal adhesion, tight junction, apoptosis, MAPK signaling, and Wnt signaling pathways, which are closely related to cardiovascular diseases. SAAS may exert its cardioprotective effect by targeting multiple pathways at both the proteome and transcriptome levels. This study has provided not only new insights into the pathogenesis of myocardial infarction but also a road map of the cardioprotective molecular mechanisms of SAAS, which may provide pharmacological evidence to aid in its clinical application."
2877,Ganoderic acid hinders renal fibrosis via suppressing the TGF-β/Smad and MAPK signaling pathways,"Renal fibrosis is considered as the pathway of almost all kinds of chronic kidney diseases (CKD) to the end stage of renal diseases (ESRD). Ganoderic acid (GA) is a group of lanostane triterpenes isolated from Ganoderma lucidum, which has shown a variety of pharmacological activities. In this study we investigated whether GA exerted antirenal fibrosis effect in a unilateral ureteral obstruction (UUO) mouse model. After UUO surgery, the mice were treated with GA (3.125, 12.5, and 50 mg· kg(−1) ·d(−)(1), ip) for 7 or 14 days. Then the mice were sacrificed for collecting blood and kidneys. We showed that GA treatment dose-dependently attenuated UUO-induced tubular injury and renal fibrosis; GA (50 mg· kg(−1) ·d(−)(1)) significantly ameliorated renal disfunction during fibrosis progression. We further revealed that GA treatment inhibited the extracellular matrix (ECM) deposition in the kidney by suppressing the expression of fibronectin, mainly through hindering the over activation of TGF-β/Smad signaling. On the other hand, GA treatment significantly decreased the expression of mesenchymal cell markers alpha-smooth muscle actin (α-SMA) and vimentin, and upregulated E-cadherin expression in the kidney, suggesting the suppression of tubular epithelial-mesenchymal transition (EMT) partially via inhibiting both TGF-β/Smad and MAPK (ERK, JNK, p38) signaling pathways. The inhibitory effects of GA on TGF-β/Smad and MAPK signaling pathways were confirmed in TGF-β1-stimulated HK-2 cell model. GA-A, a GA monomer, was identified as a potent inhibitor on renal fibrosis in vitro. These data demonstrate that GA or GA-A might be developed as a potential therapeutic agent in the treatment of renal fibrosis."
2878,Comparison of the retinal nerve fiber layer and ganglion cell complex thickness in Korean patients with unilateral exfoliation syndrome and healthy subjects,"PURPOSE: To compare retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness in patients with unilateral exfoliation syndrome (XFS) and age-matched controls using spectral domain-optical coherence tomography (SD-OCT). MATERIALS AND METHODS: This prospective case–control study included 54 eyes (the XFS-affected and the fellow eyes) of 27 unilateral XFS patients and 27 eyes of 27 age-matched control subjects. The RNFL and GCC thicknesses were measured using SD-OCT (RT-Vue 100, Optovue, Fremont, CA) after pupillary dilation. RNFL and GCC thicknesses were compared between case and control groups. RESULTS: The mean age of XFS patients was 73.3 years and that of age-matched controls was 74.3 years. Both groups demonstrated a male preponderance. Superior RNFL thickness of XFS-affected eyes were significantly thinner than those of the healthy age-matched controls (P = 0.002 by ANOVA). There were no statistically significant differences in the RNFL thickness between both eyes of unilateral XFS patients. Moreover, superior GCC thickness of both eyes in unilateral XFS patients were thinner than those in controls (P = 0.002 by ANOVA). CONCLUSIONS: Thinner RNFL and GCC thicknesses were observed in unilateral XFS patients without visual field defects. These findings imply that XFS itself might be a risk factor for development of glaucomatous optic disc and RNFL damage."
2879,Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway,"Oroxindin is a flavonoid isolated from the traditional Chinese medicine Huang-Qin, which has shown various pharmacological activities including anti-inflammatory, antitumor, antioxidant, etc. Thus far, the effect of oroxindin on colonic inflammation and the underlying mechanism remain unknown. In this study, we investigated the tissue distribution of oroxindin and its therapeutic effects on ulcerative colitis (UC) as well as the underlying mechanisms. UC model was established in mice by administrating dextran sulfate sodium (DSS) in drinking water for 7 d. We first showed that oroxindin was largely absorbed by the colon as an active ingredient after normal mice received Huang-Qin-Tang, a traditional Chinese medicine decoction. UC mice were then treated with oroxindin (12.5, 25, 50 mg ·kg(−1) ·d(−1), i.g.) for 10 d. We found that oroxindin treatment greatly suppressed massive macrophages infiltration and attenuated pathological changes in colonic tissue. Furthermore, oroxindin treatment significantly inhibited the generation of IL-1β and IL-18 in the colon via inhibiting the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome formation and activation. In cultured macrophages, LPS induced NLRP3 inflammasome formation and caspase-1 activation, which were suppressed by oroxindin (12.5–50 μM). In LPS-treated macrophages, oroxindin dose-dependently restored the expression of TXNIP protein, leading to suppressing TXNIP-dependent NF-κB activation. In conclusion, these results demonstrate that oroxindin could be absorbed by the colon and attenuate inflammatory responses via inhibiting NLRP3 inflammasome formation and activation, which is related to the inhibitory effect on TXNIP-dependent NF-κB-signaling pathway. Hence, oroxindin has the potential of becoming an effective drug for treating UC."
2880,Residual platelet reactivity is preferred over platelet inhibition rate in monitoring antiplatelet efficacy: insights using thrombelastography,"Although thrombelastography (TEG) has been widely implemented in the clinical setting of endovascular intervention, consensus on the optimal parameter for defining high ischemic risk patients is lacking due to the limited data about the relationship between various TEG parameters and clinical outcomes. In this article, we report a post hoc analysis of a prospective, single-center cohort study, including 447 patients with acute coronary syndrome (ACS). Arachidonic acid (AA)- or adenosine diphosphate (ADP)-induced platelet-fibrin clot strength (MA(AA) or MA(ADP)) was indicative of the net residual platelet reactivity after the treatment with aspirin or clopidogrel, respectively. AA% or ADP% was indices of the relative platelet inhibition rate on AA or ADP pathway. We found that each parameter alone was predictive of the risk of 6-month ischemic event, even after adjusting for confounding factors. However, the association between AA% and clinical outcome disappeared when further adjusted for MA(AA). Likewise, inclusion of MA(ADP) changed the significant relation between ADP% and clinical outcome. MA(ADP) > 47.0 mm and MA(AA) > 15.1 mm were identified as the optimal cutoffs by receiver operating characteristic analysis. High MA(AA) (HR = 3.963; 95% CI: 1.152–13.632; P = 0.029) and high MA(ADP) (HR = 5.185; 95% CI: 2.228–12.062; P < 0.001) were independent predictors when both were included in multivariable Cox regression hazards model. Interestingly, an even higher risk was found for the coexisting high MA(AA) and high MA(ADP) (HR = 7.870; 95% CI: 3.462–17.899; P < 0.001). We conclude that when performing TEG to predict clinical efficacy, residual platelet reactivity has superiority over platelet inhibition rate as a measure of thrombotic risk in patients treated with aspirin and clopidogrel after ACS."
2881,"Kanglexin, a novel anthraquinone compound, protects against myocardial ischemic injury in mice by suppressing NLRP3 and pyroptosis","Pyroptosis is a form of inflammatory cell death that could be driven by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation following myocardial infarction (MI). Emerging evidence suggests the therapeutic potential for ameliorating MI-induced myocardial damages by targeting NLRP3 and pyroptosis. In this study, we investigated the myocardial protection effect of a novel anthraquinone compound (4,5-dihydroxy-7-methyl-9,10-anthraquinone-2-ethyl succinate) named Kanglexin (KLX) in vivo and in vitro. Male C57BL/6 mice were pre-treated either with KLX (20, 40 mg· kg(−1)per day, intragastric gavage) or vehicle for 7 consecutive days prior to ligation of coronary artery to induce permanent MI. KLX administration dose-dependently reduced myocardial infarct size and lactate dehydrogenase release and improved cardiac function as compared to vehicle-treated mice 24 h after MI. We found that MI triggered NLRP3 inflammasome activation leading to conversion of interleukin-1β (IL-1β) and IL-18 into their active mature forms in the heart, which could expand the infarct size and drive cardiac dysfunction. We also showed that MI induced pyroptosis, as evidenced by increased DNA fragmentation, mitochondrial swelling, and cell membrane rupture, as well as increased levels of pyroptosis-related proteins, including gasdermin D, N-terminal GSDMD, and cleaved caspase-1. All these detrimental alterations were prevented by KLX. In hypoxia- or lipopolysaccharide (LPS)-treated neonatal mouse ventricular cardiomyocytes, we showed that KLX (10 μM) decreased the elevated levels of terminal deoxynucleotidyl transferase dUTP nick end labeling- and propidium iodide-positive cells, and pyroptosis-related proteins. We conclude that KLX prevents MI-induced cardiac damages and cardiac dysfunction at least partly through attenuating NLRP3 and subsequent cardiomyocyte pyroptosis, and it is worthy of more rigorous investigations for its potential for alleviating ischemic heart disease."
2882,Endothelin-1 enhances acid-sensing ion channel currents in rat primary sensory neurons,"Endothelin-1 (ET-1), an endogenous vasoactive peptide, has been found to play an important role in peripheral pain signaling. Acid-sensing ion channels (ASICs) are key sensors for extracellular protons and contribute to pain caused by tissue acidosis. It remains unclear whether an interaction exists between ET-1 and ASICs in primary sensory neurons. In this study, we reported that ET-1 enhanced the activity of ASICs in rat dorsal root ganglia (DRG) neurons. In whole-cell voltage-clamp recording, ASIC currents were evoked by brief local application of pH 6.0 external solution in the presence of TRPV1 channel blocker AMG9810. Pre-application with ET-1 (1−100 nM) dose-dependently increased the proton-evoked ASIC currents with an EC(50) value of 7.42 ± 0.21 nM. Pre-application with ET-1 (30 nM) shifted the concentration–response curve of proton upwards with a maximal current response increase of 61.11% ± 4.33%. We showed that ET-1 enhanced ASIC currents through endothelin-A receptor (ET(A)R), but not endothelin-B receptor (ET(B)R) in both DRG neurons and CHO cells co-expressing ASIC3 and ET(A)R. ET-1 enhancement was inhibited by blockade of G-protein or protein kinase C signaling. In current-clamp recording, pre-application with ET-1 (30 nM) significantly increased acid-evoked firing in rat DRG neurons. Finally, we showed that pharmacological blockade of ASICs by amiloride or APETx2 significantly alleviated ET-1-induced flinching and mechanical hyperalgesia in rats. These results suggest that ET-1 sensitizes ASICs in primary sensory neurons via ET(A)R and PKC signaling pathway, which may contribute to peripheral ET-1-induced nociceptive behavior in rats."
2883,"Discovery and characterization of natural products as novel indoleamine 2,3-dioxygenase 1 inhibitors through high-throughput screening","Indoleamine 2,3-dioxygenase 1 (IDO1) is emerging as a promising therapeutic target for the treatment of malignant tumors characterized by dysregulated tryptophan metabolism. However, the antitumor efficacy of existing small-molecule IDO1 inhibitors is still unsatisfactory, and the underlying mechanism remains largely undefined. To identify novel IDO1 inhibitors, an in-house natural product library of 2000 natural products was screened for inhibitory activity against recombinant human IDO1. High-throughput fluorescence-based screening identified 79 compounds with inhibitory activity > 30% at 20 μM. Nine natural products were further confirmed to inhibit IDO1 activity by > 30% using Ehrlich’s reagent reaction. Compounds 2, 7, and 8 were demonstrated to inhibit IDO1 activity in a cellular context. Compounds 2 and 7 were more potent against IDO1 than TDO2 in the enzymatic assay. The kinetic studies showed that compound 2 exhibited noncompetitive inhibition, whereas compounds 7 and 8 were graphically well matched with uncompetitive inhibition. Compounds 7 and 8 were found to bind to the ferric-IDO1 enzyme. Docking stimulations showed that the naphthalene ring of compound 8 formed “T-shaped” π–π interactions with Phe-163 and that the 6-methyl-naphthalene group formed additional hydrophobic interactions with IDO1. Compound 8 was identified as a derivative of tanshinone, and preliminary SAR analysis indicated that tanshinone derivatives may be promising hits for the development of IDO1 inhibitors. This study provides new clues for the discovery of IDO1/TDO2 inhibitors with novel scaffolds."
2884,Nanomedicines based on nanoscale metal-organic frameworks for cancer immunotherapy,"Cancer immunotherapy, with an aim to enhance host immune responses, has been recognized as a promising therapeutic treatment for cancer. A diversity of immunomodulatory agents, including tumor-associated antigens, adjuvants, cytokines and immunomodulators, has been explored for their ability to induce a cascading adaptive immune response. Nanoscale metal-organic frameworks (nMOFs), a class of crystalline-shaped nanomaterials formed by the self-assembly of organic ligands and metal nodes, are attractive for cancer immunotherapy because they feature tunable pore size, high surface area and loading capacity, and intrinsic biodegradability. In this review we summarize recent progress in the development of nMOFs for cancer immunotherapy, including cancer vaccine delivery and combination of in situ vaccination with immunomodulators to reverse immune suppression. Current challenges and future perspectives for rational design of nMOF-based cancer immunotherapy are also discussed."
2885,Mebendazole elicits potent antimyeloma activity by inhibiting the USP5/c-Maf axis,"c-Maf is a critical oncogenic transcription factor that contributes to myelomagenesis. Our previous studies demonstrated that the deubiquitinase USP5 stabilizes c-Maf and promotes myeloma cell proliferation and survival; therefore, the USP5/c-Maf axis could be a potential target for myeloma therapy. As a concept of principle, the present study established a USP5/c-Maf-based luciferase system that was used to screen an FDA-approved drug library. It was found that mebendazole, a typical anthelmintic drug, preferentially induced apoptosis in c-Maf-expressing myeloma cells. Moreover, oral administration of mebendazole delayed the growth of human myeloma xenografts in nude mice but did not show overt toxicity. Further studies showed that the selective antimyeloma activity of mebendazole was associated with the inhibition of the USP5/c-Maf axis. Mebendazole downregulated USP5 expression and disrupted the interaction between USP5 and c-Maf, thus leading to increased levels of c-Maf ubiquitination and subsequent c-Maf degradation. Mebendazole inhibited c-Maf transcriptional activity, as confirmed by both luciferase assays and expression measurements of c-Maf downstream genes. In summary, this study identified mebendazole as a USP5/c-Maf inhibitor that could be developed as a novel antimyeloma agent."
2886,In Response,
2887,Evaluating the Effectiveness of an Intervention Integrating Technology and In-Person Sexual Health Education for Adolescents (In the Know): Protocol for a Cluster Randomized Controlled Trial,"BACKGROUND: Access to a smartphone is nearly universal among American adolescents, and most of them have used the internet to seek health information. Integrating digital technologies into health program delivery may expand opportunities for youth to receive important health information, yet there are few rigorous studies assessing the effectiveness of this type of intervention. OBJECTIVE: The purpose of this study is to assess the effectiveness of In the Know (ITK), a program integrating in-person and technology-based sexual health education for underserved adolescents. METHODS: Youth were engaged in the development of the intervention, including the design of the digital technology and the curriculum content. The intervention focuses on 3 main areas: sexual health and contraceptive use, healthy relationships, and educational and career success. It includes an in-person, classroom component, along with a web-based component to complement and reinforce key content. A cluster randomized controlled trial is in progress among adolescents aged 13-19 years living in Fresno County, California. It is designed to examine the differences in self-reported health and behavioral outcomes among youth in the intervention and control groups at 3 and 9 months. Primary outcomes are condom and contraceptive use or no sex in the past 3 months and use of any clinical health services in the past 3 months. Secondary outcomes include the number of sexual partners in the past 3 months and knowledge of local clinical sexual health services. We will use mixed-effects linear and logistic regression models to assess differences between the intervention and control groups. RESULTS: Trial enrollment began in October 2017 and ended in March 2020 with a total of 1260 participants. The mean age of the participants is 15.73 (SD 1.83) years, and 69.98% (867/1239) of the participants report being Hispanic or Latino. Study results will be available in 2021. CONCLUSIONS: ITK has the potential to improve contraceptive and clinic use among underserved youth. This trial will inform future youth-focused health interventions that are considering incorporating technology. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/18060"
2888,Aung Myint and trevor Jones respond,
2889,Zooming in on protein–RNA interactions: a multi-level workflow to identify interaction partners,"Interactions between proteins and RNA are at the base of numerous cellular regulatory and functional phenomena. The investigation of the biological relevance of non-coding RNAs has led to the identification of numerous novel RNA-binding proteins (RBPs). However, defining the RNA sequences and structures that are selectively recognised by an RBP remains challenging, since these interactions can be transient and highly dynamic, and may be mediated by unstructured regions in the protein, as in the case of many non-canonical RBPs. Numerous experimental and computational methodologies have been developed to predict, identify and verify the binding between a given RBP and potential RNA partners, but navigating across the vast ocean of data can be frustrating and misleading. In this mini-review, we propose a workflow for the identification of the RNA binding partners of putative, newly identified RBPs. The large pool of potential binders selected by in-cell experiments can be enriched by in silico tools such as catRAPID, which is able to predict the RNA sequences more likely to interact with specific RBP regions with high accuracy. The RNA candidates with the highest potential can then be analysed in vitro to determine the binding strength and to precisely identify the binding sites. The results thus obtained can furthermore validate the computational predictions, offering an all-round solution to the issue of finding the most likely RNA binding partners for a newly identified potential RBP."
2890,Development of a knowledge translation platform for ataxia: Impact on readers and volunteer contributors,"BACKGROUND: Dissemination of accurate health research information to patients and families has become increasingly important with the rise of the internet as a means of finding health information. However, the public faces several barriers to accessing research information, including paywalls and technical jargon. One method to bridge this gap between patients, families, and research is using lay summaries. SCAsource is an online knowledge translation platform where peer-reviewed research papers on ataxia are translated into lay summaries. This online platform was launched in September 2018, with the goal of making ataxia research more accessible and understandable to patients and families. A secondary goal is to provide opportunities for ataxia researchers to develop and hone their knowledge translation skills, altogether improving the quality of patient communication in the ataxia community. AIM: The aim of this study was to measure the impact of SCAsource on its readers and volunteer contributors after one year of activity. This is to ensure SCAsource is meeting its goals of (1) improving access and understanding of ataxia research to lay audiences, and (2) improving knowledge translation skills of volunteer contributors. METHODS: Two online surveys were launched, one for readers and one for volunteers. Each survey had a combination of multiple-choice, Likert-scale type, and open-ended short-answer questions. Descriptive quantitative analysis was used for respondent characteristics and Likert-type data. A grounded theory coding approach was used to analyze narrative feedback data. RESULTS: We found that SCAsource has mutually beneficial outcomes for both lay person readers and volunteer contributors. Readers have an increased understanding of ataxia research and access to up-to-date information on recent publications. Volunteers develop knowledge translation skills and have increased confidence in communicating results to lay audiences. Areas of improvement were identified to be incorporated into the platform. CONCLUSION: We demonstrated that SCAsource improves access to information and understanding of research to lay audiences, while providing opportunities for researchers to develop knowledge translation skills. This framework can potentially be used by other rare disease organizations to launch and evaluate their own knowledge translation websites."
2891,Disparity in childhood stunting in India: Relative importance of community-level nutrition and sanitary practices,"Despite rapid macro-economic growth, one-third of the global burden of childhood stunting is contributed by India. This burden is characterized by wide-spread geographical variation within the country. This paper explores two research questions: (i) are the drivers of severe and moderate stunting similar? (ii) differential endowments or policy-effect, how do community-level nutrition and sanitary practices affect inter-state differences? Using data from Indian National Family and Health Survey 4, 2015–16, six states holding different ranks in the stunting continuum are compared to Tamil Nadu, taken as the benchmark state due to its laudable performance in the health care sector. Applying quantile regression approaches, the difference in state-level performance is decomposed into detailed covariate effects (differential endowments) and coefficient effects (differential strength of association between the drivers and outcome). The explanatory variables are not similarly associated with severe and moderate stunting. Decomposition results demonstrate a significant role of community-level sanitation practices compared to child nutrition behaviour in explaining the inter-state disparity. Coefficient effects play a dominant role in the lower tail of HAZ distribution for the poor performing states indicating that the worse outcomes of these states are due to weaker policy effects of the control variables on stunting. Multi-sectoral approach, identification and differentiation between severe and moderate stunting cases can be more instrumental in managing and reducing the scourge. This paper also advocates the potential benefits of customizing centrally-launched policies as per the state’s performance and introducing the concept coproduction in the existing nutrition and health policy framework. This will instigate a feeling of ownership of the problem of childhood stunting among the policy consumers and strengthen the influence of policies on the outcomes."
2892,Exercise and High-Fat Diet in Obesity: Functional Genomics Perspectives of Two Energy Homeostasis Pillars,"The heavy impact of obesity on both the population general health and the economy makes clarifying the underlying mechanisms, identifying pharmacological targets, and developing efficient therapies for obesity of high importance. The main struggle facing obesity research is that the underlying mechanistic pathways are yet to be fully revealed. This limits both our understanding of pathogenesis and therapeutic progress toward treating the obesity epidemic. The current anti-obesity approaches are mainly a controlled diet and exercise which could have limitations. For instance, the “classical” anti-obesity approach of exercise might not be practical for patients suffering from disabilities that prevent them from routine exercise. Therefore, therapeutic alternatives are urgently required. Within this context, pharmacological agents could be relatively efficient in association to an adequate diet that remains the most efficient approach in such situation. Herein, we put a spotlight on potential therapeutic targets for obesity identified following differential genes expression-based studies aiming to find genes that are differentially expressed under diverse conditions depending on physical activity and diet (mainly high-fat), two key factors influencing obesity development and prognosis. Such functional genomics approaches contribute to elucidate the molecular mechanisms that both control obesity development and switch the genetic, biochemical, and metabolic pathways toward a specific energy balance phenotype. It is important to clarify that by “gene-related pathways”, we refer to genes, the corresponding proteins and their potential receptors, the enzymes and molecules within both the cells in the intercellular space, that are related to the activation, the regulation, or the inactivation of the gene or its corresponding protein or pathways. We believe that this emerging area of functional genomics-related exploration will not only lead to novel mechanisms but also new applications and implications along with a new generation of treatments for obesity and the related metabolic disorders especially with the modern advances in pharmacological drug targeting and functional genomics techniques."
2893,Necroptosis in Immuno-Oncology and Cancer Immunotherapy,"Immune-checkpoint blockers (ICBs) have revolutionized oncology and firmly established the subfield of immuno-oncology. Despite this renaissance, a subset of cancer patients remain unresponsive to ICBs due to widespread immuno-resistance. To “break” cancer cell-driven immuno-resistance, researchers have long floated the idea of therapeutically facilitating the immunogenicity of cancer cells by disrupting tumor-associated immuno-tolerance via conventional anticancer therapies. It is well appreciated that anticancer therapies causing immunogenic or inflammatory cell death are best positioned to productively activate anticancer immunity. A large proportion of studies have emphasized the importance of immunogenic apoptosis (i.e., immunogenic cell death or ICD); yet, it has also emerged that necroptosis, a programmed necrotic cell death pathway, can also be immunogenic. Emergence of a proficient immune profile for necroptosis has important implications for cancer because resistance to apoptosis is one of the major hallmarks of tumors. Putative immunogenic or inflammatory characteristics driven by necroptosis can be of great impact in immuno-oncology. However, as is typical for a highly complex and multi-factorial disease like cancer, a clear cause versus consensus relationship on the immunobiology of necroptosis in cancer cells has been tough to establish. In this review, we discuss the various aspects of necroptosis immunobiology with specific focus on immuno-oncology and cancer immunotherapy."
2894,Assessment of Parents’ Oral Health Literacy and Its Association with Caries Experience of Their Preschool Children,"(1) Purpose: To assess the oral health literacy (OHL) of parents and its association with the caries experience of their preschool children attending the Hospital University Sains Malaysia (HUSM), Kota Bharu, Kelantan, Malaysia. (2) Materials and Methods: This is a descriptive cross-sectional study involving a systematic random sampling method, using a sample of 230 parent/preschool child dyads. Among 230 parents, 24 were males and 206 were females (mean age 31.43 ± 5.82); among 230 children, 92 were boys and 138 were girls (mean age 4.82 ± 1.04) attending the pedodontics clinic, HUSM, who participated and met the inclusion criteria. A structured, self-administered oral health literacy questionnaire including sociodemographic factors was used in this study. A child’s oral examination was performed to check the dmft (decayed, missing, filled teeth) status. Statistical analysis was done using descriptive and Spearman’s correlation analysis and multivariate regression analysis. (3) Results: The mean dmft score of children in relation to the OHL level of parents showed a significant difference (p < 0.00). The mean dmft score of children in relation to the OHL level of parents showed the following relationships: Inadequate (7.49 ± 4.10) followed by marginal (3.28 ± 2.67) and then adequate (0.55 ± 1.55). The incidence of caries amongst children in relation to parental employment was more associated with unemployed parents (6.11 ± 4.43) than with employed parents (2.79 ± 3.65). The caries experience amongst children in relation to education of their parents revealed a significant difference (p < 0.001), and the mean dmft score was high amongst preschool children with primary school qualified parents (10.7 ± 4.10) followed by high school (7.04 ± 3.68), vocational (5.81 ± 3.57), diploma (2.61 ± 2.81), and university (1.29 ± 2.27), respectively. The results revealed a valid significant difference (negative correlation, r(s) = −0.753 **) between the OHL of parents with the dmft score of their preschool children. The age and gender of parents was not significantly associated with OHL, whereas ethnicity (positive correlation, r(s) = 0.283 **), education (positive correlation, r(s) = 0.865 **), and employment (negative correlation, r(s) = −0.490 **) were found to be significant. Conclusion: We conclude that there is a significant association between the OHL of parents with the dmft score of their preschool children. The logistic regression showed that after adjustment for sociodemographic factors, parents’ gender (OR = 0.067, 95% CI: 0.012–0.360), parents’ employment status (OR = 3.247, 95% CI: 0.897–11.754), parents’ OHL score (OR = 0.042, 95% CI: 0.016–0.114), and child age (OR = 2.195, 95% CI: 1.249–3.857) were significantly associated with dental caries in children. Our study concluded that parents’ employment status, age, gender, OHL, and child’s age were significantly associated with the caries experience of their preschool children."
2895,Alveolar Type II Cells or Mesenchymal Stem Cells: Comparison of Two Different Cell Therapies for the Treatment of Acute Lung Injury in Rats,"The use of cell therapies has recently increased for the treatment of pulmonary diseases. Mesenchymal stem/stromal cells (MSCs) and alveolar type II cells (ATII) are the main cell-based therapies used for the treatment of acute respiratory distress syndrome (ARDS). Many pre-clinical studies have shown that both therapies generate positive outcomes; however, the differences in the efficiency of MSCs or ATII for reducing lung damage remains to be studied. We compared the potential of both cell therapies, administering them using the same route and dose and equal time points in a sustained acute lung injury (ALI) model. We found that the MSCs and ATII cells have similar therapeutic effects when we tested them in a hydrochloric acid and lipopolysaccharide (HCl-LPS) two-hit ALI model. Both therapies were able to reduce proinflammatory cytokines, decrease neutrophil infiltration, reduce permeability, and moderate hemorrhage and interstitial edema. Although MSCs and ATII cells have been described as targeting different cellular and molecular mechanisms, our data indicates that both cell therapies are successful for the treatment of ALI, with similar beneficial results. Understanding direct cell crosstalk and the factors released from each cell will open the door to more accurate drugs being able to target specific pathways and offer new curative options for ARDS."
2896,Neoadjuvant Treatment Options in Soft Tissue Sarcomas,"Due to the heterogeneity of soft tissue sarcomas (STS), the choice of the proper perioperative treatment regimen is challenging. Neoadjuvant therapy has attracted increasing attention due to several advantages, particularly in patients with locally advanced disease. The number of available neoadjuvant modalities is growing continuously. We may consider radiotherapy, chemotherapy, targeted therapy, radiosensitizers, hyperthermia, and their combinations. This review discusses possible neoadjuvant treatment options in STS with an emphasis on available evidence, indications for each treatment type, and related risks. Finally, we summarize current recommendations of the STS neoadjuvant therapy response assessment."
2897,Retrospective Analysis Shows That Most RHDV GI.1 Strains Circulating Since the Late 1990s in France and Sweden Were Recombinant GI.3P–GI.1d Strains,"Recombination is one of the major sources of genetic variation in viruses. RNA viruses, such as rabbit hemorrhagic disease virus (RHDV), are among the viruses with the highest recombination rates. Several recombination events have been described for RHDV, mostly as a consequence of their genomic architecture. Here, we undertook phylogenetic and recombination analyses of French and Swedish RHDV strains from 1994 to 2016 and uncovered a new intergenotypic recombination event. This event occurred in the late 1990s/early 2000s and involved nonpathogenic GI.3 strains as donors for the nonstructural part of the genome of these recombinants, while pathogenic GI.1d strains contributed to the structural part. These GI.3P–GI.1d recombinant strains did not entirely replace GI.1d (nonrecombinant) strains, but became the dominant strains in France and Sweden, likely due to a fitness advantage associated with this genomic architecture. GI.3P–GI.1d (P stands for polymerase) strains persisted until 2013 and 2016 in Sweden and France, respectively, and cocirculated with the new genotype GI.2 in France. Since strains from the first GI.2 outbreaks were GI.3P–GI.2, we hypothesize that GI.3P–GI.1d could be the parental strain. Our results confirm the outstanding recombination ability of RHDV and its importance in the evolution of lagoviruses, which was only revealed by studying complete genomic sequences."
2898,Emulsion PCR (ePCR) as a Tool to Improve the Power of DGGE Analysis for Microbial Population Studies,"To the authors’ knowledge, this is the first report of the use of emulsion-Polymerase chain reaction (e-PCR) coupled with denaturing gradient gel electrophoresis (DGGE) analysis. In the present work the effectiveness of ePCR in improving the power of the DGGE technique for microbial population studies was tested. Our results indicated that ePCR results in uniform amplification of several DNA molecules, overcoming the major limitations of conventional PCR, such as preferential amplification and DNA concentration dependence. Moreover, ePCR-DGGE resulted in higher sensitivity when compared to conventional PCR-DGGE methods used for studying microbial populations in a complex matrix. In fact, compared to conventional PCR, the DGGE profiles of ePCR products permitted the detection of a higher number of the species that were present in the tested sample."
2899,MIP-1α Expression Induced by Co-Stimulation of Human Monocytic Cells with Palmitate and TNF-α Involves the TLR4-IRF3 Pathway and Is Amplified by Oxidative Stress,"Metabolic inflammation is associated with increased expression of saturated free fatty acids, proinflammatory cytokines, chemokines, and adipose oxidative stress. Macrophage inflammatory protein (MIP)-1α recruits the inflammatory cells such as monocytes, macrophages, and neutrophils in the adipose tissue; however, the mechanisms promoting the MIP-1α expression remain unclear. We hypothesized that MIP-1α co-induced by palmitate and tumor necrosis factor (TNF)-α in monocytic cells/macrophages could be further enhanced in the presence of reactive oxygen species (ROS)-mediated oxidative stress. To investigate this, THP-1 monocytic cells and primary human macrophages were co-stimulated with palmitate and TNF-α and mRNA and protein levels of MIP-1α were measured by using quantitative reverse transcription, polymerase chain reaction (qRT-PCR) and commercial enzyme-linked immunosorbent assays (ELISA), respectively. The cognate receptor of palmitate, toll-like receptor (TLR)-4, was blunted by genetic ablation, neutralization, and chemical inhibition. The involvement of TLR4-downstream pathways, interferon regulatory factor (IRF)-3 or myeloid differentiation (MyD)-88 factor, was determined using IRF3-siRNA or MyD88-deficient cells. Oxidative stress was induced in cells by hydrogen peroxide (H(2)O(2)) treatment and ROS induction was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. The data show that MIP-1α gene/protein expression was upregulated in cells co-stimulated with palmitate/TNF-α compared to those stimulated with either palmitate or TNF-α (P < 0.05). Further, TLR4-IRF3 pathway was implicated in the cooperative induction of MIP-1α in THP-1 cells, and this cooperativity between palmitate and TNF-α was clathrin-dependent and also required signaling through c-Jun and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Notably, ROS itself induced MIP-1α and could further promote MIP-1α secretion together with palmitate and TNF-α. In conclusion, palmitate and TNF-α co-induce MIP-1α in human monocytic cells via the TLR4-IRF3 pathway and signaling involving c-Jun/NF-κB. Importantly, oxidative stress leads to ROS-driven MIP-1α amplification, which may have significance for metabolic inflammation."
2900,Generation of Marker-Free pbd-2 Knock-in Pigs Using the CRISPR/Cas9 and Cre/loxP Systems,"Porcine β-defensin 2 (PBD-2), expressed by different tissues of pigs, is a multifunctional cationic peptide with antimicrobial, immunomodulatory and growth-promoting abilities. As the latest generation of genome-editing tool, CRISPR/Cas9 system makes it possible to enhance the expression of PBD-2 in pigs by site-specific knock-in of pbd-2 gene into the pig genome. In this study, we aimed to generate marker-free pbd-2 knock-in pigs using the CRISPR/Cas9 and Cre/loxP systems. Two copies of pbd-2 gene linked by a T2A sequence were inserted into the porcine Rosa26 locus through CRISPR/Cas9-mediated homology-directed repair. The floxed selectable marker gene neoR, used for G418 screening of positive cell clones, was removed by cell-penetrating Cre recombinase with a recombination efficiency of 48.3%. Cloned piglets were produced via somatic cell nuclear transfer and correct insertion of pbd-2 genes was confirmed by PCR and Southern blot. Immunohistochemistry and immunofluorescence analyses indicated that expression levels of PBD-2 in different tissues of transgenic (TG) piglets were significantly higher than those of their wild-type (WT) littermates. Bactericidal assays demonstrated that there was a significant increase in the antimicrobial properties of the cell culture supernatants of porcine ear fibroblasts from the TG pigs in comparison to those from the WT pigs. Altogether, our study improved the protein expression level of PBD-2 in pigs by site-specific integration of pbd-2 into the pig genome, which not only provided an effective pig model to study the anti-infection mechanisms of PBD-2 but also a promising genetic material for the breeding of disease-resistant pigs."
2901,Snapshots of ADP-ribose bound to Getah virus macro domain reveal an intriguing choreography,"Alphaviruses are (re-)emerging arboviruses of public health concern. The nsP3 gene product is one of the key players during viral replication. NsP3 comprises three domains: a macro domain, a zinc-binding domain and a hypervariable region. The macro domain is essential at both early and late stages of the replication cycle through ADP-ribose (ADPr) binding and de-ADP-ribosylation of host proteins. However, both its specific role and the precise molecular mechanism of de-ADP-ribosylation across specific viral families remains to be elucidated. Here we investigate by X-ray crystallography the mechanism of ADPr reactivity in the active site of Getah virus macro domain, which displays a peculiar substitution of one of the conserved residues in the catalytic loop. ADPr adopts distinct poses including a covalent bond between the C′′1 of the ADPr and a conserved Togaviridae-specific cysteine. These different poses observed for ADPr may represent snapshots of the de-ADP-ribosylation mechanism, highlighting residues to be further characterised."
2902,Study of SARS Transmission Via Liquid Droplets in Air,"Microscale liquid droplets could act as the SARS carriers in air when released from an infected person through breathing, coughing, or sneezing. In this study, a dynamic model has been built to quantitatively investigate the effect of the relative humidity on the transport of liquid droplets in air using coupled mass transfer and momentum equations. Under higher relative humidity, the exhaled liquid droplets evaporate slowly. Larger droplets fall faster, which could reduce the probability of the droplets inhalation. This may be one of the most important factors that influence the SARS transmission in air."
2903,High HbA1c is associated with decreased 6-month survival and poor outcomes after out-of-hospital cardiac arrest: a retrospective cohort study,"BACKGROUND: To evaluate the associations between glycated hemoglobin (HbA1c) at admission and 6-month mortality and outcomes after out-of-hospital cardiac arrest (OHCA) treated by hypothermic targeted temperature management (TTM). METHODS: This single-center retrospective cohort study included adult OHCA survivors who underwent hypothermic TTM from December 2011 to December 2019. High HbA1c at admission was defined as a level higher than 6%. Poor neurological outcomes were defined as cerebral performance category scores of 3–5. The primary outcome was 6-month mortality. The secondary outcome was the 6-month neurological outcome. Descriptive statistics, log-rank tests, and multivariable regression modeling were used for data analysis. RESULTS: Of the 302 patients included in the final analysis, 102 patients (33.8%) had HbA1c levels higher than 6%. The high HbA1c group had significantly worse 6-month survival (12.7% vs. 37.5%, p < 0.001) and 6-month outcomes (89.2% vs. 73.0%, p = 0.001) than the non-high HbA1c group. Kaplan-Meier analysis and the log-rank test showed that the survival time was significantly shorter in the patients with HbA1c > 6% than in those with HbA1c ≤6%. In the multivariable logistic regression analysis, HbA1c > 6% was independently associated with 6-month mortality (OR 5.85, 95% CI 2.26–15.12, p < 0.001) and poor outcomes (OR 4.18, 95% CI 1.41–12.40, p < 0.001). CONCLUSIONS: This study showed that HbA1c higher than 6% at admission was associated with increased 6-month mortality and poor outcomes in OHCA survivors treated with hypothermic TTM. Poor long-term glycemic management may have prognostic significance after cardiac arrest."
2904,"Introduction of less invasive surfactant administration (LISA), impact on diagnostic and therapeutic procedures in early life: a historical cohort study","BACKGROUND: In preterm infants with Respiratory Distress Syndrome (RDS), Less Invasive Surfactant Administration (LISA) has been established to reduce the need of mechanical ventilation and might improve survival rates without bronchopulmonary dysplasia. The aim of this study was to investigate whether NICU care has changed after introduction of less invasive surfactant administration (LISA), with regard to diagnostic and therapeutic procedures in the first week of life. METHODS: Infants with gestational age < 32 weeks who received surfactant by LISA (June 2014 – December 2017, n = 169) were retrospectively compared to infants who received surfactant after intubation (January 2012 – May 2014, n = 155). Local protocols on indication for surfactant, early onset sepsis, blood transfusions and enteral feeding did not change between both study periods. Besides, as secondary outcome complications of prematurity were compared. Data was collected from electronic patient files and compared by univariate analysis through Students T-test, Mann Whitney-U test, Pearson Chi-Square test or Linear by Linear Association. RESULTS: All baseline characteristics of both groups were comparable. Compared to controls, LISA patients received a higher total surfactant dose (208 vs.160 mg/kg; p < 0.001), required redosing more frequently (32.5% vs. 21.3%; p = 0.023), but needed less mechanical ventilation (35.5% vs. 76.8%; p < 0.001). After LISA, infants underwent fewer X-rays (1.0 vs. 3.0, p < 0.001), blood gas examinations (3.0 vs. 5.0, p < 0.001), less inotropic drugs (9.5% vs. 18.1%; p = 0.024), blood transfusions (24.9% vs. 41.9%, p = 0.003) and had shorter duration of antibiotic therapy for suspected early onset sepsis (3.0 vs. 5.0 days, p < 0.001). Moreover, enteral feeding was advanced faster (120 vs. 100 mL/kg/d, p = 0.048) at day seven. There were no differences in complications of prematurity. CONCLUSION: The introduction of LISA is associated with significantly fewer diagnostic and therapeutic procedures in the first week of life, which emphasizes the beneficial effects of LISA."
2905,"Clinically Applicable AI System for Accurate Diagnosis, Quantitative Measurements, and Prognosis of COVID-19 Pneumonia Using Computed Tomography",
2906,Angiogenin and tRNA fragments in Parkinson’s disease and neurodegeneration,"In this review, we summarise the evidence for a role of the ribonuclease angiogenin in the pathophysiology of neurodegenerative disorders, with a specific focus on Parkinson’s disease (PD). Angiogenin is a stress-induced, secreted ribonuclease with both nuclear and cytosolic activities. Loss-of-function mutations in the angiogenin gene (ANG) have been initially discovered in familial cases of amyotrophic lateral sclerosis (ALS), however, variants in ANG have subsequently been identified in PD and Alzheimer’s disease. Delivery of angiogenin protein reduces neurodegeneration and delays disease progression in in vitro and in vivo models of ALS and in vitro models of PD. In the nucleus, angiogenin promotes ribosomal RNA transcription. Under stress conditions, angiogenin also translocates to the cytosol where it cleaves non-coding RNA into RNA fragments, in particular transfer RNAs (tRNAs). Stress-induced tRNA fragments have been proposed to have multiple cellular functions, including inhibition of ribosome biogenesis, inhibition of protein translation and inhibition of apoptosis. We will discuss recent evidence of tRNA fragment accumulation in PD, as well as their potential neuroprotective activities."
2907,"Psychosis in Parkinson’s disease and parkinsonism in antipsychotic-naive schizophrenia spectrum psychosis: clinical, nosological and pathobiological challenges","Following the formulation of operational criteria for the diagnosis of psychosis in Parkinson’s disease, a neurodegenerative disorder, the past decade has seen increasing interest in such nonmotor psychopathology that appears to be independent of dopaminergic therapy. Similarly, there has been a resurgence of interest in motor aspects of the neurodevelopmental disorder of schizophrenia, including spontaneous parkinsonism that appears to be independent of antipsychotic treatment. This review first addresses the clinical and nosological challenges of these superficially paradoxical insights and then considers pathobiological challenges. It proposes that diverse modes of disturbance to one or more element(s) in a cortical-striatal-thalamocortical neuronal network, whether neurodegenerative or neurodevelopmental, can result in movement disorder, psychosis or both. It then proposes that time- and site-dependent dysfunction in such a neuronal network may be a generic substrate for the emergence of psychosis not only in Parkinson’s disease and schizophrenia-spectrum disorders but also in other neuropsychiatric disorders in which psychosis, and sometimes movement disorders, can be encountered; these include substance abuse, cerebrovascular disease, cerebral trauma, cerebral neoplasia, epilepsy, Huntington’s disease, frontotemporal dementia, Alzheimer’s disease and multiple sclerosis."
2908,Leflunomide increased the renal exposure of acyclovir by inhibiting OAT1/3 and MRP2,"Rheumatoid arthritis patients can be prescribed a combination of immunosuppressive drug leflunomide (LEF) and the antiviral drug acyclovir to reduce the high risk of infection. Acyclovir is a substrate of organic anion transporter (OAT) 1/3 and multidrug resistance-associated protein (MRP) 2. Considering the extraordinarily long half-life of LEF’s active metabolite teriflunomide (TER) and the kidney injury risk of acyclovir, it is necessary to elucidate the potential impact of LEF on the disposition of acyclovir. Here we used a specific MRP inhibitor MK571 and probenecid (OAT1/3 and MRP2 inhibitor) to assess the effects of MRP2 and OAT1/3 on the pharmacokinetics and tissue distribution of acyclovir in rats. We showed that LEF and probenecid, but not MK571 significantly increased the plasma concentration of acyclovir. However, kidney and liver exposures of acyclovir were increased when coadministered with LEF, probenecid or MK571. The kidney/plasma ratio of acyclovir was increased to approximately 2-fold by LEF or probenecid, whereas it was increased to as much as 14.5-fold by MK571. Consistently, these drugs markedly decreased the urinary excretion of acyclovir. TER (0.5−100 μmol/L) dose-dependently increased the accumulation of acyclovir in MRP2-MDCK cells with an IC(50) value of 4.91 μmol/L. TER (5 μmol/L) significantly inhibited the uptake of acyclovir in hOAT1/3-HEK293 cells. These results suggest that LEF/TER increased the kidney accumulation of acyclovir by inhibiting the efflux transporter MRP2, which increased its kidney/plasma ratio and renal injury risk. However, the inhibitory effects of LEF/TER on OAT1/3 reduced the tubular cells’ uptake of acyclovir and increased the plasma concentration."
2909,Comparative strategies for stem cell biodistribution in a preclinical study,"Stem cell therapy represents the potential alternative effective strategy for some diseases that lack effective treatment currently. Correspondingly, it is crucial to establish high-sensitive and reliable quantification assay for tracing exogenous cell migration. In the present study, we first used both bioluminescence imaging (BLI) indirect labeling (human norepinephrine transporter-luciferase reporter system) and (89)zirconium ((89)Zr)-hNSCs direct labeling combined with positron emission tomography/computer tomography (PET/CT) system for tracking human neural stem cells (hNSCs) migration into the brain via nasal administration in preclinical study. But the above two methods failed to give the biodistribution profile due to their low sensitivity. Considering its superior sensitivity and absolute quantitation capability, we developed and validated the droplet digital PCR (ddPCR) targeting species-specific gene in frozen and paraffin sections, slices, and whole blood with the sensitivity of 100–200 hNSCs. Accurate and high throughput quantification could be performed using ddPCR with the coefficient of variation (CVs) of lower quality control (LQC) below 30%. In combination with immunohistochemistry and ddPCR, we confirmed the migration of hNSCs into the brain via nasal administration, which supported the efficacy of hNSCs in MPTP-treated mice, an animal model of Parkinson’s disease. In conclusion, the present study is the first to report the application of ddPCR in the pharmacokinetics profile description of tracking of hNSCs in preclinical studies."
2910,Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9 in hyperlipidemic rats,"Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models. High-fat diet-induced rats were treated with AE (100 mg/kg per day, ig) for 6 weeks. We found that AE administration significantly decreased the levels of total cholesterol (TC) and LDL in the serum and liver tissues. Moreover, AE administration ameliorated HPL-induced hepatic lipid aggregation. But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats. A cellular model of HPL was established in human hepatoma (HepG2) cells treated with cholesterol (20 μg/mL) and 25-hydroxycholesterol (2 μg/mL), which exhibited markedly elevated cholesterol levels. The increased cholesterol levels could be reversed by subsequent treatment with AE (30 μM). In both the in vivo and in vitro HPL models, we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 (SREBP-2) and hepatocyte nuclear factor (HNF)1α-mediated PCSK9 signaling, which in turn upregulated LDL receptor (LDLR) and promoted LDL uptake. This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway."
2911,Engineering nanomedicines through boosting immunogenic cell death for improved cancer immunotherapy,"Current cancer immunotherapy has limited response rates in a large variety of solid tumors partly due to the low immunogenicity of the tumor cells and the immunosuppressive tumor microenvironment (ITM). A number of clinical cancer treatment modalities, including radiotherapy, chemotherapy, photothermal and photodynamic therapy, have been shown to elicit immunogenicity by inducing immunogenic cell death (ICD). However, ICD-based immunotherapy is restricted by the ITM limiting its efficacy in eliciting a long-term antitumor immune response, and by severe systemic toxicity. To address these challenges, nanomedicine-based drug delivery strategies have been exploited for improving cancer immunotherapy by boosting ICD of the tumor cells. Nanosized drug delivery systems are promising for increasing drug accumulation at the tumor site and codelivering ICD inducers and immune inhibitors to simultaneously elicit the immune response and relieve the ITM. This review highlights the recent advances in nanomedicine-based immunotherapy utilizing ICD-based approaches. A perspective on the clinical translation of nanomedicine-based cancer immunotherapy is also provided."
2912,Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells,"Immunotherapy that activates the host immune system to reverse immunosuppression has emerged as a new generation of cancer treatment in both preclinical studies and clinical trials. Although immunotherapy has shown significant achievements in the treatment of various cancers, it faces challenges that limit its further evolution such as poor permeation and modest responsiveness. The development of nanoparticle drug delivery system has provided an opportunity to overcome these drawbacks and to achieve optimized immunotherapy. Based on the research of our group, we here introduce the new strategies being employed using nanoscale intelligent drug delivery systems to enhance the effects of cancer immunotherapy. We also provide a perspective on the further possible application of nanoparticles in more effective antitumor immunotherapy."
2913,A novel biphenyl compound IMB-S7 ameliorates hepatic fibrosis in BDL rats by suppressing Sp1-mediated integrin αv expression,"Chronic tissue injury with fibrosis results in the disruption of tissue architecture, organ dysfunction, and eventual organ failure. Therefore, the development of effective antifibrotic drugs is urgently required. IMB-S7 is novel biphenyl compound derived from bifendate (biphenyldicarboxylate) that is used for the treatment of chronic hepatitis in China. In the current study we investigated the potential of IMB-S7 as an antihepatic fibrosis agent. In bile duct ligation (BDL) rat model, oral administration of IMB-S7 (400 mg· kg(−1)· d(−1), for 14 days) significantly ameliorated BDL-induced liver necrosis, bile duct proliferation, and collagen accumulation. We then showed that IMB-S7 treatment markedly suppressed the TGF-β/Smad pathway in human hepatic stellate cell line LX2 and mouse primary HSCs, as well as in liver samples of BDL rats, thus inhibiting the transcription of most fibrogenesis-associated genes, including TGF-β1, COL1A1, and ACTA2. Furthermore, IMB-S7 treatment significantly suppressed the expression of integrin αv at the mRNA and protein levels in TGF-β-treated LX2 cells and liver samples of BDL rats. Using integrin αv overexpression and silencing, we demonstrated that integrin αv activity correlated positively with the activation of TGF-β/Smad pathway. Based on dual luciferase assay and DNA affinity precipitation assay, we revealed that IMB-S7 inactivated integrin αv through competitively inhibiting the binding of Sp1, a transcription factor, to the integrin αv (ITGAV) promoter (−173/−163 bp). These results suggest that IMB-S7 inhibits HSCs activation and liver fibrosis through Sp1-integrin αv signaling, and IMB-S7 may be a promising candidate to combat hepatic fibrosis in the future."
2914,Nanoengineered targeting strategy for cancer immunotherapy,"Cancer immunotherapy is rapidly changing the paradigm of cancer care and treatment by evoking host immunity to kill cancer cells. As clinical approval of checkpoint inhibitors (e.g., ipilimumab and pembrolizumab) has been accelerated by a dramatic improvement of long-term survival in a small subset of patients compared to conventional chemotherapy, growing interesting research has focused on immunotherapy. However, majority of patients have not benefited from checkpoint therapies that only partially remove the inhibition of T cell functions. Insufficient systemic T cell responses, low immunogenicity and the immunosuppressive environment of tumors, create great challenges on therapeutic efficiency. Nanotechnology can integrate multiple functions within controlled size and shape, and has been explored as a unique avenue for the development of cancer immunotherapy. In this review, we mainly address how nanoengineered vaccines can induce robust T cell responses against tumors, as well as how nanomedicine can remodel the tumor immunosuppressive microenvironment to boost antitumor immune responses."
2915,RNF6 promotes myeloma cell proliferation and survival by inducing glucocorticoid receptor polyubiquitination,"RNF6, a RING-type ubiquitin ligase, has been identified as an oncogene in various cancers but its role in multiple myeloma (MM) remains elusive. In the present study we first showed that the expression levels of RNF6 in MM were significantly elevated compared with the bone marrow cells of healthy donors. Overexpression of RNF6 in LP1 and PRMI-8266 MM cell lines promoted cell proliferation, whereas knockdown of RNF6 led to apoptosis of MM cells. Furthermore, we revealed that RNF6, as a ubiquitin ligase, interacted with glucocorticoid receptor (GR) and induced its K63-linked polyubiquitination. Different from current knowledge, RNF6 increased GR stability at both endogenous and exogenous contexts. Such an action greatly promoted GR transcriptional activity, which was confirmed by luciferase assays and by the increased expression levels of prosurvival genes including Bcl-xL and Mcl-1, two typical downstream genes of the GR pathway. Consistent with these findings, ectopic expression of RNF6 in MM cells conferred resistance to dexamethasone, a typical anti-myeloma agent. In conclusion, we demonstrate that RNF6 promotes MM cell proliferation and survival by inducing atypical polyubiquitination to GR, and RNF6 could be a promising therapeutic target for the treatment of MM."
2916,Uncarboxylated osteocalcin ameliorates hepatic glucose and lipid metabolism in KKAy mice via activating insulin signaling pathway,"Osteocalcin, expressed in osteoblasts of the bone marrow, undergoes post-translational carboxylation and deposits in mineralized bone matrix. A portion of osteocalcin remains uncarboxylated (uncarboxylated osteocalcin, GluOC) that is released into blood where it functions as a hormone to regulate insulin secretion and insulin sensitivity. As insulin resistance is closely associated with metabolic syndrome, this study is aimed to elucidate how GluOC regulates glucose and lipid metabolism in KKAy mice, an animal model displaying obese, hyperglycemia, hyperinsulinemia, insulin resistance, and hepatic steatosis. GluOC (3, 30 ng/g per day, ig) was orally administered to female KKAy mice for 4 weeks. Whole-body insulin sensitivity, glucose metabolism, hepatic steatosis, dyslipidemia were examined using routine laboratory assays. We found that GluOC administration significantly enhanced insulin sensitivity in KKAy mice by activating hepatic IRβ/PI3K/Akt pathway and elevated the whole-body insulin sensitivity with decreased FPI and HOMA-IR index. Furthermore, GluOC administration alleviated hyperglycemia through suppressing gluconeogenesis and promoting glycogen synthesis in KKAy mice and in cultured hepatocytes in vitro. Moreover, GluOC administration dose-dependently ameliorated dyslipidemia and attenuated hepatic steatosis in KKAy mice by inhibiting hepatic de novo lipogenesis and promoting fatty-acid β-oxidation. These results demonstrate that GluOC effectively enhances hepatic insulin sensitivity, improves hyperglycemia and ameliorates hepatic steatosis in KKAy mice, suggesting that GluOC could be a promising drug candidate for treating metabolic syndrome."
2917,Melatonin receptor agonist ramelteon attenuates mouse acute and chronic ischemic brain injury,"Melatonin receptors (MTs) are potential drug targets for stroke therapy. Ramelteon is a selective melatonin receptor agonist used to treat insomnia. In this study we investigated whether ramelteon could attenuate cerebral ischemia in mice. Acute focal cerebral ischemia was induced in mice via middle cerebral artery occlusion (MCAO). We found oral administration of ramelteon (3.0 mg/kg) significantly attenuated ischemic injury even when it was given 4 h after the onset of ischemia. We showed that administration of ramelteon (3.0 mg/kg) displayed comparable protective efficacy and length of effective time window as administration of edaravone (10 mg/kg, i.p.), which was used in clinic to treat ischemic stroke. Chronic ischemic brain injury was induced in mice using photothrombosis. Oral administration of ramelteon (3.0 mg · kg(−1) · d(−1)) for 7 days after ischemia significantly attenuated functional deficits for at least 15 days. The neuroprotection of ramelteon was blocked by 4-P-PDOT, a specific MT antagonist. We further revealed that ramelteon significantly inhibited autophagy in the peri-infarct cortex in both the mouse ischemia models via regulating AMPK/mTOR signaling pathway. Intracerebroventricular injection of rapamycin, an autophagy activator, compromised the neuroprotection of ramelteon, suggesting ramelteon might attenuate ischemic injury by counteracting autophagic cell death. These data demonstrate for the first time the potential benefits of ramelteon in the treatment of both acute and chronic ischemic brain injury and provide the rationale for the application of ramelteon in stroke therapy."
2918,Associating 197 Chinese herbal medicine with drug targets and diseases using the similarity ensemble approach,"Chinese herbal medicine (CHM) addresses complex diseases through polypharmacological interactions. However, systematic studies of herbal medicine pharmacology remain challenging due to the complexity of CHM ingredients and their interactions with various targets. In this study, we aim to address this challenge with computational approaches. We investigated the herb-target-disease associations of 197 commonly prescribed CHMs using the similarity ensemble approach and DisGeNET database. We demonstrated that this method can be applied to associate herbs with their putative targets. In the case study of three well-known herbs, Radix Glycyrrhizae, Flos Lonicerae, and Rhizoma Coptidis, approximately 70% of the predicted targets were supported by scientific literature. By linking 406 targets to 2439 annotated diseases, we further analyzed the pharmacological functions of 197 herbs. Finally, we proposed a strategy of target-oriented herbal formula design and illustrated the target profiles for four common chronic diseases, namely, Alzheimer’s disease, depressive disorder, hypertensive disease, and non-insulin-dependent diabetes mellitus. This computational approach holds great potential in the target identification of herbs, understanding the molecular mechanisms of CHM, and designing novel herbal formulas."
2919,Endophilin A2 regulates calcium-activated chloride channel activity via selective autophagy-mediated TMEM16A degradation,"TMEM16A Ca(2+)-activated chloride channel (CaCC) plays an essential role in vascular homeostasis. In this study we investigated the molecular mechanisms underlying downregulation of TMEM16A CaCC activity during hypertension. In cultured basilar artery smooth muscle cells (BASMCs) isolated from 2k2c renohypertesive rats, treatment with angiotensin II (0.125−1 μM) dose-dependently increased endophilin A2 levels and decreased TMEM16A expression. Similar phenomenon was observed in basilar artery isolated from 2k2c rats. We then used whole-cell recording to examine whether endophilin A2 could regulate TMEM16A CaCC activity in BASMCs and found that knockdown of endophilin A2 significantly enhanced CaCC activity, whereas overexpression of endophilin A2 produced the opposite effect. Overexpression of endophilin A2 did not affect the TMEM16A mRNA level, but markedly decreased TMEM16A protein level in BASMCs by inducing ubiquitination and autophagy of TMEM16A. Ubiquitin-binding receptor p62 (SQSTM1) could bind to ubiquitinated TMEM16A and resulted in a process of TMEM16A proteolysis in autophagosome/lysosome. These data provide new insights into the regulation of TMEM16A CaCC activity by endophilin A2 in BASMCs, which partly explains the mechanism of angiotensin-II-induced TMEM16A inhibition during hypertension-induced vascular remodeling."
2920,Bile duct ligation enhances AZT CNS toxicity partly by impairing the expression and function of BCRP in rat brain,"Breast cancer resistance protein (BCRP) is one of ATP-binding cassette (ABC) transporters in brain microvessel endothelial cells that transport their substrates from brain to blood, thus limiting substrates to crossing into brain through blood–brain barrier. Our previous works show that bile duct ligation (BDL) impairs expression and function of brain BCRP in rats. Since zidovudine (AZT) is BCRP substrate, we investigated whether impaired expression and function of BCRP increased brain distribution and toxicity of AZT in BDL-D7 rats. After administration of AZT (10 mg/kg, i.v.), BDL markedly increased brain AZT concentrations, compared with sham-operated (SO) rats. The ratio of AZT brain-to-plasma area under concentration curve (AUC) in BDL rats was increased to 1.6-folds of SO rats. After treatment with AZT (100 mg/kg every day, i.v.) for 7 days, BDL significantly impaired cognitive functions compared with SO rats, evidenced by the significantly decreased percentage of alternation in Y-maze test and prolonged escaped latency in two-way passive avoidance trial. Furthermore, AZT treatment caused significant decrease in copies of mitochondrial DNA and mitochondrial membrane potential in hippocampus of BDL rats. Moreover, AZT treatment caused a significant decrease of cortex microtubule-associated protein 2 and hippocampus synaptophysin levels in BDL rats. AZT-induced CNS adverse alterations in BDL rats were not observed in SO rats treated with AZT. In conclusion, BDL decreases the function and expression of brain BCRP in rats, leading to increased brain distribution of AZT, which in turn enhances AZT CNS toxicity, leading to mitochondrial dysfunction, neuronal damage, and ultimately cognitive dysfunction."
2921,Nrf2 activation ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain,"Paclitaxel-induced neuropathic pain (PINP) is refractory to currently used analgesics. Previous studies show a pivotal role of oxidative stress in PINP. Because the nuclear factor erythroid-2-related factor 2 (Nrf2) has been considered as the critical regulator of endogenous antioxidant defense, we here explored whether activation of Nrf2 could attenuate PINP. A rat model of PINP was established by intraperitoneal injection of paclitaxel (2 mg/kg) every other day with a final cumulative dose of 8 mg/kg. Hind paw withdrawal thresholds (PWTs) in response to von Frey filament stimuli were used to assess mechanical allodynia. We showed that a single dose of Nrf2 activator, oltipraz (10, 50, and 100 mg/kg), dose-dependently attenuated established mechanical allodynia, whereas repeated injection of oltipraz (100 mg· kg(−1)· d(−1), i.p. from d 14 to d 18) almost abolished the mechanical allodynia in PINP rats. The antinociceptive effect of oltipraz was blocked by pre-injection of Nrf2 inhibitor trigonelline (20 mg/kg, i.p.). Early treatment with oltipraz (100 mg· kg(−1)· d(−1), i.p. from d 0 to d 6) failed to prevent the development of the PINP, but delayed its onset. Western blot and immunofluorescence analysis revealed that the expression levels of Nrf2 and HO-1 were significantly upregulated in the spinal cord of PINP rats. Repeated injection of oltipraz caused further elevation of the expression levels of Nrf2 and HO-1 in the spinal cord of PINP rats, which was reversed by pre-injection of trigonelline. These results demonstrate that oltipraz ameliorates PINP via activating Nrf2/HO-1-signaling pathway in the spinal cord."
2922,6-O-angeloylplenolin exerts neuroprotection against lipopolysaccharide-induced neuroinflammation in vitro and in vivo,"Neuroinflammation is one of the critical events in neurodegenerative diseases, whereas microglia play an important role in the pathogenesis of neuroinflammation. In this study, we investigated the effects of a natural sesquiterpene lactone, 6-O-angeloylplenolin (6-OAP), isolated from the traditional Chinese medicine Centipeda minima (L.) A.Br., on neuroinflammation and the underlying mechanisms. We showed that treatment with lipopolysaccharide (LPS) caused activation of BV2 and primary microglial cells and development of neuroinflammation in vitro, evidenced by increased production of inflammatory cytokines TNF-α and IL-1β, the phosphorylation and nuclear translocation of NF-κB, and the transcriptional upregulation of COX-2 and iNOS, leading to increased production of proinflammatory factors NO and PGE(2). Moreover, LPS treatment induced oxidative stress through increasing the expression levels of NOX2 and NOX4. Pretreatment with 6-OAP (0.5−4 μM) dose-dependently attenuated LPS-induced NF-κB activation and oxidative stress, thus suppressed neuroinflammation in the cells. In a mouse model of LPS-induced neuroinflammation, 6-OAP (5−20 mg·kg(−1)·d(−1), ip, for 7 days before LPS injection) dose-dependently inhibited the production of inflammatory cytokines, the activation of the NF-κB signaling pathway, and the expression of inflammatory enzymes in brain tissues. 6-OAP pretreatment significantly ameliorated the activation of microglia and astrocytes in the brains. 6-OAP at a high dose caused a much stronger antineuroinflammatory effect than dexamethansone (DEX). Furthermore, we demonstrated that 6-OAP pretreatment could inhibit LPS-induced neurite and synaptic loss in vitro and in vivo. In conclusion, our results demonstrate that 6-OAP exerts antineuroinflammatory effects and can be considered a novel drug candidate for the treatment of neuroinflammatory diseases."
2923,Does rural primary care ophthalmology teaching need revisiting?,
2924,Synaptic and cellular plasticity in Parkinson’s disease,"Parkinson’s disease (PD) is a progressive neurodegenerative disease, which causes a tremendous socioeconomic burden. PD patients are suffering from debilitating motor and nonmotor symptoms. Cardinal motor symptoms of PD, including akinesia, bradykinesia, resting tremor, and rigidity, are caused by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. In addition, decreased amounts of dopamine (DA) level in the basal ganglia induces numerous adaptive changes at the cellular and synaptic levels in the basal ganglia circuits. These cellular and synaptic adaptations are believed to underlie the emergence and propagation of correlated, rhythmic pattern of activity throughout the interconnected cortico-basal ganglia-thalamocortical network. The widespread pathological pattern of brain activity is closely linked to the devastating motor symptoms of PD. Accumulating evidence suggests that both dopaminergic degeneration and the associated abnormal cellular and circuit activity in the basal ganglia drive the motor symptoms of PD. In this short review I summarize the recent advances in our understanding of synaptic and cellular alterations in two basal ganglia nuclei (i.e. the striatum and the subthalamic nucleus) following a complete loss of DA, and in our conceptual understanding of the cellular and circuit bases for the pathological pattern of brain activity in parkinsonian state."
2925,Preclinical PK/PD model for the combinatorial use of dexamethasone and sulpiride in the treatment of breast cancer,"Previous studies show that dopamine D(2)-like receptor (D2DR) antagonist sulpiride (SUL) enhances the antitumor efficacy of dexamethasone (DEX) in drug-resistant breast cancer involving cancer stem-like cells (CSCs). In this study, we investigated the pharmacokinetic (PK) properties of SUL in nude mice and developed a semi-mechanism PK/PD model to quantitatively characterize the synergistic effect of DEX and SUL in preclinical breast cancer xenografts. After nude mice received oral administration of a single dose of SUL (50 mg/kg, ig), plasma concentrations were assessed using LC-MS/MS. A two-compartment model with double first-order absorption rate was developed to describe the PK profiles of SUL. The pharmacodynamic (PD) study was conducted in nude mice bearing human breast cancer MCF-7/Adr xenografts, which received oral administration of DEX (1, 8 mg·kg(−1)·d(−1)) or SUL (25, 50 mg·kg(−1)·d(−1)) alone or in various combination. Tumor volumes were measured every other day. The PK model of SUL as well as that of DEX with a time-dependent clearance were integrated into the final PK/PD model both using Hill’s function, where DEX exerted its antitumor efficacy by inhibiting the proliferation of tumor cells, and SUL enhanced DEX responses by decreasing the sensitivity parameter EC(50). The PK/PD model was evaluated and subjected external validation. Finally, simulations were performed to predict the antitumor efficacy of DEX combined with SUL under various dose regimens, where changing dosing frequency of SUL had little effect, while the antitumor efficacy was predicted to be improved when DEX was given more frequently. The established PK/PD model in this study quantitatively characterizes the antitumor efficacy of the DEX combined with SUL as well as their synergism, and the simulations could provide reference for dose optimization of the combination in future studies."
2926,Protein tyrosine phosphatase L1 represses endothelial-mesenchymal transition by inhibiting IL-1β/NF-κB/Snail signaling,"Endothelial–mesenchymal transition (EnMT) plays a pivotal role in various diseases, including pulmonary hypertension (PH), and transcription factors like Snail are key regulators of EnMT. In this study we investigated how these factors were regulated by PH risk factors (e.g. inflammation and hypoxia) in human umbilical vein endothelial cells (HUVECs). We showed that treatment with interleukin 1β (IL‐1β) induced EnMT of HUVECs via activation of NF-κB/Snail pathway, which was further exacerbated by knockdown of protein tyrosine phosphatase L1 (PTPL1). We demonstrated that PTPL1 inhibited NF-κB/Snail through dephosphorylating and stabilizing IκBα. IL‐1β or hypoxia could downregulate PTPL1 expression in HUVECs. The deregulation of PTPL1/NF-κB signaling was validated in a monocrotaline-induced rat PH (MCT-PH) model and clinical PH specimens. Our findings provide novel insights into the regulatory mechanisms of EnMT, and have implications for identifying new therapeutic targets for clinical PH."
2927,SGK1 mediates the hypotonic protective effect against H(2)O(2)-induced apoptosis of rat basilar artery smooth muscle cells by inhibiting the FOXO3a/Bim signaling pathway,"Serum- and glucocorticoid-inducible kinease-1 (SGK1) is a serine/threonine kinase regulated by hypotonic stimuli, which is involved in regulation of cell cycle and apoptosis. Our previous study shows that activation of volume-regulated Cl(−) channels (VRCCs) protects rat basilar artery smooth muscle cells (BASMCs) against hydrogen peroxide (H(2)O(2))-induced apoptosis. In the present study, we investigated whether SGK1 was involved in the protective effect of VRCCs in BASMCs. We showed that hypotonic challenge significantly reduced H(2)O(2)-induced apoptosis, and increased SGK1 phosphorylation, but did not affect SGK1 protein expression. The protective effect of hypotonic challenge against H(2)O(2)-induced apoptosis was mediated through inhibiting mitochondria-dependent apoptotic pathway, evidenced by increased Bcl-2/Bax ratio, stabilizing mitochondrial membrane potential (MMP), decreased cytochrome c release from the mitochondria to the cytoplasm, and inhibition of the activation of caspase-9 and caspase-3. These protective effects of hypotonic challenge against H(2)O(2)-induced apoptosis was diminished and enhanced, respectively, by SGK1 knockdown and overexpression. We further revealed that SGK1 activation significantly increased forkhead box O3a (FOXO3a) phosphorylation, and then inhibited the translocation of FOXO3a into nucleus and the subsequent expression of Bcl-2 interacting mediator of cell death (Bim). In conclusion, SGK1 mediates the protective effect of VRCCs against H(2)O(2)-induced apoptosis in BASMCs via inhibiting FOXO3a/Bim signaling pathway. Our results provide compelling evidences that SGK1 is a critical link between VRCCs and apoptosis, and shed a new light on the treatment of vascular apoptosis-associated diseases, such as vascular remodeling, angiogenesis, and atherosclerosis."
2928,A novel derivative of valepotriate inhibits the PI3K/AKT pathway and causes Noxa-dependent apoptosis in human pancreatic cancer cells,"Natural compound valepotriate exhibits inhibitory activity against a number of cancers, but the effect of valepotriate against pancreatic cancer is unclear, and the structure–activity relationship of valepotriate has not been characterized. In this study, we performed a structure-based similarity search and found 16 hit compounds. Among the 16 hits, (1S,6S,7R)-6-(acetyloxy)-1-[(3-methylbutanoyl)oxy]-4a,5,6,7a-tetrahydro-1H-spiro[cyclopenta[c]pyran-7,2’-oxiran]-4-ylmethyl 3-methylbutanoate (denoted as Amcp) exhibited superior anticancer activity against human pancreatic cancer BxPC-3 and SW1990 cells. The anti-proliferation activity of Amcp was validated in human pancreatic cancer BxPC-3 and SW1990 cells in vitro. Amcp more effectively induced apoptosis in BxPC-3 and SW1990 cells than gemcitabine. At a concentration of 15 μM, Amcp significantly suppressed the PI3K/AKT pathway and disrupted the mitochondrial membrane equilibrium through modulation of Noxa and Mcl-1 balance in both cell lines. Meanwhile, knockdown of Noxa substantially attenuated Amcp-induced reduction of cell viability and anti-apoptotic protein Mcl-1 level in BxPC-3 cells. In addition, Amcp showed synergistic anticancer effects when combined with gemcitabine in BxPC-3 cells. To conclude, this work not only suggests that Amcp possesses a dual-inhibitory activity towards PI3K/AKT pathway and Mcl-1, but also enlightens further development of bioactive valepotriate derivatives."
2929,β-Arrestin 2 mediates arginine vasopressin-induced IL-6 induction via the ERK(1/2)-NF-κB signal pathway in murine hearts,"Evidence to date suggests that β-arrestins act beyond their role as adapter proteins. Arginine vasopressin (AVP) may be a factor in inflammation and fibrosis in the pathogenesis of heart failure. In the present study we investigated the effect of AVP on inflammatory cytokine IL-6 production in murine hearts and the impact of β-arrestin 2-dependent signaling on AVP-induced IL-6 production. We found that administration of AVP (0.5 U/kg, iv) markedly increased the levels of IL-6 mRNA in rat hearts with the maximum level occurred at 6 h. In β-arrestin 2 KO mouse hearts, deletion of β-arrestin 2 decreased AVP-induced IL-6 mRNA expression. We then performed in vitro experiments in adult rat cardiac fibroblasts (ARCFs). We found that AVP (10(−9)–10(−6) M) dose-dependently increased the expression of IL-6 mRNA and protein, activation of NF-κB signaling and ERK(1/2) phosphorylation, whereas knockdown of β-arrestin 2 blocked AVP-induced IL-6 increase, NF-κB activation and ERK(1/2) phosphorylation. Pharmacological blockade of ERK(1/2) using PD98059 diminished AVP-induced NF-κB activation and IL-6 production. The selective V(1A) receptor antagonist SR49059 effectively blocked AVP-induced NF-κB phosphorylation and activation as well as IL-6 expression in ARCFs. In AVP-treated mice, pre-injection of SR49059 (2 mg/kg, iv) abolished AVP-induced NF-κB activation and IL-6 production in hearts. The above results suggest that AVP induces IL-6 induction in murine hearts via the V(1A) receptor-mediated β-arrestin2/ERK(1/2)/NF-κB pathway, thus reveal a novel mechanism of myocardial inflammation in heart failure involving the V(1A)/β-arrestin 2/ERK(1/2)/NF-κB signaling pathway."
2930,The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis,"Mitochondria serve as sensors of energy regulation and glucose levels, which are impaired by diabetes progression. Catalpol is an iridoid glycoside that exerts a hypoglycemic effect by improving mitochondrial function, but the underlying mechanism has not been fully elucidated. In the current study we explored the effects of catalpol on mitochondrial function in db/db mice and C2C12 myotubes in vitro. After oral administration of catalpol (200 mg·kg(−1)·d(−1)) for 8 weeks, db/db mice exhibited a decreased fasting blood glucose level and restored mitochondrial function in skeletal muscle. Catalpol increased mitochondrial biogenesis, evidenced by significant elevations in the number of mitochondria, mitochondrial DNA levels, and the expression of three genes associated with mitochondrial biogenesis: peroxisome proliferator-activated receptor gammaco-activator 1 (PGC-1α), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1). In C2C12 myotubes, catalpol significantly increased glucose uptake and ATP production. These effects depended on activation of AMP-activated protein kinase (AMPK)-mediated mitochondrial biogenesis. Thus, catalpol improves skeletal muscle mitochondrial function by activating AMPK-mediated mitochondrial biogenesis. These findings may guide the development of a new therapeutic approach for type 2 diabetes."
2931,Author Correction: Plumbagin attenuates cancer cell growth and osteoclast formation in the bone microenvironment of mice,
2932,Advances in the development of imaging probes and aggregation inhibitors for alpha-synuclein,"Abnormal protein aggregation has been linked to many neurodegenerative diseases, including Parkinson’s disease (PD). The main pathological hallmark of PD is the formation of Lewy bodies (LBs) and Lewy neurites, both of which contain the presynaptic protein alpha-synuclein (α-syn). Under normal conditions, native α-syn exists in a soluble unfolded state but undergoes misfolding and aggregation into toxic aggregates under pathological conditions. Toxic α-syn species, especially oligomers, can cause oxidative stress, membrane penetration, synaptic and mitochondrial dysfunction, as well as other damage, leading to neuronal death and eventually neurodegeneration. Early diagnosis and treatments targeting PD pathogenesis are urgently needed. Given its critical role in PD, α-syn is an attractive target for the development of both diagnostic tools and effective therapeutics. This review summarizes the progress toward discovering imaging probes and aggregation inhibitors for α-syn. Relevant strategies and techniques in the discovery of α-syn-targeted drugs are also discussed."
2933,Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment,"Cancer immunotherapy has received extensive attention due to its ability to activate the innate or adaptive immune systems of patients to combat tumors. Despite a few clinical successes, further endeavors are still needed to tackle unresolved issues, including limited response rates, development of resistance, and immune-related toxicities. Accumulating evidence has pinpointed the tumor microenvironment (TME) as one of the major obstacles in cancer immunotherapy due to its detrimental impacts on tumor-infiltrating immune cells. Nanomedicine has been battling with the TME in the past several decades, and the experience obtained could be exploited to improve current paradigms of immunotherapy. Here, we discuss the metabolic features of the TME and its influence on different types of immune cells. The recent progress in nanoenabled cancer immunotherapy has been summarized with a highlight on the modulation of immune cells, tumor stroma, cytokines and enzymes to reverse the immunosuppressive TME."
2934,Low-carbohydrate-diet scores and the risk of primary open-angle glaucoma: data from three US cohorts,"BACKGROUND/OBJECTIVES: To assess the long-term association between low-carbohydrate dietary patterns and incident primary open-angle glaucoma (POAG), and POAG subtypes defined by highest untreated intraocular pressure (IOP) and by pattern of visual field (VF) loss at diagnosis. SUBJECTS/METHODS: We followed 185,638 participants of three large US prospective cohorts biennially (1976–2016, 1986–2016 and 1991–2017). Deciles of three low-carbohydrate-diet scores were calculated to represent adherence to diets lower in carbohydrate and higher in protein and fat from any source, animal sources or plant sources. We confirmed POAG cases (n = 2112) by medical record review and used Cox proportional hazards models to estimate multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs). RESULTS: There was no association between the three types of low-carbohydrate-diet scores and POAG: the MVRR for POAG in the highest vs. lowest deciles was 1.13 (95% CI, 0.91–1.39; P(trend) = 0.40) for the overall score; 1.10 (95% CI, 0.89–1.35; P(trend) = 0.38) for the animal score and 0.96 (95% CI, 0.79–1.18; P(trend) = 0.88) for the vegetable score. No differential associations by IOP level was found (P(heterogeneity) ≥ 0.06). However, the vegetable score showed a suggestive inverse association with early paracentral VF loss (highest vs. lowest decile MVRR = 0.78 [95% CI, 0.55–1.10]; P(trend) = 0.12) but not with peripheral VF loss only (MVRR = 1.09 [95% CI, 0.83–1.44]; P(trend) = 0.14; P(heterogeneity) = 0.03). CONCLUSIONS: Low-carbohydrate diets were not associated with risk of POAG. Our data suggested that higher consumption of fat and protein from vegetable sources substituting for carbohydrates was associated with lower risk of the POAG subtype with initial paracentral VF loss."
2935,Response to Comment on: Sector retinitis pigmentosa caused by mutations of the RHO gene,
2936,Donepezil attenuates vascular dementia in rats through increasing BDNF induced by reducing HDAC6 nuclear translocation,"Vascular dementia (VD) is the second most common dementia disease after Alzheimer’s diseases (AD) in the world. Donepezil is used to treat mild to moderate AD, and it has been shown to treat cognitive impairment and memory deficits caused by VD. However, the action mechanism of donepezil against VD has not been clarified. In this study, a bilateral common carotid artery occlusion (BCCAO) model was established in rats to simulate the pathology of VD. Two weeks after the surgery, the rats were administered donepezil (10 mg · kg(−1) · d(−1), ig) for 3 weeks, and then subjected to behavioral tests. We showed that donepezil treatment significantly improved the performance of BCCAO rats in Morris Water Mazes test and Step-down test. Furthermore, we showed that donepezil treatment significantly attenuated neurodegeneration and restored the synapse dendritic spines density in cortex and hippocampus. We revealed that donepezil treatment significantly increased BDNF expression in cortex and hippocampus. Interestingly, donepezil treatment significantly decreased nuclear translocation of HDAC6 and the binding between HDAC6 and BDNF promoter IV in cortex, but not in the hippocampus. The attenuated neurodegeneration by donepezil in cortex and hippocampus might due to the reduced ROS levels and increased phosphorylation of AMPK, whereas increased phosphorylation of AKT was only detected in cortex. In conclusion, our results demonstrate that donepezil attenuates neurodegeneration in cortex and hippocampus via increasing BDNF expression; the regulation of donepezil on HDAC6 occurred in cortex, but not in the hippocampus. This study further clarifies the pharmacological mechanism of donepezil, while also emphasizes the promising epigenetic regulation of HDAC6."
2937,Quantitative efficacy of three antipsychotic drugs for schizophrenia based on a real-world study in China,"Atypical antipsychotics exert remarkable long-term efficacy on the personal and social functions of schizophrenic patients. However, quantitative information on the social function of schizophrenic patients treated with atypical antipsychotics is scarce in the current clinical guidelines. In this study, we established pharmacodynamic models to quantify the time–efficacy relationship of three antipsychotic drugs based on the data from a real-world study conducted in China. A total of 373 schizophrenic patients who received antipsychotic monotherapy with olanzapine (n = 144), risperidone (n = 160), or aripiprazole (n = 69) were selected from a three-year prospective, multicenter study. The follow-up times were 13, 26, 52, 78, 104, 130, and 156 weeks after baseline. A time–efficacy model was developed with nonlinear mixed effect method based on changes in Personal and Social Performance (PSP) score compared with the baseline level. Crucial pharmacodynamic parameters, including maximum efficacy and drug onset time, were used to distinguish the efficacy of the three drugs. We quantified the time course of PSP improvement in patients after treatment with these three antipsychotics: olanzapine, risperidone, and aripiprazole reached an E(max) value of 80.3%, 68.2%, and 23.9% at weeks 56.7, 29.2, and 36.8, respectively. General psychotic symptoms, onset frequency, and illness course were identified as significant factors affecting the efficacy of these drugs. The newly constructed models provide an evidence of the benefit of long-term maintenance therapy with atypical antipsychotics in individualized schizophrenia treatment in China."
2938,Podoplanin mediates the renoprotective effect of berberine on diabetic kidney disease in mice,"Hyperglycemia-caused podocyte injury plays a crucial role in the progress of diabetic kidney disease. Podoplanin, one of the podocyte-associated molecules, is closely related to the integrity of the glomerular filtration barrier. A number of studies demonstrate that berberine could ameliorate renal dysfunction in diabetic mice with nephropathy, but the molecular mechanisms have not been fully elucidated. In this study, we explored the relationship between the renoprotective effect of berberine and podoplanin expression in streptozotocin (STZ)-induced diabetic mice as well as mouse podocytes (MPC5 cells) cultured in high glucose (HG, 30 mM) medium. We found that the expression levels of podoplanin were significantly decreased both in the renal glomerulus of STZ-induced diabetic mice and HG-cultured MPC5 cells. We also demonstrated that NF-κB signaling pathway was activated in MPC5 cells under HG condition, which downregulated the expression level of podoplanin, thus leading to increased podocyte apoptosis. Administration of berberine (100, 200 mg/kg every day, ig, for 8 weeks) significantly improved hyperglycemia and the renal function of STZ-induced diabetic mice and restored the expression level of podoplanin in renal glomerulus. In high glucose-cultured MPC5 cells, treatment with berberine (30–120 μM) dose-dependently decreased the apoptosis rate, increased the expression of podoplanin, and inhibited the activation of NF-κB signaling pathway. When podoplanin expression was silenced with shRNA, berberine treatment still inhibited the NF-κB signaling pathway, but its antiapoptotic effect on podocytes almost disappeared. Our results suggest that berberine inhibits the activation of NF-κB signaling pathway, thus increasing the podoplanin expression to exert renoprotective effects."
2939,A novel compound AB38b attenuates oxidative stress and ECM protein accumulation in kidneys of diabetic mice through modulation of Keap1/Nrf2 signaling,"Extracellular matrix (ECM) deposition following reactive oxygen species (ROS) overproduction has a key role in diabetic nephropathy (DN), thus, antioxidant therapy is considered as a promising strategy for treating DN. Here, we investigated the therapeutic effects of AB38b, a novel synthetic α, β-unsaturated ketone compound, on the oxidative stress (OS) and ECM accumulation in type 2 diabetes mice, and tried to clarify the mechanisms underlying the effects in high glucose (HG, 30 mm)-treated mouse glomerular mesangial cells (GMCs). Type 2 diabetes model was established in mice with high-fat diet feeding combined with streptozocin intraperitoneal administration. The diabetic mice were then treated with AB38b (10, 20, 40 mg· kg(−1)· d(−1), ig) or a positive control drug resveratrol (40 mg· kg(−1)· d(−1), ig) for 8 weeks. We showed that administration of AB38b or resveratrol prevented the increases in malondialdehyde level, lactate dehydrogenase release, and laminin and type IV collagen deposition in the diabetic kidney. Simultaneously, AB38b or resveratrol markedly lowered the level of Keap1, accompanied by evident activation of Nrf2 signaling in the diabetic kidney. The underlying mechanisms of antioxidant effect of AB38b were explored in HG-treated mouse GMCs. AB38b (2.5−10 μM) or resveratrol (10 μM) significantly alleviated OS and ECM accumulation in HG-treated GMCs. Furthermore, AB38b or resveratrol treatment effectively activated Nrf2 signaling by inhibiting Keap1 expression without affecting the interaction between Keap1 and Nrf2. Besides, AB38b treatment effectively suppressed the ubiquitination of Nrf2. Taken together, this study demonstrates that AB38b ameliorates experimental DN through antioxidation and modulation of Keap1/Nrf2 signaling pathway."
2940,Cancer nanomedicine meets immunotherapy: opportunities and challenges,"Cancer nanomedicines have shown promise in combination immunotherapy, thus far mostly preclinically but also already in clinical trials. Combining nanomedicines with immunotherapy aims to reinforce the cancer-immunity cycle, via potentiating key steps in the immune reaction cascade, namely antigen release, antigen processing, antigen presentation, and immune cell-mediated killing. Combination nano-immunotherapy can be realized via three targeting strategies, i.e., by targeting cancer cells, targeting the tumor immune microenvironment, and targeting the peripheral immune system. The clinical potential of nano-immunotherapy has recently been demonstrated in a phase III trial in which nano-albumin paclitaxel (Abraxane®) was combined with atezolizumab (Tecentriq®) for the treatment of patients suffering from advanced triple-negative breast cancer. In the present paper, besides strategies and initial (pre)clinical success stories, we also discuss several key challenges in nano-immunotherapy. Taken together, nanomedicines combined with immunotherapy are gaining significant attention, and it is anticipated that they will play an increasingly important role in clinical cancer therapy."
2941,Metoprolol prevents neuronal dendrite remodeling in a canine model of chronic obstructive sleep apnea,"Obstructive sleep apnea (OSA) is closely associated with central nervous system diseases and could lead to autonomic nerve dysfunction, which is often seen in neurodegenerative diseases. Previous studies have shown that metoprolol prevents several chronic OSA-induced cardiovascular diseases through inhibiting autonomic nerve hyperactivity. It remains unclear whether chronic OSA can lead to dendritic remodeling in the brain, and whether metoprolol affects the dendritic remodeling. In this study we investigated the effect of metoprolol on dendrite morphology in a canine model of chronic OSA, which was established in beagles through clamping and reopening the endotracheal tube for 4 h every other day for 12 weeks. OSA beagles were administered metoprolol (5 mg· kg(−1)· d(−1)). The dendritic number, length, crossings and spine density of neurons in hippocampi and prefrontal cortices were assessed by Golgi staining. And the protein levels of hypoxia-inducible factor-1α (HIF-1α) and brain-derived neurotrophic factor (BDNF) were measured by Western blotting. We showed that chronic OSA successfully induced significant brain hypoxia evidenced by increased HIF-1α levels in CA1 region and dentate gyrus of hippocampi, as well as in prefrontal cortex. Furthermore, OSA led to markedly decreased dendrite number, length and intersections, spine loss as well as reduced BDNF levels. Administration of metoprolol effectively prevented the dendritic remodeling and spine loss induced by chronic OSA. In addition, administration of metoprolol reversed the decreased BDNF, which might be associated with the metoprolol-induced neuronal protection. In conclusion, metoprolol protects against neuronal dendritic remodeling in hippocampi and prefrontal cortices induced by chronic OSA in canine."
2942,Somatic and germline mutations in the tumor suppressor gene PARK2 impair PINK1/Parkin-mediated mitophagy in lung cancer cells,"PARK2, which encodes Parkin, is a disease-causing gene for both neurodegenerative disorders and cancer. Parkin can function as a neuroprotector that plays a crucial role in the regulation of mitophagy, and germline mutations in PARK2 are associated with Parkinson’s disease (PD). Intriguingly, recent studies suggest that Parkin can also function as a tumor suppressor and that somatic and germline mutations in PARK2 are associated with various human cancers, including lung cancer. However, it is presently unknown how the tumor suppressor activity of Parkin is affected by these mutations and whether it is associated with mitophagy. Herein, we show that wild-type (WT) Parkin can rapidly translocate onto mitochondria following mitochondrial damage and that Parkin promotes mitophagic clearance of mitochondria in lung cancer cells. However, lung cancer-linked mutations inhibit the mitochondrial translocation and ubiquitin-associated activity of Parkin. Among all lung cancer-linked mutants that we tested, A46T Parkin failed to translocate onto mitochondria and could not recruit downstream mitophagic regulators, including optineurin (OPTN) and TFEB, whereas N254S and R275W Parkin displayed slower mitochondrial translocation than WT Parkin. Moreover, we found that deferiprone (DFP), an iron chelator that can induce mitophagy, greatly increased the death of A46T Parkin-expressing lung cancer cells. Taken together, our results reveal a novel mitophagic mechanism in lung cancer, suggesting that lung cancer-linked mutations in PARK2 are associated with impaired mitophagy and identifying DFP as a novel therapeutic agent for PARK2-linked lung cancer and possibly other types of cancers driven by mitophagic dysregulation."
2943,Identification of nagilactone E as a protein synthesis inhibitor with anticancer activity,"Norditerpenoids and dinorditerpenoids represent diterpenoids widely distributed in the genus Podocarpus with notable chemical structures and biological activities. We previously reported that nagilactone E (NLE), a dinorditerpenoid isolated from Podocarpus nagi, possessed anticancer effects against lung cancer cells in vitro. In this study we investigated the in vivo effect of NLE against lung cancer as well as the underlying mechanisms. We administered NLE (10 mg·kg(−1)·d(−1), ip) to CB-17/SCID mice bearing human lung cancer cell line A549 xenograft for 3 weeks. We found that NLE administration significantly suppressed the tumor growth without obvious adverse effects. Thereafter, RNA sequencing (RNA-seq) analysis was performed to study the mechanisms of NLE. The effects of NLE on A549 cells have been illustrated by GO and pathway enrichment analyses. CMap dataset analysis supported NLE to be a potential protein synthesis inhibitor. The inhibitory effect of NLE on synthesis of total de novo protein was confirmed in Click-iT assay. Using the pcDNA3-RLUC-POLIRES-FLUC luciferase assay we further demonstrated that NLE inhibited both cap-dependent and cap-independent translation. Finally, molecular docking revealed the low-energy binding conformations of NLE and its potential target RIOK2. In conclusion, NLE is a protein synthesis inhibitor with anticancer activity."
2944,Chalcomoracin inhibits cell proliferation and increases sensitivity to radiotherapy in human non-small cell lung cancer cells via inducing endoplasmic reticulum stress-mediated paraptosis,"Chalcomoracin (CMR) is a kind of Diels–Alder adduct extracted from the mulberry leaves. Recent studies showed that CMR has a broad spectrum of anticancer activities and induces paraptosis in breast cancer and prostate cancer cells. In this study, we investigated the effects of CMR against human non-small cell lung cancer cells and the underlying mechanisms. We found that CMR dose-dependently inhibited the proliferation of human lung cancer H460, A549 and PC-9 cells. Furthermore, exposure to low and median doses of CMR induced paraptosis but not apoptosis, which was presented as the formation of extensive cytoplasmic vacuolation with increased expression of endoplasmic reticulum stress markers, Bip and Chop, as well as activation of MAPK pathway in the lung cancer cells. Knockdown of Bip with siRNA not only reduced the cell-killing effect of CMR, but also decreased the percentage of cytoplasmic vacuoles in H460 cells. Moreover, CMR also increased the sensitivity of lung cancer cells to radiotherapy through enhanced endoplasmic reticulum stress. In lung cancer H460 cell xenograft nude mice, combined treatment of CMR and radiation caused greatly enhanced tumor growth inhibition with upregulation of endoplasmic reticulum stress proteins and activation of pErk in xenograft tumor tissue. These data demonstrate that the anticancer activity and radiosensitization effect of CMR result from inducing paraptosis, suggesting that CMR could be considered as a potential anticancer agent and radiation sensitizer in the future cancer therapeutics."
2945,Establishment of a mouse model of cancer cachexia with spleen deficiency syndrome and the effects of atractylenolide I,"Cancer cachexia is a multifactorial metabolic syndrome that affects ∼50%–80% of cancer patients, and no effective therapy for cancer cachexia is presently available. In traditional Chinese medicine, a large portion of patients with cancer cachexia was diagnosed as spleen deficiency syndrome and treated with tonifying TCMs that produce clinic benefits. In this study we established a new animal model of spleen deficiency and cancer cachexia in mice and evaluated the therapeutic effects of atractylenolide I, an active component of tonifying TCM BaiZhu, in the mouse model. Cancer cachexia was induced in male BALB/c mice by inoculation of mouse C26 colon adenocarcinoma cells, whereas spleen deficiency syndrome was induced by treating the mice with spleen deficiency-inducing factors, including limited feeding, fatigue, and purging. The mouse model was characterized by both cachexia and spleen deficiency characteristics, including significant body weight loss, cancer growth, muscle atrophy, fat lipolysis, spleen, and thymus atrophy as compared with healthy control mice, cancer cachexia mice, and spleen deficiency mice. Oral administration of atractylenolide I (20 mg· kg(−1)per day, for 30 days) significantly ameliorated the reduction in body weight and atrophy of muscle, fat, spleen, and thymus in mice with spleen deficiency and cachexia. The established model of spleen deficiency and cancer cachexia might be useful in the future for screening possible anticachexia TCMs and clarifying their mechanisms."
2946,Ex vivo pulsed dendritic cell vaccination against cancer,"As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo, hence becoming optimal cell population for vaccination purposes. DCs can be derived ex vivo in quantity and manipulated extensively to be endowed with adequate immune-stimulating capacity. After pulsing with cancer antigens in various ways, the matured DCs are administrated back into the patient. DCs home to lymphoid organs to present antigens to and activate specific lymphocytes that react to a given cancer. Ex vivo pulsed DC vaccines have been vigorously investigated for decades, registering encouraging results in relevant immunotherapeutic clinical trials, while facing some solid challenges. With more details in DC biology understood, new theory proposed, and novel technology introduced (featuring recently emerged mRNA vaccine technology), it is becoming increasingly likely that ex vivo pulsed DC vaccine will fulfill its potential in cancer immunotherapy."
2947,Exogenous NADPH ameliorates myocardial ischemia–reperfusion injury in rats through activating AMPK/mTOR pathway,"Our previous study shows that nicotinamide adenine dinucleotide phosphate (NADPH) plays an important role in protecting against cerebral ischemia injury. In this study we investigated whether NADPH exerted cardioprotection against myocardial ischemia/reperfusion (I/R) injury. To induce myocardial I/R injury, rats were subjected to ligation of the left anterior descending branch of coronary artery for 30 min followed by reperfusion for 2 h. At the onset of reperfusion, NADPH (4, 8, 16 mg· kg(−1)· d(−1), iv) was administered to the rats. We found that NADPH concentrations in plasma and heart were significantly increased at 4 h after intravenous administration. Exogenous NADPH (8−16 mg/kg) significantly decreased myocardial infarct size and reduced serum levels of lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I). Exogenous NADPH significantly decreased the apoptotic rate of cardiomyocytes, and reduced the cleavage of PARP and caspase-3. In addition, exogenous NADPH reduced mitochondrial vacuolation and increased mitochondrial membrane protein COXIV and TOM20, decreased BNIP3L and increased Bcl-2 to protect mitochondrial function. We conducted in vitro experiments in neonatal rat cardiomyocytes (NRCM) subjected to oxygen–glucose deprivation/restoration (OGD/R). Pretreatment with NADPH (60, 500 nM) significantly rescued the cell viability and inhibited OGD/R-induced apoptosis. Pretreatment with NADPH significantly increased the phosphorylation of AMPK and downregulated the phosphorylation of mTOR in OGD/R-treated NRCM. Compound C, an AMPK inhibitor, abolished NADPH-induced AMPK phosphorylation and cardioprotection in OGD/R-treated NRCM. In conclusion, exogenous NADPH exerts cardioprotection against myocardial I/R injury through the activation of AMPK/mTOR pathway and inhibiting mitochondrial damage and cardiomyocyte apoptosis. NADPH may be a potential candidate for the prevention and treatment of myocardial ischemic diseases."
2948,Clcn3 deficiency ameliorates high-fat diet-induced obesity and adipose tissue macrophage inflammation in mice,"Obesity induces accumulation of adipose tissue macrophages (ATMs) and ATM-driven inflammatory responses that promote the development of glucose and lipid metabolism disorders. ClC-3 chloride channel/antiporter, encoded by the Clcn3, is critical for some basic cellular functions. Our previous work has shown significant alleviation of type 2 diabetes in Clcn3 knockout (Clcn3(−/−)) mice. In the present study we investigated the role of Clcn3 in high-fat diet (HFD)-induced obesity and ATM inflammation. To establish the mouse obesity model, both Clcn3(−/−) mice and wild-type mice were fed a HFD for 4 or 16 weeks. The metabolic parameters were assessed and the abdominal total adipose tissue was scanned using computed tomography. Their epididymal fat pad tissue and adipose tissue stromal vascular fraction (SVF) cells were isolated for analyses. We found that the HFD-fed Clcn3(−/−) mice displayed a significant decrease in obesity-induced body weight gain and abdominal visceral fat accumulation as well as an improvement of glucose and lipid metabolism as compared with HFD-fed wild-type mice. Furthermore, the Clcn3 deficiency significantly attenuated HFD-induced ATM accumulation, HFD-increased F4/80(+) CD11c(+) CD206(−) SVF cells as well as HFD-activated TLR-4/NF-κB signaling in epididymal fat tissue. In cultured human THP-1 macrophages, adenovirus-mediated transfer of Clcn3 specific shRNA inhibited, whereas adenovirus-mediated cDNA overexpression of Clcn3 enhanced lipopolysaccharide-induced activation of NF-κB and TLR-4. These results demonstrate a novel role for Clcn3 in HFD-induced obesity and ATM inflammation."
2949,"Author Correction: The natural product 4,10-aromadendranediol induces neuritogenesis in neuronal cells in vitro through activation of the ERK pathway",
2950,Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IκB/NF-κB/BACE1 signaling pathway,"β-amyloid (Aβ) is one of the inducing factors of astrocytes activation and neuroinflammation, and it is also a crucial factor for the development of Alzheimer’s disease (AD). Icariside II (ICS II) is an active component isolated from a traditional Chinese herb Epimedium, which has shown to attnuate lipopolysaccharide (LPS)-induced neuroinflammation through regulation of NF-κB signaling pathway. In this study we investigated the effects of ICS II on LPS-induced astrocytes activation and Aβ accumulation. Primary rat astrocytes were pretreated with ICS II (5, 10, and 20 μM) or dexamethasone (DXMS, 1 μM) for 1 h, thereafter, treated with LPS for another 24 h. We found that ICS II pretreatment dose dependently mitigated the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) in the astrocytes. Moreover, ICS II not only exerted the inhibitory effect on LPS-induced IκB-α degradation and NF-κB activation, but also decreased the levels of Aβ(1–40), Aβ(1–42), amyloid precursor protein (APP) and beta secretase 1 (BACE1) in the astrocytes. Interestingly, molecular docking revealed that ICS II might directly bind to BACE1. It is concluded that ICS II has potential value as a new therapeutic agent to treat neuroinflammation-related diseases, such as AD."
2951,Comparing the immunogenicity of glycosidase-directed resiquimod prodrugs mediated by cancer cell metabolism,"We have recently developed an enzyme-directed immunostimulant (EDI) prodrug motif, which is metabolized to active immunostimulant by cancer cells and, following drug efflux, activates nearby immune cells, resulting in immunogenicity. In this study, we synthesized several EDI prodrugs featuring an imidazoquinoline immunostimulant resiquimod (a Toll-like receptor 7/8 agonist) covalently modified with glycosidase enzyme-directing groups selected from substrates of β-glucuronidase, α-mannosidase, or β-galactosidase. We compared the glycosidase-dependent immunogenicity elicited by each EDI in RAW-Blue macrophages following conversion to active immunostimulant by complementary glycosidase. At a cellular level, we examined EDI metabolism across three cancer cell lines (B16 melanoma, TC2 prostate, and 4T1 breast cancer). Comparing the relative immunogenicity elicited by each EDI/cancer cell combination, we found that B16 cells produced the highest EDI prodrug immunogenicity, achieving >95% of that elicited by unmodified resiquimod, followed by TC2 and 4T1 cells (40% and 30%, respectively). Immunogenicity elicited was comparable for a given cell type and independent of the glycosidase substrate in the EDIs or differences in functional glycosidase activity between cell lines. Measuring drug efflux of the immunostimulant payload and efflux protein expression revealed that EDI/cancer cell-mediated immunogenicity was governed by efflux potential of the cancer cells. We determined that, following EDI conversion, immunostimulant efflux occurred through both P-glycoprotein-dependent and P-glycoprotein-independent transport mechanisms. Overall, this study highlights the broad ability of EDIs to couple immunogenicity to the metabolism of many cancers that exhibit drug efflux and suggests that designing future generations of EDIs with immunostimulant payloads that are optimized for drug efflux could be particularly beneficial."
2952,"IgD-Fc-Ig fusion protein, a new biological agent, inhibits T cell function in CIA rats by inhibiting IgD-IgDR-Lck-NF-κB signaling pathways","IgD-Fc-Ig fusion protein, a new biological agent, is constructed by linking a segment of human IgD-Fc with a segment of human IgG1-Fc, which specifically blocks the IgD-IgDR pathway and selectively inhibits the abnormal proliferation, activation, and differentiation of T cells. In this study we investigated whether IgD-Fc-Ig exerted therapeutic effects in collagen-induced arthritis (CIA) rats. CIA rats were treated with IgD-Fc-Ig (1, 3, and 9 mg/kg) or injected with biological agents etanercept (3 mg/kg) once every 3 days for 40 days. In the PBMCs and spleen lymphocytes of CIA rats, both T and B cells exhibited abnormal proliferation; the percentages of CD3(+) total T cells, CD3(+)CD4(+) Th cells, CD3(+)CD4(+)CD25(+)-activated Th cells, Th1(CD4(+)IFN-γ(+)), and Th17(CD4(+)IL-17(+)) were significantly increased, whereas the Treg (CD4(+)CD25(+)Foxp3(+)) cell percentage was decreased. IgD-Fc-Ig administration dose-dependently decreased the indicators of arthritis; alleviated the histopathology of spleen and joint; reduced serum inflammatory cytokines levels; decreased the percentages of CD3(+) total T cells, CD3(+)CD4(+) Th cells, CD3(+)CD4(+)CD25(+)-activated Th cells, Th1 (CD4(+)IFN-γ(+)), and Th17(CD4(+)IL-17(+)); increased Treg (CD4(+)CD25(+)Foxp3(+)) cell percentage; and down-regulated the expression of key molecules in IgD-IgDR-Lck-NF-κB signaling (p-Lck, p-ZAP70, p-P38, p-NF-κB65). Treatment of normal T cells with IgD (9 μg/mL) in vitro promoted their proliferation. Co-treatment with IgD-Fc-Ig (0.1–10 μg/mL) dose-dependently decreased IgD-stimulated T cell subsets percentages and down-regulated the IgD-IgDR-Lck-NF-κB signaling. In summary, this study demonstrates that IgD-Fc-Ig alleviates CIA and regulates the functions of T cells through inhibiting IgD-IgDR-Lck-NF-κB signaling."
2953,Combined proteomics and transcriptomics reveal the genetic basis underlying the differentiation of skin appendages and immunity in pangolin,"Pangolin (Mains javanica) is an interesting endangered mammal with special morphological characteristics. Here, we applied proteomics and transcriptomics to explore the differentiation of pangolin skin appendages at two developmental stages and to compare gene expression profiles between abdomen hair and dorsal scale tissues. We identified 4,311 genes and 91 proteins differentially expressed between scale-type and hair-type tissue, of which 6 genes were shared by the transcriptome and proteome. Differentiation altered the abundance of hundreds of proteins and mRNA in the two types of skin appendages, many of which are involved in keratinocyte differentiation, epidermal cell differentiation, and multicellular organism development based on GO enrichment analysis, and FoxO, MAPK, and p53 signalling pathways based on KEGG enrichment analysis. DEGs in scale-type tissues were also significantly enriched in immune-related terms and pathways compared with that in hair-type tissues. Thus, we propose that pangolins have a normal skin innate immune system. Compared with the abdomen, the back skin of pangolins had more genes involved in the regulation of immune function, which may be an adaptive adjustment for the vulnerability of scaly skin to infection and injury. This investigation provides a scientific basis for the study of development and immunity of pangolin skin, which may be helpful in the protection of wild pangolin in China."
2954,Nanomedicine and cancer immunotherapy,
2955,Aggravated ulcerative colitis caused by intestinal Metrnl deficiency is associated with reduced autophagy in epithelial cells,"Metrnl is a newly identified secreted protein highly expressed in the intestinal epithelium. This study aimed to explore the role and mechanism of intestinal epithelial Metrnl in ulcerative colitis. Metrnl(−/−) (intestinal epithelial cell-specific Metrnl knockout) mice did not display any phenotypes of colitis under basal conditions. However, under administration of 3% dextran sodium sulfate (DSS) drinking water, colitis was more severe in Metrnl(−/−) mice than in WT mice, as indicated by comparisons of body weight loss, the presence of occult or gross blood per rectum, stool consistency, shrinkage in the colon, intestinal damage, and serum levels of inflammatory factors. DSS-induced colitis activated autophagy in the colon. This activation was partially inhibited by intestinal epithelial Metrnl deficiency, as indicated by a decrease in Beclin-1 and LC3-II/I and an increase in p62 in DSS-treated Metrnl(−/−) mice compared with WT mice. These phenomena were further confirmed by observation of autophagosomes and immunofluorescence staining for LC3 in epithelial cells. The autophagy-related AMPK-mTOR-p70S6K pathway was also activated in DSS-induced colitis, and this pathway was partially blocked by intestinal epithelial Metrnl deficiency, as indicated by a decrease in AMPK phosphorylation and an increase in mTOR and p70S6K phosphorylation in DSS-treated Metrnl(−/−) mice compared with WT mice. Therefore, Metrnl deficiency deteriorated ulcerative colitis at least partially through inhibition of autophagy via the AMPK-mTOR-p70S6K pathway, suggesting that Metrnl is a therapeutic target for ulcerative colitis."
2956,"[1,2,4]Triazolo[1,5-a]pyrimidine derivative (Mol-5) is a new NS5-RdRp inhibitor of DENV2 proliferation and DENV2-induced inflammation","Dengue fever is an acute infectious disease caused by dengue virus (DENV) and transmitted by Aedes mosquitoes. There is no effective vaccine or antiviral drug available to date to prevent or treat dengue disease. Recently, RNA-dependent RNA polymerase (RdRp), a class of polymerases involved in the synthesis of complementary RNA strands using single-stranded RNA, has been proposed as a promising drug target. Hence, we screened new molecules against DENV RdRp using our previously constructed virtual screening method. Mol-5, [1,2,4]triazolo[1,5-a]pyrimidine derivative, was screened out from an antiviral compound library (~8000 molecules). Using biophysical methods, we confirmed the direct interactions between mol-5 and purified DENV RdRp protein. In luciferase assay, mol-5 inhibited NS5-RdRp activity with an IC(50) value of 1.28 ± 0.2 μM. In the cell-based cytopathic effect (CPE) assay, mol-5 inhibited DENV2 infectivity with an EC(50) value of 4.5 ± 0.08 μM. Mol-5 also potently inhibited DENV2 RNA replication as observed in immunofluorescence assay and qRT-PCR. Both the viral structural (E) and non-structural (NS1) proteins of DENV2 were dose-dependently decreased by treatment with mol-5 (2.5–10 μM). Mol-5 treatment suppressed DENV2-induced inflammation in host cells, but had no direct effect on host defense (JAK/STAT-signaling pathway). These results demonstrate that mol-5 could be a novel RdRp inhibitor amenable for further research and development."
2957,The evolutionarily conserved function of TBR1 in controlling the size of anterior commissure in human and mouse brains,
2958,Emerging novel approaches to drug research and diagnosis of Parkinson’s disease,
2959,Author Correction: Targeting Hsp90 with FS-108 circumvents gefitinib resistance in EGFR mutant non-small cell lung cancer cells,
2960,CB-Dock: a web server for cavity detection-guided protein–ligand blind docking,"As the number of elucidated protein structures is rapidly increasing, the growing data call for methods to efficiently exploit the structural information for biological and pharmaceutical purposes. Given the three-dimensional (3D) structure of a protein and a ligand, predicting their binding sites and affinity are a key task for computer-aided drug discovery. To address this task, a variety of docking tools have been developed. Most of them focus on docking in the preset binding sites given by users. To automatically predict binding modes without information about binding sites, we developed a user-friendly blind docking web server, named CB-Dock, which predicts binding sites of a given protein and calculates the centers and sizes with a novel curvature-based cavity detection approach, and performs docking with a popular docking program, Autodock Vina. This method was carefully optimized and achieved ~70% success rate for the top-ranking poses whose root mean square deviation (RMSD) were within 2 Å from the X-ray pose, which outperformed the state-of-the-art blind docking tools in our benchmark tests. CB-Dock offers an interactive 3D visualization of results, and is freely available at http://cao.labshare.cn/cb-dock/."
2961,The novel quinolizidine derivate IMB-HDC inhibits STAT5a phosphorylation at 694 and 780 and promotes DNA breakage and cell apoptosis via blocking STAT5a nuclear translocation,"Sophoridine is a quinolizidine natural product and the exploration of its derivatives has been carried out, and the potent anticancer compound IMB-HDC was acquired. Although previous studies have revealed that some sophoridine derivatives could induce DNA breakage, the underlying mechanisms of inhibition of DNA damage repair (ATR inactivation) and the apoptosis independent of p53, have not been elucidated. Our research reveals a novel DNA response mechanism different from general DNA-damaging agents, and that sophoridine derivate inhibits the phosphorylation of Tyr694 and Ser780 of STAT5a to induce the lessened shuttle from the cytoplasm to the nucleus, and leads to the decreased nuclear STAT5a and subsequently inhibits the expression of STAT5a target gene RAD51 that contributes to the checkpoint activation, thus inhibiting ATR activation. Meanwhile, IMB-HDC that induced the diminished expression of STAT5a target gene contributes to proliferation and leads to apoptosis. More importantly, we give the first evidence that promoting the effect of Tyr694 phosphorylation on nuclear location and subsequent STAT5a target gene transcription depends on Ser780 increased or unchanged phosphorylation and was not correlated with Ser726 phosphorylation."
2962,Cocaine potently blocks neuronal α(3)β(4) nicotinic acetylcholine receptors in SH-SY5Y cells,"Cocaine is one of the most abused illicit drugs worldwide. It is well known that the dopamine (DA) transporter is its major target; but cocaine also acts on other targets including nicotinic acetylcholine receptors (nAChRs). In this study, we investigated the effects of cocaine on a special subtype of neuronal nAChR, α(3)β(4)-nAChR expressed in native SH-SY5Y cells. α(3)β(4)-nAChR-mediated currents were recorded using whole-cell recordings. Drugs were applied using a computer-controlled U-tube drug perfusion system. We showed that bath application of nicotine induced inward currents in a concentration-dependent manner with an EC(50) value of 20 µM. Pre-treatment with cocaine concentration-dependently inhibited nicotine-induced current with an IC(50) of 1.5 μM. Kinetic analysis showed that cocaine accelerated α(3)β(4)-nAChR desensitization, which caused a reduction of the amplitude of nicotine-induced currents. Co-application of nicotine and cocaine (1.5 μM) depressed the maximum response on the nicotine concentration-response curve without changing the EC(50) value, suggesting a non-competitive mechanism. The cocaine-induced inhibition of nicotine response exhibited both voltage- and use-dependence, suggesting an open-channel blocking mechanism. Furthermore, intracellular application of GDP-βS (via recording electrode) did not affect cocaine-induced inhibition, suggesting that cocaine did not alter receptor internalization. Moreover, intracellular application of cocaine (30 µM) failed to alter the nicotine response. Finally, cocaine (1.5 μM) was unable to inhibit the nicotine-induced inward current in heterologous expressed α(6)/α(3)β(2)β(3)-nAChRs and α(4)β(2)-nAChRs expressed in human SH-EP1 cells. Collectively, our results suggest that cocaine is a potent blocker for native α(3)β(4)-nAChRs expressed in SH-SY5Y cells."
2963,Population pharmacokinetics of cyclosporine in Chinese children receiving hematopoietic stem cell transplantation,"Cyclosporine (CsA) is characterized by a narrow therapeutic window and high interindividual pharmacokinetic variability, particularly in juvenile patients. The aims of this study were to build a population pharmacokinetic model of CsA in Chinese children with hematopathy who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify covariates affecting CsA pharmacokinetics. A total of 86 Chinese children aged 8.4 ± 3.8 years (range 1.1–16.8 years) who received allo-HSCT were enrolled. Whole blood samples were collected before allo-HSCT. Genotyping was performed using an Agena MassARRAY system. A total of 1010 trough plasma concentration values of CsA and clinical data were collected. The population pharmacokinetic model of CsA was constructed using nonlinear mixed-effects modeling (NONMEM) software. The stability and performance of the final model were validated using bootstrapping and normalized prediction distribution errors. We showed that a one-compartment model with first-order elimination adequately described the pharmacokinetics of CsA. The typical values for clearance (CL) and volume of distribution (V) were 42.3 L/h and 3100 L, respectively. Body weight, postoperative days, CYP3A4*1 G genotype, estimated glomerular filtration rate and coadministration of triazole antifungal drugs were identified as significant covariates for CL. Weight and postoperative days were significant covariates for the V of CsA. Our model can be adopted to optimize the CsA dosing regimen for Chinese children with hematopathy receiving allo-HSCT."
2964,EPHA2 feedback activation limits the response to PDEδ inhibition in KRAS-dependent cancer cells,"KRAS is one of the most important proto-oncogenes. Its mutations occur in almost all tumor types, and KRAS mutant cancer is still lack of effective therapy. Prenyl-binding protein phosphodiesterase-δ (PDEδ) is required for the plasma membrane association and subsequent activation of KRAS oncogenic signaling. Recently, targeting PDEδ has provided new promise for KRAS mutant tumors. However, the therapeutic potential of PDEδ inhibition remains obscure. In this study, we explored how PDEδ inhibition was responded in KRAS mutant cancer cells, and identified KRAS mutant subset responsive to PDEδ inhibition. We first performed siRNA screen of KRAS growth dependency of a small panel of human cancer lines, and identified a subset of KRAS mutant cancer cells that were highly dependent on KRAS signaling. Among these cells, only a fraction of KRAS-dependent cells responded to PDEδ depletion, though KRAS plasma membrane association was effectively impaired. We revealed that the persistent RAF/MEK/ERK signaling seemed responsible for the lack of response to PDEδ depletion. A kinase array further identified that the feedback activation of EPH receptor A2 (EPHA2) accounted for the compensatory activation of RAF/MEK/ERK signaling in these cells. Simultaneous inhibition of EPHA2 and PDEδ led to the growth inhibition of KRAS mutant cancer cells. Together, this study gains a better understanding of PDEδ-targeted therapeutic strategy and suggests the combined inhibition of EPHA2 and PDEδ as a potential therapy for KRAS mutant cancer."
2965,Antiangiogenesis effect of timosaponin AIII on HUVECs in vitro and zebrafish embryos in vivo,"Timosaponin AIII (Timo AIII) is a natural steroidal saponin isolated from the traditional Chinese herb Anemarrhena asphodeloides Bge with proved effectiveness in the treatment of numerous cancers. However, whether Timo AIII suppresses tumor angiogenesis remains unclear. In the present study, we investigated the antiangiogenesis effects of Timo AIII and the underlying mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish embryos in vivo. We showed that treatment with Timo AIII (0.5–2 µM) partially disrupted the intersegmental vessels (ISVs) and subintestinal vessels (SIVs) growth in transgenic zebrafish Tg(fli-1a: EGFP)(y1). Timo AIII (0.5–4 µM) dose-dependently inhibited VEGF-induced proliferation, migration, invasion, and tube formation of HUVECs, but these inhibitory effects were not due to its cytotoxicity. We further demonstrated that Timo AIII treatment significantly suppressed the expression of VEGF receptor (VEGFR) and the phosphorylation of Akt, MEK1/2, and ERK1/2 in HUVECs. Timo AIII treatment also significantly inhibited VEGF-triggered phosphorylation of VEGFR2, Akt, and ERK1/2 in HUVECs. Moreover, we conducted RNA-Seq and analyzed the transcriptome changes in both HUVECs and zebrafish embryos following Timo AIII treatment. The coexpression network analysis results showed that various biological processes and signaling pathways were enriched including angiogenesis, cell motility, cell adhesion, protein serine/threonine kinase activity, transmembrane signaling receptor activity, growth factor activity, etc., which was consistent with the antiangiogenesis effects of Timo AIII in HUVECs and zebrafish embryos. We conclude that the antiangiogenesis effect of Timo AIII is mediated through VEGF/PI3K/Akt/MAPK signaling cascade; Timo AIII potentially exerts antiangiogenesis effect in cancer treatment."
2966,DL0410 ameliorates cognitive deficits in APP/PS1 transgenic mice by promoting synaptic transmission and reducing neuronal loss,"At present, few available drugs can be used to either improve pathological features or prevent the progression of Alzheimer’s disease (AD). DL0410 ((1,1′-([1,1′-biphenyl]-4,4′-diyl) bis (3-(piperidin-1-yl) propan-1-one) dihydrochloride) is a multiple-target small molecule that has been found to reverse cognitive impairment in different animal models of AD. In this study we evaluated the cognition-improving effects of DL0410 in APP/PS1 transgenic mice and explored the underlying mechanisms. APP/PS1 transgenic mice were administered DL0410 (3, 10, 30 mg· kg(−1)· d(−1), ig) for 2 months. We found that DL0410 administration significantly ameliorated cognitive deficits in both the nest-building and Morris water maze tests. In electrophysiological analysis of hippocampal slices, we showed that DL0410 administration significantly enhanced the field EPSP slope and HFS-induced LTP in CA1 area. Furthermore, we revealed that DL0410 administration significantly increased the phosphorylation of AKT and the activity of GSK-3β in the hippocampus and cortex. Moreover, DL0410 administration dose-dependently increased the expression level of phosphorylated ERK1/2 in the hippocampus and cortex. In addition, DL0410 dose-dependently decreased the neuronal loss by decreasing the production of Aβ deposition, inhibited glial overactivation, and the production of inflammatory cytokines such as TNF-α, IL-1β, and IL-6. We conclude that DL0410 ameliorates cognitive deficits in APP/PS1 transgenic mice by promoting synaptic transmission via activating the AKT/GSK-3β and MAPK/ERK signaling pathway and reducing neuronal loss. DL0410 may be an effective agent for AD treatment in the future."
2967,Nanomedicine-mediated alteration of the pharmacokinetic profile of small molecule cancer immunotherapeutics,"The advent of immunotherapy is a game changer in cancer therapy with monoclonal antibody- and T cell-based therapeutics being the current flagships. Small molecule immunotherapeutics might offer advantages over the biological drugs in terms of complexity, tissue penetration, manufacturing cost, stability, and shelf life. However, small molecule drugs are prone to rapid systemic distribution, which might induce severe off-target side effects. Nanotechnology could aid in the formulation of the drug molecules to improve their delivery to specific immune cell subsets. In this review we summarize the current efforts in changing the pharmacokinetic profile of small molecule immunotherapeutics with a strong focus on Toll-like receptor agonists. In addition, we give our vision on limitations and future pathways in the route of nanomedicine to the clinical practice."
2968,Publisher Correction: Integrating yeast chemical genomics and mammalian cell pathway analysis,
2969,"Cycloastragenol upregulates SIRT1 expression, attenuates apoptosis and suppresses neuroinflammation after brain ischemia","Cycloastragenol (CAG) is the active form of astragaloside IV isolated from Astragalus Radix, which displays multiple pharmacological effects. Silent information regulator 1 (SIRT1), a class III histone deacetylase, has been shown to play an important role in neuroprotection against cerebral ischemia. In this study, we investigated whether CAG protected against ischemic brain injury and, if so, whether the beneficial effects were associated with the regulation of SIRT1 in the ischemic brain. Mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. CAG (5, 10, 20 mg/kg) was injected intraperitoneally at the onset of reperfusion, 12 h later and then twice daily for up to three days. CAG dose-dependently reduced brain infarct volume, significantly ameliorated functional deficits, and prevented neuronal cell loss in MCAO mice. Meanwhile, CAG significantly reduced matrix metalloproteinase-9 activity, prevented tight junction degradation and subsequently ameliorated blood-brain barrier disruption. Moreover, CAG significantly upregulated SIRT1 expression in the ischemic brain but did not directly activate its enzymatic activity. Concomitant with SIRT1 upregulation, CAG reduced p53 acetylation and the ratio of Bax to Bcl-2 in the ischemic brain. CAG also inhibited NF-κB p65 nuclear translocation. As a result, CAG suppressed the mRNA expression of pro-inflammatory cytokines, including TNF-α and IL-1β, and inhibited the activation of microglia and astrocytes in the ischemic brain. Our findings suggest that CAG is neuroprotective against ischemic brain injury in mice and that its beneficial effect may involve SIRT1 upregulation and the inhibition of apoptosis and neuroinflammation in the ischemic brain."
2970,Antiepileptic geissoschizine methyl ether is an inhibitor of multiple neuronal channels,"Geissoschizine methyl ether (GM) is an indole alkaloid isolated from Uncaria rhynchophyll (UR) that has been used for the treatment of epilepsy in traditional Chinese medicine. An early study in a glutamate-induced mouse seizure model demonstrated that GM was one of the active ingredients of UR. In this study, electrophysiological technique was used to explore the mechanism underlying the antiepileptic activity of GM. We first showed that GM (1−30 μmol/L) dose-dependently suppressed the spontaneous firing and prolonged the action potential duration in cultured mouse and rat hippocampal neurons. Given the pivotal roles of ion channels in regulating neuronal excitability, we then examined the effects of GM on both voltage-gated and ligand-gated channels in rat hippocampal neurons. We found that GM is an inhibitor of multiple neuronal channels: GM potently inhibited the voltage-gated sodium (Na(V)), calcium (Ca(V)), and delayed rectifier potassium (I(K)) currents, and the ligand-gated nicotinic acetylcholine (nACh) currents with IC(50) values in the range of 1.3−13.3 μmol/L. In contrast, GM had little effect on the voltage-gated transient outward potassium currents (I(A)) and four types of ligand-gated channels (γ-amino butyric acid (GABA), N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainite (AMPA/KA receptors)). The in vivo antiepileptic activity of GM was validated in two electricity-induced seizure models. In the maximal electroshock (MES)-induced mouse seizure model, oral administration of GM (50−100 mg/kg) dose-dependently suppressed generalized tonic-clonic seizures. In 6-Hz-induced mouse seizure model, oral administration of GM (100 mg/kg) reduced treatment-resistant seizures. Thus, we conclude that GM is a promising antiepileptic candidate that inhibits multiple neuronal channels."
2971,"Correction: Chronic maternal interleukin-17 and autism-related cortical gene expression, neurobiology, and behavior",
2972,"Correction: Selective laser trabeculoplasty: past, present, and future",
2973,"Montgomery in, Bolam out: are trainee surgeons ‘material risks’ when taking consent for cataract surgery?","Trainee involvement in cataract surgery is vital to allow proper training of the next generation of ophthalmic surgeons. However, recent changes in the UK Law, coupled with open publication of National Cataract Dataset results, lead us to conclude that the status of being a trainee is itself a material risk that now needs to be divulged to patients during the consent process. The opinions of current trainee surgeons in the UK were sampled via questionnaire and clinical negligence counsel was involved in the authorship of the paper in order to analyse the legal issues at stake. Attitudes towards consent regarding trainee involvement in UK cataract surgery need to change."
2974,The lncRNA Malat1 functions as a ceRNA to contribute to berberine-mediated inhibition of HMGB1 by sponging miR-181c-5p in poststroke inflammation,"Long non-coding RNAs (lncRNAs) have been identified as essential mediators in neurological dysfunction. Our previous study shows that berberine (BBR) hampers the nuclear-to-cytosolic translocation of high-mobility group box 1 (HMGB1) in the process of poststroke inflammation. In this study, we explored the role of lncRNA metastasis‐associated lung adenocarcinoma transcript 1 (Malat1) in the process of BBR-induced inhibition of HMGB1 in ischemic brain. Before the 60-min MCAO surgery, the mice were pretreated with BBR (50 mg· kg(−1) per day, ig) for 14 days or ICV injected with specific lentiviral vector or shRNA. We showed that MCAO caused marked increase in the expression Malat1 and HMGB1 in the ipsilateral cortex, which was significantly attenuated by pretreatment with BBR. Knockdown of Malat1 attenuated the inflammatory injury after brain ischemia, whereas overexpression of Malat1 exacerbated ischemic brain inflammation. Overexpression of Malat1 also reversed BBR-induced reduction of HMGB1 and proinflammatory cytokines. The above results suggested a potential correlation between Malat1 and stroke inflammation. Based on informatics analysis we predicted that HMGB1 was a direct downstream target of miR-181c-5p, whereas Malat1 acted as a competitive endogenous RNA (ceRNA) for miR-181c-5p targeted the 3′-UTR of HMGB1 to promote inflammation after ischemic stroke. Knockdown of Malat1 significantly decreased HMGB1 level, which could be abrogated by transfection with miR-181c-5p inhibitors. Taken together, our results demonstrate for the first time that Malat1/miR-181c-5p/HMGB1 axis may be a key pathway of BBR-induced antiinflammation effects in stroke, and they may provide a novel avenue for targeted therapy."
2975,TLR4 deficiency has a protective effect in the MPTP/probenecid mouse model of Parkinson’s disease,"Parkinson’s disease (PD) is a multifactorial disorder characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) and the presence of Lewy bodies (LBs) consisting of misfolded α-synuclein protein. The etiology of PD is still not clear but systemic inflammation is proved to trigger and exacerbate DA neurons degeneration. Toll-like receptor 4 (TLR4) is a pattern-recognition receptor (PRR) and plays a major role in promoting the host immune. TLR4-mediated signal pathways induce the release of many inflammatory cytokines. It is reasonable to hypothesize that TLR4 is the mediator in microglia contributing to the damage of DA neurons in the SNpc. In this study, we evaluated the role of TLR4 in the chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/probenecid mouse model. Both TLR4-deficient and wild-type (WT) mice were injected with probenecid (250 mg/kg, i.p.) followed by injection of MPTP (25 mg/kg, s.c.) every 4 days for 10 times. From D43 to D47, the behavioral performance in pole test and wire hang test was assessed. Then the mice were euthanized, and SN and striatum were dissected out for biochemical tests. We showed that compared with MPTP-treated WT mice, TLR4 deficiency significantly attenuated MPTP-induced motor deficits and TH-protein expression reduction in SNpc and striatum, suppressed MPTP-induced α-synuclein abnormality and neuroinflammation mediated through oxidative stress, glial activation, NF-κB and the NLRP3 inflammasome signaling pathways. These findings highlight the neuroprotective effect of TLR4-pathways in the chronic MPTP-induced PD mouse model."
2976,Silicone elastomer gel impregnated with 20(S)-protopanaxadiol-loaded nanostructured lipid carriers for ordered diabetic ulcer recovery,"Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20(S)-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing."
2977,A comparative pharmacogenomic analysis of three classic TCM prescriptions for coronary heart disease based on molecular network modeling,"Traditional Chinese medicine (TCM) has evolved over several thousands of years, which has been shown to be efficacious in the treatment of ischemic heart disease. Three classical TCM prescriptions, namely Xuefu Zhuyu Decoction, Zhishi Xiebai Guizhi Decoction, and Gualou Xiebai Banxia Decoction, have been extensively used in the treatment of coronary heart disease (CHD). Based on molecular network modeling, we performed a comparative pharmacogenomic analysis to systematically determine the drug-targeting spectrum of the three prescriptions at molecular level. Wide-area target molecules of CHD were covered, which was a common feature of the three decoctions, demonstrating their therapeutic functions. Meanwhile, collective signaling involved metabolic/pro-metabolic pathways, driving and transferring pathways, neuropsychiatric pathways, and exocrine or endocrine pathways. These organized pharmacological disturbance was mainly focused on almost all stages of CHD intervention, such as anti-atherosclerosis, lipid metabolism, inflammation, vascular wall function, foam cells formation, platelets aggregation, thrombosis, arrhythmia, and ischemia-reperfusion injury. In addition, heterogeneity analysis of the global pharmacological molecular spectrum revealed that signaling crosstalk, cascade convergence, and key targets were tendentious among the three decoctions. After all, it is unadvisable to rank the findings on targeting advantages of the three decoctions. Comparative pharmacological evidence may provide an appropriate decoction scheme for individualized intervention of CHD."
2978,Evaluation of a novel monoclonal antibody mAb109 by immuno-PET/fluorescent imaging for noninvasive lung adenocarcinoma diagnosis,"Monoclonal antibodies are believed to be magic bullets and hold great potential for lots of biological process. About 100 μg of mAb109 was expressed in 5 × 10(6) cells after 10 days’ immunization. (64)Cu-NOTA-mAb109 was synthesized with the specific activity of 0.74 MBq/μg and high in vitro stability. The binding affinity of (64)Cu-NOTA-mAb109 in A549 cells was determined to be 29.64 nM. (64)Cu-NOTA-mAb109 displayed prominent tumor accumulation from 2 h to 60 h p.i. (9.34 ± 0.67 %ID/g). NIRF imaging of Cy5.5-mAb109 showed high accumulation till 9 days p.i., while tumors nearly can not be observed in negative groups, which was confirmed by autoradiography. Immunohistological study confirmed that mAb109 had strong and specific capacity to bind lung adenocarcinoma (concentration to 58 nM). Our study demonstrated mAb109 was a new platform for the development of novel agent for lung adenocarcinoma noninvasive imaging. The resulted (64)Cu-NOTA-mAb109/Cy5.5-mAb109 show favorable imaging properties/specificity for A549 tumor and high sensitivity to human lung adenocarcinoma tissues."
2979,"3-Deoxy-2β,16-dihydroxynagilactone E, a natural compound from Podocarpus nagi, preferentially inhibits JAK2/STAT3 signaling by allosterically interacting with the regulatory domain of JAK2 and induces apoptosis of cancer cells","The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathways, especially the JAK2/STAT3 pathway, play vital roles in the development of many malignancies. Overactivation of STAT3 promotes cancer cell survival and proliferation. Therefore, the JAK2/STAT3-signaling pathway has been considered a promising target for cancer therapy. In this study, we identified a natural compound 3-deoxy-2β,16-dihydroxynagilactone E (B6) from the traditional Chinese medicinal plant Podocarpus nagi as a potent inhibitor of STAT3 signaling. B6 preferentially inhibited the phosphorylation of STAT3 by interacting with and inactivating JAK2, the main upstream kinase of STAT3. B6 dose-dependently inhibited IL-6-induced STAT3 signaling with an IC(50) of 0.2 μM. In contrast to other JAK2 inhibitors, B6 did not interact with the catalytic domain but instead with the FERM-SH2 domain of JAK2. This interaction was JAK-specific since B6 had little effect on other tyrosine kinases. Furthermore, B6 potently inhibited the growth and induced apoptosis of MDA-MB-231 and MDA-MB-468 breast cancer cells with overactivated STAT3. Taken together, our study uncovers a novel compound and a novel mechanism for the regulation of JAK2 and offers a new therapeutic approach for the treatment of cancers with overactivated JAK2/STAT3."
2980,"23,24-Dihydrocucurbitacin B promotes lipid clearance by dual transcriptional regulation of LDLR and PCSK9","23,24-Dihydrocucurbitacin B (designated as C95 in this article) is a cucurbitane triterpenoid that has been shown to possess a variety of pharmacological activities, such as anti-inflammatory and anti-HIV-1 activities etc. In this study, we investigated the effects of 23,24-dihydrocucurbitacin B on lipid regulation. We showed that 23,24-dihydrocucurbitacin B (1–5 μM) dose-dependently promoted DiI-LDL uptake in HepG2 cells by upregulating low-density lipoprotein receptor (LDLR) protein. In HepG2 cells, 23,24-dihydrocucurbitacin B (1–10 μM) dose-dependently enhanced LDLR promoter activity by elevating the mature form of SREBP2 (sterol regulatory element binding protein 2) protein levels on one hand, and inhibited PCSK9 (proprotein convertase subtilisin/kexin type 9) promoter activity by attenuating HNF1α (hepatocyte nuclear factor-1α) protein levels in nuclei on the other hand. Consequently, the expression of LDLR protein markedly increased, whereas the PCSK9-mediated LDLR protein degradation decreased. In a high-cholesterol LVG golden Syrian Hamster model, administration of 23,24-dihydrocucurbitacin B (30 mg · kg(−1)⋅ d(−1), intragastric, for 3 weeks) significantly decreased the serum LDL-cholesterol (LDL-C) levels. PCSK9 protein levels in the serum and liver tissues were significantly decreased, whereas LDLR protein levels in liver tissues were significantly increased in the treated animals as compared with the control animals. In conclusion, our study demonstrates for the first time that 23,24-dihydrocucurbitacin B exhibits dual transcriptional regulation of LDLR and PCSK9 in HepG2 cells by increasing SREBP2 protein levels and decreasing HNF1α protein levels in the nuclei. These results propose a new strategy to simultaneously manage LDLR and PCSK9 protein expression and provide a promising lead compound for drug development."
2981,Tissue-specific relaxin-2 is differentially associated with the presence/size of an arterial aneurysm and the severity of atherosclerotic disease in humans,"Circulating or tissue-related biomarkers are of clinical value for risk stratification in patients with abdominal aortic aneurysms. Relaxin-2 (RL2) has been linked to the presence and size of arterial aneurysms, and to the extent of atherosclerosis in human subjects. Here, we assessed the expression levels of RL2 in aneurysmal (AA, n = 16) and atherosclerotic (ATH, n = 22) arteries, and established the correlation between RL2 levels and the presence/size of AA and the clinical severity of atherosclerosis. The expression levels of metalloproteinases (MMPs) and endothelial nitric oxide synthetase (eNOS) were also detected for correlations with different phenotypes of atherosclerosis and AA. Temporal artery biopsy specimens (n = 6) and abdominal aortic tissues harvested from accident victims during autopsy (n = 10) were used as controls. Quantitative tissue biomarker analysis revealed that tissue-specific RL2 was increased in patients with larger or symptomatic AA compared to subjects with atherosclerotic disease and healthy controls. In situ RL2 levels were proportional to the size and the severity of aneurysmatic disease, and were substantially elevated in patients with symptomatic aneurysm of any diameter or asymptomatic aneurysm of a diameter >350% of that of the normal artery. In contrast, tissue RL2 was inversely associated with the clinical severity of atherosclerotic lesions. Correlation between RL2 and MMP2 was different between ATH1 and ATH2, depending on atherosclerosis grade. Overall, tissue RL2 is differentially associated with discrete phenotypes of arterial disease and might exert multipotent biological effects on vascular wall integrity and remodeling in human subjects."
2982,"Asiatic acid prevents renal fibrosis in UUO rats via promoting the production of 15d-PGJ2, an endogenous ligand of PPAR-γ","Renal fibrosis is an inevitable outcome of all kinds of progressive chronic kidney disease (CKD). Recently, asiatic acid (AA), a triterpenoid compound from Chinese medicine Centella asiatica, has been found to attenuate renal fibrosis. In the current study, we explored the mechanisms underlying antifibrotic effect of AA on UUO model. SD rats and ICR mice were subjected to unilateral ureteral occlusion (UUO) surgery. Prior the surgery, rats were administered AA (10 mg·kg(−1) per day, ig) for 7 days, whereas the mice received AA (15 mg·kg(−1) per day, ig) for 3 days. UUO group displayed significant degree of renal dysfunction, interstitial fibrosis, oxidative stress, and activation of the TGF-β/Smad and Wnt/β-catenin signaling pathway in the kidney, these pathological changes were greatly ameliorated by pretreatment with AA. In addition, we found that co-treatment with GW9662, a selective PPAR-γ antagonist (1 mg·kg(−1) per day, ip) for 7 days, abolished the protective effects of AA. We further revealed that AA pretreatment did not significantly change the expression levels of PPAR-γ in the kidney, but markedly increase the plasma levels of 15d-PGJ2, an endogenous ligand of PPAR-γ. In UUO mice, pretreatment with 15d-PGJ2 (24 μg·kg(−1) per day, ip, for 7 days) produced similar protective effect as AA. Moreover, AA pretreatment upregulated the expression levels of active, nuclear-localized SREBP-1 (nSREBP-1), whereas fatostatin, a specific inhibitor of SREBP-1, decreased the expression of nSREBP-1, as well as the level of 15d-PGJ2. These results provide new insight into the antifibrotic mechanism of AA and endogenous metabolites might become a new clue for investigation of drug mechanism."
2983,Acid sphingomyelinase downregulation alleviates vascular endothelial leptin resistance in rats,"Leptin resistance in endothelial cells leads to vascular endothelial dysfunction, which is the beginning and crucial link of atherosclerosis. However, the mechanism of leptin resistance remains obscure. Acid sphingomyelinase (ASM) catalyzes the hydrolysis of sphingomyelin to produce ceramide, which plays an important role in the progression of metabolic and cardiovascular diseases. In this study, we investigated whether ASM could regulate leptin resistance in vascular endothelial cells. We induced endothelial leptin resistance in rat aortic endothelial cells through treatment with palmitic acid (0.3 mM) or knockdown of leptin receptor (Ob-Rb), which resulted in the increase of suppressor of cytokine signaling 3 expression, the decrease of Ob-Rb expression, and signal transducer and activator of transcription 3 (STAT3) phosphorylation at Tyr705. We found that these indicators of leptin resistance were reversed by knockdown of ASM or by the selective ASM inhibitors amitriptyline (AMI) and imipramine (IMI). Supplementation of ceramide inhibited Ob-Rb expression and STAT3 phosphorylation by inhibiting extracellular signal-regulated kinase 1/2 activation. Furthermore, we found that knockdown of ASM enhanced endothelial nitric oxide (NO) synthase activity and NO production, as well as the Akt phosphorylation at ser473, which was regulated by STAT3. High-fat diet (HFD) feeding-induced leptin resistance in rats in vivo; administration of AMI and IMI (10 mg· kg(−1) per day, intraperitoneally, for 2 weeks) increased the release of endothelial NO to relieve the vasodilatory response and improved the endothelial leptin resistance in the aorta of HFD-fed rats. These results suggest that ASM downregulation reverses endothelial leptin resistance, and consequently improves vascular endothelial dysfunction. This study highlighted ASM as a potential therapeutic target for endothelial leptin resistance."
2984,Discovery of aryl sulfonamide-selective Nav1.7 inhibitors with a highly hydrophobic ethanoanthracene core,"Nav1.7 channels are mainly distributed in the peripheral nervous system. Blockade of Nav1.7 channels with small-molecule inhibitors in humans might provide pain relief without affecting the central nervous system. Based on the facts that many reported Nav1.7-selective inhibitors contain aryl sulfonamide fragments, as well as a tricyclic antidepressant, maprotiline, has been found to inhibit Nav1.7 channels, we designed and synthesized a series of compounds with ethanoanthracene and aryl sulfonamide moieties. Their inhibitory activity on sodium channels were detected with electrophysiological techniques. We found that compound 10o potently inhibited Nav1.7 channels stably expressed in HEK293 cells (IC(50) = 0.64 ± 0.30 nmol/L) and displayed a high Nav1.7/Nav1.5 selectivity. In mouse small-sized dorsal root ganglion neurons, compound 10o (10, 100 nmol/L) dose-dependently decreased the sodium currents and dramatically suppressed depolarizing current-elicited neuronal discharge. Preliminary in vivo experiments showed that compound 10o possessed good analgesic activity: in a mouse visceral pain model, administration of compound 10o (30−100 mg/kg, i.p.) effectively and dose-dependently suppressed acetic acid-induced writhing."
2985,Propofol affects mouse embryonic fibroblast survival and proliferation in vitro via ATG5- and calcium-dependent regulation of autophagy,"Propofol is a commonly used intravenous anesthetic agent, which has been found to affect cell survival and proliferation especially in early life. Our previous studies show that propofol-induced neurodegeneration and neurogenesis are closely associated with cell autophagy. In the present study we explored the roles of autophagy-related gene 5 (ATG5) in propofol-induced autophagy in mouse embryonic fibroblasts (MEF) in vitro. We showed that ATG5 was functionally related to propofol-induced cell survival and damage: propofol significantly enhanced cell survival and proliferation at a clinically relevant dose (10 µM), but caused cell death at an extremely high concentration (200 µM) in ATG5(−/−) MEF, but not in WT cells. The dual effects found in ATG5(−/−) MEF could be blocked by intracellular Ca(2+) channel antagonists. We also found that propofol evoked a moderate (promote cell growth) and extremely high (cause apoptosis) cytosolic Ca(2+) elevation at the concentrations of 10 µM and 200 µM, respectively, only in ATG5(−/−) MEF. In addition, ATG5(−/−) MEF themselves released more Ca(2+) in cytosolic space and endoplasmic reticulum compared with WT cells, suggesting that autophagy deficiency made intracellular calcium signaling more vulnerable to external stimuli (propofol). Altogether, our results reveal that ATG5 plays a crucial role in propofol regulation of cell survival and proliferation by affecting intracellular Ca(2+) homeostasis."
2986,"RepSox, a small molecule inhibitor of the TGFβ receptor, induces brown adipogenesis and browning of white adipocytes","Unlike white adipose tissue (WAT), brown adipose tissue (BAT) is mainly responsible for energy expenditure via thermogenesis by uncoupling the respiratory chain. Promoting the differentiation of brown fat precursor cells and the browning of white fat have become a research hotspot for the treatment of obesity and associated metabolic diseases. Several secreted factors and a number of small molecules have been found to promote brown adipogenesis. Here we report that a single small-molecule compound, RepSox, is sufficient to induce adipogenesis from mouse embryonic fibroblasts (MEFs) in fibroblast culture medium. RepSox is an inhibitor of the transforming growth factor-beta receptor I (TGF-β-RI), other inhibitors of TGF-β pathway such as SB431542, LY2157299, A83-01, and Tranilast are also effective in inducing adipogenesis from MEFs. These adipocytes express brown adipocyte-specific transcription factors and thermogenesis genes, and contain a large number of mitochondria and have a high level of mitochondrial respiratory activity. More interestingly, RepSox has also been found to promote the differentiation of the brown fat precursor cells and induce browning of the white fat precursor cells. These findings suggest that inhibitors of TGF-β signaling pathway might be developed as new therapeutics for obesity and type 2 diabetes."
2987,Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway,"Microglia-mediated neuroinflammation is a crucial risk factor for neurological disorders. Recently, dopamine receptors have been found to be involved in multiple immunopathological processes and considered as valuable therapeutic targets for inflammation-associated neurologic diseases. In this study we investigated the anti-neuroinflammation effect of isosibiricin, a natural coumarin compound isolated from medicinal plant Murraya exotica. We showed that isosibiricin (10−50 μM) dose-dependently inhibited lipopolysaccharide (LPS)-induced BV-2 microglia activation, evidenced by the decreased expression of inflammatory mediators, including nitrite oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-18 (IL-18). By using transcriptomics coupled with bioinformatics analysis, we revealed that isosibiricin treatment mainly affect dopamine receptor signalling pathway. We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. Treatment with dopamine D1/2 receptor antagonists SCH 23390 (1 μM) or sultopride (1 μM) could reverse the inhibitory effects of isosibiricin on NLRP3 expression as well as the cleavages of caspase-1 and IL-1β. Collectively, this study demonstrates a promising therapeutic strategy for neuroinflammation by targeting dopamine D1/2 receptors."
2988,Garcinol inhibits esophageal cancer metastasis by suppressing the p300 and TGF-β1 signaling pathways,"Metastasis causes the main lethality in esophageal cancer patient. Garcinol, a natural compound extracted from Gambogic genera, is a histone acetyltransferase (HAT) inhibitor that has shown anticancer activities such as cell cycle arrest and apoptosis induction. In this study, we investigated the effects of garcinol on the metastasis of esophageal cancer in vitro and in vivo. We found that garcinol (5–15 μM) dose-dependently inhibited the migration and invasion of human esophageal cancer cell lines KYSE150 and KYSE450 in wound healing, transwell migration, and Matrigel invasion assays. Furthermore, garcinol treatment dose-dependently decreased the protein levels of p300/CBP (transcriptional cofactors and HATs) and p-Smad2/3 expression in the nucleus, thus impeding tumor cell proliferation and metastasis. Knockdown of p300 could inhibit cell metastasis, but CBP knockdown did not affect the cell mobility. It has been reported that TGF-β1 stimulated the phosphorylation of Smad2/3, which directly interact with p300/CBP in the nucleus, and upregulating HAT activity of p300. We showed that garcinol treatment dose-dependently suppressed TGF-β1-activated Smad and non-Smad pathway, inhibiting esophageal cancer cell metastasis. In a tail vein injection pulmonary metastasis mouse model, intraperitoneal administration of garcinol (20 mg/kg) or 5-FU (20 mg/kg) significantly decreased the number of lung tumor nodules and the expression levels of Ki-67, p300, and p-Smad2/3 in lung tissues. In conclusion, our study demonstrates that garcinol inhibits esophageal cancer metastasis in vitro and in vivo, which might be related to the suppression of p300 and TGF-β1 signaling pathways, suggesting the therapeutic potential of Garcinol for metastatic tumors."
2989,Huperzine A ameliorates obesity-related cognitive performance impairments involving neuronal insulin signaling pathway in mice,"Type 2 diabetes (T2D) and Alzheimer’s disease (AD) share several common pathophysiological features. Huperzine A (Hup A), a Lycopodium alkaloid extracted from the Chinese herb moss Huperzia serrata, is a specific and reversible inhibitor of acetylcholinesterase, which is clinically used for the treatment of AD. In this study, we investigated whether Hup A improved the metabolic and cognitive functions in the high fat-induced (HFD) obese mice and genetic ob/ob mice. HFD and ob/ob mice were treated with Hup A (0.1, 0.3 mg · kg(−1) · d(−1), ig) for 3 months. Body weight was monitored and glucose tolerance tests were performed. Novel object recognition test and Morris water maze assay were conducted to evaluate the cognitive functions. We found that the Hup A treatment had no significant effect on peripheral metabolism of obese mice, whereas Hup A (0.1, mg · kg(−1) · d(−1)) improved both the abilities of object recognition and spatial memory in HFD-fed mice, but not in ob/ob mice. Furthermore, Hup A treatment significantly upregulated the insulin and phosphorylated Akt levels in the cortex of HFD-fed mice, but not ob/ob mice. In addition, Hup A (0.3, mg · kg(−1) · d(−1)) significantly decreased cortical β-secretase (BACE1) expression. In conclusion, these results demonstrate that treatment with Hup A (0.1, mg · kg(−1) · d(−1)) can effectively improve the cognitive functions, at least in diet-induced obese mice."
2990,Reply to Hsueh YP et al.,
2991,Serum biomarkers combined with ultrasonography for early diagnosis of non-alcoholic fatty liver disease confirmed by magnetic resonance spectroscopy,"Magnetic resonance spectroscopy (MRS) is notably accurate for even minimal degree of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). But routine use of MRS is limited by its cost and availability. In this study, we developed a diagnostic model combining ultrasonography with biomarkers to identify mild NAFLD, with MRS as the reference standard. A total of 422 eligible subjects were enrolled. The serum levels of fibroblast growth factor 21 (FGF21), cytokeratin 18 M65ED, proteinase 3, neutrophil elastase, alpha-1 antitrypsin, and neutrophil elastase/alpha-1 antitrypsin were measured using ELISA assays. We found that among the six biomarkers, only serum FGF21 was independently associated with intrahepatic triglyceride content (IHTC, standardized β = 0.185, P < 0.001) and was an independent risk factor for mild NAFLD. Thus, we established a Mild NAFLD Model based on FGF21, alanine transaminase, triglycerides, and body mass index. The area under the receiver-operating characteristic curve of the Mild NAFLD Model was 0.853 (95% confidence interval: 0.816–0.886). Furthermore, a two-step approach combining ultrasonography with the Mild NAFLD Model displayed a better sensitivity for diagnosing mild NAFLD compared with each method alone, with a sensitivity of 97.32% and a negative predictive value of 85.48%. This two-step approach combining ultrasonography and the Mild NAFLD Model derived from serum FGF21 improves the diagnosis of mild NAFLD and can be applied to the early diagnosis of NAFLD in clinical practice."
2992,Nimesulide increases the aldehyde oxidase activity of humans and rats,"An increasing number of drugs are metabolized by aldehyde oxidase (AOX), but AOX-mediated drug interactions are seldom reported due to the lack of appropriate inhibitors and inducers. A recent study reported that nimesulide (NIM) could increase the liver injury risk of methotrexate. The latter was mainly metabolized by AOX to form hepatotoxic 7-hydroxymethotrexate (7-OH MTX). Thus, we speculated that NIM could induce AOX. In this study, we investigated the potential induction of AOX activity by NIM using methotrexate as the probe substrate. Treatment of primary human and rat hepatocytes with NIM (20 μM) for 24 h caused a 2.0- and 3.1-fold, respectively, increase in 7-OH MTX formation. Oral administration of NIM (100 mg·kg(−1)·d(−1), for 5 days) to rats significantly increased the systematic exposure (6.5-fold), liver distribution (2.5-fold), and excretion (5.2-fold for urinary excretion and 2.1-fold for fecal excretion) of 7-OH MTX. The 7-OH MTX formation in liver cytosol from rats pretreated with 20, 50, and 100 mg·kg(−1)·d(−1) NIM for 5 days increased by 1.9-, 3.2-, and 3.7-fold, respectively, compared with that of rats pretreated with the vehicle. We revealed that the elevation of AOX activity was accompanied by an increase in AOX1 protein levels but not the corresponding mRNA levels. Collectively, our results demonstrate for the first time that NIM can increase the AOX activity of humans and rats, and may raise concerns regarding the risk of drug interactions between NIM and AOX substrates in clinical practice."
2993,Zinc protects against cadmium-induced toxicity in neonatal murine engineered cardiac tissues via metallothionein-dependent and independent mechanisms,"Cadmium (Cd) is a nonessential heavy metal and a prevalent environmental toxin that has been shown to induce significant cardiomyocyte apoptosis in neonatal murine engineered cardiac tissues (ECTs). In contrast, zinc (Zn) is a potent metallothionein (MT) inducer, which plays an important role in protection against Cd toxicity. In this study, we investigated the protective effects of Zn against Cd toxicity in ECTs and explore the underlying mechanisms. ECTs were constructed from neonatal ventricular cells of wild-type (WT) mice and mice with global MT gene deletion (MT-KO). In WT-ECTs, Cd (5−20 μM) caused a dose-dependent toxicity that was detected within 8 h evidenced by suppressed beating, apoptosis, and LDH release; Zn (50−200 μM) dose-dependently induced MT expression in ECTs without causing ECT toxicity; co-treatment of ECT with Zn (50 µM) prevented Cd-induced toxicity. In MT-KO ECTs, Cd toxicity was enhanced; but unexpectedly, cotreatment with Zn provided partial protection against Cd toxicity. Furthermore, Cd, but not Zn, significantly activated Nrf2 and its downstream targets, including HO-1; inhibition of HO-1 by a specific HO-1 inhibitor, ZnPP (10 µM), significantly increased Cd-induced toxicity, but did not inhibit Zn protection against Cd injury, suggesting that Nrf2-mediated HO-1 activation was not required for Zn protective effect. Finally, the ability of Zn to reduce Cd uptake provided an additional MT-independent mechanism for reducing Cd toxicity. Thus, Zn exerts protective effects against Cd toxicity for murine ECTs that are partially MT-mediated. Further studies are required to translate these findings towards clinical trials."
2994,Prostaglandin E1 attenuates high glucose-induced apoptosis in proximal renal tubular cells by inhibiting the JNK/Bim pathway,"Proximal renal tubular damage is a critical process underlying diabetic kidney disease (DKD). Our previous study shows that prostaglandin E1 (PGE1) reduces the apoptosis of renal tubular cells in DKD rats. But its underlying mechanisms remain unclear. In this study we investigated the protective effects of PGE1 in DKD rats and high glucose (HG, 30 mM)-treated HK-2 proximal tubular cells. Four weeks after uninephrectomized streptozotocin-induced diabetic rats were established, the DKD rats were administered PGE1 (10 µg· kg(−1)· d(−1), iv.) for 10 consecutive days. We showed that PGE1 administration did not change blood glucose levels, but alleviated diabetic kidney injury in the DKD rats, evidenced by markedly reduced proteinuria and renal tubular apoptosis. In the in vitro experiments, PGE1 (0.1–100 µM) significantly enhanced HG-reduced HK-2 cell viability. In HG-treated HK-2 cells, PGE1 (10 µM) significantly suppressed the c-Jun N-terminal kinase (JNK) and the mitochondrial apoptosis-related protein expressions such as Bim, Bax, caspase-3 and cleaved caspase-3; similar changes were also observed in the kidney of PGE1-treated DKD rats. By using two pharmacological tools-JNK activator anisomycin (AM) and JNK inhibitor SP600125, we revealed that PGE1 blocked HG-triggered activation of JNK/Bim pathway in HK-2 cells; JNK was an upstream regulator of Bim. In conclusion, our results demonstrate that the nephroprotective effects of PGE1 against apoptosis of proximal renal tubule in DKD rats via suppressing JNK-related Bim signaling pathway."
2995,Recent advances in dopaminergic strategies for the treatment of Parkinson’s disease,"Parkinson’s disease (PD) is the second most common progressive neurodegenerative disease worldwide. However, there is no available therapy reversing the neurodegenerative process of PD. Based on the loss of dopamine or dopaminergic dysfunction in PD patients, most of the current therapies focus on symptomatic relief to improve patient quality of life. As dopamine replacement treatment remains the most effective symptomatic pharmacotherapy for PD, herein we provide an overview of the current pharmacotherapies, summarize the clinical development status of novel dopaminergic agents, and highlight the challenge and opportunity of emerging preclinical dopaminergic approaches aimed at managing the features and progression of PD."
2996,Gut microbiota dysbiosis-induced activation of the intrarenal renin–angiotensin system is involved in kidney injuries in rat diabetic nephropathy,"Some studies have shown that gut microbiota along with its metabolites is closely associated with diabetic mellitus (DM). In this study we explored the relationship between gut microbiota and kidney injuries of early diabetic nephropathy (DN) and its underlying mechanisms. Male SD rats were intraperitoneally injected with streptozotocin to induce DM. DM rats were orally administered compound broad-spectrum antibiotics for 8 weeks. After the rats were sacrificed, their blood, urine, feces, and renal tissues were harvested for analyses. We found that compared with the control rats, DM rats had abnormal intestinal microflora, increased plasma acetate levels, increased proteinuria, thickened glomerular basement membrane, and podocyte foot process effacement in the kidneys. Furthermore, the protein levels of angiotensin II, angiotensin-converting enzyme, and angiotensin II type 1 receptor in the kidneys of DM rats were significantly increased. Administration of broad-spectrum antibiotics in DM rats not only completely killed most intestinal microflora, but also significantly lowered the plasma acetate levels, inhibited intrarenal RAS activation, and attenuated kidney damage. Finally, we showed that plasma acetate levels were positively correlated with intrarenal angiotensin II protein expression (r = 0.969, P < 0.001). In conclusion, excessive acetate produced by disturbed gut microbiota might be involved in the kidney injuries of early DN through activating intrarenal RAS."
2997,Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies,"Schizandrol A (SA) is an bioactive component isolated from the Schisandra chinensis (Turcz.) Baill., which has been used as a remedy to prevent oxidative injury. However, whether the cardioprotective effect of SA is associated with regulating endogenous metabolites remains unclear, thus we performed comprehensive metabolomics profiling in acute myocardial ischemia (AMI) mice following SA treatment. AMI was induced in ICR mice by coronary artery ligation, then SA (6 mg·kg(−1)·d(−1), ip) was administered. SA treatment significantly decreased the infarct size, preserved the cardiac function, and improved the biochemical indicators and cardiac pathological alterations. Moreover, SA (10, 100 M) significantly decreased the apoptotic index in OGD-treated H8c2 cardiomycytes in vitro. By using HPLC-Q-TOF/MS, we conducted metabonomics analysis to screen the significantly changed endogenous metabolites and construct the network in both serum and urine. The results revealed that SA regulated the pathways of glycine, serine and threonine metabolism, lysine biosynthesis, pyrimidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, valine, leucine and isoleucine biosynthesis under the pathological conditions of AMI. Furthermore, we selected the regulatory enzymes related to heart disease, including ecto-5’-nucleotidase (NT5E), guanidinoacetate N-methyltransferase (GAMT), platelet-derived endothelial cell growth factor (PD-ECGF) and methionine synthase (MTR), for validation. In addition, SA was found to facilitate PI3K/Akt activation and inhibit the expression of NOX2 in AMI mice and OGD-treated H9c2 cells. In conclusion, we have elucidated SA-regulated endogenous metabolic pathways and constructed a regulatory metabolic network map. Furthermore, we have validated the new potential therapeutic targets and underlying molecular mechanisms of SA against AMI, which might provide a reference for its future application in cardiovascular diseases."
2998,TSPO ligands prevent the proliferation of vascular smooth muscle cells and attenuate neointima formation through AMPK activation,"Abnormal growth of the intimal layer of blood vessels (neointima formation) contributes to the progression of atherosclerosis and in-stent restenosis. Recent evidence shows that the 18-kDa translocator protein (TSPO), a mitochondrial membrane protein, is involved in diverse cardiovascular diseases. In this study we investigated the role of endogenous TSPO in neointima formation after angioplasty in vitro and in vivo. We established a vascular injury model in vitro by using platelet-derived growth factor-BB (PDGF-BB) to stimulate rat thoracic aortic smooth muscle cells (A10 cells). We found that treatment with PDGF-BB (1–20 ng/mL) dose-dependently increased TSPO expression in A10 cells, which was blocked in the presence of PKC inhibitor or MAPK inhibitor. Overexpression of TSPO significantly promoted the proliferation and migration in A10 cells, whereas downregulation of TSPO expression by siRNA or treatment with TSPO ligands PK11195 or Ro5-4864 (10(4) nM) produced the opposite effects. Furthermore, we found that PK11195 (10−10(4) nM) dose-dependently activated AMPK in A10 cells. PK11195-induced inhibition on the proliferation and migration of PDGF-BB-treated A10 cells were abolished by compound C (an AMPK-specific inhibitor, 10(3) nM). In rats with balloon-injured carotid arteries, TSPO expression was markedly upregulated in the carotid arteries. Administration of PK11195 (3 mg/kg every 3 days, ip), starting from the initial balloon injury and lasting for 2 weeks, greatly attenuated carotid neointima formation by suppressing balloon injury-induced phenotype switching of VSMCs (increased α-SMA expression). These results suggest that TSPO is a vascular injury-response molecule that promotes VSMC proliferation and migration and is responsible for the neointima formation after vascular injury, which provides a novel therapeutic target for various cardiovascular diseases including atherosclerosis and restenosis."
2999,PK/PD modeling based on NO-ET homeostasis for improving management of sunitinib-induced hypertension in rats,"Sunitinib is an oral small molecule multitargeted tyrosine kinase inhibitor, which is currently used to treat severe cancers. Clinical research has shown that patients treated with sunitinib develop hypertension. As soon as sunitinib-induced hypertension appears, it is usual to administer anti-hypertension agent. But this treatment may cause acute blood pressure fluctuation which may lead to additional cardiovascular risk. The aim of this study is to establish a mathematical model for managing sunitinib-induced hypertension and blood pressure fluctuation. A mechanism-based PK/PD model was developed based on animal experiments. Then this model was used to perform simulations, thus to propose an anti-hypertension indication, according to which the anti-hypertension treatment might yield relative low-level AUC and fluctuation of blood pressure. The simulation results suggest that the anti-hypertension agent may yield low-level AUC and fluctuation of blood pressure when relative ET-1 level ranges from −15% to 5% and relative NO level is more than 10% compared to control group. Finally, animal experiments were conducted to verify the simulation results. Macitentan (30 mg/kg) was administered based on the above anti-hypertension indication. Compared with the untreated group, the optimized treatment significantly reduced the AUC of blood pressure; meanwhile the fluctuation of blood pressure in optimized treatment group was 70% less than that in immediate treatment group. This work provides a novel model with potential translational value for managing sunitinib-induced hypertension."
3000,Wie lange dauert eine Langzeitanwendung?,
3001,A prospective observational study on critically ill children with diaphragmatic dysfunction: clinical outcomes and risk factors,"BACKGROUND: Diaphragmatic dysfunction (DD) has a great negative impact on clinical outcomes, and it is a well-recognized complication in adult patients with critical illness. However, DD is largely unexplored in the critically ill pediatric population. The aim of this study was to identify risk factors associated with DD, and to investigate the effects of DD on clinical outcomes among critically ill children. METHODS: Diaphragmatic function was assessed by diaphragm ultrasound. According to the result of diaphragmatic ultrasound, all enrolled subjects were categorized into the DD group (n = 24) and the non-DD group (n = 46). Collection of sample characteristics in both groups include age, sex, height, weight, primary diagnosis, complications, laboratory findings, medications, ventilatory time and clinical outcomes. RESULTS: The incidence of DD in this PICU was 34.3%. The level of CRP at discharge (P = 0.003) in the DD group was higher than the non-DD group, and duration of elevated C-reactive protein (CRP) (P < 0.001), sedative days (P = 0.008) and ventilatory treatment time (P < 0.001) in the DD group was significantly longer than the non-DD group. Ventilatory treatment time and duration of elevated CRP were independently risk factors associated with DD. Patients in the DD group had longer PICU length of stay, higher rate of weaning or extubation failure and higher mortality. CONCLUSION: DD is associated with poorer clinical outcomes in critically ill childern, which include a longer PICU length of stay, higher rate of weaning or extubation failure and a higher mortality. The ventilatory treatment time and duration of elevated CRP are main risk factors of DD in critically ill children. TRIAL REGISTRATION: Current Controlled Trials ChiCTR1800020196, Registered 01 Dec 2018."
3002,Towards harmonization of microscopy methods for malaria clinical research studies,"Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies. These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research."
3003,FLAVi: An Enhanced Annotator for Viral Genomes of Flaviviridae,"Responding to the ongoing and severe public health threat of viruses of the family Flaviviridae, including dengue, hepatitis C, West Nile, yellow fever, and Zika, demands a greater understanding of how these viruses emerge and spread. Updated phylogenies are central to this understanding. Most cladograms of Flaviviridae focus on specific lineages and ignore outgroups, hampering the efficacy of the analysis to test ingroup monophyly and relationships. This is due to the lack of annotated Flaviviridae genomes, which has gene content variation among genera. This variation makes analysis without partitioning difficult. Therefore, we developed an annotation pipeline for the genera of Flaviviridae (Flavirirus, Hepacivirus, Pegivirus, and Pestivirus, named “Fast Loci Annotation of Viruses” (FLAVi; http://flavi-web.com/), that combines ab initio and homology-based strategies. FLAVi recovered 100% of the genes in Flavivirus and Hepacivirus genomes. In Pegivirus and Pestivirus, annotation efficiency was 100% except for one partition each. There were no false positives. The combined phylogenetic analysis of multiple genes made possible by annotation has clear impacts over the tree topology compared to phylogenies that we inferred without outgroups or data partitioning. The final tree is largely congruent with previous hypotheses and adds evidence supporting the close phylogenetic relationship between dengue and Zika."
3004,Recent Progress in the Detection of Bacteria Using Bacteriophages: A Review,"Bacteria will likely become our most significant enemies of the 21st century, as we are approaching a post-antibiotic era. Bacteriophages, viruses that infect bacteria, allow us to fight infections caused by drug-resistant bacteria and create specific, cheap, and stable sensors for bacteria detection. Here, we summarize the recent developments in the field of phage-based methods for bacteria detection. We focus on works published after mid-2017. We underline the need for further advancements, especially related to lowering the detection (below 1 CFU/mL; CFU stands for colony forming units) and shortening the time of analysis (below one hour). From the application point of view, portable, cheap, and fast devices are needed, even at the expense of sensitivity."
3005,Nephrotic syndrome in The Netherlands: a population-based cohort study and a review of the literature,"Nephrotic syndrome (NS) is a clinical diagnosis with proteinuria, hypoalbuminaemia and oedema. NS is rare in children, and its incidence in The Netherlands is unknown. The aim of this study was to estimate the incidence of idiopathic NS in the Netherlands. All paediatric patients (age 0–18 years) with a newly diagnosed NS in the Netherlands were registered by the Dutch Pediatric Surveillance Unit during the years 2003 until 2006, secondary NS was excluded. All paediatricians filled out questionnaires about the first clinical findings of the patients and incidences were calculated. A literature review on incidences of childhood NS was conducted. The incidence of NS in children in the Netherlands in the years 2003 until 2006 was 1.52/ 100, 000 children/ year. The median age at diagnosis was 3.88 years with a mean age of 5.08 years. A significant male:female ratio of 2.04:1 was found. This prospective study of NS in the Netherlands revealed an incidence of 1.52:100, 000 children/year, and is similar to the incidences found all over the world."
3006,"Sighting characteristics and photo-identification of Cuvier’s beaked whales (Ziphius cavirostris) near San Clemente Island, California: a key area for beaked whales and the military?","The relationship between beaked whales and certain anthropogenic sounds remains poorly understood and of great interest. Although Cuvier’s beaked whales (Ziphius cavirostris) are widely distributed, little is known of their behavior and population structure throughout much of their range. We conducted a series of five combined visual-acoustic marine mammal surveys from 2006 to 2008 in the southern San Nicolas Basin, a site of frequent naval activity off the southern California coast, west of San Clemente Island. The study area was defined by a 1,800 km(2) array of 88 bottom-mounted hydrophones at depths up to 1,850 m. The array was used to vector visual observers toward vocalizing marine mammal species. Thirty-seven groups of Cuvier’s beaked whales were encountered during the study period. The overall encounter rate was one group for every 21.0 h of survey effort, and was as high as one group per 10.2 h of effort during the October 2007 survey. Whales were encountered in the deepest portion of the study area, at a mean bottom depth of 1,580 m (SD 138). The average group size was 3.8 individuals (SD 2.4), which was higher than has been reported from other studies of this species. Twenty-four groups were observed over multiple surfacings (median = 4 surfacings, range 2–15). The mean encounter duration of extended sightings was 104 min (SD 98, range 12–466 min) and the mean distance moved over the course of sightings was 1.66 km (SD 1.56, range 0.08–6.65 km). Temporal surfacing patterns during extended encounters were similar to dive behavior described from Cuvier’s beaked whales carrying time-depth recording tags. Seventy-eight photographic identifications were made of 58 unique individuals, for an overall resighting rate of 0.26. Whales were sighted on up to 4 days, with duration from first to last sighting spanning 2–79 days. For those whales sighted on subsequent days, the mean distance between subsequent sightings was 8.6 km (SD 7.9). Individuals resighted over 2–3 days were usually in association with previous group members. Approximately one-third of groups contained more than one adult male, and many of the repeated associations involved adult males. These observations suggest the basin west of San Clemente Island may be an important region for Cuvier’s beaked whales, and also one which affords an unusual opportunity to collect detailed data on this species. Given its status as an active military range, it can also provide the ability to monitor the behavior of individuals in the presence of naval sonar, a critical step in the management of this and other beaked whale populations worldwide."
3007,Recruitment and ontogenetic habitat shifts of the yellow snapper (Lutjanus argentiventris) in the Gulf of California,"We examined recruitment and ontogenetic habitat shifts of the yellow snapper Lutjanus argentiventris in the Gulf of California, by conducting surveys and collections in multiple mangrove sites and major marine coastal habitats from 1998 to 2007. Over 1,167 juvenile individuals were collected and 516 otoliths were aged to describe the temporal pattern of the settlement. L. argentiventris recruits in mangroves, where juveniles remain until they are approximately 100 mm in length or 300-days-old. Back-calculated settlement dates and underwater surveys indicated a major recruitment peak during September and October, around 8 days before and after the full moon. The majority of mangrove sites in the Gulf of California had a similar L. argentiventris average size at the beginning of the settlement season for the cohort of 2003; although there were significant differences in individual sizes at the end of the nursery stage. When sub-adults leave mangroves, they live in shallow rocky reefs and later become abundant in deeper rocky reefs. The density of migratory individuals (10–20 cm SL) decreased exponentially as the distance between a reef and a nearby mangrove site increased. This finding has important implications for local fishery regulations and coastal management plans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00227-009-1271-5) contains supplementary material, which is available to authorized users."
3008,Implementation and experiments for interactive lyrics transcreation system,"The evolution of the Internet has enabled us to enjoy the music created in various countries. But still, it is often difficult to understand the lyrics written in foreign languages. Professional translators have published many international songs with lyrics that fit the melody so that the ordinary people can enjoy the lyrics of such international songs. This paper discusses lyrics transcreation into the Japanese language. Also, the paper presents an interactive visual lyrics transcreation system and describes the details of its implementation. This system allows users to select temporary lyrics from a set of tentative translations and then freely modify the lyrics with a real-time visualization mechanism. We also propose a lyrics translation algorithm that solves an essential problem of lyrics translation into Japanese. In this study, we interviewed two experts regarding problems with lyrics translation and received reviews of our presented system. We also conducted preliminary experiments with 19 participants to determine the best combination of user interface components for our system. We performed additional user experiments inviting 12 participants to compare lyrics transcreation using the presented system to manual lyrics transcreation. Lyrics transcreation by the presented system brought better results against those of manual transcreation."
3009,Restoration of renal function in zebrafish models of ciliopathies,"The ciliopathies are a class of rare human genetic disease whose aetioligies lie in defective primary cilia. Typical ciliopathies include Bardet–Biedl syndrome (BBS), nephronophthisis (NPHP), Jeune, Joubert, oro-facial-digital (OFD1) and Meckel (MKS) syndromes. All ciliopathies have the common denominator of renal disease, often including tubular cysts. In this study, we have modelled a range of ciliopathies in zebrafish and shown in all cases that knocking down these genes causes cystic lesions in the kidney. We have identified two drugs, rapamycin and roscovitine, which ameliorate the renal phenotype, both morphologically and functionally. This is the first study in which zebrafish has been used to identify potential therapeutic modalities for ciliopathic renal disease, and the results pave the way for further investigations in mammalian models."
3010,"Distribution and phylogenetic analysis of Dabieshan tick virus in ticks collected from Zhoushan, China","Dabieshan tick virus (DBV) belongs to Phlebovirus and its pathogenicity to human and animals is unknown. To investigate the presence of Dabieshan tick virus in Zhoushan, 353 ticks were collected from May 2018 to October 2019. The detection result showed that the average prevalence rate among these samples was 30.3% (107 positives out of 353 samples), which means DBVs are widely distributed in tick populations in Zhoushan of China. In a phylogenetic analysis based on the nucleotide sequences of the L and S segments of the virus (ZS-DBS-2018 tick virus) in the study, it clustered with Dabieshan tick virus (KM817666.1, KM817733.1) with a 97.1% and 99.6% nucleotide identity, respectively. Further studies involving virus isolation are required to characterize Dabieshan tick virus and to expand the geographical distribution of the sampled ticks."
3011,A Novel Virus Alters Gene Expression and Vacuolar Morphology in Malassezia Cells and Induces a TLR3-Mediated Inflammatory Immune Response,"Most fungal viruses have been identified in plant pathogens, whereas the presence of viral particles in human-pathogenic fungi is less well studied. In the present study, we observed extrachromosomal double-stranded RNA (dsRNA) segments in various clinical isolates of Malassezia species. Malassezia is the most dominant fungal genus on the human skin surface, and species in this group are considered etiological factors of various skin diseases including dandruff, seborrheic dermatitis, and atopic dermatitis. We identified novel dsRNA segments, and our sequencing results revealed that the virus, named MrV40, belongs to the Totiviridae family and contains an additional satellite dsRNA segment encoding a novel protein. The transcriptome of virus-infected Malassezia restricta cells was compared to that of virus-cured cells, and the results showed that transcripts involved in ribosomal biosynthesis were downregulated and those involved in energy production and programmed cell death were upregulated. Moreover, transmission electron microscopy revealed significantly larger vacuoles in virus-infected M. restricta cells, indicating that MrV40 infection dramatically altered M. restricta physiology. Our analysis also revealed that viral nucleic acid from MrV40 induced a TLR3 (Toll-like receptor 3)-mediated inflammatory immune response in bone marrow-derived dendritic cells, suggesting that a viral element contributes to the pathogenicity of Malassezia."
3012,Dimethyl fumarate alleviates the nitroglycerin (NTG)-induced migraine in mice,"BACKGROUND: Oxidative stress and inflammatory pathways are involved in migraine and endogenous antioxidant defense system has a role in the prevention of hyperalgesia in migraine. In this study, we aimed to evaluate the role of the most pharmacologically effective molecules among the fumaric acid esters (FAEs), dimethyl fumarate, nuclear factor E2-related factor 2/antioxidant response element (Nrf-2/ARE) pathway-mediated, in regulating the hypersensitivity in a mouse model of nitroglycerine (NTG)-induced migraine. METHODS: Mice were orally administered with DMF at the doses of 10, 30, and 100 mg/kg, 5 min after NTG intraperitoneal injections. We performed histological and molecular analysis on the whole brain and behavioral tests after 4 h by NTG-migraine induction. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) subunit p65, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (IκBα), inducible nitrite oxide synthase (iNOS), cyclooxygenase 2 (COX-2), Nrf-2, manganese superoxide dismutase (Mn-SOD), and heme-oxygenase-1 (HO-1) were detected by Western blot. Tail flick, hot plate, orofacial formalin, and photophobia tests were used to evaluate migraine-like pain and migraine-related light sensitivity. Moreover, we evaluate Nrf-2-dependent mechanism by the in vitro stimulation of cells extracted by trigeminal ganglia with diethylenetriamine/nitric oxide (DETA/NO), a nitric oxide (NO) donor. The cells were pre-treated with DMF and an antagonist of Nrf-2, trigonelline (TR) 2 h before DETA/NO stimulation. RESULTS: DMF treatment notably reduced histological damage as showed by cresyl violet staining; also, regulating both NF-κB and Nrf-2 pathway, DMF treatment decreased the severity of inflammation and increased the protective antioxidant action. Moreover, the headache was significantly reduced. The protective effect of DMF treatment, via Nrf-2, was confirmed in in vitro studies, through inhibition of Nrf-2 by trigonelline. Cytotoxicity, iNOS, and MnSOD expression were evaluated. CONCLUSION: These results provided the evidence that DMF, by Nrf-2 modulation, has a protective effect on central sensitization induced by NTG, suggesting a new insight into the potential application of DMF as novel candidates in drug development for migraine."
3013,Methylmercury toxic mechanism related to protein degradation and chemokine transcription,"Methylmercury is an environmental pollutant that causes neurotoxicity. Recent studies have reported that the ubiquitin-proteasome system is involved in defense against methylmercury toxicity through the degradation of proteins synthesizing the pyruvate. Mitochondrial accumulation of pyruvate can enhance methylmercury toxicity. In addition, methylmercury exposure induces several immune-related chemokines, specifically in the brain, and may cause neurotoxicity. This summary highlights several molecular mechanisms of methylmercury-induced neurotoxicity."
3014,Mechanical circulatory support in refractory cardiogenic shock due to influenza virus-related myocarditis,"BACKGROUND: There is scarce evidence for mechanical circulatory support (MCS) in patients with influenza-related myocarditis complicated by refractory cardiogenic shock (rCS). We sought to investigate the impact of MCS using combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and micro-axial flow pumps (the ECMELLA concept) in influenza-related myocarditis complicated by rCS. METHODS: This is a prospective, observational analysis from the single centre HAnnover Cardiac Unloading REgistry (HACURE) from two recent epidemic influenza seasons. We analysed patients with verified influenza-associated myocarditis complicated by rCS who were admitted to our intensive care unit (ICU) on MCS. Subsequently, we performed a propensity score (PS) matched analysis to patients with acute myocardial infarction (AMI) complicated by rCS and non-ischaemic cardiomyopathy (DCM) related rCS. RESULTS: We describe a series of seven patients with rCS-complicated influenza-related myocarditis (mean age 56±10 years, 58% male, influenza A (n=2)/influenza B (n=5)). No patient had been vaccinated prior to the influenza season. MCS was provided using combined VA-ECMO and Impella micro-axial flow pump. In two patients with out-of-hospital cardiac arrest, VA-ECMO had been implanted for extracorporeal cardiopulmonary resuscitation. All patients died within 18 days of hospital admission. By PS-based comparison to patients with AMI- or DCM-related rCS and combined MCS, 30-day mortality was significantly higher in influenza-related rCS. CONCLUSION: Despite initial stabilisation with combined MCS in patients with rCS-complicated influenza-related myocarditis, the detrimental course of shock could not be stopped and all patients died. Influenza virus infection potentially critically affects other organs besides the heart, leading to irreversible end-organ damage that MCS cannot compensate for and, therefore, results in a devastating outcome."
3015,Timing of surgery after recovery from coronavirus disease 2019 (COVID-19) infection,
3016,Will there be any more classical scrapie cases in sheep in Great Britain? A modelling study to predict future cases,"The aim of this study was to apply a back-calculation model to Great Britain (GB) classical scrapie surveillance data, and use this model to estimate how many more cases might be expected, and over what time frame these cases might occur. A back-calculation model was applied to scrapie surveillance data between 2005 and 2019 to estimate the annual rate of decline of classical scrapie. This rate was then extrapolated to predict the number of future cases each year going forward. The model shows that there may be yet further cases of classical scrapie in GB. These will most likely occur in the fallen stock scheme, with approximately a 25% probability of at least 1 further scrapie positive, with a very low probability (~0.2%) of having up to three additional scrapie positives. This highlights the difficulty of completely eliminating all further cases, even in the presence of very effective control measures."
3017,Myocardial infarction evaluation from stopping time decision toward interoperable algorithmic states in reinforcement learning,"BACKGROUND: The Elliot wave principle commonly characterizes the impulsive and corrective wave trends for both financial market trends and electrocardiograms. The impulsive wave trends of electrocardiograms can annotate several wave components of heart-beats including pathological heartbeat waveforms. The stopping time inquires which ordinal element satisfies the assumed mathematical condition within a numerical set. The proposed work constitutes several algorithmic states in reinforcement learning from the stopping time decision, which determines the impulsive wave trends. Each proposed algorithmic state is applicable to any relevant algorithmic state in reinforcement learning with fully numerical explanations. Because commercial electrocardiographs still misinterpret myocardial infarctions from extraordinary electrocardiograms, a novel algorithm needs to be developed to evaluate myocardial infarctions. Moreover, differential diagnosis for right ventricle infarction is required to contraindicate a medication such as nitroglycerin. METHODS: The proposed work implements the stopping time theory to impulsive wave trend distribution. The searching process of the stopping time theory is equivalent to the actions toward algorithmic states in reinforcement learning. The state value from each algorithmic state represents the numerically deterministic annotated results from the impulsive wave trend distribution. The shape of the impulsive waveform is evaluated from the interoperable algorithmic states via least-first-power approximation and approximate entropy. The annotated electrocardiograms from the impulsive wave trend distribution utilize a structure of neural networks to approximate the isoelectric baseline amplitude value of the electrocardiograms, and detect the conditions of myocardial infarction. The annotated results from the impulsive wave trend distribution consist of another reinforcement learning environment for the evaluation of impulsive waveform direction. RESULTS: The accuracy to discern myocardial infarction was found to be 99.2754% for the data from the comma-separated value format files, and 99.3579% for those containing representative beats. The clinical dataset included 276 electrocardiograms from the comma-separated value files and 623 representative beats. CONCLUSIONS: Our study aims to support clinical interpretation on 12-channel electrocardiograms. The proposed work is suitable for a differential diagnosis under infarction in the right ventricle to avoid contraindicated medication during emergency. An impulsive waveform that is affected by myocardial infarction or the electrical direction of electrocardiography is represented as an inverse waveform."
3018,Intravenous calcium as a pressor in a swine model of hypoxic pseudo-pulseless electrical mechanical activity—a preliminary report,"BACKGROUND: Pseudo-pulseless electrical activity (pseudo-PEA) is a lifeless form of profound cardiac shock characterized by measurable cardiac mechanical activity without clinically detectable pulses. Pseudo-PEA may constitute up to 40% of reported cases of cardiac arrest. Resuscitation from pseudo-PEA is often associated with hypotension refractory to catecholamine pressors. We hypothesized that this post-resuscitation state may be associated with hypocalcemic hypotension responsive to intravenous calcium. METHODS: Using pre-existing data from our hypoxic swine pseudo-PEA model, we measured blood pressure, hemodynamics, and electrolytes. Physiological data were analyzed on a heartbeat by heartbeat basis. The midpoint of the calcium response was defined using change of curvature feature detection. Hemodynamic parameters were shifted such that the value at the midpoint was equal to zero. RESULTS: In 9 animals with refractory hypotension, we administered 37 boluses of intravenous calcium in the dosage range of 5-20 mg. Comparisons were made between the average values in the time period 40-37 s before the midpoint and 35-40 s after the midpoint. Of the 37 administered boluses, 34 manifested a change in the blood pressure, with mean aortic pressure, systolic and diastolic pressures all increasing post bolus administration. CONCLUSIONS: Administration of intravenous calcium may be associated with a pressor-like response in refractory hypotension after resuscitation from pseudo-PEA. Relative ionized hypocalcemia may cause hypotension after resuscitation from pseudo-PEA. Therapy with intravenous calcium should be further investigated in this setting."
3019,Outbreak of multi-drug-resistant (MDR) Shigella flexneri in northern Australia due to an endemic regional clone acquiring an IncFII plasmid,"Epidemiological surveillance of Shigella spp. in Australia is conducted to inform public health response. Multi-drug resistance has recently emerged as a contributing factor to sustained local transmission of Shigella spp. All data were collected as part of routine public health surveillance, and strains were whole-genome sequenced for further molecular characterisation. 108 patients with an endemic regional Shigella flexneri strain were identified between 2016 and 2019. The S. flexneri phylogroup 3 strain endemic to northern Australia acquired a multi-drug resistance conferring bla(DHA) plasmid, which has an IncFII plasmid backbone with virulence and resistance elements typically found in IncR plasmids. This is the first report of multi-drug resistance in Shigella sp. in Australia that is not associated with men who have sex with men. This strain caused an outbreak of multi-drug-resistant S. flexneri in northern Australia that disproportionality affects Aboriginal and Torres Strait Islander children. Community controlled public health action is recommended. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-020-04029-w) contains supplementary material, which is available to authorized users."
3020,Neurally adjusted ventilatory assist in acute respiratory failure: a randomized controlled trial,"PURPOSE: We hypothesized that neurally adjusted ventilatory assist (NAVA) compared to conventional lung-protective mechanical ventilation (MV) decreases duration of MV and mortality in patients with acute respiratory failure (ARF). METHODS: We carried out a multicenter, randomized, controlled trial in patients with ARF from several etiologies. Intubated patients ventilated for ≤ 5 days expected to require MV for ≥ 72 h and able to breathe spontaneously were eligible for enrollment. Eligible patients were randomly assigned based on balanced treatment assignments with a computerized randomization allocation sequence to two ventilatory strategies: (1) lung-protective MV (control group), and (2) lung-protective MV with NAVA (NAVA group). Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days (VFDs) at 28 days. Secondary outcome was all-cause hospital mortality. All analyses were done according to the intention-to-treat principle. RESULTS: Between March 2014 and October 2019, we enrolled 306 patients and randomly assigned 153 patients to the NAVA group and 153 to the control group. Median VFDs were higher in the NAVA than in the control group (22 vs. 18 days; between-group difference 4 days; 95% confidence interval [CI] 0 to 8 days; p = 0.016). At hospital discharge, 39 (25.5%) patients in the NAVA group and 47 (30.7%) patients in the control group had died (between-group difference − 5.2%, 95% CI − 15.2 to 4.8, p = 0.31). Other clinical, physiological or safety outcomes did not differ significantly between the trial groups. CONCLUSION: NAVA decreased duration of MV although it did not improve survival in ventilated patients with ARF. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06181-5) contains supplementary material, which is available to authorized users."
3021,Insulin Injection Practices in a Population of Canadians with Diabetes: An Observational Study,"INTRODUCTION: Proper insulin injection technique has demonstrated positive clinical outcomes in patients with diabetes. A Canadian-based practice reflective was undertaken to evaluate the current state of understanding of injection technique practices by patients administering insulin, and the importance physicians place on proper injection technique. METHODS: Twenty-four sites across Canada completed a practice profile survey and enrolled adult non-pregnant patients with either type 1 or type 2 diabetes injecting insulin using an insulin pen. Seven areas of proper injection technique to be evaluated were identified by the study steering committee: size of injection site, use of a skin lift, needle reuse, length of the needle, duration of the needle in the skin, injection into lipohypertrophic tissue, and applied injection force. During a scheduled visit, each patient filled out the Injection Technique Survey and the physician documented the answers via an electronic database. RESULTS: Almost all physicians surveyed agreed (96%) that proper insulin injection technique is important or very important and 80% indicated they were either completely confident or fairly confident in discussing overall insulin injection technique. All patients surveyed were making at least one insulin injection technique error within the following categories: applied injection force (76%), area size of injection site (64%), duration of pen needle in skin (61%), pen needle reuse (39%), performs a skin lift with a 4 or 5 mm needle (38%), uses a longer pen needle than required (34%), and injection of insulin into lipohypertrophic tissue (37%). CONCLUSION: Patients commonly make insulin injection errors. Patient and physician education on optimal insulin injection technique continues to be an unmet medical need for the treatment of patients with diabetes. Prospective trials examining the impact of new technology, diabetes educational teams, and e-learning as educational interventions are potential avenues to explore in future studies to support improved insulin injection technique. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-020-00913-y) contains supplementary material, which is available to authorized users."
3022,Ultrasonographic assessment of parasternal intercostal muscles during mechanical ventilation,"Although mechanical ventilation is a lifesaving treatment, abundant evidence indicates that its prolonged use (1 week or more) promotes respiratory muscle weakness due to both contractile dysfunction and atrophy. Along with the diaphragm, the intercostal muscles are one of the most important groups of respiratory muscles. In recent years, muscular ultrasound has become a useful bedside tool for the clinician to identify patients with respiratory muscle dysfunction related to critical illness and/or invasive mechanical ventilation. Images obtained over the course of illness can document changes in muscle dimension and can be used to estimate changes in function. Recent evidence suggests the clinical usefulness of ultrasound imaging in the assessment of intercostal muscle function. In this narrative review, we summarize the current literature on ultrasound imaging of the parasternal intercostal muscles as used to assess the extent of muscle activation and muscle weakness and its potential impact during discontinuation of mechanical ventilation. In addition, we proposed a practical flowchart based on recent evidence and experience of our group that can be applied during the weaning phase. This approach integrates multiple predictive parameters of weaning success with respiratory muscle ultrasound."
3023,"Cessation of breastfeeding and associated factors in the era of elimination of mother to child transmission of HIV at Ndejje health center, Uganda: a retrospective cohort study","BACKGROUND: Breastfeeding an infant exposed to Human Immunodeficiency Virus (HIV) carries the risk of HIV acquisition whilst not breastfeeding poses a higher risk of death from malnutrition, diarrhea, and pneumonia. In Uganda, mothers living with HIV are encouraged to discontinue breastfeeding at 12 months but data are limited. We examined the frequency and factors associated with cessation of breastfeeding at 1 year among mothers living with HIV at Ndejje Health Center IV, a large peri-urban health facility in Uganda. METHODS: This retrospective cohort study involved all mothers living with HIV and enrolled in HIV care for ≥12 months between June 2014 and June 2018. We abstracted data from registers, held focus group discussions with mothers living with HIV and key informant interviews with healthcare providers. Cessation of breastfeeding was defined as the proportion of mothers living with HIV who had discontinued breastfeeding at 1 year. We summarized quantitative data descriptively, tested differences in outcome using Chi-square and t - tests, and established independently associated factors using modified Poisson regression analysis at 5% statistical significance level. We thematically analyzed qualitative data to enrich and triangulate the quantitative results. RESULTS: Of 235 participants, 150 (63.8%) had ceased breastfeeding at 1 year and this was independently associated with the infant being male (Adjusted Risk Ratio [aRR] 1.25, 95% confidence interval [CI] 1.04, 1.50), the mother being multiparous (aRR 1.26, 95% CI 1.04–1.53), and the initiation of breastfeeding being on the same-day as birth (aRR 0.06, 95% CI 0.01–0.41). The reasons for ceasing breastfeeding included male infants over breastfeed than females, maternal literacy and knowledge adequacy about breastfeeding, support and reminders from the partner, and boys can bite once they get teeth. CONCLUSION: Suboptimal proportion of infants were ceased from breastfeeding at 1 year and this might increase the risk of mother to child transmission of HIV. Cessation of breastfeeding was more likely among male infants and multiparous mothers but less likely when breastfeeding was initiated on the same-day as birth. Interventions to enhance cessation of breastfeeding should target none multiparous mothers and those with female infants."
3024,A limbic circuit selectively links active escape to food suppression,"Stress has pleiotropic physiologic effects, but the neural circuits linking stress to these responses are not well understood. Here, we describe a novel population of lateral septum neurons expressing neurotensin (LS(Nts)) in mice that are selectively tuned to specific types of stress. LS(Nts) neurons increase their activity during active escape, responding to stress when flight is a viable option, but not when associated with freezing or immobility. Chemogenetic activation of LS(Nts) neurons decreases food intake and body weight, without altering locomotion and anxiety. LS(Nts) neurons co-express several molecules including Glp1r (glucagon-like peptide one receptor) and manipulations of Glp1r signaling in the LS recapitulates the behavioral effects of LS(Nts) activation. Activation of LS(Nts) terminals in the lateral hypothalamus (LH) also decreases food intake. These results show that LS(Nts) neurons are selectively tuned to active escape stress and can reduce food consumption via effects on hypothalamic pathways."
3025,Predicting the treatment response of certolizumab for individual adult patients with rheumatoid arthritis: protocol for an individual participant data meta-analysis,"BACKGROUND: A model that can predict treatment response for a patient with specific baseline characteristics would help decision-making in personalized medicine. The aim of the study is to develop such a model in the treatment of rheumatoid arthritis (RA) patients who receive certolizumab (CTZ) plus methotrexate (MTX) therapy, using individual participant data meta-analysis (IPD-MA). METHODS: We will search Cochrane CENTRAL, PubMed, and Scopus as well as clinical trial registries, drug regulatory agency reports, and the pharmaceutical company websites from their inception onwards to obtain randomized controlled trials (RCTs) investigating CTZ plus MTX compared with MTX alone in treating RA. We will request the individual-level data of these trials from an independent platform (http://vivli.org). The primary outcome is efficacy defined as achieving either remission (based on ACR-EULAR Boolean or index-based remission definition) or low disease activity (based on either of the validated composite disease activity measures). The secondary outcomes include ACR50 (50% improvement based on ACR core set variables) and adverse events. We will use a two-stage approach to develop the prediction model. First, we will construct a risk model for the outcomes via logistic regression to estimate the baseline risk scores. We will include baseline demographic, clinical, and biochemical features as covariates for this model. Next, we will develop a meta-regression model for treatment effects, in which the stage 1 risk score will be used both as a prognostic factor and as an effect modifier. We will calculate the probability of having the outcome for a new patient based on the model, which will allow estimation of the absolute and relative treatment effect. We will use R for our analyses, except for the second stage which will be performed in a Bayesian setting using R2Jags. DISCUSSION: This is a study protocol for developing a model to predict treatment response for RA patients receiving CTZ plus MTX in comparison with MTX alone, using a two-stage approach based on IPD-MA. The study will use a new modeling approach, which aims at retaining the statistical power. The model may help clinicians individualize treatment for particular patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number pending (ID#157595)."
3026,A multi-omics supervised autoencoder for pan-cancer clinical outcome endpoints prediction,"BACKGROUND: With the rapid development of sequencing technologies, collecting diverse types of cancer omics data become more cost-effective. Many computational methods attempted to represent and fuse multiple omics into a comprehensive view of cancer. However, different types of omics are related and heterogeneous. Most of the existing methods do not consider the difference between omics, so the biological knowledge of individual omics may not be fully excavated. And for a given task (e.g. predicting overall survival), these methods prefer to use sample similarity or domain knowledge to learn a more reasonable representation of omics, but it’s not enough. METHODS: For the purpose of learning more useful representation for individual omics and fusing them to improve the prediction ability, we proposed an autoencoder-based method named MOSAE (Multi-omics Supervised Autoencoder). In our method, a specific autoencoder were designed for each omics according to their size of dimension to generate omics-specific representations. Then, a supervised autoencoder was constructed based on specific autoencoder by using labels to enforce each specific autoencoder to learn both omics-specific and task-specific representations. Finally, representations of different omics that generate from supervised autoencoders were fused in a traditional but powerful way, and the fused representation was used for subsequent predictive tasks. RESULTS: We applied our method over TCGA Pan-Cancer dataset to predict four different clinical outcome endpoints (OS, PFI, DFI, and DSS). Compared with traditional and state-of-the-art methods, MOSAE achieved better predictive performance. We also tested the effects of each improvement, which all have a positive effect on predictive performance. CONCLUSIONS: Predicting clinical outcome endpoints are very important for precision medicine and personalized medicine. And multi-omics fusion is an effective way to solve this problem. MOSAE is a powerful multi-omics fusion method, which can generate both omics-specific and task-specific representation for given endpoint predictive tasks and improve the predictive performance."
3027,Hepatitis a virus infection in Central-West Tunisia: an age structured model of transmission and vaccination impact,"BACKGROUND: The epidemiological pattern of hepatitis A infection has shown dynamic changes in many parts of the world due to improved socio-economic conditions and the accumulation of seronegative subjects, which leads to possible outbreaks and increased morbidity rate. In Tunisia, the epidemiological status of hepatits A virus is currently unknown. However, over the past years higher numbers of symptomatic hepatitis A virus infection in school attendants and several outbreaks were reported to the Ministry of Health, especially from regions with the lowest socio-economic levels in the country. The aim of this study was to investigate the current seroprevalence of hepatitis A virus antibodies in central-west Tunisia and assess the impact of hepatitis A virus vaccination on hepatitis A epidemiology. METHODS: Serum samples from 1379 individuals, aged 5–75 years, were screened for hepatitis A virus antibodies. Adjusted seroprevalence, incidence and force of infection parameters were estimated by a linear age structured SEIR (Susceptible-Exposed-Infectious-Recovered) compartmental model. A vaccine model was then constructed to assess the impact on hepatitis A virus epidemiology of 3 scenarios of vaccination strategies: one dose at 12-months of age, one dose at 6-years and one dose at 12-months and another at 6-years of age during 6 years. RESULTS: A rapid increase in anti-hepatitis A virus seroprevalence was noted during infancy and adolescence: 47% of subjects under 10-years-old are infected; the prevalence increases to 77% at 15-years and reaches 97% in subjects aged 30-years. The force of infection is highest between 10 and 30-years of age and the incidence declines with increasing age. The vaccine model showed that the 3-scenarios lead to a significant reduction of the fraction of susceptibles. The two doses scenario gives the best results. Single-dose vaccination at 6-years of age provides more rapid decrease of disease burden in school-aged children, as compared to single-dose vaccination at 12-months, but keeps with a non-negligible fraction of susceptibles among children < 6-years. CONCLUSIONS: Our study confirms the epidemiological switch from high to intermediate endemicity of hepatitis A virus in Tunisia and provides models that may help undertake best decisions in terms of vaccinations strategies."
3028,Long-read-based human genomic structural variation detection with cuteSV,"Long-read sequencing is promising for the comprehensive discovery of structural variations (SVs). However, it is still non-trivial to achieve high yields and performance simultaneously due to the complex SV signatures implied by noisy long reads. We propose cuteSV, a sensitive, fast, and scalable long-read-based SV detection approach. cuteSV uses tailored methods to collect the signatures of various types of SVs and employs a clustering-and-refinement method to implement sensitive SV detection. Benchmarks on simulated and real long-read sequencing datasets demonstrate that cuteSV has higher yields and scaling performance than state-of-the-art tools. cuteSV is available at https://github.com/tjiangHIT/cuteSV."
3029,Designing a novel hybrid healthcare teleconsultation network: a benchtop study of telepathology in Iran and a systematic review,"BACKGROUND: Growing demand for medical services has increased patient waiting time due to the limited number or unbalanced distribution of healthcare centers. Healthcare teleconsultation networks are one of the potentially powerful systems to overcome this problem. Medical pathology can hugely benefit from teleconsultation networks because having second opinions is precious for many cases; however, resource planning (i.e., assignment and distribution of pathology consultation requests) is challenging due to bulky medical images of patients. This results in high setup and operational costs. The aim of this study is to design an optimal teleconsultation network for pathology labs under the supervision of medical sciences universities in Tehran, Iran. METHODS: To avoid the setup cost, we first propose a modified hybrid peer-to-peer (P2P) overlay architecture for our telepathology network, using Iran’s National Healthcare Information Network (SHAMS) as the underlying infrastructure. Then we apply optimization techniques to solve the request assignment and distribution problems in the network. Finally, we present a novel mathematical model with the objective of minimizing the variable operational costs of the system. RESULTS: The efficiency of the proposed method was evaluated by a set of practical-sized network instances simulated based on the characteristics of SHAMS. The results show that the presented model and architecture can obtain optimal solutions for network instances up to 350 nodes, which covers our target network. CONCLUSIONS: We believe that the proposed method can be beneficial for designing large-scale medical teleconsultation networks by adjusting the constraints according to the rules and conditions of each country. Our findings showed that teleconsultation networks in countries with strong information technology (IT) infrastructures are under the influence of consultation fees, while in countries with weak IT infrastructure, the transmission costs are more critical. To the best of our knowledge, no research has so far addressed resource planning in medical teleconsultation networks using optimization techniques. Besides, the target network, i.e., pathology labs under the supervision of medical sciences universities in Tehran and the SHAMS network, are discussed for the first time in this work."
3030,Improved RIDIT statistic approach provides more intuitive and informative interpretation of EQ-5D data,"BACKGROUND: EQ-5D is generic measure of health-related quality of life. Studies using EQ-5D generate ordinal data that are interpreted as categories ordered by severity. New analytic approaches taking into account the ordinal nature of the health dimension severity and leading to a better interpretation of EQ-5D data are needed to better elucidate differences in health-related quality of life. We propose utilizing the Improved RIDIT statistical method to analyze EQ-5D outcomes. METHODS: 556 Moroccan participants aged over 18 years representing four chronic diseases: back pain (n = 158), renal insufficiency (n = 56), diabetes (n = 82) or hypertension (n = 80) and healthy subjects (n = 180). All participants received the two EQ-5D versions. Two other published data sets were included. The first was extracted from a diabetic Spain study and the second was extracted from a clinical trial study. The Improved RIDIT analyses were carried out using an R statistic program we developed. RESULTS: Applying the Improved RIDIT on the EQ-5D data allowed estimating for the first time the ordinal odds, the Absolute Risk Reduction (ARR) or the Absolute Risk Increase (ARI) and the Number Needed to Treat. The ARI values estimated for Moroccan patients showed that (i) hypertension increased anxiety/depression by 66% and reduced mobility by 65%; (ii) back pain increased pain/discomfort by 69%; (iii) renal insufficiency impacts mobility (ARI = 57%, odds(ordinal) = 9.95) and usual activities (ARI = 44%, odds(ordinal) = 6.41) and (iv) diabetes acts only on anxiety/depression (ARI = 50%, odds(ordinal) = 4.8). Also, we demonstrated that the approach works well in clinical trials. CONCLUSIONS: Improved RIDIT provides more intuitive and informative interpretation of the EQ-5D data by (1) taking into account the level severity; estimating (2) the odds ordinal, (3) the ARR/ARI and the NNT; (4) analyzing the five dimensions of the EQ-5D separately, which gives clinical teams more precision in understanding the treatment/pathology impacts on the health status and completes the EQ-5D data analysis based on score utilities."
3031,Thrombomodulin facilitates peripheral nerve regeneration through regulating M1/M2 switching,"BACKGROUND: Excessive inflammation within damaged tissue usually leads to delayed or insufficient regeneration, and nerves in the peripheral nervous system (PNS) generally do not recover fully following damage. Consequently, there is growing interest in whether modulation of the inflammatory response could help to promote nerve regeneration in the PNS. However, to date, there are no practical therapeutic strategies for manipulating inflammation after nerve injury. Thrombomodulin (TM) is a transmembrane glycoprotein containing five domains. The lectin-like domain of TM has the ability to suppress the inflammatory response. However, whether TM can modulate inflammation in the PNS during nerve regeneration has yet to be elucidated. METHODS: We investigated the role of TM in switching proinflammatory type 1 macrophages (M1) to anti-inflammatory type 2 macrophages (M2) in a human monocytic cell line (THP-1) and evaluated the therapeutic application of TM in transected sciatic nerve injury in rats. RESULTS: The administration of TM during M1 induction significantly reduced the expression levels of inflammatory cytokines, including TNF-a (p < 0.05), IL-6 (p < 0.05), and CD86 (p < 0.05), in THP-1 cells. Simultaneously, the expression levels of M2 markers, including IL-10 (p < 0.05) and CD206 (p < 0.05), were significantly increased in TM-treated THP-1 cells. Inhibition of IL-4R-c-Myc-pSTAT6-PPARγ signaling abolished the expression levels of IL-10 (p < 0.05) and CD206 (p < 0.05). The conditioned medium (CM) collected from M1 cells triggered an inflammatory response in primary Schwann cells, while CM collected from M1 cells treated with TM resulted in a dose-dependent reduction in inflammation. TM treatment led to better nerve regeneration when tested 6 weeks after injury and preserved effector muscle function. In addition, TM treatment reduced macrophage infiltration at the site of injury and led to potent M1 to M2 transition, thus indicating the anti-inflammatory capacity of TM. CONCLUSIONS: Collectively, our findings demonstrate the anti-inflammatory role of TM during nerve regeneration. Therefore, TM represents a potential drug for the promotion and modulation of functional recovery in peripheral nerves that acts by regulating the M1/M2 ratio."
3032,A semi-supervised approach for extracting TCM clinical terms based on feature words,"BACKGROUND: A semi-supervised model is proposed for extracting clinical terms of Traditional Chinese Medicine using feature words. METHODS: The extraction model is based on BiLSTM-CRF and combined with semi-supervised learning and feature word set, which reduces the cost of manual annotation and leverage extraction results. RESULTS: Experiment results show that the proposed model improves the extraction of five types of TCM clinical terms, including traditional Chinese medicine, symptoms, patterns, diseases and formulas. The best F1-value of the experiment reaches 78.70% on the test dataset. CONCLUSIONS: This method can reduce the cost of manual labeling and improve the result in the NER research of TCM clinical terms."
3033,"Characterization and genomic analysis of a diesel-degrading bacterium, Acinetobacter calcoaceticus CA16, isolated from Canadian soil","BACKGROUND: With the high demand for diesel across the world, environmental decontamination from its improper usage, storage and accidental spills becomes necessary. One highly environmentally friendly and cost-effective decontamination method is to utilize diesel-degrading microbes as a means for bioremediation. Here, we present a newly isolated and identified strain of Acinetobacter calcoaceticus (‘CA16’) as a candidate for the bioremediation of diesel-contaminated areas. RESULTS: Acinetobacter calcoaceticus CA16 was able to survive and grow in minimal medium with diesel as the only source of carbon. We determined through metabolomics that A. calcoaceticus CA16 appears to be efficient at diesel degradation. Specifically, CA16 is able to degrade 82 to 92% of aliphatic alkane hydrocarbons (C(n)H(n + 2); where n = 12–18) in 28 days. Several diesel-degrading genes (such as alkM and xcpR) that are present in other microbes were also found to be activated in CA16. CONCLUSIONS: The results presented here suggest that Acinetobacter strain CA16 has good potential in the bioremediation of diesel-polluted environments."
3034,Simulating transmission of ESKAPE pathogens plus C. difficile in relevant clinical scenarios,"BACKGROUND: The prevalence of healthcare-acquired infections (HAI) and rising levels of antimicrobial resistance places significant economic and public health burdens on modern healthcare systems. A group of highly drug resistant pathogens known as the ESKAPE pathogens, along with C. difficile, are the leading causes of HAIs. Interactions between patients, healthcare workers, and environmental conditions impact disease transmission. Studying pathogen transfer under varying contact scenarios in a controlled manner is critical for understanding transmission and disinfectant strategies. In lieu of human subject research, this method has the potential to contribute to modeling the routes of pathogen transmission in healthcare settings. METHODS: To overcome these challenges, we have developed a method that utilizes a synthetic skin surrogate to model both direct (skin-to-skin) and indirect (skin-to fomite-to skin) pathogen transfer between infected patients and healthy healthcare workers. This surrogate material includes a background microbiome community simulating typical human skin flora to more accurately mimic the effects of natural flora during transmission events. RESULTS: We demonstrate the ability to modulate individual bacterial concentrations within this microbial community to mimic bacterial concentrations previously reported on the hands of human subjects. We also explore the effect of various decontamination approaches on pathogen transfer between human subjects, such as the use of handwashing or surface disinfectants. Using this method, we identify a potential outlier, S. aureus, that may persist and retain viability in specific transfer conditions better than the overall microbial community during decontamination events. CONCLUSIONS: Our work describes the development of an in vitro method that uses a synthetic skin surrogate with a defined background microbiota to simulate skin-to-skin and skin-to fomite-to skin contact scenarios. These results illustrate the value of simulating a holistic microbial community for transfer studies by elucidating differences in different pathogen transmission rates and resistance to common decontamination practices. We believe this method will contribute to improvements in pathogen transmission modeling in healthcare settings and increase our ability to assess the risk associated with HAIs, although additional research is required to establish the degree of correlation of pathogen transmission by skin or synthetic alternatives."
3035,The psychosis analysis in real-world on a cohort of large-scale patients with schizophrenia,"BACKGROUND: With China experiencing unprecedented economic development and social change over the past three decades, Chinese policy makers and health care professionals have come to view mental health as an important outcome to monitor. Our study conducted an epidemiological study of psychosis in Guangdong province, with 20 million real-world follow-up records in the last decade. METHODS: Data was collected from Guangdong mental health information platform from 2010 to 2019, which had standardized disease registration and follow-up management for nearly 600,000 patients with six categories of mental diseases and 400,000 patients with schizophrenia. We conducted clinical staging for the disease course of the patients and divided the data with various factors into different stages of disease. Quantitative analysis was utilized to investigate the high relevant indicators to the disease. The results were projected on geography map for regional distribution analysis. RESULTS: The majority cases of mental disease incidence were between the age of 15 and 29, while the peak age for both male and female was between 20 to 24 years old. The disease course with the largest number of patients’ cases was between 5 to 10 years. The therapeutic effect of patients gradually decreased with the development of disease course, while the risk increased with the disease course. The analysis of influencing factors showed that poor economic conditions incurred higher risk scores, and good medication adherence was effective in improving treatment outcomes. In addition, receiving good education contributed to the reduction of the risk of schizophrenia and the improvement of the efficiency of early treatment. Through the analysis of regional distribution of schizophrenia disease, developed economic conditions and favorable resource conditions could promote the reduction of disease risk, while in economically backward regions, it often accompanied with lower therapeutic effect and higher disease risk. CONCLUSIONS: Certain demographic factors had a relatively prominent impact on the therapeutic effect and risk of schizophrenia, such as high-quality medication adherence. Therapeutic effect and risk were highly correlated. Backward economic conditions often associated with poor efficacy and higher risk assessment, and the developed economy and better medical resource are beneficial for the treatment of psychotic."
3036,Simulation-based assessment of model selection criteria during the application of benchmark dose method to quantal response data,"BACKGROUND: To employ the benchmark dose (BMD) method in toxicological risk assessment, it is critical to understand how the BMD lower bound for reference dose calculation is selected following statistical fitting procedures of multiple mathematical models. The purpose of this study was to compare the performances of various combinations of model exclusion and selection criteria for quantal response data. METHODS: Simulation-based evaluation of model exclusion and selection processes was conducted by comparing validity, reliability, and other model performance parameters. Three different empirical datasets for different chemical substances were analyzed for the assessment, each having different characteristics of the dose-response pattern (i.e. datasets with rich information in high or low response rates, or approximately linear dose-response patterns). RESULTS: The best performing criteria of model exclusion and selection were different across the different datasets. Model averaging over the three models with the lowest three AIC (Akaike information criteria) values (MA-3) did not produce the worst performance, and MA-3 without model exclusion produced the best results among the model averaging. Model exclusion including the use of the Kolmogorov-Smirnov test in advance of model selection did not necessarily improve the validity and reliability of the models. CONCLUSIONS: If a uniform methodological suggestion for the guideline is required to choose the best performing model for exclusion and selection, our results indicate that using MA-3 is the recommended option whenever applicable."
3037,High-yield expression of recombinant soybean agglutinin in plants using transient and stable systems,"Soybean agglutinin (SBA) is a specific N-acetylgalactosamine-binding plant lectin that can agglutinate a wide variety of cells. SBA has great potential for medical and biotechnology-focused applications, including screening and treatment of breast cancer, isolation of fetal cells from maternal blood for genetic screening, the possibility as a carrier system for oral drug delivery, and utilization as an affinity tag for high-quality purification of tagged proteins. The success of these applications, to a large degree, critically depends on the development of a highly efficient expression system for a source of recombinant SBA (rSBA). Here, we demonstrate the utility of transient and stable expression systems in Nicotiana benthamiana and potato, respectively, for the production of rSBA, with the transgenic protein accumulated to 4% of total soluble protein (TSP) in Nicotiana benthamiana leaves and 0.3% of TSP in potato tubers. Furthermore, we show that both plant-derived rSBAs retain their ability to induce the agglutination of red blood cells, are similarly glycosylated when compared with native SBA, retained their binding specificity for N-acetylgalactosamine, and were highly resistant to degradation in simulated gastric and intestinal fluids. Affinity column purification using N-acetylgalactosamine as a specific ligand resulted in high recovery and purity of rSBA. This work is the first step toward use of rSBA for various new applications, including the development of rSBA as a novel affinity tag for simplified purification of tagged proteins and as a new carrier molecule for delivery of oral drugs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11248-010-9419-0) contains supplementary material, which is available to authorized users."
3038,The role of vegetative cell fusions in the development and asexual reproduction of the wheat fungal pathogen Zymoseptoria tritici,"BACKGROUND: The ability of fungal cells to undergo cell-to-cell communication and anastomosis, the process of vegetative hyphal fusion, allows them to maximize their overall fitness. Previous studies in a number of fungal species have identified the requirement of several signaling pathways for anastomosis, including the so far best characterized soft (So) gene, and the MAPK pathway components MAK-1 and MAK-2 of Neurospora crassa. Despite the observations of hyphal fusions’ involvement in pathogenicity and host adhesion, the connection between cell fusion and fungal lifestyles is still unclear. Here, we address the role of anastomosis in fungal development and asexual reproduction in Zymoseptoria tritici, the most important fungal pathogen of wheat in Europe. RESULTS: We show that Z. tritici undergoes self-fusion between distinct cellular structures, and its mechanism is dependent on the initial cell density. Contrary to other fungi, cell fusion in Z. tritici only resulted in cytoplasmic mixing but not in multinucleated cell formation. The deletion of the So orthologous ZtSof1 disrupted cell-to-cell communication affecting both hyphal and germling fusion. We show that Z. tritici mutants for MAPK-encoding ZtSlt2 (orthologous to MAK-1) and ZtFus3 (orthologous to MAK-2) genes also failed to undergo anastomosis, demonstrating the functional conservation of this signaling mechanism across species. Additionally, the ΔZtSof1 mutant was severely impaired in melanization, suggesting that the So gene function is related to melanization. Finally, we demonstrated that anastomosis is dispensable for pathogenicity, but essential for the pycnidium development, and its absence abolishes the asexual reproduction of Z. tritici. CONCLUSIONS: We demonstrate the role for ZtSof1, ZtSlt2, and ZtFus3 in cell fusions of Z. tritici. Cell fusions are essential for different aspects of the Z. tritici biology, and the ZtSof1 gene is a potential target to control septoria tritici blotch (STB) disease."
3039,MCC-SP: a powerful integration method for identification of causal pathways from genetic variants to complex disease,"BACKGROUND: Genome-wide association studies (GWAS) have successfully identified genetic susceptible variants for complex diseases. However, the underlying mechanism of such association remains largely unknown. Most disease-associated genetic variants have been shown to reside in noncoding regions, leading to the hypothesis that regulation of gene expression may be the primary biological mechanism. Current methods to characterize gene expression mediating the effect of genetic variant on diseases, often analyzed one gene at a time and ignored the network structure. The impact of genetic variant can propagate to other genes along the links in the network, then to the final disease. There could be multiple pathways from the genetic variant to the final disease, with each having the chain structure since the first node is one specific SNP (Single Nucleotide Polymorphism) variant and the end is disease outcome. One key but inadequately addressed question is how to measure the between-node connection strength and rank the effects of such chain-type pathways, which can provide statistical evidence to give the priority of some pathways for potential drug development in a cost-effective manner. RESULTS: We first introduce the maximal correlation coefficient (MCC) to represent the between-node connection, and then integrate MCC with K shortest paths algorithm to rank and identify the potential pathways from genetic variant to disease. The pathway importance score (PIS) was further provided to quantify the importance of each pathway. We termed this method as “MCC-SP”. Various simulations are conducted to illustrate MCC is a better measurement of the between-node connection strength than other quantities including Pearson correlation, Spearman correlation, distance correlation, mutual information, and maximal information coefficient. Finally, we applied MCC-SP to analyze one real dataset from the Religious Orders Study and the Memory and Aging Project, and successfully detected 2 typical pathways from APOE genotype to Alzheimer’s disease (AD) through gene expression enriched in Alzheimer’s disease pathway. CONCLUSIONS: MCC-SP has powerful and robust performance in identifying the pathway(s) from the genetic variant to the disease. The source code of MCC-SP is freely available at GitHub (https://github.com/zhuyuchen95/ADnet)."
3040,"Frequency of congenital cytomegalovirus infections in newborns in the Sao Paulo State, 2010-2018","Human cytomegalovirus (HCMV) infections remain a neglected public health issue. The aim of the present study was to evaluate the frequency of HCMV congenital infections in newborns up to 1 month in the Sao Paulo State, from 2010 to 2018. The molecular characterization of HCMV-positive samples was also undertaken. Urine samples from 275 potential congenital HCMV-infected patients were tested by real-time Polymerase Chain Reaction (qPCR). HCMV-positive samples were amplified by conventional PCR targeting the UL89 gene, sequenced and searched for mutations. A total of 32 (11.6%) positive-HCMV cases were detected (mean Ct 30.59); mean and median age of 10.3 and 6 days old, respectively. Children aged between 0-3 weeks had higher HCMV detection rates (84.4%; 27/32). UL89 gene was successfully sequenced in two samples, both classified as the human betaherpesvirus 5. No described resistance-associated mutations were identified. A routine screening in newborns coupled with the genetic characterization of key viral genes is vital to decrease sequels associated with congenital HCMV infections."
3041,Effects and safety of tanreqing injection on viral pneumonia: A protocol for systematic review and meta-analysis,"BACKGROUND: Viral pneumonia is a common respiratory disease that leads to high mortality around the world. Tanreqing (TRQ) injection has been widely used to treat viral pneumonia in China. However, the efficiency and safety of TRQ injection for viral pneumonia have not been scientifically and methodically evaluated up to now. Thus, this protocol describes a plan of performing a systematic review and meta-analysis to evaluate the efficacy and safety of TRQ injection on patients with viral pneumonia. METHODS: Only randomized controlled trials will be enrolled in our study, and we will search eligible studies in the following electronic databases: PubMed, Embase, Cochrane Central Register of Controlled Trials, Clinical Trials, China National Knowledge Infrastructure, the Wanfang database, the Chinese Scientific Journal Database, and the Sinomed. The total effective rate of clinical efficacy will be used as primary outcome. Time to relieve symptoms, incidence of adverse reactions, and the laboratory parameters will be used as secondary outcomes. Any side effects and adverse events will be recorded and assessed as safety outcomes. Study inclusion, data extraction, and quality assessment will be performed independently by 2 reviewers, and any disagreement will be resolved by a third reviewer. After that, data synthesis and subgroup analysis will be conducted with the Review Manager V.5.3.3 software. RESULTS: This review will provide a high-quality synthesis to assess the effectiveness and safety of TRQ injection for viral pneumonia patients. CONCLUSION: Our study will provide comprehensive evidence to decide whether TRQ injection is effective and safe for viral pneumonia patients. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42020164164"
3042,A comparison of COVID-19 mortality rates between European and Asian States,
3043,Metabolic Dysregulation in Idiopathic Pulmonary Fibrosis,"Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disorder limited to the lung. New findings, starting from our proteomics studies on IPF, suggest that systemic involvement with altered molecular mechanisms and metabolic disorder is an underlying cause of fibrosis. The role of metabolic dysregulation in the pathogenesis of IPF has not been extensively studied, despite a recent surge of interest. In particular, our studies on bronchoalveolar lavage fluid have shown that the renin–angiotensin–aldosterone system (RAAS), the hypoxia/oxidative stress response, and changes in iron and lipid metabolism are involved in onset of IPF. These processes appear to interact in an intricate manner and to be related to different fibrosing pathologies not directly linked to the lung environment. The disordered metabolism of carbohydrates, lipids, proteins and hormones has been documented in lung, liver, and kidney fibrosis. Correcting these metabolic alterations may offer a new strategy for treating fibrosis. This paper focuses on the role of metabolic dysregulation in the pathogenesis of IPF and is a continuation of our previous studies, investigating metabolic dysregulation as a new target for fibrosis therapy."
3044,Naturally-Occurring Alkaloids of Plant Origin as Potential Antimicrobials against Antibiotic-Resistant Infections,"Antibiotic resistance is now considered a worldwide problem that puts public health at risk. The onset of bacterial strains resistant to conventional antibiotics and the scarcity of new drugs have prompted scientific research to re-evaluate natural products as molecules with high biological and chemical potential. A class of natural compounds of significant importance is represented by alkaloids derived from higher plants. In this review, we have collected data obtained from various research groups on the antimicrobial activities of these alkaloids against conventional antibiotic-resistant strains. In addition, the structure–function relationship was described and commented on, highlighting the high potential of alkaloids as antimicrobials."
3045,Should Networks Supplant Tree Building?,"Recent studies suggested that network methods should supplant tree building as the basis of genealogical analysis. This proposition is based upon two arguments. First is the observation that bacterial and archaeal lineages experience processes oppositional to bifurcation and hence the representation of the evolutionary process in a tree like structure is illogical. Second is the argument tree building approaches are circular—you ask for a tree and you get one, which pins a verificationist label on tree building that, if correct, should be the end of phylogenetic analysis as we currently know it. In this review, we examine these questions and suggest that rumors of the death of the bacterial tree of life are exaggerated at best."
3046,Antibacterial Activity of Manganese Dioxide Nanosheets by ROS-Mediated Pathways and Destroying Membrane Integrity,"Manganese dioxide (MnO(2)) nanosheets have shown exciting potential in nanomedicine because of their ultrathin thickness, large surface area, high near-infrared (NIR) absorbance and good biocompatibility. However, the effect of MnO(2) nanosheets on bacteria is still unclear. In this study, MnO(2) nanosheets were shown for the first time to possess highly efficient antibacterial activity by using Salmonella as a model pathogen. The growth curve and surface plate assay uncovered that 125 μg/mL MnO(2) nanosheets could kill 99.2% of Salmonella, which was further verified by fluorescence-based live/dead staining measurement. Mechanism analysis indicated that MnO(2) nanosheet treatment could dramatically induce reactive oxygen species production, increase ATPase activity and cause the leakage of electrolytes and protein contents, leading to bacterial death. These results uncover the previously undefined role of MnO(2) nanosheets and provide novel strategies for developing antimicrobial agents."
3047,Graphene Oxide-Linezolid Combination as Potential New Anti-Tuberculosis Treatment,"Global pandemic management represents a serious issue for health systems. In some cases, repurposing of existing medications might help find compounds that have the unexpected potential to combat microorganisms. In the same way, changing cell–drug interaction by nanotechnology could represent an innovative strategy to fight infectious diseases. Tuberculosis (TB) remains one of the most alarming worldwide infectious diseases and there is an urgent need for new drugs and treatments, particularly for the emergence and spread of drug-resistant Mycobacterium tuberculosis (Mtb) strains. New nanotechnologies based on carbon nanomaterials are now being considered to improve anti-TB treatments, and graphene oxide (GO) showed interesting properties as an anti-TB drug. GO, which preferentially accumulates in the lungs and is degraded by macrophagic peroxidases, can trap Mycobacterium smegmatis and Mtb in a dose-dependent manner, reducing the entry of bacilli into macrophages. In this paper, combinations of isoniazid (INH), amikacin (AMK) and linezolid (LZD) and GO anti-mycobacterial properties were evaluated against Mtb H37Rv by using a checkerboard assay or an in vitro infection model. Different GO effects have been observed when incubated with INH, AMK or LZD. Whereas the INH and AMK anti-mycobacterial activities were blocked by GO co-administration, the LZD bactericidal effect increased in combination with GO. GO-LZD significantly reduced extracellular mycobacteria during infection and was able to kill internalized bacilli. GO-LZD co-administration is potentially a new promising anti-TB treatment at the forefront in fighting emerging antibiotic-resistant Mtb strains where LZD administration is suggested. This innovative pharmacological approach may lead to reduced treatment periods and decreased adverse effects. More importantly, we demonstrate how nanomaterials–drugs combinations can represent a possible strategy to quickly design drugs for pandemics treatment."
3048,The effect of copartisan justice ministers on human rights in presidential democracies,"A body of literature suggests that states with independent courts are more likely to protect human rights. A recent article challenges this notion by arguing that when both the president and his or her justice minister share the same party—i.e., they are copartisans—that state is less likely to protect human rights, as justice ministers may value their loyalty to the president over their duty to enforce court decisions. In this article, I estimate government respect for human rights accounting for both copartisan justice ministers and an independent judiciary. In the end, I find copartisan justice ministers to be negatively associated with high government respect for human rights, even after controlling for judicial independence. Many constitutions already seek to ensure an independent judiciary, but if copartisan justice ministers increase the likelihood that governments repress, then perhaps constitutional engineers should also consider options that would reduce the likelihood that both the president and his or her justice minister share the same party."
3049,Sensitivity optimisation of tuberculosis bioaerosol sampling,"INTRODUCTION: Detection of Mycobacterium tuberculosis (Mtb) in patient-derived bioaerosol is a potential tool to measure source case infectiousness. However, current bioaerosol sampling approaches have reported low detection yields in sputum-positive TB cases. To increase the utility of bioaerosol sampling, we present advances in bioaerosol collection and Mtb identification that improve detection yields. METHODS: A previously described Respiratory Aerosol Sampling Chamber (RASC) protocol, or “RASC-1”, was modified to incorporate liquid collection of bioaerosol using a high-flow wet-walled cyclone (RASC-2). Individuals with GeneXpert-positive pulmonary TB were sampled pre-treatment over 60-minutes. Putative Mtb bacilli were detected in collected fluid by fluorescence microscopy utilising DMN-Trehalose. Exhaled air and bioaerosol volumes were estimated using continuous CO(2) monitoring and airborne particle counting, respectively. Mtb capture was calculated per exhaled air volume sampled and bioaerosol volume for RASC-1 (n = 35) and for RASC-2 (n = 21). Empty chamber samples were collected between patients as controls. RESULTS: The optimised RASC-2 protocol sampled a median of 258.4L (IQR: 226.9–273.6) of exhaled air per patient compared with 27.5L (IQR: 23.6–30.3) for RASC-1 (p<0.0001). Bioaerosol volume collection was estimated at 2.3nL (IQR: 1.1–3.6) for RASC-2 compared with 0.08nL (IQR: 0.05–0.10) for RASC-1 (p<0.0001). The detection yield of viable Mtb improved from 43% (median 2 CFU, range: 1–14) to 95% (median 20.5 DMN-Trehalose positive bacilli, range: 2–155). These improvements represent a lowering of the limit of detection in the RASC-2 platform to 0.9 Mtb bacilli per 100L of exhaled air from 3.3 Mtb bacilli per 100L (RASC-1). CONCLUSION: This study demonstrates that technical improvements in particle collection together with sensitive detection enable rapid quantitation of viable Mtb in bioaerosols of sputum positive TB cases. Increased sampling sensitivity may allow future TB transmission studies to be extended to sputum-negative and subclinical individuals, and suggests the potential utility of bioaerosol measurement for rapid intervention in other airborne infectious diseases."
3050,Detection of latent forms of Mycobacterium avium subsp. paratuberculosis infection using host biomarker-based ELISAs greatly improves paratuberculosis diagnostic sensitivity,"Bovine paratuberculosis (PTB) is a chronic granulomatous enteritis, caused by Mycobacterium avium subsp. paratuberculosis (MAP), responsible for important economic losses in the dairy industry. Current diagnostic methods have low sensitivities for detection of latent forms of MAP infection, defined by focal granulomatous lesions and scarce humoral response or MAP presence. In contrast, patent infections correspond to multifocal and diffuse types of enteritis where there is increased antibody production, and substantial mycobacterial load. Our previous RNA-Seq analysis allowed the selection of five candidate biomarkers overexpressed in peripheral blood of MAP infected Holstein cows with focal (ABCA13 and MMP8) and diffuse (FAM84A, SPARC and DES) lesions vs. control animals with no detectable PTB-associated lesions in intestine and regional lymph nodes. The aim of the current study was to assess the PTB diagnostic potential of commercial ELISAs designed for the specific detection of these biomarkers. The ability of these ELISAs to identify animals with latent and/or patent forms of MAP infection was investigated using serum from naturally infected cattle (n = 88) and non-infected control animals (n = 67). ROC analysis revealed that the ABCA13-based ELISA showed the highest diagnostic accuracy for the detection of infected animals with focal lesions (AUC 0.837, sensitivity 79.25% and specificity 88.06%) and with any type of histological lesion (AUC 0.793, sensitivity 69.41% and specificity 86.57%) improving on the diagnostic performance of the popular IDEXX ELISA and other conventional diagnostic methods. SPARC and MMP8 showed the highest diagnostic accuracy for the detection of animals with multifocal (AUC 0.852) and diffuse lesions (AUC 0.831), respectively. In conclusion, our results suggest that quantification of ABCA13, SPARC and MMP8 by ELISA has the potential for implementation as a diagnostic tool to reliably identify MAP infection, greatly improving early detection of MAP latent infections when antibody responses and fecal shedding are undetectable using conventional diagnostic methods."
3051,"Erratum: Vol. 69, No. 32",
3052,EDF1 coordinates cellular responses to ribosome collisions,"Translation of aberrant mRNAs induces ribosomal collisions, thereby triggering pathways for mRNA and nascent peptide degradation and ribosomal rescue. Here we use sucrose gradient fractionation combined with quantitative proteomics to systematically identify proteins associated with collided ribosomes. This approach identified Endothelial differentiation-related factor 1 (EDF1) as a novel protein recruited to collided ribosomes during translational distress. Cryo-electron microscopic analyses of EDF1 and its yeast homolog Mbf1 revealed a conserved 40S ribosomal subunit binding site at the mRNA entry channel near the collision interface. EDF1 recruits the translational repressors GIGYF2 and EIF4E2 to collided ribosomes to initiate a negative-feedback loop that prevents new ribosomes from translating defective mRNAs. Further, EDF1 regulates an immediate-early transcriptional response to ribosomal collisions. Our results uncover mechanisms through which EDF1 coordinates multiple responses of the ribosome-mediated quality control pathway and provide novel insights into the intersection of ribosome-mediated quality control with global transcriptional regulation."
3053,Metatranscriptomic Analysis of Virus Diversity in Urban Wild Birds with Paretic Disease,"Wild birds are major natural reservoirs and potential dispersers of a variety of infectious diseases. As such, it is important to determine the diversity of viruses they carry and use this information to help understand the potential risks of spillover to humans, domestic animals, and other wildlife. We investigated the potential viral causes of paresis in long-standing, but undiagnosed, disease syndromes in wild Australian birds. RNA from diseased birds was extracted and pooled based on tissue type, host species, and clinical manifestation for metagenomic sequencing. Using a bulk and unbiased metatranscriptomic approach, combined with clinical investigation and histopathology, we identified a number of novel viruses from the families Astroviridae, Adenoviridae, Picornaviridae, Polyomaviridae, Paramyxoviridae, Parvoviridae, and Circoviridae in common urban wild birds, including Australian magpies, magpie larks, pied currawongs, Australian ravens, and rainbow lorikeets. In each case, the presence of the virus was confirmed by reverse transcription (RT)-PCR. These data revealed a number of candidate viral pathogens that may contribute to coronary, skeletal muscle, vascular, and neuropathology in birds of the Corvidae and Artamidae families and neuropathology in members of the Psittaculidae. The existence of such a diverse virome in urban avian species highlights the importance and challenges in elucidating the etiology and ecology of wildlife pathogens in urban environments. This information will be increasingly important for managing disease risks and conducting surveillance for potential viral threats to wildlife, livestock, and human health. IMPORTANCE Wildlife naturally harbor a diverse array of infectious microorganisms and can be a source of novel diseases in domestic animals and human populations. Using unbiased RNA sequencing, we identified highly diverse viruses in native birds from Australian urban environments presenting with paresis. This research included the clinical investigation and description of poorly understood recurring syndromes of unknown etiology: clenched claw syndrome and black and white bird disease. As well as identifying a range of potentially disease-causing viral pathogens, this study describes methods that can effectively and efficiently characterize emergent disease syndromes in free-ranging wildlife and promotes further surveillance for specific pathogens of potential conservation and zoonotic concern."
3054,Coumarin carbonic anhydrase inhibitors from natural sources,"Coumarins constitute a relatively new class of inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), possessing a unique inhibition mechanism, acting as “prodrug inhibitors.” They undergo the hydrolysis of the lactone ring mediated by the esterase activity of CA. The formed 2-hydroxy-cinnamic acids thereafter bind within a very particular part of the enzyme active site, at its entrance, where a high variability of amino acid residues among the different mammalian CA isoforms is present, and where other inhibitors classes were not seen bound earlier. This explains why coumarins are among the most isoform-selective CA inhibitors known to date among the many chemotypes endowed with such biological activity. As coumarins are widespread secondary metabolites in some bacteria, plants, fungi, and ascidians, many such compounds from various natural sources have been investigated for their CA inhibitory properties and for possible biomedical applications, mainly as anticancer agents targeting hypoxic tumours."
3055,Ezrin is essential for the entry of Japanese encephalitis virus into the human brain microvascular endothelial cells,"Japanese encephalitis virus (JEV) remains the predominant cause of viral encephalitis worldwide. It reaches the central nervous system upon crossing the blood–brain barrier through pathogenic mechanisms that are not completely understood. Here, using a high-throughput siRNA screening assay combined with verification experiments, we found that JEV enters the primary human brain microvascular endothelial cells (HBMEC) through a caveolae-mediated endocytic pathway. The role of ezrin, an essential host factor for JEV entry based on our screening, in caveolae-mediated JEV internalization was investigated. We observed that JEV internalization in HBMEC is largely dependent on ezrin-mediated actin cytoskeleton polymerization. Moreover, Src, a protein predicted by a STRING database search, was found to be required in JEV entry. By a variety of pharmacological inhibition and immunoprecipitation assays, we found that Src, ezrin, and caveolin-1 were sequentially activated and formed a complex during JEV infection. A combination of in vitro kinase assay and subcellular analysis demonstrated that ezrin is essential for Src-caveolin-1 interactions. In vivo, both Src and ezrin inhibitors protected ICR suckling mice against JEV-induced mortality and diminished mouse brain viral load. Therefore, JEV entry into HBMEC requires the activation of the Src-ezrin-caveolin-1 signalling axis, which provides potential targets for restricting JEV infection."
3056,Platelet and Vascular Biomarkers Associate With Thrombosis and Death in Coronavirus Disease,
3057,Impact of COVID-19 on Public Mental Health and the Buffering Effect of a Sense of Coherence,"INTRODUCTION: It is claimed that the coronavirus disease 2019 (COVID-19) pandemic has had a negative impact on mental health. However, to date, prospective studies are lacking. Moreover, it is important to identify which factors modulate the stress response to the pandemic. Previously, sense of coherence (SOC) has emerged as a particularly important resistance factor. OBJECTIVE: This prospective study aimed to assess the impact of the COVID-19 outbreak on mental health and to investigate the ability of pre-outbreak SOC levels to predict changes in psychopathological symptoms. METHODS: This study assessed psychopathological symptoms and SOC before and after the COVID-19 outbreak as well as post-outbreak COVID-19-related traumatic distress in a German-speaking sample (n =1,591). Bivariate latent change score (BLCS) modeling was used to analyze pre- to post-outbreak changes in psychopathological symptoms and the ability of SOC to predict symptom changes. RESULTS: Overall, there was no change in psychopathological symptoms. However, on an individual-respondent level, 10% experienced a clinically significant increase in psychopathological symptoms and 15% met cut-off criteria for COVID-19-related traumatic distress. Using BLCS modeling, we identified a high-stress group experiencing an increase in psychopathological symptoms and a decrease in SOC and a low-stress group showing the reversed pattern. Changes in SOC and psychopathological symptoms were predicted by pre-outbreak SOC and psychopathological symptom levels. CONCLUSIONS: Although mental health was stable in most respondents, a small group of respondents characterized by low levels of SOC experienced increased psychopathological symptoms from pre- to post-outbreak. Thus, SOC training might be a promising approach to enhance the resistance to stressors."
3058,Histopathology of Parasellar Neoplasms,"The anatomical and histological complexity of the parasellar region as well as the presence of embryonic remnants determine the huge diversity of parasellar neoplasms. Some of them are only located in the parasellar region, whereas others can occur elsewhere, within or outside the central nervous system. Their spectrum ranges from histologically benign and low-grade malignant to high-grade malignant tumours. Although rare, metastases can pose differential diagnostic dilemmas. The severity of the clinical picture, the challenges of surgery and the risk of adverse sequelae related to surgery or radiotherapy make parasellar tumours interesting entities for the clinicians irrespective of their histological malignancy grade. Due to the different cell origins of parasellar tumours, the World Health Organization classification system does not categorise them as a distinct group. Detailed criteria for classification and malignancy grading are presented in the classification systems covering central nervous system tumours, haematological malignancies and tumours of the soft tissue and bone. In the last few years, molecular genetic features have been integrated into the diagnosis of several types of the parasellar tumours enhancing diagnostic accuracy and providing information of the value for targeting therapies. In this review, we will present histopathological and molecular genetic features, updated classification criteria and recent advances in the diagnostics and rationale for novel pharmacological therapies of selected types of parasellar neoplasms."
3059,Differences in Lung and Lobe Volumes between Supine and Standing Positions Scanned with Conventional and Newly Developed 320-Detector-Row Upright CT: Intra-Individual Comparison,"BACKGROUND: No clinical studies to date have compared unilateral lung or lobe volumes between the supine and standing positions. OBJECTIVES: To compare lung/lobe volumes on computed tomography (CT) between these two positions and evaluate the correlation between the total lung volume and total lung capacity (TLC) on pulmonary function tests (PFTs). METHODS: Thirty-two asymptomatic volunteers underwent both conventional CT (supine position) and upright CT (standing position), during deep inspiration breath-hold, and PFTs on the same day. We measured lung/lobe volumes on CT in each position. Paired t tests were used for statistical analysis. RESULTS: The volumes of the total lung (10.9% increase), right lung (10.3% increase), right upper lobe (8.6% increase), right lower lobe (14.6% increase), left lung (11.6% increase), left upper lobe (7.1% increase), and left lower lobe (16.0% increase) were significantly greater in the standing position than in the supine position (all p < 0.0001). The right middle lobe volume was similar between the two positions (p = 0.16). Intraclass correlation coefficients for agreement between total lung volumes on CT in the supine/standing positions and the TLC on PFT were 0.891/0.938, respectively. CONCLUSIONS: While the volumes of the bilateral upper and lower lobes and bilateral lungs were significantly greater in the standing than in the supine position, with lower lobes showing larger changes, the right middle lobe volume did not change significantly between positions. The total lung volume on upright CT in the standing position was more similar to TLC on PFT than that in the supine position."
3060,"Diagnosis, Background, and Treatment of Hypothalamic Damage in Craniopharyngioma","Craniopharyngiomas (CP) are rare brain tumors managed primarily with surgery and radiotherapy. There are 2 phenotypes of CP, i.e., one with a rather good outcome without hypothalamic damage and another with hypothalamic damage. With hypothalamic damage, progressive disease with recurrent operations and additional cranial radiotherapy often result in hypothalamic obesity, an affected psychosocial life, and cognitive dysfunction. The morbidity and mortality are increased for particularly cerebrovascular diseases. Preoperative hypothalamic involvement to predict hypothalamic damage is important for decision making for hypothalamus-sparing surgery. Also a postoperative hypothalamic damage evaluation with the use of hypothalamus volume measurement can predict hypothalamic obesity, which is important for early treatment options. The morbidity of CP includes cognitive dysfunction with attention deficits and impaired episodic memory and processing speed. Again patients with hypothalamic damage are more affected. Treatment options of hypothalamic obesity in the chronic phase are scarce and not convincingly successful. The most optimal situation is to try to hinder or stop the evolution of hypothalamic obesity. Prevention of hypothalamic damage is recommended, with special regard to hypothalamus-sparing therapeutic approaches that respect the integrity of essential nuclei located in both the medial and the posterior hypothalamic areas."
3061,Abstracts from the 2020 Annual Scientific Meeting of the British and Irish Hypertension Society (BIHS),
3062,"Trends in acute myocardial infarction admissions during the COVID-19 pandemic in Ankara, Turkey",
3063,Serotype specific epitopes identified by neutralizing antibodies underpin immunogenic differences in Enterovirus B,"Echovirus 30 (E30), a serotype of Enterovirus B (EV-B), recently emerged as a major causative agent of aseptic meningitis worldwide. E30 is particularly devastating in the neonatal population and currently no vaccine or antiviral therapy is available. Here we characterize two highly potent E30-specific monoclonal antibodies, 6C5 and 4B10, which efficiently block binding of the virus to its attachment receptor CD55 and uncoating receptor FcRn. Combinations of 6C5 and 4B10 augment the sum of their individual anti-viral activities. High-resolution structures of E30-6C5-Fab and E30-4B10-Fab define the location and nature of epitopes targeted by the antibodies. 6C5 and 4B10 engage the capsid loci at the north rim of the canyon and in-canyon, respectively. Notably, these regions exhibit antigenic variability across EV-Bs, highlighting challenges in development of broad-spectrum antibodies. Our structures of these neutralizing antibodies of E30 are instructive for development of vaccines and therapeutics against EV-B infections."
3064,"BBIQ, a pure TLR7 agonist, is an effective influenza vaccine adjuvant","Better adjuvants are needed for vaccines against seasonal influenza. TLR7 agonists are potent activators of innate immune responses and thereby may be promising adjuvants. Among the imidazoquinoline compounds, 1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (BBIQ) was reported to be a highly active TLR7 agonist but has remained relatively unexplored because of its commercial unavailability. Indeed, in silico molecular modeling studies predicted that BBIQ had a higher TLR7 docking score and binding free energy than imiquimod, the gold standard TLR7 agonist. To circumvent the availability issue, we developed an improved and higher yield method to synthesize BBIQ. Testing BBIQ on human and mouse TLR7 reporter cell lines confirmed it to be TLR7 specific with significantly higher potency than imiquimod. To test its adjuvant potential, BBIQ or imiquimod were admixed with recombinant influenza hemagglutinin protein and administered to mice as two intramuscular immunizations 2 weeks apart. Serum anti-influenza IgG responses assessed by ELISA 2 weeks after the second immunization confirmed that the mice that received vaccine admixed with BBIQ had significantly higher anti-influenza IgG1 and IgG2c responses than mice immunized with antigen alone or admixed with imiquimod. This confirmed BBIQ to be a TLR7-specific adjuvant able to enhance humoral immune responses."
3065,Puromycin reactivity does not accurately localize translation at the subcellular level,"Puromycin is a tyrosyl-tRNA mimic that blocks translation by labeling and releasing elongating polypeptide chains from translating ribosomes. Puromycin has been used in molecular biology research for decades as a translation inhibitor. The development of puromycin antibodies and derivatized puromycin analogs has enabled the quantification of active translation in bulk and single-cell assays. More recently, in vivo puromycylation assays have become popular tools for localizing translating ribosomes in cells. These assays often use elongation inhibitors to purportedly inhibit the release of puromycin-labeled nascent peptides from ribosomes. Using in vitro and in vivo experiments in various eukaryotic systems, we demonstrate that, even in the presence of elongation inhibitors, puromycylated peptides are released and diffuse away from ribosomes. Puromycylation assays reveal subcellular sites, such as nuclei, where puromycylated peptides accumulate post-release and which do not necessarily coincide with sites of active translation. Our findings urge caution when interpreting puromycylation assays in vivo."
3066,"Update Alert 2: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings",
3067,Beliefs and Information Seeking in Patients With Cancer in Southwest China: Survey Study,"BACKGROUND: Although previous studies have reported the cancer information-seeking behaviors among patients in high-income countries, the cancer information-seeking practices of patients living in low- and middle-income areas are less known. OBJECTIVE: This study investigated the beliefs and information-seeking patterns of cancer patients in southwest China. METHODS: A questionnaire was designed, and data were collected in two hospitals (N=285) in southwest China. Statistical analyses included bivariate analyses and regressions. RESULTS: Patients’ attitudes towards cancer fatalism were significantly influenced by marital status (P<.001), education (P<.001), and household income (P<.001). Moreover, endorsing fatalistic belief was positively associated with age (r=0.35, P<.001). The regression model showed that younger patients (odds ratio [OR] 0.96, 95% CI 0.93-0.99) and those with higher education (OR 1.75, 95% CI 1.09-2.81) were more likely to seek information. Additionally, patients who were less confident in getting information were more likely to find information (OR 1.70, 95% CI 1.15-2.52), while fatalism belief was not significant in the regression (OR 0.65, 95% CI 0.22-1.95). CONCLUSIONS: This study explored the information-seeking patterns of cancer patients in southwest China. It was found that many Chinese people endorsed cancer fatalism. These pessimistic beliefs about the potential to prevent and to cure cancer correlate with rather than cause cancer-related information seeking. However, self-efficacy about the confidence in finding needed cancer information was a significant predictor of information-seeking."
3068,Host Transcriptional Response to Persistent Infection with a Live-Attenuated Porcine Reproductive and Respiratory Syndrome Virus Strain,"Both virulent and live-attenuated porcine reproductive and respiratory syndrome virus (PRRSV) strains can establish persistent infection in lymphoid tissues of pigs. To investigate the mechanisms of PRRSV persistence, we performed a transcriptional analysis of inguinal lymphoid tissue collected from pigs experimentally infected with an attenuated PRRSV strain at 46 days post infection. A total of 6404 differentially expressed genes (DEGs) were detected of which 3960 DEGs were upregulated and 2444 DEGs were downregulated. Specifically, genes involved in innate immune responses and chemokines and receptors associated with T-cell homing to lymphoid tissues were down regulated. As a result, homing of virus-specific T-cells to lymphoid tissues seems to be ineffective, evidenced by the lower frequencies of virus-specific T-cell in lymphoid tissue than in peripheral blood. Genes associated with T-cell exhaustion were upregulated. Likewise, genes involved in the anti-apoptotic pathway were upregulated. Collectively, the data suggested that the live-attenuated PRRSV strain establishes a pro-survival microenvironment in lymphoid tissue by suppressing innate immune responses, T-cell homing, and preventing cell apoptosis."
3069,Self-quarantined: becoming accustomed to being a semi-prisoner,
3070,National reporting of deaths after enhanced Ebola surveillance in Sierra Leone,"BACKGROUND: Sierra Leone experienced the largest documented epidemic of Ebola Virus Disease in 2014–2015. The government implemented a national tollfree telephone line (1-1-7) for public reporting of illness and deaths to improve the detection of Ebola cases. Reporting of deaths declined substantially after the epidemic ended. To inform routine mortality surveillance, we aimed to describe the trends in deaths reported to the 1-1-7 system and to quantify people’s motivations to continue reporting deaths after the epidemic. METHODS: First, we described the monthly trends in the number of deaths reported to the 1-1-7 system between September 2014 and September 2019. Second, we conducted a telephone survey in April 2017 with a national sample of individuals who reported a death to the 1-1-7 system between December 2016 and April 2017. We described the reported deaths and used ordered logistic regression modeling to examine the potential drivers of reporting motivations. FINDINGS: Analysis of the number of deaths reported to the 1-1-7 system showed that 12% of the expected deaths were captured in 2017 compared to approximately 34% in 2016 and over 100% in 2015. We interviewed 1,291 death reporters in the survey. Family members reported 56% of the deaths. Nearly every respondent (94%) expressed that they wanted the 1-1-7 system to continue. The most common motivation to report was to obey the government’s mandate (82%). Respondents felt more motivated to report if the decedent exhibited Ebola-like symptoms (adjusted odds ratio 2.3; 95% confidence interval 1.8–2.9). CONCLUSIONS: Motivation to report deaths that resembled Ebola in the post-outbreak setting may have been influenced by knowledge and experiences from the prolonged epidemic. Transitioning the system to a routine mortality surveillance tool may require a robust social mobilization component to match the high reporting levels during the epidemic, which exceeded more than 100% of expected deaths in 2015."
3071,The Need to Develop Standard Measures of Patient Adherence for Big Data: Viewpoint,"Despite half a century of dedicated studies, medication adherence remains far from perfect, with many patients not taking their medications as prescribed. The magnitude of this problem is rising, jeopardizing the effectiveness of evidence-based therapies. An important reason for this is the unprecedented demographic change at the beginning of the 21st century. Aging leads to multimorbidity and complex therapeutic regimens that create a fertile ground for nonadherence. As this scenario is a global problem, it needs a worldwide answer. Could this answer be provided, given the new opportunities created by the digitization of health care? Daily, health-related information is being collected in electronic health records, pharmacy dispensing databases, health insurance systems, and national health system records. These big data repositories offer a unique chance to study adherence both retrospectively and prospectively at the population level, as well as its related factors. In order to make full use of this opportunity, there is a need to develop standardized measures of adherence, which can be applied globally to big data and will inform scientific research, clinical practice, and public health. These standardized measures may also enable a better understanding of the relationship between adherence and clinical outcomes, and allow for fair benchmarking of the effectiveness and cost-effectiveness of adherence-targeting interventions. Unfortunately, despite this obvious need, such standards are still lacking. Therefore, the aim of this paper is to call for a consensus on global standards for measuring adherence with big data. More specifically, sound standards of formatting and analyzing big data are needed in order to assess, uniformly present, and compare patterns of medication adherence across studies. Wide use of these standards may improve adherence and make health care systems more effective and sustainable."
3072,What You Need to Know Before Implementing a Clinical Research Data Warehouse: Comparative Review of Integrated Data Repositories in Health Care Institutions,"BACKGROUND: Integrated data repositories (IDRs), also referred to as clinical data warehouses, are platforms used for the integration of several data sources through specialized analytical tools that facilitate data processing and analysis. IDRs offer several opportunities for clinical data reuse, and the number of institutions implementing an IDR has grown steadily in the past decade. OBJECTIVE: The architectural choices of major IDRs are highly diverse and determining their differences can be overwhelming. This review aims to explore the underlying models and common features of IDRs, provide a high-level overview for those entering the field, and propose a set of guiding principles for small- to medium-sized health institutions embarking on IDR implementation. METHODS: We reviewed manuscripts published in peer-reviewed scientific literature between 2008 and 2020, and selected those that specifically describe IDR architectures. Of 255 shortlisted articles, we found 34 articles describing 29 different architectures. The different IDRs were analyzed for common features and classified according to their data processing and integration solution choices. RESULTS: Despite common trends in the selection of standard terminologies and data models, the IDRs examined showed heterogeneity in the underlying architecture design. We identified 4 common architecture models that use different approaches for data processing and integration. These different approaches were driven by a variety of features such as data sources, whether the IDR was for a single institution or a collaborative project, the intended primary data user, and purpose (research-only or including clinical or operational decision making). CONCLUSIONS: IDR implementations are diverse and complex undertakings, which benefit from being preceded by an evaluation of requirements and definition of scope in the early planning stage. Factors such as data source diversity and intended users of the IDR influence data flow and synchronization, both of which are crucial factors in IDR architecture planning."
3073,The peroxisome counteracts oxidative stresses by suppressing catalase import via Pex14 phosphorylation,"Most of peroxisomal matrix proteins including a hydrogen peroxide (H(2)O(2))-decomposing enzyme, catalase, are imported in a peroxisome-targeting signal type-1 (PTS1)-dependent manner. However, little is known about regulation of the membrane-bound protein import machinery. Here, we report that Pex14, a central component of the protein translocation complex in peroxisomal membrane, is phosphorylated in response to oxidative stresses such as H(2)O(2) in mammalian cells. The H(2)O(2)-induced phosphorylation of Pex14 at Ser232 suppresses peroxisomal import of catalase in vivo and selectively impairs in vitro the interaction of catalase with the Pex14-Pex5 complex. A phosphomimetic mutant Pex14-S232D elevates the level of cytosolic catalase, but not canonical PTS1-proteins, conferring higher cell resistance to H(2)O(2). We thus suggest that the H(2)O(2)-induced phosphorylation of Pex14 spatiotemporally regulates peroxisomal import of catalase, functioning in counteracting action against oxidative stress by the increase of cytosolic catalase."
3074,A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1,"Primary Ovarian Insufficiency (POI) is a major cause of infertility, but its etiology remains poorly understood. Using whole-exome sequencing in a family with three cases of POI, we identified the candidate missense variant S167L in HSF2BP, an essential meiotic gene. Functional analysis of the HSF2BP-S167L variant in mouse showed that it behaves as a hypomorphic allele compared to a new loss-of-function (knock-out) mouse model. Hsf2bp(S167L/S167L) females show reduced fertility with smaller litter sizes. To obtain mechanistic insights, we identified C19ORF57/BRME1 as a strong interactor and stabilizer of HSF2BP and showed that the BRME1/HSF2BP protein complex co-immunoprecipitates with BRCA2, RAD51, RPA and PALB2. Meiocytes bearing the HSF2BP-S167L variant showed a strongly decreased staining of both HSF2BP and BRME1 at the recombination nodules and a reduced number of the foci formed by the recombinases RAD51/DMC1, thus leading to a lower frequency of crossovers. Our results provide insights into the molecular mechanism of HSF2BP-S167L in human ovarian insufficiency and sub(in)fertility."
3075,Using social media to analyze public psychological status during the recovery period of COVID-19 in China,"BACKGROUND: During the outbreak, billions of people were eager to get information about COVID-19 through social media. Social media can not only deliver reliable information to the public but can in turn reflect changes in the public’s psychological status. Insight into the public’s hotspots of concern and mental status through media background tools contributes to the formulation of public health policies and the clarification of epidemic development mode. METHODS: WeChat is the largest social media in China. Taking the recovery period of COVID-19 in China, for example, we collected WeChat Index data and analyzed the public’s concern about the course of COVID-19 and the restoration of emotional tendency through keywords search. RESULTS: With the gradual control of the COVID-19 in China, the public psychological status changes from negative to neutral, accompanied by a weakening of negative emotions and an increase in positive emotions. Every obvious inflection point of improvement in social operation is reflected in the increase of public attention and the relaxation of lifestyle. CONCLUSIONS: Social media can be used to monitor the public psychological status and the development mode and trend of infection in one country during a pandemic."
3076,Religions in action: the role of interreligious dialogue in the COVID-19 pandemic,"Recent correspondence letters to the editor of this journal pointed on the praxis of faith in the context of COVID-19 pandemic. The #ChurchinAction presents the role of religious interventions in times of COVID-19. However, a question is raised: how to promote interreligious dialogue in the context of COVID-19 pandemic? To address this question, people of different faiths/religions should come together in promoting the life and dignity of the human person, a sense of community, and participation, respecting the rights and responsibilities of each person, helping the poor and vulnerable sectors of the society, respecting the dignity of work and the rights of the workers, solidarity and caring for the whole creation. In this perspective, interreligious dialogue highlighted the importance of world religions in order to provide a spiritual intervention. The dialogue of life, dialogue of action, dialogue of theological exchange, and dialogue of religious experiences promote interreligious dialogue in the context of COVID-19 pandemic."
3077,COVID-19: The need to heed distress calls of healthcare workers,
3078,Corrigendum to: Descriptive analysis of social determinant factors in urban communities affected by COVID-19,
3079,Recommendations for the assessment and monitoring of skeletal manifestations in children with Gaucher disease,
3080,A Decade of Genetic Counseling in Frontotemporal Dementia Affected Families: Few Counseling Requests and much Familial Opposition to Testing,"A decade of genetic counseling of frontotemporal dementia (FTD) affected families has generated two important observations. First, the uptake rate for presymptomatic testing for FTD is low in our department of Clinical Genetics at the Erasmus Medical Center in the Netherlands. Second, FTD at-risk counselees reported substantial familial opposition to genetic testing, which is distinct from the attitude in Huntington Disease affected families. We hypothesize that the low acceptance for FTD genetic counseling is consequential to the familial opposition and explain this within the theoretical framework of separation-individuation. Furthermore, we hypothesize that separation-individuation problems do not similarly influence the acceptance of HD genetic counseling, due to the educative role of the well-organised patient organization for HD in the Netherlands. We offer counseling recommendations that serve to facilitate the individuation of the counselee with respect to the FTD genetic test."
3081,Examining the Relationship Between Genetic Counselors’ Attitudes Toward Deaf People and the Genetic Counseling Session,Given the medical and cultural perspectives on deafness it is important to determine if genetic counselors’ attitudes toward deaf people can affect counseling sessions for deafness genes. One hundred fifty-eight genetic counselors recruited through the National Society of Genetic Counselors Listserv completed an online survey assessing attitudes toward deaf people and scenario-specific comfort levels discussing and offering genetic testing for deafness. Respondents with deaf/Deaf friends or who work in prenatal or pediatric settings had more positive attitudes toward deaf people than those without deaf/Deaf friends or those working in ‘other’ settings. More positive attitudes toward deaf people correlated with higher comfort level talking about genetic testing for the two scenarios involving culturally Deaf clients; and correlated with higher comfort level offering genetic testing to culturally Deaf clients wishing to have a deaf child. Attitudes and comfort level were not correlated in the scenarios involving hearing or non-culturally deaf clients. These results suggest that genetic counselors’ attitudes could affect information provision and the decision making process of culturally Deaf clients. Cultural sensitivity workshops in genetic counseling training programs that incorporate personal interactions with culturally Deaf individuals are recommended. Additional suggestions for fostering personal interactions are provided.
3082,Publishing a Master’s Thesis: A Guide for Novice Authors,"Publication of original research, clinical experiences, and critical reviews of literature are vital to the growth of the genetic counseling field, delivery of genetic counseling services, and professional development of genetic counselors. Busy clinical schedules, lack of time and funding, and training that emphasizes clinical skills over research skills may make it difficult for new genetic counselors to turn their thesis projects into publications. This paper summarizes and elaborates upon a presentation aimed at de-mystifying the publishing process given at the 2008 National Society of Genetic Counselors Annual Education Conference. Specific topics include familiarizing prospective authors, particularly genetic counseling students, with the basics of the publication process and related ethical considerations. Former students’ experiences with publishing master’s theses also are described in hopes of encouraging new genetic counselors to submit for publication papers based on their thesis projects."
3083,Pre-counseling Education for Low Literacy Women at Risk of Hereditary Breast and Ovarian Cancer (HBOC): Patient Experiences Using the Cancer Risk Education Intervention Tool (CREdIT),"The Cancer Risk Education Intervention Tool (CREdIT) is a computer-based (non-interactive) slide presentation designed to educate low-literacy, and ethnically and racially diverse public hospital patients at risk of Hereditary Breast and Ovarian Cancer (HBOC) about genetics. To qualitatively evaluate participants’ experience with and perceptions of a genetic education program as an adjunct to genetic counseling, we conducted direct observations of the intervention, semi-structured in person interviews with 11 women who viewed CREdIT, and post-counseling questionnaires with the two participating genetic counselors. Five themes emerged from the analysis of interviews: (1) genetic counseling and testing for breast/ovarian cancer was a new concept; (2) CREdIT’s story format was particularly appealing; (3) changes in participants’ perceived risk for breast cancer varied; (4) some misunderstandings about individual risk and heredity persisted after CREdIT and counseling; (5) the context for viewing CREdIT shaped responses to the presentation. Observations demonstrated ways to make the information provided in CREdIT and by genetic counselors more consistent. In a post-session counselor questionnaire, counselors’ rating of the patient’s preparedness before the session was significantly higher for patients who viewed CREdIT prior to their appointments than for other patients. This novel educational tool fills a gap in HBOC education by tailoring information to women of lower literacy and diverse ethnic/racial backgrounds. The tool was well received by interview participants and counselors alike. Further study is needed to examine the varied effects of CREdIT on risk perception. In addition, the implementation of CREdIT in diverse clinical settings and the cultural adaptation of CREdIT to specific populations reflect important areas for future work."
3084,Effect of Pre-test Genetic Counseling for Deaf Adults on Knowledge of Genetic Testing,"Empirical data on genetic counseling outcomes in the deaf population are needed to better serve this population. This study was an examination of genetics knowledge before and after culturally and linguistically appropriate pre-test genetic counseling in a diverse deaf adult sample. Individuals ≥18 years old with early-onset sensorineural deafness were offered connexin-26/30 testing and genetic counseling. Participants completed questionnaires containing 10 genetics knowledge items at baseline and following pre-test genetic counseling. The effects of genetic counseling, prior beliefs about etiology, and participant’s preferred language on genetics knowledge scores were assessed (n = 244). Pre-test genetic counseling (p = .0007), language (p < .0001), prior beliefs (p < .0001), and the interaction between counseling and beliefs (p = .035) were predictors of genetics knowledge. American Sign Language (ASL)-users and participants with “non-genetic/unknown” prior beliefs had lower knowledge scores than English-users and participants with “genetic” prior beliefs, respectively. Genetics knowledge improved after genetic counseling regardless of participants’ language; knowledge change was greater for the “non-genetic/unknown” beliefs group than the “genetic” beliefs group. ASL-users’ lower knowledge scores are consistent with evidence that ethnic and cultural minority groups have less genetics knowledge, perhaps from exposure and access disparities. Culturally and linguistically appropriate pre-test genetic counseling significantly improved deaf individuals’ genetics knowledge. Assessing deaf individuals’ prior beliefs is important for enhancing genetics knowledge."
3085,Focusing on Patient Needs and Preferences May Improve Genetic Counseling for Colorectal Cancer,"During cancer genetic counseling, different items which counselors consider important are discussed. However, relatively little empirical evidence exists regarding the needs and preferences of counselees. In this study needs and preferences were assessed from counselees with a personal and/or family history of colorectal cancer (CRC), who were referred for genetic counseling regarding CRC. They received a slightly modified version of the QUOTE-GENE(ca) questionnaire prior to their first visit to the Hereditary Cancer Clinic. Response rate was 60 % (48/80 participants). Counselees rated the importance of 45 items assessing their needs and preferences regarding the content and process of genetic counseling. Participants rated the items regarding discussion of information about their familial CRC risk (100 %) and preventive options (98 %) as important or very important. Fewer participants rated items concerning general information on genetics as important. Sensitive communication during counseling was considered very important by a large percentage of counselees. Generally, no major differences were seen between participants in relation to individual characteristics. Our data suggest that focusing on familial CRC risk and surveillance options, in combination with sensitive communication may lead to better satisfaction with genetic counseling."
3086,Counseling Customers: Emerging Roles for Genetic Counselors in the Direct-to-Consumer Genetic Testing Market,"Individuals now have access to an increasing number of internet resources offering personal genomics services. As the direct-to-consumer genetic testing (DTC GT) industry expands, critics have called for pre- and post-test genetic counseling to be included with the product. Several genetic testing companies offer genetic counseling. There has been no examination to date of this service provision, whether it meets critics’ concerns and implications it may have for the genetic counseling profession. Considering the increasing relevance of genetics in healthcare, the complexity of genetic information provided by DTC GT, the mediating role of the internet in counseling, and potential conflicts of interest, this is a topic which deserves further attention. In this paper we offer a discourse analysis of ways in which genetic counseling is represented on DTC GT websites, blogs and other online material. This analysis identified four types of genetic counseling represented on the websites: the integrated counseling product; discretionary counseling; independent counseling; and product advice. Genetic counselors are represented as having the following roles: genetics educator; mediator; lifestyle advisor; risk interpreter; and entrepreneur. We conclude that genetic counseling as represented on DTC GT websites demonstrates shifting professional roles and forms of expertise in genetic counseling. Genetic counselors are also playing an important part in how the genetic testing market is taking shape. Our analysis offers important and timely insights into recent developments in the genetic counseling profession, which have relevance for practitioners, researchers and policy makers concerned with the evolving field of personal genomics."
3087,Glioma infiltration of the corpus callosum: early signs detected by DTI,"The most frequent primary brain tumors, anaplastic astrocytomas (AA) and glioblastomas (GBM): tend to invasion of the surrounding brain. Histopathological studies found malignant cells in macroscopically unsuspicious brain parenchyma remote from the primary tumor, even affecting the contralateral hemisphere. In early stages, diffuse interneural infiltration with changes of the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) is suspected. The purpose of this study was to investigate the value of DTI as a possible instrument of depicting evidence of tumor invasion into the corpus callosum (CC). Preoperatively, 31 patients with high-grade brain tumors (8 AA and 23 GBM) were examined by MRI at 3 T, applying a high-resolution diffusion tensor imaging (DTI) sequence. ADC- and FA-values were analyzed in the tumor-associated area of the CC as identified by fiber tracking, and were compared to matched healthy controls. In (MR-)morphologically normal appearing CC the ADC values were elevated in the tumor patients (n = 22; 0.978 × 10(−3) mm²/s) compared to matched controls (0.917 × 10(−3) mm²/s, p < 0.05), and the corresponding relative FA was reduced (rFA: 88 %, p < 0.01). The effect was pronounced in case of affection of the CC visible on MRI (n = 9; 0.978 × 10(−3) mm²/s, p < 0.05; rFA: 72 %, p < 0.01). Changes in diffusivity and anisotropy in the CC can be interpreted as an indicator of tumor spread into the contralateral hemisphere not visible on conventional MRI."
3088,An Assessment of Time Involved in Pre-test Case Review and Counseling for a Whole Genome Sequencing Clinical Research Program,"Whole genome sequencing (WGS) is being used for evaluation of individuals with undiagnosed disease of suspected genetic origin. Implementing WGS into clinical practice will place an increased burden upon care teams with regard to pre-test patient education and counseling about results. To quantitate the time needed for appropriate pre-test evaluation of participants in WGS testing, we documented the time spent by our clinical research group on various activities related to program preparation, participant screening, and consent prior to WGS. Participants were children or young adults with autism, intellectual or developmental disability, and/or congenital anomalies, who have remained undiagnosed despite previous evaluation, and their biologic parents. Results showed that significant time was spent in securing allocation of clinical research space to counsel participants and families, and in acquisition and review of participant’s medical records. Pre-enrollment chart review identified two individuals with existing diagnoses resulting in savings of $30,000 for the genome sequencing alone, as well as saving hours of personnel time for genome interpretation and communication of WGS results. New WGS programs should plan for costs associated with additional pre-test administrative planning and patient evaluation time that will be required to provide high quality care. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10897-014-9697-4) contains supplementary material, which is available to authorized users."
3089,Counselees’ Expressed Level of Understanding of the Risk Estimate and Surveillance Recommendation are Not Associated with Breast Cancer Surveillance Adherence,"We studied counselees’ expressed understanding of the risk estimate and surveillance recommendation in the final consultation for breast cancer genetic counseling in relation with their risk perception, worry and cancer surveillance adherence 1 year post-counseling. Consecutive counselees were included from 2008 to 2010. Counselees with an indication for diagnostic DNA-testing for themselves or a breast cancer affected relative were requested to complete online questionnaires before and after counseling and one year after counseling (N = 152–124). Self-reported surveillance was compared to surveillance recommendations. Consultations were videotaped. Counselees’ reactions to the risks and recommendations were coded. Statements about the risk perception and surveillance intentions of breast cancer unaffected counselees were transcribed. Associations with outcomes were explored. Almost all breast cancer unaffected counselees (>90 %) reacted to their risk estimate with an utterance indicating understanding and this reaction was not significantly associated with their post-visit risk perception alignment. Over one-third (38.6 %) overestimated their risk post-counseling. Few counselees (5.8 %) expressed surveillance intentions. One year after counseling, about three-quarters (74.0 %) of the breast cancer unaffected counselees had adhered to the surveillance recommendation. Almost one-quarter (23.3 %) had performed more mammograms/MRI scans than recommended, which was associated with prior mammography uptake (n = 47; X(2) = 5.2; p = .02). Counselees’ post-counseling overestimation of their risk, high levels of worry and high surveillance uptake were not reflected in their reactions to the counselor’s information during the final visit. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10897-015-9869-x) contains supplementary material, which is available to authorized users."
3090,Genetic Counselors’ Perspectives and Practices Regarding Expanded Carrier Screening after Initial Clinical Availability,"Expanded carrier screening (ECS), introduced in 2009, identifies carriers for dozens or hundreds of recessive diseases. At the time of its introduction into clinical use, perspectives of the genetic counseling community regarding ECS were unknown. We conducted a survey in early 2012 of GCs and report the results here. They represent a snapshot of opinions and usage at that time, providing a baseline for comparison as the technology continues to evolve and as usage increases. The survey assessed personal perspectives, opinions on clinical implementation and clinical utilization of ECS. The sample included 337 GCs of varying clinical fields, of whom 150 reported practicing in reproductive settings. Our findings demonstrate that, at the time, GCs indicated general agreement with ECS as a concept – for example, most GCs agreed that carrier screening should address diseases outside of current guidelines and also indicated personal interest in electing ECS. There were also disagreements or concerns expressed regarding appropriate pre- and post-test counseling (e.g., the content and delivery mode of adequate informed consent) and practical implementation (e.g., the amount of time available for follow-up care). This was the first quantitative study of a large number of GCs and it revealed initial overall support for ECS among the GC profession. The authors plan to re-administer a similar survey, which may reveal changes in opinions and/or utilization over time. A follow up survey would also allow further exploration of questions uncovered by these data."
3091,A Systematic Review of the Impact of Genetic Counseling on Risk Perception Accuracy,"This review presents an overview of the impact of genetic counseling on risk perception accuracy in papers published between January 2000 and February 2007. The results suggest that genetic counseling may have a positive impact on risk perception accuracy, though some studies observed no impact at all, or only for low-risk participants. Several implications for future research can be deduced. First, future researchers should link risk perception changes to objective risk estimates, define risk perception accuracy as the correct counseled risk estimate, and report both the proportion of individuals who correctly estimate their risk and the average overestimation of the risk. Second, as the descriptions of the counseling sessions were generally poor, future research should include more detailed description of these sessions and link their content to risk perception outcomes to allow interpretation of the results. Finally, the effect of genetic counseling should be examined for a wider variety of hereditary conditions. Genetic counselors should provide the necessary context in which counselees can understand risk information, use both verbal and numerical risk estimates to communicate personal risk information, and use visual aids when communicating numerical risk information."
3092,Reactions to and Desire for Prognostic Testing in Choroidal Melanoma Patients,"To determine if choroidal melanoma patients want cytogenetic prognostic information. Ninety-nine choroidal melanoma patients completed a questionnaire regarding their opinions about receiving prognostic information. The perceived usefulness of prognostic information was evaluated in patients who had undergone cytogenetic testing. Depressive symptoms, quality of life, and interest in supportive counseling during test receipt were assessed. Ninety-seven percent of respondents reported that they would have wanted prognostic information at the time of their treatment and 98% of respondents reported that supportive counseling should be offered when prognostic information is given. Patients who had received a more favorable prognostic result were more likely to endorse the usefulness of cytogenetic testing than were patients who had received a less favorable prognostic result. Psychological status did not vary significantly as a function of cytogenetic test result. Prognostic information was important to patients with choroidal melanoma, even in the absence of prophylactic measures which might improve prognosis."
3093,Vestibular prognosis in idiopathic sudden sensorineural hearing loss with vestibular dysfunction treated with oral or intratympanic glucocorticoids: a protocol for randomized controlled trial,"BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a rapid-onset sensorineural hearing impairment with unclear etiology and unsatisfying treatment effects. Vestibular dysfunction has been considered as a poor indicator in the clinical manifestations and prognosis of ISSNHL, which occurred in approximately 28–57% cases. Glucocorticoids, administered through oral or intratympanic way, are currently regularly and standardly applied for ISSNHL to improve the hearing outcome. However, the vestibular prognosis of ISSNHL after routine treatments remains seldom explored. This study aims to compare the effectiveness of oral and intratympanic glucocorticoids in ISSNHL with vestibular dysfunction in terms of the pattern and trajectory of possible process of vestibular function recovery. METHODS/DESIGN: A randomized, outcome-assessor- and analyst-blinded, controlled, clinical trial (RCT) will be carried out. Seventy-two patients with ISSNHL complaining of vestibular dysfunction appearing as vertigo or imbalance will be recruited and randomized into either oral or intratympanic glucocorticoid therapy group with a 1:1 allocation ratio. The primary outcomes will be vestibular function outcomes assessed by sensory organization test, caloric test, video head impulse test, cervical vestibular evoked myogenic potential, and ocular vestibular evoked myogenic potential; the secondary outcomes include self-reported vestibular dysfunction symptoms; dizziness-related handicap, visual analogue scale for vertigo and tinnitus; and pure tone audiometry. Assessments of primary outcomes will be performed at baseline and at 4 and 8 weeks post-randomization, while assessments of secondary outcomes will be performed at baseline and 1, 2, 4, and 8 weeks post-randomization. DISCUSSION: Previous intervention studies of ISSNHL included only hearing outcomes, with little attention paid on the prognosis of vestibular dysfunction. This trial will be the first RCT study focusing on the progress and prognosis of vestibular dysfunction in ISSNHL. The efficacy of two commonly used therapies of glucocorticoids will be compared in both auditory and vestibular function fields, rather than in the hearing outcome alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT03974867. Registered on 23 July 2019"
3094,Is the allocation of medical and health resources effective? Characteristic facts from regional heterogeneity in China,"BACKGROUND: Over the last decade, the expenditure on public medical and health has increased greatly in China, however, problems as low efficiency and unfairness still exist. How to accurately describe the effectiveness of existing medical and health resources in combination with regional heterogeneity is of great significance to China’s medical and health reform. METHODS: Based on provincial panel data for the period of 2005 to 2017, combining expected output and unexpected output, this paper constructs a super-efficiency three-stage SBM-DEA model, to measure and analyze the spatial-temporal heterogeneity characteristics and influencing factors of public medical and health efficiency (PMHE). RESULTS: (1) After the impacts of random error and external environmental factors are removed, the mean value of overall PMHE is 0.9274, failing to reach DEA efficiency, and PMHE shows a fluctuated downward trend. (2) The adjusted PMHE level shows a prominent spatial imbalance at the stage 3. The average efficiency level is ranked by the East > the West > the Central > the Northeast. (3) The increases of GDP per capita and population density are beneficial to the improvement of PMHE, while income level and education level are disadvantageous to PMHE, and last, the urbanization level, an uncertain effect. (4) There is no σ convergence of the PMHE in the East, the Central and the West, that is, the internal differences may gradually expand in the future, while the Northeast shows a significant σ convergence trending of PMHE. (5) The state’s allocation of medical and health resources has undergone major changes during “The Twelfth Five-Year Plan”. CONCLUSION: This study innovatively incorporates undesired outputs of health care into the efficiency evaluation framework by constructing the main efficiency evaluation indicators. The results of the robust evaluation conclude that China’s existing investment in medical and health resources is generally not effective. Therefore, although China’s health care reform has made certain achievement, it is still necessary to expand the investment in health care resources."
3095,"The clinical, immunological and genetic features of 12 Chinese patients with STAT3 mutations","BACKGROUND: Loss-of-function (LOF) mutations in signal transducer and activator of transcription 3 (STAT3) is one of the causes of STAT3 hyperimmunoglobulin E (IgE) syndrome (STAT3-HIES), while gain-of-function (GOF) mutations in STAT3 lead to immune dysregulation diseases. We retrospectively analyzed the age, common clinical symptoms, immunologic and molecular manifestations in 11 patients with LOF STAT3 mutations and 1 patient with a GOF STAT3 mutation. METHODS: Twelve patients were enrolled in our study. Serum immunoglobulin measurements, lymphocyte subset detection and whole-exome sequencing were performed. RESULTS: The median age at diagnosis of STAT3-HIES patients was 4.74 years. Eczema, recurrent respiratory infections, fevers, abscesses and Staphylococcus aureus infections were the classic manifestations. Elevated serum IgE levels are not always observed in conjunction with high eosinophil counts. A moderate viral DNA load was also measured in peripheral blood mononuclear cells. We noticed that c. 1144C>T was the most common mutation site, followed by c.1311C>A. Additionally, c.1311C>A and c. 1826G>C are two novel mutations. Eight patients achieved notable improvement after receiving intravenous immunoglobulin. CONCLUSION: We updated the current knowledge of this topic. We found an earlier median age at diagnosis, a higher survival rate, and a general lack of nonimmunological abnormalities; we also described the treatment details and novel mutations involve in STAT3-HIES and compared STAT3 LOF and GOF mutations."
3096,Gene expression and regulatory factors of the mechanistic target of rapamycin (mTOR) complex 1 predict mammalian longevity,"Species longevity varies significantly across animal species, but the underlying molecular mechanisms remain poorly understood. Recent studies and omics approaches suggest that phenotypic traits of longevity could converge in the mammalian target of rapamycin (mTOR) signalling pathway. The present study focuses on the comparative approach in heart tissue from 8 mammalian species with a ML ranging from 3.5 to 46 years. Gene expression, protein content, and concentration of regulatory metabolites of the mTOR complex 1 (mTORC1) were measured using droplet digital PCR, western blot, and mass spectrometry, respectively. Our results demonstrate (1) the existence of differences in species-specific gene expression and protein content of mTORC1, (2) that the achievement of a high longevity phenotype correlates with decreased and inhibited mTORC1, (3) a decreased content of mTORC1 activators in long-lived animals, and (4) that these differences are independent of phylogeny. Our findings, taken together, support an important role for mTORC1 downregulation in the evolution of long-lived mammals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11357-020-00210-3) contains supplementary material, which is available to authorized users."
3097,Modified Asano-Ohya-Khrennikov quantum-like model for decision-making process in a two-player game with nonlinear self- and cross-interaction terms of brain’s amygdala and prefrontal-cortex,"In this report, we propose a modification on the Asano-Ohya-Khrennikov quantum-like decision-making process model of a two-player game by adding additional nonlinear terms to the related comparison step dynamical equation. The additions are in the form of a self-interaction and cross-interaction of the brain’s amygdala and prefrontal cortex. We show that the cross-interaction significantly determines the final decision of a player, whether it becomes a rational or an irrational choice. In contrast, the nonlinear self-interaction term provides a feedback mechanism that speeds up the corresponding decision-making process. We also suggest the form of expectation values of the overall reaction rate coefficients of those nonlinear terms by making an analogy with the original model formulation."
3098,Useful parameters for the motion analysis of facial skin care in Japanese women,"BACKGROUND: Facial skin care (FSC) is an important routine for Japanese women. Hand motions during FSC physically affect psychological state. However, it is very difficult to evaluate hand motions during personal and complex FSC. The objective of this study was to find out objective and quantitative parameters for hand motions during facial skin care (FSC). Women who enjoy and soothe during FSC (Enjoyment group (E group), n = 20) or not (non-enjoyment group (NE group), n = 19) were recruited by an advance questionnaire. The same lotion, emulsion, and cream were provided to all subjects, and they used sequentially in the same way as the women’s daily FSC. The motion of the marker on the back side of the right middle finger during FSC was tracked by a motion capture system. The heart rate variability (HRV) was also measured before and after FSC for evaluating psychological effect. RESULTS: The averaged acceleration (Avg. ACC), approximate entropy (ApEn), and power law scaling exponent (Rest γ) of the cumulative duration of slow motion from the sequential data of acceleration were evaluated. Compared to the NE group, the E group showed a lower Avg. ACC when using emulsion (p = 0.005) and cream (p = 0.007), a lower ApEn when using emulsion (p = 0.003), and a lower Rest γ (p = 0.024) when using all items, suggesting that compared to the NE group, the E group had more tender and regular motion, and sustainable slow motions, especially in the use of emulsion. In the E group, the low/high-frequency component of HRV decreased significantly after FSC, suggesting suppression of sympathetic activity (p = 0.045). NE group did not. For all subjects, ApEn and Rest γ showed significantly positive correlation with the increase in the low/high-frequency component of HRV after FSC (p < 0.01). ApEn showed significantly negative correlation with the increase in the high-frequency component of HRV after FSC (p < 0.05). Avg. ACC did not show significant correlation with them. These results suggested that the behavior of FSC influences the autonomic nerve system. CONCLUSIONS: ApEn and Rest γ are useful parameters for evaluating quality of hand motions during FSC."
3099,Assessment of a biofluid mechanics-based model for calculating portal pressure in canines,"BACKGROUND: Portal hypertension is a severe complication caused by various chronic liver diseases. The standard methods for detecting portal hypertension (hepatic venous pressure gradient and free portal pressure) are available in only a few hospitals due to their technical difficulty and invasiveness; thus, non-invasive measuring methods are needed. This study aimed to establish and assess a novel model to calculate free portal pressure based on biofluid mechanics. RESULT: Comparison of each dog’s virtual and actual free portal pressure showed that a biofluid mechanics-based model could accurately predict free portal pressure (mean difference: -0.220, 95% CI: − 0.738 to 0.298; upper limit of agreement: 2.24, 95% CI: 1.34 to 3.14; lower limit of agreement: -2.68, 95% CI: − 3.58 to − 1.78; intraclass correlation coefficient: 0.98, 95% CI: 0.96 to 0.99; concordance correlation coefficient: 0.97, 95% CI: 0.93 to 0.99) and had a high AUC (0.984, 95% CI: 0.834 to 1.000), sensitivity (92.3, 95% CI: 64.0 to 99.8), specificity (91.7, 95% CI: 61.5 to 99.8), positive likelihood ratio (11.1, 95% CI: 1.7 to 72.8), and low negative likelihood ratio (0.08, 95% CI: 0.01 to 0.6) for detecting portal hypertension. CONCLUSIONS: Our study suggests that the biofluid mechanics-based model was able to accurately predict free portal pressure and detect portal hypertension in canines. With further research and validation, this model might be applicable for calculating human portal pressure, detecting portal hypertensive patients, and evaluating disease progression and treatment efficacy."
3100,Assessing and decomposing inequality of opportunity in access to child health and nutrition in sub-Saharan Africa: evidence from three countries with low human development index,"BACKGROUND: Inequality of opportunity in health and nutrition is a major public health issue in the developing regions. This study analyzed the patterns and extent of inequality of opportunity in health and nutrition among children under-five across three countries sub-Saharan Africa with low Human development index (HDI). METHODS: We used data from the Multiple Indicator Cluster Survey of the Democratic Republic of Congo (20,792 households, 21,756 women aged 15 to 49 and 21,456 children under five), Guinea Bissau (6601 households, 10,234 women aged 15–49 and 7573 children under five) and Mali (11,830 households, 18,409 women in 15–49 years and 16,468 children under five) to compute the human opportunity index (HOI) and the dissimilarity index (D-index). Secondly, the Shapley decomposition method was used to estimate the relative contribution of circumstances that are beyond the control of children under-five and affecting their development outcomes in later life stages. RESULTS: The study revealed that children belonging to the most favorable group had higher access rates for immunization (93.64%) and water and sanitation facilities (73.59%) in Guinea Bissau. In Congo DR, the access rate was high for immunization (93.9%) for children in the most favorable group. In Mali, access rates stood at 6.56% for children in the most favorable group. In Guinea Bissau, the inequality of opportunity was important in access to health services before and after delivery (43.85%). In Congo DR, the inequality of opportunity was only high for the immunization composite indicator (83.79%) while in Mali, inequality of opportunity was higher for access to health services before and after delivery (41.67%). CONCLUSION: The results show that there are efforts in some places to promote access to health and nutrition services in order to make access equal without distinction linked to the socio-economic and demographic characteristics in which the children live. However, the inequalities of opportunity observed between the children of the most favorable group and those of the least favorable group, remain in general at significant levels and call on government of these countries to implement policies taking them into account."
3101,The Small Protein RmpD Drives Hypermucoviscosity in Klebsiella pneumoniae,"Klebsiella pneumoniae has a remarkable ability to cause a wide range of human diseases. It is divided into two broad classes: classical strains that are a notable problem in health care settings due to multidrug resistance, and hypervirulent (hv) strains that are historically drug sensitive but able to establish disease in immunocompetent hosts. Alarmingly, there has been an increased frequency of clinical isolates that have both drug resistance and hv-associated genes. One such gene, rmpA, encodes a transcriptional regulator required for maximal capsule (cps) gene expression and confers hypermucoviscosity (HMV). This link has resulted in the assumption that HMV is caused by elevated capsule production. However, we recently reported a new cps regulator, RmpC, and ΔrmpC mutants have reduced cps expression but retain HMV, suggesting that capsule production and HMV may be separable traits. Here, we report the identification of a small protein, RmpD, that is essential for HMV but does not impact capsule. RmpD is 58 residues with a putative N-terminal transmembrane domain and highly positively charged C-terminal half, and it is conserved among other hv K. pneumoniae strains. Expression of rmpD in trans complements both ΔrmpD and ΔrmpA mutants for HMV, suggesting that RmpD is the key driver of this phenotype. The rmpD gene is located between rmpA and rmpC, within an operon regulated by RmpA. These data, combined with our previous work, suggest a model in which the RmpA-associated phenotypes are largely due to RmpA activating the expression of rmpD to produce HMV and rmpC to stimulate cps expression."
3102,Recurrent processes support a cascade of hierarchical decisions,"Perception depends on a complex interplay between feedforward and recurrent processing. Yet, while the former has been extensively characterized, the computational organization of the latter remains largely unknown. Here, we use magneto-encephalography to localize, track and decode the feedforward and recurrent processes of reading, as elicited by letters and digits whose level of ambiguity was parametrically manipulated. We first confirm that a feedforward response propagates through the ventral and dorsal pathways within the first 200 ms. The subsequent activity is distributed across temporal, parietal and prefrontal cortices, which sequentially generate five levels of representations culminating in action-specific motor signals. Our decoding analyses reveal that both the content and the timing of these brain responses are best explained by a hierarchy of recurrent neural assemblies, which both maintain and broadcast increasingly rich representations. Together, these results show how recurrent processes generate, over extended time periods, a cascade of decisions that ultimately accounts for subjects’ perceptual reports and reaction times."
3103,Identification of protein-protected mRNA fragments and structured excised intron RNAs in human plasma by TGIRT-seq peak calling,"Human plasma contains > 40,000 different coding and non-coding RNAs that are potential biomarkers for human diseases. Here, we used thermostable group II intron reverse transcriptase sequencing (TGIRT-seq) combined with peak calling to simultaneously profile all RNA biotypes in apheresis-prepared human plasma pooled from healthy individuals. Extending previous TGIRT-seq analysis, we found that human plasma contains largely fragmented mRNAs from > 19,000 protein-coding genes, abundant full-length, mature tRNAs and other structured small non-coding RNAs, and less abundant tRNA fragments and mature and pre-miRNAs. Many of the mRNA fragments identified by peak calling correspond to annotated protein-binding sites and/or have stable predicted secondary structures that could afford protection from plasma nucleases. Peak calling also identified novel repeat RNAs, miRNA-sized RNAs, and putatively structured intron RNAs of potential biological, evolutionary, and biomarker significance, including a family of full-length excised intron RNAs, subsets of which correspond to mirtron pre-miRNAs or agotrons."
3104,Genipin inhibits rotavirus-induced diarrhea by suppressing viral replication and regulating inflammatory responses,"Rotavirus is the leading cause of acute gastroenteritis among young children worldwide. However, agents specifically designed to treat rotavirus infection have not been developed yet. In this study, the anti-rotavirus and anti-inflammatory effects of genipin, a chemical compound found in the fruit of Gardenia jasminoides, were evaluated. Genipin had an antiviral effect against the human rotavirus Wa and SA-11 strains in vitro, and it inhibited two distinct stages of the viral replication cycle: attachment and penetration (early stage) in pre-treatment and assembly and release (late stage) in post-treatment. Additionally, genipin downregulated nitric oxide synthase and pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 cells and rotavirus-infected Caco-2 cells. Oral administration of genipin before and after viral infection with the murine rotavirus epidemic diarrhea of infant mice strain led to a reduced duration of diarrhea and faecal viral shedding and to decreased destruction of the enteric epithelium. Genipin could have potential as a natural compound with preventive and therapeutic effects against infection and colitis caused by rotavirus."
3105,An ER translocon for multi-pass membrane protein biogenesis,"Membrane proteins with multiple transmembrane domains play critical roles in cell physiology, but little is known about the machinery coordinating their biogenesis at the endoplasmic reticulum. Here we describe a ~ 360 kDa ribosome-associated complex comprising the core Sec61 channel and five accessory factors: TMCO1, CCDC47 and the Nicalin-TMEM147-NOMO complex. Cryo-electron microscopy reveals a large assembly at the ribosome exit tunnel organized around a central membrane cavity. Similar to protein-conducting channels that facilitate movement of transmembrane segments, cytosolic and luminal funnels in TMCO1 and TMEM147, respectively, suggest routes into the central membrane cavity. High-throughput mRNA sequencing shows selective translocon engagement with hundreds of different multi-pass membrane proteins. Consistent with a role in multi-pass membrane protein biogenesis, cells lacking different accessory components show reduced levels of one such client, the glutamate transporter EAAT1. These results identify a new human translocon and provide a molecular framework for understanding its role in multi-pass membrane protein biogenesis."
3106,Genetic mapping of etiologic brain cell types for obesity,"The underlying cell types mediating predisposition to obesity remain largely obscure. Here, we integrated recently published single-cell RNA-sequencing (scRNA-seq) data from 727 peripheral and nervous system cell types spanning 17 mouse organs with body mass index (BMI) genome-wide association study (GWAS) data from >457,000 individuals. Developing a novel strategy for integrating scRNA-seq data with GWAS data, we identified 26, exclusively neuronal, cell types from the hypothalamus, subthalamus, midbrain, hippocampus, thalamus, cortex, pons, medulla, pallidum that were significantly enriched for BMI heritability (p<1.6×10(−4)). Using genes harboring coding mutations associated with obesity, we replicated midbrain cell types from the anterior pretectal nucleus and periaqueductal gray (p<1.2×10(−4)). Together, our results suggest that brain nuclei regulating integration of sensory stimuli, learning and memory are likely to play a key role in obesity and provide testable hypotheses for mechanistic follow-up studies."
3107,Detection of Focal and Non-Focal Electroencephalogram Signals Using Fast Walsh-Hadamard Transform and Artificial Neural Network,"The discrimination of non-focal class (NFC) and focal class (FC), is vital in localizing the epileptogenic zone (EZ) during neurosurgery. In the conventional diagnosis method, the neurologist has to visually examine the long hour electroencephalogram (EEG) signals, which consumes time and is prone to error. Hence, in this present work, automated diagnosis of FC EEG signals from NFC EEG signals is developed using the Fast Walsh–Hadamard Transform (FWHT) method, entropies, and artificial neural network (ANN). The FWHT analyzes the EEG signals in the frequency domain and decomposes it into the Hadamard coefficients. Five different nonlinear features, namely approximate entropy (ApEn), log-energy entropy (LogEn), fuzzy entropy (FuzzyEn), sample entropy (SampEn), and permutation entropy (PermEn) are extracted from the decomposed Hadamard coefficients. The extracted features detail the nonlinearity in the NFC and the FC EEG signals. The judicious entropy features are supplied to the ANN classifier, with a 10-fold cross-validation method to classify the NFC and FC classes. Two publicly available datasets such as the University of Bonn and Bern-Barcelona dataset are used to evaluate the proposed approach. A maximum sensitivity of 99.70%, the accuracy of 99.50%, and specificity of 99.30% with the 3750 pairs of NFC and FC signal are achieved using the Bern-Barcelona dataset, while the accuracy of 92.80%, the sensitivity of 91%, and specificity of 94.60% is achieved using University of Bonn dataset. Compared to the existing technique, the proposed approach attained a maximum classification performance in both the dataset."
3108,SPRINT: a Cas13a-based platform for detection of small molecules,"Recent efforts in biological engineering have made detection of nucleic acids in samples more rapid, inexpensive and sensitive using CRISPR-based approaches. We expand one of these Cas13a-based methods to detect small molecules in a one-batch assay. Using SHERLOCK-based profiling of in vitrotranscription (SPRINT), in vitro transcribed RNA sequence-specifically triggers the RNase activity of Cas13a. This event activates its non-specific RNase activity, which enables cleavage of an RNA oligonucleotide labeled with a quencher/fluorophore pair and thereby de-quenches the fluorophore. This fluorogenic output can be measured to assess transcriptional output. The use of riboswitches or proteins to regulate transcription via specific effector molecules is leveraged as a coupled assay that transforms effector concentration into fluorescence intensity. In this way, we quantified eight different compounds, including cofactors, nucleotides, metabolites of amino acids, tetracycline and monatomic ions in samples. In this manner, hundreds of reactions can be easily quantified in a few hours. This increased throughput also enables detailed characterization of transcriptional regulators, synthetic compounds that inhibit transcription, or other coupled enzymatic reactions. These SPRINT reactions are easily adaptable to portable formats and could therefore be used for the detection of analytes in the field or at point-of-care situations."
3109,"Bovine viral diarrhea virus: An updated American College of Veterinary Internal Medicine consensus statement with focus on virus biology, hosts, immunosuppression, and vaccination","Control of bovine viral diarrhea virus (BVDV) in cattle populations across most of the world has remained elusive in spite of advances in knowledge about this viral pathogen. A central feature of virus perseverance in cattle herds is the unique mechanism of persistent infection. Managing BVDV infection in herds involves controlling persistently infected carrier animals using a multidimensional approach of vaccination, biosecurity, and identification of BVDV reservoirs. A decade has passed since the original American College of Veterinary Internal Medicine consensus statement on BVDV. While much has remained the same with respect to clinical signs of disease, pathogenesis of infection including persistent infection, and diagnosis, scientific articles published since 2010 have led to a greater understanding of difficulties associated with control of BVDV. This consensus statement update on BVDV presents greater focus on topics currently relevant to the biology and control of this viral pathogen of cattle, including changes in virus subpopulations, infection in heterologous hosts, immunosuppression, and vaccination."
3110,"Persistent lentivirus infection induces early myeloid suppressor cells expansion to subvert protective memory CD8 T cell response(✰,✰✰)","BACKGROUND: Memory CD8(+)T cell responses play an essential role in protection against persistent infection. However, HIV-1 evades vaccine-induced memory CD8(+)T cell response by mechanisms that are not fully understood. METHODS: We analyzed the temporal dynamics of CD8(+)T cell recall activity and function during EcoHIV infection in a potent PD1-based vaccine immunized immunocompetent mice. FINDINGS: Upon intraperitoneal EcoHIV infection, high levels of HIV-1 GAG-specific CD8(+)T lymphocytes recall response reduced EcoHIV-infected cells significantly. However, this protective effect diminished quickly after seven days, followed by a rapid reduction of GAG-specific CD8(+)T cell number and activity, and viral persistence. Mechanistically, EcoHIV activated dendritic cells (DCs) and myeloid cells. Myeloid cells were infected and rapidly expanded, exhibiting elevated PD-L1/-L2 expression and T cell suppressive function before day 7, and were resistant to CD8(+)T cell-mediated apoptosis. Depletion of myeloid-derived suppressor cells (MDSCs) reduced EcoHIV infection and boosted T cell responses. INTERPRETATION: This study provides an overview of the temporal interplay of persistent virus, DCs, MDSCs and antigen-specific CD8(+)T cells during acute infection. We identify MDSCs as critical gatekeepers that restrain antiviral T cell memory responses, and highlight MDSCs as an important target for developing effective vaccines against chronic human infections. FUNDING: Hong Kong Research Grant Council (T11–709/18-N, HKU5/CRF/13G), General Research Fund (17122915 and 17114114), Hong Kong Health and Medical Research Fund (11100752, 14130582, 16150662), Grant RGC-ANR A-HKU709/14, the San-Ming Project of Medicine (SZSM201512029), University Development Fund of the University of Hong Kong and Li Ka Shing Faculty of Medicine Matching Fund to HKU AIDS Institute."
3111,Influence of severity of infection on the effect of appropriate antimicrobial therapy for Acinetobacter baumannii bacteremic pneumonia,"BACKGROUND: The impact of appropriate antimicrobial therapy for A. baumannii bacteremic pneumonia has not been well established due to the inclusion of the three phenotypically indistinguishable Acinetobacter species and confounding factors including underlying diseases and severity of infection. This retrospective study aimed to evaluate the impact of appropriate antimicrobial therapy on 14-day mortality in A. baumannii bacteremic pneumonia patients after adjusting for risk factors. METHODS: This study was conducted at five medical centers in Taiwan between July 2012 and June 2016. A. baumannii species identification was performed using reference molecular methods. Risk factors for 14-day mortality were analyzed via logistic regression. The interaction between the Acute Physiology and Chronic Health Evaluation (APACHE) II score and appropriate antimicrobial therapy was assessed using the logistic model. RESULTS: A total of 336 patients with monomicrobial A. baumannii bacteremic pneumonia were included in this study. The overall 14-day mortality rate was 47.3%. The crude mortality of appropriate antimicrobial therapy was 35.9% (57 of 151 patients). Appropriate antimicrobial therapy was associated with a lower mortality after multivariate adjustment (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.34–0.97; p = 0.04), and the effect was influenced by APACHE II score (OR for interaction term, 0.0098; 95% CI, 0.0005–0.1885; p = 0.002). Further analysis demonstrated that appropriate antimicrobial therapy significantly reduced 14-day mortality among the patients with an APACHE II score > 35 (OR 0.0098; 95% CI 0.0005–0.1885). CONCLUSION: Appropriate antimicrobial therapy decreases 14-day mortality of the most severely ill patients with A. baumannii bacteremic pneumonia."
3112,"Vergleich von Chest Pain Units und Stroke Units: Elementare Bausteine der vaskulären Akutversorgung: Vergleich von Struktur, Zertifizierung, Qualitätserfassung und Vergütung","BACKGROUND: Chest pain units (CPU) and stroke units (SU) have both become established as essential components of clinical emergency care. For both instances dedicated certification processes are installed. Up to summer 2020, 290 CPUs and 335 SUs have been successfully certified. OBJECTIVE: The aim of this review is to compare the structures and the current certification situation of CPUs and SUs. Also, the younger CPU certification process is compared to the long established SU certification standard. MATERIAL UND METHODS: The comparison includes the historical background, the certification process, quality benchmarking, possible additive structures, the current status of certification in Germany, the transfer of the concept to the European level as well as reimbursement issues. RESULTS: Both certification concepts show clear analogies. Evidence for SUs is supported by a positive Cochrane analysis and for CPUs there are many studies from the German CPU registry. The main differences include a uniform CPU system versus a multistep SU system of certification. Furthermore, SU have obligatory elements of quality documentation but only facultative quality indicator assessment for CPUs. From an economic viewpoint operation and procedural key (OPS) numbers guarantee a better reflection of the use of resources in the complex treatment of stroke, which could not yet be established for CPUs. CONCLUSION: The well-established CPU concept could additionally benefit from a superordinate quality control. Adequate quality benchmarking appears to be fundamental for gap analyses and for the establishment of a separate remuneration structure. In this respect the German Society for Cardiology as the certifying institution is required to establish an appropriate mechanism within the framework of regular updates of criteria."
3113,"Prospective, observational study to assess the performance of CAA measurement as a diagnostic tool for the detection of Schistosoma haematobium infections in pregnant women and their child in Lambaréné, Gabon: study protocol of the freeBILy clinical trial in Gabon","BACKGROUND: Schistosoma antigen detection in urine is a valuable diagnostic approach for schistosomiasis control programmes because of the higher sensitivity compared to parasitological methods and preferred sampling of urine over stool. Highly accurate diagnostics are important in low Schistosoma transmission areas. Pregnant women and young children could particularly benefit from antigen testing as praziquantel (PZQ) can be given to only confirmed Schistosoma cases. This prevents the unborn baby from unnecessary exposure to PZQ. We present here the protocol of a diagnostic study that forms part of the freeBILy project. The aim is to evaluate the accuracy of circulating anodic antigen (CAA) detection for diagnosis of Schistosoma haematobium infections in pregnant women and to validate CAA as an endpoint measure for anti-Schistosoma drug efficacy. The study will also investigate Schistosoma infections in infants. METHODS: A set of three interlinked prospective, observational studies is conducted in Gabon. The upconverting phosphor lateral flow (UCP-LF) CAA test is the index diagnostic test that will be evaluated. The core trial, sub-study A, comprehensively evaluates the accuracy of the UCP-LF CAA urine test against a set of other Schistosoma diagnostics in a cross-sectional trial design. Women positive for S. haematobium will proceed with sub-study B and will be randomised to receive PZQ treatment immediately or after delivery followed by weekly sample collection. This approach includes comparative monitoring of CAA levels following PZQ intake and will also contribute further data for safety of PZQ administration during pregnancy. Sub-study C is a longitudinal study to determine the incidence of S. haematobium infection as well as the age for first infection in life-time. DISCUSSION: The freeBILy trial in Gabon will generate a comprehensive set of data on the accuracy of the UCP-LF CAA test for the detection of S. haematobium infection in pregnant women and newborn babies and for the use of CAA as a marker to determine PZQ efficacy. Furthermore, incidence of Schistosoma infection in infants will be reported. Using the ultrasensitive diagnostics, this information will be highly relevant for Schistosoma prevalence monitoring by national control programs as well as for the development of medicaments and vaccines. TRIAL REGISTRATION: The registration number of this study is NCT03779347 (clinicaltrials.gov, date of registration: 19 December 2018)."
3114,Identification of quality gaps in healthcare services using the SERVQUAL instrument and importance-performance analysis in medical intensive care: a prospective study at a medical center in Taiwan,"BACKGROUND: Assessing patients’ expectations and perceptions of health service delivery is challenging. To understand the service quality in intensive care units (ICUs), we investigated the expected and perceived service quality of ICU care. METHODS: We conducted this study at an ICU of a university-affiliated medical center in Taiwan from April to September 2019. Admitted patients or their family members responded to a questionnaire survey adopted from the SERVQUAL instrument consisting of 22 items in five dimensions. The questionnaire was provided on ICU admission for expectation and before ICU discharge for perception. We analyzed the quality gaps between the surveys and applied important-performance analysis (IPA). RESULTS: A total of 117 patients were included (62.4% males, average age: 65.9 years, average length of stay: 10.1 days, and 76.9% survival to ICU discharge). The overall weighted mean scores for the surveys were similar (4.57 ± 0.81 and 4.58 ± 0.52, respectively). The ‘tangibles’ dimension had a higher perception than expectation (3.99 ± 0.55 and 4.31 ± 0.63 for expectation and perception, respectively, p < 0.001). IPA showed that most of the items in ‘reliability,’ ‘responsiveness’ and ‘assurance’ were located in the quadrant of high expectation and high perception, whereas most of the items in ‘tangibles’ and ‘empathy’ were located in the quadrant of low expectation and low perception. One item (item 1 for ‘tangibles’) was found in the quadrant of high expectation and low perception. CONCLUSIONS: The SERVQUAL approach and IPA might provide useful information regarding the feedback by patients and their families for ICU service quality. In most aspects, the performance of the ICU satisfactorily matched the needs perceived by the patients and their families."
3115,Sequence identification and expression profile of seven Dermacentor marginatus glutathione S-transferase genes,"Dermacentor marginatus is a widespread tick species and a vector of many pathogens in Eurasia. Due to the medical importance of D. marginatus, control measures are needed for this tick species. Currently tick control approaches rely mostly on acaricide application, whereas wrong and irrational acaricide use may result in drug resistance and residue problems. Vaccination as an alternative approach for tick control has been proven to be effective towards some tick species. However, immunization against D. marginatus has not yet reached satisfactory protection. The effort of in silico based analysis could predict antigenicity and identify candidates for anti-tick vaccine development. We carried out an in silico analysis of D. marginatus glutathione S-transferases (DmGSTs) in order to identify blood-feeding induced GSTs as antigens that can be used in anti-tick vaccine development. Phylogenetic analysis, linear B-cell epitope prediction, homology modeling, and conformational B-cell epitope mapping on the GST models were performed to identify highly antigenic DmGSTs. Relative gene expressions of the seven GSTs were profiled through real-time quantitative PCR (RT-qPCR) to outline GSTs up-regulated during blood feeding. The phylogenetic analysis indicated that the seven GSTs belonged to four classes of GST, including one in epsilon-class, one in zeta-class, one in omega-class, and four in mu-class. Linear B-cell epitope prediction revealed mu-class GSTs share similar conserved antigenic regions. The conformational B-cell epitope mapped on the homology model of the GSTs displayed that GSTs of mu-class showed stronger antigenicity than that of other classes. RT-qPCR revealed DmGSTM1 and DmGSTM2 were positively related to blood feeding. In sum, the data suggest that DmGSTM1 and DmGSTM2 could be tested for potential anti-tick vaccine trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10493-020-00546-7) contains supplementary material, which is available to authorized users."
3116,Vaccines against components of the renin–angiotensin system,"Even though effective drugs for treating hypertension are available, a great percentage of patients have inadequate control of their blood pressure. Unwanted side effects and inappropriate oral drug adherence are important factors that contribute to the global problem of uncontrolled hypertension. Vaccination could provide a revolutionary therapy with long-lasting effects, increasing patient compliance and therefore better control of high blood pressure. Nowadays, current immunization approaches against hypertension target renin, angiotensin I, angiotensin II, and angiotensin II type 1 receptor, key elements of the renin–angiotensin system. This article reviews the different vaccination attempts with proteins and peptides against the different molecules of the renin–angiotensin system in the last two decades, safety issues, and other novel prospects biomarkers in hypertension, and summarizes the potential of this immunomodulatory approach in clinical practice."
3117,Systematic review of modifiable risk factors shows little evidential support for most current practices in Cryptosporidium management in bovine calves,"Cryptosporidiosis is common in young calves, causing diarrhoea, delayed growth, poor condition and excess mortality. No vaccine or cure exists, although symptomatic onset may be delayed with some chemoprophylactics. Other response and management strategies have focused on nutritional status, cleanliness and biosecurity. We undertook a systematic review of observational studies to identify risk or protective factors that could prevent Cryptosporidium parvum infection in calves. Included studies used multivariate analysis within cohort, cross-sectional or case-control designs, of risk factors among young calves, assessing C. parvum specifically. We tabulated data on characteristics and study quality and present narrative synthesis. Fourteen eligible studies were found; three of which were higher quality. The most consistent evidence suggested that risk of C. parvum infection increased when calves had more contact with other calves, were in larger herds or in organic production. Hard flooring reduced risk of infection and calves tended to have more cryptosporidiosis during warm and wet weather. While many other factors were not found to be associated with C. parvum infection, analyses were usually badly underpowered, due to clustering of management factors. Trials are needed to assess effects of manipulating calf contact, herd size, organic methods, hard flooring and temperature. Other factors need to be assessed in larger observational studies with improved disaggregation of potential risk factors. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00436-020-06890-2) contains supplementary material, which is available to authorized users."
3118,The burden of disease among Brazilian older adults and the challenge for health policies: results of the Global Burden of Disease Study 2017,"BACKGROUND: Brazil is the world’s fifth most populous nation, and is currently experimenting a fast demographic aging process in a context of scarce resources and social inequalities. To understand the health profile of older adults in Brazil is fundamental for planning public policies. METHODS: The estimates were derived from data obtained through the collaboration between the Brazilian Ministry of Health and the Institute of Health Metrics and Evaluation of the University of Washington. The Brazilian Institute of Geography and Statistics provided the population estimates. Data on causes of death came from the Mortality Information System. To calculate morbidity, population-based studies on the prevalence of diseases in Brazil were comprehensively searched, in addition to information obtained from national databases such as the Hospital Information System, the Outpatient Information System, and the Injury Information System. We presented the Global Burden of Disease (GBD) 2017 estimates among Brazilian older adults (60+ years old) for life expectancy at birth (LE), healthy life expectancy (HALE), cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs), from 2000 to 2017. RESULTS: LE at birth significantly increased from 71.3 years (95% UI to 70.9-71.8) to 75.2 years (95% UI 74.7-75.7). There was a trend of increasing HALE, from 62.2 years (95% UI 59.54-64.5) to 65.5 years (95% UI 62.6-68.0). The proportion of DALYs among older adults increased from 7.3 to 10.3%. Chronic noncommunicable diseases are the leading cause of death among middle aged and older adults, while Alzheimer’s disease is a leading cause only among older adults. Mood disorders, musculoskeletal pain, and hearing or vision losses are among the leading causes of disability. CONCLUSIONS: The increase in LE and the decrease of the DALYs rates are probably results of the improvement of social conditions and health policies. However, the smaller increase of HALE than LE means that despite living more, people spend a substantial time of their old age with disability and illness. Preventable or potentially controllable diseases are responsible for most of the burden of disease among Brazilian older adults. Health investments are necessary to obtain longevity with quality of life in Brazil."
3119,"Healthcare Resource Utilization of Ceftolozane/Tazobactam Versus Meropenem for Ventilated Nosocomial Pneumonia from the Randomized, Controlled, Double-Blind ASPECT-NP Trial","INTRODUCTION: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP) are associated with significant healthcare resource utilization (HCRU). This a priori, exploratory, secondary analysis from the ASPECT-NP clinical trial evaluated resource utilization among patients with ventilated HABP (vHABP)/VABP treated with ceftolozane/tazobactam or meropenem. METHODS: This analysis used data from the randomized, double-blind, noninferiority phase 3 ASPECT-NP trial of patients with vHABP/VABP randomized to receive ceftolozane/tazobactam 3 g (ceftolozane 2 g/tazobactam 1 g) or meropenem 1 g for 8–14 days. Day 28 outcomes included hospital length of stay (LOS), intensive care unit (ICU) LOS, and time to mechanical ventilation extubation in the microbiological intention-to-treat (mITT) population and in an HCRU population. The HCRU population, a subset of patients from the mITT population that were alive at day 28, was used to remove resource use bias influenced by mortality rates. RESULTS: Ceftolozane/tazobactam-treated versus meropenem-treated patients, respectively, had fewer deaths (20.1% vs. 25.5%), fewer hospital discharges (30.7% vs. 32.4%), and higher ICU discharges (60.0% vs. 58.3%) and extubations (51.9% vs. 48.2%) by day 28. In the HCRU population, adjusted LOS differences (95% confidence intervals) for ceftolozane/tazobactam compared with meropenem were 0.1 (− 1.4 to 1.6) hospitalization days, − 1.4 (− 2.9 to 0.2) ICU days, and − 0.9 (− 2.4 to 0.7) mechanical ventilation days. Patterns were similar among the VABP and Pseudomonas aeruginosa subgroups. CONCLUSION: Similar 28-day resource utilization outcomes were observed between ceftolozane/tazobactam and meropenem in the mITT population of patients from ASPECT-NP with vHABP/VABP due to gram-negative pathogens. ASPECT-NP was not powered to detect differences in resource utilization outcomes between treatment groups; however, numerical differences in ICU LOS and duration of mechanical ventilation were noted. Further study is needed to assess resource utilization in the real-world practice setting, especially among patients excluded from ASPECT-NP, including those with resistant P. aeruginosa infections. TRIAL REGISTRATIONS: ClinicalTrials.gov: NCT02070757, registered February 25, 2014; EudraCT: 2012-002862-11. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40121-020-00343-0) contains supplementary material, which is available to authorized users."
3120,"From Monovalent to Multivalent Vaccines, the Exploration for Potential Preventive Strategies Against Hand, Foot, and Mouth Disease (HFMD)","Hand, foot, and mouth disease (HFMD) recently emerged as a global public threat. The licensure of inactivated enterovirus A71 (EV-A71) vaccine was the first step in using a vaccine to control HFMD. New challenges arise from changes in the pathogen spectrum while vaccines directed against other common serotypes are in the preclinical stage. The mission of a broad-spectrum prevention strategy clearly favors multivalent vaccines. The development of multivalent vaccines was attempted via the simple combination of potent monovalent vaccines or the construction of chimeric vaccines comprised of epitopes derived from different virus serotypes. The present review summarizes recent advances in HFMD vaccine development and discusses the next steps toward a safe and effective HFMD vaccine that is capable of establishing a cross-protective antibody response."
3121,Early mechanical ventilation in patients with Guillain-Barré syndrome at high risk of respiratory failure: a randomized trial,"INTRODUCTION: About 30% of patients with Guillain-Barré syndrome become ventilator dependent, of whom roughly 75% develop pneumonia. This trial aimed at assessing the impact of early mechanical ventilation (EMV) on pneumonia occurrence in GBS patients. We hypothesize that EMV will reduce the incidence of pneumonia. METHODS: This was a single centre, open-label, randomized controlled trial performed on two parallel groups. 50 intensive care unit adults admitted for Guillain-Barré syndrome and at risk for acute respiratory failure. Patients were randomized to early mechanical ventilation via face-mask or endotracheal intubation owing to the presence or absence of impaired swallowing (experimental arm), or to conventional care (control arm). The primary outcome was the incidence of pneumonia up to intensive care unit discharge (or 90 days, pending of which occurred first). FINDINGS: Twenty-five patients were randomized in each group. There was no significant difference between groups for the incidence of pneumonia (10/25 (40%) vs 9/25 (36%), P = 1). There was no significant difference between groups for the time to onset of pneumonia (P = 0.50, Gray test). During follow-up, there were 16/25 (64%) mechanically ventilated patients in the control group, and 25/25 (100%) in the experimental arm (P < 000·1). The time on ventilator was non-significantly shorter in the experimental arm (14 [7; 29] versus 21.5 [17.3; 35.5], P = 0.10). There were no significant differences between groups for length of hospital stay, neurological scores, the proportion of patients who needed tracheostomy, in-hospital death, or any serious adverse events. CONCLUSIONS: In the present study including adults with Guillain-Barré syndrome at high risk of respiratory failure, we did not observe a prevention of pneumonia with early mechanical ventilation. Trial registration: ClinicalTrials.gov under the number NCT00167622. Registered 9 September 2005, https://clinicaltrials.gov/ct2/show/NCT00167622?cond=Guillain-Barre+Syndrome&cntry=FR&draw=2&rank=1"
3122,Prediction of Directional Changes of Influenza A Virus Genome Sequences with Emphasis on Pandemic H1N1/09 as a Model Case,"Influenza virus poses a significant threat to public health, as exemplified by the recent introduction of the new pandemic strain H1N1/09 into human populations. Pandemics have been initiated by the occurrence of novel changes in animal sources that eventually adapt to human. One important issue in studies of viral genomes, particularly those of influenza virus, is to predict possible changes in genomic sequence that will become hazardous. We previously established a clustering method termed ‘BLSOM’ (batch-learning self-organizing map) that does not depend on sequence alignment and can characterize and compare even 1 million genomic sequences in one run. Strategies for comparing a vast number of genomic sequences simultaneously become increasingly important in genome studies because of remarkable progresses in nucleotide sequencing. In this study, we have constructed BLSOMs based on the oligonucleotide and codon composition of all influenza A viral strains available. Without prior information with regard to their hosts, sequences derived from strains isolated from avian or human sources were successfully clustered according to the hosts. Notably, the pandemic H1N1/09 strains have oligonucleotide and codon compositions that are clearly different from those of human seasonal influenza A strains. This enables us to infer future directional changes in the influenza A viral genome."
3123,Sea change in coastal science,"Coastal regions are disproportionately affected by the impacts of climate change. Preserving the ecological, economic and societal benefits of these environments will rely on synergy across disciplines."
3124,Public Disclosure on Social Media of Identifiable Patient Information by Health Professionals: Content Analysis of Twitter Data,"BACKGROUND: Respecting patient privacy and confidentiality is critical for doctor-patient relationships and public trust in medical professionals. The frequency of potentially identifiable disclosures online during periods of active engagement is unknown. OBJECTIVE: The objective of this study was to quantify potentially identifiable content shared on social media by physicians and other health care providers using the hashtag #ShareAStoryInOneTweet. METHODS: We accessed and searched Twitter’s API using Symplur software for tweets that included the hashtag #ShareAStoryInOneTweet. We identified 1206 tweets by doctors, nurses, and other health professionals out of 43,374 tweets shared in May 2018. Tweet content was evaluated in January 2019 to determine the incidence of instances where names or potentially identifiable information about patients were shared; content analysis of tweets in which information about others had been disclosed was performed. The study also evaluated whether participants raised concerns about privacy breaches and estimated the frequency of deleted tweets. The study used dual, blinded coding for a 10% sample to estimate intercoder reliability using Cohen κ statistic for identifying the potential identifiability of tweet content. RESULTS: Health care professionals (n=656) disclosing information about others included 486 doctors (74.1%) and 98 nurses (14.9%). Health care professionals sharing stories about patient care disclosed the time frame in 95 tweets (95/754, 12.6%) and included patient names in 15 tweets (15/754, 2.0%). It is estimated that friends or families could likely identify the clinical scenario described in 242 of the 754 tweets (32.1%). Among 348 tweets about potentially living patients, it was estimated that 162 (46.6%) were likely identifiable by patients. Intercoder reliability in rating the potential identifiability demonstrated 86.8% agreement, with a Cohen κ of 0.8 suggesting substantial agreement. We also identified 78 out of 754 tweets (6.5%) that had been deleted on the website but were still viewable in the analytics software data set. CONCLUSIONS: During periods of active sharing online, nurses, physicians, and other health professionals may sometimes share more information than patients or families might expect. More study is needed to determine whether similar events arise frequently and to understand how to best ensure that patients’ rights are adequately respected."
3125,Medical Insurance Information Systems in China: Mixed Methods Study,"BACKGROUND: Since the People’s Republic of China (PRC), or China, established the basic medical insurance system (MIS) in 1998, the medical insurance information systems (MIISs) in China have effectively supported the operation of the MIS through several phases of development; the phases included a stand-alone version, the internet, and big data. In 2018, China’s national medical security systems were integrated, while MIISs were facing reconstruction. We summarized China’s experience in medical insurance informatization over the past 20 years, aiming to provide a reference for the building of a new basic MIS for China and for developing countries. OBJECTIVE: This paper aims to sort out medical insurance informatization policies throughout the years, use questionnaires to determine the status quo of provincial MIIS-building in China and the relevant policies, provide references and suggestions for the top-level design and implementation of the information systems in the transitional period of China’s MIS reform, and provide a reference for the building of MIISs in developing countries. METHODS: We conducted policy analysis by collecting the laws, regulations, and policy documents—issued from 1998 to 2020—on China's medical insurance and its informatization; we also analyzed the US Health Insurance Portability and Accountability Act and other relevant policies. We conducted a questionnaire survey by sending out questionnaires to 31 Chinese, provincial, medical security bureaus to collect information about network links, system functions, data exchange, standards and specifications, and building modes, among other items. We conducted a literature review by searching for documents about relevant laws and policies, building methods, application results, and other documents related to MIISs; we conducted searches using PubMed, Elsevier, China National Knowledge Infrastructure, and other major literature databases. We conducted telephone interviews to verify the results of questionnaires and to understand the focus issues concerning the building of China’s national MIISs during the period of integration and transition of China's MIS. RESULTS: In 74% (23/31) of the regions in China, MIISs were networked through dedicated fiber optic lines. In 65% (20/31) of the regions in China, MIISs supported identity recognition based on both ID cards and social security cards. In 55% (17/31) of the regions in China, MIISs at provincial and municipal levels were networked and have gathered basic medical insurance data, whereas MIISs were connected to health insurance companies in 35% (11/31) of the regions in China. China’s MIISs are comprised of 11 basic functional modules, among which the modules of business operation, transregional referral, reimbursement, and monitoring systems are widely applied. MIISs in 83% (20/24) of Chinese provinces have stored data on coverage, payment, and settlement compensation of medical insurance. However, in terms of data security and privacy protection, pertinent policies are absent and data utilization is not in-depth enough. Respondents to telephone interviews universally reflected on the following issues and suggestions: in the period of integration and transition of MISs, close attention should be paid to the top-level design, and repeated investment should be avoided for the building of MIISs; MIISs should be adapted to the health care reform, and efforts should be made to strengthen the informatization support for the reform of payment methods; and MIISs should be adapted for the widespread application of mobile phones and should provide insured persons with more self-service functions. CONCLUSIONS: In the future, the building of China’s basic MIISs should be deployed at the national, provincial, prefectural, and municipal levels on a unified basis. Efforts should be made to strengthen the development of standard codes, data exchange, and data utilization. Work should be done to formulate the rules and regulations for security and privacy protection and to balance the right to be informed with the mining and utilization of big data. Efforts should be made to intensify the interconnectivity between MISs and other health systems and to strengthen the application of medical insurance information in public health monitoring and early warning systems; this would ultimately improve the degree of trust from stakeholders, including individuals, medical service providers, and public health institutions, in the basic MIISs."
3126,Using tooth enamel microstructure to identify mammalian fossils at an Eocene Arctic forest,"Lower Eocene (Wasatchian-aged) sediments of the Margaret Formation on Ellesmere Island in Canada’s High Arctic preserve evidence of a rainforest inhabited by alligators, turtles, and a diverse mammalian fauna. The mammalian fossils are fragmentary and often poorly preserved. Here, we offer an alternative method for their identification. Among the best preserved and extensive of the Eocene Arctic forests is the Strathcona Fiord Fossil Forest, which contains permineralized in situ tree stumps protruding from a prominent coal seam, but a paucity of vertebrate fossils. In 2010 and 2018, we recovered mammalian tooth fragments at the fossil forest, but they are so incomplete as to be undiagnostic by using their external morphology. We used a combination of light microscopy and SEM analysis to study the enamel microstructure of two tooth fragments from the fossil forest—NUFV2092B and 2092E. The results of our analysis indicate that NUFV2092B and 2092E have Coryphodon-enamel, which is characterized by vertical bodies that manifest as bands of nested chevrons or treelike structures visible in the tangential section under light microscopy. This enamel type is not found in other mammals known from the Arctic. Additionally, when studied under SEM, the enamel of NUFV2092B and 2092E has rounded prisms that open to one side and are surrounded by interprismatic matrix that is nearly parallel to the prisms, which also occurs in Coryphodon enamel, based on prior studies. The tooth fragments reported here, along with some poorly preserved bone fragments, thus far are the only documented vertebrate fossils from the Strathcona Fiord Fossil Forest. However, fossils of Coryphodon occur elsewhere in the Margaret Formation, so its presence at the fossil forest is not surprising. What is novel in our study is the way in which we identified the fossils using their enamel microstructure."
3127,Assessing the application of big data technology in platform business model: A hierarchical framework,"This research aims to create a hierarchical framework for the development of a platform business model based on big data. However, this hierarchical framework must consider unnecessary attributes and the interrelationships between the aspects and the criteria. Hence, fuzzy set theory is used for screening out the unnecessary attributes, a decision-making and trial evaluation laboratory (DEMATEL) is proposed to manage the complex interrelationships among the aspects and attributes, and interpretive structural modeling (ISM) is used to divide the hierarchy and finally construct a hierarchical framework. The results reveal that (1) value proposition and community building in value production are fundamental links; (2) information technology and information management in value production are technical supports; (3) customer development in value marketing is the power source; and (4) value acquisition is the last link, which is established on the basis of and influenced by value marketing and value network. This hierarchical framework aims to guide the platform toward the application of big data. This study also proposes engagement of stakeholders for promoting value creation and establishing a sound business model from multiple levels and links."
3128,De-simplifying single-tablet antiretroviral treatments for cost savings in France: From the patient perspectives to a 6-month follow-up on generics,"In developed countries, most people living with HIV/AIDS are treated with costly brand single-tablet regimens. Given the economic impact, French guidelines recommend using generic antiretroviral therapy when possible to decrease antiretroviral therapy costs. We aimed to study HIV-infected patients’ acceptability to switch from a brand single-tablet regimens [abacavir/lamivudine/dolutegravir (Triumeq(®)) or emtricitabine/tenofovir disoproxil fumarate/rilpivirine (Eviplera(®))] to a treatment comprising of two pills: one is a fixed-dose generic combination of 2 Nucleoside Analogs and the second tablet is the third antiretroviral. This study was a prospective observational study in a French hospital. During their follow-up, patients on stable single-tablet regimens were made aware of the possible cost-saving. They were questioned about their willingness and barriers accepting the substitution. Participants chose between the two regimens, either to remain on single-tablet regimens or switch to the de-simplified regimen. Six months later, a second survey was given to the patient who chose to de-simplify and HIV viral load was controlled. The study included 98 patients: 60 receiving emtricitabine/tenofovir disoproxil fumarate/rilpivirine (Eviplera(®)) and 38 on abacavir/lamivudine/dolutegravir (Triumeq(®)). Forty-five patients accepted the de-simplified treatment, 37 refused and 16 were undecided and followed the decision offered by their physician. The main reason for unwillingness to switch is the number of pills (77.3%). In multivariate model analysis, male patients (p = 0.001) who have taken antiretroviral therapy for over 20 years (p = 0.04) and who retrieve their treatment in their community hospital (p = 0.03) are more likely to accept the switch. Fifty-one patients accepted to replace their single-tablet regimens and six months later, the majority was satisfied; only four returned to single-tablet regimens because of suspected side effects. Half of the people living with HIV/AIDS in our cohort accepted to switch from brand single-tablet regimens to a two-tablet regimen containing generic drugs within a process that emphasizes health expenditure savings."
3129,Involvement of dopaminergic signaling in the cross talk between the renin-angiotensin system and inflammation,"The renin-angiotensin system (RAS) is a fundamental regulator of blood pressure and has emerged as an important player in the control of inflammatory processes. Accordingly, imbalance on RAS components either systemically or locally might trigger the development of inflammatory disorders by affecting immune cells. At the same time, alterations in the dopaminergic system have been consistently involved in the physiopathology of inflammatory disorders. Accordingly, the interaction between the RAS and the dopaminergic system has been studied in the context of inflammation of the central nervous system (CNS), kidney, and intestine, where they exert antagonistic actions in the regulation of the immune system. In this review, we summarized, integrated, and discussed the cross talk of the dopaminergic system and the RAS in the regulation of inflammatory pathologies, including neurodegenerative disorders, such as Parkinson’s disease. We analyzed the molecular mechanisms underlying the interaction between both systems in the CNS and in systemic pathologies. Moreover, we also analyzed the impact of the commensal microbiota in the regulation of RAS and dopaminergic system and how it is involved in inflammatory disorders. Furthermore, we summarized the therapeutic approaches that have yielded positive results in preclinical or clinical studies regarding the use of drugs targeting the RAS and dopaminergic system for the treatment of inflammatory conditions. Further understanding of the molecular and cellular regulation of the RAS-dopaminergic cross talk should allow the formulation of new therapies consisting of novel drugs and/or repurposing already existing drugs, alone or in combination, for the treatment of inflammatory disorders."
3130,Jitendra Nath Pande (14.06.1941 - 23.05.2020),
3131,Navigating the new normal in ophthalmology,
3132,Commentary: Telemedicine: The unsung corona warrior,
3133,Insights into the prognosis of lipidomic dysregulation for death risk in patients with coronary artery disease,"BACKGROUND: Dyslipidaemia contributes to the progression of coronary artery disease (CAD) toward adverse outcomes. Plasma lipidomic measure may improve the prognostic performances of clinical endpoints of CAD. Our research is designed to identify the correlations between plasma lipid species and the risks of death, major adverse cardiovascular event (MACE) and left ventricular (LV) remodeling in patients with CAD. METHODS: A total of 1569 Chinese patients with CAD, 1011 single‐centre patients as internal training cohort, and 558 multicentre patients as external validation cohort, were enrolled. The concentration of plasma lipids in both cohorts was determined through widely targeted lipidomic profiling. Least absolute shrinkage and selection operator Cox and multivariate Cox regressions were used to develop prognostic models for death and MACE, respectively. RESULTS: Ten (Cer(d18:1/20:1), Cer(d18:1/24:1), PE(30:2), PE(32:0), PE(32:2), PC(O‐38:2), PC(O‐36:4), PC(16:1/22:2), LPC(18:2/0:0) and LPE(0:0/24:6)) and two (Cer(d18:1/20:1) and LPC(20:0/0:0)) lipid species were independently related to death and MACE, respectively. Cer(d18:1/20:1) and Cer(d18:1/24:1) were correlated with LV remodeling (P < .05). The lipidic panel incorporating 10 lipid species and two traditional biomarkers for predicting 5‐year death risk represented a remarkable higher discrimination than traditional model with increased area under the curve from 76.56 to 83.65%, continuous NRI of 0.634 and IDI of 0.131. Furthermore, the panel was successfully used in differentiating multicentre patients with low, middle, or high risks (P < .0001). Further analysis indicated that the number of double bonds of phosphatidyl choline and the content of carbon atoms of phosphatidyl ethanolamines were negatively associated with death risk. CONCLUSIONS: Improvement in the prediction of death confirms the effectiveness of plasma lipids as predictors to risk classification in patients with CAD. The association between the structural characteristics of long‐chain polyunsaturated fatty acids and death risk highlights the need for mechanistic research that characterizes the role of individual lipid species in disease pathogenesis."
3134,Construction of a dictionary of sequence motifs that characterize groups of related proteins,"An automatic procedure is proposed to identify, from the protein sequence database, conserved amino acid patterns (or sequence motifs) that are exclusive to a group of functionally related proteins. This procedure is applied to the PIR database and a dictionary of sequence motifs that relate to specific superfamilies constructed. The motifs have a practical relevance in identifying the membership of specific superfamilies without the need to perform sequence database searches in 20% of newly determined sequences. The sequence motifs identified represent functionally important sites on protein molecules. When multiple blocks exist in a single motif they are often close together in the 3-D structure. Furthermore, occasionally these motif blocks were found to be split by introns when the correlation with exon structures was examined."
3135,Just in TIME: Trauma-Informed Medical Education,"Numerous organizations implement a trauma-informed approach. This model assists institutions in providing care and education that delivers support to members who have undergone traumatic experiences, and many institutions apply the principles as a universal precaution. Student and trainee experiences in medical education reveal a hidden curriculum that may deliver conflicting messages about the values of an institution, in which equity is promoted, but biased and discriminatory practices are commonplace. Implicit racial bias has been identified in the patient-provider interaction and may also extend its impact on the learner experience. Bias and discrimination inflict trauma on its targets via emotional injury. Applying the principles of the trauma-informed approach, we advocate for trauma-informed medical education (TIME). TIME fosters awareness that students and trainees can experience trauma from a biased system and culture and advocates for the establishment of policies and practices that support learners to prevent further re-traumatization. TIME will serve as a means to deliver just and equitable education."
3136,Zebra Hunting: How Caring Is Lost When We Chase Diseases,
3137,"Rapid (30-second), equipment-free purification of nucleic acids using easy-to-make dipsticks","The complexity of current nucleic acid isolation methods limits their use outside of the modern laboratory environment. Here, we describe a fast and affordable method to purify nucleic acids from animal, plant, viral and microbial samples using a cellulose-based dipstick. Nucleic acids can be purified by dipping in-house-made dipsticks into just three solutions: the extract (to bind the nucleic acids), a wash buffer (to remove impurities) and the amplification reaction (to elute the nucleic acids). The speed and simplicity of this method make it ideally suited for molecular applications, both within and outside the laboratory, including limited-resource settings such as remote field sites and teaching institutions. Detailed instructions for how to easily manufacture large numbers of dipsticks in house are provided. Using the instructions, readers can create more than 200 dipsticks in <30 min and perform dipstick-based nucleic acid purifications in 30 s."
3138,High-Flow Nasal Cannula in Critically III Patients with Severe COVID-19,
3139,A Lifetime Oncogenicity Study in Rats with Acrylamide,"A lifetime oncogenicity study in Fischer 344 rats was conducted to accurately characterize the carcinogenic potency of acrylamide. Acrylamide was administered in drinking water throughout the 106-week study at concentrations required to provide a dose of 0, 0.1, 0.5, or 2.0 mg/kg/day to males or 0, 1.0, or 3.0 mg/kg/day to females. Complete necropsy and gross pathology examinations were performed on all study animals. Histopathology examinations were conducted on selected tissues of all high-dose and control animals. Selected tissues from intermediate and low-dose groups were subjected to histopathological examinations as required to clarify high- and controldose group observations. There was no visual observation of neurotoxicity in any study animal but sciatic nerve degeneration was observed in the male and female high-dose groups. Increased mortality related to acrylamide was observed in the high- dose male group from Month 17 to the end of the study and in the high-dose females during Month 24. Mesotheliomas of the testicular tunic were significantly increased in the high-dose male group. The combined incidence of mammary gland adenocarcinomas and fibroadenomas was significantly increased in both acrylamide-dosed female groups. Males and females in the high-dose groups as well as females of the low-dose group had significantly (p<0.001) increased thyroid follicular cell adenomas and adenocarcinomas. A variety of other tumor types observed with increased incidence in a previous acrylamide onco genicity study (i.e., combined CNS glial neoplasms, papillomas of the oral cavity, adenomas of the clitoral gland, and uterine adenocarcinomas) were not observed to be present at increased incidence in this study. This study confirms previously described acrylamide induction of benign tumors of the thyroid and mammary glands as well as mesotheliomas of the testis. By using a larger number of animals with an unbalanced study design, this study showed that acrylamide did not induce glial tumors and demonstrated that the no-observable-effect level for scrotal mesotheliomas is 0.5 mg/kg. It also demonstrated that the in creased incidence of mammary tumors was again within historical control ranges."
3140,Triprolidine: 104-Week Feeding Study in Rats,"The antihistamine, triprolidine hydrochloride, was fed at dietary concentrations of 0, 250, 1000, or 2000 ppm (as the free base) to groups of 60 Fischer 344 (F344) rats of each sex for up to 2 years to evaluate its potential carcinogenicity. Up to 12 per sex from each group were killed at 65 weeks, and hematology, clinical chemistry, and histopathology were evaluated. A complete histopatho-logical evaluation was performed on all other animals; survivors were killed at 2 years. Survival was significantly extended in tri-prolidine-treated males and females, particularly at the high dose. At the close of the study high-dose males and females had gained significantly less body weight than controls. Among rats killed at 65 weeks females in the mid- and high-dose groups weighed significantly less than controls, but weights of control and dosed males were not significantly different. The incidences of numerous lesions tended to decrease with increasing triprolidine dose. In females, clitoral gland adenomas, thyroid c-cell hyperplasia and neoplasia, mammary gland hyperplasia and fibroadenomas, and uterine stromal polyps, and in males, anterior pituitary gland adenomas, preputial gland neoplasia, thyroid c-cell hyperplasia, pancreatic islet neoplasia, mononuclear cell leukemia, and the combination of lymphocytic, histiocytic, and undifferentiated cell malignant lymphomas and mononuclear leukemia, all exhibited negative dose trends. Cytoplasmic alterations of the parotid gland and numerous liver lesions tended to be more frequent in treated than in control animals. Liver lesions that exhibited positive dose trends include chronic inflammation and centrilobular fatty change in both sexes, mixed cell foci, and the combination of mixed cell foci and eosinophilic foci in females, and in males, basophilic foci and eosinophilic foci. Triprolidine was not carcinogenic in F344 rats."
3141,Comparative Pulmonary Toxicities and Carcinogenicities of Chronically Inhaled Diesel Exhaust and Carban Black in F344 Rats,"Diesel exhaust (DE) is a known pulmonary carcinogen in rats, and the carcinogenic response is known to require the presence of soot. Many estimates of human lung cancer risk from inhaled DE have been developed from rat bioassay data or from the comparative mutagenic potencies of DE soot extract and known human chemical carcinogens. To explore the importance of the DE soot-associated organic compounds in the lung tumor response of rats, male and female F344 rats were exposed chroni cally to diluted whole DE or aerosolized carbon black (CB) 16 hr/day, 5 days/week at target particle concentrations of 2.5 mg/m(3) (LDE, LCB) or 6.5 mg/m(3) (HDE, HCB) or to filtered air. The CB served as a surrogate for the elemental carbon matrix of DE soot. Considering both the mass fraction of solvent-extractable matter and its mutagenicity in the Ames Salmonella assay, the mutagenicity in revertants per unit particle mass of the CB was three orders of magnitude less than that of the DE soot. Both DE soot and CB particles accumulated progressively in the lungs of exposed rats, but the rate of accumulation was higher for DE soot. In general, DE and CB caused similar, dose-related, nonneoplastic lesions. CB and DE caused significant, exposure concentration-related increases, of similar magnitudes, in the incidences and prevalences of the same types of malignant and benign lung neoplasms in female rats. The incidences of neoplasms were much lower in males than females, and the mci dences were slightly higher among DE- than CB-exposed males. Survival was shortened in the CB-exposed males, and the short ened survival may have suppressed the expression of carcinoge nicity as measured by crude incidence. Logistic regression mod eling did not demonstrate significant differences between the carcinogenic potencies of CB and DE in either gender. The re sults suggest that the organic fraction of DE may not play an important role in the carcinogenicity of DE in rats."
3142,Ozone Adaptation in Rats after Chronic Exposure to a Simulated Urban Profile of Ozone(1),"Studies in both humans and rats have indicated that certain pulmonary responses induced by exposure to an acute provocative concentration of ozone (O(3)) will eventually attenuate if the exposure is repeated on a daily basis. This phenomenon is commonly referred to as O(3) adaptation. Whether or not a “state” of adaptation develops due to long-term low level O(3) exposure is unknown. Two human studies have reported adaptation in subjects living in Los Angeles during periods when ambient O(3) concentrations have been relatively high. At present, however, we are not aware of comparable information from rats. This study assessed O(3) adaptation in rats following chronic (12 or 18 months) exposure and after a 4-month recovery period. A chronic exposure pattern, similar to that found in an urban area during the summer (0.06 ppm O(3) for 13 hr/day, 7 days/week; Monday–Friday, peak to 0.25 ppm O(3), over 9 hr), was used. To assess whether adaptation had occurred and/or persisted, awake rats were challenged with high provocative concentrations of O(3) for up to 2 hr. During a challenge, rats were monitored for typical O(3)-induced alterations in spontaneous breathing parameters (e.g., increase in breathing frequency and decrease in tidal volume). Adaptation was defined as attenuation of breathing response during the challenge in rats chronically exposed to O(3) as compared to that in “control” rats (chronically exposed to air). Adaptation was found in the rats within 8 hr following the chronic O(3) exposure but not after the 4-month recovery period. Spontaneous breathing parameters that were significantly attenuated in the chronically exposed rats were breathing frequency, tidal volume, inspiratory and expiratory times, and maximum expiratory flow. We conclude that rats demonstrated adaptation to O(3) after long-term exposure to an urban-type O(3) profile and that the adaptation was not seen 4 months postexpo-sure. These results suggest that exposure to environmental O(3) in Los Angeles air may have been responsible for the adaptation found in residential subjects."
3143,Near-Lifetime Exposure of the Rat to a Simulated Urban Profile of Nitrogen Dioxide: Pulmonary Function Evaluation(1),"To investigate the potential for up to a near-lifetime exposure to high-ambient levels of nitrogen dioxide (NO(2)) to induce functional lung damage, groups of rats were exposed to air or a simulated urban profile of NO(2) (0.5 ppm background, 1.5 ppm peak) for 1, 3, 13, 52, or 78 weeks. The dynamic, static, and diffusional characteristics of the lung were evaluated postex-posure in anesthetized rats. Furthermore, for the 13-, 52-, and 78-week groups, additional animals were tested after a 6-, 26-, or 17-week period in filtered air, respectively. No significant NO(2) differences between exposed and control animals were found for the nitrogen washout, compliance, lung volume, or diffusion capacity of carbon monoxide measurements. At 78 weeks, however, a reduction in δFEF(25%), an estimate of convexity in the later portion of the forced expiratory flow volume curve, was observed. Breathing patterns and mechanics were also assessed postexposure in a parallel group of similarly exposed unanesthetized rats. These rats were examined during a filtered air, 4 and 8% carbon dioxide (CO(2)) challenge. In the unanesthetized rat, frequency of breathing was significantly decreased and tidal volume, expiratory resistance, and inspiratory and expiratory times tended to increase. For several of these variables, the largest response also occurred at 78 weeks and seemed to be exacerbated by CO(2) challenge. For both unanesthetized and anesthetized test groups, the magnitude of the changes in pulmonary function were small and their significance was borderline, thus indicating that near-lifetime exposure to the rat of a high ambient urbanprofile of N(O2) does not lead to dysfunction suggestive of degenerative lung disease."
3144,Sources of Variability in Rodent Carcinogenicity Studies,"Sources of Variability in Rodent Carcinogenicity Studies. HASEMAN, J. E., HUFF, J. E., RAO, G. K, AND EUSTIS, S. L. (1989). Fundam. Appl Toxicol. 12, 793–804. A number of factors may influence tumor rates in rodent carcinogenicity studies, including the animal room environment, genetic differences, food consumption/weight gain, survival/age of the animals, identification of gross lesions, pathology sampling procedures and preparation of the histology slides, and histopathologic diagnosis The relative importance of these factors is evaluated, making use of laboratory animal carcinogenicity data from the National Toxicology Program and from other sources. An investigator must be aware of these potentially confounding factors, so that appropriate measures can be taken to reduce or eliminate their impact on the interpretation of study results. Certain potential sources of within-study variability can be controlled by appropriate experimental design and by proper conduct according to standard operating procedures. The effect of certain factor influencing tumor prevalence may be magnified when variability from study to study is considered, and thus it may be difficult to formulate a biologically meaningful statistical analysis that uses historical control data in a formal testing framework."
3145,Sequence differences between glycosylated and non-glycosylated Asn-X-Thr/Ser acceptor sites: implications for protein engineering,"In N-glycosylated glycoproteins, carbohydrate is attached to Asn in the sequence Asn-X-Ser/Thr, where X denotes any amino acid. However, the presence of this consensus peptide does not always lead to glycosylation. We have compiled an extensive collection of glycosylated and non-glycosylated Asn-X-Thr/Ser sites and present a statistical study based on this data set. Our results indicate that non-glycosylated sites tend to be found more frequently towards the C termini of glycoproteins, and that proline residues in positions X and Y in the consensus Asn-X-Thr/Ser-Y strongly reduce the likelihood of N-linked glycosylation. Beyond this, there are no obvious local sequence features that seem to correlate with the absence or presence of N-linked glycosylation. These findings are discussed in terms of the prediction and engineering of glycosylation sites in secretory proteins."
3146,Implications of Left Ventricular Dysfunction at Presentation for Infants with Coarctation of the Aorta,"Infants with aortic coarctation may present with left ventricular (LV) dysfunction which may complicate the postoperative course and lead to increased healthcare costs. We aimed to define the prevalence of moderate to severe left ventricular (LV) systolic dysfunction, evaluate time to recovery, and compare health care costs. Single-center retrospective cohort study at a tertiary care hospital was conducted. Infants < 6 months old at diagnosis with aortic coarctation were identified using surgical codes for coarctation repair between January 2010 and May 2018. Moderate to severe dysfunction was defined as ejection fraction (EF) < 40%. Of 160 infants studied, 18 (11%) had moderate to severe LV dysfunction at presentation. Compared to those with better LV function, infants with moderate to severe LV dysfunction were older at presentation (12 vs. 6 days, p = 0.004), had more postoperative cardiac intensive care unit (ICU) days (5 vs. 3, p < 0.001), and more ventilator days (3.5 vs. 1, p < 0.001). The median time to normal LV EF (≥ 55%) was 6 days postoperatively (range 1–230 days). Infants presenting with moderate to severe LV dysfunction had higher index hospitalization costs ($90,560 vs. $59,968, p = 0.02), but no difference in cost of medical follow-up for the first year following discharge ($3,078 vs. $2,568, p = 0.46). In the current era, > 10% of infants with coarctation present with moderate to severe LV dysfunction that typically recovers. Those with moderate to severe dysfunction had longer duration of mechanical ventilation and postoperative cardiac ICU stays, likely driving higher costs of index hospitalization."
3147,Digitalisierung in der Kopfschmerzbehandlung,"BACKGROUND: Digitalization offers support and innovative approaches in the diagnosis and therapy of headaches. With the German digital health care act (Digitale-Versorgung-Gesetz) it is now possible to integrate this into regular care for the first time. However, it is currently difficult to assess the various offers; quality standards and conclusive studies to determine the efficacy and safety are missing. AIM: Overview of current digital approaches in headache treatment and presentation of two specific examples (App M‑sense and DMKG headache registry). MATERIALS AND METHODS: Literature research, product information, and presentations by the project managers. RESULTS: Most digital offers for headache treatment are currently headache calendars, mostly as a smartphone app. However, there are also promising extensions (e.g. trigger analysis) and new approaches such as digital instructions for relaxation and endurance sports, chatbots for patients, as well as support for doctors through structured collection of patient data and processing for diagnostic purposes. CONCLUSION: Different digital approaches could support practitioners and patients effectively in headache treatment and therapy guidance in the near future. However, high-quality studies are necessary to evaluate their benefits and efficacy."
3148,Abstracts from 2020 national congress of the Italian Society of Hypertension (SIIA),
3149,"Closely related reovirus lab strains induce opposite expression of RIG-I/IFN-dependent versus -independent host genes, via mechanisms of slow replication versus polymorphisms in dsRNA binding σ3 respectively","The Dearing isolate of Mammalian orthoreovirus (T3D) is a prominent model of virus-host relationships and a candidate oncolytic virotherapy. Closely related laboratory strains of T3D, originating from the same ancestral T3D isolate, were recently found to exhibit significantly different oncolytic properties. Specifically, the T3D(PL) strain had faster replication kinetics in a panel of cancer cells and improved tumor regression in an in vivo melanoma model, relative to T3D(TD). In this study, we discover that T3D(PL) and T3D(TD) also differentially activate host signalling pathways and downstream gene transcription. At equivalent infectious dose, T3D(TD) induces higher IRF3 phosphorylation and expression of type I IFNs and IFN-stimulated genes (ISGs) than T3D(PL). Using mono-reassortants with intermediate replication kinetics and pharmacological inhibitors of reovirus replication, IFN responses were found to inversely correlate with kinetics of virus replication. In other words, slow-replicating T3D strains induce more IFN signalling than fast-replicating T3D strains. Paradoxically, during co-infections by T3D(PL) and T3D(TD), there was still high IRF3 phosphorylation indicating a phenodominant effect by the slow-replicating T3D(TD). Using silencing and knock-out of RIG-I to impede IFN, we found that IFN induction does not affect the first round of reovirus replication but does prevent cell-cell spread in a paracrine fashion. Accordingly, during co-infections, T3D(PL) continues to replicate robustly despite activation of IFN by T3D(TD). Using gene expression analysis, we discovered that reovirus can also induce a subset of genes in a RIG-I and IFN-independent manner; these genes were induced more by T3D(PL) than T3D(TD). Polymorphisms in reovirus σ3 viral protein were found to control activation of RIG-I/ IFN-independent genes. Altogether, the study reveals that single amino acid polymorphisms in reovirus genomes can have large impact on host gene expression, by both changing replication kinetics and by modifying viral protein activity, such that two closely related T3D strains can induce opposite cytokine landscapes."
3150,Navigating maternity service redesign in a global pandemic: A report from the field,
3151,Leveraging immunizations and your team to improve vaccination rates,
3152,"A multi-center, randomized controlled trial by the Integrative Management in Japan for Epidemic Disease (IMJEDI study-RCT) on the use of Kampo medicine, kakkonto with shosaikotokakikyosekko, in mild-to-moderate COVID-19 patients for symptomatic relief and prevention of severe stage: a structured summary of a study protocol for a randomized controlled trial","OBJECTIVES: We aimed to test our hypothesis that additional administration of traditional Japanese (Kampo) medicine, kakkonto (kakkon-to: KT) and shosaikotokakikyosekko (sho-saiko-to-ka-kikyo-sekko: SSKKS), is more effective in relieving symptoms and preventing the onset of severe infection in mild-to-moderate COVID-19 patients compared to those treated only with conventional treatment. TRIAL DESIGN: The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator-sponsored, two-arm study. PARTICIPANTS: Patients and inpatients will be recruited from 8 Japanese academic and non-academic hospitals. The inclusion and exclusion criteria are as follows: Inclusion criteria 1. Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2. Clinical stages of mild-to-moderate COVID-19. 3. Symptomatic; 4. ≥ 20 years of age. 5. Male or female. 6. Ability to communicate in Japanese. 7. Outpatients and inpatients. 8. Provided informed consent. Exclusion criteria 1. Difficulty in providing informed consent due to dementia, psychosis, or psychiatric symptoms. 2. Allergic to Kampo or Western medicines used in this study. 3. Pregnant and lactating. 4. Unable to follow up. 5. Participating in another clinical trial or interventional study. 6. Hypokalemic or taking oral furosemide or steroids. 7. Determined unsuitable for this study by the physician. INTERVENTION AND COMPARATOR: Patients in the control group will receive conventional treatment with antipyretics, painkillers, or antitussives for symptoms that occurred after they contracted the SARS-CoV-2 infection. Patients in the Kampo group will receive 2.5 g of KT (TJ-1@TSUMURA and Co.) and 2.5 g of SSKKS (TJ-109@TSUMURA and Co.) 3 times a day, orally, for 14 days in addition to the conventional treatment as mentioned above. MAIN OUTCOMES: The number of days till at least one of the symptoms (fever, cough, sputum, malaise, shortness of breath) improves in the first 14 days of treatment. To assess the cough, sputum, malaise, and shortness of breath, a numeric rating scale will be used to define improvement in terms of a 2-point decrease in the number of days from the start of treatment for at least 2 days. Fever will be defined as an improvement when the temperature is less than 37 °C. RANDOMIZATION: Patients are randomized (1:1 ratio) to each group using the minimization method, with balancing of the arms with severity of disease stage and patient age (< 65, 65 to < 75, or ≥ 75 years). Computer-generated random numbers will be used for the minimization method. BLINDING (MASKING): Open-label with no blinding NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): The main research hypothesis of this study is that the combination of Kampo medicine and conventional treatment will significantly improve the patients’ symptoms (fever, fatigue, cough, sputum, and shortness of breath) during the first 14 days of treatment as compared with conventional treatment alone. Concerning the analysis of the primary endpoint, the duration of time before improvement of at least one of the common cold-like symptoms (fever, malaise, cough, sputum, and shortness of breath) will be estimated using the Kaplan-Meier method, and the survival curves will be compared between groups using the log-rank test. Assuming this method of analysis and based on previous studies reporting the efficacy of Kampo medicine for COVID-19 and H1N1 influenza patients, the median survival time in the Kampo medicine group is estimated as 3 days; this time will be 1.5 times longer in the control group. Assuming a one-sided significance level of 5%, a power of 70%, and an allocation ratio of 1:1, the required sample size is calculated as 126 cases. To compensate for a loss in follow-up, we plan to include 150 cases in both groups (Kampo group = 75, control group = 75). TRIAL STATUS: Protocol version 1.2 as of August 20, 2020 Recruitment start (expected): October 1, 2020 Recruitment finish (expected): October 31, 2023 TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) jRCTs021200020. Registered on August 25, 2020 FULL PROTOCOL: The full protocol is attached as an additional file and is accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol."
3153,Versorgungsrealität des Schlaganfalls in Deutschland,
3154,A putative enoyl-CoA hydratase contributes to biofilm formation and the antibiotic tolerance of Achromobacter xylosoxidans,"Achromobacter xylosoxidans has attracted increasing attention as an emerging pathogen in patients with cystic fibrosis. Intrinsic resistance to several classes of antimicrobials and the ability to form robust biofilms in vivo contribute to the clinical manifestations of persistent A. xylosoxidans infection. Still, much of A. xylosoxidans biofilm formation remains uncharacterized due to the scarcity of existing genetic tools. Here we demonstrate a promising genetic system for use in A. xylosoxidans; generating a transposon mutant library which was then used to identify genes involved in biofilm development in vitro. We further described the effects of one of the genes found in the mutagenesis screen, encoding a putative enoyl-CoA hydratase, on biofilm structure and tolerance to antimicrobials. Through additional analysis, we find that a fatty acid signaling compound is essential to A. xylosoxidans biofilm ultrastructure and maintenance. This work describes methods for the genetic manipulation of A. xylosoxidans and demonstrated their use to improve our understanding of A. xylosoxidans pathophysiology."
3155,Identification of hyper-rewired genomic stress non-oncogene addiction genes across 15 cancer types,"Non-oncogene addiction (NOA) genes are essential for supporting the stress-burdened phenotype of tumours and thus vital for their survival. Although NOA genes are acknowledged to be potential drug targets, there has been no large-scale attempt to identify and characterise them as a group across cancer types. Here we provide the first method for the identification of conditional NOA genes and their rewired neighbours using a systems approach. Using copy number data and expression profiles from The Cancer Genome Atlas (TCGA) we performed comparative analyses between high and low genomic stress tumours for 15 cancer types. We identified 101 condition-specific differential coexpression modules, mapped to a high-confidence human interactome, comprising 133 candidate NOA rewiring hub genes. We observe that most modules lose coexpression in the high-stress state and that activated stress modules and hubs take part in homoeostasis maintenance processes such as chromosome segregation, oxireductase activity, mitotic checkpoint (PLK1 signalling), DNA replication initiation and synaptic signalling. We furthermore show that candidate NOA rewiring hubs are unique for each cancer type, but that their respective rewired neighbour genes largely are shared across cancer types."
3156,Hierarchical graphical model reveals HFR1 bridging circadian rhythm and flower development in Arabidopsis thaliana,"To study systems-level properties of the cell, it is necessary to go beyond individual regulators and target genes to study the regulatory network among transcription factors (TFs). However, it is difficult to directly dissect the TFs mediated genome-wide gene regulatory network (GRN) by experiment. Here, we proposed a hierarchical graphical model to estimate TF activity from mRNA expression by building TF complexes with protein cofactors and inferring TF’s downstream regulatory network simultaneously. Then we applied our model on flower development and circadian rhythm processes in Arabidopsis thaliana. The computational results show that the sequence specific bHLH family TF HFR1 recruits the chromatin regulator HAC1 to flower development master regulator TF AG and further activates AG’s expression by histone acetylation. Both independent data and experimental results supported this discovery. We also found a flower tissue specific H3K27ac ChIP-seq peak at AG gene body and a HFR1 motif in the center of this H3K27ac peak. Furthermore, we verified that HFR1 physically interacts with HAC1 by yeast two-hybrid experiment. This HFR1–HAC1–AG triplet relationship may imply that flower development and circadian rhythm are bridged by epigenetic regulation and enrich the classical ABC model in flower development. In addition, our TF activity network can serve as a general method to elucidate molecular mechanisms on other complex biological regulatory processes."
3157,"Publisher Correction: npj Systems Biology and Applications, volume 5",
3158,Mechanistically detailed systems biology modeling of the HGF/Met pathway in hepatocellular carcinoma,"Hepatocyte growth factor (HGF) signaling through its receptor Met has been implicated in hepatocellular carcinoma tumorigenesis and progression. Met interaction with integrins is shown to modulate the downstream signaling to Akt and ERK (extracellular-regulated kinase). In this study, we developed a mechanistically detailed systems biology model of HGF/Met signaling pathway that incorporated specific interactions with integrins to investigate the efficacy of integrin-binding peptide, AXT050, as monotherapy and in combination with other therapeutics targeting this pathway. Here we report that the modeled dynamics of the response to AXT050 revealed that receptor trafficking is sufficient to explain the effect of Met–integrin interactions on HGF signaling. Furthermore, the model predicted patient-specific synergy and antagonism of efficacy and potency for combination of AXT050 with sorafenib, cabozantinib, and rilotumumab. Overall, the model provides a valuable framework for studying the efficacy of drugs targeting receptor tyrosine kinase interaction with integrins, and identification of synergistic drug combinations for the patients."
3159,Candida albicans biofilm development is governed by cooperative attachment and adhesion maintenance proteins,"The opportunistic fungal pathogen Candida albicans is capable of adhering to the oral mucosa despite forces created by salivary flow. Although many fungal adhesion proteins have been identified, less is known about the temporal development of cell adhesion and biofilm growth in a flow environment. In this study, we use a flow system with real-time imaging of C. albicans cells as they adhere and grow. Rates of cell attachment and dispersion of C. albicans knockout strains of putative adhesins, transcription factors, and deletions with a hyperfilamentous phenotype were quantified during 18 h of biofilm development. Cell adhesion under flow is a multi-phase process initiated with cell rolling, then an initial firm attachment to the substrate occurs. After attachment, cells enter a growth phase where cells either commit to adherence or disperse. C. albicans Δeap1, Δhwp2, Δhyr1, and Δihd1 cells had significantly reduced initial attachment and subsequent adhesion, while Δals1/Δals3 had no change in initial attachment but reduced adhesion maintenance. WT cells had increased adhesion during the late growth phase when hyphae were more highly expressed. Hyperfilamentous strains had 10-fold higher total biofilm growth, a result of significantly reduced detachment rates, showing that hyphal morphogenesis is important for adhesion maintenance in the developing biofilm. The rate of C. albicans biomass dispersion was most important for determining the density of the mature biomass. Adhesion maintenance was mediated in part by Ywp1, a protein previously thought to regulate dispersion, thus it functions as an adhesion maintenance protein in C. albicans."
3160,Biofilm formation inhibition and dispersal of multi-species communities containing ammonia-oxidising bacteria,"Despite considerable research, the biofilm-forming capabilities of Nitrosomonas europaea are poorly understood for both mono and mixed-species communities. This study combined biofilm assays and molecular techniques to demonstrate that N. europaea makes very little biofilm on its own, and relies on the activity of associated heterotrophic bacteria to establish a biofilm. However, N. europaea has a vital role in the proliferation of mixed-species communities under carbon-limited conditions, such as in drinking water distribution systems, through the provision of organic carbon via ammonia oxidation. Results show that the addition of nitrification inhibitors to mixed-species nitrifying cultures under carbon-limited conditions disrupted biofilm formation and caused the dispersal of pre-formed biofilms. This dispersal effect was not observed when an organic carbon source, glucose, was included in the medium. Interestingly, inhibition of nitrification activity of these mixed-species biofilms in the presence of added glucose resulted in increased total biofilm formation compared to controls without the addition of nitrification inhibitors, or with only glucose added. This suggests that active AOB partially suppress or limit the overall growth of the heterotrophic bacteria. The experimental model developed here provides evidence that ammonia-oxidising bacteria (AOB) are involved in both the formation and maintenance of multi-species biofilm communities. The results demonstrate that the activity of the AOB not only support the growth and biofilm formation of heterotrophic bacteria by providing organic carbon, but also restrict and limit total biomass in mixed community systems."
3161,Author Correction: Forecasting cell fate during antibiotic exposure using stochastic gene expression,
3162,Surgical management of a complex case of Charcot arthropathy of the spine: a case report,"INTRODUCTION: The authors present a case of a 55-year-old male with T10 complete paraplegia diagnosed with Charcot arthropathy of the spine (CAS). CASE PRESENTATION: He presented to an outside institution with vomiting and productive cough with subsequent computed tomography (CT) and MRI imaging revealing L5 osteomyelitis and a paraspinal abscess. Given the patient’s inability to remain in good posture in his wheelchair he underwent a multilevel vertebrectomy and thoracolumbar fusion. Due to multiple co-morbidities, surgical recovery was complex, ultimately requiring revision circumferential fixation. DISCUSSION: CAS is an uncommon, long-term complication of traumatic spinal cord injury (SCI). Surgical management is often complex and associated with significant complications. Currently, a consensus on CAS prevention, specific surgical fixation techniques and post-surgical nursing care management is lacking. In this case report we provide our experience in the management of a complex case of CAS to aid in decision making for future neurosurgeons who encounter this sequela of traumatic SCI."
3163,Improving quality of life after spinal cord injury in India with telehealth,"INTRODUCTION: Despite adequate inpatient rehabilitation, a number of spinal cord injury (SCI) individuals suffer from difficulties at home and in their local environments. This is mainly prevalent in low–middle-income countries (LMIC) due to a lack of qualified personal caregivers. This issue could be addressed with the help of telehealth technology, which may be used in LMICs without economic concerns. CASE PRESENTATIONS: A 44-year-old male with C3 AIS C SCI and a 35-year-old female with T12 AIS A SCI were discharged after successful rehabilitation from a tertiary care spinal center. The patients demonstrated gradual loss in their independence, which was evident by monitoring their home activities biweekly for 4 weeks via a combination of telephone calls, live video chat, and WhatsApp. Subsequently after 4 weeks of consistent guidance, pre–post scores after teletherapy were analyzed for the self-care and mobility subcomponents of the self-reported SCIM III. DISCUSSION: After consistent supervised guidance via telehealth, self-care scores improved in the C3 AIS C case from 3 to 15 and in the T12 AIS A case from 4 to 15, while mobility scores respectively improved from 14 to 27 and 4 to 16. Identification of individual competencies, performance, and capacity in activities of daily living and participation, self-assessment, caregiver training, and home integration contributed toward successful community integration. This case series documents the benefits of using telehealth and home goal planning in the aftercare of SCI individuals, in order to improve quality of life in their local environment."
3164,A case of postprandial hypotension in an individual with cervical spinal cord injury: treatment with acarbose,"INTRODUCTION: Postprandial hypotension (PPH) is a postmeal drop in systolic blood pressure that may or may not be symptomatic. While the etiologies of PPH are incompletely understood, it is thought to occur when glucose absorption causes increased splanchnic blood flow or “pooling” in people who lack sufficient compensatory responses to support their systemic blood pressure. Postprandial hypotension is well described in individuals with neurodegenerative diseases, yet only rarely in people living with spinal cord injury (SCI). Acarbose is an alpha-glucosidase inhibitor that treats PPH by slowing gastric transit time and reducing glucose uptake in the small intestine, hence decreasing superior mesenteric artery blood flow. CASE PRESENTATION: A 62-year-old woman with long-standing cervical SCI presented with 5 years of worsening postprandial lightheadedness, visual “flashes”, and neck pain. She had had multiple episodes of near and frank syncope and her prior medical team had initiated midodrine three times daily. We began treatment with acarbose, starting at 50 mg with each meal and rapidly titrating to 100 mg at mealtime. She noticed an immediate improvement in her symptoms and an attenuation of postmeal drops in both systolic and diastolic blood pressures. DISCUSSION: To our knowledge, this is one of the first described cases of PPH among people living with SCI. Given the autonomic dysfunction that frequently accompanies higher-level of injuries, it is possible that many more people with SCI have this condition, whether or not it is symptomatic. Acarbose is one of the several established treatments for PPH, and proved effective and tolerable for our patient."
3165,Incidence and characteristics of heterotopic ossification after spinal cord injury: a single institution study in India,"STUDY DESIGN: This was a single-centre, retrospective, descriptive, hospital-based study in persons with spinal cord injuries (SCI) patients. OBJECTIVES: To study the incidence and characteristics of heterotopic ossification (HO) after SCI. SETTING: The in-patient services of the Department of Physical Medicine and Rehabilitation of a tertiary care institute in India between January 2001 and December 2017. METHODS: Medical records of all consecutive patients with diagnosis of SCI in the age group of 15–60 years were reviewed for presence of HO (diagnosed by clinical signs, laboratory investigations (ALP, ESR and X-rays)) and characteristics of HO. R-Ver 3.4.2 was used for analysis and correlations. Results were considered significant at P < 0.05. RESULTS: A total of 303 patients satisfied inclusion criteria. Nineteen individuals (6.3%) had developed HO. Seven (37%) were diagnosed within 3 months of SCI. Twelve (63%) patients developed unilateral HO. The most common site for HO was hip joint (73%). A significant association was found between the presence of a pressure ulcer and development of HO (P = 0.01). CONCLUSIONS: The incidence of HO was 6.3% in our institution and the hip joint is the most common site. Due to the presence of limited treatment options it is important to diagnose HO early in patients with SCI based on clinical features and later confirmed with laboratory tests and imaging."
3166,Current practice trends of oedema management in the hands of people with tetraplegia in Australia,"STUDY DESIGN: Survey research design. OBJECTIVES: To describe current practice methods for oedema management in people with tetraplegia. SETTING: Australia. METHODS: Online survey with open and closed questions regarding clinical practice trends in the assessment and treatment of oedema in the hands in people with tetraplegia. RESULTS: Seventeen occupational therapists working in spinal cord injury (SCI) in Australia completed the survey. Oedema was identified by visual inspection (n = 17, 100%) and recorded using circumferential tape measurement (n = 13, 76%). Elevation was used by all participants in conjunction with compression gloves (n = 13, 76%), retrograde massage (n = 13, 76%), compression bandaging (n = 12, 71%) and the boxing glove splint (n = 9, 53%). Participants stated that oedema presented challenges to patients with difficulty exercising (n = 11, 65%), changes to body image (n = 5, 29%) and pain (n = 4, 24%). CONCLUSION: Assessment and treatment practices were not consistent. Oedema in the hands in people with tetraplegia was perceived to have various impacts on a person’s rehabilitation and hand function. The findings highlight the need for research evidence to guide practice."
3167,Role of lordotic rod contouring in thoracic myelopathy: a technical note,"INTRODUCTION: Decompressive surgery for thoracic myelopathy due to anterior pathology can be challenging. Direct decompression through anterior approaches is associated with approach-related complications, whereas anterior decompression through posterior approaches is technically demanding and may result in neurological deterioration. We present a simple and effective surgical technique of indirect decompression through lordotic rod contouring to reduce such complications. CASE PRESENTATION: Patients who presented to our center between March 2016 and March 2017 with symptoms and signs suggestive of thoracic myelopathy predominantly due to anterior pathologies such as ossification of the thoracic posterior longitudinal ligament, posterior bony spur, and thoracic disc herniation were evaluated in our study. The indications for surgical treatment were progressive neurological impairment and severe myelopathy (grade III or more on Nurick grade). Only those patients classified as grade III and above on American Society of Anaesthesiologists (ASA) physical status scale were included in the study. All the cases were operated by a single surgeon by a posterior-only approach. We have used this technique in four patients with thoracic myelopathy due to combined or predominant anterior pathology. Postoperative imaging confirmed adequate decompression of the spinal cord. All the cases improved substantially in terms of clinical outcome. DISCUSSION: This surgical technique could be a useful alternative to direct anterior decompression in patients who present with symptoms of progressive severe myelopathy due to anterior compression and could be the standard of care in those at high risk for major surgery."
3168,The effect of selective serotonin reuptake inhibitors on cognitive function in patients with Alzheimer’s disease and vascular dementia: focusing on fluoxetine with long follow-up periods,
3169,History and progress of hypotheses and clinical trials for Alzheimer’s disease,"Alzheimer’s disease (AD) is a neurodegenerative disease characterized by progressive memory loss along with neuropsychiatric symptoms and a decline in activities of daily life. Its main pathological features are cerebral atrophy, amyloid plaques, and neurofibrillary tangles in the brains of patients. There are various descriptive hypotheses regarding the causes of AD, including the cholinergic hypothesis, amyloid hypothesis, tau propagation hypothesis, mitochondrial cascade hypothesis, calcium homeostasis hypothesis, neurovascular hypothesis, inflammatory hypothesis, metal ion hypothesis, and lymphatic system hypothesis. However, the ultimate etiology of AD remains obscure. In this review, we discuss the main hypotheses of AD and related clinical trials. Wealthy puzzles and lessons have made it possible to develop explanatory theories and identify potential strategies for therapeutic interventions for AD. The combination of hypometabolism and autophagy deficiency is likely to be a causative factor for AD. We further propose that fluoxetine, a selective serotonin reuptake inhibitor, has the potential to treat AD."
3170,Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles,"The application of nanomedicines is increasing rapidly with the promise of targeted and efficient drug delivery. Nanomedicines address the shortcomings of conventional therapy, as evidenced by several preclinical and clinical investigations indicating site-specific drug delivery, reduced side effects, and better treatment outcome. The development of suitable and biocompatible drug delivery vehicles is a prerequisite that has been successfully achieved by using simple and functionalized liposomes, nanoparticles, hydrogels, micelles, dendrimers, and mesoporous particles. A variety of drug delivery vehicles have been established for the targeted and controlled delivery of therapeutic agents in a wide range of chronic diseases, such as diabetes, cancer, atherosclerosis, myocardial ischemia, asthma, pulmonary tuberculosis, Parkinson’s disease, and Alzheimer’s disease. After successful outcomes in preclinical and clinical trials, many of these drugs have been marketed for human use, such as Abraxane®, Caelyx®, Mepact®, Myocet®, Emend®, and Rapamune®. Apart from drugs/compounds, novel therapeutic agents, such as peptides, nucleic acids (DNA and RNA), and genes have also shown potential to be used as nanomedicines for the treatment of several chronic ailments. However, a large number of extensive clinical trials are still needed to ensure the short-term and long-term effects of nanomedicines in humans. This review discusses the advantages of various drug delivery vehicles for better understanding of their utility in terms of current medical needs. Furthermore, the application of a wide range of nanomedicines is also described in the context of major chronic diseases."
3171,miR-124/VAMP3 is a novel therapeutic target for mitigation of surgical trauma-induced microglial activation,"Activation of microglia and the subsequently elevated inflammatory cytokine release in the brain during surgery predispose individuals to cognitive dysfunction, also known as postoperative cognitive dysfunction (POCD). miR-124 is one of the most abundant microRNAs in the brain that regulates microglial function. Elucidating the role of miR-124 in microglial activation in the context of surgery may therefore promote understanding of as well as therapeutic development for post-surgical disorders involving microglial activation. The downstream targets of miR-124 were investigated using bioinformatic screening and dual-luciferase reporter assay validation, and vesicle-associated membrane protein 3 (VAMP3) was identified as a potential target. The kinetics of miR-124/VAMP3 expression was first examined in vitro in microglial cells (primary microglia and BV2 microglial cells) following lipopolysaccharide (LPS) stimulation. LPS induced a time-dependent decrease of miR-124 and upregulated the expression of VAMP3. Manipulating miR-124/VAMP3 expression by using miR-124 mimics or VAMP3-specific siRNA in LPS-stimulated BV2 microglial cells inhibited BV2 microglial activation-associated inflammatory cytokine release. To further examine the role of miR-124/VAMP3 in a surgical setting, we employed a rat surgical trauma model. Significant microglial activation and altered miR-124/VAMP3 expression were observed following surgical trauma. We also altered miR-124/VAMP3 expression in the rat surgical trauma model by administration of exogenous miR-124 and by using electroacupuncture, which is a clinically applicable treatment that modulates microglial function and minimizes postoperative disorders. We determined that electroacupuncture treatment specifically increases the expression of miR-124 in the hypothalamus and hippocampus. Increased miR-124 expression with a concomitant decrease in VAMP3 expression resulted in decreased inflammatory cytokine release related to microglial activation post-surgery. Our study indicates that miR-124/VAMP3 is involved in surgery-induced microglial activation and that targeting miR-124/VAMP3 could be a potential therapeutic strategy for postoperative disorders involving microglial activation."
3172,Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis,"Metastasis is a major cause of chemotherapeutic failure and death. Degradation of a specific component of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) affects the physical barrier of the tumor microenvironment (TME) and induces metastasis. Here, lysolipid-containing thermosensitive liposomes (LTSLs) were prepared to deliver an MMP inhibitor, marimastat (MATT), to the TME to inhibit MMP activity and expression. LTSLs rapidly released their payloads at 42 °C. Compared with the saline control, MATT-LTSLs exhibited enhanced accumulation in the tumor and a 20-fold decrease in tumor growth in 4T1 tumor-bearing mice; moreover, MATT-LTSLs reduced MMP-2 and MMP-9 activity by 50% and 43%, respectively, and downregulated MMP-2 and MMP-9 expression in vivo by 30% and 43%, respectively. Most importantly, MATT-LTSL treatment caused a 7-fold decrease in metastatic lung nodules and a 6-fold reduction in microvessels inside the tumor. We believe this study provides an effective approach for the suppression of metastasis, and the use of a cytotoxic agent in combination with MATT is a potential strategy for metastatic cancer treatment."
3173,Author Correction: A novel cancer vaccine with the ability to simultaneously produce anti-PD-1 antibody and GM-CSF in cancer cells and enhance Th1-biased antitumor immunity,
3174,More on the Tuskegee Study of Untreated Syphilis,
3175,Using telemedicine and wearable technology to establish a virtual clinic for people with Parkinson’s disease,"BACKGROUND: To develop an effective, patient-centred and sustainable service, we set up a virtual clinic (VC) for patients with Parkinson’s disease, combining phone consultations and reports from wearable technology. The Parkinson’s Kinetigraph (PKG) is a wrist-worn device providing objective motor assessment, generating a report used by clinicians to optimise medication regimens. INTERVENTIONS: A pilot study of VC was designed using quality improvement methodology. For a VC appointment, patients were phoned by a clinician. After discussing symptoms and reviewing the PKG report, the clinician could decide on any medication changes or other interventions and relay this to the patient’s general practitioner in a clinic letter. Patient feedback was gathered via questionnaires and data collected on the outcomes and timings of the consultations. RESULTS: Over 12 clinics, 61 patients had VC appointments. Of questionnaire respondents, 89% were satisfied with VC (n=41). At VC, the clinician was able to make a treatment decision comparable to a face-to-face clinic in 79% of cases (n=48). Reasons appointments were deemed unsuccessful included issues with the PKG, speech or hearing problems and complex phase of disease. VC appointments, including administration time, last on average 22 min. This compares to 20 min face-to-face appointments but these do not include administration time. CONCLUSIONS: We have demonstrated a safe and effective VC template. Most VC appointments are equivalent to face-to-face clinic in terms of treatment outcome. Success could be further improved by appropriate patient selection. Using VC is time saving and can result in releasing face-to-face appointment slots for those in urgent need or newly referred patients. Further cost analysis is required; the cost of the PKG alone is more expensive than a face-to-face appointment, but this does not take into account other value added, such as patient convenience and satisfaction, and reduced need for ambulance transport."
3176,Assessment of competences in rheumatology training: results of a systematic literature review to inform EULAR points to consider,"OBJECTIVE: To summarise the literature on the assessment of competences in postgraduate medical training. METHODS: A systematic literature review was performed within a EULAR taskforce on the assessment of competences in rheumatology training and other related specialities (July 2019). Two searches were performed: one search for rheumatology and one for related medical specialities. Two reviewers independently identified eligible studies and extracted data on assessment methods. Risk of bias was assessed using the medical education research study quality instrument. RESULTS: Of 7335 articles in rheumatology and 2324 reviews in other specialities, 5 and 31 original studies were included, respectively. Studies in rheumatology were at variable risk of bias and explored only direct observation of practical skills (DOPS) and objective structured clinical examinations (OSCEs). OSCEs, including clinical, laboratory and imaging stations, performed best, with a good to very good internal consistency (Cronbach’s α=0.83–0.92), and intrarater reliability (r=0.80–0.95). OSCEs moderately correlated with other assessment tools: r=0.48 vs rating by programme directors; r=0.2–0.44 vs multiple-choice questionnaires; r=0.48 vs DOPS. In other specialities, OSCEs on clinical skills had a good to very good inter-rater reliability and OSCEs on communication skills demonstrated a good to very good internal consistency. Multisource feedback and the mini-clinical evaluation exercise showed good feasibility and internal consistency (reliability), but other data on validity and reliability were conflicting. CONCLUSION: Despite consistent data on competence assessment in other specialities, evidence in rheumatology is scarce and conflicting. Overall, OSCEs seem an appropriate tool to assess the competence of clinical skills and correlate well with other assessment strategies. DOPS, multisource feedback and the mini-clinical evaluation exercise are feasible alternatives."
3177,Towards a conceptual framework of the working alliance in a blended low-intensity cognitive behavioural therapy intervention for depression in primary mental health care: a qualitative study,"OBJECTIVES: To examine and adapt a conceptual framework of the working alliance (WA) in the context of a low-intensity blended (psychological well-being practitioner (PWP) plus computerised program) cognitive behavioural therapy intervention (b-CBT) for depression. DESIGN: Patient involvement was enlisted to collaboratively shape the design of the project from the onset, before data collection. In-depth semi-structured interviews were carried out with participants who experienced b-CBT as part of the E-compared trial. A thematic analysis was conducted using a constant comparative method informed by grounded theory. SETTING: Recruitment was carried out in four psychological primary care services across the UK. PARTICIPANTS: Nineteen trial participants with major depressive disorder who completed at least one computerised program and face-to-face session with a PWP in the b-CBT arm were recruited to the study. RESULTS: Qualitative interviews that were guided by WA theory and patient involvement, revealed four themes: (1) a healthcare provider (PWP and computerised program) with good interpersonal competencies for building a working relationship with the client (‘bond’); (2) collaborative efforts between the client and the provider to appropriately identify what the client hopes to achieve through therapy (‘goals’); (3) the selection of acceptable therapeutic activities that address client goals and the availability of responsive support (‘task’) and (4) the promotion of active engagement and autonomous problem solving (‘usability heuristics’). Participants described how the PWP and computerised program uniquely and collectively contributed to different WA needs. CONCLUSIONS: This study is the first to offer a preliminary conceptual framework of WA in b-CBT for depression, and how such demands can be addressed through blended PWP-computerised program delivery. These findings can be used to promote WA in technological design and clinical practice, thereby promoting engagement to b-CBT interventions and effective deployment of practitioner and program resources. TRIAL REGISTRATION NUMBER: ISRCTN12388725."
3178,Trends in Cardiovascular Disease Prevalence by Income Level in the United States,"IMPORTANCE: Income disparity between persons with the most resources (the top 20% of earners) and the remainder of the population in the United States has dramatically widened over the past few decades. Given the well-established association between income and health, this increasing income gap may provide insights into the dynamics of cardiovascular disease (CVD) burden among adults in the US. OBJECTIVE: To quantify the contribution of people in the highest-resources group and the remainder of the population to the burden of CVD, and to estimate the trends in the prevalence of CVD for the 2 groups in the United States from 1999 to 2016. DESIGN, SETTING, AND PARTICIPANTS: This serial cross-sectional analysis used nationally representative data from 9 cycles of the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2016. Survey participants were adults 20 years or older. Statistical analysis of the data was conducted in December 2019. MAIN OUTCOMES AND MEASURES: Age-standardized prevalence of CVD was calculated using the 2010 census estimates. Participants were stratified by income group using the NHANES income to poverty ratio, which was converted into a binary variable: a ratio of 5 or greater for the highest-resources group and a ratio of less than 5 for the remainder of the population. RESULTS: This analysis included 44 986 participants. Among the 7926 participants in the highest-resources group, 3290 (50.3%) were in the 40- to 59-year age group and 4094 (51.9%) were men. Among the 37 060 participants in the remainder of the population, 10 840 (34.1%) were in the 40- to 59-year age group and 19 470 (53.2%) were women. The age-standardized prevalence of CVD decreased in the highest-resources group during the study period (1999-2016): angina from 3.4% (n = 24) to 0.3% (n = 5), heart attack from 3.2% (n = 24) to 1.4% (n = 19), congestive heart failure (CHF) from 1.2% (n = 11) to 0.5% (n = 7), and stroke from 1.1% to 1.0% (n = 8). In the remainder of the population, the prevalence of angina decreased from 3.3% (n = 131) in 1999 to 2.6% (n = 118) in 2016 and heart attack from 4.0% (n = 160) in 1999 to 3.6% (n = 201) in 2016. Conversely, an increase was observed in the prevalence of CHF from 2.6% (n = 123) in 1999 to 2.8% (n = 176) in 2016 and stroke from 2.9% (n = 152) in 1999 to 3.2% (n = 178) in 2016. Over time, the odds of reporting angina (odds ratio [OR], 0.80; 95% CI, 0.73-0.87; P < .001), heart attack (OR, 0.91; 95% CI, 0.86-0.97; P = .003), and CHF (OR, 0.90; 95% CI, 0.82-0.99; P = .03) decreased among those in the highest-resources group, while there was no significant change in the odds of reporting stroke (OR, 0.97; 95% CI, 0.90-1.05; P = .43). Among the remainder of the population, the odds of reporting angina (OR, 0.95; 95% CI, 0.92-0.99; P < .05) and heart attack (OR, 0.99; 95% CI, 0.97-1.02; P = .06) decreased over time. Conversely, there was no statistically significant change in the odds of reporting CHF (OR, 1.02; 95% CI, 1.00-1.05; P = .08) and stroke (OR, 1.02; 95% CI, 0.99-1.04; P = .21). CONCLUSIONS AND RELEVANCE: This study found substantial and increasing disparities in CVD prevalence between the richest and poorest participants in the NHANES from 1999 to 2016, with lower CVD rate reported among the highest-resources group. Additional research into the dynamics of income inequality and health outcomes as well as policy and public health efforts to mitigate this inequality are needed."
3179,A year at the helm,
3180,Diagnóstico diferencial de la neumonía en los tiempos del COVID-19,
3181,The Spanish flu and the fiction literature,"This review focuses on the fictional literature in which the Spanish flu is represented either as an anecdotal or as a historical aspect and the effect on the author or fictional character. We examine this sociocultural period in the press and mainly in Anglo-Saxon literary works and from other countries, including Spanish and Latin American literature that is not very represented in some international reviews on the subject. Also, we include books about the previous and subsequent influenza pandemics to the Spanish flu."
3182,Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances the learning of cue-reward contingency,The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found that ACh levels and nucleus basalis of Meynert (NBM) cholinergic terminal activity in the BLA (NBM-BLA) increased sharply in response to reward-related events and shifted as mice learned the cue-reward contingency. BLA CaMKIIα neuron activity followed reward retrieval and moved to the reward-predictive cue after task acquisition. Optical stimulation of cholinergic NBM-BLA terminal fibers led to a quicker acquisition of the cue-reward contingency. These results indicate BLA ACh signaling carries important information about salient events in cue-reward learning and provides a framework for understanding how ACh signaling contributes to shaping BLA responses to emotional stimuli.
3183,The United States Postal Service: an Essential Public Health Agency?,
3184,“Optimal surfactant delivery protocol using the bovine lipid extract surfactant: a quality improvement study”,"IMPORTANCE: Episodes of severe airway obstruction (SAO) are reported during surfactant administration. OBJECTIVE: To evaluate adherence to and impact of a surfactant protocol on adverse events. METHODS: An evidence-based protocol for surfactant administration was developed (2011), implemented (2012) and re-implemented (2014), including three major steps: lung recruitment, manual bagging, and bolus instillation. Three epochs were evaluated: E(0) (2010), E(1) (2015) and E(2) (2018). Adherence was defined as compliance with all steps. Adverse events such as hypoxia (<80%) and severe airway obstruction (SAO) were investigated. RESULTS: 197 infants (246 administrations) were included: E(0) 81 (110), E(1) 52 (63), and E(2) 64 (73). Adherence improved from 49% (E(1)) to 67% (E(2)). Full adherence to protocol significantly decreased SAO from 26% to 1.25% (E(2); p < 0.005) and hypoxia/bradycardia events (5 to 0% E(2); p < 0.005), without any side effects. CONCLUSIONS: Adherence to a surfactant administration protocol improved over time and significantly decreased important adverse events."
3185,A descriptive survey of porcine epidemic diarrhea in pig populations in northern Vietnam,"Porcine epidemic diarrhea (PED) virus (PEDV) is a globally emerging and re-emerging epizootic swine virus that causes massive economic losses in the swine industry, with high mortality in piglets. In Vietnam, PED first emerged in 2009 and has now developed to an endemic stage. This is the first cross-sectional survey performed to evaluate the proportion of PEDV-positive swine farms in Vietnam from January 2018 to February 2019. Fecal samples from 327 pig farms in northern Vietnam were collected and tested for PEDV infection by reverse transcription-loop-mediated isothermal amplification (RT-LAMP) method. The proportion of PEDV-positive farms was 30.9% and PEDV-positive farms were distributed throughout the study area. The highest proportion of PEDV-positive farms was 70% (7/10) among nucleus production type farms (P < 0.05). Higher proportions of PEDV-positive farms were found in the Northeast and Red River Delta areas, which are the major areas of pig production (P < 0.05). The proportion of PEDV-positive farms was higher among larger farms (P < 0.05). Our findings illustrate the high proportion of PEDV-positive farms in the Vietnamese pig population and will help to better understand the epidemiological dynamics of PED infection, to estimate impact, and establish and improve prevention and control measures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11250-020-02416-1) contains supplementary material, which is available to authorized users."
3186,An experience of subglottic airway foreign body removal in a patient under tracheal intubation: a case report,"BACKGROUND: Removal of an airway foreign body is challenging to anesthesiologists. We report successful removal of an extremely rare foreign body between a tracheal tube and the trachea in patients under tracheal intubation. CASE PRESENTATION: A 57-year-old male received total aortic arch replacement and postoperative mechanical ventilation. An airway foreign body was detected just below the glottis, outside the tracheal tube during mechanical ventilation after surgery in the intensive care unit. Before the removal procedure, we planned multiple strategies to cope with unexpected airway and breathing troubles. As a result, the foreign body was successfully removed orally by using a bronchial fiber, without extubation of the tracheal tube, under general anesthesia with dexmedetomidine and ketamine. CONCLUSIONS: We reported the successful removal of a foreign body in the subglottic airway of a patient under tracheal intubation."
3187,Diaphragmatic activity and neural breathing variability during a 5-min endotracheal continuous positive airway pressure trial in extremely preterm infants,"BACKGROUND: Extremely preterm infants are often exposed to endotracheal tube continuous positive airway pressure (ETT-CPAP) trials to assess extubation readiness. The effects of ETT-CPAP trial on their diaphragmatic activity (Edi) and breathing variability is unknown. METHODS: Prospective observational study enrolling infants with birth weight ≤1250 g undergoing their first extubation attempt. Diaphragmatic activity, expressed as the absolute minimum (Edi min) and maximum values (Edi max), area under the Edi signal, and breath-by-breath analyses for breath areas, amplitudes, widths, and neural inspiratory and expiratory times, were analyzed during mechanical ventilation (MV) and ETT-CPAP. Neural breathing variability of each of these parameters was also calculated and compared between MV and ETT-CPAP. RESULTS: Thirteen infants with median (interquartile range) birth weight of 800 g [610–920] and gestational age of 25.4 weeks [24.4–26.3] were included. Diaphragmatic activity significantly increased during ETT-CPAP when compared to MV:Edi max (44.2 vs. 38.1 μV), breath area (449 vs. 312 μV·s), and amplitude (10.12 vs. 7.46 μV). Neural breathing variability during ETT-CPAP was characterized by increased variability for amplitude and area under the breath, and decreased for breath time and width. CONCLUSIONS: A 5-min ETT-CPAP in extremely preterm infants undergoing extubation imposed significant respiratory load with changes in respiratory variability. IMPACT: ETT-CPAP trials are often used to assess extubation readiness in extremely preterm infants, but its effects upon their respiratory system are not well known. Diaphragmatic activity analysis demonstrated that these infants are able to mount an important response to a short trial. A 5-min trial imposed a significant respiratory load evidenced by increased diaphragmatic activity and changes in breathing variability. Differences in breathing variability were observed between successful and failed extubations, which should be explored further in extubation readiness investigations. This type of trial cannot be recommended for preterm infants in clinical practice until clear standards and accuracy are established."
3188,Dissociable mesolimbic dopamine circuits control responding triggered by alcohol-predictive discrete cues and contexts,"Context can influence reactions to environmental cues and this elemental process has implications for substance use disorder. Using an animal model, we show that an alcohol-associated context elevates entry into a fluid port triggered by a conditioned stimulus (CS) that predicted alcohol (CS-triggered alcohol-seeking). This effect persists across multiple sessions and, after it diminishes in extinction, the alcohol context retains the capacity to augment reinstatement. Systemically administered eticlopride and chemogenetic inhibition of ventral tegmental area (VTA) dopamine neurons reduce CS-triggered alcohol-seeking. Chemogenetically silencing VTA dopamine terminals in the nucleus accumbens (NAc) core reduces CS-triggered alcohol-seeking, irrespective of context, whereas silencing VTA dopamine terminals in the NAc shell selectively reduces the elevation of CS-triggered alcohol-seeking in an alcohol context. This dissociation reveals new roles for divergent mesolimbic dopamine circuits in the control of responding to a discrete cue for alcohol and in the amplification of this behaviour in an alcohol context."
3189,Dental Calculus as a Tool to Study the Evolution of the Mammalian Oral Microbiome,"Dental calculus, the calcified form of the mammalian oral microbial plaque biofilm, is a rich source of oral microbiome, host, and dietary biomolecules and is well preserved in museum and archaeological specimens. Despite its wide presence in mammals, to date, dental calculus has primarily been used to study primate microbiome evolution. We establish dental calculus as a valuable tool for the study of nonhuman host microbiome evolution, by using shotgun metagenomics to characterize the taxonomic and functional composition of the oral microbiome in species as diverse as gorillas, bears, and reindeer. We detect oral pathogens in individuals with evidence of oral disease, assemble near-complete bacterial genomes from historical specimens, characterize antibiotic resistance genes, reconstruct components of the host diet, and recover host genetic profiles. Our work demonstrates that metagenomic analyses of dental calculus can be performed on a diverse range of mammalian species, which will allow the study of oral microbiome and pathogen evolution from a comparative perspective. As dental calculus is readily preserved through time, it can also facilitate the quantification of the impact of anthropogenic changes on wildlife and the environment."
3190,PIQMEE: Bayesian Phylodynamic Method for Analysis of Large Data Sets with Duplicate Sequences,"Next-generation sequencing of pathogen quasispecies within a host yields data sets of tens to hundreds of unique sequences. However, the full data set often contains thousands of sequences, because many of those unique sequences have multiple identical copies. Data sets of this size represent a computational challenge for currently available Bayesian phylogenetic and phylodynamic methods. Through simulations, we explore how large data sets with duplicate sequences affect the speed and accuracy of phylogenetic and phylodynamic analysis within BEAST 2. We show that using unique sequences only leads to biases, and using a random subset of sequences yields imprecise parameter estimates. To overcome these shortcomings, we introduce PIQMEE, a BEAST 2 add-on that produces reliable parameter estimates from full data sets with increased computational efficiency as compared with the currently available methods within BEAST 2. The principle behind PIQMEE is to resolve the tree structure of the unique sequences only, while simultaneously estimating the branching times of the duplicate sequences. Distinguishing between unique and duplicate sequences allows our method to perform well even for very large data sets. Although the classic method converges poorly for data sets of 6,000 sequences when allowed to run for 7 days, our method converges in slightly more than 1 day. In fact, PIQMEE can handle data sets of around 21,000 sequences with 20 unique sequences in 14 days. Finally, we apply the method to a real, within-host HIV sequencing data set with several thousand sequences per patient."
3191,Loss of bacterial diversity in the sinuses is associated with lower smell discrimination scores,"Olfactory impairment affects ~ 20% of the population and has been linked to various serious disorders. Microbes in the nasal cavity play a key role in priming the physiology of the olfactory epithelium and maintaining a normal sense of smell by the host. The aim of this study was to explore the link between olfactory dysfunction and nasal bacterial communities. A total of 162 subjects were recruited for this study from a specialized olfactory dysfunction clinic and placed into one of three groups: anosmia, hyposmia or normosmia. Swabs from the nasal middle meatus were collected from each subject then processed for bacterial 16S rRNA gene sequencing. No overall differences in bacterial diversity or composition were observed between the three cohorts in this study. However, the relative abundances of Corynebacterium spp. and Streptococcus spp. were significantly (p < 0.05) different in subjects with olfactory loss. Furthermore, subjects with deficiencies in discriminating between smells (based on discrimination scores) had a lower bacterial diversity (Simpson’s evenness p < 0.05). While these results are preliminary in nature, potential bacterial biomarkers for olfactory loss were identified. These findings need to be further validated and biologically tested in animal models."
3192,"BiteOscope, an open platform to study mosquito biting behavior","Female mosquitoes need a blood meal to reproduce, and in obtaining this essential nutrient they transmit deadly pathogens. Although crucial for the spread of mosquito-borne diseases, blood feeding remains poorly understood due to technological limitations. Indeed, studies often expose human subjects to assess biting behavior. Here, we present the biteOscope, a device that attracts mosquitoes to a host mimic which they bite to obtain an artificial blood meal. The host mimic is transparent, allowing high-resolution imaging of the feeding mosquito. Using machine learning, we extract detailed behavioral statistics describing the locomotion, pose, biting, and feeding dynamics of Aedes aegypti, Aedes albopictus, Anopheles stephensi, and Anopheles coluzzii. In addition to characterizing behavioral patterns, we discover that the common insect repellent DEET repels Anopheles coluzzii upon contact with their legs. The biteOscope provides a new perspective on mosquito blood feeding, enabling the high-throughput quantitative characterization of this lethal behavior."
3193,Extensive and diverse patterns of cell death sculpt neural networks in insects,"Changes to the structure and function of neural networks are thought to underlie the evolutionary adaptation of animal behaviours. Among the many developmental phenomena that generate change programmed cell death (PCD) appears to play a key role. We show that cell death occurs continuously throughout insect neurogenesis and happens soon after neurons are born. Mimicking an evolutionary role for increasing cell numbers, we artificially block PCD in the medial neuroblast lineage in Drosophila melanogaster, which results in the production of ‘undead’ neurons with complex arborisations and distinct neurotransmitter identities. Activation of these ‘undead’ neurons and recordings of neural activity in behaving animals demonstrate that they are functional. Focusing on two dipterans which have lost flight during evolution we reveal that reductions in populations of flight interneurons are likely caused by increased cell death during development. Our findings suggest that the evolutionary modulation of death-based patterning could generate novel network configurations."
3194,Reply,See related letter
3195,Every cloud has a silver lining,
3196,Phylogenetic analysis of SARS‐CoV‐2 IN THE FIRST MONTHS SINCE ITS EMERGENCE,"During the first months of SARS‐CoV‐2 evolution in a new host, contrasting hypotheses have been proposed about the way the virus has evolved and diversified worldwide. The aim of this study was to perform a comprehensive evolutionary analysis to describe the human outbreak and the evolutionary rate of different genomic regions of SARS‐CoV‐2. The molecular evolution in nine genomic regions of SARS‐CoV‐2 was analyzed using three different approaches: phylogenetic signal assessment, emergence of amino acid substitutions, and Bayesian evolutionary rate estimation in eight successive fortnights since the virus emergence. All observed phylogenetic signals were very low and tree topologies were in agreement with those signals. However, after four months of evolution, it was possible to identify regions revealing an incipient viral lineage formation despite the low phylogenetic signal, since fortnight 3. Finally, the SARS‐CoV‐2 evolutionary rate for regions nsp3 and S, the ones presenting greater variability, was estimated as 1.37 x 10(‐3) and 2.19 x 10(‐3) substitution/site/year, respectively. In conclusion, results from this work about the variable diversity of crucial viral regions and determination of the evolutionary rate are consequently decisive to understand essential features of viral emergence. In turn, findings may allow the first time characterization of the evolutionary rate of S protein, crucial for vaccine development. This article is protected by copyright. All rights reserved."
3197,"Biomarkers of Aging: Prediction of Longevity by Using Age-Sensitive T-Cell Subset Determinations in a Middle-Aged, Genetically Heterogeneous Mouse Population","Seven T-cell subset values were measured in each of 559 mice at 8 months of age, and then again in the 494 animals that reached 18 months of age. The group included virgin males, virgin females, and mated females, and it was produced by using a four-way cross-breeding system that generates genetic heterogeneity equivalent to a very large sibship. An analysis of covariance showed that four T-cell subsets—CD4, CD4 memory, CD4 naïve, and CD4 cells expressing P-glycoprotein—were significant predictors (p< .003) of longevity when measured at 18 months of age after adjustment for the possible effects of gender and mating. The subset marked by CD4 and P-glycoprotein expression showed a significant interaction effect: this subset predicted longevity only in males. Among subsets measured when the mice were 8 months of age, only the levels of CD8 memory cells predicted longevity (p= .016); the prognostic value of this subset was largely limited to mated females. A cluster analysis that separated mice into two groups based upon similarity of T-cell subset patterns measured at 18 months showed that these two groups differed in life expectancy. Specifically, mice characterized by relatively low levels of CD4 and CD8 memory cells, high levels of CD4 naïve cells, and low levels of CD4 cells with P-glycoprotein (64% of the total) lived significantly longer (50 days = 6%; p< .0007) than mice in the other cluster. The results are consistent with the hypothesis that patterns of T-cell subsets vary among mice in a manner than can predict longevity in middle age, and they suggest that these subsets may prove to be useful for further studies of the genetics of aging and age-sensitive traits."
3198,"COproduction VALUE creation in healthcare service (CO-VALUE): an international multicentre protocol to describe the application of a model of value creation for use in systems of coproduced healthcare services and to evaluate the initial feasibility, utility and acceptability of associated system-level value creation assessment approaches","INTRODUCTION: Coproduction introduces a fundamental shift in how healthcare service is conceptualised. The mechanistic idea of healthcare being a ‘product’ generated by the healthcare system and delivered to patients is replaced by that of a service co-created by the healthcare system and the users of healthcare services. Fjeldstad et al offer an approach for conceptualising value creation in complex service contexts that we believe is applicable to coproduction of healthcare service. We have adapted Fjeldstad’s value creation model based on a detailed case study of a renal haemodialysis service in Jonkoping, Sweden, which demonstrates coproduction characteristics and key elements of Fjeldstad’s model. METHODS AND ANALYSIS: We propose a five-part coproduction value creation model for healthcare service: (1) value chain, characterised by a standardised set of processes that serve a commonly occurring need; (2) value shop, which offers a customised response for unique cases; (3) a facilitated value network, which involves groups of individuals struggling with similar challenges; (4) interconnection between shop, chain and network elements and (5) leadership. We will seek to articulate and assess the value creation model through the work of a community of practice comprised of a diverse international workgroup with representation from executive, financial and clinical leaders as well as other key stakeholders from multiple health systems. We then will conduct pilot studies of a qualitative self-assessment process in participating health systems, and ultimately develop and test quantitative measures for assessing coproduction value creation. ETHICS AND DISSEMINATION: This study has been approved by the Dartmouth-Hitchcock Health Institutional Review Board (D-HH IRB) as a minimal risk research study. Findings and scholarship will be disseminated broadly through continuous engagement with health system stakeholders, national and international academic presentations and publications and an internet-based electronic platform for publicly accessible study information."
3199,Racism and social injustice as determinants of child health: the American Pediatric Society Issue of the Year,
3200,Challenges of academic pediatric medicine: the American Pediatric Society and Society for Pediatric Research Virtual Chat Series,
3201,Angiotensin-converting enzyme 2 activity in patients with chronic kidney disease,"BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is a novel regulator of the renin–angiotensin system that counteracts the adverse effects of angiotensin II. In heart failure patients, elevated plasma ACE2 activity predicted adverse events and greater myocardial dysfunction. We aimed to describe plasma ACE2 activity and its clinical associations in patients with kidney disease. METHODS: Patients recruited from a single centre comprised of chronic kidney disease Stage III/IV (CKD), haemodialysis patients and kidney transplant recipients (KTRs). Plasma ACE2 enzyme activity was measured using a fluorescent substrate assay in plasma, collected at baseline and stored at −80°C. Linear regression was performed in both males and females separately to determine the covariates associated with log-transformed ACE2. RESULTS: The median (interquartile range) plasma ACE2 activity in pmol/mL/min was 15.9 (8.4–26.1) in CKD (n = 59), 9.2 (3.9–18.2) in haemodialysis (n = 100) and 13.1 (5.7–21.9) in KTR (n = 80; P < 0.01). In male haemodialysis patients, ACE2 activity was 12.1 (6.8–19.6) compared with 4.4 (2.5–10.3) in females (P < 0.01). Log-transformed ACE2 plasma activity was associated with post-haemodialysis systolic blood pressure in females [β-coefficient 0.04, 95% confidence interval (95% CI) 0.01–0.06, P = 0.006]. In males, log-transformed ACE2 plasma activity was associated with B-type natriuretic peptide (β-coefficient 0.39, 95% CI 0.19–0.60, P < 0.001). Plasma ACE2 activity was not associated with mortality. CONCLUSIONS: Plasma ACE2 activity is reduced in haemodialysis patients compared with CKD patients, and in female haemodialysis patients compared with male. The different associations of plasma ACE2 activity between male and female haemodialysis patients indicate that the role of ACE2 in cardiovascular disease may differ by gender."
3202,Lecythophora hoffmannii isolated from a case of canine osteomyelitis in Japan,"A 2-year-old spayed female mongrel dog showed claudication with abnormal ossification containing fungal cells detected by biopsy. The dog was treated with ketoconazole and itraconazole perorally for 5 months; however, the osteomyelitis became aggravated, and an amputation from the scapula was performed. The right superficial cervical lymph node became swollen 5 months after the operation. The lymph node contained PAS positive fungal elements and a portion of tissue produced mycelial fungal growth on potato dextrose agar supplemented with chloramphenicol. The culture was identified as Lecythophora hoffmannii based on morphology, physiology and 100% identity in the sequence of the D1/D2 domain of the large subunit ribosomal RNA gene of the fungal species in the GenBank database (accession number AB100627). In addition, the sequence from the present isolate was submitted as AB189164. The isolate showed resistance to antifungal agents, i.e., amphotericin B, 5-FC, fluconazole, itraconazole, miconazole and micafungin. The dog developed cachexia 2 months after the onset of lymphadenopathy, and was euthanized on the 459th day after onset of clinical symptoms. This was the first disseminated case of L. hoffmannii infection in Japan."
3203,Practical identification of eight medically important Trichosporon species by reverse line blot hybridization (RLB) assay and rolling circle amplification (RCA),"We developed a reverse line blot (RLB) hybridization-, and rolling circle amplification (RCA)-based assays for the identification of Trichoporon species and evaluated them with 48 isolates that had been previously recognized as belonging to eight species (Trichosporon asahii, T. cutaneum, T. dermatis, T. domesticum, T. inkin, T. japonicum, T. jirovecii, and T. laibachii). Results were compared to those obtained with DNA sequencing of three rRNA gene loci, i.e., the internal transcribed spacer (ITS) region, D1/D2 domain of the 28S rRNA gene and intergenic spacer 1 (IGS1) region. Using species-specific, or group-specific probes targeted at the ITS region and the D1/D2 domain, the RLB assay permitted accurate species identification of all 48 isolates with 100% specificity. Species-specific RLB probes correctly assigned 45/48 (94%) of the isolates (six species) with the exception of T. dermatis and T. japonicum isolates which were not targeted by the assay. Identification of T. dermatis relied on a positive hybridization result with the group-specific probe hybridizing with T. dermatis and T. jirovecii and the absence of a signal with the T. jirovecii-specific probe. T. japonicum strains were first assigned to the T. asahii-T. japonicum group by hybridization with the two species group-specific probe and then as T. japonicum by the absence of signal with a T. asahii-specific probe. Twelve species-specific RCA probes targeting the eight species studied detected templates of all 48 Trichosporon isolates and an artificial template of T. asteroides, all with good specificity. Both RLB and RCA are potential alternatives to DNA sequencing for the identification of Trichosporon species. The RLB approach is suited for the batched simultaneous analysis of large numbers of isolates, while RCA is more appropriate for the immediate study of single isolates. Comparative costs are US$7 and US$2 per assay for the RLB and RCA methods, respectively."
3204,Insights from Parasite-Specific Serological Tools in Eco-Immunology,"Eco-immunology seeks evolutionary explanations for the tremendous variation in immune defense observed in nature. Assays to quantify immune phenotypes often are crucial to this endeavor. To this end, we suggest that more use could (and arguably should) be made of the veterinary and clinical serological toolbox. For example, measuring the magnitude and half-life of parasite-specific antibodies across a range of host taxa may provide new ways of testing theories in eco-immunology. Here, we suggest that antibody assays developed in veterinary and clinical immunology and epidemiology provide excellent tools—or at least excellent starting points for development of tools—for tests of such hypotheses. We review how such assays work and how they may be optimized for new questions and new systems in eco-immunology. We provide examples of the application of such tools to eco-immunological studies of seabirds and mammals, and suggest a decision-tree to aid development of assays. We expect that addition of such tools to the eco-immunological toolbox will promote progress in the field and help elucidate how immune systems function and why they vary in nature."
3205,Combining evolutionary information extracted from frequency profiles with sequence-based kernels for protein remote homology detection,"Motivation: Owing to its importance in both basic research (such as molecular evolution and protein attribute prediction) and practical application (such as timely modeling the 3D structures of proteins targeted for drug development), protein remote homology detection has attracted a great deal of interest. It is intriguing to note that the profile-based approach is promising and holds high potential in this regard. To further improve protein remote homology detection, a key step is how to find an optimal means to extract the evolutionary information into the profiles. Results: Here, we propose a novel approach, the so-called profile-based protein representation, to extract the evolutionary information via the frequency profiles. The latter can be calculated from the multiple sequence alignments generated by PSI-BLAST. Three top performing sequence-based kernels (SVM-Ngram, SVM-pairwise and SVM-LA) were combined with the profile-based protein representation. Various tests were conducted on a SCOP benchmark dataset that contains 54 families and 23 superfamilies. The results showed that the new approach is promising, and can obviously improve the performance of the three kernels. Furthermore, our approach can also provide useful insights for studying the features of proteins in various families. It has not escaped our notice that the current approach can be easily combined with the existing sequence-based methods so as to improve their performance as well. Availability and implementation: For users’ convenience, the source code of generating the profile-based proteins and the multiple kernel learning was also provided at http://bioinformatics.hitsz.edu.cn/main/∼binliu/remote/ Contact: bliu@insun.hit.edu.cn or bliu@gordonlifescience.org Supplementary information: Supplementary data are available at Bioinformatics online."
3206,"Seroincidence of Influenza Among HIV-infected and HIV-uninfected Men During the 2009 H1N1 Influenza Pandemic, Bangkok, Thailand","Among 368 Thai men who have sex with men with paired serum samples collected before and during the 2009 H1N1 influenza pandemic, we determined influenza A (H1N1)pdm09 seroconversion rates (≥4-fold rise in antibody titers by hemagglutination inhibition or microneutralization assays). Overall, 66 of 232 (28%) participants seroconverted after the first year of A(H1N1)pdm09 activity, and 83 of 234 (35%) participants seroconverted after the second year. Influenza A(H1N1)pdm09 seroconversion did not differ between human immunodeficiency virus (HIV)-infected (55 of 2157 [35%]) and HIV-uninfected (71 of 2211 [34%]) participants (P = .78). Influenza A(H1N1)pdm09 seroconversion occurred in approximately one third of our Thai study population and was similar among HIV-infected and HIV-uninfected participants."
3207,Influenza Circulation in United States Army Training Camps Before and During the 1918 Influenza Pandemic: Clues to Early Detection of Pandemic Viral Emergence,"Background. Surveillance for respiratory diseases in domestic National Army and National Guard training camps began after the United States’ entry into World War I, 17 months before the “Spanish influenza” pandemic appeared. Methods. Morbidity, mortality, and case-fatality data from 605 625 admissions and 18 258 deaths recorded for 7 diagnostic categories of respiratory diseases, including influenza and pneumonia, were examined over prepandemic and pandemic periods. Results. High pandemic influenza mortality was primarily due to increased incidence of, but not increased severity of, secondary bacterial pneumonias. Conclusions. Two prepandemic incidence peaks of probable influenza, in December 1917–January 1918 and in March–April 1918, differed markedly from the September–October 1918 pandemic onset peak in their clinical-epidemiologic features, and they may have been caused by seasonal or endemic viruses. Nevertheless, rising proportions of very low incidence postinfluenza bronchopneumonia (diagnosed at the time as influenza and bronchopneumonia) in early 1918 could have reflected circulation of the pandemic virus 5 months before it emerged in pandemic form. In this study, we discuss the possibility of detecting pandemic viruses before they emerge, by surveillance of special populations."
3208,Evaluation of the Safety and Immunogenicity of a Candidate Pandemic Live Attenuated Influenza Vaccine (pLAIV) Against Influenza A(H7N9),"Background. We evaluated a candidate A/Anhui/2013(H7N9) pandemic live attenuated influenza vaccine (pLAIV) in healthy adults, and assessed the ability of 1 or 2 doses to induce immune memory. Methods. Healthy subjects in 2 age groups (18–49 years and 50–70 years) with undetectable hemagglutination-inhibiting (HAI) antibody to H7N9 were enrolled. Younger subjects received either 1 or 2 intranasal doses of 10(7.0) fluorescent focus units of A/Anhui/1/2013 pLAIV, while older subjects received a single dose. All subjects received a single 30-µg dose of unadjuvanted, antigenically matched A/Shanghai2/2013(H7N9) pandemic inactivated influenza vaccine (pIIV) 12 weeks after their first dose of pLAIV. Results. Both vaccines were well tolerated. Serum HAI antibody responses were detected in 0 of 32 younger subjects and 1 of 17 older subjects after 1 dose of pLAIV and in 2 of 16 younger subjects after a second dose. Strong serum antibody responses were detected after a single subsequent dose of pIIV that was broadly reactive against H7 influenza viruses. Conclusions. An A(H7N9) pLAIV candidate was safe in both age groups. Priming with pLAIV resulted in responses to subsequent pIIV that exceeded those seen in naive subjects in previous reports. The A(H7N9) pLAIV induces strong immune memory that can be demonstrated by exposure to subsequent antigenic challenge. Clinical Trials Registration. NCT01995695 and NCT02274545."
3209,Outbreak of Variant Influenza A(H3N2) Virus in the United States,"Background. Variant influenza virus infections are rare but may have pandemic potential if person-to-person transmission is efficient. We describe the epidemiology of a multistate outbreak of an influenza A(H3N2) variant virus (H3N2v) first identified in 2011. Methods. We identified laboratory-confirmed cases of H3N2v and used a standard case report form to characterize illness and exposures. We considered illness to result from person-to-person H3N2v transmission if swine contact was not identified within 4 days prior to illness onset. Results. From 9 July to 7 September 2012, we identified 306 cases of H3N2v in 10 states. The median age of all patients was 7 years. Commonly reported signs and symptoms included fever (98%), cough (85%), and fatigue (83%). Sixteen patients (5.2%) were hospitalized, and 1 fatal case was identified. The majority of those infected reported agricultural fair attendance (93%) and/or contact with swine (95%) prior to illness. We identified 15 cases of possible person-to-person transmission of H3N2v. Viruses recovered from patients were 93%–100% identical and similar to viruses recovered from previous cases of H3N2v. All H3N2v viruses examined were susceptible to oseltamivir and zanamivir and resistant to adamantane antiviral medications. Conclusions. In a large outbreak of variant influenza, the majority of infected persons reported exposures, suggesting that swine contact at an agricultural fair was a risk for H3N2v infection. We identified limited person-to-person H3N2v virus transmission, but found no evidence of efficient or sustained person-to-person transmission. Fair managers and attendees should be aware of the risk of swine-to-human transmission of influenza viruses in these settings."
3210,Relative accuracy of social and medical determinants of suicide in electronic health records,"OBJECTIVE: This paper compares the accuracy of predicting suicide from Social Determinants of Health (SDoH) or history of illness. POPULATION STUDIED: 5 313 965 Veterans who at least had two primary care visits between 2008 and 2016. STUDY DESIGN: The dependent variable was suicide or intentional self‐injury. The independent variables were 10 495 International Classification of Disease (ICD) Version 9 codes, age, and gender. The ICD codes included 40 V‐codes used for measuring SDoH, such as family disruption, family history of substance abuse, lack of education, legal impediments, social isolation, unemployment, and homelessness. The sample was randomly divided into training (90 percent) and validation (10 percent) sets. Area under the receiver operating characteristic (AROC) was used to measure accuracy of predictions in the validation set. PRINCIPAL FINDINGS: Separate analyses were done for inpatient and outpatient codes; the results were similar. In the hospitalized group, the mean age was 67.2 years, and 92.1 percent were male. The mean number of medical diagnostic codes during the study period was 37; and 12.9 percent had at least one SDoH V‐code. At least one episode of suicide or intentional self‐injury occurred in 1.89 percent of cases. SDoH V‐codes, on average, elevated the risk of suicide or intentional self‐injury by 24‐fold (ranging from 4‐ to 86‐fold). An index of 40 SDoH codes predicted suicide or intentional self‐injury with an AROC of 0.64. An index of 10 445 medical diagnoses, without SDoH V‐codes, had AROC of 0.77. The combined SDoH and medical diagnoses codes also had AROC of 0.77. CONCLUSION: In predicting suicide or intentional self‐harm, SDoH V‐codes add negligible information beyond what is already available in medical diagnosis codes. IMPLICATIONS FOR PRACTICE: Policies that affect SDoH (eg, housing policies, resilience training) may not have an impact on suicide rates, if they do not change the underlying medical causes of SDoH."
3211,Prospects for detecting early warning signals in discrete event sequence data: Application to epidemiological incidence data,"Early warning signals (EWS) identify systems approaching a critical transition, where the system undergoes a sudden change in state. For example, monitoring changes in variance or autocorrelation offers a computationally inexpensive method which can be used in real-time to assess when an infectious disease transitions to elimination. EWS have a promising potential to not only be used to monitor infectious diseases, but also to inform control policies to aid disease elimination. Previously, potential EWS have been identified for prevalence data, however the prevalence of a disease is often not known directly. In this work we identify EWS for incidence data, the standard data type collected by the Centers for Disease Control and Prevention (CDC) or World Health Organization (WHO). We show, through several examples, that EWS calculated on simulated incidence time series data exhibit vastly different behaviours to those previously studied on prevalence data. In particular, the variance displays a decreasing trend on the approach to disease elimination, contrary to that expected from critical slowing down theory; this could lead to unreliable indicators of elimination when calculated on real-world data. We derive analytical predictions which can be generalised for many epidemiological systems, and we support our theory with simulated studies of disease incidence. Additionally, we explore EWS calculated on the rate of incidence over time, a property which can be extracted directly from incidence data. We find that although incidence might not exhibit typical critical slowing down properties before a critical transition, the rate of incidence does, presenting a promising new data type for the application of statistical indicators."
3212,RNA Interference Targeted to the Conserved Dimerization Initiation Site (DIS) of HIV-1 Restricts Virus Escape Mutation,"Short hairpin RNAs (shRNA) targeting viral or cellular genes can effectively inhibit human immunodeficiency virus type 1 (HIV-1) replication. This inhibition, however, may induce mutations in the targeted gene, leading to rapid escape from the shRNA-induced inhibition. We generated a lymphoid cell line that stably expressed a 19-bp shRNA targeting a well-conserved dimerization initiation site (DIS) of HIV-1, which strongly inhibited viral replication, thereby delaying virus escape. Furthermore, treatment of HIV-1 infection with DIS- and vif-shRNA combination therapy resulted in superior anti-viral responses compared to vif-shRNA monotherapy. Continuous challenge with HIV-1, however, generated virus mutants that could overcome the RNA interference restriction. Such anti-genes may be promising tools for HIV-1 gene therapy for HIV/acquired immunodeficiency syndrome."
3213,High Viral Load and Respiratory Failure in Adults Hospitalized for Respiratory Syncytial Virus Infections,"A prospective study among adults hospitalized for polymerase chain reaction–confirmed respiratory syncytial virus infections (n = 123) showed frequent occurrence of lower respiratory-tract complications causing respiratory insufficiency (52.8%), requirement for assisted ventilation (16.3%), and intensive care unit admission/death (12.2%). High viral RNA concentration was detected at time of hospitalization, including in patients who presented later than 2 days of illness (day 1–2, 7.29 ± 1.47; day 3–4, 7.28 ± 1.41; day 5–8, 6.66 ± 1.87 log(10) copies/mL). RNA concentration was independently associated with risk of complications and respiratory insufficiency (adjusted odds ratio 1.40 per log(10) copies/mL increase, 95% confidence interval, 1.03–1.90; P = .034). Our data indicate the need and provide a basis for clinical research on antiviral therapy in this population."
3214,Endothelium-Derived Steroidogenic Factor Enhances Angiotensin II-Stimulated Aldosterone Release by Bovine Zona Glomerulosa Cells,"Endothelium-derived steroidogenic factor (EDSF) is an endothelial peptide that stimulates aldosterone release from bovine adrenal zona glomerulosa (ZG) cells. The regulation of aldosterone release by combinations of EDSF and angiotensin II (AII) or EDSF and ACTH was investigated. Endothelial cells (ECs) and EC-conditioned media (ECCM) increased aldosterone release from ZG cells, an activity attributed to EDSF. AII (10(−12) to 10(−8)m) and ACTH (10(−12) to 10(−9)m) also stimulated the release of aldosterone from ZG cells. The stimulation by AII, but not ACTH, was greatly enhanced when ZG cells were coincubated with ECs. AII was metabolized by ECs to peptides identified by mass spectrometry as angiotensin (1-7) and angiotensin IV. There was very little metabolism of AII by ZG cells. Neither of these two AII metabolites altered aldosterone release from ZG cells, so they could not account for the enhanced response with ECs. AII-induced aldosterone release from ZG cells was enhanced by ECCM but not cell-free conditioned medium. This enhanced response was not due to increased EDSF release from ECs by AII. The synergistic effect of EDSF and AII was apparent when AII was added during or after the generation of ECCM and not observed when the AII component of the enhancement was blocked by the AII antagonist, losartan. These studies indicate that EDSF enhances the steroidogenic effect of AII. In the adrenal gland, ECs are in close anatomical relationship with ZG cells and may sensitize ZG cells to the steroidogenic action of AII by releasing EDSF."
3215,2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC) Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS),
3216,"Maternal Exposure to the Cannabinoid Agonist WIN 55,12,2 during Lactation Induces Lasting Behavioral and Synaptic Alterations in the Rat Adult Offspring of Both Sexes","Consumption of cannabis during pregnancy and the lactation period is a rising public health concern (Scheyer et al., 2019). Exposure to synthetic or plant-derived cannabinoids via lactation disrupts the development of GABAergic neurons in the prefrontal cortex (PFC) and alters early-life behaviors (Scheyer et al., 2020b). Recently, additional data revealed that Δ9-tetrahydrocannabinol (THC) perinatal exposure via lactation causes lasting behavioral and neuronal consequences (Scheyer et al., 2020a). Here, the long-term effects in adult offspring of maternal exposure to the synthetic cannabinoid agonist WIN 55,12,2 are reported. The data demonstrate that rats exposed during lactation to WIN display social and motivational deficits at adulthood. These behavioral changes were paralleled by a specific loss of endocannabinoid-mediated long-term depression (eCB-LTD) in the PFC and nucleus accumbens (NAc), while other forms of synaptic plasticity remained intact. Thus, similarly to THC, perinatal WIN exposure via lactation induces behavioral and synaptic abnormalities lasting into adulthood."
3217,Influenza A(H1N1)v pandemic in the dialysis population: first wave results from an international survey,"Background. After the first cases of influenza A(H1N1)v in Mexico and the USA became public, Fresenius Medical Care established a case-based reporting of cases for all of its dialysis clinics located in Europe, Middle East, Africa and Latin America. This paper aims to describe mortality rates of patients on dialysis and to assess the risk profiles. Methods. The survey was developed in Lotus Notes with a secure browser-based form. The form was open to 602 Fresenius Medical Care clinics located in Europe, Middle East, Africa and Latin America. Results. As of 3 September 2009, 306 cases have been reported by 85 clinics located in Argentina, Chile, Brazil, UK and Spain. The mean age was 52.7 ± 17.7 years. The majority of cases (70.6%) were from 20- to 44-year-old and 45- to 64-year-old subgroups. Moreover, 35.3% had no associated comorbidity, 20.3% had two and 4.6% three comorbidities, with heart disease being the most frequent. Fever was the most common symptom, present in 94.4% of the cases, followed by cough (78.8%) and muscle and joint pain (69.3%). Eighty-seven percent were treated with antiviral agents, the majority with oseltamivir. One hundred and three patients (34%) were admitted to hospital because of influenza. Pneumonia was reported for 69 cases, out of which 52 patients belonged to a high-risk group. Mortality rate of all the patients (confirmed, probable and suspected cases) was around 5%. Conclusion. End-stage renal disease patients should be included in first ranks of the priority list for the influenza A (H1N1)v vaccine, as already advocated by some healthcare authorities."
3218,Direct imaging of pH1N1 2009 influenza virus replication in alveolar pneumocytes in fatal cases by transmission electron microscopy,"Human influenza virus pandemics constitute a major global public health issue. Although studies on autopsy specimens from the recent pandemic by the 2009 influenza A (H1N1) virus have revealed a broad spectrum of pathologic findings, direct electron microscopic studies of the lung tissue from influenza fatalities are few. In this study, we examined five well-preserved pulmonary necropsy specimens from fatal cases of laboratory-confirmed pH1N1 from India. The novel observations in comparison with earlier reports included direct imaging of influenza virus budding within dilated cisternae of pneumocytes, cell-free virus emerging from the cell membrane of a pneumocyte in the alveolar lumen, presence of polymorphonuclear cells with red blood cells as inflammatory exudates close to hyaline membranes and extensive cytoplasmic degeneration of epithelial cells of the alveolar lining. These observations are in consistent with the earlier findings and emphasize the possible role of this virus directly infecting cells of the lower respiratory tract as a key event in the rapid pathogenesis of pH1N1 disease process."
3219,Does Expert Opinion Trump Evidence?,
3220,Corrigendum to: The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2,
3221,"Television exposure is related to fear of avian flu, an Ecological Study across 23 member states of the European Union","Background: A pandemic outbreak of H5N1 avian influenza is believed to coincide with large-scale panic. Even without an outbreak fear of infection may be widespread. Mass media coverage of the risks of a pandemic may lead to higher levels of fear. Methods: An ecological study looked at data from 23 member states of the European Union and controlled for population size, level of education, age distribution and income and wealth. Results: When the findings for Cyprus were excluded each additional hour of average TV viewing was associated with a 15.6% increase in the proportion of people worrying about the virus. TV viewing explained 52% of the variance. Conclusion: Fear of a pandemic precedes any real pandemic and may have to be dealt with separately. Exposure to television is highly associated with worrying about the virus. This relationship merits further study."
3222,Remote Learning for Medical Students in Nigeria During a Pandemic,
3223,"Age-dependent carriage of alleles and haplotypes of Plasmodium falciparum sera5, eba-175, and csp in a region of intense malaria transmission in Uganda","BACKGROUND: The development of malaria vaccines is constrained by genetic polymorphisms exhibited by Plasmodium falciparum antigens. The project the age-dependent distribution of alleles or haplotypes of three P. falciparum malaria vaccine candidates, Circumsporozoite Protein (csp), Erythrocyte Binding Antigen 175 (eba-175) and Serine Repeat Antigen 5 (sera5) in a region of intense malaria transmission in Uganda. METHODS: A cross-sectional study was carried out between August and November 2009 in which 250 study participants were selected from a population of 600. Finger prick blood samples were collected after informed consent from participants below 5 years, 5–10 years, and above 10 years of age. Blood was used for microscopy, RDT and dried blood spots. Plasmodium falciparum DNA was extracted by chelex method. Alleles of sera5 and eba-175 were determined by polymerase chain reaction (PCR) amplification followed by resolution of products by agarose gel electrophoresis. Allele calling was done using gel photographs from ethiduim bromide stained gels. Haplotypes of csp were identified by sequencing 63 PCR products using the P. falciparum 7G8 laboratory strain sequence as a reference. The data were analysed using SPSS 16, EQX for windows and Chi-square test was used to calculate associations (P-values), Excel was used to generate graphs. The BioEdit and NCBI blast software programs were used to analyse the sequences from which csp haplotypes map was constructed. RESULTS: Eba-175 FCR3 (48/178) and CAMP (16/178) alleles were observed, the FCR3 (24/67) allele being predominant among children aged below 5 years old while the CAMP (12/67) allele was predominant among older participants. Sera5 alleles ORI (6/204) and ORII (103/204) were observed in the population, ORII was more prevalent and was significantly associated with age (P values < 0.0001), parasite density (P-value < 0.0001) and clinical outcomes (P value = 0.018). There was marked csp diversity in the Th2/Th3 region. Out of 63 sequences, 16 conformed to the reference strain and one (1/16) was similar to a West African haplotype and the majority (14/16) of the haplotypes were unique to this study region. There was an age-dependent distribution of csp haplotypes with more haplotypes being harbored by children < 5-year of age, (10/16) compared to adults (2/16). Interestingly, the csp haplotype corresponding to 3D7 whose prototypical sequence is identical to the sequence of the leading malaria vaccine candidate RTS, S was not observed. CONCLUSION: This data suggest that the eba-175 FCR3 allele, sera5 ORII allele, and csp haplotypes are targets of host immunity and under immune selection pressure in Apac District. These molecules could provide alternative malaria vaccine candidates as sub-unit vaccines."
3224,Procalcitonin and lung ultrasound algorithm to diagnose severe pneumonia in critical paediatric patients (PROLUSP study). A randomised clinical trial,"BACKGROUND: Lung ultrasound (LUS) in combination with a biomarker has not yet been studied. We propose a clinical trial where the primary aims are: 1. To assess whether an algorithm with LUS and procalcitonin (PCT) may be useful for diagnosing bacterial pneumonia; 2. To analyse the sensitivity and specificity of LUS vs chest X-ray (CXR). METHODS/DESIGN: A 3-year clinical trial. Inclusion criteria: children younger than 18 years old with suspected pneumonia in a Paediatric Intensive Care Unit. Patients will be randomised into two groups: Experimental Group: LUS will be performed as first lung image. Control Group: CXR will be performed as first pulmonary image. Patients will be classified according to the image and the PCT: a) PCT < 1 ng/mL and LUS/CXR are not suggestive of bacterial pneumonia (BN), no antibiotic will be prescribed; b) LUS/CXR are suggestive of BN, regardless of the PCT, antibiotic therapy is recommended; c) LUS/CXR is not suggestive of BN and PCT > 1 ng/mL, antibiotic therapy is recommended. CONCLUSION: This algorithm will help us to diagnose bacterial pneumonia and to prescribe the correct antibiotic treatment. A reduction of antibiotics per patient, of the treatment length, and of the exposure to ionizing radiation and in costs is expected. TRIAL REGISTRATION: NCT04217980."
3225,"18th Annual Meeting, Neurocritical Care Society September 22–25, 2020 Phoenix, Arizona",
3226,Inhibition of overexpressed Kv3.4 augments HPV in endotoxemic mice,"BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is a reaction of the pulmonary vasculature upon hypoxia, diverting blood flow into ventilated areas to preserve oxygenation. It is impaired in endotoxemia or ARDS. Voltage gated potassium channels have been shown to play a key role in the regulation of HPV. The aim of the study was to identify a voltage gated potassium channel involved in dysregulated HPV during endotoxemia. METHODS: Lungs of male C57BL/6 mice with and without endotoxemia (n = 6 ea. group) were analyzed for Kv3.4 gene and protein expression. HPV was examined in isolated perfused lungs of mice with and without endotoxemia and with and without selective Kv3.4 blocker BDS-I (n = 7 ea. group). Pulmonary artery pressure (PAP) and pressure-flow curves were measured during normoxic (FiO(2) 0.21) and hypoxic (FiO(2) 0.01) ventilation. HPV was quantified as the increase in perfusion pressure in response to hypoxia in percent of baseline perfusion pressure (ΔPAP) in the presence and absence of BDS-I. RESULTS: Kv3.4 gene (3.2 ± 0.5-fold, p < 0.05) and protein (1.5 ± 0.1-fold p < 0.05) expression levels were increased in endotoxemic mouse lungs. Endotoxemia reduced HPV (∆PAP control: 121.2 ± 8.7% vs. LPS 19.5 ± 8.0%, means ± SEM) while inhibition of Kv3.4 with 50 nM BDS-I augmented HPV in endotoxemic but not in control lungs (∆PAP control BDS-I: 116.6 ± 16.0% vs. LPS BDS-I 84.4 ± 18.2%, means ± SEM). CONCLUSIONS: Kv3.4 gene and protein expressions are increased in endotoxemic mouse lungs. Selective inhibition of Kv3.4 augments HPV in lungs of endotoxemic mice, but not in lungs of control mice."
3227,Ethical Guidelines and Psychological Distress in a Pandemic,
3228,"Liver infusion tryptose (LIT): the best choice for growth, viability, and infectivity of Leishmania infantum parasites","Leishmania spp. parasites have a complex biological cycle presenting basically two different morphological stages, the amastigote and promastigote forms. In vitro cultivation allows a more complete study of the biological aspects of these parasites, indicating better conditions for infection, immunoassay tests, drug evaluations, and vaccines. Thus, we evaluated the three most used culture media for Leishmania spp., Grace’s insect cell culture medium (Grace’s), liver infusion tryptose (LIT), and Schneider’s insect medium (Schneider’s), without supplementation or supplemented with fetal calf serum (FCS) and bovine serum albumin (Albumin) to evaluate the growth, viability, and infectivity of the L. infantum promastigotes. It was observed that promastigote forms have a better growth in LIT and Schneider’s with or without FCS when compared to that in Grace’s. The supplementation with albumin promoted greater viability of the parasites independent of the medium. For in vitro infection of J774.A1 macrophages using light microscopy and flow cytometry analyses, FCS-supplemented LIT and Grace’s promoted higher percentage of infected macrophages and parasite load compared with Schneider’s media. Taken together, our results demonstrated that the supplementation of LIT culture medium with FCS is the most suitable strategy to cultivate Leishmania infantum parasites enabling the maintenance of growth and infective parasites for research uses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00436-020-06893-z) contains supplementary material, which is available to authorized users."
3229,Mitteilungen der DGU,
3230,Temporal trends of outcomes of neutropenic patients with ARDS enrolled in therapeutic clinical trials,
3231,Self-management and HeAlth Promotion in Early-stage dementia with e-learning for carers (SHAPE): study protocol for a multi-centre randomised controlled trial,"BACKGROUND: With an increasing number of people with dementia worldwide and limited advancement in medical treatments, the call for new and cost-effective approaches is crucial. The utility of self-management has been proven in certain chronic conditions. However, very little work has been undertaken regarding self-management in people with dementia. METHODS: The SHAPE trial will include 372 people with mild to moderate dementia to evaluate the effectiveness and cost-effectiveness of an educational programme combining approaches of self-management, health promotion, and e-learning for care partners. The study is a multi-site, single-randomised, controlled, single-blinded trial with parallel arms. The intervention arm is compared with treatment as usual. The intervention comprises a 10-week course delivered as group sessions for the participants with dementia. The sessions are designed to develop self-management skills and to provide information on the nature of the condition and the development of healthy behaviours in a supportive learning environment. An e-learning course will be provided for care partners which covers similar and complementary material to that discussed in the group sessions for the participant with dementia. DISCUSSION: This trial will explore the effect of the SHAPE group intervention on people with mild to moderate dementia in terms of self-efficacy and improvement in key health and mental health outcomes and cost-effectiveness, along with carer stress and knowledge of dementia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04286139, registered prospectively February 26, 2020, https://clinicaltrials.gov/ct2/show/NCT04286139"
3232,Influenza virus-flow from insects to humans as causative for influenza seasonality,"Virus biomass outweighs human biomass, and insects biomass outweighs human biomass. Insects are regularly habited by viruses as well as humans, humans are further inhabited via insects. A model of viral flow is described and specified to explain influenza virus seasonality, which, in temperate climate, usually evolves when insects have mostly disappeared. With this hypothesis a coherent description of regular seasonal influenza and other seasonal respiratory virus infections in temperate climates is possible. The incidence of influenza under different circumstances e.g. temperature, humidity, or tropical conditions and different aspects like synchronicity of infections or in respect to evolutionary conditions do sustain this hypothesis if the behaviour of insects is considered."
3233,"Systems Science Approaches for Global Environmental Health Research: Enhancing Intervention Design and Implementation for Household Air Pollution (HAP) and Water, Sanitation, and Hygiene (WASH) Programs","BACKGROUND: Two of the most important causes of global disease fall in the realm of environmental health: household air pollution (HAP) and poor water, sanitation, and hygiene (WASH) conditions. Interventions, such as clean cookstoves, household water treatment, and improved sanitation facilities, have great potential to yield reductions in disease burden. However, in recent trials and implementation efforts, interventions to improve HAP and WASH conditions have shown few of the desired health gains, raising fundamental questions about current approaches. OBJECTIVES: We describe how the failure to consider the complex systems that characterize diverse real-world conditions may doom promising new approaches prematurely. We provide examples of the application of systems approaches, including system dynamics, network analysis, and agent-based modeling, to the global environmental health priorities of HAP and WASH research and programs. Finally, we offer suggestions on how to approach systems science. METHODS: Systems science applied to environmental health can address major challenges by a) enhancing understanding of existing system structures and behaviors that accelerate or impede aims; b) developing understanding and agreement on a problem among stakeholders; and c) guiding intervention and policy formulation. When employed in participatory processes that engage study populations, policy makers, and implementers, systems science helps ensure that research is responsive to local priorities and reflect real-world conditions. Systems approaches also help interpret unexpected outcomes by revealing emergent properties of the system due to interactions among variables, yielding complex behaviors and sometimes counterintuitive results. DISCUSSION: Systems science offers powerful and underused tools to accelerate our ability to identify barriers and facilitators to success in environmental health interventions. This approach is especially useful in the context of implementation research because it explicitly accounts for the interaction of processes occurring at multiple scales, across social and environmental dimensions, with a particular emphasis on linkages and feedback among these processes. https://doi.org/10.1289/EHP7010"
3234,Loss of dynamic regulation of G protein-coupled receptor kinase 2 by nitric oxide leads to cardiovascular dysfunction with aging,"Nitric oxide (NO) and S-nitrosothiol (SNO) are considered cardio- and vasoprotective substances. We now understand that one mechanism in which NO/SNOs provide cardiovascular protection is through their direct inhibition of cardiac G protein-coupled receptor (GPCR) kinase 2 (GRK2) activity via S-nitrosylation of GRK2 at cysteine 340 (C340). This maintains GPCR homeostasis, including β-adrenergic receptors, through curbing receptor GRK2-mediated desensitization. Previously, we have developed a knockin mouse (GRK2-C340S) where endogenous GRK2 is resistant to dynamic S-nitrosylation, which led to increased GRK2 desensitizing activity. This unchecked regulation of cardiac GRK2 activity resulted in significantly more myocardial damage after ischemic injury that was resistant to NO-mediated cardioprotection. Although young adult GRK2-C340S mice show no overt phenotype, we now report that as these mice age, they develop significant cardiovascular dysfunction due to the loss of SNO-mediated GRK2 regulation. This pathological phenotype is apparent as early as 12 mo of age and includes reduced cardiac function, increased cardiac perivascular fibrosis, and maladaptive cardiac hypertrophy, which are common maladies found in patients with cardiovascular disease (CVD). There are also vascular reactivity and aortic abnormalities present in these mice. Therefore, our data demonstrate that a chronic and global increase in GRK2 activity is sufficient to cause cardiovascular remodeling and dysfunction, likely due to GRK2’s desensitizing effects in several tissues. Because GRK2 levels have been reported to be elevated in elderly CVD patients, GRK2-C340 mice can give insight into the aged-molecular landscape leading to CVD. NEW & NOTEWORTHY Research on G protein-coupled receptor kinase 2 (GRK2) in the setting of cardiovascular aging is largely unknown despite its strong established functions in cardiovascular physiology and pathophysiology. This study uses a mouse model of chronic GRK2 overactivity to further investigate the consequences of long-term GRK2 on cardiac function and structure. We report for the first time that chronic GRK2 overactivity was able to cause cardiac dysfunction and remodeling independent of surgical intervention, highlighting the importance of GRK activity in aged-related heart disease."
3235,Sex differences in the structure and function of rat middle cerebral arteries,"Epidemiological studies demonstrate that there are sex differences in the incidence, prevalence, and outcomes of cerebrovascular disease (CVD). The present study compared the structure and composition of the middle cerebral artery (MCA), neurovascular coupling, and cerebrovascular function and cognition in young Sprague-Dawley (SD) rats. Wall thickness and the inner diameter of the MCA were smaller in females than males. Female MCA exhibited less vascular smooth muscle cells (VSMCs), diminished contractile capability, and more collagen in the media, and a thicker internal elastic lamina with fewer fenestrae compared with males. Female MCA had elevated myogenic tone, lower distensibility, and higher wall stress. The stress/strain curves shifted to the left in female vessels compared with males. The MCA of females failed to constrict compared with a decrease of 15.5 ± 1.9% in males when perfusion pressure was increased from 40 to 180 mmHg. Cerebral blood flow (CBF) rose by 57.4 ± 4.4 and 30.1 ± 3.1% in females and males, respectively, when perfusion pressure increased from 100 to 180 mmHg. The removal of endothelia did not alter the myogenic response in both sexes. Functional hyperemia responses to whisker-barrel stimulation and cognition examined with an eight-arm water maze were similar in both sexes. These results demonstrate that there are intrinsic structural differences in the MCA between sexes, which are associated with diminished myogenic response and CBF autoregulation in females. The structural differences do not alter neurovascular coupling and cognition at a young age; however, they might play a role in the development of CVD after menopause. NEW & NOTEWORTHY Using perfusion fixation of the middle cerebral artery (MCA) in calcium-free solution at physiological pressure and systematically randomly sampling the sections prepared from the same M2 segments of MCA, we found that there are structural differences that are associated with altered cerebral blood flow (CBF) autoregulation but not neurovascular coupling and cognition in young, healthy Sprague-Dawley (SD) rats. Understanding the intrinsic differences in cerebrovascular structure and function in males and females is essential to develop new pharmaceutical treatments for cerebrovascular disease (CVD)."
3236,"A guide to human microbiome research: study design, sample collection, and bioinformatics analysis","The purpose of this review is to provide medical researchers, especially those without a bioinformatics background, with an easy-to-understand summary of the concepts and technologies used in microbiome research. First, we define primary concepts such as microbiota, microbiome, and metagenome. Then, we discuss study design schemes, the methods of sample size calculation, and the methods for improving the reliability of research. We emphasize the importance of negative and positive controls in this section. Next, we discuss statistical analysis methods used in microbiome research, focusing on problems with multiple comparisons and ways to compare β-diversity between groups. Finally, we provide step-by-step pipelines for bioinformatics analysis. In summary, the meticulous study design is a key step to obtaining meaningful results, and appropriate statistical methods are important for accurate interpretation of microbiome data. The step-by-step pipelines provide researchers with insights into newly developed bioinformatics analysis methods."
3237,"Public responses to the Salisbury Novichok incident: a cross-sectional survey of anxiety, anger, uncertainty, perceived risk and avoidance behaviour in the local community","OBJECTIVES: Malicious incidents involving chemical agents sometimes trigger high public concern. We aimed to (1) identify levels of emotion, perceived risk and behaviour change with regard to visiting Salisbury, 1 month after three people were poisoned with a nerve agent; and (2) test whether factors including receipt of information, beliefs about personal exposure and trust in government were associated with these outcomes. DESIGN: A cross-sectional telephone survey of a random sample of Salisbury residents. SETTING: Conducted between 5 and 13 April 2018. PARTICIPANTS: 500 residents aged 18 or over. OUTCOME MEASURES: Self-reported anxiety, anger, uncertainty, perceived risk to self and avoidance of Salisbury. RESULTS: Any degree of anxiety, anger and uncertainty was reported by 40.6%, 29.8% and 30.6% of participants, respectively. For the majority, the level of emotion reported was mild. Only 7.0% met the criteria for high anxiety and 5.2% reported feeling any risk to their health, whereas 18.6% reported avoiding Salisbury. Factors associated with avoidance of Salisbury included being female, unable to rule out exposure for oneself or of loved ones, believing the incident was targeted against the general public, and lower trust in the government and responding agencies. Hearing a lot or a little about the recovery support (eg, financial packages), as opposed to nothing at all, and being satisfied with this information were associated with reduced avoidance. CONCLUSIONS: Although the March 2018 Salisbury incident had a relatively modest impact on emotion and risk perception in the community, the number who reported avoiding the city was notable. In this, and in future incidents, assuring people that contamination resulted from a targeted, rather than indiscriminate, incident; demonstrating that contamination is contained within specific areas; improving communication about any financial support; and promoting trust in responding agencies should help provide additional reassurance to the community."
3238,Residency redeployment during a pandemic: Lessons for balancing service and learning,
3239,Teaching an educational simulation elective outside the simulation center,
3240,Being a post-positivist is exhausting: The daunting commitment to an uncertain truth,
3241,Modern day superheroes,
3242,Multiple Traditional Chinese Medicine interventions for idiopathic pulmonary fibrosis: A protocol for systematic review and meta-analysis of overview,"BACKGROUND: The therapeutic strategies of idiopathic pulmonary fibrosis (IPF) tend to be comprehensive. Improving the major symptoms and quality of life (QoL) is as important as postponing the process of fibrosis. However, only pirfenidone and nintedanib conditionally recommended by guidelines and no definite proof indicate that they can significantly ameliorate the main symptoms and QoL of IPF sufferers. At present, multiple types of Traditional Chinese Medicine (TCM) interventions alone or in combination with conventional western medicine managements are widespreadly applied in IPF treatment, which seemingly have a promising clinical effect, especially in ameliorating the main symptoms and improving QoL. Subsequently, the number of relevant studies in systematic reviews(SRs) and meta-analyses of randomized controlled trials(RCTs) increased significantly. Hence, we plan to implement an overview to collect, evaluate, and summarize the results of these SRs. METHODS: An all-round literature retrieval will be conducted in 9 electronic databases, including PubMed, EMBASE, CINAHL, Cochrane Library, Epistemonikos, CNKI, CBM, Wanfang, and VIP. We will focus on the systematic review and meta-analysis of RCTs for multiple TCM interventions alone or in combination with routine western medicine measures in IPF treatment. The main outcomes we follow with interest include the improvement of major symptoms (cough, dyspnea) and QoL. Secondary outcomes will consist of minor symptoms improvement, clinical total effective rate, lung function, blood gas analysis, 6-minute walk text, adverse events, acute exacerbation, all-cause mortality, and IPF-related mortality. Two reviewers will independently select the SRs satisfactory with the enrolling criteria, extract key characteristics, and datas on predefined form, evaluate methodological quality by AMSTAR-2, ROBIS and PRISMA tools, and the quality of evidences adopting GRADE method. In case of any divergence will be reached an agreement by discussion or adjudicated by a third senior reviewer. We will perform a narrative synthesis of the proofs from SRs included. RESULTS: The findings of this overvew will be presented at relevant conferences and submitted for peer-review publication. CONCLUSIONS: We expect to obtain comprehensive and reliable evidence of IPF treated by diversified TCM interventions from the potential standard SRs, which may provide suggestions for future RCTs and SRs. REGISTRATION NUMBER: INPLASY 202080110"
3243,Effect of traditional Chinese medicine injections on severe pneumonia: A protocol for systematic review and meta-analysis,"BACKGROUND: Traditional Chinese medicine injections (TCMJ) used in the treatment of severe pneumonia have been widely implemented in clinical practice, but their overall efficacy and safety remain unclear. This paper aims to evaluate the efficacy and safety of TCMJ in the treatment of severe pneumonia. METHODS: PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, and the Chongqing VIP Chinese Science and Technology Periodical Database were all searched for randomized controlled trials focusing on the administration of TCMJ for severe pneumonia. Two researchers independently screened titles, abstracts, full texts, and extracted relevant data. The RevMan 5.3 software (The Cochrane Collaboration, Software Update, Oxford, UK) and Stata 14 software (STATA Corporation, College Station, TX) were used for statistical analysis. RESULTS: This study summarizes the related randomized controlled trials to assess the effect and safety of TCMJ in the treatment of severe pneumonia. CONCLUSION: This article provides theoretical support for the clinical application of TCMJ in the treatment of severe pneumonia. PROSPERO REGISTRATION NUMBER: CRD42020185072"
3244,Protective barrier enclosure during upper gastrointestinal endoscopy,
3245,Human Cytomegalovirus Envelope Protein gpUL132 Regulates Infectious Virus Production through Formation of the Viral Assembly Compartment,"The human cytomegalovirus (HCMV) UL132 open reading frame encodes a 270-amino-acid type I envelope glycoprotein, gpUL132. The deletion of UL132 (ΔUL132) from the HCMV genome results in a pronounced deficit in virus yield, with an approximately 2-log decrease in the production of infectious virus compared to the wild-type (WT) virus. Characterization of the ΔUL132 mutant virus indicated that it was less infectious with a high particle-to-infectious unit ratio and an altered composition of virion proteins compared to the WT virus. In addition, the viral assembly compartment (AC) failed to form in cells infected with the ΔUL132 mutant virus. The expression of gpUL132 in trans rescued the defects in the morphogenesis of the AC in cells infected with the ΔUL132 mutant virus and in infectious virus production. Furthermore, using cell lines expressing chimeric proteins, we demonstrated that the cytosolic domain of gpUL132 was sufficient to rescue AC formation and WT levels of virus production. Progeny virions from ΔUL132-infected cells expressing the cytosolic domain of gpUL132 exhibited particle-to-infectious unit ratios similar to those of the WT virus. Together, our findings argue that gpUL132 is essential for HCMV AC formation and the efficient production of infectious particles, thus highlighting the importance of this envelope protein for the virus-induced reorganization of intracellular membranes and AC formation in the assembly of infectious virus."
3246,Recurrence rates suggest delayed identification of plantar ulceration for patients in diabetic foot remission,"INTRODUCTION: Foot ulcers are a common and costly complication of diabetes, and delays in treatment can result in impaired healing, infection, hospitalization, and lower extremity amputation. RESEARCH DESIGN AND METHODS: We aimed to determine whether patterns in plantar diabetic foot ulcer (DFU) recurrence coincided with typical intervals between routine preventive care appointments, which would suggest that delays exist between ulcer development and identification. We completed an analysis of existing data from two multicenter studies in 300 total participants. We analyzed unadjusted counts of DFU binned in weekly intervals and defined ‘exam periods’ as intervals from 2 to 4 weeks, from 6 to 8 weeks, within 1 week of 3 months and within 1 week of 6 months. We tested whether recurrence rates during exam periods were equivalent to rates outside exam periods. We estimated the delay between DFU development and DFU identification such that the rate of development would have been constant. RESULTS: During exam periods, a total of 43 DFUs were identified (43/86=50%) despite the fact that these periods represent only 23.5% of follow-up in aggregate. Accounting for censoring, the annualized incidence during exam periods was 0.68 DFU/year (CI 0.48 to 0.89) in contrast to 0.25 DFU/year (CI 0.18 to 0.32) outside exam periods (incidence ratio=2.8, CI 1.8 to 4.3). We estimated delays between DFU occurrence and identification to average 15.3 days (IQR 7.4–23.7 days). CONCLUSIONS: These findings have potential implications for practice, particularly related to the value of telehealth and in-home monitoring of patients in diabetic foot remission. Additionally, there are implications for study design, which should consider the impact of interval censoring and attempt to control for confounders related to frequency and timing of exams."
3247,Authors’ response,
3248,Authors’ response,
3249,Microsuffering: Lessons From a Pinky Finger,
3250,A newly found handbook for developing vaccines during World War II in China: the legacy of global responses to crises,
3251,Crop switching reduces agricultural losses from climate change in the United States by half under RCP 8.5,"A key strategy for agriculture to adapt to climate change is by switching crops and relocating crop production. We develop an approach to estimate the economic potential of crop reallocation using a Bayesian hierarchical model of yields. We apply the model to six crops in the United States, and show that it outperforms traditional empirical models under cross-validation. The fitted model parameters provide evidence of considerable existing climate adaptation across counties. If crop locations are held constant in the future, total agriculture profits for the six crops will drop by 31% for the temperature patterns of 2070 under RCP 8.5. When crop lands are reallocated to avoid yield decreases and take advantage of yield increases, half of these losses are avoided (16% loss), but 57% of counties are allocated crops different from those currently planted. Our results provide a framework for identifying crop adaptation opportunities, but suggest limits to their potential."
3252,Deciphering and predicting CD4(+) T cell immunodominance of influenza virus hemagglutinin,"The importance of CD4(+) T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4(+) T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4(+) T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry–based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance."
3253,Authentic self-expression on social media is associated with greater subjective well-being,"Social media users face a tension between presenting themselves in an idealized or authentic way. Here, we explore how prioritizing one over the other impacts users’ well-being. We estimate the degree of self-idealized vs. authentic self-expression as the proximity between a user’s self-reported personality and the automated personality judgements made on the basis Facebook Likes and status updates. Analyzing data of 10,560 Facebook users, we find that individuals who are more authentic in their self-expression also report greater Life Satisfaction. This effect appears consistent across different personality profiles, countering the proposition that individuals with socially desirable personalities benefit from authentic self-expression more than others. We extend this finding in a pre-registered, longitudinal experiment, demonstrating the causal relationship between authentic posting and positive affect and mood on a within-person level. Our findings suggest that the extent to which social media use is related to well-being depends on how individuals use it."
3254,Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes,"Type 1 diabetes (T1D) has increased over the past half century and has now become the second most frequent autoimmune disease in childhood and one of major public health concern worldwide. Evidence suggests that modern lifestyles and rapid environmental changes are driving factors that underlie this increase. The integration of these two factors brings about changes in food intake. This, in turn, alters epigenetic regulations of the genome and intestinal microbiota composition, which may ultimately play a role in pathogenesis of T1D. Recent evidence shows that dysbiosis of the gut microbiota is closely associated with T1D and that a dietary intervention can influence epigenetic changes associated with this disease and may modify gene expression patterns through epigenetic mechanisms. In this review focus on how a diet can shape the gut microbiome, its effect on the epigenome in T1D, and the future of T1D management by microbiome therapy."
3255,People-centred surveillance: a narrative review of community-based surveillance among crisis-affected populations,"Outbreaks of disease in settings affected by crises grow rapidly due to late detection and weakened public health systems. Where surveillance is underfunctioning, community-based surveillance can contribute to rapid outbreak detection and response, a core capacity of the International Health Regulations. We reviewed articles describing the potential for community-based surveillance to detect diseases of epidemic potential, outbreaks, and mortality among populations affected by crises. Surveillance objectives have included the early warning of outbreaks, active case finding during outbreaks, case finding for eradication programmes, and mortality surveillance. Community-based surveillance can provide sensitive and timely detection, identify valid signals for diseases with salient symptoms, and provide continuity in remote areas during cycles of insecurity. Effectiveness appears to be mediated by operational requirements for continuous supervision of large community networks, verification of a large number of signals, and integration of community-based surveillance within the routine investigation and response infrastructure. Similar to all community health systems, community-based surveillance requires simple design, reliable supervision, and early and routine monitoring and evaluation to ensure data validity. Research priorities include the evaluation of syndromic case definitions, electronic data collection for community members, sentinel site designs, and statistical techniques to counterbalance false positive signals."
3256,Operative and Technical Modifications to the Coriolis(®) µ Air Sampler That Improve Sample Recovery and Biosafety During Microbiological Air Sampling,"Detecting infectious aerosols is central for gauging and countering airborne threats. In this regard, the Coriolis(®) µ cyclonic air sampler is a practical, commercial collector that can be used with various analysis methods to monitor pathogens in air. However, information on how to operate this unit under optimal sampling and biosafety conditions is limited. We investigated Coriolis performance in aerosol dispersal experiments with polystyrene microspheres and Bacillus globigii spores. We report inconsistent sample recovery from the collector cone due to loss of material when sampling continuously for more than 30 min. Introducing a new collector cone every 10 min improved this shortcoming. Moreover, we found that several surfaces on the device become contaminated during sampling. Adapting a high efficiency particulate air-filter system to the Coriolis prevented contamination without altering collection efficiency or tactical deployment. A Coriolis modified with these operative and technical improvements was used to collect aerosols carrying microspheres released inside a Biosafety Level-3 laboratory during simulations of microbiological spills and aerosol dispersals. In summary, we provide operative and technical solutions to the Coriolis that optimize microbiological air sampling and improve biosafety."
3257,Are long telomeres better than short? Relative contributions of genetically predicted telomere length to neoplastic and non-neoplastic disease risk and population health burden,"BACKGROUND: Mendelian Randomization (MR) studies exploiting single nucleotide polymorphisms (SNPs) predictive of leukocyte telomere length (LTL) have suggested that shorter genetically determined telomere length (gTL) is associated with increased risks of degenerative diseases, including cardiovascular and Alzheimer’s diseases, while longer gTL is associated with increased cancer risks. These varying directions of disease risk have long begged the question: when it comes to telomeres, is it better to be long or short? We propose to operationalize and answer this question by considering the relative impact of long gTL vs. short gTL on disease incidence and burden in a population. METHODS AND FINDINGS: We used odds ratios (OR) of disease associated with gTL from a recently published MR meta-analysis to approximate the relative contributions of gTL to the incidence and burden of neoplastic and non-neoplastic disease in a European population. We obtained incidence data of the 9 cancers associated with long gTL and 4 non-neoplastic diseases associated with short gTL from the Institute of Health Metrics (IHME). Incidence rates of individual cancers from SEER, a database of United States cancer records, were used to weight the ORs in order to align with the available IHME data. These data were used to estimate the excess incidences due to long vs. short gTL, expressed as per 100,000 persons per standard deviation (SD) change in gTL. To estimate the population disease burden, we used the Disability Adjusted Life Years (DALY) metric from the IHME, a measure of overall disease burden that accounts for both mortality and morbidity, and similarly calculated the excess DALY associated with long vs. short gTL. RESULTS: Our analysis shows that, despite the markedly larger ORs of neoplastic disease, the large incidence of degenerative diseases causes the excess incidence attributable to gTL to balance that of neoplastic diseases. Long gTL is associated with an excess incidence of 94.04 cases/100,000 persons/SD (45.49–168.84, 95%CI) from the 9 cancer, while short gTL is associated with an excess incidence of 121.49 cases/100,000 persons/SD (48.40–228.58, 95%CI) from the 4 non-neoplastic diseases. When considering disease burden using the DALY metric, long gTL is associated with an excess 1255.25 DALYs/100,000 persons/SD (662.71–2163.83, 95%CI) due to the 9 cancers, while short gTL is associated with an excess 1007.75 DALYs/100,000 persons/SD (411.63–1847.34, 95%CI) due to 4 non-neoplastic diseases. CONCLUSIONS: Our results show that genetically determined long and short telomere length are associated with disease risk and burden of approximately equal magnitude. These results provide quantitative estimates of the relative impact of genetically-predicted short vs. long TL in a human population, and provide evidence in support of the cancer-aging paradox, wherein human telomere length is balanced by opposing evolutionary forces acting to minimize both neoplastic and non-neoplastic diseases. Importantly, our results indicate that odds ratios alone can be misleading in different clinical scenarios, and disease risk should be assessed from both an individual and population level in order to draw appropriate conclusions about the risk factor’s role in human health."
3258,US primary care in 2029: A Delphi survey on the impact of machine learning,"OBJECTIVE: To solicit leading health informaticians’ predictions about the impact of AI/ML on primary care in the US in 2029. DESIGN: A three-round online modified Delphi poll. PARTICIPANTS: Twenty-nine leading health informaticians. METHODS: In September 2019, health informatics experts were selected by the research team, and invited to participate the Delphi poll. Participation in each round was anonymous, and panelists were given between 4–8 weeks to respond to each round. In Round 1 open-ended questions solicited forecasts on the impact of AI/ML on: (1) patient care, (2) access to care, (3) the primary care workforce, (4) technological breakthroughs, and (5) the long-future for primary care physicians. Responses were coded to produce itemized statements. In Round 2, participants were invited to rate their agreement with each item along 7-point Likert scales. Responses were analyzed for consensus which was set at a predetermined interquartile range of ≤ 1. In Round 3 items that did not reach consensus were redistributed. RESULTS: A total of 16 experts participated in Round 1 (16/29, 55%). Of these experts 13/16 (response rate, 81%), and 13/13 (response rate, 100%), responded to Rounds 2 and 3, respectively. As a result of developments in AI/ML by 2029 experts anticipated workplace changes including incursions into the disintermediation of physician expertise, and increased AI/ML training requirements for medical students. Informaticians also forecast that by 2029 AI/ML will increase diagnostic accuracy especially among those with limited access to experts, minorities and those with rare diseases. Expert panelists also predicted that AI/ML-tools would improve access to expert doctor knowledge. CONCLUSIONS: This study presents timely information on informaticians’ consensus views about the impact of AI/ML on US primary care in 2029. Preparation for the near-future of primary care will require improved levels of digital health literacy among patients and physicians."
3259,Influenza A virus co-opts ERI1 exonuclease bound to histone mRNA to promote viral transcription,"Cellular exonucleases involved in the processes that regulate RNA stability and quality control have been shown to restrict or to promote the multiplication cycle of numerous RNA viruses. Influenza A viruses are major human pathogens that are responsible for seasonal epidemics, but the interplay between viral proteins and cellular exonucleases has never been specifically studied. Here, using a stringent interactomics screening strategy and an siRNA-silencing approach, we identified eight cellular factors among a set of 75 cellular proteins carrying exo(ribo)nuclease activities or involved in RNA decay processes that support influenza A virus multiplication. We show that the exoribonuclease ERI1 interacts with the PB2, PB1 and NP components of the viral ribonucleoproteins and is required for viral mRNA transcription. More specifically, we demonstrate that the protein-protein interaction is RNA dependent and that both the RNA binding and exonuclease activities of ERI1 are required to promote influenza A virus transcription. Finally, we provide evidence that during infection, the SLBP protein and histone mRNAs co-purify with vRNPs alongside ERI1, indicating that ERI1 is most probably recruited when it is present in the histone pre-mRNA processing complex in the nucleus."
3260,Diagnostic Infectious Diseases Testing Outside Clinics: A Global Systematic Review and Meta-analysis,"BACKGROUND: Most people around the world do not have access to facility-based diagnostic testing, and the gap in availability of diagnostic tests is a major public health challenge. Self-testing, self-sampling, and institutional testing outside conventional clinical settings are transforming infectious disease diagnostic testing in a wide range of low- and middle-income countries (LMICs). We examined the delivery models of infectious disease diagnostic testing outside clinics to assess the impact on test uptake and linkage to care. METHODS: We conducted a systematic review and meta-analysis, searching 6 databases and including original research manuscripts comparing testing outside clinics with conventional testing. The main outcomes were test uptake and linkage to care, delivery models, and adverse outcomes. Data from studies with similar interventions and outcomes within thematic areas of interest were pooled, and the quality of evidence was assessed using GRADE. This study was registered in PROSPERO (CRD42019140828). We identified 10 386 de-duplicated citations, and 76 studies were included. Data from 18 studies were pooled in meta-analyses. Studies focused on HIV (48 studies), chlamydia (8 studies), and multiple diseases (20 studies). HIV self-testing increased test uptake compared with facility-based testing (9 studies: pooled odds ratio [OR], 2.59; 95% CI, 1.06–6.29; moderate quality). Self-sampling for sexually transmitted infections increased test uptake compared with facility-based testing (7 studies: pooled OR, 1.74; 95% CI, 0.97–3.12; moderate quality). Conclusions. Testing outside of clinics increased test uptake without significant adverse outcomes. These testing approaches provide an opportunity to expand access and empower patients. Further implementation research, scale-up of effective service delivery models, and policies in LMIC settings are needed."
3261,"Effectiveness and cost-effectiveness of a progressive, individualised walking and education programme for prevention of low back pain recurrence in adults: study protocol for the WalkBack randomised controlled trial","INTRODUCTION: Low back pain (LBP) is recognised globally as a prevalent, costly and disabling condition. Recurrences are common and contribute to much of the burden of LBP. Current evidence favours exercise and education for prevention of LBP recurrence, but an optimal intervention has not yet been established. Walking is a simple, widely accessible, low-cost intervention that has yet to be evaluated. This randomised controlled trial (RCT) aims to establish the effectiveness and cost-effectiveness of a progressive and individualised walking and education programme (intervention) for the prevention of LBP recurrences in adults compared with no treatment (control). METHODS AND ANALYSIS: A pragmatic, two-armed RCT comparing walking and education (n=349) with a no treatment control group (n=349). Inclusion criteria are adults recovered from an episode of non-specific LBP within the last 6 months. Those allocated to the intervention group will receive six sessions (three face to face and three telephone delivered) with a trained physiotherapist to facilitate a progressive walking programme and education over a 6-month period. The primary outcome will be days to first recurrence of an episode of activity-limiting LBP. The secondary outcomes include days to recurrence of an episode of LBP, days to recurrence of an episode of LBP leading to care seeking, disability and quality of life measured at 3, 6, 9 and 12 months and costs associated with LBP recurrence. All participants will be followed up monthly for a minimum of 12 months. The primary intention-to-treat analysis will assess difference in survival curves (days to recurrence) using the log-rank statistic. The cost-effectiveness analysis will be conducted from the societal perspective. ETHICS AND DISSEMINATION: Approved by Macquarie University Human Research Ethics Committee (Reference: 5201949218164, May 2019). Findings will be disseminated through publication in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12619001134112."
3262,Akuter und chronischer Husten – gibt es etwas Neues?,"The most frequent cause of acute cough (lasting up to 3 weeks) or subacute cough (3–8 weeks) is a viral infection, which is mostly a self-limiting disease in otherwise healthy persons. Some herbal compounds, the antitussive dextromethorphan and ambroxol are effective for symptom relief. Antibiotics are ineffective and should not be used due to resistance development. If after appropriate diagnostic procedures the cause of chronic cough, i.e. cough lasting more than 8 weeks, cannot be attributed to a well-established respiratory disease, it meets the definition of a disease in its own right, chronic idiopathic (unexplained) cough (CIH). This is caused by hypersensitivity of the cough reflex. Thus, even weak low threshold stimuli, e.g. changing temperature, extensive speaking and odors can trigger the cough reflex. In the case of nonresponse to guideline-conform treatment the definition of chronic refractory cough is met."
3263,"Preoperative opioid, sedative, and antidepressant use is associated with increased postoperative hospital costs in colorectal surgery","BACKGROUND: Opioid (OPD), sedative (SDT), and antidepressant (ADM) prescribing has increased dramatically over the last 20 years. This study evaluated preoperative OPD, SDT, and ADM use on hospital costs in patients undergoing colorectal resection at a single institution. METHODS: This study was a retrospective record review. The local ACS-NSQIP database was queried for adult patients (age ≥ 18 years) undergoing open/laparoscopic, partial/total colectomy, or proctectomy from January 1, 2013 to December 31, 2016. Individual patient medical records were reviewed to determine preoperative OPD, SDT, and AD use. Hospital cost data from index admission were captured by the hospital cost accounting system and matched to NSQIP query-identified cases. All ACS-NSQIP categorical patient characteristic, operative risk, and outcome variables were compared in medication groups using chi-square tests or Fisher’s exact tests, and continuous variables were compared using Mann–Whitney U tests. RESULTS: A total of 1185 colorectal procedures were performed by 30 different surgeons. Of these, 27.6% patients took OPD, 18.5% SDT, and 27.8% ADM preoperatively. Patients taking OPD, SDT, and ADM were found to have increased mean total hospital costs (MTHC) compared to non-users (30.8 vs 23.6 for OPD, 31.6 vs 24.4 for SDT, and 30.7 vs 23.8 for ADM). OPD and SDT use were identified as independent risk factors for increased MTHC on multivariable analysis. CONCLUSION: Preoperative OPD and SDT use can be used to predict increased MTHC in patients undergoing colorectal resections."
3264,Less is more: critically ill status is not a carte blanche for unlimited antibiotic use,
3265,Verfügbar: tetravalenter Grippe-Impfstoff,
3266,British Association for the Study of Community Dentistry,
3267,QQMedizin,
3268,Column,
3269,Royal Army Dental Corps to celebrate centenary in 2021,
3270,Bio-fuel from PPE,
3271,Teaching remote consultation,
3272,Tijdelijk uit balans,
3273,Redeployed as a district nurse,
3274,medische coronaclaims,
3275,Testing the limits of UDCs,
3276,Dental tour all set to treat fishermen in Cornwall and Devon,
3277,PE TER PAUL van Benthem,
3278,Clinical features of 47 secondary hemophagocytic lymphohistiocytosis patients complicated with capillary leak syndrome,"The clinical features of patients with secondary hemophagocytic lymphohistiocytosis (sHLH) complicated with capillary leak syndrome (CLS) remain controversial. The data of 259 sHLH patients were retrospectively analyzed. The clinical manifestations, laboratory findings, treatment, and prognosis of the CLS-sHLH group and non-CLS-sHLH group were compared. The levels of fibrinogen, albumin, and serum calcium in the CLS-sHLH group were lower than in the non-CLS-sHLH group, and serum triglycerides in the CLS-sHLH group were higher than in the non-CLS-sHLH group (P < 0.05). Univariate analysis showed that fibrinogen level was an independent prognostic factor in sHLH patients complicated with CLS. The median survival time was significantly shorter in patients with fibrinogen ≤ 1.3 g/L than in patients with fibrinogen > 1.3 g/L (P < 0.05). Patients with improved CLS conditions in the CLS-sHLH group had significantly increased albumin and serum calcium after treatment (P < 0.05); patients without improved conditions in the CLS-sHLH group also had significantly increased albumin after treatment (P < 0.05), but the serum calcium did not change significantly (P > 0.05). sHLH patients complicated with CLS had significantly worse prognosis than without CLS. Significant reduction in fibrinogen may be an independent prognostic factor for poor prognosis in sHLH patients complicated with CLS."
3279,Not entirely accurate,
3280,Inbreng in het bestuur voor verpleeg- kundigen: Bestuursraad Martini Ziekenhuis uitgebreid,
3281,Eddie Crouch is new BDA Chair,
3282,Incidence of heparin-induced thrombocytopenia in patients with 2019 coronavirus disease(),
3283,Olfactory dysfunction during COVID-19 pandemic(),
3284,Re “The Elephant in the Operating Room”,
3285,Cross-reactions between rheumatoid factor and IgM SARS-CoV-2(),
3286,The body in isolation: The physical health impacts of incarceration in solitary confinement,"We examine how solitary confinement correlates with self-reported adverse physical health outcomes, and how such outcomes extend the understanding of the health disparities associated with incarceration. Using a mixed methods approach, we find that solitary confinement is associated not just with mental, but also with physical health problems. Given the disproportionate use of solitary among incarcerated people of color, these symptoms are most likely to affect those populations. Drawing from a random sample of prisoners (n = 106) in long-term solitary confinement in the Washington State Department of Corrections in 2017, we conducted semi-structured, in-depth interviews; Brief Psychiatric Rating Scale (BPRS) assessments; and systematic reviews of medical and disciplinary files for these subjects. We also conducted a paper survey of the entire long-term solitary confinement population (n = 225 respondents) and analyzed administrative data for the entire population of prisoners in the state in 2017 (n = 17,943). Results reflect qualitative content and descriptive statistical analysis. BPRS scores reflect clinically significant somatic concerns in 15% of sample. Objective specification of medical conditions is generally elusive, but that, itself, is a highly informative finding. Using subjective reports, we specify and analyze a range of physical symptoms experienced in solitary confinement: (1) skin irritations and weight fluctuation associated with the restrictive conditions of solitary confinement; (2) un-treated and mis-treated chronic conditions associated with the restrictive policies of solitary confinement; (3) musculoskeletal pain exacerbated by both restrictive conditions and policies. Administrative data analyses reveal disproportionate rates of racial/ethnic minorities in solitary confinement. This analysis raises the stakes for future studies to evaluate comparative prevalence of objective medical diagnoses and potential causal mechanisms for the physical symptoms specified here, and for understanding differential use of solitary confinement and its medically harmful sequelae."
3287,Behind the mask: demedicalising race and mental health in professional football,
3288,Targeted Temperature Management for Treatment of Cardiac Arrest,"PURPOSE OF REVIEW: Cardiac arrest is a common condition associated with high mortality and a substantial risk of neurological injury among survivors. Targeted temperature management (TTM) is the only strategy shown to reduce the risk of neurologic disability cardiac arrest patients. In this article, we provide a comprehensive review of TTM with an emphasis on recent trials. RECENT FINDINGS: After early studies demonstrating the benefit of TTM in out-of-hospital cardiac arrest due to a shockable rhythm, newer studies have extended the benefit of TTM to patients with a nonshockable rhythm and in-hospital cardiac arrest. A target temperature of 33 °C was not superior to 36 °C, suggesting that a lenient targeted temperature may be appropriate especially for patients unable to tolerate lower temperatures. Although early initiation of TTM appears to be beneficial, the benefit of prehospital cooling has not been shown and use of intravenous cold saline in the prehospital setting may be harmful. SUMMARY: There is substantial risk of neurological injury in cardiac arrest survivors who remain comatose. TTM is an effective treatment that can lower the risk of neurological disability in such patients and ideally delivered as part of a comprehensive, goal-directed post-resuscitation management by a multidisciplinary team in a tertiary medical center."
3289,Introduction to SI: Homeownership and housing divide in China,
3290,"American Dairy Science Association® Journal of Dairy Science®, July 19–23 2016, Salt Lake City, UT",
3291,Less daily oral hygiene is more in the ICU: yes,
3292,Cocci Are in the Air,"The San Joaquin Valley in Central California is a semiarid region that is known to be highly endemic for coccidioidomycosis infections in high-risk groups. Coccidioidomycosis, also known as valley fever, is caused by the fungal spore Coccidioides, which can be found in the soil in arid and semiarid regions in the Southwest United States and parts of Central and South America. When soil is disturbed through excavation, agricultural activities, or with any other soil movement, these activities can release the fungal spores into air; people who are in close proximity can potentially inhale them. The purpose of this clinical case study is to address the need for coccidioidomycosis infection awareness and educate primary care providers to determine the diagnostic reasoning and process. A simple algorithm and template will aid them to accurately diagnose and treat patients with valley fever earlier in the disease process."
3293,Once-weekly vs. twice-weekly carfilzomib dosing in a subgroup of Japanese relapsed and refractory multiple myeloma patients from a randomized phase 3 trial (A.R.R.O.W.) and comparison with ENDEAVOR,"A.R.R.O.W. evaluated the superiority of once-weekly carfilzomib plus dexamethasone (Kd) 20/70 mg/m(2) vs. twice-weekly Kd 20/27 mg/m(2) based on progression-free survival (PFS) in relapsed and/or refractory multiple myeloma patients. Forty Japanese patients (once-weekly arm, n = 26; twice-weekly arm, n = 14) were randomized in A.R.R.O.W. In the Japanese subgroup of A.R.R.O.W., median PFS was 14.8 months (95% confidence interval [CI], 7.5–not evaluable [NE]) and 9.7 months (95% CI, 3.8–NE) in the once- and twice-weekly arms, respectively. The overall response rate (ORR) was 73.1% (19/26; 95% CI, 52.2–88.4) and 57.1% (8/14; 95% CI, 28.9–82.3) in each arm. The adverse events (AEs) incidence was 100% in both arms. Grade ≥ 3 AE incidence was 80.8% (21/26) and 78.6% (11/14) in each arm. Two fatal treatment-related AEs (acute lung injury and acute respiratory distress syndrome) occurred in the once-weekly arm. In exploratory unadjusted analyses of A.R.R.O.W. (once-weekly Kd 20/70 mg/m(2)) vs. ENDEAVOR (twice-weekly Kd 20/56 mg/m(2)), median PFS was 14.8 months vs. NE due to not yet being reached, and ORR was 73.1% (19/26) vs. 42.9% (3/7). In the Japanese subgroup, once-weekly Kd tended to improve ORR vs. twice-weekly Kd. Results from A.R.R.O.W. tended to be consistent with results from ENDEAVOR. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12185-020-03013-6) contains supplementary material, which is available to authorized users."
3294,Diagnosis and Management of Lymphatic Disorders in Congenital Heart Disease,"PURPOSE OF REVIEW: Lymphatic disorders have received an increasing amount of attention over the last decade. Sparked primarily by improved imaging modalities and the dawn of lymphatic interventions, understanding, diagnostics, and treatment of lymphatic complications have undergone considerable improvements. Thus, the current review aims to summarize understanding, diagnostics, and treatment of lymphatic complications in individuals with congenital heart disease. RECENT FINDINGS: The altered hemodynamics of individuals with congenital heart disease has been found to profoundly affect morphology and function of the lymphatic system, rendering this population especially prone to the development of lymphatic complications such as chylous and serous effusions, protein-losing enteropathy and plastic bronchitis. SUMMARY: Although improved, a full understanding of the pathophysiology and targeted treatment for lymphatic complications is still wanting. Future research into pharmacological improvement of lymphatic function and continued implementation of lymphatic imaging and interventions may improve knowledge, treatment options, and outcome for affected individuals."
3295,"The Effect of Low-Level Light Therapy on Capsaicin-Induced Peripheral and Central Sensitization in Healthy Volunteers: A Double-Blinded, Randomized, Sham-Controlled Trial","INTRODUCTION: Several clinical trials have demonstrated that low-level light therapy (LLLT), a method of photobiomodulation, is an effective analgetic treatment. However, the mechanism of action has not yet been finally clarified. In particular, unanswered questions include whether it only affects peripheral or whether it also affects the spinal or supraspinal level. This study aimed to evaluate the effect of low-level light therapy on primary and secondary hyperalgesia in a human pain model. METHODS: This study was planned as a randomized, sham-controlled, and double-blinded trial with repeated measures within subject design. Capsaicin was applied on both forearms of ten healthy volunteers to induce peripheral and central sensitization. One forearm was treated with low-level light therapy; the other served as sham control. RESULTS: Low-level light therapy significantly increased the mechanical pain threshold, heat pain threshold, and decreased pain intensity. CONCLUSIONS: Our data indicate that low-level light therapy is effective at reducing the heat and mechanical pain threshold in a human pain model, pointing to a significant modulating effect on peripheral and central sensitization. These effects—especially in the absence of reported side effects—make low-level light therapy a promising tool in pain management. The application of low-level light therapy to treat chronic pain should be considered for further clinical trials."
3296,"An intronic variant in BRAT1 creates a cryptic splice site, causing epileptic encephalopathy without prominent rigidity","BRAT1-related neurodevelopmental disorders are characterized by heterogeneous phenotypes with varying levels of clinical severity. Since the discovery of BRAT1 variants as the molecular etiology of lethal neonatal rigidity and multifocal seizure syndrome (RMFSL, OMIM 614498), these variants have also been identified in patients with milder clinical forms including neurodevelopmental disorder with cerebellar atrophy and with or without seizures (NEDCAS, OMIM 618056), epilepsy of infancy with migrating focal seizures (EIMFS), and congenital ataxia (CA). This study aims to examine the consequences and pathogenicity of a novel homozygous splice site variant in BRAT1 in a patient presenting with migrating focal seizures since birth without prominent rigidity. The patient was born from a consanguineous marriage and has had seizures since the neonatal period. He presented with dysmorphic features, pontocerebellar hypoplasia, and migrating focal seizures. Despite supportive treatment, his symptoms rapidly progressed to intractable myoclonic seizures, bouts of apnea and bradycardia, and arrest of head growth, with no acquisition of developmental milestones. Clinical exome sequencing yielded a novel homozygous splice variant in BRAT1. Genetic analysis based on reverse transcription of the patient’s RNA followed by PCR amplifications performed on synthesized cDNA and Sanger sequencing was undertaken, and the functional effect of a BRAT1 variant on splicing machinery was demonstrated for the first time. The severe clinical presentation of migrating focal seizures and pontocerebellar hypoplasia in the absence of rigidity further expands the genotypic and phenotypic spectrum of BRAT1-related neurodevelopmental disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13760-020-01513-0) contains supplementary material, which is available to authorized users."
3297,International collaboration in Brazilian science: financing and impact,"The study of international collaborations can help in understanding the benefits of such relationships and aid in developing national financing policies. In this paper, the international collaboration of Brazilian scientists was studied using SciVal(®) and Incites(®) database, looking at its effect on the universities, financing agencies and different areas of knowledge and research topic clusters. Cluster and principal component analyses of scientometric data were carried out. While the results confirmed known knowledge that international collaboration increases impact, this study shows that Brazilian researchers are contributing to prominent research topics worldwide, in all areas of knowledge. This finding is contrary to several points of view that identify Brazil as a regional and not an international partner in science. Important also to note the impact of Brazilian authors in international collaboration that is well above the world mean. The collaboration of Brazil with foreign partners brings benefits for both sides, creating the opportunity of Brazilian research access to financing from international agencies. Increases in measures of impact are also seen for both sides. Foreign partners likewise benefit from higher impact factors in the same topic cluster, when collaborating with Brazilian partners. Publishing open access in high impact journals is fundamental for maintaining Brazilian science at the forefront. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11192-020-03728-7) contains supplementary material, which is available to authorized users."
3298,Lessons learned during my hand surgery career,
3299,Safety of Remdesivir in Patients with Acute or Chronic Kidney Disease,
3300,Performance of a capnodynamic method estimating cardiac output during respiratory failure - before and after lung recruitment,"Respiratory failure may cause hemodynamic instability with strain on the right ventricle. The capnodynamic method continuously calculates cardiac output (CO) based on effective pulmonary blood flow (CO(EPBF)) and could provide CO monitoring complementary to mechanical ventilation during surgery and intensive care. The aim of the current study was to evaluate the ability of a revised capnodynamic method, based on short expiratory holds (CO(EPBFexp)), to estimate CO during acute respiratory failure (LI) with high shunt fractions before and after compliance-based lung recruitment. Ten pigs were submitted to lung lavage and subsequent ventilator-induced lung injury. CO(EPBFexp), without any shunt correction, was compared to a reference method for CO, an ultrasonic flow probe placed around the pulmonary artery trunk (CO(TS)) at (1) baseline in healthy lungs with PEEP 5 cmH(2)O (HL(P5)), (2) LI with PEEP 5 cmH(2)O (LI(P5)) and (3) LI after lung recruitment and PEEP adjustment (LI(Padj)). CO changes were enforced during LI(P5) and LI(Padj) to estimate trending. LI resulted in changes in shunt fraction from 0.1 (0.03) to 0.36 (0.1) and restored to 0.09 (0.04) after recruitment manoeuvre. Bias (levels of agreement) and percentage error between CO(EPBFexp) and CO(TS) changed from 0.5 (− 0.5 to 1.5) L/min and 30% at HL(P5) to − 0.6 (− 2.3 to 1.1) L/min and 39% during LI(P5) and finally 1.1 (− 0.3 to 2.5) L/min and 38% at LI(Padj). Concordance during CO changes improved from 87 to 100% after lung recruitment and PEEP adjustment. CO(EPBFexp) could possibly be used for continuous CO monitoring and trending in hemodynamically unstable patients with increased shunt and after recruitment manoeuvre. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-019-00421-w) contains supplementary material, which is available to authorized users."
3301,Pulmonary function in extremely low birth weight infants with bronchopulmonary dysplasia before hospital discharge,"OBJECTIVE: To compare pulmonary function in extremely low birth weight (ELBW) infants with bronchopulmonary dysplasia (BPD) studied at 34–36 weeks postmenstrual age (PMA) with a reference group of “healthy” infants born at 34–36 weeks. We hypothesized that ELBW infants have decreased functional residual capacity (FRC) and respiratory compliance (Crs). STUDY DESIGN: Pulmonary function testing was performed at 34–36 weeks PMA in infants with BPD and within 96 h of age in infants delivered at 34–36 weeks. RESULTS: Twenty BPD patients and 20 healthy infants were studied. FRC (18.9 versus 26.2 mL/kg; adjusted 95% CI 5.0, 10.9; P < 0.001) and Crs (0.80 versus 1.29-mL/cm H(2)O/kg; 95% CI 0.31, 0.71; P < 0.001) were decreased in BPD patients. Respiratory resistance was increased in BPD patients. CONCLUSIONS: ELBW infants with BPD have decreased pulmonary function compared to healthy infants delivered at 34–36 weeks. This suggests that infants with BPD have smaller lung volumes."
3302,Pancytopenia during SARS-CoV-2 infection(),
3303,One-year experience of hybrid closed-loop system in children and adolescents with type 1 diabetes previously treated with multiple daily injections: drivers to successful outcomes,"OBJECTIVE: To evaluate the effect of a 1-year hybrid closed-loop (HCL) system on glycemic control in children and adolescents with type 1 diabetes (T1D) previously treated with multiple daily injections (MDI). METHODS: This was a 1-year observational study, as a continuation of the previous 3 months prospective study of pediatric patients with T1D conducted at Sidra Medicine in Qatar. The study enrolled individuals aged 7–18 years with T1D > 1 year, on MDI with self-monitoring of blood glucose or continuous glucose monitoring, with no prior pump experience, and with an HbA1c level < 12.5% (< 113 mmol/mol). After the first 3 months of HCL use, patients were followed at 6, 9 and 12 months, where HbA1c was obtained and pump data were collected. RESULTS: All 30 participants (age 10.24 ± 2.6 years) who initiated HCL completed 12 months of HCL system use in Auto Mode. The participants used the sensor 88.4 ± 6.5% of the time with Auto Mode usage 85.6 ± 7.4% during 12 months of HCL system use. HbA1c decreased from 8.2 ± 1.4% (66 ± 15.3 mmol/mol) at baseline, to 6.7 ± 0.5% (50 ± 5.5 mmol/mol) at 3 months (p = 0.02) and remained stable to 7.1 ± 0.6 (54 ± 6.6 mmol/mol) at 12 months (p = 0.02). TIR (70–180 mg/dL) increased from 46.9% at baseline to 71.9% at 1 month and remained above 70% during the 12 months of HCL use. CONCLUSION: HCL system (MiniMed 670G) in children and adolescents previously treated with MDI significantly improves glycemic outcomes (HbA1c and Time in Ranges) immediately during the first month. This improved glycemic control was maintained over the 1 year following Auto Mode initiation."
3304,Mitteilungen der DGRh - Veranstaltungen der Rheumaakademie,
3305,Outcomes and management approaches of resuscitative endovascular balloon occlusion of the aorta based on the income of countries,"BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) could provide a survival benefit to severely injured patients as it may improve their initial ability to survive the hemorrhagic shock. Although the evidence supporting the use of REBOA is not conclusive, its use has expanded worldwide. We aim to compare the management approaches and clinical outcomes of trauma patients treated with REBOA according to the countries’ income based on the World Bank Country and Lending Groups. METHODS: We used data from the AORTA (USA) and the ABOTrauma (multinational) registries. Patients were stratified into two groups: (1) high-income countries (HICs) and (2) low-to-middle income countries (LMICs). Propensity score matching extracted 1:1 matched pairs of subjects who were from an LMIC or a HIC based on age, gender, the presence of pupillary response on admission, impeding hypotension (SBP ≤ 80), trauma mechanism, ISS, the necessity of CPR on arrival, the location of REBOA insertion (emergency room or operating room) and the amount of PRBCs transfused in the first 24 h. Logistic regression (LR) was used to examine the association of LMICs and mortality. RESULTS: A total of 817 trauma patients from 14 countries were included. Blind percutaneous approach and surgical cutdown were the preferred means of femoral cannulation in HICs and LIMCs, respectively. Patients from LMICs had a significantly higher occurrence of MODS and respiratory failure. LR showed no differences in mortality for LMICs when compared to HICs; neither in the non-matched cohort (OR = 0.63; 95% CI: 0.36‑1.09; p = 0.1) nor in the matched cohort (OR = 1.45; 95% CI: 0.63‑3,33; p = 0.3). CONCLUSION: There is considerable variation in the management practices of REBOA and the outcomes associated with this intervention between HICs and LMICs. Although we found significant differences in multiorgan and respiratory failure rates, there were no differences in the risk-adjusted odds of mortality between the groups analyzed. Trauma surgeons practicing REBOA around the world should joint efforts to standardize the practice of this endovascular technology worldwide."
3306,Hämatoonkologie und Intensivmedizin: Vom Tabu zur Conditio sine qua non,"Intensivists are confronted with a broad spectrum of specific clinical problems while caring for critically ill cancer patients. These include defining proper goals of intensive care treatment, managing acute respiratory failure with diverse differential considerations, treating immunologic side-effects of ever new and innovative cancer therapies, as well as numerous clinical scenarios which may exclusively arise in cancer patients. To help clinicians handle such challenges, the initiative Intensive Care in Hematologic and Oncologic Patients (iCHOP) has been dealing with these topics for several years. Supported by several Austrian and German medical societies of intensive care medicine, hematology and oncology, the first “Consensus statement for cancer patients requiring intensive care support” has only recently been released. Acute respiratory failure and its management continues to be a major focus in critically ill cancer patients due to its frequency and its prognostic impact. While noninvasive oxygenation strategies were considered the gold standard of therapy, more recent high-quality data do not show clinical benefits of such techniques including high flow nasal oxygen. On the contrary, several studies revealed an unidentified etiology of an acute respiratory failure as the only potentially modifiable risk factor for adverse outcome. Consequently, evidence-based and rigorously applied diagnostic algorithms are of utmost importance in these patients. Furthermore, intensivists are increasingly confronted with the rising incidence of various and new immunotherapy-associated toxicities and their management."
3307,Fluid management in ARDS: an evaluation of current practice and the association between early diuretic use and hospital mortality,"BACKGROUND: Acute respiratory distress syndrome (ARDS) and volume overload are associated with increased hospital mortality. Evidence supports conservative fluid management in ARDS, but whether current practice reflects the implementation of that evidence has not been described. This study reports the variability in contemporary fluid management for ICU patients with ARDS. We compared routine care to trial protocols and analyzed whether more conservative management with diuretic medications in contemporary, usual care is associated with outcomes. METHODS: We performed a retrospective cohort study in nine ICUs at two academic hospitals during 2016 and 2017. We included 234 adult patients with ARDS in an ICU at least 3 days after meeting moderate-severe ARDS criteria (PaO(2):FIO(2) ≤ 150). The primary exposure was any diuretic use in 48 to 72 h after meeting ARDS criteria. The primary outcome was hospital mortality. Unadjusted statistical analyses and multivariable logistic regression were used. RESULTS: In 48–72 h after meeting ARDS criteria, 116 patients (50%) received a diuretic. In-hospital mortality was lower in the group that received diuretics than in the group that did not (14% vs 25%; p = 0.025). At ARDS onset, both groups had similar Sequential Organ Failure Assessment scores and ICU fluid balances. During the first 48 h after ARDS, the diuretic group received less crystalloid fluid than the no diuretic group (median [inter-quartile range]: 1.2 L [0.2–2.8] vs 2.4 L [1.2-5.0]; p < 0.001), but both groups received more fluid from medications and nutrition than from crystalloid. At 48 h, the prevalence of volume overload (ICU fluid balance >10% of body weight) in each group was 16% and 25%(p = 0.09), respectively. During 48–72 h after ARDS, the overall prevalence of shock was 44% and similar across both groups. Central venous pressure was recorded in only 18% of patients. Adjusting for confounders, early diuretic use was independently associated with lower hospital mortality (AOR 0.46, 95%CI [0.22, 0.96]). CONCLUSIONS: In this sample of ARDS patients, volume overload was common, and early diuretic use was independently associated with lower hospital mortality. These findings support the importance of fluid management in ARDS and suggest opportunities for further study and implementation of conservative fluid strategies into usual care."
3308,"Hostility, compassion and role reversal in West Virginia’s long opioid overdose emergency","BACKGROUND: West Virginia is a largely rural state with strong ties of kinship, mutual systems of support and charitable giving. At the same time, wealth inequalities are extreme and the state’s drug overdose fatality rate stands above all others in the USA at 51.5/100,000 in 2018, largely opioid-related. In recent years, harm reduction services have been active in the state but in 2018 Charleston’s needle and syringe program was forced to close. This paper considers the risk environment in which the state’s drug-related loss of life, and those attempting to prevent it, exist. METHODS: This rapid ethnographic study involved semi-structured interviews (n = 21), observation and video recordings of injection sequences (n = 5), initially recruiting people who inject heroin/fentanyl (PWIH) at the Charleston needle and syringe program. Snowball sampling led the research team to surrounding towns in southern West Virginia. Telephone interviews (n = 2) with individuals involved in service provision were also carried out. RESULTS: PWIH in southern West Virginia described an often unsupportive, at times hostile risk environment that may increase the risk of overdose fatalities. Negative experiences, including from some emergency responders, and fears of punitive legal consequences from calling these services may deter PWIH from seeking essential help. Compassion fatigue and burnout may play a part in this, along with resentment regarding high demands placed by the overdose crisis on impoverished state resources. We also found low levels of knowledge about safe injection practices among PWIH. CONCLUSIONS: Hostility faced by PWIH may increase their risk of overdose fatalities, injection-related injury and the risk of HIV and hepatitis C transmission by deterring help-seeking and limiting the range of harm reduction services provided locally. Greater provision of overdose prevention education and naloxone for peer distribution could help PWIH to reverse overdoses while alleviating the burden on emergency services. Although essential for reducing mortality, measures that address drug use alone are not enough to safeguard longer-term public health. The new wave of psychostimulant-related deaths underline the urgency of addressing the deeper causes that feed high-risk patterns of drug use beyond drugs and drug use."
3309,DASFAA 20202 Special Issue Editorial,
3310,Treatment of Giant Cell Arteritis and Takayasu Arteritis—Current and Future,"PURPOSE OF REVIEW: Guidelines for the management of large vessel vasculitides have been recently updated by several scientific societies. We have evaluated the current recommendations for treatment of giant cell arteritis (GCA) and Takayasu arteritis (TA) and addressed potential future therapeutic strategies. RECENT FINDINGS: While glucocorticoids (GCs) remain the gold standard for induction of remission, many patients relapse and acquire high cumulative GC exposure. Thus, GC-sparing therapies such as methotrexate are recommended for selected patients with GCA and all patients with TA. Recent high-quality evidence shows that tocilizumab is an effective GC-sparing agent in GCA. Non-biologic and biologic immunomodulators also appear to have GC-sparing properties in TA. SUMMARY: Tocilizumab is now considered to be part of the standard treatment for GCA, particularly with relapsing disease, but questions on its use such as length of treatment and monitoring of disease activity remain open. High-quality evidence to guide treatment of TA is still lacking."
3311,Strategies for having a more effective and less toxic CAR T-cell therapy for acute lymphoblastic leukemia,"In the recent years, using genetically modified T cells has been known as a rapid developing therapeutic approach due to the heartwarming results of clinical trials with patients suffering from relapsed or refractory (R/R) hematologic malignancies such as R/R Acute Lymphoblastic Leukemia (R/R ALL). One of these renowned approaches is Chimeric antigen receptors (CARs). CARs are synthetic receptors with the ability to be expressed on the surface of T lymphocytes and are specifically designed to target a tumor-associated antigen (TAA) of interest. CAR-expressing T cells have the capability of proliferating and maintaining their immunological functionality in the recipient body but like any other therapeutic approach, the safety, effectiveness, and specificity enhancement of CAR T cells still lingers in the ambiguity arena. Genetic manipulation methods, expansion protocols, infusion dosage, and conditioning regimens are all among crucial factors which can affect the efficacy of CAR T cell-based cancer therapy. In this article, we discuss the studies that have focused on various aspects that affect the efficacy and persistence of CAR T-cell therapy for ALL treatment and provide a widespread overview regarding the practical approaches capable of elevating the effectiveness and lessening the relative toxicities attributed to it."
3312,Evaluation and Management Coding Initiative,
3313,Implementation of virtual focus groups for qualitative data collection in a global pandemic,
3314,Biomarker testing in oncology – Requirements for organizing external quality assessment programs to improve the performance of laboratory testing: revision of an expert opinion paper on behalf of IQNPath ABSL,"In personalized medicine, predictive biomarker testing is the basis for an appropriate choice of therapy for patients with cancer. An important tool for laboratories to ensure accurate results is participation in external quality assurance (EQA) programs. Several providers offer predictive EQA programs for different cancer types, test methods, and sample types. In 2013, a guideline was published on the requirements for organizing high-quality EQA programs in molecular pathology. Now, after six years, steps were taken to further harmonize these EQA programs as an initiative by IQNPath ABSL, an umbrella organization founded by various EQA providers. This revision is based on current knowledge, adds recommendations for programs developed for predictive biomarkers by in situ methodologies (immunohistochemistry and in situ hybridization), and emphasized transparency and an evidence-based approach. In addition, this updated version also has the aim to give an overview of current practices from various EQA providers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00428-020-02928-z) contains supplementary material, which is available to authorized users."
3315,Kawasaki-Erkrankung oder Hyperinflammations-Syndrom?,
3316,Schulbeginn für Kinder mit Asthma: Anfang September startete wieder der Alltag,
3317,Update from the Editor in Chief,
3318,DGSM-Jahrestagung und Abstractband 2020,
3319,Correction to: A matched case-control study of risk factors associated with multiple sclerosis in Kuwait,
3320,Lungenbeteiligung bei Tumorkrankheiten,"The lungs are often involved in tumors and are affected in a wide variety of ways. Lung cancer comprises one of the most common cancer entities and has been characterized by a vast expansion of treatment approaches in recent years. Moreover, the lungs are a common metastatic site of multiple other cancer entities. Various treatment modalities, such as tyrosine kinase inhibitors, checkpoint inhibitors, chimeric antigen receptor cell therapy, and radiotherapy approaches can cause pulmonary side effects. Finally, many patients suffer from pulmonary comorbidities which may mutually impact the clinical course and prognosis of the cancer disease. As examples, various aspects, such as pulmonary veno-occlusive disease, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis are discussed."
3321,Dante Gatteschi: on the Occasion of His 75th Birthday,
3322,"Eine kritische Weihnachtsgeschichte: Essay über Anämie, Ersticken, Verhungern und andere Behandlungsverfahren der Intensivmedizin – im Stil von Dickens","Somewhere in the USA, shortly before Christmas, tipsy Charlie Cratchit intends to cross a street but is hit by an oncoming city bus und suffers severe trauma: serial rib fracture, femoral fracture, fibula fracture, splenic, pancreatic and bowel ruptures. He is operated on in a maximum care hospital and then transferred to the critical care unit. From then on, an anonymous, very experienced physician continuously takes care of him. Four nights before Christmas, the ghost of the famous British physiologist Ernest Henry Starling appears at the patient’s bed. The ghost involves the anonymous physician in a dialogue and is very interested in the inserted Swan-Ganz catheter, then he disappears. He repeats his visits the next 3 nights. On the first occasion he is displeased with Cratchit’s low haematocrit, the second time he dislikes the mechanical ventilator settings, and on his final visit he is concerned with Cratchit’s clinical nutrition. At first, the anonymous physician is indignant with the ghost’s criticism and indoctrinations, but then recognizes that ultimately they are the key to Cratchit’s convalescence and acts accordingly. Successfully! Following the ghost’s proposals, he changes the ventilator settings, transfuses 3 units of packed red blood cells, and starts clinical nutrition. Shortly thereafter, Cratchit’s trachea is extubated, and on New Year’s Day he is ready to be discharged from the critical care unit. In this essay, Robert Bartlett transposed Charles Dickens’ “Christmas Carol” into the world of critical care. Its intention is to encourage the intensivist to scrutinize common therapeutic measures, such as mechanical ventilation, haemodynamic interventions and transfusion of blood products. Background information and comments on the addressed problems of modern intensive care are provided subsequent to the essay."
3323,"Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial","PURPOSE: Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). METHODS: This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). RESULTS: Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76–1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54–1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84–5.34). CONCLUSION: There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06266-1) contains supplementary material, which is available to authorized users."
3324,The threads of history: why record your pandemic experiences for the RCPI archive?,
3325,"Response to “Registry reports in COVID-19 patients: juggling with big data, poor data, and no data”",
3326,Analysis of Amino Acid Mutations of the Foot-and-Mouth Disease Virus Serotype O Using both Heparan Sulfate and JMJD6 Receptors,"Foot-and-mouth disease (FMD) is an economically devastating animal disease. Adapting the field virus to cells is critical to the vaccine production of FMD viruses (FMDV), and heparan sulfate (HS) and Jumonji C-domain-containing protein 6 (JMJD6) are alternative receptors of cell-adapted FMDV. We performed serial passages of FMDV O/SKR/Andong/2010, classified as the O/Mya-98 topotype/lineage and known as a highly virulent strain, to develop a vaccine seed virus. We traced changes in the amino acid sequences of the P1 region, plaque phenotypes, and the receptor usage of the viruses, and then structurally analyzed the mutations. VP3 H56R and D60G mutations were observed in viruses using the HS receptor and led to changes in the hydrogen bonding between VP3 56 and 60. A VP1 P208L mutation was observed in the virus using the JMJD6 receptor during cell adaptation, enabling the interaction with JMJD6 through the formation of a new hydrogen bond with JMJD6 residue 300. Furthermore, VP1 208 was near the VP1 95/96 amino acids, previously reported as critical mutations for JMJD6 receptor interactions. Thus, the mutation at VP1 208 could be critical for cell adaptation related to the JMJD6 receptor and may serve as a basis for mechanism studies on FMDV cell adaptation."
3327,"The Impact of Diet, Nutrition and Nutraceuticals on Oral and Periodontal Health","Oral and periodontal diseases can determine severe functional, phonatory and aesthetic impairments and are the main cause of adult tooth loss. They are caused by some specific bacteria that provoke an intense local inflammatory response and affect—with particular gravity—susceptible subjects, because of reasons related to genetics and lifestyles (e.g., smoking and home oral hygiene habits). They are more frequent in the disadvantaged segments of society and, in particular, in subjects who have difficulty accessing preventive services and dental care. Some systemic diseases, such as uncontrolled diabetes, can increase their risk of development and progression. Recently, in addition to the obvious considerations of severe alterations and impairments for oral health and well-being, it has been noted that periodontitis can cause changes in the whole organism. Numerous clinical and experimental studies have highlighted the presence of a strong association between periodontitis and some systemic diseases, in particular, cardiovascular diseases, diabetes, lung diseases and complications of pregnancy. The purpose of this editorial is to provide a current and thoughtful perspective on the relationship of diet and natural agents on oral, periodontal diseases, and chewing disorder preventions which may reflect good systemic conditions and related quality of life or to analyze indirect effects through the contribution of diet and nutrition to systemic health in order to obtain a modern diagnostic–therapeutic approach."
3328,Exploring Language Learning as a Potential Tool against Cognitive Impairment in Late-Life Depression: Two Meta-Analyses and Suggestions for Future Research,"Late-life depression (LLD) affects about an eighth of community-dwelling seniors. LLD impacts well-being, with loneliness and small social networks being typical. It has also been linked to cognitive dysfunction and an increased risk of developing dementia. Safety and efficacy of pharmacological treatments for LLD have been debated, and cognitive dysfunction often persists even after remission. Various cognitive interventions have been proposed for LLD. Among these, one has received special attention: foreign language learning could serve as a social intervention that simultaneously targets brain structures affected in LLD. Lifelong bilingualism may significantly delay the onset of cognitive impairment symptoms by boosting cognitive reserve. Even late-life foreign language learning without lifelong bilingualism can train cognitive flexibility. It is then counterintuitive that the effects of language learning on LLD have never been examined. In order to create a theoretical basis for further interdisciplinary research, this paper presents a status quo of current work through two meta-analyses investigating cognitive functioning in LLD on the one hand and in senior bilinguals or seniors following a language course on the other hand. While LLD was consistently associated with cognitive dysfunction, inconsistent results were found for bilingualism and language learners. Possible reasons for this and suggestions for future research are subsequently discussed."
3329,STAU1 selectively regulates the expression of inflammatory and immune response genes and alternative splicing of the nerve growth factor receptor signaling pathway,"Double-stranded RNA-binding protein Staufen homolog 1 (STAU1) is a highly conserved multifunctional double-stranded RNA-binding protein, and is a key factor in neuronal differentiation. RNA sequencing was used to analyze the overall transcriptional levels of the upregulated cells by STAU1 and control cells, and select alternative splicing (AS). It was determined that the high expression of STAU1 led to changes in the expression levels of a variety of inflammatory and immune response genes, including IFIT2, IFIT3, OASL, and CCL2. Furthermore, STAU1 was revealed to exert a significant regulatory effect on the AS of genes related to the ‘nerve growth factor receptor signaling pathway’. This is of significant importance for neuronal survival, differentiation, growth, post-damage repair, and regeneration. In conclusion, overexpression of STAU1 was associated with immune response and regulated AS of pathways related to neuronal growth and repair. In the present study, the whole transcriptome of STAU1 expression was first analyzed, which laid a foundation for further understanding the key functions of STAU1."
3330,An overview of moonlighting proteins in Staphylococcus aureus infection,"Staphylococcus aureus is responsible for numerous instances of superficial, toxin-mediated, and invasive infections. The emergence of methicillin-resistant (MRSA), as well as vancomycin-resistant (VRSA) strains of S. aureus, poses a massive threat to human health. The tenacity of S. aureus to acquire resistance against numerous antibiotics in a very short duration makes the effort towards developing new antibiotics almost futile. S. aureus owes its destructive pathogenicity to the plethora of virulent factors it produces among which a majority of them are moonlighting proteins. Moonlighting proteins are the multifunctional proteins in which a single protein, with different oligomeric conformations, perform multiple independent functions in different cell compartments. Peculiarly, proteins involved in key ancestral functions and metabolic pathways typically exhibit moonlighting functions. Pathogens mainly employ those proteins as virulent factors which exhibit high structural conservation towards their host counterparts. Consequentially, the host immune system counteracts these invading bacterial virulent factors with minimal protective action. Additionally, many moonlighting proteins also play multiple roles in various stages of pathogenicity while augmenting the virulence of the bacterium. This has necessitated elaborative studies to be conducted on moonlighting proteins of S. aureus that can serve as drug targets. This review is a small effort towards understanding the role of various moonlighting proteins in the pathogenicity of S. aureus."
3331,Discoveries of Exoribonuclease-Resistant Structures of Insect-Specific Flaviviruses Isolated in Zambia,"To monitor the arthropod-borne virus transmission in mosquitoes, we have attempted both to detect and isolate viruses from 3304 wild-caught female mosquitoes in the Livingstone (Southern Province) and Mongu (Western Province) regions in Zambia in 2017. A pan-flavivirus RT-PCR assay was performed to identify flavivirus genomes in total RNA extracted from mosquito lysates, followed by virus isolation and full genome sequence analysis using next-generation sequencing and rapid amplification of cDNA ends. We isolated a newly identified Barkedji virus (BJV Zambia) (10,899 nt) and a novel flavivirus, tentatively termed Barkedji-like virus (BJLV) (10,885 nt) from Culex spp. mosquitoes which shared 96% and 75% nucleotide identity with BJV which has been isolated in Israel, respectively. These viruses could replicate in C6/36 cells but not in mammalian and avian cell lines. In parallel, a comparative genomics screening was conducted to study evolutionary traits of the 5′- and 3′-untranslated regions (UTRs) of isolated viruses. Bioinformatic analyses of the secondary structures in the UTRs of both viruses revealed that the 5′-UTRs exhibit canonical stem-loop structures, while the 3′-UTRs contain structural homologs to exoribonuclease-resistant RNAs (xrRNAs), SL-III, dumbbell, and terminal stem-loop (3′SL) structures. The function of predicted xrRNA structures to stop RNA degradation by Xrn1 exoribonuclease was further proved by the in vitro Xrn1 resistance assay."
3332,Infection Dynamics of Swine Influenza Virus in a Danish Pig Herd Reveals Recurrent Infections with Different Variants of the H1N2 Swine Influenza A Virus Subtype,"Influenza A virus (IAV) in swine, so-called swine influenza A virus (swIAV), causes respiratory illness in pigs around the globe. In Danish pig herds, a H1N2 subtype named H1N2dk is one of the main circulating swIAV. In this cohort study, the infection dynamic of swIAV was evaluated in a Danish pig herd by sampling and PCR testing of pigs from two weeks of age until slaughter at 22 weeks of age. In addition, next generation sequencing (NGS) was used to identify and characterize the complete genome of swIAV circulating in the herd, and to examine the antigenic variability in the antigenic sites of the virus hemagglutinin (HA) and neuraminidase (NA) proteins. Overall, 76.6% of the pigs became PCR positive for swIAV during the study, with the highest prevalence at four weeks of age. Detailed analysis of the virus sequences obtained showed that the majority of mutations occurred at antigenic sites in the HA and NA proteins of the virus. At least two different H1N2 variants were found to be circulating in the herd; one H1N2 variant was circulating at the sow and nursery sites, while another H1N2 variant was circulating at the finisher site. Furthermore, it was demonstrated that individual pigs had recurrent swIAV infections with the two different H1N2 variants, but re-infection with the same H1N2 variant was also observed. Better understandings of the epidemiology, genetic and antigenic diversity of swIAV may help to design better health interventions for the prevention and control of swIAV infections in the herds."
3333,Age-Related Changes and Sex-Related Differences in Brain Iron Metabolism,"Iron is an essential element that participates in numerous cellular processes. Any disruption of iron homeostasis leads to either iron deficiency or iron overload, which can be detrimental for humans’ health, especially in elderly. Each of these changes contributes to the faster development of many neurological disorders or stimulates progression of already present diseases. Age-related cellular and molecular alterations in iron metabolism can also lead to iron dyshomeostasis and deposition. Iron deposits can contribute to the development of inflammation, abnormal protein aggregation, and degeneration in the central nervous system (CNS), leading to the progressive decline in cognitive processes, contributing to pathophysiology of stroke and dysfunctions of body metabolism. Besides, since iron plays an important role in both neuroprotection and neurodegeneration, dietary iron homeostasis should be considered with caution. Recently, there has been increased interest in sex-related differences in iron metabolism and iron homeostasis. These differences have not yet been fully elucidated. In this review we will discuss the latest discoveries in iron metabolism, age-related changes, along with the sex differences in iron content in serum and brain, within the healthy aging population and in neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke."
3334,Antiviral Properties of Flavonoids and Delivery Strategies,"This review summarizes the latest advancements in phytochemicals as functional antiviral agents. We focused on flavonoids, like apigenin, vitexin, quercetin, rutin and naringenin, which have shown a wide range of biological effects including antiviral activities. The molecular mechanisms of their antiviral effects mainly consist in the inhibition of viral neuraminidase, proteases and DNA/RNA polymerases, as well as in the modification of various viral proteins. Mixtures of different flavonoids or combination of flavonoids with antiviral synthetic drugs provide an enhancement of their antiviral effects. Recent strategies in drug delivery significantly contribute to overcoming the low bioavailability of flavonoids. Frequent viral infections worldwide have led to the need for new effective antiviral agents, which can be identified among the various phytochemicals. In this light, screening the antiviral activities of a cocktail of flavonoids would be advantageous in order to prevent viral infections and improve current antiviral therapies."
3335,"The Husavirus Posa-Like Viruses in China, and a New Group of Picornavirales","Novel posa-like viral genomes were first identified in swine fecal samples using metagenomics and were designated as unclassified viruses in the order Picornavirales. In the present study, nine husavirus strains were identified in China. Their genomes share 94.1–99.9% similarity, and alignment of these nine husavirus strains identified 697 nucleotide polymorphism sites across their full-length genomes. These nine strains were directly clustered with the Husavirus 1 lineage, and their genomic arrangement showed similar characteristics. These posa-like viruses have undergone a complex evolutionary process, and have a wide geographic distribution, complex host spectrum, deep phylogenetic divergence, and diverse genomic organizations. The clade of posa-like viruses forms a single group, which is evolutionarily distinct from other known families and could represent a distinct family within the Picornavirales. The genomic arrangement of Picornavirales and the new posa-like viruses are different, whereas the posa-like viruses have genomic modules similar to the families Dicistroviridae and Marnaviridae. The present study provides valuable genetic evidence of husaviruses in China, and clarifies the phylogenetic dynamics and the evolutionary characteristics of Picornavirales."
3336,The Monoclonal Antibody Recognized the Open Reading Frame Protein in Porcine Circovirus Type 2-Infected Peripheral Blood Mononuclear Cells,"The purpose of this study in the context of the open reading frame 3 (ORF3) protein of porcine circovirus type 2 (PCV2) was especially its location and its relation to the capsid protein and the apoptosis protein in PCV2-infected porcine peripheral blood mononuclear cells (PBMCs). To detect the ORF3 protein, monoclonal antibodies (mAbs) were generated in this study. The mAb 7D3 binds to the ORF3 peptide (residues 35–66) and the native ORF3 protein in PCV2-infected PBMCs, as shown by immunofluorescence assay (IFA). The data show that 3–5% of PBMCs were positive for ORF3 protein or p53 protein. Further, 78–82% of PBMCs were positive for the capsid. This study confirmed the ORF3 protein not only colocalized with the capsid protein but also colocalized with the p53 protein in PBMCs. Immunoassays were conducted in this study to detect the capsid protein, the ORF3 protein, anti-capsid IgG, and anti-ORF3 IgG. The data show the correlation (r = 0.758) of the ORF3 protein and the capsid protein in the blood samples from the PCV2-infected herd. However, each anti-viral protein IgG had a different curve of the profile in the same herd after vaccination. Overall, this study provides a blueprint to explore the ORF3 protein in PCV2-infected PBMCs."
3337,Induction of the Unfolded Protein Response during Bovine Alphaherpesvirus 1 Infection,"Bovine herpesvirus 1 (BoHV-1) is an alphaherpesvirus that causes great economic losses in the cattle industry. Herpesvirus infection generally induces endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR) in infected cells. However, it is not clear whether ER stress and UPR can be induced by BoHV-1 infection. Here, we found that ER stress induced by BoHV-1 infection could activate all three UPR sensors (the activating transcription factor 6 (ATF6), the inositol-requiring enzyme 1 (IRE1), and the protein kinase RNA-like ER kinase (PERK)) in MDBK cells. During BoHV-1 infection, the ATF6 pathway of UPR did not affect viral replication. However, both knockdown and specific chemical inhibition of PERK attenuated the BoHV-1 proliferation, and chemical inhibition of PERK significantly reduced the viral replication at the post-entry step of the BoHV-1 life cycle. Furthermore, knockdown of IRE1 inhibits BoHV-1 replication, indicating that the IRE1 pathway may promote viral replication. Further study revealed that BoHV-1 replication was enhanced by IRE1 RNase activity inhibition at the stage of virus post-entry in MDBK cells. Furthermore, IRE1 kinase activity inhibition and RNase activity enhancement decrease BoHV1 replication via affecting the virus post-entry step. Our study revealed that BoHV-1 infection activated all three UPR signaling pathways in MDBK cells, and BoHV-1-induced PERK and IRE1 pathways may promote viral replication. This study provides a new perspective for the interactions of BoHV-1 and UPR, which is helpful to further elucidate the mechanism of BoHV-1 pathogenesis."
3338,Diagnostic Challenges in Canine Parvovirus 2c in Vaccine Failure Cases,"In this study, three different diagnostic tests for parvovirus were compared with vaccination status and parvovirus genotype in suspected canine parvovirus cases. Faecal samples from vaccinated (N17) and unvaccinated or unknown vaccination status (N41) dogs that had clinical signs of parvovirus infection were tested using three different assays of antigen tests, conventional and quantitative PCR tests. The genotype of each sample was determined by sequencing. In addition to the suspected parvovirus samples, 21 faecal samples from apparently healthy dogs were tested in three diagnostic tests to evaluate the sensitivity and specificity of the tests. The antigen test was positive in 41.2% of vaccinated dogs and 73.2% of unvaccinated diseased dogs. Conventional PCR and qPCR were positive for canine parvovirus (CPV) in 82.4% of vaccinated dogs and 92.7% of unvaccinated dogs. CPV type-2c (CPV-2c) was detected in 82.75% of dogs (12 vaccinated and 36 unvaccinated dogs), CPV-2b was detected in 5.17% dogs (one vaccinated and two unvaccinated) and CPV-2a in 1.72% vaccinated dog. Mean Ct values in qPCR for vaccinated dogs were higher than the unvaccinated dogs (p = 0.049), suggesting that vaccinated dogs shed less virus, even in clinical forms of CPV. CPV-2c was the dominant subtype infecting dogs in both vaccinated and unvaccinated cases. Faecal antigen testing failed to identify a substantial proportion of CPV-2c infected dogs, likely due to low sensitivity. The faecal samples from apparently healthy dogs (n = 21) showed negative results in all three tests. Negative CPV faecal antigen results should be viewed with caution until they are confirmed by molecular methods."
3339,Understanding the Mechanisms Underlying Host Restriction of Insect-Specific Viruses,"Arthropod-borne viruses contribute significantly to global mortality and morbidity in humans and animals. These viruses are mainly transmitted between susceptible vertebrate hosts by hematophagous arthropod vectors, especially mosquitoes. Recently, there has been substantial attention for a novel group of viruses, referred to as insect-specific viruses (ISVs) which are exclusively maintained in mosquito populations. Recent discoveries of novel insect-specific viruses over the past years generated a great interest not only in their potential use as vaccine and diagnostic platforms but also as novel biological control agents due to their ability to modulate arbovirus transmission. While arboviruses infect both vertebrate and invertebrate hosts, the replication of insect-specific viruses is restricted in vertebrates at multiple stages of virus replication. The vertebrate restriction factors include the genetic elements of ISVs (structural and non-structural genes and the untranslated terminal regions), vertebrate host factors (agonists and antagonists), and the temperature-dependent microenvironment. A better understanding of these bottlenecks is thus warranted. In this review, we explore these factors and the complex interplay between ISVs and their hosts contributing to this host restriction phenomenon."
3340,N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle,"Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification. Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated. The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein. Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking. Using a ZIKV infectious clone, we found that when the N-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant. Further, by using ZIKV prME constructs, we found that N-glycosylation was necessary for effective secretion of ZIKV virions. The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment. The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization. In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker. To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly."
3341,Inflammatory Correlated Response in Two Lines of Rabbit Selected Divergently for Litter Size Environmental Variability,"SIMPLE SUMMARY: Animal welfare is a priority objective for the livestock industry. Litter size environmental variability has been related to environmental sensitivity. A divergent selection experiment for environmental variance of litter size variance was carried out successfully in rabbits over thirteen generations. The low line showed a lower inflammatory response and susceptibility to infectious disorders than the high line. In conclusion, the decrease of environmental sensitivity seems to increase the adaptation of the animal to the environment, and thus, its welfare. ABSTRACT: A divergent selection experiment for environmental variance of litter size variance was carried out in rabbits over thirteen generations. The aim of this study was to evaluate the inflammatory response in the two lines of the experiment, in order to analyse the effect of selection on susceptibility to diseases after challenging to stressful situations, such as 24 h after the first delivery. A total of 78 females were used in this study, 39 from each line. The line selected for litter size heterogeneity (the high line) showed lower white blood leukocyte count (WBC; −0.87 × 10(3)/µL), lower percentage of basophils (−0.11%), higher concentration of TNF-α (+13.8 pg/mL), and greater concentration of CRP (+38.1 µg/mL) than the line selected for litter size homogeneity (the low line). The high line had also higher concentrations of bilirubin, cholesterol, gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) compared to the low line (difference between lines were +0.08 µmol/L, +0.14 µmol/L, +0.35 U/L and +2.4 U/L, respectively). The high line showed higher inflammatory response than the low line, in accordance with a larger susceptibility to infectious disorders. In conclusion, the line selected to increase litter size environmental variability seems to have poor capacity coping with environmental stressors. Therefore, selection for litter size environmental variability can be a useful way to improve animal welfare."
3342,"Dietary Supplementation of Probiotic Lactobacillus acidophilus Modulates Cholesterol Levels, Immune Response, and Productive Performance of Laying Hens","SIMPLE SUMMARY: Chicken eggs provide a considerable source of high-quality nutrients for human food and health. However, egg consumption may harm some people for its high contents of cholesterol and association with cardiovascular disease risk. Therefore, we investigated the possible effect of using Lactobacillus acidophilus (LA) as a probiotic additive in the laying hens’ diets on lowering egg-yolk cholesterol and also evaluated the immune responses and the productive performance of laying hens. The obtained results display the ability of LA, when supplemented in hen diets, to decrease the plasma triglycerides and cholesterol levels and the liver and egg yolk cholesterols in the hen. The beneficial effects of LA were also explored on some important humoral and cell-mediated immune responses in the laying hens. These positive effects led to an improvement in the productive performance of laying hens. Therefore, dietary LA supplementation could be recommended as a nutritional strategy for commercial lower-cholesterol egg production in addition to positive impacts on the performance and health of laying hens. ABSTRACT: This study examines the effect of dietary supplementation with Lactobacillus acidophilus (LA) on the cholesterol levels, immune response, and productive performance of laying hens. A total of 216, 40-week-old, commercial Hy-Line brown chicken layers were randomly assigned into four treatment groups (18 birds × three replicates per group) and fed diet supplemented with 0 (control), 1 × 10(9), 21 × 10(9), and 31 × 10(9) colony forming units (CFUs) of Lactobacillus acidophilus (LA) per kg of feed for six consecutive weeks. Results show that plasma triglycerides, low-density lipoprotein (LDL) and total cholesterols became lesser, while high-density lipoprotein (HDL) cholesterol became higher in LA-supplemented groups compared to the control. In addition, a significant reduction occurred in the liver and egg yolk cholesterol by LA supplementation. Moreover, the immunological parameters including antibody titer against sheep red blood cells (SRBCs), phytohemagglutinin (PHA)-wattle swelling test, and T- & B-lymphocyte proliferation were enhanced in laying hens supplemented with LA compared to the control hens. While the heterophil to lymphocyte (H/L) ratio decreased with LA supplementation, indicating low stress conditions in the treated hens. These positive effects for LA were further reflected on the productive performance of laying hens and improved egg production, egg weight, egg mass, and feed efficiency. Our findings indicate that LA probiotic could be recommended in laying hens’ diets for lowering egg yolk cholesterol with positive impacts on health and performance."
3343,"Prevalence of ticks (Acari: Ixodidae) and Theileria lestoquardi in sheep at El Huda and El Nuhud animals production research stations, Sudan","A cross-sectional study was performed 200 blood samples and 314 tick samples in El Huda and El Nuhud animals production research stations, Sudan, in May (summer) and December (winter) in 2016, to determine the prevalence of Theileria lestoquardi in sheep and the potential risk factors associated with the infection. A total of 200 blood samples and 314 tick samples were collected from El Huda (n = 103 blood, 97 tick) and El Nuhud (n = 97 blood, 217 tick) stations. Data on the risk factors, such as age, sex, ecotype of sheep, body condition score and seasons were recorded. The overall prevalence of Theileria lestoquardi was 13% (26/200) using PCR. A significant variation in the prevalence of Theileria lestoquardi was observed between the stations and the ecotype of sheep (p ≤ 0.05), whereas the highest prevalence was recorded in El-Huda station (19.4%) as well as in Shugor (22.8%). Other risk factors, like age, sex, body condition, and seasons were not found to be significantly associated with infection. However, the highest prevalence rate was recorded in old animals (21.6%) than the other, in males (17.9%) than females (12.2%), in animals with poor body condition (26.1%) than the other, and in winter (16%) than summer (10%). Four tick species i.e. Rhipicephalus evertsi evertsi (63.1%), Hyalomma anatolicum (13.8%), Hyalomma dromedarii (8.8%), and Hyalomma impeltatum (14.3%) were recorded in El Nuhud station. While in El Huda station, only Rhipicephalus evertsi evertsi (79.4%), Hyalomma anatolicum (20.6%) were recorded. This study revealed that 13% of sheep were suffering from Theileria lestoquardi which is a considerable number at the stations. Therefore, further epidemiological investigations on disease throughout the year are required in order to set a well-coordinated control program."
3344,"A Randomized, Placebo-Controlled Clinical Trial of Famciclovir in Shelter Cats with Naturally Occurring Upper Respiratory Tract Disease","SIMPLE SUMMARY: Upper respiratory tract disease (URTD) impacts the health and welfare of shelter cats. Mitigation strategies include stress reduction and population-level approaches; effective treatment plans focus on reducing the clinical signs in cats affected by URTD. This study evaluated the use of famciclovir, an antiviral therapy, in reducing clinical signs in shelter cats with URTD when administered at a target dose range of 40–90 mg/kg twice daily for up to 21 days. Cats were randomized into either a famciclovir treatment group (n = 11) or placebo group (n = 11). Testing for viral pathogen identification was performed at enrollment in the study, and clinical scoring was completed daily to evaluate the severity of signs. With each day of treatment, cats in both groups were less likely to experience worsening clinical scores; however, cats in the famciclovir treatment group had a significantly lower risk of worsening clinical signs with each day compared to the placebo group. Feline herpesvirus, a common pathogen causing URTD, was identified in 11/21 cats. The results of this small study justify the need for further research to determine the utility of famciclovir as part of treatment protocols for improving clinical signs and overall impacts of URTD in shelter cats. ABSTRACT: Upper respiratory tract disease (URTD) is a clinically relevant infectious disease in shelter cats, with individual and population-level welfare implications. The purpose of this study was to evaluate the effectiveness of famciclovir in reducing clinical signs of URTD in shelter cats during a therapeutic period of up to 21 days. Cats at two Northeastern United States animal shelters with URTD clinical signs were enrolled in a pragmatic, prospective, randomized, placebo-controlled clinical trial. Cats received either famciclovir (n = 11, target dose range 40–90 mg/kg) or placebo (n = 11), administered orally twice daily for up to 21 days with once-daily clinical scoring. At enrollment, conjunctival and oropharyngeal samples were collected for respiratory pathogen identification by RT-PCR. Zero-inflated Poisson regression was used to evaluate the treatment group effects and changes in clinical scoring over time. With each day of treatment, cats in both groups were less likely to experience worsening clinical scores; however, the risk of worsening scores with each day of treatment was significantly less in the famciclovir group compared to placebo (p = 0.006). Feline herpesvirus (FHV-1) DNA was detected in 11/21 cats. The findings justify further pragmatic studies to determine whether famciclovir treatment can contribute to a clinically relevant reduction in URTD morbidity in shelter cats."
3345,Elementary Classroom Teachers’ Self-Reported Use of Movement Integration Products and Perceived Facilitators and Barriers Related to Product Use,"Movement integration (MI) products are designed to provide children with physical activity during general education classroom time. The purpose of this study was to examine elementary classroom teachers’ self-reported use of MI products and subsequent perceptions of the facilitators of and barriers to MI product use. This study utilized a mixed-methods design. Elementary classroom teachers (n = 40) at four schools each tested four of six common MI products in their classroom for one week. Teachers completed a daily diary, documenting duration and frequency of product use. Following each product test, focus groups were conducted with teachers to assess facilitators and barriers. MI product use lasted for 11.2 (Standard Deviation (SD) = 7.5) min/occasion and MI products were used 4.1 (SD = 3.5) times/week on average. Activity Bursts in the Classroom for Fitness, GoNoodle, and Physical Activity Across the Curriculum were most frequently used. Facilitators of and barriers to MI product use were identified within three central areas—logistics, alignment with teaching goals, and student needs and interests. Teachers were receptive to MI products and used them frequently throughout the week. When considering the adoption of MI products, teachers, administrators, and policy makers should consider products that are readily usable, align with teaching goals, and are consistent with student needs and interests."
3346,"Anmerkung zu OVG Niedersachsen, Beschl. v. 3.3.2020 – 13 LA 51/19 (VG – Braunschweig)",
3347,Red cell volume measurement: using technetium as a replacement for chromium,
3348,Clinical leadership training: a clinician's perspective,
3349,We’ve never seen a patient with ARDS!,
3350,Decision making processes underlying avoidance of mandatory child vaccination in Croatia – a qualitative study,"Despite extensive research evidencing child vaccination is safe and effective, we are witnessing a trend of increasing vaccine hesitancy which is listed among the top ten global health threats. Although some countries incorporate mandatory vaccination programs, no particularly efficient strategies for addressing vaccine avoidance have so far been identified. Within this study we investigated perceptions and reasoning of vaccine hesitant parents from Croatia where child vaccination is mandatory. The aims were to reveal different strategies by which they avoid mandatory vaccination schedules and hypothetical situations in which they would reconsider vaccinating, as well as to identify features of related decision-making. We conducted 25 semi-structured interviews with vaccine hesitant parents and analyzed the data using the framework of thematic analyses. The identified themes were related to the parents’ decision-making process, reflection as well as justification of their decision, avoidance behavior of mandatory vaccination schedules and related consequences, dealing with outcomes of the decision and reconsidering vaccinating. The results support and extend previous findings regarding vaccine reasoning, linking hesitancy with the experientially intuitive thinking style and social intuitionist model of moral reasoning. The findings provide important insights into vaccination avoidance and potential for reconsideration, as well as dealing with related risks. Furthermore, we offer a general framework as well as practical guidelines that may help the development of strategies aimed at increasing vaccination rates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12144-020-01110-7) contains supplementary material, which is available to authorized users."
3351,A pilot study for smartphone photography to assess bleb morphology and vasculature post-trabeculectomy,"PURPOSE: The current grading systems used for bleb morphology assessment in patients post-trabeculectomy are based on standardized slit-lamp photographs and anterior segment imaging devices. The lack of availability of these expensive and non-portable devices in resource-deficient settings is a significant deterrent in their widespread utilization for proper post-operative management. The rapidly evolving utilization of smartphone photography has significantly benefited diagnostics of posterior segment disorders and is now being increasingly utilized for monitoring anterior segment pathologies as well as post-surgical course. In this study, we study a novel use of smartphones for bleb photography for assessing the morphological characteristics as vascularity and microcysts. METHODS: In this pilot, observational study, we compared the trabeculectomy bleb images of five subjects, obtained by iPhone X (dual lens) and iPhone 6S (single lens). We captured two image sets with both smartphones first with a focussed torchlight and then with a built-in flash video light. RESULTS: The images resulting from the newer iPhone X were substantially superior than those from iPhone 6S. For the 12-megapixel dual-camera set-up on the iPhone X, the 1 × lens resulted in better images than the 2 × lens with contrast and overall clarity of the area of interest. While the macro-lens attachment had promising results at 1 × zoom, there is no added advantage of the macro-lens attachment as it resulted in considerable loss of image quality at twice the zoom. Using a 20 D lens helped attain higher magnification and better framing as it reduced the focussing distance needed to get sharp images. The images obtained from both smartphones were of higher quality when illuminated from an external source when compared to the native iPhone flash due to even exposure and fewer autofocus artefacts. CONCLUSION: Analyses of all image sets showed that the current generation in-built camera app on IOS and newer iPhone camera optics resulted in high-quality images of the ocular surface with high magnification without any loss in clarity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10792-020-01598-9) contains supplementary material, which is available to authorized users."
3352,Correction to Lancet Diabetes Endocrinol 2020; 8: 782–92,
3353,Maternal and child mortality worsens in Latin America and the Caribbean,
3354,Nursing's seat at the research roundtable,
3355,First human efficacy study of a plant-derived influenza vaccine,
3356,"Toto, I’ve a Feeling We’re Not in Kansas Anymore: Navigating the Mid-career Transition to Academic Medicine","When physicians, nurse practitioners, and physician assistants transition from a community setting to a university-based academic environment during mid-career, it can be challenging. Strategic planning is needed to ensure success. Institutions can assist experienced providers making such a transition, and there are steps the provider can take to self-advocate. As a group of four medical professionals who began their careers in patient care community practices for up to 18 years before transitioning to an academic medical center, we have had to navigate an unfamiliar landscape. We collectively offer our tips for a successful mid-career transition to academic medicine."
3357,Tracheostomy in Pediatric Intensive Care Unit: Experience from Eastern India,"OBJECTIVE: Tracheostomy is one of the most commonly used surgical intervention in sick children in the intensive care unit. The literature in the pediatric population is limited, therefore, we conducted this study to evaluate the indications, timing, complications, and outcomes of tracheostomy among the children at our center. METHODS: This retrospective study was conducted from January 2016 through December 2019. Data was collected from the patients’ records and analyzed. RESULTS: During this study period, 283 children were ventilated, of which 26 (9.1%) required tracheostomy. Among this 73% were boys. The median age of the children who underwent tracheostomy was 6.32 y. The most common indication for tracheostomy was prolonged mechanical ventilation [24 cases (92%)] followed by upper airway obstruction [2 cases (8%)]. The average time of tracheostomy was 11.65 d, range (1–21 d). Complications were seen in 14 patients (55%). The most common complications were accidental decannulation, occlusion, pneumothorax, and granulation tissue. Twenty one (80%) patients were successfully discharged, out of which 16 (61%) patients were discharged after decannulation and 5 (21%) were sent home with a tracheostomy tube in situ. Overall mortality in present study was 11.5%; none was directly related to tracheostomy. CONCLUSIONS: The indication for tracheostomy has been changed from emergency to more elective one. Prolonged mechanical ventilation is the most common indication for tracheostomy. Although the timing of tracheostomy is not fixed, two weeks time is reasonable and it can be done safely at the bedside in pediatric intensive care."
3358,Reflecting on the Impact of Cardiovascular Nurses in Australia and New Zealand in the International Year of the Nurse and Midwife,
3359,Emergency laparoscopic treated the spontaneous bleeding and cystobiliary communication of multiple liver cysts,
3360,Erratum regarding previously published articles,
3361,Conceptual Physical Education: A course for the future,"The conceptual physical education (CPE) innovation began in the mid-20th century as an alternative approach to college-level, activity-only basic instruction classes. In addition to physical activity sessions, CPE courses (classes) use text material and classroom sessions to teach kinesiology concepts and principles of health-related fitness and health-enhancing physical activity. CPE courses are now offered in nearly all college programs as either required or electives classes. Two decades later, the high school CPE innovation began, and Kindergarten-8 programs followed. In this commentary, I argue that historian Roberta Park was correct in her assessment that physical education has the potential to be the renaissance field of the 21st century. Scientific contributions of researchers in kinesiology will lead the way, but science-based CPE and companion fitness education (FE) programs that align with physical education content standards and FE benchmarks will play a significant role. CPE courses have been shown to be effective in promoting knowledge, attitudes, and out-of-school physical activity and have the potential to elevate physical education as we chart the course of our future."
3362,From Mouse to Man and Back: Closing the Correlation Gap between Imaging and Histopathology for Lung Diseases,"Lung diseases such as fibrosis, asthma, cystic fibrosis, infection and cancer are life-threatening conditions that slowly deteriorate quality of life and for which our diagnostic power is high, but our knowledge on etiology and/or effective treatment options still contains important gaps. In the context of day-to-day practice, clinical and preclinical studies, clinicians and basic researchers team up and continuously strive to increase insights into lung disease progression, diagnostic and treatment options. To unravel disease processes and to test novel therapeutic approaches, investigators typically rely on end-stage procedures such as serum analysis, cyto-/chemokine profiles and selective tissue histology from animal models. These techniques are useful but provide only a snapshot of disease processes that are essentially dynamic in time and space. Technology allowing evaluation of live animals repeatedly is indispensable to gain a better insight into the dynamics of lung disease progression and treatment effects. Computed tomography (CT) is a clinical diagnostic imaging technique that can have enormous benefits in a research context too. Yet, the implementation of imaging techniques in laboratories lags behind. In this review we want to showcase the integrated approaches and novel developments in imaging, lung functional testing and pathological techniques that are used to assess, diagnose, quantify and treat lung disease and that may be employed in research on patients and animals. Imaging approaches result in often novel anatomical and functional biomarkers, resulting in many advantages, such as better insight in disease progression and a reduction in the numbers of animals necessary. We here showcase integrated assessment of lung disease with imaging and histopathological technologies, applied to the example of lung fibrosis. Better integration of clinical and preclinical imaging technologies with pathology will ultimately result in improved clinical translation of (therapy) study results."
3363,State of the Art Review on Genetics and Precision Medicine in Arrhythmogenic Cardiomyopathy,"Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterised by ventricular arrhythmia and an increased risk of sudden cardiac death (SCD). Numerous genetic determinants and phenotypic manifestations have been discovered in ACM, posing a significant clinical challenge. Further to this, wider evaluation of family members has revealed incomplete penetrance and variable expressivity in ACM, suggesting a complex genotype-phenotype relationship. This review details the genetic basis of ACM with specific genotype-phenotype associations, providing the reader with a nuanced perspective of this condition; whilst also proposing a future roadmap to delivering precision medicine-based management in ACM."
3364,"Effects of p-Cresol on Senescence, Survival, Inflammation, and Odontoblast Differentiation in Canine Dental Pulp Stem Cells","Aging, defined by a decrease in the physical and functional integrity of the tissues, leads to age-associated degenerative diseases. There is a relation between aged dental pulp and the senescence of dental pulp stem cells (DPSCs). Therefore, it is important to investigate the molecular processes underlying the senescence of DPSCs to elucidate the dental pulp aging mechanisms. p-Cresol (PC), a uremic toxin, is strongly related to cellular senescence. Here, age-related phenotypic changes including senescence, apoptosis, inflammation, and declining odontoblast differentiation in PC-treated canine DPSCs were investigated. Under the PC condition, cellular senescence was induced by decreased proliferation capacity and increased cell size, senescence-associated β-galactosidase (SA-β-gal) activity, and senescence markers p21, IL-1β, IL-8, and p53. Exposure to PC could stimulate inflammation by the increased expression of IL-6 and cause the distraction of the cell cycle by the increased level of Bax protein and decreased Bcl-2. The levels of odontoblast differentiation markers, dentin sialophosphoprotein (DSPP), dentin matrix protein 1, and osterix, were decreased. Consistent with those findings, the alizarin red staining, alkaline phosphatase, and DSPP protein level were decreased during the odontoblast differentiation process. Taken together, these findings indicate that PC could induce cellular senescence in DPSCs, which may demonstrate the changes in aging dental pulp."
3365,Identification of Gastritis Subtypes by Convolutional Neuronal Networks on Histological Images of Antrum and Corpus Biopsies,"Background: Gastritis is a prevalent disease and commonly classified into autoimmune (A), bacterial (B), and chemical (C) type gastritis. While the former two subtypes are associated with an increased risk of developing gastric intestinal adenocarcinoma, the latter subtype is not. In this study, we evaluated the capability to classify common gastritis subtypes using convolutional neuronal networks on a small dataset of antrum and corpus biopsies. Methods: 1230 representative 500 × 500 µm images of 135 patients with type A, type B, and type C gastritis were extracted from scanned histological slides. Patients were allocated randomly into a training set (60%), a validation set (20%), and a test set (20%). One classifier for antrum and one classifier for corpus were trained and optimized. After optimization, the test set was analyzed using a joint result from both classifiers. Results: Overall accuracy in the test set was 84% and was particularly high for type B gastritis with a sensitivity of 100% and a specificity of 93%. Conclusions: Classification of gastritis subtypes is possible using convolutional neural networks on a small dataset of histopathological images of antrum and corpus biopsies. Deep learning strategies to support routine diagnostic pathology merit further evaluation."
3366,Signalling Pathways Implicated in Alzheimer′s Disease Neurodegeneration in Individuals with and without Down Syndrome,"Down syndrome (DS), the most common cause of intellectual disability of genetic origin, is characterized by alterations in central nervous system morphology and function that appear from early prenatal stages. However, by the fourth decade of life, all individuals with DS develop neuropathology identical to that found in sporadic Alzheimer’s disease (AD), including the development of amyloid plaques and neurofibrillary tangles due to hyperphosphorylation of tau protein, loss of neurons and synapses, reduced neurogenesis, enhanced oxidative stress, and mitochondrial dysfunction and neuroinflammation. It has been proposed that DS could be a useful model for studying the etiopathology of AD and to search for therapeutic targets. There is increasing evidence that the neuropathological events associated with AD are interrelated and that many of them not only are implicated in the onset of this pathology but are also a consequence of other alterations. Thus, a feedback mechanism exists between them. In this review, we summarize the signalling pathways implicated in each of the main neuropathological aspects of AD in individuals with and without DS as well as the interrelation of these pathways."
3367,Improving Phylogenetic Signals of Mitochondrial Genes Using a New Method of Codon Degeneration,"Recovering deep phylogeny is challenging with animal mitochondrial genes because of their rapid evolution. Codon degeneration decreases the phylogenetic noise and bias by aiming to achieve two objectives: (1) alleviate the bias associated with nucleotide composition, which may lead to homoplasy and long-branch attraction, and (2) reduce differences in the phylogenetic results between nucleotide-based and amino acid (AA)-based analyses. The discrepancy between nucleotide-based analysis and AA-based analysis is partially caused by some synonymous codons that differ more from each other at the nucleotide level than from some nonsynonymous codons, e.g., Leu codon TTR in the standard genetic code is more similar to Phe codon TTY than to synonymous CTN codons. Thus, nucleotide similarity conflicts with AA similarity. There are many such examples involving other codon families in various mitochondrial genetic codes. Proper codon degeneration will make synonymous codons more similar to each other at the nucleotide level than they are to nonsynonymous codons. Here, I illustrate a “principled” codon degeneration method that achieves these objectives. The method was applied to resolving the mammalian basal lineage and phylogenetic position of rheas among ratites. The codon degeneration method was implemented in the user-friendly and freely available DAMBE software for all known genetic codes (genetic codes 1 to 33)."
3368,Databases and Bioinformatic Tools for Glycobiology and Glycoproteomics,"Glycosylation plays critical roles in various biological processes and is closely related to diseases. Deciphering the glycocode in diverse cells and tissues offers opportunities to develop new disease biomarkers and more effective recombinant therapeutics. In the past few decades, with the development of glycobiology, glycomics, and glycoproteomics technologies, a large amount of glycoscience data has been generated. Subsequently, a number of glycobiology databases covering glycan structure, the glycosylation sites, the protein scaffolds, and related glycogenes have been developed to store, analyze, and integrate these data. However, these databases and tools are not well known or widely used by the public, including clinicians and other researchers who are not in the field of glycobiology, but are interested in glycoproteins. In this study, the representative databases of glycan structure, glycoprotein, glycan–protein interactions, glycogenes, and the newly developed bioinformatic tools and integrated portal for glycoproteomics are reviewed. We hope this overview could assist readers in searching for information on glycoproteins of interest, and promote further clinical application of glycobiology."
3369,ERRATUM,
3370,Reply to GASTRO-D-20-01179,
3371,Assessing the public perceptions of treated wastewater reuse: opportunities and implications for urban communities in developing countries,"Wastewater reuse has become an integral part of Integrated Water Resources Management and thus plays a role in securing the water needs for future generations. This study aimed at determining the perceptions of Canaanland, an emerging urban community in Ogun State, Nigeria, on treated wastewater reuse for several purposes. Data were collected through questionnaires administered to the city residents (n = 244). Findings revealed that the city was aware of the economic and environmental benefits of wastewater reuse but would prefer reuse schemes that involved less human contact such as flushing toilets, electricity generation, building construction, and car wash. The least preferred option was for potable purposes. The community also revealed that they would be willing to accept wastewater reuse as long as it is endorsed by medical doctors, university professors, and experts. However, 45.5% of the respondents were from the Covenant University academic environment. Also, an assessment was carried out to ascertain the implications and opportunities for wastewater reuse in the city. Findings indicated that wastewater reuse involves several complexities and interlinkages, which revolve around political and decisional factors, economic and social factors, environmental factors, and technological factors. From the study, policy and decisional suggestions and a wastewater process flow were developed for more efficient wastewater management within developing cities. A study was carried out on eight cities from developing nations that have created a framework for wastewater management using several approaches. Also, a summary of findings reveals that if adequately researched, cheap and alternative means of wastewater treatment and reuse could be developed for electricity generation, carwash, and firefighting for developing nations. The result of this research can be used to address public anxieties regarding wastewater-reuse practices. Additionally, this study hopes to aid successful wastewater management schemes in the foreseeable future."
3372,"Complex Family Planning: a newly accredited, landmark fellowship",
3373,Do we have a new drug for heart rate control in patients with permanent atrial fibrillation? Response,
3374,Intensive care accessibility and outcomes in pandemics,
3375,Treating postpartum depression in rural veterans using internet delivered CBT: program evaluation of MomMoodBooster,"Depression in the postpartum period impacts approximately 13–26% of the general population. This number can be much higher for rural veteran women who face additional barriers to accessing specialized mental health services due to isolation and cultural factors. This study reports on a program evaluation of MomMoodBooster, a coach-supported internet-delivered CBT program for the treatment of maternal depression in veteran women. Repeated measures ANOVA, run with this sample of 326 women, demonstrated an overall positive effect size across outcome measures and engagement with no differences found between rural women and their urban counterparts. Some differences between urban and rural participants were found in total and average time spent with coaches as well as ratings of coach helpfulness, possibly indicating some cultural differences between coaches and rural women that need to be addressed. These results and the results of earlier trials suggest that MomMoodBooster can be a valid and efficacious option for reaching under-served veteran populations with specialized postpartum mental health support and is as effective with rural women as with urban women"
3376,Non-invasive indirect monitoring of intra-abdominal pressure using microwave reflectometry: system design and proof-of-concept clinical trial,"Monitoring intra-abdominal pressure (IAP) has become a standard in intensive care units. Correlation between the abdominal wall’s thickness (AWTh) and IAP has been reported previously. The abdominal wall can be modeled as a compound of parallel dielectric slabs; changes in their width have a direct effect on the reflection coefficient of the abdominal wall at microwave frequencies. This work describes the design of a reflectometry system and its proof-of-concept trial on five patients during laparoscopic surgery. The system complies with IEEE Std. C95.1-2005 concerning exposure of humans to microwave electromagnetic fields in controlled environments. The results putatively show an inverse correlation between IAP and the reflection coefficient, and a strong dependence on the body mass index. A better understanding of the dynamics in the changes of the AWTh (during intra-abdominal hypertension) will allow further development of a microwave-based technique for the continuous non-invasive indirect monitoring of IAP in critical patients."
3377,"Gerontologie, Geriatrie und Robotikforschung: Blick zurück nach vorn","Assistive robotics as a gerontological geriatric field of research so far seem to be perceived more as “recalcitrant”. Predominant is a reserved attitude as to whether this should be considered a research topic to be taken seriously. The reliability of research results and the scientific half-life period are questioned as digital technique generations change exceedingly rapidly and also only a few sustainable standards and guidelines are established. In this context there is a danger that essential developments will be missed in gerontology and geriatrics, then the momentum is active right now and can now be shaped. In the scientific gerontology and geriatrics these developments should not be missed out on but must be grasped with pioneering spirit and proactively co-created. This can be achieved by further research endeavors, public activities and the utilization of knowledge from clinical and nursing practice with each having feedback into development and research."
3378,The contribution of the network “Health Behavior in School-aged Children” to the health of young people in Central and Eastern Europe,
3379,Dramatic presentation of acquired thrombotic thrombocytopenic purpura associated with COVID-19,
3380,Thromboinflammatory mechanisms in sickle cell disease – challenging the hemostatic balance,"Sickle cell disease (SCD) is an inherited hemoglobinopathy that is caused by the presence of abnormal hemoglobin S (HbS) in red blood cells, leading to alterations in red cell properties and shape, as the result of HbS dexoygenation and subsequent polymerization. The pathophysiology of SCD is characterized by chronic inflammatory processes, triggered by hemolytic and vaso-occlusive events, which lead to the va - ried complications, organ damage and elevated mortality seen in individuals with the disease. In association with activation of the endothelium and leukocytes, hemostatic alterations and thrombotic events are welldocumented in SCD. Here, we discuss the role of inflammatory pathways in modulating coagulation and inducing platelet activation in SCD, due to tissue factor activation, adhesion molecule expression, inflammatory mediator production and the induction of innate immune responses, among other mechanisms. Thromboinflammatory pathways may play a significant role in some of the major complications of SCD, such as stroke, venous thromboembolism and possibly acute chest syndrome, besides exacerbating the chronic inflammation and cellular interactions that trigger vaso-occlusion, ischemia-reperfusion processes, and eventually organ damage."
3381,Emerging role of bacterial extracellular vesicles in cancer,"Shedding of microbial extracellular vesicles constitutes a universal mechanism for inter-kingdom and intra-kingdom communication that is conserved among prokaryotic and eukaryotic microbes. In this review we delineate fundamental aspects of bacterial extracellular vesicles (BEVs) including their biogenesis, cargo composition, and interactions with host cells. We critically examine the evidence that BEVs from the host gut microbiome can enter the circulatory system to disseminate to distant organs and tissues. The potential involvement of BEVs in carcinogenesis is evaluated and future research ideas explored. We further discuss the potential of BEVs in microbiome-based liquid biopsies for cancer diagnostics and bioengineering strategies for cancer therapy."
3382,The economics of long work hours: how economic incentives influence workplace practice,
3383,Biomarkers in the ICU: less is more? No,
3384,From the Editor's Desk…,
3385,Epithor,
3386,Approval of oliceridine (TRV130) for intravenous use in moderate to severe pain in adults,
3387,Adapting to ensure brachytherapy remains a vital component of our future,
3388,"In Patients with ARDS, Optimal PEEP Should Not Be Determined Using the Intersection of Relative Collapse and Relative Overdistention",
3389,"Reply to van den Berg and van der Hoeven: In Patients with ARDS, Optimal PEEP Should Not Be Determined Using the Intersection of Relative Collapse and Relative Overdistention",
3390,Mental health matters,
3391,Insights Into Addressing Structural Barriers and Building Specialty Diversity Through a Successful Pipeline Pathway Program,
3392,Correction to Lancet Psychiatry 7: e60,
3393,Global health: time for radical change?,
3394,Broadening the Tent with Intentional Spaces,
3395,Psychiatry in Lebanon,
3396,The USA and its discontents,
3397,Geospatial analysis: a new frontier in humanitarian health research?,
3398,India–China border standoff raises concerns on drug supplies,
3399,Bollywood on the brain: gender and mental health in Hindi cinema,
3400,External location of touch is constructed post-hoc based on limb choice,"When humans indicate on which hand a tactile stimulus occurred, they often err when their hands are crossed. This finding seemingly supports the view that the automatically determined touch location in external space affects limb assignment: the crossed right hand is localized in left space, and this conflict presumably provokes hand assignment errors. Here, participants judged on which hand the first of two stimuli, presented during a bimanual movement, had occurred, and then indicated its external location by a reach-to-point movement. When participants incorrectly chose the hand stimulated second, they pointed to where that hand had been at the correct, first time point, though no stimulus had occurred at that location. This behavior suggests that stimulus localization depended on hand assignment, not vice versa. It is, thus, incompatible with the notion of automatic computation of external stimulus location upon occurrence. Instead, humans construct external touch location post-hoc and on demand."
3401,Editorial for “Methods to characterize virus small RNAs and RNA structures”,
3402,Humanizing ICU COVID care,
3403,"Cost-effectiveness of hepatitis C virus screening, and subsequent monitoring or treatment among pregnant women in the Netherlands","BACKGROUND: The prevalence of diagnosed chronic hepatitis C virus (HCV) infection among pregnant women in the Netherlands is 0.26%, yet many cases remain undiagnosed. HCV screening and treatment of pregnant HCV carriers could reduce the burden of disease and limit vertical transmission from mother to child. We assessed the impact of HCV screening and subsequent treatment with new direct-acting antivirals (DAAs) among pregnant women in the Netherlands. METHODS: An HCV natural history Markov transition state model was developed, to evaluate the public-health and economic impact of HCV screening and treatment. Besides all 179,000 pregnant women in the Netherlands (cohort 1), we modelled 3 further cohorts: all 79,000 first-time pregnant women (cohort 2), 33,000 pregnant migrant women (cohort 3) and 16,000 first-time pregnant migrant women (cohort 4). Each cohort was analyzed in various scenarios: i no intervention, i.e., the current practice, ii screen-and-treat, i.e., the most extensive approach involving treatment of all individuals found HCV-positive, and iii screen-and-treat/monitor, i.e., a strategy involving treatment of symptomatic (F1–F4) patients and follow-up of asymptomatic (F0) HCV carriers with subsequent treatment only at progression. RESULTS: For all cohorts, comparison between scenarios (ii) and (i) resulted in ICERs between €9,306 and €10,173 per QALY gained and 5 year budget impacts varying between €6,283,830 and €19,220,405. For all cohorts, comparison between scenarios (iii) and (i) resulted in ICERs between €1,739 and €2,749 per QALY gained and budget impacts varying between €1,468,670 and €5,607,556. For all cohorts, the ICERs (scenario iii versus ii) involved in delayed treatment of asymptomatic (F0) HCV carriers varied between €56,607 and €56,892, well above the willingness-to-pay (WTP) threshold of €20,000 per QALY gained and even above a threshold of €50,000 per QALY gained. CONCLUSION: Universal screening for HCV among all pregnant women in the Netherlands is cost-effective. However, it would be reasonable to consider smaller risk groups in view of the budget impact of the intervention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10198-020-01236-2) contains supplementary material, which is available to authorized users."
3404,Optimal Management of Public Perceptions During A Flu Outbreak: A Game-Theoretic Perspective,"Public perceptions and sentiments play a crucial role in the success of vaccine uptake in the community. While vaccines have proven to be the best preventive method to combat the flu, the attitude and knowledge about vaccines are a major hindrance to higher uptake in most of the countries. The yearly coverage, especially in the vulnerable groups in the population, often remains below the herd immunity level despite the Flu Awareness Campaign organized by WHO every year worldwide. This brings immense challenges to the nation’s public health protection agency for strategic decision-making in controlling the flu outbreak every year. To understand the impact of public perceptions and vaccination decisions while designing optimal immunization policy, we model the individual decision-making as a two-strategy pairwise contest game, where pay-off is considered as a function of public health effort for the campaign. We use Pontryagin’s maximum principle to identify the best possible strategy for public health to implement vaccination and reduce infection at a minimum cost. Our optimal analysis shows that the cost of public health initiatives is qualitatively and quantitatively different under different public perceptions and attitudes towards vaccinations. When individual risk perception evolves with vaccine uptake or disease induced death, our model demonstrates a feed-forward mechanism in the dynamics of vaccination and exhibits an increase in vaccine uptake. Using numerical simulation, we also observe that the optimal cost can be minimized by putting the effort in the beginning and later part of the outbreak rather than during the peak. It confers that public health efforts towards disseminating disease severity or actual vaccination risk might accelerate the vaccination coverage and mitigate the infection faster."
3405,Certify Medical Students to Respond to National Crises,
3406,Phylogenetic analysis of infectious bronchitis virus circulating in southern China in 2016–2017 and evaluation of an attenuated strain as a vaccine candidate,"Avian infectious bronchitis (IB) is a highly contagious viral respiratory disease, caused by infectious bronchitis virus (IBV), that poses an important economic threat to the poultry industry. In recent years, genotypes GI-7, GI-13, and GI-19 have been the most prevalent IBV strains in China. However, in this study, we found that most IBV strains from southern China in 2016–2017 belonged to genotype GVI-1. This genotype, for which there is no vaccine, has been reported sporadically in the region. The GDTS13 strain, which caused severe IB outbreaks on the farms where it was isolated, was evaluated as a candidate vaccine strain. GDTS13 was serially passaged in specific-pathogen-free embryonated chicken eggs for 100 generations to produce GDTS13-F100. Safety testing indicated that GDTS13-F100 had no pathogenic effect on chickens. Additionally, GDTS13-F100 showed an excellent protective effect against GDTS13, with no clinical signs or virus shedding observed in immunized chickens challenged with the parent strain. These findings indicate that GVI-1 has become the most prevalent IBV genotype in southern China and that GDTS13-F100 may serve as an attenuated vaccine to protect against infection with this genotype. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04851-9) contains supplementary material, which is available to authorized users."
3407,Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins,"Protein ADP-ribosylation is a reversible post-translational modification that regulates important cellular functions. The identification of modified proteins has proven challenging and has mainly been achieved via enrichment methodologies. Random mutagenesis was used here to develop an engineered Af1521 ADP-ribose binding macro domain protein with 1000-fold increased affinity towards ADP-ribose. The crystal structure reveals that two point mutations K35E and Y145R form a salt bridge within the ADP-ribose binding domain. This forces the proximal ribose to rotate within the binding pocket and, as a consequence, improves engineered Af1521 ADPr-binding affinity. Its use in our proteomic ADP-ribosylome workflow increases the ADP-ribosylated protein identification rates and yields greater ADP-ribosylome coverage. Furthermore, generation of an engineered Af1521 Fc fusion protein confirms the improved detection of cellular ADP-ribosylation by immunoblot and immunofluorescence. Thus, this engineered isoform of Af1521 can also serve as a valuable tool for the analysis of cellular ADP-ribosylation under in vivo conditions."
3408,Digitalisierung in Orthopädie und Unfallchirurgie: Stand 2020 in Klinik und Praxis,"This article deals with the current state mid-2020 in the clinical and practical aspects from the perspective of orthopedics and trauma surgery. The risks, difficulties, potentials and options are discussed in detail. The following topics are specifically debated: infrastructure of telematics, apps and mobile health, online video consultation, electronic medical records and data protection. The advantages and disadvantages and the current state of each topic in the special case of orthopedics and trauma surgery are discussed. Additionally, seven meaningful examples from the field of digital applications are named. A survey of members of the Professional Association of Orthopedic and Trauma Surgeons (BVOU) is described and analyzed. In a concluding perspective the current hurdles and future topics that need clarification are addressed."
3409,"Antiseptic mouthwash, the nitrate–nitrite–nitric oxide pathway, and hospital mortality: a hypothesis generating review","Meta-analyses and several large cohort studies have demonstrated that antiseptic mouthwashes are associated with mortality in hospitalized patients. A clear pathogenic mechanism is lacking, leading to controversy and a reluctance to abandon or limit the use of antiseptic mouthwashes. Here, we generate the hypothesis that a disturbance in nitric oxide homeostasis by antiseptic mouthwashes may be responsible for the observed increase in mortality risk. Nitric oxide is essential in multiple physiological processes, and a reduction in nitric oxide bioavailability is associated with the occurrence or worsening of pathologies, such as atherosclerosis, diabetes, and sepsis. Oral facultative anaerobic bacteria are essential for the enterosalivary nitrate–nitrite–nitric oxide pathway due to their capacity to reduce nitrate to nitrite. Nitrate originates from dietary sources or from the active uptake by salivary glands of circulating nitrate, which is then excreted in the saliva. Because antiseptic mouthwashes eradicate the oral bacterial flora, this nitric oxide-generating pathway is abolished, which may result in nitric oxide-deficient conditions potentially leading to life-threatening complications such as ischaemic heart events or sepsis."
3410,"Phylogeny, recombination, and invasiveness of group B Streptococcus revealed by genomic comparisons of its global strains","Capsular polysaccharide (CPS) genes and pilus islands encode important virulence factors for group B Streptococcus (GBS) genomes. This study aims to detect phylogenetic inconsistency in CPS genes and pilus islands in GBSs and to explore its relationship with invasiveness. A total of 1016 GBS genomes were downloaded from the NCBI public database. The multi-locus sequence typing (MLST) and Bayesian analysis of Population Structure (BAPS) analyses were both conducted for phylogeny construction. Serotyping and pilus typing were determined in silico using the genomic sequences. The CPS and pilus typing results were generally consistent with MLST and BAPS clustering. GBS isolates of serotype II and of the PI-1 + PI-2b and PI-2a types were more prone to phylogenetic inconsistency than the others. Isolates of serotype Ib and of PI-1 + PI-2a were more likely to appear as colonizing strains, whereas PI-2b was more likely to appear in invasive strains. For serotype V, phylogenetic inconsistency occurred more commonly in colonizing isolates, while for serotype III, the opposite occurred. The present study profiles for the first time the phylogenetic inconsistency of CPS genes and pilus islands in global GBS isolates, which is helpful for infection control and the development of new vaccines for the prevention of GBS occurrence. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-020-04067-4) contains supplementary material, which is available to authorized users."
3411,Structural and functional analysis of protective antibodies targeting the threefold plateau of enterovirus 71,"Enterovirus 71 (EV71)-neutralizing antibodies correlate with protection and have potential as therapeutic agents. We isolate and characterize a panel of plasmablast-derived monoclonal antibodies from an infected child whose antibody response focuses on the plateau epitope near the icosahedral 3-fold axes. Eight of a total of 19 antibodies target this epitope and three of these potently neutralize the virus. Representative neutralizing antibodies 38-1-10A and 38-3-11A both confer effective protection against lethal EV71 challenge in hSCARB2-transgenic mice. The cryo-electron microscopy structures of the EV71 virion in complex with Fab fragments of these potent and protective antibodies reveal the details of a conserved epitope formed by residues in the BC and HI loops of VP2 and the BC and HI loops of VP3 spanning the region around the 3-fold axis. Remarkably, the two antibodies interact with the epitope in quite distinct ways. These plateau-binding antibodies provide templates for promising candidate therapeutics."
3412,ZIKV viral proteins and their roles in virus-host interactions,"The re-emergence of Zika virus (ZIKV) and its associated neonatal microcephaly and Guillain-Barré syndrome have led the World Health Organization to declare a global health emergency. Until today, many related studies have successively reported the role of various viral proteins of ZIKV in the process of ZIKV infection and pathogenicity. These studies have provided significant insights for the treatment and prevention of ZIKV infection. Here we review the current research advances in the functional characterization of the interactions between each ZIKV viral protein and its host factors."
3413,Early-onset sepsis in term infants admitted to neonatal intensive care units (2011–2016),"OBJECTIVES: Investigate characteristics of term infants culture-evaluated for early-onset sepsis (EOS) in neonatal intensive care units (NICUs), frequencies of organisms causing EOS, and factors associated with EOS. STUDY DESIGN: Using a cohort design, we identified term infants evaluated for EOS with blood, cerebrospinal fluid, or urine cultures in 326 NICUs (2011–2016). Using multivariable logistic regression, we investigated the association between EOS and demographic characteristics. RESULTS: Of 142,410 infants, 1197 (0.8%) had EOS, most commonly caused by group B Streptococcus (GBS; 40.6%). Lower EOS risk was associated with low Apgar score, Cesarean delivery, small for gestational age, prenatal antibiotic exposure, and positive or unknown maternal GBS screening result. Increased risk was associated with prolonged rupture of membranes, maternal age <19 years, vasopressor treatment, and ventilator support. CONCLUSION(S): GBS was the most frequent cause of EOS. Early risk factor recognition may help daily management of term infants in NICUs."
3414,"Efficacy of a Fosfomycin-Containing Regimen for Treatment of Severe Pneumonia Caused by Multidrug-Resistant Acinetobacter baumannii: A Prospective, Observational Study","INTRODUCTION: Severe pneumonia caused by multidrug-resistant Acinetobacter baumannii (MDR-AB) remains a difficult-to-treat infection. Considering the poor lung penetration of most antibiotics, the choice of the better antibiotic regimen is debated. METHODS: We performed a prospective, observational, multicenter study conducted from January 2017 to June 2020. All consecutive hospitalized patients with severe pneumonia due to MDR-AB were included in the study. The primary endpoint of the study was to evaluate risk factors associated with survival or death at 30 days from pneumonia onset. A propensity score for receiving therapy with fosfomycin was added to the model. RESULTS: During the study period, 180 cases of hospital-acquired pneumonia, including ventilator-associated pneumonia, caused by MDR-AB strains were observed. Cox regression analysis of factors associated with 30-day mortality, after propensity score, showed that septic shock, and secondary bacteremia were associated with death, while a fosfomycin-containing regimen was associated with 30-day survival. Antibiotic combinations with fosfomycin in definitive therapy for 44 patients were: fosfomycin + colistin in 11 (25%) patients followed by fosfomycin + carbapenem + tigecycline in 8 (18.2%), fosfomycin + colistin + tigecycline in 7 (15.9%), fosfomycin + rifampin in 7 (15.9%), fosfomycin + tigecycline in 6 (13.6%), fosfomycin + carbapenem in 3 (6.8%), and fosfomycin + aminoglycoside in 2 (4.5%). CONCLUSIONS: This real-life clinical experience concerning the therapeutic approach to severe pneumonia caused by MDR-AB provides useful suggestions to clinicians, showing the use of different antibiotic regimens with a predominant role for fosfomycin. Further randomized clinical trials are necessary to confirm or exclude these observations."
3415,51st Annual Meeting of the Society of Gynecologic Oncology(),
3416,Effect of Integrating Machine Learning Mortality Estimates With Behavioral Nudges to Clinicians on Serious Illness Conversations Among Patients With Cancer: A Stepped-Wedge Cluster Randomized Clinical Trial,"IMPORTANCE: Serious illness conversations (SICs) are structured conversations between clinicians and patients about prognosis, treatment goals, and end-of-life preferences. Interventions that increase the rate of SICs between oncology clinicians and patients may improve goal-concordant care and patient outcomes. OBJECTIVE: To determine the effect of a clinician-directed intervention integrating machine learning mortality predictions with behavioral nudges on motivating clinician-patient SICs. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial was conducted across 20 weeks (from June 17 to November 1, 2019) at 9 medical oncology clinics (8 subspecialty oncology and 1 general oncology clinics) within a large academic health system in Pennsylvania. Clinicians at the 2 smallest subspecialty clinics were grouped together, resulting in 8 clinic groups randomly assigned to the 4 intervention wedge periods. Included participants in the intention-to-treat analyses were 78 oncology clinicians who received SIC training and their patients (N = 14 607) who had an outpatient oncology encounter during the study period. INTERVENTIONS: (1) Weekly emails to oncology clinicians with SIC performance feedback and peer comparisons; (2) a list of up to 6 high-risk patients (≥10% predicted risk of 180-day mortality) scheduled for the next week, estimated using a validated machine learning algorithm; and (3) opt-out text message prompts to clinicians on the patient’s appointment day to consider an SIC. Clinicians in the control group received usual care consisting of weekly emails with cumulative SIC performance. MAIN OUTCOMES AND MEASURES: Percentage of patient encounters with an SIC in the intervention group vs the usual care (control) group. RESULTS: The sample consisted of 78 clinicians and 14 607 patients. The mean (SD) age of patients was 61.9 (14.2) years, 53.7% were female, and 70.4% were White. For all encounters, SICs were conducted among 1.3% in the control group and 4.6% in the intervention group, a significant difference (adjusted difference in percentage points, 3.3; 95% CI, 2.3-4.5; P < .001). Among 4124 high-risk patient encounters, SICs were conducted among 3.6% in the control group and 15.2% in the intervention group, a significant difference (adjusted difference in percentage points, 11.6; 95% CI, 8.2-12.5; P < .001). CONCLUSIONS AND RELEVANCE: In this stepped-wedge cluster randomized clinical trial, an intervention that delivered machine learning mortality predictions with behavioral nudges to oncology clinicians significantly increased the rate of SICs among all patients and among patients with high mortality risk who were targeted by the intervention. Behavioral nudges combined with machine learning mortality predictions can positively influence clinician behavior and may be applied more broadly to improve care near the end of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03984773"
3417,"Oseltamivir and inhaled zanamivir as influenza prophylaxis in Thai health workers: a randomized, double-blind, placebo-controlled safety trial over 16 weeks","OBJECTIVES: Long-term chemoprophylaxis using neuraminidase inhibitors may be needed during influenza epidemics but safety data are limited to several weeks. We sought to assess the tolerability of oseltamivir and zanamivir as primary prophylaxis over 16 weeks. METHODS: We conducted a parallel group, double blind, 2 (active drug) :1 (placebo) randomized trial of oral oseltamivir/placebo or inhaled zanamivir/placebo over 16 weeks in healthy, Thai hospital professionals at two Bangkok hospitals. The primary endpoint was study withdrawal due to drug-related (possibly, probably, definitely) serious or adverse events (AEs) graded ≥2. RESULTS: Recruited subjects numbered 129 oseltamivir/65 placebo and 131 zanamivir/65 placebo. A total of 102 grade ≥2 AEs were reported or detected in 69 subjects: 23/129 (17.8%) versus 15/65 (23.1%) (P = 0.26), and 23/131 (17.6%) versus 8/65 (12.3%) (P = 0.28). Intercurrent infections/fevers [26/102 (25.5%)], abnormal biochemistry [25/102 (24.5%)] and gastrointestinal symptoms [18/102 (17.6%)] were the most frequently reported AEs. There were no drug-related study withdrawals. Eight serious AEs were all due to intercurrent illnesses. Laboratory, lung function and ECG parameters were similar between drugs and placebos. CONCLUSIONS: Oseltamivir and zanamivir were well tolerated in healthy hospital professionals. Both drugs can be recommended for primary influenza prophylaxis for up to 16 weeks."
3418,Effect of Influenza A(H5N1) Vaccine Prepandemic Priming on CD4(+) T-Cell Responses,"Introduction. Previous priming with avian influenza vaccines results in more rapid and more robust neutralizing antibody responses upon revaccination, but the role CD4(+) T cells play in this process is not currently known. Methods. Human subjects previously enrolled in trials of inactivated influenza A(H5N1) vaccines and naive subjects were immunized with an inactivated subunit influenza A/Indonesia/5/05(H5N1) vaccine. Neutralizing antibody responses were measured by a microneutralization assay, and hemagglutinin (HA)-specific and nucleoprotein (NP)-specific CD4(+) T-cell responses were quantified using interferon γ enzyme-linked immunosorbent spot assays. Results. While vaccination induced barely detectable CD4(+) T-cell responses specific for HA in the previously unprimed group, primed subjects had readily detectable HA-specific memory CD4(+) T cells at baseline and mounted a more robust response to HA-specific epitopes after vaccination. There were no differences between groups when conserved NP-specific CD4(+) T-cell responses were examined. Interestingly, neutralizing antibody responses following revaccination were significantly higher in individuals who mounted a CD4(+) T-cell response to the H5 HA protein, a correlation not observed for NP-specific responses. Conclusions. These findings suggest that prepandemic vaccination results in an enriched population of HA-specific CD4(+) T cells that are recruited on rechallenge with a drifted vaccine variant and contribute to more robust and more rapid neutralizing antibody responses."
3419,Is arthroplaSty bEtter than interNal fixation for undiSplaced femoral nEck fracture? A national pragmatic RCT: the SENSE trial,"INTRODUCTION: Undisplaced femoral neck fractures (FNFs) are usually treated by internal fixation (IF) but two randomised controlled trials (RCTs) have demonstrated advantages of treatment with arthroplasty. The complication rate was lowered but there were no clinically improved patient-reported outcome measures (PROM), which could be due to underpowering or choice of selected PROM as the studies do appear to report a better functional outcome. We will conduct an RCT comparing IF with arthroplasties in patients aged over 65 years with an undisplaced FNF. METHODS AND ANALYSIS: All hospitals in Denmark treating patients with hip fracture can provide patients for this study; therefore, the study can be considered a national RCT. Patients over 65 years old with an undisplaced FNF will be screened for eligibility and patients will only be excluded if they are unable to understand the study information (due to dementia or language), if they have a posterior tilt >20°, a pathological fracture or they cannot walk. Participants will be electronically randomised (in alternating blocks of 4 or 6) into either IF or arthroplasty. Postoperative care will follow the department standards. Primary and secondary outcomes and measuring points have been established in collaboration with patients with hip fracture by focus group interviews. The primary outcome measure is the New Mobility Score assessed after 1 year. Secondary outcomes are the Oxford Hip Score, EuroQol 5 domain (EQ-5D-5L), degree of posterior tilt, pain Verbal Rating Scale, reoperation and mortality. ETHICS AND DISSEMINATION: The study is approved by the Danish Data Protection Agency (19/7429) and the scientific ethics committee (S-20180036). All participants will sign an informed consent before entering the trial. Because this is a national trial, all relevant healthcare professionals in Denmark will automatically receive the trial results that will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04075461)."
3420,"Burnout, anxiety and depression risk in medical doctors working in KwaZulu-Natal Province, South Africa: Evidence from a multi-site study of resource-constrained government hospitals in a generalised HIV epidemic setting","Globally, burnout in medical doctors (MDs) is concerning, with higher rates reported in studies conducted in South Africa (SA). This psychological syndrome leads to serious health consequences, and jeopardises patient care. Despite this, there is no data pertaining to these potential adverse mental health outcomes in KwaZulu-Natal (KZN) Province, SA, where it is overshadowed by the fight against priorities such as HIV and AIDS/TB. This study therefore aimed to establish the nature and extent of burnout, anxiety and depressive symptoms and their associations among public sector MDs in KZN. A cross sectional study was conducted among MDs at five KZN public sector training hospitals to investigate their associations with practitioner (individual) and organisational factors using the Maslach Burnout Inventory–Human Services Survey (MBI-HSS), the Generalised Anxiety Disorder-7 (GAD-7) questionnaire and the Patient Health Questionnaire-9 (PHQ-9). Of the 150 participants, 88 (59.0%) screened positive for burnout, as indicated by high scores on the emotional exhaustion or depersonalisation subscales in the MBI-HSS. One fifth screened positive for anxiety (n = 30) and depressive symptoms (n = 32). Burnout was significantly associated with individual factors of anxiety (p<0.01) and depressive (p<0.01) symptoms based on adjusted logistic regression models. Organisational factors, such as lack of clinical supervisor support (p<0.01) and hospital resources (p<0.01), were significantly associated with burnout based on the bivariate analyses. Burnout, anxiety and depressive symptoms in MDs are highly prevalent and intertwined in resource constrained KZN public training hospitals. Addressing burnout at individual and organisational levels is important to mitigate its adverse effects."
3421,"Editor’s introduction to this issue (G&I 18:3, 2020)",
3422,Students’ perspectives on interventions to reduce stress in medical school: A qualitative study,"The mental health of medical students remains to be a matter of concern. Numerous setting-based and individual-based interventions for student mental health have been proposed in the literature. However, the student perspective on those interventions has been largely neglected. This study aims to explore how medical students perceive different interventions and if they desire any additional changes with regard to their studies. Eight focus groups with 71 participants were conducted at a large German medical school. Focus groups were recorded, transcribed and content-analyzed using MAXQDA 18. We found that medical students prefer setting-based interventions. Most proposed interventions were on a setting-based level. For instance, students asked for more information on the university’s psychosocial counseling services and for better information management regarding contact persons. Interventions proposed in the literature received mixed reactions: Several participants did not favour a pass/fail grading system. Students considered a peer-to-peer mentoring program for freshmen very helpful. Students had diverse attitudes towards Balint groups. They approved of several self-management courses, most of them being related to time or stress management. Interestingly, the most urgently wanted interventions appear to be rather easy to implement (e.g. a mentoring program). This study explored the medical student perspective on student mental health interventions. Additionally, our study illustrates the benefit and feasibility of involving students early on in the conception of interventions. Further research with a representative sample is needed to obtain broader information on the acceptance of the suggested interventions."
3423,Using a patient-reported outcome to improve detection of cognitive impairment and dementia: The patient version of the Quick Dementia Rating System (QDRS),"INTRODUCTION: Community detection of mild cognitive impairment (MCI) and Alzheimer’s disease and related disorders (ADRD) is a challenge. While Gold Standard assessments are commonly used in research centers, these methods are time consuming, require extensive training, and are not practical in most clinical settings or in community-based research projects. Many of these methods require an informant (e.g., spouse, adult child) to provide ratings of the patients’ cognitive and functional abilities. A patient-reported outcome that captures the presence of cognitive impairment and corresponds to Gold Standard assessments could improve case ascertainment, clinical care, and recruitment into clinical research. We tested the patient version of the Quick Dementia Rating System (QDRS) as a patient-reported outcome to detect MCI and ADRD. METHODS: The patient QDRS was validated in a sample of 261 consecutive patient-caregiver dyads compared with the informant version of the QDRS, the Clinical Dementia Rating (CDR), neuropsychological tests, and Gold Standard measures of function, behavior, and mood. Psychometric properties including item variability, floor and ceiling effects, construct, concurrent, and known-groups validity, and internal consistency were determined. RESULTS: The patient QDRS strongly correlated with Gold Standard measures of cognition, function, mood, behavior, and global staging methods (p-values < .001) and had strong psychometric properties with excellent data quality and internal consistency (Cronbach alpha = 0.923, 95%CI:0.91–0.94). The patient QDRS had excellent agreement with the informant QDRS, the CDR and its sum of boxes (Intraclass Correlation Coefficients: 9.781–0.876). Receiver operator characteristic curves showed excellent discrimination between normal controls from CDR 0.5 (AUC:0.820;95% CI: 0.74–0.90) and for normal controls from any cognitive impairment (AUC:0.885;95% CI: 0.83–0.94). DISCUSSION: The patient QDRS validly and reliably differentiates individuals with and without cognitive impairment and can be completed by patients through all stages of dementia. The patient QDRS is highly correlated with Gold Standard measures of cognitive, function, behavior, and global staging. The patient QDRS provides a rapid method to screen patients for MCI and ADRD in clinical practice, determine study eligibility, improve case ascertainment in community studies."
3424,Treatment of severe pneumonia by hinokitiol in a murine antimicrobial-resistant pneumococcal pneumonia model,"Streptococcus pneumoniae is often isolated from patients with community-acquired pneumonia. Antibiotics are the primary line of treatment for pneumococcal pneumonia; however, rising antimicrobial resistance is becoming more prevalent. Hinokitiol, which is isolated from trees in the cypress family, has been demonstrated to exert antibacterial activity against S. pneumoniae in vitro regardless of antimicrobial resistance. In this study, the efficacy of hinokitiol was investigated in a mouse pneumonia model. Male 8-week-old BALB/c mice were intratracheally infected with S. pneumoniae strains D39 (antimicrobial susceptible) and NU4471 (macrolide resistant). After 1 h, hinokitiol was injected via the tracheal route. Hinokitiol significantly decreased the number of S. pneumoniae in the bronchoalveolar lavage fluid (BALF) and the concentration of pneumococcal DNA in the serum, regardless of whether bacteria were resistant or susceptible to macrolides. In addition, hinokitiol decreased the infiltration of neutrophils in the lungs, as well as the concentration of inflammatory cytokines in the BALF and serum. Repeated hinokitiol injection at 18 h intervals showed downward trend in the number of S. pneumoniae in the BALF and the concentration of S. pneumoniae DNA in the serum with the number of hinokitiol administrations. These findings suggest that hinokitiol reduced bacterial load and suppressed excessive host immune response in the pneumonia mouse model. Accordingly, hinokitiol warrants further exploration as a potential candidate for the treatment of pneumococcal pneumonia."
3425,Association of host proteins with the broad host range filamentous phage NgoΦ6 of Neisseria gonorrhoeae,"All Neisseria gonorrhoeae strains contain multiple copies of integrated filamentous phage genomes with undefined structures. In this study, we sought to characterize the capsid proteins of filamentous N. gonorrhoeae bacteriophage NgoΦ6 and phagemids propagated in different bacteria. The data demonstrate that purified phage contain phage-encoded structural proteins and bacterial host proteins; host proteins consistently copurified with the phage particles. The bacterial host proteins associated with the phage filament (as identified by mass spectrometry) tended to be one of the predominant outer membrane components of the host strain, plus minor additional host proteins. We were able to copurify a functional ß-lactamase, a phagemid-encoded protein, with phage filaments. We used protein modeling and immunological analysis to identify the major phage encoded structural proteins. The antigenic properties of these proteins depended on the bacterium where the phages were propagated. Polyclonal antibodies against N. gonorrhoeae phage NgoΦ6 recognized phage-encoded proteins if the phage was propagated in N. gonorrhoeae or H. influenzae cells but not if it was propagated in Salmonella or E. coli. We show that the phage filaments isolated from gonococci and Haemophilus are glycosylated, and this may explain the antigenic diversity seen. Taken en toto, the data demonstrate that while the neisserial filamentous phage are similar to other Inovirus with respect to overall genomic organization, their ability to closely associate with host proteins suggests that they have unique surface properties and are secreted by a here-to-fore unknown secretory pathway."
3426,Resensitizing carbapenem- and colistin-resistant bacteria to antibiotics using auranofin,"Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, bla(MBL) and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-β-lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of β-lactam and COL resistance. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-β-lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs."
3427,COVID-19 virus case fatality rate: how to avoid errors in calculation of data during the outbreak?,
3428,Primum non nocere (first do no harm). The SARS-CoV-2 pandemic course in oldest in Italy,"Dramatic outcomes of Covid-19 pandemia in Italy, in particular in the North, must be discussed. Maybe a bad strategy and lack of timely intervention togheter with concurrent social events, comorbidities of oldest persons, bed rest, inadequate nutritional support and drugs’ side effects and infection of health professionals proved fatal for many. (www.actabiomedica.it)"
3429,COVID-19 and Cities: from Urban Health strategies to the pandemic challenge. A Decalogue of Public Health opportunities,"BACKGROUND AND AIM OF THE WORK. The ongoing pandemic of COVID-19, which nowadays has exceeded 2.5 million notified infections in the world and about 200,000 deaths, is a strong reminder that urbanization has changed the way that people and communities live, work, and interact, and it’s necessary to make the systems and local capacities resilient to prevent the spread of infectious diseases. How we can re-design the concept of Public Health in relation to the built environment and the contemporary cities? METHODS. According to the previous statements and scenario, aim of this paper is to integrate the Urban Health strategic objectives, focusing the possible responses, both immediate and medium-long term, to the current environmental, social, and economic aspects of the “period” of physical distancing. RESULTS. Immediate Actions are 01. program the flexibility of city schedules; 02. plan a smart and sustainable mobility network; 03. define a neighborhood services’ plan; 04. develop a digitization of the urban context, promoting the smart communities; 05. re-think the accessibility to the places of culture and tourism. Medium-long term Actions are 06. design the indoor flexibility of domestic living spaces; 07. re-think building typologies, fostering the presence of semi-private or collective spaces; 08. renovate the basic care services’ network; 09. integrate the existing environmental emergency plans, with those related to the health emergencies; 10. improve stakeholders’ awareness of the factors affecting Public Health in the cities. CONCLUSIONS. The Decalogue of Public Health opportunities may provide a useful basis for Designers (Architects and Urban Planners), Policy Makers, Public Health experts and Local Health Agencies, in promoting actions and policies aimed to transform our cities in healthier and Salutogenic living environments. (www.actabiomedica.it)"
3430,The death rate for COVID-19 is positively associated with gross domestic products,
3431,AGP: A Multimethods Web Server for Alignment-Free Genome Phylogeny,"Phylogenetic analysis based on alignment method meets huge challenges when dealing with whole-genome sequences, for example, recombination, shuffling, and rearrangement of sequences. Thus, various alignment-free methods for phylogeny construction have been proposed. However, most of these methods have not been implemented as tools or web servers. Researchers cannot use these methods easily with their data sets. To facilitate the usage of various alignment-free methods, we implemented most of the popular alignment-free methods and constructed a user-friendly web server for alignment-free genome phylogeny (AGP). AGP integrated the phylogenetic tree construction, visualization, and comparison functions together. Both AGP and all source code of the methods are available at http://www.herbbol.org:8000/agp (last accessed February 26, 2013). AGP will facilitate research in the field of whole-genome phylogeny and comparison."
3432,"Fighting Flu: Military Pathology, Vaccines, and the Conflicted Identity of the 1918–19 Pandemic in Britain","This article explores the decisive role of British military medicine in shaping official approaches to the 1918 influenza pandemic. It contends that British approaches were defined through a system of military pathology, which had been established by the War Office as part of the mobilization of medicine for the First World War. Relying on the bacteriological laboratory for the identification and control of pathogenic agents, military pathology delivered therapeutic and preventive measures against a range of battlefield diseases, and military and civilian authorities trusted that it could do the same with influenza. This article traces how it shaped efforts to establish the etiology of the pandemic and to produce a general influenza vaccine. It highlights the challenges involved in both strategies. Understanding the central role of military pathology helps make sense of the nature, direction, scale, and limitations of medical mobilization against the pandemic in Britain and the authority accorded to specific medical bodies for elaborating and coordinating strategies. Crucially, it demands that we rethink the relationship between the war and pandemic as one about the social organization of medical knowledge and institutions."
3433,How Low Is the Risk of Influenza A(H5N1) Infection?,
3434,"Buy now, saved later? The critical impact of time-to-pandemic uncertainty on pandemic cost-effectiveness analyses","Background Investment in pandemic preparedness is a long-term gamble, with the return on investment coming at an unknown point in the future. Many countries have chosen to stockpile key resources, and the number of pandemic economic evaluations has risen sharply since 2009. We assess the importance of uncertainty in time-to-pandemic (and associated discounting) in pandemic economic evaluation, a factor frequently neglected in the literature to-date. Methods We use a probability tree model and Monte Carlo parameter sampling to consider the cost effectiveness of antiviral stockpiling in Cambodia under parameter uncertainty. Mean elasticity and mutual information (MI) are used to assess the importance of time-to-pandemic compared with other parameters. We also consider the sensitivity to choice of sampling distribution used to model time-to-pandemic uncertainty. Results Time-to-pandemic and discount rate are the primary drivers of sensitivity and uncertainty in pandemic cost effectiveness models. Base case cost effectiveness of antiviral stockpiling ranged between is US$112 and US$3599 per DALY averted using historical pandemic intervals for time-to-pandemic. The mean elasticities for time-to-pandemic and discount rate were greater than all other parameters. Similarly, the MI scores for time to pandemic and discount rate were greater than other parameters. Time-to-pandemic and discount rate were key drivers of uncertainty in cost-effectiveness results regardless of time-to-pandemic sampling distribution choice. Conclusions Time-to-pandemic assumptions can “substantially” affect cost-effectiveness results and, in our model, is a greater contributor to uncertainty in cost-effectiveness results than any other parameter. We strongly recommend that cost-effectiveness models include probabilistic analysis of time-to-pandemic uncertainty."
3435,A phenolic small molecule inhibitor of RNase L prevents cell death from ADAR1 deficiency,"The oligoadenylate synthetase (OAS)–RNase L system is an IFN-inducible antiviral pathway activated by viral infection. Viral double-stranded (ds) RNA activates OAS isoforms that synthesize the second messenger 2-5A, which binds and activates the pseudokinase-endoribonuclease RNase L. In cells, OAS activation is tamped down by ADAR1, an adenosine deaminase that destabilizes dsRNA. Mutation of ADAR1 is one cause of Aicardi-Goutières syndrome (AGS), an interferonopathy in children. ADAR1 deficiency in human cells can lead to RNase L activation and subsequent cell death. To evaluate RNase L as a possible therapeutic target for AGS, we sought to identify small-molecule inhibitors of RNase L. A 500-compound library of protein kinase inhibitors was screened for modulators of RNase L activity in vitro. We identified ellagic acid (EA) as a hit with 10-fold higher selectivity against RNase L compared with its nearest paralog, IRE1. SAR analysis identified valoneic acid dilactone (VAL) as a superior inhibitor of RNase L, with 100-fold selectivity over IRE1. Mechanism-of-action analysis indicated that EA and VAL do not bind to the pseudokinase domain of RNase L despite acting as ATP competitive inhibitors of the protein kinase CK2. VAL is nontoxic and functional in cells, although with a 1,000-fold decrease in potency, as measured by RNA cleavage activity in response to treatment with dsRNA activator or by rescue of cell lethality resulting from self dsRNA induced by ADAR1 deficiency. These studies lay the foundation for understanding novel modes of regulating RNase L function using small-molecule inhibitors and avenues of therapeutic potential."
3436,Transcriptional host–pathogen responses of Pseudogymnoascus destructans and three species of bats with white-nose syndrome,"Understanding how context (e.g., host species, environmental conditions) drives disease susceptibility is an essential goal of disease ecology. We hypothesized that in bat white-nose syndrome (WNS), species-specific host–pathogen interactions may partly explain varying disease outcomes among host species. We characterized bat and pathogen transcriptomes in paired samples of lesion-positive and lesion-negative wing tissue from bats infected with Pseudogymnoascus destructans in three parallel experiments. The first two experiments analyzed samples collected from the susceptible Nearctic Myotis lucifugus and the less-susceptible Nearctic Eptesicus fuscus, following experimental infection and hibernation in captivity under controlled conditions. The third experiment applied the same analyses to paired samples from infected, free-ranging Myotis myotis, a less susceptible, Palearctic species, following natural infection and hibernation (n = 8 sample pairs/species). Gene expression by P. destructans was similar among the three host species despite varying environmental conditions among the three experiments and was similar within each host species between saprophytic contexts (superficial growth on wings) and pathogenic contexts (growth in lesions on the same wings). In contrast, we observed qualitative variation in host response: M. lucifugus and M. myotis exhibited systemic responses to infection, while E. fuscus up-regulated a remarkably localized response. Our results suggest potential phylogenetic determinants of response to WNS and can inform further studies of context-dependent host–pathogen interactions."
3437,Effects of walkability on physical activity and obesity: a prospective observational study protocol,"INTRODUCTION: The prevalence of overweight and obesity is increasing worldwide, which could lead to a set of chronic and metabolic diseases. Physical activity is a modifiable factor for obesity, which was reported to be correlated with the built environment. However, the effects of the built environment on physical activity are not consistent. Walkability is a convenient way to assess the built environment. We aim to prospectively explore the relationship among walkability, physical activity and obesity in Chinese participants in Chongqing, a hilly city and provide evidence for future urban planning. METHODS AND ANALYSIS: Participants will be recruited from people who receive health examination in the Health Management Centre, the First Affiliated Hospital to Army Medical University. Exposure variables are WalkScores calculated within the areas around workplace and residential addresses of participants. The primary outcomes are body mass index measured through health examination at baseline and follow-ups, and daily walking steps recorded by WeChat mini application for 30 days after every time of health examination. Other health-related data of the participants will also be collected. Multivariate regression analysis will be performed to examine the relationship between exposure variables and outcomes. ETHICS AND DISSEMINATION: The Protocol is approved by the Ethics Committee of the First Affiliated Hospital to Army Medical University (KY201839). The results will be actively disseminated through peer-review journals and conference publications. REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1800017680)."
3438,Delayed Antibiotic Prescription by General Practitioners in the UK: A Stated-Choice Study,"Delayed antibiotic prescription in primary care has been shown to reduce antibiotic consumption, without increasing risk of complications, yet is not widely used in the UK. We sought to quantify the relative importance of factors affecting the decision to give a delayed prescription, using a stated-choice survey among UK general practitioners. Respondents were asked whether they would provide a delayed or immediate prescription in fifteen hypothetical consultations, described by eight attributes. They were also asked if they would prefer not to prescribe antibiotics. The most important determinants of choice between immediate and delayed prescription were symptoms, duration of illness, and the presence of multiple comorbidities. Respondents were more likely to choose a delayed prescription if the patient preferred not to have antibiotics, but consultation length had little effect. When given the option, respondents chose not to prescribe antibiotics in 51% of cases, with delayed prescription chosen in 21%. Clinical features remained important. Patient preference did not affect the decision to give no antibiotics. We suggest that broader dissemination of the clinical evidence supporting use of delayed prescription for specific presentations may help increase appropriate use. Establishing patient preferences regarding antibiotics may help to overcome concerns about patient acceptance. Increasing consultation length appears unlikely to affect the use of delayed prescription."
3439,Molecular Mechanisms of Immune Escape for Foot-and-Mouth Disease Virus,"Foot-and-mouth disease virus (FMDV) causes a highly contagious vesicular disease in cloven-hoofed livestock that results in severe consequences for international trade, posing a great economic threat to agriculture. The FMDV infection antagonizes the host immune responses via different signaling pathways to achieve immune escape. Strategies to escape the cell immune system are key to effective infection and pathogenesis. This review is focused on summarizing the recent advances to understand how the proteins encoded by FMDV antagonize the host innate and adaptive immune responses."
3440,Facile Synthesis of Antimicrobial Aloe Vera-“Smart” Triiodide-PVP Biomaterials,"Antibiotic resistance is an eminent threat for the survival of mankind. Nosocomial infections caused by multidrug resistant microorganisms are a reason for morbidity and mortality worldwide. Plant-based antimicrobial agents are based on synergistic mechanisms which prevent resistance and have been used for centuries against ailments. We suggest the use of cost-effective, eco-friendly Aloe Vera Barbadensis Miller (AV)-iodine biomaterials as a new generation of antimicrobial agents. In a facile, one-pot synthesis, we encapsulated fresh AV gel with polyvinylpyrrolidone (PVP) as a stabilizing agent and incorporated iodine moieties in the form of iodine (I(2)) and sodium iodide (NaI) into the polymer matrix. Ultraviolet-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), x-ray diffraction (XRD), microstructural analysis by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) verified the composition of AV-PVP-I(2), AV-PVP-I(2)-NaI. AV, AV-PVP, AV-PVP-I(2), AV-PVP-I(2)-NaI, and AV-PVP-NaI were tested in-vitro by disc diffusion assay and dip-coated on polyglycolic acid (PGA) sutures against ten microbial reference strains. All the tested pathogens were more susceptible towards AV-PVP-I(2) due to the inclusion of “smart” triiodides with halogen bonding in vitro and on dip-coated sutures. The biocomplexes AV-PVP-I(2), AV-PVP-I(2)-NaI showed remarkable antimicrobial properties. “Smart” biohybrids with triiodide inclusions have excellent antifungal and promising antimicrobial activities, with potential use against surgical site infections (SSI) and as disinfecting agents."
3441,Flavonoids as Potential anti-MRSA Agents through Modulation of PBP2a: A Computational and Experimental Study,"Recently, the interest in plant-derived antimicrobial agents has increased. However, there are no sufficient studies dealing with their modes of action. Herein, we investigate an in-house library of common plant-based phenolic compounds for their potential antibacterial effects against the methicillin-resistant Staphylococcus aureus (MRSA), a widespread life-threatening superbug. Flavonoids, which are considered major constituents in the plant kingdom, were found to be a promising class of compounds against MRSA, particularly the non-glycosylated ones. On the other hand, the glycosylated derivatives, along with the flavonolignan silibinin A, were able to restore the inhibitory activity of ampicillin against MRSA. To explore the mode of action of this class, they were subjected to an extensive inverse virtual screening (IVS), which suggested penicillin-binding protein 2a (PBP2a) as a possible target that mediates both the antibacterial and the antibiotic-synergistic effects of this class of compounds. Further molecular docking and molecular dynamic simulation experiments were conducted to support the primary IVS and the in vitro results and to study their binding modes with PBP2a. Our findings shed a light on plant-derived natural products, notably flavonoids, as a promising and readily available source for future adjuvant antimicrobial therapy against resistant strains."
3442,Color-Variable Photodynamic Antimicrobial Wool/Acrylic Blended Fabrics,"Towards the goal of developing scalable, economical and effective antimicrobial textiles to reduce infection transmission, here we prepared color-variable photodynamic materials comprised of photosensitizer (PS)-loaded wool/acrylic (W/A) blends. Wool fibers in the W/A blended fabrics were loaded with the photosensitizer rose bengal (RB), and the acrylic fibers were dyed with a variety of traditional cationic dyes (cationic yellow, cationic blue and cationic red) to broaden their color range. Investigations on the colorimetric and photodynamic properties of a series of these materials were implemented through CIELab evaluation, as well as photooxidation and antibacterial studies. Generally, the photodynamic efficacy of these dual-dyed fabrics was impacted by both the choice, and how much of the traditional cationic dye was employed in the dyeing of the W/A fabrics. When compared with the PS-only singly-dyed material, RB-W/A, that showed a 99.97% (3.5 log units; p = 0.02) reduction of Staphylococcus aureus under visible light illumination (λ ≥ 420 nm, 60 min), the addition of cationic dyes led to a slight decrease in the photoinactivation ability of the dual-dyed fabrics, but was still able to achieve a 99.3% inactivation of S. aureus. Overall, our findings demonstrate the feasibility and potential applications of low cost and color variable RB-loaded W/A blended fabrics as effective self-disinfecting textiles against pathogen transmission."
3443,A Novel Technique to Increase the Thickness of TiO₂ of Dental Implants by Nd: DPSS Q-sw Laser Treatment,"High bone–implant contact is a crucial factor in the achievement of osseointegration and long time clinical success of dental implants. Micro, nano, microtopography, and oxide layer of dental implants influence tissue response. The lasers were used for achieving an implant surface with homogeneous micro texturing and uncontaminated surface. The present study aimed to characterize the implant surfaces treated by Nd: DPSS Q-sw Laser treatment compared to machined implants. A total of 10 machined implants and 10 lasered surface implants were evaluated in this study. The implant surfaces were evaluated by X-ray Photoelectron Spectroscopy (XPS), Auger Electron Spectroscopy (AES), and metallography to characterize and measure the thickness of the oxide layer on the implant titanium surface. The machined surfaces showed a non-homogeneous oxide layer ranging between 20 and 30 nm. The lasered implant surfaces showed a homogeneous oxide layer ranging between 400 nm and 460 nm in the area of the laser holes, while outside the layer, thickness ranged between 200 nm and 400 nm without microcracks or evidence of damage. Another exciting result after this laser treatment is a topographically controlled, repeatable, homogeneous, and clean surface. This technique can obtain the implant surface without leaving residues of foreign substances on it. The study results indicate that the use of Nd: DPSS Q-sw laser produces a predictable and reproducible treatment able to improve the titanium oxide layer on the dental implant surface."
3444,The power of knowledge about dementia in Latin America across health professionals working on aging,"INTRODUCTION: Expert knowledge is critical to fight dementia in inequitable regions like Latin American and Caribbean countries (LACs). However, the opinions of aging experts on public policies’ accessibility and transmission, stigma, diagnostic manuals, data‐sharing platforms, and use of behavioral insights (BIs) are not well known. METHODS: We investigated opinions among health professionals working on aging in LACs (N = 3365) with regression models including expertise‐related information (public policies, BI), individual differences (work, age, academic degree), and location. RESULTS: Experts specified low public policy knowledge (X(2) = 41.27, P < .001), high levels of stigma (X(2) = 2636.37, P < .001), almost absent BI knowledge (X(2) = 56.58, P < .001), and needs for regional diagnostic manuals (X(2) = 2893.63, df = 3, P < .001) and data‐sharing platforms (X(2) = 1267.5, df = 3, P < .001). Lack of dementia knowledge was modulated by different factors. An implemented BI‐based treatment for a proposed prevention program improved perception across experts. DISCUSSION: Our findings help to prioritize future potential actions of governmental agencies and non‐governmental organizations (NGOs) to improve LACs’ dementia knowledge."
3445,"Factors associated with low contraceptive use amongst vulnerable mothers in South West State, Nigeria","BACKGROUND: Young mothers tend to be more prone to high maternal and perinatal risks and are thus deemed vulnerable to adverse sexual and reproductive health rights (SRHR) in terms of their right to choose contraceptives of their choice to enhance their maternal well-being and childbirth spacing should be well discussed. Achieving sufficient SRHR may be averted if the use of family planning by disadvantaged groups is not given required attention. AIM: This study aimed to identify and analyse the factors associated with the low use of contraceptives amongst vulnerable women in the South West region in Nigeria. SETTING: The study area was purposively chosen to capture contraceptive use amongst vulnerable women in Osun State, Nigeria. METHODS: A primary data collection was done in three senatorial districts of Osun State, Nigeria, with 140 respondents each to give a total of 420 respondents. Collected data were analysed using univariate, bivariate and multivariate measures. RESULTS: The result showed a magnitude of association and relationship at both levels of analyses. Living arrangements and family types were 89% and 88.3%, respectively, associated with family planning use. In the same vein, living arrangement and family types were also statistically significant at p < 0.05with an odds ratio of 0.23 (95% CI: 0.1184–0.4583) and an odds ratio of 0.35 (95% CI: 0.1756–0.6970) with family planning use, respectively. CONCLUSION: We concluded that policies and interventions to accelerate and encourage contraceptives use amongst vulnerable mothers in South West, Nigeria should be targeted at those whose husbands lived elsewhere and those whose husbands have more than one wife."
3446,"Figuring it out by yourself: Perceptions of home-based care of stroke survivors, family caregivers and community health workers in a low-resourced setting, South Africa","BACKGROUND: In less resourced settings, formal rehabilitation services for stroke survivors were often absent. Stroke survivors were referred to community health workers (CHWs) who were untrained in rehabilitation. AIM: To describe the experience and perceived needs of stroke survivors, their caregivers and CHWs in a context with limited access to and support from formal rehabilitation services. SETTING: The Breede Valley subdistrict, Western Cape, South Africa, a rural, less resourced setting. METHODS: A descriptive exploratory qualitative study. Four focus group interviews were held with purposively selected stroke survivors and caregivers and four with CHWs. A thematic approach and the framework method were used to analyse the transcripts. FINDINGS: A total of 41 CHWs, 21 caregivers and 26 stroke survivors participated. Four main themes and 11 sub-themes were identified. Because of the lack of knowledge, training and rehabilitation services, the main theme for all groups was having to ‘figure things out’ independently, with incontinence management being particularly challenging. Secondly was the need for emotional support for stroke survivors and caregivers. Thirdly, contextual factors such as architectural barriers and lack of assistive products negatively impacted care and function. Lastly, the organisation of health and rehabilitation services negatively impacted home-based services and professional support. CONCLUSIONS: With appropriate training, the CHWs can be pivotal in the training and support of family caregivers and stroke survivors. Care pathways and the role and scope of both CHWs and therapists in home-based stroke rehabilitation should be defined and restructured, including the links with formal services."
3447,Evolving consensus on managing vitreo-retina and uvea practice in post-COVID-19 pandemic era,
3448,Mitteilungen der DGKFO,
3449,Protection against Borreliella burgdorferi infection mediated by a synthetically engineered DNA vaccine,"Lyme disease is the most common vector-borne disease in North America. The etiological agent is the spirochete Borreliella burgdorferi, transmitted to mammalian hosts by the Ixodes tick. In recent years there has been an increase in the number of cases of Lyme disease. Currently, there is no vaccine on the market for human use. We describe the development of a novel synthetically engineered DNA vaccine, pLD1 targeting the outer-surface protein A (OspA) of Borreliella burgdorferi. Immunization of C3 H/HeN mice with pLD1 elicits robust humoral and cellular immune responses that confer complete protection against a live Borreliella burgdorferi bacterial challenge. We also assessed intradermal (ID) delivery of pLD1 in Hartley guinea pigs, demonstrating the induction of robust and durable humoral immunity that lasts at least 1 year. We provide evidence of the potency of pLD1 by showing that antibodies targeting the OspA epitopes which have been associated with protection are prominently raised in the immunized guinea pigs. The described study provides the basis for the advancement of pDL1 as a potential vaccine for Lyme disease control."
3450,Neutralization of hepatitis B virus by a novel DNA-encoded monoclonal antibody,"Hepatitis B virus (HBV) causes a potentially life-threatening liver infection that frequently results in life-long chronic infection. HBV is responsible for 887,000 deaths each year, most resulting from chronic liver diseases and hepatocellular carcinoma. Presently, there are 250 million chronic HBV carriers worldwide who are at a high risk for developing cirrhosis and hepatocellular carcinoma (HCC). HCC is the most common type of liver cancer with a strong association with HBV infection. HBV transmission through blood transfusions and perinatal transfer from infected mother to child have been common routes of infection. In the present study, we describe the development of a synthetic DNA plasmid encoding an anti-HBV human monoclonal antibody specific for the common “a determinant region” of HBsAg of hepatitis B virus and demonstrate the ability of this platform at directing in vivo antibody expression. In vivo delivery of this DNA encoded monoclonal antibody (DMAb) plasmid in mice resulted in expression of human IgG over a period of one month following a single injection. Serum antibody was found to recognize the relevant conformational epitope from plasma purified native HBsAg as well as bound HBV in HepG2.2.15 cells. The serum DMAb efficiently neutralized HBV and prevented infection of HepaRG cells in vitro. Additional study of these HBV-DMAb as a possible therapy or immunoprophylaxis for HBV infection is warranted."
3451,Inhibiting the two-component system GraXRS with verteporfin to combat Staphylococcus aureus infections,"Infections caused by Staphylococcus aureus pose a serious and sometimes fatal health issue. With the aim of exploring a novel therapeutic approach, we chose GraXRS, a Two-Component System (TCS) that determines bacterial resilience against host innate immune barriers, as an alternative target to disarm S. aureus. Following a drug repurposing methodology, and taking advantage of a singular staphylococcal strain that lacks the whole TCS machinery but the target one, we screened 1.280 off-patent FDA-approved drug for GraXRS inhibition. Reinforcing the connection between this signaling pathway and redox sensing, we found that antioxidant and redox-active molecules were capable of reducing the expression of the GraXRS regulon. Among all the compounds, verteporfin (VER) was really efficient in enhancing PMN-mediated bacterial killing, while topical administration of such drug in a murine model of surgical wound infection significantly reduced the bacterial load. Experiments relying on the chemical mimicry existing between VER and heme group suggest that redox active residue C227 of GraS participates in the inhibition exerted by this FDA-approved drug. Based on these results, we propose VER as a promising candidate for sensitizing S. aureus that could be helpful to combat persistent or antibiotic-resistant infections."
3452,Real-time PCR on skin biopsies for super-spreaders’ detection in bovine besnoitiosis,"BACKGROUND: Bovine besnoitiosis, an emerging disease in Europe that can be transmitted by vectors, is caused by the apicomplexan Besnoitia besnoiti. Bovine besnoitiosis is difficult to control due to the complexity of its diagnosis in the acute stage of the disease, poor treatment success and chronically asymptomatic cattle acting as parasite reservoirs. When serological prevalence is low, detection and specific culling of seropositive cattle is feasible; however, economic considerations preclude this approach when serological prevalence is high. The aims of this study were to evaluate the accuracy of detection of super-spreaders in highly infected herds and to test their selective elimination as a new control strategy for bovine besnoitiosis. METHODS: Previous real-time PCR analyses performed on skin tissues from 160 asymptomatic animals sampled at slaughterhouses showed that the tail base was the best location to evaluate the dermal parasite DNA load. All seropositive animals (n = 518) from eight dairy or beef cattle farms facing a high serological prevalence of besnoitiosis were sampled at the tail base and their skin sample analysed by real-time PCR. A recommendation of rapid and selective culling of super-spreaders was formulated and provided to the cattle breeders. Subsequent serological monitoring of naïve animals was used to evaluate the interest of this control strategy over time. RESULTS: Among the 518 seropositive animals, a low proportion of individuals (14.5%) showed Cq values below 36, 17.8% had doubtful results (36 < Cq ≤ 40) and 67.8% had negative PCR results. These proportions were grossly similar on the eight farms, regardless of their production type (beef or dairy cattle), size, geographical location or history of besnoitiosis. Within two weeks of the biopsy, the rapid culling of super-spreaders was implemented on only three farms. The numbers of newly infected animals were lower on these farms compared to those where super-spreaders were maintained in the herd. CONCLUSIONS: Real-time PCR analyses performed on skin biopsies of seropositive cattle showed huge individual variabilities in parasite DNA load. The rapid culling of individuals considered as super-spreaders seems to be a new and encouraging strategy for bovine besnoitiosis control. [Image: see text]"
3453,Is There a Genetic Predisposition to Postoperative Adhesion Development?,"Adhesions are permanent fibrovascular bands between peritoneal surfaces, which develop following virtually all body cavity surgeries. The susceptibility to develop, and the severity, of adhesions following intra-abdominal surgery varies within and between individuals, suggesting that heritable factors influence adhesion development. In this manuscript, we discuss the pathophysiology of adhesion development from the perspective of genetic susceptibility. We restrict our discussion to genes and single-nucleotide polymorphisms (SNPs) that are specifically involved in, or that cause modification of, the adhesion development process. We performed a literature search using the PubMed database for all relevant English language articles up to March 2020 (n = 186). We identified and carefully reviewed all relevant articles addressing genetic mutations or single-nucleotide polymorphisms (SNPs) that impact the risk for adhesion development. We also reviewed references from these articles for additional information. We found several reported SNPs, genetic mutations, and upregulation of messenger RNAs that directly or indirectly increase the propensity for postoperative adhesion development, namely in genes for transforming growth factor beta, vascular endothelial growth factor, interferon-gamma, matrix metalloproteinase, plasminogen activator inhibitor-1, and the interleukins. An understanding of genetic variants could provide insight into the pathophysiology of adhesion development. The information presented in this review contributes to a greater understanding of adhesion development at the genetic level and may allow modification of these genetic risks, which may subsequently guide management in preventing and treating this challenging complication of abdominal surgery. In particular, the information could help identify patients at greater risk for adhesion development, which would make them candidates for anti-adhesion prophylaxis. Currently, agents to reduce postoperative adhesion development exist, and in the future, development of agents, which specifically target individual genetic profile, would be more specific in preventing intraperitoneal adhesion development."
3454,"Gravitational distribution of regional opening and closing pressures, hysteresis and atelectrauma in ARDS evaluated by electrical impedance tomography","BACKGROUND: The physiological behavior of lungs affected by the acute respiratory distress syndrome (ARDS) differs between inspiration and expiration and presents heterogeneous gravity-dependent distribution. This phenomenon, highlighted by the different distribution of opening/closing pressure and by the hysteresis of the pressure–volume curve, can be studied by CT scan, but the technique expose the patient to radiations, cannot track changes during time and is not feasible at the bedside. Electrical impedance tomography (EIT) could help in assessing at the bedside regional inspiratory and expiratory mechanical properties. We evaluated regional opening/closing pressures, hysteresis and atelectrauma during inspiratory and expiratory low-flow pressure–volume curves in ARDS using electrical impedance tomography. METHODS: Pixel-level inspiratory and expiratory PV curves (PV(pixel)) between 5 and 40 cmH(2)O were constructed integrating EIT images and airway opening pressure signal from 8 ARDS patients. The lower inflection point in the inspiratory and expiratory PV(pixel) were used to find opening (OP(pixel)) and closing (CP(pixel)) pressures. A novel atelectrauma index (AtI) was calculated as the percentage of pixels opening during the inspiratory and closing during the expiratory PV curves. The maximal hysteresis (HysMax) was calculated as the maximal difference between normalized expiratory and inspiratory PV curves. Analyses were conducted in the global, dependent and non-dependent lung regions. RESULTS: Gaussian distribution was confirmed for both global OP(pixel) (r(2) = 0.90) and global CP(pixel) (r(2) = 0.94). The two distributions were significantly different with higher values for OP(pixel) (p < 0.0001). Regional OP(pixel) and CP(pixel) distributions were Gaussian, and in the dependent lung regions, both were significantly higher than in the non-dependent ones (p < 0.001). Both AtI and the HysMax were significantly higher in the dependent regions compared to the non-dependent ones (p < 0.05 for both). CONCLUSIONS: Gravity impacts the regional distribution of opening and closing pressure, hysteresis and atelectrauma, with higher values in the dorsal lung. Regional differences between inspiratory and expiratory lung physiology are detectable at the bedside using EIT and could allow in-depth characterization of ARDS phenotypes and guide personalized ventilation settings. GRAPHIC ABSTRACT: [Image: see text]"
3455,Mitteilungen der DGIM,
3456,Mitteilungen des BDI,
3457,Webinar zur S1-Leitlinie: „Interdisziplinär abgestimmte Empfehlungen zum Personal- und Patientenschutz bei Durchführung planbarer Eingriffe zur Zeit der SARS-CoV-2-Pandemie“,
3458,Severe bronchopulmonary dysplasia: outcomes before and after the implementation of an inpatient multidisciplinary team,"OBJECTIVE: Severe bronchopulmonary dysplasia (sBPD) can lead to long term morbidity. We created a sBPD multidisciplinary team in 2011 to optimize care and improve outcomes. STUDY DESIGN: Retrospective chart review of three groups between 2008 and 2016: patients with sBPD born before 2011, patients with sBPD born after 2011, and patients with moderate BPD born after 2011. RESULTS: Infants with sBPD after 2011 had a shorter NICU length of stay compared with children born before 2011 (mean 140 days vs 170 days p < 0.007), weighed more at discharge (z-score −0.8 vs −1.35 p = 0.01), had less failure to thrive post discharge (32% vs 51% p = 0.05) and had more well visits in the first six months of life (mean 6.7 vs 5.3 p = 0.04). No difference was observed in the rate of readmissions in the first two years of life. CONCLUSION: Our multidisciplinary team has improved the inpatient management of patients with sBPD."
3459,Prediction of rifampicin resistance beyond the RRDR using structure-based machine learning approaches,"Rifampicin resistance is a major therapeutic challenge, particularly in tuberculosis, leprosy, P. aeruginosa and S. aureus infections, where it develops via missense mutations in gene rpoB. Previously we have highlighted that these mutations reduce protein affinities within the RNA polymerase complex, subsequently reducing nucleic acid affinity. Here, we have used these insights to develop a computational rifampicin resistance predictor capable of identifying resistant mutations even outside the well-defined rifampicin resistance determining region (RRDR), using clinical M. tuberculosis sequencing information. Our tool successfully identified up to 90.9% of M. tuberculosis rpoB variants correctly, with sensitivity of 92.2%, specificity of 83.6% and MCC of 0.69, outperforming the current gold-standard GeneXpert-MTB/RIF. We show our model can be translated to other clinically relevant organisms: M. leprae, P. aeruginosa and S. aureus, despite weak sequence identity. Our method was implemented as an interactive tool, SUSPECT-RIF (StrUctural Susceptibility PrEdiCTion for RIFampicin), freely available at https://biosig.unimelb.edu.au/suspect_rif/."
3460,Shifts in broadband power and alpha peak frequency observed during long-term isolation,"Prolonged periods of social isolation and spatial confinement do not only represent an issue that needs to be faced by a few astronauts during space missions, but can affect all of us as recently shown during pandemic situations. The fundamental question, how the brain adapts to periods of sensory deprivation and re-adapts to normality, has only received little attention. Here, we use eyes closed and eyes open resting-state electroencephalographic (EEG) recordings to investigate how neural activity is altered during 120 days of isolation in a spatially confined, space-analogue environment. After disentangling oscillatory patterns from 1/f activity, we show that isolation leads to a reduction in broadband power and a flattening of the 1/f spectral slope. Beyond that, we observed a reduction in alpha peak frequency during isolation, but did not find strong evidence for isolation-induced changes that are of oscillatory nature. Critically, all effects reversed upon release from isolation. These findings suggest that isolation and concomitant sensory deprivation lead to an enhanced cortical deactivation which might be explained by a reduction in the mean neuronal population firing rate."
3461,Endotracheales Absaugen,
3462,FDS calls for dentistry 'to be kept open' throughout pandemic,
3463,Thank you Covidentologists,
3464,Why PAPR suits us,
3465,Neuromuscular blocking agents in acute respiratory distress syndrome: updated systematic review and meta-analysis of randomized trials,"PURPOSE: Existing clinical practice guidelines support the use of neuromuscular blocking agents (NMBA) in acute respiratory distress syndrome (ARDS); however, a recent large randomized clinical trial (RCT) has questioned this practice. Therefore, we updated a previous systematic review to determine the efficacy and safety of NMBAs in ARDS. METHODS: We searched MEDLINE, EMBASE (October 2012 to July 2019), the Cochrane (Central) database, and clinical trial registries (ClinicalTrials.gov, ISRCTN Register, and WHO ICTRP) for RCTs comparing the effects of NMBA as a continuous infusion versus placebo or no NMBA infusion (but allowing intermittent NMBA boluses) on patient-important outcomes for adults with ARDS. Two independent reviewers assessed the methodologic quality of the primary studies and abstracted data. RESULTS: Seven RCTs, including four new RCTs, met eligibility criteria for this review. These trials enrolled 1598 patients with moderate to severe ARDS at centers in the USA, France, and China. All trials assessed short-term continuous infusions of cisatracurium or vecuronium. The pooled estimate for mortality outcomes showed significant statistical heterogeneity, which was only explained by a subgroup analysis by depth of sedation in the control arm. A continuous NMBA infusion did not improve mortality when compared to a light sedation strategy with no NMBA infusion (relative risk [RR] 0.99; 95% CI 0.86–1.15; moderate certainty; P = 0.93). On the other hand, continuous NMBA infusion reduced mortality when compared to deep sedation with as needed NMBA boluses (RR 0.71; 95% CI 0.57–0.89; low certainty; P = 0.003). Continuous NMBA infusion reduced the rate of barotrauma (RR 0.55; 95% CI 0.35–0.85, moderate certainty; P = 0.008) across eligible trials, but the effect on ventilator-free days, duration of mechanical ventilation, and ICU-acquired weakness was uncertain. CONCLUSIONS: Inconsistency in study methods and findings precluded the pooling of all trials for mortality. In a pre-planned sensitivity analysis, the impact of NMBA infusion on mortality depends on the strategy used in the control arm, showing reduced mortality when compared to deep sedation, but no effect on mortality when compared to lighter sedation. In both situations, a continuous NMBA infusion may reduce the risk of barotrauma, but the effects on other patient-important outcomes remain unclear. Future research, including an individual patient data meta-analysis, could help clarify some of the observed findings in this updated systematic review."
3466,Dental Fallow Time Calculator launched,
3467,Storytelling,
3468,BAOMS welcomes call for ring-fenced hospital beds,
3469,Winter is coming,
3470,Frugal solutions,
3471,"Ripples, under-currents and tsunamis",
3472,An equity-oriented rethink of global rankings with complex networks mapping development,"Nowadays, world rankings are promoted and used by international agencies, governments and corporations to evaluate country performances in a specific domain, often providing a guideline for decision makers. Although rankings allow a direct and quantitative comparison of countries, sometimes they provide a rather oversimplified representation, in which relevant aspects related to socio-economic development are either not properly considered or still analyzed in silos. In an increasingly data-driven society, a new generation of cutting-edge technologies is breaking data silos, enabling new use of public indicators to generate value for multiple stakeholders. We propose a complex network framework based on publicly available indicators to extract important insight underlying global rankings, thus adding value and significance to knowledge provided by these rankings. This approach enables the unsupervised identification of communities of countries, establishing a more targeted, fair and meaningful criterion to detect similarities. Hence, the performance of states in global rankings can be assessed based on their development level. We believe that these evaluations can be crucial in the interpretation of global rankings, making comparison between countries more significant and useful for citizens and governments and creating ecosystems for new opportunities for development."
3473,The Value of Case Reports in Systematic Reviews from Rare Diseases. The Example of Enzyme Replacement Therapy (ERT) in Patients with Mucopolysaccharidosis Type II (MPS-II),Background: Case reports are usually excluded from systematic reviews. Patients with rare diseases are more dependent on novel individualized strategies than patients with common diseases. We reviewed and summarized the novelties reported by case reports in mucopolysaccharidosis type II (MPS-II) patients treated with enzyme replacement therapy (ERT). Methods: We selected the case reports included in a previous meta-analysis of patients with MPS-II treated with ERT. Later clinical studies evaluating the same topic of those case reports were reported. Our primary aim was to summarize novelties reported in previous case reports. Secondary objectives analyzed the number of novelties evaluated in subsequent clinical studies and the time elapsed between the publication of the case report to the publication of the clinical study. Results: We identified 11 innovative proposals in case reports that had not been previously considered in clinical studies. Only two (18.2%) were analyzed in subsequent nonrandomized cohort studies. The other nine novelties (81.8%) were analyzed in later case reports (five) or were not included in ulterior studies (four) after more than five years from their first publication. Conclusions: Case reports should be included in systematic reviews of rare disease to obtain a comprehensive summary of the state of research and offer valuable information for healthcare practitioners.
3474,Immunoinformatic-Based Prediction of Candidate Epitopes for the Diagnosis and Control of Paratuberculosis (Johne’s Disease),"Paratuberculosis is an infectious disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). MAP is an intracellular pathogen with a possible zoonotic potential since it has been successfully isolated from the intestine and blood of Crohn’s disease patients.Since no cure is available, after the detection of the disease, animal culling is the sole applicable containment strategy. However, the difficult detection of the disease in its subclinical form, facilitates its spread raising the need for the development of effective diagnosis and vaccination strategies. The prompt identification and isolation of the infected animals in the subclinical stage would prevent the spread of the infection.In the present study, an immunoinformatic approach has been used to investigate the immunogenic properties of 10 MAP proteins. These proteins were chosen according to a previously published immunoproteomics approach. For each previously-described immunoreactive protein, we predicted the epitopes capable of eliciting an immune response by binding both B-cells and/or class I MHC antigens. The retrieved peptide sequences were analyzed for their specificity and cross-reactivity. The final aim is to employ the discovered peptides sequences as a filtered library useful for early-stage diagnosis and/or to be used in novel multi-subunit or recombinant vaccine formulations."
3475,Echocardiography in Autoimmune Rheumatic Diseases for Diagnosis and Prognosis of Cardiovascular Complications,"Autoimmune rheumatic diseases are systemic diseases frequently affecting the heart and vessels. The main cardiovascular complications are pericarditis, myocarditis, valvular disease, obstructive coronary artery disease and coronary microcirculatory dysfunction, cardiac failure and pulmonary hypertension. Echocardiography, including transthoracic two and three-dimensional echocardiography, Doppler imaging, myocardial deformation and transesophageal echo, is an established and widely available imaging technique for the identification of cardiovascular manifestations that are crucial for prognosis in rheumatic diseases. Echocardiography is also important for monitoring the impact of drug treatment on cardiac function, coronary microcirculatory function, valvular function and pulmonary artery pressures. In this article we summarize established and evolving knowledge on the role of echocardiography for diagnosis and prognosis of cardiovascular abnormalities in rheumatic diseases."
3476,Are Health Literacy and Lifestyle of Undergraduates Related to the Educational Field? An Italian Survey,"Background: Health literacy (HL) is a fundamental ability to successfully deal with health and illness issues. This study aimed to assess HL among undergraduates from healthcare and non-healthcare degree courses of two Italian universities and the association between their HL, lifestyles, and BMI assumed as health outcome. Methods: The Health Literacy Assessment Tool (HLAT-8) and the Newest Vital Sign (NVS) were used to assess health literacy dimensions. Demographic and anthropometric data, adherence to Mediterranean diet (MD), physical activity levels, and smoking habits were assessed in the enrolled sample to highlight possible associations. Results: A total sample of 806 undergraduates (46% males, mean age 21.01 ± 1.78 years) was recruited. Higher HL scores were found among healthcare rather than non-healthcare students (28.7 ± 4.5 vs. 26.7 ± 4.2 for HLAT-8 and 4.9 ± 1.5 vs. 3.9 ± 1.8 for NVS, p < 0.01). However, healthcare undergraduates were more likely to report unhealthy behaviors. Body Mass Index (BMI) was associated with literacy and numeracy skills only in non-healthcare undergraduates. Significant associations were found between HL scores and adherence to MD in both groups. In the regression analysis, educational field and MD were shown to be predictors of HL scores. Conclusions: Attending a healthcare related degree course was associated with higher HL scores but not with healthy behaviors. This issue should be addressed considering the role that healthcare professionals may have in educating patients towards a healthy lifestyle. Adherence to MD seems to be related to higher HL scores."
3477,Organoids in Translational Oncology,"Translational medicine aims to translate the most promising preclinical research into clinical practice. Oncology is a continuously growing medical field: the scientific research on cancer biology is currently based on in vitro experiments, carried out on tissue culture plates (TCPs) and other 2D samples. In this context, 3D printing has greatly improved the biofabrication of new biological matrices that mimic the extracellular environments, which may characterize healthy from cancerous tissues. Organoids have recently been described in several reports on scientific literature. The term that better describes such organoids-based tumoral tissues is “tumoroids”. Tumoroids are substantially “tumor-like organoids”, typically deriving from primary tumors harvested from patients. This topical review aims to give an update on organoids applied in translational medicine, paying specific attention to their use in the investigation of the main molecular mechanisms of cancer onset and growth, and on the most impacting strategies for effective targeted therapies."
3478,Back Pain in Rare Diseases: A Comparison of Neck and Back Pain between Spinal Cord Ischemia and Spinal Dural Arteriovenous Fistula,"Neck and back pain may be noted like a first symptom in rare diseases: spinal cord ischemia and spinal dural arteriovenous fistula (SDAVF). Spinal cord ischemia is a rarer pathology, compared with cerebral ischemia, yet the morbidity and mortality are comparable in both cases; furthermore, classifying the acute loss of function in the spine, encountered in spinal cord ischemia as an important neurological entity. SDAVF presents the same clinical symptoms as spinal cord ischemia, but even though it has a progressive character, the impact in the quality of patients’ lives being equally as important. Between August 2012–August 2017 we admitted through the hospital emergency department 21 patients with spinal cord ischemia and 11 patients with SDAVF (only self-casuistry). Demographic (age, gender), clinical, imagistic (Magnetic Resonance Angiography, Magnetic Resonance Imaging), paraclinical data as well as history, time to diagnosis, the visual analogue scale for pain (VAS score), risk factors, surgical and medical treatment, evolution, neurorehabilitation, were all used to compare the two lots of patients. The aim of this study was to observe potential differences in the demographics, symptomatology, VAS scores and treatment in comparison for spinal cord ischemia and SDAVF, to facilitate the further recognition and management in these diseases. In group A we have 21 patients with spinal cord ischemia (14 females, 7 males). The median age was 41.3 years (range 19–64). The median time to diagnosis was 7 h. The most frequent symptoms were acute neck or back pain at onset (100%), motor deficits (95.24%), sensory loss (85.72%), and sphincters problems (90.48%). The most common location was the lumbosacral spine (14 cases; 66.67%; p-value = 0.03) for spinal cord ischemia and the thoracic spine (7 cases, 63.64%; p-value = 0.065) for SDAVF. The treatment of spinal cord ischemia was medical. In group B we included 11 patients (6 females, 5 males). The median age was 52.6 years (range 28–74). The median time to diagnosis was 3 months (range 2 days–14 months). Patients have progressive symptoms: neck or back pain (100%), gait disturbances (100%) and abnormalities of micturition (100%). The treatment of SDAVF was surgical occlusion of fistula. The proportion of severe VAS score (7–10) in patients with spinal cord ischemia was significantly higher than that in patients with SDAVF (100% vs. 18, 19%; p-value = 0.051). Taking into consideration that the usual findings and diagnosis of spinal cord ischemia and SDAVF are still challenging for neurologists and in some cases the difficulties are related to technical limitations, we consider these entities to be rare but very important for the life of our patients. Patients were grouped into spinal cord ischemia and SDAVF status and those with acute or chronic pain conditions, measured by the VAS score. Patients with spinal cord ischemia develop acute neurological symptoms. They are much younger than the patients with SDAVF and the recovery rate is higher. Patients with SDAVF develop a progressive myelopathy and they suffer considerable neurological deficits. Imaging the lesions with MR angiography or MRI, we can confirm the diagnosis."
3479,Selective Apheresis of C-Reactive Protein for Treatment of Indications with Elevated CRP Concentrations,"Almost every kind of inflammation in the human body is accompanied by rising C-reactive protein (CRP) concentrations. This can include bacterial and viral infection, chronic inflammation and so-called sterile inflammation triggered by (internal) acute tissue injury. CRP is part of the ancient humoral immune response and secreted into the circulation by the liver upon respective stimuli. Its main immunological functions are the opsonization of biological particles (bacteria and dead or dying cells) for their clearance by macrophages and the activation of the classical complement pathway. This not only helps to eliminate pathogens and dead cells, which is very useful in any case, but unfortunately also to remove only slightly damaged or inactive human cells that may potentially regenerate with more CRP-free time. CRP action severely aggravates the extent of tissue damage during the acute phase response after an acute injury and therefore negatively affects clinical outcome. CRP is therefore a promising therapeutic target to rescue energy-deprived tissue either caused by ischemic injury (e.g., myocardial infarction and stroke) or by an overcompensating immune reaction occurring in acute inflammation (e.g., pancreatitis) or systemic inflammatory response syndrome (SIRS; e.g., after transplantation or surgery). Selective CRP apheresis can remove circulating CRP safely and efficiently. We explain the pathophysiological reasoning behind therapeutic CRP apheresis and summarize the broad span of indications in which its application could be beneficial with a focus on ischemic stroke as well as the results of this therapeutic approach after myocardial infarction."
3480,"Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects","In 2019, an ‘influenza pandemic’ and ‘vaccine hesitancy’ were listed as two of the top 10 challenges to global health by the WHO. The skin is a unique vaccination site, due to its immune-rich milieu, which is evolutionarily primed to respond to challenge, and its ability to induce both humoral and cellular immunity. Vaccination into this dermal compartment offers a way of addressing both of the challenges presented by the WHO, as well as opening up avenues for novel vaccine formulation and dose-sparing strategies to enter the clinic. This review will provide an overview of the diverse range of vaccination techniques available to target the dermal compartment, as well as their current state, challenges, and prospects, and touch upon the formulations that have been developed to maximally benefit from these new techniques. These include needle and syringe techniques, microneedles, DNA tattooing, jet and ballistic delivery, and skin permeabilization techniques, including thermal ablation, chemical enhancers, ablation, electroporation, iontophoresis, and sonophoresis."
3481,"Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity","SIMPLE SUMMARY: Healthy diet and physical activity are able to induce beneficial molecular modifications that have been associated with a lower risk of breast cancer (BC) incidence and a better prognosis for BC patients. Although the beneficial effects of healthy lifestyle have been described, the beneficial epigenetic modifications induced by dietary and exercise intervention in BC patients have not been elucidated yet. On these bases, the aim of the present study was to computationally identify microRNAs (miRNAs) strictly associated with BC progression and with dietary and exercise interventions. Through several computational approaches, a set of miRNAs modulated by diet and exercise and useful as diagnostic and prognostic biomarkers for BC was identified. The results obtained represent the starting point for further validation analyses performed on BC patients undergoing lifestyle interventions to propose the miRNAs here identified as novel biomarkers for BC management. ABSTRACT: Background: Several studies have shown that healthy lifestyles prevent the risk of breast cancer (BC) and are associated with better prognosis. It was hypothesized that lifestyle strategies induce microRNA (miRNA) modulation that, in turn, may lead to important epigenetic modifications. The identification of miRNAs associated with BC, diet, and physical activity may give further insights into the role played by lifestyle interventions and their efficacy for BC patients. To predict which miRNAs may be modulated by diet and physical activity in BC patients, the analyses of different miRNA expression datasets were performed. Methods: The GEO DataSets database was used to select miRNA expression datasets related to BC patients, dietary interventions, and physical exercise. Further bioinformatic approaches were used to establish the value of selected miRNAs in BC development and prognosis. Results: The analysis of datasets allowed the selection of modulated miRNAs associated with BC development, diet, and physical exercise. Seven miRNAs were also associated with the overall survival of BC patients. Conclusions: The identified miRNAs may play a role in the development of BC and may have a prognostic value in patients treated with integrative interventions including diet and physical activity. Validation of such modulated miRNAs on BC patients undergoing lifestyle strategies will be mandatory."
3482,Patient General Condition at Diagnosis: A Systematic Evaluation for Adults Diagnosed with Hematologic Malignancies,"Several societies have published recommendations for evaluating older adults with cancer in standard conditions. It is vital to assure a proper systematic patient condition evaluation, not only in the oldest (geriatric assessment) but in all adult patients. We have investigated the feasibility of a systematic evaluation of the general condition of all patients diagnosed with hematologic malignancies, and the degree of acceptance by the clinical team, in a prospective cohort of 182 consecutive adults, by using the ECOG performance status scale (ECOG, age 18 and over, 18+), Lee Index for Older Adults (LEE, 50+), Geriatric Assessment in Hematology (GAH, 65+), and the Comprehensive Geriatric Assessment (CGA, 75+). Clinical team acceptance was analyzed with a visual analogue scale, and the objective feasibility was calculated as the proportion of patients that could be finally evaluated with each tool. Acceptance was high, but the objective feasibility was progressively lower as the complexity of the different tools increased (ECOG 100%, LEE 99.4%, GAH 93.2%, and CGA 67.9%). LEE and GAH categories showed a weak concordance (Cohen’s Kappa 0.24) that was slight between LEE and CGA (Kappa 0.18). Unexpectedly, we found no significant association between the GAH and CGA categories (p = 0.16). We confirm that a systematic evaluation of all adult patients diagnosed with hematologic malignancies is feasible in daily practice by using an age-adapted approach. Direct comparisons among the different predictive tools in regard to patients’ tolerance to treatments of different intensities must be a priority research subject in the coming years."
3483,Computational Analysis of Clinical and Molecular Markers and New Theranostic Possibilities in Primary Open-Angle Glaucoma,"Primary open-angle glaucoma (POAG) is a paramount cause of irreversible visual disability worldwide. We focus on identifying clinical and molecular facts that may help elucidating the pathogenic mechanisms of the disease. By using ophthalmological approaches (biomicroscopy, ocular fundus, optical coherence tomography, and perimetry) and experimental tests (enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), and Western blot/immunoblotting) directed to evaluate the oxidative stress, inflammation, apoptosis, and neurodegeneration processes, we gather information to build a network of data to perform a computational bioinformatics analysis. Our results showed strong interaction of the above players and its downstream effectors in POAG pathogenesis. In conclusion, specific risk factors were identified, and molecules involved in multiple pathways were found in relation to anterior and posterior eye segment glaucoma changes, pointing to new theranostic challenges for better managing POAG progression."
3484,High-Yield Expression and Purification of Recombinant Influenza Virus Proteins from Stably-Transfected Mammalian Cell Lines,"Influenza viruses infect millions of people each year, resulting in significant morbidity and mortality in the human population. Therefore, generation of a universal influenza virus vaccine is an urgent need and would greatly benefit public health. Recombinant protein technology is an established vaccine platform and has resulted in several commercially available vaccines. Herein, we describe the approach for developing stable transfected human cell lines for the expression of recombinant influenza virus hemagglutinin (HA) and recombinant influenza virus neuraminidase (NA) proteins for the purpose of in vitro and in vivo vaccine development. HA and NA are the main surface glycoproteins on influenza virions and the major antibody targets. The benefits for using recombinant proteins for in vitro and in vivo assays include the ease of use, high level of purity and the ability to scale-up production. This work provides guidelines on how to produce and purify recombinant proteins produced in mammalian cell lines through either transient transfection or generation of stable cell lines from plasmid creation through the isolation step via Immobilized Metal Affinity Chromatography (IMAC). Collectively, the establishment of this pipeline has facilitated large-scale production of recombinant HA and NA proteins to high purity and with consistent yields, including glycosylation patterns that are very similar to proteins produced in a human host."
3485,Structural Insight into CVB3-VLP Non-Adjuvanted Vaccine,"Coxsackievirus B (CVB) enteroviruses are common pathogens that can cause acute and chronic myocarditis, dilated cardiomyopathy, aseptic meningitis, and they are hypothesized to be a causal factor in type 1 diabetes. The licensed enterovirus vaccines and those currently in clinical development are traditional inactivated or live attenuated vaccines. Even though these vaccines work well in the prevention of enterovirus diseases, new vaccine technologies, like virus-like particles (VLPs), can offer important advantages in the manufacturing and epitope engineering. We have previously produced VLPs for CVB3 and CVB1 in insect cells. Here, we describe the production of CVB3-VLPs with enhanced production yield and purity using an improved purification method consisting of tangential flow filtration and ion exchange chromatography, which is compatible with industrial scale production. We also resolved the CVB3-VLP structure by Cryo-Electron Microscopy imaging and single particle reconstruction. The VLP diameter is 30.9 nm on average, and it is similar to Coxsackievirus A VLPs and the expanded enterovirus cell-entry intermediate (the 135s particle), which is ~2 nm larger than the mature virion. High neutralizing and total IgG antibody levels, the latter being a predominantly Th2 type (IgG1) phenotype, were detected in C57BL/6J mice immunized with non-adjuvanted CVB3-VLP vaccine. The structural and immunogenic data presented here indicate the potential of this improved methodology to produce highly immunogenic enterovirus VLP-vaccines in the future."
3486,Immune-Enhancing Activity of Aqueous Extracts from Artemisia rupestris L. via MAPK and NF-kB Pathways of TLR4/TLR2 Downstream in Dendritic Cells,"Artemisia rupestris L. has long been used as a traditional herbal medicine owing to its immunomodulatory activity. Aqueous extracts of Artemisia rupestris L. (AEAR) contain the main functional component and can activate the maturation of dendritic cells (DCs) and enhance the adaptive immunity as the adjuvant against infections. To explore the underlying mechanism of immunomodulatory activities of AEAR, DCs were produced from bone-marrow cells of mice and the effects of AEAR on cell viability were assessed by the Cell Counting Kit 8 (CCK8) method and annexin V/propidium iodide staining assays. Then, the effects of AEAR on the morphology, maturation, and function of DCs were detected using a microscope, flow cytometry-based surface receptor characterization, and endocytosis assays. The secretion levels of cytokines were then analyzed with enzyme-linked immunosorbent assay (ELISA). The activation state of DCs was evaluated by the mixed lymphocyte reaction (MLR). The activity of MAPKs and NF-κB pathways, which were involved in the regulation of AEAR on DCs, was further detected by Western blot. AEAR did not have a cytotoxic effect on DCs or mouse splenocytes. AEAR remarkably enhanced the phenotypic maturation of DCs and promoted the expression of costimulatory molecules and the secretion of cytokines in DCs. AEAR also significantly decreased the phagocytic ability of DCs and augmented the abilities of DCs to present antigens and stimulate allogeneic T-cell proliferation. Simultaneously, AEAR potently activated toll-like receptor (TLR)4-/TLR2-related MAPKs and induced the degradation of IκB and the translocation of NF-κB. In short, AEAR can profoundly enhance the immune-modulating activities of DCs via TLR4-/TLR2-mediated activation of MAPKs and NF-κB signaling pathways and is a promising candidate immunopotentiator for vaccines."
3487,Porcine Reproductive and Respiratory Syndrome Virus Interferes with Swine Influenza A Virus Infection of Epithelial Cells,"Respiratory infections are still a major concern in pigs. Amongst the involved viruses, the porcine reproductive and respiratory syndrome virus (PRRSV) and the swine influenza type A virus (swIAV) have a major impact. These viruses frequently encounter and dual infections are reported. We analyzed here the molecular interactions between viruses and porcine tracheal epithelial cells as well as lung tissue. PRRSV-1 species do not infect porcine respiratory epithelial cells. However, PRRSV-1, when inoculated simultaneously or shortly before swIAV, was able to inhibit swIAV H1N2 infection, modulate the interferon response and alter signaling protein phosphorylations (ERK, AKT, AMPK, and JAK2), in our conditions. SwIAV inhibition was also observed, although at a lower level, by inactivated PRRSV-1, whereas acid wash treatment inactivating non-penetrated viruses suppressed the interference effect. PRRSV-1 and swIAV may interact at several stages, before their attachment to the cells, when they attach to their receptors, and later on. In conclusion, we showed for the first time that PRRSV can alter the relation between swIAV and its main target cells, opening the doors to further studies on the interplay between viruses. Consequences of these peculiar interactions on viral infections and vaccinations using modified live vaccines require further investigations."
3488,Membrane Transporters for Amino Acids as Players of Cancer Metabolic Rewiring,"Cancer cells perform a metabolic rewiring to sustain an increased growth rate and compensate for the redox stress caused by augmented energy metabolism. The metabolic changes are not the same in all cancers. Some features, however, are considered hallmarks of this disease. As an example, all cancer cells rewire the amino acid metabolism for fulfilling both the energy demand and the changed signaling routes. In these altered conditions, some amino acids are more frequently used than others. In any case, the prerequisite for amino acid utilization is the presence of specific transporters in the cell membrane that can guarantee the absorption and the traffic of amino acids among tissues. Tumor cells preferentially use some of these transporters for satisfying their needs. The evidence for this phenomenon is the over-expression of selected transporters, associated with specific cancer types. The knowledge of the link between the over-expression and the metabolic rewiring is crucial for understanding the molecular mechanism of reprogramming in cancer cells. The continuous growth of information on structure–function relationships and the regulation of transporters will open novel perspectives in the fight against human cancers."
3489,"Overview of the Development, Impacts, and Challenges of Live-Attenuated Oral Rotavirus Vaccines","Safety, efficacy, and cost-effectiveness are paramount to vaccine development. Following the isolation of rotavirus particles in 1969 and its evidence as an aetiology of severe dehydrating diarrhoea in infants and young children worldwide, the quest to find not only an acceptable and reliable but cost-effective vaccine has continued until now. Four live-attenuated oral rotavirus vaccines (LAORoVs) (Rotarix(®), RotaTeq(®), Rotavac(®), and RotaSIIL(®)) have been developed and licensed to be used against all forms of rotavirus-associated infection. The efficacy of these vaccines is more obvious in the high-income countries (HIC) compared with the low- to middle-income countries (LMICs); however, the impact is far exceeding in the low-income countries (LICs). Despite the rotavirus vaccine efficacy and effectiveness, more than 90 countries (mostly Asia, America, and Europe) are yet to implement any of these vaccines. Implementation of these vaccines has continued to suffer a setback in these countries due to the vaccine cost, policy, discharging of strategic preventive measures, and infrastructures. This review reappraises the impacts and effectiveness of the current live-attenuated oral rotavirus vaccines from many representative countries of the globe. It examines the problems associated with the low efficacy of these vaccines and the way forward. Lastly, forefront efforts put forward to develop initial procedures for oral rotavirus vaccines were examined and re-connected to today vaccines."
3490,"Whole Genome Sequencing Characterization of HEV3-e and HEV3-f Subtypes among the Wild Boar Population in the Abruzzo Region, Italy: First Report","Hepatitis E virus (HEV) is an emergent zoonotic pathogen, causing worldwide acute and chronic hepatitis in humans. HEV comprises eight genotypes and several subtypes. HEV genotypes 3 and 4 (HEV3 and HEV4) are zoonotic. In Italy, the most part of HEV infections (80%) is due to autochthonous HEV3 circulation of the virus, and the key role played by wild animals is generally accepted. Abruzzo is an Italian region officially considered an HEV “hot spot”, with subtype HEV3-c being up to now the only one reported among wild boars. During the year 2018–2019, a group of wild boars in Abruzzo were screened for HEV; positive RNA liver samples were subjected to HEV characterization by using the whole genome sequencing (WGS) approach methodology. This represents the first report about the detection of HEV-3 subtypes e and f in the wild boar population in this area. Since in Italy human infections from HEV 3-e and f have been associated with pork meat consumption, our findings deserve more in-depth analysis with the aim of evaluating any potential correlation between wild animals, the pork chain production and HEV human infections."
3491,The impact of delayed treatment of uncomplicated P. falciparum malaria on progression to severe malaria: A systematic review and a pooled multicentre individual-patient meta-analysis,"BACKGROUND: Delay in receiving treatment for uncomplicated malaria (UM) is often reported to increase the risk of developing severe malaria (SM), but access to treatment remains low in most high-burden areas. Understanding the contribution of treatment delay on progression to severe disease is critical to determine how quickly patients need to receive treatment and to quantify the impact of widely implemented treatment interventions, such as ‘test-and-treat’ policies administered by community health workers (CHWs). We conducted a pooled individual-participant meta-analysis to estimate the association between treatment delay and presenting with SM. METHODS AND FINDINGS: A search using Ovid MEDLINE and Embase was initially conducted to identify studies on severe Plasmodium falciparum malaria that included information on treatment delay, such as fever duration (inception to 22nd September 2017). Studies identified included 5 case–control and 8 other observational clinical studies of SM and UM cases. Risk of bias was assessed using the Newcastle–Ottawa scale, and all studies were ranked as ‘Good’, scoring ≥7/10. Individual-patient data (IPD) were pooled from 13 studies of 3,989 (94.1% aged <15 years) SM patients and 5,780 (79.6% aged <15 years) UM cases in Benin, Malaysia, Mozambique, Tanzania, The Gambia, Uganda, Yemen, and Zambia. Definitions of SM were standardised across studies to compare treatment delay in patients with UM and different SM phenotypes using age-adjusted mixed-effects regression. The odds of any SM phenotype were significantly higher in children with longer delays between initial symptoms and arrival at the health facility (odds ratio [OR] = 1.33, 95% CI: 1.07–1.64 for a delay of >24 hours versus ≤24 hours; p = 0.009). Reported illness duration was a strong predictor of presenting with severe malarial anaemia (SMA) in children, with an OR of 2.79 (95% CI:1.92–4.06; p < 0.001) for a delay of 2–3 days and 5.46 (95% CI: 3.49–8.53; p < 0.001) for a delay of >7 days, compared with receiving treatment within 24 hours from symptom onset. We estimate that 42.8% of childhood SMA cases and 48.5% of adult SMA cases in the study areas would have been averted if all individuals were able to access treatment within the first day of symptom onset, if the association is fully causal. In studies specifically recording onset of nonsevere symptoms, long treatment delay was moderately associated with other SM phenotypes (OR [95% CI] >3 to ≤4 days versus ≤24 hours: cerebral malaria [CM] = 2.42 [1.24–4.72], p = 0.01; respiratory distress syndrome [RDS] = 4.09 [1.70–9.82], p = 0.002). In addition to unmeasured confounding, which is commonly present in observational studies, a key limitation is that many severe cases and deaths occur outside healthcare facilities in endemic countries, where the effect of delayed or no treatment is difficult to quantify. CONCLUSIONS: Our results quantify the relationship between rapid access to treatment and reduced risk of severe disease, which was particularly strong for SMA. There was some evidence to suggest that progression to other severe phenotypes may also be prevented by prompt treatment, though the association was not as strong, which may be explained by potential selection bias, sample size issues, or a difference in underlying pathology. These findings may help assess the impact of interventions that improve access to treatment."
3492,Impacts of the 1918 flu on survivors' nutritional status: A double quasi-natural experiment,"Robust empirical evidence supports the idea that embryonic and, more generally, intrauterine disruptions induced by the 1918-flu pandemic had long-term consequences on adult health status and other conditions. In this paper we assess the 1918-flu long-term effects not just of in utero exposure but also during infancy and early childhood. A unique set of events that took place in Puerto Rico during 1918–1919 generated conditions of a “double quasi-natural experiment”. We exploit these conditions to empirically identify effects of exposure to the 1918 flu pandemic and those of the devastation left by an earthquake-tsunami that struck the island in 1918. Because the earthquake-tsunami affected mostly the Western coast of the island whereas early (in utero and postnatal) exposure to the flu was restricted to those born in the interval 1917–1920, we use geographic variation to identify the effects of the quake and timing of birth variation to identify those of the flu. We benefit from availability of information on markers of nutritional status in a nationally representative sample of individuals aged 75 and older in 2002. We make two contributions. First, unlike most fetal-origins research that singles out early nutritional status as a determinant of adult health, we hypothesize that the 1918 flu damaged the nutritional status of adult survivors who, at the time of the flu, were in utero or infants. Second, we target markers of nutritional status largely set when the adult survivors were infants and young children. Estimates of effects of the pandemic are quite large mostly among females and those who were exposed to the earthquake-tsunami. Impacts of the flu in areas less affected by the earthquake are smaller but do vary by area flu severity. These findings constitute empirical evidence supporting the conjecture that effects of the 1918 flu and/or the earthquake are associated not just with disruption experienced during the fetal period but also postnatally."
3493,Does the size of rewards influence performance in cognitively demanding tasks?,"Classic micro-economic and psychology theories propose different implications of monetary incentives on performance. Empirical studies in sports settings show that athletes generally perform worse when the stakes are higher, while a range of lab studies involving cognitively demanding tasks have led to diverging results, supporting positive, negative and null-effects of higher (vs. lower) stakes. In order to further investigate this issue, we present a pre-registered, randomized, controlled trial of 149 participants solving both anagrams and math addition tasks. We do not find a statistically significant effect of the size of the reward on neither performance, self-reported effort nor intrinsic motivation. We propose that future studies should contrast the potential impact of rewards on different kinds of task, e.g. compare tasks that solely require cognitive effort vs. tasks that require motor skills, as in sports."
3494,A cautionary note on the use of unsupervised machine learning algorithms to characterise malaria parasite population structure from genetic distance matrices,"Genetic surveillance of malaria parasites supports malaria control programmes, treatment guidelines and elimination strategies. Surveillance studies often pose questions about malaria parasite ancestry (e.g. how antimalarial resistance has spread) and employ statistical methods that characterise parasite population structure. Many of the methods used to characterise structure are unsupervised machine learning algorithms which depend on a genetic distance matrix, notably principal coordinates analysis (PCoA) and hierarchical agglomerative clustering (HAC). PCoA and HAC are sensitive to both the definition of genetic distance and algorithmic specification. Importantly, neither algorithm infers malaria parasite ancestry. As such, PCoA and HAC can inform (e.g. via exploratory data visualisation and hypothesis generation), but not answer comprehensively, key questions about malaria parasite ancestry. We illustrate the sensitivity of PCoA and HAC using 393 Plasmodium falciparum whole genome sequences collected from Cambodia and neighbouring regions (where antimalarial resistance has emerged and spread recently) and we provide tentative guidance for the use and interpretation of PCoA and HAC in malaria parasite genetic epidemiology. This guidance includes a call for fully transparent and reproducible analysis pipelines that feature (i) a clearly outlined scientific question; (ii) a clear justification of analytical methods used to answer the scientific question along with discussion of any inferential limitations; (iii) publicly available genetic distance matrices when downstream analyses depend on them; and (iv) sensitivity analyses. To bridge the inferential disconnect between the output of non-inferential unsupervised learning algorithms and the scientific questions of interest, tailor-made statistical models are needed to infer malaria parasite ancestry. In the absence of such models speculative reasoning should feature only as discussion but not as results."
3495,Correlates of HIV self-testing among female sex workers in China: implications for expanding HIV screening,"BACKGROUND: Human immunodeficiency virus (HIV) self-testing may help improve test uptake among female sex workers. China has implemented many HIV self-testing programs among men who have sex with men, creating an opportunity for promotion among female sex workers. However, there is a limited literature on examining HIV self-testing among female sex workers. This study aimed to examine HIV self-testing experiences and its determinants among female sex workers in China. METHODS: A venue-based, cross-sectional study was conducted among Chinese female sex workers in 2019. Participants completed a survey including social-demographic characteristics, sexual behaviors, and HIV self-testing history, the distribution of which were analyzed using descriptive analysis. Multivariable logistic regression was conducted to identify associations with HIV self-testing. RESULTS: Among 1287 Chinese female sex workers, 1072 (83.3%, 95% confidence interval [CI] 81.2–85.3%) had ever tested for HIV, and 103 (8.0%, 95% CI 6.6–9.6%) had ever used HIV self-testing. More than half reported that the self-test was their first HIV test (59.2%, 61/103), around one-fifth reported HIV self-testing results influenced the price of sex (21.4%, 22/103). A minority of individuals reported ever experiencing pressure to undertake HIV self-testing (6.8%, 7/103). After adjusting for covariates, HIV self-testing was positively associated with receiving anal sex in the past month (adjusted odds ratio [aOR] = 2.2, 95% CI 1.4–3.5), using drugs before or during sex (aOR = 2.8, 95% CI 1.8–4.5), injecting drugs in the past 6 months (aOR = 2.6, 95% CI 1.2–6.0), being diagnosed with other sexually transmitted infections (aOR = 1.6, 95% CI 1.0–2.5), tested for other sexually transmitted infections in the past six months (aOR = 3.4, 95% CI 2.1–5.5), ever tested in the hospital (aOR = 3.4, 95% CI 2.0–5.6), and ever tested in the community (aOR = 1.5, 95% CI 1.2–1.9). CONCLUSIONS: Our findings suggest that HIV self-testing could expand overall HIV testing uptake, increase HIV testing frequency, reach sub-groups of high-risk female sex workers and has limited potential harms among female sex workers. HIV self-testing should be incorporated among Chinese female sex workers as a complement to facility-based HIV testing services."
3496,Women in the Pharmaceutical Sciences: Honoring Our Pioneers,[Figure: see text]
3497,An increasing trend in geriatric trauma patients undergoing surgical stabilization of rib fractures,"PURPOSE: The proportion of geriatric trauma patients (GTPs) (age ≥ 65 years old) with chest wall injury undergoing surgical stabilization of rib fractures (SSRF) nationally is unknown. We hypothesize a growing trend of GTPs undergoing SSRF, and sought to evaluate risk of respiratory complications and mortality for GTPs compared to younger adults (18–64 years old) undergoing SSRF. METHODS: The Trauma Quality Improvement Program (2010–2016) was queried for patients with rib fracture(s) who underwent SSRF. GTPs were compared to younger adults. A multivariable logistic regression analysis was performed. RESULTS: From 21,517 patients undergoing SSRF, 3,001 (16.2%) were GTPs. Of all patients undergoing SSRF in 2010, 10.6% occurred on GTPs increasing to 17.9% in 2016 (p < 0.001) with a geometric-mean-annual increase of 11.5%. GTPs had a lower median injury severity score (18 vs. 22, p < 0.001), but had a higher rate of mortality (4.7% vs. 1.2%, p < 0.001). After controlling for covariates, GTPs had an increased associated risk of mortality (OR 4.80, CI 3.62–6.36, p < 0.001). On a separate multivariate analysis for all trauma patients with isolated chest Abbreviated Injury Scale 3, GTPs were associated with a similar four-fold risk of mortality (OR 4.21, CI 1.98–6.32, p < 0.001). CONCLUSION: Spanning 7 years of data, the proportion of GTPs undergoing SSRF increased by over 7%. Although GTPs undergoing SSRF had lesser injuries, their risk of mortality was four times higher than other adult trauma patients undergoing SSRF, which was similar to their increased background risk of mortality. Ultimately, SSRF in GTPs should be considered on an individualized basis with careful attention to risk–benefit ratio. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00068-020-01526-7) contains supplementary material, which is available to authorized users."
3498,Feasibility and safety of bedside percutaneous biliary drainage in patients with severe cholangitis,"PURPOSE: To evaluate the safety and feasibility of bedside percutaneous transhepatic biliary drainage (PTBD) as a salvage procedure in patients with severe cholangitis in the intensive care unit (ICU). METHODS: This retrospective study evaluated records of consecutive patients with severe cholangitis who were admitted in the ICU. Bedside PTBD was performed using ultrasound guidance. The level and cause of biliary obstruction were recorded. The technical success of the procedure and complications were recorded. RESULTS: Ten patients (six males, mean age 53.8 years) underwent bedside PTBD. Six patients had distal common bile duct blockade [periampullary carcinoma (n = 2), carcinoma pancreas (n = 2), choledocholithiasis (n = 1), and benign stricture (n = 1)]. Four patients had malignant hilar stricture [cholangiocarcinoma (n = 3) and carcinoma gallbladder (n = 1)]. Technical success was achieved in all. One patient underwent bilateral PTBD. Left and right PTBD were performed in 5 and 4 patients, respectively. There were no major complications. Transient hemobilia occurred in two patients. CONCLUSION: Bedside PTBD is safe and technically feasible. Prospective studies are required to establish this procedure into routine clinical practice."
3499,Reflections on a Patient Suicide in the Time of COVID-19,
3500,Arachidonic acid metabolism is elevated in Mycoplasma gallisepticum and Escherichia coli co-infection and induces LTC4 in serum as the biomarker for detecting poultry respiratory disease,"Outbreaks of multiple respiratory diseases with high morbidity and mortality have been frequently reported in poultry industry. Metabolic profiling has showed widespread usage in metabolic and infectious disease for identifying biomarkers and understanding of complex mechanisms. In this study, the non-targeted metabolomics were used on Mycoplasma gallisepticum (MG) and Escherichia coli (E.coli) co-infection model in serum, which showed that Leukotriene C4 (LTC4), Leukotriene D4 (LTD4), Chenodeoxycholate, Linoleate and numerous energy metabolites were varied significantly. KEGG enrichment analysis revealed that the metabolic pathways of linoleic acid, taurine and arachidonic acid (AA) were upregulated. To further characterize the consequences of co-infection, we performed an AA metabolic network pathway with metabolic products and enzyme genes. The results showed that the expression of LTC4 increased extremely significant and accompanied with different degree of infection. Meanwhile, the AA network performed the changes and differences of various metabolites in the pathway when multiple respiratory diseases occurred. Taken together, co-infection induces distinct alterations in the serum metabolome owing to the activation of AA metabolism. Furthermore, LTC4 in serum could be used as the biomarker for detecting poultry respiratory disease. ABBREVIATIONS: MG: Mycoplasma gallisepticum; E.coli: Escherichia coli; AA: Arachidonic acid; LTC4: Leukotriene C4; CRD: chronic respiratory diseases; KEGG: Kyoto Encyclopedia of Genes and Genomes; LTs: leukotrienes; PGs: prostaglandins; NO: nitric oxide; HIS: histamine; PCA: Principal Component Analysis; PLS-DA: Partial Least Squares Discriminant Analysis; CCU: color change unit; UPLC: ultra-performance liquid chromatography; MS: mass spectrometry; DEMs: differentially expressed metabolites; ELISA: enzyme-linked immunosorbent assay; SD: standard deviation; VIP: Variable importance in the projection"
3501,Nuclear Receptors as Autophagy-Based Antimicrobial Therapeutics,"Autophagy is an intracellular process that targets intracellular pathogens for lysosomal degradation. Autophagy is tightly controlled at transcriptional and post-translational levels. Nuclear receptors (NRs) are a family of transcriptional factors that regulate the expression of gene sets involved in, for example, metabolic and immune homeostasis. Several NRs show promise as host-directed anti-infectives through the modulation of autophagy activities by their natural ligands or small molecules (agonists/antagonists). Here, we review the roles and mechanisms of NRs (vitamin D receptors, estrogen receptors, estrogen-related receptors, and peroxisome proliferator-activated receptors) in linking immunity and autophagy during infection. We also discuss the potential of emerging NRs (REV-ERBs, retinoic acid receptors, retinoic acid-related orphan receptors, liver X receptors, farnesoid X receptors, and thyroid hormone receptors) as candidate antimicrobials. The identification of novel roles and mechanisms for NRs will enable the development of autophagy-adjunctive therapeutics for emerging and re-emerging infectious diseases."
3502,Fibrotic Changes and Endothelial-to-Mesenchymal Transition Promoted by VEGFR2 Antagonism Alter the Therapeutic Effects of VEGFA Pathway Blockage in a Mouse Model of Choroidal Neovascularization,"Many patients with wet age-related macular degeneration do not respond well to anti- vascular endothelial growth factor A (VEGFA) therapy for choroidal neovascularization (CNV), and the efficacy of anti-VEGFA decreases over time. We investigated the hypothesis that fibrotic changes, in particular via endothelial-to-mesenchymal transition (EndoMT), play a role in CNV and alter the therapeutic effects of VEGFA pathway blockage. Induction of EndoMT of primary human retinal endothelial cells led to a significantly reduced response to VEGFA at the level of gene expression, cellular proliferation, migration, and tube formation. Suppression of EndoMT restored cell responsiveness to VEGFA. In a mouse model of spontaneous CNV, fibrotic changes and EndoMT persisted as the CNV lesions became more established over time. VEGFA receptor-2 (VEGFR2) antagonism further induced fibrosis and EndoMT in the CNV. The combination of VEGFR2 antagonism and fibrosis/EndoMT inhibition was more effective than either individual treatment in reducing CNV. Our data indicate that fibrosis and EndoMT are involved in the progression of CNV, are exacerbated by VEGFR2 inhibition, and could provide an explanation for the reduced efficacy of anti-VEGFA treatment over time."
3503,Transcriptional Spatial Profiling of Cancer Tissues in the Era of Immunotherapy: The Potential and Promise,"SIMPLE SUMMARY: In recent years, immunotherapy has emerged as a pillar in the fight against cancer. However, the heterogeneity within the tumor microenvironment poses challenges to the efficacy of immunotherapy treatment strategies and may contribute to treatment resistance, progression and relapse. Hence, researchers have used transcriptional spatial profiling techniques to uncover the complex cancer immune profile while retaining critical spatial information of different cell types. This would help identify the source of tumor heterogeneity and uncover pathogenic mechanisms, potential drug targets and novel biomarkers. In this review, we discuss various approaches for transcriptional spatial profiling of cancer tissues such as in situ hybridization, digital spatial profiling and an emerging technology known as Visium Spatial Gene Expression Solution. We highlight the strengths and limitations of the different technologies and the potential and promise they hold in the advancement of cancer immunotherapy. ABSTRACT: Intratumoral heterogeneity poses a major challenge to making an accurate diagnosis and establishing personalized treatment strategies for cancer patients. Moreover, this heterogeneity might underlie treatment resistance, disease progression, and cancer relapse. For example, while immunotherapies can confer a high success rate, selective pressures coupled with dynamic evolution within a tumour can drive the emergence of drug-resistant clones that allow tumours to persist in certain patients. To improve immunotherapy efficacy, researchers have used transcriptional spatial profiling techniques to identify and subsequently block the source of tumour heterogeneity. In this review, we describe and assess the different technologies available for such profiling within a cancer tissue. We first outline two well-known approaches, in situ hybridization and digital spatial profiling. Then, we highlight the features of an emerging technology known as Visium Spatial Gene Expression Solution. Visium generates quantitative gene expression data and maps them to the tissue architecture. By retaining spatial information, we are well positioned to identify novel biomarkers and perform computational analyses that might inform on novel combinatorial immunotherapies."
3504,Non-Immersive Virtual Reality for Post-Stroke Upper Extremity Rehabilitation: A Small Cohort Randomized Trial,"Immersive and non-immersive virtual reality (NIVR) technology can supplement and improve standard physiotherapy and neurorehabilitation in post-stroke patients. We aimed to use MIRA software to investigate the efficiency of specific NIVR therapy as a standalone intervention, versus standardized physiotherapy for upper extremity rehabilitation in patients post-stroke. Fifty-five inpatients were randomized to control groups (applying standard physiotherapy and dexterity exercises) and experimental groups (applying NIVR and dexterity exercises). The two groups were subdivided into subacute (<six months post-stroke) and chronic (>six months to four years post-stroke survival patients). The following standardized tests were applied at baseline and after two weeks post-therapy: Fugl–Meyer Assessment for Upper Extremity (FMUE), the Modified Rankin Scale (MRS), Functional Independence Measure (FIM), Active Range of Motion (AROM), Manual Muscle Testing (MMT), Modified Ashworth Scale (MAS), and Functional Reach Test (FRT). The Kruskal–Wallis test was used to determine if there were significant differences between the groups, followed with pairwise comparisons. The Wilcoxon Signed-Rank test was used to determine the significance of pre to post-therapy changes. The Wilcoxon Signed-Rank test showed significant differences in all four groups regarding MMT, FMUE, and FIM assessments pre- and post-therapy, while for AROM, only experimental groups registered significant differences. Independent Kruskal–Wallis results showed that the subacute experimental group outcomes were statistically significant regarding the assessments, especially in comparison with the control groups. The results suggest that NIVR rehabilitation is efficient to be administered to post-stroke patients, and the study design can be used for a further trial, in the perspective that NIVR therapy can be more efficient than standard physiotherapy within the first six months post-stroke."
3505,Applications of Genome-Wide Screening and Systems Biology Approaches in Drug Repositioning,"SIMPLE SUMMARY: Drug repurposing is an accelerated route for drug development and a promising approach for finding medications for orphan and common diseases. Here, we compiled databases that comprise both computationally- or experimentally-derived data, and categorized them based on quiddity and origin of data, further focusing on those that present high throughput omic data or drug screens. These databases were then contextualized with genome-wide screening methods such as CRISPR/Cas9 and RNA interference, as well as state of art systems biology approaches that enable systematic characterizations of multi-omic data to find new indications for approved drugs or those that reached the latest phases of clinical trials. ABSTRACT: Modern drug discovery through de novo drug discovery entails high financial costs, low success rates, and lengthy trial periods. Drug repositioning presents a suitable approach for overcoming these issues by re-evaluating biological targets and modes of action of approved drugs. Coupling high-throughput technologies with genome-wide essentiality screens, network analysis, genome-scale metabolic modeling, and machine learning techniques enables the proposal of new drug–target signatures and uncovers unanticipated modes of action for available drugs. Here, we discuss the current issues associated with drug repositioning in light of curated high-throughput multi-omic databases, genome-wide screening technologies, and their application in systems biology/medicine approaches."
3506,Neutralizing Antibodies Targeting the Conserved Stem Region of Influenza Hemagglutinin,"Influenza continues to be a public health threat despite the availability of annual vaccines. While vaccines are generally effective at inducing strain-specific immunity, they are sub-optimal or ineffective when drifted or novel pandemic strains arise due to sequence changes in the major surface glycoprotein hemagglutinin (HA). The discovery of a large number of antibodies targeting the highly conserved stem region of HAs that are capable of potently neutralizing a broad range of virus strains and subtypes suggests new ways to protect against influenza. The structural characterization of HA stem epitopes and broadly neutralizing antibody paratopes has enabled the design of novel proteins, mini-proteins, and peptides targeting the HA stem, thus providing a foundation for the design of new vaccines. In this narrative, we comprehensively review the current knowledge about stem-directed broadly neutralizing antibodies and the structural features contributing to virus neutralization."
3507,Development of Monoclonal Antibodies and Antigen-Capture ELISA for Human Parechovirus Type 3,"Human parechovirus type 3 (HPeV3) is an etiologic agent of respiratory diseases, meningitis, and sepsis-like illness in both infants and adults. Monoclonal antibodies (mAbs) can be a promising diagnostic tool for antigenic diseases such as virus infection, as they offer a high specificity toward a specific viral antigen. However, to date, there is no specific mAb available for the diagnosis of HPeV3 infection. In this study, we developed and characterized mAbs specific for HPeV3 capsid protein VP0. We used cell-free, wheat germ-synthesized viral VP0 protein for immunizing BALB/c mice to generate hybridomas. From the resultant hybridoma clones, we selected nine clones producing mAbs reactive to the HPeV3-VP0 antigen, based on enzyme-linked immunosorbent assay (ELISA). Epitope mapping showed that these mAbs recognized three distinct domains in HPeV3 VP0. Six mAbs recognized HPeV3 specifically and the other three mAbs showed cross-reactivity with other HPeVs. Using the HPeV3-specific mAbs, we then developed an ELISA for viral antigen detection that could be reliably used for laboratory diagnosis of HPeV3. This ELISA system exhibited no cross-reactivity with other related viruses. Our newly developed mAbs would, thus, provide a useful set of tools for future research and ensure HPeV3-specific diagnosis."
3508,Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes,"Resveratrol, the most widely studied natural phytochemical, has been shown to interact with different target proteins. Previous studies show that resveratrol binds and inhibits DNA polymerases and some other enzymes; however, the binding and functioning mechanisms remain unknown. The elucidated knowledge of inhibitory mechanisms of resveratrol will assist us in new drug discovery. We utilized molecular docking and molecular dynamics (MD) simulation to reveal how resveratrol and structurally similar compounds bind to various nucleotide-dependent enzymes, specifically, DNA polymerases, HIV-1 reverse transcriptase, and ribonucleotide reductase. The results show that resveratrol and its analogs exert their inhibitory effects by competing with the substrate dNTPs in these enzymes and blocking elongation of chain polymerization. In addition, the results imply that resveratrol binds to a variety of other ATP-/NTP-binding proteins."
3509,Association of Infectious Disease Physician Approval of Peripherally Inserted Central Catheter With Appropriateness and Complications,"IMPORTANCE: Peripherally inserted central catheters (PICCs) are frequently used to deliver intravenous antimicrobial therapy. However, inappropriate PICC use may lead to patient harm. OBJECTIVE: To evaluate whether infectious disease physician approval prior to PICC placement for intravenous antimicrobials is associated with more appropriate device use and fewer complications. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of 21 653 PICCs placed for a primary indication of intravenous antimicrobial therapy between January 1, 2015, and July 26, 2019, was conducted in 42 hospitals participating in a quality collaborative across Michigan among hospitalized medical patients. MAIN OUTCOMES AND MEASURES: Appropriateness of PICCs was defined according to the Michigan Appropriateness Guide for Intravenous Catheters as a composite measure of (1) single-lumen catheter use, (2) avoiding use of PICCs for 5 days or less, and (3) avoiding use of PICCs for patients with chronic kidney disease (defined as an estimated glomerular filtration rate <45 mL/min/1.73 m(2)). Complications related to PICCs included catheter occlusion, deep vein thrombosis, and central line–associated bloodstream infection. The association between infectious disease physician approval, device appropriateness, and catheter complications was assessed using multivariable models, adjusted for patient comorbidities and hospital clustering. Results were expressed as odds ratios with 95% CIs. RESULTS: A total of 21 653 PICCs were placed for intravenous antimicrobials (11 960 PICCs were placed in men [55.2%]; median age, 64.5 years [interquartile range, 53.4-75.4 years]); 10 238 PICCs (47.3%) were approved by an infectious disease physician prior to placement. Compared with PICCs with no documented approval, PICCs with approval by an infectious disease physician were more likely to be appropriately used (72.7% [7446 of 10 238] appropriate with approval vs 45.4% [5180 of 11 415] appropriate without approval; odds ratio, 3.53; 95% CI, 3.29-3.79; P < .001). Furthermore, approval was associated with lower odds of a PICC-related complication (6.5% [665 of 10 238] with approval vs 11.3% [1292 of 11 415] without approval; odds ratio, 0.55; 95% CI, 0.50-0.61). CONCLUSIONS AND RELEVANCE: This cohort study suggests that, when PICCs were placed for intravenous antimicrobial therapy, infectious disease physician approval of PICC insertion was associated with more appropriate device use and fewer complications. Policies aimed at ensuring infectious disease physician approval prior to PICC placement for antimicrobials may improve patient safety."
3510,Integrating Genomics and Clinical Data for Statistical Analysis by Using GEnome MINIng (GEMINI) and Fast Healthcare Interoperability Resources (FHIR): System Design and Implementation,"BACKGROUND: The introduction of next-generation sequencing (NGS) into molecular cancer diagnostics has led to an increase in the data available for the identification and evaluation of driver mutations and for defining personalized cancer treatment regimens. The meaningful combination of omics data, ie, pathogenic gene variants and alterations with other patient data, to understand the full picture of malignancy has been challenging. OBJECTIVE: This study describes the implementation of a system capable of processing, analyzing, and subsequently combining NGS data with other clinical patient data for analysis within and across institutions. METHODS: On the basis of the already existing NGS analysis workflows for the identification of malignant gene variants at the Institute of Pathology of the University Hospital Erlangen, we defined basic requirements on an NGS processing and analysis pipeline and implemented a pipeline based on the GEMINI (GEnome MINIng) open source genetic variation database. For the purpose of validation, this pipeline was applied to data from the 1000 Genomes Project and subsequently to NGS data derived from 206 patients of a local hospital. We further integrated the pipeline into existing structures of data integration centers at the University Hospital Erlangen and combined NGS data with local nongenomic patient-derived data available in Fast Healthcare Interoperability Resources format. RESULTS: Using data from the 1000 Genomes Project and from the patient cohort as input, the implemented system produced the same results as already established methodologies. Further, it satisfied all our identified requirements and was successfully integrated into the existing infrastructure. Finally, we showed in an exemplary analysis how the data could be quickly loaded into and analyzed in KETOS, a web-based analysis platform for statistical analysis and clinical decision support. CONCLUSIONS: This study demonstrates that the GEMINI open source database can be augmented to create an NGS analysis pipeline. The pipeline generates high-quality results consistent with the already established workflows for gene variant annotation and pathological evaluation. We further demonstrate how NGS-derived genomic and other clinical data can be combined for further statistical analysis, thereby providing for data integration using standardized vocabularies and methods. Finally, we demonstrate the feasibility of the pipeline integration into hospital workflows by providing an exemplary integration into the data integration center infrastructure, which is currently being established across Germany."
3511,Patient-perceived treatment burden of tuberculosis treatment,"BACKGROUND: Treatment for tuberculosis lasts for a minimum of 6 months. The treatment burden experienced by patients in a low-incidence setting where directly observed therapy is the standard of care is not well-known. METHODS: Patients receiving tuberculosis treatment through the chest clinic at a tertiary hospital in Sydney, Australia, participated in a semi-structured interview. The interviews explored the treatment burden experienced by patients and possible solutions to ameliorate this burden. Interviews were conducted until data saturation was achieved. They were recorded, transcribed and analysed using NVivo 12 software. RESULTS: Twenty participants (80% male, mean age 40 years) with pulmonary (n = 13) and extra-pulmonary (n = 7) tuberculosis were interviewed. Participants experienced healthcare, financial, social and medication burdens along with lifestyle changes due to treatment. Medication intake was challenging due to the high number of pills, and 55% (n = 11) of patients experienced fatigue amongst other side effects. Patients found clinic-based directly observed therapy inconvenient, especially those working and/or studying. Suggestions to lessen treatment burden included reducing medication burden and better access to health services. CONCLUSION: Tuberculosis treatment is associated with substantial treatment burden for patients. Measures to reduce treatment burden including alternative treatment delivery methods which are more accommodating to patients than clinic-based directly observed therapy, such as video directly observed therapy or partially self -administered treatment, should be considered on a case-by-case basis."
3512,Novel PGK1 determines SKP2-dependent AR stability and reprograms granular cell glucose metabolism facilitating ovulation dysfunction,"BACKGROUND: Disordered folliculogenesis is a core characteristic of polycystic ovary syndrome (PCOS) and androgen receptors (ARs) are closely associated with hyperandrogenism and abnormalities in folliculogenesis in PCOS. However, whether the new AR binding partner phosphoglycerate kinase 1 (PGK1) in granulosa cells (GCs) plays a key role in the pathogenesis of PCOS remains unclear. METHODS: We identified the new AR binding partner PGK1 by co-IP (co-immunoprecipitation) in luteinized GCs, and reconfirmed by co-IP, co-localization and GST pull down assay, and checked PGK1 expression levels with qRT-PCR and western blotting. Pharmaceuticals rescue assays in mice, and metabolism assay, AR protein stability and RNA-seq of PGK1 targets in cells proved the function in PCOS. FINDINGS: PGK1 and AR are highly expressed in PCOS luteinized GCs and PCOS-like mouse ovarian tissues. PGK1 regulated glucose metabolism and deteriorated PCOS-like mouse metabolic disorder, and paclitaxel rescued the phenotype of PCOS-like mice and reduced ovarian PGK1 and AR protein levels. PGK1 inhibited AR ubiquitination levels and increased AR stability in an E3 ligase SKP2-dependent manner. Additionally, PGK1 promoted AR nuclear translocation, and RNA-seq data showed that critical ovulation-related genes were regulated by the PGK1-AR axis. INTERPRETATION: PGK1 regulated GCs metabolism and interacted with AR to regulate the expression of key ovulation genes, and also mediated cell proliferation and apoptosis, which resulted in the etiology of PCOS. This work highlights the pathogenic mechanism and represents a novel therapeutic target for PCOS. FUNDING: National Key Research and Development Program of China; National Natural Science Foundation of China grant."
3513,Doctor’s burnout and interventions,
3514,"Insights into the genetic diversity, recombination, and systemic infections with evidence of intracellular maturation of hepadnavirus in cats","Hepatitis B virus (HBV) is a human pathogen of global concern, while a high diversity of viruses related to HBV have been discovered in other animals during the last decade. Recently, the novel mammalian hepadnavirus, tentatively named domestic cat hepadnavirus (DCH), was detected in an immunocompromised cat. Herein, a collection of 209 cat sera and 15 hepato-diseased cats were screened for DCH using PCR, resulting in 12.4% and 20% positivity in the tested sera and necropsied cats, respectively. Among the DCH-positive sera, a significantly high level of co-detection with retroviral infection was found, with the highest proportion being co-detection with feline immunodeficiency virus (FIV). Full-length genome characterization of DCH revealed the genetic diversity between the nine Thai DCH sequences obtained, and that they phylogenetically formed three distinct monophyletic clades. A putative DCH recombinant strain was found, suggesting a possible role of recombination in DCH evolution. Additionally, quantitative PCR was used to determine the viral copy number in various organs of the DCH-moribund cats, while the pathological findings were compared to the viral localization in hepatocytes, adjacent to areas of hepatic fibrosis, by immunohistochemical (IHC) and western blot analysis. In addition to the liver, positive-DCH immunoreactivity was found in various other organs, including kidneys, lung, heart, intestine, brain, and lymph nodes, providing evidence of systemic infection. Ultrastructure of infected cells revealed electron-dense particles in the nucleus and cytoplasm of hepatocytes, bronchial epithelial cells, and fibroblasts. We propose the intracellular development mechanism of this virus. Although the definitive roles of pathogenicity of DCH remains undetermined, a contributory role of the virus associated with systemic diseases is possible."
3515,Orchard layout and plant traits influence fruit yield more strongly than pollinator behaviour and density in a dioecious crop,"Mutualistic plant-pollinator interactions are critical for the functioning of both non-managed and agricultural systems. Mathematical models of plant-pollinator interactions can help understand key determinants in pollination success. However, most previous models have not addressed pollinator behavior and plant biology combined. Information generated from such a model can inform optimal design of crop orchards and effective utilization of managed pollinators like western honey bees (Apis mellifera), and help generate hypotheses about the effects of management practices and cultivar selection. We expect that the number of honey bees per flower and male to female flower ratio will influence fruit yield. To test the relative importance of these effects, both singly and simultaneously, we utilized a delay differential equation model combined with Latin hypercube sampling for sensitivity analysis. Empirical data obtained from historical records and collected in kiwifruit (Actinidia chinensis) orchards in New Zealand were used to parameterize the model. We found that, at realistic bee densities, the optimal orchard had 65-75% female flowers, and the most benefit was gained from the first 6-8 bees/1000 flowers, with diminishing returns thereafter. While bee density significantly impacted fruit production, plant-based parameters-flower density and male:female flower ratio-were the most influential. The predictive model provides strategies for improving crop management, such as choosing cultivars which have their peak bloom on the same day, increasing the number of flowers with approximately 70% female flowers in the orchard, and placing enough hives to maintain more than 6 bees per 1000 flowers to optimize yield."
3516,Mental Health of Medical Workers in COVID-19 Pandemic: Restrictions and Barriers,
3517,Lingual Osseous Choristoma Causing Odynophagia in a Young Female,
3518,Discovery and Validation of Urinary Molecular Signature of Early Sepsis,"OBJECTIVES: Identify alterations in gene expression unique to systemic and kidney-specific pathophysiologic processes using whole-genome analyses of RNA isolated from the urinary cells of sepsis patients. DESIGN: Prospective cohort study. SETTING: Quaternary care academic hospital. PATIENTS: A total of 266 sepsis and 82 control patients enrolled between January 2015 and February 2018. INTERVENTIONS: Whole-genome transcriptomic analysis of messenger RNA isolated from the urinary cells of sepsis patients within 12 hours of sepsis onset and from control subjects. MEASUREMENTS AND MAIN RESULTS: The differentially expressed probes that map to known genes were subjected to feature selection using multiple machine learning techniques to find the best subset of probes that differentiates sepsis from control subjects. Using differential expression augmented with machine learning ensembles, we identified a set of 239 genes in urine, which show excellent effectiveness in classifying septic patients from those with chronic systemic disease in both internal and independent external validation cohorts. Functional analysis indexes disrupted biological pathways in early sepsis and reveal key molecular networks driving its pathogenesis. CONCLUSIONS: We identified unique urinary gene expression profile in early sepsis. Future studies need to confirm whether this approach can complement blood transcriptomic approaches for sepsis diagnosis and prognostication."
3519,Current Insight of Collagen Biomatrix for Gingival Recession: An Evidence-Based Systematic Review,"Collagen (Col) is a naturally available material and is widely used in the tissue engineering and medical field owing to its high biocompatibility and malleability. Promising results on the use of Col were observed in the periodontal application and many attempts have been carried out to inculcate Col for gingival recession (GR). Col is found to be an excellent provisional bioscaffold for the current treatment in GR. Therefore, the aim of this paper is to scrutinize an overview of the reported Col effect focusing on in vitro, in vivo, and clinical trials in GR application. A comprehensive literature search was performed using EBSCOhost, Science Direct, Springer Link, and Medline & Ovid databases to identify the potential articles on particular topics. The search query was accomplished based on the Boolean operators involving keywords such as (1) collagen OR scaffold OR hybrid scaffold OR biomaterial AND (2) gingiva recession OR tissue regeneration OR dental tissue OR healing mechanism OR gingiva. Only articles published from 2015 onwards were selected for further analysis. This review includes the physicochemical properties of Col scaffold and the outcome for GR. The comprehensive literature search retrieved a total of 3077 articles using the appropriate keywords. However, on the basis of the inclusion and exclusion criteria, only 15 articles were chosen for further review. The results from these articles indicated that Col promoted gingival tissue regeneration for GR healing. Therefore, this systematic review recapitulated that Col enhances regeneration of gingival tissue either through a slow or rapid process with no sign of cytotoxicity or adverse effect."
3520,"Insulator Based Dielectrophoresis: Micro, Nano, and Molecular Scale Biological Applications","Insulator based dielectrophoresis (iDEP) is becoming increasingly important in emerging biomolecular applications, including particle purification, fractionation, and separation. Compared to conventional electrode-based dielectrophoresis (eDEP) techniques, iDEP has been demonstrated to have a higher degree of selectivity of biological samples while also being less biologically intrusive. Over the past two decades, substantial technological advances have been made, enabling iDEP to be applied from micro, to nano and molecular scales. Soft particles, including cell organelles, viruses, proteins, and nucleic acids, have been manipulated using iDEP, enabling the exploration of subnanometer biological interactions. Recent investigations using this technique have demonstrated a wide range of applications, including biomarker screening, protein folding analysis, and molecular sensing. Here, we review current state-of-art research on iDEP systems and highlight potential future work."
3521,Separation of Glycyrrhizic Acid and Its Derivants from Hydrolyzation in Subcritical Water by Macroporous Resin,"Glycyrrhizic acid (GL) and its derivants, glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG) and glycyrrhetinic acid (GA) hydrolyzed in subcritical water, are bioactive substances and edulcorators. In this work, a separation strategy for these three substances was established. The effects of adsorbent and eluent were investigated by static/dynamic adsorption and multi-stage desorption with the mechanism analysis. The adsorption of them onto EXA50 resin was well fitted by the pseudo second-order kinetic model. The optimal dynamic adsorption flow rate was 6 bed volume (BV)/h, and water of pH = 12 was used to elute GL at 4 BV/h, then n-buthanol was used subsequently to elute GA at 1 BV/h, and finally 90% ethanol was applied to elute GAMG at 2 BV/h. As a result, purities of these compounds increased, which demonstrated that this adsorption-desorption technology was simple and efficient, and indicated the potential for large-scale purification and preparation of GL and its derivants in the future."
3522,Radiomics for Gleason Score Detection through Deep Learning,"Prostate cancer is classified into different stages, each stage is related to a different Gleason score. The labeling of a diagnosed prostate cancer is a task usually performed by radiologists. In this paper we propose a deep architecture, based on several convolutional layers, aimed to automatically assign the Gleason score to Magnetic Resonance Imaging (MRI) under analysis. We exploit a set of 71 radiomic features belonging to five categories: First Order, Shape, Gray Level Co-occurrence Matrix, Gray Level Run Length Matrix and Gray Level Size Zone Matrix. The radiomic features are gathered directly from segmented MRIs using two free-available dataset for research purpose obtained from different institutions. The results, obtained in terms of accuracy, are promising: they are ranging between 0.96 and 0.98 for Gleason score prediction."
3523,Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide,"Recently, the research community has become increasingly concerned with the receptor αvβ5, a member of the well-known integrin family. Different ongoing studies have evidenced that αvβ5 integrin regulates not only physiological processes but also a wide array of pathological events, suggesting the receptor as a valuable biomarker to specifically target for therapeutic/diagnostic purposes. Remarkably, in some tumors the involvement of the receptor in cell proliferation, tumor dissemination and angiogenesis is well-documented. In this scenario, the availability of a selective αvβ5 antagonist without ‘off-target’ protein effects may improve survival rate in patients with highly aggressive tumors, such as hepatocellular carcinoma. We recently reported a cyclic peptide, RGDechi15D, obtained by structure-activity studies. To our knowledge it represents the first peptide-based molecule reported in the literature able to specifically bind αvβ5 integrin and not cross react with αvβ3. Here we demonstrated the ability of the peptide to diminish both adhesion and invasion of HepG2 cells, an in vitro model system for hepatocellular carcinoma, to reduce the cell proliferation through an apoptotic process, and to interfere with the PI3K pathway. The peptide, also decreases the formation of new vessels in endothelial cells. Taken together these results indicate that the peptide can be considered a promising molecule with properties suited to be assessed in the future for its validation as a selective therapeutic/diagnostic weapon in hepatocarcinoma."
3524,Cytotoxicity of Oleandrin Is Mediated by Calcium Influx and by Increased Manganese Uptake in Saccharomyces cerevisiae Cells,"Oleandrin, the main component of Nerium oleander L. extracts, is a cardiotoxic glycoside with multiple pharmacological implications, having potential anti-tumoral and antiviral characteristics. Although it is accepted that the main mechanism of oleandrin action is the inhibition of Na(+)/K(+)-ATPases and subsequent increase in cell calcium, many aspects which determine oleandrin cytotoxicity remain elusive. In this study, we used the model Saccharomyces cerevisiae to unravel new elements accounting for oleandrin toxicity. Using cells expressing the Ca(2+)-sensitive photoprotein aequorin, we found that oleandrin exposure resulted in Ca(2+) influx into the cytosol and that failing to pump Ca(2+) from the cytosol to the vacuole increased oleandrin toxicity. We also found that oleandrin exposure induced Mn(2+) accumulation by yeast cells via the plasma membrane Smf1 and that mutants with defects in Mn(2+) homeostasis are oleandrin-hypersensitive. Our data suggest that combining oleandrin with agents which alter Ca(2+) or Mn(2+) uptake may be a way of controlling oleandrin toxicity."
3525,"Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor","The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1β and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1β signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1β-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1β induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1β-stimulated PBMC."
3526,Pollution Weather Prediction System: Smart Outdoor Pollution Monitoring and Prediction for Healthy Breathing and Living,"Air pollution has been a looming issue of the 21st century that has also significantly impacted the surrounding environment and societal health. Recently, previous studies have conducted extensive research on air pollution and air quality monitoring. Despite this, the fields of air pollution and air quality monitoring remain plagued with unsolved problems. In this study, the Pollution Weather Prediction System (PWP) is proposed to perform air pollution prediction for outdoor sites for various pollution parameters. In the presented research work, we introduced a PWP system configured with pollution-sensing units, such as SDS021, MQ07-CO, NO2-B43F, and Aeroqual Ozone (O(3)). These sensing units were utilized to collect and measure various pollutant levels, such as PM2.5, PM10, CO, NO(2), and O(3), for 90 days at Symbiosis International University, Pune, Maharashtra, India. The data collection was carried out between the duration of December 2019 to February 2020 during the winter. The investigation results validate the success of the presented PWP system. In the conducted experiments, linear regression and artificial neural network (ANN)-based AQI (air quality index) predictions were performed. Furthermore, the presented study also found that the customized linear regression methodology outperformed other machine-learning methods, such as linear, ridge, Lasso, Bayes, Huber, Lars, Lasso-lars, stochastic gradient descent (SGD), and ElasticNet regression methodologies, and the customized ANN regression methodology used in the conducted experiments. The overall AQI values of the air pollutants were calculated based on the summation of the AQI values of all the presented air pollutants. In the end, the web and mobile interfaces were developed to display air pollution prediction values of a variety of air pollutants."
3527,Feasibility and Reliability of SmartWatch to Obtain 3-Lead Electrocardiogram Recordings,"Some of the recently released smartwatch products feature a single-lead electrocardiogram (ECG) recording capability. The reliability of obtaining 3-lead ECG with smartwatches is yet to be confirmed in a large study. This study aimed to assess the feasibility and reliability of smartwatch to obtain 3-lead ECG recordings, the classical Einthoven ECG leads I-III compared to standard ECG. To record lead I, the watch was worn on the left wrist and the right index finger was placed on the digital crown for 30 s. For lead II, the watch was placed on the lower abdomen and the right index finger was placed on the digital crown for 30 s. For lead III, the same process was repeated with the left index finger. Spearman correlation and Bland-Altman tests were used for data analysis. A total of 300 smartwatch ECG tracings were successfully obtained. ECG waves’ characteristics of all three leads obtained from the smartwatch had a similar duration, amplitude, and polarity compared to standard ECG. The results of this study suggested that the examined smartwatch (Apple Watch Series 4) could obtain 3-lead ECG tracings, including Einthoven leads I, II, and III by placing the smartwatch on the described positions."
3528,Dibromopinocembrin and Dibromopinostrobin Are Potential Anti-Dengue Leads with Mild Animal Toxicity,"Dengue infection is one of the most deleterious public health concerns for two-billion world population being at risk. Plasma leakage, hemorrhage, and shock in severe cases were caused by immunological derangement from secondary heterotypic infection. Flavanone, commonly found in medicinal plants, previously showed potential as anti-dengue inhibitors for its direct antiviral effects and suppressing the pro-inflammatory cytokine from dengue immunopathogenesis. Here, we chemically modified flavanones, pinocembrin and pinostrobin, by halogenation and characterized them as potential dengue 2 inhibitors and performed toxicity tests in human-derived cells and in vivo animal model. Dibromopinocembrin and dibromopinostrobin inhibited dengue serotype 2 at the EC(50)s of 2.0640 ± 0.7537 and 5.8567 ± 0.5074 µM with at the CC(50)s of 67.2082 ± 0.9731 and >100 µM, respectively. Both of the compounds also showed minimal toxicity against adult C57BL/6 mice assessed by ALT and Cr levels in day one, three, and eight post-intravenous administration. Computational studies suggested the potential target be likely the NS5 methyltransferase at SAM-binding pocket. Taken together, these two brominated flavanones are potential leads for further drug discovery investigation."
3529,Providing Guidance During a Global Viral Pandemic for the Care of Patients With Inflammatory Bowel Disease,
3530,Flavonoid Profiles of Two New Approved Romanian Ocimum Hybrids,"Basil (Ocimum spp.) is a traditional herbal medicine abundant in antioxidants such as phenolic compounds. As part of a diet, this herb is proved to have some roles in decreasing the risk of cancer, and in the treatment of inflammation and neurodegenerative diseases. This study aims to explore the total phenolic and flavonoid content of two new basil hybrids growing in Romania, namely “Aromat de Buzau” (AB) and “Macedon” (MB). The antioxidant capacity of those two species was also analyzed by DPPH and cyclic voltammetry. Six different flavonoids, such as catechin (+), rutin, hyperoside, naringin, naringenin, and genistein, were separated, identified, and quantified by HPLC–DAD chromatography, for the first time, from romanian basil hybrids. The main flavonoid of the extracts was found to be naringin which is present in the highest amount (26.18 mg/kg) in “Aromat de Buzau” (O. basilicum) methanolic extract. These results suggest that dietary intake of these new hybrids can be a source of antioxidant compounds."
3531,"Potential Treatment of Breast and Lung Cancer Using Dicoma anomala, an African Medicinal Plant","Globally, cancer has been identified as one of the leading causes of death in public health. Its etiology is based on consistent exposure to carcinogenic. Plant-derived anticancer compounds are known to be less toxic to the normal cells and are classified into acetylenic compounds, phenolics, terpenes, and phytosterols. Dicoma anomala is a perennial herb belonging to the family Asteraceae and is widely distributed in Sub-Saharan Africa and used in the treatment of cancer, malaria, fever, diabetes, ulcers, cold, and cough. This review aimed at highlighting the benefits of D. anomala in various therapeutic applications with special reference to the treatment of cancers and the mechanisms through which the plant-derived agents induce cell death."
3532,An Injectable Hyaluronan–Methylcellulose (HAMC) Hydrogel Combined with Wharton’s Jelly-Derived Mesenchymal Stromal Cells (WJ-MSCs) Promotes Degenerative Disc Repair,"Intervertebral disc (IVD) degeneration is one of the predominant causes of chronic low back pain (LBP), which is a leading cause of disability worldwide. Despite substantial progress in cell therapy for the treatment of IVD degeneration, significant challenges remain for clinical application. Here, we investigated the effectiveness of hyaluronan–methylcellulose (HAMC) hydrogels loaded with Wharton’s Jelly-derived mesenchymal stromal cell (WJ-MSCs) in vitro and in a rat coccygeal IVD degeneration model. Following induction of injury-induced IVD degeneration, female Sprague-Dawley rats were randomized into four groups to undergo a single intradiscal injection of the following: (1) phosphate buffered saline (PBS) vehicle, (2) HAMC, (3) WJ-MSCs (2 × 10(4) cells), and (4) WJ-MSCs-loaded HAMC (WJ-MSCs/HAMC) (n = 10/each group). Coccygeal discs were removed following sacrifice 6 weeks after implantation for radiologic and histologic analysis. We confirmed previous findings that encapsulation in HAMC increases the viability of WJ-MSCs for disc repair. The HAMC gel maintained significant cell viability in vitro. In addition, combined implantation of WJ-MSCs and HAMC significantly promoted degenerative disc repair compared to WJ-MSCs alone, presumably by improving nucleus pulposus cells viability and decreasing extracellular matrix degradation. Our results suggest that WJ-MSCs-loaded HAMC promotes IVD repair more effectively than cell injection alone and supports the potential clinical use of HAMC for cell delivery to arrest IVD degeneration or to promote IVD regeneration."
3533,Synthesis of “All-Cis” Trihydroxypiperidines from a Carbohydrate-Derived Ketone: Hints for the Design of New β-Gal and GCase Inhibitors,"Pharmacological chaperones (PCs) are small compounds able to rescue the activity of mutated lysosomal enzymes when used at subinhibitory concentrations. Nitrogen-containing glycomimetics such as aza- or iminosugars are known to behave as PCs for lysosomal storage disorders (LSDs). As part of our research into lysosomal sphingolipidoses inhibitors and looking in particular for new β-galactosidase inhibitors, we report the synthesis of a series of alkylated azasugars with a relative “all-cis” configuration at the hydroxy/amine-substituted stereocenters. The novel compounds were synthesized from a common carbohydrate-derived piperidinone intermediate 8, through reductive amination or alkylation of the derived alcohol. In addition, the reaction of ketone 8 with several lithium acetylides allowed the stereoselective synthesis of new azasugars alkylated at C-3. The activity of the new compounds towards lysosomal β-galactosidase was negligible, showing that the presence of an alkyl chain in this position is detrimental to inhibitory activity. Interestingly, 9, 10, and 12 behave as good inhibitors of lysosomal β-glucosidase (GCase) (IC(50) = 12, 6.4, and 60 µM, respectively). When tested on cell lines bearing the Gaucher mutation, they did not impart any enzyme rescue. However, altogether, the data included in this work give interesting hints for the design of novel inhibitors."
3534,Photodynamic Inactivation of Methicillin-Resistant Staphylococcus aureus by a Natural Food Colorant (E-141ii),"This study evaluates the photosensitizing effectiveness of sodium copper chlorophyllin, a natural green colorant commonly used as a food additive (E-141ii), to inactivate methicillin-sensitive and methicillin-resistant Staphylococcus aureus under red-light illumination. Antimicrobial photodynamic inactivation (aPDI) was tested on a methicillin-sensitive reference strain (ATCC 25923) and a methicillin-resistant Staphylococcus aureus strain (GenBank accession number Mh087437) isolated from a clinical sample. The photoinactivation efficacy was investigated by exposing the bacterial strains to different E-141ii concentrations (0.0, 1.0, 2.5, 5.0, 10.0, and 20.0 µM) and to red light (625 nm) at 30 J cm(−2). The results showed that E-141ii itself did not prevent bacterial growth for all tested concentrations when cultures were placed in the dark. By contrast, E-141ii photoinactivated both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) under red-light illumination. However, different dose responses were observed for MSSA and MRSA. Whilst the MSSA growth was inhibited to the detection limit of the method with E-141ii at 2.5 µM, >10 µM concentrations were required to inhibit the growth of MRSA. The data also suggest that E-141ii can produce reactive oxygen species (ROS) via Type I reaction by electron transfer from its first excited singlet state to oxygen molecules. Our findings demonstrate that the tested food colorant has great potential to be used in aPDI of MRSA."
3535,‘Be on the TEAM’ Study (Teenagers Against Meningitis): protocol for a controlled clinical trial evaluating the impact of 4CMenB or MenB-fHbp vaccination on the pharyngeal carriage of meningococci in adolescents,"INTRODUCTION: Capsular group B Neisseria meningitidis (MenB) is the most common cause of invasive meningococcal disease (IMD) in many parts of the world. A MenB vaccine directed against the polysaccharide capsule remains elusive due to poor immunogenicity and safety concerns. The vaccines licensed for the prevention of MenB disease, 4CMenB (Bexsero) and MenB-fHbp (Trumenba), are serogroup B ‘substitute’ vaccines, comprised of subcapsular proteins and are designed to provide protection against most MenB disease-causing strains. In many high-income countries, such as the UK, adolescents are at increased risk of IMD and have the highest rates of meningococcal carriage. Beginning in the late 1990s, immunisation of this age group with the meningococcal group C conjugate vaccine reduced asymptomatic carriage and disrupted transmission of this organism, resulting in lower group C IMD incidence across all age groups. Whether vaccinating teenagers with the novel ‘MenB’ protein-based vaccines will prevent acquisition or reduce duration of carriage and generate herd protection was unknown at the time of vaccine introduction and could not be inferred from the effects of the conjugate vaccines. 4CMenB and MenB-fHbp may also impact on non-MenB disease-causing capsular groups as well as commensal Neisseria spp. This study will evaluate the impact of vaccination with 4CMenB or MenB-fHbp on oropharyngeal carriage of pathogenic meningococci in teenagers, and consequently the potential for these vaccines to provide broad community protection against MenB disease. METHODS AND ANALYSIS: The ‘Be on the TEAM’ (Teenagers Against Meningitis) Study is a pragmatic, partially randomised controlled trial of 24 000 students aged 16–19 years in their penultimate year of secondary school across the UK with regional allocation to a 0+6 month schedule of 4CMenB or MenB-fHbp or to a control group. Culture-confirmed oropharyngeal carriage will be assessed at baseline and at 12 months, following which the control group will be eligible for 4CMenB vaccination. The primary outcome is the carriage prevalence of potentially pathogenic meningococci (defined as those with genogroups B, C, W, Y or X), in each vaccine group compared separately to the control group at 12 months post-enrolment, that is, 12 months after the first vaccine dose and 6 months after the second vaccine dose. Secondary outcomes include impact on carriage of: genogroup B meningococci; hyperinvasive meningococci; all meningococci; those meningococci expressing vaccine antigens and; other Neisseria spp. A sample size of 8000 in each arm will provide 80% power to detect a 30% reduction in meningococcal carriage, assuming genogroup B, C, W, Y or X meningococci carriage of 3.43%, a design effect of 1.5, a retention rate of 80% and a significance level of 0.05. Study results will be available in 2021 and will inform the UK and international immunisation policy and future vaccine development. ETHICS AND DISSEMINATION: This study is approved by the National Health Service South Central Research Ethics Committee (18/SC/0055); the UK Health Research Authority (IRAS ID 239091) and the UK Medicines and Healthcare products Regulatory Agency. Publications arising from this study will be submitted to peer-reviewed journals. Study results will be disseminated in public forums, online, presented at local and international conferences and made available to the participating schools. TRIAL REGISTRATION NUMBERS: ISRCTN75858406; Pre-results, EudraCT 2017-004609-42."
3536,A Software Architecture for the Industrial Internet of Things—A Conceptual Model,"The Internet of Things (IoT) is an emerging concept that has revolutionized the use of new technologies in everyday life. The economic impact of IoT becoming very important, and it began to be used in the industrial environment under the name of the Industrial Internet of Things (IIoT) concept, which is a sub-domain of IoT. The IIoT changes the way industrial processes are controlled and monitored, increasing operating efficiency. This article proposes a software architecture for IIoT that has a low degree of abstraction compared to the reference architectures presented in the literature. The architecture is organized on four-layer and it integrates the latest concepts related to fog and edge computing. These concepts are activated through the use of fog/edge/gateway nodes, where the processing of data acquired from things is performed and it is the place where things interact with each other in the virtual environment. The main contributions of this paper are the proposal and description of a complete IIoT software architecture, the use of a unified address space, and the use of the computing platform based on SoC (System on Chip) with specialized co-processors in order to be able to execute in real-time certain time-critical operations specific to the industrial environment."
3537,Therapeutic Uses of Red Macroalgae,"Red Seaweed “Rhodophyta” are an important group of macroalgae that include approximately 7000 species. They are a rich source of structurally diverse bioactive constituents, including protein, sulfated polysaccharides, pigments, polyunsaturated fatty acids, vitamins, minerals, and phenolic compounds with nutritional, medical, and industrial importance. Polysaccharides are the main components in the cell wall of red algae and represent about 40–50% of the dry weight, which are extensively utilized in industry and pharmaceutical compounds, due to their thickening and gelling properties. The hydrocolloids galactans carrageenans and agars are the main red seaweed cell wall polysaccharides, which had broad-spectrum therapeutic characters. Generally, the chemical contents of seaweed are different according to the algal species, growth stage, environment, and external conditions, e.g., the temperature of the water, light intensity, nutrient concentrations in the ecosystem. Economically, they can be recommended as a substitute source for natural ingredients that contribute to a broad range of bioactivities like cancer therapy, anti-inflammatory agents, and acetylcholinesterase inhibitory. This review touches on the main points of the pharmaceutical applications of red seaweed, as well as the exploitation of their specific compounds and secondary metabolites with vital roles."
3538,Factors Associated With Influential Health-Promoting Messages on Social Media: Content Analysis of Sina Weibo,"BACKGROUND: Social media is a powerful tool for the dissemination of health messages. However, few studies have focused on the factors that improve the influence of health messages on social media. OBJECTIVE: To explore the influence of goal-framing effects, information organizing, and the use of pictures or videos in health-promoting messages, we conducted a case study of Sina Weibo, a popular social media platform in China. METHODS: Literature review and expert discussion were used to determine the health themes of childhood obesity, smoking, and cancer. Web crawler technology was employed to capture data on health-promoting messages. We used the number of retweets, comments, and likes to evaluate the influence of a message. Statistical analysis was then conducted after manual coding. Specifically, binary logistic regression was used for the data analyses. RESULTS: We crawled 20,799 Sina Weibo messages and selected 389 health-promoting messages for this study. Results indicated that the use of gain-framed messages could improve the influence of messages regarding childhood obesity (P<.001), smoking (P=.03), and cancer (P<.001). Statistical expressions could improve the influence of messages about childhood obesity (P=.02), smoking (P=.002), and cancer (P<.001). However, the use of videos significantly improved the influence of health-promoting messages only for the smoking-related messages (P=.009). CONCLUSIONS: The findings suggested that gain-framed messages and statistical expressions can be successful strategies to improve the influence of messages. Moreover, appropriate pictures and videos should be added as much as possible when generating health-promoting messages."
3539,A one-year time frame for voice prosthesis management. What should the physician expect? Is it an overrated job?,"Management of late complications represents the main reason for reluctance in using voice prosthesis rehabilitation. The aim of this paper is to report our experience by describing the one-year management of a large cohort of patients in order to clarify how demanding management is in terms of burden on clinicians. Between June 2017 and June 2018, each access made at the Otolaryngology Clinic of our Institute for issues related to prosthesis by 70 laryngectomised patients rehabilitated by voice prosthesis was registered in a specific database. A review of the data provided information on the incidence, management and outcomes of adverse events encountered during the selected time frame. In addition, a T test was used to evaluate the differences between irradiated and non-irradiated patients and between primary and secondary tracheo-oesophageal-puncture. Leakage through the prosthesis was the most common cause for access (51.86%). The median number of accesses per patient per year was 3.47. The speech therapist autonomously managed 18.1% of accesses. The median number of accesses per patient per year needing a physician was 2.84. The median lifetime of the prosthesis was 4.85 months. Radiotherapy or modality (primary or secondary) of the puncture did not influence the number of accesses per year or the prosthesis lifetime. This retrospective analysis of results highlighted the most frequent issues and the most effective measures to deal with them, which allowed us to define a systematic algorithm to standardise and ease long-term outpatient management."
3540,Artificial Intelligence and Health in Nepal,"The growth in information technology and computer capacity has opened up opportunities to deal with much and much larger data sets than even a decade ago. There has been a technological revolution of big data and Artificial Intelligence (AI). Perhaps many readers would immediately think about robotic surgery or self-driving cars, but there is much more to AI. This Short Communication starts with an overview of the key terms, including AI, machine learning, deep learning and Big Data. This Short Communication highlights so developments of AI in health that could benefit a low-income country like Nepal and stresses the need for Nepal’s health and education systems to track such developments and apply them locally. Moreover, Nepal needs to start growing its own AI expertise to help develop national or South Asian solutions. This would require investing in local resources such as access to computer power/capacity as well as training young Nepali to work in AI."
3541,Contemporary Patterns of Multiple Organ Dysfunction in Trauma: Erratum,
3542,The Emerging Role of Community Pharmacists in Remote Patient Monitoring Services,"Remote physiologic monitoring (RPM) services involve the transmission of patient-collected physiologic data to the healthcare team. These data are then analyzed to determine what changes may be needed to enhance patient care. While pharmacists may not be recognized as billing providers through some payers, there are opportunities for pharmacist collaboration with providers to enhance patient access to RPM services. Community pharmacist services are traditionally tied to a product, but pharmacists are skilled in medication management, disease state evaluation, and patient counseling, which are skills that can contribute to an elevated RPM program."
3543,Is There a Role for Absorbable Metals in Surgery? A Systematic Review and Meta-Analysis of Mg/Mg Alloy Based Implants,"Magnesium (Mg) alloys have received attention in the literature as potential biomaterials for use as absorbable implants in oral and maxillofacial and orthopedic surgery applications. This study aimed to evaluate the available clinical studies related to patients who underwent bone fixation (patients), and received conventional fixation (intervention), in comparison to absorbable metals (comparison), in terms of follow-up and complications (outcomes). A systematic review and meta-analysis were performed in accordance with the PRISMA statement and PROSPERO (CRD42020188654), PICO question, ROBINS-I, and ROB scales. The relative risk (RR) of complications and failures were calculated considering a confidence interval (CI) of 95%. Eight studies (three randomized clinical trial (RCT), one retrospective studies, two case-control studies, and two prospective studies) involving 468 patients, including 230 Mg screws and 213 Titanium (Ti) screws, were analyzed. The meta-analysis did not show any significant differences when comparing the use of Mg and Ti screws for complications (p = 0.868). The estimated complication rate was 13.3% (95% CI: 8.3% to 20.6%) for the comparison group who received an absorbable Mg screw. The use of absorbable metals is feasible for clinical applications in bone surgery with equivalent outcomes to standard metal fixation devices."
3544,Heterogeneous Influences of Social Support on Physical and Mental Health: Evidence from China,"Employing a national representative survey (the China Labor-force Dynamics Survey 2016, CLDS2016) data (N = 14246), this paper examines the heterogeneous influences of social support on individual physical and mental health in China. Social support is characterized by four dimensions: emotional support, tangible or instrumental support, interaction or exchange support, and community support. Physical health is measured by self-rated health and body mass index (BMI), while mental health is measured by depression, hopelessness, failure, fear, loneliness, and meaninglessness. The results indicate that different dimensions of social support have heterogeneous effects on individual physical and mental health. Specifically, the correlation between emotional support and individual physical health is not significant, but emotional support is significantly related to some mental health variables. Tangible or instrumental support is significantly related to individual self-rated physical health but not to BMI or mental health. Interaction or exchange support is significantly correlated with individual self-rated health and some mental health variables. In general, there are significant correlations between community support, and individual physical and mental health. The results also suggest that the influences of social support on physical and mental health of individuals at different ages (<60 years and ≥60 years) are heterogeneous. The results of this study provide direction for the dimension selection of social support to promote individual health."
3545,Community Pharmacists’ Perceptions of Patient Care Services within an Enhanced Service Network,"Background: Pharmacists are positioned as an accessible source of patient care services (PCS). Despite the adversity community pharmacies continue to face, the expanding opportunity of offering PCS continues to be a pathway forward. Objective: To identify community pharmacists’ perceptions to deliver PCS within an enhanced service network. Methods: One-on-one semi-structured phone interviews were conducted as part of a mixed-methods approach. Interview transcripts were analyzed using a consensus codebook to draft thematic findings. Participants were recruited from an electronic survey targeting community pharmacists from the New York chapters of the Community Pharmacy Enhanced Services Network (CPESN). Results: Twelve pharmacists were interviewed with four main themes identified. The majority of study participants were pharmacy owners (92%) devoting an average of 15 h/week to PCS and 8 h/week addressing social barriers. The main themes identified include: (1) perceptions of pharmacy profession, (2) reimbursement models and sustainability of PCS, (3) provision of patient care services, and (4) how PCS address social determinants of health. Conclusions: Offering PCS opportunities for patients is a direction many community pharmacists have embraced and are working to succeed. Ongoing research is needed focusing on community pharmacists’ self-perceptions of the clinical impact and role they hold in an evolving healthcare system."
3546,Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach,"The cyclooxygenase-2 receptor is a therapeutic target for planning potential drugs with anti-inflammatory activity. The selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was selected as a pivot molecule to perform virtual ligand-based screening from six commercial databases. We performed the search for similarly shaped Rapid Overlay of Chemical Structures (ROCS) and electrostatic (EON) compounds. After, we used pharmacokinetic and toxicological parameters to determine the best potential compounds, obtained through the softwares QikProp and Derek, respectively. Then, the compounds proceeded to the molecular anchorage study, which showed promising results of binding affinity with the hCOX-2 receptor: LMQC72 (∆G = −11.0 kcal/mol), LMQC36 (∆G = −10.6 kcal/mol), and LMQC50 (∆G = −10.2 kcal/mol). LMQC72 and LMQC36 showed higher binding affinity compared to rofecoxib (∆G = −10.4 kcal/mol). Finally, molecular dynamics (MD) simulations were used to evaluate the interaction of the compounds with the target hCOX-2 during 150 ns. In all MD simulation trajectories, the ligands remained interacting with the protein until the end of the simulation. The compounds were also complexing with hCOX-2 favorably. The compounds obtained the following affinity energy values: rofecoxib: ΔGbind = −45.31 kcal/mol; LMQC72: ΔGbind = −38.58 kcal/mol; LMQC36: ΔGbind = −36.10 kcal/mol; and LMQC50: ΔGbind = −39.40 kcal/mol. The selected LMQC72, LMQC50, and LMQC36 structures showed satisfactory pharmacokinetic results related to absorption and distribution. The toxicological predictions of these compounds did not display alerts for possible toxic groups and lower risk of cardiotoxicity compared to rofecoxib. Therefore, future in vitro and in vivo studies are needed to confirm the anti-inflammatory potential of the compounds selected here with bioinformatics approaches based on rofecoxib ligand."
3547,"Promoting Equity, Social Justice, and Saving Lives with Life Jacket and Clothing Policies","Worldwide, diverse racial/ethnic groups have disproportionately higher drowning rates. Learning to swim and wearing life jackets decrease drowning risk. We evaluated aquatic facilities’ policies regarding use of life jackets, clothing, and diapers through a lens of social justice, equity, and inclusion to ensure they met the needs of the diverse high-risk groups they serve and changing aquatic activities and programs. Public recreational pools, beach and waterpark facilities in the US and international organizations were surveyed regarding their policies on life jacket use, clothing, and diapers between 2015 and 2016. A total of 562 facilities responded, mostly pools. Almost all facilities allowed wearing life jackets in the shallow end but less so in the deep end, and wearing of T-shirts, shorts, and clothes for modesty reasons. Policies varied most on wearing non-swim clothes. Almost universal requirement of diapers applied to infants only. Respondents’ reported themes included cost, access, safety, hygiene and equipment maintenance. Reviewed policies generally reflected facilities’ responsiveness to diverse populations’ specific needs. However, policy variations around wearing clothing and swim diapers could be costly, confusing, and impede participation in aquatic activities by vulnerable populations, specifically young children and racial and ethnic minorities. Standardization of these policies could assist aquatic facilities and their users. A best-practices-based policy is outlined."
3548,"Associations of Socio-Demographic, Clinical and Biochemical Parameters with Healthcare Cost, Health- and Renal-Related Quality of Life in Hemodialysis Patients: A Clinical Observational Study","We examined factors associated with healthcare cost, health-related quality of life (HRQOL), and kidney disease quality of life (KDQOL) in hemodialysis patients. We conducted a cross-sectional study on 160 patients from January to April 2019 at a hemodialysis center. Socio-demographic, clinical, and laboratory parameters and quality of life (QOL) (using KDQOL-SF-v1.3) were assessed. Monthly healthcare costs were extracted from the hospital information system. The means of healthcare cost, HRQOL, and KDQOL were VND 9.4 ± 1.6 million, VND 45.1 ± 21.9 and VND 51.3 ± 13.0, respectively. In the multivariate analysis, the healthcare cost was higher in patients with a longer hemodialysis vintage (regression coefficient (B): 0.74; 95% confidence interval (95% CI): 0.25; 1.23), comorbidity (B: 0.77; 95% CI: 0.24; 1.31); and lower in those with a higher hematocrit concentration (B: −0.07; 95% CI: −0.13; −0.01). Patients that lived in urban areas (B: 9.08; 95% CI: 2.30; 15.85) had a better HRQOL; those with a comorbidity (B: −14.20; 95% CI: −21.43; −6.97), and with hypoalbuminemia (B: −9.31; 95% CI: −16.58; −2.04) had a poorer HRQOL. Patients with a higher level of education (B: 5.38~6.29) had a better KDQOL; those with a comorbidity had a poorer KDQOL (B: −6.17; 95% CI: −10.49; −1.85). In conclusion, a longer hemodialysis vintage, a comorbidity and a lower hematocrit concentration were associated with higher healthcare costs. Patients who lived in urban areas had a better HRQOL and a higher level of education led to a better KDQOL. Patients with a comorbidity had a lower HRQOL and KDQOL. Malnourished patients had a lower HRQOL."
3549,Psychosocial Aspects of Female Breast Cancer in the Middle East and North Africa,"Breast cancer, the most common cancer among women in the Middle East and North Africa (MENA) region, is associated with social and psychological implications deriving from women’s socio-cultural contexts. Examining 74 articles published between 2007 and 2019, this literature/narrative review explores the psychosocial aspects of female breast cancer in the MENA region. It highlights socio-cultural barriers to seeking help and socio-political factors influencing women’s experience with the disease. In 17 of 22 Arab countries, common findings emerge which derive from shared cultural values. Findings indicate that women lack knowledge of breast cancer screening (BCS) and breast cancer self-examination (BSE) benefits/techniques due to a lack of physicians’ recommendations, fear, embarrassment, cultural beliefs, and a lack of formal and informal support systems. Women in rural areas or with low socioeconomic status further lack access to health services. Women with breast cancer, report low self-esteem due to gender dynamics and a tendency towards fatalism. Collaboration between mass media, health and education systems, and leading social-religious figures plays a major role in overcoming psychological and cultural barriers, including beliefs surrounding pain, fear, embarrassment, and modesty, particularly for women of lower socioeconomic status and women living in crises and conflict zones."
3550,Resting-State Isolated Effective Connectivity of the Cingulate Cortex as a Neurophysiological Biomarker in Patients with Severe Treatment-Resistant Schizophrenia,"Background: The neural basis of treatment-resistant schizophrenia (TRS) remains unclear. Previous neuroimaging studies suggest that aberrant connectivity between the anterior cingulate cortex (ACC) and default mode network (DMN) may play a key role in the pathophysiology of TRS. Thus, we aimed to examine the connectivity between the ACC and posterior cingulate cortex (PCC), a hub of the DMN, computing isolated effective coherence (iCoh), which represents causal effective connectivity. Methods: Resting-state electroencephalogram with 19 channels was acquired from seventeen patients with TRS and thirty patients with non-TRS (nTRS). The iCoh values between the PCC and ACC were calculated using sLORETA software. We conducted four-way analyses of variance (ANOVAs) for iCoh values with group as a between-subject factor and frequency, directionality, and laterality as within-subject factors and post-hoc independent t-tests. Results: The ANOVA and post-hoc t-tests for the iCoh ratio of directionality from PCC to ACC showed significant findings in delta (t(45) = 7.659, p = 0.008) and theta (t(45) = 8.066, p = 0.007) bands in the left side (TRS < nTRS). Conclusion: Left delta and theta PCC and ACC iCoh ratio may represent a neurophysiological basis of TRS. Given the preliminary nature of this study, these results warrant further study to confirm the importance of iCoh as a clinical indicator for treatment-resistance."
3551,Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus,"The sequence of non-structural protein NS1 of bluetongue virus (BTV), which contains immunodominant CD8+ T cell epitopes, is highly conserved among BTV serotypes, and has therefore become a major tool in the development of a universal BTV vaccine. In this work, we have engineered multiserotype BTV vaccine candidates based on recombinant chimpanzee adenovirus (ChAdOx1) and modified vaccinia virus Ankara (MVA) vectors expressing the NS1 protein of BTV-4 or its truncated form NS1-Nt. A single dose of ChAdOx1-NS1 or ChAdOx1-NS1-Nt induced a moderate CD8+ T cell response and protected IFNAR(-/-) mice against a lethal dose of BTV-4/MOR09, a reassortant strain between BTV-1 and BTV-4, although the animals showed low viremia after infection. Furthermore, IFNAR(-/-) mice immunized with a single dose of ChAdOx1-NS1 were protected after challenge with a lethal dose of BTV-8 in absence of viremia nor clinical signs. Additionally, the heterologous prime-boost ChAdOx1/MVA expressing NS1 or NS1-Nt elicited a robust NS1 specific CD8+ T cell response and protected the animals against BTV-4/MOR09 even 16 weeks after immunization, with undetectable levels of viremia at any time after challenge. Subsequently, the best immunization strategy based on ChAdOx1/MVA-NS1 was assayed in sheep. Non-immunized animals presented fever and viremia levels up to 10(4) PFU/mL after infection. In contrast, although viremia was detected in immunized sheep, the level of virus in blood was 100 times lower than in non-immunized animals in absence of clinical signs."
3552,"True Negatives: Disseminating Research on Null, Inconclusive, and Confirmatory Findings in Cardiovascular Science",
3553,Correlation study between blood cytokines and lymphocytes in early postoperative critical patients with compromised immune function,"Major surgery due to traumatic injury can activate early systemic postoperative pro-inflammatory responses and postoperative immunosuppression. However, the interaction between them is complex and not entirely clear. This study was performed in postoperative patients admitted to the intensive care unit (ICU) to elucidate the correlation between the systemic cellular immunity function and circulating cytokines levels in the early postoperative period. Twenty-four cases of postoperative patients admitted to the ICU were enrolled in this study. Twelve hours after admission, blood routine examination and measurement of circulating cytokines (interleukin-2 [IL-2], IL-4, IL-6, IL-10, IL-17A, interferon-γ, tumor necrosis factor-alpha [TNF-α], TNF-β, granulocyte-colony stimulating factor [G-CSF], and granulocyte-macrophage colony-stimulating factor [GM-CSF]) were performed. The correlation analysis between cytokines levels and absolute peripheral blood lymphocyte count or lymphocytes/neutrophils ratio was analyzed. The cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, G-CSF, and GM-CSF) levels were increased above the normal upper limit at 12 hours after surgery. The number of leukocytes and neutrophils were markedly increased. In contrast, the absolute count and relative ratio of lymphocytes decreased below the lower normal limit. Spearman correlation analysis showed a moderate negative correlation between absolute peripheral blood lymphocyte count and IL-2 or IL-4 level. A low-negative correlation between absolute peripheral blood lymphocyte count and GM-CSF levels was detected. We also found that lymphocytes/neutrophils ratio was also negatively correlated with plasma IL-2, IL-4, or GM-CSF level. In ICU patients with compromised immune function in the early postoperative period, the elevated levels of IL-2, IL-4, and GM-CSF may be the compensatory responses to systemic immunosuppression."
3554,Erratum,
3555,A second C-reactive protein (CRP) test to detect inflammatory burst in patients with acute bacterial infections presenting with a first relatively low CRP,"A first C-reactive protein (CRP) test, as often performed by clinicians during the presentation of patients with an acute bacterial infection, might be misleading. The aim of our study was to explore the dynamic between a second CRP test taken within 12 hours from admission CRP test in a cohort of patients diagnosed with acute bacterial infection in comparison to CRP in a control group of apparently healthy individuals. This was a historical cohort study comprised of all patients admitted to the Sourasky Tel-Aviv Medical Center, Israel, between July 2007 and March 2016. The study cohort included adult patients who were diagnosed as having an infection, assumed to be of bacterial etiology (cellulitis and erysipelas, pneumonia, cholecystitis, pyelonephritis, or septicemia), who had a CRP test during the first 6 hours of hospital admission (baseline CRP), and a successive CRP test up to 12 hours from the first one (recurrent CRP). The control group was of healthy subjects who attended our medical center for a routine annual check-up. The study included 950 patients. Baseline CRP ranged from 0.04 to 454 mg/L. The median CRP velocity was 0.53 mg/L/h. Patients were grouped by baseline CRP into 4 groups (CRP < 10, 10–74.9, 75–199.9, ≥200). There was an increase in median CRP velocity between the first (0.48 mg/L/h) and the second (0.93 mg/L/h) groups, which then was decreased in the next 2 groups (0.46 and −2.58 mg/L/h, respectively). In 45 of 103 (44%) patients of the group of baseline CRP concentration less than 10 mg/dL with bacterial diagnosis, there was a complete overlap with CRP values of apparently healthy individuals during their routine annual checkup. A first single low CRP result cannot exclude the presence of a significant bacterial infection. Patients with acute bacterial infection might present with a relatively low CRP value that at times correspond to normal limit CRP concentrations. A second test, obtained within 12 hours of admission, might serve as an important tool to identify patient with an evolving inflammatory burst commonly seen during acute bacterial infection."
3556,"Knowledge, Attitudes, and Intentions towards HIV Pre-Exposure Prophylaxis among Nursing Students in Spain","Human immunodeficiency virus (HIV) infection is one of the main causes of morbidity and mortality worldwide. Among the preventive approaches proposed to control this disease is pre-exposure prophylaxis (PrEP), whose effectiveness depends on the medication adherence. The aim of the present study was to determine the knowledge and attitudes about PrEP among a sample of Spanish nursing students as well as their intentions of receiving it in case it was indicated. An observational cross-sectional descriptive study was carried out. A total of 570 nursing students from the University of Santiago de Compostela (Spain), ≥18 years old and of both sexes were invited to self-complete a questionnaire between February and March 2020. A total of 352 students decided to participate in the study. Participants had low knowledge [overall knowledge score 1(0–2)] and a neutral attitude towards PrEP. The intention of receiving PrEP improved significantly after the completion of the questionnaire and the administration of information about PrEP (p = 0.039; before: 23.58% and after: 93.77%). Nursing staff play an important role in the prevention of sexually transmitted diseases, so their training in preventive strategies, such as PrEP, could help to reduce the incidence of new cases of HIV infection."
3557,Towards Distributed Recycling with Additive Manufacturing of PET Flake Feedstocks,"This study explores the potential to reach a circular economy for post-consumer Recycled Polyethylene Terephthalate (rPET) packaging and bottles by using it as a Distributed Recycling for Additive Manufacturing (DRAM) feedstock. Specifically, for the first time, rPET water bottle flake is processed using only an open source toolchain with Fused Particle Fabrication (FPF) or Fused Granular Fabrication (FGF) processing rather than first converting it to filament. In this study, first the impact of granulation, sifting, and heating (and their sequential combination) is quantified on the shape and size distribution of the rPET flakes. Then 3D printing tests were performed on the rPET flake with two different feed systems: an external feeder and feed tube augmented with a motorized auger screw, and an extruder-mounted hopper that enables direct 3D printing. Two Gigabot X machines were used, each with the different feed systems, and one without and the latter with extended part cooling. 3D print settings were optimized based on thermal characterization, and both systems were shown to 3D print rPET directly from shredded water bottles. Mechanical testing showed the importance of isolating rPET from moisture and that geometry was important for uniform extrusion. The mechanical strength of 3D-printed parts with FPF and inconsistent flow is lower than optimized fused filament, but adequate for a wide range of applications. Future work is needed to improve consistency and enable water bottles to be used as a widespread DRAM feedstock."
3558,Upper and Lower Respiratory Signs and Symptoms in Workers Occupationally Exposed to Flour Dust,"A group of 142 bakers was studied in order to investigate the relationship between higher/lower respiratory signs/symptoms and inflammation biomarkers and occupational exposure to flour dust. A complete upper and lower respiratory tract evaluation was performed. Seven percent of bakers complained of lower respiratory symptoms, while 22% of them complained of upper respiratory symptoms. Fifty five percent of the bakers were allergic, and 37.1% showed sensitization to occupational allergens. Abnormal spirometries were found in 15% of bakers, while fractional exhaled nitric oxide (FeNO) was above the normal reference in 24.5% of them. Moreover, 23.8% of bakers were found to be hyposmic. Population mean peak nasal inspiratory flow (PNIF) was in the normal range even if almost all the workers suffered from neutrophilic rhinitis at nasal cytology with the number of nasal neutrophils increasing with the increase of the duration of exposure to flour dust (p = 0.03). PNIF and FEV1 (forced expiratory volume in the 1st second) showed a positive correlation (p = 0.03; r = 0.19). The Tiffeneau index decreased with the increase of dust (p = 0.017). A similar result was obtained once we divided our population into smokers and non-smokers (p = 0.021). Long-term exposure to bakery dusts can lead to a status of minimal nasal inflammation and allergy."
3559,Do Protected Areas Matter? A Systematic Review of the Social and Ecological Impacts of the Establishment of Protected Areas,"There is growing interest in evaluating the effects of establishing protected areas (PAs). However, the mechanisms through which the establishment of PAs achieved significant positive effects remain unclear, and how different conservation mechanisms have achieved significant positive social and ecological benefits has also not been sufficiently studied. In this study, we systematically reviewed exemplary cases from Asia, Africa, and South America, using panel data to assess the conservation effectiveness of nature reserves and national parks. By surveying 629 literature samples reported in 31 studies, we found that the establishment of PAs has positive influences on poverty reduction, family incomes, household expenditure, employment, forest cover, biodiversity, carbon sequestration, and a reduction in forest fragmentation. Furthermore, we analyzed the specific aspects that influence the publication of a paper in a high-impact journal. We found that publication is more likely when the research uses panel data, matching methods of data analysis, large samples, and plots or PAs as research units and has significant evaluation results. Our results suggest that future studies should use panel data and matching method analysis to assess the impacts of PAs from multiple perspectives and focus on the effectiveness of specific conservation mechanisms in achieving positive effects."
3560,Improvement of Dietary Diversity and Attitude toward Recommended Feeding through Novel Community Based Nutritional Education Program in Coastal Kenya—An Intervention Study,"Community-based nutritional intervention to improve the practice of dietary diversity and child nutrition by community health workers (CHWs) involving Nyumba Kumi as small neighborhood units (SNUs) in communities has not yet been explored. This study was conducted in two villages in rural Kenya between 2018 and 2019. In total, 662 participants (control vs. intervention: n = 339 vs. n = 323) were recruited. The intervention group received education on maternal and child nutrition and follow-up consultations. The custom-tailored educational guidelines were made based on Infant and Young Child Feeding and the mother and child health booklet. The educational effects on household caregivers’ feeding practice attitude and child nutritional status were analyzed using multiple linear regression. After the intervention, a total of 368 household caregivers (187 vs. 181) and 180 children (113 vs. 67) were analyzed separately. Between the groups, no significant difference was found in their background characteristics. This study successfully improved the dietary diversity score (β = 0.54; p < 0.01) and attitude score (β = 0.29; p < 0.01). The results revealed that the interventions using CHWs and SNUs were useful to improve dietary diversity and caregivers’ attitudes toward recommended feeding. This research has the potential to be successfully applied in other regions where child undernutrition remains."
3561,The Thermal Conductivity of 3D Printed Plastic Insulation Materials—The Effect of Optimizing the Regular Structure of Closures,"In the interest of environmental protection, attention should be paid to improving energy efficiency, through the use of appropriate insulations. They can be used in the construction industry, for plastic window frames, and the thermal insulation of buildings. It is also possible to use these materials in the electronics industry, for hermetic casings of devices, in the aviation industry, as well as in the food industry, as collective packaging for frozen food. The technology of using additive 3D printing to create prototype insulating materials made of plastic is proposed in this article. Multi-layer materials, with quadrangle, hexagonal, and triangle closures were designed and printed. A mathematical model was developed, and then experimentally verified. Quadrangle and hexagonal structures were shown to be useful, and triangle structures to be of little use. The optimal size of closure was determined to be 10 mm, with no convection, and 6 mm, with possible convection. The lowest thermal conductivity of the insulation was 0.0591 W/(m·K) for 10 mm single-layer quadrangle and hexagonal closures with an insulation density of 180 kg/m(3)."
3562,Downside: The Perpetrator of Violence in the Representations of Social and Health Professionals,"Gender-based violence is a widespread phenomenon and pandemic that affects women’s lives. Many interventions have been activated for perpetrators, but the dropout rate is still high. In order to draw up guidelines for responsibly and sustainably dealing with the phenomenon, this study is aimed at investigating the professionals’ perception of the perpetrator as a useful element in designing innovative intervention policies. Open interviews were carried out with welfare and health professionals and the Grounded Theory Methodology was used to analyze the collected data. These results detect attitudes of social health personnel and their feelings of impotence towards gender-based perpetrators because of the emergence of an inevitable repetitiveness of the violent behavior, as well as the “normality of violence” in a patriarchal culture and its “transversality”. This reflective knowledge allows for the opportunity to develop best transformative attitudes toward the phenomenon. According to the results, it is urgent to establish an active and convinced alliance with the healthy part of the man, through specific prevention paths, in order to activate an authentic motivation for change and its sustainability."
3563,Nursing Education in Catalonia: Novice Professionals’ Appraisal of Its Quality and Usefulness. Does Mobility Play a Role?,"The present study aimed to examine the relationship between the quality of undergraduate education perceived by novice nurses and their retrospective satisfaction with their education. It also studied the relationships between the perceived usefulness of their education for their current jobs and the quality of the jobs held by novice nursing professionals. The moderator role of mobility in this relationship was also analyzed, as it reflects a boundary condition in which additional preparation or job opportunities may occur. The study used data from the graduates’ survey carried out by the Agència per a la Qualitat del Sistema Universitari de Catalunya (AQU) in 2017. The analysis of data from 644 graduates of Catalan Universities in 2014 highlights different functions of two types of knowledge and skills; those directly related to science and the practice of nursing are stronger predictors of retrospective satisfaction with nursing education. In turn, the perception of the usefulness of horizontal skills, such as transversal and communication skills, plays a stronger role in predicting job quality. The results about the role of mobility were not conclusive, and more research is needed to clarify its influence on nursing education and subsequent professional practice."
3564,The Importance of Genuineness in Public Engagement—An Exploratory Study of Pediatric Communication on Social Media in China,"There is a growing need for the public to interact with pediatricians through social media in China, and genuineness is a crucial factor contributing to effective communication, but few studies have examined the relationship between genuineness and its effect on public engagement. This study developed a four-dimension framework including self-disclosure, genuine response, functional interactivity, and genuineness in Chinese culture to investigate the effect of genuineness in the communication of Chinese social media influencers in pediatrics on public engagement. Content analysis was employed to examine these dimensions and the related public engagement in 300 social media posts on the largest microblogging site in China. The findings indicate that genuine response was positively associated with the number of comments and positive comments, while negatively related to the number of shares. Functional interactivity made the site more appealing, resulting in likes and shares. Genuineness in Chinese culture was reflected in engagement through sharing posts by the public. This study is the first to develop an integrated framework to measure genuineness in online health communication and contributes to the understanding of the effect of genuineness on Chinese public engagement in social media."
3565,Tuberculosis and Other Airborne Microbes in Occupational Health and Safety,"Airborne pathogens and non-malignant infectious diseases such as tuberculosis are highly contagious and can have severe effects on healthcare workers. The symptoms of these diseases take time to manifest, which can prevent workers from noticing that they have been exposed until symptoms appear. The current paper sought to assess the occupational safety and preventative measures taken in laboratories in Spain, and to compare these measures with those reported by other studies worldwide. A cross-sectional study of workers (35–50 years old) was conducted using a web survey (N = 30), and a bibliometric analysis was carried out in the Scopus database (92 documents were selected). The occupational safety and health measures were inadequate, according to the opinions of the workers. The training (p < 0.01), the amount of work (p < 0.05), and how the workers followed their protocols (p < 0.001) were linked to incidents and exposure to airborne pathogens. The most significant previous publication was a report (848 citations) stating that the previous variables linked to exposure are vital for prevention. Most works focused on countries like the U.S.A. (p = 0.009) were reviews, with a limited number of studies focused on occupational safety."
3566,University Students’ Purchase Intention and Willingness to Pay for Carbon-Labeled Food Products: A Purchase Decision-Making Experiment,"Carbon labeling describes carbon dioxide emissions across food lifecycles, contributing to enhancing consumers’ low-carbon awareness and promoting low-carbon consumption behaviors. In a departure from the existing literature on carbon labeling that heavily relies on interviews or questionnaire surveys, this study forms a hybrid of an auction experiment and a consumption experiment to observe university students’ purchase intention and willingness to pay for a carbon-labeled food product. In this study, students from a university in a city (Chengdu) of China, the largest carbon emitter, are taken as the experimental group, and cow’s milk is selected as the experimental food product. The main findings of this study are summarized as follows: (1) the purchase of carbon-labeled milk products is primarily influenced by price; (2) the willingness to pay for carbon-labeled milk products primarily depends on the premium; and (3) the students are willing to accept a maximum price premium of 3.2%. This study further offers suggestions to promote the formation of China’s carbon product-labeling system and the marketization of carbon-labeled products and consequently facilitate low-carbon consumption in China."
3567,Modeling Product Manufacturing Reliability with Quality Variations Centered on the Multilayered Coupling Operational Characteristics of Intelligent Manufacturing Systems,"For intelligent manufacturing systems, there are many deviations in operational characteristics, and the coupling effect of harmful operational characteristics leads to the variations in quality of the work-in-process (WIP) and the degradation of the reliability of the finished product, which is reflected as a loss of product manufacturing reliability. However, few studies on the modeling of product manufacturing reliability and mechanism analysis consider the operating mechanism and the coupling of characteristics. Thus, a novel modeling approach based on quality variations centered on the coupling of operational characteristics is proposed to analyze the formation mechanism of product manufacturing reliability. First, the PQR chain containing the co-effects among the manufacturing system performance (P), the manufacturing process quality (Q), and the product manufacturing reliability (R) is elaborated. The connotation of product manufacturing reliability is defined, multilayered operational characteristics are determined, and operational data are collected by smart sensors. Second, on the basis of the coupling effect in the PQR chain, a multilayered product quality variation model is proposed by mining operational characteristic data obtained from sensors. Third, an integrated product manufacturing reliability model is presented on the basis of the variation propagation mechanism of the multilayered product quality variation model. Finally, a camshaft manufacturing reliability analysis is conducted to verify the validity of the proposed method. The method proposed in this paper proved to be effective for evaluating and predicting the product reliability in the smart manufacturing process."
3568,Spanish Costaleros’ Physical Activity and Their Quality of Life,"(1) Physical activity is one of the most influencing factors in people’ quality of life. Likewise, the costaleros of the Holy Week of Andalusia (Spain) carry out an important effort with high intensity during an extended time without any preparation. This study was the aim of knowing the intensity of the physical activity practiced by the costaleros in relation to their quality of life. (2) A transversal study was carried out with 1057 costaleros in Andalusia (Spain), where 930 were male and 127 female, between the ages of 18–61 years old (31.26 ± 7.60). For this purpose, descriptive, inferential, and correlative analyses were developed. Accelerometers (ActiGraph) were used during the procession to know the intensity of physical activity and the SF-36 test to know the self-perceived state of health and quality of life. (3) The intensity of physical activity practiced by costaleros is moderate, and it is related with their quality of life. In addition, positive associations are found between general health and physical activity. (4) Participants’ quality of life is associated with physical activity and freedom from injury. In addition, the measurement by accelerometry provides real data on the intensity of the effort made."
3569,"Metabolomics in Sleep, Insomnia and Sleep Apnea","Sleep-wake disorders are highly prevalent disorders, which can lead to negative effects on cognitive, emotional and interpersonal functioning, and can cause maladaptive metabolic changes. Recent studies support the notion that metabolic processes correlate with sleep. The study of metabolite biomarkers (metabolomics) in a large-scale manner offers unique opportunities to provide insights into the pathology of diseases by revealing alterations in metabolic pathways. This review aims to summarize the status of metabolomic analyses-based knowledge on sleep disorders and to present knowledge in understanding the metabolic role of sleep in psychiatric disorders. Overall, findings suggest that sleep-wake disorders lead to pronounced alterations in specific metabolic pathways, which might contribute to the association of sleep disorders with other psychiatric disorders and medical conditions. These alterations are mainly related to changes in the metabolism of branched-chain amino acids, as well as glucose and lipid metabolism. In insomnia, alterations in branched-chain amino acid and glucose metabolism were shown among studies. In obstructive sleep apnea, biomarkers related to lipid metabolism seem to be of special importance. Future studies are needed to examine severity, subtypes and treatment of sleep-wake disorders in the context of metabolite levels."
3570,Analysis of the Codon Usage Pattern of HA and NA Genes of H7N9 Influenza A Virus,"Novel H7N9 influenza virus transmitted from birds to human and, since March 2013, it has caused five epidemic waves in China. Although the evolution of H7N9 viruses has been investigated, the evolutionary changes associated with codon usage are still unclear. Herein, the codon usage pattern of two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), was studied to understand the evolutionary changes in relation to host, epidemic wave, and pathogenicity. Both genes displayed a low codon usage bias, with HA higher than NA. The codon usage was driven by mutation pressure and natural selection, although the main contributing factor was natural selection. Additionally, the codon adaptation index (CAI) and deoptimization (RCDI) illustrated the strong adaptability of H7N9 to Gallus gallus. Similarity index (SiD) analysis showed that Homo sapiens posed a stronger selection pressure than Gallus gallus. Thus, we assume that this may be related to the gradual adaptability of the virus to human. In addition, the host strong selection pressure was validated based on CpG dinucleotide content. In conclusion, this study analyzed the usage of codons of two genes of H7N9 and expanded our understanding of H7N9 host specificity. This aids into the development of control measures against H7N9 influenza virus."
3571,The Application of Porphyrins and Their Analogues for Inactivation of Viruses,"The problem of treating viral infections is extremely relevant due to both the emergence of new viral diseases and to the low effectiveness of existing approaches to the treatment of known viral infections. This review focuses on the application of porphyrin, chlorin, and phthalocyanine series for combating viral infections by chemical and photochemical inactivation methods. The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10–15 years in order to identify the most promising areas."
3572,Adaptive Estimation for Epidemic Renewal and Phylogenetic Skyline Models,"Estimating temporal changes in a target population from phylogenetic or count data is an important problem in ecology and epidemiology. Reliable estimates can provide key insights into the climatic and biological drivers influencing the diversity or structure of that population and evidence hypotheses concerning its future growth or decline. In infectious disease applications, the individuals infected across an epidemic form the target population. The renewal model estimates the effective reproduction number, R, of the epidemic from counts of observed incident cases. The skyline model infers the effective population size, N, underlying a phylogeny of sequences sampled from that epidemic. Practically, R measures ongoing epidemic growth while N informs on historical caseload. While both models solve distinct problems, the reliability of their estimates depends on p-dimensional piecewise-constant functions. If p is misspecified, the model might underfit significant changes or overfit noise and promote a spurious understanding of the epidemic, which might misguide intervention policies or misinform forecasts. Surprisingly, no transparent yet principled approach for optimizing p exists. Usually, p is heuristically set, or obscurely controlled via complex algorithms. We present a computable and interpretable p-selection method based on the minimum description length (MDL) formalism of information theory. Unlike many standard model selection techniques, MDL accounts for the additional statistical complexity induced by how parameters interact. As a result, our method optimizes p so that R and N estimates properly and meaningfully adapt to available data. It also outperforms comparable Akaike and Bayesian information criteria on several classification problems, given minimal knowledge of the parameter space, and exposes statistical similarities among renewal, skyline, and other models in biology. Rigorous and interpretable model selection is necessary if trustworthy and justifiable conclusions are to be drawn from piecewise models. [Coalescent processes; epidemiology; information theory; model selection; phylodynamics; renewal models; skyline plots]"
3573,Full-Spectrum Analysis of Bioactive Compounds in Rosemary (Rosmarinus officinalis L.) as Influenced by Different Extraction Methods,"Rosmarinus officinalis is a potent antioxidant herb rich in polyphenols. Ultra-high-performance liquid chromatography, coupled with electrospray ionization and quadrupole-time of flight mass spectrometry (UHPLC-ESI-QTOF-MS), enables an exhaustive, full-spectrum analysis of the molecular constituents of natural products. The study aimed to develop a rapid UHPLC method to contribute new insights into the phytochemical composition of rosemary and to assess the performance of nine different procedures for extraction. These include fresh tissue homogenization, fresh and dry leaf decoction, and their respective fermentation, Soxhlet extraction, and sonication using water and methanol. Different extraction methods were found to recover quite different groups of polyphenols within 11 min during 20 min of analysis. Soxhlet extraction, yielded very high concentrations of rosmarinic acid (33,491.33 ± 86.29 µg/g), luteolin-7-O-glucoside (209.95 ± 8.78 µg/g), carnosic acid (2915.40 ± 33.23 µg/g), carnosol (22,000.67 ± 77.39 µg/g), and ursolic acid (5144.27 ± 28.68 µg/g). UHPLC-ESI-QTOF-MS enabled the detection of more than 50 polyphenols, including phenolic acids, flavonoids, and terpenoids in the various extracts. Of these, sagerinic acid ([M − H](−) m/z 719.16), salvianolic acid A ([M − H](−) m/z 493.11) and B ([M − H](−) m/z 717.15), and a pentacyclic triterpenoid corosolic acid ([M − H](−) m/z 471.34) were detected for the first time in rosemary. Soxhlet extraction was found to be the most efficient method, followed by dry leaf decoction. The UHPLC-ESI-QTOF-MS methodology for the analysis proved to be very efficient in the identification and characterization of targeted and untargeted bioactive molecules in the rosemary."
3574,Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem?,"The recent identification of senescent cells in periodontal tissues has the potential to provide new insights into the underlying mechanisms of periodontal disease etiology. DNA damage-driven senescence is perhaps one of the most underappreciated delayed consequences of persistent Gram-negative bacterial infection and inflammation. Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. What happens to those healthy cells that reside in this harmful environment? Emerging evidence indicates that cells that survive irreparable genomic damage undergo cellular senescence, a crucial intermediate mechanism connecting DNA damage and the immune response. In this review, we hypothesize that sustained Gram-negative bacterial challenge, chronic inflammation itself, and the constant renewal of damaged tissues create a permissive environment for the abnormal accumulation of senescent cells. Based on emerging data we propose a model in which the dysfunctional presence of senescent cells may aggravate the initial immune reaction against pathogens. Further understanding of the role of senescent cells in periodontal disease pathogenesis may have clinical implications by providing more sophisticated therapeutic strategies to combat tissue destruction."
3575,Molecular Characterization and Developing a Point-of-Need Molecular Test for Diagnosis of Bovine Papillomavirus (BPV) Type 1 in Cattle from Egypt,"SIMPLE SUMMARY: Bovine papillomatosis is a disease caused by bovine papillomavirus (BPV), which is a diverse group of oncogenic viruses that challenge cattle industry, resulting in significant economic losses. The present study investigated the occurrence of bovine papillomatosis among cattle (n = 308) with cutaneous warts on the head and neck from New valley Province, Egypt through molecular detection of BPV-1, -2, -4, -5, and -10. The work also involved a phylogenetic analysis of the positive samples for detection of the genetic relatedness of the virus. Interestingly, BPV-1 DNA was detected in 84.6% of the collected samples. Furthermore, the study included the development of an isothermal nucleic acid amplification test, which is a field test combining molecular and lateral flow immunoassays for point-of-need testing appropriate for veterinary use in resource-limited settings. Collectively, our study provided interesting data related to the combined use of molecular and immunoassays methods in the detection of the virus besides better understanding the genetic relatedness of the circulating genotypes of BPV-1 in Egypt. Our study suggested further research to explore more about the other genotypes of BPV in the Egyptian environment that could be helpful for the implementation of control strategies for combating this disease. ABSTRACT: Bovine papillomatosis is a viral disease of cattle causing cutaneous warts. A diagnosis of this viral infection is very mandatory for combating the resulting economic losses. Given the limited data available about bovine papillomavirus (BPV) in Egypt, the present study involved the molecular diagnosis of bovine papillomavirus type-1 (BPV-1), -2, -4, -5, and -10 in cattle presenting cutaneous warts on the head and neck from New Valley Province, Egypt. The phylogenetic analysis of the detected types of BPV was also performed, followed by developing a point-of-need molecular assay for the rapid identification of identified BPV types. In this regard, a total of 308 cattle from private farms in Egypt were clinically examined, of which 13 animals presented cutaneous warts due to suspected BPV infection. The symptomatic animals were treated surgically, and biopsies from skin lesions were collected for BPV-1, -2, -4, -5, and -10 molecular identification using polymerase chain reaction (PCR). The presence of BPV-1 DNA was confirmed in 11 collected samples (84.6%), while BPV-2, -4, -5, and -10 were not detected. Sequencing of the PCR products suggested the Egyptian virus is closely related to BPV found in India. An isothermal nucleic acid amplification test (NAAT) with labeled primers specific for the BPV-1 L1 gene sequence, and based on recombinase polymerase amplification (RPA), in combination with a lateral flow strip assay for the detection of RPA products, was developed and tested. The point-of-need molecular assay demonstrated a diagnostic utility comparable to PCR-based testing. Taken together, the present study provides interesting molecular data related to the occurrence of BPV-1 in Egypt and reveals the genetic relatedness of the Egyptian BPV-1 with BPV-1 found in buffalo in India. In addition, a simple, low-cost combined test was also validated for diagnosis of the infection. The present study suggests the necessity of future investigations about the circulating strains of the virus among the cattle in Egypt to assess their genetic relatedness and better understand the epidemiological pattern of the disease."
3576,Rapid Expansion of Virus-Specific CD4(+) T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus,"The infection of susceptible mice with Theiler’s murine encephalomyelitis virus (TMEV) induces a T cell-mediated demyelinating disease. This system has been studied as a relevant infection model for multiple sclerosis (MS). Therefore, defining the type of T cell responses and their functions is critically important for understanding the relevant pathogenic mechanisms. In this study, we adoptively transferred naive VP2-specific TCR-Tg CD4(+) T cells into syngeneic susceptible SJL mice and monitored the development of the disease and the activation and proliferation of CD4(+) T cells during the early stages of viral infection. The preexisting VP2-specific naive CD4(+) T cells promoted the pathogenesis of the disease in a dose-dependent manner. The transferred VP2-specific CD4(+) T cells proliferated rapidly in the CNS starting at 2–3 dpi. High levels of FoxP3(+)CD4(+) T cells were found in the CNS early in viral infection (3 dpi) and persisted throughout the infection. Activated VP2-specific FoxP3(+)CD4(+) T cells inhibited the production of IFN-γ, but not IL-17, via the same VP2-specific CD4(+) T cells without interfering in proliferation. Thus, the early presence of regulatory T cells in the CNS with viral infection may favor the induction of pathogenic Th17 cells over protective Th1 cells in susceptible mice, thereby establishing the pathogenesis of virus-induced demyelinating disease."
3577,High-Precision CO(2) Column Length Analysis on the Basis of a 1.57-μm Dual-Wavelength IPDA Lidar,"For high-precision measurements of the CO(2) column concentration in the atmosphere with airborne integrated path differential absorption (IPDA) Lidar, the exact distance of the Lidar beam to the scattering surface, that is, the length of the column, must be measured accurately. For the high-precision inversion of the column length, we propose a set of methods on the basis of the actual conditions, including autocorrelation detection, adaptive filtering, Gaussian decomposition, and optimized Levenberg–Marquardt fitting based on the generalized Gaussian distribution. Then, based on the information of a pair of laser pulses, we use the direct adjustment method of unequal precision to eliminate the error in the distance measurement. Further, the effect of atmospheric delay on distance measurements is considered, leading to further correction of the inversion results. At last, an airborne experiment was carried out in a sea area near Qinhuangdao, China on 14 March 2019. The results showed that the ranging accuracy can reach 0.9066 m, which achieved an excellent ranging accuracy on 1.57-μm IPDA Lidar and met the requirement for high-precision CO(2) column length inversion."
3578,Targeted Therapy of Hepatocellular Carcinoma Using Gemcitabine-Incorporated GPC3 Aptamer,"Hepatocellular carcinoma (HCC) is the most common malignancy of the liver, which can progress rapidly and has a poor prognosis. Glypican-3 (GPC3) has been proposed to be an important diagnostic biomarker and therapeutic target for HCC. Aptamers have emerged as promising drug delivery vehicles because of their high binding affinity for target molecules. Herein, we developed G12msi, a gemcitabine-incorporated DNA aptamer, targeting GPC3, and evaluated its binding specificity and anti-tumor efficacy in GPC3-overexpressing HCC cell lines and murine xenograft models. GPC3-targeted aptamers were selected by using the SELEX process and the chemotherapy drug gemcitabine was internally incorporated into the aptamer. To determine the binding affinity and internalization of the G12msi, flow cytometry and confocal microscopy were performed on GPC3-positive HepG2, Hep3B, and Huh7 cells, as well as a GPC3-negative A431 cell. The anti-tumor activities of G12msi were evaluated with in vitro and in vivo models. We found that G12msi binds to GPC3-overexpressing HCC tumor cells with high specificity and is effectively internalized. Moreover, G12msi treatment inhibited the cell proliferation of GPC3-positive HCC cell lines with minimal cytotoxicity in control A431 cells. In vivo systemic administration of G12msi significantly inhibited tumor growth of HCC HepG2 cells in xenograft models without causing toxicity. These results suggest that gemcitabine-incorporated GPC3 aptamer-based drug delivery may be a promising strategy for the treatment of HCC."
3579,Roma Health: An Overview of Communicable Diseases in Eastern and Central Europe,"The Roma are Europe’s largest minority. They are also one of its most disadvantaged, with low levels of education and health and high levels of poverty. Research on Roma health often reveals higher burdens of disease in the communities studied. This paper aims to review the literature on communicable diseases among Roma across Eastern and Central Europe. A PubMed search was carried out for communicable diseases among Roma in these parts of Europe, specifically in Romania, Bulgaria, Hungary, Serbia, Slovakia, the Czech Republic and North Macedonia. The papers were then screened for relevance and utility. Nineteen papers were selected for review; most of them from Slovakia. Roma continue to have a higher prevalence of communicable diseases and are at higher risk of infection than the majority populations of the countries they live in. Roma children in particular have a particularly high prevalence of parasitic disease. However, these differences in disease prevalence are not present across all diseases and all populations. For example, when Roma are compared to non-Roma living in close proximity to them, these differences are often no longer significant."
3580,Improving the Quality of Care in Care Homes Using the Quality Improvement Collaborative Approach: Lessons Learnt from Six Projects Conducted in the UK and The Netherlands,"The Breakthrough Series Quality Improvement Collaborative (QIC) initiative is a well-developed and widely used approach, but most of what we know about it has come from healthcare settings. In this article, those leading QICs to improve care in care homes provide detailed accounts of six QICs and share their learning of applying the QIC approach in the care home sector. Overall, five care home-specific lessons were learnt: (i) plan for the resources needed to support collaborative teams with collecting, processing, and interpreting data; (ii) create encouraging and safe working environments to help collaborative team members feel valued; (iii) recruit collaborative teams, QIC leads, and facilitators who have established relationships with care homes; (iv) regularly check project ideas are aligned with team members’ job roles, responsibilities, and priorities; and (v) work flexibly and accept that planned activities may need adapting as the project progresses. These insights are targeted at teams delivering QICs in care homes. These insights demonstrate the need to consider the care home context when applying improvement tools and techniques in this setting."
3581,Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H(+)-Centered Anticancer Paradigm of the Late Post-Warburg Era,"A brand new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this unitarian perspective, based upon the hydrogen ion (H(+)) dynamics of cancer, allows for the understanding and integration of the many dualisms, confusions, and paradoxes of the disease. The new H(+)-related, wide-ranging model can embrace, from a unique perspective, the many aspects of the disease and, at the same time, therapeutically interfere with most, if not all, of the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC reviewed here may be beneficial for all types and stages of the disease. In this vein, we have attempted a megasynthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide-ranging approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of the pH-related drugs that are available nowadays for the treatment of breast cancer is advanced."
3582,Antibody Response to Canine Adenovirus-2 Virus Vaccination in Healthy Adult Dogs,"Background: Re-vaccination against canine adenovirus (CAV) is performed in ≤3-year-intervals but its necessity is unknown. The study determined anti-CAV antibodies within 28 days of re-vaccination and factors associated with the absence of antibodies and vaccination response. Methods: Ninety-seven healthy adult dogs (last vaccination ≥12 months) were re-vaccinated with a modified live CAV-2 vaccine. Anti-CAV antibodies were measured before vaccination (day 0), and after re-vaccination (day 7, 28) by virus neutralization. A ≥4-fold titer increase was defined as vaccination response. Fisher’s exact test and multivariate regression analysis were performed to determine factors associated with the absence of antibodies and vaccination response. Results: Totally, 87% of dogs (90/97; 95% CI: 85.61–96.70) had anti-CAV antibodies (≥10) before re-vaccination. Vaccination response was observed in 6% of dogs (6/97; 95% CI: 2.60–13.11). Time since last vaccination (>3–5 years, OR = 9.375, p = 0.020; >5 years, OR = 25.000, p = 0.006) was associated with a lack of antibodies. Dogs from urban areas were more likely to respond to vaccination (p = 0.037). Conclusion: Many dogs had anti-CAV pre-vaccination antibodies, even those with an incomplete vaccination series. Most dogs did not respond to re-vaccination. Based on this study, dogs should be re-vaccinated every 3 years or antibodies should be determined."
3583,Effect of Tourist Activities on Fecal and Salivary Glucocorticoids and Immunoglobulin A in Female Captive Asian Elephants in Thailand,"SIMPLE SUMMARY: How tourist camp activities affect individual elephant welfare is an important and highly debated topic. Saliva and fecal samples were collected monthly for 1 year from 44 female Asian elephants that participated in three programs (saddle-, bareback-, or no-riding), and analyzed for glucocorticoids (GC) and immunoglobulin A (IgA). The hypothesis was that better welfare would be associated with low GC and high IgA concentrations. Both biomarkers showed significant variation with respect to camp size, riding activities, tourist-to-elephant ratios and seasonality, but not always consistently between feces and saliva, and not always in the predicted direction. However, there was no clear indication that riding per se negatively affected these two biomarkers. The lack of consistent responses highlights the difficulty in interpreting physiological data in relation to management factors, and suggests more work is needed to differentiate between potential chronic (feces) and acute (saliva) responses. ABSTRACT: Asian elephants have been an important part of wildlife ecotourism in Thailand for over two decades. Elephants in tourist camps are exposed to a variety of management styles and daily activities that can potentially affect health and welfare. This study investigated relationships between a novel welfare biomarker, immunoglobulin A (IgA), and daily camp activities, and compared results to glucocorticoid (GC) measures. Often no-riding camps are portrayed as providing better welfare than camps that offer riding. Therefore, we predicted that elephants at no-riding camps would have lower GC and higher IgA concentrations, and a low GC/IgA ratio. Forty-four female elephants from six elephant camps were divided into three groups based on riding activities: saddle-riding, bareback-riding, and no-riding. Fecal and salivary samples were collected monthly for 1 year along with evaluations of body condition, foot health, and wounding. Camp environment and management varied among camps, although the major difference was in riding activities. Concentrations of GCs and IgA varied among the working groups, but not always consistently between sample matrices. Overall fecal glucocorticoid metabolite concentrations were lowest in the saddle-riding group. Only in one bareback-riding camp did the elephants exhibit a potentially positive welfare response with a low GC/IgA ratio over time. Other results varied between the two biomarkers, with considerable variability across camps, suggesting there is more to good welfare than whether elephants participate in riding or not. Several other human-induced stressors, like chaining, ankus use, and limited social opportunities are likely to be impacting well-being and should be considered to ensure management practices meet physical and psychological welfare needs."
3584,Extracellular Vesicle-Based Nucleic Acid Delivery: Current Advances and Future Perspectives in Cancer Therapeutic Strategies,"Extracellular vesicles (EVs) are sophisticated and sensitive messengers released by cells to communicate with and influence distant and neighboring cells via selective transfer of bioactive content, including protein lipids and nucleic acids. EVs have therefore attracted broad interest as new and refined potential therapeutic systems in many diseases, including cancer, due to their low immunogenicity, non-toxicity, and elevated bioavailability. They might serve as safe and effective vehicles for the transport of therapeutic molecules to specific tissues and cells. In this review, we focus on EVs as a vehicle for gene therapy in cancer. We describe recent developments in EV engineering to achieve efficient intracellular delivery of cancer therapeutics and avoid off-target effects, to provide an overview of the potential applications of EV-mediated gene therapy and the most promising biomedical advances."
3585,Neuronal octopamine signaling regulates mating-induced germline stem cell increase in female Drosophila melanogaster,"Stem cells fuel the development and maintenance of tissues. Many studies have addressed how local signals from neighboring niche cells regulate stem cell identity and their proliferative potential. However, the regulation of stem cells by tissue-extrinsic signals in response to environmental cues remains poorly understood. Here we report that efferent octopaminergic neurons projecting to the ovary are essential for germline stem cell (GSC) increase in response to mating in female Drosophila. The neuronal activity of the octopaminergic neurons is required for mating-induced GSC increase as they relay the mating signal from sex peptide receptor-positive cholinergic neurons. Octopamine and its receptor Oamb are also required for mating-induced GSC increase via intracellular Ca(2+) signaling. Moreover, we identified Matrix metalloproteinase-2 as a downstream component of the octopamine-Ca(2+) signaling to induce GSC increase. Our study provides a mechanism describing how neuronal system couples stem cell behavior to environmental cues through stem cell niche signaling."
3586,"Mortality prediction models, causal effects, and end-of-life decision making in the intensive care unit",
3587,"Detection of West Nile virus in a common whitethroat (Curruca communis) and Culex mosquitoes in the Netherlands, 2020","On 22 August, a common whitethroat in the Netherlands tested positive for West Nile virus lineage 2. The same bird had tested negative in spring. Subsequent testing of Culex mosquitoes collected in August and early September in the same location generated two of 44 positive mosquito pools, providing first evidence for enzootic transmission in the Netherlands. Sequences generated from the positive mosquito pools clustered with sequences that originate from Germany, Austria and the Czech Republic."
3588,"Molecular Characterization of Influenza C Viruses from Outbreaks in Hong Kong SAR, China","In 2014, the Centre for Health Protection in Hong Kong introduced screening for influenza C virus (ICV) as part of its routine surveillance for infectious agents in specimens collected from patients presenting with symptoms of respiratory viral infection, including influenza-like illness (ILI). A retrospective analysis of ICV detections up to week 26 of 2019 revealed persistent low-level circulation, with two outbreaks having occurred in the winters of 2015 to 2016 and 2017 to 2018. These outbreaks occurred at the same time as, and were dwarfed by, seasonal epidemics of influenza types A and B. Gene sequencing studies on stored ICV-positive clinical specimens from the two outbreaks have shown that the hemagglutinin-esterase (HE) genes of the viruses fall into two of the six recognized genetic lineages (represented by C/Kanagawa/1/76 and C/São Paulo/378/82), with there being significant genetic drift compared to earlier circulating viruses within both lineages. The location of a number of encoded amino acid substitutions in hemagglutinin-esterase fusion (HEF) glycoproteins suggests that antigenic drift may also have occurred. Observations of ICV outbreaks in other countries, with some of the infections being associated with severe disease, indicates that ICV infection has the potential to have significant clinical and health care impacts in humans. IMPORTANCE Influenza C virus infection of humans is common, and reinfection can occur throughout life. While symptoms are generally mild, severe disease cases have been reported, but knowledge of the virus is limited, as little systematic surveillance for influenza C virus is conducted and the virus cannot be studied by classical virologic methods because it cannot be readily isolated in laboratories. A combination of systematic surveillance in Hong Kong SAR, China, and new gene sequencing methods has been used in this study to assess influenza C virus evolution and provides evidence for a 2-year cycle of disease outbreaks. The results of studies like that reported here are key to developing an understanding of the impact of influenza C virus infection in humans and how virus evolution might be associated with epidemics."
3589,Pneumomediastino em um paciente com COVID-19,
3590,Forecasting influenza in Europe using a metapopulation model incorporating cross-border commuting and air travel,"Past work has shown that models incorporating human travel can improve the quality of influenza forecasts. Here, we develop and validate a metapopulation model of twelve European countries, in which international translocation of virus is driven by observed commuting and air travel flows, and use this model to generate influenza forecasts in conjunction with incidence data from the World Health Organization. We find that, although the metapopulation model fits the data well, it offers no improvement over isolated models in forecast quality. We discuss several potential reasons for these results. In particular, we note the need for data that are more comparable from country to country, and offer suggestions as to how surveillance systems might be improved to achieve this goal."
3591,Three-gene prognostic biomarkers for seminoma identified by weighted gene co-expression network analysis,"Testicular germ cell tumors (TGCTs) are common in young males, and seminoma accounts for a large proportion of TGCTs. However, there are limited records on the exploration of novel biomarkers for seminoma. Hence, we aimed to identify new biomarkers associated with overall survival in seminoma. mRNA-seq and clinical traits of TGCTs were downloaded from UCSC XENA and analyzed by weighted gene co-expression network analysis. After intersection with differentially expressed genes in GSE8607, common genes were subjected to protein-protein interaction (PPI) network construction and enrichment analyses. Then, the top 10 common genes were investigated by Kaplan–Meier (KM) survival analyses and univariate Cox regression analyses. Ultimately, TYROBP, CD68, and ITGAM were considered three prognostic biomarkers in seminoma. Based on correlation analysis between these genes and immune infiltrates, we suggest that the three biomarkers influence the survival of seminoma patients, possibly through regulating the infiltration of immune cells. In conclusion, our study demonstrated that TYROBP, CD68, and ITGAM could be regarded as prognostic biomarkers and therapeutic targets for seminoma patients."
3592,DDX56 Binds to Chikungunya Virus RNA To Control Infection,"DEAD box RNA helicases regulate diverse facets of RNA biology. Proteins of this family carry out essential cellular functions, and emerging literature is revealing additional roles in immune defense. Using RNA interference screening, we identified an evolutionarily conserved antiviral role for the helicase DDX56 against the alphavirus Sindbis virus (SINV), a mosquito-transmitted pathogen that infects humans. Depletion of DDX56 enhanced infection in Drosophila and human cells. Furthermore, we found that DDX56 also controls the emerging alphavirus chikungunya virus (CHIKV) through an interferon-independent mechanism. Using cross-linking immunoprecipitation (CLIP-Seq), we identified a predicted stem-loop on the viral genomic RNA bound by DDX56. Mechanistically, we found that DDX56 levels increase in the cytoplasm during CHIKV infection. In the cytoplasm, DDX56 impacts the earliest step in the viral replication cycle by binding and destabilizing the incoming viral genomic RNA, thereby attenuating infection. Thus, DDX56 is a conserved antiviral RNA binding protein that controls alphavirus infection."
3593,"Global health education in medical schools (GHEMS): a national, collaborative study of medical curricula","BACKGROUND: Global health is the study, research, and practice of medicine focused on improving health and achieving health equity for all persons worldwide. International and national bodies stipulate that global health be integrated into medical school curricula. However, there is a global paucity of data evaluating the state of global health teaching in medical schools. This study aimed to evaluate the extent of global health teaching activities at United Kingdom (UK) medical schools. METHODS: A national, cross-sectional study assessing all timetabled teachings sessions within UK medical courses for global health content during the academic year 2018/19. Global health content was evaluated against a comprehensive list of global health learning outcomes for medical students. RESULTS: Data from 39 medical courses representing 86% (30/36) of eligible medical schools was collected. Typically, medical courses reported timetabled teaching covering over three-quarters of all global health learning outcomes. However, a wide degree of variation existed among granular global health learning objectives covered within the different medical courses. On average, each learning outcome had a 79% [95% CI: 73, 83%] probability of being included in course curricula. There were a number of learning outcomes that had a lower probability, such as ‘access to surgeons with the necessary skills and equipment in different countries’ (36%) [95% CI: 21, 53%], ‘future impact of climate change on health and healthcare systems’ (67%) [95% CI: 50, 81%], and ‘role of the WHO’ (54%) [95% CI: 28, 60%]. CONCLUSIONS: This study served as the first national assessment of global health education and curricula within UK medical schools. Through a formalised assessment of teaching events produced by medical schools around the country, we were able to capture a national picture of global health education, including the strengths of global health prioritisation in the UK, as well as areas for improvement. Overall, it appears broad-level global health themes are widely discussed; however, the granularities of key, emerging areas of concern are omitted by curricula. In particular, gaps persist relating to international healthcare systems, multilateral global health agencies such as the WHO, global surgery, climate change and more."
3594,Diagnosing skull fracture in children with closed head injury using point-of-care ultrasound vs. computed tomography scan,"Diagnostic and therapeutic interventions in children for traumatic brain injury, which is known as the most important complication in trauma, require special attention. This study aimed to evaluate the accuracy of point-of-care ultrasound (POCUS) in diagnosing skull fracture in children with closed head injury in comparison with computed tomography (CT) scan. The current prospective cross-sectional study was conducted on children (0–14 years old), who were referred to the emergency department of a general teaching hospital in Shiraz, southern Iran (January–March 2018), with close head injury and were suspected of bone fracture. The participants were selected using a convenience sampling. The results of POCUS performed by emergency medicine (EM) residents were compared with the results of CT scan, which was reported by radiologists and considered a gold standard. Then, diagnostic tests were calculated. A total of 168 children were enrolled, with the mean ± standard deviation age of 6.21 ± 3.99. The most affected areas in the skull were the frontal (34.5%) and occipital areas (33.3%). POCUS had a sensitivity and specificity of 81.8% (95%CI, 48.2–97.7%) and 100% (95%CI, 97.7–100%), respectively. Positive and negative predictive values were 100% and 98.7%, with an accuracy of 98.8% in comparison with CT scan in the diagnosis of skull fracture. Conclusion: The results showed that POCUS with a portable ultrasonography machine, performed by the EM’s physicians, have high diagnostic precision and can be considered a tool in the management of patients with closed head injury."
3595,Evaluation of semi-quantitative compared to quantitative cultures of tracheal aspirates for the yield of culturable respiratory pathogens – a cross-sectional study,"BACKGROUND: Diagnosis of lower respiratory tract infections (LRTI) depends on the presence of clinical, radiological and microbiological findings. Endotracheal suction aspirate (ETSA) is the commonest respiratory sample sent for culture from intubated patients. Very few studies have compared quantitative and semi-quantitative processing of ETSA cultures for LRTI diagnosis. We determined the diagnostic accuracy of quantitative and semi-quantitative ETSA culture for LRTI diagnosis, agreement between the quantitative and semi quantitative culture techniques and the yield of respiratory pathogens with both methods. METHODS: This was a cross-sectional study conducted at the Aga Khan University clinical laboratory, Karachi, Pakistan. One hundred and seventy-eight ETSA samples sent for routine bacteriological cultures were processed quantitatively as part of regular specimen processing method and semi-quantitatively. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy was calculated for both methods using clinical diagnosis of pneumonia as reference standard. Agreement between the quantitative and semi quantitative methods was assessed via the kappa statistic test. Pathogen yield between the two methods was compared using Pearson’s chi-square test. RESULTS: The quantitative and semi-quantitative methods yielded pathogens in 81 (45.5%) and 85 (47.8%) cases respectively. There was complete concordance of both techniques in 155 (87.1%) ETSA samples. No growth was observed in 45 (25.3%) ETSA specimens with quantitative culture and 37 (20.8%) cases by semi-quantitative culture. The diagnostic accuracy of both techniques were comparable; 64.6% for quantitative and 64.0% for semi-quantitative culture. The kappa agreement was found to be 0.84 (95% CI, 0.77–0.91) representing almost perfect agreement between the two methods. Although semi-quantitative cultures yielded more pathogens (47.8%) as compared to quantitative ETSA cultures (45.5%), the difference was only 2.3%. However, this difference achieved statistical (chi-square p-value < 0.001) favoring semi-quantitative culture methods over quantitative culture techniques for processing ETSA. CONCLUSION: In conclusion, there is a strong agreement between the performances of both methods of processing ETSA cultures in terms of accuracy of LRTI diagnosis. Semi-quantitative cultures of ETSA yielded more pathogens as compared to quantitative cultures. Although both techniques were comparable, we recommend processing of ETSA using semi-quantitative technique due to its ease and reduced processing time."
3596,Chronic disorders of consciousness: a case report with longitudinal evaluation of disease progression using 7 T magnetic resonance imaging,"BACKGROUND: Outcome prediction for patients with disorders of consciousness (DOC) is essential yet challenging. Evidence showed that patients with DOC lasting 1 year or longer after a brain injury were less likely to recover. However, the reasons why outcomes of DOC patients differ greatly remain unclear. With a variety of analytical methods and through quantitative behavioral assessments, we aimed to track the progression of a patient with severe brain injury, in order to advance our understanding of the underlying mechanisms of DOC. CASE PRESENTATION: We performed a longitudinal study for a 52-year-old male DOC patient who has remained in the state for 1.5 years with comprehensive rehabilitative therapies. The patient underwent 3 times of assessments of Coma Recovery Scale-Revised (CRS-R) and ultra-high-field 7 T magnetic resonance imaging (MRI). Both topologic properties and brain microstructure were analyzed to track disease progression. We observed dynamic increases of fiber densities with measurements at three time points (t1:1.5 M, t2:7.5 M t3:17.5 M). Specifically, fiber densities of the superior longitudinal fasciculus and arcuate fasciculus nerve fiber bundles improved mostly in the visual, verbal, and auditory subscales, which was consistent with the CRS-R scores. Moreover, the graph-theory analyses demonstrated that network topologic properties showed an improvement although the disease duration exceeded 1 year. CONCLUSIONS: DOC patients with a course longer than 1 year remain possible to improve, and including evaluation methods such as WM connectome analysis and graph theory could be potentially valuable for a more precise assessment of patients with a longer course of DOC."
3597,Impact of systematic screening for AmpC-hyperproducing Enterobacterales intestinal carriage in intensive care unit patients,"BACKGROUND: Empirical antimicrobial therapy (EAT) is a challenge for community-acquired, hospital-acquired and ventilator-associated pneumonia, particularly in the context of the increasing occurrence of third-generation cephalosporin-resistant Enterobacterales (3GCR-E), including extended-spectrum beta-lactamase Enterobacterales (ESBL-E) and high-level expressed AmpC cephalosporinase-producing Enterobacterales (HLAC-E). To prevent the overuse of broad-spectrum antimicrobial therapies, such as carbapenems, we assessed the performance of screening for intestinal carriage of HLAC-E in addition to ESBL-E to predict 3GCR-E (ESBL-E and/or HLAC-E) presence or absence in respiratory samples in ICU, and to evaluate its potential impact on carbapenem prescription. MATERIALS AND METHODS: This monocentric retrospective observational study was performed in a surgical ICU during a 4-year period (January 2013–December 2016). Patients were included if they had a positive culture on a respiratory sample and a previous intestinal carriage screening performed by rectal swabbing within 21 days. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios were calculated for the screening for intestinal carriage of ESBL-E, HLAC-E and 3GCR-E (ESBL-E and/or HLAC-E) as predictor of their absence/presence in respiratory samples. Impact of HLAC-E and ESBL-E reporting on EAT was also studied. RESULTS: 765 respiratory samples, retrieved from 468 patients, were analyzed. ESBL-E prevalence was 23.8% in rectal swab and 4.4% in respiratory samples. HLAC-E prevalence was 9.0% in rectal swabs and 3.7% in respiratory samples. Overall, the 3GCR-E prevalence was 31.8% in rectal swabs and 7.7% in respiratory samples. NPVs were 98.8%, 98.0% and 96.6% for ESBL-E, HLAC-E and 3GCR-E, respectively. Over the study period, empirical antimicrobial therapy was initiated for 315 episodes of respiratory infections: 228/315 (72.4%) were associated with negative intestinal carriage screening for both HLAC-E and ESBL-E, of whom 28/228 (12.3%) were treated with carbapenems. Of 23/315 (7.3%) cases with screening for positive intestinal carriage with HLAC-E alone, 10/23 (43.5%) were treated with carbapenems. CONCLUSION: Systematic screening and reporting of HLAC-E in addition to ESBL-E in intestinal carriage screening could help to predict the absence of 3GCR-E in respiratory samples of severe surgical ICU patients. This could improve the appropriateness of EAT in ICU patients with HAP and may prevent the overuse of carbapenems."
3598,"Correlation Between the Clinical Severity, Bacterial Load, and Inflammatory Reaction in Children with Mycoplasma Pneumoniae Pneumonia","Given the lack of defining features in the clinical manifestations and radiographic findings for children with mycoplasma pneumoniae pneumonia (MPP), quantitative polymerase chain reaction (qPCR) has become a useful diagnostic method. This study was performed to explore the relationship between the qPCR findings, clinical symptoms, and inflammatory markers in children with MPP. Four hundred children with MPP have been enrolled in this retrospective analysis. All clinical and analytical information, including mycoplasma pneumoniae (MP) PCR results, has been collected. Based on the PCR results, the patients were divided into groups with load values (copy number) < 10(5) (54 cases), ≥10(5) and <10(6) (71 cases), ≥10(6) and <10(7) (112 cases), ≥10(7) and ≤10(8) (114 cases), and >10(8) (49 cases). The clinical features (including symptoms and signs) and inflammatory indicators were compared among the groups. The incidence of high fever (above 39°C), thermal peak during the entire hospitalization period, fever duration, days of hospitalization, and plasma lactate dehydrogenase (LDH) levels were statistically correlated with the MP PCR load value in children with MPP. The analysis of relevance degree showed the correlative order as a thermal peak of hospitalization > duration of fever > period of hospitalization > LDH value > C-reactive protein value. The host immune response was significantly greater in the complication group than in the non-complication group."
3599,The qSOFA score combined with the initial red cell distribution width as a useful predictor of 30 day mortality among older adults with infection in an emergency department,"PURPOSE: This study aimed to investigate whether the qSOFA and initial red cell distribution width (RDW) in the emergency department (ED) are associated with mortality in older adults with infections who visited the ED. METHODS: This was a retrospective study conducted in 5 EDs between November 2016 and February 2017. We recorded age, sex, comorbidities, body temperature, clinical findings, and initial laboratory results, including the RDW. The initial RDW values and the qSOFA criteria were obtained at the time of the ED visit. The primary outcome was 30 day mortality. RESULTS: A total of 1,446 patients were finally included in this study, of which 134 (9.3%) died within 30 days and the median (IQR) age was 77 (72, 82) years. In the multivariable analysis, the RDW (14.0–15.4%) and highest RDW (> 15.4%) quartile were shown to be independent risk factors for 30 day mortality (OR 2.12; 95% CI 1.12–4.02; p = 0.021) (OR 3.35; 95% CI 1.83–6.13; p < 0.001). The patients with qSOFA 2 and 3 were shown to have the high odds ratios of 30-day mortality (OR 3.50; 95% CI 2.09–5.84; p < 0.001) (OR 11.30; 95% CI 5.06–25.23; p < 0.001). The qSOFA combined with the RDW quartile for the prediction of 30 day mortality showed an AUROC value of 0.710 (0.686–0.734). CONCLUSION: The qSOFA combined with the initial RDW value was associated with 30-day mortality among older adults with infections in the ED. The initial RDW may help emergency physicians predict mortality in older adults with infections visiting the ED."
3600,Breath-synchronized electrical stimulation of the expiratory muscles in mechanically ventilated patients: a randomized controlled feasibility study and pooled analysis,"BACKGROUND: Expiratory muscle weakness leads to difficult ventilator weaning. Maintaining their activity with functional electrical stimulation (FES) may improve outcome. We studied feasibility of breath-synchronized expiratory population muscle FES in a mixed ICU population (“Holland study”) and pooled data with our previous work (“Australian study”) to estimate potential clinical effects in a larger group. METHODS: Holland: Patients with a contractile response to FES received active or sham expiratory muscle FES (30 min, twice daily, 5 days/week until weaned). Main endpoints were feasibility (e.g., patient recruitment, treatment compliance, stimulation intensity) and safety. Pooled: Data on respiratory muscle thickness and ventilation duration from the Holland and Australian studies were combined (N = 40) in order to estimate potential effect size. Plasma cytokines (day 0, 3) were analyzed to study the effects of FES on systemic inflammation. RESULTS: Holland: A total of 272 sessions were performed (active/sham: 169/103) in 20 patients (N = active/sham: 10/10) with a total treatment compliance rate of 91.1%. No FES-related serious adverse events were reported. Pooled: On day 3, there was a between-group difference (N = active/sham: 7/12) in total abdominal expiratory muscle thickness favoring the active group [treatment difference (95% confidence interval); 2.25 (0.34, 4.16) mm, P = 0.02] but not on day 5. Plasma cytokine levels indicated that early FES did not induce systemic inflammation. Using a survival analysis approach for the total study population, median ventilation duration and ICU length of stay were 10 versus 52 (P = 0.07), and 12 versus 54 (P = 0.03) days for the active versus sham group. Median ventilation duration of patients that were successfully extubated was 8.5 [5.6–12.2] versus 10.5 [5.3–25.6] days (P = 0.60) for the active (N = 16) versus sham (N = 10) group, and median ICU length of stay was 10.5 [8.0–14.5] versus 14.0 [9.0–19.5] days (P = 0.36) for those active (N = 16) versus sham (N = 8) patients that were extubated and discharged alive from the ICU. During ICU stay, 3/20 patients died in the active group versus 8/20 in the sham group (P = 0.16). CONCLUSION: Expiratory muscle FES is feasible in selected ICU patients and might be a promising technique within a respiratory muscle-protective ventilation strategy. The next step is to study the effects on weaning and ventilator liberation outcome. Trial registration: ClinicalTrials.gov, ID NCT03453944. Registered 05 March 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03453944."
3601,“En la Lucha”: Strategies to Improve HIV Care for Puerto Ricans with Opioids Use Disorders,"BACKGROUND: Clínica Bienestar is a comprehensive HIV primary care clinic for Spanish-speaking Latinx with opioids use disorders (OUD). This article describes the barriers and trajectories to HIV viral suppression for Puerto Ricans with a transnational profile and dual diagnoses (HIV and OUD), and the strategies applied to increase retention in care. METHODS: Case study methodology was used to select two patient life histories that illustrate the most common pathways to success in reducing HIV viral load to undetectable and achieving OUD long-term recovery. RESULTS AND DISCUSSION: Patients’ major challenges included: (1) Persistent migrating while seeking substance use treatment services with limited or no support from their sending and hosting communities; (2) Intersectional stigmas; (3) Untreated trauma; (4) Language and cultural barriers. Clínica Bienestar’s service model included ten strategies to retain patients in care (e.g., Case management to identify cases with high social isolation), six emerged as central to addressing transnational challenges."
3602,Pediatric Resident Engagement With an Online Critical Care Curriculum During the Intensive Care Rotation*,"Residents are often assigned online learning materials as part of blended learning models, superimposed on other patient care and learning demands. Data that describe the time patterns of when residents interact with online learning materials during the ICU rotation are lacking. We describe resident engagement with assigned online curricula related to time of day and ICU clinical schedules, using website activity data. DESIGN: Prospective cohort study examining curriculum completion data and cross-referencing timestamps for pre- and posttest attempts with resident schedules to determine the hours that they accessed the curriculum and whether or not they were scheduled for clinical duty. Residents at each site were cohorted based on two differing clinical schedules—extended duration (>24 hr) versus shorter (maximum 16 hr) shifts. SETTING: Two large academic children’s hospitals. SUBJECTS: Pediatric residents rotating in the PICU from July 2013 to June 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred and fifty-seven pediatric residents participated in the study. The majority of residents (106/157; 68%) completed the curriculum, with no statistically significant association between overall curriculum completion and schedule cohort at either site. Residents made more test attempts at nighttime between 6 pm and 6 am (1,824/2,828; 64%) regardless of whether they were scheduled for clinical duty. Approximately two thirds of test attempts (1,785/2,828; 63%) occurred when residents were not scheduled to work, regardless of time of day. Forty-two percent of all test attempts (1,199/2,828) occurred between 6 pm and 6 am while off-duty, with 12% (342/2,828) occurring between midnight and 6 am. CONCLUSIONS: Residents rotating in the ICU completed online learning materials mainly during nighttime and off-duty hours, including usage between midnight and 6 am while off-duty. Increasing nighttime and off-duty workload may have implications for educational design and trainee wellness, particularly during busy, acute clinical rotations, and warrants further examination."
3603,The Influence of Essential Oils on Gut Microbial Profiles in Pigs,"SIMPLE SUMMARY: In recent years, the intake of ultra-processed foods has increased dramatically worldwide. Missing natural foods in the diet raise the need of biologically active food components that could compensate for this deficiency and help maintain proper immune status. In this study, the microbial changes in pigs as experimental animals were assessed as influenced by consumption of oregano extract combination with peppermint and thyme essential oils. The results demonstrated that the combination of plant extracts had a positive effect on the gastrointestinal tract of animals by increasing the number of probiotic bacteria. Based on the results obtained it may be outlined that the combination of oregano extract and peppermint and thyme essential oils can be promising ingredient as a functional component for the development of the new nutraceutical preparation. ABSTRACT: In recent years, the intake of ultra-processed foods has increased dramatically worldwide. Missing natural foods in the diet raise the need of biologically active food components that could compensate for this deficiency and help maintain proper immune status. This study used pigs as an animal model for the assessment of the impact of consumption of Origanum vulgare plant extract combined with Mentha piperita and Thymus vulgaris essential oils on microbial profile in intestines. A single group of weaned pigs received basal diet, while the other group basal diet supplemented with plant extract and two essential oils in the form of bilayer tablets prepared using “liquid/solid” phase technology. Metagenomic sequencing was performed with the aim to investigate changes of microbial communities in ileum, caecum, and colon. The results demonstrated that the combination of essential oils was non cytotoxic, and had a positive effect on the microbial composition in the large intestine of pigs due to significant increase in the number of probiotic bacteria. The amount of Lactobacillus was 2.5 times and Bifidobacterium 1.9 times higher in the animal group fed with supplement. The combination, however, had some negative impact on the variety of minor species in the distal part of the ileum. Additional studies need to be performed to obtain knowledge on how combinations of essential oils can change bacterial variety in the proximal part of the gastrointestinal tract."
3604,Identification of Modulators of HIV-1 Proviral Transcription from a Library of FDA-Approved Pharmaceuticals,"Human immunodeficiency virus 1 (HIV-1) is the most prevalent human retrovirus. Recent data show that 34 million people are living with HIV-1 worldwide. HIV-1 infections can lead to AIDS which still causes nearly 20,000 deaths annually in the USA alone. As this retrovirus leads to high morbidity and mortality conditions, more effective therapeutic regimens must be developed to treat these viral infections. A key target for intervention for which there are no current FDA-approved modulators is at the point of proviral transcription. One successful method for identifying novel therapeutics for treating infectious diseases is the repurposing of pharmaceuticals that are approved by the FDA for alternate indications. Major benefits of using FDA-approved drugs include the fact that the compounds have well established toxicity profiles, approved manufacturing processes, and immediate commercial availability to the patients. Here, we demonstrate that pharmaceuticals previously approved for other indications can be utilized to either activate or inhibit HIV-1 proviral transcription. Specifically, we found febuxostat, eltrombopag, and resveratrol to be activators of HIV-1 transcription, while mycophenolate was our lead inhibitor of HIV-1 transcription. Additionally, we observed that the infected cells of lymphoid and myeloid lineage responded differently to our lead transcriptional modulators. Finally, we demonstrated that the use of a multi-dose regimen allowed for enhanced activation with our transcriptional activators."
3605,"Phenolome of Asian Agrimony Tea (Agrimonia asiatica Juz., Rosaceae): LC-MS Profile, α-Glucosidase Inhibitory Potential and Stability","Functional beverages constitute the rapidly increasing part of the functional food section and represent an area with a wide range of products including herbal-based beverages. We carried out screening investigations of the extracts of 85 Rosaceous tea plants. Among the extracts analyzed Agrimonia asiatica herb extract demonstrated the highest inhibitory activity against the enzyme α-glucosidase (20.29 µg/mL). As a result of chromato-mass-spectrometric profiling of A. asiatica herb with high-performance liquid chromatography with photodiode array and electrospray triple quadrupole mass-spectrometric detection (HPLC-PDA-ESI-tQ-MS) 60 compounds were identified, including catechins, ellagitannins, flavones, flavonols, gallotannins, hydroxycinnamates, procyanidins, most for the very first time. The analysis of the seasonal variation of metabolites in A. asiatica herb demonstrated that the phenolic content was highest in summer samples and lower in spring and autumn. HPLC activity-based profiling was utilized to identify compounds of A. asiatica herb with the maximal α-glucosidase inhibitory activity. The most pronounced inhibition of α-glucosidase was observed for agrimoniin, while less significant results of inhibition were revealed for ellagic acid and isoquercitrin. The evaluation of phenolic content in A. asiatica herbal teas with the subsequent determination of α-glucosidase inhibiting potential was discovered. Maximum inhibition of α-glucosidase was observed for hot infusion (75.33 µg/mL) and the minimum for 30 min decoction (159.14 µg/mL). Our study demonstrated that A. asiatica herbal tea is a prospective functional beverage in which dietary intake may help to reduce blood glucose."
3606,Grape (Vitis vinifera L.) Seed Oil: A Functional Food from the Winemaking Industry,"Wine production is an ancient human activity that generates several by-products, which include some constituents known for their potential in health care and for their role in the food or cosmetic industries. Any variety of grape (Vitis vinifera L.) contains nutrients and bioactive compounds available from their juice or solid parts. Grape seed extract has demonstrated many activities in disease prevention, such as antioxidant effects, which make it a potential source of nutraceuticals. Grape seed is a remarkable winery industry by-product due to the bioactivity of its constituents. Methods for recovery of oil from grape seeds have evolved to improve both the quantity and quality of the yield. Both the lipophilic and hydrophilic chemicals present in the oil of V. vinifera L. make this wine by-product a source of natural nutraceuticals. Food and non-food industries are becoming novel targets of oil obtained from grape seeds given its various properties. This review focuses on the advantages of grape seed oil intake in our diet regarding its chemical composition in industries not related to wine production and the economic and environmental impact of oil production."
3607,Current Societal Views about Sustainable Wildlife Management and Conservation: A Survey of College Students in China,"SIMPLE SUMMARY: Wildlife conservation and management has become a very complex public policy issue in China as concerns about animal welfare and empathy for animals have emerged, especially in the younger generation. Science-based conservation policy and strategy that focus on sustainable management are perceived as less irrelevant today and can often be in conflict with emerging attitudes and values. Sustainable wildlife management adheres to the conservation concept of effective combination of species conservation and sustainable utilization, with an aim to establish a long-acting species conservation model that promotes all-round development of ecology, society, and economy, and has traditionally formed the basis of conservation management. This study designed a semi-structured questionnaire, which aimed to assess attitudes of Chinese college students towards sustainable wildlife management and wildlife conservation, and investigate the role of demographic and other characteristics on attitude. From October 2018 to April 2019, nine universities (including “Double First-Class” universities, first-tier universities, second-tier universities), and four three-year colleges in China were selected as survey sites, where face-to-face interviews were conducted among students. The results show that students broadly support the sustainable wildlife management but not in issues relating to “Animal Welfare and Rights” and “Trophy Hunting”. Students with lowest support for the theory and practice of sustainable wildlife management are vegetarians, freshmen, and those who have taken environmental protection electives in their educational program. ABSTRACT: Wildlife conservation and management has become a very complex public policy issue in China as concerns over on animal welfare and empathy for animals have grown. Science-based conservation strategies that are oriented toward sustainable wildlife management (SWM) are under threat as these new attitudes and values emerge and take hold. This study accesses the attitudes of college students towards SWM and wildlife conservation, and investigates demographic characteristics influencing their attitudes in China, a country that is traditionally associated with consumptive use of wildlife and SWM, but where new ideas about wildlife conservation are emerging. From October 2018 to April 2019, nine universities (including “Double First-Class” universities, first-tier universities, second-tier universities), and four three-year colleges in China were selected as survey locations, and face-to-face interviews were conducted with 1991 students. A total of 1977 questionnaires were recovered, of which 1739 were valid, with a completion rate of 88%. A Likert seven-point scale method was used to score students’ attitudes, and a classification and regression tree (CART) was used to analyze whether their attitudes were affected by their demographic characteristics. The results show that although students are broadly supportive of the theory of SWM, some are deeply antagonistic about on SWM on issues that arouse strong emotions such as “Animal Welfare and Rights” and “Trophy Hunting”. Demographic characteristics of students affect their degree of support for the SWM with support for SWM lower among vegetarians, freshmen, and students who have taken environmental protection electives. This research suggests that the theory of SWM requires to be refreshed and adapted to appeal to the younger generation of Chinese students, with SWM principles integrated into the environmental education programs of universities and three-year colleges. More attention should also be attached to media publicity by the government about wildlife conservation so as to enhance awareness of the need for SWM."
3608,Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model,"For decades, scientists have relied on animals to understand the risks and consequences of space travel. Animals remain key to study the physiological alterations during spaceflight and provide crucial information about microgravity-induced changes. While spaceflights may appear common, they remain costly and, coupled with limited cargo areas, do not allow for large sample sizes onboard. In 1979, a model of hindlimb unloading (HU) was successfully created to mimic microgravity and has been used extensively since its creation. Four decades later, the first model of mouse partial weight-bearing (PWB) was developed, aiming at mimicking partial gravity environments. Return to the Lunar surface for astronauts is now imminent and prompted the need for an animal model closer to human physiology; hence in 2018, our laboratory created a new model of PWB for adult rats. In this review, we will focus on the rat model of PWB, from its conception to the current state of knowledge. Additionally, we will address how this new model, used in conjunction with HU, will help implement new paradigms allowing scientists to anticipate the physiological alterations and needs of astronauts. Finally, we will discuss the outstanding questions and future perspectives in space research and propose potential solutions using the rat PWB model."
3609,Plant Disease Classification: A Comparative Evaluation of Convolutional Neural Networks and Deep Learning Optimizers,"Recently, plant disease classification has been done by various state-of-the-art deep learning (DL) architectures on the publicly available/author generated datasets. This research proposed the deep learning-based comparative evaluation for the classification of plant disease in two steps. Firstly, the best convolutional neural network (CNN) was obtained by conducting a comparative analysis among well-known CNN architectures along with modified and cascaded/hybrid versions of some of the DL models proposed in the recent researches. Secondly, the performance of the best-obtained model was attempted to improve by training through various deep learning optimizers. The comparison between various CNNs was based on performance metrics such as validation accuracy/loss, F1-score, and the required number of epochs. All the selected DL architectures were trained in the PlantVillage dataset which contains 26 different diseases belonging to 14 respective plant species. Keras with TensorFlow backend was used to train deep learning architectures. It is concluded that the Xception architecture trained with the Adam optimizer attained the highest validation accuracy and F1-score of 99.81% and 0.9978 respectively which is comparatively better than the previous approaches and it proves the novelty of the work. Therefore, the method proposed in this research can be applied to other agricultural applications for transparent detection and classification purposes."
3610,Chicken Astrovirus (CAstV) Molecular Studies Reveal Evidence of Multiple Past Recombination Events in Sequences Originated from Clinical Samples of White Chick Syndrome (WCS) in Western Canada,"In this study, we aimed to molecularly characterize 14 whole genome sequences of chicken astrovirus (CAstV) isolated from samples obtained from white chick syndrome (WCS) outbreaks in Western Canada during the period of 2014–2019. Genome sequence comparisons showed all these sequences correspond to the novel Biv group from which no confirmed representatives were published in GenBank. Molecular recombination analyses using recombination detection software (i.e., RDP5 and SimPlot) and phylogenetic analyses suggest multiple past recombination events in open reading frame (ORF)1a, ORF1b, and ORF2. Our findings suggest that recombination events and the accumulation of point mutations may have contributed to the substantial genetic variation observed in CAstV and evidenced by the current seven antigenic sub-clusters hitherto described. This is the first paper that describes recombination events in CAstV following analysis of complete CAstV sequences originated in Canada."
3611,"Searching for New Directions for Energy Policy: Testing Three Causal Models of Risk Perception, Attitude, and Behavior in Nuclear Energy Context","Although many risk studies investigate perceptions, attitudes, and behaviors, the causal relationships among them have not yet been verified. Thus, further investigations of these relationships are necessary. This study analyzes three causal models consisting of three components: perceptions (i.e., perceived risk in this study), attitudes (i.e., satisfaction), and behavior (i.e., support for policy). This study checks these relationships in the context of nuclear energy policy. Using a hierarchical regression model, this study tests three different models between the three components: (1) Model 1 (a high-involvement model), (2) Model 2 (a low-involvement model), and (3) Model 3 (a hedonic model). First, in the high-involvement model, behavior is affected by perceptions and attitudes. In particular, attitudes mediate the relationship between risk perceptions and satisfaction. Second, in the low-involvement model, attitudes indirectly affect perceptions through behaviors. Third, in the hedonic model, behaviors affect attitudes, and risk perceptions do not mediate that relationship. This causal model does not depend on perceptions of the benefits and drawbacks of nuclear power. Our analysis shows that Model 1 is fully significant, and Model 2 and 3 are only partially significant."
3612,Sustainable Production of Hydrogen by Steam Reforming of Ethanol Using Cobalt Supported on Nanoporous Zeolitic Material,"Cobalt catalysts supported on Y zeolite and mesoporized Y zeolite (Y-mod) have been studied in steam reforming of ethanol (SRE). Specifically, the effect of the mesoporosity and the acidity of the y zeolite as a support has been explored. Mesoporous were generated on Y zeolite by treatment with NH4F and the acidity was neutralized by Na incorporation. Four cobalt catalysts supported on Y zeolite have been prepared, two using Y zeolite without mesoporous (Co/Y, Co/Y-Na), and two using Y zeolite with mesoporous (Co/Y-mod and Co/Y-mod-Na). All catalysts showed a high activity, with ethanol conversion values close to 100%. The main differences were found in the distribution of the reaction products. Co/Y and Co/Y-mod catalysts showed high selectivity to ethylene and low hydrogen production, which was explained by their high acidity. On the contrary, neutralization of the acid sites could explain the higher hydrogen selectivity and the lower ethylene yields exhibited by the Co/Y-Na and Co/Y-mod-Na. In addition, the physicochemical characterization of these catalysts by XRD, BET surface area, temperature-programmed reduction (TPR), and TEM allowed to connect the presence of mesoporous with the formation of metallic cobalt particles with small size, high dispersion, and with high interaction with the zeolitic support, explaining the high reforming activity exhibited by the co/y-mod-Na sample as well as its higher hydrogen selectivity. It has been also observed that the formation of coke is affected by the presence of mesoporous and acidity. Both properties seem to have an opposite effect on the reforming catalyst, decreasing and increasing the coke deposition, respectively."
3613,Blockage of Store-Operated Ca(2+) Influx by Synta66 is Mediated by Direct Inhibition of the Ca(2+) Selective Orai1 Pore,"SIMPLE SUMMARY: Store-operated calcium channels constituted from the proteins Orai and STIM are important targets for development of new drugs, especially for the treatment of auto-immune diseases. Also, interference with channel function is linked to reduced cancer cell progression, making these channels potential targets for anti-cancer drug development. Therefore, inhibitors need to be evaluated for both their binding selectivity and their potential to interfere with cancer progression. Here, we investigated the inhibitor Synta66 and determined its site of binding via both patch clamp recordings and computational approaches and evaluated its potency as anti-cancer agent in glioblastoma multiforme cells. Our findings show that Synta66 is a highly selective ligand to the Orai1 pore and efficiently blocks store operated calcium entry in glioblastoma cells. Still, in the tested cell lines, Synta66 did not reduce cell viability. We therefore suggest Synta66 as a precise tool to observe interference of store-operated Orai1 channel function in vitro and of resulting downstream effects. ABSTRACT: The Ca(2+) sensor STIM1 and the Ca(2+) channel Orai1 that form the store-operated Ca(2+) (SOC) channel complex are key targets for drug development. Selective SOC inhibitors are currently undergoing clinical evaluation for the treatment of auto-immune and inflammatory responses and are also deemed promising anti-neoplastic agents since SOC channels are linked with enhanced cancer cell progression. Here, we describe an investigation of the site of binding of the selective inhibitor Synta66 to the SOC channel Orai1 using docking and molecular dynamics simulations, and live cell recordings. Synta66 binding was localized to the extracellular site close to the transmembrane (TM)1 and TM3 helices and the extracellular loop segments, which, importantly, are adjacent to the Orai1-selectivity filter. Synta66-sensitivity of the Orai1 pore was, in fact, diminished by both Orai1 mutations affecting Ca(2+) selectivity and permeation of Na(+) in the absence of Ca(2+). Synta66 also efficiently blocked SOC in three glioblastoma cell lines but failed to interfere with cell viability, division and migration. These experiments provide new structural and functional insights into selective drug inhibition of the Orai1 Ca(2+) channel by a high-affinity pore blocker."
3614,Healthcare Professional in the Loop (HPIL): Classification of Standard and Oral Cancer-Causing Anomalous Regions of Oral Cavity Using Textural Analysis Technique in Autofluorescence Imaging,"Oral mucosal lesions (OML) and oral potentially malignant disorders (OPMDs) have been identified as having the potential to transform into oral squamous cell carcinoma (OSCC). This research focuses on the human-in-the-loop-system named Healthcare Professionals in the Loop (HPIL) to support diagnosis through an advanced machine learning procedure. HPIL is a novel system approach based on the textural pattern of OML and OPMDs (anomalous regions) to differentiate them from standard regions of the oral cavity by using autofluorescence imaging. An innovative method based on pre-processing, e.g., the Deriche–Canny edge detector and circular Hough transform (CHT); a post-processing textural analysis approach using the gray-level co-occurrence matrix (GLCM); and a feature selection algorithm (linear discriminant analysis (LDA)), followed by k-nearest neighbor (KNN) to classify OPMDs and the standard region, is proposed in this paper. The accuracy, sensitivity, and specificity in differentiating between standard and anomalous regions of the oral cavity are 83%, 85%, and 84%, respectively. The performance evaluation was plotted through the receiver operating characteristics of periodontist diagnosis with the HPIL system and without the system. This method of classifying OML and OPMD areas may help the dental specialist to identify anomalous regions for performing their biopsies more efficiently to predict the histological diagnosis of epithelial dysplasia."
3615,Quantification of the Ability of Natural Products to Prevent Herpes Virus Infection,"Background: Herpes simplex virus (HSV) is usually dormant and becomes apparent when body conditions decline. We investigated the anti-HSV activity of various natural and synthetic compounds for future clinical application. Methods: Mock- and HSV-infected Vero cells were treated for three days with various concentrations of samples. For short exposure, 100-fold concentrated virus were preincubated for 3 min with samples, diluted to normal multiplicity of infection (MOI), before the addition to the cells. Anti-HSV activity was evaluated by the chemotherapy index. Results: Alkaline extracts of the leaves of Sasa sp. (SE) and pine cone (PCE) showed higher anti-HSV activity than 20 Japanese traditional herb medicines (Kampo formulas), four popular polyphenols, and 119 chromone-related compounds. Exposure of HSV to SE or PCE for 3 min almost completely eliminated the infectivity of HSV, whereas much longer exposure time was required for Kakkonto, the most active Kampo formulae. Anti-HSV activity of PCE and Kakkonto could be detected only when they were dissolved by alkaline solution (pH 8.0), but not by neutral buffer (pH 7.4). Anti-HSV activity of SE and povidone iodine was stable if they were diluted with neutral buffer. Conclusions: The present study suggests the applicability of SE and PCE for treatment of oral HSV and possibly other viruses."
3616,Short-Term Exercise Progression of Cardiovascular Patients throughout Cardiac Rehabilitation: An Observational Study,"Cardiac rehabilitation (CR) is a highly recommended secondary prevention measure for patients with diagnosed cardiovascular disease. Unfortunately, participation rates are low due to enrollment and adherence issues. As such, new CR delivery strategies are of interest, as to improve overall CR delivery. The goal of the study was to obtain a better understanding of the short-term progression of functional capacity throughout multidisciplinary CR, measured as the change in walking distance between baseline six-minute walking test (6MWT) and four consecutive follow-up tests. One-hundred-and-twenty-nine patients diagnosed with cardiovascular disease participated in the study, of which 89 patients who completed the whole study protocol were included in the statistical analysis. A one-way repeated measures ANOVA was conducted to determine whether there was a significant change in mean 6MWT distance (6MWD) throughout CR. A three-way-mixed ANOVA was performed to determine the influence of categorical variables on the progression in 6MWD between groups. Significant differences in mean 6MWD between consecutive measurements were observed. Two subgroups were identified based on the change in distance between baseline and end-of-study. Patients who increased most showed a linear progression. In the other group progression leveled off halfway through rehabilitation. Moreover, the improvement during the initial phase of CR seemed to be indicative for overall progression. The current study adds to the understanding of the short-term progression in exercise capacity of patients diagnosed with cardiovascular disease throughout a CR program. The results are not only of interest for CR in general, but could be particularly relevant in the setting of home-based CR."
3617,Use of Hyaluronic Acid (HA) in Chronic Airway Diseases,"Hyaluronic acid (HA) is a key component of the extracellular matrix of the lungs. A unique attribute of HA is its water-retaining properties, so HA has a major role in the regulation of fluid balance in the lung interstitium. Hyaluronic acid has been widely used in the treatment of eyes, ears, joints and skin disorders, but in the last years, it has been also proposed in the treatment of certain lung diseases, including airway diseases, due to its anti-inflammatory and water-binding capacities. Hyaluronic acid aerosol decreases the severity of elastase-induced emphysema in murine models, prevents bronchoconstriction in asthmatics and improves some functional parameters in chronic obstructive pulmonary disease (COPD) patients. Due to the protection of HA against bronchoconstriction and its hydration properties, inhaled HA would increase the volume of airway surface liquid, resulting in mucus hydration, increased mucous transport and less mucous plugging of the airways. In addition, it has been seen in human studies that the treatment with nebulised HA improves the tolerability of nebulised hypertonic saline (even at 6% or 7% of concentration), which has been demonstrated to be an effective treatment in bronchial secretion management in patients with cystic fibrosis and bronchiectasis. Our objective is to review the role of HA treatment in the management of chronic airway diseases."
3618,"Effects of the Human Gut Microbiota on Cognitive Performance, Brain Structure and Function: A Narrative Review","Enhancing or preserving cognitive performance of personnel working in stressful, demanding and/or high tempo environments is vital for optimal performance. Emerging research suggests that the human gut microbiota may provide a potential avenue to enhance cognition. This review examines the relationship between the human gut microbiota, including modulators of the microbiota on cognition and/or brain function. For this narrative review, a total of n = 17 relevant human research items of a possible 1765 published between January 2010 and November 2018 were identified. Two overarching design methods for synthesis were observed: correlational or pre/post intervention. Limited correlational design studies linking microbiota to cognitive/brain structure endpoints existed (n = 5); however, correlations between microbiota diversity and enhanced cognitive flexibility and executive function were observed. Gut microbiota intervention studies to improve cognition or brain function (n = 12) generally resulted in improved cognition (11/12), in which improvements were observed in visuospatial memory, verbal learning and memory, and aspects of attentional vigilance. Limited studies were available to draw a detailed conclusion; however, available evidence suggests that gut microbiota is linked to cognitive performance and that manipulation of gut microbiota could be a promising avenue for enhancing cognition which warrants further research."
3619,Analyzing Malaria Disease Using Effective Deep Learning Approach,"Medical tools used to bolster decision-making by medical specialists who offer malaria treatment include image processing equipment and a computer-aided diagnostic system. Malaria images can be employed to identify and detect malaria using these methods, in order to monitor the symptoms of malaria patients, although there may be atypical cases that need more time for an assessment. This research used 7000 images of Xception, Inception-V3, ResNet-50, NasNetMobile, VGG-16 and AlexNet models for verification and analysis. These are prevalent models that classify the image precision and use a rotational method to improve the performance of validation and the training dataset with convolutional neural network models. Xception, using the state of the art activation function (Mish) and optimizer (Nadam), improved the effectiveness, as found by the outcomes of the convolutional neural model evaluation of these models for classifying the malaria disease from thin blood smear images. In terms of the performance, recall, accuracy, precision, and F1 measure, a combined score of 99.28% was achieved. Consequently, 10% of all non-dataset training and testing images were evaluated utilizing this pattern. Notable aspects for the improvement of a computer-aided diagnostic to produce an optimum malaria detection approach have been found, supported by a 98.86% accuracy level."
3620,Optimization of Point-Shear Wave Elastography by Skin-to-Liver Distance to Assess Liver Fibrosis in Patients Undergoing Bariatric Surgery,"Background: Obesity is a primary limiting factor in liver stiffness measurement (LSM). The impact of obesity has always been evaluated in terms of body mass index (BMI), without studying the effects of skin-to-liver distance (SLD) on LSM. We studied the impact of SLD on LSM in a cohort of obese patients undergoing bariatric surgery and intra-operatory liver biopsy. Materials and Methods: 299 patients underwent LSM by point-shear wave elastography (ElastPQ protocol), with two different ultrasound machines. SLD was measured as the distance between the skin and the liver capsule, perpendicular to where the region of interest (ROI) was positioned. We used the following arbitrary cut-offs: <5.7 kPa, F0–1; 5.7–7.99 kPa, F2; ≥8 kPa, F3–4. Results: We developed two logistic regression models using elastography–histology agreement (EHA) as the dependent variable and SLD as the independent variable. The model based on the second machine showed strongly more performant discriminative and calibration metrics (AIC 38.5, BIC 44.2, Nagelkerke Pseudo-R2 0.894, AUROC 0.90). The SLD cut-off value of 34.5 mm allowed a correct EHA with a sensitivity of 100%, a specificity of 93%, negative predictive value of 100%, positive predictive value of 87%, an accuracy of 96%, and positive likelihood ratio of 3.56. Conclusion: The impact of SLD is machine-dependent and should be taken into consideration when interpreting LSM. We believe that our findings may serve as a reference point for appropriate fibrosis stratification by liver elastography in obese patients."
3621,Born to Eat Wild: An Integrated Conservation Approach to Secure Wild Food Plants for Food Security and Nutrition,"Overlooked in national reports and in conservation programs, wild food plants (WFPs) have been a vital component of food and nutrition security for centuries. Recently, several countries have reported on the widespread and regular consumption of WFPs, particularly by rural and indigenous communities but also in urban contexts. They are reported as critical for livelihood resilience and for providing essential micronutrients to people enduring food shortages or other emergency situations. However, threats derived from changes in land use and climate, overexploitation and urbanization are reducing the availability of these biological resources in the wild and contributing to the loss of traditional knowledge associated with their use. Meanwhile, few policy measures are in place explicitly targeting their conservation and sustainable use. This can be partially attributed to a lack of scientific evidence and awareness among policymakers and relevant stakeholders of the untapped potential of WFPs, accompanied by market and non-market barriers limiting their use. This paper reviews recent efforts being undertaken in several countries to build evidence of the importance of WFPs, while providing examples of cross-sectoral cooperation and multi-stakeholder approaches that are contributing to advance their conservation and sustainable use. An integrated conservation approach is proposed contributing to secure their availability for future generations."
3622,The Effects of Frequency and Duration of Handling on the Development of Feline Upper Respiratory Infections in a Shelter Setting,"SIMPLE SUMMARY: Stress in cats residing in a shelter environment is a significant contributor to the development of upper respiratory disease (URD). Previous studies have shown that positive interactions can reduce stress and enhance the immune system. However, little is known on how the frequency and duration of daily handling affects a cat’s likelihood of developing URD. The goal of this study was to record the daily frequency and duration of handling of clinically healthy cats that were relinquished at a closed admission shelter and determine if these parameters were associated with a statistically significant increased risk of developing URD. While no parameters were statistically significantly associated with an increased hazard of developing URD, we found that cats that did not develop URD were handled more frequently than cats that did develop URD. Our results suggest that increased frequency and duration of handling does not appear to increase the risk of URD signs and may reduce the incidence of URD development. These results are important for the shelter community in developing handling and hygiene protocols for shelter cats. ABSTRACT: Reducing stress is important to maintaining the health of shelter cats and decreasing the risk of upper respiratory disease (URD). The aim of this study was to determine if the frequency and/or duration of daily routine handling of shelter cats affects the likelihood of URD development. At a closed admission shelter, each cat free of URD on intake was given a cage card for recording handling data. These data included: date and times when the cat was handled, duration of handling, if and when the cat developed signs of URD, and the handler identity. Cox regression was used to determine the relationship between these factors and URD development. We found cats that did not develop URD were handled significantly more than cats that did (1.1 times per day vs. 0.7 times per day, p < 0.001). Increased frequency of handling had a borderline significant effect on the hazard of developing URD (HR 0.37; CI: 0.13–1.1; p = 0.066). No other parameters were significantly associated with the development of URD; however, small sample size may be responsible for this finding. A larger study is needed to elucidate the relationship between handling and URD development."
3623,Retrospective Case-Control Study of 2017 G2P[4] Rotavirus Epidemic in Rural and Remote Australia,"Background: A widespread G2P[4] rotavirus epidemic in rural and remote Australia provided an opportunity to evaluate the performance of Rotarix and RotaTeq rotavirus vaccines, ten years after their incorporation into Australia’s National Immunisation Program. Methods: We conducted a retrospective case-control analysis. Vaccine-eligible children with laboratory-confirmed rotavirus infection were identified from jurisdictional notifiable infectious disease databases and individually matched to controls from the national immunisation register, based on date of birth, Aboriginal status and location of residence. Results: 171 cases met the inclusion criteria; most were Aboriginal and/or Torres Strait Islander (80%) and the median age was 19 months. Of these cases, 65% and 25% were fully or partially vaccinated, compared to 71% and 21% of controls. Evidence that cases were less likely than controls to have received a rotavirus vaccine dose was weak, OR 0.79 (95% CI, 0.46–1.34). On pre-specified subgroup analysis, there was some evidence of protection among children <12 months (OR 0.48 [95% CI, 0.22–1.02]), and among fully vs. partially vaccinated children (OR 0.65 [95% CI, 0.42–1.01]). Conclusion: Despite the known effectiveness of rotavirus vaccination, a protective effect of either rotavirus vaccine during a G2P[4] outbreak in these settings among predominantly Aboriginal children was weak, highlighting the ongoing need for a more effective rotavirus vaccine and public health strategies to better protect Aboriginal children."
3624,Screening of Fish Cell Lines for Piscine Orthoreovirus-1 (PRV-1) Amplification: Identification of the Non-Supportive PRV-1 Invitrome,"Piscine reovirus (PRV) is the causative agent of heart and skeletal muscle inflammation (HSMI), which is detrimental to Atlantic Salmon (AS) aquaculture, but so far has not been cultivatable, which impedes studying the disease and developing a vaccine. Homogenates of head kidney and red blood cells (RBC) from AS in which PRV-1 had been detected were applied to fish cell lines. The cell lines were from embryos, and from brain, blood, fin, gill, gonads, gut, heart, kidney, liver, skin, and spleen, and had the shapes of endothelial, epithelial, fibroblast, and macrophage cells. Most cell lines were derived from the Neopterygii subclass of fish, but one was from subclass Chondrostei. Cultures were examined by phase contrast microscopy for appearance, and by quantitative polymerase chain reaction (qPCR) for PRV-1 RNA amplification and for the capacity to transfer any changes to new cultures. No changes in appearance and Ct values were observed consistently or transferable to new cultures. Therefore, 31 cell lines examined were unable to support PRV-1 amplification and are described as belonging to the non-supportive PRV-1 invitrome. However, these investigations and cell lines can contribute to understanding PRV-1 cellular and host tropism, and the interactions between virus-infected and bystander cells."
3625,Quantification of Receptor Occupancy by Ligand—An Understudied Class of Potential Biomarkers,"SIMPLE SUMMARY: Molecular complexes, such as those comprised of ligands such as hormones binding to their target receptors, are key determinants of health and disease. While research has focused on measuring receptors or ligands independently as biomarkers, very little attention has been given to measuring ligand-receptor complexes, in part, due to the limited availability of suitable technologies to do such measurements. This has led to underappreciation of ligand-receptor complexes as biomarkers in disease, including in cancer. In this commentary, the potential role of ligand-receptor complexes and their importance as biomarkers in cancer is discussed. We also describe a novel RNA aptamer-based technology, designated as ligand-receptor complex-binding aptamers (LIRECAP), that can provide precise measurement of the ligand occupancy of receptors and has potential use as a biomarker discovery platform. ABSTRACT: Molecular complexes, such as ligand–receptor complexes, are vital for both health and disease and can be shed into the circulation in soluble form. Relatively little is known about the biology of soluble ligand–receptor complexes. The functional importance of such complexes and their potential use as clinical biomarkers in diagnosis and therapy remains underappreciated. Most traditional technologies used to study ligand–receptor complexes measure the individual levels of soluble ligands or receptors rather than the complexes themselves. The fraction of receptors occupied by ligand, and the potential clinical relevance of such information, has been largely overlooked. Here, we review the biological significance of soluble ligand–receptor complexes with a specific focus on their potential as biomarkers of cancer and other inflammatory diseases. In addition, we discuss a novel RNA aptamer-based technology, designated ligand–receptor complex-binding aptamers (LIRECAP), that can provide precise measurement of the fraction of a soluble receptor occupied by its ligand. The potential applicability of the LIRECAP technology as a biomarker discovery platform is also described."
3626,Induction of Chicken Host Defense Peptides within Disease-Resistant and -Susceptible Lines,"Host defense peptides (HDPs) are multifunctional immune molecules that respond to bacterial and viral pathogens. In the present study, bone marrow-derived cells (BMCs) and chicken embryonic fibroblasts (CEFs) were cultured from a Leghorn line (Ghs6) and Fayoumi line (M15.2), which are inbred chicken lines relatively susceptible and resistant to various diseases, respectively. The cells were treated by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly(I:C)) and, subsequently, mRNA expression of 20 chicken HDPs was analyzed before and after the stimulation. At homeostasis, many genes differed between the chicken lines, with the Fayoumi line having significantly higher expression (p < 0.05) than the Leghorn line: AvBD1, 2, 3, 4, 6, and 7 in BMCs; CATH1, CATH3, and GNLY in CEFs; and AvDB5, 8, 9, 10, 11, 12, 13 in both BMCs and CEFs. After LPS treatment, the expression of AvBD1, 2, 3, 4, 5, 9, 12, CATH1, and CATHB1 was significantly upregulated in BMCs, but no genes changed expression in CEFs. After poly(I:C) treatment, AvBD2, 11, 12, 13, CATHB1 and LEAP2 increased in both cell types; CATH2 only increased in BMCs; and AvBD3, 6, 9, 14, CATH1, CATH3, and GNLY only increased in CEFs. In addition, AvBD7, AvBD14, CATH1, CATH2, GNLY, and LEAP2 showed line-specific expression dependent upon cell type (BMC and CEF) and stimulant (LPS and poly(I:C)). The characterization of mRNA expression patterns of chicken HDPs in the present study suggests that their functions may be associated with multiple types of disease resistance in chickens."
3627,Well-Being at Work after Return to Work (RTW): A Systematic Review,"Background: Employees’ well-being at work after the return to work (RTW) is considered a key aspect of rehabilitation and maintenance of workability. This systematic review aimed at identifying the common psychosocial factors that predict the subjective and psychological well-being in RTW processes after having a long-standing health problem or disability. Objective: To evaluate the subjective and psychological well-being at work of employees with chronic or long-standing health problems or those returning to work after any cause of disability. Data source: Systematic review of articles published in English or Spanish using PsycINFO, PsycARTICLES, MEDLINE, Psychology, and Behavioral Sciences Collection, and Pubpsych. An additional study was identified by contacting expert academics in the field. The search equations used included terms such as Return to Work, Long-Standing Health Problems or Disability, Work Health Balance, and job satisfaction or subjective well-being. Eligibility criteria for the studies: Studies that included a measure of employees’ well-being at work following return to work were selected for the review. Evaluation of the studies and synthesis methods: The studies were selected using predefined fields which included quality criteria. Results: Of the 264 articles returned by the initial search, a total of 20 were finally selected. Results were organized around the three different theoretical approaches for understanding RTW and its antecedents and consequences: (a) RTW and autonomy at work have a positive effect on psychological well-being; (b) job demand is linked to less job satisfaction, whereas a higher level on the work–health balance is associated with job satisfaction and work engagement; (c) internal and external support is linked to job satisfaction in the case of a disease. Limitations: The evidence provided by the results is restricted by the limited availability of studies focusing on well-being at work following return to work. Moreover, the studies identified are of different kinds, thereby preventing comparisons. Conclusions and implications of the main findings: Employees’ subjective well-being after return to work has received very little attention to date. Given its importance in the current configuration of the labor market, it should be the object of more research."
3628,"Trust, Connection and Equity: Can Understanding Context Help to Establish Successful Campus Community Gardens?","Campus community gardens (CCGs) can potentially improve student health and wellbeing, mitigate social and ecological problems, and nurture university-community relationships. However, CCGs are located in complex socio-political and ecological settings and many community gardens struggle or fail. However, few studies have assessed the socio-political/ecological context of a garden setting prior to its development to understand the potential barriers and enablers of success. Our study assessed the socio-spatial context of a proposed CCG at a student university accommodation site. We engaged diverse university and community stakeholders through interviews, focus groups and a survey to explore their perceptions of the space generally and the proposed garden specifically. Visual observations and public life surveying were used to determine patterns of behavior. Results confirmed known problems associated with an underutilized site that provides little opportunity for lingering or contact with nature; and unknown barriers, including socially disconnected stakeholders and community distrust of the university. The research also uncovered positive enablers, such as stakeholder appreciation of the social, wellbeing and ecological benefits that a CCG could deliver. Our findings suggest that an in-depth exploration of a proposed garden context can be an important enabler of its success."
3629,Plasmonic Sensors for Monitoring Biological and Chemical Threat Agents,"Sensors are excellent options owing to their ability to figure out a large number of problems and challenges in several areas, including homeland security, defense, medicine, pharmacology, industry, environment, agriculture, food safety, and so on. Plasmonic sensors are used as detection devices that have important properties, such as rapid recognition, real-time analysis, no need labels, sensitive and selective sensing, portability, and, more importantly, simplicity in identifying target analytes. This review summarizes the state-of-art molecular recognition of biological and chemical threat agents. For this purpose, the principle of the plasmonic sensor is briefly explained and then the use of plasmonic sensors in the monitoring of a broad range of biological and chemical threat agents is extensively discussed with different types of threats according to the latest literature. A conclusion and future perspectives are added at the end of the review."
3630,"Keeping It Together: Structures, Functions, and Applications of Viral Decoration Proteins","Decoration proteins are viral accessory gene products that adorn the surfaces of some phages and viral capsids, particularly tailed dsDNA phages. These proteins often play a “cementing” role, reinforcing capsids against accumulating internal pressure due to genome packaging, or environmental insults such as extremes of temperature or pH. Many decoration proteins serve alternative functions, including target cell recognition, participation in viral assembly, capsid size determination, or modulation of host gene expression. Examples that currently have structures characterized to high-resolution fall into five main folding motifs: β-tulip, β-tadpole, OB-fold, Ig-like, and a rare knotted α-helical fold. Most of these folding motifs have structure homologs in virus and target cell proteins, suggesting horizontal gene transfer was important in their evolution. Oligomerization states of decoration proteins range from monomers to trimers, with the latter most typical. Decoration proteins bind to a variety of loci on capsids that include icosahedral 2-, 3-, and 5-fold symmetry axes, as well as pseudo-symmetry sites. These binding sites often correspond to “weak points” on the capsid lattice. Because of their unique abilities to bind virus surfaces noncovalently, decoration proteins are increasingly exploited for technology, with uses including phage display, viral functionalization, vaccination, and improved nanoparticle design for imaging and drug delivery. These applications will undoubtedly benefit from further advances in our understanding of these versatile augmenters of viral functions."
3631,Systematic Review and Meta-Analysis of Vesical Imaging-Reporting and Data System (VI-RADS) Inter-Observer Reliability: An Added Value for Muscle Invasive Bladder Cancer Detection,"SIMPLE SUMMARY: In our systematic review and meta-analysis of eight observational studies including a total of 1016 patients, we demonstrated excellent pooled inter-observer agreement among Genito-Urinary radiologists when adopting the novel Vesical Imaging-Reporting and Data System (VI-RADS) criteria in the pre-trans-urethral resection of bladder tumor (TURBT) assessment for non-muscle (NMIBC) vs. muscle-invasive bladder cancer (MIBC) detection. ABSTRACT: The Vesical Imaging-Reporting and Data System (VI-RADS) has been introduced to provide preoperative bladder cancer staging and has proved to be reliable in assessing the presence of muscle invasion in the pre-TURBT (trans-urethral resection of bladder tumor). We aimed to assess through a systematic review and meta-analysis the inter-reader variability of VI-RADS criteria for discriminating non-muscle vs. muscle invasive bladder cancer (NMIBC, MIBC). PubMed, Web of Science, Cochrane, and Embase were searched up until 30 July 2020. The Quality Appraisal of Diagnostic Reliability (QAREL) checklist was utilized to assess the quality of included studies and a pooled measure of inter-rater reliability (Cohen’s Kappa [κ] and/or Intraclass correlation coefficients (ICCs)) was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate the contribution of moderators to heterogeneity. In total, eight studies between 2018 and 2020, which evaluated a total of 1016 patients via 21 interpreting genitourinary (GU) radiologists, met inclusion criteria and were critically examined. No study was considered to be significantly flawed with publication bias. The pooled weighted mean κ estimate was 0.83 (95%CI: 0.78–0.88). Heterogeneity was present among the studies (Q = 185.92, d.f. = 7, p < 0.001; I2 = 92.7%). Meta-regression analyses showed that the relative % of MIBC diagnosis and cumulative reader’s experience to influence the estimated outcome (Coeff: 0.019, SE: 0.007; p= 0.003 and 0.036, SE: 0.009; p = 0.001). In the present study, we confirm excellent pooled inter-reader agreement of VI-RADS to discriminate NMIBC from MIBC underlying the importance that standardization and reproducibility of VI-RADS may confer to multiparametric magnetic resonance (mpMRI) for preoperative BCa staging."
3632,Longitudinal Predictors of Self-Regulation at School Entry: Findings from the All Our Families Cohort,"Self-regulation is the ability to manage emotions, modulate behaviors, and focus attention. This critical skill begins to develop in infancy, improves substantially in early childhood and continues through adolescence, and has been linked to long-term health and well-being. The objectives of this study were to determine risk factors and moderators associated with the three elements of self-regulation (i.e., inattention, emotional control, or behavioral control) as well as overall self-regulation, among children at age 5. Participants were mother–child dyads from the All Our Families study (n = 1644). Self-regulation was assessed at age 5. Risk factors included income, maternal mental health, child sex, and screen time, and potential moderation by parenting and childcare. Adjusted odds ratios of children being at risk for poor self were estimated using multivariable logistic regression. Twenty-one percent of children had poor self-regulation skills. Risk factors for poor self-regulation included lower income, maternal mental health difficulties, and male sex. Childcare and poor parenting did not moderate these associations and hostile and ineffective parenting was independently associated with poor self-regulation. Excess screen time (>1 h per day) was associated with poor self-regulation. Self-regulation involves a complex and overlapping set of skills and risk factors that operate differently on different elements. Parenting and participation in childcare do not appear to moderate the associations between lower income, maternal mental health, male sex, and screen time with child self-regulation."
3633,Quercitrin Ameliorates Hyperlipidemia and Hepatic Steatosis in Ovariectomized Mice,"Nonalcoholic fatty liver disease (NAFLD) is associated with progressive metabolic diseases. Estrogen deficiency increases the NAFLD risk among postmenopausal women. Thus, effective agents to prevent and treat NAFLD in postmenopausal women are required. Quercitrin (Quer) is a natural glycosylated flavonoid with antimicrobial, anti-inflammatory, and hypolipidemic effects. This study investigated whether Quer improves dysregulated lipid metabolism and suppresses hepatic steatosis in ovariectomized (OVX) mice as an experimental model mimicking postmenopausal women. Mice were assigned to the following four groups: SHAM, OVX, OVX + β-estradiol (0.4 mg/kg diet), and OVX + Quer (500 mg/kg diet). Mice were administered a diet with or without Quer for three months. OVX mice displayed significantly higher body mass, epidermal fat, and liver weights than those of SHAM mice. However, these levels were reduced in Quer-treated mice. Quer treatment reduced the levels of serum lipid metabolites, including triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Furthermore, Quer reduced liver lipid steatosis and inhibited the expression of proinflammatory cytokines, such as tumor necrosis factor-α, IL-6, and IL-1β. The results of the present study indicate that Quer improves dysregulated lipid metabolism and reduces hepatic steatosis and inflammation by compensating for estrogen deficiency, suggesting that Quer may potentially exert protective effects during hepatic steatosis in postmenopausal women."
3634,"The Impact of Experience, Length of Service, and Workplace Preparedness in Physicians’ Readiness in the Response to Disasters","With an increasing number of natural and man-made disasters, the need for preparedness in all levels of management is obvious. Among healthcare professionals responding to these emergencies, physicians are of particular importance due to their significant roles as leaders and frontline workers in minimizing morbidity and mortality of the affected population. This study analyses the preparedness of 549 physicians from all medical centers in Lublin, Poland to formulate their observations, suggestions, and recommendations concerning the improvement of the chain of response in disaster management. The results of this study show that the perceived preparedness of physicians for disaster management and response is not as high as it should be, and the majority of the respondents perceived their disaster preparedness insufficient. Training of physicians in disaster management and principles of disaster medicine is needed, by focusing on the specificity of rescue response to emergencies following disasters, and medical and non-medical aspects of the response with particular emphasis on a management approach covering all hazards."
3635,Curcumin: Could This Compound Be Useful in Pregnancy and Pregnancy-Related Complications?,"Curcumin, the main polyphenol contained in turmeric root (Curcuma longa), has played a significant role in medicine for centuries. The growing interest in plant-derived substances has led to increased consumption of them also in pregnancy. The pleiotropic and multi-targeting actions of curcumin have made it very attractive as a health-promoting compound. In spite of the beneficial effects observed in various chronic diseases in humans, limited and fragmentary information is currently available about curcumin’s effects on pregnancy and pregnancy-related complications. It is known that immune-metabolic alterations occurring during pregnancy have consequences on both maternal and fetal tissues, leading to short- and long-term complications. The reported anti-inflammatory, antioxidant, antitoxicant, neuroprotective, immunomodulatory, antiapoptotic, antiangiogenic, anti-hypertensive, and antidiabetic properties of curcumin appear to be encouraging, not only for the management of pregnancy-related disorders, including gestational diabetes mellitus (GDM), preeclampsia (PE), depression, preterm birth, and fetal growth disorders but also to contrast damage induced by natural and chemical toxic agents. The current review summarizes the latest data, mostly obtained from animal models and in vitro studies, on the impact of curcumin on the molecular mechanisms involved in pregnancy pathophysiology, with the aim to shed light on the possible beneficial and/or adverse effects of curcumin on pregnancy outcomes."
3636,Clinical Impact of Small Bowel Capsule Endoscopy in Obscure Gastrointestinal Bleeding,"Background and objectives: The most frequent indications for small bowel capsule endoscopy (SBCE) are obscure gastrointestinal bleeding (OGIB) and iron deficiency anemia (IDA). The aim of this study was to evaluate the diagnostic yield (DY) of SBCE in overt and occult OGIB, as well as its impact on the clinical outcome. Materials and Methods: This study retrospectively included all cases of OGIB investigated by SBCE in a tertiary care referral center, between 1st January 2016 and 31st December 2018. OGIB was defined by overt or occult gastrointestinal bleeding, with negative upper and lower endoscopy. Occult gastrointestinal bleeding was either proved by a fecal test or presumptively incriminated as a cause for IDA. DY was defined as the detection rate for what were thought to be clinically significant findings. DYs for overt and occult bleeding were assessed and compared. Gender, age, hemoglobin levels, NSAID consumption and the use of anticoagulants were recorded. Following SBCE results, individual therapeutic decisions were made, and follow-up data were recorded. Results: 224 SBCE examinations were performed for OGIB, of which 148 were for overt OGIB, and 76 for unexplained IDA. Positive findings were found in 139 patients, resulting in an overall DY for OGIB of 62%, higher in overt OGIB (75%) compared to IDA (37%). The most frequent findings were small bowel angioectasias (62.2% in overt OGIB and 78.5% in IDA). On multivariate logistic regression analysis, only hemoglobin level <10 g/dL and anticoagulants were the variables independently associated with positive findings. All patients received medical, endoscopic or surgical treatment and had good clinical outcome during follow-up. Conclusion: SBCE has a high diagnostic yield and a positive impact on management of patients with OGIB."
3637,Immunological Perspective for Ebola Virus Infection and Various Treatment Measures Taken to Fight the Disease,"Ebolaviruses, discovered in 1976, belongs to the Filoviridae family, which also includes Marburg and Lloviu viruses. They are negative-stranded RNA viruses with six known species identified to date. Ebola virus (EBOV) is a member of Zaire ebolavirus species and can cause the Ebola virus disease (EVD), an emerging zoonotic disease that results in homeostatic imbalance and multi-organ failure. There are three EBOV outbreaks documented in the last six years resulting in significant morbidity (>32,000 cases) and mortality (>13,500 deaths). The potential factors contributing to the high infectivity of this virus include multiple entry mechanisms, susceptibility of the host cells, employment of multiple immune evasion mechanisms and rapid person-to-person transmission. EBOV infection leads to cytokine storm, disseminated intravascular coagulation, host T cell apoptosis as well as cell mediated and humoral immune response. In this review, a concise recap of cell types targeted by EBOV and EVD symptoms followed by detailed run-through of host innate and adaptive immune responses, virus-driven regulation and their combined effects contributing to the disease pathogenesis has been presented. At last, the vaccine and drug development initiatives as well as challenges related to the management of infection have been discussed."
3638,Evaluating the Efficacy of a Mobile App (Drinks:Ration) and Personalized Text and Push Messaging to Reduce Alcohol Consumption in a Veteran Population: Protocol for a Randomized Controlled Trial,"BACKGROUND: Alcohol misuse is higher in the UK Armed Forces than in the general population. Previous research has shown that interventions delivered via smartphones are efficacious in promoting self-monitoring of alcohol use, have utility in reducing alcohol consumption, and have a broad reach. OBJECTIVE: This single-blinded randomized controlled trial (RCT) aims to assess the efficacy of a 28-day brief alcohol intervention delivered via a smartphone app (Drinks:Ration) in reducing weekly self-reported alcohol consumption between baseline and 3-month follow-up among veterans who drink at a hazardous or harmful level and receive or have received support for mental health symptoms in a clinical setting. METHODS: In this two-arm, single-blinded RCT, a smartphone app that includes interactive features designed to enhance participants’ motivation and personalized messaging is compared with a smartphone app that provides only government guidance on alcohol consumption. The trial will be conducted in a veteran population that has sought help through Combat Stress, a UK veteran’s mental health charity. Recruitment, consent, and data collection will be carried out automatically through the Drinks:Ration platform. The primary outcome is the change in self-reported weekly alcohol consumption between baseline (day 0) and 3-month follow-up (day 84) as measured using the Time-Line Follow back for Alcohol Consumption. Secondary outcome measures include (1) change in the baseline to 3-month follow-up (day 84) Alcohol Use Disorder Identification Test score and (2) change in the baseline to 3-month follow-up (day 84) World Health Organization Quality of Life-BREF score to assess the quality of adjusted life years. Process evaluation measures include (1) app use and (2) usability ratings as measured by the mHealth App Usability Questionnaire. The primary and secondary outcomes will also be reassessed at the 6-month follow-up (day 168) to assess the longer-term benefits of the intervention, which will be reported as a secondary outcome. RESULTS: The study will begin recruitment in October 2020 and is expected to require 12 months to complete. The study results will be published in 2022. CONCLUSIONS: This study assesses whether a smartphone app is efficacious in reducing self-reported alcohol consumption in a veteran population that has sought help through Combat Stress using personalized messaging and interactive features. This innovative approach, if successful, may provide a means to deliver a low-cost health promotion program that has the potential to reach large groups, in particular those who are geographically dispersed, such as military personnel. TRIAL REGISTRATION: ClinicalTrials.gov NCT04494594; https://clinicaltrials.gov/ct2/show/NCT04494594 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/19720"
3639,Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis,"The Type I Interferons (IFN-Is) are innate antiviral cytokines that include 12 different IFNα subtypes and IFNβ that signal through the IFN-I receptor (IFNAR), inducing hundreds of IFN-stimulated genes (ISGs) that comprise the ‘interferome’. Quantitative differences in IFNAR binding correlate with antiviral activity, but whether IFN-Is exhibit qualitative differences remains controversial. Moreover, the IFN-I response is protective during acute HIV-1 infection, but likely pathogenic during the chronic stages. To gain a deeper understanding of the IFN-I response, we compared the interferomes of IFNα subtypes dominantly-expressed in HIV-1-exposed plasmacytoid dendritic cells (1, 2, 5, 8 and 14) and IFNβ in the earliest cellular targets of HIV-1 infection. Primary gut CD4 T cells from 3 donors were treated for 18 hours ex vivo with individual IFN-Is normalized for IFNAR signaling strength. Of 1,969 IFN-regulated genes, 246 ‘core ISGs’ were induced by all IFN-Is tested. However, many IFN-regulated genes were not shared between the IFNα subtypes despite similar induction of canonical antiviral ISGs such as ISG15, RSAD2 and MX1, formally demonstrating qualitative differences between the IFNα subtypes. Notably, IFNβ induced a broader interferome than the individual IFNα subtypes. Since IFNβ, and not IFNα, is upregulated during chronic HIV-1 infection in the gut, we compared core ISGs and IFNβ-specific ISGs from colon pinch biopsies of HIV-1-uninfected (n = 13) versus age- and gender-matched, antiretroviral-therapy naïve persons with HIV-1 (PWH; n = 19). Core ISGs linked to inflammation, T cell activation and immune exhaustion were elevated in PWH, positively correlated with plasma lipopolysaccharide (LPS) levels and gut IFNβ levels, and negatively correlated with gut CD4 T cell frequencies. In sharp contrast, IFNβ-specific ISGs linked to protein translation and anti-inflammatory responses were significantly downregulated in PWH, negatively correlated with gut IFNβ and LPS, and positively correlated with plasma IL6 and gut CD4 T cell frequencies. Our findings reveal qualitative differences in interferome induction by diverse IFN-Is and suggest potential mechanisms for how IFNβ may drive HIV-1 pathogenesis in the gut."
3640,Krankenhausmedizinische Interventionen in der neurologischen Anschlussrehabilitation,"Treatment in hospitals differs from treatment in rehabilitation centers from a legal perspective because German law mandates that in hospitals physicians and other qualified personnel must be on duty at all times. This is not required for inpatient rehabilitation centers. Since this Act was passed more than 30 years ago, more acute medical interventions are now carried out and the number of older people in the population has increased. As a result patients are nowadays older, more multimorbid and therefore have a greater risk for medical complications. This is especially true for postacute neurological care. For this reason, the original legal framework for neurological rehabilitation treatment has become questionable. Therefore, we prospectively tested how often patients in inpatient neurorehabilitation suffer from complications that require immediate attention by qualified personnel. In 759 patients observed over a period of 6 months we found 602 complications requiring immediate interventions by physicians (e.g. falls, urinary tract infections, other forms of fever, diarrhea associated with Clostridium difficile, pneumonia, respiratory insufficiency, sepsis, epileptic seizures and arrhythmia). On average at least three acute care interventions occurred per day at the facility examined. We conclude that neurological inpatient rehabilitation has outgrown its legal foundations and now incorporates hospital care."
3641,In This Issue: December 2020,
3642,"No evidence for sylvatic cycles of chikungunya, dengue and Zika viruses in African green monkeys (Chlorocebus aethiops sabaeus) on St. Kitts, West Indies","BACKGROUND: Dengue, chikungunya and Zika viruses (DENV, CHIKV and ZIKV) are transmitted in sylvatic transmission cycles between non-human primates and forest (sylvan) mosquitoes in Africa and Asia. It remains unclear if sylvatic cycles exist or could establish themselves elsewhere and contribute to the epidemiology of these diseases. The Caribbean island of St. Kitts has a large African green monkey (AGM) (Chlorocebus aethiops sabaeus) population and is therefore ideally suited to investigate sylvatic cycles. METHODS: We tested 858 AGM sera by ELISA and PRNT for virus-specific antibodies and collected and identified 9704 potential arbovirus vector mosquitoes. Mosquitoes were homogenized in 513 pools for testing by viral isolation in cell culture and by multiplex RT-qPCR after RNA extraction to detect the presence of DENV, CHIKV and ZIKVs. DNA was extracted from 122 visibly blood-fed individual mosquitoes and a polymorphic region of the hydroxymethylbilane synthase gene (HMBS) was amplified by PCR to determine if mosquitoes had fed on AGMs or humans. RESULTS: All of the AGMs were negative for DENV, CHIKV or ZIKV antibodies. However, one AGM did have evidence of an undifferentiated Flavivirus infection. Similarly, DENV, CHIKV and ZIKV were not detected in any of the mosquito pools by PCR or culture. AGMs were not the source of any of the mosquito blood meals. CONCLUSION: Sylvatic cycles involving AGMs and DENV, CHIKV and ZIKV do not currently exist on St. Kitts. [Image: see text]"
3643,Electroencephalographic features in patients undergoing extracorporeal membrane oxygenation,"BACKGROUND: Neurologic injury is one of the most frequent causes of death in patients undergoing extracorporeal membrane oxygenation (ECMO). As neurological examination is often unreliable in sedated patients, additional neuromonitoring is needed. However, the value of electroencephalogram (EEG) in adult ECMO patients has not been well assessed. Therefore, the aim of this study was to assess the occurrence of electroencephalographic abnormalities in patients treated with extracorporeal membrane oxygenation (ECMO) and their association with 3-month neurologic outcome. METHODS: Retrospective analysis of all patients undergoing venous–venous (V–V) or venous–arterial (V–A) ECMO with a concomitant EEG recording (April 2009–December 2018), either recorded intermittently or continuously. EEG background was classified into four categories: mild/moderate encephalopathy (i.e., mostly defined by the presence of reactivity), severe encephalopathy (mostly defined by the absence of reactivity), burst-suppression (BS) and suppressed background. Epileptiform activity (i.e., ictal EEG pattern, sporadic epileptiform discharges or periodic discharges) and asymmetry were also reported. EEG findings were analyzed according to unfavorable neurological outcome (UO, defined as Glasgow Outcome Scale < 4) at 3 months after discharge. RESULTS: A total of 139 patients (54 [41–62] years; 60 (43%) male gender) out of 596 met the inclusion criteria and were analyzed. Veno–arterial (V–A) ECMO was used in 98 (71%); UO occurred in 99 (71%) patients. Continuous EEG was performed in 113 (81%) patients. The analysis of EEG background showed that 29 (21%) patients had severe encephalopathy, 4 (3%) had BS and 19 (14%) a suppressed background. In addition, 11 (8%) of patients had seizures or status epilepticus, 10 (7%) had generalized periodic discharges or lateralized periodic discharges, and 27 (19%) had asymmetry on EEG. In the multivariate analysis, the occurrence of ischemic stroke or intracranial hemorrhage (OR 4.57 [1.25–16.74]; p = 0.02) and a suppressed background (OR 10.08 [1.24–82.20]; p = 0.03) were independently associated with UO. After an adjustment for covariates, an increasing probability for UO was observed with more severe EEG background categories. CONCLUSIONS: In adult patients treated with ECMO, EEG can identify patients with a high likelihood of poor outcome. In particular, suppressed background was independently associated with unfavorable neurological outcome."
3644,Gene and Cell-Based Therapies for Parkinson’s Disease: Where Are We?,"Parkinson’s disease (PD) is a neurodegenerative disorder that carries large health and socioeconomic burdens. Current therapies for PD are ultimately inadequate, both in terms of symptom control and in modification of disease progression. Deep brain stimulation and infusion therapies are the current mainstay for treatment of motor complications of advanced disease, but these have very significant drawbacks and offer no element of disease modification. In fact, there are currently no agents that are established to modify the course of the disease in clinical use for PD. Gene and cell therapies for PD are now being trialled in the clinic. These treatments are diverse and may have a range of niches in the management of PD. They hold great promise for improved treatment of symptoms as well as possibly slowing progression of the disease in the right patient group. Here, we review the current state of the art for these therapies and look to future strategies in this fast-moving field. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00940-4) contains supplementary material, which is available to authorized users."
3645,Comparison of oral versus intravenous tranexamic acid in total knee and hip arthroplasty: A GRADE analysis and meta-analysis,"BACKGROUND: The efficacy and safety of oral tranexamic acid (TXA) remain controversial because of the small number of clinical studies. The aim of the present study was to compare the efficacy and safety of oral TXA with intravenous TXA in patients undergoing total hip arthroplasty and total knee arthroplasty in a systematic review and meta-analysis. METHODS: We conducted a meta-analysis to identify randomized controlled trials (RCTs) involving oral and intravenous TXA in total hip arthroplasty and total knee arthroplasty up to December 2019 by searching databases including PubMed, Web of Science, Embase, the Cochrane Controlled Trials Register, the Cochrane Library China Biology Medicine, China National Knowledge Infrastructure, China Science and Technology Journal Database and Wanfang. The mean difference or standard mean difference was used to assess continuous outcomes such as hemoglobin (Hb) drop, total blood loss, drain blood loss, and length of hospital stay, with a 95% confidence interval. Relative risks with a 95% confidence interval were used to assess dichotomous outcomes such as transfusion rate and the incidence of deep venous thrombosis and calf muscular vein thrombosis. Review Manager was used for the meta-analysis. RESULTS: Ten RCTs containing 1080 participants met the inclusion criteria. We found no significant differences in terms of the average Hb drop (P = .60), total blood loss (P = .60), transfusion rate (P = .99), drain blood loss (P = .91), length of hospital stay (P = .95), and the incidence of deep venous thrombosis (P = .55) and calf muscular vein thrombosis (P = .19) between oral and IV TXA. CONCLUSIONS: Compared with the IV TXA, oral TXA has similar effects on reducing the Hb drop, total blood loss, transfusion rate, drain blood loss, and length of hospital stay without increasing the risk of calf muscular vein thrombosis and deep venous thrombosis. Furthermore, oral TXA is easy to access and administer, which decreases the workload of nurses and even delivers cost-saving benefits to the health care system. We thus conclude that oral TXA may be an optimal approach in total joint arthroplasty. However, more high-quality and multicenter RCTs are still needed to confirm our conclusions. REGISTRATION: The current meta-analysis was registered on PROSPERO (International Prospective Register of Systematic Reviews), and the registration number was CRD42018111291."
3646,"Structural equation modeling test of the pre-intentional phase of the health action process approach (HAPA) model on condom use intention among senior high school students in Tianjin, China","Based on the Theory of Health Action Process Approach (HAPA) Model, this study aimed to investigate factors associated with condom use intention in Chinese adolescents. In 2017, we conducted a cross-sectional study using stratified cluster, convenience sampling method to assess condom use intention among senior high school students in Tianjin, China. One thousand eighty two senior high school students were anonymously surveyed through self-administered questionnaires. Structural equation modelling was used to assess the pre-intentional phase of HAPA model. Among the participants, 41.5% (449/1082) were male, 54.1% (585/1082) were female, 4.4% (48/1082) were gender-deficient. The average age was 16.7 years. The final pre-intentional phase of HAPA model was acceptable (CFI = 0.95; GFI = 0.94; RMSEA = 0.06). Action self-efficacy (r = 0.60) had a strong direct effect on condom use intention. The pre-intentional phase of HAPA model is valid to assess condom use intention among Chinese senior high school students. The pre-intention phase of the HAPA model could be applied to guide AIDS health educations of students, and further research is needed to evaluate the effect."
3647,Integrated TCGA and GEO analysis showed that SMAD7 is an independent prognostic factor for lung adenocarcinoma,"The lack of effective markers leads to missed optimal treatment times, resulting in poorer prognosis in most cancers. Drosophila mothers against decapentaplegic protein (SMAD) family members are important cytokines in the transforming growth factor-beta family. They jointly regulate the processes of cell growth, differentiation, and apoptosis. However, the expression of SMAD family genes in pan-cancers and their impact on prognosis have not been elucidated. Perl software and R software were used to perform expression analysis and survival curve analysis on the data collected by TCGA, GTEx, and GEO, and the potential regulatory pathways were determined through gene ontology enrichment and kyoto encyclopedia of genes and genomes enrichment analysis. It was found that SMAD7 and SMAD9 expression decreased in lung adenocarcinoma (LUAD), and their expression was positively correlated with survival time. Additionally, SMAD7 could be used as an independent prognostic factor for LUAD. In general, SMAD7 and SMAD9 can be used as prognostic markers of LUAD. Further, SMAD7 is expected to become a therapeutic target for LUAD."
3648,Clinical implications and nomogram prediction of long noncoding RNA FRGCA as diagnostic and prognostic indicators in colon adenocarcinoma,"Colorectal cancer, especially colon adenocarcinoma (COAD), is associated with significant morbidity and mortality worldwide. Long noncoding RNA (lncRNA) has been implicated in tumorigenesis. The aim of the present study was to elucidate the potential diagnostic and prognostic values of lncRNA FRGCA in COAD. The data of 438 COAD patients were retrieved for analysis. Diagnostic significance was evaluated using tumor and nontumor tissues. Prognostic significance was evaluated using a Cox proportional regression model. Stratified analysis was performed to identify associations between clinical factors and lncRNA FRGCA expression. A nomogram was constructed using the clinical factors and lncRNA FRGCA for survival prediction. Enrichment analysis identified gene ontologies and metabolic pathways of mRNAs with high Pearson correlation coefficients with lncRNA FRGCA. lncRNA FRGCA was highly expressed in tumor tissues of COAD and demonstrated diagnostic value (area under curve = 0.763, P < .0001). Prognostic significance analysis indicated that lncRNA FRGCA had prognostic value in COAD [adjusted P < .001, hazard ratio (HR) = 0.444, 95% confidence interval (95% CI) = 0.288–0.685] and high expression of lncRNA FRGCA indicated better survival in COAD. A nomogram was evaluated for prediction of survival at 1, 3, and 5 years. Enrichment analysis revealed many mRNAs involved in the structural constituents of the mitochondrial inner membrane and translational termination, protein binding, translation, ribosome, oxidative phosphorylation, and metabolic pathways, especially the nucleoplasm. Differentially expressed in tumor vs nontumor tissues, lncRNA FRGCA had both diagnostic and prognostic implications in COAD, which may be associated with ribosome metabolism, oxidative phosphorylation, and nucleoplasm-related metabolic pathways."
3649,Full-endoscopic decompression for thoracic ossification of ligamentum flavum: surgical techniques and clinical outcomes: A retrospective clinical study,"BACKGROUND: Many complications are associated with thoracic open decompression surgery, such as dural tears and neurological deficits. The clinical outcomes are also not satisfactory. Full-endoscopic decompression of the lumbar spinal canal has achieved satisfactory results for the treatment of lumbar spinal stenosis. This surgery may be used for the treatment of thoracic ossification of the ligamentum flavum (OLF) under local anesthesia. The aim of our study is to introduce the surgical techniques used for full-endoscopic decompression for thoracic OLF and to evaluate its safety and efficacy. METHODS: Fourteen patients with thoracic OLF (4 combined with dural ossification) underwent full-endoscopic decompression surgery. An interlaminar approach was performed. The anchoring method was used to establish the working passage. Spinal cord exposure began at a space between the ossification and the spinal cord, and dorsal and contralateral decompression were performed with the “Over the Top” technique. The modified Japanese Orthopedic Association score (11 points) was used to evaluate the efficacy during follow-up. At the same time, the visual analogue scale score for assessing back pain before and after the operation was evaluated. RESULTS: The average operation time was 159.73 ± 62.09 minutes, and the hospitalization time was 7.43 ± 1.79 days. The follow-up period ranged from 8 to 22 months. Neurological function was improved. There were no serious complications. Dural tears occurred in 5 patients, intraoperative neurological deterioration occurred in 1 patient, and intraoperative headache and neck pain occurred in 1 patient. CONCLUSION: Full-endoscopic decompression is an effective, safe surgical technique for thoracic OLF even the cases combined with dural ossification."
3650,Placebo use and outcome quality: A protocol for systematic review and meta-analysis,"BACKGROUND: The Pharmaceutical industry sponsorship, research outcome and quality has been already evaluated for clinical trials in order to analyze if this kind of sponsorship affects the results of clinical trials. In this sense, this study has the aim to investigate whether placebo use allows positive outcomes regarding efficacy and safety compared to synthetic medicines. METHODS: We designed and registered a study protocol for a systematic review for methodology data. We will only randomized clinical trials that use placebo as comparator. The main outcome will be the evaluation of placebo use regarding the tendency for positive results (efficacy and security) when comparing to synthetic medicines. PubMed, Cochrane, LILACS (BVS), Web of Science, Scopus, and Excerpta Medica dataBASE (EMBASE) databases will be searched. Gray literature will be identified through the databases Proquest (Dissertation and Theses), OpenGrey and Google Scholar. Two review authors will independently assess trial quality and will extract data in accordance with standard Cochrane methodology. If necessary, we will also contact authors for additional information. The Cochrane Collaboration's risk of bias tool will be used. If feasible, it means homogenous data, we will conduct random effects meta-analysis. Subgroup analyses will be conducted for different justifications for placebo use and for studies sponsored/not sponsored by the pharmaceutical industry. RESULTS: Our present findings will indicate the effects of placebo use as comparator regarding efficacy and safety of the oral synthetic medicines. DISCUSSION: This systematic review will identify, summarize, and analyze if there is a trend for positive efficacy and safety results for synthetic medicines in clinical trials when compared with placebo and if the justification for placebo use is considered ethically acceptable. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018110829"
3651,A delayed diagnosis of late-onset pulmonary hemorrhage in a toddler with Henoch-Schönlein purpura after regression of skin rash: A case report and literature review,"RATIONALE: Pulmonary hemorrhage is a rare but fatal complication of Henoch-Schönlein purpura (HSP), and more easily ignored in children than in adults due to the absence of clinically evident hemoptysis. Moreover, despite being sporadically reported, given that pulmonary hemorrhage may develop after regression and even disappearance of skin rash, the asynchronous progression of skin and lung lesions poses escalating challenges in the timely diagnosis. We herein presented a delayed diagnosis of late-onset pulmonary hemorrhage in a child with HSP after regression of purpuric rash. PATIENT CONCERNS: A 6-year and 3-month child with a history of self-resolved purpuric rash three weeks ago, presented acutely with cough and dyspnea but without fever. DIAGNOSES: The decreased hemoglobin and diffuse ground-glass opacities of both lungs on CT scan weren’t comprehensively evaluated. The child was initially misdiagnosed as pneumonia. INTERVENTIONS: Antibiotic treatment was initiated. However, no improvement of respiratory status was found following aggressive combination therapy. Bronchoscopy was subsequently performed. OUTCOMES: An diffuse alveolar hemorrhage with low inflammatory profile was noted after a bronchoscopy. Considering the history of HSP, the diagnosis of HSP-associated pulmonary hemorrhage was ultimately confirmed and the patient received corticosteroids with satisfactory results. LESSONS: Pulmonary hemorrhage could occur in children with HSP at late onset of disease after regression of skin rash. New-onset respiratory symptoms in patients with a history of HSP should heighten suspicion for pulmonary hemorrhage, particularly if presenting with lack of fever, sudden drop of hemoglobin, new pulmonary infiltrates and unresponsiveness to antibiotics therapy. Bronchoscopy should be performed early to confirm the diagnosis, specifically for children."
3652,Predicting article citations using data of 100 top-cited publications in the journal Medicine since 2011: A bibliometric analysis,"BACKGROUND: Publications regarding the 100 top-cited articles in a given discipline are common, but studies reporting the association between article topics and their citations are lacking. Whether or not reviews and original articles have a higher impact factor than case reports is a point for verification in this study. In addition, article topics that can be used for predicting citations have not been analyzed. Thus, this study aims to: (1).. provide a visualization dashboard for the 100 top-cited articles related to article types and (2).. inspect major medical subject headings (i.e., MeSH terms in PubMed) to help predict citations. METHODS: We searched PubMed Central and downloaded 100 top-cited abstracts in the journal Medicine (Baltimore) since 2011. Four article types and 7 topic categories (denoted by MeSH terms) were extracted from abstracts. Contributors to these 100 top-cited articles were analyzed. Social network analysis and Sankey diagram analysis were performed to identify influential article types and topic categories. MeSH terms were applied to predict the number of article citations. We then examined the prediction power with the correlation coefficients between MeSH weights and article citations. RESULTS: The citation counts for the 100 articles ranged from 24 to 127, with an average of 39.1 citations. The most frequent article types were journal articles (82%) and comparative studies (10%), and the most frequent topics were epidemiology (48%) and blood and immunology (36%). The most productive countries were the United States (24%) and China (23%). The most cited article (PDID = 27258521) with a count of 135 was written by Dr Shang from Shandong Provincial Hospital Affiliated to Shandong University (China) in 2016. MeSH terms were evident in the prediction power of the number of article citations (correlation coefficients = 0.49, t = 5.62). CONCLUSION: The breakthrough was made by developing dashboards showing the overall concept of the 100 top-cited articles using the Sankey diagram. MeSH terms can be used for predicting article citations. Analyzing the 100 top-cited articles could help future academic pursuits and applications in other academic disciplines."
3653,Impact of neurological diseases on family planning: A single-center experience,"This cross-sectional study aimed to assess the impact of epilepsy, myasthenia gravis (MG), and multiple sclerosis (MS) on pregnancy and family planning decision-making in a cohort of Saudi women. Women with epilepsy, MG, and MS were recruited consecutively at the time of their follow-up visits at a neurology clinic. Data were collected using 3 standardized questionnaires, and presented using descriptive statistics. A logistic regression was performed to determine variables associated with decisions regarding abstaining from pregnancy and encouraging other women to conceive. A total of 272 (83 epilepsy, 69 MG, and 120 MS) women with a mean age of 29.9 ± 8.0 years participated. The proportion of women who abstained from or postponed pregnancy was 41.2% and 31.4%, respectively. The concerns mentioned most often were disease worsening during pregnancy, peripartum and postpartum, side effects of medications on the unborn child, and inability to care for the child. Older age was independently associated with the decision to abstain from pregnancy (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04 - 1.25). Higher knowledge levels were independently associated with encouraging other women to have children (OR 1.3, 95% CI 1.11–1.53). Over 50% of women reported that they were not counseled on issues related to pregnancy and childbirth. In conclusion, we identified a major influence of epilepsy, MG, and MS on pregnancy and family planning. Comprehensive counseling programs are needed to help women with these neurological diseases make informed family-planning decisions."
3654,Erythropoietin combined with traditional Chinese medicine for chemotherapy-induced anemias: A protocol of systematic review and meta-analysis,"BACKGROUND: As far as we know, several systematic review and meta-analysis have assessed the safety and efficacy of erythropoiesis-stimulating agents (ESAs) in the patients with chemotherapy-induced anemia (CIA). But no study assesses the safety and efficacy of ESAs combined with traditional Chinese medicine (TCM). The aim of our study is to assess the efficacy and safety of ESAs combination with TCM for patients with CIA and will provide a higher level of evidence for clinical applications. METHODS: This protocol adheres to the preferred reporting items for systematic reviews and meta-analysis protocol statement. The source of literature will be a structured search of the following 7 electronic databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Database. Records will be independently evaluated by 2 reviewers. Disagreements will be resolved through consensus or third-party adjudication. Review Manager 5.3 software (Cochrane Collaboration, Copenhagen Denmark) will be used to perform meta-analysis. For dichotomous variables, odds ratio with 95% confidence intervals will be obtained by the Mantel–Haenszel method. For continuous data, mean difference with 95% confidence intervals will be used. P < 0.05 will be considered to be statistically significant. RESULTS: This study will be performed to test the efficacy and safety of ESAs combined with TCM for CIA in patients with cancer. CONCLUSIONS: The result of this study will be promoted mainly in 2 ways: publish in peer-reviewed journals in the fastest way; and promotion in domestic and foreign conferences. INPLASY REGISTRATION NUMBER: INPLASY202080041."
3655,Small but protective social capital against suicide ideation in poor communities: A community-based cross-sectional study,"Coupled with the lowest level of social connectedness, South Korea has the highest suicide rate among the Organization for Economic Co-operation and Development countries. A possible link between community and suicide is social capital imprinted in social connectedness. This study explores whether social capital is protective against suicide ideation in relation to the poverty level of communities, and whether the associations are specific to certain elements of social capital. A total of 908 participants were included to assess cross-sectional association of social capital at individual level with suicide ideation by comparing between poor (government-leased apartments) and non-poor communities (nongovernment-leased apartments). Logistic regression analyses were performed to examine various social capital dimensions in relation to suicide ideation. Suicide ideation was far higher among those living in the poor communities (poor communities 12%; non poor communities 6.3%) and the level of social capital was lower in the poor communities. Nevertheless, the protective effect of social capital, in particular, the cognitive dimension against suicide ideation was demonstrated only in the poor communities (eg, odds ratio = 0.27, 95% confidence interval: 0.12–0.58 for trust in the poor communities). Low income was significantly associated with suicide ideation only in the poor communities, but depression and resilience were associated with suicide ideation both in the poor and non-poor communities. To increase the reliability of the results, established measures based on relevant literature were utilized, but measures on bridging social capital and social network might have relatively low reliability. As to protection against suicide ideation, the extent of reliance on social capital was higher in poor communities than in non-poor communities, in particular, the cognitive dimension was likely to activate in this regard."
3656,Emerging Pandemic Diseases: How We Got to COVID-19,
3657,Chemogenetic Inhibition of Infralimbic Prefrontal Cortex GABAergic Parvalbumin Interneurons Attenuates the Impact of Chronic Stress in Male Mice,"Hypofunction of the prefrontal cortex (PFC) contributes to stress-related neuropsychiatric illnesses. Mechanisms leading to prefrontal hypoactivity remain to be determined. Prior evidence suggests that chronic stress leads to an increase in activity of parvalbumin (PV) expressing GABAergic interneurons (INs) in the PFC. The purpose of the study was to determine whether reducing PV IN activity in the Infralimbic (IL) PFC would prevent stress-related phenotypes. We used a chemogenetic approach to inhibit IL PFC PV INs during stress. Mice were first tested in the tail suspension test (TST) to determine the impact of PV IN inhibition on behavioral responses to acute stress. The long-term impact of PV IN inhibition during a modified chronic variable stress (CVS) was tested in the forced swim test (FST). Acute PV IN inhibition reduced active (struggling) and increased passive coping behaviors (immobility) in the TST. In contrast, inhibition of PV INs during CVS increased active and reduced passive coping behaviors in the FST. Moreover, chronic inhibition of PV INs attenuated CVS-induced changes in Fos expression in the prelimbic cortex (PrL), basolateral amygdala (BLA), and ventrolateral periaqueductal gray (vlPAG) and also attenuated adrenal hypertrophy and body weight loss associated with chronic stress. Our results suggest differential roles of PV INs in acute versus chronic stress, indicative of distinct biological mechanisms underlying acute versus chronic stress responses. Our results also indicate a role for PV INs in driving chronic stress adaptation and support literature evidence suggesting cortical GABAergic INs as a therapeutic target in stress-related illnesses."
3658,"Respiratory, growth, and survival outcomes of infants with tracheostomy and ventilator dependence","BACKGROUND: Outcome of infants with tracheostomy have not been well described in the literature. Our objective was to describe the respiratory, growth, and survival outcomes of infants with tracheostomy. METHODS: A retrospective study was conducted on 204 infants born between 2005 and 2015 with tracheostomy at <1 year of age and follow-up in the Infant Tracheostomy and Home Ventilator Clinic up to 4 years of age. RESULTS: The mean age at tracheostomy was 4.5 months with median age of 3 months. Median age of decannulation was 32 months. The time from tracheostomy placement to complete discontinuation of mechanical ventilation was 15.4 months and from tracheostomy to decannulation was 33.8 months. Mortality rate was 21% and median age of death was 18 months. Preterm infants with acquired airway and lung disease (BPD) and born at <28 weeks’ gestation had a significantly higher survival rate compared to term infants. The z-scores for weight and weight for length improved from the time of discharge (mean chronological age 6.5 months) to first year and remained consistent through 3 years. CONCLUSIONS: Premature infants had a higher rate of discontinuation of mechanical ventilation and decannulation compared to term infants. These infants showed consistent growth and comparable survival rate. IMPACT: Infants with tracheostomy and ventilator dependence followed in a multidisciplinary clinic model may have improved survival, growth, and earlier time to decannulation. Preterm infants with acquired airway and lung disease (BPD) with tracheostomy had a higher survival rate compared to term infants with various tracheostomy indications. The age at tracheostomy in infants was 4.5 months and of decannulation was 37 months. Time from tracheostomy to complete discontinuation of mechanical ventilation was 15.4 months. Addition of this data to the sparse literature will be crucial in counseling the families and education of medical staff."
3659,Systemic IL-6 and Severe Asthma,
3660,Interleukin-1β induces human cementoblasts to support osteoclastogenesis,"Injury of the periodontium followed by inflammatory response often leads to root resorption. Resorption is accomplished by osteoclasts and their generation may depend on an interaction with the cells in direct contact with the root, the cementoblasts. Our study aimed to investigate the role of human cementoblasts in the formation of osteoclasts and the effect of interleukin (IL)-1β hereupon. Extracted teeth from healthy volunteers were subjected to sequential digestion by type I collagenase and trypsin. The effect of enzymatic digestion on the presence of cells on the root surface was analyzed by histology. Gene expression of primary human cementoblasts (pHCB) was compared with a human cementoblast cell line (HCEM). The pHCBs were analyzed for their expression of IL-1 receptors as well as of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG). In a co-culture system consisting of osteoclast precursors (blood monocytes) and pHCBs, the formation of osteoclasts and their resorptive activity was assessed by osteo-assay and ivory slices. The cells obtained after a 120 min enzyme digestion expressed the highest level of bone sialoprotein, similar to that of HCEM. This fraction of isolated cells also shared a similar expression pattern of IL-1 receptors (IL1-R1 and IL1-R2). Treatment with IL-1β potently upregulated RANKL expression but not of OPG. pHCBs were shown to induce the formation of functional osteoclasts. This capacity was significantly stimulated by pretreating the pHCBs with IL-1β prior to their co-culture with human blood monocytes. Our study demonstrated that cementoblasts have the capacity to induce osteoclastogenesis, a capacity strongly promoted by IL-1β. These results may explain why osteoclasts can be formed next to the root of teeth."
3661,Flux sampling is a powerful tool to study metabolism under changing environmental conditions,"The development of high-throughput ‘omic techniques has sparked a rising interest in genome-scale metabolic models, with applications ranging from disease diagnostics to crop adaptation. Efficient and accurate methods are required to analyze large metabolic networks. Flux sampling can be used to explore the feasible flux solutions in metabolic networks by generating probability distributions of steady-state reaction fluxes. Unlike other methods, flux sampling can be used without assuming a particular cellular objective. We have undertaken a rigorous comparison of several sampling algorithms and concluded that the coordinate hit-and-run with rounding (CHRR) algorithm is the most efficient based on both run-time and multiple convergence diagnostics. We demonstrate the power of CHRR by using it to study the metabolic changes that underlie photosynthetic acclimation to cold of Arabidopsis thaliana plant leaves. In combination with experimental measurements, we show how the regulated interplay between diurnal starch and organic acid accumulation defines the plant acclimation process. We confirm fumarate accumulation as a requirement for cold acclimation and further predict γ–aminobutyric acid to have a key role in metabolic signaling under cold conditions. These results demonstrate how flux sampling can be used to analyze the feasible flux solutions across changing environmental conditions, whereas eliminating the need to make assumptions which introduce observer bias."
3662,Logical design of oral glucose ingestion pattern minimizing blood glucose in humans,"Excessive increase in blood glucose level after eating increases the risk of macroangiopathy, and a method for not increasing the postprandial blood glucose level is desired. However, a logical design method of the dietary ingestion pattern controlling the postprandial blood glucose level has not yet been established. We constructed a mathematical model of blood glucose control by oral glucose ingestion in three healthy human subjects, and predicted that intermittent ingestion 30 min apart was the optimal glucose ingestion patterns that minimized the peak value of blood glucose level. We confirmed with subjects that this intermittent pattern consistently decreased the peak value of blood glucose level. We also predicted insulin minimization pattern, and found that the intermittent ingestion 30 min apart was optimal, which is similar to that of glucose minimization pattern. Taken together, these results suggest that the glucose minimization is achieved by suppressing the peak value of insulin concentration, rather than by enhancing insulin concentration. This approach could be applied to design optimal dietary ingestion patterns."
3663,"Author Correction: Human motor cortex relies on sparse and action-specific activation during laughing, smiling and speech production",
3664,Utilizing genome-scale models to optimize nutrient supply for sustained algal growth and lipid productivity,"Nutrient availability is critical for growth of algae and other microbes used for generating valuable biochemical products. Determining the optimal levels of nutrient supplies to cultures can eliminate feeding of excess nutrients, lowering production costs and reducing nutrient pollution into the environment. With the advent of omics and bioinformatics methods, it is now possible to construct genome-scale models that accurately describe the metabolism of microorganisms. In this study, a genome-scale model of the green alga Chlorella vulgaris (iCZ946) was applied to predict feeding of multiple nutrients, including nitrate and glucose, under both autotrophic and heterotrophic conditions. The objective function was changed from optimizing growth to instead minimizing nitrate and glucose uptake rates, enabling predictions of feed rates for these nutrients. The metabolic model control (MMC) algorithm was validated for autotrophic growth, saving 18% nitrate while sustaining algal growth. Additionally, we obtained similar growth profiles by simultaneously controlling glucose and nitrate supplies under heterotrophic conditions for both high and low levels of glucose and nitrate. Finally, the nitrate supply was controlled in order to retain protein and chlorophyll synthesis, albeit at a lower rate, under nitrogen-limiting conditions. This model-driven cultivation strategy doubled the total volumetric yield of biomass, increased fatty acid methyl ester (FAME) yield by 61%, and enhanced lutein yield nearly 3 fold compared to nitrogen starvation. This study introduces a control methodology that integrates omics data and genome-scale models in order to optimize nutrient supplies based on the metabolic state of algal cells in different nutrient environments. This approach could transform bioprocessing control into a systems biology-based paradigm suitable for a wide range of species in order to limit nutrient inputs, reduce processing costs, and optimize biomanufacturing for the next generation of desirable biotechnology products."
3665,Osmolyte homeostasis controls single-cell growth rate and maximum cell size of Saccharomyces cerevisiae,"Cell growth is well described at the population level, but precisely how nutrient and water uptake and cell wall expansion drive the growth of single cells is poorly understood. Supported by measurements of single-cell growth trajectories and cell wall elasticity, we present a single-cell growth model for yeast. The model links the thermodynamic quantities, such as turgor pressure, osmolarity, cell wall elasto-plasticity, and cell size, applying concepts from rheology and thin shell theory. It reproduces cell size dynamics during single-cell growth, budding, and hyper-osmotic or hypo-osmotic stress. We find that single-cell growth rate and final size are primarily governed by osmolyte uptake and consumption, while bud expansion requires additionally different cell wall extensibilities between mother and bud. Based on first principles the model provides a more accurate description of size dynamics than previous attempts and its analytical simplification allows for easy combination with models for other cell processes."
3666,Local delivery of arsenic trioxide nanoparticles for hepatocellular carcinoma treatment,"Hepatocellular carcinoma (HCC) is a malignancy with a poor prognosis. Surgery combined with chemotherapy has been recommended as a curative regimen for HCC. Nevertheless, the anticancer mechanisms of chemicals in hepatocellular carcinoma remain unclear. Pyroptosis is a type of programmed necrosis, and its mechanism in hepatocellular carcinoma is poorly understood. The efficacy and mechanism of arsenic trioxide nanoparticles in the treatment of HCC were explored in this research. Arsenic trioxide alone and arsenic trioxide nanoparticles were conveniently administered to mice intratumorally using a needle. Compared with As(2)O(3), As(2)O(3) nanoparticles (As(2)O(3)-NPs) showed better inhibition, promoted greater LDH release, and induced cell morphology indicative of pyroptosis in vitro. Compared with the free drug, As(2)O(3)-NPs increased GSDME-N expression and decreased Dnmt3a, Dnmt3b, and Dnmt1 expression in Huh7 cells. In vivo, As(2)O(3)-NPs induced a significant decrease in the expression of Dnmt3a, Dnmt3b and Dnmt1, but significantly upregulated the expression of GSDME-N (gasdermin E (GSDME) was originally found to be related to deafness; recently, it has been defined as a gasdermin family member associated with pyroptosis). As(2)O(3)-NPs inhibited tumor growth more strongly than As(2)O(3) or control, a finding likely attributed to the downregulation of PCNA and DNMT-related proteins and the upregulation of GSDME-N."
3667,BE-PIGS: a base-editing tool with deaminases inlaid into Cas9 PI domain significantly expanded the editing scope,
3668,Genetically engineered T cells for cancer immunotherapy,"T cells in the immune system protect the human body from infection by pathogens and clear mutant cells through specific recognition by T cell receptors (TCRs). Cancer immunotherapy, by relying on this basic recognition method, boosts the antitumor efficacy of T cells by unleashing the inhibition of immune checkpoints and expands adaptive immunity by facilitating the adoptive transfer of genetically engineered T cells. T cells genetically equipped with chimeric antigen receptors (CARs) or TCRs have shown remarkable effectiveness in treating some hematological malignancies, although the efficacy of engineered T cells in treating solid tumors is far from satisfactory. In this review, we summarize the development of genetically engineered T cells, outline the most recent studies investigating genetically engineered T cells for cancer immunotherapy, and discuss strategies for improving the performance of these T cells in fighting cancers."
3669,E6-induced selective translation of WNT4 and JIP2 promotes the progression of cervical cancer via a noncanonical WNT signaling pathway,"mRNA translation reprogramming occurs frequently in many pathologies, including cancer and viral infection. It remains largely unknown whether viral-induced alterations in mRNA translation contribute to carcinogenesis. Most cervical cancer is caused by high-risk human papillomavirus infection, resulting in the malignant transformation of normal epithelial cells mainly via viral E6 and E7 oncoproteins. Here, we utilized polysome profiling and deep RNA sequencing to systematically evaluate E6-regulated mRNA translation in HPV18-infected cervical cancer cells. We found that silencing E6 can cause over a two-fold change in the translation efficiency of ~653 mRNAs, most likely in an eIF4E- and eIF2α-independent manner. In addition, we identified that E6 can selectively upregulate the translation of WNT4, JIP1, and JIP2, resulting in the activation of the noncanonical WNT/PCP/JNK pathway to promote cell proliferation in vitro and tumor growth in vivo. Ectopic expression of WNT4/JIP2 can effectively rescue the decreased cell proliferation caused by E6 silencing, strongly suggesting that the WNT4/JIP2 pathway mediates the role of E6 in promoting cell proliferation. Thus, our results revealed a novel oncogenic mechanism of E6 via regulating the translation of mRNAs."
3670,dIAP: Knowledge Sharing Amidst the Pandemic,
3671,Multisystem Inflammatory Syndrome in Children (MIS-C) — Recent Updates,
3672,Diverse Pathophysiology of Sudden Unexpected Death in Epilepsy in Children,
3673,Therapeutic Clowning in Pediatric Practice: A Novel Concept to Think About in India,
3674,Role of Flexible Bronchoscopy in Ventilator-Dependent Neonates,OBJECTIVE: To assess the usefulness and safety of flexible bronchoscopy in ventilated neonates with extubation failure. METHOD: This was a prospective observational study. Flexible bronchoscopy was done in eligible patients with failure of extubation form invasive ventilation. The main outcome measure was to find the presence of any anatomic or dynamic abnormalities of the airways of these patients and the organism profile of bronchoalveolar lavage (BAL) fluid. RESULTS: Forty-eight babies (68.8% preterm) were enrolled in the study. The most common finding on bronchoscopy was airway edema seen in 13 (27%) patients. BAL culture was positive in 29 (74%) patients. Overall treatment was modified in 35 (73%) patients based on bronchoscopy findings/BAL culture. Majority of infants (83.3%) tolerated the procedure very well. CONCLUSION: Flexible bronchoscopy provides useful information in the management of newborn babies with extubation failure.
3675,Effect of Robot-Assisted Gait Training on Selective Voluntary Motor Control in Ambulatory Children with Cerebral Palsy,"This pilot study investigated the efficacy of a four week robot-assisted gait training in twelve children with spastic diparesis. Short-term results and a 3-month follow-up showed statistically significantly increased selective motor control, walking farther distances, gross motor score, and decreased joint contractures."
3676,Author Correction: Activation of SIRT6 by DNA hypomethylating agents and clinical consequences on combination therapy in leukemia,
3677,Is puberty a risk factor for back pain in the young? a systematic critical literature review,"BACKGROUND: Back pain is a common condition that starts early in life and seems to increase markedly during puberty. A systematic review was performed in order to investigate the link between puberty and back pain, using some Bradford Hill criteria for causality. OBJECTIVES: We sought to obtain answers to the following questions: 1) Is there an association between puberty and back pain? If so, how strong is this association? And do the results remain unchanged also when controlling for age and sex? 2) Are the results of the studies consistent? 3) Is there a dose–response, showing a link between the increasing stages of puberty and the subsequent prevalence of back pain? 4) Is there a temporal link between puberty and back pain? DESIGN: A systematic critical literature review. METHODS: Systematic searches were made in March 2014 in PubMed, Embase, CINAHL and PsycINFO including longitudinal or cross-sectional studies on back pain for subjects <19 years, written in French or English. The review process followed the AMSTAR recommendations. Interpretation was made using some of the Bradford-Hill criteria for causality. RESULTS: Four articles reporting five studies were included, two of which were longitudinal. 1) Some studies show a weak and others a strong positive association between puberty and back pain, which remains after controlling for age and sex; 2) Results were consistent across the studies; 3) There was a linear increase of back pain according to the stage of puberty 4) Temporality has not been sufficiently studied. CONCLUSION: All our criteria for causality were fulfilled or somewhat fulfilled indicating the possibility of a causal link between puberty and back pain. Future research should focus on specific hypotheses, for example investigating if there could be a hormonal or a biomechanical aspect to the development of back pain at this time of life. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12998-014-0027-6) contains supplementary material, which is available to authorized users."
3678,Immunization Coverage in Migrant School Children Along the Thailand-Myanmar Border,"The objective of this project was to document and increase vaccine coverage in migrant school children on the Thailand-Myanmar border. Migrant school children (n = 12,277) were enrolled in a school-based immunization program in four Thai border districts. The children were evaluated for vaccination completion and timing, for six different vaccines: Bacille Calmette-Guerin (BCG); Oral Polio vaccine (OPV); Hepatitis B vaccine (HepB); Diphtheria, Pertussis and Tetanus vaccine (DTP); Measles Containing Vaccine or Measles, Mumps and Rubella vaccine (MMR); Tetanus and Diphtheria containing vaccine (Td). Vaccine coverage proportions for BCG, OPV3, DTP3, HepB3 and measles containing vaccine were 92.3, 85.3, 63.8, 72.2, and 90.9 % respectively. Most children were able to receive vaccines in a time appropriate manner. School-based immunization programs offer a suitable vaccine delivery mechanism for hard-to-reach populations. However, these data suggest overall low vaccine coverage in migrant populations. Further efforts toward improving appropriate vaccine coverage and methods of retaining documentation of vaccination in mobile migrant populations are necessary for improved health."
3679,Treatment of at-level spinal cord injury pain with botulinum toxin A,"STUDY DESIGN: Randomized, double-blinded, placebo-controlled, cross-over study. OBJECTIVE: To explore whether botulinum toxin A (BoNTA) could be effective for treating at-level spinal cord injury (SCI) pain. SETTING: Outpatient SCI clinic, New York, USA. METHODS: Participants were randomized to receive subcutaneous injections of either placebo or BoNTA with follow-up (office visit, telephone, or e-mail) at 2, 4, 8, and 12 weeks to assess the magnitude of pain relief post injection. Crossover of participants was then performed. Those who received placebo received BoNTA, and vice versa, with follow-up at 2, 4, 8, and 12 weeks. RESULTS: Eight participants completed at least one of the two crossover study arms. Four completed both arms. The median age of the eight participants was 45 years (range 32–61 years) and 75% were male. All had traumatic, T1-L3 level, complete SCI. Although our data did not meet statistical significance, we noted a higher proportion of participants reporting a marked change in average pain intensity from baseline to 8 and 12 weeks post-BoNTA vs. post-placebo (33% vs. 0%). At 2 and 4 weeks post-BoNTA, almost all participants reported some degree of reduced pain, while the same was not seen post-placebo (83% vs. 0%). CONCLUSION: The subcutaneous injection of BoNTA may be a feasible approach for the control of at-level SCI pain and is worthy of further study. SPONSORSHIP: The onabotulinumtoxinA (BOTOX) used in this study was provided by Allergan (Irvine, CA)."
3680,Restoration of hand function with long-term paired associative stimulation after chronic incomplete tetraplegia: a case study,"INTRODUCTION: This case study explores the gains in hand function in an individual with a chronic spinal cord injury (SCI). The intervention was long-term paired associative simulation (PAS). We aimed to provide PAS until full recovery of hand muscle strength occurred, or until improvements ceased. CASE PRESENTATION: A 46-year-old man with traumatic C7 AIS B tetraplegia was administered PAS three times per week. After 24 weeks, PAS was combined with concomitant motor training of the remaining weak hand muscles. Outcome measures included the manual muscle test (MMT), motor-evoked potentials (MEPs), F-responses, hand functional tests, and the spinal cord independence measure (SCIM). DISCUSSION: After 47 weeks of PAS the subject had improved self-care and indoor mobility and was able to perform complex motor tasks (SCIM score improved from 40 to 56). His left hand regained maximum MMT score (total 75; increase of score from baseline condition 19); the effect remained stable in the 32-week follow up. In the right-hand muscles, MMT scores of 4–5 were observed in follow up (total 71; increase from baseline 48). Improved values were also observed in other outcomes. This is the first demonstration of long-term PAS restoring muscle strength corresponding to MMT scores of 4–5 in an individual with chronic SCI. The effect persisted for several months, indicating that PAS induces stable plastic changes in the corticospinal pathway."
3681,Chronic prostatitis effectively managed by transurethral prostatectomy (TURP) in a spinal cord injury male,"INTRODUCTION: Spinal cord injury (SCI), specifically suprasacral SCI, results in high intravesical pressures, elevated post-void residual and urinary incontinence which are all risk factors for urinary tract infections (UTIs). The management of UTIs usually is conservative medical antibiotic treatment. However, recurrent UTIs in the SCI patient population warrant further investigation. The method of urinary drainage (intermittent or indwelling urinary catheters, urinary diversion) and untreated complications of NLUTD (vesicoureteral reflux, stone formation, chronic incomplete emptying of the bladder) are risk factors for recurrent UTIs (rUTIs). Removal of these UTI risk factors and improving urinary drainage are goals of urologic management; however, when conservative interventions do not succeed, surgery may be a viable solution in select cases of rUTIs. CASE PRESENTATION: We present a case of complicated persisting rUTIs and associated urethral discharge in a middle-aged SCI male who manages his bladder with intermittent catheterization (IC). We detail the evaluation and management approach that leads to an eventual transurethral prostatectomy (TURP) as a final solution for his rUTIs. Fortunately, the surgical intervention was successful, and the patient is free of UTIs after 4 years of follow-up. DISCUSSION: In SCI male patients with rUTIs and suspected chronic prostatitis, TURP may be a valuable treatment option once all predisposing factors have been remediated."
3682,Targeted therapeutic options and future perspectives for HER2-positive breast cancer,"Over the past 2 decades, there has been an extraordinary progress in the regimens developed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1) are commonly recommended anti-HER2 target agents by the U.S. Food and Drug Administration. This review summarizes the most significant and updated research on clinical scenarios related to HER2-positive breast cancer management in order to revise the guidelines of everyday clinical practices. In this article, we present the data on anti-HER2 clinical research of neoadjuvant, adjuvant, and metastatic studies from the past 2 decades. We also highlight some of the promising strategies that should be critically considered. Lastly, this review lists some of the ongoing clinical trials, findings of which may soon be available."
3683,Artificial intelligence that determines the clinical significance of capsule endoscopy images can increase the efficiency of reading,"Artificial intelligence (AI), which has demonstrated outstanding achievements in image recognition, can be useful for the tedious capsule endoscopy (CE) reading. We aimed to develop a practical AI-based method that can identify various types of lesions and tried to evaluate the effectiveness of the method under clinical settings. A total of 203,244 CE images were collected from multiple centers selected considering the regional distribution. The AI based on the Inception-Resnet-V2 model was trained with images that were classified into two categories according to their clinical significance. The performance of AI was evaluated with a comparative test involving two groups of reviewers with different experiences. The AI summarized 67,008 (31.89%) images with a probability of more than 0.8 for containing lesions in 210,100 frames of 20 selected CE videos. Using the AI-assisted reading model, reviewers in both the groups exhibited increased lesion detection rates compared to those achieved using the conventional reading model (experts; 34.3%–73.0%; p = 0.029, trainees; 24.7%–53.1%; p = 0.029). The improved result for trainees was comparable to that for the experts (p = 0.057). Further, the AI-assisted reading model significantly shortened the reading time for trainees (1621.0–746.8 min; p = 0.029). Thus, we have developed an AI-assisted reading model that can detect various lesions and can successfully summarize CE images according to clinical significance. The assistance rendered by AI can increase the lesion detection rates of reviewers. Especially, trainees could improve their efficiency of reading as a result of reduced reading time using the AI-assisted model."
3684,A non-enveloped arbovirus released in lysosome-derived extracellular vesicles induces super-infection exclusion,"Recent developments on extracellular vesicles (EVs) containing multiple virus particles challenge the rigid definition of non-enveloped viruses. However, how non-enveloped viruses hijack cell machinery to promote non-lytic release in EVs, and their functional roles, remain to be clarified. Here we used Bluetongue virus (BTV) as a model of a non-enveloped arthropod-borne virus and discovered that the majority of viruses are released in EVs. Based on the cellular proteins detected in these EVs, and use of inhibitors targeting the cellular degradation process, we demonstrated that these extracellular vesicles are derived from secretory lysosomes, in which the acidic pH is neutralized upon the infection. Moreover, we report that secreted EVs are more efficient than free-viruses for initiating infections, but that they trigger super-infection exclusion that only free-viruses can overcome."
3685,Full-length cDNA sequence analysis of 85 avian leukosis virus subgroup J strains isolated from chickens in China during the years 1988–2018: coexistence of 2 extremely different clusters that are highly dependent upon either the host genetic background or the geographic location,"During the process of transmission and spread of avian leukosis virus subgroup J (ALV-J) in chickens worldwide, the viral genome is constantly changing. A comprehensive and systematic study of the evolutionary process of ALV-J in China is needed. In this study, we amplified the full-length viral cDNA sequences of 16 ALV-J isolates of Yellow-chicken origin and analyzed and compared these sequences with another 69 ALV-J strains isolated during the years 1988–2018. These isolates were then sorted into 2 clusters: cluster I included isolates that mainly originated from the layers and White-feather broilers from northern China; cluster II included isolates mainly from the Yellow-chicken, most of them being from southern China. According to the sequence homologies of the whole genome and gag, pol, gp85, and gp37 genes, the ALV-J strains are more likely to randomly change in different directions from the original strain HPRS-103 as time passes. The results of entropy analysis of the sequences of gag, pol, and env revealed that the env gene had the largest variation, and the gag gene nonconserved sites are mainly concentrated in p19, p10, and p12. In addition, 84.71% (72/85) of the isolates had the 205-nucleotide (nt) deletion in the 3′UTR region, and 30.59% (26/85) of the isolates had the 125-nt to 127-nt deletion in the E element. Our study provides evidence for the coexistence of 2 extremely different clusters of ALV-J prevailing in China and in some other countries during the period of 1988–2018 and implies that the clusters are highly dependent on the host genetic background and the geographic location."
3686,Sunflower seed oil containing ginseng stem–leaf saponins (E515-D) is a safe adjuvant for Newcastle disease vaccine,"Vaccination is an effective method to prevent Newcastle disease (ND) in chickens. Marcol 52 and #10 white oil are mineral-based adjuvants and can be found in commercial inactivated ND virus vaccines. The present study demonstrated that a vegetable origin oil E515-D had lower polycyclic aromatic hydrocarbons and higher flash point than the commercial products Marcol 52 and #10 white oil. E515-D could be mixed with an aqueous phase containing ND virus antigen to form a stable water-in-oil vaccine emulsion and exhibited more potent adjuvant effects on the immune response than Marcol 52 and #10 white oil. Moreover, the absorption of E515-D–adjuvanted vaccine was faster than absorption of Marcol 52- and #10 white oil-adjuvanted vaccines when ND virus vaccines were injected in broilers. Therefore, E515-D was safe and could be a suitable adjuvant used in vaccines for food animals. In addition，E515-D is not easy to be flammable during shipping and storage owing to its higher flash point."
3687,Finding and Closing the Gaps in the Tuberculosis Elimination Campaign,
3688,Urtication (flogging with stinging nettles) and flagellation (beating with rods) in the treatment of paralysis,"Urtication and flagellation were used as a last resort in the treatment of paralysis when all other means were exhausted, and very few cases are reported in the literature. Two cases were identified and reviewed, one of urtication (flogging with nettles) and one of flagellation (beating with rods). In both cases the symptoms were alleviated, but there was insufficient detail to evaluate the therapeutic value of each treatment."
3689,Effect of overground locomotor training on ventilatory kinetics and rate of perceived exertion in persons with cervical motor-incomplete spinal cord injury,"STUDY DESIGN: Pre-post, pilot study. OBJECTIVES: To characterize ventilatory (V(E)) responses to exercise following warm-up walking in individuals with chronic incomplete spinal cord injury (iSCI) during constant work rate (CWR) exercise. Secondarily, to investigate V(E) and tidal volume (V(T)) variability, and ratings of perceived exertion (RPE) before and after overground locomotor training (OLT). SETTING: Research laboratory. METHODS: A 6-min CWR walking bout at preferred pace was used as a warm-up followed by 6 min of rest and a second 6-min CWR bout at above preferred walking pace. The second CWR bout was analyzed. Breath-by-breath ventilatory data were examined using a curvilinear least squares fitting procedure with a mono-exponential model. V(E) and V(T) variability was calculated as the difference between the observed and predicted values and RPE was taken every 2 min. RESULTS: Participants (n = 3, C4–C5) achieved a hyperpneic response to exercise in V(E) and V(T). OLT resulted in faster ventilatory kinetics and reductions of 24 and 29% for V(E) and V(T) variability, respectively. A 30% reduction in RPE was concurrent with the reductions in ventilatory variability. CONCLUSIONS: OLT may improve ventilatory control during CWR in patients with cervical motor-iSCI. These data suggest that in some participants with iSCI, ventilation may influence RPE during walking. Future research should investigate mechanisms of ventilatory variability and its implications in walking performance in patients with iSCI."
3690,Correction: Effect of behavioral change intervention around new-born care practices among most marginalized women in self-help groups in rural India: analyses of three cross-sectional surveys between 2013 and 2016,
3691,"Effect of surgical intraocular pressure lowering on retinal structures—nerve fibre layer, foveal avascular zone, peripapillary and macular vessel density: 1 year results",
3692,Correction to: Cancer immunotherapy with γδ T cells: many paths ahead of us,
3693,Perinatal THC exposure via lactation induces lasting alterations to social behavior and prefrontal cortex function in rats at adulthood,"Cannabis is the world’s most widely abused illicit drug and consumption amongst women during and surrounding the period of pregnancy is increasing. Previously, we have shown that cannabinoid exposure via lactation during the early postnatal period disrupts early developmental trajectories of prefrontal cortex maturation and induces behavioral abnormalities during the first weeks of life in male and female rat progeny. Here, we investigated the lasting consequences of this postnatal cannabinoid exposure on synaptic and behavioral parameters in the adult offspring of ∆9-tetrahydrocannabinol (THC)-treated dams. At adulthood, these perinatally THC-exposed rats exhibits deficits in social discrimination accompanied by an overall augmentation of social exploratory behavior. These behavioral alterations were further correlated with multiple abnormalities in synaptic plasticity in the prefrontal cortex, including lost endocannabinoid-mediated long-term depression (LTD), lost long-term potentiation and augmented mGlu2/3-LTD. Finally, basic parameters of intrinsic excitability at prefrontal cortex pyramidal neurons were similarly altered by the perinatal THC exposure. Thus, perinatal THC exposure via lactation induces lasting deficits in behavior and synaptic function which persist into adulthood life in male and female progeny."
3694,Essential roles of S100A10 in Toll-like receptor signaling and immunity to infection,"Toll-like receptors (TLRs) are key pattern recognition receptors that mediate innate immune responses to infection. However, uncontrolled TLR activation can lead to severe inflammatory disorders such as septic shock. The molecular mechanisms through which TLR responses are regulated are not fully understood. Here, we demonstrate an essential function of S100A10 in TLR signaling. S100A10 was constitutively expressed in macrophages, but was significantly downregulated upon TLR activation. S100A10-deficient macrophages were hyperresponsive to TLR stimulation, and S100A10-deficient mice were more sensitive to endotoxin-induced lethal shock and Escherichia coli-induced abdominal sepsis. Mechanistically, S100A10 regulated macrophage inflammatory responses by interfering with the appropriate recruitment and activation of the receptor-proximal signaling components and eventually inhibited TLR-triggered downstream signaling. These findings expand our understanding of TLR signaling and establish S100A10 as an essential negative regulator of TLR function and a potential therapeutic target for treating inflammatory diseases."
3695,"Correction to: Is psychosis a multisystem disorder? A meta-review of central nervous system, immune, cardiometabolic, and endocrine alterations in first-episode psychosis and perspective on potential models",
3696,Correction to: Abstracts: 31st European Congress of Pathology,
3697,Erratum,
3698,Clinical and genetic characterization of nephropathy in patients with nail-patella syndrome,"Nail-patella syndrome (NPS) is a multi-system disorder characterized by hypoplastic nails, hypoplastic patella, skeletal deformities, and iliac horns, which is caused by heterozygous variants of LMX1B. Nephropathy ranging from mild urinary abnormality to end-stage renal disease occurs in some individuals with NPS. Because of the low prevalence of NPS and the lack of longitudinal studies of its kidney involvement, the clinical, pathological, and genetic features characterizing severe nephropathy remain unclear. We conducted a Japanese survey of NPS with nephropathy, and analyzed their clinical course, pathological features, and factors associated with severe renal phenotype. LMX1B gene analysis and luciferase reporter assay were also performed. Among 13 NPS nephropathy cases with genetic validation, 5 patients who had moderate-to-massive proteinuria progressed to advanced chronic kidney disease or end-stage renal disease. Pathological findings in the early phase did not necessarily correlate with renal prognosis. Variants associated with deteriorated renal function including a novel variants were confined to the N-terminal region of the LIM domain and a short sequence in the LMX1B homeodomain, which were distinct from reported variants found in isolated nephropathy without extrarenal manifestation (LMX1B-associated nephropathy). Luciferase reporter analysis demonstrated that variants in patients with severe renal phenotype caused haploinsufficiency, but no dominant-negative effects on promoter activation. A distinct proportion of NPS nephropathy patients progressed to end-stage renal disease in adolescence or young adulthood. Patients with moderate or severe proteinuria, especially those with variants in specific regions of LMX1B, should be monitored for potential deterioration of renal function."
3699,Efficacy and safety of subthreshold micropulse laser compared with threshold conventional laser in central serous chorioretinopathy,"PURPOSE: To compare the efficacy and safety of subthreshold micropulse laser (SML) with threshold conventional laser (TCL) in central serous chorioretinopathy (CSC). METHODS: Prospective, randomized, double-masked, non-inferiority, 12-week clinical trial. Patients were randomly assigned 1:1 to SML group or TCL group. Patients in the SML group were treated with 577 nm micropulse laser. The spot size was 160 µm, the duty cycle was 5% and exposure time was 0.2 s. The power was 50% threshold tested. Patients in the TCL group were treated with 577 nm continuous laser. The power was 100% threshold tested. The primary outcome was the mean change in best-corrected visual acuity (BCVA) at week 12, with a non-inferiority limit of five letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts. RESULTS: Eighty-eight patients were enroled. Seventy-seven patients were male. Forty-four patients were in SML group and 44 in TCL group. At week 12, SML was equivalent to TCL with a gain of 6.23 ± 8.59 and 6.61 ± 6.35 letters, respectively, (SML–TCL difference: −0.38 letters; 95% confidence interval (CI):−3.58–2.81; P(non-inferiority) = 0.0026). There was no statistically significant difference between the two groups (t = 0.240, P = 0.811). At week 12, the proportion of patients whose SRF had been totally absorbed was 63.63 and 81.82% respectively for SML and TCL groups. There was no statistically significant difference between the two groups (χ(2) = 3.67, P = 0.056). CONCLUSIONS: Both SML and TCL can improve visual acuity in CSC. SML was non-inferior to TCL in the improvement of BCVA."
3700,Recommendations by a UK expert panel on an aflibercept treat-and-extend pathway for the treatment of neovascular age-related macular degeneration,"OBJECTIVES: This report aims to provide clear recommendations and practical guidance from a panel of UK retinal experts on an aflibercept treat-and-extend (T&E) pathway that can be implemented in clinical practice. These recommendations may help service providers across the NHS intending to implement a T&E approach, with the aim of effectively addressing the capacity and resource issues putting strain on UK neovascular age-related macular degeneration (nAMD) services while promoting patients’ best interests throughout. METHODS: Two structured roundtable meetings of retinal specialists were held in London, UK on 7 December 2018 and 1 March 2019. These meetings were organised and funded by Bayer. RESULTS: The panel provided recommendations for an aflibercept T&E pathway and developed specific criteria based on visual acuity, retinal morphology and optical coherence tomography imaging to guide reduction, maintenance and extension of injection intervals. They also discussed the extension of treatment intervals by 2- or 4-week adjustments to a maximum treatment interval of 16 weeks, the management of retinal fluid and the stopping of treatment. CONCLUSIONS: The long-term benefits of implementing a T&E pathway may include superior visual outcomes compared with a pro re nata (PRN; as needed) protocol, and a lower treatment burden compared with a fixed protocol, which is likely to improve service capacity. Furthermore, the predictable nature of a T&E approach compared with a PRN service may aid capacity planning for the future nAMD treatment demand."
3701,Accuracy of IOL power calculations in the very elderly,"BACKGROUND/OBJECTIVES: To analyze the refractive predictability and outcomes of cataract surgery in the very elderly (≥85 years old). SUBJECTS/METHODS: A retrospective case-series performed at the Shiley Eye Institute, University of California San Diego, USA. Electronically pulled data of 2444 surgeries revealed 147 surgeries on 133 very elderly patients. Chart review was conducted for all very elderly and corresponding control patients (75–84 years old). The first operated eyes of patients with final best-corrected visual acuity ≥20/40, axial length (AL) 22–26 mm, and implanted SN60WF IOL were included. Patients with ocular comorbidities and/or intra- or post-operative complications were excluded. Prediction errors of refractive outcome and percentage of eyes within ±0.50D and ±1.00D were compared between the groups for the Holladay 1 and Barrett Universal II (Barrett) formulas. Logistic regression analysis for achievement of ±1.00D was conducted. RESULTS: Final analysis included 90 eyes (n = 44, very elderly, n = 46, control patients). Median absolute refractive error (MedAE) with Holladay 1, but not Barrett formula, was significantly higher in the older group (p = 0.02 and p = 0.07, respectively). The MedAE in the older group was lower using the Barrett compared to Holladay 1 (p = 0.02). Fewer older patients than younger patients achieved refraction within ±0.50D and ±1.00D from goal, using the Holladay 1 (p = 0.049 and p = 0.002 respectively). Logistic regression analysis supported the relationship between Holladay 1 predictive refractive error of >1.00D and patient’s age (p = 0.046). CONCLUSIONS: Very elderly patients undergoing cataract surgery may be prone to reduced refractive precision, particularly with utilization of the Holladay 1 formula."
3702,sFRP1 protects H9c2 cardiac myoblasts from doxorubicin-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway,"Doxorubicin (Dox) is an effective chemotherapy drug against a wide range of cancers, including both hematological and solid tumors. However, the serious cardiotoxic effect restricted its clinical application. We previously have illuminated the protective role of canonical Wnt/β-catenin signaling in Dox-induced cardiotoxicity. Secreted frizzled-related protein 1 (sFRP1) is one of the endogenous inhibitors of both canonical and noncanonical Wnt signaling. In this study, we investigated the relationship between sFRP1 and noncanonical Wnt/PCP-JNK (Wnt/planar cell polarity-c-Jun N-terminal kinase) pathway in Dox-induced cardiotoxicity in vitro and in vivo. We showed that treatment of H9c2 cardiac myoblasts with Dox (1 μM) time-dependently suppressed cell viability accompanied by significantly decreased sFRP1 protein level and increased Wnt/PCP-JNK signaling. Pretreatment with SP600125, the Wnt/PCP-JNK signaling inhibitor, attenuated Dox-induced apoptosis of H9c2 cells. Overexpression of sFRP1 protected H9c2 cells from Dox-induced apoptosis by inhibiting the Wnt/PCP-JNK pathway. After intraperitoneal injection of a cumulative dose of 15 mg/kg Dox, rats displayed significant cardiac dysfunction; their heart showed inhibited Wnt/β-catenin signaling and activated Wnt/PCP-JNK signaling. These results suggest that sFRP1 may be a novel target for Dox-induced cardiotoxicity."
3703,Erratum zu: Ocrelizumab zur Behandlung der Multiplen Sklerose,
3704,Macular ganglion cell complex thinning in children with visual field defects due to central nervous system pathology,"PURPOSE: To study the relationship between macular ganglion cell complex (GCC) thickness and visual field defects (VFD) caused by central nervous system (CNS) lesions in children and evaluate the possibility of predicting VFD according to GCC maps. METHODS: The GCC maps of a group of children with VFD due to CNS lesions with respect of the vertical meridian in at least one eye (study group), as well as of children with other neuro-ophthalmological problems and healthy children were presented to two masked evaluators, who were asked to predict the patients’ VFD on the basis of GCC damage: the evaluators classified VFD as normal, hemianopia (homonymous or heteronymous) or diffuse. RESULTS: Seventeen patients were included in the study group, with a median age of 12 years. Fifteen had brain tumours and two epilepsy. The mean MD of the affected hemifields was −26.00 dB (SD 7.89 dB) versus −5.51 dB (SD 3.52 dB) for the nonaffected hemifields, p < 0.001. The mean GCC thickness was of 56.04 μm (SD 11.95 μm) in the affected hemiretinas versus 74.31 μm (SD 10.64 μm) for the non-affected, p < 0.001. Kappa coefficients between VFD and those estimated by the evaluators were 0.705 and 0.658 (p < 0.001) for evaluators 1 and 2. CONCLUSIONS: GCC thickness can reflect damage to the visual pathway and GCC maps may be useful to identify chiasmal and retrochiasmal lesions, since GCC atrophy in most of these cases respects the vertical meridian. GCC maps might be used as a surrogate marker for visual damage in patients unable to perform perimetry."
3705,Correction: Allogeneic hematopoietic stem cell transplantation should be in preference to conventional chemotherapy as post-remission treatment for adults with lymphoblastic lymphoma,
3706,RNA and the PIEZO force sensor,
3707,Erratum: Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise,
3708,Correction: Measurement of blood pressure in people with atrial fibrillation,
3709,Lack of efficacy of eplerenone for treatment of active central serous chorioretinopathy,
3710,Management of recurrent sebaceous gland carcinoma,"OBJECTIVE: To evaluate the incidence and management of recurrent periocular sebaceous gland carcinoma at a tertiary ocular oncology service in the United Kingdom. METHODS: This was a retrospective cohort study of 62 patients with sebaceous gland carcinoma treated between 2004 and 2017. A total of 10 eyes were treated for local recurrence. The following variables were recorded: age and sex of patient; tumour location, histological subtype; recurrence type; treatment and outcome. RESULTS: Of the 62 cases with eyelid SGC, 10 (16%) had recurrences during the study period and satisfied inclusion criteria. There were six (60%) females and four males in the recurrent group. The mean time interval between initial excision and tumour recurrence was 37 months (median 23 months; range 4 to 84 months). Four patients received cryotherapy to the lids and conjunctiva to control recurrent disease and two patients were treated with topical or intralesional chemotherapy. Four patients (40%) underwent orbital exenteration during the study period. Metastasis occurred in 20% over a mean follow-up of 113 months (median 106; range 47–184 months). CONCLUSIONS: The risk factors for local recurrence of SGC after wide excision with paraffin section control were reported, and an approach to these recurrent lesions was proposed. The results of this study will help guide surgeons dealing with the medical and surgical conundrum of recurrent disease. The risk of recurrence is highest in the first 2 years after initial excision."
3711,A second cohort of CHD3 patients expands the molecular mechanisms known to cause Snijders Blok-Campeau syndrome,"There has been one previous report of a cohort of patients with variants in Chromodomain Helicase DNA-binding 3 (CHD3), now recognized as Snijders Blok-Campeau syndrome. However, with only three previously-reported patients with variants outside the ATPase/helicase domain, it was unclear if variants outside of this domain caused a clinically similar phenotype. We have analyzed 24 new patients with CHD3 variants, including nine outside the ATPase/helicase domain. All patients were detected with unbiased molecular genetic methods. There is not a significant difference in the clinical or facial features of patients with variants in or outside this domain. These additional patients further expand the clinical and molecular data associated with CHD3 variants. Importantly we conclude that there is not a significant difference in the phenotypic features of patients with various molecular disruptions, including whole gene deletions and duplications, and missense variants outside the ATPase/helicase domain. This data will aid both clinical geneticists and molecular geneticists in the diagnosis of this emerging syndrome."
3712,Whole-genome sequencing of 508 patients identifies key molecular features associated with poor prognosis in esophageal squamous cell carcinoma,"Esophageal squamous cell carcinoma (ESCC) is a poor-prognosis cancer type with limited understanding of its molecular etiology. Using 508 ESCC genomes, we identified five novel significantly mutated genes and uncovered mutational signature clusters associated with metastasis and patients’ outcomes. Several functional assays implicated that NFE2L2 may act as a tumor suppressor in ESCC and that mutations in NFE2L2 probably impaired its tumor-suppressive function, or even conferred oncogenic activities. Additionally, we found that the NFE2L2 mutations were significantly associated with worse prognosis of ESCC. We also identified potential noncoding driver mutations including hotspot mutations in the promoter region of SLC35E2 that were correlated with worse survival. Approximately 5.9% and 15.2% of patients had high tumor mutation burden or actionable mutations, respectively, and may benefit from immunotherapy or targeted therapies. We found clinically relevant coding and noncoding genomic alterations and revealed three major subtypes that robustly predicted patients’ outcomes. Collectively, we report the largest dataset of genomic profiling of ESCC useful for developing ESCC-specific biomarkers for diagnosis and treatment."
3713,Cochrane corner: Atropine: an ancient remedy for a twenty-first century problem?,
3714,Global distribution of a chlorophyll f cyanobacterial marker,"Some cyanobacteria use light outside the visible spectrum for oxygenic photosynthesis. The far-red light (FRL) region is made accessible through a complex acclimation process that involves the formation of new phycobilisomes and photosystems containing chlorophyll f. Diverse cyanobacteria ranging from unicellular to branched-filamentous forms show this response. These organisms have been isolated from shaded environments such as microbial mats, soil, rock, and stromatolites. However, the full spread of chlorophyll f-containing species in nature is still unknown. Currently, discovering new chlorophyll f cyanobacteria involves lengthy incubation times under selective far-red light. We have used a marker gene to detect chlorophyll f organisms in environmental samples and metagenomic data. This marker, apcE2, encodes a phycobilisome linker associated with FRL-photosynthesis. By focusing on a far-red motif within the sequence, degenerate PCR and BLAST searches can effectively discriminate against the normal chlorophyll a-associated apcE. Even short recovered sequences carry enough information for phylogenetic placement. Markers of chlorophyll f photosynthesis were found in metagenomic datasets from diverse environments around the globe, including cyanobacterial symbionts, hypersaline lakes, corals, and the Arctic/Antarctic regions. This additional information enabled higher phylogenetic resolution supporting the hypothesis that vertical descent, as opposed to horizontal gene transfer, is largely responsible for this phenotype’s distribution."
3715,MiRNA-210 induces microglial activation and regulates microglia-mediated neuroinflammation in neonatal hypoxic-ischemic encephalopathy,"Neuroinflammation is a major contributor to secondary neuronal injury that accounts for a significant proportion of final brain cell loss in neonatal hypoxic-ischemic encephalopathy (HIE). However, the immunological mechanisms that underlie HIE remain unclear. MicroRNA-210 (miR-210) is the master “hypoxamir” and plays a key role in hypoxic-ischemic tissue damage. Herein, we report in an animal model of neonatal rats that HIE significantly upregulated miR-210 expression in microglia in the neonatal brain and strongly induced activated microglia. Intracerebroventricular administration of miR-210 antagomir effectively suppressed microglia-mediated neuroinflammation and significantly reduced brain injury caused by HIE. We demonstrated that miR-210 induced microglial M1 activation partly by targeting SIRT1, thereby reducing the deacetylation of the NF-κB subunit p65 and increasing NF-κB signaling activity. Thus, our study identified miR-210 as a novel regulator of microglial activation in neonatal HIE, highlighting a potential therapeutic target in the treatment of infants with hypoxic-ischemic brain injury."
3716,Watch this space: a systematic review of the use of video-based media as a patient education tool in ophthalmology,"Effective clinician-patient communication is particularly important in ophthalmology where long-term adherence to treatment is often required. However, in the context of increasingly pressurised clinics, there is a tendency to resort to written information leaflets not suited to patients with visual impairment, non-English speakers or those with low levels of literacy. Video-based media could be harnessed to enhance clinician-patient communication. This systematic review aimed to assess the efficacy of using video-based media for patient education in ophthalmology. A pre-defined search strategy was used by two independent researchers to systematically review the PubMed, MEDLINE, EMBASE and PsycINFO databases. Eligible articles included peer-reviewed studies involving ophthalmology patients, who received a solely video-based educational intervention to assess for improvement in patient knowledge, behaviour and overall health-related outcomes. The search yielded 481 studies of which 31 passed initial screening. Following full-text analysis, 12 studies met the inclusion criteria, of which seven studies (58.3%) were randomised controlled trials. The majority of studies (58.3%) reported outcomes on patient comprehension with 5/7 (71%) showing statistically significant improvement after video intervention. Four studies (33.3%) reported on patient performance in a task (e.g. drop application method) or overall health-related outcome with 2/4 (50%) showing statistically significant improvement after intervention. Though more evidence is needed, the use of video-based media appears to be effective in improving patient understanding and in certain cases may ameliorate overall outcome. There is a paucity of well-designed studies and future research is required to fully examine the role of video-based media in patient education."
3717,Functional interaction between sensory neurons and mast cells in the early stage of house dust mite-induced type 2 inflammation and itch: a novel therapeutic target of allergic disease,
3718,Author Correction: Climate change: an enduring challenge for vector-borne disease prevention and control,
3719,Correction: Airway epithelial cells prime plasmacytoid dendritic cells to respond to pathogens via secretion of growth factors,
3720,"Correction: Despite mutation acquisition in hematopoietic stem cells, JMML-propagating cells are not always restricted to this compartment",
3721,Interruption of continuous opioid exposure exacerbates drug-evoked adaptations in the mesolimbic dopamine system,"Drug-evoked adaptations in the mesolimbic dopamine system are postulated to drive opioid abuse and addiction. These adaptations vary in magnitude and direction following different patterns of opioid exposure, but few studies have systematically manipulated the pattern of opioid administration while measuring neurobiological and behavioral impact. We exposed male and female mice to morphine for one week, with administration patterns that were either intermittent (daily injections) or continuous (osmotic minipump infusion). We then interrupted continuous morphine exposure with either naloxone-precipitated or spontaneous withdrawal. Continuous morphine exposure caused tolerance to the psychomotor-activating effects of morphine, whereas both intermittent and interrupted morphine exposure caused long-lasting psychomotor sensitization. Given links between locomotor sensitization and mesolimbic dopamine signaling, we used fiber photometry and a genetically encoded dopamine sensor to conduct longitudinal measurements of dopamine dynamics in the nucleus accumbens. Locomotor sensitization caused by interrupted morphine exposure was accompanied by enhanced dopamine signaling in the nucleus accumbens. To further assess downstream consequences on striatal gene expression, we used next-generation RNA sequencing to perform genome-wide transcriptional profiling in the nucleus accumbens and dorsal striatum. The interruption of continuous morphine exposure exacerbated drug-evoked transcriptional changes in both nucleus accumbens and dorsal striatum, dramatically increasing differential gene expression and engaging unique signaling pathways. Our study indicates that opioid-evoked adaptations in brain function and behavior are critically dependent on the pattern of drug administration, and exacerbated by interruption of continuous exposure. Maintaining continuity of chronic opioid administration may, therefore, represent a strategy to minimize iatrogenic effects on brain reward circuits."
3722,Erratum: A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence,
3723,Running interference on miR-33: a new amplification loop for type I interferon in the host antiviral response,
3724,Harmful vimentin manifests itself as multiorgan failure,
3725,Gastrodin protects H9c2 cardiomyocytes against oxidative injury by ameliorating imbalanced mitochondrial dynamics and mitochondrial dysfunction,"Gastrodin (GAS) is the main bioactive component of Tianma, a traditional Chinese medicine widely used to treat neurological disorders as well as cardio- and cerebrovascular diseases. In the present study, the protective effects of GAS on H9c2 cells against ischemia–reperfusion (IR)-like injury were found to be related to decreasing of oxidative stress. Furthermore, GAS could protect H9c2 cells against oxidative injury induced by H(2)O(2). Pretreatment of GAS at 20, 50, and 100 μM for 4 h significantly ameliorated the decrease in cell viability and increase in apoptosis of H9c2 cells treated with 400 μM H(2)O(2) for 3 h. Furthermore, we showed that H(2)O(2) treatment induced fragmentation of mitochondria and significant reduction in networks, footprint, and tubular length of mitochondria; H(2)O(2) treatment strongly inhibited mitochondrial respiration; H(2)O(2) treatment induced a decrease in the expression of mitochondrial fusion factors Mfn2 and Opa1, and increase in the expression of mitochondrial fission factor Fis1. All these alterations in H(2)O(2)-treated H9c2 cells could be ameliorated by GAS pretreatment. Moreover, we revealed that GAS pretreatment enhanced the nuclear translocation of Nrf2 under H(2)O(2) treatment. Knockdown of Nrf2 expression abolished the protective effects of GAS on H(2)O(2)-treated H9c2 cells. Our results suggest that GAS may protect H9c2 cardiomycytes against oxidative injury via increasing the nuclear translocation of Nrf2, regulating mitochondrial dynamics, and maintaining the structure and functions of mitochondria."
3726,A 20-year audit of retinoblastoma treatment outcomes,"OBJECTIVES: To evaluate the long-term treatment outcomes in intraocular retinoblastoma (RB) including the associated factors for eventual treatment with external beam radiotherapy (EBRT) and enucleation as well as to analyse the risk factors for metastasis and death in extraocular RB. METHODS: Retrospective analysis of 390 eyes from 256 (89.8%) intraocular RB and 29 (10.2%) extraocular RB cases diagnosed and treated between October 1998 and May 2018 at one of the largest tertiary care centers in Turkey. RESULTS: Of 351 intraocular RB eyes, 53.3% had group D/E disease at presentation. 75 (21.4%) of 351 eyes underwent primary enucleation. Of the remaining 276 eyes undergoing eye-conserving treatments, 201 (72.8%) were salvaged. Most of these eyes were treated using intravenous chemotherapy and/or focal treatments [transpupillary thermotherapy (TTT) and cryotherapy] initially. EBRT was eventually required in 48 (17.4%) eyes and secondary enucleation in 75 (27.2%) eyes. At mean follow-ups of 76.7 and 39.7 months for intraocular and extraocular RB cohorts, respectively, 180 (46.2%) eyes underwent primary/secondary enucleation and exenteration. Overall, 13 cases developed metastasis and 9 died. Two patients with trilateral RB also expired. Multivariable risk factors for enucleation were the presence of vitreous seeds (p < 0.001), absence of EBRT administration (p = 0.033), 5–9 TTT applications compared with no TTT (p = 0.031), and each 1 mm increase in tumour base diameter (p < 0.001). Univariate factors predictive of metastasis were the presence of extraocular RB detected by imaging methods (p < 0.001) and extrascleral/optic nerve cut end involvement at histopathological examination (p < 0.001). CONCLUSIONS: In our series, 72.8% of the intraocular RB eyes undergoing eye-conserving treatments were saved. The globe salvage rate for all intraocular and extraocular RB eyes was 53.8% and the overall survival rate was 96.1%."
3727,Correction: Validation of the use of p-aminobenzoic acid to determine completeness of 24 h urine collections in surveys of diet and nutrition,
3728,Correction: Control of PD-L1 expression by miR-140/142/340/383 and oncogenic activation of the OCT4–miR-18a pathway in cervical cancer,
3729,Brolucizumab—another anti-VEGF or beyond,
3730,Galactose supramolecular docking orchestrates macrophage phenotype,
3731,Correction: The phenotypic spectrum of WWOX-related disorders: 20 additional cases of WOREE syndrome and review of the literature,
3732,"Alflutinib (AST2818), primarily metabolized by CYP3A4, is a potent CYP3A4 inducer","Alflutinib (AST2818) is a third-generation epidermal growth factor receptor (EGFR) inhibitor that inhibits both EGFR-sensitive mutations and T790M mutations. Previous study has shown that after multiple dosages, alflutinib exhibits nonlinear pharmacokinetics and displays a time- and dose-dependent increase in the apparent clearance, probably due to its self-induction of cytochrome P450 (CYP) enzyme. In this study, we investigated the CYP isozymes involved in the metabolism of alflutinib and evaluated the enzyme inhibition and induction potential of alflutinib and its metabolites. The data showed that alflutinib in human liver microsomes (HLMs) was metabolized mainly by CYP3A4, which could catalyze the formation of AST5902. Alflutinib did not inhibit CYP isozymes in HLMs but could induce CYP3A4 in human hepatocytes. Rifampin is a known strong CYP3A4 inducer and is recommended by the FDA as a positive control in the CYP3A4 induction assay. We found that the induction potential of alflutinib was comparable to that of rifampin. The E(max) of CYP3A4 induction by alflutinib in three lots of human hepatocytes were 9.24-, 11.2-, and 10.4-fold, while the fold-induction of rifampin (10 μM) were 7.22-, 19.4- and 9.46-fold, respectively. The EC(50) of alflutinib-induced CYP3A4 mRNA expression was 0.25 μM, which was similar to that of rifampin. In addition, AST5902 exhibited much weak CYP3A4 induction potential compared to alflutinib. Given the plasma exposure of alflutinib and AST5902, both are likely to affect the pharmacokinetics of CYP3A4 substrates. Considering that alflutinib is a CYP3A4 substrate and a potent CYP3A4 inducer, drug–drug interactions are expected during alflutinib treatment."
3733,Author Correction: NICE’s rejection of pembrolizumab for platinum-refractory urothelial carcinoma: is there a greater good?,
3734,Erratum to: Abstracts: XXXI International Congress of the IAP and 28th Congress of the ESP,
3735,Activation of tyrosine phosphatase PTP1B in pyramidal neurons impairs endocannabinoid signaling by tyrosine receptor kinase trkB and causes schizophrenia-like behaviors in mice,"Schizophrenia is a debilitating disorder affecting young adults displaying symptoms of cognitive impairment, anxiety, and early social isolation prior to episodes of auditory hallucinations. Cannabis use has been tied to schizophrenia-like symptoms, indicating that dysregulated endogenous cannabinoid signaling may be causally linked to schizophrenia. Previously, we reported that glutamatergic neuron-selective ablation of Lmo4, an endogenous inhibitor of the tyrosine phosphatase PTP1B, impairs endocannabinoid (eCB) production from the metabotropic glutamate receptor mGluR5. These Lmo4-deficient mice display anxiety-like behaviors that are alleviated by local shRNA knockdown or pharmacological inhibition of PTP1B that restores mGluR5-dependent eCB production in the amygdala. Here, we report that these Lmo4-deficient mice also display schizophrenia-like behaviors: impaired working memory assessed in the Y maze and defective sensory gating by prepulse inhibition of the acoustic startle response. Modulation of inhibitory inputs onto layer 2/3 pyramidal neurons of the prefrontal cortex relies on eCB signaling from the brain-derived neurotrophic factor receptor trkB, rather than mGluR5, and this mechanism was defective in Lmo4-deficient mice. Genetic ablation of PTP1B in the glutamatergic neurons lacking Lmo4 restored tyrosine phosphorylation of trkB, trkB-mediated eCB signaling, and ameliorated schizophrenia-like behaviors. Pharmacological inhibition of PTP1B with trodusquemine also restored trkB phosphorylation and improved schizophrenia-like behaviors by restoring eCB signaling, since the CB1 receptor antagonist 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide blocked this effect. Thus, activation of PTP1B in pyramidal neurons contributes to schizophrenia-like behaviors in Lmo4-deficient mice and genetic or pharmacological intervention targeting PTP1B ameliorates schizophrenia-related deficits."
3736,Author Correction: Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes,
3737,Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling,"Sepsis-induced multiple organ dysfunction and inflammatory response are life-threatening symptoms without effective treatment. Fisetin, a dietary flavonoid extracted from berries and family Fabaceae, has displayed neuroprotective and anti-oxidant activities. In this study we investigated whether fisetin exerted a protective effect against sepsis-induced multiple organ dysfunction in mouse cecum ligation and puncture (CLP) model. The mice were injected with fisetin (10 mg/kg, ip) 0.5 h prior to CLP, and sacrificed 18 h after CLP. We found that fisetin administration significantly alleviated CLP-induced lung, liver and kidney injury, as well as the expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β in bronchoalveolar lavage fluid (BALF). In lipopolysaccharide (LPS)-treated mouse bone marrow-derived macrophages (BMDMs), application of fisetin (3–10 μM) dose-dependently inhibited the expression levels of IL-6, TNF-α, IL-1β, and inducible nitric oxide synthase (iNOS). Furthermore, fisetin dose-dependently inhibited the phosphorylation of p38 MAPK, MK2, and transforming growth factor-β-activated kinase (TAK) 1 via attenuating the interaction between TAK1 and TAK-binding proteins (TAB) 1. These results demonstrate that fisetin is a promising agent for protecting against sepsis-induced inflammatory response and organ injury via inhibiting macrophage activation."
3738,Wnt signaling and Loxl2 promote aggressive osteosarcoma,"Osteosarcoma (OS) is the most frequent primary malignant bone tumor in urgent need of better therapies. Using genetically modified mouse models (GEMMs), we demonstrate that Wnt signaling promotes c-Fos-induced OS formation via the actions of the collagen-modifying enzyme Loxl2. c-Fos/AP-1 directly regulates the expression of the Wnt ligands Wnt7b and Wnt9a in OS cells through promoter binding, and Wnt7b and Wnt9a in turn promote Loxl2 expression in murine and human OS cells through the transcription factors Zeb1 and Zeb2. Concordantly, inhibition of Wnt ligand secretion by inactivating the Wnt-less (Wls) gene in osteoblasts in c-Fos GEMMs either early or in a therapeutic setting reduces Loxl2 expression and progression of OS. Wls-deficient osteosarcomas proliferate less, are less mineralized and are enriched in fibroblastic cells surrounded by collagen fibers. Importantly, Loxl2 inhibition using either the pan-Lox inhibitor BAPN or a specific inducible shRNA reduces OS cell proliferation in vitro and decreases tumor growth and lung colonization in murine and human orthotopic OS transplantation models. Finally, OS development is delayed in c-Fos GEMMs treated with BAPN or with specific Loxl2 blocking antibodies. Congruently, a strong correlation between c-FOS, LOXL2 and WNT7B/WNT9A expression is observed in human OS samples, and c-FOS/LOXL2 co-expression correlates with OS aggressiveness and decreased patient survival. Therefore, therapeutic targeting of Wnt and/or Loxl2 should be considered to potentiate the inadequate current treatments for pediatric, recurrent, and metastatic OS."
3739,What is the optimal glaucoma treatment: reducing aqueous humour production or facilitating its outflow?,
3740,Author Correction: Chemosynthetic symbionts of marine invertebrate animals are capable of nitrogen fixation,
3741,Erratum: Clinical impact of bone marrow morphology for the diagnosis of essential thrombocythemia: comparison between the BCSH and the WHO criteria,
3742,Depth-dependent mycoplankton glycoside hydrolase gene activity in the open ocean—evidence from the Tara Oceans eukaryote metatranscriptomes,"Mycoplankton are widespread components of marine ecosystems, yet the full extent of their functional role remains poorly known. Marine mycoplankton are likely functionally analogous to their terrestrial counterparts, including performing saprotrophy and degrading high-molecular weight organic substrates using carbohydrate-active enzymes (CAZymes). We investigated the prevalence of transcribed oceanic fungal CAZyme genes using the Marine Atlas of Tara Ocean Unigenes database. We revealed an abundance of unique transcribed fungal glycoside hydrolases in the open ocean, including a particularly high number that act upon cellulose in surface waters and the deep chlorophyll maximum (DCM). A variety of other glycoside hydrolases acting on a range of biogeochemically important polysaccharides including β-glucans and chitin were also found. This analysis demonstrates that mycoplankton are active saprotrophs in the open ocean and paves the way for future research into the depth-dependent roles of marine fungi in oceanic carbon cycling, including the biological carbon pump."
3743,Correction: Cancer from the perspective of stem cells and misappropriated tissue regeneration mechanisms,
3744,Author Correction: Regulation of sister chromatid cohesion by nuclear PD-L1,
3745,mGlu5 receptor availability in youth at risk for addictions: effects of vulnerability traits and cannabis use,"The excitatory neurotransmitter glutamate has been implicated in experience-dependent neuroplasticity and drug-seeking behaviors. Type 5 metabotropic glutamate (mGlu5) receptors might be particularly important. They are critically involved in synaptic plasticity and their availability has been reported to be lower in people with alcohol, tobacco, and cocaine use disorders. Since these reductions could reflect effects of drug use or pre-existing traits, we used positron emission tomography to measure mGlu5 receptor availability in young adults at elevated risk for addictions. Fifty-nine participants (age 18.5 ± 0.6) were recruited from a longitudinal study that has followed them since birth. Based on externalizing traits that predict future substance use problems, half were at low risk, half were at high risk. Cannabis use histories varied markedly and participants were divided into three subgroups: zero, low, and high use. Compared to low risk volunteers, those at elevated risk had lower [(11)C]ABP688 binding potential (BP(ND)) values in the striatum, amygdala, insula, and orbitofrontal cortex (OFC). Cannabis use by risk group interactions were observed in the striatum and OFC. In these regions, low [(11)C]ABP688 BP(ND) values were only seen in the high risk group that used high quantities of cannabis. When these high risk, high cannabis use individuals were compared to all other participants, [(11)C]ABP688 BP(ND) values were lower in the striatum, OFC, and insula. Together, these results provide evidence that mGlu5 receptor availability is low in youth at elevated risk for addictions, particularly those who frequently use cannabis."
3746,Setting a new standard in cystic fibrosis newborn screening illustrates controversial issues as new data emerge,
3747,Biallelic PDE2A variants: a new cause of syndromic paroxysmal dyskinesia,"Cause of complex dyskinesia remains elusive in some patients. A homozygous missense variant leading to drastic decrease of PDE2A enzymatic activity was reported in one patient with childhood-onset choreodystonia preceded by paroxysmal dyskinesia and associated with cognitive impairment and interictal EEG abnormalities. Here, we report three new cases with biallelic PDE2A variants identified by trio whole-exome sequencing. Mitochondria network was analyzed after Mitotracker™ Red staining in control and mutated primary fibroblasts. Analysis of retrospective video of patients’ movement disorder and refinement of phenotype was carried out. We identified a homozygous gain of stop codon variant c.1180C>T; p.(Gln394*) in PDE2A in siblings and compound heterozygous variants in young adult: a missense c.446C>T; p.(Pro149Leu) and splice-site variant c.1922+5G>A predicted and shown to produce an out of frame transcript lacking exon 22. All three patients had cognitive impairment or developmental delay. The phenotype of the two oldest patients, aged 9 and 26, was characterized by childhood-onset refractory paroxysmal dyskinesia initially misdiagnosed as epilepsy due to interictal EEG abnormalities. The youngest patient showed a proven epilepsy at the age of 4 months and no paroxysmal dyskinesia at 15 months. Interestingly, analysis of the fibroblasts with the biallelic variants in PDE2A variants revealed mitochondria network morphology changes. Together with previously reported case, our three patients confirm that biallelic PDE2A variants are a cause of childhood-onset refractory paroxysmal dyskinesia with cognitive impairment, sometimes associated with choreodystonia and interictal baseline EEG abnormalities or epilepsy."
3748,Ligand recognition by the γδ TCR and discrimination between homeostasis and stress conditions,"T lymphocytes comprise cells expressing either an αβ or a γδ TCR. The riddle how αβ TCRs are triggered by specific peptides presented in the context of MHC was elucidated some time ago. In contrast, the mechanisms that underlie antigen recognition by γδ TCRs are still baffling the scientific community. It is clear that activation of γδ TCRs does not necessarily depend on MHC antigen presentation. To date, diverse and largely host-cell-derived molecules have been identified as cognate antigens for the γδ TCR. However, for most γδ TCRs, the activating ligand is still unknown and many open questions with regard to physiological relevance and generalizable concepts remain. Especially the question of how γδ T cells can distinguish homeostatic from stress conditions via their TCR remains largely unresolved. Recent discoveries in the field might have paved the way towards a better understanding of antigen recognition by the γδ TCR and have made it conceivable to revise the current knowledge and contextualize the new findings."
3749,Potential application of endocannabinoid system agents in neuropsychiatric and neurodegenerative diseases—focusing on FAAH/MAGL inhibitors,"The endocannabinoid system (ECS) has received extensive attention for its neuroprotective effect on the brain. This system comprises endocannabinoids, endocannabinoid receptors, and the corresponding ligands and proteins. The molecular players involved in their regulation and metabolism are potential therapeutic targets for neuropsychiatric diseases including anxiety, depression and neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). The inhibitors of two endocannabinoid hydrolases, i.e., fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), have the capacity to increase the level of endocannabinoids indirectly, causing fewer side effects than those associated with direct supplementation of cannabinoids. Their antidepressant and anxiolytic mechanisms are considered to modulate the hypothalamic-pituitary-adrenal axis and regulate synaptic and neural plasticity. In terms of AD/PD, treatment with FAAH/MAGL inhibitors leads to reduction in amyloid β-protein deposition and inhibition of the death of dopamine neurons, which are commonly accepted to underlie the pathogenesis of AD and PD, respectively. Inflammation as the cause of depression/anxiety and PD/AD is also the target of FAAH/MAGL inhibitors. In this review, we summarize the application and involvement of FAAH/MAGL inhibitors in related neurological diseases. Focus on the latest research progress using FAAH/MAGL inhibitors is expected to facilitate the development of novel approaches with therapeutic potential."
3750,Correction: Src and SHP2 coordinately regulate the dynamics and organization of vimentin filaments during cell migration,
3751,Presumed ocular tuberculosis in the United Kingdom: a British Ophthalmological Surveillance Unit (BOSU) study,"INTRODUCTION: Ocular tuberculosis (TB) is an extrapulmonary manifestation of mycobacterium infection that most commonly presents as uveitis. This is the first prospective incidence study of presumed ocular tuberculosis performed in the United Kingdom (UK). METHOD: New cases of ocular tuberculosis presenting to hospitals in the UK were prospectively ascertained between October 2016 and November 2017 with the aid of the British Ophthalmological Surveillance Unit (BOSU). Initial presentation data and 1-year follow-up data was collected using questionnaires. RESULTS: Forty-eight patients were recruited giving an overall incidence for ocular TB of 0.73 per million population per annum. The origin of birth for 71% of the patients was a non-UK country and 87.5% had their initial diagnosis of TB made by an ophthalmologist. The most common first line treatment was isoniazid, rifampicin, ethambutol and pyrazinamide which 71% of patients were treated with 60% of patients were commenced on a reducing course of oral steroids. At 1-year follow-up, 29 patients (83%) had complete resolution of active clinical signs. Mean best corrected visual acuity (BCVA) at presentation was +0.41 LogMAR(SD = 0.62), compared to +0.31 LogMAR (SD = 0.56) at 12-month follow-up. DISCUSSION: It is increasingly the responsibility of the ophthalmologist to diagnose ocular TB and although it remains a rare condition, consensus on diagnostic criteria and treatment is required. Increasing recognition and accessibility to gamma-interferon testing should enable earlier detection. Treatment with quadruple ATT treatment regimens for at least 6 months shows good clinical outcomes. However, it is still unclear whether steroid use is beneficial. Further large studies with longer follow-up would be warranted to answer these questions."
3752,Comment on: ‘Giant cell arteritis in patients of Indian subcontinental descent in the UK’,
3753,"Correction to: The Intensive Care Global Study on Severe Acute Respiratory Infection (IC-GLOSSARI): a multicenter, multinational, 14-day inception cohort study",
3754,Correction to: Accelerating evidence gathering and approval of precision medicine therapies: the FDA takes aim at rare mutations,
3755,Pachydrusen: the epidemiology of pachydrusen and its relevance to progression of pachychoroid disease spectrum,
3756,Trends in licence approvals for ophthalmic medicines in the United Kingdom,"OBJECTIVES: The grant of marketing authorisation (MA) for new medicines requires comprehensive assessment by regulatory authorities. This study sought to identify ophthalmic medicines granted United Kingdom MA and consider trends in licence approvals. METHODS: This retrospective study reviewed published lists of products granted MA by the UK Medicines & Healthcare products Regulatory Agency between January 2001 and December 2018, inclusive. Eye drops and medicinal products intended for ophthalmic use were identified. All regulatory data sources consulted are in the public domain. Data analyses were descriptive. RESULTS: A total of 295 MAs were issued for ophthalmic products between 2001 and 2018, inclusive. Of these 229 (78%) were for single-active substances and 66 (22%) fixed-dose combination (FDC). Approvals for products with single-active substance included ocular hypotensives (115; 50%), antibiotics (48; 22%), allergy medicines (30; 13%), lubricants (18; 8%) and anti-inflammatories (11; 5%). Approvals for FDCs were predominantly ocular hypotensives (56; 85%), with timolol combined with carbonic anhydrase inhibitors (27; 48%) and prostaglandin analogues (26; 46%) accounting for the majority of glaucoma FDCs. Other FDCs were approved for antibiotic/inflammatory (5; 7.5%), pupillary mydriasis (2; 3%), allergy (2; 3%) and ocular surface lubrication (1; 1.5%) products. A median of 16 licences were approved per year (range 7 [2005] to 35 [2011]). CONCLUSIONS: The majority of MAs granted were for single-agent products, particularly ocular hypotensives and antibiotic preparations. Most products were generic versions of well-established active substances. A trend for increased approvals for FDCs is evident, particularly for the treatment of raised IOP."
3757,The Association with rhegmatogenous retinal detachment and paediatric atopic dermatitis: a 12-year Nationwide Cohort Study,"PURPOSE: Historically, atopic dermatitis (AD) is associated with an increased risk of rhegmatogenous retinal detachment (RRD). However, uncertainty remained regarding the effect of AD itself and comorbidities (e.g., allergic diseases, cataract surgery) on RRD occurrence in a large, population-based paediatric population. PATIENTS AND METHODS: We analysed the 12-year National Health Insurance Service database (2002–2013) covering the entire Korean population to estimate the association between AD and RRD in people aged under 20 years. RESULTS: We identified 3142 RRD patients, and matched 18,852 controls (six controls to each RRD patient); therefore, we included 21,994 peoples under aged 20 years in the analyses. AD was more prevalent in the RRD group (329 patients, 10.47%) than the control group (1043 patients, 5.53%; P < 0.001), and so were severe AD (153 patients [4.87%] and 223 patients [1.18%], respectively; P < 0.001). In conditional logistic regression analysis, AD was associated with RRD (OR, 1.61; 95% CI, 1.93–1.87) even after adjusting for allergic conditions, connective tissue disease, uveitis, and cataract surgery. In addition, severity of AD was associated with an increased risk of RRD (OR for non-severe AD and severe AD, 1.26 [95% CI, 1.05–1.51] and 2.88 [95% CI, 2.25–3.68]). CONCLUSION: This study suggests that AD itself is a risk factor of RRD in children by showing the association between AD and RRD occurrence and the biologic gradient even after adjustment for known confounders including allergic conditions, uveitis, and cataract surgery."
3758,Correction: Evaluation of medical and surgical decompression in patients with dysthyroid optic neuropathy,
3759,Nintedanib inhibits keloid fibroblast functions by blocking the phosphorylation of multiple kinases and enhancing receptor internalization,"Keloid is a benign skin tumor characterized by its cell hyperproliferative activity, invasion into normal skin, uncontrolled growth, overproduction and deposition of extracellular matrices and high recurrence rate after various therapies. Nintedanib is a receptor tyrosine kinase inhibitor targeting VEGF, PDGF, FGF, and TGF-β receptors with proved efficacy in anti-angiogenesis and in treating various types of cancers. In this study, we investigated the effects of nintedanib on keloid fibroblasts in both in vitro and ex vivo models. Keloid fibroblasts were prepared from 54 keloid scar samples in active stages collected from 49 patients. We found that nintedanib (1−4 μM) dose-dependently suppressed cell proliferation, induced G(0)/G(1) cell cycle arrest, and inhibited migration and invasion of keloid fibroblasts. The drug also significantly inhibited the gene and protein expression of collagen I (COL-1) and III (COL-3), fibronectin (FN), and connective growth factor (CTGF), as well as the gene expression of other pathological factors, such as alpha smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), FK506-binding protein 10 (FKBP10), and heat shock protein 47 (HSP47) in keloid fibroblasts. Furthermore, nintedanib treatment significantly suppressed the phosphorylation of p38, JNK, ERK, STAT3, and Smad, enhanced endocytosis of various growth factor receptors. Using an ex vivo tissue explant model, we showed that nintedanib significantly suppressed cell proliferation, migration, and collagen production. The drug also significantly disrupted microvessel structure ex vivo. In summary, our results demonstrate that nintedanib is likely to become a potential targeted drug for keloid systemic therapy."
3760,A survey of current practices by the British Oculoplastic Surgery Society (BOPSS) and recommendations for delivering a sustainable multidisciplinary approach to thyroid eye disease in the United Kingdom,"BACKGROUND: The Royal College of Physicians (RCP) and Thyroid Eye Disease Amsterdam Declaration Implementation Group (TEAMeD-5) have the common goal of improving access to high quality care for thyroid eye disease (TED). The TEAMeD-5 programme recommends all patients with moderate-to-severe TED should have access to multidisciplinary clinics (MDT) with combined Ophthalmology and Endocrinology expertise. METHODS: The British Oculoplastic Surgery Society represents oculoplastic surgeons who usually lead TED care in the UK. A two-stage survey of the membership was conducted to ascertain current practice of existing resources. RESULTS: Seventy percent (45/65) of respondents in Survey 1 were aware of current RCP guidance, but only 49% (22/45) rated it as a good means of improving access to comprehensive TED service. Sixty percent (39/65) of respondents are working in a multidisciplinary TED clinic with co-location of ophthalmologists and endocrinologists. Care for TED appears not to be provided in a multidisciplinary context in up to 31% (20/65). Thirty five (54%) of the respondents rated their relationship with endocrinology colleagues as good. Best practice guidelines recommend routine quality of life assessments but only 6/28 (21%) of respondents use this modality in current practice. Six percent (4/65) of areas appear not to be using intravenous steroids. In many areas (25%, 16/65), second-line immunosuppression is provided in a different trust and in 8% (5/65), it appears not to be used at all. CONCLUSION: This survey is a ‘snapshot’ of current TED management in the UK and findings suggest scope for improvement. We recommend a framework for more robust collaboration across specialties and propose standards endorsed by multidisciplinary stakeholder societies."
3761,Short-term nicotine deprivation alters dorsal anterior cingulate glutamate concentration and concomitant cingulate-cortical functional connectivity,"Most cigarette smokers who wish to quit too often relapse within the first few days of abstinence, primarily due to the aversive aspects of the nicotine withdrawal syndrome (NWS), which remains poorly understood. Considerable research has suggested that the dorsal anterior cingulate cortex (dACC) plays a key role in nicotine dependence, with its functional connections between other brain regions altered as a function of trait addiction and state withdrawal. The flow of information between dACC and fronto-striatal regions is secured through different pathways, the vast majority of which are glutamatergic. As such, we investigated dACC activity using resting state functional connectivity (rsFC) with functional magnetic resonance imaging (fMRI) and glutamate (Glu) concentration with magnetic resonance spectroscopy (MRS). We also investigated the changes in adenosine levels in plasma during withdrawal as a surrogate for brain adenosine, which plays a role in fine-tuning synaptic glutamate transmission. Using a double-blind, placebo-controlled, randomized crossover design, nontreatment seeking smoking participants (N = 30) completed two imaging sessions, one while nicotine sated and another after 36 h nicotine abstinence. We observed reduced dACC Glu (P = 0.029) along with a significant reduction in plasma adenosine (P = 0.03) and adenosine monophosphate (AMP; P < 0.0001) concentrations during nicotine withdrawal in comparison with nicotine sated state. This withdrawal state manipulation also led to an increase in rsFC strength (P < 0.05) between dACC and several frontal cortical regions, including left superior frontal gyrus (LSFG), and right middle frontal gyrus (RMFG). Moreover, the state-trait changes in dACC Glu and rsFC strength between the dACC and both SFG and MFG were positively correlated (P = 0.012, and P = 0.007, respectively). Finally, the change in circuit strength between dACC and LSFG was negatively correlated with the change in withdrawal symptom manifestations as measured by the Wisconsin Smoking Withdrawal Scale (P = 0.04) and Tobacco Craving Questionnaire (P = 0.014). These multimodal imaging-behavioral findings reveal the complex cascade of changes induced by acute nicotine deprivation and call for further investigation into the potential utility of adenosine- and glutamate-signaling as novel therapeutic targets to treat the NWS."
3762,Correction to: 14 Years’ experience of esophageal replacement surgeries,
3763,Correction: A 20-year audit of retinoblastoma treatment outcomes,
3764,Correction: Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma,
3765,Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis,
3766,Correction: Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHV(mut) and IgHV(unmut) subgroups,
3767,Choroidal thickness and the retinal ganglion cell complex in chronic Leberʼs hereditary optic neuropathy: a prospective study using swept-source optical coherence tomography,"BACKGROUND/OBJECTIVES: Choroidal thinning has been suggested in Leber’s hereditary optic neuropathy (LHON). No study has been conducted of the choroid in relation to the retinal ganglion cell-inner plexiform layer (RGC-IPL). We sought to measure choroidal thickness in chronic LHON and to correlate thickness changes with the RGC-IPL. SUBJECTS/METHODS: Chronic LHON, 11778 mitochondrial DNA (mtDNA) mutation, patients (26 eyes; mean age: 35.1 ± 16.1 years) were prospectively recruited at Doheny Eye Center, University of California Los Angeles from March 2016 to July 2017. Age-matched healthy controls (27 eyes; mean age: 32.4 ± 11.1 years) were enroled for comparison. Swept-source optical coherence tomography (SS-OCT) imaging was performed in chronic LHON patients and compared with age-matched healthy controls. RESULTS: The macular choroid was significantly thinner in chronic LHON (250.5 ± 62.2 μm) compared with controls (313.9 ± 60.2 μm; p < 0.0001). The peripapillary choroid was also significantly thinner in chronic LHON (135.7 ± 51.4 μm) compared with controls (183.0 ± 61.8 μm, p < 0.001). Choroidal thickness strongly correlated with retinal nerve fibre layer (RNFL) thickness in both the macular (R(2) = 0.72; 95% CI, 0.57–0.84) and peripapillary regions (R(2) = 0.53; 95% CI, 0.31–0.70). Choroidal thickness was also significantly correlated with macular RGC-IPL thickness (R(2) = 0.51; 95% CI, 0.26–0.73). CONCLUSIONS: Choroidal thinning in chronic LHON correlated strongly with both RNFL and RGC-IPL thicknesses. These findings may suggest a pathophysiological mechanism involving vascular pathology of the choroid in relation to the retinal ganglion cell complex in LHON."
3768,The Msi1-mTOR pathway drives the pathogenesis of mammary and extramammary Paget’s disease,"Mammary and extramammary Paget’s Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways — including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD."
3769,Is HSPG2 a modifier gene for Marfan syndrome?,"Marfan syndrome (MFS) is a connective tissue disease caused by variants in the FBN1 gene. Nevertheless, other genes influence the manifestations of the disease, characterized by high clinical variability even within families. We mapped modifier loci for cardiovascular and skeletal manifestations in the mg∆(loxPneo) mouse model for MFS and the synthenic loci in the human genome. Corroborating our findings, one of those loci was identified also as a modifier locus in MFS patients. Here, we investigate the HSPG2 gene, located in this region, as a candidate modifier gene for MFS. We show a correlation between Fbn1 and Hspg2 expression in spinal column and aorta in non-isogenic mg∆(loxPneo) mice. Moreover, we show that mice with severe phenotypes present lower expression of Hspg2 than those mildly affected. Thus, we propose that HSPG2 is a strong candidate modifier gene for MFS and its role in modulating disease severity should be investigated in patients."
3770,CryoEM structure of the tegumented capsid of Epstein-Barr virus,"Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and has been shown to be closely associated with various malignancies. Here, we present a complete atomic model of EBV, including the icosahedral capsid, the dodecameric portal and the capsid-associated tegument complex (CATC). Our in situ portal from the tegumented capsid adopts a closed conformation with its channel valve holding the terminal viral DNA and with its crown region firmly engaged by three layers of ring-like dsDNA, which, together with the penton flexibility, effectively alleviates the capsid inner pressure placed on the portal cap. In contrast, the CATCs, through binding to the flexible penton vertices in a stoichiometric manner, accurately increase the inner capsid pressure to facilitate the pressure-driven genome delivery. Together, our results provide important insights into the mechanism by which the EBV capsid, portal, packaged genome and the CATCs coordinately achieve a pressure balance to simultaneously benefit both viral genome retention and ejection."
3771,Author Correction: Increasing the bactofection capacity of a mammalian expression vector by removal of the f1 ori,
3772,ERCC6L2 promotes DNA orientation-specific recombination in mammalian cells,"Programmed DNA recombination in mammalian cells occurs predominantly in a directional manner. While random DNA breaks are typically repaired both by deletion and by inversion at approximately equal proportions, V(D)J and class switch recombination (CSR) of immunoglobulin heavy chain gene overwhelmingly delete intervening sequences to yield productive rearrangement. What factors channel chromatin breaks to deletional CSR in lymphocytes is unknown. Integrating CRISPR knockout and chemical perturbation screening we here identify the Snf2-family helicase-like ERCC6L2 as one such factor. We show that ERCC6L2 promotes double-strand break end-joining and facilitates optimal CSR in mice. At the cellular levels, ERCC6L2 rapidly engages in DNA repair through its C-terminal domains. Mechanistically, ERCC6L2 interacts with other end-joining factors and plays a functionally redundant role with the XLF end-joining factor in V(D)J recombination. Strikingly, ERCC6L2 controls orientation-specific joining of broken ends during CSR, which relies on its helicase activity. Thus, ERCC6L2 facilitates programmed recombination through directional repair of distant breaks."
3773,Erratum to: 38(th) EUROPEAN SOCIETY OF NEURORADIOLOGY Diagnostic and Interventional ANNUAL MEETING,
3774,Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials,"Cannabidiol (CBD) is being investigated as a treatment for several medical disorders but there is uncertainty about its safety. We conducted the first systematic review and meta-analysis of the adverse effects of CBD across all medical indications. Double-blind randomized placebo-controlled clinical trials lasting ≥7 days were included. Twelve trials contributed data from 803 participants to the meta-analysis. Compared with placebo, CBD was associated with an increased likelihood of withdrawal for any reason (OR 2.61, 95% CI: 1.38–4.96) or due to adverse events (OR 2.65, 95% CI: 1.04–6.80), any serious adverse event (OR 2.30, 95% CI: 1.18–4.48), serious adverse events related to abnormal liver function tests (OR 11.19, 95% CI: 2.09–60.02) or pneumonia (OR 5.37, 95% CI: 1.17–24.65), any adverse event (OR 1.55, 95% CI: 1.03–2.33), adverse events due to decreased appetite (OR 3.56, 95% CI: 1.94–6.53), diarrhoea (OR 2.61, 95% CI: 1.46–4.67), somnolence (OR 2.23, 95% CI: 1.07–4.64) and sedation (OR 4.21, 95% CI: 1.18–15.01). Associations with abnormal liver function tests, somnolence, sedation and pneumonia were limited to childhood epilepsy studies, where CBD may have interacted with other medications such as clobazam and/or sodium valproate. After excluding studies in childhood epilepsy, the only adverse outcome associated with CBD treatment was diarrhoea (OR 5.03, 95% CI: 1.44–17.61). In summary, the available data from clinical trials suggest that CBD is well tolerated and has relatively few serious adverse effects, however interactions with other medications should be monitored carefully. Additional safety data from clinical trials outside of childhood epilepsy syndromes and from studies of over-the-counter CBD products are needed to assess whether the conclusions drawn from clinical trials can be applied more broadly."
3775,Changes in the corneal thickness and limbus after 1 year of scleral contact lens use,"PURPOSE: To assess the physiological changes in the cornea over time in patients with irregular cornea fitted with Rose K2 XL gas-permeable scleral contact lenses. METHODS: Prospective study of 16 eyes of patients who did not tolerate gas-permeable corneal contact lenses and were fitted with Rose K2 XL scleral lenses. We assessed the central vault and the corneal thickness centrally and at peripheral regions (2 to 5 mm annulus). All these measures were obtained by anterior segment optical coherence tomography. The measurements were taken immediately after fitting the lenses and 1, 6 and 12 months later. Prior to the study and at 1 year, we performed an objective test for diagnosing limbal stem cell deficiency (Limbokit). RESULTS: The mean vault was 201.7 ± 82.3 µm 20 min after fitting the contact lens; 189.4 ± 94.0 µm at 1 month; 165.1 ± 75.9 µm at 6 months and 142.1 ± 76.8 µm at 1 year, the values at 6 and 12 months being significantly different to baseline. After 1 year, the central corneal thickness had increased by 2.3% (IQR = 5.6), but the changes were only significant for the superior thickness. There is no limbal stem cell deficiency after 1 year of scleral contact lens use. CONCLUSIONS: After use of Rose K2 XL scleral contact lenses, the corneal physiology of patients with an irregular cornea remains unchanged, as assessed by corneal thickness measurements and the Limbokit test. In all cases, however, the vault decreased over time."
3776,Correction: BOADICEA: a comprehensive breast cancer risk prediction model incorporating genetic and nongenetic risk factors,
3777,Erratum to: Survival of Hendra Virus in the Environment: Modelling the Effect of Temperature,
3778,Comment on: ‘Ophthalmology Specialist Trainee Survey in the United Kingdom’. The need to increase familiarity with the management of predictable cataract surgery complications via simulation—ensuring competence to improve confidence,
3779,Correction: Corrigendum: Prediction of CYP2D6 phenotype from genotype across world populations,
3780,Improved therapeutic consistency and efficacy of mesenchymal stem cells expanded with chemically defined medium for systemic lupus erythematosus,
3781,Author Correction: The Apostasia genome and the evolution of orchids,
3782,Unconventional CD45RA+ memory CD8 T cells to control HIV infection during antiretroviral therapy,
3783,Correction: Whole exome sequencing reveals mutations in FAT1 tumor suppressor gene clinically impacting on peripheral T-cell lymphoma not otherwise specified,
3784,Effect of chemogenetic actuator drugs on prefrontal cortex-dependent working memory in nonhuman primates,"The most common chemogenetic neuromodulatory system, designer receptors exclusively activated by designer drugs (DREADDs), uses a non-endogenous actuator ligand to activate a modified muscarinic acetylcholine receptor that is insensitive to acetylcholine. It is crucial in studies using these systems to test the potential effects of DREADD actuators prior to any DREADD transduction, so that effects of DREADDs can be attributed to the chemogenetic system rather than the actuator drug, particularly in experiments using nonhuman primates. We investigated working memory performance after injections of three DREADD actuators, clozapine, olanzapine, and deschloroclozapine, in four male rhesus monkeys tested in a spatial delayed response task before any DREADD transduction took place. Performance at 0.1 mg/kg clozapine and 0.1 mg/kg deschloroclozapine did not differ from vehicle in any of the four subjects. 0.2 mg/kg clozapine impaired working memory function in three of the four monkeys. Two monkeys were impaired after 0.1 mg/kg olanzapine and two were impaired after 0.3 mg/kg deschloroclozapine. We speculate that the unique neuropharmacology of prefrontal cortex function makes the primate prefrontal cortex especially vulnerable to off-target effects of DREADD actuator drugs with affinity for endogenous monoaminergic receptor systems. These findings underscore the importance of within-subject controls for DREADD actuator drugs in the specific tasks under study to confirm that effects following DREADD receptor transduction are not owing to the actuator drug itself. They also suggest that off-target effects of DREADD actuators may limit translational applications of chemogenetic neuromodulation."
3785,Correction: The landscape of epilepsy-related GATOR1 variants,
3786,Correction: Integrative approach to sporadic Alzheimer’s disease: deficiency of TYROBP in cerebral Aβ amyloidosis mouse normalizes clinical phenotype and complement subnetwork molecular pathology without reducing Aβ burden,
3787,Correction: SSRIs target prefrontal to raphe circuits during development modulating synaptic connectivity and emotional behavior,
3788,"Correction: MYC-containing amplicons in acute myeloid leukemia: genomic structures, evolution, and transcriptional consequences",
3789,Development and validation of a measure of comprehension of genomic screening—negative results (CoG-NR),"To realize the promise of population genomic screening for rare medically actionable conditions, critical challenges in the return of normal/negative results must be understood and overcome. Our study objective was to assess the functioning of a new 13-item measure (CoG-NR) of understanding of and knowledge about normal/negative genomic screening results for three highly actionable conditions: Lynch Syndrome, Hereditary Breast and Ovarian Cancer, and Familial Hypercholesterolemia. Based on our prior research and expert review, we developed CoG-NR and tested how well it functioned using hypothetical scenarios in three Qualtrics surveys. We report on its psychometric properties and performance across the three different conditions. The measure performed similarly for the three conditions. Examinations of item difficulty, internal reliability, and differential item functioning indicate that the items perform well, with statistically significant positive correlations with genomic knowledge, health literacy, and objective numeracy. CoG-NR assesses understanding of normal/negative results for each of the conditions. The next step is to examine its performance among individuals who have actually undergone such tests, and subsequent use in clinical or research situations. The CoG-NR measure holds great promise as a tool to enhance benefits of population genomic screening by bringing to light the prevalence of incorrect interpretation of negative results."
3790,Comment on: ‘Recent advances in anterior chamber angle imaging’,
3791,Correction: Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer,
3792,Anthranilic acid from Ralstonia solanacearum plays dual roles in intraspecies signalling and inter-kingdom communication,"Quorum sensing (QS) signals are widely utilized by bacteria to regulate biological functions in response to cell population density. Previous studies have demonstrated that Ralstonia solanacearum employs two different types of QS systems. We report here that anthranilic acid controls important biological functions and the production of QS signals in R. solanacearum. It was demonstrated that the biosynthesis of anthranilic acid is mainly performed by TrpEG. The accumulation of anthranilic acid and the transcription of trpEG occur in a cell density-dependent manner in R. solanacearum. Both the anthranilic acid and TrpEG homologues are conserved in various bacterial species. Moreover, we show that Sporisorium scitamineum sexual mating and hypha formation are strongly inhibited by the addition of exogenous anthranilic acid. Our results suggest that anthranilic acid is important for the physiology of bacteria in addition to its role in inter-kingdom communication."
3793,Correction: Candidate-gene criteria for clinical reporting: diagnostic exome sequencing identifies altered candidate genes among 8% of patients with undiagnosed diseases,
3794,"Relationship between ocular involvement and clinical manifestations, laboratory findings, and coronary artery dilatation in Kawasaki disease","OBJECTIVES: To assess the incidence of ocular manifestations of Kawasaki disease (KD) in children and to evaluate the relationship between ocular manifestations and the other clinical manifestations, laboratory findings, and echocardiographic findings. METHODS: Complete ophthalmologic examination and echocardiography were performed in 36 patients with KD during the acute phase before starting the treatment. Clinical manifestations and laboratory data including white blood cell (WBC) count, neutrophil-to-lymphocyte ratio, platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were obtained from all the patients. All the clinical and laboratory findings were compared between the group with ocular involvement and the one without ocular involvement. RESULTS: The incidence of bilateral non-exudative conjunctivitis was 63.9%. It was significantly higher in patients with skin rashes (P < 0.05). The incidence of uveitis was 36.1%, which consisted primarily of grade 1+ or 2+ acute anterior uveitis. Neutrophil count and CRP levels were significantly higher in the uveitis group than in the group without uveitis (P < 0.05). Coronary artery dilatation showed significant correlation with uveitis (P < 0.05). Uveitis did not show a significant correlation with other clinical manifestations, ESR, ALT level, AST level, and platelet count (P > 0.05). CONCLUSION: In children with Kawasaki disease, uveitis is associated with coronary artery dilatation, higher neutrophil count, and higher CRP level."
3795,Alien ectomycorrhizal plants differ in their ability to interact with co-introduced and native ectomycorrhizal fungi in novel sites,"Alien plants represent a potential threat to environment and society. Understanding the process of alien plants naturalization is therefore of primary importance. In alien plants, successful establishment can be constrained by the absence of suitable fungal partners. Here, we used 42 independent datasets of ectomycorrhizal fungal (EcMF) communities associated with alien Pinaceae and Eucalyptus spp., as the most commonly introduced tree species worldwide, to explore the strategies these plant groups utilize to establish symbioses with EcMF in the areas of introduction. We have also determined the differences in composition of EcMF communities associated with alien ectomycorrhizal plants in different regions. While alien Pinaceae introduced to new regions rely upon association with co-introduced EcMF, alien Eucalyptus often form novel interactions with EcMF species native to the region where the plant was introduced. The region of origin primarily determines species composition of EcMF communities associated with alien Pinaceae in new areas, which may largely affect invasion potential of the alien plants. Our study shows that alien ectomycorrhizal plants largely differ in their ability to interact with co-introduced and native ectomycorrhizal fungi in sites of introduction, which may potentially affect their invasive potential."
3796,Retraction Note: Interferon-mediated antiviral activities of Angelica tenuissima Nakai and its active components,
3797,Correction: BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration,
3798,Prognostic factors for TB-associated uveitis in the Asia-Pacific Region: results of a modified Delphi survey,"BACKGROUND: Prognostic factors for TB-associated uveitis (TBU) remain mostly unknown, due to the challenges in interpretation of patient data. We present consensus list of prognostic factors for resolution of inflammation in TBU, by experts across the Asia-Pacific region. METHODS: We applied a modified Delphi technique to generate consensus on prognostic factors influencing the resolution of inflammation in TB-associated: anterior uveitis (AU), retinal vasculitis (RV), and multifocal serpiginoid choroiditis (MSC). The initial questionnaire was developed through a face-to-face meeting. Sixteen uveitis experts from eleven Asia-Pacific countries were included. A single investigator circulated the questionnaire electronically and received the responses. Participants scored each item on 4-point Likert scale, in three successive rounds. After each round, a number of items were reduced based on response, and summary of responses was provided to participants. At the end of Round 3, items were considered significant if they: (1) achieved a median ≥2, and interquartile range ≤1, and (2) ≥75% of the respondents agreed on whether the item was a positive or negative prognostic factor. RESULTS: Forty-two putative questionnaire items were considered. At the end of Rounds 3, 4, 9, and 8 items in AU, RV, and MSC, respectively, met significance criteria. These included duration of disease, previous corticosteroid/immunosuppressive therapy, co-existent HIV, disease-specific imaging features, multidrug resistant TB, and duration of anti-TB therapy. CONCLUSIONS: Consensus were achieved on multiple ocular and systemic factors that influence resolution of inflammation in TBU. These will form the groundwork for validation in prospective clinical trials."
3799,Erratum: Autophagy suppresses Ras-driven epithelial tumourigenesis by limiting the accumulation of reactive oxygen species,
3800,Deep learning-based behavioral analysis reaches human accuracy and is capable of outperforming commercial solutions,"To study brain function, preclinical research heavily relies on animal monitoring and the subsequent analyses of behavior. Commercial platforms have enabled semi high-throughput behavioral analyses by automating animal tracking, yet they poorly recognize ethologically relevant behaviors and lack the flexibility to be employed in variable testing environments. Critical advances based on deep-learning and machine vision over the last couple of years now enable markerless tracking of individual body parts of freely moving rodents with high precision. Here, we compare the performance of commercially available platforms (EthoVision XT14, Noldus; TSE Multi-Conditioning System, TSE Systems) to cross-verified human annotation. We provide a set of videos—carefully annotated by several human raters—of three widely used behavioral tests (open field test, elevated plus maze, forced swim test). Using these data, we then deployed the pose estimation software DeepLabCut to extract skeletal mouse representations. Using simple post-analyses, we were able to track animals based on their skeletal representation in a range of classic behavioral tests at similar or greater accuracy than commercial behavioral tracking systems. We then developed supervised machine learning classifiers that integrate the skeletal representation with the manual annotations. This new combined approach allows us to score ethologically relevant behaviors with similar accuracy to humans, the current gold standard, while outperforming commercial solutions. Finally, we show that the resulting machine learning approach eliminates variation both within and between human annotators. In summary, our approach helps to improve the quality and accuracy of behavioral data, while outperforming commercial systems at a fraction of the cost."
3801,Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers,"Glutamate neurotransmission is a prioritized target for antipsychotic drug development. Two metabotropic glutamate receptor 2/3 (mGluR2/3) agonists (pomaglumetad [POMA] and TS-134) were assessed in two Phase Ib proof of mechanism studies of comparable designs and using identical clinical assessments and pharmacoBOLD methodology. POMA was examined in a randomized controlled trial under double-blind conditions for 10-days at doses of 80 or 320 mg/d POMA versus placebo (1:1:1 ratio). The TS-134 trial was a randomized, single-blind, 6-day study of 20 or 60 mg/d TS-134 versus placebo (5:5:2 ratio). Primary outcomes were ketamine-induced changes in pharmacoBOLD in the dorsal anterior cingulate cortex (dACC) and symptoms reflected on the Brief Psychiatric Rating Scale (BPRS). Both trials were conducted contemporaneously. 95 healthy volunteers were randomized to POMA and 63 to TS-134. High-dose POMA significantly reduced ketamine-induced BPRS total symptoms within and between-groups (p < 0.01, d = −0.41; p = 0.04, d = −0.44, respectively), but neither POMA dose significantly suppressed ketamine-induced dACC pharmacoBOLD. In contrast, low-dose TS-134 led to moderate to large within and between group reductions in both BPRS positive symptoms (p = 0.02, d = −0.36; p = 0.008, d = −0.82, respectively) and dACC pharmacoBOLD (p = 0.004, d = −0.56; p = 0.079, d = −0.50, respectively) using pooled across-study placebo data. High-dose POMA exerted significant effects on clinical symptoms, but not on target engagement, suggesting a higher dose may yet be needed, while the low dose of TS-134 showed evidence of symptom reduction and target engagement. These results support further investigation of mGluR2/3 and other glutamate-targeted treatments for schizophrenia."
3802,A novel bacterial thiosulfate oxidation pathway provides a new clue about the formation of zero-valent sulfur in deep sea,"Zero-valent sulfur (ZVS) has been shown to be a major sulfur intermediate in the deep-sea cold seep of the South China Sea based on our previous work, however, the microbial contribution to the formation of ZVS in cold seep has remained unclear. Here, we describe a novel thiosulfate oxidation pathway discovered in the deep-sea cold seep bacterium Erythrobacter flavus 21–3, which provides a new clue about the formation of ZVS. Electronic microscopy, energy-dispersive, and Raman spectra were used to confirm that E. flavus 21–3 effectively converts thiosulfate to ZVS. We next used a combined proteomic and genetic method to identify thiosulfate dehydrogenase (TsdA) and thiosulfohydrolase (SoxB) playing key roles in the conversion of thiosulfate to ZVS. Stoichiometric results of different sulfur intermediates further clarify the function of TsdA in converting thiosulfate to tetrathionate ((−)O(3)S–S–S–SO(3)(−)), SoxB in liberating sulfone from tetrathionate to form ZVS and sulfur dioxygenases (SdoA/SdoB) in oxidizing ZVS to sulfite under some conditions. Notably, homologs of TsdA, SoxB, and SdoA/SdoB widely exist across the bacteria including in Erythrobacter species derived from different environments. This strongly indicates that this novel thiosulfate oxidation pathway might be frequently used by microbes and plays an important role in the biogeochemical sulfur cycle in nature."
3803,Erratum: Diurnal variation of urinary sodium-to-potassium ratio in free-living Japanese individuals,
3804,Erratum: miR-194-5p/BCLAF1 deregulation in AML tumorigenesis,
3805,The effect of sample size on polygenic hazard models for prostate cancer,"We determined the effect of sample size on performance of polygenic hazard score (PHS) models in prostate cancer. Age and genotypes were obtained for 40,861 men from the PRACTICAL consortium. The dataset included 201,590 SNPs per subject, and was split into training and testing sets. Established-SNP models considered 65 SNPs that had been previously associated with prostate cancer. Discovery-SNP models used stepwise selection to identify new SNPs. The performance of each PHS model was calculated for random sizes of the training set. The performance of a representative Established-SNP model was estimated for random sizes of the testing set. Mean HR(98/50) (hazard ratio of top 2% to average in test set) of the Established-SNP model increased from 1.73 [95% CI: 1.69–1.77] to 2.41 [2.40–2.43] when the number of training samples was increased from 1 thousand to 30 thousand. Corresponding HR(98/50) of the Discovery-SNP model increased from 1.05 [0.93–1.18] to 2.19 [2.16–2.23]. HR(98/50) of a representative Established-SNP model using testing set sample sizes of 0.6 thousand and 6 thousand observations were 1.78 [1.70–1.85] and 1.73 [1.71–1.76], respectively. We estimate that a study population of 20 thousand men is required to develop Discovery-SNP PHS models while 10 thousand men should be sufficient for Established-SNP models."
3806,"A randomised, prospective study of ‘off-the-shelf’ use of toric intraocular lenses for cataract patients with pre-existing corneal astigmatism in the NHS","BACKGROUND/OBJECTIVES: To compare visual and refractive outcomes of monofocal intraocular lenses (IOLs) with limbal relaxing incisions (LRI) with ‘off-the-shelf’ use of toric IOLs (TIOLs), with a fixed 2-dioptre cylinder (DC) correction, for cataract patients with pre-existing corneal astigmatism in a public-sector setting. SUBJECTS/METHODS: Seventy-seven patients (77 eyes, first treated eye) with visually significant cataract and pre-operative corneal astigmatism ≥2.00 DC were randomised to receive either ‘off-the-shelf’ TIOLs, with a fixed 2.00 DC cylinder correction (39 eyes), or monofocal IOLs (38 eyes) with LRIs. The concept of fixing the cylindrical correction was to minimise costs, allow a full TIOL bank to be available and eliminate the need for individual TIOL ordering. Outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA) and refraction. Astigmatic changes were evaluated using the Alpins vector method. RESULTS: Mean UDVA improved from logMAR 0.88 (SD 0.56)[~20/150] pre-operatively to 0.18 (SD 0.19)[~20/30] post-operatively in TIOL group, versus 0.82 (SD 0.55)[~20/130] to 0.27 (SD 0.15)[~20/40] in monofocal/LRI group (P = 0.02; 95% CI: −0.17, −0.01). Mean CDVA improved from logMAR 0.40 (SD 0.26)[~20/50] to 0.01 (SD 0.12)[~20/20] in TIOL group, and 0.41 (SD 0.38)[~20/40] to 0.06 (SD 0.12)[~20/25] in LRI group (P = 0.07; 95% CI: −0.11, 0.01). Average post-operative refractive cylinder in TIOL group was 1.35 DC (SD 0.84 DC) and in LRI group 1.91 DC (SD 1.07 DC) (P = 0.01; 95% CI: −1, −0.12). Mean difference vector magnitude was 1.92 DC (SD 1.08 DC) in LRI group and 1.37 DC (SD 0.84 DC) in TIOL group (P = 0.02; 95% CI: 0.11, 0.99). CONCLUSIONS: TIOLs with a fixed 2.00 DC correction during cataract surgery may improve UDVA, reduce post-operative cylinder and result in a more reliable astigmatic correction compared with monofocal IOLs with LRIs."
3807,Author Correction: Origin and evolution of the octoploid strawberry genome,
3808,Tear analysis as the next routine body fluid test,
3809,Correction: Corrigendum: Sources of discordance among germ-line variant classifications in ClinVar,
3810,Earlier parasite arrival reduces the repeatability of host adaptive radiation,"Although parasites are known to have various effects on their hosts, we know little about their role in the assembly of diversifying host populations. Using an experimental bacterium (Pseudomonas fluorescens SBW25)-bacteriophage (ϕ2) system, we show that earlier parasite arrival significantly reduced the repeatability of host diversification. Earlier parasite arrival amplified the priority effects associated with the stochastic emergence of novel SBW25 phenotypes, translating into greater historical contingency in SBW25 diversification. Our results highlight the important role of parasite-host interactions in driving host adaptive radiation."
3811,"Correction: Cultivation and characterization of Candidatus Nitrosocosmicus exaquare, an ammonia-oxidizing archaeon from a municipal wastewater treatment system",
3812,Correction: Population genomic screening of all young adults in a health-care system: a cost-effectiveness analysis,
3813,Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration,"Peripheral nerve injury (PNI), one of the most common concerns following trauma, can result in a significant loss of sensory or motor function. Restoration of the injured nerves requires a complex cellular and molecular response to rebuild the functional axons so that they can accurately connect with their original targets. However, there is no optimized therapy for complete recovery after PNI. Supplementation with exogenous growth factors (GFs) is an emerging and versatile therapeutic strategy for promoting nerve regeneration and functional recovery. GFs activate the downstream targets of various signaling cascades through binding with their corresponding receptors to exert their multiple effects on neurorestoration and tissue regeneration. However, the simple administration of GFs is insufficient for reconstructing PNI due to their short half‑life and rapid deactivation in body fluids. To overcome these shortcomings, several nerve conduits derived from biological tissue or synthetic materials have been developed. Their good biocompatibility and biofunctionality made them a suitable vehicle for the delivery of multiple GFs to support peripheral nerve regeneration. After repairing nerve defects, the controlled release of GFs from the conduit structures is able to continuously improve axonal regeneration and functional outcome. Thus, therapies with growth factor (GF) delivery systems have received increasing attention in recent years. Here, we mainly review the therapeutic capacity of GFs and their incorporation into nerve guides for repairing PNI. In addition, the possible receptors and signaling mechanisms of the GF family exerting their biological effects are also emphasized."
3814,Correction: Deficiency of calcium/calmodulin-dependent serine protein kinase disrupts the excitatory-inhibitory balance of synapses by downregulating GluN2B,
3815,Correction: The effect of NOTCH3 pathogenic variant position on CADASIL disease severity: NOTCH3 EGFr 1–6 pathogenic variant are associated with a more severe phenotype and lower survival compared with EGFr 7–34 pathogenic variant,
3816,Potential utilization of terrestrially derived dissolved organic matter by aquatic microbial communities in saline lakes,"Lakes receive large amounts of terrestrially derived dissolved organic matter (tDOM). However, little is known about how aquatic microbial communities interact with tDOM in lakes. Here, by performing microcosm experiments we investigated how microbial community responded to tDOM influx in six Tibetan lakes of different salinities (ranging from 1 to 358 g/l). In response to tDOM addition, microbial biomass increased while dissolved organic carbon (DOC) decreased. The amount of DOC decrease did not show any significant correlation with salinity. However, salinity influenced tDOM transformation, i.e., microbial communities from higher salinity lakes exhibited a stronger ability to utilize tDOM of high carbon numbers than those from lower salinity. Abundant taxa and copiotrophs were actively involved in tDOM transformation, suggesting their vital roles in lacustrine carbon cycle. Network analysis indicated that 66 operational taxonomic units (OTUs, affiliated with Alphaproteobacteria, Actinobacteria, Bacteroidia, Bacilli, Gammaproteobacteria, Halobacteria, Planctomycetacia, Rhodothermia, and Verrucomicrobiae) were associated with degradation of CHO compounds, while four bacterial OTUs (affiliated with Actinobacteria, Alphaproteobacteria, Bacteroidia and Gammaproteobacteria) were highly associated with the degradation of CHOS compounds. Network analysis further revealed that tDOM transformation may be a synergestic process, involving cooperation among multiple species. In summary, our study provides new insights into a microbial role in transforming tDOM in saline lakes and has important implications for understanding the carbon cycle in aquatic environments."
3817,Innate lymphoid cells: Potent early mediators of the host immune response during sepsis,
3818,"Erratum to: Health-exploring complexity: an interdisciplinary systems approach HEC2016: 28 August–2 September 2016, Munich, Germany",
3819,Prevalence and risk factors of childhood blepharoptosis in Koreans: the Korea National Health and Nutrition Examination Survey,"PURPOSE: Childhood blepharoptosis may cause cosmetic and functional problems in children, but there is a paucity of studies about its epidemiology. This study aimed to investigate the prevalence of childhood blepharoptosis and associated risk factors in a representative Korean population. METHODS: This cross-sectional nation-wide study analysed the data set acquired from the Korea National Health and Nutrition Examination Survey 2008–2012. A total of 8218 children aged 3–18 years were included. The prevalence of childhood blepharoptosis, defined as a margin reflex distance (MRD) of < 2 mm in either eye, was estimated, and the risk factors were identified using multivariate logistic regression analysis. RESULTS: The mean age of participants was 11.3 ± 0.1 years, and 52.8 ± 0.6% were boys. The overall prevalence of childhood blepharoptosis in Korea was 8.0% (95% CI, 6.9–9.1%). Boys exhibited a higher prevalence of blepharoptosis than girls at most of ages. Levator function increased with age in the normal general population. The proportion of subjects exhibiting MRD1 ≥ 4.0 mm also increased significantly with age (p < 0.001). Male gender, higher body mass index, and urban residency were significantly associated with childhood blepharoptosis. CONCLUSIONS: The prevalence of childhood blepharoptosis is higher in urban obese boys. The increase of levator function with age should be considered in evaluations of childhood ptosis."
3820,Digenic inheritance of subclinical variants in Noonan Syndrome patients: an alternative pathogenic model?,"Noonan syndrome (NS) is an autosomal-dominant disorder with variable expressivity and locus heterogeneity. Despite several RAS pathway genes were implicated in NS, 20–30% of patients remain without molecular diagnosis, suggesting the involvement of further genes or multiple mechanisms. Eight patients out of 60, negative for conventional NS mutation analysis, with heterogeneous NS phenotype were investigated by means of target resequencing of 26 RAS/MAPK pathway genes. A trio was further characterized by means of whole-exome sequencing. Protein modeling and in silico prediction of protein stability allowed to identify possible pathogenic RAS pathway variants in four NS patients. A new c.355T>C variant in LZTR1 was found in patient 43. Two patients co-inherited variants in LRP1 and LZTR1 (patient 53), or LRP1 and SOS1 genes (patient 67). The forth patient (56) carried a compound heterozygote of RASAL3 gene variants and also an A2ML1 variant. While these subclinical variants are singularly present in healthy parents, they co-segregate in patients, suggesting their addictive effect and supporting a digenic inheritance, as alternative model to a more common monogenic transmission. The ERK1/2 and SAPK/JNK activation state, assessed on immortalized lymphocytes from patients 53 and 67 showed highest phosphorylation levels compared to their asymptomatic parents. These findings together with the lack of their co-occurrence in the 1000Genomes database strengthen the hypothesis of digenic inheritance in a subset of NS patients. This study suggests caution in the exclusion of subclinical variants that might play a pathogenic role providing new insights for alternative hereditary mechanisms."
3821,Foraging postures are a potential communicative signal in female bonobos,"Body postures are essential in animal behavioural repertoires and their communicative role has been assessed in a wide array of taxa and contexts. Some body postures function as amplifiers, a class of signals that increase the detection likelihood of other signals. While foraging on the ground, bonobos (Pan paniscus) can adopt different crouching postures exposing more or less of their genital area. To our knowledge, their potential functional role in the sociosexual life of bonobos has not been assessed yet. Here we show, by analysing more than 2,400 foraging events in 21 captive bonobos, that mature females adopt a rear-exposing posture (forelimb-crouch) and do so significantly more often when their anogenital region is swollen than during the non-swollen phase. In contrast, mature males almost completely avoid this posture. Moreover, this strong difference results from a diverging ontogeny between males and females since immature males and females adopt the forelimb-crouch at similar frequencies. Our findings suggest that the forelimb-crouch posture may play a communicative role of amplification by enhancing the visibility of female sexual swellings, a conspicuous signal that is very attractive for both males and females. Given the high social relevance of this sexual signal, our study emphasizes that postural signalling in primates probably deserves more attention, even outside of reproductive contexts."
3822,Using an integrative machine learning approach utilising homology modelling to clinically interpret genetic variants: CACNA1F as an exemplar,"Advances in DNA sequencing technologies have revolutionised rare disease diagnostics and have led to a dramatic increase in the volume of available genomic data. A key challenge that needs to be overcome to realise the full potential of these technologies is that of precisely predicting the effect of genetic variants on molecular and organismal phenotypes. Notably, despite recent progress, there is still a lack of robust in silico tools that accurately assign clinical significance to variants. Genetic alterations in the CACNA1F gene are the commonest cause of X-linked incomplete Congenital Stationary Night Blindness (iCSNB), a condition associated with non-progressive visual impairment. We combined genetic and homology modelling data to produce CACNA1F-vp, an in silico model that differentiates disease-implicated from benign missense CACNA1F changes. CACNA1F-vp predicts variant effects on the structure of the CACNA1F encoded protein (a calcium channel) using parameters based upon changes in amino acid properties; these include size, charge, hydrophobicity, and position. The model produces an overall score for each variant that can be used to predict its pathogenicity. CACNA1F-vp outperformed four other tools in identifying disease-implicated variants (area under receiver operating characteristic and precision recall curves = 0.84; Matthews correlation coefficient = 0.52) using a tenfold cross-validation technique. We consider this protein-specific model to be a robust stand-alone diagnostic classifier that could be replicated in other proteins and could enable precise and timely diagnosis."
3823,Erratum: Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials,
3824,Response to ‘Comment on: ‘A new era for giant cell arteritis’’,
3825,Access to intraoperative tumour margin control: a survey of the British Oculoplastic Surgery Society,"BACKGROUND: Periocular malignancy is common and in most cases will undergo excision with pre-determined margins and subsequent histological examination. Intraoperative margin control (IOMC) modalities such as fast frozen section (FFS), fast paraffin (FP) and Mohs micrographic surgery (MMS) are being increasingly widely used, though there is a lack of information regarding utility. The aim of this study was to survey members of the British Oculoplastic Surgery Society (BOPSS) to determine attitudes and access to different modalities of IOMC. METHODS: A 12-question online survey was disseminated via an e-mail to full members of the BOPSS. The survey was hosted using Qualtrics software via the University of Sussex. RESULTS: The overall response rate was 64 of 165 (38.8%). MMS was readily available in a neighbouring trust to 23 of 64 respondents (35.9%). Seven respondents (10.9%) reported no regional access to MMS. Twenty-nine members had readily available access to FFS (45.3%) and 37 of 64 to FP (57.8%) in their own institution. There is variation in what tumour types would be considered appropriate for IOMC, though most thought clinically ill-defined (morphoeic) basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) should undergo one form of IOMC (90.6% and 81.3%, respectively). CONCLUSION: This study highlights variation in availability and utilisation of IOMC amongst oculoplastic surgeons and in different regions of the UK. While the exact place of IOMC in periocular tumour excision is debated, there is a consistent view that it should be available for some tumours. Greater consistency in provision may improve patient outcomes."
3826,BANK1 interacts with TRAF6 and MyD88 in innate immune signaling in B cells,"Evidence supports a possible role of BANK1 in innate immune signaling in B cells. In the present study, we investigated the interaction of BANK1 with two key mediators in interferon and inflammatory cytokine production, TRAF6 and MyD88. We revealed by coimmunoprecipitation (CoIP) analyses the binding of BANK1 with TRAF6 and MyD88, which were mediated by the BANK1 Toll/interleukin-1 receptor (TIR) domain. In addition, the natural BANK1–40C variant showed increased binding to MyD88. Next, we demonstrated in mouse splenic B cells that BANK1 colocalized with Toll-like receptor (TLR) 7 and TLR9 and that after stimulation with TLR7 and TLR9 agonists, the number of double-positive BANK1–TLR7, –TLR9, –TRAF6, and –MyD88 cells increased. Furthermore, we identified five TRAF6-binding motifs (BMs) in BANK1 and confirmed by point mutations and decoy peptide experiments that the C-terminal domain of BANK1-full-length (-FL) and the N-terminal domain of BANK1–Delta2 (-D2) are necessary for this binding. Functionally, we determined that the absence of the TIR domain in BANK1–D2 is important for its lysine (K)63-linked polyubiquitination and its ability to produce interleukin (IL)-8. Overall, our study describes a specific function of BANK1 in MyD88–TRAF6 innate immune signaling in B cells, clarifies functional differences between the two BANK1 isoforms and explains for the first time a functional link between autoimmune phenotypes including SLE and the naturally occurring BANK1–40C variant."
3827,"Response to ‘Comment on: ‘You have got dry macular degeneration, end of story’: a qualitative study into the experience of living with non-neovascular age-related macular degeneration’",
3828,Correction to: 2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference,
3829,Correction to: Trends in erectile dysfunction research from 2008 to 2018: a bibliometric analysis,
3830,The tsAPOBEC3 proteins restrict HBV replication and may limit the establishment of persistent infection in tree shrews,
3831,Correction: Novel evidence that extracellular nucleotides and purinergic signaling induce innate immunity-mediated mobilization of hematopoietic stem/progenitor cells,
3832,Nesfatin-1 puts the brakes on reward-based feeding,
3833,Correction: The Relative Contribution of Metabolic and Structural Abnormalities to Diastolic Dysfunction in Obesity,
3834,Correction: USP17 mediates macrophage-promoted inflammation and stemness in lung cancer cells by regulating TRAF2/TRAF3 complex formation,
3835,"The Royal College of Ophthalmologists’ National Ophthalmology Database study of cataract surgery: Report 7, immediate sequential bilateral cataract surgery in the UK: Current practice and patient selection","BACKGROUND: Cataract extraction is the most frequently performed surgical intervention in the world and demand is rising due to an ageing demography. One option to address this challenge is to offer selected patients immediate sequential bilateral cataract surgery (ISBCS). This study aims to investigate patient and operative characteristics for ISBCS and delayed bilateral cataract surgery (DSCS) in the UK. METHODS: Data were analysed from the Royal College of Ophthalmologists’ National Ophthalmology Database Audit (NOD) of cataract surgery. Eligible patients were those undergoing bilateral cataract extraction from centres with a record of at least one ISBCS operation between 01/04/2010 and 31/08/2018. Variable frequency comparison was undertaken with chi-square tests. RESULTS: During the study period, 1073 patients had ISBCS and 248,341 DSCS from 73 centres. A higher proportion of ISBCS patients were unable to lie flat (11.3% vs. 1.8%; p < 0.001), unable to cooperate (9.7% vs. 2.7%; p < 0.001); underwent general anaesthesia (58.7% vs. 6.6% (p < 0.001)); had brunescent/white/mature cataracts (odds ratio (OR) 5.118); no fundal view/vitreous opacities (OR 8.381); had worse pre-operative acuity 0.60 LogMAR ISBCS vs. 0.50 (first) and 0.40 (second eye) DSCS and were younger (mean ages, 71.5 vs. 75.6 years; p < 0.001). Posterior capsular rupture (PCR) rates adjusted for case complexity were comparable (0.98% ISBCS and 0.78% DSCS). CONCLUSIONS: ISBCS was performed on younger patients, with difficulty cooperating and lying flat, worse pre-operative vision, higher rates of known PCR risk factors and more frequent use of general anaesthesia than DSCS in centres recorded on NOD."
3836,"Erratum: Fluoxetine effects on molecular, cellular and behavioral endophenotypes of depression are driven by the living environment",
3837,Publisher Correction: A patient-level pooled analysis of treatment-shortening regimens for drug-susceptible pulmonary tuberculosis,
3838,Correction to: Abstracts: 31(st) European Congress of Pathology,
3839,Erratum: Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats,
3840,Cancer Surveillance Guideline for individuals with PTEN hamartoma tumour syndrome,"PTEN hamartoma tumour syndrome is a diverse multi-system disorder predisposing to the development of hamartomatous growths, increasing risk of breast, thyroid, renal cancer, and possibly increasing risk of endometrial cancer, colorectal cancer and melanoma. There is no international consensus on cancer surveillance in PHTS and all current guidelines are based on expert opinion. A comprehensive literature review was undertaken and guidelines were developed by clinicians with expertise from clinical genetics, gynaecology, endocrinology, dermatology, radiology, gastroenterology and general surgery, together with affected individuals and their representatives. Recommendations were put forward for surveillance for breast, thyroid and renal cancers. Limited recommendations were developed for other sites including endometrial, colon and skin. The proposed cancer surveillance recommendations for PHTS require a coordinated multidisciplinary approach and significant patient commitment. The evidence base for cancer surveillance in this guideline are limited, emphasising the need for prospective evaluation of the effectiveness of surveillance in the PHTS population."
3841,A novel case and review of paediatric Horner syndrome,
3842,Correction to: Bone morphogenetic protein 2 is a depot-specific regulator of human adipogenesis,
3843,Erratum: A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence,
3844,Publisher Correction: Image Data Resource: a bioimage data integration and publication platform,
3845,Erratum to: JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects,
3846,Correction: TANGO2: expanding the clinical phenotype and spectrum of pathogenic variants,
3847,Glutamatergic hypo-function in the left superior and middle temporal gyri in early schizophrenia: a data-driven three-dimensional proton spectroscopic imaging study,"Proton magnetic resonance spectroscopy ((1)H-MRS) studies have examined glutamatergic abnormalities in schizophrenia, mostly in single voxels. Though the critical brain nodes remain unknown, schizophrenia involves networks with broad abnormalities. Hence, glutamine plus glutamate (Glx) and other metabolites were examined with whole-brain (1)H-MRS, in early schizophrenia. Three dimensional (1)H-MRS was acquired in young schizophrenia subjects (N = 36, 19 antipsychotic-naïve and 17 antipsychotic-treated) and healthy controls (HC, N = 29). Glx (as well as N-acetylaspartate, choline, myo-inositol and creatine) group contrasts from all individual voxels that met spectral quality, were analyzed in common brain space, followed by cluster-corrected level alpha-value (CCLAV ≤ 0.05). Schizophrenia subjects had lower Glx in the left superior (STG) and middle temporal gyri (16 voxels, CCLAV = 0.04) and increased creatine in two clusters involving left temporal, parietal and occipital regions (32, and 18 voxels, CCLAV = 0.02 and 0.04, respectively). Antipsychotic-treated and naïve patients (vs HC) had similar Glx reductions (8/16 vs 10/16 voxels respectively, but CCLAV’s > 0.05). However, creatine was higher in antipsychotic-treated vs HC’s in a larger left hemisphere cluster (100 voxels, CCLAV = 0.01). Also in treated patients, choline was increased in left middle frontal gyrus (18 voxels, CCLAV = 0.04). Finally in antipsychotic-naive patients, NAA was reduced in right frontal gyri (19 voxels, CCLAV = 0.05) and myo-inositol was reduced in the left cerebellum (34 voxels, CCLAV = 0.02). We conclude that data-driven spectroscopic brain examination supports that reductions in Glx in the left STG may be critical to the pathophysiology of schizophrenia. Postmortem and neuromodulation schizophrenia studies focusing on left STG, may provide critical mechanistic and therapeutic advancements, respectively."
3848,Author Correction: Telemedicine — maintaining quality during times of transition,
3849,Alternative Checkpoints as Targets for Immunotherapy,"PURPOSE OF REVIEW: Immunotherapy has shown an unprecedented response in treatment of tumors. However, challenges such as lack of cytotoxic lymphocytes to mount an immune response or development of resistance to therapy can limit efficacy. Here, we discuss alternative checkpoints that can be targeted to improve cytotoxic lymphocyte function while harnessing other components of the immune system. RECENT FINDINGS: Blockade of alternative checkpoints has improved anti-tumor immunity in mouse models and is being tested clinically with encouraging findings. In addition to modulating T cell function directly, alternative checkpoints can also regulate activity of myeloid cells and regulatory T cells to affect anti-tumor response. SUMMARY: Combination of immune checkpoint inhibitors can improve treatment of tumors by activating multiple arms of the immune system."
3850,Optical coherence tomography angiography (OCTA) applications in ocular oncology,"Optical coherence tomography angiography (OCTA) is a revolutionary method in the visualization of the vascular system in different retinal and choroidal layers. During the last 4 years since the commercial availability of different OCTA devices, attempts have been made to utilize this technology in various aspects of ocular oncology from the differentiation of benign and malignant lesions to assisting in evaluation of post-treatment complications, such as radiation retinopathy. However, current OCTA technology is restricted by various artefacts and inherent limitations, some of which are more pronounced in the presence of elevated tumoural lesions. Imminent advancements in OCTA systems and image acquisition processes promise a great potential for application of OCTA in ocular oncology."
3851,Erratum: Prediction of human population responses to toxic compounds by a collaborative competition,
3852,Correction to: Abstracts: 31st European Congress of Pathology,
3853,Correction: Increasing the bactofection capacity of a mammalian expression vector by removal of the f1 ori,
3854,Publisher Correction: The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group,
3855,Observation of topical tacrolimus on high-risk penetrating keratoplasty patients: a randomized clinical trial study,"BACKGROUND/OBJECTIVES: To evaluate the clinical efficacy of topical tacrolimus 0.1% and cyclosporine 1% on high-risk penetrating keratoplasty (PKP) patients. SUBJECTS/METHODS: A series of 49 high-risk PKP patients (49 eyes), 20 males, 29 females from the age of 4 months to 74 years of age with the mean of 32.5 from 2012 to 2017 were recruited in this study. The patients were randomly divided into two groups by receiving either topical tacrolimus 0.1% or cyclosporine 1% respectively. Twenty five patients were treated with topical tacrolimus 0.1% and 24 patients with topical cyclosporine 1%. The traditional baseline management on these two groups were Tobramycin and Dexamethasone eye drops in the first 3 weeks and then tapered off. Clinical procedures and postoperative follow-up were documented. RESULTS: After 6–54 months follow-up, with the average of 24 months, 11 of 24 high-risk patients (11 eyes) had graft rejection, the rejection rate was 45.8% in topical cyclosporine 1% group. The rejections occurred from 35 days to 20 months after PKP. Three patients had irreversible rejection. On topical tacrolimus 0.1% group, the rejection occurred in four patients (four eyes) with rejection rate of 16%, and no irreversible rejection was observed. The graft rejection episodes were documented between 23 days and 24 months. As compared with the topical cyclosporine 1%, topical tacrolimus 0.1%, a key immunosuppressant, significantly decreased corneal graft rejection rate (p = 0.02). CONCLUSIONS: Topical tacrolimus 01% on high-risk PKP patients significantly prevented corneal graft rejection, and it had less adverse effects and was very safe to high-risk patients as to topical cyclosporine 1%. Further case controlled randomized clinical trial studies are needed to establish the best management option for these high-risk patients."
3856,Variants of innate CD8(+) T cells are associated with Grip2 and Klf15 genes,
3857,Retraction Note: Resveratrol rescues hyperglycemia-induced endothelial dysfunction via activation of Akt,
3858,Erratum: A high-salt diet enhances leukocyte adhesion in association with kidney injury in young Dahl salt-sensitive rats,
3859,Evaluation of medical and surgical decompression in patients with dysthyroid optic neuropathy,"PURPOSE: To evaluate the effectiveness of steroid-pulse therapy and three-wall orbital decompression in patients with dysthyroid optic neuropathy (DON). METHODS: Twenty-five patients (46 eyes) with a diagnosis of DON between 2008 and 2015 were included in the study. The first group (7 patients, 16 eyes) consisted of patients with a steroid-pulse treatment only and the second group (18 patients, 30 eyes) included patients with medical and surgical decompression. RESULTS: Twenty patients were female; five patients were male. After the diagnosis of DON, all patients were treated with steroid-pulse treatment (intravenous 500 mg prednisolon twice/week for 4 weeks, 250 mg twice/week for 2 weeks) as a first-line treatment (medical decompression). In 30 eyes (18 patients) out of 46 eyes, (25 patients) an orbital decompression was needed to preserve the optic nerve function. In those therapy-resistant cases (surgical decompression group), the orbital decompression led to statistically significant improvements in best-corrected visual acuity (BCVA), protan and tritan value of the color vision (p = 0.007, p < 0.0001, p = 0.019, respectively, comparison of first visit to last visit). CONCLUSION: According to our data, the mild cases of DON with better initial visual acuity (in our case series mean: 0.3 logMAR) seem to respond well to steroid treatment. However, therapy-resistant cases with an impaired initial BCVA (in our case series, mean: 0.6 logMAR) seem to need the surgery to preserve the optic nerve function. In conclusion, this retrospective study confirms the effectiveness of surgical decompression in therapy-resistant cases of DON."
3860,Inflammasome genetics and complex diseases: a comprehensive review,"The inflammasome is a cytoplasmic multiprotein complex responsible for the activation of inflammatory caspases (caspase-1, -4, and -5) in response to pathogen- and/or damage-associated molecular patterns or to homeostasis-altering molecular pathways, and for the consequent release of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-18. Taking in account the complexity of inflammasome activation and that several regulatory steps are involved in maintaining its physiologic role in homeostasis and innate immune response, it does not surprise that several genetic variants in inflammasome components have been associated with common pathologies in the general population, such as autoimmune disorders, cardiovascular diseases, obesity and associated metabolic syndrome, neurodegenerative diseases, and cancer. Moreover, the susceptibility to infectious agents and/or to develop severe complications during infections also has been related to inflammasome genetics. In this work, we revised genetic association studies about polymorphisms of main inflammasome genes in sterile as well as infectious diseases, trying to depict the genetic contribution of inflammasome in disease pathogenesis."
3861,Warning wristbands for patients with intra-ocular gas,
3862,Correction: High-risk additional chromosomal abnormalities at low blast counts herald death by CML,
3863,Correction: Healthy dietary indices and risk of depressive outcomes: a systematic review and meta-analysis of observational studies,
3864,Erratum: Wnt7a is a novel inducer of β-catenin-independent tumor-suppressive cellular senescence in lung cancer,
3865,"Erratum zu: Epidemiologie des Ebolafiebers und anderer, in Deutschland seltener hochkontagiöser, lebensbedrohlicher Erkrankungen",
3866,Erratum to: Is this critically ill patient immunocompromised?,
3867,Correction to: Abstracts: 31(st) European Congress of Pathology,
3868,Correction to: Schistosomiasis—from immunopathology to vaccines,
3869,Correction to: Atorvastatin-loaded solid lipid nanoparticles as eye drops: proposed treatment option for age-related macular degeneration (AMD),
3870,Elevated fatty acid amide hydrolase in the prefrontal cortex of borderline personality disorder: a [(11)C]CURB positron emission tomography study,"Amygdala-prefrontal cortex (PFC) functional impairments have been linked to emotion dysregulation and aggression in borderline personality disorder (BPD). Fatty acid amide hydrolase (FAAH), the major catabolic enzyme for the endocannabinoid anandamide, has been proposed as a key regulator of the amygdala-PFC circuit that subserves emotion regulation. We tested the hypothesis that FAAH levels measured with [(11)C]CURB positron emission tomography in amygdala and PFC would be elevated in BPD and would relate to hostility and aggression. Twenty BPD patients and 20 healthy controls underwent FAAH genotyping (rs324420) and scanning with [(11)C]CURB. BPD patients were medication-free and were not experiencing a current major depressive episode. Regional differences in [(11)C]CURB binding were assessed using multivariate analysis of covariance with PFC and amygdala [(11)C]CURB binding as dependent variables, diagnosis as a fixed factor, and sex and genotype as covariates. [(11)C]CURB binding was marginally elevated across the PFC and amygdala in BPD (p = 0.08). In a priori selected PFC, but not amygdala, [(11)C]CURB binding was significantly higher in BPD (11.0%, p = 0.035 versus 10.6%, p = 0.29). PFC and amygdala [(11)C]CURB binding was positively correlated with measures of hostility in BPD (r > 0.4; p < 0.04). This study is the first to provide preliminary evidence of elevated PFC FAAH binding in any psychiatric condition. Findings are consistent with the model that lower endocannabinoid tone could perturb PFC circuitry that regulates emotion and aggression. Replication of these findings could encourage testing of FAAH inhibitors as innovative treatments for BPD."
3871,"Erratum to: The Intensive Care Global Study on Severe Acute Respiratory Infection (IC‑GLOSSARI): a multicenter, multinational, 14-day inception cohort study",
3872,The novel cereblon modulator CC-885 inhibits mitophagy via selective degradation of BNIP3L,"Mitophagy is a degradative pathway that mediates the degradation of the entire mitochondria, and defects in this process are implicated in many diseases including cancer. In mammals, mitophagy is mediated by BNIP3L (also known as NIX) that is a dual regulator of mitochondrial turnover and programmed cell death pathways. Acute myeloid leukemia (AML) cells with deficiency of BNIP3L are more sensitive to mitochondria-targeting drugs. But small molecular inhibitors for BNIP3L are currently not available. Some immunomodulatory drugs (IMiDs) have been proved by FDA for hematologic malignancies, however, the underlining molecular mechanisms are still elusive, which hindered the applications of BNIP3L inhibition for AML treatment. In this study we carried out MS-based quantitative proteomics analysis to identify the potential neosubstrates of a novel thalidomide derivative CC-885 in A549 cells. In total, we quantified 5029 proteins with 36 downregulated in CRBN(+/+) cell after CC-885 administration. Bioinformatic analysis showed that macromitophagy pathway was enriched in the negative pathway after CC-885 treatment. We further found that CC-885 caused both dose- and time-dependent degradation of BNIP3L in CRBN(+/+), but not CRBN(−/−) cell. Thus, our data uncover a novel role of CC-885 in the regulation of mitophagy by targeting BNIP3L for CRL4CRBN E3 ligase-dependent ubiquitination and degradation, suggesting that CC-885 could be used as a selective BNIP3L degradator for the further investigation. Furthermore, we demonstrated that CC-885 could enhance AML cell sensitivity to the mitochondria-targeting drug rotenone, suggesting that combining CC-885 and mitochondria-targeting drugs may be a therapeutic strategy for AML patients."
3873,Publisher Correction: Systematic review of defibrotide studies in the treatment of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS),
3874,Correction: A molecular portrait of epithelial–mesenchymal plasticity in prostate cancer associated with clinical outcome,
3875,"Ritanserin blocks Ca(V)1.2 channels in rat artery smooth muscles: electrophysiological, functional, and computational studies","Ca(V)1.2 channel blockers or 5-HT(2) receptor antagonists constitute effective therapy for Raynaud’s syndrome. A functional link between the inhibition of 5-HT(2) receptors and Ca(V)1.2 channel blockade in arterial smooth muscles has been hypothesized. Therefore, the effects of ritanserin, a nonselective 5-HT(2) receptor antagonist, on vascular Ca(V)1.2 channels were investigated through electrophysiological, functional, and computational studies. Ritanserin blocked Ca(V)1.2 channel currents (I(Ca1.2)) in a concentration-dependent manner (K(r) = 3.61 µM); I(Ca1.2) inhibition was antagonized by Bay K 8644 and partially reverted upon washout. Conversely, the ritanserin analog ketanserin (100 µM) inhibited I(Ca1.2) by ~50%. Ritanserin concentration-dependently shifted the voltage dependence of the steady-state inactivation curve to more negative potentials (K(i) = 1.58 µM) without affecting the slope of inactivation and the activation curve, and decreased I(Ca1.2) progressively during repetitive (1 Hz) step depolarizations (use-dependent block). The addition of ritanserin caused the contraction of single myocytes not yet dialyzed with the conventional method. Furthermore, in depolarized rings, ritanserin, and to a lesser extent, ketanserin, caused a concentration-dependent relaxation, which was antagonized by Bay K 8644. Ritanserin and ketanserin were docked at a region of the Ca(V)1.2 α(1C) subunit nearby that of Bay K 8644; however, only ritanserin and Bay K 8644 formed a hydrogen bond with key residue Tyr-1489. In conclusion, ritanserin caused in vitro vasodilation, accomplished through the blockade of Ca(V)1.2 channels, which was achieved preferentially in the inactivated and/or resting state of the channel. This novel activity encourages the development of ritanserin derivatives for their potential use in the treatment of Raynaud’s syndrome."
3876,Lowered endogenous mu-opioid receptor availability in subclinical depression and anxiety,"Major depressive disorder is associated with lowered mood, anxiety, anhedonia, sleep problems, and cognitive impairments. Many of these functions are regulated by μ-opioid receptor (MOR) system. Preclinical, in vivo, and post-mortem studies have however yielded inconclusive results regarding the role of the MOR in depression and anxiety. Moreover, it is not known whether alterations in MOR are already present in subclinical depression and anxiety. In a large-scale retrospective cross-sectional study we pooled data from 135 (113 males and 22 females) healthy subjects whose brain’s MOR availability was measured with positron emission tomography (PET) using an agonist radioligand [(11)C]carfentanil that has high affinity for MORs. Depressive and anxious symptomology was addressed with BDI-II and STAI-X questionnaires, respectively. Both anxiety and depression scores in the subclinical range were negatively associated with MOR availability in cortical and subcortical areas, notably in amygdala, hippocampus, ventral striatum, and orbitofrontal and cingulate cortices. We conclude that dysregulated MOR availability is involved in altered mood and pathophysiology of depression and anxiety disorders."
3877,Brolucizumab and immunogenicity,
3878,Erratum to: Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer’s Disease,
3879,Correction: Estimating the burden and economic impact of pediatric genetic disease,
3880,Erratum to: Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies,
3881,Differential DNA methylation in allergen-specific immunotherapy of asthma,
3882,Correction: Sequencing as a first-line methodology for cystic fibrosis carrier screening,
3883,Correction: Active PLK1-driven metastasis is amplified by TGF-β signaling that forms a positive feedback loop in non-small cell lung cancer,
3884,"Erratum: Strains, functions and dynamics in the expanded Human Microbiome Project",
3885,What do we do and how do we do it? Assessing genetic counselling in the modern era,
3886,Publisher Correction: Precision and accuracy of single-molecule FRET measurements—a multi-laboratory benchmark study,
3887,Correction to: The landscape of epilepsy-related GATOR1 variants,
3888,Assessing the stability of biobank donor preferences regarding sample use: evidence supporting the value of dynamic consent,"Dynamic consent has been proposed as a strategy for addressing the limitations of traditional, broad consent for biobank participation. Although the argument for dynamic consent has been made on theoretical grounds, empirical studies evaluating the potential utility of dynamic consent are needed to enhance deliberations about the merits of dynamic consent. Few studies have assessed such considerations as whether donor preferences may change over time or if participants would use a dynamic consent mechanism to modify preferences when they change. We administered a 66-item survey to participants in a large DNA biobank. The survey sought to gauge the stability of donor preferences specified at the time of biobank enrollment, specifically the stability of donors’ preference regarding posthumous availability of biospecimens to next-of-kin. We received 1164 completed surveys for a response rate of 72%. Forty percent of respondents indicated a preference regarding sample availability on the survey (T2) that was inconsistent with the preference they had expressed when they enrolled in the biobank (T1). Most (94%) individuals with inconsistent preferences regarding sample availability had initially restricted sample availability at T1 but were comfortable with broader availability when asked at the time of the survey (T2). Our findings demonstrate that preferences regarding sample use expressed at the time of enrollment in a DNA biobank may not be reliable indicators of donor preferences over time. These findings lend empirical support to the case for a dynamic consent model in which biobank participants are approached over time to clarify their views regarding sample use."
3889,Management of information within Portuguese families with Huntington disease: a transgenerational process for putting the puzzle together,"Huntington disease (HD) is a rare progressive neurological disease, with no cure, inherited in an autosomal dominant fashion, significantly impacting family relations, health and well-being. So far, no studies have reported how Portuguese families deal with information about HD, from a transgenerational perspective. This qualitative study aims to fill in that gap, and focuses on how families acquire knowledge about HD and management of information within the family and in their social relationships. The study adopted semi-structured interviews with 10 participants from HD families. Interviews were transcribed and analysed thematically. Findings suggested that management of information in the family started with the search for a diagnosis in an affected family member. Diagnosis led to a process of “making sense of HD in the family”, which activated a transgenerational process to understand HD in the family context, marked by improved awareness and different ways family members manage it (closedness and openness). These results should be relevant for health-care professionals, bringing further insight into the process of acquiring knowledge about HD, and highlighting the relevance of continued efforts for enhanced pre- and post-test counselling and ongoing support to the HD families."
3890,Opioid antagonists are associated with a reduction in the symptoms of schizophrenia: a meta-analysis of controlled trials,"Current treatments for the symptoms of schizophrenia are only effective for positive symptoms in some individuals, and have considerable side effects that impact compliance. Thus, there is a need to investigate the efficacy of other compounds in treating both positive and negative symptoms. We conducted a meta-analysis of English language placebo-controlled clinical trials of naloxone, naltrexone, nalmefene, and buprenorphine in patients with schizophrenia to determine whether opioid antagonists have therapeutic efficacy on positive, negative, total, or general symptoms. We searched online databases Ovid Medline and PsychINFO, PubMed, EMBASE, Scopus, Cochrane library/CENTRAL, Web of Science, and Google Scholar from 1970 through February 2019. Following PRISMA guidelines, Hedges g was calculated for each study. Primary study outcomes were the within-subject change on any symptom assessment scale for positive, negative, total, or general symptoms of schizophrenia between active drug and placebo conditions. Thirty studies were included with 434 total patients. We found a significant effect of all drugs on all scales combined with both a standard random effects model: (g = 0.26; P = 0.02; k = 22; CI = 0.03–0.49) and a more inclusive bootstrap model: (g = 0.26; P = 0.0002; k = 30; CI = 0.11–0.51) and a significant effect on total scales with the bootstrap model (g = 0.25288; P = 0.015; k = 19; CI = 0.04–0.35). We also observed a significant effect of all drugs on all positive scales combined with both the random effects (g = 0.33; P = 0.015; k = 17; CI = 0.07–0.60) and bootstrap models (g = 0.32; P < 0.0001; k = 21; CI = 0.13–1.38). This evidence provides support for further testing in randomized clinical trials of a new class of non-D2-receptor drugs, based on opioid mechanisms, for the treatment of positive and negative symptoms of schizophrenia."
3891,Association of congenital cardiovascular malformation and neuropsychiatric phenotypes with 15q11.2 (BP1–BP2) deletion in the UK Biobank,"Deletion of a non-imprinted 500kb genomic region at chromosome 15q11.2, between breakpoints 1 and 2 of the Prader–Willi/Angelman locus (BP1–BP2 deletion), has been associated in previous studies with phenotypes including congenital cardiovascular malformations (CVM). Previous studies investigating association between BP1–BP2 deletion and CVM have tended to recruit cases with rarer and more severe CVM phenotypes; the impact of CVM on relatively unselected population cohorts, anticipated to contain chiefly less severe but commoner CHD phenotypes, is relatively unexplored. More precisely defining the impact of BP1–BP2 deletion on CVM risk could be useful to guide genetic counselling, since the deletion is frequently identified in the neurodevelopmental clinic. Using the UK Biobank (UKB) cohort of ~500,000 individuals, we identified individuals with CVM and investigated the association with deletions at the BP1–BP2 locus. In addition, we assessed the association of BP1–BP2 deletions with neuropsychiatric diagnoses, cognitive function and academic achievement. Cases of CVM had an increased prevalence of the deletion compared with controls (0.64%; OR = 1.73 [95% CI 1.08–2.75]; p = 0.03), as did those with neuropsychiatric diagnoses (0.68%; OR = 1.84 [95% CI 1.23–2.75]; p = 0.004). We conclude that BP1–BP2 deletion moderately increases the risk of the generally milder, but commoner, CVM phenotypes seen in this unselected population, in addition to its previously demonstrated association in case/control studies ascertained for CVM."
3892,Δ(9)-Tetrahydrocannabinol (THC) impairs visual working memory performance: a randomized crossover trial,"With the increasing prevalence of legal cannabis use and availability, there is an urgent need to identify cognitive impairments related to its use. It is widely believed that cannabis, or its main psychoactive component Δ(9)-tetrahydrocannabinol (THC), impairs working memory, i.e., the ability to temporarily hold information in mind. However, our review of the literature yielded surprisingly little empirical support for an effect of THC or cannabis on working memory. We thus conducted a study with three main goals: (1) quantify the effect of THC on visual working memory in a well-powered sample, (2) test the potential role of cognitive effects (mind wandering and metacognition) in disrupting working memory, and (3) demonstrate how insufficient sample size and task duration reduce the likelihood of detecting a drug effect. We conducted two double-blind, randomized crossover experiments in which healthy adults (N = 23, 23) performed a reliable and validated visual working memory task (the “Discrete Whole Report task”, 90 trials) after administration of THC (7.5 and/or 15 mg oral) or placebo. We also assessed self-reported “mind wandering” (Exp 1) and metacognitive accuracy about ongoing task performance (Exp 2). THC impaired working memory performance (d = 0.65), increased mind wandering (Exp 1), and decreased metacognitive accuracy about task performance (Exp 2). Thus, our findings indicate that THC does impair visual working memory, and that this impairment may be related to both increased mind wandering and decreased monitoring of task performance. Finally, we used a down-sampling procedure to illustrate the effects of task length and sample size on power to detect the acute effect of THC on working memory."
3893,Cheaters shape the evolution of phenotypic heterogeneity in Bacillus subtilis biofilms,"Biofilms are closely packed cells held and shielded by extracellular matrix composed of structural proteins and exopolysaccharides (EPS). As matrix components are costly to produce and shared within the population, EPS-deficient cells can act as cheaters by gaining benefits from the cooperative nature of EPS producers. Remarkably, genetically programmed EPS producers can also exhibit phenotypic heterogeneity at single-cell level. Previous studies have shown that spatial structure of biofilms limits the spread of cheaters, but the long-term influence of cheating on biofilm evolution is not well understood. Here, we examine the influence of EPS nonproducers on evolution of matrix production within the populations of EPS producers in a model biofilm-forming bacterium, Bacillus subtilis. We discovered that general adaptation to biofilm lifestyle leads to an increase in phenotypical heterogeneity of eps expression. However, prolonged exposure to EPS-deficient cheaters may result in different adaptive strategy, where eps expression increases uniformly within the population. We propose a molecular mechanism behind such adaptive strategy and demonstrate how it can benefit the EPS producers in the presence of cheaters. This study provides additional insights on how biofilms adapt and respond to stress caused by exploitation in long-term scenario."
3894,Correction: Corrigendum: Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea,
3895,Comment on: ‘A new era for giant cell arteritis’,
3896,Author Correction: Nitrogen-fixing populations of Planctomycetes and Proteobacteria are abundant in surface ocean metagenomes,
3897,"Publisher Correction: Delphine Parrott, a pioneer of T cell biology",
3898,Neurodegeneration in Alzheimer’s disease and glaucoma: overlaps and missing links,"The eye is said to be the window into the brain. Alzheimer’s disease (AD) and glaucoma both being diseases of the elderly, have several epidemiological and histological overlaps in pathogenesis. Both these diseases are neurodegenerative conditions. Over the years, a consensus has developed that both may be two ends of a singular spectrum of diseases. Epidemiological studies have shown that more Alzheimer’s patients may be suffering from glaucoma than general healthy population. Retinal ganglion cell damage is a characteristic of both diseases, along with discovery of amyloid-β and tau protein deposition in the retina and aqueous humor of eye. The latter two proteins are known to be pathognomonic of AD. Other pathways such as the insulin receptor pathway also seem to be affected in both diseases similarly. In spite of these overlaps, there are few missing links which still need more evidence, namely, intraocular pressure mechanisms, cerebrospinal fluid pressure and trans-lamina cribrosa pressure gradients, vascular autoregulation factors, etc. Several factors point towards a common pathogenesis at some level for both diseases and prospective studies are necessary to study the natural course of both diseases."
3899,AAV-mediated FOXG1 gene editing in human Rett primary cells,"Variations in the Forkhead Box G1 (FOXG1) gene cause FOXG1 syndrome spectrum, including the congenital variant of Rett syndrome, characterized by early onset of regression, Rett-like and jerky movements, and cortical visual impairment. Due to the largely unknown pathophysiological mechanisms downstream the impairment of this transcriptional regulator, a specific treatment is not yet available. Since both haploinsufficiency and hyper-expression of FOXG1 cause diseases in humans, we reasoned that adding a gene under nonnative regulatory sequences would be a risky strategy as opposed to a genome editing approach where the mutated gene is reversed into wild-type. Here, we demonstrate that an adeno-associated viruses (AAVs)-coupled CRISPR/Cas9 system is able to target and correct FOXG1 variants in patient-derived fibroblasts, induced Pluripotent Stem Cells (iPSCs) and iPSC-derived neurons. Variant-specific single-guide RNAs (sgRNAs) and donor DNAs have been selected and cloned together with a mCherry/EGFP reporter system. Specific sgRNA recognition sequences were inserted upstream and downstream Cas9 CDS to allow self-cleavage and inactivation. We demonstrated that AAV serotypes vary in transduction efficiency depending on the target cell type, the best being AAV9 in fibroblasts and iPSC-derived neurons, and AAV2 in iPSCs. Next-generation sequencing (NGS) of mCherry(+)/EGFP(+) transfected cells demonstrated that the mutated alleles were repaired with high efficiency (20–35% reversion) and precision both in terms of allelic discrimination and off-target activity. The genome editing strategy tested in this study has proven to precisely repair FOXG1 and delivery through an AAV9-based system represents a step forward toward the development of a therapy for Rett syndrome."
3900,Cognitive and affective outcomes of genetic counselling in the Netherlands at group and individual level: a personalized approach seems necessary,"We performed a large outcome study at group and individual level in which the goals of genetic counselling were operationalized into cognitive and affective outcomes: empowerment, perceived personal control and anxiety. We then examined which socio-demographic and clinical variables were associated with changes in these outcomes. Data came from 1479 counselees who completed questionnaires (GCOS-18, PPC and STAI) at three time points: before the start of genetic counselling, after the first consultation and after the results of genetic counselling were disclosed. Results showed that at group level empowerment, perceived personal control and anxiety improved significantly after the whole genetic counselling process. Effect-sizes were medium for empowerment and small for the other outcomes. At individual level, 48% of counselees improved in empowerment, 21% in perceived personal control and 17% in anxiety. Around 10% of counselees worsened on all outcomes. Only ‘reason for referral’ and ‘genetic test result’ were significantly associated with changes in outcomes. This study demonstrated improvements among counselees in cognitive and affective outcomes after genetic counselling at group level. However, our results also suggest that there are opportunities for improvement at individual level, as many counselees remained stable and some even worsened on all outcomes. Routine outcome monitoring could help to explore the needs of counselees and could help to identify counselees who worsen."
3901,Correction: NG2 antigen is involved in leukemia invasiveness and central nervous system infiltration in MLL-rearranged infant B-ALL,
3902,Author Correction: Metagenomic sequencing with spiked primer enrichment for viral diagnostics and genomic surveillance,
3903,Revaluating the relationship between keratoplasty and intraocular lenses,
3904,Correction to: Acute respiratory failure and the kinetics of neutrophil recovery in pediatric hematopoietic cell transplantation: a multicenter study,
3905,Correction: (18)F-FIBT may expand PET for β-amyloid imaging in neurodegenerative diseases,
3906,Correction: Genomic mosaicism in the pathogenesis and inheritance of a Rett syndrome cohort,
3907,Predictive genetic testing in Huntington’s disease: should a neurologist be involved?,"International guidelines on Huntington’s Disease recommend neurological examination in the predictive testing trajectory. Experiences and personal wishes of persons at risk of Huntington’s Disease regarding this topic have never been evaluated. The objective was to provide an overview of the experiences of Dutch at-risk persons, opting for predictive testing, in consulting a neurologist before and after DNA analysis. Persons who were counseled in four Dutch clinics between 2017 and 2019 were retrospectively or prospectively approached for a questionnaire which listed topics as experiences with consultation and personal wishes. From 71 participants, 44 participants visited a neurologist. 41 participants indicated their visit to a neurologist as positive (93.2%). The majority of participants (n = 59) desired consulting a neurologist. Thirty-two participants indicated consultation shortly after (Desired After Group) and twenty-seven before DNA analysis (Desired Before Group) as personal wish. The Desired Before Group consisted of a significantly higher number of participants who actually consulted a neurologist before predictive testing (n = 26) compared with the number of participants who actually consulted a neurologist after DNA analysis in the Desired After Group (n = 11) (p < 0.001). The Desired After Group (n = 19) had a significantly higher number of Huntington’s disease gene expansion carriers compared with the Desired Before Group (n = 5) (p 0.003). Participants are content with consultation. However, persons without the gene expansion still feel the need to get in touch with a neurologist. Therefore, offering a consultation with a neurologist before DNA analysis might be beneficial for all."
3908,Wdfy1 deficiency impairs Tlr3-mediated immune responses in vivo,
3909,Correction: The induction of core pluripotency master regulators in cancers defines poor clinical outcomes and treatment resistance,
3910,Erratum to: A murine colitis model developed using a combination of dextran sulfate sodium and Citrobacter rodentium,
3911,Correction: PDGFB-expressing mesenchymal stem cells improve human hematopoietic stem cell engraftment in immunodeficient mice,
3912,Acute onset binocular diplopia: a retrospective observational study of 100 consecutive cases managed at a tertiary eye centre in Saudi Arabia,"OBJECTIVE: To evaluate the demography, aetiology and clinical course of acute onset binocular diplopia (AOBD) in patients presented as emergency and managed at the neuroophthalmology clinic of a tertiary eye care centre in Saudi Arabia. PATIENTS AND METHODS: A retrospective review of the medical records of 100 consecutive patients who attended the emergency department of Dhahran Eye Specialist Hospital with isolated, AOBD. The exclusion criteria were: (a) monocular diplopia, (b) binocular diplopia accompanied with neurological deficits other than ocular muscles dysfunction and (c) thyroid eye disease. All patients were followed until resolution of the diplopia or onward referral to another specialty for further management. RESULTS: Male:female ratio was 2:1. Median age of the cohort was 56 years (range 18–90 years). Associated nerve palsy included: abducens nerve (n = 57 patients), oculomotor (n = 32 patients) and trochlear nerve (n = 3 patients). Microvascular ischaemia and ocular myasthenia gravis were two most common pathogenic mechanisms. AOBD resolved spontaneously in 98% of patients. CONCLUSION: AOBD, though an alarming and distressing condition, carries reassuringly good prognosis in majority of patients. High risk factors for vascular disease in Middle-Eastern population are reflected in microvascular aetiology as the major cause."
3913,Correction: Neurotensin and its receptors mediate neuroendocrine transdifferentiation in prostate cancer,
3914,Modulating microglia activation prevents maternal immune activation induced schizophrenia-relevant behavior phenotypes via arginase 1 in the dentate gyrus,"Prenatal infection during pregnancy increases the risk for developing neuropsychiatric disorders such as schizophrenia. This is linked to an inflammatory microglial phenotype in the offspring induced by maternal immune activation (MIA). Microglia are crucial for brain development and maintenance of neuronal niches, however, whether and how their activation is involved in the regulation of neurodevelopment remains unclear. Here, we used a MIA rodent model in which polyinosinic: polycytidylic acid (poly (I:C)) was injected into pregnant mice. We found fewer parvalbumin positive (PV+) cells and impaired GABAergic transmission in the dentate gyrus (DG), accompanied by schizophrenia-like behavior in the adult offspring. Minocycline, a potent inhibitor of microglia activation, successfully prevented the above-mentioned deficits in the offspring. Furthermore, by using microglia-specific arginase 1 (Arg1) ablation as well as overexpression in DG, we identified a critical role of Arg1 in microglia activation to protect against poly (I:C) imparted neuropathology and altered behavior in offspring. Taken together, our results highlight that Arg1-mediated alternative activation of microglia are potential therapeutic targets for psychiatric disorders induced by MIA."
3915,"Erratum to: Abstracts of the 53rd Annual Meeting of the EASD, Lisbon 2017. Abstract 788: ‘Pharmacokinetics and tolerability of oral semaglutide in subjects with renal impairment’",
3916,Correction: Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia,
3917,Correction: Management of nystagmus in children: a review of the literature and current practice in UK specialist services,
3918,Correction: Association of ACE2 genetic polymorphisms with hypertension-related target organ damages in south Xinjiang,
3919,Trainee experience with capsular tension rings in Scotland—the need for structured simulation exposure to surgical adjuncts,
3920,A pan-cancer blueprint of the heterogeneous tumor microenvironment revealed by single-cell profiling,"The stromal compartment of the tumor microenvironment consists of a heterogeneous set of tissue-resident and tumor-infiltrating cells, which are profoundly moulded by cancer cells. An outstanding question is to what extent this heterogeneity is similar between cancers affecting different organs. Here, we profile 233,591 single cells from patients with lung, colorectal, ovary and breast cancer (n = 36) and construct a pan-cancer blueprint of stromal cell heterogeneity using different single-cell RNA and protein-based technologies. We identify 68 stromal cell populations, of which 46 are shared between cancer types and 22 are unique. We also characterise each population phenotypically by highlighting its marker genes, transcription factors, metabolic activities and tissue-specific expression differences. Resident cell types are characterised by substantial tissue specificity, while tumor-infiltrating cell types are largely shared across cancer types. Finally, by applying the blueprint to melanoma tumors treated with checkpoint immunotherapy and identifying a naïve CD4(+) T-cell phenotype predictive of response to checkpoint immunotherapy, we illustrate how it can serve as a guide to interpret scRNA-seq data. In conclusion, by providing a comprehensive blueprint through an interactive web server, we generate the first panoramic view on the shared complexity of stromal cells in different cancers."
3921,Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis,
3922,Parallel reductive genome evolution in Desulfovibrio ectosymbionts independently acquired by Trichonympha protists in the termite gut,"Several Trichonympha protist species in the termite gut have independently acquired Desulfovibrio ectosymbionts in apparently different stages of symbiosis. Here, we obtained the near-complete genome sequence of Desulfovibrio phylotype ZnDsv-02, which attaches to the surface of Trichonympha collaris cells, and compared it with a previously obtained genome sequence of ‘Candidatus Desulfovibrio trichonymphae’ phylotype Rs-N31, which is almost completely embedded in the cytoplasm of Trichonympha agilis. Single-nucleotide polymorphism analysis indicated that although Rs-N31 is almost clonal, the ZnDsv-02 population on a single host cell is heterogeneous. Despite these differences, the genome of ZnDsv-02 has been reduced to 1.6 Mb, which is comparable to that of Rs-N31 (1.4 Mb), but unlike other known ectosymbionts of protists with a genome similar in size to their free-living relatives. Except for the presence of a lactate utilization pathway, cell-adhesion components and anti-phage defense systems in ZnDsv-02, the overall gene-loss pattern between the two genomes is very similar, including the loss of genes responsive to environmental changes. Our study suggests that genome reduction can occur in ectosymbionts, even when they can be transmitted horizontally and obtain genes via lateral transfer, and that the symbiont genome size depends heavily on their role in the symbiotic system."
3923,"The role of dopamine dysregulation and evidence for the transdiagnostic nature of elevated dopamine synthesis in psychosis: a positron emission tomography (PET) study comparing schizophrenia, delusional disorder, and other psychotic disorders","There have been few studies performed to examine the pathophysiological differences between different types of psychosis, such as between delusional disorder (DD) and schizophrenia (SZ). Notably, despite the different clinical characteristics of DD and schizophrenia (SZ), antipsychotics are deemed equally effective pharmaceutical treatments for both conditions. In this context, dopamine dysregulation may be transdiagnostic of the pathophysiology of psychotic disorders such as DD and SZ. In this study, an examination is made of the dopamine synthesis capacity (DSC) of patients with SZ, DD, other psychotic disorders, and the DSC of healthy subjects. Fifty-four subjects were recruited to the study, comprising 35 subjects with first-episode psychosis (11 DD, 12 SZ, 12 other psychotic disorders) and 19 healthy controls. All received an (18)F-DOPA positron emission tomography (PET)/magnetic resonance (MR) scan to measure DSC (K(occ;30–60) value) within 1 month of starting antipsychotic treatment. Clinical assessments were also made, which included Positive and Negative Syndrome Scale (PANSS) measurements. The mean K(occ;30–60) was significantly greater in the caudate region of subjects in the DD group (ES = 0.83, corrected p = 0.048), the SZ group (ES = 1.40, corrected p = 0.003) and the other psychotic disorder group (ES = 1.34, corrected p = 0.0045), compared to that of the control group. These data indicate that DD, SZ, and other psychotic disorders have similar dysregulated mechanisms of dopamine synthesis, which supports the utility of abnormal dopamine synthesis in transdiagnoses of these psychotic conditions."
3924,s-HBEGF/SIRT1 circuit-dictated crosstalk between vascular endothelial cells and keratinocytes mediates sorafenib-induced hand–foot skin reaction that can be reversed by nicotinamide,"Hand–foot skin reaction (HFSR), among the most significant adverse effects of sorafenib, has been limiting the clinical benefits of this frontline drug in treating various malignant tumors. The mechanism underlying such toxicity remains poorly understood, hence the absence of effective intervention strategies. In the present study, we show that vascular endothelial cells are the primary cellular target of sorafenib-induced HFSR wherein soluble heparin-binding epidermal growth factor (s-HBEGF) mediates the crosstalk between vascular endothelial cells and keratinocytes. Mechanistically, s-HBEGF released from vascular endothelial cells activates the epidermal growth factor receptor (EGFR) on keratinocytes and promotes the phosphorylation of c-Jun N-terminal kinase 2 (JNK2), which stabilizes sirtuin 1 (SIRT1), an essential keratinization inducer, and ultimately gives rise to HFSR. The administration of s-HBEGF in vivo could sufficiently induce hyper-keratinization without sorafenib treatment. Furthermore, we report that HBEGF neutralization antibody, Sirt1 knockdown, and a classic SIRT1 inhibitor nicotinamide could all significantly reduce the sorafenib-induced HFSR in the mouse model. It is noteworthy that nicotinic acid, a prodrug of nicotinamide, could substantially reverse the sorafenib-induced HFSR in ten patients in a preliminary clinical study. Collectively, our findings reveal the mechanism of vascular endothelial cell-promoted keratinization in keratinocytes and provide a potentially promising therapeutic strategy for the treatment of sorafenib-induced HFSR."
3925,"Comment on: ‘You’ve got dry macular degeneration, end of story: a qualitative study into the experience of living with non-neovascular age-related macular degeneration’",
3926,Author Correction: USP29 maintains the stability of cGAS and promotes cellular antiviral responses and autoimmunity,
3927,Erratum: Host and viral traits predict zoonotic spillover from mammals,
3928,Unconventional secretion: cargo channeling by TMED10,
3929,Erratum to: Abstracts: XXXI International Congress of the IAP and 28th Congress of the ESP,
3930,"Correction: Corrigendum: Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing",
3931,Erratum: Functional proteomics identifies miRNAs to target a p27/Myc/phospho-Rb signature in breast and ovarian cancer,
3932,Genetic aspects of congenital nephrotic syndrome: a consensus statement from the ERKNet–ESPN inherited glomerulopathy working group,"Congenital nephrotic syndrome (CNS) is a heterogeneous group of disorders presenting with massive proteinuria within the first 3 months of life almost inevitably leading to end-stage kidney disease. The Work Group for the European Reference Network for Kidney Diseases (ERKNet) and the European Society for Pediatric Nephrology (ESPN) has developed consensus statement on genetic aspects of CNS diagnosis and management. The presented expert opinion recommends genetic diagnostics as the key diagnostic test to be ordered already during the initial evaluation of the patient, discusses which phenotyping workup should be performed and presents known genotype–phenotype correlations."
3933,Correction: gr/gr deletion predisposes to testicular germ cell tumour independently from altered spermatogenesis: results from the largest European study,
3934,Correction to: Hybridization capture-based next-generation sequencing reliably detects FLT3 mutations and classifies FLT3-internal tandem duplication allelic ratio in acute myeloid leukemia: a comparative study to standard fragment analysis,
3935,Publisher Correction: Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus,
3936,Household cleaning product-related ocular exposures reported to the United States poison control centres,"BACKGROUND/OBJECTIVES: To investigate ocular exposures associated with household cleaning products in the United States. SUBJECTS/METHODS: A retrospective analysis of ocular exposures associated with household cleaning products was conducted using data from the National Poison Data System from 2000 through 2016. RESULTS: From January 2000 through December 2016, poison control centres in the United States received 319,508 calls for household cleaning product-related ocular exposures, averaging 18,795 exposures annually. The annual frequency of exposures decreased significantly by 28.8% during the study period. The rate of exposures per 100,000 US residents was 28.4 among young children (<6 years), 4.8 among older children (6–12 years), 4.2 among teenagers (13–19 years), and 4.2 among adults (≥20 years); children 2 years old had the highest rate of exposure (62.8). Bleaches (25.9%), wall/floor/tile cleaners (13.4%), disinfectants (10.8%), laundry detergents (6.1%), and glass cleaners (5.3%) were the non-miscellaneous product subcategories most commonly associated with ocular exposures. The product subcategories associated with the greatest proportion of major medical outcomes were drain cleaners (1.4%), oven cleaners (1.1%), and automatic dishwasher detergents (0.4%). CONCLUSIONS: On average, the United States poison control centres received approximately two reports of household cleaning product-related ocular exposures every hour during the 17-year study period. Although the annual number and rate of exposures declined during this time, the number of these exposures remains high, especially among young children, underscoring the need for additional prevention efforts. Contrary to the overall trend, ocular exposures to laundry detergent packets have increased significantly and merit special preventive action."
3937,Author Correction: Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia,
3938,Correction: Recent development of AAV-based gene therapies for inner ear disorders,
3939,Erratum: Extended survival and reduced risk of AML progression in erythroid-responsive lenalidomide-treated patients with lower-risk del(5q) MDS,
3940,USP29 maintains the stability of cGAS and promotes cellular antiviral responses and autoimmunity,"Cyclic GMP-AMP synthase (cGAS) is an essential sensor of cytosolic DNA and critically mediates innate immune responses and autoimmunity. Modulating the activity and stability of cGAS provides potential strategies for treating viral or autoimmune diseases. Here, we report that ubiquitin-specific protease 29 (USP29) deubiquitinates and stabilizes cGAS and promotes cellular antiviral responses and autoimmunity. Knockdown or knockout of USP29 severely impairs Herpes simplex virus 1 (HSV-1)- or cytosolic DNA-induced expression of type I interferons (IFNs) and proinflammatory cytokines. Consistently, Usp29(m/m) mice produce decreased type I IFNs and proinflammatory cytokines after HSV-1 infection and are hypersensitive to HSV-1 infection compared to the wild-type littermates. In addition, genetic ablation of USP29 in Trex1(−/−) mice eliminated the detectable pathological and molecular autoimmune phenotypes. Mechanistically, USP29 constitutively interacts with cGAS, deconjugates K48-linked polyubiquitin chains from cGAS and stabilizes cGAS in uninfected cells or after HSV-1 infection. Reconstitution of cGAS into Usp29(−/−) cells fully rescues type I IFN induction and cellular antiviral responses after HSV-1 infection. Our findings thus reveal a critical role of USP29 in the innate antiviral responses against DNA viruses and autoimmune diseases and provide insight into the regulation of cGAS."
3941,"Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa",
3942,Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions,"Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment."
3943,Erratum to: JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects,
3944,"Erratum zu: Impfen bei Immundefizienz: Anwendungshinweise zu den von der Ständigen Impfkommission empfohlenen Impfungen. (III) Impfen bei hämatologischen und onkologischen Erkrankungen (antineoplastische Therapie, Stammzelltransplantation), Organtransplantation und Asplenie",
3945,Correction: Inotuzumab ozogamicin in pediatric patients with relapsed/refractory acute lymphoblastic leukemia,
3946,Longitudinal follow-up of dome-shaped macula,"BACKGROUND/OBJECTIVES: To determine if the presence of sub-retinal fluid (SRF) was associated with reduced vision in dome-shaped macula (DSM), and to assess its effect and response to treatment during follow-up. METHODS: Patients were identified retrospectively. Baseline and follow-up data were recorded. The diagnosis of DSM, and presence or absence of SRF and intra-retinal fluid (IRF) was confirmed using Spectral Domain-Optical Coherence Tomography (SD-OCT). Decisions to treat oedema were based on clinician preference. RESULTS: 193 eyes of 106 patients (71 female) were confirmed to have DSM. Overall mean duration of follow-up for this cohort was 3.5 years. Mean BRVA for all eyes at baseline was 0.38 (range: −0.20 to ‘light perception’). A significant difference was noted in mean baseline BRVA between those eyes with SRF compared with those without SRF at baseline (0.48 vs. 0.31, p < 0.001). Intra-retinal fluid moderately correlated with poorer baseline BRVA (r = 0.31, p < 0.003). No significant change in BRVA was noted during follow-up. No significant effect of treatment on BRVA was observed. CONCLUSIONS: The presence of SRF at baseline was associated with poorer vision. Vision appears to remain stable irrespective of the presence or absence of SRF at baseline. The treatments administered in this cohort did not affect final vision or SRF."
3947,Reconstruction of cell spatial organization from single-cell RNA sequencing data based on ligand-receptor mediated self-assembly,"Single-cell RNA sequencing (scRNA-seq) has revolutionized transcriptomic studies by providing unprecedented cellular and molecular throughputs, but spatial information of individual cells is lost during tissue dissociation. While imaging-based technologies such as in situ sequencing show great promise, technical difficulties currently limit their wide usage. Here we hypothesize that cellular spatial organization is inherently encoded by cell identity and can be reconstructed, at least in part, by ligand-receptor interactions, and we present CSOmap, a computational tool to infer cellular interaction de novo from scRNA-seq. We show that CSOmap can successfully recapitulate the spatial organization of multiple organs of human and mouse including tumor microenvironments for multiple cancers in pseudo-space, and reveal molecular determinants of cellular interactions. Further, CSOmap readily simulates perturbation of genes or cell types to gain novel biological insights, especially into how immune cells interact in the tumor microenvironment. CSOmap can be a widely applicable tool to interrogate cellular organizations based on scRNA-seq data for various tissues in diverse systems."
3948,Correction to: Povidone iodine gargle and mouthwash,
3949,Correction to: Don’t Drive Blind: Driving Pressure to Optimize Ventilator Management in ECMO,
3950,Generation of human hepatocytes from extended pluripotent stem cells,
3951,Publisher Correction: Looking forward 25 years: the future of medicine,
3952,"NPP statement on racism, discrimination, and abuse of power",
3953,"Correlation of serum amyloid A levels, clinical manifestations, treatment, and disease activity in patients with acute anterior uveitis","PURPOSE: To investigate the association between serum amyloid A (SAA) protein and the clinical features of acute anterior uveitis (AAU), and to evaluate the disease activity and treatment effect in relation to SAA levels. METHODS: AAU patients and healthy individuals were recruited from October 2016 to August 2017 at the Department of Uveitis, in the Eye Hospital of Wenzhou Medical University. Related demographic, clinical characteristics, and therapeutic data were analyzed. RESULTS: One hundred and eight AAU patients and 18 healthy controls were included in this study. Serum SAA levels in AAU patients were significantly higher than those of healthy controls (p all < 0.0001). Significantly higher SAA levels were found in AS(+)AAU patients than those in AS(−)AAU patients (p < 0.05). SAA levels were also significantly higher in patients with HLA-B27(+)AAU compared with those with HLA-B27(−)AAU (p < 0.05). Furthermore, in each of the AAU subgroups, higher SAA levels were observed in the active state than those in the inactive state (p all < 0.05). In addition, SAA levels were positively correlated to anterior chamber cell counts (r = 0.492, p < 0.0001). ROC curve analysis revealed that SAA had an AUC value of 0.727 for detecting active inflammation (Youden’s index = 0.38). SAA decreased with effective treatments (p = 0.0002). CONCLUSION: Serum levels of SAA were elevated in AAU patients. The increased levels of SAA were correlated with AS and HLA-B27 status. SAA levels were also positively correlated to disease activity and decreased with effective treatments. These findings suggest that SAA is associated with AAU, with a potential role in monitoring inflammatory processes and assessing the efficacy of therapy."
3954,Who ever heard of 16p11.2 deletion syndrome? Parents’ perspectives on a susceptibility copy number variation syndrome,"Chromosomal microarray analysis is an important diagnostic tool to identify copy number variations (CNV). Some of the CNVs affect susceptibility regions, which means that deletions or duplications in these regions have partial penetrance and often give an increased risk for a spectrum of neurocognitive disorders. Not much is known about the impact of rare CNV susceptibility syndromes on the life of patients or their parents. In this study, we focus on one specific susceptibility CNV disorder, 16p11.2 deletion syndrome. This rare condition is characterised by an increased risk of mild intellectual disability, autism spectrum disorder, epilepsy, and obesity. We aimed to explore the impact of such a disorder on the family members involved in the daily care of children with this syndrome. Three focus group discussions were held with 23 Dutch (grand)parents. Thematic analysis was performed by two independent researchers. The following five themes emerged: (1) the end of a diagnostic odyssey and response to the diagnosis, (2) after the diagnosis—life with a child with 16p11.2 deletion syndrome, (3) access to medical care and support services, (4) nobody knows what 16p11.2 deletion syndrome is, and (5) future perspective—ideal care. The participants experienced a lack of knowledge among involved professionals. Together with the large variability of the syndrome, this led to fragmented care and unfulfilled needs regarding healthcare, social, and/or educational assistance. Care for children with a CNV susceptibility syndrome could be improved by a multidisciplinary approach or central healthcare professional, providing education and information for all involved professionals."
3955,"The exhaustive genomic scan approach, with an application to rare-variant association analysis","Region-based genome-wide scans are usually performed by use of a priori chosen analysis regions. Such an approach will likely miss the region comprising the strongest signal and, thus, may result in increased type II error rates and decreased power. Here, we propose a genomic exhaustive scan approach that analyzes all possible subsequences and does not rely on a prior definition of the analysis regions. As a prime instance, we present a computationally ultraefficient implementation using the rare-variant collapsing test for phenotypic association, the genomic exhaustive collapsing scan (GECS). Our implementation allows for the identification of regions comprising the strongest signals in large, genome-wide rare-variant association studies while controlling the family-wise error rate via permutation. Application of GECS to two genomic data sets revealed several novel significantly associated regions for age-related macular degeneration and for schizophrenia. Our approach also offers a high potential to improve genome-wide scans for selection, methylation, and other analyses."
3956,Drought and plant litter chemistry alter microbial gene expression and metabolite production,"Drought represents a significant stress to microorganisms and is known to reduce microbial activity and organic matter decomposition in Mediterranean ecosystems. However, we lack a detailed understanding of the drought stress response of microbial decomposers. Here we present metatranscriptomic and metabolomic data on the physiological response of in situ microbial communities on plant litter to long-term drought in Californian grass and shrub ecosystems. We hypothesised that drought causes greater microbial allocation to stress tolerance relative to growth pathways. In grass litter, communities from the decade-long ambient and reduced precipitation treatments had distinct taxonomic and functional profiles. The most discernable physiological signatures of drought were production or uptake of compatible solutes to maintain cellular osmotic balance, and synthesis of capsular and extracellular polymeric substances as a mechanism to retain water. The results show a clear functional response to drought in grass litter communities with greater allocation to survival relative to growth that could affect decomposition under drought. In contrast, communities on chemically more diverse and complex shrub litter had smaller physiological differences in response to long-term drought but higher investment in resource acquisition traits across precipitation treatments, suggesting that the functional response to drought is constrained by substrate quality. Our findings suggest, for the first time in a field setting, a trade off between microbial drought stress tolerance, resource acquisition and growth traits in plant litter microbial communities."
3957,Correction: Toosendanin demonstrates promising antitumor efficacy in osteosarcoma by targeting STAT3,
3958,Orbital mycoses in an adult subtropical population,"BACKGROUND/OBJECTIVES: To report the spectrum of fungal infections involving the orbit encountered in an Australian subtropical population with respect to presentation, host risk factors, involved pathogens, treatment and outcomes. SUBJECTS/METHODS: A retrospective chart review was performed on all adult patients with orbital mycosis treated by the senior author (TJS) from 1986 to 2017 in a tertiary setting. RESULTS: Thirty cases of fungal infection involving the orbit were included in this case series. Of these, 26 patients had invasive disease and four patients had non-invasive disease. Causative organisms included mucormycosis (16), aspergillus (8) and other fungi (7). Common risk factors included haematological disorders or malignancy, neutropenia, corticosteroid use and diabetes mellitus. Mucormycosis in three immunocompetent patients was caused by Apophysomyces elegans. Orbital apex syndrome was observed in approximately one third of patients at initial ophthalmological assessment. Amphotericin B was used in most cases of mucormycosis, while there was a more varied spectrum of anti-fungal use in other fungal infections. Seven patients with mucormycosis proceeded to orbital exenteration with a survival rate of 43%. No patients with other orbital fungal infections were exenterated. CONCLUSIONS: Orbital mycoses are not only opportunistic but true pathogenic infections. While initial symptoms may be varied, the development of orbital apex syndrome should raise suspicion for this condition, regardless of patient immune status or age. Survival and visual outcomes are often poor with invasive disease. Multidisciplinary team management with early orbital specialist involvement is essential."
3959,Publisher Correction: The UMBRELLA SIOP–RTSG 2016 Wilms tumour pathology and molecular biology protocol,
3960,Clinical outcomes and aetiology of fourth cranial nerve palsy with acute vertical diplopia in adults,"BACKGROUND: We investigated the clinical outcomes of fourth cranial nerve (CN4) palsy with acute vertical diplopia in adults. METHODS: A total of 80 patients with acute CN4 palsy who underwent at least 3 months of follow-up were included in this study. We retrospectively investigated the aetiology, rate of recovery, and factors associated with recovery between March 2016 and January 2019. RESULTS: The average age of patients with CN4 palsy was about 60 years, and the duration of recovery was 1.5 months: 48 (60.0%) patients had a vascular aetiology and 17 (21.3%) patients had a trauma history. Brain lesions were found in four (5.0%) patients and decompensated cause accounted for four (5.0%) cases. Among the total of 80 patients, 13 (16.3%) failed to completely recover. Non-isolated CN4 palsy with other cranial nerve palsies were recorded in seven cases. The comparison between recovery and non-recovery groups showed that initial deviation angle, aetiology, fundus extorsion, and head tilt status were significantly different factors. CONCLUSION: The recovery rate of acute CN4 palsy was about 80% and duration of recovery was 1.5 months. However, the varying rates and duration of recovery was presented according to aetiology thus we should consider the prognosis by aetiology."
3961,Soluble cytokine receptor levels in aqueous humour of patients with specific autoimmune uveitic entities: sCD30 is a biomarker of granulomatous uveitis,"PURPOSE: Soluble cytokine receptors are potential biomarkers for immune activation and have a promising potential as immunotherapeutic agents. We investigated the levels of soluble cytokine receptors in aqueous humour (AH) samples from patients with specific autoimmune uveitic entities. METHODS: Patients with active uveitis associated with Behçet’s disease (BD) (n = 13), sarcoidosis (n = 8), HLA-B27-related inflammation (n = 12), Vogt–Koyanagi–Harada (VKH) disease (n = 12) and control subjects (n = 9) were included. AH samples were analyzed with the use of multiplex assays for the proinflammatory cytokine tumour necrosis factor (TNF)-α and the soluble cytokine receptors sCD30, sCD163, sgp130, sIL-6 receptor-α (sIL-6R), sTNFRI and sTNFRII. RESULTS: TNF-α and soluble cytokine receptor AH levels were significantly higher in uveitis patients (n = 45) compared with controls (n = 9). When nongranulomatous uveitis (BD and HLA-B27-associated uveitis) was compared with granulomatous uveitis (sarcoidosis and VKH disease), the levels of sCD30 and sTNFRI/TNF-α and sTNFRII/TNF-α ratios were significantly enhanced in granulomatous uveitis. Finally, when comparing the profile in the specific uveitis entities, sCD30 levels were highest in patients with VKH disease. sgp130, sCD163, sIL-6R, sTNFRI and sTNFRII did not differ significantly between the four different clinical uveitic subgroups. CONCLUSIONS: Soluble cytokine receptors are significantly upregulated in autoimmune uveitis. CD30(+) T cells might contribute to the inflammatory process in granulomatous uveitis, particularly in VKH disease. Granulomatous uveitis is also characterized by significantly higher sTNFRs/TNF-α ratios than nongranulomatous uveitis."
3962,Erratum: Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner,
3963,"Correction: Epalrestat, an Aldose Reductase Inhibitor, Restores Erectile Function in Streptozocin-induced Diabetic Rats",
3964,Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation,
3965,Correction: IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients,
3966,"Judging in the genomic era: judges’ genetic knowledge, confidence and need for training","Genetic information is increasingly used in many contexts, including health, insurance, policing and sentencing—with numerous potential benefits and risks. Protecting from the related risks requires updates to laws and procedures by justice systems. These updates depend to a large extent on what the key stakeholders—the judiciary—know and think about the use of genetic information. This study used a battery of 25 genetic knowledge items to collect data from 73 supreme court judges from the same country (Romania) on their knowledge of genetic information. Their responses were compared with those of two other groups: lawyers (but not judges; N = 94) and non-lawyers (N = 116) from the same country. The data were collected at approximately the same time from the three groups. The judges’ results were also compared to the results obtained from a general population data collection (N = 5310). The results showed that: (1) judges had overall better knowledge of genetics than the other groups, but their knowledge was uneven across different genetic concepts; (2) judges were overall more confident in their knowledge than the other two groups, but their confidence was quite low; and (3) the correlation between knowledge and confidence was moderate for judges, weak for lawyers and not significant for non-lawyers. Finally, 100% of the judges agreed that information on gene-environment processes should be included in judges’ training. Increasing genetic expertise of the justice stakeholders is an important step towards achieving adequate legal protection against genetic data misuse."
3967,Correction: Diabetic retinopathy and diabetic macular oedema pathways and management: UK Consensus Working Group,
3968,Correction: PIM2-mediated phosphorylation of hexokinase 2 is critical for tumor growth and paclitaxel resistance in breast cancer,
3969,"Correction: Corrigendum: Distributive justice, diversity, and inclusion in precision medicine: what will success look like?",
3970,Medium-coverage DNA sequencing in the design of the genetic association study,"DNA sequencing is a widely used tool in genetic association study. Sequencing cost remains a major concern in sequencing-based study, although the application of next generation sequencing has dramatically decreased the sequencing cost and increased the efficiency. The choice of sequencing depth and the sequencing sample size will largely determine the final study investment and performance. Many studies have been conducted to find a cost-effective design of sequencing depth that can achieve certain sequencing accuracy using minimal sequencing cost. The strategies previously studied can be classified into two groups: (1) single-stage to sequence all the samples using either high (>~30×) or low (<~10×) sequencing depth; and (2) two-stage to sequence an affordable number of individuals at a high-coverage followed by a large sample of low-coverage sequencing. However, limited studies examined the performance of the medium-coverage (10–30×) sequencing depth for a genetic association study, where the optimum sequencing depth may exist. In this study, using a published simulation framework, we comprehensively compared the medium-coverage sequencing (MCS) to the single- and two-stage high/low-coverage sequencing in terms of the power and type I error of the variant discovery and association testing. We found, given certain sequencing effort, MCS yielded a comparable discovery power and better type I error control compared with the best (highest power) scenarios using other high- and low-coverage single-stage or two-stage designs. However, MCS was not as competent as other designs with respect to the association power, especially for the rare variants and when the sequencing investment was limited."
3971,Functional biology of the Steel syndrome founder allele and evidence for clan genomics derivation of COL27A1 pathogenic alleles worldwide,"Previously we reported the identification of a homozygous COL27A1 (c.2089G>C; p.Gly697Arg) missense variant and proposed it as a founder allele in Puerto Rico segregating with Steel syndrome (STLS, MIM #615155); a rare osteochondrodysplasia characterized by short stature, congenital bilateral hip dysplasia, carpal coalitions, and scoliosis. We now report segregation of this variant in five probands from the initial clinical report defining the syndrome and an additional family of Puerto Rican descent with multiple affected adult individuals. We modeled the orthologous variant in murine Col27a1 and found it recapitulates some of the major Steel syndrome associated skeletal features including reduced body length, scoliosis, and a more rounded skull shape. Characterization of the in vivo murine model shows abnormal collagen deposition in the extracellular matrix and disorganization of the proliferative zone of the growth plate. We report additional COL27A1 pathogenic variant alleles identified in unrelated consanguineous Turkish kindreds suggesting Clan Genomics and identity-by-descent homozygosity contributing to disease in this population. The hypothesis that carrier states for this autosomal recessive osteochondrodysplasia may contribute to common complex traits is further explored in a large clinical population cohort. Our findings augment our understanding of COL27A1 biology and its role in skeletal development; and expand the functional allelic architecture in this gene underlying both rare and common disease phenotypes."
3972,T-cell expression of Bruton’s tyrosine kinase promotes autoreactive T-cell activation and exacerbates aplastic anemia,"The role of Bruton’s tyrosine kinase (BTK) in BCR signaling is well defined, and BTK is involved in B-cell development, differentiation, and malignancies. However, the expression of Btk in T cells and its role in T-cell function remain largely unknown. Here, we unexpectedly found high expression and activation of BTK in T cells. Deficiencies in BTK resulted in the impaired activation and proliferation of autoreactive T cells and ameliorated bone marrow failure (BMF) in aplastic anemia. Mechanistically, BTK is activated after TCR engagement and then phosphorylates PLCγ1, thus promoting T-cell activation. Treatment with acalabrutinib, a selective BTK inhibitor, decreased T-cell proliferation and ameliorated BMF in mice with aplastic anemia. Our results demonstrate an unexpected role of BTK in optimal T-cell activation and in the pathogenesis of autoimmune aplastic anemia, providing insights into the molecular regulation of T-cell activation and the pathogenesis of T-cell-mediated autoimmune disease."
3973,Validation of a nicotine vapor self-administration model in rats with relevance to electronic cigarette use,"The debate about electronic cigarettes is dividing healthcare professionals, policymakers, manufacturers, and communities. A key limitation in our understanding of the cause and consequences of vaping is the lack of animal models of nicotine vapor self-administration. Here, we developed a novel model of voluntary electronic cigarette use in rats using operant behavior. We found that rats voluntarily exposed themselves to nicotine vapor to the point of reaching blood nicotine levels that are similar to humans. The level of responding on the active (nicotine) lever was similar to the inactive (air) lever and lower than the active lever that was associated with vehicle (polypropylene glycol/glycerol) vapor, suggesting low positive reinforcing effects and low nicotine vapor discrimination. Lever pressing behavior with nicotine vapor was pharmacologically prevented by the α4β2 nicotinic acetylcholine receptor partial agonist and α7 receptor full agonist varenicline in rats that self-administered nicotine but not vehicle vapor. Moreover, 3 weeks of daily (1 h) nicotine vapor self-administration produced addiction-like behaviors, including somatic signs of withdrawal, allodynia, anxiety-like behavior, and relapse-like behavior after 3 weeks of abstinence. Finally, 3 weeks of daily (1 h) nicotine vapor self-administration produced cardiopulmonary abnormalities and changes in α4, α3, and β2 nicotinic acetylcholine receptor subunit mRNA levels in the nucleus accumbens and medial prefrontal cortex. These findings validate a novel animal model of nicotine vapor self-administration in rodents with relevance to electronic cigarette use in humans and highlight the potential addictive properties and harmful effects of chronic nicotine vapor self-administration."
3974,The microbiome of alpine snow algae shows a specific inter-kingdom connectivity and algae-bacteria interactions with supportive capacities,"Mutualistic interactions within microbial assemblages provide a survival strategy under extreme conditions; however, little is known about the complexity of interaction networks in multipartite, free-living communities. In the present study, the interplay within algae-dominated microbial communities exposed to harsh environmental influences in the Austrian Alps was assessed in order to reveal the interconnectivity of eukaryotic and prokaryotic inhabitants. All analyzed snowfields harbored distinct microbial communities. Network analyses revealed that mutual exclusion prevailed among microalgae in the alpine environment, while bacteria were mainly positively embedded in the interaction networks. Especially members of Proteobacteria, with a high prevalence of Oxalobacteraceae, Pseudomonadaceae, and Sphingomonadaceae showed genus-specific co-occurrences with distinct microalgae. Co-cultivation experiments with algal and bacterial isolates confirmed beneficial interactions that were predicted based on the bioinformatic analyses; they resulted in up to 2.6-fold more biomass for the industrially relevant microalga Chlorella vulgaris, and up to 4.6-fold increase in biomass for the cryophilic Chloromonas typhlos. Our findings support the initial hypothesis that microbial communities exposed to adverse environmental conditions in alpine systems harbor inter-kingdom supportive capacities. The insights into mutualistic inter-kingdom interactions and the ecology of microalgae within complex microbial communities provide explanations for the prevalence and resilience of such assemblages in alpine environments."
3975,Correction to: Critical Care Canada Forum 2019 Abstracts,
3976,"Correction to: Physical activity intensity, bout-duration, and cardiometabolic risk markers in children and adolescents",
3977,Correction to: Socioeconomic inequalities in childhood-to-adulthood BMI tracking in three British birth cohorts,
3978,Cancer-host battles: measures and countermeasures in radiation-induced caspase activation and tumor immunogenicity,
3979,Correction: Corrigendum: Structure and functions of angiotensinogen,
3980,Author Correction: The genome of Prasinoderma coloniale unveils the existence of a third phylum within green plants,
3981,"Correction: Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond",
3982,Using prefrontal transcranial direct current stimulation (tDCS) to enhance proactive cognitive control in schizophrenia,"The goal of this study was to use transcranial direct current stimulation (tDCS) to examine the role of the prefrontal cortex (PFC) in neural oscillatory activity associated with proactive cognitive control in schizophrenia. To do so, we tested the impact of PFC-targeted tDCS on behavioral and electrophysiological markers of proactive cognitive control engagement in individuals with schizophrenia. Using a within-participants, double-blinded, sham-controlled crossover design, we recorded EEG while participants with schizophrenia completed a proactive cognitive control task (the Dot Pattern Expectancy (DPX) Task), after receiving 20 min of active prefrontal stimulation at 2 mA or sham stimulation. We hypothesized that active stimulation would enhance proactive cognitive control, leading to changes in behavioral performance on the DPX task and in activity in the gamma frequency band during key periods of the task designed to tax proactive cognitive control. The results showed significant changes in the pattern of error rates and increases in EEG gamma power as a function of tDCS condition (active or sham), that were indicative of enhanced proactive cognitive control. These findings, considered alongside our previous work in healthy adults, provides novel support for the role gamma oscillations in proactive cognitive control and they suggest that frontal tDCS may be a promising approach to enhance proactive cognitive control in schizophrenia."
3983,Diverse coral reef invertebrates exhibit patterns of phylosymbiosis,"Microbiome assemblages of plants and animals often show a degree of correlation with host phylogeny; an eco-evolutionary pattern known as phylosymbiosis. Using 16S rRNA gene sequencing to profile the microbiome, paired with COI, 18S rRNA and ITS1 host phylogenies, phylosymbiosis was investigated in four groups of coral reef invertebrates (scleractinian corals, octocorals, sponges and ascidians). We tested three commonly used metrics to evaluate the extent of phylosymbiosis: (a) intraspecific versus interspecific microbiome variation, (b) topological comparisons between host phylogeny and hierarchical clustering (dendrogram) of host-associated microbial communities, and (c) correlation of host phylogenetic distance with microbial community dissimilarity. In all instances, intraspecific variation in microbiome composition was significantly lower than interspecific variation. Similarly, topological congruency between host phylogeny and the associated microbial dendrogram was more significant than would be expected by chance across all groups, except when using unweighted UniFrac distance (compared with weighted UniFrac and Bray–Curtis dissimilarity). Interestingly, all but the ascidians showed a significant positive correlation between host phylogenetic distance and associated microbial dissimilarity. Our findings provide new perspectives on the diverse nature of marine phylosymbioses and the complex roles of the microbiome in the evolution of marine invertebrates."
3984,Communicating genetic information to family members: analysis of consent forms for diagnostic genomic sequencing,"Communicating results from genomic sequencing to family members can play an essential role allowing access to surveillance, prevention, treatment or prophylactic measures. Yet, many patients struggle with communication of these results and it is unclear to what extent this is discussed during the consent process. We conducted an online systematic search and used content analysis to explore how consent forms for genomic sequencing address communication of genetic information to family members. Our search yielded 68 consent forms from 11 countries. Although 57 forms alluded to the familial nature of results, forms varied in their discussion of the potential familial implications of results. Only 11 addressed communication of genetic information with family members, with differences in who would be responsible for this process. Several forms offered patients options regarding communication, even in countries where national guidelines and legislation allow for the disclosure of results in the absence of patient consent. These findings are concerning because they show how forms may potentially mislead patients and health care professionals about whether communication is permissible in cases where the patient does not consent. We suggest that providers and health care professionals reconsider how consent forms address communicating genetic information to family members."
3985,Opioid dose regimen shapes mesolimbic adaptations,
3986,IL-18: throwing off the shackles to boost anti-tumor immunity,
3987,Publisher Correction: Federated discovery and sharing of genomic data using Beacons,
3988,A systematic review of real-world evidence of the management of macular oedema secondary to branch retinal vein occlusion,"This review assessed the real-world evidence of the management of macular oedema secondary to branch retinal vein occlusion (BRVO). A meta-analysis of 2530 eyes from 48 real-world studies of therapies for macular oedema secondary to BRVO was conducted. Baseline characteristics, visual, anatomical and safety outcomes were recorded. The weighted mean and weighted estimates from random-effects models were calculated for visual acuity (VA) and central subfield thickness (CST) changes at 6, 12 and 24 months. Primary outcome was change in VA (logMAR letters) at 12 months. Study quality was assessed using the quality appraisal checklist for case series developed by Institute of Health Economics. The mean baseline VA for the pooled data was 54.0 (51.5, 56.5) letters and the mean baseline CST was 501.3 (483.5, 519.1) µm. The random-effects estimate for mean (95% CI) change in VA was 14.6 (12.5, 16.7) letters at 12 months (n = 1727). The random-effects estimate for mean (95% CI) change in CST was −181.7 (−230.7, −132.7) µm at 12 months (n = 1325). The quality of studies varied considerably. Ocular and systemic adverse events were discussed in 79% and 42% of treatment arms respectively, with possible under-reporting. Visual and anatomical gains achieved in the real-world for anti-VEGF therapy were not as impressive as seminal RCTs, possibly due to reduced injection frequency in the real world and differences in baseline characteristics. There is an urgent need for consensus on the minimum efficacy, treatment burden and safety data to collect to strengthen the real-world evidence base."
3989,Correction to: Behavioral Health Emergencies Encountered by Community Paramedics: Lessons from the Field and Opportunities for Skills Advancement,
3990,Optic disc drusen in children: morphologic features using EDI-OCT,"AIMS: This study aimed to investigate morphologic features of optic disc drusen (ODD) and peripapillary hyperreflective ovoid mass-like structures (PHOMS) in children, using enhanced depth imaging optical coherence tomography (EDI-OCT). It also assessed if the presence of these features were associated with decreased peripapillary retinal nerve fibre layer (RNFL) thickness. METHODS: Retrospective observational study of children with ODD. All subjects underwent complete ophthalmic examination and multimodal imaging. ODD were identified on EDI-OCT as circumscribed hyporeflective spheroidal elements located in front of lamina cribrosa, fully or partially surrounded by a hyperreflective border. PHOMS were identified as hyperreflective ovoid structures located in the peripapillary circumference. Both associations between ODD and RNFL loss and PHOMS and RNFL loss were tested using chi-squared test. RESULTS: In total, 38 eyes of 20 children were analysed. PHOMS were present in 90% of patients. ODD and PHOMS were predominantly found in the nasal, superonasal and inferonasal sectors. A significant positive association was found between ODD and decreased RNFL thickness in the nasal (p = 0.02), superonasal (p = 0.05) and inferotemporal (p = 0.04) sectors. There was no significant association found with the presence of PHOMS. CONCLUSION: EDI-OCT allowed morphological analysis of ODD and PHOMS in children. Drusen were found to be distinct from PHOMS both in their appearance and impact on the RNFL. ODD are hyporeflective and appear on the ONH above the lamina cribrosa and were associated with decreased thickness of the RNFL. On the contrary, PHOMS are hyperreflective structures located around the ONH and were not associated with RNFL loss."
3991,Ten-year outcomes of antivascular endothelial growth factor therapy in neovascular age-related macular degeneration,"PURPOSE: Single center, noninterventional cohort study to assess 10-year visual and anatomical outcomes following initiation of treatment with antivascular endothelial growth factor (anti-VEGF) agents in neovascular age-related macular degeneration (AMD) patients. Neovascular AMD patients initiated on intravitreal anti-VEGF injections in 2008–2009 and continued to be followed up for at least 10 years were included in this study. METHODS: The Moorfields OpenEyes database was searched for all patients who were initiated on anti-VEGF therapy for neovascular AMD in 2008–2009 and the visual acuity (VA) in Early Diabetic Retinopathy Study (ETDRS) letters and injection records were analyzed for those who have had at least 10-year follow-up. The spectral-domain optical coherence tomography (SD-OCT) scans, color fundus photos, and fundus fluorescein angiography (FA) were graded by two retinal physicians. The outcomes were also compared between those with good and poor VA outcomes based on pre-defined criteria. The primary end point was change in VA at 10 years; secondary outcomes included percentage with VA of 20/40 or better, 20/70 or better, VA gains and losses, anatomic outcomes and number of injections. RESULTS: After a mean of 10.04 years after initiation of anti-VEGF therapy, the mean decline in VA from baseline was −2.1 ETDRS letters (SD 19.9, p = 0.65). One hundred eyes (67.1%) achieved a VA threshold of 20/70 or better, 33.5% achieved a VA of 20/40 or better, and 76.5% eyes maintained VA defined as a loss of less than 15 letters. Fourteen percent of study eyes had VA of 20/200 or worse and 23.5% declined by 15 letters or more. 87.5% of eyes were switched from ranibizumab to aflibercept during the course of 10 years and the eyes received a mean of 52.2 (SD 18.1) injections over 10 years. From this cohort, 87 (58.3%) eyes are having on-going treatment. On OCT, 34.9% had persistent fluid at the last visit, 6.7% patients showed new onset atrophy compared to baseline, and 43.7% had increased area of macular atrophy. The mean area of atrophy at the final visit was 4.15 mm(2). Comparison between the good and worse visual outcome groups showed lower baseline VA, fovea-involving atrophy and final area of atrophy had a statistically significant negative effect on the final visual outcome (p < 0.05). CONCLUSIONS: Regular monitoring and anti-VEGF treatment over 10 years reduce the risk of visual loss of 15 letters or more in patients with neovascular AMD. The most common cause of substantial visual decline was macular atrophy."
3992,Author Correction: Data visualisation to support obesity policy: case studies of data tools for planning and transport policy in the UK,
3993,High-throughput screening campaign identifies a small molecule agonist of the relaxin family peptide receptor 4,"Relaxin/insulin-like family peptide receptor 4 (RXFP4) is a class A G protein-coupled receptor (GPCR), and insulin-like peptide 5 (INSL5) is its endogenous ligand. Although the precise physiological role of INSL5/RXFP4 remains elusive, a number of studies have suggested it to be a potential therapeutic target for obesity and other metabolic disorders. Since selective agonists of RXFP4 are scarcely available and peptidic analogs of INSL5 are hard to make, we conducted a high-throughput screening campaign against 52,000 synthetic and natural compounds targeting RXFP4. Of the 109 initial hits discovered, only 3 compounds were confirmed in secondary screening, with JK0621-D008 displaying the best agonism at human RXFP4. Its S-configuration stereoisomer (JK1) was subsequently isolated and validated by a series of bioassays, demonstrating a consistent agonistic effect in cells overexpressing RXFP4. This scaffold may provide a valuable tool to further explore the biological functions of RXFP4."
3994,Correction: Nuclear receptor HNF4α performs a tumor suppressor function in prostate cancer via its induction of p21-driven cellular senescence,
3995,New insights into the evasion of host innate immunity by Mycobacterium tuberculosis,"Mycobacterium tuberculosis (Mtb) is an extremely successful intracellular pathogen that causes tuberculosis (TB), which remains the leading infectious cause of human death. The early interactions between Mtb and the host innate immune system largely determine the establishment of TB infection and disease development. Upon infection, host cells detect Mtb through a set of innate immune receptors and launch a range of cellular innate immune events. However, these innate defense mechanisms are extensively modulated by Mtb to avoid host immune clearance. In this review, we describe the emerging role of cytosolic nucleic acid-sensing pathways at the host–Mtb interface and summarize recently revealed mechanisms by which Mtb circumvents host cellular innate immune strategies such as membrane trafficking and integrity, cell death and autophagy. In addition, we discuss the newly elucidated strategies by which Mtb manipulates the host molecular regulatory machinery of innate immunity, including the intranuclear regulatory machinery, the ubiquitin system, and cellular intrinsic immune components. A better understanding of innate immune evasion mechanisms adopted by Mtb will provide new insights into TB pathogenesis and contribute to the development of more effective TB vaccines and therapies."
3996,Mitochondrial Ca(2+) regulation in the etiology of heart failure: physiological and pathophysiological implications,"Heart failure (HF) represents one of the leading causes of cardiovascular diseases with high rates of hospitalization, morbidity and mortality worldwide. Ample evidence has consolidated a crucial role for mitochondrial injury in the progression of HF. It is well established that mitochondrial Ca(2+) participates in the regulation of a wide variety of biological processes, including oxidative phosphorylation, ATP synthesis, reactive oxygen species (ROS) generation, mitochondrial dynamics and mitophagy. Nonetheless, mitochondrial Ca(2+) overload stimulates mitochondrial permeability transition pore (mPTP) opening and mitochondrial swelling, resulting in mitochondrial injury, apoptosis, cardiac remodeling, and ultimately development of HF. Moreover, mitochondria possess a series of Ca(2+) transport influx and efflux channels, to buffer Ca(2+) in the cytoplasm. Interaction at mitochondria-associated endoplasmic reticulum membranes (MAMs) may also participate in the regulation of mitochondrial Ca(2+) homeostasis and plays an essential role in the progression of HF. Here, we provide an overview of regulation of mitochondrial Ca(2+) homeostasis in maintenance of cardiac function, in an effort to identify novel therapeutic strategies for the management of HF."
3997,Deep phenotyping detects a pathological CD4(+) T-cell complosome signature in systemic sclerosis,
3998,The metabolic regulator Lamtor5 suppresses inflammatory signaling via regulating mTOR-mediated TLR4 degradation,"Comprehensive immune responses are essential for eliminating pathogens but must be tightly controlled to avoid sustained immune activation and potential tissue damage. The engagement of TLR4, a canonical pattern recognition receptor, has been proposed to trigger inflammatory responses with different magnitudes and durations depending on TLR4 cellular compartmentalization. In the present study, we identify an unexpected role of Lamtor5, a newly identified component of the amino acid-sensing machinery, in modulating TLR4 signaling and controlling inflammation. Specifically, Lamtor5 associated with TLR4 via their LZ/TIR domains and facilitated their colocalization at autolysosomes, preventing lysosomal tethering and the activation of mTORC1 upon LPS stimulation and thereby derepressing TFEB to promote autophagic degradation of TLR4. The loss of Lamtor5 was unable to trigger the TFEB-driven autolysosomal pathway and delay degradation of TLR4, leading to sustained inflammation and hence increased mortality among Lamtor5 haploinsufficient mice during endotoxic shock. Intriguingly, nutrient deprivation, particularly leucine deprivation, blunted inflammatory signaling and conferred protection to endotoxic mice. This effect, however, was largely abrogated upon Lamtor5 deletion. We thus propose a homeostatic function of Lamtor5 that couples pathogenic insults and nutrient availability to optimize the inflammatory response; this function may have implications for TLR4-associated inflammatory and metabolic disorders."
3999,Author Correction: Next-generation influenza vaccines: opportunities and challenges,
4000,Erratum: Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder,
4001,Orbital exenteration and conjunctival melanoma: a 14-year study at the Jules Gonin Eye Hospital,"PURPOSE: To report our 14-year experience with orbital exenteration and assess risk factors for poor prognosis by focusing on conjunctival melanoma. PATIENTS AND METHOD: A retrospective study was conducted in our tertiary care centre (Jules Gonin Eye Hospital, Lausanne, Switzerland) between 2003 and 2017. Inclusion criteria were patients aged ≥18 years with a follow-up >12 months, without metastatic spread at the time of surgery. Data recorded were age, gender, tumour histology, surgical technique, postoperative complications, surgical margin status, local recurrence, postoperative radiation beam therapy and metastatic status. RESULTS: Twenty-five patients with a mean age of 63.2 years (38–92) were included. Conjunctival melanoma was the most frequently identified tumour (n = 14, 56%) followed by conjunctival squamous cell carcinoma (n = 4, 16%), sebaceous carcinoma (n = 3, 12%), choroidal melanoma (n = 2, 8%) and basal cell carcinoma (n = 2, 8%). Eighteen tumours (72%) originated from the conjunctival tissue. Clear surgical margins were achieved in 21 (84%) patients. Fourteen (56%) patients experienced distant metastases and died from metastatic spread after a mean follow-up of 52.3 months (6–120). The 1-, 3- and 5-year overall survival (OS) was 96%, 72% and 60%, respectively. In the univariate analysis, positive surgical margins, local recurrence and metachronous metastases were associated with a decreased OS (p = 0.002, p = 0.005 and p = 0.007, respectively). In the multivariate analysis, positive surgical margins and metachronous metastases were also associated with a decreased OS (p = 0.02 and p = 0.042, respectively). Conjunctival melanoma was not associated with a poorer prognosis (p = 0.280). CONCLUSION: Free surgical margins are needed to increase OS. To achieve clearer surgical margins, neoadjuvant targeted therapies/immunotherapies may be considered."
4002,Author Correction: Antiviral agents: Targeting vesicle size,
4003,RIP1 promotes proliferation through G2/M checkpoint progression and mediates cisplatin-induced apoptosis and necroptosis in human ovarian cancer cells,"Receptor-interacting protein 1 (RIP1, also known as RIPK1) is not only a tumor-promoting factor in several cancers but also mediates either apoptosis or necroptosis in certain circumstances. In this study we investigated what role RIP1 plays in human ovarian cancer cells. We showed that knockout (KO) of RIP1 substantially suppressed cell proliferation, accompanied by the G2/M checkpoint arrest in two human ovarian cancer cell lines SKOV3 and A2780. On the other hand, RIP1 KO remarkably attenuated cisplatin-induced cytotoxicity, which was associated with reduction of the apoptosis markers PARP cleavage and the necroptosis marker phospho-MLKL. We found that RIP1 KO suppressed cisplatin-induced ROS accumulation in both SKOV3 and A2780 cells. ROS scavenger BHA, apoptosis inhibitor Z-VAD or necroptosis inhibitor NSA could effectively suppress cisplatin’s cytotoxicity in the control cells, suggesting that ROS-mediated apoptosis and necroptosis were involved in cisplatin-induced cell death. In addition, blocking necroptosis with MLKL siRNA effectively attenuated cisplatin-induced cytotoxicity. In human ovarian cancer A2780 cell line xenograft nude mice, RIP1 KO not only significantly suppressed the tumor growth but also greatly attenuated cisplatin’s anticancer activity. Our results demonstrate a dual role of RIP1 in human ovarian cancer: it acts as either a tumor-promoting factor to promote cancer cell proliferation or a tumor-suppressing factor to facilitate anticancer effects of chemotherapeutics such as cisplatin."
4004,Correction: LCE: an open web portal to explore gene expression and clinical associations in lung cancer,
4005,Heterozygous SOD2 deletion deteriorated chronic intermittent hypoxia-induced lung inflammation and vascular remodeling through mtROS-NLRP3 signaling pathway,"Oxidative stress caused by chronic intermittent hypoxia (CIH) is the hallmark of obstructive sleep apnea (OSA). Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (SOD2). In this study, wild-type (WT) and SOD2-heterozygous knockout (SOD2(+/−)) mice were exposed to CIH or normoxic (Nor) conditions. After 4 weeks, pulmonary artery pressure was measured, and the mice were processed to harvest either serum for cytokine assays or lungs for flow cytometry and histopathological studies. Herein, we showed that heterozygous deletion of SOD2 markedly deteriorated pulmonary remodeling and increased the oxidative stress, especially promoted the infiltration of macrophages in the lungs of CIH mouse. Moreover, in the intermittent hypoxia (IH)-treated RAW264.7 cells, SOD2 knockdown increased the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation accompanied with the IL-1β elevation and caspase-1 activity. Additionally, mitochondrial ROS (mtROS) scavenger mito-TEMPO abolished NLRP3 inflammasome activation in IH-treated RAW264.7 cells. Collectively, our results supported that SOD2 contributed to the pathogenesis of CIH-induced lung remodeling. Meanwhile, SOD2 knockdown exacerbates oxidative damage through assembly and activation of NLRP3 inflammasome in macrophages. SOD2 may be a novel therapeutic target for CIH-induced pulmonary inflammation and arteriole remodeling."
4006,Outcome measures in juvenile X-linked retinoschisis: A systematic review,"X-linked retinoschisis (XLRS) is a leading cause of hereditary juvenile macular degeneration in males resulting in significant vision impairment. Outcome measures to monitor disease progression or therapeutic interventions have evolved with technology. A systematic review was undertaken to evaluate outcome measures for XLRS. Inclusion criteria were all publications examining outcome measures for natural history studies or following an interventional approach for patients with XLRS. Studies which did not present follow-up data were excluded. We searched medical databases including CENTRAL, Ovid Medline, pre-Medline and ahead of Print up to February 2019. Two authors independently assessed the risk of bias. Twelve studies meet the inclusion criteria with four prospective and eight retrospective case series. Five series were natural history observational studies and seven were interventional series using either topical or systemic carbonic anhydrase inhibitors. Visual acuity (VA) declined very slowly in the natural history studies equivalent to 0.22–0.5 letters per year. Five of the six interventional studies showed an improvement in VA and four a reduction in spectral domain optical coherence tomography (SD-OCT) parameters for central macular thickness (CMT). The full-field electroretinogram identified the 30-Hz latency as a further parameter to monitor function. VA was the measure most likely to show a statistically significant outcome. How functionally meaningful this is, requires further evaluation. CMT SD-OCT outcomes are variable depending on cystic changes. More refined measures are required to better correlate structure with function."
4007,Advanced robotic surgical systems in ophthalmology,"In this paper, an overview of advanced robotic surgical systems in ophthalmology is provided. The systems are introduced as representative examples of the degree of human vs. robotic control during surgical procedures. The details are presented on each system and the latest advancements of each are described. Future potential applications for surgical robotics in ophthalmology are discussed in detail, with representative examples provided alongside recent progress."
4008,Antibodies clamp down on NET nucleosomes,
4009,Forced solar gazing—a common technique of torture?,"BACKGROUND: Forced solar gazing (FSG) appears to be more regularly employed as a method of torture in certain parts of the world than has previously been documented. SUBJECTS AND METHODS: This study is a retrospective analysis of a case set of 17 torture survivors subjected to FSG, who were seen by the UK Charity Freedom from Torture in the period 2009–2019. RESULTS: All clients in our case set had experienced serious physical and sexual assaults, in addition to the FSG, as part of their mistreatment. All clients suffered with serious psychological conditions as a result of their torture, including depression and post-traumatic stress disorder (PTSD). These mental health conditions made ophthalmic assessment difficult, not simply because of the clients’ associated anxiety, but also because of avoidant behaviour and dissociation which was manifested in the clinical setting. In the two clients who could be examined by an ophthalmologist, both had visible retinal changes and a degree of impairment of visual acuity. CONCLUSION: FSG appears to be a method of torture which is regularly employed, and in our case set is seen with other serious manifestations of mistreatment, both physical, psychological and sexual. Psychiatric comorbidities present challenges in the clinical assessment of these cases. Ophthalmic examination can carry a risk of re-traumatisation of individuals who have experienced FSG in a context of torture."
4010,"Author Correction: Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells",
4011,Management of nystagmus in children: a review of the literature and current practice in UK specialist services,"Nystagmus is an eye movement disorder characterised by abnormal, involuntary rhythmic oscillations of one or both eyes, initiated by a slow phase. It is not uncommon in the UK and regularly seen in paediatric ophthalmology and adult general/strabismus clinics. In some cases, it occurs in isolation, and in others, it occurs as part of a multisystem disorder, severe visual impairment or neurological disorder. Similarly, in some cases, visual acuity can be normal and in others can be severely degraded. Furthermore, the impact on vision goes well beyond static acuity alone, is rarely measured and may vary on a minute-to-minute, day-to-day or month-to-month basis. For these reasons, management of children with nystagmus in the UK is varied, and patients report hugely different experiences and investigations. In this review, we hope to shine a light on the current management of children with nystagmus across five specialist centres in the UK in order to present, for the first time, a consensus on investigation and clinical management."
4012,EMQN best practice guidelines for genetic testing in dystrophinopathies,"Dystrophinopathies are X-linked diseases, including Duchenne muscular dystrophy and Becker muscular dystrophy, due to DMD gene variants. In recent years, the application of new genetic technologies and the availability of new personalised drugs have influenced diagnostic genetic testing for dystrophinopathies. Therefore, these European best practice guidelines for genetic testing in dystrophinopathies have been produced to update previous guidelines published in 2010. These guidelines summarise current recommended technologies and methodologies for analysis of the DMD gene, including testing for deletions and duplications of one or more exons, small variant detection and RNA analysis. Genetic testing strategies for diagnosis, carrier testing and prenatal diagnosis (including non-invasive prenatal diagnosis) are then outlined. Guidelines for sequence variant annotation and interpretation are provided, followed by recommendations for reporting results of all categories of testing. Finally, atypical findings (such as non-contiguous deletions and dual DMD variants), implications for personalised medicine and clinical trials and incidental findings (identification of DMD gene variants in patients where a clinical diagnosis of dystrophinopathy has not been considered or suspected) are discussed."
4013,Erratum: Modeling psychiatric disorders: from genomic findings to cellular phenotypes,
4014,Opacified hydrophilic intraocular lens following DMEK,
4015,Chromatin accessibility analysis reveals that TFAP2A promotes angiogenesis in acquired resistance to anlotinib in lung cancer cells,"Anlotinib, a multitarget tyrosine kinase inhibitor, is effective as a third-line treatment against non-small cell lung cancer (NSCLC). However, acquired resistance occurs during its administration. To understand the molecular mechanisms of anlotinib resistance, we characterized chromatin accessibility in both the parental and anlotinib-resistant lung cancer cell line NCI-H1975 through ATAC-seq. Compared with the parental cells, we identified 2666 genomic regions with greater accessibility in anlotinib-resistant cells, in which angiogenesis-related processes and the motifs of 21 transcription factors were enriched. Among these transcription factors, TFAP2A was upregulated. TFAP2A knockdown robustly diminished tumor-induced angiogenesis and partially rescued the anti-angiogenic activity of anlotinib. Furthermore, transcriptome analysis indicated that 2280 genes were downregulated in anlotinib-resistant cells with TFAP2A knocked down, among which the PDGFR, TGF-β, and VEGFR signaling pathways were enriched. Meanwhile, we demonstrated that TFAP2A binds to accessible sites within BMP4 and HSPG2. Collectively, this study suggests that TFAP2A accelerates anlotinib resistance by promoting tumor-induced angiogenesis."
4016,Phase separation as a therapeutic target in tight junction-associated human diseases,"Tight junctions (TJs) play an important role in the maintenance of epithelial and endothelial barriers. Zonula occludens (ZO) proteins are scaffolding molecules essential for the formation of TJ complexes, and abnormalities in ZO proteins have been implicated in various TJ-associated human diseases such as tumor invasion and metastasis, and barrier dysfunction. Recent studies reveal that liquid–liquid phase separation of ZO proteins drives the polymerization of TJ proteins into a continuous belt, which then recruits various proteins to form the TJ complex to regulate selective paracellular permeability and signal transduction. Herein, we describe recent advances on how ZO phase separation contributes to TJ formation and discuss the potential of phase separation as a target for the treatment of TJ-associated diseases."
4017,Genome and sequence determinants governing the expression of horizontally acquired DNA in bacteria,"While horizontal gene transfer is prevalent across the biosphere, the regulatory features that enable expression and functionalization of foreign DNA remain poorly understood. Here, we combine high-throughput promoter activity measurements and large-scale genomic analysis of regulatory regions to investigate the cross-compatibility of regulatory elements (REs) in bacteria. Functional characterization of thousands of natural REs in three distinct bacterial species revealed distinct expression patterns according to RE and recipient phylogeny. Host capacity to activate foreign promoters was proportional to their genomic GC content, while many low GC regulatory elements were both broadly active and had more transcription start sites across hosts. The difference in expression capabilities could be explained by the influence of the host GC content on the stringency of the AT-rich canonical σ70 motif necessary for transcription initiation. We further confirm the generalizability of this model and find widespread GC content adaptation of the σ70 motif in a set of 1,545 genomes from all major bacterial phyla. Our analysis identifies a key mechanism by which the strength of the AT-rich σ70 motif relative to a host’s genomic GC content governs the capacity for expression of acquired DNA. These findings shed light on regulatory adaptation in the context of evolving genomic composition."
4018,Correction: Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis,
4019,Publisher Correction: IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure,
4020,Correction: DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes,
4021,Correction: Micheliolide ameliorates renal fibrosis by suppressing the Mtdh/BMP/MAPK pathway,
4022,Correction: Association of anxiety with subcortical amyloidosis in cognitively normal older adults,
4023,Correction to: Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells,
4024,CMIP is a negative regulator of T cell signaling,"Upon their interaction with cognate antigen, T cells integrate different extracellular and intracellular signals involving basal and induced protein–protein interactions, as well as the binding of proteins to lipids, which can lead to either cell activation or inhibition. Here, we show that the selective T cell expression of CMIP, a new adapter protein, by targeted transgenesis drives T cells toward a naïve phenotype. We found that CMIP inhibits activation of the Src kinases Fyn and Lck after CD3/CD28 costimulation and the subsequent localization of Fyn and Lck to LRs. Video microscopy analysis showed that CMIP blocks the recruitment of LAT and the lipid raft marker cholera toxin B at the site of TCR engagement. Proteomic analysis identified several protein clusters differentially modulated by CMIP and, notably, Cofilin-1, which is inactivated in CMIP-expressing T cells. Moreover, transgenic T cells exhibited the downregulation of GM3 synthase, a key enzyme involved in the biosynthesis of gangliosides. These results suggest that CMIP negatively impacts proximal signaling and cytoskeletal rearrangement and defines a new mechanism for the negative regulation of T cells that could be a therapeutic target."
4025,Erratum to: Changes of myocardial gene expression and protein composition in patients with dilated cardiomyopathy after immunoadsorption with subsequent immunoglobulin substitution,
4026,"Taking the scenic route: an endogenous gut lipid messenger curbs binge eating in rats: A research highlight on ‘Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge eating disorder’ by Romano et al., 2020",
4027,Correction: Epistasis between Pax6(Sey) and genetic background reinforces the value of defined hybrid mouse models for therapeutic trials,
4028,"Retraction Note to: Radiographic characteristics that delineate abusive from accidental skull fractures, including the significance of fracture extension to sutures",
4029,"Erratum: Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis",
4030,Correction: Benchmarking of survival outcomes following haematopoietic stem cell transplantation: A review of existing processes and the introduction of an international system from the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE),
4031,Correction: Extra-mitochondrial citrate synthase initiates calcium oscillation and suppresses age-dependent sperm dysfunction,
4032,Epigenetics in modulating immune functions of stromal and immune cells in the tumor microenvironment,"Epigenetic regulation of gene expression in cancer cells has been extensively studied in recent decades, resulting in the FDA approval of multiple epigenetic agents for treating different cancer types. Recent studies have revealed novel roles of epigenetic dysregulation in altering the phenotypes of immune cells and tumor-associated stromal cells, including fibroblasts and endothelial cells. As a result, epigenetic dysregulation of these cells reshapes the tumor microenvironment (TME), changing it from an antitumor environment to an immunosuppressive environment. Here, we review recent studies demonstrating how specific epigenetic mechanisms drive aspects of stromal and immune cell differentiation with implications for the development of solid tumor therapeutics, focusing on the pancreatic ductal adenocarcinoma (PDA) TME as a representative of solid tumors. Due to their unique ability to reprogram the TME into a more immunopermissive environment, epigenetic agents have great potential for sensitizing cancer immunotherapy to augment the antitumor response, as an immunopermissive TME is a prerequisite for the success of cancer immunotherapy but is often not developed with solid tumors. The idea of combining epigenetic agents with cancer immunotherapy has been tested both in preclinical settings and in multiple clinical trials. In this review, we highlight the basic biological mechanisms underlying the synergy between epigenetic therapy and immunotherapy and discuss current efforts to translate this knowledge into clinical benefits for patients."
4033,Cancer immunotherapy with γδ T cells: many paths ahead of us,"γδ T cells play uniquely important roles in stress surveillance and immunity for infections and carcinogenesis. Human γδ T cells recognize and kill transformed cells independently of human leukocyte antigen (HLA) restriction, which is an essential feature of conventional αβ T cells. Vγ9Vδ2 γδ T cells, which prevail in the peripheral blood of healthy adults, are activated by microbial or endogenous tumor-derived pyrophosphates by a mechanism dependent on butyrophilin molecules. γδ T cells expressing other T cell receptor variable genes, notably Vδ1, are more abundant in mucosal tissue. In addition to the T cell receptor, γδ T cells usually express activating natural killer (NK) receptors, such as NKp30, NKp44, or NKG2D which binds to stress-inducible surface molecules that are absent on healthy cells but are frequently expressed on malignant cells. Therefore, γδ T cells are endowed with at least two independent recognition systems to sense tumor cells and to initiate anticancer effector mechanisms, including cytokine production and cytotoxicity. In view of their HLA-independent potent antitumor activity, there has been increasing interest in translating the unique potential of γδ T cells into innovative cellular cancer immunotherapies. Here, we discuss recent developments to enhance the efficacy of γδ T cell-based immunotherapy. This includes strategies for in vivo activation and tumor-targeting of γδ T cells, the optimization of in vitro expansion protocols, and the development of gene-modified γδ T cells. It is equally important to consider potential synergisms with other therapeutic strategies, notably checkpoint inhibitors, chemotherapy, or the (local) activation of innate immunity."
4034,Correction: Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia,
4035,Correction: Cerebrospinal fluid markers of inflammation and infections in schizophrenia and affective disorders: a systematic review and meta-analysis,
4036,Correction: Corrigendum: Minimum information about a single amplified genome (MISAG) and a metagenome-assembled genome (MIMAG) of bacteria and archaea,
4037,Erratum zu: Händehygiene in Einrichtungen des Gesundheitswesens: Empfehlung der Kommission für Krankenhaushygiene und Infektionsprävention (KRINKO) beim Robert Koch-Institut,
4038,Correction to: Restoring the unrestorable! Developing coronal tooth tissue with a minimally invasive surgical extrusion technique,
4039,Guidelines for the Li–Fraumeni and heritable TP53-related cancer syndromes,"Fifty years after the recognition of the Li–Fraumeni syndrome (LFS), our perception of cancers related to germline alterations of TP53 has drastically changed: (i) germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history. This justifies the expansion of the LFS concept to a wider cancer predisposition syndrome designated heritable TP53-related cancer (hTP53rc) syndrome; (ii) the interpretation of germline TP53 variants remains challenging and should integrate epidemiological, phenotypical, bioinformatics prediction, and functional data; (iii) the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher cancer risk) and on modifying factors; (iv) whole-body MRI (WBMRI) allows early detection of tumours in variant carriers and (v) in cancer patients with germline disease-causing TP53 variants, radiotherapy, and conventional genotoxic chemotherapy contribute to the development of subsequent primary tumours. It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies. In children, the recommendations are to perform clinical examination and abdominal ultrasound every 6 months, annual WBMRI and brain MRI from the first year of life, if the TP53 variant is known to be associated with childhood cancers. In adults, the surveillance should include every year clinical examination, WBMRI, breast MRI in females from 20 until 65 years and brain MRI until 50 years."
4040,Retraction Note: Selected TLR7/8 agonist and type I interferon (IFN‑α) cooperatively redefine the microglia transcriptome,
4041,Correction: Integrative network biology analysis identifies miR-508-3p as the determinant for the mesenchymal identity and a strong prognostic biomarker of ovarian cancer,
4042,Erratum: Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival,
4043,Expanding cultural and ancestral representation in psychiatric genetic studies,
4044,Correction to: A transgenerational toxicokinetic model and its use in derivation of Minnesota PFOA water guidance,
4045,"Meibomian gland dysfunction, dropout and distress: emerging therapies",
4046,Erratum,
4047,Correction: S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells,
4048,Publisher Correction: Ecological and evolutionary approaches to managing honeybee disease,
4049,Erratum to: Inhibitory effects of bee venom and its components against viruses in vitro and in vivo,
4050,Drug development in targeting ion channels for brain edema,"Cerebral edema is a pathological hallmark of various central nervous system (CNS) insults, including traumatic brain injury (TBI) and excitotoxic injury such as stroke. Due to the rigidity of the skull, edema-induced increase of intracranial fluid significantly complicates severe CNS injuries by raising intracranial pressure and compromising perfusion. Mortality due to cerebral edema is high. With mortality rates up to 80% in severe cases of stroke, it is the leading cause of death within the first week. Similarly, cerebral edema is devastating for patients of TBI, accounting for up to 50% mortality. Currently, the available treatments for cerebral edema include hypothermia, osmotherapy, and surgery. However, these treatments only address the symptoms and often elicit adverse side effects, potentially in part due to non-specificity. There is an urgent need to identify effective pharmacological treatments for cerebral edema. Currently, ion channels represent the third-largest target class for drug development, but their roles in cerebral edema remain ill-defined. The present review aims to provide an overview of the proposed roles of ion channels and transporters (including aquaporins, SUR1-TRPM4, chloride channels, glucose transporters, and proton-sensitive channels) in mediating cerebral edema in acute ischemic stroke and TBI. We also focus on the pharmacological inhibitors for each target and potential therapeutic strategies that may be further pursued for the treatment of cerebral edema."
4051,Attitudes of relatives of mucopolysaccharidosis type III patients toward preconception expanded carrier screening,"Preconception expanded carrier screening (ECS) aims to detect carrier couples of autosomal recessive (AR) disorders before pregnancy in order to increase reproductive autonomy of prospective parents. Genetic knowledge and knowledge gained from experience influence decision making on participation in genetic testing and understanding carrier test results. In this study we assessed whether parents and relatives of patients with the severe AR condition mucopolysaccharidosis type III (MPS III), who are expected to have genetic and experiential knowledge, have more positive attitudes toward ECS than the Dutch reference group. Parents of all MPS III patients known to the Dutch expert center were invited to participate and asked to invite first and second degree relatives. The online questionnaire started with an educational text, and assessed attitudes toward ECS, genetic knowledge and perceived MPS III severity. Results were compared with the Dutch population. Parents and relatives of MPS III patients (n = 159) scored higher on the genetic knowledge test and perceived MPS III as more severe compared with the general Dutch population (n = 781). Parents and relatives reported to be more likely to participate in ECS (84.3% and 62.5%, respectively) compared with the public (31%) (p < 0.001). Being a relative of a MPS III patient was the strongest variable in the regression analyses for intended ECS participation. Our results show that genetic knowledge influences ECS decision making. Therefore, appropriate information on ECS and genetic counseling is needed to enable prospective parents from the general population, including relatives of patients with severe hereditary disorders, to make informed decisions."
4052,Structures of the four Ig-like domain LILRB2 and the four-domain LILRB1 and HLA-G1 complex,"Leukocyte immunoglobulin (Ig)-like receptors (LILRs), also known as CD85 and immunoglobulin-like transcripts (ILTs), play pivotal roles in regulating immune responses. These receptors define an immune checkpoint that immune therapy can target. Through cis or trans interactions with human leukocyte antigen (HLA)-G, the two most abundantly expressed inhibitory LILRs, LILRB1, and LILRB2 (LILRB1/2, also known as CD85j/d and ILT2/4), are involved in immunotolerance in pregnancy and transplantation, autoimmune diseases, and immune evasion by tumors. Although the discrete domains of LILRB1/2 are clear, the assembly mode of the four extracellular Ig-like domains (D1, D2, D3, and D4) remains unknown. Previous data indicate that D1D2 is responsible for binding to HLA class I (HLA-I), but the roles of D3D4 are still unclear. Here, we determined the crystal structure of the four Ig-like domain LILRB2 and four-domain LILRB1 in complex with HLA-G1. The angles between adjacent domains and the staggered assembly of the four domains suggest limited flexibility and limited plasticity of the receptors during ligand binding. The complex structure of four-domain LILRB1 and HLA-G1 supports the model that D1D2 is responsible for HLA-I binding, while D3D4 acts as a scaffold. Accordingly, cis and trans binding models for HLA-I binding to LILRB1/2 are proposed. The geometries of LILRB1/2 in complex with dimeric and monomeric HLA-G1 suggest the accessibility of the dimeric receptor, which in turn, transduces more inhibitory signals. The assembly of LILRB1/2 and its binding to HLA-G1 could aid in the design of immune regulators and benefit immune interference."
4053,Omission of previous publications by an author should be corrected,
4054,"The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals","Metabolic diseases are the most common and rapidly growing health issues worldwide. The massive population-based human genetics is crucial for the precise prevention and intervention of metabolic disorders. The China Metabolic Analytics Project (ChinaMAP) is based on cohort studies across diverse regions and ethnic groups with metabolic phenotypic data in China. Here, we describe the centralized analysis of the deep whole genome sequencing data and the genetic bases of metabolic traits in 10,588 individuals from the ChinaMAP. The frequency spectrum of variants, population structure, pathogenic variants and novel genomic characteristics were analyzed. The individual genetic evaluations of Mendelian diseases, nutrition and drug metabolism, and traits of blood glucose and BMI were integrated. Our study establishes a large-scale and deep resource for the genetics of East Asians and provides opportunities for novel genetic discoveries of metabolic characteristics and disorders."
4055,Erratum: A TLR7 agonist enhances the antitumor efficacy of obinutuzumab in murine lymphoma models via NK cells and CD4 T cells,
4056,Correction: Mapping the genomic landscape of inherited retinal disease genes prioritizes genes prone to coding and noncoding copy-number variations,
4057,Geng et al. reply,
4058,Shifting to very early endoscopic DCR in acute suppurative dacryocystitis,"PURPOSE: We aimed to show the outcome of very early endoscopic dacryocystorhinostomy (VE-EDCR) in a routine pool of patients with acute dacryocystitis (AD) and abscess formation compared with the standard late external dacryocystorhinostomy L-ExDCR. METHODS: This was a prospective nonrandomized comparative study conducted from June 2013 to March 2016. Patients with AD and abscess formation were referred to our oculo-facial clinic in a university-based hospital. All patients received systemic antibiotics and were assigned to either of treatment groups. Patients in group 1 underwent late external transcutaneous DCR (L-ExDCR) and group 2 underwent EDCR within 3 days after first visit, named VE-EDCR. Primary outcome measure was success of surgery. RESULTS: Forty-one eyes of 41 patients with acute suppurative AD, were included from June 2013 to March 2016. Twenty-two patients underwent VE-EDCR and 19 underwent L-ExDCR. Mean age of patients was 43.41 (SD = 19.84, range 14–98) years. Mean follow-up was 14 (SD = 2.4) months. Anatomic, functional, and overall success in L-ExDCR and VE-EDCR groups were (89.5 and 86.4%, p = 0.99) (89.5% and 86.4%, p = 0.99) (89.5% and 81.8%, p = 0.66) respectively. Mean duration of cellulitis in VE-EDCR and L-ExDCR were 8.00 (SD = 4.63) and 16.11 (SD = 11.58) days, respectively (p = 0.027). No remarkable adverse event was found. CONCLUSIONS: Success of very early endonasal endoscopic DCR is comparable with the traditional late external DCR. Duration of cellulitis is shorter in VE-EDCR. This therapeutic approach can be considered in patients with acute suppurative dacryocystitis."
4059,Seeing is believing: a novel tool for quantitating mitophagy,
4060,Outcomes and complications of iris-fixated intraocular lenses in cases with inadequate capsular support and complex ophthalmic history,"BACKGROUND: To report the indications, visual outcomes, and intra-operative and post-operative complications of iris-sutured posterior chamber intraocular lens (IOL) in eyes with inadequate capsular support and complex ocular history. METHODS: A chart review and data analysis of eyes that underwent iris fixation of posterior chamber (PC) IOL for correction of aphakia, dislocated and subluxed IOLs, ectopia lentis, and IOL exchange. Data included clinical risk factors, associated eye conditions, previous surgeries, and concomitant procedures. The pre-operative and post-operative vision, manifest refraction, endothelial cell density, intraocular pressure (IOP), as well as intra-operative and post-operative complications were also recorded. RESULTS: One hundred and seventeen eyes from 114 patients were examined with a mean follow-up of 22.4 months. The most common identifiable predisposing risk factor was high myopia in 23 eyes. A significant improvement in uncorrected and best corrected visual acuity compared with baseline was observed. The most common post-operative complications included recurrent IOL subluxation in 16 (13.7%) eyes, IOP spike in 7 (5.9%) eyes, cystoid macular oedema in 5 (4.3%) eyes, and epiretinal membrane formation in 4 (3.4%) eyes. There was one (0.85%) case of sterile endophthalmitis. CONCLUSIONS: Iris suture fixation of PC IOLs is a good treatment option for eyes with inadequate capsular support and complex ocular history."
4061,Erratum: Arc expression identifies the lateral amygdala fear memory trace,
4062,SRD5A3 defective congenital disorder of glycosylation: clinical utility gene card,
4063,Erratum: Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia,
4064,A serine protease inhibitor induces type 1 regulatory T cells through IFN-γ/STAT1 signaling,
4065,Response to ‘Comment on: ophthalmology specialist trainee survey in the United Kingdom’,
4066,Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge eating disorder,"Binge eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell (“frustration stress”). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg(−1)) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior."
4067,Correction to: Transpiration and growth of young African mahogany plants subject to different water regimes,
4068,Erratum: PML is required for telomere stability in non-neoplastic human cells,
4069,"Erratum: Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention",
4070,Correction: The atypical ubiquitin ligase RNF31 stabilizes estrogen receptor α and modulates estrogen-stimulated breast cancer cell proliferation,
4071,"Correction: Connectomics of bipolar disorder: a critical review, and evidence for dynamic instabilities within interoceptive networks",
4072,"Amblyopia, deprivation and health disparities research: challenges in 2020",
4073,Professional duties are now considered legal duties of care within genomic medicine,"The legal duty to protect patient confidentiality is common knowledge amongst healthcare professionals. However, what may not be widely known, is that this duty is not always absolute. In the United Kingdom, both the General Medical Council governing the practice of all doctors, as well as many other professional codes of practice recognise that, under certain circumstances, it may be appropriate to break confidentiality. This arises when there is a wider duty to protect the health of others, and when the risk of non-disclosure outweighs the potential harm from breaking confidentiality. We discuss this situation specifically in relation to genomic medicine where relatives in a family may have differing views on the sharing of familial genetic information. Overruling a patient’s wishes is predicated on balancing the duty of care towards the patient versus protecting their relative from serious harm. We discuss the practice implications of a pivotal legal case that concluded recently in the High Court of Justice in England and Wales, ABC v St Georges Healthcare NHS Trust & Ors. Professional guidance is already clear that genetic healthcare professionals must undertake a balancing exercise to weigh up contradictory duties of care. However, the judge has provided a new legal weighting to these professional duties: ‘The scope of the duty extends not only to conducting the necessary balancing exercise but also to acting in accordance with its outcome’ [1: 189]. In the context of genomic medicine, this has important consequences for clinical practice."
4074,A systematic review of simulation-based training tools for technical and non-technical skills in ophthalmology,"To evaluate all simulation models for ophthalmology technical and non-technical skills training and the strength of evidence to support their validity and effectiveness. A systematic search was performed using PubMed and Embase for studies published from inception to 01/07/2019. Studies were analysed according to the training modality: virtual reality; wet-lab; dry-lab models; e-learning. The educational impact of studies was evaluated using Messick’s validity framework and McGaghie’s model of translational outcomes for evaluating effectiveness. One hundred and thirty-one studies were included in this review, with 93 different simulators described. Fifty-three studies were based on virtual reality tools; 47 on wet-lab models; 26 on dry-lab models; 5 on e-learning. Only two studies provided evidence for all five sources of validity assessment. Models with the strongest validity evidence were the Eyesi Surgical, Eyesi Direct Ophthalmoscope and Eye Surgical Skills Assessment Test. Effectiveness ratings for simulator models were mostly limited to level 2 (contained effects) with the exception of the Sophocle vitreoretinal surgery simulator, which was shown at level 3 (downstream effects), and the Eyesi at level 5 (target effects) for cataract surgery. A wide range of models have been described but only the Eyesi has undergone comprehensive investigation. The main weakness is in the poor quality of study design, with a predominance of descriptive reports showing limited validity evidence and few studies investigating the effects of simulation training on patient outcomes. More robust research is needed to enable effective implementation of simulation tools into current training curriculums."
4075,A dominant vimentin variant causes a rare syndrome with premature aging,"Progeroid syndromes are a group of rare genetic disorders, which mimic natural aging. Unraveling the molecular defects in such conditions could impact our understanding of age-related syndromes such as Alzheimer’s or cardiovascular diseases. Here we report a de novo heterozygous missense variant in the intermediate filament vimentin (c.1160 T > C; p.(Leu387Pro)) causing a multisystem disorder associated with frontonasal dysostosis and premature aging in a 39-year-old individual. Human vimentin p.(Leu387Pro) expression in zebrafish perturbed body fat distribution, and craniofacial and peripheral nervous system development. In addition, studies in patient-derived and transfected cells revealed that the variant affects vimentin turnover and its ability to form filaments in the absence of wild-type vimentin. Vimentin p.(Leu387Pro) expression diminished the amount of peripilin and reduced lipid accumulation in differentiating adipocytes, recapitulating key patient’s features in vivo and in vitro. Our data highlight the function of vimentin during development and suggest its contribution to natural aging."
4076,Correction to: ROS and diseases: role in metabolism and energy supply,
4077,Correction: CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer,
4078,Publisher Correction: Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus,
4079,Training in and comfort with diagnosis and management of ophthalmic emergencies among emergency medicine physicians in the United States,"BACKGROUND/OBJECTIVES: Patients with ophthalmic emergencies often present to emergency rooms. Emergency medicine (EM) physicians should feel comfortable encountering these conditions. We assessed EM physicians’ comfort working up, diagnosing, and managing ophthalmic emergencies. SUBJECTS/METHODS: 329 EM physicians participated in this cross-sectional multicentre survey. Questions inquired about the amount, type, and self-perceived adequacy of ophthalmic training. Likert scales were used to assess confidence and comfort working up, diagnosing, and managing ophthalmic emergencies. RESULTS: Participants recall receiving a median of 5 and 10 h of ophthalmic training in medical school and residency, respectively. Few feel this prepared them for residency (16.5%) or practice (52.0%). Only 50.6% feel confident with their ophthalmic exam. Most (75.0%) feel confident in their ability to identify an ophthalmic emergency, but 58.8% feel well prepared to work them up. Responders feel more comfortable diagnosing acute retrobulbar hematoma (72.5%), retinal detachment (69.8%), and acute angle closure glaucoma (78.0%) than central retinal artery occlusion (28.9%) or giant cell arteritis (53.2%). Only 60.2% feel comfortable determining if canthotomy and cantholysis is necessary in the setting of acute retrobulbar hematoma, and 40.3% feel comfortable performing the procedure. There was a trend towards attending physicians and providers in urban and academic settings feeling more comfortable diagnosing and managing ophthalmic emergencies compared to trainees, non-urban, and non-academic physicians. CONCLUSIONS: Many participants do not feel comfortable using ophthalmic equipment, performing an eye exam, making vision or potentially life-saving diagnoses, or performing vision-saving procedures, suggesting the need to increase ophthalmic training in EM curricula."
4080,Correction: Corrigendum: Genetic diagnosis of Duchenne/Becker muscular dystrophy using next-generation sequencing: validation analysis of DMD mutations,
4081,Making ends meet in class switch recombination,
4082,The choice of analysis of variance models in repeated measurements analysis—on the effect of glaucoma surgery on retinal structures,
4083,Author Correction: Biofortification of field-grown cassava by engineering expression of an iron transporter and ferritin,
4084,Correction: Comment on: ‘Recent advances in anterior chamber angle imaging’,
4085,High rate of HDR in gene editing of p.(Thr158Met) MECP2 mutational hotspot,"Rett syndrome is a progressive neurodevelopmental disorder which affects almost exclusively girls, caused by variants in MECP2 gene. Effective therapies for this devastating disorder are not yet available and the need for tight regulation of MECP2 expression for brain to properly function makes gene replacement therapy risky. For this reason, gene editing with CRISPR/Cas9 technology appears as a preferable option for the development of new therapies. To study the disease, we developed and characterized a human neuronal model obtained by genetic reprogramming of patient-derived primary fibroblasts into induced Pluripotent Stem Cells. This cellular model represents an important source for our studies, aiming to correct MECP2 variants in neurons which represent the primarily affected cell type. We engineered a gene editing toolkit composed by a two-plasmid system to correct a hotspot missense variant in MECP2, c.473 C > T (p.(Thr158Met)). The first construct expresses the variant-specific sgRNA and the Donor DNA along with a fluorescent reporter system. The second construct brings Cas9 and targets for auto-cleaving, to avoid long-term Cas9 expression. NGS analysis on sorted cells from four independent patients demonstrated an exceptionally high editing efficiency, with up to 80% of HDR and less than 1% of indels in all patients, outlining the relevant potentiality of the approach for Rett syndrome therapy."
4086,Correction: O-GlcNAcylation promotes colorectal cancer metastasis via the miR-101-O-GlcNAc/EZH2 regulatory feedback circuit,
4087,Correction: Disruption of gap junctions attenuates acute myeloid leukemia chemoresistance induced by bone marrow mesenchymal stromal cells,
4088,EMQN best practice guidelines for molecular genetic testing and reporting of 21-hydroxylase deficiency,"Molecular genetic testing for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is offered worldwide and is of importance for differential diagnosis, carrier detection and adequate genetic counseling, particularly for family planning. In 2008 the European Molecular Genetics Quality Network (EMQN) for the first time offered a European-wide external quality assessment scheme for CAH (due to 21-OH deficiency). The interest was great and over the last years at about 60 laboratories from Europe, USA and Australia regularly participated in that scheme. These best practice guidelines were drafted on the basis of the extensive knowledge and experience got from those annually organized CAH-schemes. In order to obtain the widest possible consultation with practicing laboratories the draft was therefore circulated twice by EMQN to all laboratories participating in the EQA-scheme for CAH genotyping and was updated by that input. The present guidelines address quality requirements for diagnostic molecular genetic laboratories, as well as criteria for CYP21A2 genotyping (including carrier-testing and prenatal diagnosis). A key aspect of that article is the use of appropriate methodologies (e.g., sequencing methods, MLPA (multiplex ligation dependent probe amplification), mutation specific assays) and respective limitations and analytical accuracy. Moreover, these guidelines focus on classification of variants, and the interpretation and standardization of the reporting of CYP21A2 genotyping results. In addition, the article provides a comprehensive list of common as well as so far unreported CYP21A2-variants."
4089,Quality of life drives patients’ preferences for secondary findings from genomic sequencing,"There is growing impetus to include measures of personal utility, the nonmedical value of information, in addition to clinical utility in health technology assessment (HTA) of genomic tests such as genomic sequencing (GS). However, personal utility and clinical utility are challenging to define and measure. This study aimed to explore what drives patients’ preferences for hypothetically learning medically actionable and non-medically actionable secondary findings (SF), capturing clinical and personal utility; this may inform development of measures to evaluate patient outcomes following return of SF. Semi-structured interviews were conducted with adults with a personal or family cancer history participating in a trial of a decision aid for selection of SF from genomic sequencing (GS) (www.GenomicsADvISER.com). Interviews were analyzed thematically using constant comparison. Preserving health-related and non-health-related quality of life was an overarching motivator for both learning and not learning SF. Some participants perceived that learning SF would help them “have a good quality of life” through informing actions to maintain physical health or leading to psychological benefits such as emotional preparation for disease. Other participants preferred not to learn SF because results “could ruin your quality of life,” such as by causing negative psychological impacts. Measuring health-related and non-health-related quality of life may capture outcomes related to clinical and personal utility of GS and SF, which have previously been challenging to measure. Without appropriate measures, generating and synthesizing evidence to evaluate genomic technologies such as GS will continue to be a challenge, and will undervalue potential benefits of GS and SF."
4090,Erratum: Infrequently expressed miRNAs in colorectal cancer tissue and tumor molecular phenotype,
4091,Ecological succession in the vaginal microbiota during pregnancy and birth,"The mother’s vaginal microbiota represents the first microbes to which a child is exposed when delivered vaginally. However, little is known about the composition and development of the vaginal microbiota during pregnancy and birth. Here, we analyzed the vaginal microbiota of 57 women in pregnancy week 24, 36 and at birth after rupture of membranes but before delivery, and further compared the composition with that of the gut and airways of the 1-week-old child. The vaginal community structure had dramatic changes in bacterial diversity and taxonomic distribution, yet carried an individual-specific signature. The relative abundance of most bacterial taxa increased stepwise from week 24 of pregnancy until birth, with a gradual decline of Lactobacillus. Mother-to-child vertical transfer, as suggested by sharing, was modest, with the strongest transfer being for Clostridiales followed by Lactobacillales and Enterobacteriales. In conclusion, late gestation is associated with an increase in maternal vaginal microbiota diversity, and vaginal bacteria at birth only modestly predict the composition of the neonatal microbiota."
4092,"Linking perturbations to temporal changes in diversity, stability, and compositions of neonatal calf gut microbiota: prediction of diarrhea","Perturbations in early life gut microbiota can have long-term impacts on host health. In this study, we investigated antimicrobial-induced temporal changes in diversity, stability, and compositions of gut microbiota in neonatal veal calves, with the objective of identifying microbial markers that predict diarrhea. A total of 220 samples from 63 calves in first 8 weeks of life were used in this study. The results suggest that increase in diversity and stability of gut microbiota over time was a feature of “healthy” (non-diarrheic) calves during early life. Therapeutic antimicrobials delayed the temporal development of diversity and taxa–function robustness (a measure of microbial stability). In addition, predicted genes associated with beta lactam and cationic antimicrobial peptide resistance were more abundant in gut microbiota of calves treated with therapeutic antimicrobials. Random forest machine learning algorithm revealed that Trueperella, Streptococcus, Dorea, uncultured Lachnospiraceae, Ruminococcus 2, and Erysipelatoclostridium may be key microbial markers that can differentiate “healthy” and “unhealthy” (diarrheic) gut microbiota, as they predicted early life diarrhea with an accuracy of 84.3%. Our findings suggest that diarrhea in veal calves may be predicted by the shift in early life gut microbiota, which may provide an opportunity for early intervention (e.g., prebiotics or probiotics) to improve calf health with reduced usage of antimicrobials."
4093,Correction: A transgenerational toxicokinetic model and its use in derivation of Minnesota PFOA water guidance,
4094,"Free fatty acid receptor 4 (FFA4) activation ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by increasing regulatory T cells in mice","High dose intake of docosahexaenoic acid showed beneficial effects on atopic dermatitis in patients and was found to increase regulatory T cells in mice, but its molecular target has not been identified. Free fatty acid receptor 4 (FFA4, also known as GPR120) is a receptor sensing polyunsaturated long-chain fatty acids including docosahexaenoic acid. In the present study, we examined whether FFA4 acted as a therapeutic target of docosahexaenoic acid for treating atopic dermatitis. Experimental atopic dermatitis was induced in mice by 2,4-dinitrochlorobenzene (DNCB) sensitization on day 0, followed by repeated DNCB challenges from D7 to D48. The mice were treated with a selective agonist compound A (30 mg· kg(−1)· d(−1), ip) from D19 to D48, and sacrificed on D49. We found that DNCB-induced atopic dermatitis-like skin lesions, i.e. hypertrophy and mast cell infiltration in skin tissues, as well as markedly elevated serum IgE levels. Administration of compound A significantly suppressed the atopic responses in ears and lymph nodes, such as hypertrophy and mast cell infiltration in the ears, enlarged sizes of lymph nodes, and elevated serum IgE and levels of cytokines IL-4, IL-13, IL-17, and IFN-γ in ear tissue. The therapeutic effects of compound A were abolished by FFA4 knockout. Similarly, increased CD4(+)Foxp3(+) regulatory T-cell population in lymph nodes was observed in wide-type mice treated with compound A, but not seen in FFA4-deficient mice. In conclusion, we demonstrate that activation of FFA4 ameliorates atopic dermatitis by increasing CD4(+)Foxp3(+) regulatory T cells, suggesting FFA4 as a therapeutic target for atopic dermatitis."
4095,Author Correction: 863 genomes reveal the origin and domestication of chicken,
4096,Publisher Correction: Definitions and guidelines for research on antibiotic persistence,
4097,Erratum: Common alleles contribute to schizophrenia in CNV carriers,
4098,Correction: The Epstein–Barr virus nuclear antigen-1 upregulates the cellular antioxidant defense to enable B-cell growth transformation and immortalization,
4099,Author Correction: Liriodendron genome sheds light on angiosperm phylogeny and species–pair differentiation,
4100,Cinnamaldehyde protects against rat intestinal ischemia/reperfusion injuries by synergistic inhibition of NF-κB and p53,"Our preliminary study shows that cinnamaldehyde (CA) could protect against intestinal ischemia/reperfusion (I/R) injuries, in which p53 and NF-κB p65 play a synergistic role. In this study, we conducted in vivo and in vitro experiments to verify this proposal. SD rats were pretreated with CA (10 or 40 mg · kg(−1) · d(−1), ig) for 3 days, then subjected to 1 h mesenteric ischemia followed by 2 h reperfusion. CA pretreatment dose-dependently ameliorated morphological damage and reduced inflammation evidenced by decreased TNF-α, IL-1β, and IL-6 levels and MPO activity in I/R-treated intestinal tissues. CA pretreatment also attenuated oxidative stress through restoring SOD, GSH, LDH, and MDA levels in I/R-treated intestinal tissues. Furthermore, CA pretreatment significantly reduced the expression of inflammation/apoptosis-related NF-κB p65, IKKβ, IK-α, and NF-κB p50, and downregulated apoptotic protein expression including p53, Bax, caspase-9 and caspase-3, and restoring Bcl-2, in I/R-treated intestinal tissues. We pretreated IEC-6 cells in vitro with CA for 24 h, followed by 4 h hypoxia and 3 h reoxygenation (H/R) incubation. Pretreatment with CA (3.125, 6.25, and 12.5 μmol · L(−1)) significantly reversed H/R-induced reduction of IEC-6 cell viability. CA pretreatment significantly suppressed oxidative stress, NF-κB activation and apoptosis in H/R-treated IEC-6 cells. Moreover, CA pretreatment significantly reversed mitochondrial dysfunction in H/R-treated IEC-6 cells. CA pretreatment inhibited the nuclear translocation of p53 and NF-κB p65 in H/R-treated IEC-6 cells. Double knockdown or overexpression of p53 and NF-κB p65 caused a synergistic reduction or elevation of p53 compared with knockdown or overexpression of p53 or NF-κB p65 alone. In H/R-treated IEC-6 cells with double knockdown or overexpression of NF-κB p65 and p53, CA pretreatment caused neither further decrease nor increase of NF-κB p65 or p53 expression, suggesting that CA-induced synergistic inhibition on both NF-κB and p53 played a key role in ameliorating intestinal I/R injuries. Finally, we used immunoprecipitation assay to demonstrate an interaction between p53 and NF-κB p65, showing the basis for CA-induced synergistic inhibition. Our results provide valuable information for further studies."
4101,Prediction of culture-positive sepsis and selection of empiric antibiotics in critically ill patients with complicated intra-abdominal infections: a retrospective study,"PURPOSE: To compare the mortality rates between culture-positive and culture-negative sepsis in complicated intra-abdominal infections (cIAI) and investigate the predictors of culture-positivity and their causative microorganisms. MATERIALS AND METHODS: The medical records of 1581 adult patients who underwent emergency gastrointestinal surgery between January 2013 and December 2018 were reviewed retrospectively. A total of 239 patients with sepsis or septic shock who were admitted to an emergency department, underwent emergency surgery for cIAI, and needed postoperative intensive care unit care were included and divided into two groups according to their initial blood and peritoneal culture results. RESULTS: Among the 239 patients, 200 were culture-negative and 39 were culture-positive. The culture-positive group had higher in-hospital (35.9% vs 14.5%; P = .001) and 30-day mortality (30.8% vs 12.0%; P = .003) than the culture-negative group. Colon involvement (OR 4.211; 95% CI 1.909–9.287; P < .001) and higher Sequential Organ Failure Assessment (SOFA) score (OR 1.169; 95% CI 1.065–1.282; P = .001) were shown to be the predictors of culture-positive sepsis for cIAI. Regarding antibiotic sensitivity, 31.6% of the gram-positive bacteria were methicillin-resistant and 42.1% of the gram-negative bacteria were extended spectrum β-lactamase-producing Enterobacteriaceae. CONCLUSIONS: Patients with cIAI had higher mortality rates in culture-positive sepsis than in culture-negative sepsis. High SOFA score and colon involvement were the risk factors associated with culture-positivity. The most common single species grown in the blood or peritoneal cultures was Escherichia coli, and the most common group was Gram-positive cocci. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00068-020-01535-6) contains supplementary material, which is available to authorized users."
4102,Cellular Imprinting Proteomics Assay: A Novel Method for Detection of Neural and Ocular Disorders Applied to Congenital Zika Virus Syndrome,"[Image: see text] Congenital Zika syndrome was first described due to increased incidence of congenital abnormalities associated with Zika virus (ZIKV) infection. Since the eye develops as part of the embryo central nervous system (CNS) structure, it becomes a specialized compartment able to display symptoms of neurodegenerative diseases and has been proposed as a noninvasive approach to the early diagnosis of neurological diseases. Ocular lesions result from defects that occurred during embryogenesis and can become apparent in newborns exposed to ZIKV. Furthermore, the absence of microcephaly cannot exclude the occurrence of ocular lesions and other CNS manifestations. Considering the need for surveillance of newborns and infants with possible congenital exposure, we developed a method termed cellular imprinting proteomic assay (CImPA) to evaluate the ocular surface proteome specific to infants exposed to ZIKV during gestation compared to nonexposure. CImPA combines surface cells and fluid capture using membrane disks and a large-scale quantitative proteomics approach, which allowed the first-time report of molecular alterations such as neutrophil degranulation, cell death signaling, ocular and neurological pathways, which are associated with ZIKV infection with and without the development of congenital Zika syndrome, CZS. Particularly, infants exposed to ZIKV during gestation and without early clinical symptoms could be detected using the CImPA method. Lastly, this methodology has broad applicability as it could be translated in the study of several neurological diseases to identify novel diagnostic biomarkers. Data are available via ProteomeXchange with identifier PXD014038."
4103,Age-Dependent Glycomic Response to the 2009 Pandemic H1N1 Influenza Virus and Its Association with Disease Severity,"[Image: see text] Influenza A viruses cause a spectrum of responses, from mild coldlike symptoms to severe respiratory illness and death. Intrinsic host factors, such as age, can influence disease severity. Glycosylation plays a critical role in influenza pathogenesis; however, the molecular drivers of influenza outcomes remain unknown. In this work, we characterized the host glycomic response to the H1N1 2009 pandemic influenza A virus (H1N1pdm09) as a function of age-dependent severity in a ferret model. Using our dual-color lectin microarray technology, we examined baseline glycosylation and glycomic response to infection in newly weaned and aged animals, models for young children and the elderly, respectively. Compared to adult uninfected ferrets, we observed higher levels of α-2,6-sialosides, the receptor for H1N1pdm09, in newly weaned and aged animals. We also observed age-dependent loss of O-linked α-2,3-sialosides. The loss of these highly charged groups may impact viral clearance by mucins, which corresponds to the lower clearance rates observed in aged animals. Upon infection, we observed dramatic changes in the glycomes of aged animals, a population severely impacted by the virus. In contrast, no significant alterations were observed in the newly weaned animals, which show mild to moderate responses to the H1N1pdm09. High mannose, a glycan recently identified as a marker of severity in adult animals, increased with severity in the aged population. However, the response was delayed, in line with the delayed development of pneumonia observed. Overall, our results may help explain the differential susceptibility to influenza A infection and severity observed as a function of age."
4104,Ebola Virus VP35 Protein: Modeling of the Tetrameric Structure and an Analysis of Its Interaction with Human PKR,"[Image: see text] The Viral Protein 35 (VP35), a crucial protein of the Zaire Ebolavirus (EBOV), interacts with a plethora of human proteins to cripple the human immune system. Despite its importance, the entire structure of the tetrameric assembly of EBOV VP35 and the means by which it antagonizes the autophosphorylation of the kinase domain of human protein kinase R (PKR(K)) is still elusive. We consult existing structural information to model a tetrameric assembly of the VP35 protein where 93% of the protein is modeled using crystal structure templates. We analyze our modeled tetrameric structure to identify interchain bonding networks and use molecular dynamics simulations and normal-mode analysis to unravel the flexibility and deformability of the different regions of the VP35 protein. We establish that the C-terminal of VP35 (VP35(C)) directly interacts with PKR(K) to prevent it from autophosphorylation. Further, we identify three plausible VP35(C)–PKR(K) complexes with better affinity than the PKR(K) dimer formed during autophosphorylation and use protein design to establish a new stretch in VP35(C) that interacts with PKR(K). The proposed tetrameric assembly will aid in better understanding of the VP35 protein, and the reported VP35(C)–PKR(K) complexes along with their interacting sites will help in the shortlisting of small molecule inhibitors."
4105,Molecular Characterization of the Coproduced Extracellular Vesicles in HEK293 during Virus-Like Particle Production,"[Image: see text] Vaccine therapies based on virus-like particles (VLPs) are currently in the spotlight due to their potential for generating high immunogenic responses while presenting fewer side effects than conventional vaccines. These self-assembled nanostructures resemble the native conformation of the virus but lack genetic material. They are becoming a promising platform for vaccine candidates against several diseases due to the ability of modifying their membrane with antigens from different viruses. The coproduction of extracellular vesicles (EVs) when producing VLPs is a key phenomenon currently still under study. In order to characterize this extracellular environment, a quantitative proteomics approach has been carried out. Three conditions were studied: non-transfected, transfected with an empty plasmid as control, and transfected with a plasmid coding for HIV-1 Gag polyprotein. A shift in EV biogenesis has been detected upon transfection, changing the production from large to small EVs. Another remarkable trait found was the presence of DNA being secreted within vesicles smaller than 200 nm. Studying the protein profile of these biological nanocarriers, it was observed that EVs were reflecting an overall energy homeostasis disruption via mitochondrial protein deregulation. Also, immunomodulatory proteins like ITGB1, ENO3, and PRDX5 were identified and quantified in VLP and EV fractions. These findings provide insight on the nature of the VLP extracellular environment defining the characteristics and protein profile of EVs, with potential to develop new downstream separation strategies or using them as adjuvants in viral therapies."
4106,Cannabidiol interactions with voltage-gated sodium channels,"Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for the treatment of neurological diseases. Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations. This study used high-resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels. CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD. In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels."
4107,Correction: Data visualisation to support obesity policy: case studies of data tools for planning and transport policy in the UK,
4108,Structures of the Mononegavirales Polymerases,"Mononegavirales, known as nonsegmented negative-sense (NNS) RNA viruses, are a class of pathogenic and sometimes deadly viruses that include rabies virus (RABV), human respiratory syncytial virus (HRSV), and Ebola virus (EBOV). Unfortunately, no effective vaccines and antiviral therapeutics against many Mononegavirales are currently available. Viral polymerases have been attractive and major antiviral therapeutic targets. Therefore, Mononegavirales polymerases have been extensively investigated for their structures and functions. Mononegavirales mimic RNA synthesis of their eukaryotic counterparts by utilizing multifunctional RNA polymerases to replicate entire viral genomes and transcribe viral mRNAs from individual viral genes as well as synthesize 5′ methylated cap and 3′ poly(A) tail of the transcribed viral mRNAs. The catalytic subunit large protein (L) and cofactor phosphoprotein (P) constitute the Mononegavirales polymerases. In this review, we discuss the shared and unique features of RNA synthesis, the monomeric multifunctional enzyme L, and the oligomeric multimodular adapter P of Mononegavirales. We outline the structural analyses of the Mononegavirales polymerases since the first structure of the vesicular stomatitis virus (VSV) L protein determined in 2015 and highlight multiple high-resolution cryo-electron microscopy (cryo-EM) structures of the polymerases of Mononegavirales, namely, VSV, RABV, HRSV, human metapneumovirus (HMPV), and human parainfluenza virus (HPIV), that have been reported in recent months (2019 to 2020). We compare the structures of those polymerases grouped by virus family, illustrate the similarities and differences among those polymerases, and reveal the potential RNA synthesis mechanisms and models of highly conserved Mononegavirales. We conclude by the discussion of remaining questions, evolutionary perspectives, and future directions."
4109,Forward into the second century of Haematologica,
4110,Biosynthesis of lanthionine-constrained agonists of G protein-coupled receptors,"The conformation with which natural agonistic peptides interact with G protein-coupled receptor(s) (GPCR(s)) partly results from intramolecular interactions such as hydrogen bridges or is induced by ligand–receptor interactions. The conformational freedom of a peptide can be constrained by intramolecular cross-links. Conformational constraints enhance the receptor specificity, may lead to biased activity and confer proteolytic resistance to peptidic GPCR agonists. Chemical synthesis allows to introduce a variety of cross-links into a peptide and is suitable for bulk production of relatively simple lead peptides. Lanthionines are thioether bridged alanines of which the two alanines can be introduced at different distances in chosen positions in a peptide. Thioether bridges are much more stable than disulfide bridges. Biosynthesis of lanthionine-constrained peptides exploiting engineered Gram-positive or Gram-negative bacteria that contain lanthionine-introducing enzymes constitutes a convenient method for discovery of lanthionine-stabilized GPCR agonists. The presence of an N-terminal leader peptide enables dehydratases to dehydrate serines and threonines in the peptide of interest after which a cyclase can couple the formed dehydroamino acids to cysteines forming (methyl)lanthionines. The leader peptide also guides the export of the formed lanthionine-containing precursor peptide out of Gram-positive bacteria via a lanthipeptide transporter. An engineered cleavage site in the C-terminus of the leader peptide allows to cleave off the leader peptide yielding the modified peptide of interest. Lanthipeptide GPCR agonists are an emerging class of therapeutics of which a few examples have demonstrated high efficacy in animal models of a variety of diseases. One lanthipeptide GPCR agonist has successfully passed clinical Phase Ia."
4111,Kardiale Magnetresonanztomographie: Trends und Entwicklungen,"BACKGROUND: In its almost 25 years of clinical use, cardiac magnetic resonance imaging (CMR) has been developed for a wide range of indications due to the development of robust techniques and their comprehensive validation. CMR-based assessment of cardiac volumes and systolic ventricular function as well as the characterization of focal myocardial scars belongs today to standard cardiac imaging. More recently, the introduction of accelerated acquisition techniques, quantitative myocardial T1- and T2-mapping methods and 4‑dimensional (4D) flow measurements as well as new postprocessing techniques such as myocardial feature tracking have attracted attention. METHODS: This review is based on a comprehensive literature search in the PubMed database on new CMR techniques and their clinical application. RESULTS AND CONCLUSION: This article provides an overview of the latest technical developments in the field of CMR and their possible applications based on the most important clinical MR issues."
4112,Review of therapeutic options for infections with carbapenem-resistant Klebsiella pneumoniae,"Infections with multi-drug resistant (MDR) bacteria including carbapenem-resistant Klebsiella pneumoniae are emerging worldwide but are difficult to treat with the currently available antibiotic compounds and therefore constitute serious threats to human health. This prompted us to perform a literature survey applying the MEDLINE database and Cochrane Register of Controlled Trials including clinical trials comparing different treatment regimens for infections caused by carbapenem-resistant K. pneumoniae. Our survey revealed that a combined application of antibiotic compounds such as meropenem plus vaborbactam, meropenem plus colistin and carbapenem plus carbapenem, resulted in significantly increased clinical cure and decreased mortality rates as compared to respective control treatment. However, further research on novel antibiotic compounds, but also on antibiotic-independent molecules providing synergistic or at least resistance-modifying properties needs to be undertaken in vitro as well as in large clinical trials to provide future options in the combat of emerging life-threatening infections caused by MDR bacteria."
4113,Ameliorative effects of the traditional Chinese medicine formula Qing-Mai-Yin on arteriosclerosis obliterans in a rabbit model,"ContextQing-Mai-Yin (QMY) is a clinically used herbal formula for treating arteriosclerosis obliterans (ASO). Objective To evaluate the chemical constituents and effects of QMY on ASO rabbit model. Materials and methods Forty-eight New Zealand rabbits were divided into six groups (n = 8): normal (normal rabbits treated with 0.5% CMC-Na), vehicle (ASO rabbits treated with 0.5% CMC-Na), positive (simvastatin, 1.53 mg/kg), and QMY treatment (300, 600, and 1200 mg/kg). ASO rabbit model was prepared by high fatty feeding, roundly shortening artery, and bovine serum albumin immune injury. QMY (300, 600 and 1200 mg/kg) was orally administered for 8 weeks. The effects and possible mechanisms of QMY on ASO rabbits were evaluated by pathological examination, biochemical assays, and immunohistochemical assays. The compositions of QMY were analysed using HPLC-Q-TOF-MS/MS analysis. Results Compared to the vehicle rabbit, QMY treatment suppressed plaque formation and intima thickness in aorta, and decreased intima thickness, whereas increased lumen area of femoral artery. Additionally, QMY treatment decreased TC, TG and LDL, decreased CRP and ET, and increased NO and 6-K-PGF1α in serum. Furthermore, the potential mechanisms studied revealed that QMY treatment could suppress expression of TNF-α, IL-6, ICAM-1 and NF-κB in endothelial tissues, and increase IκB. In addition, HPLC analysis showed QMY had abundant anthraquinones, stilbenes, and flavonoids. Conclusion QMY has ameliorative effects on ASO rabbit, and the potential mechanisms are correlated to reducing inflammation and down-regulating NF-κB. Our study provides a scientific basis for the future application and investigation of QMY."
4114,"Linking humans, their animals, and the environment again: a decolonized and more-than-human approach to “One Health”","This article considers a broad perspective of “One Health” that includes local and animal knowledge. Drawing from various colonial efforts to link human, animal, and environmental health, it first shows that the current “One Health” initiative has its roots in colonial engagement and coincides with a need to secure the health of administrators (controlling that of local populations), while pursing use of resources. In our contemporary period of repeated epidemic outbreaks, we then discuss the need for greater inclusion of social science knowledge for a better understanding of complex socio-ecological systems. We show how considering anthropology and allied sub-disciplines (anthropology of nature, medical anthropology, and human-animal studies) highlights local knowledge on biodiversity as well as the way social scientists investigate diversity in relation to other forms of knowledge. Acknowledging recent approaches, specifically multispecies ethnography, the article then aims to include not only local knowledge but also non-human knowledge for a better prevention of epidemic outbreaks. Finally, the conclusion stresses the need to adopt the same symmetrical approach to scientific and profane knowledge as a way to decolonize One Health, as well as to engage in a more-than-human approach including non-human animals as objects-subjects of research."
4115,An initial accuracy focus reduces the effect of prior exposure on perceived accuracy of news headlines,"The illusory truth effect occurs when the repetition of a claim increases its perceived truth. Previous studies have demonstrated the illusory truth effect with true and false news headlines. The present study examined the effects that different ratings made during initial exposure have on the illusory truth effect with news headlines. In two experiments, participants (total N = 575) rated a set of news headlines in one of two conditions. Some participants rated how interesting they were, and others rated how truthful they were. Participants later rated the perceived accuracy of a larger set of headlines that included previously rated and new headlines. In both experiments, prior exposure increased perceived accuracy for participants who made initial interest ratings, but not for participants who made initial truthfulness ratings. The increase in perceived accuracy that accompanies repeated exposure was attenuated when participants considered the accuracy of the headlines at initial exposure. Experiment 2 also found evidence for a political bias: participants rated politically concordant headlines as more accurate than politically discordant headlines. The magnitude of this bias was related to performance on a cognitive reflection test; more analytic participants demonstrated greater political bias. These results highlight challenges that fake news presents and suggest that initially encoding headlines’ perceived truth can serve to combat the illusion that a familiar headline is a truthful one."
4116,Mutation of N-glycosylation Sites in Salmonid Alphavirus (SAV) Envelope Proteins Attenuate the Virus in Cell Culture,"Salmonid alphavirus (SAV) is the cause of pancreas disease and sleeping disease in farmed salmonid fish in Europe. The spread of these diseases has been difficult to control with biosecurity and current vaccination strategies, and increased understanding of the viral pathogenesis could be beneficial for the development of novel vaccine strategies. N-glycosylation of viral envelope proteins may be crucial for viral virulence and a possible target for its purposed attenuation. In this study, we mutated the N-glycosylation consensus motifs of the E1 and E2 glycoproteins of a SAV3 infectious clone using site-directed mutagenesis. Mutation of the glycosylation motif in E1 gave a complete inactivation of the virus as no viral replication could be detected in cell culture and infectious particles could not be rescued. In contrast, infectious virus particles could be recovered from the SAV3 E2 mutants (E2319Q, E2319A), but not if they were accompanied by lack of N-glycosylation in E1. Compared to the non-mutated infectious clone, the SAV3-E2319Q and SAV3-E2319A recombinant viruses produced less cytopathic effects in cell culture and lower amounts of infectious viral particles. In conclusion, the substitution in the N-linked glycosylation site in E2 attenuated SAV3 in cell culture. The findings could be useful for immunization strategies using live attenuated vaccines and testing in fish will be desirable to study the clone’s properties in vivo."
4117,High Levels of miR-7-5p Potentiate Crizotinib-Induced Cytokilling and Autophagic Flux by Targeting RAF1 in NPM-ALK Positive Lymphoma Cells,"SIMPLE SUMMARY: Anaplastic lymphoma kinase positive anaplastic large cell lymphomas are a pediatric disease, which still needs treatment improvement. Crizotinib was the first ALK-targeted inhibitor used in clinics, but relapses are now known to occur. Current research efforts indicate that combined therapies could represent a superior strategy to eradicate malignant cells and prevent tumor recurrence. Autophagy is a self-digestion cellular process, known to be induced upon diverse cancer therapies. Our present work demonstrates that the potentiation of the crizotinib-induced autophagy flux, through the serine/threonine kinase RAF1 downregulation, drives ALK+ ALCL cells to death. These results should encourage further investigations on the therapeutic modulation of autophagy in this particular cancer settings and other ALK-related malignancies. ABSTRACT: Anaplastic lymphoma kinase positive anaplastic large cell lymphomas (ALK+ ALCL) are an aggressive pediatric disease. The therapeutic options comprise chemotherapy, which is efficient in approximately 70% of patients, and targeted therapies, such as crizotinib (an ALK tyrosine kinase inhibitor (TKI)), used in refractory/relapsed cases. Research efforts have also converged toward the development of combined therapies to improve treatment. In this context, we studied whether autophagy could be modulated to improve crizotinib therapy. Autophagy is a vesicular recycling pathway, known to be associated with either cell survival or cell death depending on the cancer and therapy. We previously demonstrated that crizotinib induced cytoprotective autophagy in ALK+ lymphoma cells and that its further intensification was associated with cell death. In line with these results, we show here that combined ALK and Rapidly Accelerated Fibrosarcoma 1 (RAF1) inhibition, using pharmacological (vemurafenib) or molecular (small interfering RNA targeting RAF1 (siRAF1) or microRNA-7-5p (miR-7-5p) mimics) strategies, also triggered autophagy and potentiated the toxicity of TKI. Mechanistically, we found that this combined therapy resulted in the decrease of the inhibitory phosphorylation on Unc-51-like kinase-1 (ULK1) (a key protein in autophagy initiation), which may account for the enforced autophagy and cytokilling effect. Altogether, our results support the development of ALK and RAF1 combined inhibition as a new therapeutic approach in ALK+ ALCL."
4118,Exaggerated Autophagy in Stanford Type A Aortic Dissection: A Transcriptome Pilot Analysis of Human Ascending Aortic Tissues,"Stanford type A aortic dissection (TAAD) is one of the most dangerous diseases of acute aortic syndrome. Molecular pathological studies on TAAD can aid in understanding the disease comprehensively and can provide insights into new diagnostic markers and potential therapeutic targets. In this study, we defined the molecular pathology of TAAD by performing transcriptome sequencing of human ascending aortic tissues. Pathway analysis revealed that activated inflammation, cell death and smooth muscle cell degeneration are the main pathological changes in aortic dissection. However, autophagy is considered to be one of the most important biological processes, regulating inflammatory reactions and degenerative changes. Therefore, we focused on the pathological role of autophagy in aortic dissection and identified 10 autophagy-regulated hub genes, which are all upregulated in TAAD. These results indicate that exaggerated autophagy participates in the pathological process of aortic dissection and may provide new insight for further basic research on TAAD."
4119,"Over-activation of primate subgenual cingulate cortex enhances the cardiovascular, behavioral and neural responses to threat","Stress-related disorders such as depression and anxiety are characterized by enhanced negative emotion and physiological dysfunction. Whilst elevated activity within area 25 of the subgenual anterior cingulate cortex (sgACC/25) has been implicated in these illnesses, it is unknown whether this over-activity is causal. By combining targeted intracerebral microinfusions with cardiovascular and behavioral monitoring in marmosets, we show that over-activation of sgACC/25 reduces vagal tone and heart rate variability, alters cortisol dynamics during stress and heightens reactivity to proximal and distal threat. (18)F-FDG PET imaging shows these changes are accompanied by altered activity within a network of brain regions including the amygdala, hypothalamus and dorsolateral prefrontal cortex. Ketamine, shown to have rapid antidepressant effects, fails to reverse elevated arousal to distal threat contrary to the beneficial effects we have previously demonstrated on over-activation induced reward blunting, illustrating the symptom-specificity of its actions."
4120,Structure of human steroid 5α-reductase 2 with the anti-androgen drug finasteride,"Human steroid 5α-reductase 2 (SRD5A2) is an integral membrane enzyme in steroid metabolism and catalyzes the reduction of testosterone to dihydrotestosterone. Mutations in the SRD5A2 gene have been linked to 5α-reductase deficiency and prostate cancer. Finasteride and dutasteride, as SRD5A2 inhibitors, are widely used antiandrogen drugs for benign prostate hyperplasia. The molecular mechanisms underlying enzyme catalysis and inhibition for SRD5A2 and other eukaryotic integral membrane steroid reductases remain elusive due to a lack of structural information. Here, we report a crystal structure of human SRD5A2 at 2.8 Å, revealing a unique 7-TM structural topology and an intermediate adduct of finasteride and NADPH as NADP-dihydrofinasteride in a largely enclosed binding cavity inside the transmembrane domain. Structural analysis together with computational and mutagenesis studies reveal the molecular mechanisms of the catalyzed reaction and of finasteride inhibition involving residues E57 and Y91. Molecular dynamics simulation results indicate high conformational dynamics of the cytosolic region that regulate NADPH/NADP(+) exchange. Mapping disease-causing mutations of SRD5A2 to our structure suggests molecular mechanisms for their pathological effects. Our results offer critical structural insights into the function of integral membrane steroid reductases and may facilitate drug development."
4121,Implementing effective e-Learning for scaling up global capacity building: findings from the malnutrition elearning course evaluation in Ghana,"BACKGROUND: Global demand for capacity building has increased interest for eLearning. As eLearning resources become more common, effective implementation is required to scale up utilization in Low- and Middle-Income Countries (LMICs). OBJECTIVE: This paper describes the process of implementing a malnutrition eLearning course, effectiveness of course delivery models devised, factors affecting course completion, and cost comparison between the models and face-to-face training at healthcare and academic institutions in Ghana. METHODS: Four delivery models: Mobile Training Centre (MTC), Online Delivery (OD), Institutional Computer Workstation (ICW) and Mixed Delivery (MD) – a combination of OD and ICW – were determined. Participants were enabled to access the course using one of the four models where contextually appropriate. Pre and post-assessments and questionnaires were administered to compare participants’ completion status and knowledge gain between delivery models. The effect of access to computer and Internet at home and relevance of course to job and academic progression on course completion were further investigated. Comparison of delivery model costs against face-to-face training was also undertaken. RESULTS: Of 9 academic and 7 healthcare institutions involving 915 people, 9 used MTC (34.8%), 3 OD (18.8%), 3 ICW (34.2%) and 1 MD (12.2%). Course completion was higher among institutions where the course was relevant to job or implemented as part of required curriculum activities. Knowledge gain was significant among most institutions, but higher among participants who found the course relevant to job or academic progression. The implementation costs per participant for training with MTC were £51.0, OD £2.2, ICW £1.2 and MD £1.1, compared with a face-to-face training estimate of £105.0 (1 GHS = 0.14 GBP). CONCLUSION: The malnutrition eLearning course makes global capacity building in malnutrition management achievable. Adopting contextually appropriate delivery models and ensuring training is relevant to job/academic progression can enhance eLearning effectiveness in LMICs."
4122,Role of export industries on ozone pollution and its precursors in China,"This study seeks to estimate how global supply chain relocates emissions of tropospheric ozone precursors and its impacts in shaping ozone formation. Here we show that goods produced in China for foreign markets lead to an increase of domestic non-methane volatile organic compounds (NMVOCs) emissions by 3.5 million tons in 2013; about 13% of the national total or, equivalent to half of emissions from European Union. Production for export increases concentration of NMVOCs (including some carcinogenic species) and peak ozone levels by 20–30% and 6–15% respectively, in the coastal areas. It contributes to an estimated 16,889 (3,839–30,663, 95% CI) premature deaths annually combining the effects of NMVOCs and ozone, but could be reduced by nearly 40% by closing the technology gap between China and EU. Export demand also alters the emission ratios between NMVOCs and nitrogen oxides and hence the ozone chemistry in the east and south coast."
4123,Psychiatry peer review groups in Australia: a mixed-methods exploration of structure and function,"OBJECTIVES: The purpose of this study was to examine Australian psychiatrists’ experience of participation in a small group learning format of continuing professional development, known as peer review groups (PRGs), with a particular emphasis on group structure and functions. METHOD: An exploratory mixed-methods study comprising a survey (n=77) and semistructured interviews (n=6) with Australian psychiatrists participating in a PRG in the previous 12 months. RESULTS: Qualitative findings indicate that PRGs address experiential learning through a focus on both breadth and specificity of work, as well as participants’ experiences. Participants described using PRGs as a forum to manage difficult and complex work (through critiquing work, learning from one another, considering theory and guidelines, benchmarking, validating, reflecting and generalising learning) and to manage stress and well-being associated with crises, everyday stress and professional isolation. Particular structural aspects of PRGs considered essential to achieve these functions were self-selection of members, self-direction of meeting content and provision of a safe environment. These findings were convergent with the quantitative findings from scale survey data. Difficulties experienced during PRG participation are also described. CONCLUSION: Qualitative and quantitative findings from psychiatry PRGs demonstrate how practice-based professional experience functions as both a source of learning and of collegial connection that contributes to well-being and reduction in professional stress. Study limitations and future research directions are discussed."
4124,Telehealth: improving maternity services by modern technology,"Hypertension is considered one of the most common medical disorders causing complexities in pregnancy. It could be a newly developed pregnancy-induced hypertension (PIH) or a pre-existing hypertension developing into superimposed pre-eclamptic toxaemia. PIH affects approximately 10% of pregnancies and can have a serious impact on both maternal and fetal well-being; hence requires frequent monitoring and timely intervention. National Institute for Health and Care Excellence (NICE) guidelines recommends once or twice weekly monitoring of blood pressure for such patients. The required frequent monitoring comes with certain implications for patients and healthcare services. An average patient with PIH would need to see her healthcare provider once or twice a week until delivery and 6 weeks thereafter. This certainly increases pressure on limited National Health Service (NHS) resources. Home-based monitoring using Telehealth technology can represent a potential solution for achieving good-quality care for the patient without increasing the workload for healthcare providers. We used ‘Florence’, a text-based technology platform to support home monitoring. We tested its acceptability, feasibility and safety to replace face-to-face appointments for blood pressure monitoring in selected patients with PIH. We implemented our project in three progressive phases using a plan, do, study, act methodology. Florence, telehealth technology was used for blood pressure monitoring instead of face-to-face appointments, and the effect of this innovative technology on the services and the patient experience was studied and necessary modifications were made before progression into the next phase. We recruited 75 patients over 12 months through the progressive phases and replaced around 800 face-to-face appointments by remotely supervised monitoring sessions with Florence successfully, with improved care and patient satisfaction. We also achieved better compliance with the NICE guidelines for blood pressure monitoring in PIH. Our project concluded that Telehealth can be a potential solution for improving care in maternity services, with lesser burden on NHS resources."
4125,The urgent need for a global commitment to protect healthcare workers,
4126,"Respiratory function and respiratory complications in spinal cord injury: protocol for a prospective, multicentre cohort study in high-income countries","INTRODUCTION: Pneumonia is one of the leading complications and causes of death after a spinal cord injury (SCI). After a cervical or thoracic lesion, impairment of the respiratory muscles decreases respiratory function, which increases the risk of respiratory complications. Pneumonia substantially reduces patient’s quality of life, may prolong inpatient rehabilitation time, increase healthcare costs or at worse, lead to early death. Respiratory function and coughing can be improved through various interventions after SCI, but the available evidence as to which aspect of respiratory care should be optimised is inconclusive. Furthermore, ability of respiratory function parameters to predict pneumonia risk is insufficiently established. This paper details the protocol for a large-scale, multicentre research project that aims to evaluate the ability of parameters of respiratory function to predict and understand variation in inpatient risk of pneumonia in SCI. METHODS AND ANALYSIS: RESCOM, a prospective cohort study, began recruitment in October 2016 across 10 SCI rehabilitation centres from Australia, Austria, Germany, the Netherlands and Switzerland. Inpatients with acute SCI, with complete or incomplete cervical or thoracic lesions, 18 years or older and not/no more dependent on 24-hour mechanical ventilation within the first 3 months after injury are eligible for inclusion. The target sample size is 500 participants. The primary outcome is an occurrence of pneumonia; secondary outcomes include pneumonia-related mortality and quality of life. We will use the longitudinal data for prognostic models on inpatient pneumonia risk factors. ETHICS AND DISSEMINATION: The study has been reviewed and approved by all local ethics committees of all participating centres. Study results will be disseminated to the scientific community through peer-reviewed journals and conference presentations, to the SCI community, other stakeholders and via social media, newsletters and engagement activities. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov NCT02891096."
4127,Changing mortality trends in countries and cities of the UK: a population-based trend analysis,"OBJECTIVES: Previously improving life expectancy and all-cause mortality in the UK has stalled since the early 2010s. National analyses have demonstrated changes in mortality rates for most age groups and causes of death, and with deprived populations most affected. The aims here were to establish whether similar changes have occurred across different parts of the UK (countries, cities), and to examine cause-specific trends in more detail. DESIGN: Population-based trend analysis. PARTICIPANTS/SETTING: Whole populations of countries and selected cities of the UK. PRIMARY AND SECONDARY OUTCOME MEASURES: European age-standardised mortality rates (calculated by cause of death, country, city, year (1981–2017), age group, sex and—for all countries and Scottish cities—deprivation quintiles); changes in rates between 5-year periods; summary measures of both relative (relative index of inequality) and absolute (slope index of inequality) inequalities. RESULTS: Changes in mortality from around 2011/2013 were observed throughout the UK for all adult age groups. For example, all-age female rates decreased by approximately 4%–6% during the 1980s and 1990s, approximately 7%–9% during the 2000s, but by <1% between 2011/2013 and 2015/2017. Equivalent figures for men were 4%–7%, 8%–12% and 1%–3%, respectively. This later period saw increased mortality among the most deprived populations, something observed in all countries and cities analysed, and for most causes of death: absolute and relative inequalities therefore increased. Although similar trends were seen across all parts of the UK, particular issues apply in Scotland, for example, higher and increasing drug-related mortality (with the highest rates observed in Dundee and Glasgow). CONCLUSIONS: The study presents further evidence of changing mortality in the UK. The timing, geography and socioeconomic gradients associated with the changes appear to support suggestions that they may result, at least in part, from UK Government ‘austerity’ measures which have disproportionately affected the poorest."
4128,Mapping the epigenetic modifications of DNA and RNA,"Over 17 and 160 types of chemical modifications have been identified in DNA and RNA, respectively. The interest in understanding the various biological functions of DNA and RNA modifications has lead to the cutting-edged fields of epigenomics and epitranscriptomics. Developing chemical and biological tools to detect specific modifications in the genome or transcriptome has greatly facilitated their study. Here, we review the recent technological advances in this rapidly evolving field. We focus on high-throughput detection methods and biological findings for these modifications, and discuss questions to be addressed as well. We also summarize third-generation sequencing methods, which enable long-read and single-molecule sequencing of DNA and RNA modification."
4129,La nécessité des approches interdisciplinaires et collaboratives pour évaluer l’impact de la COVID-19 sur les personnes âgées et le vieillissement: déclaration conjointe de l’ACG / CAG et de la RCV / CJA,"The COVID-19 pandemic and subsequent state of public emergency have significantly affected older adults in Canada and worldwide. It is imperative that the gerontological response be efficient and effective. In this statement, the board members of the Canadian Association on Gerontology/L’Association canadienne de gérontologie (CAG/ACG) and the Canadian Journal on Aging/La revue canadienne du vieillissement (CJA/RCV) acknowledge the contributions of CAG/ACG members and CJA/RCV readers. We also profile the complex ways that COVID-19 is affecting older adults, from individual to population levels, and advocate for the adoption of multidisciplinary collaborative teams to bring together different perspectives, areas of expertise, and methods of evaluation in the COVID-19 response."
4130,Letter to the editor on “Asymptomatic infection by SARS 2 coronavirus: Invisible but invincible” by Nikolai et al. 2020,
4131,Glycomic analysis of host response reveals high mannose as a key mediator of influenza severity,"Influenza virus infections cause a wide variety of outcomes, from mild disease to 3 to 5 million cases of severe illness and ∼290,000 to 645,000 deaths annually worldwide. The molecular mechanisms underlying these disparate outcomes are currently unknown. Glycosylation within the human host plays a critical role in influenza virus biology. However, the impact these modifications have on the severity of influenza disease has not been examined. Herein, we profile the glycomic host responses to influenza virus infection as a function of disease severity using a ferret model and our lectin microarray technology. We identify the glycan epitope high mannose as a marker of influenza virus-induced pathogenesis and severity of disease outcome. Induction of high mannose is dependent upon the unfolded protein response (UPR) pathway, a pathway previously shown to associate with lung damage and severity of influenza virus infection. Also, the mannan-binding lectin (MBL2), an innate immune lectin that negatively impacts influenza outcomes, recognizes influenza virus-infected cells in a high mannose-dependent manner. Together, our data argue that the high mannose motif is an infection-associated molecular pattern on host cells that may guide immune responses leading to the concomitant damage associated with severity."
4132,A natural variant of the essential host gene MMS21 restricts the parasitic 2-micron plasmid in Saccharomyces cerevisiae,"Antagonistic coevolution with selfish genetic elements (SGEs) can drive evolution of host resistance. Here, we investigated host suppression of 2-micron (2μ) plasmids, multicopy nuclear parasites that have co-evolved with budding yeasts. We developed SCAMPR (Single-Cell Assay for Measuring Plasmid Retention) to measure copy number heterogeneity and 2μ plasmid loss in live cells. We identified three S. cerevisiae strains that lack endogenous 2μ plasmids and reproducibly inhibit mitotic plasmid stability. Focusing on the Y9 ragi strain, we determined that plasmid restriction is heritable and dominant. Using bulk segregant analysis, we identified a high-confidence Quantitative Trait Locus (QTL) with a single variant of MMS21 associated with increased 2μ instability. MMS21 encodes a SUMO E3 ligase and an essential component of the Smc5/6 complex, involved in sister chromatid cohesion, chromosome segregation, and DNA repair. Our analyses leverage natural variation to uncover a novel means by which budding yeasts can overcome highly successful genetic parasites."
4133,Evolution of multicellularity by collective integration of spatial information,"At the origin of multicellularity, cells may have evolved aggregation in response to predation, for functional specialisation or to allow large-scale integration of environmental cues. These group-level properties emerged from the interactions between cells in a group, and determined the selection pressures experienced by these cells. We investigate the evolution of multicellularity with an evolutionary model where cells search for resources by chemotaxis in a shallow, noisy gradient. Cells can evolve their adhesion to others in a periodically changing environment, where a cell’s fitness solely depends on its distance from the gradient source. We show that multicellular aggregates evolve because they perform chemotaxis more efficiently than single cells. Only when the environment changes too frequently, a unicellular state evolves which relies on cell dispersal. Both strategies prevent the invasion of the other through interference competition, creating evolutionary bi-stability. Therefore, collective behaviour can be an emergent selective driver for undifferentiated multicellularity."
4134,"An open-label, parallel-group, randomised controlled trial of antiseptic mouthwash versus antibiotics for oropharyngeal gonorrhoea treatment (OMEGA2)","New treatments for oropharyngeal gonorrhoea are required to address rising antimicrobial resistance. We aimed to examine the efficacy of a 14-day course of mouthwash twice daily compared to standard treatment (antibiotic) for the treatment of oropharyngeal gonorrhoea. The OMEGA2 trial was a parallel-group and open-labelled randomised controlled trial among men with untreated oropharyngeal gonorrhoea that was conducted between September 2018 and February 2020 at Melbourne Sexual Health Centre in Australia. Men were randomised to the intervention (rinsing, gargling and spraying mouthwash twice daily for 14 days) or control (standard treatment) arm and followed for 28 days. Participants in both arms were advised to abstain from sex and kissing with anyone for 14 days after enrolment. Oropharyngeal swabs were collected at baseline, Day 14 and Day 28 and tested for Neisseria gonorrhoeae by nucleic acid amplification test (NAAT) and culture. The primary outcome was the detection of oropharyngeal N. gonorrhoeae by NAAT at Day 14 after treatment. This trial was registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12618001380280). This trial stopped early due to a high failure rate in the mouthwash arm. Twelve men were randomly assigned to either mouthwash (n = 6) or standard treatment (n = 6). Of the 11 men who returned at Day 14, the cure rate for oropharyngeal gonorrhoea in the mouthwash arm was 20% (95% CI 1–72%; 1/5) and in the standard treatment arm was 100% (95% CI 54–100%; 6/6). A 14-day course of mouthwash failed to cure a high proportion of oropharyngeal gonorrhoea cases."
4135,The approximately universal shapes of epidemic curves in the Susceptible-Exposed-Infectious-Recovered (SEIR) model,"Compartmental transmission models have become an invaluable tool to study the dynamics of infectious diseases. The Susceptible-Infectious-Recovered (SIR) model is known to have an exact semi-analytical solution. In the current study, the approach of Harko et al. (Appl. Math. Comput. 236:184–194, 2014) is generalised to obtain an approximate semi-analytical solution of the Susceptible-Exposed-Infectious-Recovered (SEIR) model. The SEIR model curves have nearly the same shapes as the SIR ones, but with a stretch factor applied to them across time that is related to the ratio of the incubation to infectious periods. This finding implies an approximate characteristic timescale, scaled by this stretch factor, that is universal to all SEIR models, which only depends on the basic reproduction number and initial fraction of the population that is infectious."
4136,Whole-exome sequencing in patients with protein aggregate myopathies reveals causative mutations associated with novel atypical phenotypes,"BACKGROUND: Myofibrillar myopathies (MFM) are a subgroup of protein aggregate myopathies (PAM) characterized by a common histological picture of myofibrillar dissolution, Z-disk disintegration, and accumulation of degradation products into inclusions. Mutations in genes encoding components of the Z-disk or Z-disk-associated proteins occur in some patients whereas in most of the cases, the causative gene defect is still unknown. We aimed to search for pathogenic mutations in genes not previously associated with MFM phenotype. METHODS: We performed whole-exome sequencing in four patients from three unrelated families who were diagnosed with PAM without aberrations in causative genes for MFM. RESULTS: In the first patient and her affected daughter, we identified a heterozygous p.(Arg89Cys) missense mutation in LMNA gene which has not been linked with PAM pathology before. In the second patient, a heterozygous p.(Asn4807Phe) mutation in RYR1 not previously described in PAM represents a novel, candidate gene with a possible causative role in the disease. Finally, in the third patient and his symptomatic daughter, we found a previously reported heterozygous p.(Cys30071Arg) mutation in TTN gene that was clinically associated with cardiac involvement. CONCLUSIONS: Our study identifies a new genetic background in PAM pathology and expands the clinical phenotype of known pathogenic mutations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10072-020-04876-7."
4137,"Initial introduction of robot-assisted, minimally invasive esophagectomy using the microanatomy-based concept in the upper mediastinum","BACKGROUND: We have recently standardized upper mediastinal lymph node dissection (UMLND) using a microanatomy-based concept in thoracoscopic esophagectomy in the prone position (TEPP), and introduced robot-assisted minimally invasive esophagectomy (RAMIE) using the same concept as in TEPP while aiming at solo surgery. The purpose of this study was to investigate the outcomes of RAMIE using the microanatomy-based concept in the initial introduction phase. METHODS: We have performed more than 500 TEPP procedures as minimally invasive esophagectomy (MIE). After performing about 400 cases of MIE, we established a microanatomy-based standardization of UMLND. In October 2018, we introduced RAMIE, and have performed 75 procedures in 20 months. Two groups were analyzed: a group after microanatomy-based standardization in TEPP (100 cases after completing 400 cases of TEPP) and a RAMIE group (75 cases). Finally, 51 paired cases were matched using a propensity score. Furthermore, the change in postoperative short-term outcome for RAMIE in the initial introduction phase was analyzed. RESULTS: Although there were no significant differences between the two groups in the number of upper mediastinal lymph nodes dissected, there was a significant decrease (P = 0.036) in intraoperative blood loss volume with RAMIE, representing a definite benefit for patients. The thoracoscopic operative time for RAMIE decreased by almost 100 min following less than 50 cases of experience, reaching the same level as that for recent TEPP, but with only one-tenth the operator experience. There were no significant differences in the total postoperative morbidity rate including the recurrent laryngeal nerve palsy rate. CONCLUSION: RAMIE has been introduced safely and smoothly using the microanatomy-based concept established in TEPP."
4138,Hereditary Hypofibrinogenemia with Hepatic Storage,"Fibrinogen is a 340-kDa plasma glycoprotein constituted by two sets of symmetrical trimers, each formed by the Aα, Bβ, and γ chains (respectively coded by the FGA, FGB, and FGG genes). Quantitative fibrinogen deficiencies (hypofibrinogenemia, afibrinogenemia) are rare congenital disorders characterized by low or unmeasurable plasma fibrinogen antigen levels. Their genetic basis is represented by mutations within the fibrinogen genes. To date, only eight mutations, all affecting a small region of the fibrinogen γ chain, have been reported to cause hereditary hypofibrinogenemia with hepatic storage (HHHS), a disorder characterized by protein aggregation in the endoplasmic reticulum, hypofibrinogenemia, and liver disease of variable severity. Here, we will briefly review the clinic characteristics of HHHS patients and the histological feature of their hepatic inclusions, and we will focus on the molecular genetic basis of this peculiar type of coagulopathy."
4139,Acute Systemic Inflammatory Response Alters Transcription Profile of Genes Related to Immune Response and Ca(2+) Homeostasis in Hippocampus; Relevance to Neurodegenerative Disorders,"Acute systemic inflammatory response (SIR) triggers an alteration in the transcription of brain genes related to neuroinflammation, oxidative stress and cells death. These changes are also characteristic for Alzheimer’s disease (AD) neuropathology. Our aim was to evaluate gene expression patterns in the mouse hippocampus (MH) by using microarray technology 12 and 96 h after SIR evoked by lipopolysaccharide (LPS). The results were compared with microarray analysis of human postmortem hippocampal AD tissues. It was found that 12 h after LPS administration the expression of 231 genes in MH was significantly altered (FC > 2.0); however, after 96 h only the S100a8 gene encoding calgranulin A was activated (FC = 2.9). Gene ontology enrichment analysis demonstrated the alteration of gene expression related mostly to the immune-response including the gene Lcn2 for Lipocalin 2 (FC = 237.8), involved in glia neurotoxicity. The expression of genes coding proteins involved in epigenetic regulation, histone deacetylases (Hdac4,5,8,9,11) and bromo- and extraterminal domain protein Brd3 were downregulated; however, Brd2 was found to be upregulated. Remarkably, the significant increase in expression of Lcn2, S100a8, S100a9 and also Saa3 and Ch25h, was found in AD brains suggesting that early changes of immune-response genes evoked by mild SIR could be crucial in AD pathogenesis."
4140,Infectious Causation of Abnormal Host Behavior: Toxoplasma gondii and Its Potential Association With Dopey Fox Syndrome,"The apicomplexan parasite Toxoplasma gondii, the causative agent of toxoplasmosis, can infect all warm-blooded animals. T. gondii can subtly alter host behaviors—either through manipulation to enhance transmission to the feline definitive host or as a side-effect, or “constraint,” of infection. In humans, T. gondii infection, either alone or in association with other co-infecting neurotropic agents, has been reliably associated with both subtle behavioral changes and, in some cases, severe neuropsychiatric disorders, including schizophrenia. Research on the potential impact of T. gondii on the behavior of other long-lived naturally infected hosts is lacking. Recent studies reported a large number of wild red foxes exhibiting a range of aberrant behavioral traits, subsequently classified as Dopey Fox Syndrome (DFS). Here we assessed the potential association between T. gondii and/or other neurotropic agents with DFS. Live, captive foxes within welfare centers were serologically tested for T. gondii and, if they died naturally, PCR-tested for vulpine circovirus (FoxCV). Post-mortem pseudo-control wild foxes, obtained from pest management companies, were PCR-tested for T. gondii, FoxCV, canine distemper virus (CDV), canine adenovirus type (CAV)-1 and CAV-2. We also assessed, using non-invasive assays, whether T. gondii–infected foxes showed subtle behavioral alterations as observed among infected rodent (and other) hosts, including altered activity, risk, and stress levels. All foxes tested negative for CAV, CDV, CHV, and DogCV. DFS was found to be associated with singular T. gondii infection (captives vs. pseudo-controls, 33.3% (3/9) vs. 6.8% (5/74)) and singular FoxCV infection (66.7% (6/9) vs. 11.1% (1/9)) and with T. gondii/FoxCV co-infection (33.3% (3/9) vs. 11.1% (1/9)). Overall, a higher proportion of captive foxes had signs of neuroinflammation compared to pseudo-controls (66.7% (4/6) vs. 11.1% (1/9)). Consistent with behavioral changes seen in infected rodents, T. gondii–infected foxes displayed increased attraction toward feline odor (n=6 foxes). These preliminary results suggest that wild foxes with DFS are infected with T. gondii and likely co-infected with FoxCV and/or another co-infecting neurotropic agent. Our findings using this novel system have important implications for our understanding of both the impact of parasites on mammalian host behavior in general and, potentially, of the infectious causation of certain neuropsychiatric disorders."
4141,Mechanistic Insights Into the Anticancer Properties of the Auranofin Analog Au(PEt(3))I: A Theoretical and Experimental Study,"Au(PEt(3))I (AF-I hereafter), the iodide analog of the FDA-approved drug auranofin (AF hereafter), is a promising anticancer agent that produces its pharmacological effects through interaction with non-genomic targets such as the thioredoxin reductase system. AF-I is endowed with a very favorable biochemical profile showing potent in vitro cytotoxic activity against several cancer types including ovarian and colorectal cancer. Remarkably, in a recent publication, some of us reported that AF-I induces an almost complete and rapid remission in an orthotopic in vivo mouse model of ovarian cancer. The cytotoxic potency does not bring about highly severe side effects, making AF-I very well-tolerated even for higher doses, even more so than the pharmacologically active ones. All these promising features led us to expand our studies on the mechanistic aspects underlying the antitumor activity of AF-I. We report here on an integrated experimental and theoretical study on the reactivity of AF-I, in comparison with auranofin, toward relevant aminoacidic residues or their molecular models. Results point out that the replacement of the thiosugar moiety with iodide significantly affects the overall reactivity toward the amino acid residues histidine, cysteine, methionine, and selenocysteine. Altogether, the obtained results contribute to shed light into the enhanced antitumoral activity of AF-I compared with AF."
4142,Host Immunity and Inflammation to Pulmonary Helminth Infections,"Helminths, including nematodes, cestodes and trematodes, are complex parasitic organisms that infect at least one billion people globally living in extreme poverty. Helminthic infections are associated with severe morbidity particularly in young children who often harbor the highest burden of disease. While each helminth species completes a distinct life cycle within the host, several helminths incite significant lung disease. This impact on the lungs occurs either directly from larval migration and host immune activation or indirectly from a systemic inflammatory immune response. The impact of helminths on the pulmonary immune response involves a sophisticated orchestration and activation of the host innate and adaptive immune cells. The consequences of activating pulmonary host immune responses are variable with several helminthic infections leading to severe, pulmonary compromise while others providing immune tolerance and protection against the development of pulmonary diseases. Further delineation of the convoluted interface between helminth infection and the pulmonary host immune responses is critical to the development of novel therapeutics that are critically needed to prevent the significant global morbidity caused by these parasites."
4143,Comparative Lipidomic Analyses Reveal Different Protections in Preterm and Term Breast Milk for Infants,"Aim: Neonates are notably vulnerable, however they have improved outcomes if they are fed human milk. Human milk lipids constitute the primary constituents of human milk and serve a pivotal role in safeguarding infants from diseases. We assessed the lipid differences between preterm and term human milk and predicted the prospective impacts of these lipids on the development of neonates. Methods and results: We collected colostrum from healthy breast-feeding mothers who had delivered either term or preterm infants. We analyzed the lipid profiles of preterm, as well as term human milk using an LC-MS/MS metabolomics strategy. The orthogonal partial least-squares discriminant analysis score plots revealed remarkable distinction of lipids in preterm and term human milk. In total, 16 subclasses of 235 differential lipids (variable importance in projection > 1, P < 0.05) were identified. Notably, phosphatidylethanolamine and phosphatidylcholine were robustly increased in preterm human milk, while diacylglycerol and ceramide were markedly decreased in preterm human milk. Pathway analysis revealed that these dysregulated lipids are closely associated with glycerophospholipid metabolism, sphingolipid metabolism, Reelin signaling in neurons, and LXR/RXR activation. Conclusion: The results show that the lipids in preterm and term human colostrum vary, which may be critical for neonatal development."
4144,Cardiovascular and Quality of Life Outcomes of a 3-Month Physical Exercise Program in Two Brazilian Communities,"Background: A reduction in physical activity levels in older people is associated with declining quality of life and lower cardiorespiratory fitness levels associated with cardiovascular disease outcomes and mortality from all causes. Evidence supports the positive effect of community-based exercise (CEXE) programs on cardiovascular health and quality of life. This research aimed to examine the effects of a 3-month CEXE on health-related quality of life and cardiovascular risk factors in two Brazilian populations. Methods: Adults with an average age of 70.2 ± 5.4 years were recruited to engage in an individually designed group based CEXE program two to three times/week (aerobic exercise, circuit resistance training, and stretching exercises for 1 h each time). Once a week, competitions were held to improve socialization and collaboration capacity among group members. The CEXE group was compared with a sedentary group. Cardiovascular outcomes were blood pressure, triglycerides, body mass index, waist circumference, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, total cholesterol, and glycemia. Health-related quality of life was evaluated using the Short Form-36. Results: Of the cardiovascular outcomes studied, the CEXE program significantly reduced systolic blood pressure [5.7 (95% CI 0.2 to 11.3), p < 0.05] and the triglyceride–HDL-C ratio [0.8 (95% CI 0.05 to 1.5), p < 0.05], whereas HDL-C was significantly increased [4.4 (95% CI 0.02 to 8.8), p < 0.05]. A significant improvement in the Short Form-36 subscales occurred in CEXE but not in the control group: physical functioning score [increase of 24.2 (95% CI 11.8 to 36.5) vs. −9.2 (95% CI −21.5 to 3.2), p < 0.001], physical role functioning score [increase of 35.4 (95% CI 12.8 to 58.0) vs. 16.7 (95% CI −6.0 to 39.3), p < 0.01], and general health score [increase of 23.7 (95% CI: 36.9. to 10.4) vs. 2.4 (95% CI −10.9 to 15.7), p < 0.001]. Conclusion: This study shows that in older adults, a 12-week physical activity program can significantly decrease cardiovascular risk and improve health-related quality of life measures. An important transferable sociocultural strategy of our exercise program was to establish social interactions during and outside the CEXE program."
4145,Turning the ′Tides on Neuropsychiatric Diseases: The Role of Peptides in the Prefrontal Cortex,"Recent advancements in technology have enabled researchers to probe the brain with the greater region, cell, and receptor specificity. These developments have allowed for a more thorough understanding of how regulation of the neurophysiology within a region is essential for maintaining healthy brain function. Stress has been shown to alter the prefrontal cortex (PFC) functioning, and evidence links functional impairments in PFC brain activity with neuropsychiatric disorders. Moreover, a growing body of literature highlights the importance of neuropeptides in the PFC to modulate neural signaling and to influence behavior. The converging evidence outlined in this review indicates that neuropeptides in the PFC are specifically impacted by stress, and are found to be dysregulated in numerous stress-related neuropsychiatric disorders including substance use disorder, major depressive disorder (MDD), posttraumatic stress disorder, and schizophrenia. This review explores how neuropeptides in the PFC function to regulate the neural activity, and how genetic and environmental factors, such as stress, lead to dysregulation in neuropeptide systems, which may ultimately contribute to the pathology of neuropsychiatric diseases."
4146,The Risk Factors of VTE and Survival Prognosis of Patients With Malignant Cancer: Implication for Nursing and Treatment,"Venous thromboembolism (VTE) is very common in patients with malignant cancer. We aimed to conduct a retrospective analysis on the risk factors of VTE and its survival prognosis of patients with malignant cancer, to provide evidence into the management of VTE. Patients with malignant cancer treated in our hospital were selected. The characteristic of patients and related lab detection results including activated partial thromboplastin time (APTT), plasma prothrombin time (PT) and thrombin coagulation time (TT), fibrinogen (FIB), thrombin AT-Ⅲ complex (TAT) and D-dimer (D-D) were collected and analyzed. And logistic regression analyses were performed to identify the potential risk factors. And ROC curves were established to evaluate their predictive ability of VTE for patients with malignant cancers. A total of 286 patients were included, of which 63 patients had VTE, the incidence of VTE in patients with malignant cancers was 22.03%. There were significant differences on the D-D, TAT level between VTE and no VTE patients (all P < 0.05). The survival condition of VTE patients was significantly worse than that of no VTE patients(P = 0.017). D-D (RR7.895, 3.228∼19.286) and TAT (6.122, 2.244∼16.695) were risk factors of VTE for patients with cancers (all P < 0.05). The area under the curve (AUC) of D-D, TAT and combined use was 0.764, 0.698, 0.794 respectively, and the cutoff value for D-D, TAT was 1.835mg/L and 4.58μg/L respectively. For cancer patients with D-D >1.835 mg/L and TAT >4.58 μg/L, early interventions are needed for the prophylaxis of VTE."
4147,Les manifestations cutanées au cours du COVID-19: état des lieux,
4148,Identifying Isl1 Genetic Lineage in the Developing Olfactory System and in GnRH-1 Neurons,"During embryonic development, symmetric ectodermal thickenings [olfactory placodes (OP)] give rise to several cell types that comprise the olfactory system, such as those that form the terminal nerve ganglion (TN), gonadotropin releasing hormone-1 neurons (GnRH-1ns), and other migratory neurons in rodents. Even though the genetic heterogeneity among these cell types is documented, unidentified cell populations arising from the OP remain. One candidate to identify placodal derived neurons in the developing nasal area is the transcription factor Isl1, which was recently identified in GnRH-3 neurons of the terminal nerve in fish, as well as expression in neurons of the nasal migratory mass (MM). Here, we analyzed the Isl1 genetic lineage in chemosensory neuronal populations in the nasal area and migratory GnRH-1ns in mice using in situ hybridization, immunolabeling a Tamoxifen inducible Isl1Cre(ERT) and a constitutive Isl1(Cre) knock-in mouse lines. In addition, we also performed conditional Isl1 ablation in developing GnRH neurons. We found Isl1 lineage across non-sensory cells of the respiratory epithelium and sustentacular cells of OE and VNO. We identified a population of transient embryonic Isl1 + neurons in the olfactory epithelium and sparse Isl1 + neurons in postnatal VNO. Isl1 is expressed in almost all GnRH neurons and in approximately half of the other neuron populations in the MM. However, Isl1 conditional ablation alone does not significantly compromise GnRH-1 neuronal migration or GnRH-1 expression, suggesting compensatory mechanisms. Further studies will elucidate the functional and mechanistic role of Isl1 in development of migratory endocrine neurons."
4149,The 14th International Symposium on Alcoholic Liver and Pancreatic Diseases and Cirrhosis (ISALPDC),
4150,Ecological Niche Modeling: An Introduction for Veterinarians and Epidemiologists,"Most infectious diseases in animals are not distributed randomly. Instead, diseases in livestock and wildlife are predictable in terms of the geography, time, and species affected. Ecological niche modeling approaches have been crucial to the advancement of our understanding of diversity and diseases distributions. This contribution is an introductory overview to the field of distributional ecology, with emphasis on its application for spatial epidemiology. A new, revised modeling framework is proposed for more detailed and replicable models that account for both the biology of the disease to be modeled and the uncertainty of the data available. Considering that most disease systems need at least two organisms interacting (i.e., host and pathogen), biotic interactions lie at the core of the pathogen's ecological niche. As a result, neglecting interacting organisms in pathogen dynamics (e.g., maintenance, reproduction, and transmission) may limit efforts to forecast disease distributions in veterinary epidemiology. Although limitations of ecological niche modeling are noted, it is clear that the application and value of ecological niche modeling to epidemiology will increase in the future. Potential research lines include the examination of the effects of biotic variables on model performance, assessments of protocols for model calibration in disease systems, and new tools and metrics for robust model evaluation. Epidemiologists aiming to employ ecological niche modeling theory and methods to reconstruct and forecast epidemics should familiarize themselves with ecological literature and must consider multidisciplinary collaborations including veterinarians to develop biologically sound, statistically robust analyses. This review attempts to increase the use of tools from ecology in disease mapping."
4151,High Expression of IL-36γ in Influenza Patients Regulates Interferon Signaling Pathway and Causes Programmed Cell Death During Influenza Virus Infection,"As a severe complication of influenza infection, acute respiratory distress syndrome (ARDS) has higher morbidity and mortality. Although IL-36γ has been proven to promote inflammation at epithelial sites and protect against specific pathogen infection, the detailed roles in severe influenza infection remain poorly understood. In this study, we have found that the expression of IL-36γ is higher in influenza-induced ARDS patients than healthy individuals. IL-36γ was induced in human lung epithelial cells and peripheral blood mononuclear cells by Influenza A virus (IAV) infection, and its induction was synergistically correlated with initiation of the cyclooxygenase-2 (COX-2)/Prostaglandin E2 (PGE2) axis. We also have found that expression of superficial IL-36R was elevated in severe influenza patients and in IAV-stimulated cells. Furthermore, although IL-36γ enhanced the induction of type I and III interferons (IFNs), which promoted IAV-mediated IFN-stimulated STAT1 and STAT2 phosphorylated inhibition in lung epithelial cells, the downstream interferon-stimulated genes (ISGs) were not affected. Finally, we have revealed that IL-36γ treatment could promote apoptosis and inhibit autophagy in the early stages of IAV infection. Overall, these findings demonstrated IL-36γ is a critical host immune factor in response to IAV infection. It has potential activity in the regulation of the interferon signaling pathway and was involved in different types of programmed cell death in human airway epithelial cells as well."
4152,A Qualitative Market Analysis Applied to Mini-FLOTAC and Fill-FLOTAC for Diagnosis of Helminth Infections in Ruminants,"Helminth infections, mainly by gastrointestinal nematodes (GIN), are one of the main concerns for animal health, welfare and productivity in grazing ruminant livestock worldwide. The use of a sensitive, precise, accurate, low-cost, and easy-to-perform copromicroscopic technique is of pivotal importance to perform reliable fecal egg count (FEC) and fecal egg count reduction test (FECRT), in order to determine the need of anthelmintic treatment, but also anthelmintic efficacy or resistance. This approach is fundamental to a correct and efficient control of GIN. Unfortunately, in worldwide ruminant farm practice, repeated anthelmintic treatments are carried out, without prior diagnosis of infection, contributing to the spread of Anthelmintic Resistance (AR). Tackling this phenomenon, improving mainly the GIN diagnosis and AR status in farm animals, is a priority of the European COST Action “COMBAR—COMBatting Anthelmintic Resistance in Ruminants” and of the STAR-IDAZ International Research Consortium on Animal Health. One of the specific objectives of the COMBAR Working Group 1 (WG1) is to conduct an European market analysis of new diagnostics and develop a business plan for commercial test introduction, leveraging technical know-how of participants. Since the Mini-FLOTAC in combination with the Fill-FLOTAC may be considered a good candidate for a standardized FEC and FECRT in the laboratory, as well as directly in the field, the aim of this study was to conduct SWOT (Strength—Weaknesses—Opportunities—Threats) and PESTEL (Political, Economic, Social, Technological, Environmental, and Legal) analyses of these tools in 20 European countries involved in the COMBAR WG1, in order to identify the opportunities, barriers, and challenges that might affect the Mini-FLOTAC and Fill-FLOTAC commercialization in Europe."
4153,Hematological Toxicity During Concomitant Treatment With Ruxolitinib and Avelumab for Merkel Cell Carcinoma,"Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer. It frequently emerges in the presence of immunosuppression states such as myeloproliferative syndrome (MS). MS is treated with ruxolitinib, a selective JAK1 and JAK2 inhibitor. Avelumab, an anti PDL-1 inhibitor, is the standard treatment for MCC. To date it is unknown if avelumab and ruxolitinib have a synergistic or antagonistic effect when used together. Methods: We have identified all patients diagnosed with MCC, treated with avelumab, concomitant ruxolitinib, belonging to Tortora Hospital, Pagani and Santa Maria La Pietà Hospital, Nola, Italy between June 1 2019 and April 1 2020. Results: Among six MCC patients, we have found two patients in treatment with concomitant drugs. Both patients were being treated with ruxolitinib for MS as a standard regimen without suffering any hematological side effects. After starting doses of avelumab, we found thrombocytopenia, leukopenia, and anemia after cycle 1 and cycle 4, respectively, and decided to suspend both treatments. Following the suspension, the hematological values improved allowing us to restart treatment with avelumab without the need to resume ruxolitinib treatment. Conclusions: The combined treatment of ruxolitinib and avelumab demonstrated severe toxicity. Modifying the schedule or reducing the dose of both drugs needs to be studied in order to be able to treat both pathologies."
4154,Disruption of STAT6 Signal Promotes Cardiac Fibrosis Through the Mobilization and Transformation of CD11b(+) Immature Myeloid Cells,"Cardiac fibrosis is an important pathological basis of various cardiovascular diseases. The roles of STAT6 signal in allergy, immune regulation, tumorigenesis, and renal fibrosis have been documented. However, the function and mechanism of STAT6 signal in sympathetic overactivation-induced cardiac fibrosis have not been fully elucidated. This study explores the novel role of STAT6 signal in isoproterenol (ISO)–induced cardiac fibrosis through the regulation of inflammatory response and the differentiation of macrophages from immature myeloid cells. The expression levels of STAT6, β1-adrenergic receptor (β1-AR), and inflammatory factors [interleukin α (IL-1α), IL-6, IL-18, and transforming growth factor β (TGF-β)] in CD11b(+) myeloid cells were analyzed with a microarray study. The levels of IL-6 and TGF-β1 in the CD11b(+) myeloid cells–derived macrophages were detected with reverse transcriptase–polymerase chain reaction (RT-PCR). STAT6–knockout (KO) and WT mice were used to establish a murine cardiac fibrosis model by ISO injection. Cardiac fibroblasts were isolated from the hearts of newborn STAT6-KO and WT mice, and STAT6 expression was measured by Western blotting and RT-PCR after ISO stimulation, while α-smooth muscle actin (α-SMA) expression was detected by immunofluorescence and immunohistochemistry staining. Cardiac function and pathological characteristics were examined by echocardiography and immunohistochemistry staining, respectively. Immunohistochemistry staining with anti-CD11b was performed to detect the infiltration of CD11b(+) myeloid cells in heart tissue. Flow cytometry analysis was used to measure the percentages of CD11b(+) myeloid cells and CD11b(+)Ly6C(+) macrophages in the peripheral blood. The results showed that STAT6 was highly expressed in CD11b(+) myeloid cells located in injured hearts, and STAT6 expression in cardiac fibroblasts was down-regulated after ISO treatment. STAT6 deficiency further aggravated ISO-induced increased expression of α-SMA in cardiac fibroblasts, myocardial fibrosis, and cardiac dysfunction. The activation of ISO/β1-AR signal aggravated cardiac inflammatory infiltration, promoted CD11b(+) myeloid cell mobilization, and enhanced CD11b(+)Ly6C(+/low) macrophage differentiation, which was further exacerbated by STAT6 deficiency. Furthermore, β1-AR mRNA expression significantly increased in splenic CD11b(+) myeloid cells compared to their bone marrow–derived controls, and STAT6 deficiency promoted β1-AR expression in an MI-induced sensitive cardiac fibrosis mouse model. The spleen-derived CD11b(+) myeloid cells of STAT6-KO mice produced more IL-1α, IL-18, and TGF-β than their WT counterparts. Taken together, these results suggest that STAT6 signal plays a critical role in ISO-induced β1-AR overactivation and systemic inflammatory cascades, contributing to cardiac fibrogenesis. STAT6 should be a promising cardioprotective target against myocardial fibrosis and heart failure after β1-AR overactivation–induced myocardial injury."
4155,Rift Valley Fever – assessment of effectiveness of surveillance and control measures in the EU,"Effectiveness of surveillance and control measures against Rift Valley Fever (RVF) in Mayotte (overseas France) and in continental EU were assessed using mathematical models. Surveillance for early detection of RVF virus circulation implies very low design prevalence values and thus sampling a high number of animals, so feasibility issues may rise. Passive surveillance based on notified abortions in ruminants is key for early warning and at present the only feasible surveillance option. The assessment of vaccination and culling against RVF in Mayotte suggests that vaccination is more effective when quickly implemented throughout the population, e.g. at a rate of 200 or 2,000 animals vaccinated per day. Test and cull is not an option for RVF control in Mayotte given the high number of animals that would need to be tested. If the risk of RVFV introduction into the continental EU increases, ruminant establishments close to possible points of disease incursion should be included in the surveillance. An enhanced surveillance on reproductive disorders should be applied during summer in risk areas. Serosurveillance targets of 0.3% animals should be at least considered. RVF control measures possibly applied in the continental EU have been assessed in the Netherlands, as an example. Culling animals on farms within a 20 km radius of detected farms appears as the most effective measure to control RVF spread, although too many animals should be culled. Alternative measures are vaccination in a 50 km radius around detection, ring vaccination between 20 and 50 km and culling of detected farms. The assessment of zoning showed that, following RVFV introduction and considering an R(0) = 2, a mean vector dispersal of 10 km and 10 farms initially detected, RVFV would spread beyond a radius of up to 100 km or 50 km from the infected area with 10% or 55% probability, respectively."
4156,Implementing an intensive care registry in India: preliminary results of the case-mix program and an opportunity for quality improvement and research,"Background: The epidemiology of critical illness in India is distinct from high-income countries. However, limited data exist on resource availability, staffing patterns, case-mix and outcomes from critical illness. Critical care registries, by enabling a continual evaluation of service provision, epidemiology, resource availability and quality, can bridge these gaps in information. In January 2019, we established the Indian Registry of IntenSive care to map capacity and describe case-mix and outcomes. In this report, we describe the implementation process, preliminary results, opportunities for improvement, challenges and future directions. Methods: All adult and paediatric ICUs in India were eligible to join if they committed to entering data for ICU admissions. Data are collected by a designated representative through the electronic data collection platform of the registry. IRIS hosts data on a secure cloud-based server and access to the data is restricted to designated personnel and is protected with standard firewall and a valid secure socket layer (SSL) certificate. Each participating ICU owns and has access to its own data. All participating units have access to de-identified network-wide aggregate data which enables benchmarking and comparison. Results: The registry currently includes 14 adult and 1 paediatric ICU in the network (232 adult ICU beds and 9 paediatric ICU beds). There have been 8721 patient encounters with a mean age of 56.9 (SD 18.9); 61.4% of patients were male and admissions to participating ICUs were predominantly unplanned (87.5%). At admission, most patients (61.5%) received antibiotics, 17.3% needed vasopressors, and 23.7% were mechanically ventilated. Mortality for the entire cohort was 9%. Data availability for demographics, clinical parameters, and indicators of admission severity was greater than 95%. Conclusions: IRIS represents a successful model for the continual evaluation of critical illness epidemiology in India and provides a framework for the deployment of multi-centre quality improvement and context-relevant clinical research."
4157,Seroprevalence of anti-SARS-CoV2 Antibodies in Umbrian Persons Living with HIV,
4158,"“Hemolysis, or not Hemolysis, that is the Question”. Use of Hydroxychloroquine in a Patient with COVID-19 Infection and G6PD Deficiency",
4159,COVID-19 in Omani Children with Hemato-Oncology Diseases,
4160,Inhibitory Effect of Morin Against Candida albicans Pathogenicity and Virulence Factor Production: An in vitro and in vivo Approaches,"Candida albicans is considered an exclusive etiologic agent of candidiasis, a very common fungal infection in human. The expression of virulence factors contributes highly to the pathogenicity of C. albicans. These factors include biofilm formation, yeast-to-hyphal transition, adhesins, aspartyl proteases, and phospholipases secretion. Moreover, resistance development is a critical issue for the therapeutic failure of antifungal agents against systemic candidiasis. To circumvent resistance development, the present study investigated the virulence targeted therapeutic activity of the phyto-bioactive compound morin against C. albicans. Morin is a natural compound commonly found in medicinal plants and widely used in the pharmaceutical and cosmetic products/industries. The present study explicated the significant inhibitory potential of morin against biofilm formation and other virulence factors’ production, such as yeast-hyphal formation, phospholipase, and exopolymeric substances, in C. albicans. Further, qPCR analysis confirmed the downregulation of biofilm and virlence-related genes in C. albicans upon morin treatment, which is in correspondence with the in vitro bioassays. Further, the docking analysis revealed that morin shows strong affinity with Hwp-1 protein, which regulates the expression of biofilm and hyphal formation in C. albicans and, thereby, abolishes fungal pathogenicity. Moreover, the anti-infective potential of morin against C. albicans-associated systemic candidiasis is confirmed through an in vivo approach using biomedical model organism zebrafish (Danio rerio). The outcomes of the in vivo study demonstrate that the morin treatment effectively rescues animals from C. albicans infections and extends their survival rate by inhibiting the internal colonization of C. albicans. Histopathology analysis revealed extensive candidiasis-related pathognomonic changes in the gills, intestine, and kidney of animals infected with C. albicans, while no extensive abnormalities were observed in morin-treated animals. The results evidenced that morin has the ability to protect against the pathognomonic effect and histopathological lesions caused by C. albicans infection in zebrafish. Thus, the present study suggests that the utilization of morin could act as a potent therapeutic medication for C. albicans instigated candidiasis."
4161,Holistic Approach of Swiss Fetal Progenitor Cell Banking: Optimizing Safe and Sustainable Substrates for Regenerative Medicine and Biotechnology,"Safety, quality, and regulatory-driven iterative optimization of therapeutic cell source selection has constituted the core developmental bedrock for primary fetal progenitor cell (FPC) therapy in Switzerland throughout three decades. Customized Fetal Transplantation Programs were pragmatically devised as straightforward workflows for tissue procurement, traceability maximization, safety, consistency, and robustness of cultured progeny cellular materials. Whole-cell bioprocessing standardization has provided plethoric insights into the adequate conjugation of modern biotechnological advances with current restraining legislative, ethical, and regulatory frameworks. Pioneer translational advances in cutaneous and musculoskeletal regenerative medicine continuously demonstrate the therapeutic potential of FPCs. Extensive technical and clinical hindsight was gathered by managing pediatric burns and geriatric ulcers in Switzerland. Concomitant industrial transposition of dermal FPC banking, following good manufacturing practices, demonstrated the extensive potential of their therapeutic value. Furthermore, in extenso, exponential revalorization of Swiss FPC technology may be achieved via the renewal of integrative model frameworks. Consideration of both longitudinal and transversal aspects of simultaneous fetal tissue differential processing allows for a better understanding of the quasi-infinite expansion potential within multi-tiered primary FPC banking. Multiple fetal tissues (e.g., skin, cartilage, tendon, muscle, bone, lung) may be simultaneously harvested and processed for adherent cell cultures, establishing a unique model for sustainable therapeutic cellular material supply chains. Here, we integrated fundamental, preclinical, clinical, and industrial developments embodying the scientific advances supported by Swiss FPC banking and we focused on advances made to date for FPCs that may be derived from a single organ donation. A renewed model of single organ donation bioprocessing is proposed, achieving sustained standards and potential production of billions of affordable and efficient therapeutic doses. Thereby, the aim is to validate the core therapeutic value proposition, to increase awareness and use of standardized protocols for translational regenerative medicine, potentially impacting millions of patients suffering from cutaneous and musculoskeletal diseases. Alternative applications of FPC banking include biopharmaceutical therapeutic product manufacturing, thereby indirectly and synergistically enhancing the power of modern therapeutic armamentariums. It is hypothesized that a single qualifying fetal organ donation is sufficient to sustain decades of scientific, medical, and industrial developments, as technological optimization and standardization enable high efficiency."
4162,Dysfunctional Innate Immune Responses and Severe Dengue,"Although infection with the dengue virus (DENV) causes severe dengue, it causes a mild self-limiting illness in the majority of individuals. There is emerging evidence that an aberrant immune response in the initial stages of infection lead to severe disease. Many inflammatory cytokines, chemokines, and lipid mediators are significantly higher in patients with severe dengue compared to those who develop mild infection, during febrile phase of illness. Monocytes, mast cells, and many other cells of the immune system, when infected with the DENV, especially in the presence of poorly neutralizing antibodies, leads to production of pro-inflammatory cytokines and inhibition of interferon signaling pathways. In addition, production of immunosuppressive cytokines such as IL-10 further leads to inhibition of cellular antiviral responses. This dysregulated and aberrant immune response leads to reduced clearance of the virus, and severe dengue by inducing a vascular leak and excessive inflammation due to high levels of inflammatory cytokines. Individuals with comorbid illnesses could be prone to more severe dengue due to low grade endotoxemia, gut microbial dysbiosis and an altered phenotype of innate immune cells. The immunosuppressive and inflammatory lipid mediators and altered phenotype of monocytes are likely to further act on T cells and B cells leading to an impaired adaptive immune response to the virus. Therefore, in order to identify therapeutic targets for treatment of dengue, it would be important to further characterize these mechanisms in order for early intervention. In this review, we discuss the differences in the innate immune responses in those who progress to develop severe dengue, compared to those with milder disease in order to understand the mechanisms that lead to severe dengue."
4163,Interaction of synthetic antimicrobial peptides of the Hylin a1 family with models of eukaryotic structures: Zwitterionic membranes and DNA,"Antimicrobial peptides (AMPs) have been appointed as a possible alternative to traditional antibiotics in face of pathogens increasing resistance to conventional drugs. Hylin a1 (IFGAILPLALGALKNLIK), an AMP extracted from the skin secretion of a South American frog, Hypsiboas albopunctatus, was found to show a strong cytotoxicity against bacteria and fungus, but also a considerable hemolytic action. Considering the toxicity of the peptide in eukaryotic cells, this work focuses on investigating the effects of the interaction of the Hylin a1 analogues W(6)Hya1, D(0)W(6)Hya1 and K(0)W(6)Hya1 with models of eukaryotic structures, namely zwitterionic liposomes of dipalmitoyl phosphatidylcholine (DPPC) and calf-thymus DNA (CT DNA). Through intrinsic Trp fluorescence we determined that the peptide affinity for fluid DPPC bilayers follows the decreasing order: D(0)W(6)Hya1 (+2) > W(6)Hya1 (+3) » K(0)W(6)Hya1 (+4). Fluorescence data also indicate that the Trp residue in the more positively charged peptide, K(0)W(6)Hya1, is less deep in the bilayer than the residue in the other two peptides. This finding is supported by differential scanning calorimetry (DSC) data, which shows that both D(0)W(6)Hya1 and W(6)Hya1 disturb DPPC gel-fluid transition slightly more effectively than K(0)W(6)Hya1. DPPC DSC profiles are homogeneously disturbed by the three peptides, probably related to peptide-membrane diffusion. Surprisingly, the peptide that displays the lowest affinity for PC membranes and is located at the more superficial position in the bilayer, K(0)W(6)Hya1, is the most efficient in causing formation of pores on the membrane, as attested by carboxyfluorescein leakage assays. The three peptides were found to interact with CT DNA, with a deep penetration of the Trp residue into hydrophobic pockets of the double helix, as indicated by the significant blue shift on the Trp fluorescence, and the displacement of DNA-bound ethidium bromide by the peptides. The experiments of DNA electrophoresis confirm that Hylin peptides bind DNA in a concentration-dependent manner, inducing complete DNA retardation at the relative AMP/plasmid DNA weight ratio of ~17. These findings could help to better understand the AMPs toxic effects on eukaryotic cells, thus contributing to the design of healthier therapeutic agents."
4164,Health disinformation & social media: The crucial role of information hygiene in mitigating conspiracy theory and infodemics,Social media has been an effective vector for spreading disinformation about medicine and science. Informational hygiene can reduce the severity of falsehoods about health. [Image: see text]
4165,"P-Glycoprotein: One Mechanism, Many Tasks and the Consequences for Pharmacotherapy of Cancers","P-glycoprotein or multidrug resistance protein (MDR1) is an adenosine triphosphate (ATP) binding cassette transporter (ABCB1) intensely investigated because it is an obstacle to successful pharmacotherapy of cancers. P-glycoprotein prevents cellular uptake of a large number of structurally and functionally diverse compounds, including most cancer therapeutics and in this way causes multidrug resistance (MDR). To overcome MDR, and thus improve cancer treatment, an understanding of P-glycoprotein inhibition at the molecular level is required. With this goal in mind, we propose rules that predict whether a compound is a modulator, substrate, inhibitor, or inducer of P-glycoprotein. This new set of rules is derived from a quantitative analysis of the drug binding and transport properties of P-glycoprotein. We further discuss the role of P-glycoprotein in immune surveillance and cell metabolism. Finally, the predictive power of the proposed rules is demonstrated with a set of FDA approved drugs which have been repurposed for cancer therapy."
4166,Some Challenges for the Human Brain in Communication With the Digital Society,
4167,Antibiotic Resistance Profiles and Molecular Mechanisms of Campylobacter From Chicken and Pig in China,"The purpose of this research was to characterize the antibiotic resistance profiles of Campylobacter spp. derived from chicken and pig feces collected from farms in Jiangsu Province, China, and to analyze the relevant resistance mechanisms among antimicrobial-resistant Campylobacter spp. isolates. Antibiotic susceptibility to nine antibiotic agents was tested with the microdilution method in 93 Campylobacter spp. (45 C. jejuni and 25 C. coli from chickens; 23 C. coli from pigs). High rates of resistance were observed to nalidixic acid (79.6%), erythromycin (75.3%), tetracycline (68.8%), azithromycin (66.7%), ciprofloxacin (64.5%), and gentamicin (35.5%), with a lower resistance rate to florfenicol (8.6%). The prevalence of the tested antibiotic resistance in C. coli was higher than in C. jejuni from chickens. The rate of antimicrobial resistance to ciprofloxacin in C. coli isolates from chickens was 100.0%, and the C. coli isolates from pigs were all resistant to erythromycin (100%). Most of C. jejuni (64.4%) and C. coli (64.5%) isolates displayed multi-drug resistance. All the Campylobacter spp. isolates resistant to fluoroquinolones had the C257T mutation in the gyrA gene. All 64 tetracycline-resistant Campylobacter spp. isolates were positive for the tetO gene. The tetA gene was also amplified in 6.5% of Campylobacter spp. isolates, whereas tetB was not detected among the isolates. The A2075G point mutation in the 23S rRNA gene occurred in 86.1% (62/72) of the macrolides-resistant Campylobacter spp. isolates, and the ermB gene was identified in 49 Campylobacter spp. isolates (30 C. jejuni and 19 C. coli). Amino acid insertions or mutations in the L4 and L22 ribosomal proteins were not linked to macrolide resistance. These results highlight the high prevalence of resistance to multiple antibiotics, particular macrolides, among Campylobacter spp. from chickens and pigs in Jiangsu Province, China, which is probably attributable to the overuse of antimicrobials in chicken and pig production. These findings recommend the more cautious use of critical antimicrobial agents in swine and poultry production. Stringent and continuous surveillance is required to reduce the drug-resistant campylobacteriosis in food animals and humans."
4168,Use of a Low-Cost Portable 3D Virtual Reality Simulator for Psychomotor Skill Training in Minimally Invasive Surgery: Task Metrics and Score Validity,"BACKGROUND: The high cost and low availability of virtual reality simulators in surgical specialty training programs in low- and middle-income countries make it necessary to develop and obtain sources of validity for new models of low-cost portable simulators that enable ubiquitous learning of psychomotor skills in minimally invasive surgery. OBJECTIVE: The aim of this study was to obtain validity evidence for relationships to other variables, internal structure, and consequences of testing for the task scores of a new low-cost portable simulator mediated by gestures for learning basic psychomotor skills in minimally invasive surgery. This new simulator is called SIMISGEST-VR (Simulator of Minimally Invasive Surgery mediated by Gestures - Virtual Reality). METHODS: In this prospective observational validity study, the authors looked for multiple sources of evidence (known group construct validity, prior videogaming experience, internal structure, test-retest reliability, and consequences of testing) for the proposed SIMISGEST-VR tasks. Undergraduate students (n=100, reference group), surgical residents (n=20), and experts in minimally invasive surgery (n=28) took part in the study. After answering a demographic questionnaire and watching a video of the tasks to be performed, they individually repeated each task 10 times with each hand. The simulator provided concurrent, immediate, and terminal feedback and obtained the task metrics (time and score). From the reference group, 29 undergraduate students were randomly selected to perform the tasks 6 months later in order to determine test-retest reliability. RESULTS: Evidence from multiple sources, including strong intrarater reliability and internal consistency, considerable evidence for the hypothesized consequences of testing, and partial confirmation for relations to other variables, supports the validity of the scores and the metrics used to train and teach basic psychomotor skills for minimally invasive surgery via a new low-cost portable simulator that utilizes interaction technology mediated by gestures. CONCLUSIONS: The results obtained provided multiple sources of evidence to validate SIMISGEST-VR tasks aimed at training novices with no prior experience and enabling them to learn basic psychomotor skills for minimally invasive surgery."
4169,Systems Thinking About SARS-CoV-2,
4170,2019新型冠状病毒肺炎（COVID-19）对溶血性疾病发生、发展与治疗的影响,
4171,Adoption of a Personal Health Record in the Digital Age: Cross-Sectional Study,"BACKGROUND: As health care organizations strive to improve health care access, quality, and costs, they have implemented patient-facing eHealth technologies such as personal health records to better engage patients in the management of their health. In the Kingdom of Saudi Arabia, eHealth is also growing in accordance with Vision 2030 and its National Transformation Program framework, creating a roadmap for increased quality and efficiency of the health care system and supporting the goal of patient-centered care. OBJECTIVE: The aim of this study was to investigate the adoption of the personal health record of the Ministry of National Guard Health Affairs (MNGHA Care). METHODS: A cross-sectional survey was conducted in adults visiting outpatient clinics in hospitals at the Ministry of National Guard Health Affairs hospitals in Riyadh, Jeddah, Dammam, Madinah, and Al Ahsa, and primary health care clinics in Riyadh and Qassim. The main outcome measure was self-reported use of MNGHA Care. RESULTS: In the sample of 546 adult patients, 383 (70.1%) reported being users of MNGHA Care. MNGHA Care users were more likely to be younger (P<.001), high school or university educated (P<.001), employed (P<.001), have a chronic condition (P=.046), use the internet to search for health-related information (P<.001), and use health apps on their mobile phones (P<.001). CONCLUSIONS: The results of this study show that there is substantial interest for the use of MNGHA Care personal health record with 70% of participants self-reporting use. To confirm these findings, objective data from the portal usage logs are needed. Maximizing the potential of MNGHA Care supports patient engagement and is aligned with the national eHealth initiative to encourage the use of technology for high-quality, accessible patient-centered care. Future research should include health care provider perspectives, incorporate objective data, employ a mixed-methods approach, and use a theoretical framework."
4172,A methodology for predicting tissue-specific metabolic roles of receptors applied to subcutaneous adipose,"The human biological system uses ‘inter-organ’ communication to achieve a state of homeostasis. This communication occurs through the response of receptors, located on target organs, to the binding of secreted ligands from source organs. Albeit years of research, the roles these receptors play in tissues is only partially understood. This work presents a new methodology based on the enrichment analysis scores of co-expression networks fed into support vector machines (SVMs) and k-NN classifiers to predict the tissue-specific metabolic roles of receptors. The approach is primarily based on the detection of coordination patterns of receptors expression. These patterns and the enrichment analysis scores of their co-expression networks were used to analyse ~ 700 receptors and predict metabolic roles of receptors in subcutaneous adipose. To facilitate supervised learning, a list of known metabolic and non-metabolic receptors was constructed using a semi-supervised approach following literature-based verification. Our approach confirms that pathway enrichment scores are good signatures for correctly classifying the metabolic receptors in adipose. We also show that the k-NN method outperforms the SVM method in classifying metabolic receptors. Finally, we predict novel metabolic roles of receptors. These predictions can enhance biological understanding and the development of new receptor-targeting metabolic drugs."
4173,"Discovery and comparative genomic analysis of elk circovirus (ElkCV), a novel circovirus species and the first reported from a cervid host","The complete genome sequence of a novel circovirus (elk circovirus (ElkCV) Banff/2019) was determined via high throughput sequencing of liver tissue from a euthanized Rocky Mountain elk (Cervus canadensis nelsoni) from Alberta, Canada. The genome is circular and 1,787 nucleotides long, with two major ORFs encoding predicted proteins. Comparative genomic analysis to 4,164 publicly available complete and near complete circovirus genomes showed that ElkCV shares approximately 65% pairwise genome-wide nucleotide identity with the most closely related circovirus species, porcine circoviruses (PCV) 1 and 2 and bat-associated circovirus (BatACV) 11. ElkCV features a stem-loop within the origin of replication region characteristic of circoviruses. However, it differs from those found in PCV1, PCV2 and BatACV11 since it has a longer stem and contains hexamer repeats that overlap the stem in opposing orientations. Interestingly, stem-loop structures of similar length featuring repeats in a similar position and orientation are also seen in some avian circoviruses. Based on the demarcation threshold established by the International Committee on Taxonomy of Viruses (ICTV) for members of Circoviridae (80% pairwise genome-wide nucleotide identity), ElkCV represents a novel species and is the first complete circovirus genome reported from a cervid host."
4174,"Medicina de Familia, una especialidad amenazada",
4175,"Telemedicine in Heart Failure during COVID-19: Like it, Love It or Lose It?",
4176,Microbiome: an emerging new frontier in graft‑versus‑host disease,
4177,The role of Immunity in Fabry Disease and Hypertension: A Review of a Novel Common Pathway,"Fabry disease is a progressive, X-linked inherited lysosomal storage disorder where accumulation of glycosphingolipids increases the risk for early cardiovascular complications, including heart failure, stroke, and end stage renal disease. Besides disease-specific therapy, blood pressure (BP) control is of central importance in Fabry disease to reduce disease progression and improve prognosis. Both Fabry disease and hypertension are characterized by the activation of the innate component of the immune system, with Toll-like receptor 4 (TLR4) as a common trigger to the inflammatory cascade. The renin-angiotensin system (RAS) participates in the establishment of low-grade chronic inflammation and redox unbalance that contribute to organ damage in the long term. Besides exploiting the anti-inflammatory effects of RAS blockade and enzyme replacement therapy, targeted therapies acting on the immune system represent an appealing field of research in these conditions. The aim of this narrative review is to examine the issue of hypertension in the setting of Fabry disease, focusing on the possible determinants of their reciprocal relationship, as well as on the related clinical and therapeutic implications."
4178,COVID-19: Dogma Over Potential for Prolonged Droplet Dispersal in Air,
4179,Veterinarians and One Health in the Fight Against Zoonoses Such as COVID-19,
4180,Use of Heart Rate Variability Biofeedback to Reduce the Psychological Burden of Frontline Healthcare Professionals Against COVID-19,
4181,"Reply to the correspondence letter by Alonso-Ojembarrena, Almudena and Oulego-Erroz, Ignacio: How to improve precision and reliability of diaphragm ultrasonographic measurements in newborns",
4182,Tocilizumab como posible causa de colitis isquémica,
4183,Campylobacter sp.: Pathogenicity factors and prevention methods—new molecular targets for innovative antivirulence drugs?,"ABSTRACT: Infections caused by bacterial species from the genus Campylobacter are one of the four main causes of strong diarrheal enteritis worldwide. Campylobacteriosis, a typical food-borne disease, can range from mild symptoms to fatal illness. About 550 million people worldwide suffer from campylobacteriosis and lethality is about 33 million p.a. This review summarizes the state of the current knowledge on Campylobacter with focus on its specific virulence factors. Using this knowledge, multifactorial prevention strategies can be implemented to reduce the prevalence of Campylobacter in the food chain. In particular, antiadhesive strategies with specific adhesion inhibitors seem to be a promising concept for reducing Campylobacter bacterial load in poultry production. Antivirulence compounds against bacterial adhesion to and/or invasion into the host cells can open new fields for innovative antibacterial agents. Influencing chemotaxis, biofilm formation, quorum sensing, secretion systems, or toxins by specific inhibitors can help to reduce virulence of the bacterium. In addition, the unusual glycosylation of the bacterium, being a prerequisite for effective phase variation and adaption to different hosts, is yet an unexplored target for combating Campylobacter sp. Plant extracts are widely used remedies in developing countries to combat infections with Campylobacter. Therefore, the present review summarizes the use of natural products against the bacterium in an attempt to stimulate innovative research concepts on the manifold still open questions behind Campylobacter towards improved treatment and sanitation of animal vectors, treatment of infected patients, and new strategies for prevention. KEY POINTS: • Campylobacter sp. is a main cause of strong enteritis worldwide. • Main virulence factors: cytolethal distending toxin, adhesion proteins, invasion machinery. • Strong need for development of antivirulence compounds."
4184,Serological Evidence for the Association Between Epstein-Barr Virus Infection and Sjögren’s Syndrome,"BACKGROUND: Exposure to Epstein-Barr virus (EBV) infection has been hypothesized to be an important risk factor for multiple rheumatic diseases, but the serological evidence so far for its role in Sjögren’s syndrome (SjS) is not clearly established yet. This study aimed to assess the seroepidemiological associations of antibodies to EBV with SjS. METHODS: A seroepidemiological study containing 119 patients with SjS and 65 healthy controls was first performed, in which the associations of SjS with four commonly studied EBV antibodies including IgM-anti-viral capsid antigen (anti-VCA) antibody, IgG-anti-VCA antibody, IgG-anti-early antigen (anti-EA) antibody, and IgG-anti-EBV nuclear antigen 1 (anti-EBNA1) antibody were evaluated. A systematic review and meta-analysis of eligible seroepidemiological studies was also carried out, and data syntheses were performed using random-effect meta-analysis. RESULTS: In the case-control study, the patients with SjS had both a significantly higher prevalence of IgG-anti-EA antibody positivity (31.9% vs. 3.1%, P < 0.001) and high titers of IgG-anti-EA antibody (P < 0.001) than healthy controls. The titer of IgG-anti-VCA antibody was significantly increased in the patients with SjS compared with healthy controls (P < 0.001). IgG-anti-EA antibody seropositive patients with SjS had lower levels of both C3 (P = 0.002) and C4 (P = 0.02), and the titer of IgG-anti-EA antibody was inversely related to the levels of both C3 (r = -0.31, P < 0.001) and C4 (r = -0.20, P = 0.03). A total of 14 eligible studies on the serological associations between EBV infection and SjS were finally included into the meta-analysis, which suggested obvious associations of SjS with IgM-anti-VCA antibody [Odds ratio (OR) = 5.77, 95%CI 1.73–19.25, P = 0.004] and IgG-anti-EA antibody (OR = 9.97, 95%CI 4.58-21.67, P < 0.00001). CONCLUSIONS: The findings from this study provide strong serological evidence for the association between EBV infection and SjS. SjS has obvious associations with IgM-anti-VCA antibody and IgG-anti-EA antibody. IgG-anti-EA antibody is linked to low levels of C3 and C4 in the patients with SjS, the significance of which needs to be addressed in further studies."
4185,Nitrate Is Crucial for the Proliferation of Gut Escherichia coli Caused by H9N2 AIV Infection and Effective Regulation by Chinese Herbal Medicine Ageratum-Liquid,"H9N2 avian influenza virus (AIV) infection in chickens is often accompanied by secondary bacterial infection, but the mechanism is unclear. The aim of the present study was to reveal that mechanism and explore non-antibiotic treatment. 16s rRNA sequencing and metabonomics were performed in the intestinal contents of chickens infected with H9N2 AIV or H9N2 AIV and fed with ageratum-liquid (AL) to reveal the metabolite that promote intestinal Escherichia coli (E. coli) proliferation caused by H9N2 AIV, as well as to determine the regulatory effect of AL. It was found that H9N2 AIV infection led E. coli to become the dominant gut microbe and promoted E. coli translocation from the intestinal tract to the visceral tissue through the damaged intestinal barrier. H9N2 AIV infection induces inflammation in the intestinal mucosa and promotes the secretion and release of nitrate from the host intestinal epithelium. In addition, nitrate promoted E. coli proliferation in the inflamed intestinal tract following H9N2 AIV infection. Furthermore, Chinese herbal medicine AL can restore intestinal homeostasis, inhibit the production of nitrate in the intestinal epithelium and effectively prevent the proliferation and translocation of E. coli in the intestines. This is the first report on the mechanism of E. coli secondary infection induced by H9N2 AIV, where herbal medicine AL was shown to have a good preventive effect on the secondary infection."
4186,Subjective Environmental Experiences and Women’s Breastfeeding Journeys: A Survival Analysis Using an Online Survey of UK Mothers,"Local physical and social environmental factors are important drivers of human health and behaviour. Environmental perception has been linked with both reproduction and parenting, but links between subjective environmental experiences and breastfeeding remain unclear. Using retrospective data from an online survey of UK mothers of children aged 0–24 months, Cox-Aalen survival models test whether negative subjective environmental experiences negatively correlated with any and exclusive breastfeeding (max n = 473). Matching predictions, hazards of stopping any breastfeeding were increased, albeit non-significantly, across the five environmental measures (HR: 1.05–1.26) Hazards for stopping exclusive breastfeeding were however (non-significantly) reduced (HR: 0.65–0.87). Score processes found no significant time-varying effects. However, estimated cumulative coefficient graphs showed that the first few weeks postpartum were most susceptible to environmental influences and that contrary to our predictions, mothers with worse subjective environmental experiences were less likely to stop breastfeeding at this time. In addition, the hazard of stopping exclusive breastfeeding declined over time for mothers who thought that littering was a problem. The predicted increased hazards of stopping breastfeeding were only evident in the later stages of any breastfeeding and only for mothers who reported littering as a problem or that people tended not to know each other. Perceived harsher physical and social environmental conditions are assumed to deter women from breastfeeding, but this may not always be the case. Women’s hazards of stopping breastfeeding change over time and there may be particular timepoints in their breastfeeding journeys where subjective environmental experiences play a role."
4187,Are Heat Shock Proteins an Important Link between Type 2 Diabetes and Alzheimer Disease?,"Type 2 diabetes (T2D) and Alzheimer’s disease (AD) are growing in prevalence worldwide. The development of T2D increases the risk of AD disease, while AD patients can show glucose imbalance due to an increased insulin resistance. T2D and AD share similar pathological features and underlying mechanisms, including the deposition of amyloidogenic peptides in pancreatic islets (i.e., islet amyloid polypeptide; IAPP) and brain (β-Amyloid; Aβ). Both IAPP and Aβ can undergo misfolding and aggregation and accumulate in the extracellular space of their respective tissues of origin. As a main response to protein misfolding, there is evidence of the role of heat shock proteins (HSPs) in moderating T2D and AD. HSPs play a pivotal role in cell homeostasis by providing cytoprotection during acute and chronic metabolic stresses. In T2D and AD, intracellular HSP (iHSP) levels are reduced, potentially due to the ability of the cell to export HSPs to the extracellular space (eHSP). The increase in eHSPs can contribute to oxidative damage and is associated with various pro-inflammatory pathways in T2D and AD. Here, we review the role of HSP in moderating T2D and AD, as well as propose that these chaperone proteins are an important link in the relationship between T2D and AD."
4188,Sonidegib for the Treatment of Advanced Basal Cell Carcinoma,"Basal cell carcinoma (BCC) accounts for almost 80% of skin cancers, and its healthcare workload burden is substantial within dermatology departments. Although most BCCs are small, well-defined tumors amenable of surgery or conservative procedures, in a small proportion of patients, BCCs can progress to an advanced stage including locally advanced BCC. The goal of the clinician in the treatment of BCC should be the right therapeutic approach at diagnosis, and different guidelines propose treatment strategies in order to prevent relapses or disease progression. In case of unresectable and untreatable BCC with radiotherapy, the first-choice medical therapy is Hedgehog-GLI (HH) pathway inhibitors. Sonidegib was approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) as a first-line treatment for adult patients with locally advanced BCC, becoming the second HH pathway inhibitor receiving approval after vismodegib. In this review, data on pharmacology, safety, tolerability, and efficacy of sonidegib are summarized and compared to those of vismodegib. Lastly, indications on the management of advanced basal cell carcinoma based on author’s clinical experience are provided."
4189,"Three Pillars of Automated Home-Cage Phenotyping of Mice: Novel Findings, Refinement, and Reproducibility Based on Literature and Experience","Animal models of neurodegenerative and neuropsychiatric disorders require extensive behavioral phenotyping. Currently, this presents several caveats and the most important are: (i) rodents are nocturnal animals, but mostly tested during the light period; (ii) the conventional behavioral experiments take into consideration only a snapshot of a rich behavioral repertoire; and (iii) environmental factors, as well as experimenter influence, are often underestimated. Consequently, serious concerns have been expressed regarding the reproducibility of research findings on the one hand, and appropriate welfare of the animals (based on the principle of 3Rs—reduce, refine and replace) on the other hand. To address these problems and improve behavioral phenotyping in general, several solutions have been proposed and developed. Undisturbed, 24/7 home-cage monitoring (HCM) is gaining increased attention and popularity as demonstrating the potential to substitute or complement the conventional phenotyping methods by providing valuable data for identifying the behavioral patterns that may have been missed otherwise. In this review, we will briefly describe the different technologies used for HCM systems. Thereafter, based on our experience, we will focus on two systems, IntelliCage (NewBehavior AG and TSE-systems) and Digital Ventilated Cage (DVC(®), Tecniplast)—how they have been developed and applied during recent years. Additionally, we will touch upon the importance of the environmental/experimenter artifacts and propose alternative suggestions for performing phenotyping experiments based on the published evidence. We will discuss how the integration of telemetry systems for deriving certain physiological parameters can help to complement the description of the animal model to offer better translation to human studies. Ultimately, we will discuss how such HCM data can be statistically interpreted and analyzed."
4190,BSPD presents awards online,
4191,Realistic dentistry,
4192,Two-tier dental system,
4193,United to preserve antimicrobials,
4194,Exam appreciation,
4195,Racial and socioeconomic disparities in breast milk feedings in US neonatal intensive care units,"ABSTRACT: Very low birth weight (VLBW; <1500 g birth weight) infants are substantially more likely to be born to black than to non-black mothers, predisposing them to potentially preventable morbidities that increase the risk for costly lifelong health problems. Mothers’ own milk (MOM) may be considered the ultimate “personalized medicine” since milk composition and bioactive components vary among mothers and multiple milk constituents provide specific protection based on shared exposures between mother and infant. MOM feedings reduce the risks and associated costs of prematurity-associated morbidities, with the greatest reduction afforded by MOM through to NICU discharge. Although black and non-black mothers have similar lactation goals and initiation rates, black VLBW infants are half as likely to receive MOM at NICU discharge in the United States. Black mothers are significantly more likely to be low-income, single heads of household and have more children in the home, increasing the burden of MOM provision. Although rarely considered, the out-of-pocket and opportunity costs associated with providing MOM for VLBW infants are especially onerous for black mothers. When MOM is not available, the NICU assumes the costs of inferior substitutes for MOM, contributing further to disparate outcomes. Novel strategies to mitigate these disparities are urgently needed. IMPACT: Mother’s own milk exemplifies personalized medicine through its unique biologic activity. Hospital factors and social determinants of health are associated with mother’s own milk feedings for very low-birth-weight infants in the neonatal intensive care unit. Notably, out-of-pocket and opportunity costs associated with providing mother’s own milk are borne by mothers. Conceptualizing mother’s own milk feedings as an integral part of NICU care requires consideration of who bears the costs of MOM provision—the mother or the NICU?"
4196,A whole-team approach to triaging patients: is this the future?,
4197,Unaffected in Cambodia,
4198,Postgraduate periodontal education,
4199,Expert view: Robert Ireland,
4200,Punishing pandemic encumbrance,
4201,Dementia guidance please,
4202,'Wearing ear-loop blue surgical masks is a fight to win',
4203,Scientific rigour,
4204,Author Q&A: Adam Nulty,
4205,PPE update,
4206,"Honours, awards, appointments",
4207,RCSEd launches app and brand refresh,
4208,Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model,"Oral carcinogenesis involves the progression of the normal mucosa into potentially malignant disorders and finally into cancer. Tumors are heterogeneous, with different clusters of cells expressing different genes and exhibiting different behaviors. 4-nitroquinoline 1-oxide (4-NQO) and arecoline were used to induce oral cancer in mice, and the main factors for gene expression influencing carcinogenesis were identified through single-cell RNA sequencing analysis. Male C57BL/6J mice were divided into two groups: a control group (receiving normal drinking water) and treatment group (receiving drinking water containing 4-NQO (200 mg/L) and arecoline (500 mg/L)) to induce the malignant development of oral cancer. Mice were sacrificed at 8, 16, 20, and 29 weeks. Except for mice sacrificed at 8 weeks, all mice were treated for 16 weeks and then either sacrificed or given normal drinking water for the remaining weeks. Tongue lesions were excised, and all cells obtained from mice in the 29- and 16-week treatment groups were clustered into 17 groups by using the Louvain algorithm. Cells in subtypes 7 (stem cells) and 9 (keratinocytes) were analyzed through gene set enrichment analysis. Results indicated that their genes were associated with the MYC_targets_v1 pathway, and this finding was confirmed by the presence of cisplatin-resistant nasopharyngeal carcinoma cell lines. These cell subtype biomarkers can be applied for the detection of patients with precancerous lesions, the identification of high-risk populations, and as a treatment target."
4209,Regulation of Male Fertility by the Renin-Angiotensin System,"The renin-angiotensin system (RAS) is a peptidic system known mainly for its roles in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, several tissues and cells have been described to possess an intrinsic RAS that acts locally through different paracrine and autocrine mechanisms. In the male reproductive system, several components of this system have been observed in various organs and tissues, such as the testes, spermatozoa and seminal fluid. Some functions attributed to this local RAS are maintenance of seminal plasma electrolytes, regulation of steroidogenesis and spermatogenesis, and sperm functions. However, their specific actions in these locations are not fully understood. Therefore, a deep knowledge of the functions of the RAS at both the testicular and seminal levels could clarify its roles in male infertility and sperm physiology, and the different RAS elements could be used to design tools enabling the diagnosis and/or treatment of male infertility."
4210,Updated infection prevention and control guidance published,
4211,British Society of Prosthodontics,
4212,"Long but Unreal Lockdowns in Latin America. Comment on Chen, Y.T.; Yen, Y.F.; Yu, S.H.; Su, E.C. An Examination on the Transmission of COVID-19 and the Effect of Response Strategies: A Comparative Analysis. Int. J. Environ. Res. Public Health 2020, 17, E5687","Lockdowns have been important elements of epidemic control over time. During the COVID-19 pandemic, they have been implemented in many countries, at very different times, and accompanied by school or workplace closures, restrictions on mass gatherings, and public transport closure in different combinations. Recent evidence published in the International Journal of Environmental Research and Public Health suggests that SARS-CoV-19 transmission is diminished when strict lockdowns, contact tracing, and good public cooperation are implemented. However, in Latin America, not all lockdowns are real, and rapid increases in a few weeks in the number of infected, hospitalized, and deceased populations have been observed. In these cases, the effect of lockdowns is weakening of democracy."
4213,Molecular Drivers of Platelet Activation: Unraveling Novel Targets for Anti-Thrombotic and Anti-Thrombo-Inflammatory Therapy,"Cardiovascular diseases (CVDs) are the leading cause of death globally—partly a consequence of increased population size and ageing—and are major contributors to reduced quality of life. Platelets play a major role in hemostasis and thrombosis. While platelet activation and aggregation are essential for hemostasis at sites of vascular injury, uncontrolled platelet activation leads to pathological thrombus formation and provokes thrombosis leading to myocardial infarction or stroke. Platelet activation and thrombus formation is a multistage process with different signaling pathways involved to trigger platelet shape change, integrin activation, stable platelet adhesion, aggregation, and degranulation. Apart from thrombotic events, thrombo-inflammation contributes to organ damage and dysfunction in CVDs and is mediated by platelets and inflammatory cells. Therefore, in the past, many efforts have been made to investigate specific signaling pathways in platelets to identify innovative and promising approaches for novel antithrombotic and anti-thrombo-inflammatory strategies that do not interfere with hemostasis. In this review, we focus on some of the most recent data reported on different platelet receptors, including GPIb-vWF interactions, GPVI activation, platelet chemokine receptors, regulation of integrin signaling, and channel homeostasis of NMDAR and PANX1."
4214,"Association of Short-Term Exposure to Meteorological Factors and Risk of Hand, Foot, and Mouth Disease: A Systematic Review and Meta-Analysis","(1) Background: Inconsistencies were observed in studies on the relationship between short-term exposure to meteorological factors and the risk of hand, foot, and mouth disease (HFMD). This systematic review and meta-analysis was aimed to assess the overall effects of meteorological factors on the incidence of HFMD to help clarify these inconsistencies and serve as a piece of evidence for policy makers to determine relevant risk factors. (2) Methods: Articles published as of 24 October 2020, were searched in the four databases, namely, PubMed, Web of Science, Embase, and MEDLINE. We applied a meta-analysis to assess the impact of ambient temperature, relative humidity, rainfall, wind speed, and sunshine duration on the incidence of HFMD. We conducted subgroup analyses by exposure metrics, exposure time resolution, regional climate, national income level, gender, and age as a way to seek the source of heterogeneity. (3) Results: Screening by the given inclusion and exclusion criteria, a total of 28 studies were included in the analysis. We observed that the incidence of HFMD based on the single-day lag model is significantly associated with ambient temperature, relative humidity, rainfall, and wind speed. In the cumulative lag model, ambient temperature and relative humidity significantly increased the incidence of HFMD as well. Subgroup analysis showed that extremely high temperature and relative humidity significantly increased the risk of HFMD. Temperate regions, high-income countries, and children under five years old are major risk factors for HFMD. (4) Conclusions: Our results suggest that various meteorological factors can increase the incidence of HFMD. Therefore, the general public, especially susceptible populations, should pay close attention to weather changes and take protective measures in advance."
4215,“Follow the Whistle: Physical Activity Is Calling You”: Evaluation of Implementation and Impact of a Portuguese Nationwide Mass Media Campaign to Promote Physical Activity,"To raise perceived capability (C), opportunity (O) and motivation (M) for physical activity (PA) behaviour (B) among adults, the Portuguese Directorate-General of Health developed a mass media campaign named “Follow the Whistle”, based on behaviour change theory and social marketing principles. Comprehensive formative and process evaluation suggests this media-led campaign used best-practice principles. The campaign adopted a population-wide approach, had clear behavioural goals, and clear multi-strategy implementation. We assessed campaign awareness and initial impact using pre (n = 878, 57% women) and post-campaign (n = 1319, 58% women) independent adult population samples via an online questionnaire, comprising socio-demographic factors, campaign awareness and recall, and psychosocial and behavioural measures linked to the COM-B model. PA was assessed with IPAQ and the Activity Choice Index. The post-campaign recall was typical of levels following national campaigns (24%). Post-campaign measures were higher for key theory-based targets (all p < 0.05), namely self-efficacy, perceived opportunities to be more active and intrinsic motivation. The impact on social norms and self-efficacy was moderated by campaign awareness. Concerning PA, effects were found for vigorous activity (p < 0.01), but not for incidental activity. Overall the campaign impacted key theory-based intermediate outcomes, but did not influence incidental activity, which highlights the need for sustained and repeated campaign efforts."
4216,Verification of the Mediating Effect of Social Support on Physical Activity and Aging Anxiety of Korean Pre-Older Adults,"There is a lack of research on Korean prospective elderly persons. In particular, there is little research regarding whether social support has a mediating effect on the relationship between physical activity and aging anxiety. Accordingly, this study investigated how social support affected physical activity and aging anxiety in 778 prospective senior citizens (55 to 65 years old) out of a total of 1447 senior citizens who participated in the Embrain Panel Power and Panel Marketing Interactive. Participants completed the IPAQ (International Physical Activity Questionnaires), Social Support Scale, and Aging Anxiety Scale. Physical activity in these Korean pre-older adults affected aging anxiety (p < 0.001), with a fixed effect of physical activity on social support (p < 0.001). Further, social support affected aging anxiety (p < 0.001). Social support was also an important parameter in the relationship between physical activity and aging anxiety. In conclusion, high physical activity of pre-older Korean persons lowered their anxiety regarding aging. Social support acted as a mediator that lowered anxiety regarding aging in the most active pre-older persons."
4217,New Methods Used in Pharmacokinetics and Therapeutic Monitoring of the First and Newer Generations of Antiepileptic Drugs (AEDs),"The review presents data from the last few years on bioanalytical methods used in therapeutic drug monitoring (TDM) of the 1st–3rd generation and the newest antiepileptic drug (AEDs) cenobamate in patients with various forms of seizures. Chemical classification, structure, mechanism of action, pharmacokinetic data and therapeutic ranges for total and free fractions and interactions were collected. The primary data on bioanalytical methods for AEDs determination included biological matrices, sample preparation, dried blood spot (DBS) analysis, column resolution, detection method, validation parameters, and clinical utility. In conclusion, the most frequently described method used in AED analysis is the LC-based technique (HPLC, UHPLC, USLC) combined with highly sensitive mass detection or fluorescence detection. However, less sensitive UV is also used. Capillary electrophoresis and gas chromatography have been rarely applied. Besides the precipitation of proteins or LLE, an automatic SPE is often a sample preparation method. Derivatization was also indicated to improve sensitivity and automate the analysis. The usefulness of the methods for TDM was also highlighted."
4218,Insightful Valorization of the Biological Activities of Pani Heloch Leaves through Experimental and Computer-Aided Mechanisms,"Pani heloch (Antidesma montanum) is traditionally used to treat innumerable diseases and is a source of wild vegetables for the management of different pathological conditions. The present study explored the qualitative phytochemicals; quantitative phenol and flavonoid contents; in vitro antioxidant, anti-inflammatory, and thrombolytic effects; and in vivo antipyretic and analgesic properties of the methanol extract of A. montanum leaves in different experimental models. The extract exhibited secondary metabolites including alkaloids, flavonoids, flavanols, phytosterols, cholesterols, phenols, terpenoids, glycosides, fixed oils, emodines, coumarins, resins, and tannins. Besides, Pani heloch showed strong antioxidant activity (IC(50) = 99.00 µg/mL), while a moderate percentage of clot lysis (31.56%) in human blood and significant anti-inflammatory activity (p < 0.001) was achieved with the standard. Moreover, the analgesic and antipyretic properties appeared to trigger a significant response (p < 0.001) relative to in the control group. Besides, an in silico study of carpusin revealed favorable protein-binding affinities. Furthermore, the absorption, distribution, metabolism, excretion, and toxicity analysis and toxicological properties of all isolated compounds adopted Lipinski’s rule of five for drug-like potential and level of toxicity. Our research unveiled that the methanol extract of A. montanum leaves exhibited secondary metabolites that are a good source for managing inflammation, pyrexia, pain, and cellular toxicity. Computational approaches and further studies are required to identify the possible mechanism which responsible for the biological effects."
4219,Needle in a Haystack: The Naïve Repertoire as a Source of T Cell Receptors for Adoptive Therapy with Engineered T Cells,"T cell engineering with antigen-specific T cell receptors (TCRs) has allowed the generation of increasingly specific, reliable, and versatile T cell products with near-physiological features. However, a broad applicability of TCR-based therapies in cancer is still limited by the restricted number of TCRs, often also of suboptimal potency, available for clinical use. In addition, targeting of tumor neoantigens with TCR-engineered T cell therapy moves the field towards a highly personalized treatment, as tumor neoantigens derive from somatic mutations and are extremely patient-specific. Therefore, relevant TCRs have to be de novo identified for each patient and within a narrow time window. The naïve repertoire of healthy donors would represent a reliable source due to its huge diverse TCR repertoire, which theoretically entails T cells for any antigen specificity, including tumor neoantigens. As a challenge, antigen-specific naïve T cells are of extremely low frequency and mostly of low functionality, making the identification of highly functional TCRs finding a “needle in a haystack.” In this review, we present the technological advancements achieved in high-throughput mapping of patient-specific neoantigens and corresponding cognate TCRs and how these platforms can be used to interrogate the naïve repertoire for a fast and efficient identification of rare but therapeutically valuable TCRs for personalized adoptive T cell therapy."
4220,The Flame Retardancy of Polyethylene Composites: From Fundamental Concepts to Nanocomposites,"Polyethylene (PE) is one the most used plastics worldwide for a wide range of applications due to its good mechanical and chemical resistance, low density, cost efficiency, ease of processability, non-reactivity, low toxicity, good electric insulation, and good functionality. However, its high flammability and rapid flame spread pose dangers for certain applications. Therefore, different flame-retardant (FR) additives are incorporated into PE to increase its flame retardancy. In this review article, research papers from the past 10 years on the flame retardancy of PE systems are comprehensively reviewed and classified based on the additive sources. The FR additives are classified in well-known FR families, including phosphorous, melamine, nitrogen, inorganic hydroxides, boron, and silicon. The mechanism of fire retardance in each family is pinpointed. In addition to the efficiency of each FR in increasing the flame retardancy, its impact on the mechanical properties of the PE system is also discussed. Most of the FRs can decrease the heat release rate (HRR) of the PE products and simultaneously maintains the mechanical properties in appropriate ratios. Based on the literature, inorganic hydroxide seems to be used more in PE systems compared to other families. Finally, the role of nanotechnology for more efficient FR-PE systems is discussed and recommendations are given on implementing strategies that could help incorporate flame retardancy in the circular economy model."
4221,Synthesis and Antiviral Activity of a Series of 2′-C-Methyl-4′-thionucleoside Monophosphate Prodrugs,The NS5B RNA-dependent RNA polymerase of the hepatitis C virus (HCV) is a validated target for nucleoside antiviral drug therapy. We endeavored to synthesize and test a series of 4′-thionucleosides with a monophosphate prodrug moiety for their antiviral activity against HCV and other related viruses in the Flaviviridae family. Nucleoside analogs were prepared via the stereoselective Vorbrüggen glycosylation of various nucleobases with per-acetylated 2-C-methyl-4-thio-d-ribose built in a 10-step synthetic sequence from the corresponding ribonolactone. Conjugation of the thionucleoside to a ProTide phosphoramidate allowed for evaluation of the prodrugs in the cellular HCV replicon assay with anti-HCV activities ranging from single-digit micromolar (μM) to >200 μM. The diminished anti-HCV potency of our best compound compared to its 4′-oxo congener is the subject of ongoing research in our lab and is proposed to stem from changes in sugar geometry imparted by the larger sulfur atom.
4222,Inactivation of Infectious Bacteria Using Nonthermal Biocompatible Plasma Cabinet Sterilizer,"Nonthermal, biocompatible plasma (NBP) is a promising unique state of matter that is effective against a wide range of pathogenic microorganisms. This study focused on a sterilization method for bacteria that used the dielectric barrier discharge (DBD) biocompatible plasma cabinet sterilizer as an ozone generator. Reactive oxygen species play a key role in inactivation when air or other oxygen-containing gases are used. Compared with the untreated control, Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Salmonella typhimurium (sepsis) were inhibited by approximately 99%, or were nondetectable following plasma treatment. Two kinds of plasma sterilizers containing six- or three-chamber cabinets were evaluated. There was no noticeable difference between the two configurations in the inactivation of microorganisms. Both cabinet configurations were shown to be able to reduce microbes dramatically, i.e., to the nondetectable range. Therefore, our data indicate that the biocompatible plasma cabinet sterilizer may prove to be an appropriate alternative sterilization procedure."
4223,The Accuracy of Self-Reported Body Weight Is High but Dependent on Recent Weight Change and Negative Affect in Teenage Girls,"Background: Research studies often rely on self-reported weight to calculate body mass index. The present study investigated how the accuracy of self-reported body weight in adolescent girls is affected by overweight/obesity, race/ethnicity, and mental health factors. Methods: In a cohort of girls who participated in the Trial of Activity for Adolescent Girls at ages 11 and 17 (n = 588), self-reported and measured weight were compared, and linear regression models were fitted to model the over- or underreporting. The Center for Epidemiological Studies-Depression Scale (CES-D) was used to calculate depressive symptom subscales for negative affect, anhedonia and somatic symptoms. Results: Allowing 3% difference between self-reported and measured weight for the correct reporting of body weight, 59.2% of girls reported their weight correctly, 30.3% underreported (−5.8 ± 4.8 kg), and 10.5% overreported (4.3 ± 3.5 kg). The average difference between self-reported and measured body weight was −1.5 ± 4.3 kg (p < 0.001). Factors for misreporting body weight were overweight (β ± SE − 2.60 ± 0.66%), obesity (β ± SE − 2.41 ± 0.71%), weight change between ages 11 and 17 (β ± SE − 0.35 ± 0.04% for each kg), height change between ages 11 and 17 (β ± SE 0.29 ± 0.10% for each cm), and negative affect (β ± SE − 0.18 ± 0.08% for each score unit). Conclusions: The difference between self-reported and measured body weight in adolescent girls is relatively small. However, the accuracy of self-reported body weight may be lower in girls with overweight or obesity, recent weight and height change, and higher negative affect."
4224,"Comparative Analysis of PM(2.5)-Bound Polycyclic Aromatic Hydrocarbons (PAHs), Nitro-PAHs (NPAHs), and Water-Soluble Inorganic Ions (WSIIs) at Two Background Sites in Japan","Daily PM(2.5) (particulate matter with aerodynamic diameter ≤2.5 μm) samples were simultaneously collected at two background sites (Wajima Air Monitoring Station (WAMS) and Fukue-Jima Atmosphere and Aerosol Monitoring Station (FAMS)) in Japan in the East Asian winter and summer monsoon periods of 2017 and 2019, to compare the characteristics of air pollutants among different regions and to determine the possible variation during the long-range transport process. Polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (NPAHs), and water-soluble inorganic ions (WSIIs) were analyzed. Despite the PM(2.5) concentrations at FAMS (8.90–78.5 µg/m(3)) being higher than those at WAMS (2.33–21.2 µg/m(3)) in the winter monsoon period, the average concentrations of ∑PAHs, ∑NPAHs, and ∑WSIIs were similar between the two sites. Diagnostic ratios indicated PAHs mainly originated from traffic emissions and mostly aged, whereas NPAHs were mostly secondarily formed during long-range transport. WSIIs at WAMS were mainly formed via the combustion process and secondary reactions, whereas those at FAMS mainly originated from sea salt and dust. Backward trajectories revealed the air masses could not only come from Asian continental coastal regions but also distant landlocked areas in the winter monsoon period, whereas most came from the ocean in the summer monsoon period. These findings can provide basic data for the establishment of prediction models of transboundary air pollutants in East Asia."
4225,The Influence of Maturity Status on Anthropometric Profile and Body Composition of Youth Goalkeepers,"The anthropometric profile assessment is an important aspect to consider during the growth stages of youth sport practitioners due to its usefulness in controlling maturity status and overall health. We performed an anthropometric profile evaluation in a sample of youth goalkeepers (n = 42) during a training camp, dividing them into three categories based on their years from peak height velocity (YPHV). We also checked if the selection of goalkeepers was associated with the birth quartile. The results showed that most of the participants’ anthropometric parameters followed the normal trend according to the maturation stages. However, several subjects showed an overweight/obese condition and/or high waist circumference. Non-optimal values were found, mostly in the group of goalkeepers around the PHV. In addition, no selection based on birth quartile was seen. Therefore, the anthropometric profile and body composition of youth goalkeepers are physiologically affected by maturity status. However, several subjects were found to be overweight/obese and at cardiometabolic risk, suggesting that children and adolescents, although practicing sport, should pay attention to potentially contributing factors such as the attainment of the recommended levels of physical activity, lowering sedentary time, and adopt a healthy lifestyle."
4226,"In Vitro and In Silico Evaluation of Anticancer Activity of New Indole-Based 1,3,4-Oxadiazoles as EGFR and COX-2 Inhibitors","Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) are crucial targetable enzymes in cancer management. Therefore, herein, new 2-[(5-((1H-indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(thiazol/benzothiazol-2-yl)acetamides (2a–i) were designed and synthesized as EGFR and COX-2 inhibitors. The cytotoxic effects of compounds 2a–i on HCT116 human colorectal carcinoma, A549 human lung adenocarcinoma, and A375 human melanoma cell lines were determined using MTT assay. 2-[(5-((1H-Indol-3-yl)methyl)-1,3,4-oxadiazol-2-yl)thio]-N-(6-ethoxybenzothiazol-2-yl)acetamide (2e) exhibited the most significant anticancer activity against HCT116, A549, and A375 cell lines with IC(50) values of 6.43 ± 0.72 μM, 9.62 ± 1.14 μM, and 8.07 ± 1.36 μM, respectively, when compared with erlotinib (IC(50) = 17.86 ± 3.22 μM, 19.41 ± 2.38 μM, and 23.81 ± 4.17 μM, respectively). Further mechanistic assays demonstrated that compound 2e enhanced apoptosis (28.35%) in HCT116 cells more significantly than erlotinib (7.42%) and caused notable EGFR inhibition with an IC(50) value of 2.80 ± 0.52 μM when compared with erlotinib (IC(50) = 0.04 ± 0.01 μM). However, compound 2e did not cause any significant COX-2 inhibition, indicating that this compound showed COX-independent anticancer activity. The molecular docking study of compound 2e emphasized that the benzothiazole ring of this compound occupied the allosteric pocket in the EGFR active site. In conclusion, compound 2e is a promising EGFR inhibitor that warrants further clinical investigations."
4227,Antifibrotic and Regenerative Effects of Treamid in Pulmonary Fibrosis,"Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease characterized by interstitial fibrosis and progressive respiratory failure. Pirfenidone and nintedanib slow down but do not stop the progression of IPF. Thus, new compounds with high antifibrotic activity and simultaneously regenerative activity are an unmet clinical need. Recently, we showed that Treamid can help restoring the pancreas and testicular tissue in mice with metabolic disorders. We hypothesized that Treamid may be effective in antifibrotic therapy and regeneration of damaged lung tissue in pulmonary fibrosis. In this study, experiments were performed on male C57BL/6 mice with bleomycin-induced pulmonary fibrosis. We applied histological and immunohistochemical methods, ELISA, and assessed the expression of markers of endothelial and epithelial cells in primary cultures of CD31(+) and CD326(+) lung cells. Finally, we evaluated esterase activity and apoptosis of lung cells in vitro. Our data indicate that Treamid exhibits antifibrotic activity in mice with pulmonary fibrosis and has a positive effect on capillaries of the lungs. Treamid also increases the number of endothelial progenitor cells in the lungs of animals with pulmonary fibrosis. Lastly, Treamid increases esterase activity and decreases apoptosis of CD31(+) lung cells in vitro. Based on these findings, we suggest that Treamid may represent a promising compound for the development of new antifibrotic agents, which are capable of stimulating regeneration of lung endothelium in IPF patients."
4228,Pre-clustering data sets using cluster4x improves the signal-to-noise ratio of high-throughput crystallography drug-screening analysis,"Drug and fragment screening at X-ray crystallography beamlines has been a huge success. However, it is inevitable that more high-profile biological drug targets will be identified for which high-quality, highly homogenous crystal systems cannot be found. With increasing heterogeneity in crystal systems, the application of current multi-data-set methods becomes ever less sensitive to bound ligands. In order to ease the bottleneck of finding a well behaved crystal system, pre-clustering of data sets can be carried out using cluster4x after data collection to separate data sets into smaller partitions in order to restore the sensitivity of multi-data-set methods. Here, the software cluster4x is introduced for this purpose and validated against published data sets using PanDDA, showing an improved total signal from existing ligands and identifying new hits in both highly heterogenous and less heterogenous multi-data sets. cluster4x provides the researcher with an interactive graphical user interface with which to explore multi-data set experiments."
4229,Archetypes of Gamification: Analysis of mHealth Apps,"BACKGROUND: Nowadays, numerous health-related mobile apps implement gamification in an attempt to draw on the motivational potential of video games and thereby increase user engagement or foster certain health behaviors. However, research on effective gamification is still in its infancy and researchers increasingly recognize methodological shortcomings of existing studies. What we actually know about the phenomenon today stems from fragmented pieces of knowledge, and a variety of different perspectives. Existing research primarily draws on conceptual knowledge that is gained from research prototypes, and isolated from industry best practices. We still lack knowledge on how gamification has been successfully designed and implemented within the industry and whether certain gamification approaches have shown to be particularly suitable for certain health behaviors. OBJECTIVE: We address this lack of knowledge concerning best practices in the design and implementation of gamification for health-related mobile apps by identifying archetypes of gamification approaches that have emerged in pertinent health-related mobile apps and analyzing to what extent those gamification approaches are influenced by the underlying desired health-related outcomes. METHODS: A 3-step research approach is employed. As a first step, a database of 143 pertinent gamified health-related mobile apps from the Apple App Store and Google Play Store is set up. Second, the gamification approach of each app within the database is classified based on an established taxonomy for gamification in health-related apps. Finally, a 2-step cluster analysis is conducted in order to identify archetypes of the most dominant gamification approaches in pertinent gamified health-related mobile apps. RESULTS: Eight archetypes of gamification emerged from the analysis of health-related mobile apps: (1) competition and collaboration, (2) pursuing self-set goals without rewards, (3) episodical compliance tracking, (4) inherent gamification for external goals, (5) internal rewards for self-set goals, (6) continuous assistance through positive reinforcement, (7) positive and negative reinforcement without rewards, and (8) progressive gamification for health professionals. The results indicate a close relationship between the identified archetypes and the actual health behavior that is being targeted. CONCLUSIONS: By unveiling salient best practices and discussing their relationship to targeted health behaviors, this study contributes to a more profound understanding of gamification in mobile health. The results can serve as a foundation for future research that advances the knowledge on how gamification may positively influence health behavior change and guide practitioners in the design and development of highly motivating and effective health-related mobile health apps."
4230,Smartphone App to Address Loneliness Among College Students: Pilot Randomized Controlled Trial,"BACKGROUND: Loneliness is a widespread and significant problem on college campuses. Prolonged loneliness in young adulthood is a risk factor for concurrent and future mental health problems and attrition, making college a critical time for support. Cognitive and behavioral interventions show promise for decreasing loneliness and can be widely disseminated through technology. OBJECTIVE: This pilot randomized controlled trial was conducted to examine the initial efficacy, feasibility, and desirability of a smartphone app, Nod, designed to deliver cognitive and behavioral skill-building exercises to reduce loneliness during the transition to college. METHODS: First-year college students (N=221, mean age 18.7 years, 59% female) were recruited online during incoming student orientation, and randomized to either receive immediate access to Nod (experimental group, n=100) or access after 4 weeks (control group, n=121). The app delivered skills via fully automated (1) “social challenges,” suggested activities designed to build social connections; (2) reflections, brief cognitive reframing exercises; and (3) student testimonials that encouraged a growth mindset toward social connection building. Main intention-to-treat analyses were used to compare the conditions on self-assessed loneliness, depressive symptoms, and other mental health and college adjustment outcomes at week 4, controlling for baseline values on those variables. Analyses were also performed to test the hypothesis that the treatment benefits would be particularly pronounced for participants with heightened psychological vulnerability at baseline (ie, higher baseline depressive symptoms and loneliness). RESULTS: Retention was 97% at week 4, and participants viewed an average 36.7 pages of app content. There were no significant condition differences in loneliness at week 4 (F(1, 211)=0.05, P=.82; η(p)(2) <.001). However, there was a significant condition-by-baseline depression interaction to predict week-4 loneliness (F(1,209)=9.65, P=.002; η(p)(2) =.04). Simple slope analyses indicated that baseline depression positively predicted week-4 loneliness among control participants (r=0.30, t(209)=3.81, P<.001), but not among experimental participants (r=–0.09, t(209)=–0.84, P=.40), suggesting that Nod buffered participants with high baseline depression scores from experiencing heightened midquarter loneliness. Similarly, there were no significant condition differences in other week-4 outcomes. However, moderation by baseline vulnerability was found for week-4 depressive symptoms, sleep quality, and indices of college adjustment (eg, perceived social support and campus belonging). CONCLUSIONS: Although Nod exposure did not impact outcomes for the full sample, these results provide initial evidence of its benefit for vulnerable students. The results of this trial suggest that cognitive and behavioral skills delivered via a mobile app can buffer psychologically vulnerable college students against heightened loneliness and depressive symptoms, as well as other negative college adjustment outcomes. Future work will aim to improve upon app engagement, and to address loneliness among other key populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT04164654; https://clinicaltrials.gov/ct2/show/NCT04164654"
4231,The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever,"BACKGROUND: Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT. METHODS: Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT. RESULTS: The incidence of NF among the groups was reduced (64%, 44%, and 24%; P<0.001), with a non-significant decrease in hospital readmissions as well (12%, 6%, and 2%; P = 0.07). The most important variables identified for NF were: HCT-CI >2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P<0.001); and for hospital readmission: age ≥60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05). CONCLUSIONS: G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial."
4232,"Transmission of SARS-COV-2 Infections in Households — Tennessee and Wisconsin, April–September 2020",
4233,Dichloroacetate-induced metabolic reprogramming improves lifespan in a Drosophila model of surviving sepsis,"Sepsis is the leading cause of death in hospitalized patients and beyond the hospital stay and these long-term sequelae are due in part to unresolved inflammation. Metabolic shift from oxidative phosphorylation to aerobic glycolysis links metabolism to inflammation and such a shift is commonly observed in sepsis under normoxic conditions. By shifting the metabolic state from aerobic glycolysis to oxidative phosphorylation, we hypothesized it would reverse unresolved inflammation and subsequently improve outcome. We propose a shift from aerobic glycolysis to oxidative phosphorylation as a sepsis therapy by targeting the pathways involved in the conversion of pyruvate into acetyl-CoA via pyruvate dehydrogenase (PDH). Chemical manipulation of PDH using dichloroacetic acid (DCA) will promote oxidative phosphorylation over glycolysis and decrease inflammation. We tested our hypothesis in a Drosophila melanogaster model of surviving sepsis infected with Staphylococcus aureus. Drosophila were divided into 3 groups: unmanipulated, sham and sepsis survivors, all treated with linezolid; each group was either treated or not with DCA for one week following sepsis. We followed lifespan, measured gene expression of Toll, defensin, cecropin A, and drosomycin, and levels of lactate, pyruvate, acetyl-CoA as well as TCA metabolites. In our model, metabolic effects of sepsis are modified by DCA with normalized lactate, TCA metabolites, and was associated with improved lifespan of sepsis survivors, yet had no lifespan effects on unmanipulated and sham flies. While Drosomycin and cecropin A expression increased in sepsis survivors, DCA treatment decreased both and selectively increased defensin."
4234,Differences in structure and hibernation mechanism highlight diversification of the microsporidian ribosome,"Assembling and powering ribosomes are energy-intensive processes requiring fine-tuned cellular control mechanisms. In organisms operating under strict nutrient limitations, such as pathogenic microsporidia, conservation of energy via ribosomal hibernation and recycling is critical. The mechanisms by which hibernation is achieved in microsporidia, however, remain poorly understood. Here, we present the cryo–electron microscopy structure of the ribosome from Paranosema locustae spores, bound by the conserved eukaryotic hibernation and recycling factor Lso2. The microsporidian Lso2 homolog adopts a V-shaped conformation to bridge the mRNA decoding site and the large subunit tRNA binding sites, providing a reversible ribosome inactivation mechanism. Although microsporidian ribosomes are highly compacted, the P. locustae ribosome retains several rRNA segments absent in other microsporidia, and represents an intermediate state of rRNA reduction. In one case, the near complete reduction of an expansion segment has resulted in a single bound nucleotide, which may act as an architectural co-factor to stabilize a protein–protein interface. The presented structure highlights the reductive evolution in these emerging pathogens and sheds light on a conserved mechanism for eukaryotic ribosome hibernation."
4235,New Beginnings,
4236,Isolation of monoclonal antibodies from anti-synthetase syndrome patients and affinity maturation by recombination of independent somatic variants,"The autoimmune disease known as Jo-1 positive anti-synthetase syndrome (ASS) is characterized by circulating antibody titers to histidyl-tRNA synthetase (HARS), which may play a role in modulating the non-canonical functions of HARS. Monoclonal antibodies to HARS were isolated by single-cell screening and sequencing from three Jo-1 positive ASS patients and shown to be of high affinity, covering diverse epitope space. The immune response was further characterized by repertoire sequencing from the most productive of the donor samples. In line with previous studies of autoimmune repertoires, these antibodies tended to have long complementarity-determining region H3 sequences with more positive-charged residues than average. Clones of interest were clustered into groups with related sequences, allowing us to observe different somatic mutations in related clones. We postulated that these had found alternate structural solutions for high affinity binding, but that mutations might be transferable between clones to further enhance binding affinity. Transfer of somatic mutations between antibodies within the same clonal group was able to enhance binding affinity in a number of cases, including beneficial transfer of a mutation from a lower affinity clone into one of higher affinity. Affinity enhancement was seen with mutation transfer both between related single-cell clones, and directly from related repertoire sequences. To our knowledge, this is the first demonstration of somatic hypermutation transfer from repertoire sequences to further mature in vivo derived antibodies, and represents an additional tool to aid in affinity maturation for the development of antibodies."
4237,An atlas of immune cell exhaustion in HIV-infected individuals revealed by single-cell transcriptomics,"Chronic infection with human immunodeficiency virus (HIV) can cause progressive loss of immune cell function, or exhaustion, which impairs control of virus replication. However, little is known about the development and maintenance, as well as heterogeneity of immune cell exhaustion. Here, we investigated the effects of HIV infection on immune cell exhaustion at the transcriptomic level by analyzing single-cell RNA sequencing of peripheral blood mononuclear cells from four healthy subjects (37,847 cells) and six HIV-infected donors (28,610 cells). We identified nine immune cell clusters and eight T cell subclusters, and three of these (exhausted CD4(+) and CD8(+) T cells and interferon-responsive CD8(+) T cells) were detected only in samples from HIV-infected donors. An inhibitory receptor KLRG1 was identified in a HIV-1 specific exhausted CD8(+) T cell population expressing KLRG1, TIGIT, and T-bet(dim)Eomes(hi) markers. Ex-vivo antibody blockade of KLRG1 restored the function of HIV-specific exhausted CD8(+) T cells demonstrating the contribution of KLRG1(+) population to T cell exhaustion and providing an immunotherapy target to treat HIV chronic infection. These data provide a comprehensive analysis of gene signatures associated with immune cell exhaustion during HIV infection, which could be useful in understanding exhaustion mechanisms and developing new cure therapies."
4238,Something Big that Matters: The American Society of Tropical Medicine and Hygiene’s Commitment to Combat Climate Change,
4239,"Design and Evaluation of Risk Assessment Tools to Identify Pediatric Tuberculosis Infection in Bohol, the Philippines, a Low–HIV- and High–TB-Burden Setting","Identifying children with, or at substantial risk of, Mycobacterium tuberculosis infection (TBI) and providing TB preventive therapy (TPT) represent an important, yet challenging, strategy in curbing the global burden of childhood TB. Risk assessment scoring tools, which quantify risks associated with unique factors characterizing an individual, could act as a surrogate measure of TBI risk and guide effective and efficient TPT delivery. We assessed important risk factors of childhood TBI and created risk assessment tools through secondary analysis of data from a large, community-based childhood TB prevalence study in the island province of Bohol in the Philippines, a low–HIV- and high–TB-burden, post-disaster setting. We identified four factors that were statistically associated with acquiring TBI—being 5 years or older, having a known TB contact, having a known TB contact who was either the mother or another primary caregiver, and living in a high–TB-burden municipality. We created 2-item, 4-item, and 9-item scores intended to identify child TBI in this low-resource, low–HIV-, and high–TB-burden setting. In addition to the design, evaluation, and impact analysis of these generalizable and valuable risk assessment tools, our study findings emphasize the necessity of targeting both household and community-associated transmissions of childhood TBI to achieve the global goal to end TB."
4240,p53 promotes ZDHHC1-mediated IFITM3 palmitoylation to inhibit Japanese encephalitis virus replication,"The tumor suppressor p53 as an innate antiviral regulator contributes to restricting Japanese encephalitis virus (JEV) replication, but the mechanism is still unclear. The interferon-induced transmembrane protein 3 (IFITM3) is an intrinsic barrier to a range of virus infection, whether IFITM3 is responsible for the p53-mediated anti-JEV response remains elusive. Here, we found that IFITM3 significantly inhibited JEV replication in a protein-palmitoylation-dependent manner and incorporated into JEV virions to diminish the infectivity of progeny viruses. Palmitoylation was also indispensible for keeping IFITM3 from lysosomal degradation to maintain its protein stability. p53 up-regulated IFITM3 expression at the protein level via enhancing IFITM3 palmitoylation. Screening of palmitoyltransferases revealed that zinc finger DHHC domain-containing protein 1 (ZDHHC1) was transcriptionally up-regulated by p53, and consequently ZDHHC1 interacted with IFITM3 to promote its palmitoylation and stability. Knockdown of IFITM3 significantly impaired the inhibitory role of ZDHHC1 on JEV replication. Meanwhile, knockdown of either ZDHHC1 or IFITM3 expression also compromised the p53-mediated anti-JEV effect. Interestingly, JEV reduced p53 expression to impair ZDHHC1 mediated IFITM3 palmitoylation for viral evasion. Our data suggest the existence of a previously unrecognized p53-ZDHHC1-IFITM3 regulatory pathway with an essential role in restricting JEV infection and provide a novel insight into JEV-host interaction."
4241,Perspectives and practices of healthcare providers and caregivers on healthcare-associated infections in the neonatal intensive care units of two hospitals in Ghana,"Healthcare-associated infections (HAIs) remain a serious threat to patient safety worldwide, particularly in low- and middle-income countries. Reducing the burden of HAIs through the observation and enforcement of infection prevention and control (IPC) practices remains a priority. Despite growing emphasis on HAI prevention in low- and middle-income countries, limited evidence is available to improve IPC practices to reduce HAIs. This study examined the perspectives of healthcare providers (HPs) and mothers in the neonatal intensive care unit on HAIs and determined the major barriers and facilitators to promoting standard IPC practices. This study draws on data from an ethnographic study using 38 in-depth interviews, four focus group discussions and participant observation conducted among HPs and mothers in neonatal intensive care units of a secondary- and tertiary-level hospital in Ghana. The qualitative data were analysed using a grounded theory approach, and NVivo 12 to facilitate coding. HPs and mothers demonstrated a modest level of understanding about HAIs. Personal, interpersonal, community, organizational and policy-level factors interacted in complex ways to influence IPC practices. HPs sometimes considered HAI concerns to be secondary in the face of a heavy clinical workload, a lack of structured systems and the quest to protect professional authority. The positive attitudes of some HPs, and peer interactions promoted standard IPC practices. Mothers expressed interest in participation in IPC activities. It however requires systematic efforts by HPs to partner with mothers in IPC. Training and capacity building of HPs, provision of adequate resources and improving communication between HPs and mothers were recommended to improve standard IPC practices. We conclude that there is a need for institutionalizing IPC policies and strengthening strategies that acknowledge and value mothers’ roles as caregivers and partners in IPC. To ensure this, HPs should be better equipped to prioritize communication and collaboration with mothers to reduce the burden of HAIs."
4242,Protocol for a prospective descriptive prevalence study of catatonia in an acute mental health unit in urban South Africa,"INTRODUCTION: Catatonia arises from serious mental, medical, neurological or toxic conditions. The prevalence range depends on the setting and the range is anything from 7% to 63% in other countries. South African prevalence rates are currently unknown. The proposed study is a quantitative descriptive study using the Bush Francis Catatonia Screening Instrument as a screening tool with a data capturing information sheet to extract clinical information from patient folders. The study will investigate: (1) prevalence of catatonia, (2) clinical and demographic correlates associated with catatonia, (3) predictors of catatonia, (4) response to treatment and (5) subjective experience of catatonia. METHODS AND ANALYSIS: The setting is an acute mental health unit (MHU) within a regional, general medical hospital in Nelson Mandela Bay, South Africa, which accepts referrals from within the hospital and from outlying clinics. Participants will be recruited from inpatients in the MHU from beginning of September 2020 to end of August 2021. Most admissions are involuntarily, under the Mental Health Care Act of 2002 with an age range of 13 to over 65 years. Participants who screen positive for catatonia will be followed up after discharge for 3 months to measure outcomes. Primary outcomes will include the 12-month prevalence rate of catatonia, descriptive and other data on presentation and assessment of catatonia in the MHU. Secondary outcomes will include data on treatment response, participants’ report of their subjective experience of catatonia and predictors of catatonia. Descriptive statistics, multivariate binomial logistic regression and univariate analyses will be conducted to evaluate associations between catatonia and clinical or demographic data which could be predictors of catatonia. Survival analysis will be used to examine the time to recovery after diagnosis and initiation of treatment. The 95% CI will be used to demonstrate the precision of estimates. The level of significance will be p≤0.05. ETHICS AND DISSEMINATION: The study has received ethical approval from the Research and Ethics Committees of the Eastern Cape Department of Health, Walter Sisulu University and Nelson Mandela University. The results will be disseminated as follows: at various presentations and feedback sessions; as part of a PhD thesis in Psychology at Nelson Mandela University; and in a manuscript that will be submitted to a peer-reviewed journal."
4243,The Copenhagen test and treat hepatitis C in a mobile clinic study: a protocol for an intervention study to enhance the HCV cascade of care for people who inject drugs (T’N’T HepC),"INTRODUCTION: Injecting drug use is the primary driver of hepatitis C virus (HCV) infection in Europe. Despite the need for more engagement with care, people who inject drugs (PWID) are hard to reach with HCV testing and treatment. We initiated a study to evaluate the efficacy for testing and linkage to care among PWID consulting peer-based testing at a mobile clinic in Copenhagen, Denmark. METHODS AND ANALYSIS: In this intervention study, we will recruit participants at a single community-based, peer-run mobile clinic. In a single visit, we will first offer participants a point-of-care HCV antibody test, and if they test positive, then they will receive an HCV RNA test. If they are HCV-RNA+, we will administer facilitated referrals to designated ‘fast-track’ clinics at a hospital or an addiction centre for treatment. The primary outcomes for this study are the number of tested and treated individuals. Secondary outcomes include individuals lost at each step in the care cascade. ETHICS AND DISSEMINATION: The results of this study could provide a model for targeting PWID for HCV testing and treatment in Demark and other settings, which could help achieve WHO HCV elimination targets. The Health Research Ethics Committee of Denmark and the Danish Data Protection Agency confirmed (December 2018/January 2019) that this study did not require their approval. Study findings will be disseminated through peer-reviewed publications, conference presentations and social media."
4244,Cytoplasmic sharing through apical membrane remodeling,"Multiple nuclei sharing a common cytoplasm are found in diverse tissues, organisms, and diseases. Yet, multinucleation remains a poorly understood biological property. Cytoplasm sharing invariably involves plasma membrane breaches. In contrast, we discovered cytoplasm sharing without membrane breaching in highly resorptive Drosophila rectal papillae. During a six-hour developmental window, 100 individual papillar cells assemble a multinucleate cytoplasm, allowing passage of proteins of at least 62 kDa throughout papillar tissue. Papillar cytoplasm sharing does not employ canonical mechanisms such as incomplete cytokinesis or muscle fusion pore regulators. Instead, sharing requires gap junction proteins (normally associated with transport of molecules < 1 kDa), which are positioned by membrane remodeling GTPases. Our work reveals a new role for apical membrane remodeling in converting a multicellular epithelium into a giant multinucleate cytoplasm."
4245,"SAVI, in silico generation of billions of easily synthesizable compounds through expert-system type rules","We have made available a database of over 1 billion compounds predicted to be easily synthesizable, called Synthetically Accessible Virtual Inventory (SAVI). They have been created by a set of transforms based on an adaptation and extension of the CHMTRN/PATRAN programming languages describing chemical synthesis expert knowledge, which originally stem from the LHASA project. The chemoinformatics toolkit CACTVS was used to apply a total of 53 transforms to about 150,000 readily available building blocks (enamine.net). Only single-step, two-reactant syntheses were calculated for this database even though the technology can execute multi-step reactions. The possibility to incorporate scoring systems in CHMTRN allowed us to subdivide the database of 1.75 billion compounds in sets according to their predicted synthesizability, with the most-synthesizable class comprising 1.09 billion synthetic products. Properties calculated for all SAVI products show that the database should be well-suited for drug discovery. It is being made publicly available for free download from https://doi.org/10.35115/37n9-5738."
4246,"The birth of a bacterial tRNA gene by large-scale, tandem duplication events","Organisms differ in the types and numbers of tRNA genes that they carry. While the evolutionary mechanisms behind tRNA gene set evolution have been investigated theoretically and computationally, direct observations of tRNA gene set evolution remain rare. Here, we report the evolution of a tRNA gene set in laboratory populations of the bacterium Pseudomonas fluorescens SBW25. The growth defect caused by deleting the single-copy tRNA gene, serCGA, is rapidly compensated by large-scale (45–290 kb) duplications in the chromosome. Each duplication encompasses a second, compensatory tRNA gene (serTGA) and is associated with a rise in tRNA-Ser(UGA) in the mature tRNA pool. We postulate that tRNA-Ser(CGA) elimination increases the translational demand for tRNA-Ser(UGA), a pressure relieved by increasing serTGA copy number. This work demonstrates that tRNA gene sets can evolve through duplication of existing tRNA genes, a phenomenon that may contribute to the presence of multiple, identical tRNA gene copies within genomes."
4247,Soluble PD-L1 is associated with local and systemic inflammation markers in primary and secondary brain tumours,"BACKGROUND: Immune-modulatory treatments have so far shown limited clinical activity in primary brain tumours. We aimed to investigate soluble programmed death receptor ligand 1 (sPD-L1) as systemic inflammation parameter in patients with brain tumour. METHODS: EDTA plasma was collected from 81 glioma (55 glioblastoma (GBM), 26 lower-grade glioma (LGG)), 17 meningioma and 44 brain metastasis (BM) patients and 24 controls. sPD-L1 concentrations were determined by ELISA. Correlations with the local tumour microenvironment were assessed by immunohistochemical analysis for PD-L1, CD3 and CD8. RESULTS: sPD-L1 was detected in 62 out of 166 (37.7%) patients (glioma: 41/81, 50.6%; meningioma: 5/17, 29.4%; BM: 7/44, 15.9%; controls: 9/24, 37.5%; p=0.002). sPD-L1 concentrations were lower in BM than in LGG (p=0.003) or GBM (p<0.001). Membranous PD-L1 expression on tumour cells was not associated with sPD-L1 concentrations (p=0.953). sPD-L1 concentration was inversely correlated with the density of CD8+ (r=−0.713, p=0.001) and CD3+ (r=−0.484, p=0.042) tumour-infiltrating lymphocytes in LGG. sPD-L1 is correlated with neutrophil counts (r=−0.318, p=0.045) and C reactive protein levels (r=−0.363, p=0.008) in GBM. sPD-L1+ patients had longer overall survival in GBM (p=0.006) and worse OS in LGG (p=0.028). CONCLUSIONS: sPD-L1 is detectable in a fraction of patients with brain tumour. Although it is not correlated with tissue PD-L1 expression, correlations with other local and systemic inflammation parameters could be detected in LGG and GBM."
4248,Of gratitude and hope in trying times,
4249,Requirement of a prompt solution to address infection and mortality due to COVID-19 among Peruvian physicians,
4250,The Stages of CS: Clinical and Translational Update,"PURPOSE OF REVIEW: With improvements in cardiovascular care, and routine percutaneous coronary intervention for ST elevation myocardial infarction, more patients are surviving following acute coronary syndromes. However, a minority of patients develop cardiogenic shock which results in approximately 50% 30-day mortality. There are various ways to classify cardiogenic shock, and much has been written about this topic in recent years. This review will examine recent developments and put them in context. RECENT FINDINGS: The large randomized trials of cardiogenic shock treatments such as the IABP-SHOCK II trial used a clinical definition of shock including hypotension (systolic blood pressure of 90 mmHg or less, or requirement of vasopressors to maintain such a blood pressure), as well as hypoperfusion. However, while this defines a minimum standard to define cardiogenic shock, it does not distinguish between a patient on a single vasoconstrictor and one who is on multiple high dose infusions or one on extracorporeal membrane oxygenation. The Society for Cardiac Angiography and Intervention recently published an expert consensus statement defining stages of cardiogenic shock, from at risk to beginning, classic, deteriorating, and extremis cardiogenic shock stages. The simple framework has been validated rapidly in multiple populations including the intensive care unit, a post-myocardial infarction population, an out of hospital cardiac arrest population, and most recently in a multicenter shock collaborative, SUMMARY: Classification is fundamental to understanding a disease state, and crafting solutions to improve outcomes. The last 20 years has witnessed an explosion of percutaneous mechanical circulatory support devices of increasing sophistication and capability, and yet there has been little progress in improving outcomes of cardiogenic shock. Hopefully, the next 20 years will see massive advances in understanding of the complexities of the various stages of cardiogenic shock. With such knowledge, it is likely that targeted treatments will be developed and the mortality of this disease will finally plummet."
4251,Continuing professional development module: An updated introduction to electroencephalogram-based brain monitoring during intended general anesthesia,"The electroencephalogram (EEG) provides a reliable reflection of the brain’s electrical state, so it can reassure us that the anesthetic agents are actually reaching the patient’s brain, and are having the desired effect. In most patients, the EEG changes somewhat predictably in response to propofol and volatile agents, so a frontal EEG channel can guide avoidance of insufficient and excessive administration of general anesthesia. Persistent alpha-spindles (around 10 Hz) phase-amplitude coupled with slow delta waves (around 1 Hz) are commonly seen during an “appropriate hypnotic state of general anesthesia”. Such patterns can be appreciated from the EEG waveform or from the spectrogram (a colour-coded display of how the power in the various EEG frequencies changes with time). Nevertheless, there are exceptions to this. For example, administration of ketamine and nitrous oxide is generally not associated with the aforementioned alpha-spindle coupled with delta wave pattern. Also, some patients, including older adults and those with neurodegenerative disorders, are less predisposed to generate a strong electroencephalographic “alpha-spindle” pattern during general anesthesia. There might also be some rare instances when the frontal EEG shows a pattern suggestive of general anesthesia, while the patient has some awareness and is able to follow simple commands, albeit this is typically without obvious distress or memory formation. Thus, the frontal EEG alone, as currently analyzed, is an imperfect but clinically useful mirror, and more scientific insights will be needed before we can claim to have a reliable readout of brain “function” during general anesthesia."
4252,Digitoxigenin presents an effective and selective antileishmanial action against Leishmania infantum and is a potential therapeutic agent for visceral leishmaniasis,"Treatment for visceral leishmaniasis (VL) is hampered mainly by drug toxicity, their high cost, and parasite resistance. Drug development is a long and pricey process, and therefore, drug repositioning may be an alternative worth pursuing. Cardenolides are used to treat cardiac diseases, especially those obtained from Digitalis species. In the present study, cardenolide digitoxigenin (DIGI) obtained from a methanolic extract of Digitalis lanata leaves was tested for its antileishmanial activity against Leishmania infantum species. Results showed that 50% Leishmania and murine macrophage inhibitory concentrations (IC(50) and CC(50), respectively) were of 6.9 ± 1.5 and 295.3 ± 14.5 μg/mL, respectively. With amphotericin B (AmpB) deoxycholate, used as a control drug, values of 0.13 ± 0.02 and 0.79 ± 0.12 μg/mL, respectively, were observed. Selectivity index (SI) values were of 42.8 and 6.1 for DIGI and AmpB, respectively. Preliminary studies suggested that the mechanism of action for DIGI is to cause alterations in the mitochondrial membrane potential, to increase the levels of reactive oxygen species and induce accumulation of lipid bodies in the parasites. DIGI was incorporated into Pluronic® F127-based polymeric micelles, and the formula (DIGI/Mic) was used to treat L. infantum–infected mice. Miltefosine was used as a control drug. Results showed that animals treated with either miltefosine, DIGI, or DIGI/Mic presented significant reductions in the parasite load in their spleens, livers, bone marrows, and draining lymph nodes, as well as the development of a specific Th1-type response, when compared with the controls. Results obtained 1 day after treatment were corroborated with data corresponding to 15 days after therapy. Importantly, treatment with DIGI/Mic induced better parasitological and immunological responses when compared with miltefosine- and DIGI-treated mice. In conclusion, DIGI/Mic has the potential to be used as a therapeutic agent to protect against L. infantum infection, and it is therefore worth of consideration in future studies addressing VL treatment."
4253,A Targeted Computational Screen of the SWEETLEAD Database Reveals FDA-Approved Compounds with Anti-Dengue Viral Activity,"Affordable and effective antiviral therapies are needed worldwide, especially against agents such as dengue virus that are endemic in underserved regions. Many antiviral compounds have been studied in cultured cells but are unsuitable for clinical applications due to pharmacokinetic profiles, side effects, or inconsistent efficacy across dengue serotypes. Such tool compounds can, however, aid in identifying clinically useful treatments. Here, computational screening (Rapid Overlay of Chemical Structures) was used to identify entries in an in silico database of safe-in-human compounds (SWEETLEAD) that display high chemical similarities to known inhibitors of dengue virus. Inhibitors of the dengue proteinase NS2B/3, the dengue capsid, and the host autophagy pathway were used as query compounds. Three FDA-approved compounds that resemble the tool molecules structurally, cause little toxicity, and display strong antiviral activity in cultured cells were selected for further analysis. Pyrimethamine (50% inhibitory concentration [IC(50)] = 1.2 μM), like the dengue proteinase inhibitor ARDP0006 to which it shows structural similarity, inhibited intramolecular NS2B/3 cleavage. Lack of toxicity early in infection allowed testing in mice, in which pyrimethamine also reduced viral loads. Niclosamide (IC(50) = 0.28 μM), like dengue core inhibitor ST-148, affected structural components of the virion and inhibited early processes during infection. Vandetanib (IC(50) = 1.6 μM), like cellular autophagy inhibitor spautin-1, blocked viral exit from cells and could be shown to extend survival in vivo. Thus, three FDA-approved compounds with promising utility for repurposing to treat dengue virus infections and their potential mechanisms were identified using computational tools and minimal phenotypic screening."
4254,Reply to Yaroshetskiy et al.: Acute Respiratory Distress Syndrome in COVID-19: Do All These Patients Definitely Require Intubation and Mechanical Ventilation?,
4255,Bedside Evaluation of Pulmonary Embolism by Saline Contrast Electrical Impedance Tomography Method: A Prospective Observational Study,
4256,A Step Forward toward a Bedside and Timely Monitoring of Regional [Formula: see text] / [Formula: see text] Matching,
4257,Reducing Moral Distress in the Setting of a Public Health Crisis,
4258,Tuning Proton Transfer Thermodynamics in SARS-Cov-2 Main Protease: Implications for Catalysis and Inhibitor Design,"In this comutational work a hybrid quantum mechanics/molecular mechanics approach, the MD-PMM approach, is used to investigate the proton transfer reaction the activates the catalytic activity of SARS-CoV-2 main protease. The proton transfer thermodynamics is investigated for the apo ensyme (i.e., without any bound substrate or inhibitor) and in the presence of a inhibitor, N3, which was previously shown to covalently bind SARS-CoV-2 main protease."
4259,A Multi-Pronged Approach Targeting SARS-CoV-2 Proteins Using Ultra-Large Virtual Screening,"Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), previously known as 2019 novel coronavirus (2019-nCoV), has spread rapidly across the globe, creating an unparalleled global health burden and spurring a deepening economic crisis. As of July 7th, 2020, almost seven months into the outbreak, there are no approved vaccines and few treatments available. Developing drugs that target multiple points in the viral life cycle could serve as a strategy to tackle the current as well as future coronavirus pandemics. Here we leverage the power of our recently developed in silico screening platform, VirtualFlow, to identify inhibitors that target SARS-CoV-2. VirtualFlow is able to efficiently harness the power of computing clusters and cloud-based computing platforms to carry out ultra-large scale virtual screens. In this unprecedented structure-based multi-target virtual screening campaign, we have used VirtualFlow to screen an average of approximately 1 billion molecules against each of 40 different target sites on 17 different potential viral and host targets in the cloud. In addition to targeting the active sites of viral enzymes, we also target critical auxiliary sites such as functionally important protein-protein interaction interfaces. This multi-target approach not only increases the likelihood of finding a potent inhibitor, but could also help identify a collection of anti-coronavirus drugs that would retain efficacy in the face of viral mutation. Drugs belonging to different regimen classes could be combined to develop possible combination therapies, and top hits that bind at highly conserved sites would be potential candidates for further development as coronavirus drugs. Here, we present the top 200 in silico hits for each target site. While in-house experimental validation of some of these compounds is currently underway, we want to make this array of potential inhibitor candidates available to researchers worldwide in consideration of the pressing need for fast-tracked drug development."
4260,Supercomputer-Based Ensemble Docking Drug Discovery Pipeline with Application to Covid-19,"We present a supercomputer-driven pipeline for in-silico drug discovery using enhanced sampling molecular dynamics (MD) and ensemble docking. We also describe preliminary results obtained for 23 systems involving eight protein targets of the proteome of SARS CoV-2. THe MD performed is temperature replica-exchange enhanced sampling, making use of the massively parallel supercomputing on the SUMMIT supercomputer at Oak Ridge National Laboratory, with which more than 1ms of enhanced sampling MD can be generated per day. We have ensemble docked repurposing databases to ten configurations of each of the 23 SARS CoV-2 systems using AutoDock Vina. We also demonstrate that using Autodock-GPU on SUMMIT, it is possible to perform exhaustive docking of one billion compounds in under 24 hours. Finally, we discuss preliminary results and planned improvements to the pipeline, including the use of quantum mechanical (QM), machine learning, and AI methods to cluster MD trajectories and rescore docking poses."
4261,Copper(II) Inhibition of the SARS-CoV-2 Main Protease,"In an analysis of the structural stability of the coronavirus main protease (Mpro), we identified regions of the protein that could be disabled by cobalt(III)-cation binding to histidines and cysteines [1]. Here we have extended our work to include copper(II) chelates, which we have docked to HIS 41 and CYS 145 in the Mpro active-site region. We have found stable docked structures where Cu(II) could readily bond to the CYS 145 thiolate, which would be lethal to the enzyme. We also started studying the Spike Protein, PDB ID: 6VXX and the region around the D614G mutant."
4262,REDIAL-2020: A Suite of Machine Learning Models to Estimate Anti-SARS-CoV-2 Activities,"Strategies for drug discovery and repositioning are an urgent need with respect to COVID-19. We developed ""REDIAL-2020"", a suite of machine learning models for estimating small molecule activity from molecular structure, for a range of SARS-CoV-2 related assays. Each classifier is based on three distinct types of descriptors (fingerprint, physicochemical, and pharmacophore) for parallel model development. These models were trained using high throughput screening data from the NCATS COVID19 portal (https://opendata.ncats.nih.gov/covid19/index.html), with multiple categorical machine learning algorithms. The “best models” are combined in an ensemble consensus predictor that outperforms single models where external validation is available. This suite of machine learning models is available through the DrugCentral web portal (http://drugcentral.org/Redial). Acceptable input formats are: drug name, PubChem CID, or SMILES; the output is an estimate of anti-SARS-CoV-2 activities. The web application reports estimated activity across three areas (viral entry, viral replication, and live virus infectivity) spanning six independent models, followed by a similarity search that displays the most similar molecules to the query among experimentally determined data. The ML models have 60% to 74% external predictivity, based on three separate datasets. Complementing the NCATS COVID19 portal, REDIAL-2020 can serve as a rapid online tool for identifying active molecules for COVID-19 treatment. The source code and specific models are available through Github (https://github.com/sirimullalab/redial-2020), or via Docker Hub (https://hub.docker.com/r/sirimullalab/redial-2020) for users preferring a containerized version."
4263,Periarteriolar stroma cells guide T cells from the red to the white pulp in the spleen,"While both the spleen and lymph nodes are called secondary lymphoid tissues, how lymphocytes enter these tissues are quite different from each other. This is because the architecture of the two types of organs and the mode of lymphocyte migration into these organs are quite distinct. In the spleen, T cells are passively released in the blood flow from the arterioles in the red pulp and marginal zone area. In contrast, T cells in the blood are actively captured on high endothelial venules in lymph nodes by the coordinated actions of CCR7 and several adhesion molecules. A recent finding indicates that T cells, released in the red pulp and marginal zone areas, actively find their way to the white zone by utilizing the migration track created by periarteriolar stromal cells. This finding adds one more piece to our understanding of lymphocyte migration for effective adaptive immune responses in the spleen."
4264,The other side of the innate immune system: humoral arms favoring cancer,Cancer cells take advantage of NETosis to escape host immune surveillance and mediate metastasis. The pharmacological targeting of NETosis may prove beneficial in maximizing the response to cancer immunotherapy.
4265,Progranulin deficiency confers resistance to autoimmune encephalomyelitis in mice,"Progranulin is a secreted neurotrophin that assists in the autophagolysosomal pathways that contribute to MHC-mediated antigen processing, pathogen removal, and autoimmunity. We showed that patients with multiple sclerosis (MS) have high levels of circulating progranulin and that its depletion in a mouse model by a monoclonal antibody aggravates MS-like experimental autoimmune encephalomyelitis (EAE). However, unexpectedly, progranulin-deficient mice (Grn(−/−)) were resistant to EAE, and this resistance was fully restored by wild-type bone marrow transplantation. FACS analyses revealed a loss of MHC-II-positive antigen-presenting cells in Grn(−/−) mice and a reduction in the number of CD8+ and CD4+ T-cells along with a strong increase in the number of scavenger receptor class B (CD36+) phagocytes, suggesting defects in antigen presentation along with a compensatory increase in phagocytosis. Indeed, bone marrow-derived dendritic cells from Grn(−/−) mice showed stronger uptake of antigens but failed to elicit antigen-specific T-cell proliferation. An increase in the number of CD36+ phagocytes was associated with increased local inflammation at the site of immunization, stronger stimulation-evoked morphological transformation of bone marrow-derived macrophages to phagocytes, an increase in the phagocytosis of E. coli particles and latex beads and defects in the clearance of the material. Hence, the outcomes in the EAE model reflect the dichotomy of progranulin-mediated immune silencing and autoimmune mechanisms of antigen recognition and presentation, and our results reveal a novel progranulin-dependent pathway in autoimmune encephalomyelitis."
4266,Geostatistical analysis and mapping of malaria risk in children of Mozambique,"Malaria remains one of the most prevalent infectious diseases in the tropics and subtropics, and Mozambique is not an exception. To design geographically targeted and effective intervention mechanisms of malaria, an up-to-date map that shows the spatial distribution of malaria is needed. This study analyzed 2018 Mozambique Malaria Indicator Survey using geostatistical methods to: i) explore individual, household, and community-level determinants of malaria in under-five children, ii) prepare a malaria prevalence map in Mozambique, and iii) produce prediction prevalence maps and exceedence probability across the country. The results show the overall weighted prevalence of malaria was 38.9% (N = 4347, with 95% CI: 36.9%–40.8%). Across different provinces of Mozambique, the prevalence of malaria ranges from 1% in Maputo city to 57.3% in Cabo Delgado province. Malaria prevalence was found to be higher in rural areas, increased with child’s age, and decreased with household wealth index and mother’s level of education. Given the high prevalence of childhood malaria observed in Mozambique there is an urgent need for effective public health interventions in malaria hot spot areas. The household determinants of malaria infection that are identified in this study as well as the maps of parasitaemia risk could be used by malaria control program implementers to define priority intervention areas."
4267,Violence prevention accelerators for children and adolescents in South Africa: A path analysis using two pooled cohorts,"BACKGROUND: The INSPIRE framework was developed by 10 global agencies as the first global package for preventing and responding to violence against children. The framework includes seven complementary strategies. Delivering all seven strategies is a challenge in resource-limited contexts. Consequently, governments are requesting additional evidence to inform which ‘accelerator’ provisions can simultaneously reduce multiple types of violence against children. METHODS AND FINDINGS: We pooled data from two prospective South African adolescent cohorts including Young Carers (2010–2012) and Mzantsi Wakho (2014–2017). The combined sample size was 5,034 adolescents. Each cohort measured six self-reported violence outcomes (sexual abuse, transactional sexual exploitation, physical abuse, emotional abuse, community violence victimisation, and youth lawbreaking) and seven self-reported INSPIRE-aligned protective factors (positive parenting, parental monitoring and supervision, food security at home, basic economic security at home, free schooling, free school meals, and abuse response services). Associations between hypothesised protective factors and violence outcomes were estimated jointly in a sex-stratified multivariate path model, controlling for baseline outcomes and socio-demographics and correcting for multiple-hypothesis testing using the Benjamini-Hochberg procedure. We calculated adjusted probability estimates conditional on the presence of no, one, or all protective factors significantly associated with reduced odds of at least three forms of violence in the path model. Adjusted risk differences (ARDs) and adjusted risk ratios (ARRs) with 95% confidence intervals (CIs) were also calculated. The sample mean age was 13.54 years, and 56.62% were female. There was 4% loss to follow-up. Positive parenting, parental monitoring and supervision, and food security at home were each associated with lower odds of three or more violence outcomes (p < 0.05). For girls, the adjusted probability of violence outcomes was estimated to be lower if all three of these factors were present, as compared to none of them: sexual abuse, 5.38% and 1.64% (ARD: −3.74% points, 95% CI −5.31 to −2.16, p < 0.001); transactional sexual exploitation, 10.07% and 4.84% (ARD: −5.23% points, 95% CI −7.26 to −3.20, p < 0.001); physical abuse, 38.58% and 23.85% (ARD: −14.72% points, 95% CI −19.11 to −10.33, p < 0.001); emotional abuse, 25.39% and 12.98% (ARD: −12.41% points, 95% CI −16.00 to −8.83, p < 0.001); community violence victimisation, 36.25% and 28.37% (ARD: −7.87% points, 95% CI −11.98 to −3.76, p < 0.001); and youth lawbreaking, 18.90% and 11.61% (ARD: −7.30% points, 95% CI −10.50 to −4.09, p < 0.001). For boys, the adjusted probability of violence outcomes was also estimated to be lower if all three factors were present, as compared to none of them: sexual abuse, 2.39% to 1.80% (ARD: −0.59% points, 95% CI −2.24 to 1.05, p = 0.482); transactional sexual exploitation, 6.97% to 4.55% (ARD: −2.42% points, 95% CI −4.77 to −0.08, p = 0.043); physical abuse from 37.19% to 25.44% (ARD: −11.74% points, 95% CI −16.91 to −6.58, p < 0.001); emotional abuse from 23.72% to 10.72% (ARD: −13.00% points, 95% CI −17.04 to −8.95, p < 0.001); community violence victimisation from 41.28% to 35.41% (ARD: −5.87% points, 95% CI −10.98 to −0.75, p = 0.025); and youth lawbreaking from 22.44% to 14.98% (ARD −7.46% points, 95% CI −11.57 to −3.35, p < 0.001). Key limitations were risk of residual confounding and not having information on protective factors related to all seven INSPIRE strategies. CONCLUSION: In this cohort study, we found that positive and supervisory caregiving and food security at home are associated with reduced risk of multiple forms of violence against children. The presence of all three of these factors may be linked to greater risk reduction as compared to the presence of one or none of these factors. Policies promoting action on positive and supervisory caregiving and food security at home are likely to support further efficiencies in the delivery of INSPIRE."
4268,The acceptance of zinc biofortified rice in Latin America: A consumer sensory study and grain quality characterization,"Zinc deficiency is a major public health problem in vulnerable populations of Latin America and the Caribbean. Biofortification of rice (Oryza sativa L.) with zinc has the potential to alleviate zinc deficiencies. However, as plant breeding processes can alter grain culinary quality and favorable sensory attributes, grain quality and consumer acceptability need to be assessed prior to releasing a variety to the public. A grain quality characterization and a sensory acceptability analysis were carried out with two varieties of zinc biofortified rice and a local control both in Bolivia and Colombia. The aim of this study was to evaluate the physicochemical parameters that are significant in consumer acceptance and to determine the acceptability of zinc biofortified rice by consumers. Results of physicochemical parameters were analyzed using ANOVA. The sensory acceptability was evaluated in 243 adults utilizing a 7-point hedonic scale and a Wilcoxon’s signed rank test was used to determine the overall acceptability of the varieties. Biofortified rice variety T2-11 and MAC-18 -control 1- were equally accepted by consumers in Bolivia with no significant differences (p<0.05). The grain quality analysis reported that both presented long and slender rice grains (L>7.5 mm and L/B>3), an intermediate to high amylose content (>25%) and a similar level of chalkiness. In Colombia, the biofortified variety 035 presented a higher score in overall acceptance in comparison to biofortified variety 021 and the local variety CICA4 -control 2-. However, no significant differences were observed (p<0.05). Conversely to the other two varieties, the biofortified variety 035 presented the largest size grain (L/B = 2.97), a lower chalkiness and an amylose content above 25%. This study shows that the grain quality properties of rice have an influence on acceptability and that zinc biofortified rice varieties are accepted by consumers."
4269,RNA structure prediction using positive and negative evolutionary information,"Knowing the structure of conserved structural RNAs is important to elucidate their function and mechanism of action. However, predicting a conserved RNA structure remains unreliable, even when using a combination of thermodynamic stability and evolutionary covariation information. Here we present a method to predict a conserved RNA structure that combines the following three features. First, it uses significant covariation due to RNA structure and removes spurious covariation due to phylogeny. Second, it uses negative evolutionary information: basepairs that have variation but no significant covariation are prevented from occurring. Lastly, it uses a battery of probabilistic folding algorithms that incorporate all positive covariation into one structure. The method, named CaCoFold (Cascade variation/covariation Constrained Folding algorithm), predicts a nested structure guided by a maximal subset of positive basepairs, and recursively incorporates all remaining positive basepairs into alternative helices. The alternative helices can be compatible with the nested structure such as pseudoknots, or overlapping such as competing structures, base triplets, or other 3D non-antiparallel interactions. We present evidence that CaCoFold predictions are consistent with structures modeled from crystallography."
4270,Sample pooling methods for efficient pathogen screening: Practical implications,"Due to the large number of negative tests, individually screening large populations for rare pathogens can be wasteful and expensive. Sample pooling methods improve the efficiency of large-scale pathogen screening campaigns by reducing the number of tests and reagents required to accurately categorize positive and negative individuals. Such methods rely on group testing theory which mainly focuses on minimizing the total number of tests; however, many other practical concerns and tradeoffs must be considered when choosing an appropriate method for a given set of circumstances. Here we use computational simulations to determine how several theoretical approaches compare in terms of (a) the number of tests, to minimize costs and save reagents, (b) the number of sequential steps, to reduce the time it takes to complete the assay, (c) the number of samples per pool, to avoid the limits of detection, (d) simplicity, to reduce the risk of human error, and (e) robustness, to poor estimates of the number of positive samples. We found that established methods often perform very well in one area but very poorly in others. Therefore, we introduce and validate a new method which performs fairly well across each of the above criteria making it a good general use approach."
4271,A mathematical model and inference method for bacterial colonization in hospital units applied to active surveillance data for carbapenem-resistant enterobacteriaceae,"Widespread use of antibiotics has resulted in an increase in antimicrobial-resistant microorganisms. Although not all bacterial contact results in infection, patients can become asymptomatically colonized, increasing the risk of infection and pathogen transmission. Consequently, many institutions have begun active surveillance, but in non-research settings, the resulting data are often incomplete and may include non-random testing, making conventional epidemiological analysis problematic. We describe a mathematical model and inference method for in-hospital bacterial colonization and transmission of carbapenem-resistant Enterobacteriaceae that is tailored for analysis of active surveillance data with incomplete observations. The model and inference method make use of the full detailed state of the hospital unit, which takes into account the colonization status of each individual in the unit and not only the number of colonized patients at any given time. The inference method computes the exact likelihood of all possible histories consistent with partial observations (despite the exponential increase in possible states that can make likelihood calculation intractable for large hospital units), includes techniques to improve computational efficiency, is tested by computer simulation, and is applied to active surveillance data from a 13-bed rehabilitation unit in New York City. The inference method for exact likelihood calculation is applicable to other Markov models incorporating incomplete observations. The parameters that we identify are the patient–patient transmission rate, pre-existing colonization probability, and prior-to-new-patient transmission probability. Besides identifying the parameters, we predict the effects on the total prevalence (0.07 of the total colonized patient-days) of changing the parameters and estimate the increase in total prevalence attributable to patient–patient transmission (0.02) above the baseline pre-existing colonization (0.05). Simulations with a colonized versus uncolonized long-stay patient had 44% higher total prevalence, suggesting that the long-stay patient may have been a reservoir of transmission. High-priority interventions may include isolation of incoming colonized patients and repeated screening of long-stay patients."
4272,Photovoltaic modules evaluation and dry-season energy yield prediction model for NEM in Malaysia,"This study analyzes the performance of two PV modules, amorphous silicon (a-Si) and crystalline silicon (c-Si) and predicts energy yield, which can be seen as facilitation to achieve the target of 35% reduction of greenhouse gases emission by 2030. Malaysia Energy Commission recommends crystalline PV modules for net energy metering (NEM), but the climate regime is a concern for output power and efficiency. Based on rainfall and irradiance data, this study aims to categorize the climate of peninsular Malaysia into rainy and dry seasons; and then the performance of the two modules are evaluated under the dry season. A new mathematical model is developed to predict energy yield and the results are validated through experimental and systematic error analysis. The parameters are collected using a self-developed ZigBeePRO-based wireless system with the rate of 3 samples/min over a period of five days. The results unveil that efficiency is inversely proportional to the irradiance due to negative temperature coefficient for crystalline modules. For this phenomenon, efficiency of c-Si (9.8%) is found always higher than a-Si (3.5%). However, a-Si shows better shadow tolerance compared to c-Si, observed from a lesser decrease rate in efficiency of the former with the increase in irradiance. Due to better spectrum response and temperature coefficient, a-Si shows greater performance on output power efficiency (OPE), performance ratio (PR), and yield factor. From the regression analysis, it is found that the coefficient of determination (R(2)) is between 0.7179 and 0.9611. The energy from the proposed model indicates that a-Si yields 15.07% higher kWh than c-Si when luminance for recorded days is 70% medium and 30% high. This study is important to determine the highest percentage of energy yield and to get faster NEM payback period, where as of now, there is no such model to indicate seasonal energy yield in Malaysia."
4273,"Erratum: Vol. 69, No. 43",
4274,"Progress Toward Regional Measles Elimination — Worldwide, 2000–2019",
4275,"Erratum: Vol. 69, No. 43",
4276,Note from the editors: Eurosurveillance contributor survey results,
4277,Anesthesiology airway-related medicolegal cases from the Canadian Medical Protection Association,"PURPOSE: We analyzed closed civil legal cases in 2007-2016 from the Canadian Medical Protective Association (CMPA) involving specialist anesthesiologists where airway management was the central concern. METHODS: We included all airway-related civil legal cases involving specialist anesthesiologists that closed from 2007 to 2016. The following variables were abstracted by CMPA medical analysts: clinical context, peer expert opinions of contributing factors, and patient and legal outcomes. RESULTS: We found 46 of the 406 (11%) closed cases involving anesthesiologists to be airway-related. Twenty-six cases (57%) involved elective surgery and 31 patients (67%) were categorized as American Society of Anesthesiologists physical status III. Twenty-five cases (54%) occurred outside the operating room (e.g., postanesthesia care unit, intensive care unit, or other satellite locations). In 19 (42%) cases, there was at least one predictor of a difficult airway. Peer experts identified judgement failures in 30 cases (65%), most commonly inadequate airway evaluation. In 30 cases (65%), the patient died or had a permanent brain injury. The medicolegal outcome favoured the patient in 27 (59%) cases, with a median [interquartile range] payment of 422,845 [257,637-935,673] CAD. CONCLUSIONS: Severe patient harm is common when airway management is the focus of a CMPA medicolegal complaint involving anesthesiologists. Patients were otherwise typically low risk cases presenting for elective surgery. Failure to assess or to change management based on the airway exam or encountered difficulty were the most common errors. Our findings support the continued need for adoption, adherence, and practice of guidelines for anticipated and unanticipated difficult airway management for every patient encounter."
4278,Point-of-care diagnostic tests for influenza in the emergency department: A cost-effectiveness analysis in a high-risk population from a Canadian perspective,"BACKGROUND: Our objective was to assess the cost-effectiveness of novel rapid diagnostic tests: rapid influenza diagnostic tests (RIDT), digital immunoassays (DIA), rapid nucleic acid amplification tests (NAAT), and other treatment algorithms for influenza in high-risk patients presenting to hospital with influenza-like illness (ILI). METHODS: We developed a decision-analytic model to assess the cost-effectiveness of diagnostic test strategies (RIDT, DIA, NAAT, clinical judgement, batch polymerase chain reaction) preceding treatment; no diagnostic testing and treating everyone; and not treating anyone. We modeled high-risk 65-year old patients from a health payer perspective and accrued outcomes over a patient’s lifetime. We reported health outcomes, quality-adjusted life years (QALYs), healthcare costs, and net health benefit (NHB) to measure cost-effectiveness per cohort of 100,000 patients. RESULTS: Treating everyone with no prior testing was the most cost-effective strategy, at a cost-effectiveness threshold of $50,000/QALY, in over 85% of simulations. This strategy yielded the highest NHB of 15.0344 QALYs, but inappropriately treats all patients without influenza. Of the novel rapid diagnostics, NAAT resulted in the highest NHB (15.0277 QALYs), and the least number of deaths (1,571 per 100,000). Sensitivity analyses determined that results were most impacted by the pretest probability of ILI being influenza, diagnostic test sensitivity, and treatment effectiveness. CONCLUSIONS: Based on our model, treating high-risk patients presenting to hospital with influenza-like illness, without performing a novel rapid diagnostic test, resulted in the highest NHB and was most cost-effective. However, consideration of whether treatment is appropriate in the absence of diagnostic confirmation should be taken into account for decision-making by clinicians and policymakers."
4279,"Right Here, Right Now, on Purpose",
4280,Cytotoxic T cells swarm by homotypic chemokine signalling,"Cytotoxic T lymphocytes (CTLs) are thought to arrive at target sites either via random search or following signals by other leukocytes. Here, we reveal independent emergent behaviour in CTL populations attacking tumour masses. Primary murine CTLs coordinate their migration in a process reminiscent of the swarming observed in neutrophils. CTLs engaging cognate targets accelerate the recruitment of distant T cells through long-range homotypic signalling, in part mediated via the diffusion of chemokines CCL3 and CCL4. Newly arriving CTLs augment the chemotactic signal, further accelerating mass recruitment in a positive feedback loop. Activated effector human T cells and chimeric antigen receptor (CAR) T cells similarly employ intra-population signalling to drive rapid convergence. Thus, CTLs recognising a cognate target can induce a localised mass response by amplifying the direct recruitment of additional T cells independently of other leukocytes."
4281,Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis,"Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, is a progressive, irreversible, and typically lethal disease characterized by an abnormal fibrotic response involving vast areas of the lungs. Given the poor knowledge of the mechanisms underpinning IPF onset and progression, a better understanding of the cellular processes and molecular pathways involved is essential for the development of effective therapies, currently lacking. Besides a number of established IPF-associated risk factors, such as cigarette smoking, environmental factors, comorbidities, and viral infections, several other processes have been linked with this devastating disease. Apoptosis, senescence, epithelial-mesenchymal transition, endothelial-mesenchymal transition, and epithelial cell migration have been shown to play a key role in IPF-associated tissue remodeling. Moreover, molecules, such as chemokines, cytokines, growth factors, adenosine, glycosaminoglycans, non-coding RNAs, and cellular processes including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, hypoxia, and alternative polyadenylation have been linked with IPF development. Importantly, strategies targeting these processes have been investigated to modulate abnormal cellular phenotypes and maintain tissue homeostasis in the lung. This review provides an update regarding the emerging cellular and molecular mechanisms involved in the onset and progression of IPF."
4282,Mitteilungen der Deutschen Gesellschaft für Pathologie,
4283,Application of antigenic biomarkers for Mycobacterium tuberculosis,"The study and characterization of biomolecules involved in the interaction between mycobacteria and their hosts are crucial to determine their roles in the invasion process and provide basic knowledge about the biology and pathogenesis of disease. Promising new biomarkers for diagnosis and immunotherapy have emerged recently. My-cobacterium is an ancient pathogen that has developed complex strategies for its persistence in the host and environment, likely based on the complexity of the network of interactions between the molecules involved in infection. Several biomarkers have received recent attention in the process of developing rapid and reliable detection techniques for tuberculosis. Among the most widely investigated antigens are CFP-10 (10-kDa culture filtrate protein), ESAT-6 (6-kDa early secretory antigenic target), Ag85A, Ag85B, CFP-7, and PPE18. Some of these antigens have been proposed as biomarkers to assess the key elements of the response to infection of both the pathogen and host. The design of novel and accurate diagnostic methods is essential for the control of tuberculosis worldwide. Presently, the diagnostic methods are based on the identification of molecules in the humoral response in infected individuals. Therefore, these tests depend on the capacity of the host to develop an immune response, which usually is heterogeneous. In the last 20 years, special attention has been given to the design of multiantigenic diagnostic methods to improve the levels of sensitivity and specificity. In this review, we summarize the state of the art in the study and use of mycobacterium biomolecules with the potential to support novel tuberculosis control strategies."
4284,Update Thoraxpathologie 2020: Bericht der Arbeitsgemeinschaft,
4285,The impact of per diem senior pediatric radiologists in an academic setting,
4286,The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline,"PURPOSE: High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings. METHODS: We formed a guideline panel composed of clinicians, methodologists and experts in respiratory medicine. Using GRADE, the panel developed recommendations for four actionable questions. RESULTS: The guideline panel made a strong recommendation for HFNC in hypoxemic respiratory failure compared to conventional oxygen therapy (COT) (moderate certainty), a conditional recommendation for HFNC following extubation (moderate certainty), no recommendation regarding HFNC in the peri-intubation period (moderate certainty), and a conditional recommendation for postoperative HFNC in high risk and/or obese patients following cardiac or thoracic surgery (moderate certainty). CONCLUSIONS: This clinical practice guideline synthesizes current best-evidence into four recommendations for HFNC use in patients with hypoxemic respiratory failure, following extubation, in the peri-intubation period, and postoperatively for bedside clinicians. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06312-y) contains supplementary material, which is available to authorized users."
4287,"Association between pet ownership and physical activity levels, atopic conditions, and mental health in Singapore: a propensity score-matched analysis","Although existing literature increasingly suggests a positive influence of pet ownership on human physical activity levels, results from many European, American, and Japanese studies have been inconsistent. How pet ownership impacts mental health and atopy is likewise controversial and whether distinct demographic subgroups experience differential effects is unclear. This cross-sectional study surveyed participants (n = 823) via a self-administered online questionnaire. Comparisons of outcomes between pet owners and non-pet owners with subgroup analyses were performed within a propensity score-matched subset (n = 566) of respondents. There were no differences in physical activity levels or mental health scores between pet owners and non-pet owners. In subgroup analyses, compared to non-pet owners, main pet caregivers reported 14.1 (95% CI 2.79–25.3) and 19.0 (95% CI 4.70–33.3) more minutes per week of moderate- and vigorous-intensity physical activity respectively and higher SF-36 emotional well-being (β = 2.7, 95% CI 0.100–5.32) and energy scores (β = 3.8, 95% CI 0.410–7.27). Age was a significant effect modifier of the association between pet ownership and emotional well-being, energy and social functioning scores, with greater scores above the ages of 39, 35 and 39 years old respectively (interaction p = 0.043, 0.044, 0.042). Finally, pet acquisition was associated with worsening of allergic rhinitis, while pet ownership cessation was associated with improvement of allergic rhinitis and eczema symptoms. To our knowledge, this is the first study addressing the public health impact of pet ownership in Southeast Asia and its findings add contextual nuance to suggest potential benefits derived from pet ownership."
4288,Wechselwirkungen von radikaler Prostatovesikulektomie und Diagnostik des Prostatakarzinoms: Eine medizinhistorische Bestandsaufnahme anlässlich 20 Jahre robotisch assistierter Therapie,"The question of what came first—in this case the diagnosis of prostate cancer or its therapy—seems absurd at first glance and is reminiscent of the classic metaphor-like problem that preoccupied the Greek writer Plutarch (45–125). Today it is a matter of course that a reliable diagnosis is made before treating a disease, but this must be viewed as inconsistent in medical history. The beginnings of radical prostatectomy for the treatment of prostate cancer, like the first surgical therapies for kidney and bladder tumors, can be located in the pioneering period of organ surgery in the German Empire (1871–1918). The establishment of this procedure in its current form with larger numbers of cases is in turn thanks to the Nestor of American urology, Hugh Hampton Young, who carried out the first perineal prostatovesiculectomy, which from today’s perspective can be described as complete. Although the indication has remained largely unchanged since then, this intervention has undergone extensive changes in recent decades. But how has the diagnosis of prostate cancer developed in this period? Of course, much more dynamic. While the procedure prostatovesiculectomy was already established, development of prostate cancer diagnosis began first slowly in the course of the 20th century, then more dynamically. The following article uses medical (historical) original sources to present not only the basics and further developments of the established and, at the same time, subject to constant intervention in urology, but also the essential developments in the environment of neighboring medical disciplines, for example, think of laboratory medicine, radiology, nuclear medicine or rehabilitation medicine, but especially pathology. Incidentally, it was only these developments that created the basis for the correct setting of indications and the identification of alternatives to radical prostatovesiculectomy."
4289,"Evaluation of an unconditional cash transfer program targeting children’s first-1,000–days linear growth in rural Togo: A cluster-randomized controlled trial","BACKGROUND: In 2014, the government of Togo implemented a pilot unconditional cash transfer (UCT) program in rural villages that aimed at improving children’s nutrition, health, and protection. It combined monthly UCTs (approximately US$8.40 /month) with a package of community activities (including behavior change communication [BCC] sessions, home visits, and integrated community case management of childhood illnesses and acute malnutrition [ICCM-Nut]) delivered to mother–child pairs during the first “1,000 days” of life. We primarily investigated program impact at population level on children’s height-for-age z-scores (HAZs) and secondarily on stunting (HAZ < −2) and intermediary outcomes including household’s food insecurity, mother–child pairs’ diet and health, delivery in a health facility and low birth weight (LBW), women’s knowledge, and physical intimate partner violence (IPV). METHODS AND FINDINGS: We implemented a parallel-cluster–randomized controlled trial, in which 162 villages were randomized into either an intervention arm (UCTs + package of community activities, n = 82) or a control arm (package of community activities only, n = 80). Two different representative samples of children aged 6–29 months and their mothers were surveyed in each arm, one before the intervention in 2014 (control: n = 1,301, intervention: n = 1,357), the other 2 years afterwards in 2016 (control: n = 996, intervention: n = 1,035). Difference-in-differences (DD) estimates of impact were calculated, adjusting for clustering. Children’s average age was 17.4 (± 0.24 SE) months in the control arm and 17.6 (± 0.19 SE) months in the intervention arm at baseline. UCTs had a protective effect on HAZ (DD = +0.25 z-scores, 95% confidence interval [CI]: 0.01–0.50, p = 0.039), which deteriorated in the control arm while remaining stable in the intervention arm, but had no impact on stunting (DD = −6.2 percentage points [pp], relative odds ratio [ROR]: 0.74, 95% CI: 0.51–1.06, p = 0.097). UCTs positively impacted both mothers’ and children’s (18–23 months) consumption of animal source foods (ASFs) (respectively, DD = +4.5 pp, ROR: 2.24, 95% CI: 1.09–4.61, p = 0.029 and DD = +9.1 pp, ROR: 2.65, 95% CI: 1.01–6.98, p = 0.048) and household food insecurity (DD = −10.7 pp, ROR: 0.63, 95% CI: 0.43–0.91, p = 0.016). UCTs did not impact on reported child morbidity 2 week’s prior to report (DD = −3.5 pp, ROR: 0.80, 95% CI: 0.56–1.14, p = 0.214) but reduced the financial barrier to seeking healthcare for sick children (DD = −26.4 pp, ROR: 0.23, 95% CI: 0.08–0.66, p = 0.006). Women who received cash had higher odds of delivering in a health facility (DD = +10.6 pp, ROR: 1.53, 95% CI: 1.10–2.13, p = 0.012) and lower odds of giving birth to babies with birth weights (BWs) <2,500 g (DD = −11.8, ROR: 0.29, 95% CI: 0.10–0.82, p = 0.020). Positive effects were also found on women’s knowledge (DD = +14.8, ROR: 1.86, 95% CI: 1.32–2.62, p < 0.001) and physical IPV (DD = −7.9 pp, ROR: 0.60, 95% CI: 0.36–0.99, p = 0.048). Study limitations included the short evaluation period (24 months) and the low coverage of UCTs, which might have reduced the program’s impact. CONCLUSIONS: UCTs targeting the first “1,000 days” had a protective effect on child’s linear growth in rural areas of Togo. Their simultaneous positive effects on various immediate, underlying, and basic causes of malnutrition certainly contributed to this ultimate impact. The positive impacts observed on pregnancy- and birth-related outcomes call for further attention to the conception period in nutrition-sensitive programs. TRIAL REGISTRATION: ISRCTN Registry ISRCTN83330970."
4290,"Development, Application, and Quality Control of Serology Assays Used for Diagnostic Monitoring of Laboratory Nonhuman Primates","The careful development, validation, and implementation of serodiagnostic assays can provide reliable results that make them a valuable tool in microbial quality control for nonhuman primates. This article includes identification and description of the components of assay development, including formulas for calculating the number of positive serum samples needed for assay validation and methods for calculating their diagnostic sensitivity and specificity. To ensure that assays are performing within predetermined specifications, there must be a quality control system that includes appropriate system and sample suitability controls as well as mechanisms to track assay performance over time. The section on quality assurance includes definitions of precision and accuracy in assay performance, and how to interpret these two factors using the Levey-Jennings chart, Westgard's rules, and other monitoring methods. Because all serologic assays are prone to false positive and false negative results, it is essential to interpret all diagnostic test results using both the expected prevalence of disease in the population and the population-specific assay performance characteristics that are determined during assay validation. The discussion on interpreting diagnostic test results also includes guidelines for calculating the positive and negative predictive values of an assay and for interpreting results based on the disease prevalence of the test population. A glossary provides definitions of commonly used terms."
4291,Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection,"Antibodies against viral pathogens represent promising therapeutic agents for the control of infection, and their antiviral efficacy has been shown to require the coordinated function of both the Fab and Fc domains(1). The Fc domain engages a wide spectrum of receptors on discrete cells of the immune system to trigger the clearance of viruses and subsequent killing of infected cells(1–4). Here we report that Fc engineering of anti-influenza IgG monoclonal antibodies for selective binding to the activating Fcγ receptor FcγRIIa results in enhanced ability to prevent or treat lethal viral respiratory infection in mice, with increased maturation of dendritic cells and the induction of protective CD8(+) T cell responses. These findings highlight the capacity for IgG antibodies to induce protective adaptive immunity to viral infection when they selectively activate a dendritic cell and T cell pathway, with important implications for the development of therapeutic antibodies with improved antiviral efficacy against viral respiratory pathogens."
4292,"Not yet 90-90-90: A quality improvement approach to human immunodeficiency virus viral suppression in paediatric patients in the rural Eastern Cape, South Africa","BACKGROUND: A strategy implemented by the South African Department of Health to manage the high burden of human immunodeficiency virus (HIV) has been to task-shift services to primary health care clinics. Outcomes of paediatric patients with HIV are poorer than those of adults, particularly in rural areas. Viral suppression in paediatric patients at the feeder clinics of a rural South African hospital was anecdotally far below the aim of the Joint United Nations Programme on HIV/AIDS (UNAIDS) of 90%. METHODS: A quality improvement approach was used to conduct a baseline assessment of HIV viral suppression in paediatric patients and other process measures, implement a clinical mentorship intervention and evaluate its effectiveness. RESULTS: An initial audit of 235 clinical folders of paediatric patients with HIV revealed a viral suppression of 55.3%. Other poor measures included prescription accuracy, viral loads performed within schedule and response to successive high viral loads. A clinical mentorship intervention using dedicated doctor outreach was implemented and the audit repeated after 12 months (263 folders). Viral suppression improved to 67.4%, as did most other process measures. CONCLUSION: The quality improvement approach regarding the aim to significantly improve viral suppression in paediatric patients through the implementation of clinical mentorship was successful."
4293,Innovations: Innovating together while social distancing,
4294,Correction: Primary tumor-derived exosomes facilitate metastasis by regulating adhesion of circulating tumor cells via SMAD3 in liver cancer,
4295,A novel ACT-based video game to support mental health through embedded learning: a mixed-methods feasibility study protocol,"INTRODUCTION: In recent years, serious video games have been used to promote emotional regulation in individuals with mental health issues. Although these therapeutic strategies are innovative, they are limited with respect to scope of treatment, often focusing on specific cognitive skills, to help remediate a specific mental health disorder. OBJECTIVE: Here, we propose a protocol for assessing the feasibility of a novel acceptance and commitment therapy (ACT)-based video game for young adults. METHODS AND ANALYSIS: The Medical Research Council (MRC) framework will be used for developing a complex intervention to design and test the feasibility of an ACT-based video game intervention using a mixed-methods approach involving qualitative and quantitative data. The primary outcomes will include feasibility testing of recruitment processes and the acceptability of the intervention through qualitative interviews, attendance and rates of attrition. Secondary outcomes will involve a series of quantitative questionnaires to obtain effect sizes for power analysis, allowing for the ideal sample size for an appropriately powered, randomised controlled trial to be determined. ETHICS AND DISSEMINATION: This study has been approved by the Psychology Department Research Ethics Committee (2020-4929-3923) at Swansea University in the UK. Dissemination activities will involve publications in peer-reviewed journals, presentations at local and national conferences and promotion through social media. TRIAL REGISTRATION NUMBER: NCT04566042."
4296,Development of a double monoclonal antibody–based sandwich enzyme-linked immunosorbent assay for detecting canine distemper virus,"ABSTRACT: Canine distemper virus (CDV) infection causes mass mortality in diverse carnivore species. For effective virus surveillance, rapid and sensitive assays are needed to detect CDV in field samples. In this study, after BABL/c mice were immunized with recombinant CDV-fusion (F) protein, monoclonal antibodies (mAbs) against recombinant CDV-F protein (designated 1A5, 1A6, and 7D5) were produced using traditional hybridoma cell technology. Next, capture antibody (1A6, 800 ng/well) and horseradish peroxidase (HRP)–conjugated detection antibody (HRP-7D5, 1:100, 500 ng/well) were used in a double monoclonal antibody–based sandwich enzyme-linked immunosorbent assay (ELISA) for CDV detection after optimization of both mAb amounts per well using a checkerboard titration test. Based on sandwich ELISA test results for 120 known CDV-negative samples, the cutoff value for a positive result was set to an OD(450 nm) value ≥ 0.196. As compared with test results obtained from commercial immune colloidal gold test strips, the low limits of detection for the two assays were revealed to be 100 TCID(50) per 100 μL. In addition, the sandwich ELISA agreed 100% and 96.4% with commercial immune colloidal gold test strips when testing serum and stool samples. The sandwich ELISA assay provided statistically similar CDV detection. Thus, the sandwich ELISA developed here to detect CDV in fecal and serum samples provided good sensitivity, high specificity, and good reproducibility and should serve as an ideal method for large-scale surveillance of CDV infections in carnivores. KEY POINTS: • Three CDV mAbs that recognized different epitopes and bound to virion were generated. • The sandwich ELISA based mAbs to detect CDV in fecal and serum samples was developed. • The sandwich ELISA is an ideal method for detecting CDV infections in the field."
4297,Methamphetamine induces cardiomyopathy by Sigmar1 inhibition-dependent impairment of mitochondrial dynamics and function,"Methamphetamine-associated cardiomyopathy is the leading cause of death linked with illicit drug use. Here we show that Sigmar1 is a therapeutic target for methamphetamine-associated cardiomyopathy and defined the molecular mechanisms using autopsy samples of human hearts, and a mouse model of “binge and crash” methamphetamine administration. Sigmar1 expression is significantly decreased in the hearts of human methamphetamine users and those of “binge and crash” methamphetamine-treated mice. The hearts of methamphetamine users also show signs of cardiomyopathy, including cellular injury, fibrosis, and enlargement of the heart. In addition, mice expose to “binge and crash” methamphetamine develop cardiac hypertrophy, fibrotic remodeling, and mitochondrial dysfunction leading to contractile dysfunction. Methamphetamine treatment inhibits Sigmar1, resulting in inactivation of the cAMP response element-binding protein (CREB), decreased expression of mitochondrial fission 1 protein (FIS1), and ultimately alteration of mitochondrial dynamics and function. Therefore, Sigmar1 is a viable therapeutic agent for protection against methamphetamine-associated cardiomyopathy."
4298,Escalation therapy in severe traumatic brain injury: how long is intracranial pressure monitoring necessary?,"Traumatic brain injury frequently causes an elevation of intracranial pressure (ICP) that could lead to reduction of cerebral perfusion pressure and cause brain ischemia. Invasive ICP monitoring is recommended by international guidelines, in order to reduce the incidence of secondary brain injury; although rare, the complications related to ICP probes could be dependent on the duration of monitoring. The aim of this manuscript is to clarify the appropriate timing for removal and management of invasive ICP monitoring, in order to reduce the risk of related complications and guarantee adequate cerebral autoregulatory control. There is no universal consensus concerning the duration of invasive ICP monitoring and its related complications, although the pertinent literature seems to show that the longer is the monitoring maintenance, the higher is the risk of technical issues. Besides, upon 72 h of normal ICP values or less than 72 h if the first computed tomography scan is normal (none or minimal signs of injury) and the neurological exam is available (allowing to observe variations and possible occurrence of new-onset pathological response), the removal of invasive ICP monitoring can be justified. The availability of non-invasive monitoring systems should be considered to follow up patients’ clinical course after invasive ICP probe removal or for substituting the invasive monitoring in case of contraindication to its placement. Recently, optic nerve sheath diameter and straight sinus systolic flow velocity evaluation through ultrasound methods showed a good correlation with ICP values, demonstrating their potential role in place of invasive monitoring or in the early weaning phase from the invasive ICP monitoring."
4299,"Biography: Christine Stier, M.D.",
4300,Incident reports involving hospital administrative staff: analysis of data from the Japan Council for Quality Health care nationwide database,"BACKGROUND: Task shifting and task sharing in health care are rapidly becoming more common as the shortage of physicians increases. However, research has not yet examined the changing roles of hospital administrative staff. This study clarified: (1) the adverse incidents caused by hospital administrative staff, and the direct and indirect impact of these incidents on patient care; and (2) the incidents that directly involved hospital administrative staff. METHODS: This study used case report data from the Japan Council for Quality Health care collected from April 1, 2010 to March 31, 2019, including a total of 30,823 reports. In April 2020, only the 88 self-reported incidents by hospital administrative staff were downloaded, excluding incidents reported by those in medical and co-medical occupations. Data from three reports implicating pharmacists were rejected and the quantitative and textual data from the remaining 85 case reports were analyzed in terms of whether they impacted patient care directly or indirectly. RESULTS: Thirty-nine reports (45.9%) involved direct impact on patient care, while 46 (54.1%) involved indirect impact on patient care. Most incidents that directly impacted patient care involved administrative staff writing prescriptions on behalf of a doctor (n = 24, 61.5%); followed by errors related to system administration, information, and documentation (n = 7, 17.9%). Most reported errors that indirectly affected patient care were related to system administration, information, and documentation used by administrative staff (n = 22, 47.8%), or to reception (n = 9, 19.6%). Almost all errors occurred during weekdays. Most frequent incidents involved outpatients (n = 23, 27.1%), or occurred next to examination/operation rooms (n = 12, 14.1%). Further, a total of 14 cases (16.5%) involved patient misidentification. CONCLUSIONS: Incidents involving hospital administrative staff, the most common of which are medication errors from incorrect prescriptions, can lead to severe consequences for patients. Given that administrative staff now form a part of medical treatment teams, improvements in patient care may require further submission and review of incident reports involving administrative staff."
4301,Characteristics and outcomes of frail patients with suspected infection in intensive care units: a descriptive analysis from a multicenter cohort study,"BACKGROUND: Frailty is associated with morbidity and mortality in patients admitted to intensive care units (ICUs). However, the characteristics of frail patients with suspected infection remain unclear. We aimed to investigate the characteristics and outcomes of frail patients with suspected infection in ICUs. METHODS: This is a secondary analysis of a multicenter cohort study, including 22 ICUs in Japan. Adult patients (aged ≥16 years) with newly suspected infection from December 2017 to May 2018 were included. We compared baseline patient characteristics and outcomes among three frailty groups based on the Clinical Frailty Scale (CFS) score: fit (score, 1–3), vulnerable (score, 4), and frail (score, 5–9). We conducted subgroup analysis of patients with sepsis defined as per Sepsis-3 criteria. We also produced Kaplan–Meier survival curves for 90-day survival. RESULTS: We enrolled 650 patients with suspected infection, including 599 (92.2%) patients with sepsis. Patients with a median CFS score of 3 (interquartile range [IQR] 3–5) were included: 337 (51.8%) were fit, 109 (16.8%) were vulnerable, and 204 (31.4%) were frail. The median patient age was 72 years (IQR 60–81). The Sequential Organ Failure Assessment scores for fit, vulnerable, and frail patients were 7 (IQR 4–10), 8 (IQR 5–11), and 7 (IQR 5–10), respectively (p = 0.59). The median body temperatures of fit, vulnerable, and frail patients were 37.5 °C (IQR 36.5 °C–38.5 °C), 37.5 °C (IQR 36.4 °C–38.6 °C), and 37.0 °C (IQR 36.3 °C–38.1 °C), respectively (p < 0.01). The median C-reactive protein levels of fit, vulnerable, and frail patients were 13.6 (IQR 4.6–24.5), 12.1 (IQR 3.9–24.9), 10.5 (IQR 3.0–21.0) mg/dL, respectively (p < 0.01). In-hospital mortality did not statistically differ among the patients according to frailty (p = 0.19). Kaplan–Meier survival curves showed little difference in the mortality rate during short-term follow-up. However, more vulnerable and frail patients died after 30-day than fit patients; this difference was not statistically significant (p = 0.25). Compared with the fit and vulnerable groups, the rate of home discharge was lower in the frail group. CONCLUSION: Frail and vulnerable patients with suspected infection tend to have poor disease outcomes. However, they did not show a statistically significant increase in the 90-day mortality risk."
4302,Outcomes of hemi- versus whole liver transplantation in patients from mainland china with high model for end-stage liver disease scores: a matched analysis,"BACKGROUND: Adult hemiliver transplantation (AHLT) is an important approach given the current shortage of donor livers. However, the suitability of AHLT versus adult whole liver transplantation (AWLT) for recipients with high Model for End-Stage Liver Disease (MELD) scores remains controversial. METHODS: We divided patients undergoing AHLT and AWLT into subgroups according to their MELD scores (≥ 30: AHLT, n = 35; AWLT, n = 88; and < 30: AHLT, n = 323; AWLT, n = 323). Patients were matched by demographic data and perioperative conditions according to propensity scores. A cut-off value of 30 for MELD scores was determined by comparing the overall survival data of 735 cases of nontumor liver transplantation. RESULTS: Among patients with an MELD score ≥ 30 and < 30, AHLT was found to be associated with increased warm ischemia time, operative time, hospitalization time, and intraoperative blood loss compared with AWLT (P < 0.05). In the MELD ≥ 30 group, although the 5-year survival rate was significantly higher for AWLT than for AHLT (P = 0.037), there was no significant difference between AWLT and AHLT in the MELD < 30 group (P = 0.832); however, we did not observe a significant increase in specific complications following AHLT among patients with a high MELD score (≥ 30). Among these patients, the incidence of complications classified as Clavien-Dindo grade III or above was significantly higher in patients undergoing AHLT than in those undergoing AWLT (25.7% vs. 11.4%, P = 0.047). For the MELD < 30 group, there was no significant difference in the incidence of complications classified as Clavien-Dindo grade III or above for patients undergoing AHLT or AWLT. CONCLUSION: In patients with an MELD score < 30, AHLT can achieve rates of mortality and overall survival comparable to AWLT. In those with an MELD score ≥ 30, the prognosis and incidence of complications classified as Clavien-Dindo III or above are significantly worse for AHLT than for AWLT; therefore, we may need to be more cautious regarding the conclusion that patients with a high MELD score can safely undergo AHLT."
4303,"Antimicrobial Stewardship in the Intensive Care Unit: The Role of Biomarkers, Pharmacokinetics, and Pharmacodynamics","The high prevalence of infectious diseases in the intensive care unit (ICU) and consequently elevated pressure for immediate and effective treatment have led to increased antimicrobial therapy consumption and misuse. Moreover, the emerging global threat of antimicrobial resistance and lack of novel antimicrobials justify the implementation of judicious antimicrobial stewardship programs (ASP) in the ICU. However, even though the importance of ASP is generally accepted, its implementation in the ICU is far from optimal and current evidence regarding strategies such as de-escalation remains controversial. The limitations of clinical guidance for antimicrobial therapy initiation and discontinuation have led to multiple studies for the evaluation of more objective tools, such as biomarkers as adjuncts for ASP. C-reactive protein and procalcitonin can be adequate for clinical use in acute infectious diseases, the latter being the most studied for ASP purposes. Although promising, current evidence highlights challenges in biomarker application and interpretation. Furthermore, the physiological alterations in the critically ill render pharmacokinetics and pharmacodynamics crucial parameters for adequate antimicrobial therapy use. Individual pharmacokinetic and pharmacodynamic targets can reduce antimicrobial therapy misuse and risk of antimicrobial resistance."
4304,The efficacy of mesenchymal stromal cell-derived therapies for acute respiratory distress syndrome—a meta-analysis of preclinical trials,"BACKGROUND: The investigation of mesenchymal stromal cell (MSC)-conditioned medium or extracellular vesicles (exosomes or microvesicles) as a remedy for acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) has become a fast-growing field in recent years. Our purpose was to conduct a meta-analysis to investigate the efficacy of MSC-derived therapies (MDTs) for ALI/ARDS in animal models. METHODS: A meta-analysis of MDTs for ALI/ARDS in animal trials was performed. PubMed and EMBASE were searched to screen relevant preclinical trials with a predetermined search strategy. RESULTS: A total of 17 studies that compared MDT with the ALI control group were included in our study. The pooled result derived from the comparison of the two groups suggested that MDT could significantly reduce the lung injury score (standardized mean difference (SMD) = − 4.02, 95% CI [− 5.28, − 2.23], P < 0.0001) and improve animal survival (OR = − 6.45, 95% CI [2.78, 14.97], P < 0.0001). MDT mitigated the infiltration of neutrophils in alveoli (SMD = − 3.38, 95% CI [− 4.58, − 2.18], P < 0.00001). MDT also reduced the wet-dry weight ratio of the lung (SMD = − 2.34, 95% CI [− 3.42, − 1.26], P < 0.0001) and the total protein in BALF (SMD = − 2.23, 95% CI [− 3.07, − 1.40], P < 0.00001). Furthermore, MDT was found to downregulate proinflammatory mediators such as IL-1, IL-6 and TNF-a and to upregulate anti-inflammatory mediators such as IL-10. CONCLUSION: MDT reduces lung injury and improves survival in animal ARDS models since it can ameliorate lung permeability, decrease inflammatory cell infiltration, downregulate proinflammatory mediators, and upregulate anti-inflammatory mediators. However, more animal studies and human trials are needed for further investigation."
4305,Recombinant Treponema pallidum protein Tp0768 promotes proinflammatory cytokine secretion of macrophages through ER stress and ROS/NF-κB pathway,"ABSTRACT: In response to danger signals, macrophages rapidly produce many inflammatory cytokines that trigger the cascade release of inflammatory mediators, leading to tissue damage, which is an important cause of clinical manifestations of syphilis at all stages. However, we still know very little about the specific mechanism of this process. Tp0768 is an infection-stage–dependent antigen that plays an important role in the infection of Treponema pallidum. In this study, we demonstrated that Tp0768 stimulation of macrophages can cause IL-1β, IL-6, and IL-8 mRNA expression levels to increase in a dose- and time-dependent manner. Further research showed that Tp0768 activated ER stress and the ROS/NF-κB pathway in macrophages. Inhibition of ER stress and the ROS/NF-κB pathway inhibited the expression of IL-1β, IL-6, and IL-8 induced by Tp0768. In addition, pretreatment with a PERK pathway inhibitor significantly reduced the expression of the NF-κB and JNK pathways, while also downregulating the expression of IL-1β, IL-6, and IL-8. Tp0768 stimulation can activate IRE1α/XBP-1 signaling and participate in the induction of inflammatory cytokines through the JNK pathway. These findings indicate that Tp0768 promotes the secretion of proinflammatory cytokines IL-1β, IL-6, and IL-8 by macrophages through ER stress and the ROS/NF-κB pathway, which are also involved in the activation of the NF-κB and JNK pathways that are induced by the PERK pathway and activation of IRE1α/XBP-1 signaling. KEY POINTS: • This study found for the first time that the recombinant Treponema pallidum protein Tp0768 promotes the production of IL-1β, IL-6, and IL-8 by macrophages through ER stress. • Recombinant Treponema pallidum protein Tp0768 regulates the ROS/NF-κB pathway through ER stress. • ER stress-related pathway PERK induces the expression of IL-1β, IL-6, and IL-8 by activating the NF-κB pathway and the JNK pathway. • IRE1α can induce the splicing of XBP-1mRNA and activate the JNK pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00253-020-11018-8."
4306,Continuous assessment of neuro-ventilatory drive during 12 h of pressure support ventilation in critically ill patients,"INTRODUCTION: Pressure support ventilation (PSV) should allow spontaneous breathing with a “normal” neuro-ventilatory drive. Low neuro-ventilatory drive puts the patient at risk of diaphragmatic atrophy while high neuro-ventilatory drive may causes dyspnea and patient self-inflicted lung injury. We continuously assessed for 12 h the electrical activity of the diaphragm (EAdi), a close surrogate of neuro-ventilatory drive, during PSV. Our aim was to document the EAdi trend and the occurrence of periods of “Low” and/or “High” neuro-ventilatory drive during clinical application of PSV. METHOD: In 16 critically ill patients ventilated in the PSV mode for clinical reasons, inspiratory peak EAdi peak (EAdi(PEAK)), pressure time product of the trans-diaphragmatic pressure per breath and per minute (PTP(DI/b) and PTP(DI/min), respectively), breathing pattern and major asynchronies were continuously monitored for 12 h (from 8 a.m. to 8 p.m.). We identified breaths with “Normal” (EAdi(PEAK) 5–15 μV), “Low” (EAdi(PEAK) < 5 μV) and “High” (EAdi(PEAK) > 15 μV) neuro-ventilatory drive. RESULTS: Within all the analyzed breaths (177.117), the neuro-ventilatory drive, as expressed by the EAdi(PEAK), was “Low” in 50.116 breath (28%), “Normal” in 88.419 breaths (50%) and “High” in 38.582 breaths (22%). The average times spent in “Low”, “Normal” and “High” class were 1.37, 3.67 and 0.55 h, respectively (p < 0.0001), with wide variations among patients. Eleven patients remained in the “Low” neuro-ventilatory drive class for more than 1 h, median 6.1 [3.9–8.5] h and 6 in the “High” neuro-ventilatory drive class, median 3.4 [2.2–7.8] h. The asynchrony index was significantly higher in the “Low” neuro-ventilatory class, mainly because of a higher number of missed efforts. CONCLUSIONS: We observed wide variations in EAdi amplitude and unevenly distributed “Low” and “High” neuro ventilatory drive periods during 12 h of PSV in critically ill patients. Further studies are needed to assess the possible clinical implications of our physiological findings."
4307,"Knowledge of Cervical Cancer, Human Papilloma Virus (HPV) and HPV Vaccination Among Women in Northeast China","This study aimed to research the understanding and knowledge of cervical cancer, human papilloma virus (HPV), and HPV vaccination, and the acceptance of HPV vaccination, among a population of women in northeastern China. A cross-sectional survey was carried out by questionnaire to investigate knowledge of cervical cancer, HPV, and HPV vaccination. The 230 female participants were native residents of northeastern China, and their ages ranged between 18 and 65 years. Questionnaires were randomly acquired by the respondents from online and paper questionnaire distribution. The questionnaire included questions on three major aspects to record people’s perceptions of cervical cancer, HPV, and vaccines. Of the sample of 230 women surveyed, 80.9% had heard of cervical cancer, but understanding was only 15.7%; 38.3% knew about HPV; 20% knew about HPV vaccine; 39.6% agreed to receive HPV vaccination, and the remainder were mainly concerned about its safety and effectiveness. Data analysis showed that age, family income, and whether there was experience of screening all influenced knowledge of cervical cancer, but this was not statistically significant. The level of education had no obvious effect on the degree of knowledge about cervical cancer; however, with an improvement in education, women’s awareness of HPV vaccine improved significantly (p < 0.05). Women who have received cervical cancer screening had significantly greater knowledge about cervical cancer and HPV than those with no screening (p < 0.05). Women in northeastern China have little knowledge of cervical cancer, HPV, and HPV vaccine, lack disease knowledge, and hold a skeptical attitude about HPV vaccination. Medical institutions are the main channel providing information to these women."
4308,Ovine haemonchosis: a review,"Sheep farming is the backbone of a rural economy in developing countries, and haemonchosis is a major impediment in the way of its progress. Haemonchus contortus (H. contortus) infection persists all over the world particularly in the tropical and sub-tropical regions. Various review articles have been published to substantially cover one or more aspects of its morphology, prevalence, pathogenesis, symptoms, diagnosis, immune response, drug resistance, treatment, and control measure. The objective of this paper is to briefly review past and present information available in the aforementioned areas in one place to enable the readers to fully understand the problem from a broader perspective. H. contortus parasite harbours in abomasum of affected animal and feeds on its blood, producing mild to severe symptoms and even death in acute form. The parasite thus inflicts heavy production losses and is of economic importance. H. contortus has developed diverse characters over the years leading to limited success in the production of vaccines. Indiscriminate use of the anthelmintics has produced drug resistance against almost all conventional products. Efficacy of medicinal plants and non-conventional chemicals has been reported under controlled experiments; however, research on their adverse effects on growth and fertility is yet to be studied. Research on molecular tools for identification and introduction of resistant genes into the flock is also underway but still a long journey to find its field application. Crossbreeding may compromise the production traits of the existing flock. In given circumstances, a targeted selective treatment approach along with selective breeding, culling of more susceptible animals, and maintaining a good body condition score through the provision of a balanced diet remains a workable strategy to control haemonchosis in sheep."
4309,Veranstaltungstipps:,
4310,Deep-learning-assisted detection and segmentation of rib fractures from CT scans: Development and validation of FracNet,"BACKGROUND: Diagnosis of rib fractures plays an important role in identifying trauma severity. However, quickly and precisely identifying the rib fractures in a large number of CT images with increasing number of patients is a tough task, which is also subject to the qualification of radiologist. We aim at a clinically applicable automatic system for rib fracture detection and segmentation from CT scans. METHODS: A total of 7,473 annotated traumatic rib fractures from 900 patients in a single center were enrolled into our dataset, named RibFrac Dataset, which were annotated with a human-in-the-loop labeling procedure. We developed a deep learning model, named FracNet, to detect and segment rib fractures. 720, 60 and 120 patients were randomly split as training cohort, tuning cohort and test cohort, respectively. Free-Response ROC (FROC) analysis was used to evaluate the sensitivity and false positives of the detection performance, and Intersection-over-Union (IoU) and Dice Coefficient (Dice) were used to evaluate the segmentation performance of predicted rib fractures. Observer studies, including independent human-only study and human-collaboration study, were used to benchmark the FracNet with human performance and evaluate its clinical applicability. A annotated subset of RibFrac Dataset, including 420 for training, 60 for tuning and 120 for test, as well as our code for model training and evaluation, was open to research community to facilitate both clinical and engineering research. FINDINGS: Our method achieved a detection sensitivity of 92.9% with 5.27 false positives per scan and a segmentation Dice of 71.5%on the test cohort. Human experts achieved much lower false positives per scan, while underperforming the deep neural networks in terms of detection sensitivities with longer time in diagnosis. With human-computer collobration, human experts achieved higher detection sensitivities than human-only or computer-only diagnosis. INTERPRETATION: The proposed FracNet provided increasing detection sensitivity of rib fractures with significantly decreased clinical time consumed, which established a clinically applicable method to assist the radiologist in clinical practice. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. The funding sources played no role in the study design; collection, analysis, and interpretation of data; writing of the report; or decision to submit the article for publication ."
4311,Cardio-Renal-Metabolic Care Models: Toward Achieving Effective Interdisciplinary Care,
4312,Humans disrupt access to prey for large African carnivores,"Wildlife respond to human presence by adjusting their temporal niche, possibly modifying encounter rates among species and trophic dynamics that structure communities. We assessed wildlife diel activity responses to human presence and consequential changes in predator-prey overlap using 11,111 detections of 3 large carnivores and 11 ungulates across 21,430 camera trap-nights in West Africa. Over two-thirds of species exhibited diel responses to mainly diurnal human presence, with ungulate nocturnal activity increasing by 7.1%. Rather than traditional pairwise predator-prey diel comparisons, we considered spatiotemporally explicit predator access to several prey resources to evaluate community-level trophic responses to human presence. Although leopard prey access was not affected by humans, lion and spotted hyena access to three prey species significantly increased when prey increased their nocturnal activity to avoid humans. Human presence considerably influenced the composition of available prey, with implications for prey selection, demonstrating how humans perturb ecological processes via behavioral modifications."
4313,A new generation of direct X-ray detectors for medical and synchrotron imaging applications,"Large-area X-ray imaging is one of the most widely used imaging modalities that spans several scientific and technological fields. Currently, the direct X-ray conversion materials that are being commercially used for large-area (> 8 cm × 4 cm without tiling) flat panel applications, such as amorphous selenium (a-Se), have usable sensitivities of up to only 30 keV. Although there have been many promising candidates (such as polycrystalline HgI(2) and CdTe), none of the semiconductors were able to assuage the requirement for high energy (> 40 keV) large-area X-ray imaging applications due to inadequate cost, manufacturability, and long-term performance metrics. In this study, we successfully demonstrate the potential of the hybrid Methylammonium lead iodide (MAPbI(3)) perovskite-based semiconductor detectors in satisfying all the requirements for its successful commercialization in synchrotron and medical imaging. This new generation of hybrid detectors demonstrates low dark current under electric fields needed for high sensitivity X-ray imaging applications. The detectors have a linear response to X-ray energy and applied bias, no polarization effects at a moderate bias, and signal stability over long usage durations. Also, these detectors have demonstrated a stable detection response under BNL’s National Synchrotron Light Source II (NSLS-II) 70 keV monochromatic synchrotron beamline."
4314,Dynamic Change in Serum Alpha-fetoprotein Level Predicts Treatment Response and Prognosis of Alpha-fetoprotein-producing Gastric Cancer,"Alpha-fetoprotein (AFP)-producing gastric cancer (AFPGC) is rare and associated with a suboptimal prognosis. The aim of this retrospective study was to identify prognostic factors, with a particular focus on the dynamics of serum AFP levels during treatment, in AFPGC patients. Data of patients with pathologically diagnosed primary gastric cancer treated with various modalities electronically collected in the medical management systems of 2 hospitals (ie, Shihezi People's Hospital and Shihezi Hospital) in Shihezi city, northwest China, from January 2007 to October 2018 were reviewed. Patients with AFPGC were identified based on serum AFP levels. Associations of the change in serum AFP levels and clinicopathological parameters with treatment response, including the overall response rate and disease control rate, and outcomes, including overall survival (OS) and progression-free survival (PFS), were compared among different groups. Of 2354 patients diagnosed with gastric cancer, 96 patients with AFPGC were identified. The objective response rate and disease control rate were significantly higher in patients whose AFP level decreased by ≥50% than in patients whose AFP level decreased by <50% (68.8% vs. 40.6%, and 87.5% vs. 53.1%, respectively, both P < .05). The median OS and PFS were 32.0 (4-74) and 24.0 (1-66) months, respectively, in patients with a ≥50% decline in AFP, and 12.5 (0-69) and 9.0 (0-63) months, respectively, in those with a <50% decline in AFP (both P < .05). On univariate and multivariate analyses, tumor, node, metastasis staging classification stage, liver metastasis, curable surgery, and the decline in the serum AFP level were associated with OS and PFS. A significant decline in the serum AFP level was associated with good treatment response and prognosis in AFPGC. Along with a decline in the serum AFP level, tumor, node, metastasis staging classification stage, liver metastasis, and curable surgery were also independent factors associated with prognosis."
4315,Effect of home-based high-intensity interval training using telerehabilitation among coronary heart disease patients,"INTRODUCTION: Cardiovascular diseases are the world's most common causes of morbidity and mortality in the population, including Central Europe. Cardiac rehabilitation (CR) is an effective preventive approach that includes several core components. Physical training is identified as an integral and essential part of CR. Training can positively influence several cardiovascular risk factors in people diagnosed with coronary heart disease and prevent them from clinical events. Our study aims to research the method of high-intensity interval training (HIIT) in a home environment using telerehabilitation. We assume that the HIIT form of telerehabilitation, using a heart rate monitor as a tool for backing up training data, can improve cardiorespiratory fitness and lead to higher peak oxygen uptake than the traditional moderate-intensity continuous training (MICT). METHODS: This study is designed as a monocentral randomized controlled trial at University Hospital Brno in the Czech Republic. After the coronary heart event, the suitable patients will be randomized (1:1 ratio) and separated into 2 groups: the experimental HIIT group and the control MICT group. Both groups undergo a 12-week telerehabilitation with a 1-year follow-up period. Study participants will be telemonitored during physical training in their home environment via a heart rate monitor and a web platform. Once a week, the patients will give their feedback and motivation by a telephone call. The primary outcome observed will be the effect of intervention expressed by changes in cardiorespiratory fitness. Secondary outcomes will be the health-related quality of life, anxiety, training adherence, body composition, safety, and satisfaction. DISCUSSION: The HIIT is widely researched predominantly in a center-based supervised form. Our study differs from others by the use of telemedicine and smart technologies in home-based settings. Previous home-based cardiac telerehabilitation studies have focused primarily on MICT, which has demonstrated feasibility, and results have shown similar improvements as center-based CR. There is a presumption that HIIT may be superior to MICT. However, it can be complicated to self-dose the method in the home environment. Investigators expect that HIIT research will provide insight into the possibilities of telemedicine feasibility, effect, and limitations of coronary heart disease patients’ use at low to moderate cardiovascular risk."
4316,Zhisou powder in treatment of postinfectious cough: A protocol for systematic review and meta-analysis,"BACKGROUND: The pathogensis of postinfectious cough (PIC) is unkown, unsatisfactory clinical curative effects of conventional western medicine have been shown. Zhisou powder (ZP) is one of the most common prescriptions in traditional Chinese medicine for the treatment of PIC. However, the effects and safety also remain uncertain. We aim to systematically review the effectiveness and safety of ZP for PIC. METHODS: We will search the following databases: PubMed, Embase, Cochrane Library, MEDLINE, the China National Knowledge Infrastructure , the Chinese Biomedical Literature Database, Cqvip Database, and Wanfang Data. The studies published from the inception of the database to May 2020 will be retrieved. The randomized controlled trials on ZP for PIC will be included. The primary outcomes were cough relief rate and cough resolution rate. We will perform the analyses using RevMan V.5.3 software. RESULTS: This study will provide high-quality evidence of ZP for PIC in the effectiveness and safety. CONCLUSIONS: This systematic review will assess whether ZP is an effective and safe prescription for PIC."
4317,"First autochthonous human West Nile virus infections in the Netherlands, July to August 2020","In October 2020, the first case of autochthonous West Nile virus neuroinvasive disease was diagnosed in the Netherlands with a presumed infection in the last week of August. Investigations revealed five more cases of local West Nile virus (WNV) infection. The cases resided in a region where WNV was detected in a bird and mosquitoes in August 2020. Molecular analysis was successful for two cases and identified the presence of WNV lineage 2."
4318,"Evaluation of two family-based intervention programs for children affected by rare disease and their families – research network (CARE-FAM-NET): study protocol for a rater-blinded, randomized, controlled, multicenter trial in a 2x2 factorial design","BACKGROUND: Families of children with rare diseases (i.e., not more than 5 out of 10,000 people are affected) are often highly burdened with fears, insecurities and concerns regarding the affected child and its siblings. Although families caring for children with rare diseases are known to be at risk for mental disorders, the evaluation of special programs under high methodological standards has not been conducted so far. Moreover, the implementation of interventions for this group into regular care has not yet been accomplished in Germany. The efficacy and cost-effectiveness of a family-based intervention will be assessed. METHODS/DESIGN: The study is a 2x2 factorial randomized controlled multicenter trial conducted at 17 study centers throughout Germany. Participants are families with children and adolescents affected by a rare disease aged 0 to 21 years. Families in the face-to-face intervention CARE-FAM, online intervention WEP-CARE or the combination of both will be treated over a period of roughly 6 months. Topics discussed in the interventions include coping, family relations, and social support. Families in the control condition will receive treatment as usual. The primary efficacy outcome is parental mental health, measured by the Structured Clinical Interview for DSM-IV (SCID-I) by blinded external raters. Further outcomes will be assessed from the parents’ as well as the children’s perspective. Participants are investigated at baseline, 6, 12 and 18 months after randomization. In addition to the assessment of various psychosocial outcomes, a comprehensive health-economic evaluation will be performed. DISCUSSION: This paper describes the implementation and evaluation of two family-based intervention programs for Children Affected by Rare Disease and their Family’s Network (CARE-FAM-NET) in German standard care. A methodologically challenging study design is used to reflect the complexity of the actual medical care situation. This trial could be an important contribution to the improvement of care for this highly burdened group. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00015859 (registered 18 December 2018) and ClinicalTrials.gov: NCT04339465 (registered 8 April 2020). Protocol Version: 15 August 2020 (Version 6.1). Trial status: Recruitment started on 1 January 2019 and will be completed on 31 March 2021. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12875-020-01312-9."
4319,Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease,"Progressive multifocal leukoencephalopathy (PML) is a devastating CNS infection caused by JC virus (JCV), a polyomavirus that commonly establishes persistent, asymptomatic infection in the general population. Emerging evidence that PML can be ameliorated with novel immunotherapeutic approaches calls for reassessment of PML pathophysiology and clinical course. PML results from JCV reactivation in the setting of impaired cellular immunity, and no antiviral therapies are available, so survival depends on reversal of the underlying immunosuppression. Antiretroviral therapies greatly reduce the risk of HIV-related PML, but many modern treatments for cancers, organ transplantation and chronic inflammatory disease cause immunosuppression that can be difficult to reverse. These treatments — most notably natalizumab for multiple sclerosis — have led to a surge of iatrogenic PML. The spectrum of presentations of JCV-related disease has evolved over time and may challenge current diagnostic criteria. Immunotherapeutic interventions, such as use of checkpoint inhibitors and adoptive T cell transfer, have shown promise but caution is needed in the management of immune reconstitution inflammatory syndrome, an exuberant immune response that can contribute to morbidity and death. Many people who survive PML are left with neurological sequelae and some with persistent, low-level viral replication in the CNS. As the number of people who survive PML increases, this lack of viral clearance could create challenges in the subsequent management of some underlying diseases."
4320,Saturation oxygenation pressure index: a non-invasive bedside measure for severity of respiratory disease in neonates on CPAP,"The treatment of respiratory distress in neonates ranges from non-invasive continuous positive airway pressure (CPAP) to advanced invasive mechanical ventilation. Monitoring on CPAP is often done by calculating oxygenation after blood gas analysis which is an invasive procedure. Saturation oxygen pressure index (SOPI) is a simple, non-invasive, bedside tool to monitor the severity of respiratory illness in neonates on CPAP. This study was aimed at validation of SOP index against AaDO2 and determine the cut-off values of SOPI for A-aDO2 of 70, 85 and100. This was a prospective observational study on 126 neonates with respiratory distress and treated with CPAP. The correlation between SOPI and A-aDO2 was validated using Bootstrap method. There was a significant positive correlation between SOPI and A-aDO2 with the Spearman correlation coefficient (rho) being 0.815 (p = 0). The mean coefficient of correlation after Bootstrap was 0.827 (p value < 0.0001). SOPI values of 1.52, 1.57 and 1.6 predicted A-aDO2 value of 70, 85 and 100 with a sensitivity of above 80% and specificity above 90%, respectively. Conclusion: SOPI has a significant positive correlation of 82.7% against A-aDO2 and can be a valuable tool to assess respiratory distress in neonates without arterial blood gas."
4321,A Generalist Lifestyle Allows Rare Gardnerella spp. to Persist at Low Levels in the Vaginal Microbiome,"Gardnerella spp. are considered a hallmark of bacterial vaginosis, a dysbiosis of the vaginal microbiome. There are four cpn60 sequence-based subgroups within the genus (A, B, C and D), and thirteen genome species have been defined recently. Gardnerella spp. co-occur in the vaginal microbiome with varying abundance, and these patterns are shaped by a resource-dependent, exploitative competition, which affects the growth rate of subgroups A, B and C negatively. The growth rate of rarely abundant subgroup D, however, increases with the increasing number of competitors, negatively affecting the growth rate of others. We hypothesized that a nutritional generalist lifestyle and minimal niche overlap with the other more abundant Gardnerella spp. facilitate the maintenance of subgroup D in the vaginal microbiome through negative frequency-dependent selection. Using 40 whole-genome sequences from isolates representing all four subgroups, we found that they could be distinguished based on the content of their predicted proteomes. Proteins associated with carbohydrate and amino acid uptake and metabolism were significant contributors to the separation of subgroups. Subgroup D isolates had significantly more of their proteins assigned to amino acid metabolism than the other subgroups. Subgroup D isolates were also significantly different from others in terms of number and type of carbon sources utilized in a phenotypic assay, while the other three could not be distinguished. Overall, the results suggest that a generalist lifestyle and lack of niche overlap with other Gardnerella spp. leads to subgroup D being favoured by negative frequency-dependent selection in the vaginal microbiome. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00248-020-01643-1."
4322,Probing the ionotropic activity of glutamate GluD2 receptor in HEK cells with genetically-engineered photopharmacology,"Glutamate delta (GluD) receptors belong to the ionotropic glutamate receptor family, yet they don’t bind glutamate and are considered orphan. Progress in defining the ion channel function of GluDs in neurons has been hindered by a lack of pharmacological tools. Here, we used a chemo-genetic approach to engineer specific and photo-reversible pharmacology in GluD2 receptor. We incorporated a cysteine mutation in the cavity located above the putative ion channel pore, for site-specific conjugation with a photoswitchable pore blocker. In the constitutively open GluD2 Lurcher mutant, current could be rapidly and reversibly decreased with light. We then transposed the cysteine mutation to the native receptor, to demonstrate with high pharmacological specificity that metabotropic glutamate receptor signaling triggers opening of GluD2. Our results assess the functional relevance of GluD2 ion channel and introduce an optogenetic tool that will provide a novel and powerful means for probing GluD2 ionotropic contribution to neuronal physiology."
4323,Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis,"Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses. In experimental sepsis, MAIT-deficient mice had significantly increased mortality and bacterial load, and reduced tissue-specific cytokine responses. MAIT cells of WT mice expressed lower levels of IFN-γ and IL-17a during sepsis compared to sham surgery, changes not seen in non-MAIT T cells. MAIT cells of patients at sepsis presentation were significantly reduced in frequency compared to healthy donors, and were more activated, with decreased IFN-γ production, compared to both healthy donors and paired 90-day samples. Our data suggest that MAIT cells are highly activated and become dysfunctional during clinical sepsis, and contribute to tissue-specific cytokine responses that are protective against mortality during experimental sepsis."
4324,Patient Triage by Topic Modeling of Referral Letters: Feasibility Study,"BACKGROUND: Musculoskeletal conditions are managed within primary care, but patients can be referred to secondary care if a specialist opinion is required. The ever-increasing demand for health care resources emphasizes the need to streamline care pathways with the ultimate aim of ensuring that patients receive timely and optimal care. Information contained in referral letters underpins the referral decision-making process but is yet to be explored systematically for the purposes of treatment prioritization for musculoskeletal conditions. OBJECTIVE: This study aims to explore the feasibility of using natural language processing and machine learning to automate the triage of patients with musculoskeletal conditions by analyzing information from referral letters. Specifically, we aim to determine whether referral letters can be automatically assorted into latent topics that are clinically relevant, that is, considered relevant when prescribing treatments. Here, clinical relevance is assessed by posing 2 research questions. Can latent topics be used to automatically predict treatment? Can clinicians interpret latent topics as cohorts of patients who share common characteristics or experiences such as medical history, demographics, and possible treatments? METHODS: We used latent Dirichlet allocation to model each referral letter as a finite mixture over an underlying set of topics and model each topic as an infinite mixture over an underlying set of topic probabilities. The topic model was evaluated in the context of automating patient triage. Given a set of treatment outcomes, a binary classifier was trained for each outcome using previously extracted topics as the input features of the machine learning algorithm. In addition, a qualitative evaluation was performed to assess the human interpretability of topics. RESULTS: The prediction accuracy of binary classifiers outperformed the stratified random classifier by a large margin, indicating that topic modeling could be used to predict the treatment, thus effectively supporting patient triage. The qualitative evaluation confirmed the high clinical interpretability of the topic model. CONCLUSIONS: The results established the feasibility of using natural language processing and machine learning to automate triage of patients with knee or hip pain by analyzing information from their referral letters."
4325,Hat mein Patient wirklich nur eine Erkältung?: Unterscheidungshilfe,
4326,COVID-19: Risiken und schwere Verläufe: Neuer Risiko-Score,
4327,"Je höher der Blutzucker, desto gefährlicher die SARS-CoV-2-Infektion: COVID-19 bei Diabetikern",
4328,"HIV: ""Wir behandeln heute die Folgen der Gesundung""",
4329,Die erste Seite,
4330,"Mechanistic Approaches of Internalization, Subcellular Trafficking, and Cytotoxicity of Nanoparticles for Targeting the Small Intestine","Targeting the small intestine employing nanotechnology has proved to be a more effective way for site-specific drug delivery. The drug targeting to the small intestine can be achieved via nanoparticles for its optimum bioavailability within the systemic circulation. The small intestine is a remarkable candidate for localized drug delivery. The intestine has its unique properties. It has a less harsh environment than the stomach, provides comparatively more retention time, and possesses a greater surface area than other parts of the gastrointestinal tract. This review focuses on elaborating the intestinal barriers and approaches to overcome these barriers for internalizing nanoparticles and adopting different cellular trafficking pathways. We have discussed various factors that contribute to nanocarriers’ cellular uptake, including their surface chemistry, surface morphology, and functionalization of nanoparticles. Furthermore, the fate of nanoparticles after their uptake at cellular and subcellular levels is also briefly explained. Finally, we have delineated the strategies that are adopted to determine the cytotoxicity of nanoparticles."
4331,Transformation of the Tanzania medical stores department through global fund support: an impact assessment study,"BACKGROUND: The Tanzania government sought support from The Global Fund to Fight AIDs, Tuberculosis and Malaria to reform its Medical Stores Department, with the aim of improving performance. The study sought to assess the impact of the reforms and document the lessons learnt. METHODS: Quantitative and qualitative research methods were applied to assess the impact of the reforms. The quantitative part entailed a review of operational and financial data covering the period before and after the implementation of the reforms. Interrupted time series analysis was used to determine the change in average availability of essential health commodities at health zones. Qualitative data were collected through 41 key informant interviews. Participants were identified through stakeholder mapping, purposive and snowballing sampling techniques and responses were analysed through thematic content analysis. RESULTS: Availability of essential health commodities increased significantly by 12.6% (95% CI 9.6% to 15.6%) after the reforms and continued to increase on a monthly basis by 0.2% (95%CI 0.0% to 0.3%) relative to the preintervention trend. Sales increased by 56.6% while the cost of goods sold increased by 88.6% between 2014/2015 and 2017/2018. Surplus income increased by 56.4% between 2014/2015 and 2017/2018 with reductions in rent and fuel expenditure. There was consensus among study participants that the reforms were instrumental in improving performance of the Medical Stores Department. CONCLUSION: Positive results were realised through the reforms. However, despite the progress, there were risks such as the increasing government receivable that could jeopardise the sustainability of the gains. Therefore, multistakeholder efforts are necessary to make progress and expand public health."
4332,Using alt text to make science Twitter more accessible for people with visual impairments,"Scientists increasingly post images and photos on social media to share their research activities. However, posting images and photos could potentially exclude people with visual impairments. Here, we outline actions that should be taken to foster accessibility and inclusion in posting scientific images on social media."
4333,LC3B in Malignant Cells Correlates With Immune Infiltrate in Hypopharyngeal Squamous Cell Carcinoma,"The objective of this study was to investigate the between autophagy activity and local immune response in hypopharyngeal squamous cell carcinoma (HSCC). Herein, we observed the expression of autophagy marker microtubule-associated protein light chain 3B (MAP1LC3B), CD8 cytotoxic T lymphocytes (CTLs), CD39 (regulatory T cells Tregs) and CD163 (tumor-associated macrophages TAMs) in HSCC, and determined the prognostic roles of CD8(+)/CD39(+) and CD8(+)/CD163(+) in patients with HSCC. The expression of light chain 3B (LC3B) and CD8(+)/CD39(+) was found to be significantly lower in HSCC tissues than in adjacent non-tumor mucosa tissue samples; LC3B expression was positively correlated with the infiltration rate of CD8(+)/CD39(+) in HSCC. Further studies revealed that the ratio of CD8(+)/CD39(+) immune cells was negatively correlated with tumor lymph node metastasis and TNM classification, while the ratio of CD8(+)/CD163(+) immune cells was negatively correlated with TNM classification. Moreover, the expression of LC3B was analyzed and the patients were grouped according to their immune infiltration characteristics. The 5-year cumulative survival rates of LC3B(+), CD8(+)/CD39(+), and CD8(+)/CD163(+) patients were significantly higher than those of other group patients. Collectively, our studies indicated that the expression of LC3B in HSCC was correlated with the infiltration ratio of immune cells, and a change in autophagy activity may affect the cellular immunity in HSCC. The ratios of tCD8(+)/CD39(+) and tCD8(+)/CD163(+) may serve as prognostic factors for HSCC."
4334,Simple transport and cryopreservation of cold-stored mouse embryos,"The cold storage of two-cell embryos is a useful technique for transporting genetically engineered mice without the shipment of live animals. However, the developmental ability of cold-stored embryos decreases with prolonged storage periods. Therefore, the transported embryos must be readily transferred to recipient mice upon arrival. The cryopreservation of cold-transported embryos may improve the flexibility of the schedule of embryo transfer. In this paper, we examined the viability and developmental ability of vitrified-warmed mouse embryos at the two-cell stage after cold storage in refrigerated temperatures for 0, 24, 48, 72, or 96 h. The viability of vitrified-warmed embryos after cold storage was comparable to vitrified-warmed embryos without cold storage. Vitrified-warmed embryos after cold storage also developed normally to pups by embryo transfer. In addition, live pups were obtained from vitrified-warmed embryos after cold-transportation from Asahikawa Medical University. In summary, cold-stored embryos can be used for the transportation and archive of genetically engineered mice."
4335,"‘I do what a woman should do’: a grounded theory study of women’s menstrual experiences at work in Mukono District, Uganda","Menstrual health has received increasing recognition as an essential issue for public health and gender equality. A growing body of research has elucidated adolescent girls’ menstrual needs and informed policy and practice responses. However, the experiences of adult women have received little attention, particularly in the workplace where many spend a significant proportion of their lives. To address this gap, we took a grounded theory approach to generate a nuanced understanding of working women’s menstrual experiences, and the impact of menstruation on their work and health in Mukono District, Uganda. In-depth interviews were undertaken with 35 women aged 18–49. This included 21 women working in markets, 7 teachers and 7 healthcare facility workers. Frequent collaborative analysis sessions throughout data collection, coding of interview transcripts, and generation of participant, workplace, and category memos facilitated analysis. Our core category and underlying theory, ‘being a responsible woman’, underpinned women’s experiences. ‘Being responsible’ meant keeping menstruation secret, and the body clean, at all times. These gendered expectations meant that any difficulty managing menses represented a failure of womanhood, met with disgust and shame. Difficulties with menstrual pain and heavy bleeding were excepted from these expectations and perceived as requiring compassion. Commercial menstrual products were expensive for most women, and many expressed concerns about the quality of cheaper brands. Workplace infrastructure, particularly unreliable water supply and cleanliness, was problematic for many women who resorted to travelling home or to other facilities to meet their needs. Menstruation presented a burden at work, causing some women to miss work and income, and many others to endure pain, discomfort and anxiety throughout their day. Our findings can inform norm and resource-focused responses to improve experiences and should provoke critical reflection on the discourse used in menstrual health advocacy in Uganda."
4336,"Service, science, and fortitude: Our thanks and salute to Dr. Anthony S. Fauci, October 2020",
4337,Dermpath & Clinic: Where the shoe pinches — painful plantar plaque,
4338,International growth of individual placement and support,
4339,Shedding light on those who provide support,An eLife survey explores the experiences of those in the research community who support colleagues struggling with their mental health.
4340,Potential factors that influence usage of complementary and alternative medicine worldwide: a systematic review,"OBJECTIVES: To determine similarities and differences in the reasons for using or not using complementary and alternative medicine (CAM) amongst general and condition-specific populations, and amongst populations in each region of the globe. METHODS: A literature search was performed on Pubmed, ScienceDirect and EMBASE. Keywords: ‘herbal medicine’ OR ‘herbal and dietary supplement’ OR ‘complementary and alternative medicine’ AND ‘reason’ OR ‘attitude’. Quantitative or qualitative original articles in English, published between 2003 and 2018 were reviewed. Conference proceedings, pilot studies, protocols, letters, and reviews were excluded. Papers were appraised using valid tools and a ‘risk of bias’ assessment was also performed. Thematic analysis was conducted. Reasons were coded in each paper, then codes were grouped into categories. If several categories reported similar reasons, these were combined into a theme. Themes were then analysed using χ(2) tests to identify the main factors related to reasons for CAM usage. RESULTS: 231 publications were included. Reasons for CAM use amongst general and condition-specific populations were similar. The top three reasons for CAM use were: (1) having an expectation of benefits of CAM (84% of publications), (2) dissatisfaction with conventional medicine (37%) and (3) the perceived safety of CAM (37%). Internal health locus of control as an influencing factor was more likely to be reported in Western populations, whereas the social networks was a common factor amongst Asian populations (p < 0.05). Affordability, easy access to CAM and tradition were significant factors amongst African populations (p < 0.05). Negative attitudes towards CAM and satisfaction with conventional medicine (CM) were the main reasons for non-use (p < 0.05). CONCLUSIONS: Dissatisfaction with CM and positive attitudes toward CAM, motivate people to use CAM. In contrast, satisfaction with CM and negative attitudes towards CAM are the main reasons for non-use. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-020-03157-2."
4341,Simvastatin Induces Unfolded Protein Response and Enhances Temozolomide-Induced Cell Death in Glioblastoma Cells,"Glioblastoma (GBM) is the most prevalent malignant primary brain tumor with a very poor survival rate. Temozolomide (TMZ) is the common chemotherapeutic agent used for GBM treatment. We recently demonstrated that simvastatin (Simva) increases TMZ-induced apoptosis via the inhibition of autophagic flux in GBM cells. Considering the role of the unfolded protein response (UPR) pathway in the regulation of autophagy, we investigated the involvement of UPR in Simva–TMZ-induced cell death by utilizing highly selective IRE1 RNase activity inhibitor MKC8866, PERK inhibitor GSK-2606414 (PERKi), and eIF2α inhibitor salubrinal. Simva–TMZ treatment decreased the viability of GBM cells and significantly increased apoptotic cell death when compared to TMZ or Simva alone. Simva–TMZ induced both UPR, as determined by an increase in GRP78, XBP splicing, eukaryote initiation factor 2α (eIF2α) phosphorylation, and inhibited autophagic flux (accumulation of LC3β-II and inhibition of p62 degradation). IRE1 RNase inhibition did not affect Simva–TMZ-induced cell death, but it significantly induced p62 degradation and increased the microtubule-associated proteins light chain 3 (LC3)β-II/LC3β-I ratio in U87 cells, while salubrinal did not affect the Simva–TMZ induced cytotoxicity of GBM cells. In contrast, protein kinase RNA-like endoplasmic reticulum kinase (PERK) inhibition significantly increased Simva–TMZ-induced cell death in U87 cells. Interestingly, whereas PERK inhibition induced p62 accumulation in both GBM cell lines, it differentially affected the LC3β-II/LC3β-I ratio in U87 (decrease) and U251 (increase) cells. Simvastatin sensitizes GBM cells to TMZ-induced cell death via a mechanism that involves autophagy and UPR pathways. More specifically, our results imply that the IRE1 and PERK signaling arms of the UPR regulate Simva–TMZ-mediated autophagy flux inhibition in U251 and U87 GBM cells."
4342,Gene Chip for Viral Discovery,
4343,SARS Resources,
4344,Structure of a Conserved RNA Element in the SARS Virus Genome Determined,
4345,Mass Spectometry–Based SARS Genotyping,
4346,New Frameshifting Pseudoknot Found in SARS Virus,
4347,A Novel Virus for Croup,
4348,Casting a Wide Net to Fight Coronaviruses,
4349,Correction: Design of Wide-Spectrum Inhibitors Targeting Coronavirus Main Proteases,
4350,The Difficulties of Predicting the Outbreak Sizes of Epidemics,
4351,Pushing and pulling,
4352,Pathological Clues to How the SARS Virus Kills,
4353,TaqMan probe array for quantitative detection of DNA targets,"To date real-time quantitative PCR and gene expression microarrays are the methods of choice for quantification of nucleic acids. Herein, we described a unique fluorescence resonance energy transfer-based microarray platform for real-time quantification of nucleic acid targets that combines advantages of both and reduces their limitations. A set of 3′ amino-modified TaqMan probes were designed and immobilized on a glass slide composing a regular microarray pattern, and used as probes in the consecutive PCR carried out on the surface. During the extension step of the PCR, 5′ nuclease activity of DNA polymerase will cleave quencher dyes of the immobilized probe in the presence of nucleic acids targets. The increase of fluorescence intensities generated by the change in physical distance between reporter fluorophore and quencher moiety of the probes were collected by a confocal scanner. Using this new approach we successfully monitored five different pathogenic genomic DNAs and analyzed the dynamic characteristics of fluorescence intensity changes on the TaqMan probe array. The results indicate that the TaqMan probe array on a planar glass slide monitors DNA targets with excellent specificity as well as high sensitivity. This set-up offers the great advantage of real-time quantitative detection of DNA targets in a parallel array format."
4354,Correction: Functional and Genetic Analysis of Coronavirus Replicase-Transcriptase Proteins,
4355,A Macaque Model of SARS,
4356,Clinical Vignettes,
4357,Authors' Response to Hogan,
4358,Epitope-based vaccines: SARS – a model,
4359,Correction: Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants,
4360,Abtracts from the 30th Annual Meeting of the Society of General Internal Medicine,
4361,Section II: Poster Sessions,
4362,Section I: Oral Sessions,
4363,Poster presentations,
4364,Coronaviruses: Molecular and Cellular Biology,Coronaviruses: Molecular and Cellular Biology
4365,Travel Medicine: Tales Behind the Science,
4366,Encyclopedia of Infectious Diseases: Modern Methodologies,
4367,"Emerging Infectious Diseases: Trends and Issues, 2nd Edition",
4368,Animal Viruses: Molecular Biology,
4369,Risky Trade: Infectious Disease in the Era of Global Trade,
4370,Section I: Oral Sessions,
4371,Resistance of livestock to viruses: mechanisms and strategies for genetic engineering,
4372,Abstract,
4373,SARS: How a global epidemic was stopped,
4374,9th Annual Conference on New and Re-emerging Infectious Diseases,
4375,Novel and Re-emerging Respiratory Viral Diseases: Novartis Foundation Symposium 290,
4376,Emerging Infections in Asia,
4377,21st ESICM Annual Congress,
4378,21st ESICM Annual Congress,
4379,"Contagion and Chaos: Disease, Ecology, and National Security in the Era of Globalization",
4380,“Nature Hath Fram’d Strange Fellows in Her Time”,
4381,Correction: In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation,
4382,10th Annual Conference on New and Re-emerging Infectious Diseases,
4383,Emerging Viruses in Human Populations,
4384,Lung recruitment and PEEP response in ARDS-related H1N1 virus patients,
4385,Large-scale implementation of a critical care surge capacity management program,
4386,"Henri Matisse (1869–1954). Icarus (from the illustrated book, Jazz, published in 1947 by E. Tériade)",
4387,The Global Threat of New and Reemerging Infectious Diseases: Reconciling U.S. National Security and Public Health Policy,
4388,Jan Steen (c. 1625–1679). Beware of Luxury (c. 1665).,
4389,"Jacques-Louis David (1748–1825). Coronation of Empress Josephine by Napoleon I at Notre Dame de Paris, 2 December 1804 (1806–1807)",
4390,Atlas of Travel Medicine and Health,
4391,Association for Molecular Pathology 2009 Meeting Abstracts,
4392,Association for Molecular Pathology 2008 Meeting Abstracts,
4393,Those Who Can See Invisible Can Do Impossible!,
4394,Bacterial contamination of platelet concentrates: pathogen detection and inactivation methods,"Whereas the reduction of transfusion related viral transmission has been a priority during the last decade, bacterial infection transmitted by transfusion still remains associated to a high morbidity and mortality, and constitutes the most frequent infectious risk of transfusion. This problem especially concerns platelet concentrates because of their favorable bacterial growth conditions. This review gives an overview of platelet transfusion-related bacterial contamination as well as on the different strategies to reduce this problem by using either bacterial detection or inactivation methods."
4395,Adoption of an infection prevention and control programme (IPCP) in the Republic of Kiribati: a case study in diffusion of innovations theory,
4396,The RNA polymerase activity of SARS-coronavirus nsp12 is primer dependent,
4397,Correction: The Murine Coronavirus Hemagglutinin-esterase Receptor-binding Site: A Major Shift in Ligand Specificity through Modest Changes in Architecture,
4398,"SISEA activities in Pasteur Institute in Nha Trang, Vietnam, during 2008–2009",
4399,Identification of viruses in Acute Lower Respiratory Infections (ALRI) in Lao People's Democratic Republic,
4400,Investigation of Antibody-Dependent Enhancement (ADE) of SARS coronavirus infection and its role in pathogenesis of SARS,
4401,The SARS coronavirus E protein interacts with the PALS1 and alters tight junction formation and epithelial morphogenesis,
4402,"Red Book: 2006 Report of the Committee on Infectious Diseases, 27th Edition",
4403,Molecular Pathogenesis of Virus Infections,
4404,"The Germ Freak's Guide to Outwitting Colds and Flu: Guerilla Tactics to Keep Yourself Healthy at Home, at Work, and in the World",
4405,Correction: SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b,
4406,"The Dictionary of Virology, 4th Edition",
4407,Relationship between reactive hemophagocytic syndrome (RHS) and multiple organ system failure (MOSF),
4408,Correction,
4409,Ethics and Epidemics,
4410,A Clinician's Dictionary of Pathogenic Microorganisms,
4411,Third Congress for the European Society for Emerging Infections,
4412,Emergence and Control of Viral Respiratory Diseases,
4413,SARS Coronaviruses and Highly Pathogenic Influenza Viruses: Safety and Occupational Health for Laboratory Workers,
4414,"Correction, vol. 10, no. 9",
4415,New and Re-Emerging Infectious Diseases,
4416,Manual of Travel Medicine and Health,Manual of Travel Medicine and Health
4417,Healthcare-related Infectious Diseases,
4418,Women and Infectious Disease—Chronic Disease Interactions,
4419,Infectious Diseases and Maternal Morbidity and Mortality,
4420,"SARS, the First Pandemic of the 21st Century",
4421,International Conference on Emerging Infectious Diseases,
4422,Malaria and the HIV virus: is there any interaction?,
4423,Respiratory Herpes simplex virus at the intensive care unit: a prospective study,
4424,Microbe: Are We Ready for the Next Plague?,
4425,"Behind the Mask: How the World Survived SARS, the First Epidemic of the 21st Century",
4426,"Acute respiratory infections, influenza-like illness and JIA: impact on disease activity and response to the influenza vaccine",
4427,Correction: Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus,
4428,The 26th Annual Symposium of The Protein Society: Abstracts,
4429,Poster Sessions,
4430,"50th Golden Jubilee Conference of Indian Society of Hematology & Transfusion Medicine ISHTM 2009, November 19–22, 2009, New Delhi, India",
4431,"Section VIII: Submitted abstracts selected for poster presentations — Session II, Friday, October 22, 2004",
4432,Thalidomide modulates macrophage-mediated inflammatory innate immune response during Klebsiella pneumoniae B5055 infection in BALB/c mice,
4433,Use of Toll-Like Receptor 3 Agonists Against Respiratory Viral Infections,"Respiratory RNA viruses are constantly evolving, thus requiring development of additional prophylactic and therapeutic strategies. Harnessing the innate immune system to non-specifically respond to viral infection has the advantage of being able to circumvent viral mutations that render the virus resistant to a particular therapeutic agent. Viruses are recognized by various cellular receptors, including Toll-like receptor (TLR) 3 which recognizes double-stranded (ds)RNA produced during the viral replication cycle. TLR3 agonists include synthetic dsRNA such as poly (IC), poly (ICLC) and poly (AU). These agents have been evaluated and found to be effective against a number of viral agents. One major limitation has been the toxicity associated with administration of these drugs. Significant time and effort have been spent to develop alternatives/modifications that will minimize these adverse effects. This review will focus on the TLR3 agonist, poly (IC)/(ICLC) with respect to its use in treatment/prevention of respiratory viral infections."
4434,"Genome sequences published outside of Standards in Genomic Sciences, October - November 2012","The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office."
4435,"Genome sequences published outside of Standards in Genomic Sciences, July - October 2012","The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office."
4436,"Abstracts of the Papers Presented in the XIX National Conference of Indian Virological Society, “Recent Trends in Viral Disease Problems and Management”, on 18–20 March, 2010, at S.V. University, Tirupati, Andhra Pradesh",
4437,High incidence of respiratory viruses in critically ill adult patients with respiratory failure,
4438,Lethal influenza virus A H1N1 infection in two relatives with autosomal dominant GATA-2 deficiency,
4439,"Abstracts of the Papers (Oral/Poster) Presented During the XXI National Conference of Indian Virological Society (IVS) on “Immunobiology and Management of Viral Diseases in 21st Century”, Held from 8–10 November, 2012, at Indian Veterinary Research Institute (IVRI) Mukteswar Campus, Mukteswar, Nainital 263138, Uttarakhand",
4440,P042: Severe influenza infections requiring intensive care during winter 2012/2013,
4441,NEWS,
4442,Savage Nature and Ecologic Exchange,
4443,NEWS,
4444,Viral encephalitis caused by respiratory viruses,
4445,Thank you to Virology Journal's peer reviewers in 2013,"The editors of Virology Journal would like to thank all our reviewers who have contributed to the journal in Volume 10 (2013). The success of any scientific journal depends on an effective and strict peer review process and Virology Journal could not operate without your contribution. We are grateful to the large number of reviewers (1026 to be exact!), who have done a great job in not only lifting the quality of the journal’s scientific peer reviewing process, but also helped us to achieve our goal of a median time to first decision of just 35 days. Our record time from submission to online, open access, publication in 2013 was 22 days for a Research Article [1] and 28 days for a Review [2]. This is a great achievement by any standard. We look forward to your continuous support of Virology Journal either as an invited reviewer or a contributing author in the years to come."
4446,"2014 ACMT Annual Scientific Meeting—March 28–30, 2014 Phoenix, AZ, USA",
4447,Truth in the Details,
4448,Middle East Respiratory Syndrome Coronavirus Infection in Dromedary Camels in Saudi Arabia,
4449,Mouse Development From Oocyte to Stem Cells,
4450,The Ups and Downs of Emerging Infectious Diseases at Your Fingertips,
4451,Correction: Triple Immunoglobulin Gene Knockout Transchromosomic Cattle: Bovine Lambda Cluster Deletion and Its Effect on Fully Human Polyclonal Antibody Production,
4452,Quiet Moment around the Campfire,
4453,Informing U.S. Federal Public Health Preparation for Emerging Virus Pandemic Threats at Ports of Entry,
4454,Village Doctors’ Acceptability to a Syndromic Surveillance System in Rural China,
4455,Searching for MERS and Novel Flu with Limited Resources,
4456,The Evolution of the WHO/NREVSS Influenza Surveillance System: The Challenges and Opportunities that Accompany Electronic Laboratory Data,
4457,Federal Interagency Interactions During Outbreaks of H7N9 Influenza and MERS-CoV,
4458,Methods To Identify Aptamers against Cell Surface Biomarkers,"Aptamers are nucleic acid-based ligands identified through a process of molecular evolution named SELEX (Systematic Evolution of Ligands by Exponential enrichment). During the last 10-15 years, numerous aptamers have been developed specifically against targets present on or associated with the surface of human cells or infectious pathogens such as viruses, bacteria, fungi or parasites. Several of the aptamers have been described as potent probes, rivalling antibodies, for use in flow cytometry or microscopy. Some have also been used as drugs by inhibiting or activating functions of their targets in a manner similar to neutralizing or agonistic antibodies. Additionally, it is straightforward to conjugate aptamers to other agents without losing their affinity and they have successfully been used in vitro and in vivo to deliver drugs, siRNA, nanoparticles or contrast agents to target cells. Hence, aptamers identified against cell surface biomarkers represent a promising class of ligands. This review presents the different strategies of SELEX that have been developed to identify aptamers for cell surface-associated proteins as well as some of the methods that are used to study their binding on living cells."
4459,Echinacea—A Source of Potent Antivirals for Respiratory Virus Infections,"Extracts of Echinacea species have been used traditionally in North America for the control of symptoms of colds, influenza, and other diseases, and some of them have become very popular as “herbal medicines”. Recent studies have revealed that preparations derived from certain species and plant parts, but not all of them, possess potent antiviral activities, at non-cytotoxic concentrations, particularly against membrane-containing viruses. Thus all strains of human and avian influenza viruses tested (including a Tamiflu-resistant strain), as well as herpes simplex virus, respiratory syncytial virus, and rhinoviruses, were very sensitive to a standardized Echinacea purpurea preparation. In mechanistic studies the influenza virus-specific hemagglutinin and neuraminidase were inhibited. In addition some extracts displayed anti-inflammatory activity in virus-infected cells, and numerous other effects on the expression of cellular genes. Multiple components, either discrete compounds or mixtures, appeared to be responsible for the various antiviral activities."
4460,Lower airway sampling greatly increases detection of respiratory viruses in critically ill patients: the COURSE study,
4461,Design and implementation of needs-specific critical care response teams,
4462,Computerised tomography (CT) in severe acute respiratory syndrome (SARS): late-stage acute respiratory disease syndrome (ARDS) and follow-up findings,
4463,Critically ill patients with severe acute respiratory syndrome (SARS) in a designated national SARS ICU: clinical features and predictors for mortality,
4464,Retrospective analysis of critically ill patients with severe acute respiratory syndrome admitted to an intensive care unit,
4465,Increase in methicillin-resistant Staphylococcus aureus acquisition and change in pathogen pattern associated with outbreaks of severe acute respiratory syndrome (SARS),
4466,"Abstracts of the XX World Allergy Congress™ 2007 December 2-6, 2007, Bangkok, Thailand",
4467,Correction: Coronaviruses Lacking Exoribonuclease Activity Are Susceptible to Lethal Mutagenesis: Evidence for Proofreading and Potential Therapeutics,
4468,Correction: Infection with MERS-CoV Causes Lethal Pneumonia in the Common Marmoset,
4469,MERS-CoV,
4470,"Year in review in Intensive Care Medicine 2014: I. Cardiac dysfunction and cardiac arrest, ultrasound, neurocritical care, ICU-acquired weakness, nutrition, acute kidney injury, and miscellaneous",
4471,"Year in review in Intensive Care Medicine 2014: II. ARDS, airway management, ventilation, adjuvants in sepsis, hepatic failure, symptoms assessment and management, palliative care and support for families, prognostication, organ donation, outcome, organisation and research methodology",
4472,Public health round-up,
4473,Public health round-up,
4474,"A survey of UK acute clinicians' knowledge of personal protective requirements for infectious diseases and chemical, biological, and radiological warfare agents",
4475,Prevalence of viral respiratory tract infections in acutely admitted and ventilated ICU patients: a prospective multicenter observational study,
4476,Middle East respiratory syndrome coronavirus (MERS-Cov) screening of exposed healthcare workers in a tertiary care hospital in Saudi Arabia,
4477,Infection prevention and control strategies for the Middle East respiratory syndrome coronavirus and outcome in Oman,
4478,Public health round-up,
4479,"Evaluation of REDCap as a Tool for Outbreak Data Management, Illinois, 2013-2014",
4480,2014 International Society for Disease Surveillance Conference Translating Research and Surveillance into Action,
4481,Response of the National Biosurveillance Integration Center to the Emergence of Porcine Epidemic Diarrhea Virus in the United States,
4482,Use of Syndromic Data for Enhanced Surveillance: MERS Like-Syndrome,
4483,Overcoming Operational Differences to Attain a National Picture for Novel Threats,
4484,"Ebola, Enterovirus, MERS, Novel Flu, and other Challenges for Public Health Surveillance Practitioners",
4485,8(th) International conference on management and rehabilitation of chronic respiratory failure: the long summaries – Part 3,"This paper summarizes the Part 3 of the proceedings of the 8(th) International Conference on Management and Rehabilitation of Chronic Respiratory Failure, held in Pescara, Italy, on 7 and 8 May, 2015. It summarizes the contributions from numerous experts in the field of chronic respiratory disease and chronic respiratory failure. The outline follows the temporal sequence of presentations. This paper (Part 3) presents a section regarding Moving Across the Spectrum of Care for Long-Term Ventilation (Moving Across the Spectrum of Care for Long-Term Ventilation, New Indications for Non-Invasive Ventilation, Elective Ventilation in Respiratory Failure - Can you Prevent ICU Care in Patients with COPD?, Weaning in Long-Term Acute Care Hospitals in the United States, The Difficult-to-Wean Patient: Comprehensive management, Telemonitoring in Ventilator-Dependent Patients, Ethics and Palliative Care in Critically-Ill Respiratory Patients, and Ethics and Palliative Care in Ventilator-Dependent Patients)."
4486,Clinical characteristics and short-term outcomes of hiv patients admitted to an african intensive care unit,
4487,"One Health: People, Animals, and the Environment",
4488,2014 ACVIM Forum Research Report Program,
4489,Oral Research Communications of the 23rd ECVIM‐CA Congress,
4490,Research Communications of the 24th ECVIM‐CA Congress,
4491,The 2014–2015 Ebola outbreak in West Africa: Hands On,"The International Consortium for Prevention and Infection Control (ICPIC) organises a biannual conference (ICPIC) on various subjects related to infection prevention, treatment and control. During ICPIC 2015, held in Geneva in June 2015, a full one-day session focused on the 2014–2015 Ebola virus disease (EVD) outbreak in West Africa. This article is a non-exhaustive compilation of these discussions. It concentrates on lessons learned and imagining a way forward for the communities most affected by the epidemic. The reader can access video recordings of all lectures delivered during this one-day session, as referenced. Topics include the timeline of the international response, linkages between the dynamics of the epidemic and infection prevention and control, the importance of community engagement, and updates on virology, diagnosis, treatment and vaccination issues. The paper also includes discussions from public health, infectious diseases, critical care and infection control experts who cared for patients with EVD in Africa, in Europe, and in the United Sates and were involved in Ebola preparedness in both high- and low-resource settings and countries. This review concludes that too little is known about the pathogenesis and treatment of EVD, therefore basic and applied research in this area are urgently required. Furthermore, it is clear that epidemic preparedness needs to improve globally, in particular through the strengthening of health systems at local and national levels. There is a strong need for culturally sensitive approaches to public health which could be designed and delivered by social scientists and medical professionals working together. As of December 2015, this epidemic killed more than 11,000 people and infected more than 28,000; it has also generated more than 17,000 survivors and orphans, many of whom face somatic and psychological complications. The continued treatment and rehabilitation of these people is a public health priority, which also requires an integration of specific medical and social science approaches, not always available in West Africa."
4492,Perspective and Surprise in the Floating World,
4493,Back Cover,
4494,Front Cover,
4495,2015 ACVIM Forum Research Abstract Program,
4496,Proceedings 26th Symposium ESVN‐ECVN,
4497,2014 ACVIM Forum Research Abstracts Program,
4498,"XXIV World Allergy Congress 2015: Seoul, Korea. 14-17 October 2015","A1 Pirfenidone inhibits TGF-b1-induced extracellular matrix production in nasal polyp-derived fibroblasts Jae-Min Shin, Heung-Man Lee, Il-Ho Park A2 The efficacy of a 2-week course of oral steroid in the treatment of chronic spontaneous urticaria refractory to antihistamines Hyun-Sun Yoon, Gyeong Yul Park A3 The altered distribution of follicular t helper cells may predict a more pronounced clinical course of primary sjögren’s syndrome Margit Zeher A4 Betamethasone suppresses Th2 cell development induced by langerhans cell like dendritic cells Katsuhiko Matsui, Saki Tamai, Reiko Ikeda A5 An evaluation of variousallergens in cases of allergic bronchial asthma at lucknow and neighbouring districts by intradermal skintest Drsushil Suri, Dranu Suri A6 Evaluation ferqency of ADHD in childhood asthma Marzieh Heidarzadeh Arani A7 Steven johnson syndrome caused by typhoid fever in a child Azwin Lubis, Anang Endaryanto A8 Chronic Bronchitis with Radio Contrast Media Hypersensitivity: A Case with Hypothesized GINA Step 1 Asthma Shinichiro Koga A9 The association between asthma and depression in Korean adult : An analysis of the fifth korea national health and nutrition examination survey (2010-2012) Lee Ju Suk A10 Management of allergic disease exacerbations in pregnancy Yasunobu Tsuzuki A11 Subcutaneous immunotherapy mouse model for atopic dermatitis Seo Hyeong Kim, Jung U Shin, Ji Yeon Noh, Shan Jin, Shan Jin, Hemin Lee, Jungsoo Lee, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee A12 Atopic disease and/or atopy are risk factors for local anesthetic allergy in patients with history of hypersensitivity reactions to drugs? Fatma Merve Tepetam A13 Food hypersensitivity in patients with atopic dermatitis in Korea Chun Wook Park, Jee Hee Son, Soo Ick Cho, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Hye One Kim, Hee Jin Cho A14 Anaphylaxis caused by an ant (Brachyponera chinensis) in Japan Yoshinori Katada, Toshio Tanaka, Akihiko Nakabayashi, Koji Nishida, Kenichi Aoyagi, Yuki Tsukamoto, Kazushi Konma, Motoo Matsuura, Jung-Won Park, Yoshinori Harada, Kyoung Yong Jeong, Akiko Yura, Maiko Yoshimura A15 Anti-allergic effect of anti-IL-33 by suppression of immunoglobulin light chain and inducible nitric oxide synthase Tae-Suk Kyung, Young Hyo Kim, Chang-Shin Park, Tae Young Jang, Min-Jeong Heo, Ah-Yeoun Jung, Seung-Chan Yang A16 Food hypersensitivity in patients with chronic urticaria in Korea Hye One Kim, Yong Se Cho, Yun Sun Byun, Yoon Seok Yang, Bo Young Chung, Jee Hee Son, Chun Wook Park, Hee Jin Cho A17 Dose optimizing study of a depigmented polymerized allergen extract of phleum pollen by means of conjunctival provocation test (CPT) Angelika Sager, Oliver Pfaar A18 Correlation of cutaneous sensitivity and cytokine response in children with asthma Amit Agarwal, Meenu Singh, Bishnupda Chatterjee, Anil Chauhan A19 Colabomycin E, a Streptomycete-Derived Secondary Metabolite, Inhibits Proinflammatory Cytokines in Human Monocytes/Macrophages Ilja Striz, Eva Cecrdlova, Katerina Petrickova, Libor Kolesar, Alena Sekerkova, Veronika Svachova, Miroslav Petricek A20 Intravenous immunoglobluin treatment in a child with resistant atopic dermatitis: A brief review on this therapeutic regimen Hyuck Hoon Kwon, Kyu Han Kim A21 Wheat allergy is difficult to diagnose then other food allergens Suman Kumar A22 The effects of spirulina (Arthrospira platensis) dietary supplement as an adjunct therapy for children aged 7 to 14 years old with asthma: A randomized - double blind placebo controlled clinical trial Lou Ver Leigh Arciaga Manzon, Pilar Agnes Gonzalez Andaya A23 The study about cause and clinicopathological findings of injection induced dermatitis Bark-Lynn Lew, Youngjun Oh, Dongwoo Suh, Woo-Young Sim A24 IgE reactivity of recombinant allergen pac c 3 of the Asian needle ant pachycondyla chinensis Kyoung Yong Jeong, Myung-Hee Yi, Mina Son, Dongpyo Lyu, Jae-Hyun Lee, Tai-Soon Yong, Chein-Soo Hong, Jung-Won Park A25 Characterization of specific IgE antibody related to antigen 5 of echinococcus granulosus Mohammadreza Siavashi A26 Development of binary forecast model of asthma exacerbation: Asthma index Hey Suk Yun, Ha-Na Kang, Jae-Won Oh, Young Jin Choi A27 Different levels in rantes, IL-5 and TNF-á between the nasal polyps of adolescents with allergic, local allergic and non-allergic rhinitis Ha-Na Kang, Jae-Won Oh, Young Jin Choi A28 Tgfβ1 level is associated with VDR gene polymorphism in children with allergy diseases Tatiana Sentsova, Ilya Vorozhko, Olga Chernyak, Vera Revyakina, Anna Timopheeva, Andrey Donnikov A29 Dynamics of immunological biomarkers in children with food allergy fed goat milk formula Tatiana Sentsova, Ilya Vorozhko, Olga Chernyak, Vera Revyakina, Anna Timopheeva A30 Association between obesity, abdominal obesity and adiposity and the prevalence of atopic dermatitis in young Korean adults: The korea national health and nutrition examination survey, 2008–2010 Ji Hyun Lee, Young Min Park, Sang Soo Choi, Kyung Do Han, Han Mi Jung, Young Hoon Youn, Jun Young Lee, Yong Gyu Park, Seung-Hwan Lee A31 Associations of natural history and environmental factors with asthma among children in rural and urban areas of guangdong, China Zhaowei Yang, Jing Li, Mulin Feng, Marjut Roponen, Bianca Schaub, Gary WK Wong A32 The effect of CO2-enriched atmospheres to producing of allergenic pollen by ragweed Young Jin Choi, Ha-Na Kang, Jae-Won Oh A33 Application evaluation of house dust mite and components specific-IgE and IgG4 in specific immunotherapy with allergic diseases Baoqing Sun, Peiyan Zheng A34 Effect of Asian dust events on asthma according to the socioeconomic status using claim data in KOREA Yoon-Sung Park A35 TSLP downregulates human â-defensin 2 through STAT3-dependent pathway in keratinocytes Sang Wook Son A36 Effects of anti-IgE on IL-4, IL-5, IL-17, and CD19,20,200 in a case of netherton syndrome (SPINK5 mutation) Arzu Didem Yalcin, Sukran Kose, Kemal Kiraz A37 Augmentation of arginase 1 expression exacerbates airway inflammation in murine asthma models Jin-Young Lee, Sehyo Yune, Jae-Won Paeng, Mi-Jung Oh, Byung-Jae Lee, Dong-Chull Choi, Young Hee Lim, Kyoung Won Ha A38 Caregivers of children with no food allergy – their experiences and perception of the condition Kiwako Yamamoto-Hanada, Masami Narita, Masaki Futamura, Yukihiro Ohya A39 Evaluation of Drug Provocation Tests in Korean Children: A Single Center Experience Jihyun Kim, Jinwha Choi, Kwanghoon Kim, Jaehee Choi, Kangmo Ahn A40 Danyoung classification 2015 update by digital HD endoscopic evaluation SUN-HO/Brian Chang A41 Effect on quality of life of the mixed house dust mite/weed pollen extract immunotherapy in polysensitized patients Lisha Li A42 Ambient desert dust and allergic symptoms: A time series analysis from a national birth cohort (JECS) Kumiko Tsuji Kanatani, Yu-Ichi Adachi A43 Individuals Allergic to Cow’s Milk Should be Vigilant When Consuming Beef Because It May be Injected Beef Shigeyuki Narabayashi, Ikuo Okafuji, Yuya Tanaka, Satoru Tsuruta, Nobue Takamatsu A44 Quality of life of chronic rhinosinusitis patients with or without nasal polyps in Korea Soo Whan Kim, Do Hyun Kim A45 House dust mite sensitization and exacerbation of asthma in the fall in children Jong-Seo Yoon, Jin Tack Kim, Hwan Soo Kim, Yoon Hong Chun, Hyun Hee Kim, Sul Mui Won A46 Evidence-based health advice for childhood eczema and household pets Kam Lun E. Hon, Chung Mo Chow, Ting Fan Leung A47 Relationship between allergic rhinitis and mental health in korea Do Hyun Kim, Soo Whan Kim A48 Oscillometric bronchodilator response in 3 to 5 years old healthy and asthmatic Filipino children Gemmalyn Esguerra, Emily Resurreccion, Kristine Elisa Kionisala, Jenni Rose Dela Cruz A49 The use of aeroallergen immunotherapy to treat eosinophilic esophagitis Muhammad Imran A50 A study of the eczema herpeticum in Korean Yun Seon Choe, Kyu Han Kim, Mira Choi A51 Specific sublingual immunotherapy in Korean patients with atopic dermatitis Byung Soo Kim, Hyun-Joo Lee, Jeong-Min Kim, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Je-Ho Mun, Hoon-Soo Kim, Margaret Song, Hyun-Chang Ko, Hyun-Chang Ko, Moon-Bum Kim A52 Association between polymorphisms in bitter taste receptors genes and clinical features in Korean asthmatics Sun-Young Yoon A53 Effect of glycosides based standardized fenugreek seed extract in bleomycin-induced pulmonary fibrosis in rats Amit Kandhare A54 A kampo formula, ogi-kenchu-to, decreases side-effects of steroid ointment for infantile atopic dermatitis: Three cases report Noriko Yahiro A55 To test use of jet nebulizers NE-C802 as a drug delivery system in the children with asthma Amit Agarwal, Meenu Singh, Jasleen Kaur, Ruby Pawankar, Pankaj Pant, Sukhmanjeet Singh A56 Immunoglobulin e to allergen components of house dust mite in Korean children with allergic disease Hwan Soo Kim, Jong-Seo Yoon, Sul Mui Won, Yoon Hong Chun, Jin Tack Kim, Hyun Hee Kim A57 Effectiveness of premedication and rapid desensitization in hypersensitivity to l-asparaginase Hwan Soo Kim, Sul Mui Won, Yoon Hong Chun, Jong-Seo Yoon, Hyun Hee Kim, Jin Tack Kim A58 Angioedema with Eosinophilia: The First Report from Thailand Thatchai Kampitak A59 Evaluation of anti-pruritic and anti-inflammatory effects of Korean red ginseng extract on atopic dermatitis murine model So Min Kim, Hyun Joo Lee, Hei Sung Kim, Jeong Deuk Lee, Sang Hyun Cho A60 Subcutaneous autologous serum therapy in chronic urticaria Kiran Godse A61 Allergic bronchopulmonary aspergillosis in asthma and lung tuberculosis Juwita Soekarno, Sarie Ratnasari, E. Alwi Datau, Eko Surachmanto, JC Matheos A62 Infantile eczema is associated with campylobacter and roseburia subpopulations but not microbial diversity in stool samples of Chinese newborns Ting Fan Leung, Jamie Sui-Lam Kwok, Christine Kit-Ching Tung, Man Fung Tang, Stephen Kwok-Wing Tsui, Gary WK Wong, Kam Lun Ellis Hon, Wing Hung Tam, Hing Yee Sy A63 Association between serum chitinase level and toll-like receptor polymorphisms in bakery workers Sohee Lee A64 IFN-gamma contributes to nasal polypogenesis by inducing epithelial-to-mesenchymal transition via non-smad pathway Hyun-Woo Shin, Mingyu Lee, Dae Woo Kim, Roza Khalmuratova A65 Management and education status of anaphylaxis patients who visit our emergency room (ER) Mi Yeoung Kim, Jaewon Jeong, Chansun Park A66 Hypoallergen-Encoding DNA Plasmids As Immunoprophylactic Vaccines of Shrimp Tropomyosin Hypersensitivity Christine Yee Yan Wai, Patrick S.C. Leung, Nicki Y.H. Leung, Ka Hou Chu A67 The relationship between sputum pentraxin 3 levels and childhood asthma Hee Seon Lee, Kyung Eun Lee, Jung Yeon Hong, Mi Na Kim, Min Jung Kim, Yoon Hee Kim, In Suk Sol, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim A68 The role of local antibody responses in the nasal inflammation of allergic rhinitis (AR) patients Ji Hye Kim, Hae-Sim Park, Yoo Seob Shin, Young Min Ye, Daehong Seo, Moon Gyeong Yoon, Young Mok Lee A69 A case of ofloxacin-induced anaphylaxis by non-IgE, but specific IgG4-mediated responses Daehong Seo, Ji Hye Kim, Young-Mok Lee, Young Min Ye, Hae-Sim Park A70 Serum LTE4 metabolite as a biomarker for aspirin exacerbated respiratory disease Ga Young Ban, Kumsun Cho, Seung-Hyun Kim, Yong Eun Kwon, Moon Gyeong Yoon, Ji Hye Kim, Yoo Seob Shin, Young Min Ye, Dong-Ho Nahm, Hae-Sim Park A71 Local and systemic reactions of dust mite subcutaneous immunotherapy (SCIT) among children in a tertiary care hospital Pilar Agnes Gonzalez Andaya A72 Effects of carboxymethyl glucan (CM-glucan) in children with allergic rhinitis and asthma: A randomized controlled trial Pilar Agnes Gonzalez Andaya A73 Autophagy mechanisms in patients with severe asthma: A new therapeutic target Ga Young Ban, Chang Gyu Jung, Seung-Ihm Lee, Duy Le Pham, Dong-Hyeon Suh, Eun-Mi Yang, Young Min Ye, Yoo Seob Shin, Hae-Sim Park A74 Aggravation of airway inflammation and hypperresponsiveness following nasal challenge with dermatophagoides pteronyssinus in perennial allergic rhinitis patients without symptoms of asthma Wan Jun Wang, MO Xian, Yan Qing Xie, Jing Ping Zheng, Jing Li A75 Serum 25-hydroxyvitamin d in early childhood is non-linearly associated with allergy Emma Merike Savilahti, Outi Mäkitie, Anna Kaarina Kukkonen, Sture Andersson, Heli Viljakainen, Erkki Savilahti, Mikael Kuitunen A76 Fric test in dermographism Kiran Godse A77 Neutrophil autophagy and extracellular trap could contribute to asthma severity Duy Le Pham, Ga Young Ban, Seung-Hyun Kim, Eun-Mi Yang, Hae-Sim Park, Ji-Ho Lee, Yong-Joon Chwae A78 Redox Modulation for the Treatment of Toluene Diisocyanates-Induced Lung Inflammation Li-Ming Chin, Chi-Chang Shieh A79 A case of occupational asthma and rhinitis with anaphylaxis to Korean ginseng and sanyak Ji Hye Kim, Hye-Soo Yoo, Moon Gyeong Yoon, Ga Young Ban, Ga Young Ban, Yoo Seob Shin, Young Min Ye, Hae-Sim Park A80 Factors of influencing epidermal permeability barrier defects in atopic dermatitis children Myong Soon Sung, Jin Uck Choi, Sung Won Kim, Yong Jin Hwang A81 Innate type 2 response to aspergillusfumigatus in a murine model of atopic dermatitis-like skin inflammation Arum Park, Eun Lee, Song-I Yang, Hyun-Ju Cho, Jinho Yu A82 Activin a receptor 1C may implicate in the development of sensitive skin Dong Hun Lee, Eun Ju Kim, Yeon Kyung Kim, Eun Jin Doh, Hee Chul Eun, Jin Ho Chung, Young Mee Lee, Seon Pil Jin A83 Genetic association and eQTL analyses of genes associated with allergy in atopic/non-atopic asthma Xingnan Li, Naftali Kaminski, Sally Wenzel, Eugene Bleecker, Deborah Meyers A84 Gastroscope feature and clinical characteristics in 172 cases of children with henoch-schonlein purpura Zeng Huasong A85 The role of TRPV1 in CD4+ t cell mediated inflammatory response of allergic rhinitis Ji-Hun Mo, Ramachandran Samivel, Eun-Hee Kim, Ji-Hye Kim, Jun-Sang Bae, Young-Jun Chung, Dae Woo Kim A86 A Phenotype of Rhinitis from School Children Is Associated with the Development of Bronchial Hyperresponsiveness Eun Lee, Si Hyeon Lee, Young-Ho Kim, Hyun-Ju Cho, Ho-Sung Yu, Mi-Jin Kang, Song-I Yang, Young-Ho Jung, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So-Yeon Lee, Ho-Jang Kwon, Soo-Jong Hong A87 Increased basal activation status was noted in adult anaphylaxis patients Sailesh Palikhe, Hae-Sim Park, Seung-Hyun Kim, Ji Hye Kim, Eun-Mi Yang A88 Clinical values of interferon-gamma enzyme-linked immunospot assays for management of antibiotic hypersensitivity in hospitalized patients Suda Sibunruang, Jettanong Klaewsongkram A89 VDR gene polymorphism and 25-hydroxy vitamin d levels in children with food allergy Tatiana Sentsova, Ilya Vorozhko, Anna Timopheeva, Olga Chernyak, Vera Revyakina, Andrey Sokolnikov A90 An analysis of 145 oral almond challenge tests Makoto Nisihino, Yu Okada, Noriyuki Yanagida, Motohiro Ebisawa, Sakura Sato, Kiyotake Ogura, Tomoyuki Asaumi, Kenichi Nagakura, Tetsuharu Manabe, Hirotoshi Unno A91 Effect of creatine supplementation in fish allergenic potential; A proteomics study Pedro M Rodrigues, Denise Schrama, Gadija Mohamed, Lizex Hüsselmann, Lizex Hüsselmann, Bongani Ndimba A92 Flagellin modulates the function of invariant NKT cells via dendritic cells in asthma patients Jae-Uoong Shim, Young Il Koh, Joon Haeng Rhee, Ji-Ung Jeong A93 Clinical and subclinical manifestations of allopurinol – induced severe cutaneous adverse reactions in Vietnam Dinh Van Nguyen, Hieu Chi Chu, Mui Thi Tran, Christopher Vidal, Suran Fernando, Sheryl Van Nunen, Sy Van Than A94 Time course of serum inhibitory activity for facilitated allergen-IgE binding during house dust mite immunotherapy Mulin Feng, Jing Li A95 Periostin is a novel biomarker in eosinophilic nasal polyps of chronic rhinosinusitis Dong-Kyu Kim, Seung-No Hong, Kyoung Mi Eun, Hong Ryul Jin, Dae Woo Kim A96 Dominance of Th1-response in children with refractory mycoplasma pneumoniae pneumonia Jun Bao, Yi-Xiao Bao A97 Studies on the role of CD14 polymorphism among pollen and mold induced asthmatics of kolkata, India Sanjoy Podder, Goutam Kumar, Shampa Dutta, Amlan Ghosh A98 House dust mite allergy – Indian perspective Goutam Kumar Saha, Sanjoy Podder, Salil Kumar Gupta A99 Increased expression of purinergic (P2Y12) receptor and cysteinyl leukotriene receptors in the lung tissue of a mouse model of allergic asthma Tu/Hoang Kim Trinh, Yoo Seob Shin, Hae-Sim Park, Jing-Nan Liu, Duy Le Pham A100 Autologous serum skin test in chronic idiopathic urticaria - relationship with autoimmune markers and disease severity Hyun-Chang Ko, Byung Soo Kim, Moon-Bum Kim A101 Anxiety and depression levels in severe asthma patients treated with omalizumab Ömer Özbudak, Fatih Üzer A102 Economic burden of refractory chronic spontaneous urticaria on Kuwait health system Mona Al-Ahmad, Maryam Alowayesh, Norman Carroll A103 IgE-mediated maize allergy in India: A 28 kd protein responsible for food-induced allergic reaction Anand Bahadur Singh A104 Liposomal encapsulation of house dust mite allergens and dexamethasone modulates allergic response in a murine model of asthma Yordanis Pérez-Llano, María Del Carmen Luzardo Lorenzo, Wendy Ramírez González, Carlos Calcines Cruz, Rady Laborde Quintana, Alain Morejón, Virgilio Bourg, Marilé Hechavarría Stoker A105 Immune Suppressive Effects of Tonsil-Derived Mesenchymal Stem Cells for Eosinophilic Rhinosinusitis with Nasal Polyps in a Mouse Model Jun-Sang Bae, Ramachandran Samivel, Eun-Hee Kim, Ji-Hye Kim, Ji-Hun Mo A106 Second line treatments of dermographic urticaria refractory to antihistamines Keiko Hanaoka, Michihiro Hide, Akio Tanaka, Makiko Hiragun, Mikio Kawai A107 Diagnostic Value of Specific IgE to Peanut and Ara h 2 in Korean Children with Peanut Allergy Kwanghoon Kim, Kwanghoon Kim, Hye-Young Kim, Jihyun Kim, Kangmo Ahn, Youngshin Han A108 Inappropriate amounts of topical tacrolimus applied on Korean patients with eczema Gun-Wook Kim, Hyun-Chang Ko, Byung Soo Kim, Moon-Bum Kim, Margaret Song A109 Identification of an IgG1-mediated anaphylaxis marker and its application in evaluating the antigenicity of infant formulas Takeshi Matsubara, Hiroshi Iwamoto, Yuki Nakazato, Kazuyoshi Namba, Yasuhiro Takeda A110 Nitric oxide as a screening tool for evaluation of postoperative state of chronic rhinosinusitis Jae Hoon Lee, Woo Yong Bae A111 Comparison of different medical treatment options for crswnp: Doxycycline, methylprednisolone, mepolizumab, omalizumab Els De Schryver, Lien Calus, Philippe Gevaert, Thibaut Van Zele, Claus Bachert A112 Successful treatment of steroid resistant asthma model by blocking CD28 signal Akio Mori, Satoshi Kouyama, Miyako Yamaguchi, Yo Iijima, Akemi Abe-Ohtomo, Hiroaki Hayashi, Kentaroh Watai, Chihiro Mitsui, Chiyako Oshikata, Kiyoshi Sekiya, Takahiro Tsuburai, Mamoru Ohtomo, Yuma Fukutomi, Masami Taniguchi A113 Serum periostin levels was not associated with allergic rhinitis and allergic sensitization in Korean children Ju Wan Kang, Jeong Hong Kim, Jeong Hong Kim, Keun-Hwa Lee, Hye-Sook Lee, Seong-Chul Hong, Jaechun Lee A114 Roles of ADAM10 and ADAM17 in allergic rhinitis Ji Won Seo, Jae Hoon Lee, Woo Yong Bae A115 Mechanism of oral and topical polyprenol action in atopic dermatitis Ivans Sergejs Kuznecovs, Galina Kuznecova A116 Technical and clinical validation of a mobile chamber for allergen exposure tests Karl-Christian Bergmann, Torsten Zuberbier, Joseph Salame, Torsten Sehlinger, Georg Bölke A117 The association between serum lead level and total immunoglobulin e according to allergic sensitization Yoo Suk Kim, Jung Hyun Chang, Jeong Hong Kim, Ju Wan Kang A118 Clinical and laboratory characteristics of nasal obstruction dominant allergic sensitization Seung-No Hong, Doo Hee Han, Chae-Seo Rhee A119 Nasal provocation test is useful for the diagnoses of allergic, non- allergic, and local allergic rhinitis Young-Joo Ko, Young Hyo Kim, Dae-Young Kim, Tae Young Jang A120 Aspirin facilitates the intestinal absorption and oral sensitization of food allergens in rats Tomoharu Yokooji, Taiki Hirano, Hiroaki Matsuo A121 Gestational Secondhand Smoke Exposure Could Affect Maternal n-Glycosylation and Cause Filaggrin Loss in Children with Atopic Dermatitis Galina Kuznecova, Ivans Sergejs Kuznecovs A122 Allergen specific immunotherapy in the treatment of allergic rhinitis and asthma--a randomized prospective study from kashmir valley-north of India Roohi Rasool Wani, Shafia Alam Syed, Ghulam Hassan, Ayaz Gul, Saniya Nissar, Zaffar Amin Shah A123 Sleep disorders in latin-American children with asthma and/or allergic rhinitis and normal controls Marilyn Urrutia Pereira, Carmen Fernandez, Dirceu Sole, Herberto Jose Chong Neto, Veronica Acosta, Alfonso Mario Cepeda, Mirta Alvarez Castello, Claudia Almendarez, Jose Santos Lozano Saenz, Juan C. Sisul, Nelson Rosario Filho, Antonio Castillo, Marylin Valentin Rostan, Jennifer Avila, Hector Badellino, Maria Carolina Manotas, Raúl Lázaro Castro Almarales, Mayda González León A124 Association between respiratory symptoms and exhaled nitric oxide in Afghanistan Woo Kyung Kim, Hae-Sun Yoon A125 ATP, a danger signal, activates human eosinophils via P2 purinergic receptors Takehito Kobayashi, Tooru Noguchi, Tomoyuki Soma, Kazuyuki Nakagome, Hidetomo Nakamoto, Hirohito Kita, Makoto Nagata A126 Atopic dermatitis and sleep disorders in latin American children Marilyn Urrutia Pereira, Dirceu Sole, Herberto Jose Chong Neto, Alfonso Mario Cepeda, Raúl Lázaro Castro Almarales, Juan C. Sisul, Marylin Valentin Rostan, Hector Badellino, Miguel Alejandro Medina Avalos, Antonio Castillo, Claudia Almendarez, Nelson Rosario Filho, Caridad Sanchez Silot, Jennifer Avila, Felicia Berroa Rodriguez, Jose Santos Lozano Saenz, Mirta Alvarez Castello, Carmen Fernandez A127 Der p 23: A Major House Dust Mite Allergen in Spite of Limited Release from Fecal Pellets and Prominent Protease Sensitivity Wai Tuck Soh, Alain Jacquet, Kiat Ruxrungtham, Emmanuel Nony, Maxime Le Mignon A128 Anaphylactic Reaction After Inhalation of Budesonide Mary Lee-Wong, Suzanne McClelland, Suzanne McClelland, Nanette B. Silverberg, Christian E. Song A129 Lipidomic analysis of mattress dust from urban and rural schoolchildren in China Zhaowei Yang, Jiukai Zhang, Wentao Zheng, Nanshan Zhong, Jing Li A130 Improvements in quality of life in children with allergic rhinitis after adenotonsillectomy Jung Ho Bae, Young Joo Cho, Joo Yeon Kim A131 The seasonal variation of asthma exacerbations in patients allergic to pollens in Greece Konstantinos Petalas, Dimitrios Vourdas, Christos Grigoreas A132 Whole-genome sequencing study in allergic rhinitis nuclear families Yuan Zhang A133 Effect of the production of extracellular matrix from nasal fibroblasts by eosinophils activated with airborne fungi Seung-Heon Shin, Mi-Kyung Ye, Jeong-Kyu Kim A134 The study of clinical characteristics, lung function and bronchodilator responsiveness in infants with RSV bronchiolitis Yong Feng, Yunxiao Shang A135 GIS-based association between PM10 and allergic diseases in seoul: Implication for health and environmental policy Sungchul Seo, Ji Tae Choung, Dohyeong Kim, Young Yoo, Hyunwook Lim A136 The relationship between rhinovirus and recurrent wheezing Wenjing Zhu, Chuanhe Liu, Li Sha, Li Chang, Min Zhao, Linqing Zhao, Yuan Qian, Yuzhi Chen A137 Dominancy of Staphylcoccus Aureus in the Skin of Atopic Dermatitis Patients Compared to Healthy Subjects through Metagenomic Analysis Min-Hye Kim, Young Joo Cho, Mina Rho, Jung-Won Kim, Yeon-Mi Kang, Kyung-Eun Yum, Hyeon-Il Choi, Jun-Pyo Choi, Han-Ki Park, Taek-Ki Min, Bok-Yang Pyun, Yoon-Keun Kim A138 Micronized Cellulose Powder Reduces the Dose of Locally Applied Glucocorticoids in Patients with Allergic Rhinitis Xueyan Wang A139 New strategy for atopic dermatitis therapy with modulation of calcium ion channels Woo Kyung Kim, Yu Ran Nam, Joo Hyun Nam A140 Difference in the Systemic Bacterial Composition of Atopic Dermatitis Patients Compared to Healthy Subjects through Metagenomic Analysis of Urine Jung-Won Kim, Min-Hye Kim, Mina Rho, Yeon-Mi Kang, Kyung-Eun Yum, Hyeon-Il Choi, Jun-Pyo Choi, Han-Ki Park, Taek-Ki Min, Young Joo Cho, Bok-Yang Pyun, Yoon-Keun Kim A141 Occurrence and physiological function of immune complexes of food proteins and IgA in human saliva Hiroshi Narita, Junko Hirose, Kumiko Kizu, Ayu Matsunaga A142 Association between DNA hypomethylation at IL13 gene and allergic rhinitis in house dust mite-sensitized subjects Jingyun Li, Yuan Zhang, Luo Zhang A143 Effect of dietary methyl donors on asthma and atopy is modified by MTHFR polymorphism Yean Jung Choi, Hye Lim Shin, Song-I Yang, So-Yeon Lee, Sung-Ok Kwon, Young-Ho Jung, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, Se-Young Oh, Ho-Jang Kwon, Eun Lee, Mi-Jin Kang, Soo-Jong Hong, Yun-Jeong Lee, Joonil Kim A144 The effect of TSLP in a murine model of allergic asthma Joon Young Choi, Ji Young Kang, Seok Chan Kim, Sei Won Kim, Seung Joon Kim, Young Kyoon Kim, Chin Kook Rhee, Hea Yon Lee, Hwa Young Lee, Sook Young Lee A145 Evaluation of Aspirin Hypersensitivity in Chronic Rhinosinusitis Patients Tae Kyung Koh, Sung Wan Kim, Kun Hee Lee, Chul Kwon, Joong-Saeng Jo, Sung-Hwa Dong, Young Seok Byun A146 Chronic cough without wheezing in young children as a manifestation of chronic sinusitis Charles Song A147 Expression of muscarinic receptors and effect of tiotropium bromide on chronic asthma according to age in a murine model Ji Young Kang, Hwa Young Lee, In Kyoung Kim, Sei Won Kim, Chin Kook Rhee, Seung Joon Kim, Seok Chan Kim, Sook Young Lee, Young Kyoon Kim, Soon Seog Kwon, Joon Young Choi A148 Discrimination between non-eosinophilic and eosinophilic chronic rhinosinusitis with nasal polyps Pona Park, Hong Ryul Jin, Dong-Kyu Kim, Dae Woo Kim A149 Significant reduction in allergic features in the offspring of mice supplemented with specific non-digestible oligosaccharides during lactation Astrid Hogenkamp A150 Allergenicity assessment of hydrolysed infant formula; A multicenter comparison of a mouse model and a Guinea pig model for cow’s milk allergy Leon Knippels, Betty C.a.m. Van Esch, Jolanda Van Bilsen, Prescilla V. Jeurink; Marjan Gros, Johan Garssen, Joost J Smit, Raymond H.H. Pieters A151 Clinical significance between the allergic test and serum eosinophil cationic protein Boo-Young Kim, Soo Whan Kim A152 Hydroclorothiazide-induced acute non-cardiogenic pulmonary edema Ramon Lleonart A153 A Synbiotic Mixture of Scgos/Lcfos and Bifidobacterium Breve M-16V Is Able to Restore the Delayed Colonization of Bifidobacterium Observed in C-Section Delivered Infants Christophe Lay, Kaouther Benamor, Chua Mei Chen, Jan Knol, Charmaine Chew, Voranush Chongsrisawat, Anne Goh, Wen Chin Chiang, Rajeshwar Rao, Surasith Chaithongwongwatthana, Nipon Khemapech A154 Atopic characteristics of patients with asthma-COPD overlap syndrome Ji Young Yhi, Sang-Heon Kim, Dong Won Park, Ji-Yong Moon, Tae Hyung Kim, Jang Won Sohn, Dong Ho Shin, Ho Joo Yoon, Seok Hyun Cho A155 Perceptions and practices of severe asthma and asthma-COPD overlap syndrome among specialists: A questionnaire survey Sang-Heon Kim, Ji-Yong Moon, Jae-Hyun Lee, Ga Young Ban, Sujeong Kim, Mi-Ae Kim, Joo-Hee Kim, Min-Hye Kim, Chan-Sun Park, Hyouk-Soo Kwon, Jae-Woo Kwon, Jae Woo Jung, Hye-Ryun Kang, Jong-Sook Park, Tae-Bum Kim, Heung Woo Park, You Sook Cho, Kwang-Ha Yoo, Yeon-Mok Oh A156 A case of surgical diagnosed eosinophilic enteritis with intussusception in adult patient Sang-Rok Lee A157 Reference values of total IgE in estonian children Kaja Julge, Maire Vasar, Tiia Voor, Tiina Rebane A158 A case of eosinophilic granulomatosis with polyangiitis accompanied by rapidly progressive glomerulonephritis Yu Jin Kim, Sang Min Lee, Shin Myung Kang, Sojeong Kim, Sun Young Kyung, Sung Hwan Jeong, Jeong-Woong Park, Hyunjung Hwang, Yong Han Seon, Sanghui Park, Sang Pyo Lee A159 Associations Between Infectious Diseases and Urticaria Marius Iordache A160 Sleep in infants in korea – finding of bisq survey Yeongsang Jeong, Sohee Eun, Byung Min Choi, Ji Tae Choung, Wonhee Seo A161 Increased Expression of Filaggrin, TSLP, Periostin, IL13 and IL-33 in Nasal Polyps Liang Zhang, Ruby Pawankar, Manabu Nonaka, Miyuki Hayashi, Shingo Yamanishi, Harumi Suzaki, Yasuhiko Itoh, So Watanabe, Hitome Kobayashi A162 Asymptomatic bacteruria increases the risk of edematous attacks in patients with hereditary angioedema due to C1 inhibitor deficency (C1-INH-HAE) Zsuzsanna Zotter, Henriette Farkas, Lilian Varga, Nora Veszeli, Eva Imreh, Gabor Kovacs, Marsel Nallbani A163 Gastric Erosions Cause Spontaneous Urticaria Independent of Helicobacter Pylori Semen Zheleznov, Galina Urzhumtseva, Natalia Petrova, Zhanna Sarsaniia, Nikolai Didkovskii, Torsten Zuberbier A164 The Effect of G2 Vaccine on the Gene Expression NKG2D and Receptor Presenting on the Surface of NK Cells in Peripheral Blood Nader Dashti Gerdabi, Ali Khodadadi, Zahra Abdoli, Mehri Ghafourian, Mohammad Ali Assarehzadegan, Khodayar Ghorban A165 Ethnic differences in lifetime prevalence and indoor environmental factors for childhood eczema Hyo-Bin Kim, Hui Zhou, Jeong Hee Kim, Rima Habre, Theresa Bastain, Frank Gilliland A166 A case of methazolamide-induced toxic epidermal necrolysis Jong-Wook Bae, Kyu-Hyung Han, Young-Koo Jee, Misoo Choi, Seung-Phil Hong, Seung-Hyun Kim A167 Inflammatory responses of human adipose-tissue derived stem cells to LPS and nanoparticles Hee-Kyoo Kim, Gil-Soon Choi, Jeonghoon Heo, Young-Ho Kim, Eun-Kee Park A168 Analysis of 71 Cashew Nut Oral Challenge Tests Takashi Inoue, Kiyotake Ogura, Noriyuki Yanagida, Hirotoshi Unno, Kenichi Nagakura, Tetsuharu Manabe, Tomoyuki Asaumi, Sakura Sato, Yu Okada, Motohiro Ebisawa A169 Fungal sensitization is associated with asthma exacerbation Min-Gu Kim, You Sook Cho, Tae-Bum Kim, Hee-Bom Moon, Jung-Hyun Kim, Hyo-Jung Kim, So-Young Park, Bomi Seo, Hyouk-Soo Kwon, Jaemoon Lee, Taehoon Lee A170 Individual therapeutic patient education and consultation in children with atopic dermatitis Hye-Soo Yoo, Jieun Kim, Inok Kim, Haejin Kim, Younhee Chang, Hae-Sim Park, Sooyoung Lee A171 Utility of Alpha-Lactalbumin Specific IgE Levels Using Immulite 2000 3gAllergy in Predicting Clinical Severity of Milk Allergy Kazuyo Kuzume, Munemitsu Koizumi, Koji Nishimura, Michiko Okamoto A172 Isoniazid/rifampicin-specific t-cell responses in patients with anti-tuberculosis –induced dress syndrome Seung-Hyun Kim, Young Min Ye, Gyu Young Hur, Hae-Sim Park, Sang-Heon Kim, Young-Koo Jee A173 Genetic biomarkers associated with aspirin-exacerbated respiratory disease (AERD) phenotype based on genome-wide association study Seung-Hyun Kim, Hyunna Choi, Young Min Ye, Hae-Sim Park A174 Assessment of ORAL drug provocation test in the diagnosis of NON-steroidal ANTI-inflammatory drugs hypersensitivity Bui VAN Khanh, Hieu Chi Chu, Nguyen Nhu Nguyet, Nguyen Hoang Phuong A175 Korean treatment guideline of atopic dermatitis Joo Young Roh, Hyun Jeong Kim, Jung Eun Kim, Bark-Lynn Lew, Kyung Ho Lee, Seung-Phil Hong, Yong Hyun Jang, Kui Young Park, Seong Jun Seo, Jung Min Bae, Eung Ho Choi, Ki Beom Suhr, Seung Chul Lee, Hyun-Chang Ko, Young Lip Park, Sang Wook Son, Young Jun Seo, Yang Won Lee, Sang Hyun Cho, Chun Wook Park A176 Systemic side reaction of subcutaneous immunotherapy(SCIT) for perennial allergic rhinitis Kun Hee Lee, Sung Wan Kim A177 Clinical baseline characteristics of Asian patients suffering from refractory chronic spontaneous urticaria (CSU) in three phase 3 omalizumab clinical trials Chia-Yu CHU, Derrick Aw, Young-Min Ye, Giovanni Bader, Fabrizio Dolfi, Nathalie Oliveira A178 A metagenomic approach through t-RFLP to the microbiome of asthma Jae Chol Choi, Jae Woo Jung, Hye-Ryun Kang, Kijeong Kim, Byoung Whui Choi A179 Clinical characteristics and ten-year trend of peripheral blood eosinophilia among health screening program recipients at a tertiary hospital of South Korea Jong Wook Shin, Jae Woo Jung, Jae Chol Choi, In Won Park, Byoung Whui Choi, Jae Yeol Kim A180 The prevalence of toxocariasis and diagnostic value of serologic tests in asymptomatic Korean adults Jin-Young Lee, Kyoung Won Ha, Yun-Jin Jeung, Sehyo Yune, Byung-Jae Lee, Dong-Chull Choi, Mi-Jung Oh, Young Hee Lim A181 Cutaneous Drug Hypersensitivity Reaction in Korean Children: An Analysis of KAERS Database on 2012-2013 Eui Jun Lee, Dongin Suh, Sung-Il Woo, Hwa Jin Cho, Eun Hee Chung, Soo Youn Chung A182 Comparison of clinical characteristics, quality of life and sleep in patients with allergic rhinitis when categorised as “sneezers and runners” and “blockers” Kamal Gera, Ashok Shah A183 Role of s-nitrosoglutathione reductase (GSNOR) in the murine strain differences of airway hyperresponsiveness Jin-Young Lee, Kyoung Won Ha, Mi-Jung Oh, Young Hee Lim, Sehyo Yune, Jae-Won Paeng, Mi-Jin Jang, Byung-Jae Lee, Dong-Chull Choi A184 Protection from airway bronchoconstriction by gsno Jin-Young Lee, Mi-Jin Jang, Jae-Won Paeng, Yun-Jin Jeung, Young Hee Lim, Mi-Jung Oh, Kyoung Won Ha, Byung-Jae Lee, Dong-Chull Choi, Sehyo Yune A185 Does EIA-targeted asthma treatment improve daily physical activity of children? Takahiro Ito A186 Wheezing as a clue to the diagnosis of cough variant asthma and nonasthmatic eosinophilic bronchitis Jihye Kim, Jin-Young Lee, Sehyo Yune, Byung-Jae Lee, Dong-Chull Choi, Mi-Jin Jang, Jae-Won Paeng, Young Eun Kim, Young Nam Kim, Yongseok Lee A187 Antagonism of microRNA-21 suppressed the airway inflammation in a mouse model of bronchial asthma Hwa Young Lee, Sook Young Lee, Soon Seog Kwon, Young Kyoon Kim, Chin Kook Rhee, Sei Won Kim, Hea Yon Lee, Joon Young Choi, In Kyoung Kim A188 Chlorhexidine anaphylaxis: A report of two cases Jose Antonio Navarro, Maria Ascension Aranzabal, Alejandro Joral, Susana Lizarza, Miguel Echenagusia, EVA Maria Lasa A189 Effects of Particulate Matter on Respiratory Allergic Diseases Considering Meteorological Factors in Busan, Korea Eun-Jung Jo, Sun-Mi Jang, Seung-Eon Song, Hae-Jung Na, Chang-Hoon Kim, Woo-Seop Lee, Hye-Kyung Park A190 Clinical characteristics of neutrophilic asthma Sachiko Miyauchi, Yoshitaka Uchida, Tomoyuki Soma, Susumu Yamazaki, Toru Noguchi, Takehito Kobayashi, Kazuyuki Nakagome, Makoto Nagata A191 Current Practice of Infants and Children with Acute Urticaria at a Single Wide Regional Emergency Medical Center Hea Lin Oh, Do Kyun Kim, Dongin Suh, Young Yull Koh A192 Discordance between sputum eosinophilia and exhaled nitric oxide Sehyo Yune, Jin-Young Lee, Byung-Jae Lee, Dong-Chull Choi, Jae-Won Paeng, Mi-Jin Jang, Jihye Kim, Young Nam Kim A193 Association between genetic polymorphisms of costimulatory molecules and antituberculosis drugs induced hepatitis Sang-Heon Kim, Sang-Hoon Kim, Jang Won Sohn, Ho Joo Yoon, Dong Ho Shin, Jae Hyung Lee, Byoung Hoon Lee, Youn-Seup Kim, Jae-Seuk Park, Young-Koo Jee A194 The prevalence of gastroesophageal reflux disease in chronic unexplained cough Sehyo Yune, Jin-Young Lee, Jae-Won Paeng, Mi-Jin Jang, Dong-Chull Choi, Byung-Jae Lee, Yongseok Lee, Young Eun Kim A195 Risk Factors of Allergic Rhinitis in Preschool Children and Clinical Utility of Feno Jisun Yoon A196 Relationship between serum 25-hydroxyvitamin d and asthma exacerbation severity in children Yong Feng, Li Zhang, Xuxu Cai A197 Usefulness of Specific IgE Antibody Levels to Wheat, Gluten and Ï-5 Gliadin for Wheat Allergy in Korean Children Jong-Seo Yoon, Kyunguk Jeong, Hye-Soo Yoo, Sooyoung Lee, Sooyoung Lee A198 Neutralization of stratum corneum accelerates the progress from atopic dermatitis to asthma-like lesion in flaky tail mice treated by house dust mite allergen Hae-Jin Lee, Noo Ri Lee, Bo-Kyung Kim, Minyoung Jung, Dong Hye Kim, Catharina S. Moniaga, Kenji Kabashima, Eung Ho Choi A199 Trends in oral food challenges in Japan: A six-year prospective study Noriyuki Yanagida, Sakura Sato, Chizuko Sugizaki, Motohiro Ebisawa A200 The Gut Microbiome in the Food Allergic Host Jamie Kiehm, Punita Ponda, Sherry Farzan, Jared Weiss, Claudia Elera, Catherine Destio, Cristina Sison, Annette Lee A201 Cord blood cytokines and maternal environmental exposure during pregnancy Soo Hyun Ri, Chang Hoon Lim A202 Rupatadine pharmacokinetics in Japanese healthy volunteers after single and repeated oral doses of 10, 20 and 40 mg Iñaki Izquierdo Pulido, Jorg Taubel, Georg Ferber, Eva Santamaria Masdeu A203 A safe and effective method to desensitize patients with wheat allergy Alireza Khayatzadeh, Masoud Movahedi, Motohiro Ebisawa, Mohammad Gharagozlou A204 RNA Binding Protein Hur Regulates CD4+ T Cell Differentiation and Is Required for Allergic Airway Inflammation and Normal IL-2 Homeostasis Ulus Atasoy, Patsharaporn Techasintana, Matt Gubin, Jacqueline Glascock, Suzanne Ridenhour, Joseph Magee A205 Time Trends in the Epidemiology of Recurrent Wheezing in Infants from South America Nelson Rosario Filho; Herberto Jose Chong Neto, Gustavo Falbo Wandalsen, Ana Caroline Dela Bianca, Carolina Aranda, Dirceu Sole, Javier Mallol, Luis Garcia-Marcos, Luis Garcia-Marcos A206 Successful Cyclophosphamide Desensitization in a Pediatric Patient with Systemic Lupus Erythematosus Jennifer Toh, Yoomie Lee, Joyce Huang, Elina Jerschow, Jenny Shliozberg A207 The Fatty Acid Binding Protein Der p 13 Is a Minor House Dust Mite Allergen Able to Activate Innate Immunity Pattraporn Satitsuksanoa, Narissara Suratannon, Jongkonnee Wongpiyabovorn, Pantipa Chatchatee, Kiat Ruxrungtham, Alain Jacquet A208 Epidemiology of Stevens-Johnson Syndrome and Toxic Epidemal Necrolysis: An Administrative Database Study Min Suk Yang; Jin Yong Lee, Ja Yeun Kim, Han-Ki Park, Ju-Young Kim, Woo-Jung Song, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Sang-Heon Cho, Kyung-up Min, Chang-Han Park, Suk-Il Chang, Sook-Hee Song A209 Regional Differences of Vitamin D and Food-Induced Anaphylaxis in Korea Si-Heon Kim, Gil-Soon Choi, Su-Chin Kim, Ji Hye Kim, Ga Young Ban, Yoo Seob Shin, Hae-Sim Park, Young Min Ye A210 Triggering Factors of Atopic Dermatitis By Severity Yoon Ha Hwang A211 Clinical Features of Adverse Drug Reactions of Monoclonal Antibodies in Korea Da Woon Sim, Kyung Hee Park, Kyung Hee Park, Hye Jung Park, Hye Jung Park, Jung-Won Park, Jung-Won Park, Jae-Hyun Lee, Jae-Hyun Lee A212 Food Allergy with Eczema Is Associated with Reduced Growth in the First Four Years of Life Katrina Allen, Cara Beck, Jennifer Koplin, Melanie Matheson, Mimi Tang, Anne-Louise Ponsonby, Lyle Gurrin, Shyamali Dharmage, Melissa Wake, Vicki Mcwilliam A213 The Preliminary Study on Clinical Efficacy and Impact Factors of One Year’s Dust Mite Specific Immunotherapy in Allergic Asthma and Rhinitis Children Sensitized to Dust Mite Xiaoying Liu, Jing Wang, Li Xiang, Qun Wang A214 Lipopolysaccharide Signaling through Toll- like Receptor 4 Could be Augmented By Dermatophagoides Farinae in the Human Middle Ear Epithelial Cell Ji-Eun Lee, Dong-Young Kim, Chae-Seo Rhee, Chae-Seo Rhee A215 Drug Allergy in Pregnant Adolescents: Relation with Familial and Personal Atopy, and Substances Use Francisco Vazquez-Nava A216 Patients and Physicians Concept of Well-Controlled Asthma: Findings from Realise Asia Sang-Heon Cho, Jaewon Jeong, Diahn-Warng Perng, David Price, Glenn Neira, Jiangtao Lin A217 The Role of Vasoactive Intestinal Peptide in the Pathophysiology of Acute Asthma Olga Semernik A218 Comparison of Serum Cytokine Levels According to the Severity in Atopic Dermatitis Ha-Su Kim, Jin-a Jung, Ji-in Jung A219 The Different Influence on the Regulatory T Cell Response Between Subcutanous Immnuotherapy(SCIT) and Sublingual Immunotherapy(SLIT) in Children with Asthma Qing Miao, Li Xiang A220 Asthma State of Affairs in Asia: Seeing through Physicians’ and Patients’ Lenses Sang-Heon Cho, Jaewon Jeong, Diahn-Warng Perng, Jiangtao Lin, David Price A221 Identification of Aspirin Exacerbated Respiratory Disease (AERD) Phenotypes Using Two Step Cluster Analysis Hyun Young Lee, Hae-Sim Park, Young Min Ye, Su Chin Kim A222 Dusty Air Pollution Are Associated with an Increase Risk of Allergic Diseases in General Population Shokrollah Farrokhi, Mohammadkazem Gheiby A223 A Genome-Wide Association Study of Antituberculosis Drugs-Induced Hepatitis Sang-Heon Kim; Heung Woo Park, Sang-Hoon Kim, Young-Koo Jee A224 The Role of peroxiredoxin6 of Bronchial Epithelial Cells in Regulating Mitochondrial Function Under Oxidative Stress By Translocation to Outside Mitochondrial Membrane Sunjoo Park, Keun Ai Moon, Hyouk-Soo Kwon, Tae-Bum Kim, You Sook Cho, Hee-Bom Moon, Kyoung Young Lee, Gyong Hwa Hong, Eun Hee Ha A225 Toxic and Adjuvant Effects of 3 Types of Silica Nanoparticles on Airway System Heejae Han, Hye Jung Park, Yoon Hee Park, Yoon-Jo Kim, Kangtaek Lee, Jung-Won Park, Jae-Hyun Lee A226 Procedure for Diagnostic and Selection of Immunotherapy Method for Children with Different Immunopathogenetic Phenotypes of Atopic Dermatitis Tatiana Slavyanskaya, Vladislava Derkach A227 Prediction of the Success of Our Desensitization Protocol with Symptoms and Results of a Skin Prick Test in Patients with Hypersensitivity to Platinum-Based Chemotherapy Hye Jung Park, Chein-Soo Hong, Jae-Hyun Lee, Jae-Hyun Lee, Sungryeol KIM, Sungryeol KIM, Kyung Hee Park, Kyung Hee Park, Choong-Kun Lee, Beodeul Kang, Seung-Hoon Beom, Sang Joon Shin, Minku Jung, Jung-Won Park, Jung-Won Park A228 Anti-Allergic Effect of Intralymphatic Injection of OVA-Flagelin Mixture in Mouse Model of Allergic Rhinitis Eun-Hee Kim, Ji-Hye Kim, Ji-Hun Mo, Young-Jun Chung A229 Serum Periostin Level Is Higher in Respiratory Type of NSAID Hypersensitivity Than Cutaneous Type Mi-Ae Kim, Hae-Sim Park, Moon Gyeong Yoon, Young-Soo Lee, Ji Hye Kim, Ga Young Ban, Hye-Soo Yoo, Yoo Seob Shin, Young Min Ye, Dong-Ho Nahm A230 A Retrospective Analysis of Allergy Blood Testing in Beijing Children’s Hospital in the Year of 2013: A Single-Center Research Qing Miao, Li Xiang A231 Role of Nrf2 in the Allergic Airway Inflammation Differ Between BALB/c and C57BL/6 Mice Ying-Ji Li, Takako Shimizu, Hirofumi Inagaki, Yukiyo Hirata, Hajime Takizawa, Arata Azuma, Masayuki Yamamoto, Tomoyuki Kawada A232 Effect of Human Mesenchymal Stem Cell on Neutrophilic Asthma Model Min-Gu Kim, Gyong Hwa Hong, Kyoung Young Lee, Eun Hee Ha, Keun Ai Moon, Sunjoo Park, Hyouk-Soo Kwon, Tae-Bum Kim, Hee-Bom Moon, You Sook Cho, Jung-Hyun Kim, Hyo-Jung Kim, So-Young Park, Bomi Seo A233 Immunomodulatory Effect of Tonsil Derived Mesenchymal Stem Cells in a Mouse Model of Allergic Rhinitis Ji-Hye Kim, Ramachandran Samivel, Eun-Hee Kim, Young-Jun Chung, Ji-Hun Mo A234 Alternative Therapy Such As Yoga May be a Low Cost Tool for Improving the Quality of Life of Patient’s with Allergic Rhinitis and Asthma Soumya M. S., G. Inbaraj, R. Chellaa, Ruby Pawankar A235 Substantial Impairment of the Quality of Life in Adult Patients with Chronic Urticaria Wonsun Choi, Hae-Sim Park, Young Min Ye, Ji Hye Kim, Ga Young Ban, Yoo-Seob Shin A236 Dietary Galacto-Oligosaccharides Reduce Airway Eosinophilia and Enhance the Th2 Suppressive Effect of Budesonide in House Dust Mite-Induced Asthma in Mice Saskia Braber, Kim Verheijden, Aletta Kraneveld, Johan Garssen, Linette Willemsen, Gert Folkerts A237 Production and Characterization of Recombinant Periplaneta americana Allergens for Component Resolved Diagnosis Stephanie Eichhorn, Fatima Ferreira, Isabel Pablos, Bianca Kastner, Bettina Schweidler, Sabrina Wildner, Peter Briza, Jung-Won Park, Naveen Arora, Stefan Vieths, Gabriele Gadermaier A238 Assessment of Characteristics of Itch in Patients with Hand Eczema Sung-Min Park, Won-Ku Lee, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Hoon-Soo Kim, Margaret Song, Hyun-Chang Ko, Moon-Bum Kim, Byung Soo Kim A239 The Hidden Culprit: A Case of Repeated Anaphylaxis from Cremophor Hypersensitivity. Young Nam Kim, Sehyo Yune, Jin-Young Lee, Jihye Kim, Young Eun Kim, Jae-Won Paeng, Mi-Jin Jang, Dong-Chull Choi, Byung-Jae Lee, Yongseok Lee A240 Spectrum of Anaphylaxis in Children and Adults at Emergency Departments in Singapore Si Hui Goh, Bee Wah Lee, Jian Yi Soh A241 Improved Quality of Life through an Integrated Health Care Service for Children with Atopic Dermatitis Hyungoo Kang; Hyunhee Kim; Hye-Yung Yum A242 Criteria Combining Autologous Serum Skin Test and Clusterin for Predicting Antihistamine-Refractoriness in Patients with Chronic Spontaneous Urticaria Young Min Ye; Hae-Sim Park; Ga-Young Ban; Ji Hye Kim; Yoo Seob Shin A243 Urinary Leukotriene E4 Levels in Wheezing Infants Takumi Takizawa, Masahiko Tabata, Akira Aizawa, Hisako Yagi, Yutaka Nishida, Hirokazu Arakawa, Akihiro Morikawa, Solongo Orosoo A244 Allergic Sensitization to Whey in Mice Is Facilitated By the Mycotoxin Deoxynivalenol (DON) Saskia Braber, Marianne Bol-Schoenmakers, Peyman Akbari, Prescilla V. Jeurink, Prescilla V. Jeurink, Priscilla De Graaff, Joost J. Smit, Betty C. A. M. Van Esch, Johan Garssen, Johan Garssen, Johanna Fink-Gremmels, Raymond H. H. Pieters A245 How to Define Chronic Cough: Based on a Systematic Review of the Epidemiological Literature Gun-Woo Kim, Eun-Jung Jo, Sujeong Kim, Woo-Jung Song, Yoon-Seok Chang, Shoaib Faruqi, Ju-Young Kim, Mingyu Kang, Min-Hye Kim, Jana Plevkova, Heung Woo Park, Sang-Heon Cho, Alyn Morice, So-Hee Lee, Sun-Sin Kim, Seoung-Eun Lee A246 Asko Study: Comparison of Behavior and Habits in Diagnosis and Treatment of Adult Asthma and COPD Patients Bilun Gemicioglu, Zeynep Misirligil, Arif Hikmet Cimrin, Hakan Gunen, Tevfik Ozlu, Aykut Cilli, Levent Akyildiz, Hasan Bayram, Esra Uzaslan, Oznur Abadoglu, Mecit Suerdem A247 Changes in Pulmonary Function in the Treatment of Obesity in Children Keigo Kainuma A248 Changes of Feno and Nasal Feno Levels after Treatment in Pediatric Allergic Rhinitis Hyun-a Kim, Ha-Su Kim, Woo Yong Bae, Jin-a Jung A249 Prevalence of Vitamin D Deficiency in Exclusively Breastfed Infants in Kenya Rose Kamenwa, William Macharia, Nusrat Said A250 In-Vitro Screening of Atopy in the Indian Population: Are Current Methods Adequate, Keeping Local IgE Seroprevalence for Common Food & Inhalant Allergens in Mind? Vidya Nerurkar, Meenal Patel, Simi Bhatia A251 Usefulness of House Dust Mites Nasal Provocation Test in Asthma Inseon S Choi, Soo-Jeong Kim, Joo-Min Won, Myeong-Soo Park A252 Biomarker-Based Treatment Option for Preschool Children with Recurrent Wheeze Mizuho Nagao A253 Anti-Tuberculosis Drugs-Induced Liver Injury in Patients with Connective Tissue Diseases Dong Won Park, Jang Won Sohn, Ji Young Yhi, Ji-Yong Moon, Sang-Heon Kim, Tae Hyung Kim, Dong Ho Shin, Ho Joo Yoon A254 Ocular Symptoms of Cedar Pollinosis in Otolaryngology Patients Yukiyoshi Hyo A255 The Clinical Characteristics of Adverse Drug Reactions Reported in a Regional University Hospital for 6 Years and the Suggestions for the Reporting System Jaechun Lee, Su Hee Kim, Eunkyoung Lee A256 Changes in Skin Prick Test Results over 3 Years in School-Aged Children Hahn Jin Jung, Jaehyun Lim, Seung-No Hong, Doo Hee Han, Chae-Seo Rhee A257 The Analysis of Risk Factors and Features of Food Allergy in Korean Children: Nationwide Cross-Sectional Survey Kun Song Lee A258 A Sequential Indirect-Direct Bronchial Provocation Test for Diagnosis of Asthma: A Pilot Study Jaechun Lee, Sun Young Yang, Mi Young Ahn, Jong Hoo Lee, Jasmina Golez A259 Association of VDR and CYP2R1 Polymorphisms with Persistent Allergic Rhinitis in a Han Chinese Population Hui-Qin Tian, Lei Cheng, Xin-Yuan Chen A260 Associations of Metabolic Syndrome with Asthma and Atopy in Korean Adults Ji-Yong Moon, Sang-Heon Kim, Tae Hyung Kim, Ji Young Yhi, Ho Joo Yoon, Jang Won Sohn, Dong Ho Shin, Dong Won Park A261 Clinical Manifestation and Treatment Outcome of Eosinophilic Gastroenteritis in Korean Children Won Im Cho, Jong Sub Choi, Dongin Suh, Gyeong Hoon Kang, Jin Soo Moon, Jae Sung Ko, Kyung Jae Lee, Shin Jie Choi A262 The Sensitization Model and Correlation of Bermuda and Timothy Grass Pollen Allergen in Allergic Patients in Southern China Wenting Luo, Baoqing Sun A263 A Pilot Study on the Outcomes of Respiratory Allergic Diseases at Pre-School Age in Chinese Infants with Atopic Dermatitis Qi Gao, Li Xiang, Kunling Shen A264 Activation of Toll like Receptor 1 and 6 By House Dust Mite Enhances the Expression of Tight Junction Protein in Epidermal Keratinocytes Yong Hyun Jang A265 Pollen Exposure in a Mobile Exposure Chamber: Comparing Real-Life Symptoms with Exposure Symptoms Karl-Christian Bergmann, Torsten Sehlinger, Georg Bölke, Uwe Berger, Torsten Zuberbier A266 Retrospective Analysis of the Incidence of Allergy in Patients with Contact Eczema Joanna Kolodziejczyk, Milena Wojciechowska, Anna Hnatyszyn-Dzikowska, Micha Chojnacki, Zbigniew Bartuzi A267 Effect of Fungal Sensitization in Patients with Severe Asthma Katsunori Masaki, Koichi Fukunaga, Takashi Kamatani, Kengo Ohtsuka, Takae Tanosaki, Masako Matsusaka, Takao Mochimaru, Hiroki Kabata, Soichiro Ueda, Yusuke Suzuki, Katsuhiko Kamei, Koichiro Asano, Tomoko Betsuyaku A268 SCIg Patient Preference Pump Versus Push Karlee Trafford A269 Fixed Drug Eruption Induced By Ornidazole and Diclofenac Ismet Bulut, Zeynep Ferhan Ozseker A270 Transepidermal Water Loss Measurement during Infancy Can Predict the Subsequent Development of Atopic Dermatitis Kenta Horimukai, Hideaki Morita, Masami Narita, Hironori Niizeki, Kenji Matsumoto, Yukihiro Ohya, Hirohisa Saito, Shigenori Kabashima, Mai Kondo, Eisuke Inoue A271 Inhalant Allergens on Soft Toys: A Literature Review Robert Siebers, Francis FS Wu A272 Fractional Exhaled Nitric Oxide in Elderly Asthmatics Robert Siebers, Francis FS Wu, Ming-Hui Ting, Hung-En Laio, Tsung-Huai Kuo, Pei-Yuan Lee A273 Dye and Preservative Challenge in Meal-Associated Urticaria and Angioedema: A Low-Yield Diagnostic Maneuver Daniel Eugene Maddox A274 The Changes of Allergic Sensitization with Age in Children with Allergic Rhinitis Gwanghui RyuHyo Yeol Kim, Hun-Jong Dhong, Sang Duk Hong, Seung-Kyu Chung A275 Component-Specific IgE and IgG4 Levels in Milk Allergy Children Tolerated Baked Milk Products Osamu Higuchi, Yu-Ichi Adachi, Toshiko Itazawa, Yoko Adachi, Miki Hamamichi, Motokazu Nakabayashi, Yasunori Ito, Takuya Wada, Gyoukei Murakami, Miki Takao, Junko Yamamoto A276 Serum Surfactant Protein(SP)-D Level: A Potential Biomarker for Aspirin-Exacerbated Respiratory Disease Hyun Jung Jin, Moon Gyeong Yoon, Young Min Ye, Yoo-Seob Shin, Seung-Hyun Kim, Hae-Sim Park A277 Clinical Characteristics of Anaphylaxis in Korean Children Taek-Ki Min, Bok-Yang Pyun, So-Yeon Lee, Hyun Hee Kim, Gwang-Cheon Jang, Jinho Yu, Dongin Suh, Sooyoung Lee, Yong Mean Park, Jeong Hee Kim, Hye-Yung Yum, Kyung Won Kim, Hyeon-Jong Yang, Kangmo Ahn, Ji-Won Kwon, Myung Hyun Sohn, Hae Ran Lee, Jung Hyun Kwon, Kyu-Earn Kim, Soo-Jong Hong A278 Immunological Changes Induced By Intramuscular Injections of Autolologous Immunoglobulin in Patients with Severe Atopic Dermatitis Su-Mi Cho A279 Identification of Subtypes in Subjects with Mild to Moderate Airflow Limitation and Their Clinical and Socioeconomic Implications Jin Hwa Lee, Chin Kook Rhee, Hye Yun Park, Woo Jin Kim, Yong Bum Park, Kwang-Ha Yoo A280 Cephalosporin-Induced Dress (Drug Rash with Eosinophilia and Systemic Symptoms) Syndrome in a 7-Year-Old Boy Heejeong Kang, Hyeon-Jong Yang, Taek-Ki Min, Bok-Yang Pyun A281 Maternal Depression Is Associated with Children’s Asthma : An Analysis of the Fifth Korea National Health and Nutrition Examination Survey (2010-2012) Lee Ju Suk, Cheol Hong Kim A282 Increased Length of Hospitalization Associated with Infiltration on Chest Radiography in Pediatric Asthma Patients Jung Hyun Kwon, Sang Hyun Lee, Wonhee Seo A283 A Case of 16-Year-Old Boy with Smoking-Induced Acute Eosinophilic Pneumonia Kang-in Kim, Young Cheon Park, Hyeon-Jong Yang, Taek-Ki Min; Bok-Yang Pyun A284 A Case of Pranlukast Induced Anaphylactic Shock Sujeong Kim, Sun Jin, Jong-Myung Lee, Hye-Jin Jung, Jung-Wha Park A285 Comparison of Asthma-Related Outcomes Between Metabolically Healthy Obese and Metabolically Unhealthy Obese Asthma Patients Hyo-Jung Kim, Tae-Bum Kim, You Sook Cho, Hee-Bom Moon, Hyouk-Soo Kwon, So Young Park, So-Young Park, Jung-Hyun Kim, Bomi Seo, Min-Gu Kim, Youn Yee Kim A286 Rick Factors Associated with Longer Length of Stay in Infants Hospitalized with Respiratory Syncytial Virus Bronchiolitis Yena Lee, Taek-Ki Min, Hyeon-Jong Yang, Bok-Yang Pyun, Suk Hee Han, Suyeon Park, Jeongho Lee, Won-Ho Hahn A287 Urinary Excretion of 9α, 11Î(2)-Prostaglandin F(2) and Leukotriene E(4) in Patients with Exercise-Induced Bronchoconstriction Youhoon Jeon, Joo-Hee Kim, Tae-Rim Shin, Cheol-Hong Kim, In-Gyu Hyun, Jeong-Hee Choi A288 The Aeroallergen Sensitization Pattern and Effect on Airway Hyperresponsiveness in Busan, Korea Sun-Mi Jang, Hae-Jung Na, Seung-Eon Song, Hye-Kyung Park, Eun-Jung Jo A289 Multicenter Questionnaires on Current Management of Atopic Dermatitis Among Korean Patients and Caregivers Dong Hun Lee, Jin-Young Lee, Yang Park, Jae-Won Oh, Mi Hee Lee, Soo-Jong Hong, Soo-Jong Hong, So-Yeon Lee, Joon Soo Park, Dong-Ho Nahm, Hye-Yung Yum, Hye-Yung Yum A290 Der p 1, Der p 2 and Der p 10 IgE Reactivities in Allergic Rhinitis Patients in Korea Kyu Young, Dong-Young Kim A291 De-Labeling Beta-Lactam Hypersensitivity: An Experience from a Tertiary Care Hospital in Thailand Sirinoot Palapinyo; Jettanong Klaewsongkram A292 Sonic Hedgehog Signaling: Evidence for Its Protective Role in Endotoxin Induced Acute Lung Injury Mouse Model Xing Chen, Yuting Jin, Xiaoming Hou, Fengqin Liu, Chunyan Guo, Yulin Wang A293 Analyses of the Factors behind the Negative Attitudes Toward the Administration of Adrenaline Auto-Injectors in School Settings Ikuo Okafuji, Yuya Tanaka, Shegeyuki Narabayashi, Satoru Tsuruta A294 Low Vitamin D Levels Are Related to High House Dust Mite Sensitization in Patients with Severe Atopic Dermatitis Yong Hyun Jang A295 Appendicular Skeletal Muscle Mass Index: A Potential Predictor of Skeletal Muscle Abnormality According to the Severity Airflow Limitation of COPD Jun-Hong Ahn, Dong-Won Lee, Jin Hong Chung, Hyun Jung Jin, Min-Su Sohn A296 Etiology and Clinical Feature of Oral Allergy Syndrome in Children Young a Park, Kyunguk Jeong, Yoon Hee Kim, In Suk Sol, Seo Hee Yoon, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Sooyoung Lee A297 Traffic-Related Pollution Levels and Poorly Controlled Asthma in Adults Ho Kim, Ja Yeun Kim A298 Anaphylaxis in Korean Children, 2009-2013 : Triggers of Anaphylaxis By Age Groups So-Yeon Lee, Taek-Ki Min, Tae-Won Song, Kangmo Ahn, Jihyun Kim, Gwang-Cheon Jang, Hyeon-Jong Yang, Bok-Yang Pyun, Ji-Won Kwon, Myung Hyun Sohn, Kyu-Earn Kim, Jinho Yu, Soo-Jong Hong, Jung-Hyun Kwon, Sung-Won Kim, Sooyoung Lee, Woo Kyung Kim, Hyung Young Kim, Hye-Young Kim, Youhoon Jeon A299 Maternal Allergy Is Associated with Acute Bronchiolitis Severity in Infant Chang Hoon Lim, Yeongsang Jeong, Su Jung Kim A300 Evaluation of Inflammatory Mediator Profiles in Sputum of Asthmatics As an Endotype for Refractory Asthma Hun Soo Chang, Jeong-Seok Heo, Da-Jeong Bae, Jong-Uk Lee, Ji-Na Kim, Chang-Gi Min, Hyun Ji Song, Jong-Sook Park, Soo Hyun Kim, Choon-Sik Park A301 Autophagy Is Associated with the Severity of Asthma in an Ovalbumin-Specific Mouse Model of Allergic Asthma Jing-Nan Liu, Youngwoo Choi, Yoo Seob Shin, Hae-Sim Park A302 Interleukin-9 and Interleukin-33 Levels in Children with Asthma Nima Rezaei, Sedigheh Bahrami Mahneh, Arezou Rezaei, Maryam Sadr, Masoud Movahedi A303 Pediatric Anaphylaxis at a University Hospital in Cheonan, Korea, 2013~2014 Jun Seak Gang, Joon Soo Park, Seung Soo Kim, Hyun Ho Bang, Kyeong Bae Park, Hye Sun Kim, Tae Ho Kim, Young Hwangbo, Hyun Jung Lee, Gyeong Hee Yoo, Young Chang Kim A304 Initial Antigen-Specific IgE Levels Predict Clinical Outcome of Rush Oral Immunotherapy for Food Anaphylaxis Sakura Sato, Noriyuki Yanagida, Motohiro Ebisawa A305 ABCC4 gene Polymorphism Is Associated with High Periostin Levels in Asthmatic Patients Sailesh Palikhe, Hae-Sim Park, Seung-Hyun Kim, Ri-Yeon Kim, Eun-Mi Yang A306 The Role of Clinical Phenotype and Allergen Sensitization at 2 Years As Predictors of Atopic Disorders at 5 Years Li Yuan Gabriella Nadine Lee, Marion Aw, Marion Aw, Bee Wah Lee, Bee Wah Lee, Evelyn Xiu Ling Loo, Yiong Huak Chan, Lynette Shek, Lynette Shek, I-Chun Kuo, I-Chun Kuo, Phaik Ling Quah, Phaik Ling Quah, Genevieve Llanora, Gerez Irvin A307 The Effect of Korean Red Ginseng (KRG) on Rhinovirus Infection in Human Nasal Epithelial Cells Joo Hyun Jung, Il Gyu Kang, Seon Tae Kim, Hyoungmin Park A308 The Effect of Korean Red Ginseng on the Symptoms and Allergic Inflammation in Patients with Allergic Rhinitis Seon Tae Kim, Joo Hyun Jung, Il Gyu Kang, Hyoungmin Park, Kwang-Pil Ko A309 Validation of the Newly Developed Multiple Allergen Simultaneous Test in Korea Jungsoo Lee, Howard Chu, Hemin Lee, Jung U Shin, Chang Ook Park, Kwang Hoon Lee, Kwang Hoon Lee, Hong Kyu Kang A310 Assessment of Symptoms Severities of Allergic Rhinitis Patients Sensitive to Multiple Allergens in Skin Prick Test Dong Chang Lee, Geun Jeon Kim, Jae Hyung Hwang, Jin Bu Ha, Su Hee Jeong A311 Diurnal Temperature Range and Emergency Department Visits for Asthma in Korea 6 Cities Ho Kim, Shinha Hwang, Whahee Lee A312 Mannan-Binding Lectin Serum Levels in Atopic Mongolian Adults Enkhbayar Bazarsad, Logii Narantsetseg, Munkhbayarlakh Sonomjamts A313 Prevalence of Doctor Diagnosed Atopic Eczema, during 2003-2014 in KOREA ; Using Big Data of 48.1 Million South Korean Health-Care Records Gwang-Cheon Jang, Hyun-Hee Lee, Chang-Jong Lee, Huynsun Lim A314 Association of Recurrent Wheeze with Lung Function and Airway Inflammation in Preschool Children Ji-Eun Soh, Dae-Jin Song, Ji-Won Kwon, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So-Yeon Lee, Gwang-Cheon Jang, Woo Kyung Kim, Young-Ho Jung, Soo-Jong Hong, Jung Yeon Shim A315 Mannan-Binding Lectin Serum Levels in Healthy Mongolian Adults Enkhbayar Bazarsad, Logii Narantsetseg, Munkhbayarlakh Sonomjamts A316 Rotanebuliser Prabhakarrao Pv, Ranjitha Nadendla A317 The Level of Serum Interleukin 13 and Interleukin 17A and Its Effect Factors in Children with Asthma Juan Fang, Jing Zhao A318 Is Vitamin D Insufficiency Also Involved in Childhood Asthma in South Korea? Dae-Jin Song, Sungchul Seo, Young Yoo, Yu-Ri Kim, Ji Tae Choung, Jee Hoo Lee A319 Collection of Nasal Secretions for Measurement of Local IgE: A Quest for the Best Method Margot Berings, Natalie De Ruyck, Claus Bachert, Philippe Gevaert, Gabriële Holtappels A320 The Role of Claudin 5 in a Murine Model of Asthma Pureun-Haneul Lee, Byeong-Gon Kim, Choon-Sik Park, George D Leikauf, An-Soo Jang A321 Claudin-4 in a Murine Model of Asthma: Modulation By Acrolein, a Highly Reactive Unsaturated Aldehyde Byeong-Gon Kim, Pureun-Haneul Lee, Choon-Sik Park, An-Soo Jang A322 Efficacy and Safety of Sublingual Immunotherapy in House Dust Mite Sensitized Children with Allergic Rhinitis Yang Park A323 The Association of Vitamine D Deficiency and Skeletal Muscle Dysfunction in Chronic Airway Disease Min-Su Sohn, Hyun Jung Jin, Dong-Won Lee, Jun-Hong Ahn, Jin Hong Chung A324 Bacteria Derived Extracellular Vesicles in Indoor Dust Is Closely Associated with Airway Disease and Lung Cancer: Analysis of Indoor Dust’s Microbiome and IgG Sensitization of Indoor Bacteria Derived Extracellular Vesicles Sae-in Kim, Han-Ki Park, Do-Yeon Kim, Mina Rho, Jun-Pyo Choi, Yoon-Keun Kim A325 Clinical Care Program for Childhood Asthma (CCP-Childhood Asthma); A Multidisciplinary Team Care at Samitivej International Children’s Hospital Wasu Kamchaisatian, Thitikul Hiranras, Surinda Wongpun, Phornthip Chiraphorn, Anupan Tantachun, Wannipa Wongrassamee, Planee Vatanasurkitt, Naratip Somboonkul, Nattipat Juthacharoenwong, Surangkana Techapaitoon, Montri Tuchinda A326 Continuous B Cell Stimulation with CD40 Ligand Induce IgE Isotype Switching Jae Ho Lee, Sejin An A327 Effects of Interleukin-9 on Allergen-Specific Immunotherapy in a Mouse Model of Allergic Rhinitis Ji-Hyeon Shin, Soo Whan Kim, Si Won Kim, Jun Myung Kang, Boo-Young Kim, Byung-Guk Kim A328 Usefulness of Exhaled Nitric Oxide for Evaluating Wheeze and Airway Hyperresponsiveness in Preschool Children Jung-Won Lee, Ji-Won Kwon, Woo Kyung Kim, Hyung Young Kim, Hyo-Bin Kim, Ju-Hee Seo, So-Yeon Lee, Gwang-Cheon Jang, Young-Ho Jung, Soo-Jong Hong, Byoung-Ju Kim, Dae-Jin Song, Jung Yeon Shim A329 Systemic Cyclosporine Treatment in Hand Eczema Patients Kyung Ho Kim A330 Lipid Profiles and Adipokines in Korean Children with Atopic Dermatitis Young Yoo, Won Suck Yoon, Sungchul Seo, In Soon Kang, Jae Won Choi, Hye-Young Lim, Ji Tae Choung A331 Validation of Montelukast and Levocetirizine Combination Tablet Versus Individual Tablets in the Treatment of Moderate to Severe Persistent Allergic Rhinitis Among Adult Filipinos Seen at the Philippine General Hospital-Outpatient Department Michelle Buela A332 Efficacy of Makyokansekito on Treatment of Wheezing Lower Respiratory Tract Infection in Children: A Retrospective Study of 68 Patients Koji Nishimura A333 Serum Eosinophilia and Total IgE Are Associated with the Risk of Allergic Sensitization and Allergic Symptoms in Two Years Follow-up, Respectively Sang Chul Park, Hyo Jin Chung, Chang-Hoon Kim, Ju Wan Kang, Seong-Chul Hong, Keun-Hwa Lee, Jaechun Lee, Hye-Sook Lee, Jeong Hong Kim A334 The Sensitization to Russian Thistle on Mongolian Patients Narantsetseg Logii A335 The Association Between Air Pollution, Allergic Sensitization to Inhalant Allergens and Airway Hyperresponsiveness in Ulaanbaatar, Mongolia Munkhbayarlakh Sonomjamts, Enkhbayar Bazarsad A336 Pre-Coseasonal Treatment with a 5-Grass Pollen Sublingual Tablet in Adults Demonstrated a Reduction on Asthma Symptoms in Réunion Island Bashir Omarjee A337 Peak Expiratory Flow Rate Reference Values for Children Aged 5-14 Years Old in Beijing Urban Area Shuo LI A338 Soybean Storage Proteins As the Main Allergen in a Patient with Food-Dependent Exercise-Induced Anaphylaxis Due to Tofu Miyuki Hayashi, Ruby Pawankar, Shingo Yamanishi, Toru Igarashi, Yasuhiko Itoh A339 A Study of Allergy Skin Prick Test with Weed Pollen Oyuntsatsral Batsaikhan, B. Gantulga, B. Enkhbayar, S. Munkhbayarlakh, L.Narantsetseg A340 The Role of Neurotrophin in a Murine Model of House Dust Mite Induced Allergic Rhinitis Pei-Chi Chen, Jiu-Yao Wang A341 Mimotopes of the Major Shellfish Allergen Tropomyosin Suppress Splenocyte Proliferation and Local Cytokine Expression in a Mouse Model of Shellfish Allergy Nicki Y. H. Leung, Christine Yee Yan Wai, Patrick S.C. Leung, Ka Hou Chu A342 A Questionnaire Survey on Understanding of Atopic Dermatitis Among Korean Patients and Caregivers Eun Jin Doh, Dong Hun Lee, Mira Choi, Hyun-Sun Yoon, Kyu Han Kim, Ji Soo Lim A343 Comparison of the Dosage of Bronchodilators in the Bronchodilator Response Test in Children Ji Hyeon Baek, Man Yong Han, Seung Jin Lee, Youhoon Jeon, Kyung Suk Lee, Young-Ho Jung, Hye Mi Jee, Youn Ho Shin A344 The Expression and Effect of Natural Killer T Lymphocytes in Chidren with Asthma Yi Jiang, Miao Liu A345 Oral Provocation Test in Non-Steroidal Anti-Inflammatory Drug Hypersensitive Patients Referred to Singapore General Hospital Chaw Su Naing, Tze Chin Tan, Yong Yeow Chong A346 Different Phenotypes of Bhr (bronchial hyperresponsiveness) By Natural Course in Children and It’s Characteristics Young-Ho Kim, Eun Lee, Song-I Yang, Hyun-Ju Cho, Hyung Young Kim, Ji-Won Kwon, Young-Ho Jung, Byoung-Ju Kim, Ju-Hee Seo, Ho-Jang Kwon, Hyo-Bin Kim, So-Yeon Lee, Soo-Jong Hong, Soo Hyun Kim A347 Spectrum of Allergens Causing Allergic Rhinitis and Asthma in Urban Bangalore, India − a Study of 120 Patients Jacqueline Elizabeth Joseph, Soumya M. S, Ruby Pawankar, Harshitha Kumar A348 High Prevalence of Wheezing Illness and Risk Factor of Atopic Asthma Progression in Korean Preschool Children Sohyoung Yang, Sung-Il Woo A349 Clinical and Laboratory Screening of Primary Immunodeficiency Diseases: International Effects Nima Rezaei A350 The Effect of Helicobacter Pylori Infection in Atopic Individuals Sukran Kose, Basak Gol Serin, Arzu Didem Yalcin, Süheyla Serin Senger, Mehmet Erden, Ertan Serin A351 Clinical Spectrum and Natural History of Chronic Urticaria in Hong Kong Children Agnes Sze-Yin Leung, Ting Fan Leung A352 Skin Prick Test Reactivity to Common Pollen Aeroallergens in Patients with Allergic Rhinitis − in Urban Bangalore, India Harshitha Kumar, Soumya M.S., Jacqueline Elizabeth Joseph, Ruby Pawankar A353 Seasonal Patterns of Asthma-Related ED Visits and Admissions in Children and Adolescents Who Visited Emergency Rooms of Korea in 2007-2012 Eun Hee Chung A354 Prevalence of Atopic Dermatitis and Its Associated Risk Factors in Elementary School Children: A Cross-Sectional Study in Gyeonggi-Do, South Korea Eunji Kim, Young Yoo, Ji Tae Choung, Sungchul Seo, In Soon Kang, Jue Seong Lee, Ji Hyen Hwang A355 Intralymphatic Immunotherapy for Dermatophagoides Farinae, Dermatophagoides Pteronyssinus, Cat, and/or Dog Allergy in Patients with Allergic Rhinitis: 1 Year Follow-up Sang Min Lee, Joo Hyun Jung, Seung Joon Choi, Eugene Joe, Hyunjung Hwang, Shin Myung Kang, Yu Jin Kim, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Sang Pyo Lee A356 Respiratory Syncytial Virus Regulates IL-33 Expression in Bronchoalveolar Cells and Lung Tissue in Vivo Alina Gaisina, Igor Shilovskiy, Aleksandra Nikonova, Oleg Kamyshnikov, Musa Khaitov, Alexander Mitin, Komogorova Viktoriya, Marina Litvina, Nina Sharova A357 The Prevalence of Parent-Perceived Food Hypersensitivity in Pre-School Children Attending a Tertiary Care Hospital in Malaysia Faizah Mohamed Jamli A358 Th2 Dominant Airway Inflammation Induced By House Dust Mite Chitin Is Dependent on TNF-a and NKT Cell Da-Il Yoon, Jun-Pyo Choi, Han-Byul Choi, Yoon-Keun Kim, Hyeon-Il Choi A359 Geographic Variations in the Patterns of Sensitization to Aeroallergens in Korean Adults: A Multi-Center Study Mingyu Kang, Mi Yeoung Kim, Sujeong Kim, Eun-Jung Jo, Seoung-Eun Lee, Woo-Jung Song, Sang Min Lee, Chansun Park, Yoon-Seok Chang, Jaechun Lee, Young-Koo Jee, Inseon S Choi, Kyung-up Min, Sang-Heon Cho A360 Experimental Mouse Model of Asthma Induced By Dust Mite Dermatophagoides Pteronyssinus allergenic Extract Anton Laskin, Oleg Kamyshnikov, Alexander Babakhin, Valentina Berzhets, Musa Khaitov A361 Severe Refractory Pulmonary Complications in Children with Mycoplasma Pneumoniae Pneumonia Sejin An, Jae Ho Lee A362 Usefulness of Interactive e-Learning Education Program for Asthma Guideline Sung-Yoon Kang, Yoon-Seok Chang, Kyung-up Min, Sang-Heon Cho, Sae-Hoon Kim, Yong Eun Kwon, Young-Koo Jee, Tae-Bum Kim, Hee-Bom Moon, Hye-Kyung Park A363 Airway Inflammation Induced By House Dust Mite Derived Vesicles Is Mainly Induced By LPS Derived from Gram Negative Bacteria in Dust Mite. Sang-Yoon Kim, Jun-Pyo Choi, Han-Ki Park, Ji-Hyun Lee, Yoon-Keun Kim A364 Changes in the Recognition of Causal Allergen, Its Avoidance, and Allergen Specific Immunotherapy after Skin Prick Test / Intradermal Test, Nasal Provocation Test, and Intralymphatic Immunotherapy in Patients with Allergic Rhinitis: 1 Year Follow-up Hyunjung Hwang, Eugene Joe, Sang Min Lee, Seung Joon Choi, Joo Hyun Jung, Yong Han Seon, Shin Myung Kang, Yu Jin Kim, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Sang Pyo Lee A365 Laboratory Diagnostic of Staphylococcal Sensitization Natalya Khramykhoverchenko A366 Th-17 Regulatory Cytokines Enhance Neutrophil Production of IL-17 during Asthma Saleh Al Muhsen, Asma Sultana, Rabih Halwani, Ahmed Bahammam A367 Diagnostic Value of Serum Total IgE and Prediction of Cut-Off Value to Recommend Mast in Allergic Rhinitis Hyung Chae Yang, Sun Kyung Kim, Kwang Il Nam A368 Diagnostic Value of an Increase in FEV1 and/or FVC >12% and >200 mL from Baseline after Bronchodilators for Diagnosis of Asthma Jeong-Eun Kim, Ju Suk Lee, Ji Hyun Lee, Kyung Woo Kang A369 Combined Use of Fractional Exhaled Nitric Oxide and Bronchodilator Response in Predicting Future Loss of Asthma Control Among Children with Atopic Asthma Je-Kyung Kim, Youn-Soo Hahn, Jae-Yub Jung A370 Antigen-Specific IgA Plays an Important Role in Mucosal Immune Response in Allergic Children : Measurement of Secretory IgA and Antigen-Specific IgA Yosuke Baba, Sususmu Yamazaki, Eisuke Inage, Mari Mori, Yoshikazu Ohtsuka, Masato Kantake, Toshiaki Shimizu, Asuka Honjoh, Tomoaki Yokokura A371 Why Teaching Pediatrics Trainees about Anaphylaxis and Its Acute Management Is Essential: Cross Sectional Survey. Mehdi Adeli, Shaza Ali Mohammed Elhassan, Caroline Beck A372 Prevalence and Clinical Characteristics of Local Allergic Rhinitis in Children Min Sun Na, Heysung Baek, Seung Jin Lee, Ji Hyeon Baek, Jungwon Yoon, Sun Hee Choi, Young-Ho Jung, Youn Ho Shin, Man Yong Han A373 House Dust Mites Sublingual Immunotherapy Can Influence the Long-Term Evolution of Severe Atopic Dermatitis and the Progression to Respiratory Allergy. Enrico Compalati, Maurizio Marogna A374 The Positive Distribution Characteristics of 90 Food Specific IgG in Patients with Allergic Diseases Huimin Huang, Baoqing Sun, Mingyu BAI, Yiting Huo, Peiyan Zheng, Nili Wei, Wenting Luo A375 Evaluation of Serum Levels of Osteopontin As a Potential Biomarker of Immune Activation in Patients with Allergic Diseases Elisa Villa, Anand Andiappan, Rosalba Minisini, Olaf Rötzschke, Elena Boggio, Luca Gigliotti, Nausicaa Clemente, Annalisa Chiocchetti, Umberto Dianzani, Mario Pirisi A376 Prevalence of Allergic Rhinitis in 3-6-Year-Old (preschool) Children in Chiba City (urban area), Japan Fumiya Yamaide, Syuji Yonekura, Naoki Shimojo, Yuzaburo Inoue, Yoshitaka Okamoto A377 Comparative Efficacy of Combination Nebulized Salbutamol and Fluticasone Propionate and Nebulized Salbutamol in Children with Mild Moderate Asthma Attack Retno Asih Setyoningrum, Landia Setiawati, Sri Sumei, Deddy Iskandar A378 Characteristics of Children Hospitalized with Asthma in West Nusa Tenggara General Hospital Mataram Indonesia Indriyani Sang Ayu Kompiyang A379 Identification of Phenotypes in Allergic Bronchopulmonary Aspergillosis Using Cluster Analysis Tsuyoshi Oguma, Jun Tanaka, Katsuyoshi Tomomatsu, Koichiro Asano A380 The Roles of Type 2 Innate Lymphoid Cells (ILC2) in Chronic Rhinosinusitis (CRS) Keisuke Uno, Yoshinori Matsuwaki, Kazuhiro Omura, Eika Hayashi, Norifumi Tatsumi, Hirohito Kita, Nobuyoshi Otori, Hiromi Kojima A381 Respiratory Symptoms, Signs and Spirometry Indexes Comparision in 7-12 Years Old Girls in Esfahan Metropolis and Its Far Suburb Mohammadreza Fatemi Khorasgani A382 Induction of Kruppel-like Transcription Factor (KLF4&5) By Baker’s Yeast Mannan in Human Bronchial Epithelial and Smooth Muscle Cells Dukhee/Betty Lew, Kim/S. Lemessurier, Joseph/a Moore, Jeoung-Eun Park, Ae-Kyung Yi, Chi/Young Song, Kafait/U Malik A383 Korean Profile in Childhood Asthma Severity Classification Dongin Suh, Ja Kyoung Kim, Hyeon-Jong Yang, Bong-Seong Kim, Youn Ho Shin, So-Yeon Lee, Geunhwa Park, Woo Kyung Kim, Hyo-Bin Kim, Heysung Baek, Dae Hyun Lim, Dae Hyun Lim, Jin Tack Kim A384 Prevalence of Food Sensitization, IgE-Mediated and Non-IgE-Mediated Food Allergy Among Pediatric Patients Diagnosed with Autism Spectrum Disorders Aimee Lou Manalo Nano A385 Component-Resolved Diagnostic Study of Dermatophagoides Pteronyssinus Major Allergen Molecules in a Southern China Wenting Luo, Baoqing Sun A386 Risk Factors for Systemic and Local Reactions to Subcutaneous Allergen Immunotherapy Hikmet Tekin Nacaroglu, Semiha Bahceci Erdem, Ozlem Sumer, Sait Karaman, Canan Sule Unsal Karkiner, Suna Asilsoy, Ilker Gunay, Demet Can A387 Literature Review and Current Treatment Options for Cyclical Anaphylaxis Danielle Kiers A388 The Effect of Surfactant Protein D in Acute Lung Injury and Pulmonary Fibrosis Induced By Bleomycin Hsu Han Yin, Jiu-Yao Wang A389 Activation of Endothelial Cells to Release Hsp90, an Activator of the Prekallikrein-High Molecular Weight Kininogen (HK) Complex Allen Kaplan, Kusumam Joseph, Baby G. Tholanikunnel A390 The Effect of Climatic Treatment in 51 Asthmatic Children from Areas Severely Polluted Environment of Northern Moravia, Czech Republic Radim Dudek A391 Comparison of Some Vitamin Groups in Asthmatic Patients Gulden Bilgin, Hatice Surer, Aytun Sadan Kilinc, Dogan Yucel A392 Sensitization in Children with Atopic Dermatitis: A Single Center Study Ji Young Lee, Jihyun Kim, Hea-Kyoung Yang, Minji Kim, Sang-Il Lee, Kangmo Ahn A393 Staphylococcal Enterotoxin IgE Sensitization: A Risk Factor for COPD Overlap in the Elderly Asthma? Sung Do Moon, Byung-Keun Kim, Sang-Heon Cho, Kyung-up Min, Yoon-Seok Chang, Heung Woo Park, Hye-Ryun Kang, Woo-Jung Song, Min-Koo Kang, Ju-Young Kim, Kyonghee Sohn, Ha Kyung Won, Seoung-Eun Lee, Kyung-Mook Kim, Claus Bachert A394 The Effects of Probiotics and PparÎ(3) on the Murine Model of Allergic Asthma Miao-Hsi Hsieh, Jiu-Yao Wang A395 Adult Patients’ Views on the Design of Adrenaline Autoinjectors Helen Smith, Clare Brown, Christina Jones, Mark Davies A396 CCL22 miRNA modulated Th1 responses and induced therapeutic effects on OVA-induced mouse model of asthma Won Suck Yoon A397 Clinical, Histological, and Skin Microbiome Characteristics of Head and Neck Dermatitis in Atopic Dermatitis Hemin Lee, Howard Chu, Jungsoo Lee, Jung U Shin, Chang Ook Park, Kwang Hoon Lee, Seo Hyeong Kim, Ji Yeon Noh, Ji Hye Kim A398 MicroRNA-432 modulates Th1 responses and induced therapeutic effects in atopic like murine model. Won Suck Yoon A399 Case Report of Near-Fatal Asthma Due to Snail Allergy in a House Dust Mite-Allergic Adult Jean-Pierre L’huillier, Jean-Eric Autegarden, Catherine Bertrand, Dominique Tardy A400 Relationship Between Gut Microbiota in the First 3 Months of Life and Infant Immune Function at Age 12 Months Intan Hakimah Ismail, Mimi Tang, Paul Licciardi, Frances Oppedisano, Robert Boyle, Roy Robins-Browne A401 A Pediatric Case of Food-Dependent Exercise-Induced Anaphylaxis Due to Spice Allergy Hisako Yagi, Harumi Koyama, Yutaka Nishida, Takumi Takizawa, Hirokazu Arakawa A402 Correlations Between Objective Severity Score and Each of the Subjective Severity Intensity in Atopic Dermatitis Hong Kyu Kang, Hemin Lee, Jungsoo Lee, Jung U Shin, Kwang Hoon Lee, Kwang Hoon Lee, Howard Chu, Chang Ook Park A403 Barrier Related Gene Mutations in Atopic Dermatitis Na Young Yoon, Hyeyoung Lee, Seong Jun Seo, Eunhee Choi, Hye-Young Wang, Minyoung Jung, Eung Ho Choi, Dong Hye Kim A404 Clinical Utility of Basophil Activation Test (BAT) in the Diagnosis of Drug Induced Anaphylaxis Joo-Hee KimYoung-Sook Jang, Jeong-Hee Choi, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung A405 Feeding Shapes the Colonization of Gut Microbiota and Associated with Total IgE in Infant Mi-Jin KangDongin Suh, Eun Lee, Kil Yong Choi, Young-Ho Jung, Song-I Yang, Bong-Soo Kim, Ha-Jung Kim, Juneyoung Koh, Hyun-Jin Kim, Kangmo Ahn, Youn Ho Shin, Hyun-Ju Cho, Byoung-Ju Kim, Young-Ho Kim, Yean Jung A406 CD8(+)T Cell-Intrinsic Smad4 Suppresses Th2 Responses in the Pathogenesis of Contact Hypersensitivity Mizuko Mamura, Jeong-Hwan Yoon, Susumu Nakae, Inkyu Lee, Isao Matsumoto, Takayuki Sumida, Jin Soo Han, Katsuko Sudo, Ji Hyeon Ju A407 Immune-Modulatory Genomic Properties Differentiate Gut Microbiotas of Infants with and without Eczema Gaik Chin Yap, Wen Tso Liu, Seungdae Oh, Pei Ying Hong, Chiung Hui Huang, Marion Aw, Lynette Shek, Bee Wah Lee A408 The Effect of Medication in OSA Patients with Allergic Rhinitis Young Seok Byun, Sung Wan Kim, Tae Kyung Koh, Joong-Saeng Jo, Kun Hee Lee, Chul Kwon, Sung-Hwa Dong A409 A Case of Generalized Pustular Psoriasis Mimicking Acute Generalized Exanthematous Pustulosis Myung Shin Kim, Chansun Park A410 Anaphylaxis Caused By Gummy Jelly Ingestion: A Case Report Han Seok Cho, Min-Ju Kim, Min Ji Kim, Young Ok Park, Hye Yeong Lee, Hee Seong Kim, Eun Lee, Hyun-Ju Cho, Jinho Yu, Soo-Jong Hong, Keum Hee Hwang A411 Serum Folliculin As a Novel Biomarker for Asthma Jung-Hyun Kim, You Sook Cho, Sae-Hoon Kim, Hyouk-Soo Kwon, Mira Yoo, Hyo-Jung Kim, So-Young Park, Bomi Shin, So Young Park, Bomi Seo, Min-Gu Kim, Hee-Bom Moon, Jin-Ah Park, Tae-Bum Kim, Jaemoon Lee A412 Corticosteroid Nasal Irrigations after Endoscopic Sinus Surgery in the Management of Chronic Rhinosinusitis with Asthma Jin Hyeok Jeong, Tae Wook Kang, Han Seok Yoo, Yong Hee Cho, Seok Hyun Cho, Kyung Rae Kim A413 Capsaicin Injection in Neonatal Period Potentiates Intensity and Duration of Atopic Dermatitis of Rats. Jue Seong Lee, Sun-Ho Kee, Sewon Kim, Young Yoo, Heung Sik Na, Seung Keun Back A414 Comparison Between the Impulse Oscillometry System, Spirometry, Feno, Lung Clearance Index and Asthma Control and Exacerbation Status. Seung Jin Lee, Bo Seon Seo, Ji Hyeon Baek, Kyung Suk Lee, Young-Ho Jung, Hye Mi Jee, Youn Ho Shin, Man Yong Han, Mi-Ae Kim A415 The Association of Exhaled Nitric Oxide and Airway Hyperresponsiveness in Patients with and without Asthma Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A416 Effects of Air Pollution on Allergic Rhinitis in Korea Jisun Park A417 Exhaled Nitric Oxide in Korean Children with Allergic Rhinitis Seung Hyun Moon A418 A Questionnaire of Children with Asthma or Asthma and Allergic Rhinitis Rong Jun Lin, Ren Zheng Guan A419 A Case of Trimebutine-Induced Morbilliform Skin Eruption Gyeong Yul Park, Hyun-Sun Yoon A420 Comparison of Methacholine and Mannitol to Predict Exercise-Induced Bronchoconstriction in Children with Asthma Woo-Hyeok Choi, Heysung Baek A421 Different Inflammatory Mechanisms of Human Metapneumovirus and Respiratory Syncytial Virus Jin-Sung Park, Eunmi Kwon, Zac Callaway, Chang-Keun Kim, Takao Fujisawa A422 Sputum Microbiota in Chinese Adults with Eosinophilic Versus Non-Eosinophilic Asthma Qingling Zhang, Rihuang Qiu, Naijian Li, Zhaowei Yang, Jing Li, Kian Fan Chung, Nanshan Zhong A423 Which Clinical Features Are Useful in Predicting Presence of Staphylococcus Aureus colonization/Infection in Childhood Atopic Dermatitis? Kam Lun E. Hon, Yin Ching K. Tsang, Ting Fan Leung A424 Clinical Significance of Increased VEGF, TGF-Î(2)(1,) and YKL-40, a Chitinase like Protein, in Serum of the Children with Asthma Yoon Young Jang, Hai Lee Chung, Seung Gook Lee, Ji Hyun Na, Jong Hoon Lee A425 Analysis of Follow-up Results of Mannitol Challenge Test in Asthma Patients Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A426 Analysis of 68 Oral Walnut Challenge Tests Mikita Yamamoto, Sakura Sato, Noriyuki Yanagida, Ayako Ogawa, Kanako Ogura, Kyohei Takahashi, Kenichi Nagakura, Shigehito Emura, Tomoyuki Asaumi, Katsuhito Iikura, Motohiro Ebisawa, Yu Okada A427 Effectiveness of Air Filters Intervention in Allergic Rhinitis Jiaying Luo, Xiao Lan, Baoqing Sun, Zhao Chen, Guiyuan Sun, Shimin Li, Jiaqing Hu A428 The Relationship Between Airway Hyperresponsiveness to Mannitol and Atopy in Asthmatic Children Woo-Hyeok Choi, Heysung Baek A429 Anaphylactoid Reactions to N-Acetylcysteine in the Treatment of Aacetaminophen Overdose Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A430 Effect of Prenatal Maternal Distress and GSDMB Polymorphism on the Development of Recurrent Wheezing in Early Childhood: COCOA Study Yean Jung Choi, Si Hyeon Lee, Young-Ho Kim, Mi-Jin Kang, Hyun-Ju Cho, Eun Lee, Song-I Yang, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Yoon Hee Kim, So-Yeon Lee, Hyoung Yoon Chang, In Ae Choi, Kyung-Sook Lee, Yee-Jin Shin A431 Vitamin D Level in Allergic Rhinitis: A Systemic Review and Meta-Analysis Yoon Hee Kim, Min Jung Kim, In Suk Sol, Seo Hee Yoon, Young a Park, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Yong Ju Lee A432 Implication of Inspiratory and Expiratory Resistance and Reactance in Children with Asthma In Suk Sol, Kyu-Earn Kim, Yoon Hee Kim, Min Jung Kim, Seo Hee Yoon, Yong Ju Lee, Kyung Won Kim, Young a Park, Myung Hyun Sohn A433 The Association of Asthma Predictive Index with Asthma in Preschool Children with Recurrent Wheeze Sung Joo Park, Ji-Won Kwon, Woo Kyung Kim, Hyung Young Kim, Hyo-Bin Kim, Ju-Hee Seo, So-Yeon Lee, Gwang-Cheon Jang, Young-Ho Jung, Soo-Jong Hong, Byoung-Ju Kim, Dae-Jin Song, Yun Seok Yang, Jung Yeon Shim A434 Clinical Significance of Serum Total IgE Levels in Children with RSV-Associated Lower Respiratory Illness Yoon Young Jang, Hai Lee Chung, Ji Hye Kim, Hyun Seok Lee, Chang Ho Lee A435 Development of a Oak Pollen Emission and Transport Modeling Framework in South Korea Changbum Cho, Yun-Kyu Lim, Kyu Rang Kim, Mijin Kim, Baek-Jo Kim A436 Temperature, Humidity, and Air Pollution Affect Atopic Dermatitis Symptoms in Infants and Young Children Young-Min Kim, Youngshin Han, Jihyun Kim, Hae-Kwan Cheong, Byoung-Hak Jeon, Kangmo Ahn A437 Effects of Compound V on Pulmonary Fibrosis Model Chuang/Yao Ming, Jiu-Yao Wang, Ye/Yi Ling A438 Vitamin D Level and the Correlation with IgE in Children with Allergic Respiratory Diseases in Guangzhou China Huimin Huang, Baoqing Sun, Yun Chen, Peiyan Zheng, Nili Wei, Wenting Luo A439 Two Case Reports of Eosinophilic Gastroenteritis Associated with Allergic Disease Do Hyeong Lee, Gil-Soon Choi, Hee-Kyoo Kim, Han Su Park A440 Genome-Wide Association Study (GWAS) May Identify Common Genetic Variations Both in Immediate and Delayed Drug So-Young Park, Hyo-Jung Kim, Bomi Seo, Jung-Hyun Kim, Min-Gu Kim, Hyouk-Soo Kwon, You Sook Cho, Hee-Bom Moon, Tae-Bum Kim, Yoon Su Lee A441 Development of a Questionnaire for Secular Change of Atopic Dermatitis from Birth to 19-Year-Old. Akio Tanaka, Satoshi Morioke, Yukihiro Ohya, Naoki Shimojo, Akira Akasawa, Michihiro Hide, Hiroko Shizukawa A442 Evaluation of the Adherence Starts with Knowledge-20 (ASK-20) to Inhaled Drug in Patients with Bronchial Asthma Naoto Watanabe A443 The Epidemiology and Clinical Manifestation of Hmpv Infection in Children during Recent 4 Years: 2011-2014 Meeyong Shin, Myeong Sun Jang A444 Neutropenia Induced By Intravenous Immunoglobulin Young-Hee Nam, Yeo Myeong Noh, Dong Sub Jeon, Hee-Joo Nam, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A445 A First Case of Lymphocytic Interstitial Pneumonitis in Healthy Child Ji-in Jung, Ha-Su Kim, Hyun-a Kim, Jin-a Jung A446 Cytokine Production upon House Dust Mite Stimulation of Cord Blood Mononuclear Cells from Caesarean Section-Delivered Singaporean Infants Anne Goh, Rajeshwar Rao, Bindu Nandanan, Ruurd Van Elburg, Chua Mei Chien, Juandy Jo, Johan Garssen, Johan Garssen, Leon Knippels, Elena Sandalova, Wen Chin Chiang A447 Dress Syndrome with Acute Interstitial Nephritis Caused By Quinolone and Nonsteroidal Anti-Inflammatory Drugs Young-Hee Nam, Ji Young Juong, Soo Jin Kim, Eun Young Kim, Su Mi Lee, Young Ki Son, Hee-Joo Nam, Ki-Ho Kim, Soo-Keol Lee A448 IL-23 Roles in the Development of House Dust Mite Allergic Sensitization and Asthma Da-Eun Park, Hye-Ryun Kang, Heung Woo Park, Hyun Seung Lee, Yoon-Seok Chang, Jung-Won Park, Sang-Heon Cho, Kyung-up Min, Woo-Jung Song A449 Exposure Profile of Indoor Risk Factors in Dwellings of Children with Atopic Dermatitis Hyunwook Lim, Sungchul Seo, Ji Tae Choung, Young Yoo, Jun-Sik Park, Byung Kwan Kim A450 Epidemiological Characterization of Blood Eosinophils in the Elderly Population Ha Kyeong Won, Hye-Ryun Kang, Byung-Keun Kim, Sung Do Moon, Ju-Young Kim, So-Hee Lee, Woo-Jung Song, Heung Woo Park, Min-Koo Kang, Sun-Sin Kim, Sang-Heon Cho, Kyung-up Min, Yoon-Seok Chang, Kyoung Hee Sohn, Kyung-Mook Kim, Ki-Woong Kim, Hak Chul Jang A451 Stevens-Johnson Syndrome Caused By Methotrexate in the Treatment of Psoriasis Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A452 Genetic Determinants for Lung Function Growth in Asthmatic Children Ting Fan Leung, Man Fung Tang, Hing Yee Sy, Wa Cheong Chan, Wilson Wai San Tam A453 The Power of Allergen Specific Ig E in the Classification of Rhinitis, Korean National Hanes 2010 Seung Kyu Chung, Sujin Kim, Sang Duk Hong, Hyo Yeol Kim Hyo Yeol Kim, Hun-Jong Dhong, Jong in Jeong A454 Analysis of Allergen Immunotherapy Practice and Patients’ Knowledge and Attitude about Allergen Immunotherapy in a Single Tertiary Hospital in Korea Young-Hee Nam, Dong Sub Jeon, Soo-Keol Lee A455 Roles of Staphylococcal Enterotoxin B in House Dust Mite-Induced Acute Asthma Models Ji Won Lee, Mingyu Kang, Soon-Hee Kim A456 A Clinical Comparison of Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome in a Single Tertiary Hospital in Korea Young-Hee Nam, Dong Sub Jeon, Hee-Joo Nam, Yeo Myeong Noh, Sang Hee Kim Kim, Ye Suel Park, Soo-Keol Lee A457 The Beneficial Effect of Lactobacillus Gasseri PM-A0005 and Its Immunoregulatory Protein PMA5P40 on Milk-Induced Allergic Enteritis Yung-I Hou, Jiu-Yao Wang A458 Relationship Between Serum Folate Levels and Risks of Allergic and Respiratory Diseases in Early Childhood: The Mothers and Children’s Environmental Health Study Ja Hyeong Kim, Seol Jae Hee, Eun-Hee Ha, Hyesook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Namsoo Chang A459 Effects of Vitamin D in Patients with Chronic Rhinosinusitis Yuta Soma, So Watanabe, Ruby Pawankar, Ruby Pawankar, Harumi Suzaki, Harumi Suzaki, Hitome Kobayashi A460 Clinical Features of Systemic Contact Dermatitis from Ingestion of Rhus Young-Hee Nam, Chansun Park, Soo-Keol Lee A461 Sublingual Immunotherapy Efficacy in Patients with Atopic Dermatitis in Korea Jongrok Lee, Jooyoung Roh, Haryeong Ryu A462 Characteristics of Serious Adverse Drug Reactions in a Tertiary University Hospital Cheol-Woo Kim, Jae Hwa Cho, Mi Ra Eom, Ji Young Kang, Hye Gyeung Lee A463 Eyelid Dermatitis: Patch Test Results during a 15-Year Period in Korea and Evaluation of Metal Contents in Eye Shadows Hae Young Choi, Hye Jin Lee, Ju Yun Woo, Ji Yeon Byun, You Won Choi A464 Relationship Between Lipid Levels and Risks of Allergic and Respiratory Diseases in Early Childhood: The Mothers and Children’s Environmental Health Study Ja Hyeong Kim, Eun-Hee Ha, Hyesook Park, Mina Ha, Yun-Chul Hong, Yangho Kim, Namsoo Chang A465 IL-32 in the Induced Sputum of Patients with Asthma Jae-Woo Kwon, Hun Soo Chang, Jeong-Seok Heo, Jong-Uk Lee, Jong-Sook Park, Eusom Kim, Soo Hyun Kim, Choon-Sik Park A466 Clinical Characteristics of Patients with Chromium Allergy in a Single University Hospital in Korea Hae Young Choi, Ji Yeon Byun, Ju Yun Woo, You Won Choi A467 Efficacy and Safety of Oral Acitretin in Chronic Hand Eczema Hyun-Ju Jin, Jin-Hwa Son, Jeong-Min Kim, Gun-Wook Kim, Je-Ho Mun, Margaret Song, Hyun-Chang Ko, Moon-Bum Kim, Hoon-Soo Kim, Byung Soo Kim A468 Atypical Antipsychotics and Anticholinergic Agents Mimicking Anaphylaxis Sheryl Van Nunen, Dinh Van Nguyen, Anthony Elias, Susannah Olivia Lauer A469 Introducing Reach (Reliable Estimation of Atopic dermatitis in ChildHood): Novel, Questionnaire-Based Diagnostic Criteria for Childhood Atopic Dermatitis Seung-Chul Lee, Ho-June Lee, Jung Min Bae A470 Comprehensive Assessment to Identify the Causative Factors in Oral Allergy Syndrome Emi Ono A471 Comparison of Interpretation Methods in Allergic Skin Test Sung-Hwa Dong, Tae Kyung Koh, Young Seok Byun, Sung Wan Kim, Joong-Saeng Jo, Chul Kwon, Kun Hee Lee A472 Refraining Aminophylline Use Increases Hospitalization Among Children with Acute Asthma: A 10-Years Retrospective Cohort Study Li-Fan Liu A473 The Prevalence and Risk Factors of Atopic Dermatitis from Nationwide Study for Korean School Students Sunghee Lee A474 Probiotic Recombination Protein Effect on Atopic Dermatitis Wei-Leng Chen, Jiu-Yao Wang A475 Allergic Sensitization Status in Various Inflammatory Skin Diseases Youin Bae, Gyeong-Hun Park A476 Two Cases of Good’s Syndrome: A Rare Acquired Immunodeficiency Associated with Thymoma Suk Yeon Kim A477 IL-23 Has a Role to Play in the Development of Asthma in Short-Term Cigarette Smoke Exposure-Induced House-Dust Mite Allergic Model Hyun Seung Lee, Woo-Jung Song, Mingyu Kang, Han-Ki Park, Da-Eun Park, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Hye-Young Kim, Kyung-up Min, Sang-Heon Cho, Ji-Won Lee, Boram Bae, Jung-Won Park A478 The Relationship Between the Relevance of Allergic Disease and the Value of Non-Specific IgE Yasuhiro Suzuki A479 Two Caces of Prawn Allergy in Adult Patients Ismet Bulut, Zeynep Ferhan Ozseker A480 Early Gut Bifidobacterium Breve and B. Catenulatum Colonisation Differentially Modulate Eczema Risk in Children at High-Risk of Developing Allergic Disease Intan Hakimah Ismail, Robert Boyle, Paul Licciardi, Frances Oppedisano, Roy Robins-Browne, Mimi Tang A481 Effects of Chronic Repeated Exposure of Staphylococcal Enterotoxin B on Allergic Asthma Model in Mice Ji Won Lee, Hyun Seung Lee, Mingyu Kang, Da-Eun Park, Han-Ki Park, Soon-Hee Kim, Woo-Jung Song, Hye-Ryun Kang, Heung Woo Park, Yoon-Seok Chang, Chang-Han Park, Suk-Il Chang, Sook-Hee Song, Kyung-up Min, Sang-Heon Cho, Boram Bae A482 Skin Prick Test Result and Allergen Immunotherapy in Children with Allergic Rhinitis Grace Shieh A483 Role of Brp-39 in RSV-Induced Airway Inflammation in Mice Min Jung Kim, Jung Yeon Hong, Seo Hee Yoon, Doo Hee Shim, In Suk Sol, Yoon Hee Kim, Mi Na Kim, Kyung Eun Lee, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim, Jae Myun Lee A484 Long-Term Outcomes of Twenty-Four Adults with Primary Immunodeficiency from a Single Centre in Singapore Hiok Hee Chng A485 Breast Feeding Increases the Risk of Food Sensitization but Does Not Affect Food Allergy in Young Children with Atopic Dermatitis Dong Chan Kim, Song-I Yang, Hae Ran Lee, An Deok Seo, So Yeon Lee A486 IgE Immunoadsorption Knocks Down Anaphylaxis. Alessandro Fiocchi, Maria Cristina Artesani, Paola Francalanci, Lamia Dahdah, Thomas Schreiner A487 Burden and Correlates of Cigarette Smoking and Respiratory Airway Obstruction: An Observation in Urban Adult Population of West Bengal (India) Kaushik Chakraborty A488 Blood Eosinophils Could Predict Sputum Eosinophilia? : A Comparison Between Asthma and Non-Asthmatic Chronic Cough in the Elderly Ha Kyeong Won, Ju-Young Kim, Eun-Jung Jo, Kyoung Hee Sohn, Kyung-Mook Kim, Heung Woo Park, Yoon-Seok Chang, Sang-Heon Cho, Woo-Jung Song, Byung-Keun Kim A489 Complementary and Alternative Medicine for Allergic Rhinitis in Japan Syuji Yonekura, Yoshitaka Okamoto A490 Impact of Cognitive Impairment on Asthma Control Status in Elderly Asthmatics Gyu Young Hur, Young Min Ye, Joo-Hee Kim, Ki-Suck Jung, Junga Kim, Jae Jeong Shim, Hae-Sim Park A491 The Association Between Respiratory Tract Infection and Reactive Oxygen Stress Kazuhiro Sekimoto, Kazuko Sugai, Keiji Tsuchimoto, Hiromi Uehara, Masanori Ikeda A492 The Risk Factors and Lung Function of Current Allergic Rhinitis Due to Dust Mite Sensitization Euncho Chung, Kang Seo Park, Yean Jung Choi, Jeewon Park, Soo-Jong Hong, So Yeon Lee A493 Cloning and Expression of Recombinant Blomia Tropicalis Dust Mite Allergen Blo t 7 Alain Jacquet, Arun Buaklin, Nat Malainual A494 Seasonal Variations of Airborne Pollen in Bangalore, India Roopashree S A495 Pollen Observation and Use of Data Kyu Rang Kim, Mijin Kim, Changbum Cho, Baek-Jo Kim, Jae-Won Oh, Mae Ja Han A496 The Effect of Cord Serum 25-Hydroxyvitamin D (25(OH)D) on the Development of Atopic Dermatitis in First 3 Years of Life : Cocoa Study Hyun-Ju Cho, Youn Ho Shin, Eun Lee, Young-Ho Kim, Darae Lee, Mi-Jin Kang, Song-I Yang, Kangmo Ahn, Kyung Won Kim, Yoon Hee Kim, Hye-Sung Won, Soo Hyun Kim, Suk-Joo Choi, Young Han Kim, Jong Kwan Jun, Eun-Jin Kim, Jeom Gyu Lee, So-Yeon Lee, Soo-Jong Hong, Dongin Suh A497 Contribution of Stem Cell Factor Autocrine/Paracrine Mechanism to Aberrant Proliferation of Mast Cells Yosuke Amagai, Akane Tanaka, Hiroshi Matsuda A498 A Randomized Dbpc Dose-Finding Multicenter Trial of Sublingual Immunotherapy (SLIT) Allergoid Tablets in House Dust Mites (HDM) Allergic Patients Ralph Mösges, Pauline Dieterich, Anatoli Astvatsatourov, Christoph Hüser, Jaswinder Singh, Kija Shah-Hosseini, Silke Allekotte, Enrico Compalati A499 Depression and Allergy in the Elderly: A Community Population Analysis Kyoung Hee Sohn, Woo-Jung Song, Byung-Keun Kim, Ju-Young Kim, Min Suk Yang, So-Hee Lee, Sae-Hoon Kim, Hye-Ryun Kang, Heung Woo Park, Sun-Sin Kim, Kyung-up Min, Sang-Heon Cho, Yoon-Seok Chang A500 The Integrated Analysis of Correlation Between Total IgE and Other Immunological Factors in Allergic Diseases Woo-Sung Chang, Ji-Hye Do, Yeon-Seop Kim, Dankyu Yoon, Hye-Sun Lim, Jeom-Kyu Lee, Eun-Jin Kim A501 Pattern of Allergic Diseases Among Military Servicemen Referred to a Clinical Immunology/Allergy Service in Singapore Bernard Thong, Yew Kuang Cheng, Jinfeng Hou, Khai Pang Leong, Justina Tan, Faith Chia, Grace Chan, Sze-Chin Tan, Teck Choon Tan, Chwee Ying Tang, Hiok Hee Chng A502 A Case of Rifampicin-Induced Hypersensitivity Diagnosed By the Lymphocyte Activation Test with Successful Desensitization Chan-Sun Park, Mi Yeoung Kim, Eun-Young Kim, Jae-Gook Shin, Jae-Hyeog Choi, Saegwang Park, Yeonye Kim A503 Analysis of Individual Case Safety Reports of Drug-Induced Anaphylaxis Based on Korea Adverse Event Reporting System Database Kyung-Hwan Lim, Jae Woo Jung, Mingyu Kang, Ju-Young Kim, Ju-Young Kim, Hyun Jeong Kim, Yeon-Ju Woo, Soo-Youn Jung, Hye-Ryun Kang, Hye-Ryun Kang A504 Impact of Processes Certification on the Liability of Anti-Dust Mites Bed Covers Thierry Porée, Nabile Boukhettala, Emeline Furon A505 Localisation Kinetics of Aluminium after Subcutaneous Injection in a Rat Model Alan David Bullimore, Matthew Heath, Simon Hewings, Murray Skinner A506 Periostin Levels in Exhaled Breath Condensate of Competitive Athletes, Asthmatics and Healthy Subjects - Associations with Outdoor Ambient Conditions Marcin Kurowski, Hubert Krysztofiak, Aleksandra Wardzynska, Marzanna Jarzebska, Janusz Jurczyk, Marek L. Kowalski A507 The Role of PKR Pathway in Acute Exacerbation of Severe Bronchial Asthma So Ri Kim, Yong Chul Lee, Dong Im Kim, Yang Keun Rhee, Heung Bum Lee, Seoung Ju Park, Yeong Hun Choe Choe, Seung Yong Park A508 Diversity of Clinical Manifestations and Treatment Responses for Idiopathic Hypereosinophilic Syndrome Joo-Hee Kim, Sunghoon Park, Young Il Hwang, Seung Hun Jang, Ki-Suck Jung A509 Effect of Dexamethasone in Th17 Cell Mediating Neutrophilic Asthma Nong Guang-Min, Jiang Min A510 Allergen Profile for Asthma/Rhinitis and Eczema Among Patients in North India: An Immunocap Allergen Specific IgE Antibodies Assay Based Study Nalin Nag A511 Clinical Profile of Allergic Rhinitis in Children in Jakarta Wahyuni Indawati A512 Preclinical Study on the Use of Micro Crystalline Tyrosine (MCT) Adjuvants in Allergy Immunotherapy Alan David Bullimore, Matthew Heath, Murray Skinner A513 Genetic Diversity of Filaggrin Mutation and Its Clinical Implication in East Asian Atopic Dermatitis Patients Seong Jun Seo, Won Jong Oh A514 Protein and MPL Adsorption Capacities for MCT in Candidate Therapeutic Formulations for Use in Immunotherapy, Compared Against Existing Adjuvants Alan David Bullimore, Murray Skinner, Matthew Heath, Andrew Bell A515 Interleukin-22 Gene Variation in Inflammatory Bowel Disease Alireza Zarebidoki, Hournaz Hasanzadeh, Salman Sadeghzade, Nima Rezaei A516 Immunomodulatory Effects of Adipose-Derived Stem Cell Secretome in a Mouse Model of Asthma Kyu-Sup Cho A517 Diffuse Alveolar Hemorrhage with Positive Anti-Neutrophil Cytoplasmic Antibody in a Child : A Case Report Sung-Woo Kim, Moo-Young Oh A518 Clinical Analys the Serum TARC Levels As the Condition Index of Atopic Dermatitis in the Early Infancy Munemitsu Koizumi, Kazuyo Kuzume A519 An Analysis of the Filaggrin Gene Polymorphism in Korean Atopic Dermatitis Patients Kui Young Park, Won Jong Oh A520 A New Protocol for Wheat Oral Immunotherapy in Patients with Anaphylaxis Delara Babaie, Mohammad Nabavi, Fariborz Zandieh, Mehrdad Amir Moini, Zahra Chavoshzadeh, Hamideh Seifi, Mitra Sahragard, Mehrnaz Mesdaghi, Mohammad Hassan Bemanian A521 Clinical Characteristics of Filaggrin-Related Atopic Dermatitis Patients in Korea Sun Young Choi, Yeon a No A522 Early Allergy Diagnosis in Children - Self- Administered Questionnaire Vs Medical Verification Andrzej M. Fal, Dorota Kiedik, Agnieszka Muszynska, Iwona Pirogowicz A523 Asthma Impact on Children with Food Induced Anaphylaxis Chikako Motomura, Masatoshi Wakatsuki, Yuko Akamine, Mihoko Iwata, Hiroshi Matsuzaki, Naohiko Taba, Yoko Murakami, Hiroshi Odajima A524 Case Reports of Stevens-Johnson Syndrome and Stevens-Johnson Syndrome-Toxic Epidermal Necrolysis in Systemic Lupus Erythematosus Reni Ghrahani A525 The Effectiveness of Oral Tolerance Induction for Wheat Allergy Using Two Different Intake Levels Yuri Takaoka A526 Association of Plasma Interleukin-25 Levels with Development of Aspirin Induced Airway Spasm in Asthma Jong-Uk Lee, Jeong-Seok Heo, Da-Jeong Bae, Hyun Ji Song, Choon-Sik Park, Jong-Sook Park A527 Transition of Allergic and Nonallergic Rhinitis after 2 Years in Korean Children: Preliminary Study Jae Hoon Cho, Ji Ho Choi A528 Early Onset of Psoriasis Juvenile Idiopathic Arthritis Budi Setiabudiawan, Fiska Febriana, Reni Ghrahani, Gartika Sapartini A529 Clinical Features of Immediate Hypersensitivity to Histamine H2 Antagonists and Their Cross Reactivity Chan-Sun Park, Young-Hee Nam, Mi Yeoung Kim, Gil-Soon Choi A530 Detection of Galacto-Oligosaccharide Specific IgE in Vitro Chiung-Hui Huang, Chiung-Hui Huang, Jian Yi Soh, Lynette Shek, Lynette Shek, Dianne J. Delsing, Bee Wah Lee, Bee Wah Lee, Si Hui Goh, Wen Chin Chiang, Wenyin Loh A531 The Association Between Serum Vitamin D Levels and Allergic Diseases in Elementary Schoolchildren Hea-Kyoung Yang, Ji Young Lee, Minji Kim, Kangmo Ahn, Jihyun Kim, Young-Min Kim, Hye-Young Kim, Yong Mean Park, Woo Kyung KIM, So-Yeon Lee A532 Serum Levels Specific IgE to Toxic Shock Syndrome Toxin Type 1 in Eosinophilic Chronic Rhinosinusitis with Nasal Polyp in Korean Jongin Jeong, Sang Duk Hong, Seung Kyu Chung, Hun-Jong Dhong, Hyo Yeol Kim Hyo Yeol Kim, Sujin KIM A533 Impacts of Rhizosphere Cleaning Effects of Potted Indoor Plants on the Symptoms and Stress of Students with Allergic Rhinitis in Newly Built Schools Yong-Won Lee, Hana Bak, Hye-Rim Son, Si-Eun Lee, Kwang-Jin Kim, Young-Wook Lim, Ho-Hyun Kim A534 A Case of Multiple Food Allergies with Recurrent Anaphylaxis Successively Controlled By Omalizumab Mi-Ae Kim, Man Yong Han, Young-Ho Jung, Hye Mi Jee, Seung Jin Lee, Kyung Suk Lee A535 Bepotastine-Induced Urticaria, Cross-Reactive with Other Antihistamines Jasmina Golez, Jaechun Lee, Eunkyoung Lee A536 Role of SLC26a4 in Ozone - Induced Airway Reactivity and Inflammation Da-Jeong Bae, Chang-Gi Min, Jong-Uk Lee, Jong-Sook Park, Hun Soo Chang, Choon-Sik Park, An-Soo Jang A537 PAR2-Antagonist Suppresses Protease-Induced Allergic Inflammation Mediated By Degradation of Lung Epithelial Tight Junction and Generation of ROS Young-Joon Kim, Bok Kyoung Jung, Seung-Hwa Lee, Mi-Jin Kang, Sekyoo Jeong, Eun Lee, Hyun-Ju Cho, Young-Ho Kim, Song-I Yang, Seo Hee Kim, Soo-Jong Hong A538 Novel Anti-IL-4Ra Nanocarrier Approach for the Efficient Control of Lung Tissue Inflammation during Asthma Rabih Halwani, Saleh Al Muhsen, Asma Sultana, Achraf Al-Faraj, Rosan Kanana, Sibtain Afzal, Roaa Al Kufaidi A539 Clinical Factors for Improved Allergen Reactivities Induced By Subcutaneous Allergen Specific Immunotherapy with House Dust Mites during 1 Year Period Hee-Kyoo Kim, Chul-Ho Oak, Gil-Soon Choi, Ye-Jin Moon, Eun-Kee Park A540 Cytokine Gene Polymorphisms in Iranian Patients with Kidney Acute Rejection Alireza Zarebidoki, Mina Abrari, Ali Akbar Amirzargar A541 Phthalate Exposure and Obesity in Atopic Dermatitis of Korean Children and Adolescents Ju-Hee Seo, Mina Ha, Soo-Jong Hong A542 Which Drives Chronicity of Cough in Adults: Based on the Knhanes 2010-2012 Mingyu Kang, Byung-Ha Cho, Han-Ki Park, Han-Ki Park, Kyung-Mook Kim, Chang-Han Park, Heung Woo Park, Heung Woo Park, Yoon-Seok Chang, Yoon-Seok Chang, Yoon-Seok Chang, Sook-Hee Song, Mi-Kyeong Kim, Mi-Kyeong Kim, Sang-Heon Cho, Suk-Il Chang, Kyung-up Min, Kyung-up Min, Alyn Morice A543 Elevated Airway CD45RO Memory Cells in Wheezing Children with Lower Respiratory Infection Jungi Choi, Yusok Han, Jin-Sung Park, Eunmi Kwon, Chang-Keun Kim A544 Quality of Life in Obese Children with or without Atopic Disease Gartika Sapartini A545 Relation of Human microRNA in Sputum of Asthma with Influenza A Virus Infection-Induced Exacerbation Ji-Na Kim, Seungwoo Shin, Hun Soo Chang, Eun-Young Shim, Ji Ah Jun, Hyeonju Lee, Jong-Sook Park, Choon-Sik Park A546 Aeropolinologic Monitoring and Distribution of Allergoallergens in Western Georgia Revaz Sepiashvili, Darejan Khachapuridze, Sofio Gamkrelidze, Manana Chikhladze A547 Extracorporeal Membrane Oxygenation As Emergency Treatment for Patients with Near-Fatal Status Asthmaticus Seung-Eun Lee, Yun-Seong Kim, Doo-Soo Jeon, Woo-Hyun Cho, Hye-Ju Yeo, Seong-Hoon Yoon, Seung-Hyun Kim A548 Relationship of S100calcium Binding Protein A9 with Neutophilic Inflammation in Murine Asthma Model Taehyeong Lee, Hyun Ji Song, Choon-Sik Park, Ji Ah Jun, Jong-Sook Park A549 Whole-Exome Sequencing of Aatopic Dermatitis in Korean Childhood Dankyu Yoon, Yeon-Seop Kim, Woo-Sung Chang, Mi-Jin Kang, Soo-Jong Hong, Jeom-Kyu Lee, Eun-Jin Kim A550 A Case of Generalized Molluscum Contagiosum in an Adult Patient with Severe Atopic Dermatitis Minkee Park A551 Discovery of Putative Macadamia Nut Allergens By Patient IgE Binding and a Label-Free Shotgun Proteomics Approach Nanju Alice Lee, Johanna Rost, Sridevi Muralidharan, Dianne Campbell, Sam Mehr A552 Anti-FcÎμri Antibody Inhibits Allergic March in Mice By Suppressing Th17 Pathway Via Suppression of FcÎμri-Mediated Mast Cells Activation Seung-Hwa Lee, Seon-Joo Yoon, Ha-Jung Kim, Eun Lee, Song-I Yang, Young-Ho Jung, Ho-Sung Yu, Hee-Suk Kim, Yeon Hee Park, So-Yeon Lee, Jun-Sung Park A553 Clinical Characteristics and the Associated Factors of ATG Hypersensitivity Reaction Ha Kyeong Won, Min-Koo Kang, Sung Do Moon, Byung-Keun Kim, Ju-Young Kim, Sang-Heon Cho, Hye-Ryun Kang, Ji-Su Shim, Soo Jie Chung A554 Reference Value and Utility of Total Serum Immunoglobulin E in Korean Schoolchildren Jaehee Choi, Kangmo Ahn, Kwanghoon Kim, Jihyun Kim, Jiyoung Lee A555 Two-Step Prescreening Skin Testing May be Useful for Reducing Immediate Hypersensitivity Reaction to Nonionic Contrast Media: Results of 7-Year Period in a Secondary Hospital Bo Bae Park, In Young Nho, Chang-Han Park, Jang Min Kim, Suk-Il Chang A556 Prevalence of Allergic Sensitization in Patients with Allergy Rhinitis; Gwangju, Jeonnam State Study Sun Kyung Kim, Hyung Chae Yang, Kwang Il Nam A557 Analysis of IgE Binding Components of Walnut in Korean Children Effect of Cooking Methods on the Allergenicity of Walnut Proteins Jeongmin Lee, Jeongmin Lee, Sooyoung Lee, Kyunguk Jeong, Se-Ah Jeon A558 Assessment of Autonomic Nervous Function in Subjects with Cholinergic Urticaria Associated with Acquired Idiopathic Generalized Anhidrosis Midori Fujiwara, Shoko Shindo, Hiroyuki Murota, Mayuko Tahara, Aya Takahashi, Ichiro Katayama A559 Interleukin 1 Beta in Sputum of Patients with Asthma: Relation with Airway Obstruction and Neutrophilc Inflammation Jae Woo Jung, Hyun Ji Song, Taehyeong Lee, An-Soo Jang, Jong-Sook Park, Hun Soo Chang, Choon-Sik Park, Byoung Whui Choi A560 Interleukin 8 in Sputum of Patients with Asthma: Relation with Neutrophilc Inflammation and Exacerbation Min-Hye Kim, Da-Jeong Bae, Hyun Ji Song, Taehyeong Lee, Ji Ah Jun, Jong-Sook Park, An-Soo Jang, Hun Soo Chang, Young Joo Cho, Choon-Sik Park A561 Prostaglandin E2 and Transforming Growth Factor-Î(2) Play a Critical Role in Suppression of Allergic Airway Inflammation By Adipose-Derived Stem Cells Sue Jean Mun A562 Inhalation of Fine Particles Kill Alveolar Macrophages to Release IL-1alpha That Promote Inducible Bronchus-Associated Lymphoid Tissue (iBALT) Formation Etsushi Kuroda, Koji Ozasa, Ken Ishii A563 Association Between Smoking and Allergic Diseases in the Korean Adult General Population Sunmi Kim, Gyeong-Hun Park A564 Relationship of S100 Calcium Binding Protein A9 with Inflammasome Activation in Murine Asthma Model Hyun Ji Song, Taehyeong Lee, Ji Ah Jun, Hun Soo Chang, Jong-Sook Park, Choon-Sik Park A565 Cluster Analysis of Asthma Phenotypes to Predict Exacerbation in Korean Population Mi-Ae Kim, Seungwoo Shin, Jong-Sook Park, Hun Soo Chang, You Sook Cho, Hae-Sim Park, Choon-Sik Park A566 Effect of AG490 on the Expression of TH17 CELLS and Tregs in the MOUSE MODEL of Neutrophilic Asthma Zhang Min A567 Association Between the Clinical Characteristics and Disease Severity in Hospitalized Bronchiolitis Patients Younger Than Two Years Old Seo Hee Yoon, In Suk Sol, Young a Park, Yoon Hee Kim, Min Jung Kim, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim A568 Comparison Between House Dust Mite and Aspergillosis Sensitization in Patients with High Level of Tige Wu Shiquan A569 The Prevalence of Metal Allergy in the Patients with Orthodontic Appliance Yongwon Lee, Hana Bak A570 Component Resolved Diagnosis and Single Nucleotide Polymorphism Analyses: Towards the Development of Specific Immunotherapy for Allergy Maricar Wisco Ching, John Donnie Ramos A571 Clinical Features of Anaphylaxis Caused By Peanut, Tree Nuts and Seeds in Children and Adolescents: Multi-Center Study with 126 Patients Kyunguk Jeong, Sooyoung Lee, Kangmo Ahn, Myung Hyun Sohn, Kyung Won Kim, So-Yeon Lee, Tae Won Song, Youhoon Jeon, Jihyun Kim, Taek Ki Min, Kyu-Earn Kim, Bok-Yang Pyun, Hyeon-Jong Yang, Hae Ran Lee, Youngmin Ahn, Ji-Won Kwon, Dae Hyun Lim, Jeong Hee Kim, Dongin Suh, Hyung Young Ki A572 A Report of Two Cases of Anaphylaxis Caused By Perilla Seed in Children Kyunguk Jeong, Byeong Sub Park, Sooyoung Lee, Se-Ah Jeon, Kyu Jung Park A573 Prenatal Fine Particulate Matter Affects Wheezing in Children with TLR4 Polymorphism: Cocoa Study Song-I Yang, Eun Lee, Hyun-Ju Cho, Young-Ho Kim, Mi-Jin Kang, Yean Jung Choi, Kil Yong Choi, Youn Ho Shin, Kangmo Ahn, Kyung Won Kim, Byoung-Ju Kim, So-Yeon Lee, Eun-Jin K A574 Intensified B Lymphocyte Depletion (IBLD) without Immunosuppressive Maintenance Treatment As a Rescue Therapy in Refractory Lupus Nephritis (LN): a 4-Year Observation. Roccatello Dario A575 Relationship Between Th17 Cells and Neutrophilic Airway Inflammation in Childhood Neutrophilic Asthma Jing Liao A576 Clinical Applications of Impulse Oscillometry in Asthma Management after Exacerbation in Preschool Children Yong Feng, Yunxiao Shang A577 Contact Allergy to Sodium Sulfite and Its Relationship to Facial Cosmetic Contact Dermatitis Yongwon Lee, Hana Bak A578 Effect of Exposure to Air Pollution on Asthma and Lung Function Development Hyung Young Kim, Byoung-Ju Kim, Ji-Won Kwon, Ju-Hee Seo, Eun Lee, So-Yeon Lee, Song-I Yang, Young-Ho Jung, Hyo-Bin Kim, Ho-Jang Kwon, Hee Ju Park A579 Role and Relational Mechanism of AG490 in Airwayinflammation in the Mouse Model of Neutrophilic Asthma Zhang Min, Nong Guang-Min, Jiang Min A580 Incidence of Adverse Reaction to Radioconstrast Media in a Single Tertiary Hospital Gyu Young Hur, Eun Jung Sim, Sora Yoon, Juwhan Choi, Junga Kim, Jae Keom Sim, Jee Youn Oh A581 Cow’s Milk Oral Food Challenge: Clinical and Laboratory Features in Korean Children Kyunguk Jeong, Byeong Sub Park, Jeong-Min Lee, Sooyoung Lee, Eunjae Cheon, Youngjoo Na, Kyu Jung Park, Eunjoo Lee A582 Validation of the Red Maple Trials Allergen Challenge Theatre for Ragweed Pollen Challenge William Yang, Suzanne Kelly, Rob Perrins, Jimmy Yang A583 Preliminary Evaluation of the Red Maple Trials Allergen Challenge Theatre for Grass Pollen William Yang, Suzanne Kelly, Rob Perrins, Jacob Karsh, Jimmy Yang A584 The Association Between Tobacco and the Risk of Asthma in Urban and Rural Children in San Francisco, Argentina Hector Badellino, Alvaro Teijeiro, Mabel Cuello, Marilyn Urrutia Pereira, Gustavo Egues A585 The Prevalence of Allergic Rhinitis in University Students in Manisa Ayse Aktas A586 Allergen Sensitization in Zimbabwean Children with Atopic Dermatitis Jin-Kyong Chun, Hilda Angela Mujuru, Elopy N Sibanda A587 Vitamin D Insufficiency in Asthmatic Patients Andreea Ioana Popescu, Raluca Greblescu A588 The Prevalence of Hypersensitivity Reactions Against Drugs Among University Students. Suheyla Rahman, Ayse Aktas A589 Sublingual Immunotherapy Among Problematic Patients, Suffering from Allergic Rhinitis. Nataly Tataurshchikova A590 A Novel Biomarker for Wheezing and Atopy in Early Infancy Eishika Dissanayake, Yuzaburo Inoue, Naoki Shimojo, Taiji Nakano A591 Prognostic Factors for Atopic Dermatitis in Spontaneously Born Babies from Low Socioeconomic Background Conny Tanjung A592 Higher IgE Antibody Levels Mediate Anti-Cancer Immunity in Transgenic KN1 Hyper-IgE Mice Erika Jensen-Jarolim, Judit Fazekas, Josef Singer, Anna Lukschal, Reinhard Horvat, Gertrude Achatz-Straussberger, Gernot Achatz A593 Fructooligosaccharides Intake during Pregnancy and Lactation Increases Gut Bifidobacterium and IL-27 in Breast Milk Yuji Fujita, Shuji Ikegami, Yoshitaka Nakamura, Yuzaburo Inoue, Naoki Shimojo, Yoichi Kohno, Shuichi Suzuki, Naoko Ozawa, Takayuki Kubota, Ken Nonaka, Osamu Ohara, Kentaro Masuda A594 Effect of Nintedanib on Asthma in Mouse Model Chin Kook Rhee, Sook Young Lee, Hwa Young Lee, Hea Yon Lee, Ji Young Kang, Sei Won Kim, Soon Seog Kwon, Young Kyoon Kim A595 Delayed Contrast Media Hypersensitivity after Coronary Angiography Gun-Woo Kim, Ju-Young Kim, Sang-Heon Cho, Hye-Ryun Kang, Hyo-Soo Kim, Jung Gyu Han, Jin Lee, Ji Young Lee, Ji Young Go, So Jung Park A596 Gene Expression Profiling in Patients with Chronic Idiopathic Urticaria Reveals Unique Gene Signature Distinct from Healthy Controls Julie Kim-Chang, Cassandra Love, Patricia Lugar A597 Failure to Recognize Lymphopenia in Newborn Leads to Undetectable Primary Immunodeficiency Endah Citraresmi A598 The Concordance Between Lung Function Test and Indonesian Version of Childhood Asthma Control Test (CACT) Nastiti Kaswandani, Cynthia Utami, Mardjanis Said A599 Synergistic Interaction Between Bronchiolitis and PM(10) Is Modified By IL-13 Polymorphism on Asthma Development: Replication from Cheer Study Young-Ho Jung, Song-I Yang, Byoung-Ju Kim, Ji-Won Kwon, Hwan-Cheol Kim, Jong-Han Leem, Ju-Hee Seo, Hyung Young Kim, So-Yeon Lee, Ho-Jang Kwon, Hyo-Bin Kim, Hyun-Ju Cho A600 The Transcription Factor Ehf Is Involved in TGF-b-Induced Suppression of Fceri and c-Kit Expression and Fceri-Mediated Activation in Mast Cells Susumu Yamazaki, Nobuhiro Nakano, Asuka Honjoh, Eisuke Inage, Yosuke Baba, Yoshikazu Ohtsuka, Toshiaki Shimizu A601 The Follow up of the Potential Immunosuppressant Effects of Marijuana (MJA) Ishaq M, Sameera MI Khan, Imran Khan, Sabeen Khan A602 Risk Factors of Allergen Sensitization at 3 Years: Results from the Gusto Study Evelyn Xiu Ling Loo, Anne Goh, Oon Hoe Teoh, Yiong Huak Chan, Seang Mei Saw, Kenneth Kwek, Peter D Gluckman, Keith M Godfrey, Hugo Van Bever, Yap Seng Chong, Bee Wah Lee, Lynette Shek, Alison Joanne Lee A603 IL-6 Blockade As a Steroid-Sparing Treatment for Rhupus Patients Daniela Rossi A604 Examination of Late Pulmonary Toxicity in Children Treated for Malignancies Agnes Nemeth A605 Technical Validation of the Repurposing of a Personal Particle Sampler to Determine House Dust Mite Exposure in the Ambient Air Torsten Sehlinger, Karl-Christian Bergmann, Frank Goergen A606 Zinc Deficiency in Children with Severe Atopic Dermatitis: More Common Than Generally Thought Mohammad S. Ehlayel, Abdul Bari Bener A607 Strong Association Between HLA-B*5801 Allele and Allopurinol – Induced Severe Cutaneous Adverse Reactions in Vietnamese Hieu Chi Chu, Nga Thi Quynh Do, Dinh Van Nguyen, Ha Thi Thu Nguyen, Huong Thi Minh Le, Sheryl Van Nunen, Christopher Vidal, Suran Fernando A608 Successful Rapid Desensitization to Glatiramer Acetate: Report of 2 Cases Fotis Psarros, Ekaterini Syrigou, Ekaterini Politi, Spyridon Chrysoulakis A609 Asthma Exacerbations Seasonal Variation in Two Perennial Phenotypes during Twenty Years (1995-2014): House Dust Mite Monosensitized and Non Atopic Patients Dimitrios Vourdas, Konstantinos Petalas A610 Occupational Allergy to Fungal Spores Among the Farmers of Paddy Fields in West Bengal, India: An Aeromycological and Immunological Approach Mouli SAHA, Kashinath Bhattacharya A611 Study of Efficacy of Sublingual Immunotherapy (SLIT) in Cases of Severe Persistent Allergic Rhinitis Subir Jain A612 Mesenchymal Stem Cells Suppress Lung Inflammation and Airway Remodeling in Chronic Asthma Rat Model Via PI3K/Akt Signaling Pathway Mesenchymal Stem Cells Suppress Lung Inflammation and Airway Remodeling in Chronic Asthma Rat Model Via PI3K/Akt Signaling Xiaolian Song, Haiyan Lin A613 Development of Allergen ELISA Kits for Dust Mites, Pollen, and Pet Dander Kyohei Nishikawa, Takashi Shimada, Hiroshi Yasueda, Tadao Enomoto, Daisuke Aizawa, Takayoshi Kobayashi A614 Yoga As a Lifestyle Modification to Improve the Quality of Life in Smokers with Allergic Rhinitis Chellaa R A615 Study of Incidence of Severe Persistent Allergic Rhinitis in Different Age Groups,Sex Prevalance and Type of Allergen” Aeroallergen or Food Allergen” Responsible for Severe Persistent Allergic Rhinitis in Central India Subir Jain A616 Causative Allergens in Cases of Severe Persistent Allergic Rhinitis in Central India Subir Jain A617 Atopic Dermatitis: A New Data on the Mechanisms of Chronic Pruritus Marina Yudina A618 The Efficacy and Safety of Peanut Oral Immunotherapy in High-Dose with Predicting Factors Ishaq M, Sameera MI Khan, Imran Khan, Sabeen Khan A619 Evaluation of Long-Term Prognosis and Topical Corticosteroid Usage after One Year of Proactive Treatment for Children with Moderate-to-Severe Atopic Dermatitis Mayako Saito A620 Allergy Symptoms in the First Two Months of Life Nurul Iman Nilam Sari A621 Factors Related to the Seasonal Variation of Allergic Rhinitis Jae Young Kim, Jaechul Song, Inah Kim, Kyeong Joon Lee, Soo Jin Park, Soo Yong Roh A622 Allergic Risk Survey in Lao Children at out-Patient Department, Children’s Hospital, Vientiane Capital, Lao PDR Somxay Billamay A623 Correlation Between Food Allergy, Aeroinhalant Allergy, Allergic Rhinitis, Atopic Dermatitis, and Acute Upper Respiratory Tract Infections and Levels of Severity of Asthma in Pediatric Medicine Department Saiful Anwar Hospital Indonesia Muchammad Fahrul Udin A624 Comparative Study of Pine, Oak, and Ginkgo Pollen Counts in Korea during Last Four Years Mae Ja Han, Jae-Won Oh, Kyu Rang Kim, Baek-Jo Kim A625 Effectiveness of Allergy-Test Directed Elimination Diets in Eosinophilic Esophagitis Jorge A Mazza, Jason Kangeun Ko, David JT Huang A626 Comparison of Cut-Off Values and Probability Curves for Egg Specific IgE in Diagnosis of Egg Allergy in Young Children Kanae Furuya, Keigo Kainuma, Takahiro Ito, Mizuho Nagao, Takao Fujisawa, Junya Hirayama, Yu Kuwahara A627 A Case of Persistent Atopic Dermatitis Associated with Parasitic Infection Rosanna Qualizza, Cristoforo Incorvaia, Anna Maraschini A628 Aeroallergenic Profile of Indoor Allergens and Their Clinical Relevance in Allergy and Asthma Patients in Saudi Arabia Syed Mohammed Hasnain, Abdulrahman Al-Frayh A629 Oral Exposure to the Amino Acid Glycine Inhibits the Onset of Allergic Disorders Anita Hartog, Jacqueline Bastiaans, Reinilde Loonstra, Lieke Rutten, Lucien Harthoorn, Jeroen Van Bergenhenegouwen, Johan Garssen, Johan Garssen A630 Cough As a Key Symptom in Asthma, Allergic Rhinitis, COPD and Rhinosinusitis and Its Impact in Korea Kwang-Ha Yoo, Sang-Heon Cho, AG Ghoshal, Abdul Razak Bin Abdul Muttalif, Horng- Chyuan Lin, Sanguansak Thanaviratananich, Shalini Bagga, Rab Faruqi, Santwona Baidya, Colman Taylor, De Yun Wang, Hae-Ryun Ahn, Soon-Kwan Hong, Jong-Woong Kim, Gui-Hyun Nam, Mee-Ja Kim, Jae-Kyoung Park A631 Cysteine Protease Allergen Def f 1 Induces Th2 Cytokines in Mouse Bone Marrow Derived Basophils Via ERK and JNK Dependent Pathways Myung-Hee Yi, Kyoung Yong Jeong, Ju-Yeong Kim, Tai-Soon Yong A632 Novel Multiple Allergy Testing Kit Using Parallel Lines Array (PLA) Technology Bum Joon Kim, Hs Joo, Kj Lim, Jae-Hyun Lee, Jung-Won Park, Kh Yoon, DS Choi A633 Quantitative Rapid Kit for Human Immunoglobulin Hanseung Joo, Bum Joon Kim, Kj Lim, MJ KIM, DS Choi, Kh Yoon A634 Total IgE Measurement By Protia Allergy-Q: Comparison Study with Immunocap Bum Joon Kim, Hanseung Joo, Woo Sang Jung, Kj Lim, DS Choi A635 Prevalence and Risk Factors of Asthma Among Korean Farmers Ji-Hoon Lee, Soon-Chan Kwon, Soo-Jin Lee, Soo Yong Roh, Hogil Kim, Kyeong Joon Lee A636 Dietary Intake and Perceived Immune Status in Young Dutch Women Aurora Van De Loo, Amanda Fernstrand, Johan Garssen, Joris Verster A637 The Effects of Antihistamine Drugs on on-Road Driving Performance Aurora Van De Loo, Johan Garssen, Joris Verster A638 Grass Is Guilty: A Case of Anaphylactic Shock and Asthmatic Status in the Same Time in an Individual Jasmina Golez A639 Cyclic Gamp-AMP(cGAMP) Induces Allergic Inflammation Koji Ozasa, Etsushi Kuroda, Ken Ishii, Ken Ishii A640 Role of Omalizumab in the Setting of Recalcitrate Dermatitis with Extremely Elevated IgE Levels Muhammad Imran, Selina Gierer, John Martinez A641 Follow-up Study on the Natural History of Prawn Allergy Lydia Wong, Bee Wah Lee, Gaik Chin Yap, Genevieve Llanora, Bernard Thong, Lynette Shek A642 Protein-Losing Dermopathy Impairing Growth in Children with Severe Atopic Dermatitis Mohammad S. Ehlayel, Ashraf Soliman A643 Airways Assessment of Aged Nursing Homes Residents Pedro Martins, João Marques, Joana Gomes-Belo, Teresa Palmeiro, Iolanda Caires, Joana Belo, Maria Amália Botelho, Paula Leiria-Pinto, Nuno Neuparth A644 Use of Skin Prick Test, Specific IgE to Shrimp and Rpen a1 to Determine Clinical Reaction to Shrimp in Area with High Prevalence of House Dust Mite Sensitization Narissara Suratannon, Jaichat Mekaroonkamol, Jarungchit Ngamphaiboon, Piyawadee Lertchanaruengrith, Pantipa Chatchatee A645 Identification of Specific IgE-Binding Proteins in Tree of Heaven (Ailanthus altissima) Pollen Gholamali Kardar, Ahmad Majd, Youcef Shahali, Farrokh Ghahremaninejad, Zahra Pourpak, Fateme Mousavi A646 Allergy Immunotherapy Well Tolerated in Children Mahnaz Sadeghi-Shabestari A647 Steinert (DM1) Patients Have IgG1 Deficiency and Should be Screened for Immune Deficiency K. Van Bilsen, O. Manusama, W.a. Dik, M. Van Der Burg, V. H. J. Van Der Velden, V.a.S. H. Dalm, P. M. Van Hagen A648 The Change of Serous Sige and Three Evaluation before and after Sublingual Immunotherapy with Dermatophagoides Farinae for Persistent Allergic Rhinitis Yongping Liu A649 Garlic Extracts Reduce Histamine-Induced Proliferation and Migration of Human Asthmatic Bronchial Smooth Muscle Cells Yi Yeong Jeong A650 A Case of Occupational Contact Dermatitis Caused By N-Acetylcysteine Ji Hye Kim, Moon Gyeong Yoon, Young Min Ye, Yoo Seob Shin, Ga Young Ban, Hae-Sim Park, Hye Min Jung A651 The Association Between Pollen Change and Asthma Attacks Soo Yong Roh, Jaechul Song, Ji-Hoon Lee, Hogil Kim, Jae Young Kim, Kyeong Joon Lee A652 Incidence of Emergency Department Visits and Hospitalizations for Asthma Exacerbations during the Lunar Month in Singapore Lydia Wong, Mohana Rajakulendran, Haripriya Santhanam, Lynette Shek, Tow Keang Lim A653 The Prevalence of Positive Reaction for Skin Prick Test in Korean Farmers and Its Occupational Risk Factors Hogil Kim, Soo-Jin Lee, Ji-Hoon Lee, Soo Yong Roh, Soon-Chan Kwon A654 Drug Allergy in Children: A Three-Years Experience at Dr. Kariadi Hospital Semarang Indonesia Wistiani, Galuh H, Ani Wistiani A655 The Identification of Morphology, Structure and Study of Seasonal Variation of Airborne Fraxinus Excelsior Pollen Grains in the Tehran Gholam Ali Kardar, Maryam Sharifshoushtari, Ahmad Majd, Taher Nejadsattari, Zahra Pourpak, Mostafa Moin A656 Sublingual Immunotherapy in Elderly Rhinitis Patients Sensitized to House Dust Mites Ji Hye Kim, Daehong Seo, Young Min Ye, Hae-Sim Park, Jung-Won Park, Jae-Hyun Lee, Yoo Seob Shin A657 Healthy Ageing Research Center (HARC) As a Platform for Multidisciplinary Approaches to Respiratory Research in the Elderly Marek L. Kowalski, Aleksandra Wardzynska, Marcin Kurowski, Malgorzata / Ewa Pawelczyk, Adam Wysokinski, Iwona Kloszewska, Janina Grzegorczyk, Wojciech Piotrowski, Joanna Makowska A658 Estimation of Cases of Work-Related Asthma Using Capture-Recapture Methods Soon-Chan Kwon, Jaechul Song, Yong-Kyu Kim A659 Primary School Students’ Parents Reported ISAAC Questionnaire in a Low Income Area of Ankara Ilknur Bostanci, Zeynep Sengul Emeksiz, Aysegul Ertugrul, Serap Ozmen, Soner Sahin A660 Usefulness of PC20 Adenosine Monophosphate in Diagnosis and Treatment in Bronchial Asthma Sang-Ha Kim, Myoung Kyu Lee, Won Yeon Lee, Suk Joong Yong, Seok Jeong Lee, Ye-Ryung Jung A661 S100 Calcium Binding Protein A9 in Sputum of Patients with Steroid Naive Asthma: Relation with Airway Obstruction and Nneutrophilc Inflammation Myung Shin Kim, Jong-Sook Park, An-Soo Jang, Choon-Sik Park A662 Risk Factor Asthma in Pediatric Pneumonia Patients Diah Asri Wulandari, Cissy Kartasasmita A663 Prevalence and Risk Factors of Childhood Asthma and Allergic Disease at Exposed Area By Emission of Cement Padang Factory Finny Fitry Yani, Rizanda Machmud, Dhina Lydia Lestari A664 Association Between Serum Level of 25-Hydroxyvitamin D with Atopic Dermatitis Occurrence and Severity in Children Rusdi Rusdi, Yurmalina Yurmalina, Eryati Darwin A665 Thiol-Disulfide Balance in Children with Atopic Dermatitis Ilknur Bostanci, Gulin Karacan, Nazli Ercan, Asuman Colak, Murat Alisik, Gulay Basarir, Ozcan Erel A666 Recurrent Mouth Ulsers Caused By Braces after Developing a Nickel Allergy in Children Ilknur Bostanci, Yasemin Keskin A667 Anaphylactic Reaction to Famotidine with Pheniramine Hypersensitivity Ilkay Koca Kalkan A668 Novel Transcriptomic and Immunoproteotomic Approaches in Identifying Cross-Reactive Allergens Between Crustacean and Molluscs Andreas/Ludwig Lopata, Kyall Zenger, Roni Nugraha, Sandip Kamath A669 Pollen Season and Climate Change in the Continental United States (CONUS) Leonard Bielory, Panos Georgopoulos, Yong Zhang, Wheat Mi, Ting Cai A670 Differences of Change in Der p IgG4 and CD4+CD25+FoxP3+ Treg Cells Between Sublingual and Subcutaneous Immunotherapy with House Dust Mite in Chinese Patients with Allergic Rhinitis MO Xian, Jing Li, Mulin Feng"
4499,Erratum to: Liberation of SARS-CoV main protease from the viral polyprotein: N-terminal autocleavage does not depend on the mature dimerization mode,
4500,ECEIM Congress 2015,
4501,Research Communications of the 25th ECVIM‐CA Congress,
4502,Spatial expansions and travelling waves of rabies in vampire bats,"A major obstacle to anticipating the cross-species transmission of zoonotic diseases and developing novel strategies for their control is the scarcity of data informing how these pathogens circulate within natural reservoir populations. Vampire bats are the primary reservoir of rabies in Latin America, where the disease remains among the most important viral zoonoses affecting humans and livestock. Unpredictable spatiotemporal dynamics of rabies within bat populations have precluded anticipation of outbreaks and undermined widespread bat culling programs. By analysing 1146 vampire bat-transmitted rabies (VBR) outbreaks in livestock across 12 years in Peru, we demonstrate that viral expansions into historically uninfected zones have doubled the recent burden of VBR. Viral expansions are geographically widespread, but severely constrained by high elevation peaks in the Andes mountains. Within Andean valleys, invasions form wavefronts that are advancing towards large, unvaccinated livestock populations that are heavily bitten by bats, which together will fuel high transmission and mortality. Using spatial models, we forecast the pathways of ongoing VBR epizootics across heterogeneous landscapes. These results directly inform vaccination strategies to mitigate impending viral emergence, reveal VBR as an emerging rather than an enzootic disease and create opportunities to test novel interventions to manage viruses in bat reservoirs."
4503,News,"There are just a few weeks left to get the early bird discount for registration at the ERS International Congress. This year's event, which will take place in London for the first time, provides a key opportunity to hear the latest research and advances from across the broad spectrum of the respiratory field."
4504,A systematic review of community-based interventions for emerging zoonotic infectious diseases in Southeast Asia,"BACKGROUND: Southeast Asia has been at the epicentre of recent epidemics of emerging and re-emerging zoonotic diseases. Community-based surveillance and control interventions have been heavily promoted but the most effective interventions have not been identified. OBJECTIVES: This review evaluated evidence for the effectiveness of community-based surveillance interventions at monitoring and identifying emerging infectious disease; the effectiveness of community-based control interventions at reducing rates of emerging infectious disease; and contextual factors that influence intervention effectiveness. INCLUSION CRITERIA: Participants Communities in Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, the Philippines, Singapore, Thailand and Viet Nam. Types of intervention(s) Non-pharmaceutical, non-vaccine, and community-based surveillance or prevention and control interventions targeting rabies, Nipah virus, dengue, SARS or avian influenza. Types of outcomes Primary outcomes: measures: of infection or disease; secondary outcomes: measures of intervention function. Types of studies Original quantitative studies published in English. SEARCH STRATEGY: Databases searched (1980 to 2011): PubMed, CINAHL, ProQuest, EBSCOhost, Web of Science, Science Direct, Cochrane database of systematic reviews, WHOLIS, British Development Library, LILACS, World Bank (East Asia), Asian Development Bank. METHODOLOGICAL QUALITY: Two independent reviewers critically appraised studies using standard Joanna Briggs Institute instruments. Disagreements were resolved through discussion. DATA EXTRACTION: A customised tool was used to extract quantitative data on intervention(s), populations, study methods, and primary and secondary outcomes; and qualitative contextual information or narrative evidence about interventions. DATA SYNTHESIS: Data was synthesised in a narrative summary with the aid of tables. Meta-analysis was used to statistically pool quantitative results. RESULTS: Fifty-seven studies were included. Vector control interventions using copepods, environmental cleanup and education are effective and sustainable at reducing dengue in rural and urban communities, whilst insecticide spraying is effective in urban outbreak situations. Community-based surveillance interventions can effectively identify avian influenza in backyard flocks, but have not been broadly applied. Outbreak control interventions for Nipah virus and SARS are effective but may not be suitable for ongoing control. Canine vaccination and education is more acceptable than culling, but still fails to reach coverage levels required to effectively control rabies. Contextual factors were identified that influence community engagement with, and ultimately effectiveness of, interventions. CONCLUSION: Despite investment in community-based disease control and surveillance in Southeast Asia, published evidence evaluating interventions is limited in quantity and quality. Nonetheless this review identified a number of effective interventions, and several contextual factors influencing effectiveness. Identification of the best programs will require comparative evidence of effectiveness acceptability, cost-effectiveness and sustainability. Implications for practice Interventions are more effective if there are high levels of community ownership and engagement. Linkages between veterinary and public health surveillance systems are essential. Interventions are not well accepted when they fail to acknowledge the importance of animals for economic activity in communities. Implications for research Evidence is needed on functioning and outcomes of current surveillance systems and novel low-cost methods of surveillance. Evaluations of control interventions should control for confounding and report measures of disease, cost and sustainability. Translational research is needed to assess generalisability and evaluate roll-out of effective interventions as regional or national programs."
4505,Pandemic,
4506,"ESICM LIVES 2016: part one: Milan, Italy. 1-5 October 2016",
4507,"ESICM LIVES 2016: part three: Milan, Italy. 1–5 October 2016",
4508,A Simple Sketch Symbolizing Self-Reliance,
4509,"The 12th Edition of the Scientific Days of the National Institute for Infectious Diseases “Prof. Dr. Matei Bals” and the 12th National Infectious Diseases Conference: Bucharest, Romania. 23–25 November 2016","A1 The outcome of patients with recurrent versus non-recurrent pneumococcal meningitis in a tertiary health-care hospital in Bucharest Cristian-Mihail Niculae, Eliza Manea, Raluca Jipa, Simona Merisor, Ruxandra Moroti, Serban Benea, Adriana Hristea A2 Influence of bacteriophages on sessile Gram-positive and Gram-negative bacteria Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Dana Mărculescu, Magdalena Lorena Andrei, Veronica Ilie, Marcela Popa, Coralia Bleotu, Carmen Chifiriuc, Mircea Ioan Popa, Adrian Streinu-Cercel A3 The utility of inflammatory biomarkers in the prognostic evaluation of septic patients – past, present and future Alina Orfanu, Cristina Popescu, Anca Leuștean, Remulus Catană, Anca Negru, Alexandra Badea, Radu Orfanu, Cătălin Tilișcan, Victoria Aramă, Ştefan Sorin Aramă A4 Etiologic and clinical features of bacterial meningitis in infants Constanța-Angelica Vișan, Anca-Cristina Drăgănescu, Anuța Bilașco, Camelia Kouris, Mădălina Merișescu, Magdalena Vasile, Diana-Maria Slavu, Sabina Vintilă, Endis Osman, Alina Oprea, Sabina Sandu, Monica Luminos A5 The diagnostic and prognostic role of neutrophil to lymphocyte count ratio in sepsis Alina Orfanu, Victoria Aramă, Ştefan Sorin Aramă, Anca Leuştean, Remulus Catană, Anca Negru, Gabriel Adrian Popescu, Cristina Popescu A6 Whooping cough in a HIV positive patient Ramona Georgiana Stanculete, Ana Vaduva Enoiu, Adelina Raluca Marinescu, Voichita Lazureanu A7 Cronobacter sakazakii sepsis in varicella patient Adelina-Raluca Marinescu, Alexandru Crișan, Voichița Lăzureanu, Virgil Musta, Narcisa Nicolescu, Ruxandra Laza A8 Anaerobes an underdiagnosed cause of prosthesis joint infection Anca-Ruxandra Negru, Daniela-Ioana Munteanu, Raluca Mihăilescu, Remulus Catană, Olga Dorobăț, Alexandru Rafila, Emilia Căpraru, Marius Niculescu, Rodica Marinescu, Olivera Lupescu, Vlad Predescu, Adrian Streinu-Cercel, Victoria Aramă, Daniela Tălăpan A9 Streptococcus pneumoniae meningitis presenting with normal CSF – case presentation Ramona Ștefania Popescu, Luminița Bradu, Dragoș Florea, Adrian Streinu-Cercel A10 Extrapulmonary manifestations of infection with Mycoplasma pneumoniae – study on 24 cases Daniela Anicuta Leca, Elena Bunea, Andra Teodor, Egidia Miftode A11 The molecular diagnosis of severe bacterial sepsis in pediatric population Mădălina Merișescu, Gheorghiță Jugulete, Adrian Streinu-Cercel, Dragoș Florea, Monica Luminos A12 Acute Staphylococcus aureus endocarditis with multiple septic complications in a patient with diabetes mellitus – case presentation Ramona Ștefania Popescu, Anamaria Dobrotă, Adina Ilie, Liliana Lucia Preoțescu A13 Is Streptococcus suis meningitis an under-diagnosed zoonosis? Adriana Hristea, Raluca Jipa, Nicoleta Irimescu, Irina Panait, Eliza Manea, Simona Merisor, Cristian Niculae, Daniela Tălăpan A14 Klebsiella pneumoniae isolated from blood. Antimicrobial resistance – past and present Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Șerban Benea, Alexandru Rafila, Olga Dorobăț, Mona Popoiu A15 Antibiotics resistance in Staphylococcus aureus isolated from blood cultures Livia Dragonu, Augustin Cupşa, Iulian Diaconescu, Irina Niculescu, Lucian Giubelan, Florentina Dumitrescu, Andreea Cristina Stoian, Camelia Guţă, Simona Puiu A16 Predominance of CTX-M enzymes in extended-spectrum β-lactamase-producing Enterobacteriaceae in two hospitals of Quebec City Bunescu Irina, Marilyse Vallée, Ann Huletsky, Dominique K. Boudreau, Ève Bérubé, Richard Giroux, Jean Longtin, Yves Longtin, Michel G. Bergeron A17 Postoperative meningoencephalitis with Acinetobacter baumannii XDR – a therapeutic challenge - Case report Cleo Nicoleta Roșculeț, Dalila-Ana Toma, Catrinel Ciuca, Daniela Tălăpan, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Tudor Vladoiu, Doina Iovănescu A18 Septic arthritis with Burkholderia cepacia Michaela Oana, Simona Costin A19 A novel approach for managing hard-to-treat infections Alina Cristina Neguț, Oana Săndulescu, Anca Streinu-Cercel, Maria Magdalena Moțoi, Mircea Ioan Popa, Adrian Streinu-Cercel A20 Nineteen months surveillance for multidrug resistant organisms (MDRO) by detecting asymptomatic colonization Daniela Tălăpan, Olga Mihaela Dorobăț, Mona Popoiu, Alexandru Mihai, Doina Iovănescu, Cleo Roşculeț, Cătălin Apostolescu, Gabriel-Adrian Popescu, Adrian Abagiu, Ruxandra Moroti-Constantinescu, Adriana Hristea, Victoria Aramă, Otilia Benea, Mădălina Simoiu, Rodica Bacruban, Adrian Streinu-Cercel, Alexandru Rafila A21 Antimicrobial resistance of Gram-positive cocci isolated from clinical specimens in the National Institute of Infectious Diseases “Prof Dr. Matei Balș” between 2009–2015 Olga Mihaela Dorobăț, Daniela Tălăpan, Alexandru Mihai, Ioana Bădicuț, Mona Popoiu, Alina Borcan, Alexandru Rafila A22 The high percentage of carbapenem-resistant Gram-negative bacilli in Romania: an analysis and some proposals Gabriel Adrian Popescu A23 Etiological, clinical and therapeutic considerations on 78 cases of healthcare associated meningitis or ventriculitis admitted in the “Sf. Parascheva” infectious diseases clinical hospital, Iași, from 2011 to 2015 Mihnea Hurmuzache, Georgiana Enache, Alexandra Ciocan, Mircea Bararu, Madalina Popazu A24 Nosocomial infection dynamics in an Intensive Care Department – an overview (epidemiological and clinical monitoring, advanced therapeutic intervention). Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz Cătălin Gabriel Apostolescu, Viorica Mitescu(,) Tudor Vladoiu, Dalila Toma, Catrinel Ciuca A25 Safety and efficacy of interferon free treatment in patients with HCV chronic hepatitis- experience of a single Internal Medicine center Laura Iliescu, Georgiana Minzala, Letitia Toma, Mihaela Baciu, Alina Tanase, Carmen Orban A26 Viusid in treatment of chronic viral hepatitis B and C Victor Pantea, Gheorghe Placinta, Valentin Cebotarescu, Lilia Cojuhari, Paulina Jimbei A27 The management of hyperbilirubinemia in HCV cirrhotic patients who underwent therapy with direct acting antivirals Cristina Popescu, Anca Leuștean, Cristina Dragomirescu, Alina Orfanu, Cristina Murariu, Laurențiu Stratan, Alexandra Badea, Cătălin Tilișcan, Daniela Munteanu, Raluca Năstase, Violeta Molagic, Mihaela Rădulescu, Remulus Catana, Victoria Aramă A28 The efficacy of ombitasvir-paritaprevir/ritonavir, dasabuvir and ribavirin in patients with genotype 1 HCV compensated cirrhosis Cristina Popescu, Laurențiu Stratan, Remulus Catana, Anca Leuștean, Cristina Dragomirescu, Alexandra Badea, Cristina Murariu, Raluca Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Mihaela Rădulescu, Alina Orfanu, Ioan Diaconu, Anca Negru, Iulia Bodosca, Violeta Niță, Victoria Aramă A29 The efficacy of direct acting antivirals regimen without ribavirin in HCV genotype 1b infected patients with compensated cirrhosis Anca Leuștean, Victoria Aramă, Alina Orfanu, Remulus Catana, Laurențiu Stratan, Cristina Dragomirescu, Cristina Murariu, Alexandra Badea, Cătălin Tilișcan, Daniela Munteanu, Violeta Molagic, Raluca Năstase, Mihaela Rădulescu, Cristina Popescu A30 Liver decompensation during ombitasvir-paritaprevir/ritonavir-dasabuvir and ribavirin regimen in HCV infected patients with Child-Pugh A cirrhosis Cristina Popescu, Cristina Dragomirescu, Anca Leuștean, Cristina Murariu, Laurențiu Stratan, Alexandra Badea, Remulus Catană, Alina Orfanu, Raluca Mihaela Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Victoria Aramă A31 The safety of direct acting antivirals in HCV compensated cirrhotic patients - an interim analysis Victoria Aramă, Remulus Catană, Cristina Dragomirescu, Cristina Murariu, Anca Leuștean, Laurențiu Stratan, Alexandra Badea, Alina Orfanu, Anca Negru, Raluca Năstase, Violeta Molagic, Daniela Munteanu, Cătălin Tilișcan, Mihaela Rădulescu, Ioan Diaconu, Violeta Niță, Iulia Bodoșca, Cristina Popescu A32 The access of patients with HCV compensated cirrhosis to the National Program of therapy with direct acting antivirals Cristina Popescu, Alexandra Badea, Anca Leuștean, Alina Orfanu, Anca Negru, Laurențiu Stratan, Cristina Dragomirescu, Remulus Catană, Cristina Murariu, Violeta Molagic, Raluca Năstase, Cătălin Tilișcan, Daniela Munteanu, Mihaela Rădulescu, Ioan Diaconu, Violeta Niță, Iulia Bodoșca, Victoria Aramă A33 Severe reactivation of chronic hepatitis B after discontinuation of nucleos(t)ide analogues – a case series Cristina Popescu, Alina Orfanu, Anca Leuștean, Alexandra Badea, Laurențiu Stratan, Remulus Catană, Cătălin Tilișcan, Victoria Aramă A34 The dynamic of hematological disorders during direct acting antivirals therapy for HCV compensated cirrhosis Cristina Popescu, Cristina Murariu, Cristina Dragomirescu, Anca Leuștean, Laurențiu Stratan, Alina Orfanu, Alexandra Badea, Remulus Catană, Anca Negru, Cătălin Tilișcan, Daniela Munteanu, Mihaela Rădulescu, Violeta Molagic, Raluca Mihaela Năstase, Ioan Alexandru Diaconu, Iulia Bodoșca, Violeta Niță, Victoria Aramă A35 Behaviors, attitudes and risk factors for viral hepatitis in international medical students vs. the general population in Romania Yagmur Erturk, Oana Săndulescu, Alina Cristina Neguț, Claudiu Mihai Șchiopu, Adrian Streinu-Cercel, Anca Streinu-Cercel A36 Characteristics of hepatitis C virus reactivation due to immunosuppressive therapy in Romanian HCV infected patients with hematological malignancies Violeta Molagic, Cătălin Tilișcan, Cristina Popescu, Raluca Mihăilescu, Daniela Munteanu, Raluca Năstase, Anca Negru, Angelica Tenita, Victoria Aramă, Ștefan Sorin Aramă A37 The dynamic IFN-gamma serum levels during successful peginterferon-a 2a/ribavirin therapy in HCV chronic infection Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos A38 Overlapping risk factors for transmission of HBV, HCV and HIV in the general population in Romania Anca Streinu-Cercel, Oana Săndulescu, Mioara Predescu, Alexandra Mărdărescu, Cătălin Tilișcan, Mihai Săndulescu, Claudiu Mihai Șchiopu, Adrian Streinu-Cercel A39 Acute hepatitis - an uncommon neurological complication Cleo Nicoleta Roșculeț, Catrinel Olimpia Ciuca, Dalila Ana Toma, Cătălin Gabriel Apostolescu, Andrei Rogoz, Cristina Elena Mitu, Andrei Stangaciu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Doina Viorica Iovănescu A40 Regression of liver fibrosis following sustained virological response in patients with chronic HCV infection and cirrhosis Oana Săndulescu, Anca Streinu-Cercel, Monica Andreea Stoica, Liliana Lucia Preoțescu, Daniela Manolache, Gabriela Jana Ceapraga, Maria Magdalena Moțoi, Luminița Bradu, Adina Ilie, Gabriela Mircea, Ionel Durbală, Adrian Streinu-Cercel A41 Preliminary results of treatment with sofosbuvir and daclatasvir of patients with chronic hepatitis C Irina Russu, Tiberiu Holban, Tatiana Pantilimonov, Galina Chiriacov, Arcadie Macvovei, Elena Scorohodico, Oleg Dmitriev A42 HIV-syphilis coinfection Diana Alexandra Costache, Anca Benea, Eliza Manea, Cristian Niculae, Raluca Jipa, Adriana Hristea, Elisabeta Benea, Ruxandra Moroti, Șerban Benea A43 Thrombophilia – additional risk factor for the evolution of pregnancy in HIV-positive patients Mihai Mitran, Carmen Georgescu, Loredana Mitran, Simona Vladareanu A44 The incidence of oropharyngeal candidiasis in hospitalized HIV infected pediatric Romanian cohort between 1 January - 31 December 2015 Andreea Ioana Magirescu, Viorica Andreev, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc A45 TB incidence in HIV infected patients during the year of 2015 Viorica Andreev, Andreea Ioana Magirescu, Ina Isac, Cristina Nicolau, Alexandra Largu, Carmen Dorobat, Carmen Manciuc A46 Retrospective analysis of HIV/AIDS deaths recorded in the Clinical Infectious Diseases Hospital, Constanța in the period 01 January 2014–30 June 2016. Epidemiological considerations. Iulia Gabriela Șerban, Ghiulendan Resul, Consuela Marcaș A47 Acute liver failure with favorable evolution in an HIV-HBV coinfected patient Iosif Marincu, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Anca Tudor, Daliborca Vlad, Livius Tirnea A48 Lifestyle impact on HIV management Nurcan Baydaroglu, Alina Cristina Neguț, Oana Săndulescu, Daniela Manolache, Gabriela Ceapraga, Monica Andreea Stoica, Anca Streinu-Cercel, Adrian Streinu-Cercel 49. HIV positive mothers newborns - clinical experience from January 2012 to June 2016 Carmen Manciuc, Mariana Pagute, Cristina Nicolau, Carmen Dorobăț, Alexandra Largu A50 Rediscovering HIV-associated progressive multifocal leukoencephalopathy and HIV encephalopathy: clinical suspicion and subsequent brain autopsies Ioan-Alexandru Diaconu, Laurențiu Stratan, Daniela Ion, Luciana Nichita, Cristina Popescu, Raluca Năstase, Daniela Munteanu, Violeta Molagic, Cătălin Tilișcan, Mihaela Rădulescu, Alexandra Diaconu, Anca Negru, Alina Orfanu, Cristina Dragomirescu, Remulus Catană, Anca Leuștean, Irina Duport-Dodot, Cristina Murariu, Iulia Bodoșca, Violeta Niță, Alexandra Badea, Victoria Aramă A51 Antenatal surveillance of pregnant women with risk behavior and its impact on mother-to-child HIV transmission in Romania Mariana Mărdărescu, Cristina Petre, Marieta Iancu, Rodica Ungurianu, Alina Cibea, Ruxandra Drăghicenoiu, Ana Maria Tudor, Delia Vlad, Sorin Petrea, Carina Matei, Dan Oțelea, Carmen Crăciun, Cristian Anghelina, Alexandra Mărdărescu A52 Noninvasive assessments (APRI, Fib-4, transient elastography) of fibrosis in patients with HIV and HIV/HBV infection Elena Dumea, Adrian Streinu-Cercel, Sorin Rugină, Lucian Cristian Petcu, Stela Halichidis, Simona Claudia Cambrea A53 Undetectable HIV viral load – the main goal in the management of HIV-infected patients Carmen Chiriac, Nina-Ioana Bodnar, Iringo-Erzsebet Zaharia-Kezdi, Cristina Gîrbovan, Andrea Incze, Anca Meda Georgescu A54 LPS serum levels and correlation with immunological, virological and clinical outcome in HIV infected patients Simona Alexandra Iacob, Diana Gabriela Iacob, Eugenia Panaitescu, Monica Luminos, Manole Cojocaru A55 LL37 human cathelicidin serum levels are positively correlated with IFN gamma and alanine aminotransferase level in HCV infection Simona Alexandra Iacob, Diana Gabriela Iacob, Monica Luminos A56 Early diagnosis of pulmonary tuberculosis in a non-compliant HIV/AIDS late presenter patient Vochita Laurențiu, Vochita Andreia, Opreanu Radu, Trinca Bogdan, Rosca Ovidiu, Marincu Iosif A57 Evolution of antiretroviral regimens in naϊve patients in 2016 Ramona Zamfir, Alina Angelescu, Alena Andreea Popa, Raluca Jipa, Ruxandra Moroti, Adriana Hristea, Liana Gavriliu, Șerban Benea, Elisabeta Benea A58 The unfavorable risk factors for HIV infected persons with positive blood cultures hospitalized at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015 Alena-Andreea Popa, Georgeta Ducu, Daniela Camburu, Alina Cozma, Manuela Podani, Roxana Dumitriu, Liana Gavriliu, Șerban Benea, Elisabeta Benea A59 Epidemiological aspects of HIV infection in Oltenia region Andreea Cristina Stoian, Florentina Dumitrescu, Augustin Cupșa, Lucian Giubelan, Irina Niculescu, Loredana Ionescu, Livia Dragonu A60 HIV risk behaviors and prevalence among patients in methadone maintenance therapy (MMT) from Arena center, Bucharest Adrian Octavian Abagiu, Loredana Nicoleta Stoica, Catrinel Blaga, Archontis Koulosousas, Roxana Ștefănescu, Alice Atomoaie, Florentina Paraschiv, Florin Matache Duna A61 Therapeutic options in a case of severe psoriasis associated with both HIV infection and hepatitis C virus previously treated with fumaric acid esters Rodica Olteanu, Roxana Ion, Alexandra Zota, Isra Ennour Jaballah, Lara Mahfoud, Georgeta Preda, Magda Constantin A62 Prevalence of autoantibodies against gangliosides in asymptomatic HIV-infected patients Ilinca Nicolae, Corina Daniela Ene, Mădălina Irina Mitran, Vasile Benea, Mircea Tampa, Simona Roxana Georgescu A63 Subclinical inflammation in HIV-infected patients undergoing antiretroviral therapy – a cross sectional study Iulia Cristina Bodoșca, Cristina Murariu, Cătălin Tilișcan, Victoria Aramă, Cristina Popescu, Daniela Munteanu, Mihaela Rădulescu, Violeta Molagic, Raluca Năstase, Alina Orfanu, Anca Leuștean, Remulus Catană, Anca Negru, Adrian Streinu-Cercel, Sorin Aramă A64 Severe Guillain-Barré syndrome occurring after chickenpox with favorable evolution Iuliana CAramăngiu, Ovidiu Rosca, Monica Cialma, Radu Opreanu, Laurențiu Vochita, Iosif Marincu A65 Echovirus 30 infection with pulmonary and cardiac complications – case report Vlad Murărescu, Marilena Palaghiță, Alina Cristina Neguț, Cornel Camburu, Adrian Streinu-Cercel A66 Herpetic encephalitis with favorable evolution in an adult immunocompetent patient Irina Duşan, Patricia Poptelecan, Bogdan Trincă, Sorina Mitrescu, Livius Tirnea, Iosif Marincu A67 Clinical-evolutional aspects in present-day measles Narcisa Nicolescu, Alexandru Crișan, Voichița Lăzureanu, Ruxandra Laza, Virgil Musta, Adelina-Raluca Marinescu, Andreea Bîrlad A68 Pneumococcal superinfection in children with influenza Victor Daniel Miron, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Daniela Pițigoi, Oana Săndulescu, Monica Luminița Luminos A69 Varicella complicated with transverse myelitis - case presentation Monica Luminos, Endis Osman, Magdalena Vasile, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Camelia Kouris, Sabina Șchiopu, Mădălina Merișescu A70 Clinical forms of enterovirus infections during the summer season of 2016 Monica Luminos, Anca Cristina Drăgănescu, Constanța-Angelica Vișan, Anuța Bilașco, Camelia Kouris, Endis Osman, Sabina Vintilă, Magda Vasile, Mădălina Merișescu A71 Face off – HIV and lymphoma – case series presentation Liana Cătălina Gavriliu, Otilia Elisabeta Benea, Alina Angelescu, Ramona Zamfir, Daniela Camburu, Georgeta Ducu, Alina Cozma, Roxana Dumitriu, Manuela Podani, Șerban Benea, Mihaela Ionică A72 Coxsackie infection complicated by pancytopenia – pediatric case report Gheorghiță Jugulete, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Lucia Tudor, Sabina Vintilă A73 Viral respiratory infections in children in the season 2015–2016 Constanța-Angelica Vișan, Anca Cristina Drăgănescu, Anuța Bilașco, Magda Vasile, Mădălina Merișescu, Camelia Kouris, Cristina Negulescu, Endis Osman, Diana-Maria Slavu, Sabina Vintilă, Daniela Pițigoi, Monica Luminos A75 The severity of A H1N1 Influenza infection in the 2015–2016 season Cleo Roșculeț, Catrinel Olimpia Ciuca, Dalila Toma, Cătălin Apostolescu, Andrei Rogoz, Andrei Stangaciu, Viorica Mitescu, Doina Iovănescu, Cornel Camburu, Bogdana Manu A76 Acute respiratory distress syndrome in a child with measles Ana Vaduva-Enoiu, Ramona Georgiana Stanculete, Adelina Raluca Marinescu, Voichita Elena Lazureanu A77 Management challenges of right-sided infectious endocarditis in an HIV positive patient – case presentation Elena-Violeta Niță, Sînziana Dumitru, Daniela-Ioana Munteanu, Anca Ruxandra Negru, Remulus Catană, Ioan Diaconu, Bogdana Manu, Ligia Ionescu, Liliana Ion, Cătălin Tilișcan, Victoria Aramă A78 Bacterial infection in critical patients with severe A H1N1 influenza virus infection (epidemiology, development, therapeutic decisions) Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz, Cătălin Apostolescu, Viorica Mitescu, Tudor Vladoiu, Dalila Toma, Catrinel Ciuca A79 Epidemiological aspects of severe acute respiratory infection cases (SARI) in the season 2015–2016, in the Clinical Hospital of Infectious Diseases – Constanța, Romania Iulia Gabriela Șerban, Marioara Neacșu A80Overexpression of IL-6 trans signaling pathway in viral infections Simona Roxana Georgescu, Vasile Benea, Corina Daniela Ene, Mircea Tampa, Cristina Iulia Mitran, Ilinca Nicolae A81 Acute viral hepatitis B with persistent HBsAg – description and evolution George Ciprian Pribac, Mirandolina Prisca, Fulvia Ursoiu, Carmen Neamtu, Bogdan Totolici, Coralia Cotoraci, Aurel Ardelean A82 Prevalence of cervical pathogens in a population of pregnant female patients monitored in a tertiary care hospital in Bucharest, Romania Simona Elena Albu, Mara Carsote, Beatrice Miclăuș, Diana Mihai, Oana Săndulescu, Cristina Vasiliu A83 Prevalence of group B Streptococcus during pregnancy in a cohort of patients monitored in a tertiary care hospital in Bucharest, Romania Cristina Vasiliu, Mara Carsote, Corina Gorgoi, Beatrice Miclăuș, Diana Mihai, Oana Săndulescu, Simona Elena Albu A84 Infectious hematoma in the gastrocnemius muscle – case presentation Amelia Blescun, Gelu Breaza A85 Reflections towards the underexplored HTLV Romanian viral circulation - adult T‐cell leukemia/lymphomas, a case series Sabina Vintila, Felicia Mihai, Meilin Omer, Cornel Dragan, Daniela Pitigoi A86 A febrile confusion syndrome with acute onset – case presentation Mirela Ciucu, Marius-Dan Ionescu, Cristina Roskanovic, Valentina Barbu, Iulian Diaconescu, Florentina Dumitrescu, Irina Niculescu A87 Retrobulbar optic neuritis in a HIV-positive patient - case report Mihaela Ionică, Ramona-Alexandra Zamfir, Alina Cozma, Otilia Elisabeta Benea A88 A rare presentation of Q fever – case presentation Alexandra-Sînziana Dumitru, Daniela-Ioana Munteanu, Violeta Niță, Cristina Popescu, Iulia Bodosca, Angelica Tenita, Viorica Ispas, Victoria Aramă A89 Tinea incognita – case presentation Vasile Benea, Simona Roxana Georgescu, Mircea Tampa, Diana Oana Leahu, Cristina Maria Safta, Mihaela Anca Benea A90 Incidence and risk factors associated with TORCH infections during pregnancy Oana Săndulescu, Octavian Munteanu, Roxana Bohâlțea, Livia Trașcă, Monica Cîrstoiu A91 Acute respiratory failure in critical patients with sepsis Doina Viorica Iovănescu, Cleo Nicoleta Roșculeț, Andrei Rogoz, Cătălin Gabriel Apostolescu, Viorica Daniela Mitescu, Tudor Gheorghe Vladoiu, Dalila Toma, Catrinel Ciuca A92 Cochleo-vestibular deficit secondary to Granulicatella elegans meningitis Mădălina Georgescu A93 Influenza 2015/2016 – clinical, epidemiological and virological characteristics of cases admitted in three infectious diseases hospitals Daniela Pițigoi, Alina Elena Ivanciuc, Mihaela Lazar, Teodora Ionescu, Carmen Maria Cherciu, Cristina Țecu, Maria Elena Mihai, Maria Nițescu, Rodica Bacruban, Delia Azamfire, Aura Dumitrescu, Elena Ianosik, Daniela Leca, Elena Duca, Andra Teodor, Codrina Bejan, Emanoil Ceaușu, Simin-Aysel Florescu, Corneliu Popescu, Grațiela Târdei, Codrina Juganariu, Emilia Lupulescu A94 Severe complications of varicella requiring hospitalization in previously healthy children in Brașov county Ligia Rodina, Maria Elena Cocuz A95 Clinical forms of Clostridium difficile colitis in children Gheorghiță Jugulete, Adina Stăncescu, Cristina Elena Popescu, Luminița Marin, Diana Zaharia, Cristina Dumitrescu, Endis Osman A96 Community-acquired pneumonia – demographic, clinical and etiological aspects Irina Niculescu, Augustin Cupșa, Iulian Diaconescu, Florentina Dumitrescu, Livia Dragonu, Andreea Stoian, Lucian Giubelan, Cristina Roskanovic A97 Acute myocarditis in an adult patient with chickenpox - Case report Ramona-Alexandra Zamfir, Mihaela Ionica, Otilia-Elisabeta Benea A98 Caustic oropharyngeal wound with acute group F streptococcal superinfection mimicking diphtheria – case report and differential diagnosis Maria-Cristina Sîrbu, AnaMaria Dobrotă, Alina Cristina Neguț, Roxana Duda, Rodica Bacruban, Daniela Pițigoi, Cristiana Cerasella Dragomirescu, Daniela Tălăpan, Olga Dorobăț, Adrian Streinu-Cercel, Anca Streinu-Cercel A99 Clostridium difficile infection in HIV-positive patients admitted in the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” in 2015 Mihaela Ionica, Ramona-Alexandra Zamfir, Alina Cozma, Otilia Elisabeta Benea A100 Title: Epidemiology of Candida oral infections (stomatitis) in Romania Sergiu Fendrihan, Ecaterina Scortan, Mircea Ioan Popa A101 Anthrax case series in south-eastern Romania Corneliu P Popescu, Șerban N Benea, Andra E Petcu, Adriana Hristea, Adrian Abagiu, Iuliana A Podea, Raluca E Jipa, Georgeta Ducu, Raluca M Hrișcă, Dragoș Florea, Manuela Nica, Eliza Manea, Simona Merișor, Cristian M Nicolae, Simin A Florescu, Irina M Dumitru, Emanoil Ceaușu, Sorin Rugină, Ruxandra V Moroti A102 Knowledge, risk perception and attitudes of healthcare workers at the National Institute for Infectious Diseases “Prof. Dr. Matei Balș” regarding Ebola Daniela Pițigoi, Teodora Ionescu, Oana Săndulescu, Maria Nițescu, Bogdan Nițescu, Iulia Monica Mustaţă, Sorina Claudia Boldeanu, Florentina Furtunescu, Adrian Streinu-Cercel A103 A case of abdominopelvic actinomycosis with successful short-term antibiotic treatment Diana Gabriela Iacob, Simona Alexandra Iacob, Mihaela Gheorghe A104 A case of pneumonia caused by Raoultella planticola Iulian Diaconescu, Irina Niculescu, Floretina Dumitrescu, Lucian Giubelan A105 Vitamin D deficiency and sepsis in childhood Adriana Slavcovici, Raluca Tripon, Roxana Iubu, Cristian Marcu, Mihaela Sabou, Monica Muntean A106 The clinical and epidemiological aspects and prophylaxis of Lyme disease among patients who presented with tick bites to the Clinical Infectious Disease Hospital “Toma Ciorbă” Ion Chiriac, Tiberiu Holban, Liviu Tazlavanu A107 Drug-resistant tuberculosis in HIV infected patients Raluca Jipa, Eliza Manea, Roxana Cernat, Kezdi Iringo, Andrei Vâță, Manuela Arbune, Teodora Moisil, Adriana Hristea A108 Kidney injury molecule-1 and urinary tract infections Corina-Daniela Ene, Ilinca Nicolae, Roxana Simona Georgescu A109 The impact of microbiological agents on serum gangliosides in patients with benign prostate hyperplasia Corina-Daniela Ene, Cosmin-Victor Ene, Roxana Simona Georgescu, Marilena Ciortea , Lucreția Dulgheru, Ilinca Nicolae A110 Toxocariasis - the experience of the Iași Infectious Diseases Hospital between 2013–2015 Mihaela Cătălina Luca, Ioana-Alina Harja-Alexa, Roxana Nemescu, Mădălina Popazu, Andrei Ștefan Luca A111 Species of anaerobic Gram-positive cocci involved in odontogenic abscesses Gabriela Bancescu, Bogdan Dabu, Adrian Bancescu A112 Clostridium difficile infection recurrences Eliza Manea, Raluca Jipa, Adriana Hristea A113 Differential diagnosis of staphylococcal and tuberculous osteodiscitis – case report Adina Elena Ilie, Săftica-Mariana Pohrib, Alina Cristina Neguț, Maria-Sabina Tache, Maria Magdalena Moțoi, Oana Săndulescu, Ion Aurel Iliescu, Adrian Streinu-Cercel A114 Severe clinical forms of respiratory syncytial virus infections Cristina Tecu, Maria-Elena Mihai, Mihaela Lazăr, Carmen Cherciu, Alina Ivanciuc, Daniela Pițigoi, Emilia Lupulescu A115 Acinetobacter baumannii postoperative sepsis associated with Clostridium difficile enterocolitis in an immune suppressed elderly patient Mirela Paliu, Manuela Curescu, Bianca Cerbu, Iosif Marincu A116 Risk factors and their impact on psychopathology and quality of life among people living with HIV/AIDS in Romania Fulvia Ursoiu, Mirandolina Prișcă, George Ciprian Pribac A117 Antivirals susceptibility of influenza viruses circulating in Romania Maria Elena Mihai, Carmen Maria Cherciu, Alina Elena Ivanciuc, Cristina Tecu, Emilia Lupulescu A118 Retrospective study of hospitalized cases of sepsis at the Hospital Clinic of Infectious Diseases “Toma Ciorbă” Irina Bunescu, Tiberiu Holban, Ana Pasnin, Stela Semeniuc, Raisa Popovici, Galina Chiriacov"
4510,In the national epidemiological bulletins – a selection from current issues,
4511,"Proceedings of Réanimation 2017, the French Intensive Care Society International Congress",
4512,"Proceedings of Réanimation 2017, the French Intensive Care Society International Congress",
4513,2016 ACVIM Forum Research Abstract Program,
4514,"Abstracts from the 8th International Congress of the Asia Pacific Society of Infection Control (APSIC): Bangkok, Thailand. 12-15 February 2017",
4515,The Exploding Aliveness of the World,
4516,"37th International Symposium on Intensive Care and Emergency Medicine (part 3 of 3): Brussels, Belgium. 21-24 March 2017",
4517,"37th International Symposium on Intensive Care and Emergency Medicine (part 1 of 3): Brussels, Belgium. 21–24 March 2017",
4518,Public Health Genomics (PHG): From Scientific Considerations to Ethical Integration,"Recent advances in our understanding of the human genome have raised high hopes for the creation of personalized medicine able to predict diseases well before they occur, or that will lead to individualized and therefore more effective treatments. This possibility of a more accurate science of the prevention and surveillance of disease also illuminates the field of public health, where the translation of genomic knowledge could provide tools enhancing the capacity of public health authorities to promote health and prevent diseases. But beyond scientific considerations, the use of genomics in public health research and interventions gives rise to several ethical and social issues of great importance. Considering the impact that PHG could have on the future of public health while still paying attention to the uncertainty surrounding the use of genomic databases for the benefit of populations, this article seeks to explore the promise of genomics in public health and the ethical issues that emerge from its application."
4519,ACRT‐AFMR‐SCTS annual meeting abstracts,
4520,Spread of Middle East Respiratory Coronavirus: Genetic versus Epidemiological Data,
4521,Interpreting specific and general respiratory indicators in syndromic surveillance,
4522,"Analysis of Daily Enhanced Syndromic Surveillance in Hillsborough County, FL, 2015",
4523,"MERS PUI Surveillance and Restrospective Identification in ESSENCE-FL, 2013-2015",
4524,Building Qatar severe respiratory failure ECMO program,
4525,ECMO retrieval: A case for Critical Care Paramedic integration into the team,
4526,"Qatar ECMO program: Past, present, and future",
4527,Extracorporeal membrane oxygenation for systemic lupus erythematosus (SLE) with severe ARDS,
4528,"Meeting abstracts from International Conference on Prevention & Infection Control (ICPIC 2017): Geneva, Switzerland. 20-23 June 2017",
4529,2017 ACVIM Forum Research Abstract Program,
4530,Characterization of a Novel RNA Virus Discovered in the Autumnal Moth Epirrita autumnata in Sweden,"A novel, 10 kb RNA virus—tentatively named ‘Abisko virus’—was discovered in the transcriptome data of a diseased autumnal moth (Epirrita autumnata) larva, as part of a search for the possible causes of the cyclical nature and mortality associated with geometrid moth dynamics and outbreaks in northern Fennoscandia. Abisko virus has a genome organization similar to that of the insect-infecting negeviruses, but phylogenetic and compositional bias analyses also reveal strong affiliations with plant-infecting viruses, such that both the primary host origin and taxonomic identity of the virus remain in doubt. In an extensive set of larval, pupal, and adult autumnal moth and winter moth (Operophtera brumata) outbreak samples, the virus was only detected in a few adult E. autumnata moths as well as the single larval transcriptome. The Abisko virus is therefore unlikely to be a factor in the Fennoscandia geometrid population dynamics."
4531,"Contents Vol. 24, 2015",
4532,Human Rhinovirus Detection by PCR in Febrile Infants and Risk of Concomitant Bacterial Infection,"BACKGROUND: Studies have shown that well-appearing febrile infants (FI) with viral respiratory infections have a reduced risk of bacterial infections (BI; urinary tract infection, bloodstream infection, meningitis). Respiratory testing by PCR allows detection of human rhinovirus (HRV), but few data exist on the risk of concomitant BI in HRV-positive FI. METHODS: We identified well-appearing FI 1–90 days old within Intermountain Healthcare evaluated in the ED or inpatient setting (IP) with viral respiratory testing by PCR (RVPCR) from August 2007 to August 2016. Respiratory viruses detected by RVPCR included: adenovirus, coronavirus, human metapneumovirus, influenza A/B, parainfluenza 1–4, RSV and HRV. We used relative risk (RR) to compare the risk of BI for infants with HRV vs. non-HRV viruses detected. Similarly, we used RR to compare risk of UTI and invasive bacterial infection (IBI; bacteremia and meningitis) for infants with HRV detected compared with those who were virus negative. RESULTS: 10,964 FI were evaluated in the ED/IP during the study period. 4037 (37%) had RVPCR and were included. 2212 (55%) FI were positive for a respiratory virus and 73% were 29–90 days old. HRV was detected alone in 1392 (34%) and non-HRV viruses were detected in 820 (20%). The overall frequency of BI in the cohort was 9.5%. FI with HRV were more likely to have BI when compared with those with non-HRV viruses [7.8% vs 3.7% P < 0.0001; RR 2.12 (95% CI; 1.43–3.15)]. When compared with virus-negative infants, HRV detection in infants 1–28 days did not decrease the risk for UTI [RR 0.87 (95% CI 0.58–1.29)]; risk of IBI was statistically decreased [RR 0.41 (95% CI 0.19–0.88)] but with wide CI approaching 1 suggesting that this may not be clinically meaningful. Similarly, UTI risk in infants 29–90 days was statistically lower with HRV detection [RR 0.78 (95% CI 0.65–0.95)], but unlikely to be clinically important. For infants 29–90 days with HRV, risk of IBI was statistically decreased [RR 0.52 (95% CI 0.34–0.80)] with possible clinical relevance. CONCLUSION: HRV detection was common in young febrile infants. Infants with HRV were at higher risk of BI than infants with non-HRV infection. Detection of HRV did not meaningfully change risk for UTI at any age or meaningfully impact risk of IBI in infants 1–28 days. HRV detection may be associated with a decreased risk for IBI in infants 29–90 days. DISCLOSURES: A. J. Blaschke, BioFire Diagnostics LLC: Collaborator, Have intellectual property in BioFire Diagnostics through the University of Utah and Investigator, Licensing agreement or royalty and Research support; J. Daly, Biofire: Grant Investigator, Grant recipient; C. L. Byington, BioFire: Collaborator and Grant Investigator, Licensing agreement or royalty and Research grant"
4533,Performance of Zoster Vaccine Live (Zostavax): A Systematic Review of 12 years of Experimental and Observational Evidence,"BACKGROUND: One in three people in the U.S. will develop herpes zoster during their life. Zoster Vaccine Live (ZVL or Zostavax™), has been licensed in the U.S. since 2006 to prevent herpes zoster. ZVL protection has been shown to wane with time and estimates of effect can be imprecise. We performed a systematic review of the duration of efficacy and effectiveness of ZVL against herpes zoster (HZ). METHODS: We systematically searched PubMed, Embase, Cochrane, and clinicaltrials.gov for vaccine efficacy or effectiveness (VE) studies of ZVL. Two authors independently screened each title and abstract, and potential VE studies were reviewed in-depth. Eligibility criteria included original data on ZVL prevention of HZ in a general population of immunocompetent recipients ≤ 60 years old. Selected articles were abstracted, independently reviewed, and discrepancies adjudicated. We attempted to locate relevant unpublished work and contacted authors for additional data, where necessary. Measures of association were illustrated on a forest plot and converted to VE (1-hazard ratio or risk ratio or odds ratio). RESULTS: We screened 1302 articles; 17 underwent full text review and 8 met inclusion criteria and were abstracted for this review. Selected studies included 1 phase III randomized controlled trial, 2 quasi experimental and 5 observational studies. One experimental and 5 observational studies estimated VE during the period from vaccination up to 4 years following vaccination; estimates across studies ranged from 33%-55%. Two quasi experimental and 3 observational studies estimated VE for ≥ 4 years following vaccination; estimates ranged from 19%-40%; the median estimate was 24% (Figure). Pooled VE was not calculated due to heterogeneity in length of follow up, age distribution of study subjects, as well as adjustment for factors such as underlying medical conditions. CONCLUSION: Most experimental and observational studies estimate VE just above 50% during the 3 years following receipt of ZVL. Beyond 3 years, ZVL protection wanes, with most studies estimating a VE of ≤24% after 4 years. Information on overall efficacy and duration of protection from ZVL will guide policy decisions regarding its use. DISCLOSURES: E. Belongia, Novavax: Investigator, Research support"
4534,Painting the Gown Red: Using a Colored Paint Quality Improvement Process to Evaluate Healthcare Worker Personal Protective Equipment for Highly Pathogenic Infections,"BACKGROUND: Personal protective equipment (PPE) and strict infection control techniques are the primary methods by which healthcare workers (HCW) can avoid exposure during the treatment of patients with highly pathogenic infections such as Ebola Virus Disease (EVD) or the Middle East Respiratory Syndrome coronavirus (MERS-CoV). There is currently no consensus for the types of PPE that are recommended to be worn by HCWs, nor is there a universal process for the donning and doffing of PPE. METHODS: HCWs from Bellevue Hospital participate in quarterly PPE trainings as part of the Special Pathogens Program (SPP), which consist of didactic sessions as well as an evaluation of donning and doffing techniques. A total of 50 HCWs completed the training curriculum in 2017. During the doffing process, PPE trainers applied corn start powder paint (Chameleon Colors; American Fork, UT) to the participants’ gloved hands between multiple steps of PPE removal. At the end of the process, the areas where paint was found on was documented including the outer surgical gown, the powered air purifying respirator (PAPR) helmet and shroud, the inner impermeable suit, the knee-high boots and boot covers, and the extended-cuff gloves. RESULTS: The areas of PPE that were most marked with paint were the lower shoulders and upper arms of the surgical gowns, the top sides of the PAPR shroud, the front upper chest area, and the center back of the inner impermeable suits. In a majority of cases no powder paint was noted on the knee-high boots. In a minority of cases, paint was observed on the inside upper chest area of the surgical gown. These paint markings were used to discuss potential breaches in PPE doffing technique in real-time, as well as identify areas to target in future PPE trainings. CONCLUSION: The powdered paint quality improvement process for donning and doffing PPE is a method to evaluate the complex PPE dressing procedure. It is particularly useful given the fact that it is incumbent on each hospital or healthcare system to develop its own processes and procedures for PPE, as well as maintain readiness through periodic trainings. Powdered paint can identify vulnerabilities in their process as well as areas that require further education. DISCLOSURES: All authors: No reported disclosures."
4535,"Broad-spectrum Investigational Agent GS-5734 for the Treatment of Ebola, MERS Coronavirus and Other Pathogenic Viral Infections with High Outbreak Potential","BACKGROUND: Recent viral outbreaks with significant mortality such as Ebola virus (EBOV), SARS-coronavirus (CoV), and MERS-CoV reinforced the need for effective antiviral therapeutics to control future epidemics. GS-5734 is a novel nucleotide analog prodrug in the development for treatment of EBOV. METHOD: Antiviral activity of GS-5734 has been established in vitro against a wide range of pathogenic RNA virus families, including filoviruses, coronaviruses, and paramyxoviruses (EC(50) = 37 to 200 nM) (Warren et al., Nature 2016; Sheahan et al., Sci Transl Med 2017; Lo et al., Sci Rep 2017). Herein, we describe the in vivo translation of the broad-spectrum activity of GS-5734 in relevant animal disease models for Ebola, Marburg, MERS-CoV, and Nipah. RESULT: Therapeutic efficacy against multiple filoviruses with 80–100% survival was observed in rhesus monkeys infected with lethal doses of EBOV (Kikwit/1995 or Makona/2014) or Marburg virus and treated with once daily intravenous (IV) administration of 5 to 10 mg/kg GS-5734 beginning 3 to 5 days post-infection (p.i.). In all rhesus monkey filovirus infection models, GS-5734 significantly reduced systemic viremia and ameliorated severe clinical disease signs and anatomic pathology. In mice infected with MERS-CoV, twice daily subcutaneous administration of 25 mg/kg GS-5734 beginning 1 day p.i. significantly reduced lung viral load and improved respiratory function. In rhesus monkeys, once-daily IV administration of 5 mg/kg GS-5734 initiated 1 day prior to MERS-CoV infection reduced lung viral load, improved clinical disease signs, and ameliorated severe lung pathology. Finally, in African green monkeys infected with a lethal dose of Nipah virus therapeutic once-daily IV administration of 10 mg/kg GS-5734, starting 1 day p.i. resulted in 100% survival to at least day 35 without any major respiratory or CNS symptoms. CONCLUSION: GS-5734 is currently being tested in a phase 2 study in male Ebola survivors with persistent viral RNA in semen. Lyophilized drug formulation has been developed that can be administered to humans via a 30-minutes IV infusion and does not require cold chain storage. Together, these results support further development of GS-5734 as a broad-spectrum antiviral to treat viral infections with high mortality and significant outbreak potential. DISCLOSURES: R. Jordan, Gilead: Employee, Salary. J. Feng, Gilead: Employee, Salary I. Trantcheva, Gilead: Employee, Salary. D. Babusis, Gilead: Employee, Salary. D. Porter-Poulin, Gilead: Employee, Salary. R. Bannister, Gilead: Employee, Salary R. Mackman, Gilead: Employee, Salary. D. Siegel, Gilead: Employee, Salary A. Ray, Gilead: Employee, Salary, T. Cihlar, Gilead: Employee, Salary."
4536,Effect of Rapid Molecular Diagnostic Testing and Antimicrobial Stewardship on Antimicrobial Therapy of Respiratory Infections,"BACKGROUND: Rapid molecular methods have created new opportunities for the clinical microbiology laboratory to affect patient care in the areas of initial diagnosis and therapy. Rapid diagnostic tests provide collaborative opportunities for antimicrobial stewardship Teams (AST) to improve patient outcomes and decrease antimicrobial use. In January of 2017 our institution initiated use of a FDA approved multiplex polymerase chain reaction (PCR) Respiratory Panel. The objective of this evaluation was to assess the clinical impact along with procalcitonin (PCT) on quality of patient care when used in conjunction with antimicrobial stewardship. METHODS: Molecular testing was performed using the BioFire FilmArray® Respiratory Panel [RP] (BioMerieux). The medical staff was encouraged to order an Influenza/RSV PCR test prior to ordering the full RP. The results of RP and PCT were available the same day as ordered. AST recommended the RP as part of its intervention on several patients and provided advice based on results. RESULTS: From January-April the results of 81 tests for the respiratory panel were evaluated. Of these 30 were positive (+) for virus (most common-Human Metapneumovirus [HMV]-13, Coronavirus-7). PCT (ng/mL) results were available on 69. Most common final diagnosis: Pneumonia-31; AECOPD-16. Effect on duration of antimicrobial therapy (ABX) and hospital length of stay (LOS): CONCLUSION: The results of the RP led to a decrease in ABX duration, which was most profound in the patients for whom AST intervened. LOS was also reduced. Utilization of RP and PCT facilitated better ABX use. DISCLOSURES: T. M. File Jr., BioMerieux: Scientific Advisor, Consulting fee"
4537,Trends of Device Utilization Ratios in Intensive Care Units During 10 Years in South Korea: Results from the Korean National Healthcare-Associated Infections Surveillance System,"BACKGROUND: Device-associated healthcare-associated infection (DA-HAI) is an important issue related to safety of patients. It is important to reduce unnecessary device utilization in order to decrease DA-HAI rates. Therefore, we investigate to the time trend of device utilization (DU) ratios and DA-HAI rates to analyzed collected data for 10 years through the Korean National Healthcare-associated Infections Surveillance System (KONIS) which is voluntarily participating in hospitals. METHODS: We investigate the time trend of DU ratios and DA-HAI rates from 2006 through 2015 in KONIS participating intensive care units (ICUs). DA-HAI rates were calculated as the numbers of infections per 1,000 device-days and DU were calculated as a ratio of device-days to patient-days. The pooled incidences of DAIs and DU ratios were calculated for each year of participation. RESULTS: Data were collected on 5,325,176 catheter-days and 6,358,829 patient-days in the 190 participating ICUs between July 2006 and June 2016. From 2006 to 2015, year-wise ventilator utilization ratio (V-UR) per 1000 patients-days increased significantly from 0.40 to 0.454 (F = 6.27, P < 0.0001), year-wise urinary catheter utilization ratio (UC-UR) show gradually increased trend from 0.83 to 0.84 but non-significantly (F = 1.66, P = 0.0951), and year-wise c-line utilization ratio (CL-UR) was gradually decreased non-significantly from 0.55 to 0.52 (F = 1.62, P = 0.1059). In subgroup analysis, Medical ICU (F = 2.79, P = 0.0034) or hospital with more than 900 beds (F = 3.07, P = 0.0015) related to increased significantly V-UR. Rate of ventilator associated pneumonia significantly decreased from 3.48 in 2006 to 1.00 in 2015 (per 1000 ventilator-days, F = 27.62, P < 0.0001). Also, rates of catheter associated UTI and c-line associated blood stream infection significantly decreased from 1.85 to 0.88 (per 1000 catheter-days, F = 10.14, P < 0.0001) and from 3.40 to 2.20 (per 1000 catheter-days, F = 14.17, P < 0.0001). CONCLUSION: In Korea, all of the DA-HAIs have shown a significant reduction in the last 10 years, however V-UR has year-wise significantly increased trend for past 10-years, also UC-UR and CL-UR have not decreased trend significantly. We need effort to make reduction of device utilization ratios. DISCLOSURES: E. J. Kim, Korean Nosocomial Infections Surveillance System (KONIS): Investigator, Research support; Y. HOURS. Choi, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research grant; H. Y. Kim, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research support; Y. G. Kwak, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research support; T. H. Kim, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research grant; H. B. Kim, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research grant; S. H. Park, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research grant; M. Lee, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research grant; S. O. Lee, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research grant; J. Y. Choi, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research grant; P. G. Choe, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research grant; S. K. Lim, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research grant; S. R. Kim, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research support; M. J. Shin, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research support; S. Y. Yoo, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research support; H. Yoo, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research support; J. Y. Choi, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research support; S. H. Han, Korean Nosocomial Infections Surveillance System (KONIS): Board Member, Research support"
4538,Asthma Exacerbations and Risk of Emergency Department Management Failure: Burden and Impact of Various Respiratory Pathogens in a Pediatric Population,"BACKGROUND: In asthmatic children, 60–80% of exacerbations are triggered by respiratory pathogens and represent an important burden of illness. The impact of pathogens on exacerbation severity and treatment response remains unclear. Our aim was to describe the prevalence of respiratory pathogens in children presenting to the emergency department (ED) and investigate the association between pathogens and (i) exacerbation severity on presentation and (ii) ED treatment failure. METHODS: We performed a secondary analysis of the DOORWAY study, a prospective multi-center cohort of children (1–17 years) presenting to the ED with moderate or severe asthma exacerbation. All received per protocol oral corticosteroids and bronchodilators. Nasopharyngeal (NPA) secretions were analyzed by RT-PCR for 30 different pathogens. Linear and logistic multivariate regression models were used to estimate absolute risks and risk differences (RD) with their 95% CI representing average marginal effects. RESULTS: Of 958 patients with NPA specimens, 591 (61.7%) were positive for ≥ 1 pathogens; human rhinovirus (HRV) was the most prevalent (29.4%). Non-HRV infection (RD -12.9%; 95% CI -19.5; -6.3), human metapneumovirus (RD -13.6%; 95% CI -23.0%; -4.3%) and parainfluenza virus (PIV) (RD -31.7%; 95% CI -44.5%; -18.9%) were negatively associated with severity; no association was found between severity and the presence of any pathogen, co-infection, or the specific viruses HRV-A, HRV-B, HRV-C, respiratory syncytial virus, influenza (INF), enterovirus serotype D68, adenovirus or coronavirus. The risk of treatment failure in the absence of a pathogen was 12.5% (95% CI 9.0%; 16.0%). The presence of any pathogen (RD 8.2%; 95% CI 3.3%; 13.1%) and non-HRV infection as a group (RD 13.1%; 95% CI 6.4%; 19.8%), and of INF and PIV specifically (RD 24.9%; 95% CI 4.7%; 45.1% and RD 34.1%; 95% CI 7.5%; 60.7%) were positively associated with treatment failure. CONCLUSION: In this large cohort of children with moderate or severe exacerbation, no single respiratory pathogen was associated with higher severity on presentation. However, in addition to any pathogen and non-HVR infection, INF and PIV were specifically associated with higher treatment failure in the ED, supporting the need for influenza prevention, pathogen identification at presentation and exploration of pathogen-therapy interaction. DISCLOSURES: All authors: No reported disclosures."
4539,Patients’ Family Empowering to Increase Hand Hygiene (HH) Compliance in Health-Care Workers (HCW) from a Hematology-Oncology Ward in Mexico City,"BACKGROUND: HH is a key component to decrease infections in hospitals, but compliance in HCW remains low. We present a six-month strategy to empower patients’ caregivers on HCW HH compliance. METHODS: HH compliance in HCWs was evaluated between June 1 and August 31, 2017 as recommended by WHO. Between September 1, 2016 and March 31, 2017 we undertook the empowering in the hematology-oncology ward (50 beds) from Instituto Nacional de Cancerologia, a cancer referral, teaching hospital in Mexico. To empower patients and their caregivers, a member of the team visited the patient and their relatives during the first 24h of hospital admission. Standarized information on HH and the importance of HCW compliance was given, along with a printed cartoon on HH opportunities (5 moments from WHO). Patients and their caregivers were trained to observe and record HH opportunties, an were invited to remind HCWs if HH omissions were observed. Data on HH compliance was collected monthly during the empowerment and 1 month after. Data was compared with the HH compliance from the 6 previous. We compared overall compliance and for each 5 HH moments before and after the empowering (chi (2) test). RESULTS: We empowered 82 caregivers (M: 25.6%) and F: 74.4%), mean age 44 years. 24.4% had completed primary education, and 13.1% had higher education. Mothers and spouses were the primary caregivers (28.1% and 36.6%). HH compliance increased in all 5 moments: Before touching a patient (M1) (B: 9.5%, A: 57.6%, P = 0.005); before a clean or aseptic procedure (M2) (B: 7.9%, A: 48%, P = 0.002); after body fluid exposure (M3) (B: 10%, A: 59%, P = 0.0005), after touching a patient (M4) (B: 7.4%, A: 57.9%, P = 0.0005), and after touching patient surroundings (M5) (B: 2.4%, A: 77.4%, P = 0.0008). Nurses achieved a higher increase on compliance compared with physicians. Caregivers recognition on HH increased for each opporunity, being more notorious for M2 (B:31.7%, A: 61.5%); M3 (B: 7.3%, A: 31.5%), and M4, (B: 36.5%, A: 68.7%). Perception on the importance of preventing health-care-related infections increased from 80.5% to 90.3%. CONCLUSION: Empowering patients’ primary caregivers was an effective intervention to increase HCWs HH compliance at a hematology-oncology ward. The effect of this intervention remains to be evaluated on the long-term basis, but demonstrate the importance of involving patients and their relatives on health-care delivery. DISCLOSURES: All authors: No reported disclosures."
4540,"Sorting the Wheat from the Chaff: Vaccine-Associated Rash Illness Occurring amidst a Large Measles Outbreak—Minnesota, 2017","BACKGROUND: During April–June 2017, Minnesota experienced the state’s largest measles outbreak in 27 years. A vaccination campaign was implemented. Numerous vaccine-associated rash illnesses (VARI) were detected. VARI is non-contagious, but difficult to distinguish from measles clinically. Often, public health control measures need to be implemented before wild-type measles can be differentiated from VARI by viral genotyping. We compared clinical characteristics of VARI and confirmed measles cases to inform testing practices. METHODS: We defined measles cases per the Council of State and Territorial Epidemiologists. VARI was defined as a rash occurring in a person within 21 days after receipt of measles, mumps, and rubella (MMR) vaccine, and in whom a measles vaccine strain (genotype A) was detected in naso/oro- pharyngeal swab or urine samples. Minnesota’s immunization information system monitored MMR doses administered. We collected clinical information through routine case investigation. RESULTS: Over 42,000 MMR doses above expected were administered during the outbreak. We identified 71 measles cases and 30 VARI. The median age of VARI patients was 1.2 years (range 10 months–48 years) and for measles cases 2.8 years (range 3 months–57 years). VARI diagnosis increased with rising MMR administration (figure); rash onset occurred a median of 11 (range 7–18) days after MMR receipt. Most VARI (97%) occurred following first MMR dose. The presence of fever was similar among VARI and measles cases (97% of VARI vs. 100% of measles cases; P = 0.12), but differences were seen in the proportion with cough (30% vs. 96%; P < 0.001), coryza (47% vs. 85%; P < 0.001), conjunctivitis (23% vs. 68%; P < 0.001), and exposure to infectious measles cases (0% vs. 96%). CONCLUSIONS: Surges in MMR administration and heightened community awareness during a measles outbreak can result in a large number of VARI, consuming considerable public health resources. When evaluating the need to suspect measles among patients with febrile rash, clinicians should consider time since MMR administration, clinical presentation, and history of measles exposure. Collecting appropriate specimens for timely virus genotyping could inform appropriate public health action. DISCLOSURES: All authors: No reported disclosures."
4541,"Week 48 Results of EMERALD: A Phase 3, Randomized, Non-inferiority Study Evaluating the Efficacy and Safety of Switching from Boosted-protease Inhibitors (bPI) Plus Emtricitabine (FTC)/Tenofovir Disoproxil Fumarate (TDF) Regimens to the Once Daily (QD), Single-tablet Regimen (STR) of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) in Virologically Suppressed, HIV-1-infected Adults","BACKGROUND: EMERALD is evaluating the efficacy and safety of switching from bPI + FTC/TDF regimens (control) to D/C/F/TAF 800/150/200/10 mg in virologically suppressed, HIV-1-infected adults. We present Week 48 primary results. METHOD: EMERALD (NCT02269917) is a randomized, active-controlled, open-label, international, multicenter, parallel-group, non-inferiority trial. Virologically suppressed (viral load [VL] < 50 c/mL for ≥2 months), HIV-1-infected adults were randomized (2:1) to switch to D/C/F/TAF or continue control. The FDA-stipulated primary endpoint was non-inferiority of D/C/F/TAF vs. control regarding % virologic rebound (confirmed VL ≥ 50 c/mL or premature discontinuations with last VL ≥ 50 c/mL) cumulative through Week 48 (4% margin). RESULT: 1141 patients were randomized and treated (N = 763 D/C/F/TAF; N = 378 control); median age 46; 18% women; 76% white; 58% on >2 previous ARVs (prior to screening regimen); 15% with previous non-DRV virologic failure (VF). Virologic rebound through Week 48 was non-inferior for D/C/F/TAF (2.5%; n = 19) vs. control (2.1%; n = 8) (Δ0.4%, 95% CI: –1.5%; 2.2%; P < 0.001). Most rebounders (12/19 [63%] vs. 4/8 [50%]) resuppressed by Week 48 without change in therapy. Week 48 virologic suppression rates (VL < 50 c/mL; FDA Snapshot) were 94.9% vs. 93.7% (Δ1.2%, 95% CI: −1.7%;4.1%) and VF rates (VL ≥ 50 c/mL; Snapshot) were 0.8% vs. 0.5% (Δ0.3%, 95% CI: −0.7%;1.2%), with no discontinuations for VF. No resistance-associated mutations related to any study drug were observed. Adverse events (AEs) were similar between arms: AE-related discontinuations (1.4% vs. 1.3%); grade 3–4 AEs (6.8% vs. 8.2%); serious AEs (4.6% vs. 4.8%); and no deaths. Renal and bone parameters favored D/C/F/TAF vs. control. TC and LDL-C slightly favored control vs. D/C/F/TAF, with no clinically significant difference in TC/HDL-C ratio between arms (Table 1). CONCLUSION: Percentage of virologic rebound after switching to D/C/F/TAF was non-inferior to control cumulative through Week 48, with high suppression rates (94.9%), no resistance development, better bone and renal safety parameters and similar TC/HDL-C ratio. D/C/F/TAF maintains the high genetic barrier to resistance of darunavir with the safety advantages of TAF, even in patients with a history of non-DRV VF. DISCLOSURES: C. Orkin, Janssen Pharmaceuticals: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker honorarium and Travel bursary to attend conference. MSD: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker honorarium and Travel bursary to attend conference. Viiv Healthcare: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker honorarium and Travel bursary to attend conference. Gilead Sciences: Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Research grant, Speaker honorarium and Travel bursary to attend conference. J. M. Molina, Merck / Gilead: Scientific Advisor, Research grant. Janssen / Viiv / BMS / Teva: Scientific Advisor, Speaker honorarium. Gilead: Speaker’s Bureau, Speaker honorarium. J. Gallant, Janssen Therapeutics: Investigator, Research support. E. Negredo, Janssen: Board Member, Scientific Advisor and Speaker’s Bureau, Speaker honorarium. J. Gathe, Janssen: Consultant and Investigator, Research grant and Speaker honorarium. J. Eron, Janssen: Consultant and Grant Investigator, Consulting fee and Grant recipient. E. Van Landuyt, Janssen: Employee and Shareholder, Salary. E. Lathouwers, Janssen: Employee and Shareholder, Salary. V. Hufkens, Janssen: Employee and Shareholder, Salary. R. Petrovic, Janssen: Employee and Shareholder, Salary. M. Opsomer, Janssen: Employee and Shareholder, Salary."
4542,The Use of Instructional Technology to Increase Independent Patient Hand Hygiene Practice of Hospitalized Adults in an Acute Care Setting,"BACKGROUND: Despite recognition that hospitalized patients carry pathogens on their hands and demonstrate poor hand hygiene practice, little attention has been given to interventions that increase hand hygiene practices. Studies that have attempted to improve patient hand hygiene practice lack sustainability due to dependability on healthcare staff, and no prior studies have tested ways to improve independent patient hand hygiene practice. One such approach is using a patient-centered multi-modal educational intervention and electronic voice-recorded reminder cue to promote self- management of hand hygiene. METHODS: This comparative effectiveness study tested two educationally-based approaches to improve patient hand hygiene in older adults hospitalized for 4 days for elective lower extremity orthopedic or podiatry surgery at a veterans’ hospital. Group 1 (n = 41) received an educational video, an educational handout and a voice-recorded electronic audio reminder (EAR) an active cue, which verbally reminded the participant to clean their hands 3 times a day (7am, 12 pm, 5pm). Group 2 (n = 34) received the educational video and handout without the EAR. There were no significant differences between the two randomly assigned groups in terms of age, ethnicity and sex. RESULTS: Figure 1 shows the daily difference in product consumption Day 0 to Day 3. The average product consumption of ABHR (alcohol-based hand rub) in Group 1 (EAR) was 29.97 grams (SD 17.13). Group 2 (No EAR) averaged 10.88 grams (9.27) (P < 0.0001). Comparing post-operative day (POD) 0 to POD 3, and controlling for covariates (Disability of Arm, Shoulder, and Hand [QuickDASH], Hand Grip Strength, Surgical Pain, MRSA in Nares, and Education), multivariate analyses indicated that the electronic audio reminder was a significant predictor (β=.468) of ABHR consumption, R(2) = .39, R(2)adj. = .34, F (6, 68) = 7.265, P < .001. CONCLUSION: This study demonstrated that a short educational intervention that included a video, a handout, and a verbal audio reminder has the potential to increase patient-centered infection prevention in the acute care settings without increasing the workload of healthcare workers. Findings can be used for future infection prevention studies in institutionalized patients to improve self-managed care. DISCLOSURES: All authors: No reported disclosures."
4543,"Impact of PBP2a Assay on Antibiotic Therapy of Patients with Non-Blood, Non-Urine Staphylococcus aureus Infections","BACKGROUND: Rapid diagnostic tests can reduce time to organism identification and susceptibility results, allowing for more rapid optimization of antibiotic therapy. We sought to determine whether a qualitative immunochromatographic assay (Alere™ PBP2a Culture Colony test) that differentiates methicillin-susceptible S. aureus (MSSA) from methicillin-resistant S. aureus (MRSA) could optimize time to appropriate therapy for patients with skin and soft-tissue infections (SSTIs) and nosocomial pneumonia caused by S. aureus. METHODS: Adult patients admitted to The Johns Hopkins Hospital with a respiratory or wound culture growing S. aureus between July-October 2015 (baseline period) and July-October 2016 (intervention period) were included. The primary outcome was time to optimal antibiotic therapy from specimen collection before and after implementation of the PBP2a assay. Secondary outcomes were (1) time to antibiotic de-escalation from specimen collection, (2) length of hospital stay, and (3) number of vancomycin levels. An unadjusted analysis was conducted using Chi-square or Fisher’s exact test for categorical variables and Wilcoxon rank-sum test for continuous variables. RESULTS: 189 patients met eligibility criteria (119 baseline, 70 intervention). There were no significant differences in characteristics of patients between periods. Overall time to optimal therapy decreased during the intervention period compared with baseline (IQR 0–24.7 hours vs. 0–64.2 hours, P = 0.02). In the subset of patients with SSTIs, time to optimal and de-escalation of antibiotic therapy was reduced during the intervention period compared with baseline (IQR 0–6.6 vs. 0-70.8, P = 0.02 and IQR 0–26.5 vs. 0-65.5, P = 0.05, respectively), but not with pneumonia. Length of hospital stay (median 6 days in each, P = 0.60) and number of vancomycin levels (median 0 vs. 1, P = 0.33) were similar before and after assay implementation. CONCLUSION: There was a reduction in time to optimal antibiotic therapy after implementation of the PBP2a assay driven by changes in SSTI regimens but not pneumonia regimens. Incorporation of a rapid test to differentiate MSSA from MRSA be a useful addition to antibiotic stewardship initiatives to optimize therapy for patients with MSSA infection. DISCLOSURES: P. Simner, bioMerieux: Research Contractor, Research support Check-Points Health BV: Research Contractor, Research support"
4544,Sensitivity and Specificity of the Quidel Sofia Influenza A+B FIA Rapid Influenza Detection Test in Long-Term Care Facilities,"BACKGROUND: Influenza is a significant pathogen for long-term care facility (LTCF) residents. As part of a randomized controlled trial to assess early detection of influenza in LTCFs, we deployed rapid influenza detection tests (RIDTs) at intervention LTCFs. Our primary objectives for this interim analysis were to evaluate the sensitivity and specificity of the Quidel Sofia® Influenza A+B Fluorescent Immunoassay RIDT in a high-risk, nontraditional population, and to describe the virology of acute respiratory infections (ARI) in LTCF residents. METHODS: Personnel at LCTFs identified cases of ARI, collected nasal specimens, and ran RIDTs from 10/21/2016 to 4/28/2017. The residual nasal swab and leftover lysis buffer were placed into a viral transport medium tube and sent to the Wisconsin State Laboratory of Hygiene for confirmatory influenza RT-PCR testing. In addition, all specimens were tested for other viruses using the Luminex NxTAG® Respiratory Pathogen Panel. Sensitivity and specificity of the Sofia RIDT were calculated using RT-PCR results as the reference standard. RESULTS: Specimens were collected from 228 residents (mean age = 71.3 ± 22.4 years). The mean time from symptom onset to specimen collection was 1.4 ± 1.6 days (range: 0-7 days). Respiratory viruses were identified in 134/228 cases (58.8%); influenza viruses (A: 7.5% and B: 14.5%) were the most commonly detected virus by PCR, followed by rhinovirus/enterovirus (13.2%), RSV (11.0%) and coronaviruses (10.1%). The sensitivities of Sofia RIDT for influenza A and influenza B were 77.8% (95% CI: 52.4–93.6%) and 80.0% (95% CI: 61.4–92.3%), respectively, with specificities of 98.4% (95.3–99.7%) and 97.1% (93.4–99.1%), respectively. Overall performance assessment for influenza A or B yielded a sensitivity of 79.2% (65.0–89.5%) and specificity of 96.1% (91.7–98.6%). The estimated likelihood of discovering one of the first two influenza cases at a LTCF using this RIDT is estimated to be ≥95.7%. CONCLUSION: Although a wide constellation of respiratory viruses cause ARIs within LTCF populations, influenza is very common. Early ARI recognition in residents, with testing shortly after symptom onset, likely contributed to high performance of the Sofia RIDT. Use of RIDTs allows early identification of influenza with high sensitivity and specificity in elderly LTCF residents. DISCLOSURES: J. Temte, Quidel: Investigator, Research support"
4545,Successful Environmental Disinfection to Prevention Transmission of Candida Auris,"BACKGROUND: Candida auris is a globally-emerging, multidrug-resistant yeast causing invasive infections and can persist on environmental surfaces if not adequately disinfected. Last summer, two patients with C. Auris infections were admitted at University of Chicago Medicine (UCM). Environmental samples were collected to assess environmental contamination before and after cleaning. METHODS: Environmental samples were collected using 3M Sponge Sticks with neutralizing Buffer during one patientÕs stay, weeks after another patientÕs stay, and after enhanced terminal cleaning. Samples were cultured directly and yeast was identified using MALDI. The following surfaces were sampled: Bathroom sink drain, bedside table, bedrail, mattress, chair and window ledge. Routine terminal cleaning includes 10% sodium hypochlorite solution applied high touch surfaces of both room and bathroom. The enhanced terminal cleaning process used for these rooms included: (1) 10% sodium hypochlorite solution applied to all high touch surfaces and walls; (2) privacy curtains removed and replaced; (3) supervision by environmental services manager; and (4) single UV disinfection cycle in room and bathroom. RESULTS: Because of delay in identification of C auris for the first patient, pre-clean samples were taken >2 weeks after the patient had been discharged. During the intervening weeks, multiple patients had occupied the room and there had been >3 routine terminal cleanings. None of these samples were positive for C auris. Pre-clean, in-residence samples indicated C auris contamination of multiple surfaces for the second patient. Because of transfers within the institution, there are three sets of post-cleaning cultures for the second patient. All post-clean environmental cultures were negative for both patients. Results are shown in Figure 1. CONCLUSION: Candida auris can contaminate environmental surfaces. While routine terminal cleaning may have been effective in removing C auris from surfaces in one patientÕs room, the enhanced terminal cleaning strategy used here was effective in our facility. DISCLOSURES: J. P. Ridgway, Gilead FOCUS: Grant Investigator, Grant recipient"
4546,"Comparison of Respiratory Pathogen Detections from Routine Hospital Testing and Expanded Systematic Testing from the Minnesota Severe Acute Respiratory Illness Surveillance Program, 2015–2016","BACKGROUND: Hospital testing for respiratory pathogens is nonsystematic, leading to potential missed detection of clinically relevant pathogens. The Minnesota Severe Acute Respiratory Illness (SARI) surveillance program monitors hospitalizations due to acute respiratory illness and conducts systematic testing for several respiratory pathogens. We assessed viruses detected by the hospital and additional detections identified by expanded testing. METHODS: Residual upper respiratory specimens collected from patients hospitalized for suspected respiratory illness for routine diagnostic testing at three hospitals, including one children’s hospital, were submitted to the Minnesota Department of Health (MDH). Specimens were tested for 18 respiratory viruses by RT-PCR. Clinical and hospital test data were collected through medical record review. RESULTS: From September 2015 to August 2016, 2,351 hospitalized SARI patients were reported, with the following age distribution: 57% <5 years, 13% 5–17 years, 30% ≥18 years. Among all SARI patients, 97% (2,273) had hospital-based, clinician-directed testing for viral pathogens. Viruses were detected among 47% (1,077) of tested patients, among which testing methods included PCR (85%), rapid antigen (13%), and culture (2%); 74% were tested on the day of admission. Most common viruses detected by clinical testing included respiratory syncytial virus (41%), rhinovirus/enterovirus (31%), and influenza (15%) (Figure 1). Systematic RT–PCR testing at MDH identified 1,600 (68%) patients positive for ≥1 respiratory virus, identifying previously unknown detections among 35% (820) of SARI patients (Figure 2). Of 1,272 patients with no virus identified at the hospital, 46% (586) had a viral detection at MDH. Patients aged <18 years were significantly more likely to have an additional pathogen detected by MDH testing than those aged ≥18 years (P < 0.01), including rhinovirus/enterovirus, adenovirus, human metapneumovirus, and coronaviruses. CONCLUSION: Systematic, expanded testing at MDH identified a higher proportion of respiratory pathogens among SARI patients compared with clinical laboratory testing. Additional testing for clinically relevant respiratory pathogens may inform medical decision-making. DISCLOSURES: All authors: No reported disclosures."
4547,The Utility of Preliminary Patient Evaluation in a Febrile Respiratory Infectious Disease Unit Outside the Emergency Department,"BACKGROUND: Acute respiratory illnesses are the leading cause of death from infectious diseases around the world, and occasional outbreaks of particularly virulent strains are can be public health disasters. Recently, a large outbreak of fatal Middle East respiratory syndrome-coronavirus (MERS-CoV) occurred following a single patient exposure in the emergency department (ED) of the Samsung Medical Center, a tertiary-care hospital in South Korea, which resulted in significant public health and economic burden. After this outbreak, a febrile respiratory infectious disease unit (FRIDU) with a negative pressure ventilation system was constructed outside the emergency department (ED) in 2015, to screen for patients with contagious diseases requiring isolation. METHODS: This is a retrospective cohort study of patients who visited the ED with febrile illness between August 2015 and July 2016. Ultimately, 1562 patients who were hospitalized after FRIDU screening were analyzed. The level of isolation recommended during their screening at the FRIDU was compared with the level deemed appropriate given their final diagnosis. RESULTS: Of the 1562 patients screened at the FRIDU, 198 (13%) were isolated, 194 (12%) were reverse isolated, and 1170 (75%) were not isolated. While hospitalized, 97 patients (6%) were confirmed to have a contagious disease requiring isolation, such as tuberculosis; 207 patients (13%) were confirmed to be immunocompromised and to require reverse isolation, mainly due to neutropenia; and the remaining 1258 patients (81%) did not require isolation. The correlation coefficient for isolation consistency was 0.565 (P < 0.001). No serious nosocomial outbreaks of contagious diseases occurred. During FRIDU screening, 114 patients were admitted to the resuscitation zone due to clinical instability, and three of these patients died. CONCLUSION: The initial isolation levels resulting from FRIDU screening were moderately well correlated with the isolation levels required by the final diagnosis, demonstrating the utility of pre-hospitalization screening units. However, the risks of deterioration during the screening process remain challenges. DISCLOSURES: All authors: No reported disclosures."
4548,Pharmacokinetics (PK) and Safety of Intravenous (IV) Brincidofovir (BCV) in Healthy Adult Subjects,"BACKGROUND: BCV is a lipid conjugate nucleotide that has shown rapid viral clearance in patients with adenovirus infection and improved survival in animal models of smallpox. In preclinical studies in rats, IV BCV dosed twice weekly for up to 29 days was not associated with gastrointestinal (GI), hematopoietic, hepatic, or renal toxicity. This study evaluated the safety and PK of IV BCV in healthy subjects. METHODS: In this double-blind study, subjects were randomized 3:1 to receive IV BCV or placebo in sequential single ascending dose cohorts (Table 1). Plasma PK samples were collected over 7 days and assayed by HPLC-MS. Plasma BCV PK parameters were determined by non-compartmental analysis and dose proportionality was assessed. Safety assessments were collected over 14 days. RESULTS: Forty healthy male subjects (18–46 years, 83% White) were enrolled and completed the study. Plasma BCV Cmax and AUC∞ increased in proportion to dose (Table 1). AEs and alanine aminotransferase (ALT) elevations were dose- and infusion duration-related (Table 1). GI AEs were mild. All AEs and ALT elevations were transient and no serious AEs occurred. CONCLUSION: Single doses of BCV 10–50 mg administered as a 2h IV infusion were well tolerated and not associated with significant clinical or laboratory abnormalities. BCV IV 10 mg and BCV IV 50 mg achieved geometric mean plasma BCV AUC∞ similar to and 4.5-fold, respectively, values achieved with BCV oral 100 mg tablets (Cmax = 251 ng/mL and AUC∞ = 1394 ng hours/mL). These data support evaluation of repeat dose administration in healthy subjects and virally-infected patients. DISCLOSURES: M. B. Wire, Chimerix: Employee and Shareholder, Salary. M. Morrison, Chimerix: Employee and Shareholder, Salary.M. Anderson, Chimerix: Employee and Shareholder, Salary. T. Arumugham, Chimerix: Employee and Shareholder, Salary. J. Dunn, Chimerix: Employee and Shareholder, Salary. O. Naderer, Chimerix: Employee and Shareholder, Salary."
4549,Shedding of Methicillin-Resistant Staphylococcus aureus (MRSA) by Hospitalized Patients during Procedures,"BACKGROUND: Contaminated environmental surfaces contribute to transmission of healthcare-associated pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). We hypothesized that medical and non-medical procedures facilitate environmental dissemination of MRSA in hospitalized patients. METHODS: We conducted an observational cohort study of hospitalized MRSA-colonized patients to determine the frequency of and risk factors for environmental shedding during procedures. Prior to each procedure, surfaces in the room and portable equipment used for procedures were disinfected. After procedures, high-touch surfaces and portable equipment were cultured; negative control cultures were collected after 1 hour in the absence of a procedure. Bivariate analyses were performed to identify factors associated with environmental shedding. RESULTS: Of 55 MRSA colonized patients, 22 (40%) had wounds and 25 (46%) had positive skin cultures. Environmental cultures were collected after 138 total procedures (range, 2 to 12 per patient). As shown in the figure, contamination of surfaces occurred frequently during procedures, but was uncommon in the absence of a procedure. Contamination occurred frequently on surfaces touched by personnel during procedures (12 of 38, 32% positive) and on portable equipment used for procedures (25 of 101, 25%). The presence of a wound was the only factor significantly associated with shedding (59% vs. 26%; P = 0.04). CONCLUSION: Environmental shedding of MRSA occurs frequently during medical and non-medical procedures in hospitalized patients. Our results suggest that there is a need for effective strategies to disinfect surfaces and equipment after procedures. DISCLOSURES: All authors: No reported disclosures."
4550,Study to Address Threats of Acute Respiratory Infections among Congregate Military Populations (ATARI),"BACKGROUND: More than 90% of active duty personnel receive influenza vaccinations yearly. Despite high coverage, influenza-like illnesses (ILI) remain a frequent cause of missed duty and hospitalizations, particularly in U.S. military recruits. More research is needed on the epidemiology and etiology of ILI to reduce the burden of respiratory infections in congregated military settings. METHODS: We conducted a prospective cohort study to assess ILI patterns among US Army recruits in a 9-week basic combat training course at Ft. Benning, GA. Demographic data, vaccination history, and information on recent illness were collected at enrollment in January 2017. Participants were divided into two platoons with staggered biweekly visit schedules. Visits occurred from reception through training, with nasal swabs and symptom surveys (all visits) and blood draws (weeks 8 and 9). Nasal specimens were used to detect clinical and colonizing pathogens using the Diatherix TEM-PCR Respiratory Panel. RESULTS: A total of 90 recruits were enrolled in the study. Twelve recruits were lost due to training attrition in the first week of the study. The participants were male and the mean age was 23 yo (SD 4.9). There were 10 (13%) cases of ILI reported among the 78 remaining participants, 6 in week 1, 3 in week 2 and 1 in week 9. The most frequently detected pathogens in the 10 symptomatic cases were coronavirus (5, 50%), rhinovirus (4, 40%), other enterovirus (3, 30%), and influenza A (2, 20%). Pathogen co-detections were common, 8 out 10 cases were associated with 2 pathogens, representing 7 unique combinations. While rhinovirus and coronavirus were most common among asymptomatic trainees, 10% had detectable influenza A. Detection of multiple pathogens was common in the first two weeks of training (50% among those who had viral detection). The study is still in progress. CONCLUSION: Symptomatic ILI was associated with coronavirus, rhinovirus, and enterovirus, in addition to influenza in the early weeks of training. Coronavirus and rhinovirus also circulated widely among healthy recruits, along with influenza. The findings will inform ILI control strategies for congregated military trainees. DISCLOSURES: E. Grigorenko, Diatherix Laboratories: Employee, Salary.L. Malone, Diatherix Laboratories: Employee, Salary."
4551,A Mortality Analysis of the Cytomegalovirus (CMV) Infection Letermovir Prophylaxis Trial in CMV-Seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation (HCT),"BACKGROUND: In a Phase III randomized, double-blind, placebo-controlled study of CMV-seropositive HCT recipients, letermovir prophylaxis significantly reduced the incidence of clinically significant CMV infections (CS-CMVi) through 24 weeks post-HCT. We investigated the impact of letermovir prophylaxis on mortality through Week 48 post-HCT. METHODS: Adult CMV-seropositive allogeneic HCT recipients with undetectable plasma CMV DNA at screening who could initiate treatment by Week 4 post-HCT were eligible. Subjects stratified by high or low CMV disease risk were randomized 2:1 to letermovir dosed at 480 mg/d (240 mg/d if on cyclosporine) or placebo PO or IV through Week 14 post-HCT. Time to all-cause mortality and non-relapse mortality (defined as death due to any reason other than the indication for HCT) through Week 48 post-HCT are presented using Kaplan–Meier (KM) plots censored at study discontinuation for reasons other than death/non-relapse death or upon study completion. Distribution of time to mortality endpoints was tested by stratified log-rank tests using two-sided P-values. RESULTS: This analysis included all 565 patients randomized and treated with ≥1 dose of study drug. Subjects began study drug a median of 9 days post-HCT; 36.5% started post-engraftment. The observed KM event rate for all-cause mortality was lower in the letermovir group (10.6%) than the placebo group (15.5%) at Week 24 post-HCT, and remained lower through Week 48 post-HCT (21.4% vs. 26.2%) (Figure 1). The observed K–M event rate for all-cause mortality in subjects who developed CS-CMVi was also lower in the letermovir group (4.6%) than the placebo group (17.1%) at Week 48 post-HCT. The observed KM event rate for non-relapse mortality was lower in the letermovir group (6.9%) vs. the placebo group (11.2%) at Week 24 post-HCT, and remained lower in the letermovir group (13.9%) than the placebo group (17.5%) through Week 48 post-HCT (Figure 2). CONCLUSION: All-cause and non-relapse mortality were reduced in the letermovir group compared with the placebo group through Week 48 post-HCT (relative risk reduction ~18% and ~21%, respectively). These results are consistent with a clinically meaningful survival benefit for letermovir prophylaxis. DISCLOSURES: J. Maertens, MSD: Consultant and Investigator, Consulting fee, Research grant and Speaker honorarium. M. Schmitt, MSD: Consultant and Investigator, Consulting fee. F. M. Marty, Merck & Co., Inc.: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient. P. Ljungman, Merck & Co., Inc.: Consultant and Investigator, Consulting fee, Research grant and Speaker honorarium. R. F. Chemaly, Merck & Co., Inc.: Consultant and Investigator, Consulting fee, Research grant and Speaker honorarium. N. A. Kartsonis, Merck & Co., Inc.: Employee, Salary and stock/stock options. J. Butterton, Merck & Co., Inc.: Employee, Salary and stock, stock options. H. Wan, Merck & Co., Inc.: Employee, Salary and stock, stock options.V. L. Teal, Merck & Co., Inc.: Employee, Salary and Stock/stock options. K. Sarratt, Merck & Co., Inc.: Employee, Salary and stock & stock options. Y. Murata, Merck & Co., Inc.: Employee, Salary and stock and stock options. R. Y. Leavitt, Merck & Co., Inc.: Employee, Salary and stock, stock options. C. Badshah, Merck & Co., Inc.: Employee, Salary and stock, stock options"
4552,"Human Coronavirus (HCoV) Infection Among Adults in Cleveland, Ohio: An Increasingly Recognized Respiratory Pathogen","BACKGROUND: Human Coronaviruses (CoV) have been long recognized as a common cause of respiratory tract disease including severe respiratory tract illness, yet there are few recent studies characterizing disease among adults in the United States. Here, we describe CoV infections and clinical characteristics among adults (>18 years) presenting with respiratory illness in Cleveland, Ohio. METHODS: Between February 1, 2016 and April 30, 2017, 2949 nasopharyngeal swab specimens were analyzed by NxTAG Respiratory Pathogen Panel in adults presenting with respiratory illness at MetroHealth Medical Center. Clinical data were collected on adults whose samples screened positive for CoV-HKU1, CoV-OC43, CoV-229E or CoV-NL63. RESULTS: Coronaviruses were detected in 192 (6.5%) adults including 105 (3.5%) OC43, 67 (2.3%) 229E, 13 (0.4%) HKU1 and 7 (0.2%) NL63. The majority of adults with coronavirus infection were females (66.2%) with a median age of 53 years. Common comorbidities included smoking (40.0%), asthma (38.0%), COPD (35.4%), and inhaled corticosteroid use (28.6%). Eighty-five (46.4%) required admission to the hospital. Common presenting symptoms included shortness of breath (42.7%) and cough (31.0%) whereas fever was uncommon (12.5%). Gastrointestinal symptoms were more common in HKU1 and NL63 infected adults. Seventy-three percent of coronavirus disease occurred between the months of January and March. Despite the recognition of coronavirus infection, 70 (36.5%) received antibiotics for their disease. CONCLUSION: This study provides needed insight into clinical characteristics and severity associated with coronavirus infection in adults. Coronavirus infection should be considered in differential diagnosis of respiratory tract illness in adults including those that require hospitalization, have a history of smoking and have pulmonary comorbidities. DISCLOSURES: All authors: No reported disclosures."
4553,"Human Coronavirus Circulation in the USA, 2014‒2017","BACKGROUND: Human coronaviruses (HCoV) OC43, 229E, NL63 and HKU1 commonly cause upper respiratory tract infections, but can also cause severe lower respiratory tract disease. Increased use of diagnostic assays for respiratory viruses has facilitated detection and, since 2014, voluntary reporting of HCoV to the National Respiratory and Enteric Virus Surveillance System (NREVSS). METHODS: We reviewed weekly aggregate test results for HCoV OC43, 229E, NL63 and HKU1 voluntarily reported to NREVSS by U.S. hospital and clinical laboratories from July 1, 2014‒April 30, 2017. Laboratories reporting any HCoV result using PCR were included, and the weekly percentage of positive HCoV tests by type was calculated. For a subset of HCoV detections reported to NREVSS via the Public Health laboratory Interoperability Project (PHLIP), which collects individual-level demographic data, we described age distribution and sex. Age distribution by HCoV type was compared using the Kruskal–Wallis test. RESULTS: 154 laboratories, across all 9 U.S. census divisions, reported 834,742 tests for HCoV; 18,514 (2.2%) were positive for HCoV-OC43, 8,363 (1.0%) for HCoV-NL63, 6,828 (0.8%) for HCoV-229E, and 5,170 (0.6%) for HCoV-HKU1. The percentage of tests positive for HCoV generally peaked between December and March (Figure 1). HCoV-OC43 showed distinct annual peaks with variation in magnitude by year. HCoV-HKU1 and NL63 had similar patterns, each with notable peaks during winter 2016 compared with 2015 or 2017. HCoV-229E showed a discernable peak in 2017 compared with the previous 2 years. Of 20,533 individuals with HCoV test results reported via PHLIP, 1,589 (7.7%) tested positive for any HCoV; 50% of HCoV-positive individuals were male, and the median age was 22 (range 0–96) years. Age distribution differed between HCoV types (P < 0.01, Figure 2). CONCLUSION: Over approximately 3 seasons, peak positivity for HCoV occurred during winter months, and annual differences in circulation by HCoV type were observed. Continued testing and surveillance for HCoV will allow for further characterization of circulation trends over time and by geographic region, and improved understanding of the contribution of HCoV to the winter respiratory virus season. DISCLOSURES: All authors: No reported disclosures."
4554,Evidence-Based Options for Controlling Respiratory Virus Transmission,
4555,National Preparedness Month — September 2017,
4556,42 Annual Congress of AOMSI Nagpur 16–18 Nov 2017,
4557,Global Health Security—An Unfinished Journey,"This supplement is a timely, comprehensive compendium of the critical work being done by the Centers for Disease Control and Prevention and various partners to enhance and expand the Global Health Security Agenda. This perspective provides a review of, and comments regarding, our past, current, and future challenges in supporting the Global Health Security Agenda."
4558,Abstract of 44th National Conference of Association of Clinical Biochemists of India (ACBICON 2017),
4559,Deadliest Enemy: Our War against Killer Germs,
4560,1125 Viral Infections In Outpatients With Medically Attended Acute Respiratory Illness During the 2012-13 Influenza Season,
4561,131 Changes in clinical presentation and epidemiology of respiratory pathogens associated with upper respiratory infection in military trainees following reintroduction of adenovirus vaccine,
4562,"787 Respiratory Pathogen Detection in Cases of Severe Acute Respiratory Illness (SARI) Among Hospitalized Patients at Two Metro-Area Hospitals, Minnesota, 2013-2014",
4563,797 Viral co-infections in hospitalized patients with respiratory tract infections,
4564,429 Diagnosis and Treatment of Respiratory Syncytial Virus in Immunocompromised Hosts in Large Midwestern Transplant Centers,
4565,807 Relationship between Respiratory Virus Infection and Pneumococcal Colonization in Children,
4566,766 Clinical Features and Outcome of Patients with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) Infection,
4567,783 Detection of Respiratory Viruses in Sputum from Adults Using Automated Multiplex Polymerase Chain Reaction (PCR),
4568,1143 GenMark ESensor Respiratory Viral Panel in an Inpatient Pediatric Population,
4569,1482 Sentinel Surveillance of Respiratory Viral Pathogens in Border Areas of Western Cambodia,
4570,"Research Communications of the 27(th) ECVIM‐CA Congress: Intercontinental, Saint Julian's, Malta, 14th to 16th September 2017",
4571,"Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies: Lausanne, Switzerland. 14-17 May 2017",
4572,SCIENTIFIC ABSTRACTS,
4573,"Abstracts of the papers presented in the XXVI conference of Indian virological society, “Viruses to Viromes in Health and Disease”, during 07–09 December, 2017, at Nitte University, Deralakatte, Mangalore-575018, India",
4574,20(th) International BioInformatics Workshop on Virus Evolution and Molecular Epidemiology,
4575,Strengthening Global Public Health Surveillance through Data and Benefit Sharing,"Equitable sharing of public health surveillance data can help prevent or mitigate the effect of infectious diseases. Equitable data sharing includes working toward more equitable sharing of the public health benefits that data sharing brings and requires the engagement of those providing the data, those interpreting and using the data generated by others, those facilitating the data-sharing process, and those deriving and contributing to the benefit. An expert consultation conducted by Chatham House outlined 7 principles to encourage the process of equitable data sharing: 1) building trust; 2) articulating the value; 3) planning for data sharing; 4) achieving quality data; 5) understanding the legal context; 6) creating data-sharing agreements; and 7) monitoring and evaluation. Sharing of public health surveillance data is best done taking into account these principles, which will help to ensure data are shared optimally and ethically, while fulfilling stakeholder expectations and facilitating equitable distribution of benefits."
4576,"A provincial Acute Febrile Illness Surveillance Network (GAFINet), South Korea",
4577,Forecasting Emergency Department Admissions for Pneumonia in Tropical Singapore,
4578,"Viral causes of Influenza Like Illness in Uganda, 2008 to 2017.",
4579,Emerging Infectious Literatures and the Zombie Condition,"The book club format has enabled expert and nonexpert exploration of infection and epidemiology as encountered in popular literature. This exploration reveals that fiction focusing on apocalyptic disease often uses the zombie as embodiment of infection, as well as an exemplar of current knowledge on emerging disease."
4580,"Proceedings of the 25th European Paediatric Rheumatology Congress (PReS 2018): Lisbon, Portugal. 5-8 September 2018",
4581,ECDC’s latest publications,
4582,Pneumococcal colonization and carriage,
4583,Pneumococcal Pneumonia---Risky Business,
4584,La prévention et le contrôle des infections au cabinet du pédiatre,"La transmission d’infections au cabinet du pédiatre est une source de préoccupation croissante. Le présent document traite des voies de transmission des infections et des principes de contrôle des infections actuellement en vigueur. La prévention englobe un aménagement du cabinet et des politiques administratives appropriés, le triage, les pratiques de soins habituelles pour tous les patients (p. ex., hygiène des mains; port de gants, de masques, d’un dispositif de protection oculaire et de blouses pour certaines interventions; nettoyage, désinfection et stérilisation des surfaces et de l’équipement, y compris les jouets; technique d’asepsie pour les interventions invasives), ainsi que les précautions additionnelles en cas d’infections particulières. Les membres du personnel doivent avoir reçu les vaccins nécessaires, et ceux qui sont atteints d’une infection doivent respecter les politiques de restriction au travail."
4585,Infection prevention and control in paediatric office settings,"Transmission of infection in the paediatric office is an issue of increasing concern. This document discusses routes of transmission of infection and the principles of current infection control measures. Prevention includes appropriate office design and administrative policies, triage, routine practices for the care of all patients (e.g., hand hygiene; use of gloves, masks, eye protection, and gowns for specific procedures; adequate cleaning, disinfection, and sterilization of surfaces and equipment, including toys; and aseptic technique for invasive procedures), and additional precautions for specific infections. Personnel should be adequately immunized, and those infected should follow work-restriction policies."
4586,871. Symptomatic Respiratory Syncytial Virus and Adenovirus Upper Respiratory Tract Infections Increase the Risk of Invasive Aspergillosis After Allogeneic Hematopoietic Cell Transplantation,"BACKGROUND: Invasive aspergillosis (IA) is a serious infectious complication following hematopoietic cell transplantation (HCT). Few studies have reported respiratory viral infections (RVIs) as a risk factor for developing IA, and data regarding specific viruses is sparse. We examined whether specific respiratory viruses were associated with increased risk of developing IA post-HCT. METHODS: In a longitudinal surveillance study of RVIs among allogeneic HCT recipients conducted 2005–2010, weekly post-HCT nasal washes were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1 year post-HCT. Nasal and bronchoalveolar lavage (BAL) samples were tested by multiplex PCR for respiratory syncytial virus (RSV), parainfluenza viruses (PIV)1–4, influenza A/B, human metapneumovirus, adenovirus (ADV), and human rhinoviruses, and coronaviruses. Only respiratory virus detections with symptoms were counted as RVI. Separate Cox proportional hazards models were used to examine adjusted associations between each RVI and the development of first proven/probable IA by 1-year post-HCT. RESULTS: Among 437 patients who survived >28 days following HCT, 39 patients developed IA by 1-year post-HCT (median 87 days, range 5–283). After adjusting for age at HCT, neutropenia, high-grade CMV viremia, and HLA status (matched related vs. others) or severe acute graft-versus-host disease (GVHD Grade 0–2 vs. 3–4), RSV and ADV upper respiratory tract infections (URTI) were associated with increased risk of developing IA (figure). Detection of any respiratory virus in the BAL was associated with IA (P < 0.001). CONCLUSION: RSV and ADV URTI are significant risk factors for development of IA post-HCT; the association between PIV URTI and development of IA approached statistical significance. Viral lower respiratory tract infection was associated with IA. Our data provide a rationale to assess IA as an endpoint in preventive studies of novel agents for respiratory viruses and further emphasize the importance of effective infection prevention practices for RVIs after HCT. [Image: see text] DISCLOSURES: J. Chien, Gilead Sciences, Inc.: Employee and Shareholder, Salary and stocks. A. Waghmare, Ablynx: Investigator, Research support. J. Englund, Gilead: Consultant and Investigator, Consulting fee and Research support. Novavax: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Alios: Investigator, Research support. MedImmune: Investigator, Research support. M. Boeckh, Asun Biopharma: Consultant and Investigator, Consulting fee and Research support. Gilead Sciences: Consultant and Investigator, Consulting fee and Research support. Chimerix Inc.: Consultant and Investigator, Consulting fee and Research support. Humabs: Consultant, Consulting fee. GSK: Investigator, Research support."
4587,1583. The Utility of the Immunodeficiency Scoring Index (ISI) to Predict Outcomes of Coronavirus (HCoV) Infections in Hematopietic Cell Transplant (HCT) Recipients,"BACKGROUND: Respiratory viral infections in HCT recipients are associated with high morbidity and mortality, especially after progression from upper respiratory tract infection (URI) to lower respiratory tract infections (LRI). Data on risk factors (RF) for LRI and mortality is lacking for HCoV infections after HCT. We aimed to validate our ISI in HCoV infections. METHODS: All adult HCT recipients with HCoV infection from 2015 to 2017 were evaluated. An ISI based on RF was used to classify patients as low (0–2), moderate (3–6), or high (7 or higher) risk for progression to LRI or death. We defined LRI as HCoV detected in nasal wash and/or bronchoalveolar lavage and new lung infiltrates on diagnostic imaging. Clinical parameters were collected and ISI were calculated for comparison. RESULTS: A total of 144 adult HCT recipients with 166 episodes of HCoV infections were analyzed. The most common HCoV serotype for LRI and URI was 229E (42.4%) and OC43 (37.6%), respectively, and most patients were infected between November and March each year (Figures 1 and 2). When compared with URI, patients with LRI were more likely in the pre-engraftment period, had multiple respiratory viruses infections, had nosocomially acquired HCoV, required hospitalization, ICU transfer, and mechanical ventilation (all, P < 0.05). Overall mortality rate was 4% at Day 30 from diagnosis and all patients who died had LRI with an 18% mortality. Among those who died, 33% had nosocomial infection, 67% were co-infected with another respiratory virus and 67% required mechanical ventilation. Using an ISI cut off of <4, the negative predictive value (NPV) for progression to LRI was 86% with a specificity of 76%. CONCLUSION: HCT recipients with HCoV LRI were more likely to have a fatal outcome. The NPV of the ISI for progression to LRI was high and could be used as a prognostic tool for future studies and for therapeutic clinical trials. DISCLOSURES: All authors: No reported disclosures."
4588,2264. The Burden of Respiratory Viral Illness in HIV-Infected Patients,"BACKGROUND: Among individuals living with human immunodeficiency virus (HIV), pulmonary complications are the most frequent cause of morbidity and mortality. Although bacterial and fungal pathogens are well-described etiologies of lung disease, the role of respiratory viruses remains poorly understood. We sought to describe the burden of respiratory viral illness in HIV-infected inpatients admitted to our tertiary care center. METHODS: All HIV-infected inpatients from August 2015 to March 2018 were approached if they presented with respiratory symptoms, defined as cough, dyspnea, sore throat, rhinorrhea, wheezing, or stridor. Eighty patients were enrolled. After obtaining informed consent, nasopharyngeal swabs and blood were collected. If the subject underwent bronchoscopy per the treating physician, excess bronchoalveolar lavage (BAL) sample was collected. Demographic and clinical data were recorded for each subject. Multiplex PCR testing of all respiratory samples was performed. RESULTS: Of the 70 HIV-infected patients that have undergone complete analysis, 23 (33%) tested positive for respiratory viruses. Of these, 11 (48%) were positive for rhinovirus, 3 were positive for influenza A (13%), 2 for parainfluenza 3 (9%), 2 for coronavirus (9%), and one each tested positive for adenovirus, parainfluenza 4, respiratory syncytial virus and influenza B. One patient had co-infection with rhinovirus and human metapneumovirus. Patients infected with a respiratory virus had severe illness as nearly half (10/23; 48%) required intensive care, 5 (22%) required mechanical ventilation, 4 (17%) were discharged to a higher level of care, and 3 (13%) died. CONCLUSION: The role of respiratory viruses on the lung health of HIV-infected patients is poorly defined. In this study, respiratory viruses were identified in over a third of HIV-infected inpatients, representing a substantial disease burden. Moreover, these patients demonstrated significant disease severity. Given these findings, there is a need for future studies of viral infections in HIV-infected individuals to elucidate mechanisms of susceptibility to reduce the burden of pulmonary morbidity in this vulnerable population. DISCLOSURES: All authors: No reported disclosures."
4589,634. Transcriptional Stimulation of Antiviral Response Components by the Structural and Accessory Human coronavirus OC43 Proteins,"BACKGROUND: In Kuwait, human coronavirus OC43 (HCoV-OC43) causes 25–30% of common cold, and 8.8% of respiratory infections in hospitalised patients. It is also associated with severe respiratory symptoms in infants, elderly, and immunocompromised patients. Our previous results showed that the expression of antiviral genes in human embryonic kidney (HEK) 293 cells is downregulated in the presence of HCoV-OC43 proteins. To understand the role of HCoV-OC43 proteins in antagonizing antiviral responses of the host, we investigated the effect of HCoV-OC43 structural and accessory proteins on the transcriptional activation of interferon-stimulated response element (ISRE), interferon-β (IFN-β) promoter, and nuclear factor kappa B response element (NF-kappaB-RE). METHODS: HCoV-OC43 ns2a, ns5a, membrane (M), and nucleocapsid (N) mRNA were amplified and cloned into the pAcGFP1-N expression vector, followed by transfection in HEK-293 cells. Two days post-transfection, the cells were co-transfected with a reporter vector containing firefly luciferase under the control of ISRE, IFN-β promoter, or NF-kappaB-RE. Renilla luciferase vector was used as an internal control for transfection efficiency. Following 24 hours of incubation, the cells were treated with either IFN or tumour necrosis factor (TNF) for 6 hours. Thereafter, promoter activity was assayed using the dual-luciferase reporter assay system. Influenza NS1 protein was used as positive control for antagonism. RESULTS: The transcriptional activity of ISRE, IFN-β promoter, and NF-kappaB-RE was downregulated in the presence of ns2a, ns5a, M, or N protein as there was a sharp fall in firefly luciferase levels. Overall, HCoV-OC43 proteins reduced firefly luciferase levels for ISRE and IFN-β promoter by at least ten fold, whereas for NF-kappaB-RE the firefly luciferase levels were reduced by at least fivefold. CONCLUSION: HCoV-OC43 has the ability to block the activation of different antiviral signaling pathways. DISCLOSURES: All authors: No reported disclosures."
4590,2518. The Role of Non-Influenza Viruses in the Seasonal Viral Respiratory Illness: A Epidemiologic Study From October 2016–March 2017,"BACKGROUND: Influenza virus (IV) is a leading cause of morbidity and mortality worldwide; however, understanding the contribution of non-influenza viruses (NIV) to the annual burden of respiratory illnesses (RI) is evolving. Improvements in diagnostic techniques, including the increasing clinical use of respiratory viral PCR panels (vPCR), have markedly advanced our understanding of the contributions of NIV to the “influenza season.” METHODS: A retrospective analysis of all vPCR results from one hospital system, collected between October 1, 2016 and March 7, 2017, including inpatient and outpatient samples was performed. 2,047 vPCR tests were reviewed; after removing those with undetermined results and internal control samples, 1,924 were analyzed. Data points abstracted included detection and identification of virus, and date of detection. We compared the total and monthly rates of NIV with IV, throughout the study period. RESULTS: Of 1,924 vPCR results, 985 (51%) were positive for a respiratory virus. Of these, 302 (31%) were IV, and 683 (69%) were NIV. For every month studied, the ratio of NIV to IV exceeded 50%, including the height of the season. The most commonly detected viruses were Influenza A (30%), Rhino/Enterovirus (24%), RSV (19%), Coronavirus OC43 (7%) and Metapneumovirus (5%). The peak influenza incidence temporally coincided with the national peak months of January and February. The NIV incidence paralleled the trend in IV incidence, dominated by Rhino/Enterovirus and RSV, but without a specific virus driving the trend. CONCLUSION: Non-influenza respiratory viruses cause substantial viral RI during the winter months. Many viral syndromes during the height of influenza season have traditionally been attributed to IV, including influenza-like-illness (ILI); however, these can now be better characterized using patient-specific vPCR panels, leading to improved understanding of NIV epidemiology. Even during the period of highest IV incidence, NIV infections were more common than IV. Understanding the high prevalence of NIV infections may improve the judicious use of both antibiotics and antivirals. There may also be a role for refinement of ILI, including best practices for diagnosis and treatment. DISCLOSURES: All Authors: No reported disclosures."
4591,1241. Surveillance for Viral Respiratory Infections in Pediatric Chronic Care Facilities,"BACKGROUND: Residents of pediatric chronic care facilities (PCCFs) are vulnerable to acute respiratory infections (ARIs) due to their underlying medical conditions and infection control challenges in congregate living. METHODS: We conducted active, prospective surveillance for ARIs (defined as ≥2 new signs/symptoms of respiratory illness) among all residents in three PCCFs near New York City from December 7, 2016 to May 7, 2017. The parents/guardians of some residents also provided consent for research specimen collection at the start of the study. In that subset, nasopharyngeal swabs were obtained ≤4 days of ARI symptom onset and weekly for 4 weeks of follow-up to assess viral shedding. Influenza, respiratory syncytial virus (RSV), rhinovirus (RV), coronavirus (229E, NL63, OC43, HKU1), parainfluenzavirus (PIV 1–4), metapneumovirus (MPV), adenovirus (AdV), bocavirus (BoV), enterovirus, parechovirus, and M. pneumoniae were tested by the Fast Track Diagnostics Respiratory Pathogens 21 real-time RT-PCR panel. RESULTS: Subset with research specimen collection: Among 79 residents (aged 0–20 years, median = 8), 60 ARIs were reported in 37 (47%) residents. Swabs were obtained at illness onset for 53/60 ARI episodes; among these, there were 25 single-virus detections and five co-detections. An additional 33 single- and five co-detections occurred in 175 follow-up swabs (table). Molecular typing of 32 RV+ specimens identified 13 RV types. All residents: During the 2016–2017 influenza season, 308/322 (96%) age-eligible residents received influenza vaccine and 168/364 (46%) received prophylactic antivirals for influenza exposures. Although influenza was not detected in research swabs, it was detected in 3/200 tests conducted for clinical purposes. CONCLUSION: ARIs were common among residents of three PCCFs, and a variety of respiratory viruses were detected. The rarity of influenza may reflect strong infection control practices in these facilities, including vaccination and prophylactic use of antivirals. DISCLOSURES: All authors: No reported disclosures."
4592,452. Spectrum of Respiratory Pathogens Detected by Multiplex PCR in a Study of Respiratory Tract Infections Among Travelers,"BACKGROUND: Respiratory tract infections (RTI) are a significant cause of health problems, accounting for about 10% of consultations in returning travelers. Nevertheless, the precise microbial etiology is not identified in many cases. METHODS: Prospectively collected 63 respiratory specimens (sputum or throat swab) from patients presented with respiratory symptoms (cough, sputum, chest pain, dyspnea, tachypnea, or abnormal findings of chest auscultation) after travel were tested using multiplex real-time PCR. The FTD Respiratory pathogens 33 (Fast-track diagnostics, Ltd.) can simultaneously detect 33 different respiratory pathogens directly from respiratory specimens. This test ran in the PCR-Only mode on BD MAX™ (Nippon Becton Dickinson Company, Ltd.) and LightCycler480 System (Roche). RESULTS: Fifty-nine consecutive cases were included in the study. Thirty-nine cases were diagnosed as non-specific upper respiratory tract infections, five cases were influenza, bronchitis, pneumonia, threecases was acute sinusitis, and one case was acute pharyngitis, dengue fever. Twenty-four cases had returned from travel in Southeast Asia, nine from Africa, and 8 from Latin America, seven from South Asia, six from middle east, threefrom North America, threefrom East Asia, 2 from Oceania, and one from Europe. Of the 59 specimens analyzed, 48 (81.4%) tested positive for pathogens whereas 11 tested negative. Commonly detected pathogens were Haemophilus influenzae (14 cases; 23.7%), influenza A (10 cases; 17.0%), rhinovirus (9 cases; 15.2%), Staphylococcus aureus (8 cases; 13.6%), Moraxella catarrhalis (8 cases; 13.6%), Streptococcus pneumonia, coronaviruses OC43, and Mycoplasma pneumoniae (4 cases; 6.8%, respectively). Multiple pathogens were detected in 30.5% of the specimens. In 14 cases (23.7%), both virus and bacteria were detected from one specimen. CONCLUSION: Not only viruses, bacterial pathogens were detected frequently than expected in the patients of RTI. Comprehensive molecular testing such as multiplex real-time PCR would change our understandings of epidemiology of RTI among travelers. [Image: see text] DISCLOSURES: All authors: No reported disclosures."
4593,"724. Neurologic Complications in Hospitalized Pediatric Patients with Influenza Infection, A Multicenter Retrospective Study in Korea","BACKGROUND: The aim of the study was to evaluate the incidence and characteristics of influenza associated neurologic complications (IANCs) in hospitalized pediatric patients in Korea. METHODS: We performed retrospective review of hospitalized cases of confirmed influenza infection from October 2010 to April 2017. Patient’s data were collected from three referral hospitals in different regions of the country. RESULTS: A total 2,002 laboratory confirmed influenza cases were identified. The median age was 3.3 years old (range 0.0–18.9 years) and 1,003 patients were male (54%). Influenza A was diagnosed in 1,357 cases (68%), influenza B in 624 (31%) and both influenza A and B in 21 (1%). Other combined respiratory virus infection was detected in 104 (5.2%) cases. Out of 2,002 cases, IANCs were identified in 167 cases (8.3%); influenza virus A was detected in 116 (69.4%), B in 50 (29.9%) and both A and B in one case (0.6%). Of 167 cases with IANCs, 25 patients (15%) had underlying neurologic diseases. Eleven patients (11/167, 6.5%) had combined respiratory viral infection (Rhinovirus = 5; respiratory syncytial virus = 3; coronavirus = 2; and bocavirus = 1). The most common diagnosis was a simple febrile seizure (112/167, 67.1%), followed by other seizures (26/167, 15.6%), encephalopathy/encephalitis (17/167, 10.2%), meningitis (7/167, 4.2%), meningism (4/167, 2.4%) and acute ataxia (1/167, 0.6%). In two patients with encephalitis/meningitis, one patient had influenza A and the other patient had influenza B detected by PCR in cerebrospinal fluid. Most of the patients were fully recovered (162/167, 97%) and no neurologic complication occurred in patients who had only initial manifestation of simple febrile seizure. Ten patients (10/167, 6.0%) required hospitalization in intensive care unit. Three patients (3/167, 1.8%) died of encephalopathy (n = 1) and combined encephalopathy/myocarditis (n = 2). Pre-existing neurologic disease was a risk factor of IANCs with an odds ratio of 3.94 (95% confidence interval 2.37 to 6.56, P < 0.0001). CONCLUSION: IANCs is not rare and may cause serious outcome including death. Clinicians should be aware of the increased risk for IANCs in certain patients with neurologic diseases. DISCLOSURES: All authors: No reported disclosures."
4594,677. Using a Multisectoral One Health Approach to Prioritize Zoonotic Diseases in the United States,"BACKGROUND: Emerging and endemic zoonoses continue to have adverse global impacts. One Health approaches promoting multisectoral, transdisciplinary collaboration are important methods to address zoonoses threats through disease surveillance, prevention, control, and response. We conducted a One Health Zoonotic Disease Prioritization (OHZDP) workshop in the United States (US) to identify zoonotic diseases of greatest national concern that should be jointly addressed by the Centers for Disease Control (CDC), US Department of Agriculture (USDA), Department of the Interior, and partners. METHODS: We used CDC’s OHZDP tool to prioritize zoonoses. Workshop participants selected criteria for prioritization, and developed questions and weights for each criterion. Questions were answered using available literature and expert opinion with subsequent scoring resulting in a ranked zoonotic disease list. After agreeing on a final prioritized disease list, participants used components of the One Health Systems Mapping and Analysis Resource Toolkit, developed by USDA and University of Minnesota, to review multidisciplinary coordination processes for the prioritized zoonotic diseases. RESULTS: Participants selected epidemic or pandemic potential, disease severity, economic impact, introduction or increased transmission potential, and national security as criteria to prioritize 56 zoonoses. The eight prioritized zoonotic diseases for the US were zoonotic influenzas, salmonellosis, West Nile virus, plague, emerging coronaviruses (e.g., SARS, MERS), rabies, brucellosis, and Lyme disease. Agencies then discussed recommendations to enhance One Health approaches to surveillance, response, prevention, and control of the prioritized zoonoses. Key themes and next steps for further implementation of One Health approaches were identified. CONCLUSION: This OHZDP workshop represents the first use of a One Health approach to zoonotic disease prioritization in the United States. It is a critical step forward in US government agency collaboration using One Health approaches. Further, the workshop created a foundation for future US government One Health systems strengthening for the prioritized zoonoses. DISCLOSURES: All authors: No reported disclosures."
4595,739. Middle East Respiratory Syndrome Coronavirus Infection Profile in Qatar: A 7-Year Retrospective Study,"BACKGROUND: A deadly zoonotic Middle East respiratory syndrome coronavirus (MERS-CoV) had emerged over the last 7 years in the Arabian Peninsula. As of February 28, 2018, 2,182 cases of MERS-CoV infection (with 779 deaths) in 27 countries were reported to WHO worldwide. The objectives of this study were to identify the clinical and epidemiological characteristics of MERS-CoV infection as well as determine its clinical outcome. METHODS: This was a retrospective-observational study of all laboratory confirmed cases of MERS-CoV infection conducted at the main seven hospitals in the State of Qatar from January, 2012 to April 2018. We used the Fast Track diagnostics real-time reverse-transcription polymerase chain reaction (rRT-PCR), targeting the upE and ORF1a genes respectively. Demographics, clinical information, potential contacts and probable risk factors were collected and analyzed by standard statistical methods. RESULTS: The mean annual incidence was 1.7 per 100,0000 person-years. Among the 24 confirmed cases of of MERS-CoV, males constituted the vast majority of cases (23 males) with a median age of 52 years (range 22–74). Fifty percent of the cases were Qatari and 42% reside in the same region. 67% of the cases had contact with camels, and 21% had contact with MERS-CoV-infected patient. Thirty-eight had travel history within 2 weeks of symptoms onset to the Kingdom of Saudi Arabia. Fifty percent were smokers and 42% had comorbidities. The median symptoms duration was 4.5 days. Most of the patient presented with flu-like symptoms, were fever was the most common presentation, followed by cough, SOB, diarrhea, abdominal pain and headache, 96%, 83%, 33%, 8%, 8% and 4%, respectively. All patients were admitted to a tertiary hospital with a median hospital stay 41 days (8–97). Forty-five percent patients developed severe sepsis with multi-organ failure and needed ICU admission. Fifty percent patients developed acute kidney injury, 29% patients were on hemodialysis and 16% needed extra-corporeal membrane oxygenation. Thirty-three percent patients died. The rest of patients had recovered from the infection and discharged home. Among those who died all had one or more comorbidities. CONCLUSION: MERS-CoV infection is a rare infection in the State of Qatar, seen in both Qataris and expatriates with and without travel history. The infection in patients with comorbidities carries high mortality. DISCLOSURES: All authors: No reported disclosures."
4596,2491. Post-Exposure Prophylaxis With Ribavirin Plus Lopinavir/Ritonavir for Middle East Respiratory Syndrome in Healthcare Workers,"BACKGROUND: In 2015, an outbreak of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection occurred in South Korea involving 186 patients, 39 of whom were healthcare workers (HCWs) exposed to the infection. An effective post-exposure prophylaxis (PEP) strategy may limit the spread of infection; however, there is no consensus regarding PEP for MERS-CoV infection. In this study, we assessed (1) the efficacy of oral ribavirin and lopinavir/ritonavir as PEP for HCWs exposed to patients with severe MERS-CoV pre-isolation pneumonia, and (2) safety of the PEP regimen. METHODS: We retrospectively enrolled 43 HCWs with high-risk exposure to MERS-CoV from 5 hospitals affected during this outbreak in South Korea. The rate of MERS-CoV infection was compared between 22 workers at 1 hospital who received PEP consisting of oral ribavirin and lopinavir/ritonavir after exposure to patients with severe MERS-CoV pre-isolation pneumonia and 21 workers at other hospitals who did not receive PEP. RESULTS: Six workers (14%) developed MERS-CoV infection; all of these subjects belonged to the non-PEP group. The attack rate was lower in the PEP group compared with the non-PEP group (0% vs. 28.6%; Odds ratio = 0.405, 95% confidence interval = 0.274–0.599; P = 0.009). The most commonly reported side effects of PEP therapy were nausea and diarrhea, but there were no severe adverse effects associated with PEP therapy. CONCLUSION: PEP with a combination of oral ribavirin and lopinavir/ritonavir appears to be effective and generally safe for preventing MERS-CoV infection after high-risk exposure in healthcare workers. DISCLOSURES: All authors: No reported disclosures."
4597,"2018 ACVIM Forum Research Report Program: Seattle, Washington, June 14 ‐ 16, 2018",
4598,"2018 ACVIM Forum Research Abstract Program: Seattle, Washington, June 14 ‐ 15, 2018",
4599,PSXIII-19 Swine Health Health and Management Evaluation in American Samoa.,"American Samoa is working to improve swine production genetics and management. Our objective was to identify health and management factors affecting swine performance. A1998 survey found six leptospirosis serovars and parvovirus and heavy parasites loads, but no brucellosis or pseudorabies. Our 2016 Artificial Insemination Training focused on improving genetics and resulted in 12 sows bred and 103 piglets born. Oour 2017 Swine Farm Evaluation surveyed 26 farms with an average of 9 sows per farm. Serological samples were tested for antibodies against Porcine Circovirus Type 2b (ELISA, 96% positive), Swine Influenza (ELISA, 31%), Senecavirus (IFA, 27%), Mycoplasma hyopneumoniae (ELISA, 15%), Porcine Epidemic Diarrhea (IFA, 15%), and Porcine Reproductive and Respiratory Syndrome (ELISA, 4%, 1 pig). o evidence was seen of Porcine Respiratory Coronavirus (ELISA), Transmissable Gastroenteritis (ELISA) or Pseudorabies (SN). Fecal samples contained Ascaris suum, Oesophagostomum dentatum, Stephanurus dentatus, and, less commonly, Strongyles nodular worm, Stronglyloides, Brachylaemus suis, Necator species, Trichuris suis, and Fasciolopsis buski. Ear scrapings and scratching behavior indicated the presence of sarcoptic mange (31% of farms). Most farms fed a 14% grain feed (88% of farms) and local feeds (coconut, vegetables, fruits, 69%); only one farm fed an 18% starter and one fed milk to young pigs. One or more thin pigs were seen on 46% of farms. Waste is managed either by wash down (85% of farms) or as dry litter (42%); some farms used both. Wastewater concerns led to water restriction on 12% of farms. In conclusion, parasites and suboptimal feeding are constraints on pig growth and performance. Management recommendations to improve production should address these, in addition to improving health and genetics."
4600,474 Productive and reproductive performance of Goat Breeds of Sindh.,"The study was carried out in Sindh province of Pakistan to investigate productive and reproductive performance of ten local goat breeds. The ten goat breeds included in the study were Kamori, Tapri, Bugi-Turi, Pateri, Kachan, Jattan, Lohri, Chappar, Barri, and Thari. The data were collected using a detailed survey on various productive (birth weight, weaning weight, weaning age, average daily gain, milk yield and lactation length) and reproductive (age at first heat, age at first kidding, kidding interval, service period, number of services per conception and twinning percentage) traits of goats. Up sixteen local farmers of each breed were visited by the investigators and information was recorded/collected on prescribed performas. The highest birth weight was observed in Pateri goat (2.90 ± 0.11kg). In case of weaning weight maximum was observed in Kachan (16.0 ± 0.50kg) and lowest in Thari (11.19 ± 0.40 kg). Moreover weaning age was lowest in Thari (3.0 ± 0.11months) and highest was in Bugi-Turi (8.0 ± 0.14months). The highest milk yield was observed in Tapri and Kamori (~ 3.50 kg) followed by Pateri (~2.90 kg), Bugi Tori, Kacchan, Jattan (~ 2.00 kg) and Lohri, Chapper, Barri and Theri (~1 kg). As far as reproductive traits are concerned; age at first heat was lowest in Pateri (around 7 months) while all other breeds ranged from 11 to 15 months). The maximum twining percentage at first kidding was observed in Chappar (25%). Jattan had lowest kidding interval (5.0 ± 0.16 months). On the basis of overall average pre-weaning growth rate of kids, Tapri and Thari appear to have higher growth potential followed by Kamori and Kachhan. It could be concluded that Tapri, Thari and Kamori may be utilized for meat production under existing circumstances in the order of priority. Similarly, Tapri, Kamori and Pateri may be better utilized as dairy goats as well. [Image: see text]"
4601,"PSXIII-12 Effects of altitudinal floor on nutrient digestibility, energy efficiency, visceral organ mass, and performance by guinea pigs.","An experiment was conducted to evaluate the effect of altitude on nutrient digestibility, energy efficiency, performance, and, visceral organ mass by guinea pigs. Twenty male guinea pigs (initial BW 1.011 ± 0.096 kg) were selected in a crossover design experiment, maintained at metabolic cages (2 animals per cage) during a total digestibility period of 25 d (2 periods of 13-d). Animals were randomly assigned at 1 of 2 altitudinal sites, 2986 and 2480 m. above the sea level (masl; 5 cages per altitude). Animals were fed 45 g of alfalfa (DM) to meet energy requirements at maintenance levels. At the end of the digestion phase, an animal from each cage was slaughter to determine body fat content from body specific gravity and visceral organ mass. A subsequent performance phase was evaluated as completely randomized design, and animals were kept at the same altitudinal floor in which they ended period 2 of the crossover period. Animals were fed ad libitum with alfalfa. At the end of the performance phase, all remaining animals were slaughtered and visceral organ mass was measured. Energy intake and Dry matter, were increased by animals at 2986 compared to animals at 2480 masl (P<0.001). Metabolizable energy tended to be lower for animals kept at 2986 masl (P=0.053). Nutrient digestibility was lower for animals kept at 2986 compared to 2480 masl. Liver, kidneys and spleen mass were greater for animals maintained at 2986 masl (P<0.012). Heart mass tended to be greater for animasl kept at 2480 masl (P=0,060). Body fat was not alterd by altitudinal site (P>0.345). Final BW, ADG, and feed conversion rate was decreased by animals fed at 2986 masl (P<0.002). Results from this experiment suggest a novel approach to determine Energy efficiency as affected by altitudinal site. Data from this experiment evidenced a 7% increase on energy requirements on ME for animals kept 516 masl higher. Further research is requiered to apply to other biological models."
4602,In Memoriam: Katrin Susanne Kohl (1964–2018),
4603,RESEARCH COMMUNICATIONS OF THE 28th ECVIM‐CA CONGRESS,
4604,Tracking renal injury using multiparametric MRI,
4605,WACEM 2018 Abstracts,"The 4(th) Annual World Academic Congress of Emergency Medicine was held in October 2018 in Doha, Qatar. The conference was organized by Trauma Surgeons, Emergency Physicians and Research Team from Qatar. WACEM 2018 was very engaging and informative congress which involved debates, discussion, lectures. competitions and many symposiums. Over 100 International Academic Leaders spoke on cutting-edge research at this congress. The following were the abstracts that were presented at WACEM 2018. There were awards for best papers. A dedicated scientific team worked on selecting and reviewing as well as judging the abstracts."
4606,"Abstracts of the papers presented in the international conference of Indian virological society, ‘‘Global viral epidemics: a challenging threat”, during 12–14 November, 2018, at PGIMER, Chandigarh, India",
4607,"Correction: Vol. 25, No. 5",
4608,Surveillance of Respiratory Viruses in Long Term Care Facilities,
4609,"Abstracts of scientific contributions to GCOM 2019: Berlin, Germany. 27 - 30 March 2019",
4610,What's in this issue?,
4611,Abstracts from the 35th Annual Meeting of the Society of General Internal Medicine,
4612,A60 Revealing the evolution of virulence in RNA viruses,"A combination of high rates of mutation and replication, coupled with strong natural selection, ensures that RNA viruses experience rapid genotypic and phenotypic evolution. Such a ‘fast-forward’ evolution enables viruses to rapidly adapt to new host species, evade host immune responses, and to develop resistance to anti-viral drugs. Similarly, rapid evolution allows viruses to attain new levels of virulence, defined as the ability to cause severe disease in hosts. We hypothesize that distinct viral groups share genetic determinants that modulate virulence that have been acquired through convergent evolution. Thus, common patterns reflecting changing virulence-related specific viral groups could be detected. The main goals for this project are (1) to understand how genetic and phenotypic diversity can be generated among different viral groups by analyzing the variation patterns and determining the selective forces behind them (impact in viral fitness) and (2) to understand how fixed mutations can modulate virulence within different viral groups by performing comparison of strains with differing virulence within a longitudinal timescale. The subject of the study is key emerging and re-emerging virus families of medical importance. Such groups include: Coronaviridae (severe acute respiratory syndrome and Middle East respiratory syndrome-associated coronaviruses), Picornaviridae (Hepatitis A virus), Flaviviridae (Yellow fever, West Nile, Hepatitis C, Dengue, and Zika viruses), Togaviridae (Rubella and Chikungunya virus), Bornaviridae (Borna-disease virus), Filoviridae (Ebola and Marburg viruses), Paramyxoviridae (Measles, Nipah, and Hendra viruses), Rhabdoviridae (Lyssaviruses), Arenaviridae (Lassa virus), Bunyaviridae (Hanta- and Crimean-Congo hemorrhagic fever viruses), and Orthomyxoviridae (Influenza A viruses). Viral genomes collected at different time points, different hosts (human and their most closely related animal reservoirs) and different locations will be compiled. Extensive molecular evolutionary analyses will be carried out to infer gene expansion/contraction within groups, rates of evolution, and changes in selection pressure, including the detection of positive selected genes and sites (adaptive evolution). Positively selected sites will be mapped onto the viral protein structures to reveal their impact on function, and hence the location of potential virulence determinants. Virulence changes among particular viral strains and types will be defined and measured according to definitions based on an increase in: (1) transmissibility, (2) host tropism, (3) immune evasion, (4) morbidity and mortality, (5) drug resistance, and by the incorporation of epidemiological data to determine whether high or low virulence strains within different hosts and localities are spreading most efficiently in nature."
4613,A48 Identification and full-genome characterization of Alpha- and Beta-Coronaviruses viruses from bats in Italy,"Bats are the natural reservoir of Coronaviruses (CoVs). Human CoVs cause mild respiratory diseases worldwide, but, in the last decade, two Beta-CoVs [Middle East respiratory syndrome (MERS)-CoV and severe acute respiratory syndrome] caused thousands of deaths and cases worldwide. Phylogenetic analysis suggested the evolutionary origin of mammalian CoVs is derived from bats. In this study, we characterized three Alpha-CoVs and two Beta-CoVs demonstrating the circulation of bat strains in Italy. Isolates were sequenced using a next-generation sequencing approach and genomes reconstructed using the online tool Galaxy Aries. Phylogenetic analyses were conducted using MEGA7 and MrBayes. Similarity plots were generated using SSE v1.2. The structure of the receptor binding domain (RBD) in the S protein was predicted by sequence-homology method using the protein data bank. Bioinformatics analysis permitted the identification of 2 Beta-CoV complete genomes of 30 kb and three Alpha-CoV of 28 kb (named BatCoV-ITA1-5). BatCoV-ITA1 and 2 formed a monophyletic group with MERS-CoV sequences. The comparison of the concatenated domains within ORF1ab confirmed their classification into the MERS-CoV species. The 3D structure of RBD of Italian strains showed two amino acid deletions located in a region corresponding to the external subdomain of MERS-RBD. BatCoV-Ita3 and BatCoV-Ita4/5 were classified into two novel Alpha-CoV species by comparison of concatenated domains within ORF1ab. Due to the high divergence with the Alpha human spike protein strains, it was impossible to establish the protein structure and the potential affinity to human receptor. The Italian strains showed the typical organization of Alpha and Beta-CoVs. We reported two Beta-CoVs closely related to MERS-CoVs from bats belonging to common Italian species (Pipistrellus kuhlii and Hypsugo savii). The analysis of the RBD in the spike protein indicates significant differences from human RBD known to date. The three Alpha-CoV strains were classified into two novel species, confirming the high heterogeneity of CoV strains in bats. Although the studies conducted cannot confirm a risk for humans, surveillance studies are needed to investigate the genetic diversity of CoVs in bats. Because this exceeds what is known for other hosts, it is compatible with bats being the major reservoir of mammalian CoVs."
4614,A52 MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity,"Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of this zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa and the Arabian Peninsula, the continuous appearance of zoonotic MERS cases in humans is confined to the Arabian Peninsula. MERS-CoV from Africa has hitherto been poorly studied. Here, we report the genetic and phenotypic characterization of MERS-CoV from dromedaries in African countries. Phylogenetically, viruses from dromedaries in Africa formed a monophyletic clade, which we have provisionally designated as virus clade C. Molecular dating analyses of MERS-CoV, including clade C viruses, suggests that the ancestral MERS-CoV in dromedaries could have spread to the two continents within a short timeframe. Camel MERS-CoVs from west and north African countries form a subclade (C1) that shares genetic signatures of a major deletion in the accessory gene ORF4b. Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung, and BF785 replicated to lower titer in lungs of human DPP4-transduced mice. However, it is still inconclusive whether ORF4b deletions may lead to the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to the zoonotic potential of MERS-CoV."
4615,A61 Large RNA genomes: Is RNA polymerase fidelity enough?,"Large-genome Nidoviruses and Nidovirus-like viruses reside at the current boundary of largest RNA genome sizes. They code for an unusually large number of gene products matching that of small DNA viruses (e.g. DNA bacteriophages). The order of appearance and distribution of enzyme genes along various virus families (e.g. helicase and ExoN) may be seen as an evolutionary marker in these large RNA genomes lying at the genome size boundary. A positive correlation exists between (+)RNA virus genome sizes and the presence of the RNA helicase and the ExoN domains. Although the mechanistic basis of the presence of the helicase is still unclear, the role of the ExoN activity has been linked to the existence of an RNA synthesis proofreading system. In large Nidovirales, ExoN is bound to a processive replicative RNA-dependent RNA polymerase (RdRp) and corrects mismatched bases during viral RNA synthesis. Over the last decade, a view of the overall process has been refined in Coronaviruses, and in particular in our lab (Ferron et al., PNAS, 2018). We have identified genetic markers of large RNA genomes that we wish to use to data-mine currently existing metagenomic datasets. We have also initiated a collaboration to sequence and explore new viromes that will be searched according to these criteria. Likewise, we have a collection of purified viral RdRps that are currently being used to generate RNA synthesis products that will be compared to existing NGS datasets of cognate viruses. We will be able to have an idea about how much genetic diversity is possibly achievable by viral RdRp (‘tunable fidelity’) versus the detectable diversity (i.e. after selection in the infected cell) that is actually produced."
4616,A53 MERS-CoV in East African dromedary camels,"Human Middle East respiratory syndrome is a zoonotic respiratory disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV) originating from camels in the Arabian Peninsula. While there are a large number of camels in East Africa, often traded to the Arabian Peninsula, no autochthonous human MERS-CoV case is reported in East Africa. Furthermore, there is limited information of MERS-CoV in East Africa. In this study, MERS-CoV in dromedary camels from Ethiopia was detected using RT-qPCR. Next-generation sequencing was used to obtain the full genome of MERS-CoV. MERS-CoV antibodies were also detected through MERS-spike pseudoparticle neutralization assay. Phylogenetic analysis of full-genome sequences and spike-genome antibodies indicates that MERS-CoV in East Africa is genetically distinct from those in the Arabian Peninsula. The results from this study show that MERS-CoV circulating in dromedary camels in East Africa are genetically distinct from those in the Arabian Peninsula. Further studies are needed to evaluate the risk of zoonotic transmission in East Africa."
4617,A54 Genomic analysis of camel-HKU23 in Nigeria dromedary camels reveals strain-specific cross-species recombination,"Coronaviruses (CoVs) are enveloped, single stranded, positive-sense RNA viruses with a large genomic size of 26–32 kilobases. The first human CoV identified in the 1960s was isolated from patients presenting with common cold symptoms. Subsequent epidemic outbreaks of novel zoonotic CoV transmission were reported, examples including HCoV-229E (229E), HCoV-OC43 (OC43), severe acute respiratory syndrome, and Middle East respiratory syndrome (MERS). The ongoing outbreak of MERS in the Middle East is originating from a zoonotic source of dromedary camels. Surveillance later revealed that three CoV species—HCoV-229E (229E), camel-HKU23, and MERS-CoV—were co-circulating in Saudi Arabia dromedary camels. Camel-HKU23 belongs to Group 2a CoV, which also includes human coronavirus OC43, bovine coronavirus, and porcine hemagglutinating encephalomyelitis virus. Recombination, resulting in the generation of different novel genotypes, has been reported previously among these CoVs. Our surveillance of dromedary camels slaughtered in a major abattoir in Nigeria identified camel-HKU23 from nasal swab samples with a prevalence of 2.2 per cent. Phylogenetic analysis showed Nigeria camel-HKU23 is distinct from those previously identified in Saudi Arabia, while still genetically similar, as they share a monophyletic origin. Recombination analysis of Nigeria camel-HKU23 revealed two recombination breakpoints at positions of 22774–24100 base pairs (bp) and 28224–29362 bp. Recombination breakpoint at position 22774, encoding the Group 2a CoV-specific hemagglutinin esterase gene, exhibited high bootstrap support for clustering with RbCoV HKU14, which was previously detected in domestic rabbits in China. The recombination signal is only observed in Nigeria camel-HKU23, suggesting a regional varied evolutionary history of camel-HKU23. Our findings extended the knowledge of the evolutionary relationship among Group 2a CoVs. Further surveillance in other African camels will be important to elucidate the evolution of camel-HKU23."
4618,"Abstracts from the 5th International Conference on Prevention & Infection Control (ICPIC 2019): Geneva, Switzerland. 10-13 September 2019",
4619,2019 ACVIM Forum Research Report Program,
4620,"Acceptability of community quarantine in contexts of communicable disease epidemics: perspectives of literate lay people living in Conakry, Guinea","During the 2014–2016 Ebola epidemic in West Africa, some communities reacted hostilely to the implementation of quarantine measures. This study's aim was to examine the views of lay people in Guinea on the acceptability of community quarantine. From June to August 2016, 302 adults indicated the acceptability of quarantine in 36 scenarios varying as a function of four factors: the infectious disease's level of contagiousness, its level of lethality, the number of cases in the community and whether persons in quarantine are provided with support services. Five clusters were identified: (1) for 18% of the participants, quarantine is never acceptable; (2) 16% considered, in contrast, that quarantine is always acceptable; (3) for 14%, it depends on the disease's level of contagiousness and lethality; (4) 36% based their judgement not only on the levels of contagiousness and lethality, but also on whether those in quarantine are provided with support services; and (5) 16% had no opinion. Interventions to increase voluntary compliance with community quarantine in Guinea must not be ‘one size fits all’, but must be multifaceted and tailored in design and implementation to match the diversity of people's concerns and needs."
4621,2002. BioFire® Filmarray® Pneumonia Panel: A Powerful Rapid Diagnostic Test for Antimicrobial Stewardship,"BACKGROUND: BioFire® Filmarray® Pneumonia Panel (BFPP) is a multiplex PCR panel that identifies 33 common bacterial and viral pathogens seen in community- and hospital-acquired pneumonias. It rapidly identifies these pathogens in addition to 7 antibiotic resistance genes on sputum and bronchioalveolar lavage samples in 1 hour. As one of the test centers for this panel, our institution utilized this panel for clinical and laboratory use. We reviewed the impact of BFPP on antimicrobial stewardship, particularly its role in early discontinuation of empiric antibiotics and prompt initiation of optimized targeted therapy. METHODS: We retrospectively reviewed all cases by which BFPP was ordered. We reviewed medical records of each case to identify the results of the panel, culture data, antibiotics used, and subsequent clinical intervention. RESULTS: 43 tests were ordered in total. 17 were for clinical use by an infectious disease specialist and 26 were randomly obtained by the microbiology lab. All 17 clinical cases were intervened upon with the following interventions: discontinuation of anti-pseudomonal antibiotics (8 cases), discontinuation of anti-MRSA antibiotics (5 cases), discontinuation of azithromycin (4 cases), discontinuation of carbapenem (1 case), prevention of inappropriate antibiotic escalation or initiation of inappropriate antibiotics (2 cases), and early IV to PO transition (3 cases). Of the random 26 samples ordered by lab, 13 had opportunities for antibiotic de-escalation if a physician were notified of the results. Viruses were identified in 15 samples with coronavirus being the most common. Virus was the sole pathogen in 9 of the 15 samples. Bacterial pathogens were identified in 20 samples that were reported as normal flora by conventional culture; none of these cases led to or potentially could have led to antibiotic escalation as the sole intervention. CONCLUSION: Clinical use of BFPP had 100% intervention rate with all interventions leading to de-escalation of antibiotics or prevention of inappropriate antibiotics use. Though over-identification of colonizers is a potential limitation, BFPP is a powerful tool for antibiotic stewardship that results in rapid interventions to achieve optimal targeted therapy. DISCLOSURES: All authors: No reported disclosures."
4622,1756. Role of Human bocavirus Respiratory Tract Infection in Hematopoietic Cell Transplant Recipients,"BACKGROUND: Limited data exist regarding the impact of human bocavirus (BoV) in hematopoietic cell transplant (HCT) recipients. We examined incidence and disease spectrum of BoV respiratory tract infection (RTI) in HCT recipients. METHODS: In a longitudinal surveillance study of viral RTIs among allogeneic HCT recipients, pre-HCT and weekly post-HCT nasal washes and symptom surveys were collected through day 100, then every 3 months, and whenever respiratory symptoms occurred through 1-year post-HCT. Samples were tested by multiplex semi-quantitative PCR for RSV, parainfluenza virus 1–4, influenza A/B, adenovirus, human metapneumovirus, rhinovirus, coronavirus, and BoV. Plasma samples from BoV+ subjects were analyzed by PCR. In addition, we conducted a retrospective review of HCT recipients with BoV detected in bronchoalveolar lavage or lung biopsy. RESULTS: Among 469 patients in the prospective cohort, 21 distinct BoV RTIs (3 pre-HCT and 18 post-HCT) were observed by 1-year post-HCT in 19 patients (median 42 years old, range 0–67) without apparent seasonality. BoV was more frequently detected in the latter half of the first 100 days post-HCT (Figure 1). The frequencies of respiratory symptoms in patients with BoV detected did not appear to be higher than those without any virus detected, with the exception of watery eyes (P < 0.01) (Figure 2). Univariable models among patients with BoV RTI post-HCT showed higher peak viral load in nasal samples (P = 0.04) and presence of respiratory copathogens (P = 0.03) were associated with presence of respiratory symptoms; however, BoV detection in plasma was not (P = 0.8). Retrospective review identified 6 allogeneic HCT recipients (range 1–64 years old) with BoV detected in lower respiratory tract specimens [incidence rate of 0.4% (9/2,385) per sample tested]. Although all 6 cases presented with hypoxemia, 4 had significant respiratory copathogens or concomitant conditions that contributed to respiratory compromise. No death was attributed mainly to BoV lower RTI. CONCLUSION: BoV is infrequently detected in respiratory tract in HCT recipients. Our studies did not demonstrate convincing evidence that BoV is a significant pathogen in either upper or lower respiratory tracts. Watery eyes were associated with BoV detection. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures."
4623,1791. Novel Metabolomics Approach for the Diagnosis of Respiratory Viruses Directly from Nasopharyngeal Specimens,"BACKGROUND: Respiratory virus infections are important causes of morbidity and mortality among pediatric and adult patients. These viruses infect respiratory epithelial cells, where they may induce specific metabolite alterations. As a proof-of-concept, we investigate the novel use of liquid chromatography (LC) combined with quadrupole time-of-flight mass spectrometry (Q-TOF) for the study of host cell metabolite alterations to diagnose and differentiate respiratory viruses. METHODS: We studied nasopharyngeal swab samples positive for respiratory viruses by the eSensor Respiratory Viral Panel (GenMark Diagnostics, Carlsbad, CA). Banked, frozen samples (−80°C) stored in viral transport media were retrieved and thawed. Aliquots of 100 μL were centrifuged at 13.3 × g for 15 minutes, and the filtrate was analyzed by Agilent 6545 Quadrupole LC/Q-TOF (Agilent Technologies, Santa Clara, CA). Compounds were separated using a novel column arrangement based on hydrophobicity and charge using a quaternary solvent manager, followed by accurate mass analysis by LC/Q-TOF. Agilent Mass Profiler 3D principal component analysis was performed, and compound identification was completed using the METLIN metabolite database. RESULTS: A total of 235 specimens were tested by LC/Q-TOF, including 195 positive specimens [including adenovirus, coronavirus, influenza A H1N1 and H3N2, influenza B, human metapneumovirus, parainfluenza viruses 1, 2, 3, and 4, respiratory syncytial virus (RSV), and rhinovirus] as well as 40 negative clinical specimens. LC/Q-TOF primary component analysis (PCA) allowed preliminary identification of key metabolites that distinguished all virus-positive specimens compared with the negative group, and differentiated respiratory viruses from one another including between influenza A 2009 H1N1 and H3N2 subtypes (Figure 1). CONCLUSION: Preliminary data from our LC/Q-TOF analysis show that respiratory viruses exhibit different host cell metabolomic profiles that allow viral differentiation to the species level, and for influenza A virus, the subtype level. This metabolomic approach has substantial potential for diagnostic applications in infectious diseases directly from patient samples, and may be eventually adapted for point-of-care testing. [Image: see text] DISCLOSURES: All authors: No reported disclosures."
4624,2786. The Role of Respiratory Panel PCR in Decreasing Antibiotic Exposure in Patients Diagnosed With a Respiratory Viral Infection,"BACKGROUND: Respiratory viral infections (RVI) are becoming increasingly recognized as an important cause of pneumonia. There is limited data regarding the role of rapid PCR testing for RVI and its effect on antibiotic duration and length of stay (LOS). METHODS: We performed a single-center, retrospective chart review in adult patients who were admitted and underwent evaluation with the FilmArray Multiplex Respiratory Panel (RP) (Biomerieux™) using a random sample from July 1, 2016 through April 1, 2018. Patient clinical and virologic characteristics, LOS, antibiotic use, and duration of treatment were collected. A Student’s t-test was performed for all comparisons. RESULTS: We identified 540 patients who were admitted and underwent RP testing. The mean age was 57.1 years (range 19–99), 50.2% were immunocompromised, 23.8% were transplant recipients, 70.4% had respiratory symptoms, and 35.7% had an admitting diagnosis of pneumonia. 55.6% required supplemental O(2) and 24.6% had an ICU admission that required either noninvasive or mechanical ventilation. 22.6% (N = 122) of these patients were diagnosed with an RVI, of which 15 were co-infected with two or more respiratory viruses. There were 41 (34%) rhinovirus/enterovirus, 41 (34%) influenza (Types A/H1, A/H3, A/H1-2209, and B), 16 (13%) RSV, 15 (12%) coronavirus (Types NL63, OC43, 229E, and HKU1), 13 (11%) metapneumovirus, and 7 (5%) parainfluenza (Types 2, 3, and 4). 85.2% (104/122) of patients with an RVI received antibiotics. The mean LOS and antibiotic duration were 9.07 days and 7.31 days for patients with an RVI when compared with 11.5 days and 10.4 days for patients without an RVI (P = 0.098; P = 0.032), respectively. In patients with an RVI and negative bacterial cultures, the mean LOS was 8.4 days and mean antibiotic duration was 5.9 days when compared with 16.4 days and 15.5 days for all patients with positive bacterial cultures (P = 0.003; P < 0.0001), respectively. The mean time from available results of + RP to antibiotic discontinuation was 5.1 days in the setting of negative bacterial cultures. CONCLUSION: Although antibiotic exposure and time to discontinuation still remained significant in patients diagnosed with an RVI, there was a marked reduction in LOS and antibiotic duration in the subset of patients with an RVI and negative bacterial cultures. DISCLOSURES: All authors: No reported disclosures."
4625,"2792. Association of Body Mass Index with Rates of Hospitalization in Patients with Respiratory Viral Infections—Puerto Rico, 2012–2018","BACKGROUND: Obesity is a serious public health problem in Puerto Rico, where 31% of the population is obese. Multiple studies have suggested that adults with influenza who are underweight, overweight, or obese have increased risk of hospitalization compared with those of normal weight. We sought to determine whether risk of hospitalization among patients infected with influenza or other respiratory viruses differs by BMI among patients in Puerto Rico. METHODS: We analyzed data from patients enrolled in the Sentinel Enhanced Dengue Surveillance System (SEDSS), a prospective study of patients with acute febrile illness (AFI), from May 2012 to September 2018. We evaluated those older than 24 months, who had height, weight, and clinical disposition recorded, and tested positive by RT–PCR for infection with influenza A (n = 1253), influenza B (n = 844), adenovirus (n = 435), respiratory syncytial virus (n = 289), parainfluenza virus (n = 361), metapneumovirus (n = 247), or coronavirus (n = 15). BMI categories were determined using standard cutoffs in adults and BMI-for-age percentiles for children and adolescents. Risk of hospitalization by BMI category was calculated using multivariate Poisson regression. RESULTS: Among the 3,388 patients included, 675 (20%) were overweight, 926 (27%) were obese, 405 (12%) were underweight, and 1382 (41%) were normal weight. Median age was 13.4 (range: 2–100 years), and 50% were male. Risk of hospitalization was not significantly different in children and adult patients infected with a respiratory virus who were overweight relative to those that had normal BMI; however, once hospitalized, obese individuals of any age had a mean length of hospital stay 1.7 days longer than normal weight persons (95% CI: 0.27–3.17 days). Among adult patients, underweight patients were nearly 3 times more likely to be hospitalized compared with normal weight patients (relative risk 2.8, 95% CI: 1.4–5.9). Underweight children were not at increased risk of hospitalization. CONCLUSION: Among patients infected with a respiratory virus, risk of hospitalization was higher among underweight adult patients, and obese patients had a longer mean length of stay once hospitalized. Body mass index should be considered when evaluating risk and managing these patients. DISCLOSURES: All authors: No reported disclosures."
4626,1675. Implementation of Electronic Travel History Screening at an Urban Medical Center,"BACKGROUND: Middle East Respiratory Syndrome (MERS), caused by a novel coronavirus, can lead to severe respiratory failure and death. CDC recommends screening patients who traveled to endemic countries for fever, respiratory symptoms, and exposure to MERS-positive contacts and healthcare facilities. UCLA is a large, academic, medical center located in a diverse city with frequent international travel. We implemented a travel screening (TS) questionnaire in our electronic medical record (EMR) (Figure 1) to identify high-risk patients in order to implement early isolation practices and testing. This study describes the use and performance of our TS for identifying suspect MERS cases. METHODS: An EMR-based tool prompts nurses to ask patients at triage or admission whether they have traveled out of the country in the past 30 days (Figure 1). If patients answer affirmatively, the EMR prompts nurses to inquire about travel to specific high-risk countries and to review symptoms and exposure risks. Upon notification of a potential MERS case, the EID physician on-call reviews the TS, clinical history, epidemiologic risks, and makes a determination whether further evaluation and/or isolation for suspect MERS is necessary. We reviewed travel history, demographics, and symptoms of patients who triggered a positive TS from April 2017 to September 2018. RESULTS: The ED completed 115,815 distinct TS on 81,197 individuals during this time period. The median time from ED arrival to TS completion was 6.4 minutes. 308 ED encounters triggered a positive TS; an additional 257 encounters in other units triggered a positive TS, resulting in 565 positive TS (Table 1). 122 (22%) expressed ≥1 MERS symptom and 29 (24%) expressed both fever and respiratory symptoms. Of these symptomatic patients, 0 had a history of contact with a MERS case; 3 had a history of contact with a healthcare facility while traveling; and 4 had a history of contact with camels. No patients were diagnosed with MERS (Table 2). CONCLUSION: A history of travel to the MERS endemic countries is relatively common at a large urban hospital. Routine electronic screening of patients is an efficient way to identify high-risk travelers. This EMR tool could be modified for other emerging pathogens, such as measles or Ebola, to identify high-risk patients. [Image: see text] [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures."
4627,2324. Respiratory Viral Coinfection in a Birth Cohort of Infants in Rural Nepal,"BACKGROUND: Acute respiratory illnesses are a leading cause of global morbidity and mortality in children. Coinfection with multiple respiratory viruses is common. Although the effects of each virus have been studied individually, the effects of coinfection on disease severity or healthcare seeking are less well-understood. METHODS: A secondary analysis was performed of a maternal influenza vaccine trial conducted between 2011 and 2014 in rural southern Nepal. Prospective weekly active household-based surveillance of infants was conducted from birth to 180 days of age. Mid-nasal swabs were collected and tested for respiratory syncytial virus (RSV), rhinovirus, influenza, human metapneumovirus (HMPV), coronavirus, parainfluenza (HPIV), and bocavirus by RT–PCR. Coinfection was defined as the presence of two or more respiratory viruses simultaneously detected as part of the same illness episode. Maternal vaccination status, infant age, prematurity, and number of children under 5 in the household were adjusted for with multivariate logistic regression. RESULTS: Of 1,730 infants with a respiratory illness, 327 (19%) had at least two respiratory viruses detected on their primary illness episode. Coinfection status did not differ by maternal vaccination status, infant age, premature birth, and number of children under 5 in the household. Of 113 infants with influenza, 23 (20%) had coinfection. Of 214 infants with RSV, 87 (41%) had coinfection. Overall, infants with coinfection had increased occurrence of fever lasting 4 or more days overall (OR 1.4, 95% CI: 1.1, 2.0), and in the subset of infants with influenza (OR 5.8, 95% CI: 1.8, 18.7). Coinfection was not associated with seeking further care (OR 1.1, 95% CI: 0.8, 1.5) or pneumonia (OR 1.2, 95% CI: 1.0, 1.6). CONCLUSION: A high proportion of infants experiencing their first respiratory illness had multiple viruses detected. Coinfection with influenza was associated with longer duration of fever compared with children with influenza alone, but was not associated with increased illness severity by other measures. [Image: see text] [Image: see text] DISCLOSURES: All authors: No reported disclosures."
4628,2626. Rhinovirus in Children Presenting to the Emergency Department: Role of Viral Load in Disease Severity and Co-Infections,"BACKGROUND: Rhinovirus (RV) quantitation by reverse transcription-quantitative PCR is limited by variable amplification efficiency across genotypes. We used a precise viral quantitation method, reverse transcription-digital PCR (RT-dPCR), to characterize the role of viral load in clinical outcomes and in viral co-infections in children presenting to a tertiary hospital emergency department (ED). METHODS: Children < 18 years with respiratory symptoms for ≤ 14 days were enrolled from December 1, 2016 to December 31, 2018. Participants had nasal and throat specimens obtained and multiplex PCR testing with a commercial assay (FilmArray; bioMerieux). RV positive samples were quantified using RT-dPCR. Samples with sufficient viral load were sequenced at a 543 bp fragment of the RV VP4/VP2 region. RV species were assigned by comparison to RV sequences in GenBank using BLAST. Clinical data were collected into REDCap. T-tests were used to compare mean viral loads between groups. RESULTS: Of 1703 children enrolled in the ED, 697 were RV/enterovirus positive by FilmArray [median age 18 months (interquartile range 9–39 months)]. Of 590 subjects with viral load available, 276 (47%) were admitted to the hospital. Among RV mono-infections (N = 434), mean viral load did not differ between subjects admitted vs. discharged from the ED (7.03 log copies/mL for both, P = 0.97). Among admitted subjects with RV mono-infection, viral load also did not differ between subjects requiring supplemental oxygen vs. not (7.01 vs. 7.10 log copies/mL, P = 0.6). Subjects with viral co-infections had lower mean RV viral loads (6.31 log copies/mL) compared with those with RV only (7.03 log copies/mL; P < 0.001) (figure). Significantly different RV viral loads were seen with co-infections with respiratory syncytial virus (RSV), metapneumovirus (MPV) and parainfluenza (PIV), but not with influenza, adenovirus or coronavirus. In 525 sequenced samples (46% RV-A, 4% RV-B, 50% RV-C), viral load did not vary between RV viral species (P = 0.09). CONCLUSION: Precise viral quantitation demonstrates children co-infected with RV and RSV, MPV or PIV have lower nasal viral loads than those with RV alone. Among RV mono-infections, RV viral load was not associated with admission or need for supplemental oxygen. [Image: see text] DISCLOSURES: All authors: No reported disclosures."
4629,"Practical Healthcare Epidemiology, 4th Edition",
4630,1642. Comparing Viral Respiratory Infections Between Children Who Do and Do Not Attend Child Care,"BACKGROUND: Out-of-home child care (CC) is a risk factor for viral acute respiratory infection (ARI) in young children. Little is known, however, about differences in frequencies of viral infection between CC children and those cared for exclusively at home. METHODS: Using surveillance data from the HIVE household cohort in southeast Michigan from 2014–2018 (4 seasons), we analyzed 1022 illness cases from 354 children aged 0–6 years. Age groups were dichotomized as infants (aged <2 years) and toddlers/preschoolers (aged 2–6 years). Households were prospectively enrolled and nasal respiratory swabs were collected from children upon report of acute illness symptoms. We used real-time RT–PCR to test for 18 respiratory viruses. RESULTS: We detected at least one virus in 855 illness cases (83% of all illnesses reported). Age at first illness onset in all four seasons was significantly younger among CC children than homecare children (P < 0.001) across all 4 years (average difference = 1.25 years). CC children <2 years had slightly lower odds of viral detection during illness (OR = 0.89, 95% CI [0.49, 1.61]) but higher odds at ages 2–6y (1.07 [0.65, 1.76]); neither was statistically significant. Neither CC nor homecare children were significantly more or less at risk for any particular pathogen—expect for rhinovirus in the <2-year group, where odds of rhinovirus infection were 58% lower (OR = 0.42) in CC children compared with homecare counterparts (95% CI, 0.21–0.83). Conversely, CC attendees under 3 more frequently had influenza, RSV, hMPV, parainfluenza, and coronavirus; however, none of these associations were significant. Odds of coinfection (> 1 virus detected) were higher among CC children, but not significant (OR = 1.4 [0.63, 2.96] and 1.2 [0.77, 1.88] in <2 year and 2–6 year age groups, respectively). Among all children <7 year, the mean number of pathogens detected was not different between CC and homecare individuals (1.20 vs. 1.23, P = 0.16). CONCLUSION: As expected, results indicated that CC attendees aged 0–6y experienced illness episodes earlier in life compared with homecare children. Our analysis also indicated that, compared with children cared for at home, CC children were less at risk for rhinovirus infection when young but could potentially be at higher risk for viruses of greater clinical concern. DISCLOSURES: All authors: No reported disclosures."
4631,2448. Clinical Presentation and Outcomes of Long-Term Care Residents with Coronavirus Respiratory Infection: A Retrospective Cohort Study,"BACKGROUND: Human coronaviruses (CoVs) are a major cause of respiratory infection and institutional outbreaks, yet the epidemiology and clinical outcomes of these viruses is poorly described among the elderly residing in long-term care facilities (LTCFs). METHODS: We performed a retrospective cohort study of LTCF residents with positive nasopharyngeal or mid-turbinate swabs for CoVs (OC43, 229E, NL63 and HKU1) between January 2013 and December 2018. Demographic and clinical data were obtained from resident charts including clinical presentation, treatment, outcome, and transmission to other residents. Variables were compared using univariate analysis. RESULTS: 3268 residents met inclusion criteria (median age 93 years, 90% male) comprising 7.5% (246/3268) of all positive respiratory virus specimens detected during the study period. 97(39%) of cases were associated with a respiratory outbreak while 149(61%) were sporadic cases that did not result in transmission. OC43 (52%) was the most commonly identified CoV and was more commonly associated with outbreak cases (76% vs. 37%; P < 0.001). In total, 87% of all cases had two or more of runny nose/congestion, cough, sore throat/hoarse voice or fever. The most common symptoms among residents were cough (85%), runny nose/congestion (79%), and sore throat/hoarse voice (59%) and only 17% of residents had a measured temperature of ≥ 37.8C. Only 6% of residents received antibiotic treatment for suspected secondary bacterial pneumonia. The 30-day mortality rate was 3.7% with 67% of deaths attributable to the CoV infection. There was no statistically significant difference in symptoms, treatment or outcomes associated with outbreaks or seasonality. CONCLUSION: CoVs make up an important proportion of respiratory viral infections among LTCF residents and may result in frequent outbreaks. Most residents remain afebrile and have self-limited illness while only a small minority develop secondary bacterial pneumonia and death. Given these findings the benefits of control measures should be weighed against the impact on resident quality of life. DISCLOSURES: All authors: No reported disclosures."
4632,Optimal fluid management in sepsis,"Sepsis clinically manifests as life-threatening organ dysfunction due to a dysregulated host response to infection.(1) Optimal fluid resuscitation is relevant for all sepsis patients, and perhaps it is most important for those with septic shock. Septic shock is defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greatest risk of mortality, and septic shock is clinically identified as sepsis patients with serum lactate level >2 mmol/L and who require vasopressor infusion to maintain a mean arterial pressure ≥ 65 mm Hg in the absence of hypovolemia. Sepsis is among the most common conditions in the intensive care unit (ICU), accounting for up to half of all hospital deaths and being the third leading cause of death overall in the United States.(2) Sepsis and septic shock are medical emergencies for which treatment and resuscitation should begin immediately. The goals of fluid resuscitation for these patients are: a) to rapidly replace intravascular volume and restore tissue perfusion, and b) to minimize organ dysfunction through timely interventions that either halt or reverse the physiologic derangements. If hypoperfusion is present, at least 30 mL/kg of IV crystalloid fluid should be given rapidly, and additional fluids should be guided by frequent reassessment of hemodynamic status, preferably using dynamic indices to indicate the likelihood of a beneficial response to fluid administration. Fluid administration should be targeted to achieve a MAP of at least 65 mm Hg, and to normalize lactate in patients with elevated lactate due to hypoperfusion.(3) Balanced crystalloids are the fluid of first choice for sepsis resuscitation based on ready availability and taking medication costs into account. Use of 0.9% saline compared to a balanced crystalloid, such as lactated Ringer's or PlasmaLyte, produces more kidney dysfunction and with a greater risk of dying.(4) The individual side effect profiles may best differentiate the natural and synthetic colloids. Albumin may be considered for administration to sepsis patients with refractory shock or who have received substantial amounts of crystalloid fluids, but should not be administered to patients with severe traumatic brain injury.(5) Hydroxyethyl starch (HES) products should not be administered to patients with sepsis because of increased risk of acute kidney injury and death. Gelatin solutions are not recommended in sepsis. Norepinephrine is the vasopressor of first choice for patients with septic shock, and should be administered to achieve a mean arterial pressure of at least 65 mm Hg after excluding hypovolemia as a cause for hypotension. The selection of a second line vasopressor, such as vasopressin, dopamine, phenylephrine, epinephrine or angiotensin-2, depends on patient factors such as underlying cardiac dysfunction, presence of arrhythmias, and current response to vasoconstrictor or inotropic agents. Dopamine should not be used for renal perfusion or protection and it should be avoided in patients with tachyarrhythmias."
4633,In Memoriam: Jay Stephen Keystone (1943–2019),
4634,Hunters Searching among Starry Nights and at the Edges of Life,
4635,Critical physiological and pathological functions of Forkhead Box O tumor suppressors,"The Forkhead box, subclass O (FOXO) proteins are critical transcription factors, ubiquitously expressed in the human body. These proteins are characterized by a remarkable functional diversity, being involved in cell cycle arrest, apoptosis, oxidative detoxification, DNA damage repair, stem cell maintenance, cell differentiation, cell metabolism, angiogenesis, cardiac development, aging and others. In addition, FOXO have critical implications in both normal and cancer stem cell biology. New strategies to modulate FOXO expression and activity may now be developed since the discovery of novel FOXO regulators and non-coding RNAs (such as microRNAs) targeting FOXO transcription factors. This review focuses on physiological and pathological functions of FOXO proteins and on their action as fine regulators of cell fate and context-dependent cell decisions. A better understanding of the structure and critical functions of FOXO transcription factors and tumor suppressors may contribute to the development of novel therapies for cancer and other diseases."
4636,"Needs, Gaps and Opportunities for Infectious Disease Research in British Columbia: A Perspective from Population and Public Health","BACKGROUND: A review of infectious disease research activity and capacity was performed in British Columbia and linked to a process for identifying needs, gaps and opportunities from a public health perspective. METHODS: The study was organized in three phases: an environmental scan to describe current research activity in BC; a consultation to identify needs, gaps and opportunities with those conducting research (key informants) and the end users of research results (stakeholders); and a prioritization of the research needs emerging from the consultation. RESULTS: Analysis and synthesis of the consultation data resulted in the identification of nine research themes, which were prioritized in the following order: efficacy and cost-benefit, disease patterns, emerging infectious disease, immunology and vaccines, disease-specific research, health promotion and communications, safe food and water, knowledge translation research and genomics. Six capacity-building themes were also identified: attraction and retention, education and training, collaboration and networks, funding, dissemination of findings, and public health input, surveillance, informatics and databases. INTERPRETATION: The findings were helpful in developing a multi-disciplinary, multi-level infectious disease research agenda linking researchers in universities, hospitals and public health institutions with practitioners and policy-makers in British Columbia’s public health system. The approach is both feasible and important to undertake at the national level. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/BF03405394 and is accessible for authorized users."
4637,Développer la capacité d’application des connaissances en santé publique: Le rôle des centres nationaux de collaboration,"Ce document dresse l’historique et la justification du programme des Centres nationaux de collaboration en santé publique, établi par l’Agence de santé publique du Canada en 2004. Les centres ne sont pas axés sur la recherche primaire, mais plutôt sur la synthèse des preuves scientifiques mondiales qui sont pertinentes pour les politiques, les programmes et les pratiques de santé publique–et leur conversion en « produits du savoir » pour les professionnels de la santé publique, les responsables des politiques et les groupes communautaires afin de guider la prise de décision en santé publique. Les grands principes de la synthèse et de l’application/échange des connaissances (SAEC) aux fins de la santé publique sont passés en revue, de même que de récents sites Web et publications décrivant des projets internationaux dans ce domaine en plein essor. Enfin, certaines pratiques exemplaires pour la SAEC en santé publique provenant d’expériences au Canada et ailleurs dans le monde sont décrites."
4638,Safety of prone positioning in critically ill patients,"Background: During the past two years, 5% of patients admitted to the Medical Intensive Care Unit (MICU) of Hamad General Hospital (HGH) had severe acute respiratory distress syndrome (ARDS) with a PaO(2)/FiO(2) ratio less than 100 mmHg. The risks associated with this condition include ventilator associated lung injury, over distension of lungs, and poor gas exchange which results in increased morbidity and mortality. With quality improvement initiatives like prone positioning, the mortality and morbidity associated with severe acute respiratory syndrome(1) can be reduced by improving hypoxemia(2) with a significant enhancement in PaO(2)/FiO(2) ratios while reducing injurious ventilation. Also, prone positioning can help prevent invasive interventions such as placing patients on extracorporeal membrane oxygenation (ECMO) therapy.(3) Methods: We evaluated the safety of prone positioning for improving hypoxemia in critically ill patients with PaO(2)/FiO(2) ratio < 100 mmHg to PaO(2)/FiO(2) ratio < 200 mmHg from 1(st) January 2017 to 31(st) December 2018, without major complications. Data collected included the PaO(2)/FiO(2) ratios based on arterial blood gases of mechanically ventilated patients before and after prone positioning. We were able to facilitate prone positioning in 72 out of 110 patients with severe ARDS having a total average PaO(2)/FiO(2) ratio of 84.4 ± 30 mmHg. The patients were proned for a maximum of 16 hours in each session where up to three sessions were incorporated. No major complications were encountered during the proning sessions. This was thought to be accomplished through the coordination of a dedicated multidisciplinary team, education and simulation classes for physicians, nurses, and respiratory therapists, following appropriate inclusion and exclusion criteria for prone positioning, and implementing quality measures through Plan-Do-Study-Act (PDSA) cycles as represented in Figure 1. Results: The total average PaO(2)/FiO(2) ratio before proning for 65% of patients (n = 72) with severe acute respiratory distress syndrome(4) was 84.4 ± 30 mmHg and after one hour of 16 hours proning, it improved to 180.3 ± 78 mmHg. The remaining 35% of patients either had traumatic fractures, unstable spinal injury, severe hemodynamic instability, or morbid obesity together with ARDS which made them unfavorable for prone positioning. Out of those who were proned, 11 (12.5%) patients did not have improvement in oxygenation after proning due to non-recruitable lungs and were put on ECMO. The PaO(2)/FiO(2) ratios before and after one hour of implementing the prone position technique in each quarter of 2017 and 2018 are represented in Figure 2. Conclusion: • Sustaining and standardizing the accomplished work of data collection. • Implementing the prone positioning technique across other critical care units of Hamad Medical Corporation. • Keeping a record of minor complications associated with prone positioning and resolving them in further sessions. • Documenting cases with contraindications to prone positioning."
4639,Veiled Dangers in an Idyllic Setting,
4640,Social Responses to Epidemics Depicted by Cinema,"Films illustrate 2 ways that epidemics can affect societies: fear leading to a breakdown in sociability and fear stimulating preservation of tightly held social norms. The first response is often informed by concern over perceived moral failings within society, the second response by the application of arbitrary or excessive controls from outside the community."
4641,EGFR-vIII downregulated H2AZK4/7AC though the PI3K/AKT-HDAC2 axis to regulate cell cycle progression,"BACKGROUND: The EGFR-vIII mutation is the most common malignant event in GBM. Epigenetic reprogramming in EGFR-activated GBM has recently been suggested to downregulate the expression of tumour suppressor genes. Histone acetylation is important for chromatin structure and function. However, the role and biological function of H2AZK4/7AC in tumours have not yet been clarified. RESULTS: In our study, we found that EGFR-vIII negatively regulated H2AZK4/7AC expression though the PI3K/AKT-HDAC2 axis. Because HDAC1 and HDAC2 are highly homologous enzymes that usually form multi-protein complexes for transcriptional regulation and epigenetic landscaping, we simultaneously knocked out HDAC1 and HDAC2 and found that H2AZK4/7AC and H3K27AC were upregulated, which partially released EGFR-vIII-mediated inhibition of USP11, negative regulator of cell cycle. In addition, we demonstrated in vitro and in vivo that FK228 induced G1/S transition arrest in GBM with EGFR-vIII mutation. FK228 could enhance anti-tumour activity by upregulating expression of the tumour suppressor USP11 in GBM cells. CONCLUSIONS: EGFR-vIII mutation downregulates H2AZK4/7AC and H3K27AC, inhibiting USP11 expression though the PI3K/AKT-HDAC1/2 axis. FK228 is an effective and promising treatment for GBM with EGFR-vIII mutation."
4642,Assessment of listing and categorisation of animal diseases within the framework of the Animal Health Law (Regulation (EU) No 2016/429): bovine viral diarrhoea (BVD),"Bovine viral diarrhoea (BVD) has been assessed according to the criteria of the Animal Health Law (AHL), in particular criteria of Article 7 on disease profile and impacts, Article 5 on the eligibility of BVD to be listed, Article 9 for the categorisation of BVD according to disease prevention and control rules as in Annex IV and Article 8 on the list of animal species related to BVD. The assessment has been performed following a methodology composed of information collection and compilation, expert judgement on each criterion at individual and, if no consensus was reached before, also at collective level. The output is composed of the categorical answer, and for the questions where no consensus was reached, the different supporting views are reported. Details on the methodology used for this assessment are explained in a separate opinion. According to the assessment performed, BVD can be considered eligible to be listed for Union intervention as laid down in Article 5(3) of the AHL. The disease would comply with the criteria as in Sections 4 and 5 of Annex IV of the AHL, for the application of the disease prevention and control rules referred to in points (d) and (e) of Article 9(1). The assessment here performed on compliance with the criteria as in Section 3 of Annex IV referred to in point (c) of Article 9(1) is inconclusive. The animal species to be listed for BVD according to Article 8(3) criteria are mainly species of the families Bovidae, Cervidae and Camelidae as susceptible species and several mammalian species as reservoirs."
4643,"iCa(2+) Flux, ROS and IL-10 Determines Cytotoxic, and Suppressor T Cell Functions in Chronic Human Viral Infections","Exhaustion of CD8(+) T cells and increased IL-10 production is well-known in chronic viral infections but mechanisms leading to loss of their cytotoxic capabilities and consequent exhaustion remain unclear. Exhausted CD8(+)T cells also called T suppressors are highly immune suppressive with altered T cell receptor signaling characteristics that mark it exclusively from their cytotoxic counterparts. Our study found that iCa(2+) flux is reduced following T cell receptor activation in T suppressor cells when compared to their effector counterpart. Importantly chronic activation of murine cytotoxic CD8(+) T cells lead to reduced iCa(2+) influx, decreased IFN-γ and enhanced IL-10 production and this profile is mimicked in Tc1 cells upon reduction of iCa(2+) flux by extracellular calcium channel inhibitors. Further reduced iCa(2+) flux induced ROS which lead to IFN-γ reduction and increased IL-10 producing T suppressors through the STAT3—STAT5 axis. The above findings were substantiated by our human data where reduced iCa(2+) flux in chronic Hepatitis infections displayed CD8(+) T cells with low IFN-γ and increased IL-10 production. Importantly treatment with an antioxidant led to increased IFN-γ and reduced IL-10 production in human chronic Hep-B/C samples suggesting overall a proximal regulatory role for iCa(2+) influx, ROS, and IL-10 in determining the effector/ suppressive axis of CD8(+) T cells."
4644,Poster Sessions 313-503,
4645,Abstracts des Kongresses für Kinder- und Jugendmedizin 2017,
4646,Die Dialektik der Wissenschaftsfreiheit vor dem Hintergrund der Bioterrorismus-Bekämpfung,"Die mikrobiologische Forschung ist durch die jüngsten Ereignisse in den USA in unerwartet scharfer Form auf den Prüfstein gestellt worden. Nach dem 11. September 2001 und den darauf folgenden Milzbrandanschlägen wurde dem Terrorismus und speziell dem Bioterrorismus in den USA die höchste Priorität eingeräumt. Damit verbunden war auch eine Problematisierung vor allem der mikrobiologische Forschungsfreiheit. Im vorliegenden Artikel wird daher der Versuch unternommen, einen Überblick über den „Dualuse“- Charakter und die möglichen Gefahren der mikrobiologischen Grundlagenforschung zu geben und auf die negativen Auswirkungen von Selbstzensur, einschränkenden Gesetzesbestimmungen und einseitiger Forschungsförderungspolitik aufmerksam zu machen."
4647,"Abstracts 2019 der GNPI und DGPI: 45. Jahrestagung der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin gemeinsam mit der 27. Jahrestagung der Deutschen Gesellschaft für Pädiatrische Infektiologie, 23.–25. Mai 2019, Leipzig",
4648,Dreizehnter Bericht nach Inkrafttreten des Gentechnikgesetzes (GenTG) für den Zeitraum vom 1.1.2002 bis 31.12.2002 : Die Arbeit der Zentralen Kommission für die Biologische Sicherheit (ZKBS) im Jahr 2002,
4649,Impfungen,
4650,Tuberkulose: Damals und heute ein Thema,
4651,Pediatric Radiology Continuing Medical Education Activity,
4652,Reply to Ñamendys-Silva and Salluh,
4653,"33rd Annual Meeting of The Japanese Society of Neuroradiology 5-7 February 2004, Osaka, Japan",
4654,Abstractband zum 120. Kongress der DGIM 2014,
4655,Oral Presentations_Tuesday,
4656,Mitteilungen der DGIM 04/2004,
4657,"Synthesis and preliminary in vitro activity of mono- and bis-1H-1,2,3-triazole-tethered β-lactam–isatin conjugates against the human protozoal pathogen Trichomonas vaginalis","In this study, we describe the synthesis of mono- and bis-1H-1,2,3-triazole-tethered β-lactam–isatin conjugates using copper-catalysed azide-alkyne cycloaddition reaction between mono- and di-propargylated azetidin-2-ones and N-alkylazido isatins. The synthesized conjugates were evaluated for their preliminary in vitro analysis against Trichomonas vaginalis at 50 μM. The efficacy of synthesized hybrids was observed to depend on the substituent at N-1 position of β-lactam ring, as well as the presence of single/double 1H-1,2,3-triazole linker. Among the synthesized conjugates, the presence of a p-tolyl substituent at N-1 of β-lactam ring was preferred for good activity profiles while the increase in spacer length did not influence the efficacy of the compounds. Compounds with high levels of potency were further analysed to determine their IC(50) values, as well as cytotoxicity profiles against mammalian cells. The most active compound in the synthesized conjugates displayed an IC(50) value of 10.49 μM against cultured G3 strain of T. vaginalis and was non-toxic to cultured mammalian HeLa cells at the same concentration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00044-014-0956-6) contains supplementary material, which is available to authorized users."
4658,Oral Presentations O1 - O184,
4659,Posters P788 - P999,
4660,Bandinhalt Band 46—2003,
4661,SPR 2012,
4662,Scientific Program,
4663,Ärztliches Berufsrecht. Hat ein Assistenzarzt bei Vertretung eines Chefarztes Anspruch auf Vergütung?,
4664,Stellungnahme der ZKBS zur Risikobewertung des SARS-assoziierten Coronavirus,
4665,Infektionen der oberen Atemwege,"BACKGROUND: Upper airway infections contribute significantly to paediatric morbidity and hospitalization especially of young children, are often treated polypragmatically, and are one of the main reasons for antibiotic prescriptions. The severity varies between mild, self-limiting and potentially life-threatening airway obstructions. DIAGNOSIS: The physician involved can normally make the right diagnosis based on the patient′s history and physical findings; additional diagnostic procedures (blood tests, imaging) should be restricted to unclear cases. THERAPY: Antibiotic stewardship should be applied. Imminent airway obstruction will require early and competent paediatric intensive care interventions. Since viral and bacterial upper airway infections can present with similar features, it is useful to approach them under topographical aspects. PREVENTION: Following immunization recommendations can prevent an enormous amount of severe potentially life threatening airway infections."
4666,Angemessene Vorbereitung gegen bioterroristische Anschläge,
4667,Management biologischer Gefahrenlagen: Überlegungen zur notwendigen Infrastruktur in Ländern und Kommunen,"Management of a terrorist or criminal attack with biological agents depends on the number of primarily contaminated cases, on the numbers of persons who need medical treatment, on the possibility of human-to-human transmission, and on the tenacity of the germs.In the event of a high rate of human-to-human transmission, the strategy of transmission control depends on the kind of transmission and the effectiveness of measurements implemented by public health authorities. In this respect, it does not differ from the management of the natural emergence of an infectious disease (for example SARS). At all times it is necessary to establish precautions for the clinical management of severely ill persons. The possibility of professional clinical management depends on the number of affected people at one time and the necessary precautions for the medical personnel and the community. Kind, time, and region of the deliberate release of new or manipulated microorganisms or the natural emergence of an infectious disease are not predictable—the risk of human transmission is of course higher in regions with high population density. It is recommended that single cases of a highly contagious, lifethreatening disease be treated in central institutions with special technical support and facilities for staff protection (isolation unit). However, in terms of an epidemic situation, every single region must establish precautions for its own management of such cases."
4668,A predictive decision-aid methodology for dynamic mitigation of influenza pandemics,"In a recent report, the Institute of Medicine has stressed the need for dynamic mitigation strategies for pandemic influenza. In response to the need, we have developed a simulation-based optimization methodology for generating dynamic predictive mitigation strategies for pandemic outbreaks affecting several regions. Our methodology can accommodate varying virus and population dynamics. It progressively allocates a limited budget to procure vaccines and antivirals, capacities for their administration, and resources required to enforce social distancing. The methodology uses measures of morbidity, mortality, and social distancing, which are translated into the costs of lost productivity and medical services. The simulation model was calibrated using historic pandemic data. We illustrate the use of our methodology on a mock outbreak involving over four million people residing in four major population centers in Florida, USA. A sensitivity analysis is presented to estimate the impact of changes in the budget availability and variability of some of the critical parameters of mitigation strategies. The methodology is intended to assist public health policy makers."
4669,"A Novel CDC42 Mutation in an 11-Year Old Child Manifesting as Syndromic Immunodeficiency, Autoinflammation, Hemophagocytic Lymphohistiocytosis, and Malignancy: A Case Report","Background: The CDC42 (Cell Division Cycle 42) gene product, CDC42, is a member of the family of small Rho GTPases, which are implicated in a broad spectrum of physiological functions in cell cycle regulation, including establishing and controlling of the cell actin cytoskeleton, vesicle trafficking, cell polarity, proliferation, motility and migration, transcription activation, reactive oxygen species production, and tumorigenesis. The CDC42 gene mutations are associated with distinct clinical phenotypes characterized by neurodevelopmental, growth, hematological, and immunological disturbances. Case presentation: We report the case of an 11-year-old boy with syndromic features, immunodeficiency, and autoinflammation who developed hemophagocytic lymphohistiocytosis and malignant lymphoproliferation. In this patient, a novel heterozygous p.Cys81Tyr mutation in the CDC42 gene was found by whole exome sequencing. Conclusions: The Cdc42 molecule plays a pivotal role in cell cycle regulation and a wide array of tissue-specific functions, and its deregulation may result in a broad spectrum of molecular and cellular dysfunctions, making patients with CDC42 gene mutations susceptible to infections, immune dysregulation, and malignancy. In the patient studied, a syndromic phenotype with facial dysmorphism, neurodevelopmental delay, immunodeficiency, autoinflammation, and hemophagocytic lymphohistiocytosis shares common features with Takenouchi–Kosaki syndrome and with C-terminal variants in CDC42. It is important to emphasize that Hodgkin's lymphoma is described for the first time in the medical literature in a pediatric patient with the novel p.Cys81Tyr mutation in the CDC42 gene. Further studies are required to delineate precisely the CDC42 genotype–phenotype correlations."
4670,Virale Atemwegsinfektionen bei Erwachsenen : Eine Übersicht,"In the course of a lifetime a decrease of the immunofunction occurs in adults, in particular of the adaptive immune system.Therefore, respiratory virus infections are usually mild and uncomplicated in young healthy people while elderly and frail adults more frequently develop serious diseases of the lower respiratory tract.Even “harmless” agents such as rhino- or coronaviruses frequently induce acute disorders or exacerbations in people with chronic cardiopulmonary diseases or asthma.For rapid diagnosis, detection of the viral antigen, viral genome, and infectivity by shell vial culture are suitable because the humoral immune response is delayed.Primarily, a nasopharyngeal sample should be used and in addition a specific local sample depending on the symptoms. The sensitivity of antigen assays is rather low. A combination of PCR and detection of infectivity increase the detection rate.Among the main respiratory viruses only influenza is preventable by vaccination.The annual revaccination of the elderly and patients with risk factors such as chronic cardiopulmonary diseases is important.Improved vaccines can enhance the immunoreaction.For therapy and prophylaxis against influenza A amantadine may be used.The neuraminidase inhibitors zanamivir and oseltamivir represent potent drugs for antiviral therapy against influenza virus A and B infection. Pleconaril, a capsid function inhibitor with effective antiviral activity against rhinovirus infection, awaits approval."
4671,Immunogenicity of a recombinant coronavirus spike glycoprotein expressed in transgenic plants,"Recently, it has been demonstrated that plants offer the possibility of producing low cost subunit vaccines that can be either parenterally or orally administered. Here we review data we obtained on the immunological response elicited by two recombinant versions of the glycoprotein S from the swine transmissible gastroenteritis coronavirus (TGEV) expressed in transgenic plants. Arabidopsis or potato plants were genetically transformed with cDNAs constructs encoding the N-terminal domain (aa residues 1–750) or the full-length glycoprotein S of TGEV, responsible for the neutralizing antibody induction against the virus, under the control of the cauliflower mosaic virus 35S (CaMV 35S) promoter. Genomic DNA and mRNA analysis of leave extracts from transformed plants demonstrated the incorporation of the foreign cDNA into the plant genomes as well as their transcription. Expression of recombinant polypeptides was observed in most transgenic plants by ELISA using specific antibodies. Mice immunized either parenterally with leave extracts from transgenic arabidopsis plants or, more interestingly, fed with potato tubers, developed antibodies that specifically reacted with TGEV in ELISA, immunoprecipitated the glycoprotein S and in some cases neutralized the virus infectivity. From the above results, we conclude that transgenic plants expressing glycoprotein S polypeptides may be potentially used as a source of recombinant antigen for vaccine production."
4672,Liste risikobewerteter Spender- und Empfängerorganismen für gentechnische Arbeiten Bekanntmachung nach § 5 Absatz 6 Gentechnik-Sicherheitsverordnung in der Fassung der Bekanntmachung vom 14.3.1995 (BGBl. I S. 297): Bekanntmachung nach § 5 Absatz 6 Gentechnik-Sicherheitsverordnung in der Fassung der Bekanntmachung vom 14.3.1995 (BGBl. I S. 297),
4673,Virology: Coronaviruses,
4674,Insect biochemistry,
4675,Gene Control: Histones—Animal and Vegetable,
4676,The virus of acute diarrhoea,
4677,Biochemistry of viruses,
4678,Cavitation as a Mechanism for the Synthesis of Natural Diamonds,"LET us grant, in accordance with Galimov's proposals(1), that cavitation can occur when flowing magma in a pipe encounters a constriction, and that in the ensuing collapse of a bubble very substantial transient dynamic pressures, of magnitude sufficient to be of thermodynamic importance for diamond synthesis, can be produced. In granting this, we overlook some quantitative details in his calculation, such as the apparent implication that the bubbles would contain gas at 10 or 20 kbar, and yet that their compression (by a factor of 64,000 in volume) can be calculated by ideal gas theory. He ignores the fundamental difference in rate control between martensitic conversion of crystals from one modification to another, which makes a product of the same chemical composition as the starting material, and other processes of crystal growth requiring a composition change. In the former class, to which production of diamond by the action of shock waves on graphite belongs, the limit on growth velocity is essentially the shock wave velocity. Thus, so far as that is concerned, quite a large diamond might be made within a few microseconds. Further characteristics of martensitic processes are, however, that the product takes the form of thin lenses, whereby the constraint by the matrix on shape change in the converting region is minimised and, second, that as a rule there is a multiplicity of orientations of the martensitic product in the parent crystal, so that a microcrystalline product results."
4679,Molecular genetics,
4680,Ecology of photosynthesis,
4681,Complementary genetics,
4682,Progress in coronaviruses,
4683,CYTOMEGALOVIREMIA IN HEALTHY ASYMPTOMATIC PREGNANT ADOLESCENTS,"Based upon clinical observations it has been deduced that human cytomegalovirus (HCMV) may be transmitted with blood. It has been estimated that approximately 5% of healthy individuals are asymptomatic carriers of HCMV in blood. Although isolation of this virus from blood is relatively easily accomplished in immunosuppressed individuals or from those with symptomatic HCMV-associated clinical conditions, efforts to recover virus from the blood of asymptomatic healthy carriers have been largely and repeatedly unsuccessful. Only one report has documented viremia in healthy individuals (in 1969 Diosi and associates reported recovery of HCMV from blood in 2 of 35 blood bank donors).¶In the course of studies of healthy pregnant adolescents in North Carolina and in Maryland, HCMV was recovered from the blood in 5 of 96 and 2 of 41 subjects respectively, or 5% in each population. There was no demonstrable association with prenatal transmission of HCMV, with subject well-being or outcome of pregnancy.¶The risk of HCMV reactivation in young pregnant women may relate to gestational and endocrine factors. It is also possible that reactivation of HCMV occurs most frequently soon after primary infection and that the risk of reactivation is inversely related to the elapsed time since virus acquisition. These observations may assist in defining risk factors for transfusion-related transmission as well as for reactivation and prenatal acquistion of HCMV."
4684,1081 BACTERIOPHAGE ARE PRESENT IN THE SPUTUM OF PATIENTS WITH BRONCHOPULMONARY Ps. AERUGINOSA INFECTIONS,"Although it is generally appreciated that Ps. aeruginosa specific-phage can be isolated from natural sources in which Ps. aeruginosa can be found, such as seawater and sewage, the presence of phage at the sites of Pseudomonas infection in man is not widely recognized. Using routine bacteriological procedures we show that species-specific phage can be consistently recovered from the sputum of patients with chronic Ps. aeruginosa bronchopulmonary infections, including 6 patients with cystic fibrosis and one non CF individual. Ps. aeruginosa specific-phage were present in sputum at concentrations ranging between 10(3) to 10(7) viable particles/ml with as many as 4 different phage strains recovered from a single individual. Of the 16 phage isolates, at least 12 different phage strains could be identified based on bacterial host sensitivity and electron microscopic morphology. It would appear that Ps. aeruginosa and its phage commonly coexist at the site of human bronchopulmonary infections, and most probably at all sites of Ps. aeruginosa infection, and should be considered as possible factors influencing the pathogenicity of Ps. aeruginosa."
4685,Prospective Evaluation of Community-Acquired and Nosocomial Viral Respiratory Tract Infections in a Neonatal and Pediatric Intensive Care Unit,
4686,"Selected Abstracts from the 100th J Project Meeting, Antalya, Turkey, March 12-14, 2014",
4687,1083 DIFFUSION OF MOXALACTAM INTO CSF OF CHILDREN WITH BACTERIAL MENINGITIS,"Moxalactam (MOX), a new oxa-β-lactam antibiotic,is active against an expanded spectrum of gram negative organisms including Haemophilus influenzae. It has also been reported to diffuse into cerebrospinal fluid. We administered IV MOX to children (6 wks-4½ yrs) receiving conventional antimicrobial therapy for bacterial meningitis. Plasma and CSF specimens were collected 2 to 3 hours after a dose and assayed for MOX concentration by HPLC (capable of detecting 1 μg/ml of MOX). Eight patients received single doses of 15 or 25 mg/kg. In 11 determinations the plasma levels ranged between 4.7 and 29.4 μg/ml but MOX was detected in the CSF in only one instance. Eight patients received 50 mg/kg of MOX every 8 hours for 3 doses, and in 5 patients the drug diffused into CSF. MOX was detectable in 3/5 of CSF specimens early in the course of illness (2nd or 3rd day) and averaged 20% (range 2.5 to 30%) of plasma concentration. It was detectable in 5/11 of CSF specimens obtained later in the illness (13th to 22nd day) and averaged 15.7% (6 to 36%) of plasma concentration. There was no correlation between the diffusion of MOX into CSF and the CSF white cell count, however MOX diffused to a greater extent in patients with higher CSF protein content. In summary, MOX diffuses into CSF but such diffusion is unpredictable. Caution must be exercised in using MOX alone in the treatment of meningitis."
4688,News items,
4689,1082 EFFECTS OF PERSISTENT MIDDLE EAR EFFUSION (PMEE) ON DEVELOPMENT OF SPEECH AND LANGUAGE (S&L),"To determine effects of PMEE occurring during the first 3 yrs. of life, we administered tests of S&L to 218 3 y.o., white, English-speaking children with normal developmental histories. All had been followed prospectively since birth; we stratified according to duration of PMEE, sex, type of health-care, and socio-economic status (SES). Below are selected results for children with PMEE (130+ days) and those without PMEE (<30 days) in a suburban, private practice (I) and an urban clinic (II). These data suggest that PMEE early in life is associated with significant impairment of S&L; children from higher SES appear at greater risk. This study does not show if such effects are permanent or transient."
4690,1084 UNUSUAL LABORATORY FINDINGS IN ECHOVIRUS-11 MENINGITIS,"Echovirus 11(E-11) was isolated from the cerebrospinal fluid (CSF) of 22 children in a 1980 summer outbreak of meningitis. Seventeen(77%) were <6 mos old(range 2 wk-9 yr). 54% had CSF cell counts >300/mm(3) and 14% had >500/mm(3)(range 0-2250). 59% had ≥50% polymorphonuclears(P) and 24% had >90% P. None had CSF glucose <40mg/dl; 41% had CSF protein ≥45mg/dl and 6% had >75mg/dl. Three patients(pts) had entirely normal CSF. In 86% peripheral WBC was 5000-15000/mm(3); only 3 had >75% P but 20% had absolute band count >500/mm(3) Four pts(<3 mos old) had repeat CSF exams. All had >50 cells/mm(3) and the two youngest(age 2 wk) still had >50% P after 1 and 3 days. CSF findings were compared with data from pts with bacterial meningitis(B). Cell count >500/mm(3), glucose ≤45mg/dl, and protein >75mg/dl were statistically associated with B. However, 14% of E-11 pts had at least one of these findings and 20% of B pts had none of these findings. CSF P >75% was as frequent in E-11 pts as in B pts. Peripheral WBC <5000 or >15000/mm(3) and absolute band count >500/mm(3) were statistically associated with B but 38% of E-ll pts had one of these abnormalities. Certain CSF findings in our pts have not been reported for E-11 and are uncharacteristic of viral meningitis: 1) leukocyte response more characteristic of bacterial meningitis: CSF P >90%, persistence of CSF P beyond 24 hrs, peripheral band count >500, and 2) entirely normal CSF."
4691,"Inhibition of RSV, Coronavirus (CV), and Rhinovirus (RV)-Induced Interleukin-8 (IL-8) Elaboration and Virus Replication by Diphenylene Iodonium Chloride (DPI)",
4692,INAPPARENT INTRAUTERINE HSV INFECTION DETECTED BY IMMUNOHISTOCHEMISTRY,"We have used glucose oxidate-avidin-biotin (GAB) immunohistochemistry to detect herpes simplex virus (HSV) 1 & 2 virion antigen in fixed tissue. Cases were selected by placental or cord pathology &/or clinical findings in the fetus/neonate. Virus was detected in placenta, umbilical cord &/or fetal/infant organs from 17 pregnancies (1 set twins; 15 newborns & 3 stillborns). Antigen was found in single mesenchymal & epithelial cells without characteristic viral cytopathology. Viral cultures were positive in one case (skin vesicles). Five mothers had clinical or laboratory evidence of HSV 1/2 infections before or during pregnancy, but none had evidence of active infection at delivery. Thirteen pregnancies ended prematurely & 5 infants/fetuses were small for gestational age. Ten newborns were severely ill. Four infants died before 7-1/2 months of age. Of 11 survivors, 2 have severe CNS abnormalities, 1 persistent pulmonary disease & 2 remain hospitalized. Diagnoses associated with GAB positive herpes virus in specific organs include NEC, hepatitis with cholestatic jaundice, interstitial pneumonitis, aseptic meningitis, progressive cystic brain degeneration, & cardiac arrhythmias. We conclude that intrauterine HSV infection is more common than believed & that intrauterine HSV infection may persist in the fetus & neonate chronically without cytopathology or detectable virus & may be associated with prematurity, intrauterine & neonatal death, organ damage, & progressive neonatal disease."
4693,"1085 DIAGNOSIS AND TREATMENT OF PURULENT NASOPHARYNGITIS – A DOUBLE-BLIND, TWO-DRUG EVALUATION","132 children with purulent nasopharyngitis and no other indication for specific treatment had gram stain and bacterial culture of nasopharyngeal discharge and were randomized to 4 treatment groups with antibiotic (A=cephalexin) or decongestant/anti-histamine (D=pseudoephedrine/triprolidine) or their corresponding placebo equivalents (A+D+, A+D−, A−D+, A−D−). Follow-up parent, physician, and bacteriologic evaluations were performed after 5 days of therapy without knowledge of active drug status. Groups were comparable for age, sex, race, number of patients withdrawn from study, days ill, fever >38.0 C, appearance of discharge, nasal crusting, and number of days until follow-up. 21% of patients grew H. influenzae type b and only 8% S. pyogenes on initial culture. Nasal crusting was significantly (p<0.01) associated with the growth of S. pneumoniae or H. influenzae type b, suggesting a possible pathologic relationship. There were, however, no significant differences between active drug and placebo treatment groups for change in nasal discharge, complications, apparent drug benefit, or change in nasal flora with active antibiotic treatment. Significantly (p<0.05) more side effects were attributed to the D+ treatment groups. Routine culture and/or treatment of purulent nasopharyngitis cannot be recommended unless properly controlled studies demonstrate a significant drug benefit."
4694,THE USE OF HOMOLOGOUS AND HETEROLOGOUS ROTAVIRUS ANTIBODIES FOR THE PREVENTION OF ROTAVIRUS GASTROENTERITIS,"Rotavirus is an important cause of serious gastroenteritis in children. One possible strategy for the prevention of rotavirus gastroenteritis is the oral administration of rotavirus specific immunoglobulin. We utilized a mouse model of rotavirus infection to examine the efficacy of rotavirus antibody for the prevention of symptomatic rotavirus diarrhea. This model consists of the feeding of seronegative infant mice a predetermined amount of murine rotavirus and antibody and then assaying the animals for intestinal antigen excretion, liquid colonic contents, and immune response. We found that mouse serum containing homologous antibodies to murine rotavirus completely protected animals from symptomatic infection and viral shedding while non-immune serum provided no protection. Neither immune nor non-immune mouse milk offered any protection from infection. In the case of heterologous sources of sera obtained from animals experimentally infected with human or bovine rotaviruses, and antibodies derived from the yolks of eggs obtained from chickens immunized with rotaviruses full protection was provided from symptomatic disease. Non-immune sera and immune human milk did not protect the animal from infection. The majority of the animals treated with effective specific immunoglobulin preparations developed a rotavirus systemic antibody response. These studies indicate that homologous and heterologous sources of rotavirus antibodies can provide protection from rotavirus diarrhea and may allow for active immunity to occur."
4695,Obituary Dr. Morten Eskildsen,
4696,DGENERATIVE CHANGES IN NEUTROPHILS-AN INDICATOR OF BACTERIAL INFECTION,"In 157 neonates in whom a sepsis work-up was performed, 195 peripheral blood smears were reviewed. Neutrophil degenerative changes (vacuolization and toxic granulation) were seen frequently in culture proven bacterial sepsis. Seventeen of 21 peripheral blood smears from neonates subsequently proven to have bacterial infection had vacuolization in neutrophils for a sensitivity of 81%, specificity of 93% and positive predictive accuracy of 59%. Comparison of relative values for predicting neonatal bacterial infection utililizing five items from a single blood sample are shown in the table: Vacuolization and toxic granulation of neutrophils are often found in the peripheral blood smear of neonates with bacterial infection and appear to be more reliable indicators of septicemia than traditional tests."
4697,Viral Upper Respiratory Infection in School Children: Effects on Middle Ear Pressures,
4698,"Hartmut Krauss, Albert Weber, Max Appel, Burkhard Enders, Henry D. Isenberg, Hans Gerd Schiefer, Werner Slenczka, Alexander von Graevenitz, and Horst Zahner. Zoonoses: infectious diseases transmissible from animals to humans, 3rd edition",
4699,1086 CORONAVIRUS-LIKE PARTICLES AND NEONATAL GASTROINTES-TINAL DISEASE,"Coronavirus-like particles (CVLP) are associated with gastrointestinal (GI) symptoms (sx) in mammals, including man. We report an intensive care nursery (NICU) outbreak of GI sx associated with CVLP, identified by electron microscopy, in the stools of affected infants. Immune aggregation of stool CVLP occurred with sera of CVLP positive (+) infants only. Prevalence of stool CVLP, ascertained by 8 NICU-wide surveys over 40 weeks, fell from 67% to less than 10%, paralleling prevalence changes in the community. Most infants surveyed were premature. Overall, 36% (32/88) of all infants were CVLP +. Prenatal or intrapartum acquisition was suggested by the finding that 34% (11/32) of the CVLP + infants were examined within 72 hours of birth. CVLP + infants were more likely to have GI sx within 7 da of survey (p<.005), including water loss stools (p<.005), and the following sx persisting for more than 2 days: gastric retention (p<.001), bilious gastric aspirates (p<.02), abdominal distention (p<.01) and gross or occult blood in the stool (p<.005). CVLP + infants were also more likely to have multiple sx and to have feeds discontinued for more than 3 days due to GI sx. We conclude that stool Coronavirus-like particles are associated with clinically significant GI disease in the newborn."
4700,DETECTION OF MEASLES IgM,"Fewer physicians have experience in diagnosis of measles as the number of cases continues to decline. For this reason an Enzyme Linked Immunosorbent Assay (ELISA) was developed to detect measles virus specific IgM antibody (MIgMA). Anti-human μ chain is affixed to a solid phase to which a 1:100 dilution of serum is added. Only 0.005 ml of patient's serum is needed. Treatment of 3 MIgMA positive sera with dithiothreitol but not Staph protein A removed MIgMA. The values for 24 cord sera (0.030 ± 0.007), 60 adult sera (0.034 ± 0.011), and 47 sera from children prior to measles immunization (0.030 ± 0.015) were used to establish a seronegative range. Sera yielding reactions greater than 3 SD of the mean for the latter group were considered to be positive for the presence of MIgMA. MIgMA was not detected in sera with high titers of rheumatoid factor. Five unpaired and the first of 14 of 17 paired sera obtained from patients with measles were positive for MIgMA. The 3 convalescent samples from patients having MIgMA negative initial sera, also were positive. MIgMA was detected as early as 1 day and as late as 41 days following onset of illness. No MIgMA could be detected in 47 vaccinees tested 2-1/2 months or more after measles vaccination. Neither recent immunization nor the presence of rheumatoid factor produce reactions which are likely to obfuscate the interpretation of this very sensitive test which, in most cases, can confirm the clinical diagnosis of measles on a single serum specimen obtained soon after onset of rash."
4701,IMMUNOLOGIC STUDIES OF ENTERIC CORONAVIRUS-LIKE PARTICLES(CVLP),"CVLP have been implicated in gastrointestinal illness sporadically among children and in an intensive care nursery outbreak at our hospital. Fecal examination by electron microscopy(EM) is the only means of diagnosis. We developed an enzyme-linked immunosorbent assay(ELISA) using ammonium sulfate precipitated CVLP from feces. The purified CVLP was immunogenic in rabbits. Sera containing antibodies against bovine enteric, canine, OC43, and 229E coronaviruses(CV) did not block binding of rabbit anti-CVLP to microtiter wells coated with purified CVLP. Immune EM using these antisera and nonaggregated CVLP also suggested that CVLP are antigenically distinct from other CV. False positives occurred when stools negative for CVLP by EM were tested. This nonspecific reaction was not blocked by sonicates of E.coli, Strep. fecalis, B.fragilis, or C.difficile, or by C.difficile antitoxin. Absorption of rabbit anti-CVLP serum with suckling mouse intestine did not improve specificity. More sophisticated purification of fecal CVLP is needed to improve ELISA sensitivity and specificity, and to characterize the antigen."
4702,Announcement,
4703,"The classification and nomenclature of viruses: Summary of results of meetings of the International Committee on Toxonomy of Viruses in Madrid, September 1975","The results of the meetings of the International Committee on Taxonomy of Viruses, held in Madrid, September 1975, are briefly reported: rules of viral nomenclature, composition of the new Executive Committee, and a list of the names so far officially agreed."
4704,The 21st meeting of the Executive Committee of the International Committee on Taxonomy of Virsues (ICTV): The ICTVdB project and other initiatives,
4705,"VIIth International Symposium on Coronaviruses and Arteriviruses Parador de Segovia, Segovia, Spain May 10 to 15th, 1997",
4706,Obituary Léon Hirth (1916–1991),
4707,Changes to virus taxonomy 2004,
4708,"Vaccine design: Innovative Approaches and Novel Strategies Edited by Rino Rappuoli and Fabio Bagnoli (2011): Caister Academic Press, Norfolk, UK, 380 pages. ISBN :978-1-904455-74-5, Hardcover. $319 from Amazon.com",
4709,Recently published papers in the field of molecular evolution,
4710,"Resistance to fatal central nervous system disease by mouse hepatitis virus, strain JHM: I. Genetic analysis",
4711,Involvement of cysteine in Semliki Forest virus (SFV) induced fusion ofAedes albopictus cells,
4712,In vitro protein synthesis by cells infected with different types of bovine herpesvirus 1,
4713,Recently published papers in the field of molecular evolution,
4714,Gene expression,
4715,Detection of viruses by electron microscopy in fecal samples from patients with gastroenteritis in the canton of Vaud,
4716,Recently published papers in the field of molecular evolution: General aspects,
4717,Recently published papers in the field of molecular evolution,
4718,Bovine herpesvirus 1 and caprine herpesvirus 1: Viral polypeptides exhibiting shared and unique antigenic determinants,
4719,Recently published papers in the field of molecular evolution,
4720,Announcements,
4721,News from the Internet,
4722,"Contents of Volume 31, 2005",
4723,Oral Presentations,
4724,"Viral agents in marmoset colitis: Dr. Robert Russell, University of Washington, Seattle, and Dr. David Brian, University of Tennessee, Knoxville",
4725,"Book Review: AN INTRODUCTION TO THE U.S. HEALTH CARE SYSTEM. Fifth Edition. By Steven Jonas, New York: Springer Publishing Company, 2003, 233 pp., $36.95 (softcover)",
4726,Examining the Links between Biodiversity and Human Health: An Interdisciplinary Research Initiative at the U.S. Environmental Protection Agency,"Under the U.S. Environmental Protection Agency’s mission to protect human health and the environment, the agency seeks to conduct research on the structure and function of ecosystems and to improve our understanding of the processes that contribute to the sustained health of the nation’s ecosystems and the well-being of human populations. Changes in biodiversity can profoundly impact the ability of ecosystems to provide clean water, energy, food, recreation, and other services that contribute to human well-being. In addition, changes in biodiversity can affect the transmission of infectious disease to humans, particularly vectorborne diseases such as malaria and Lyme disease. The Environmental Protection Agency’s new initiative supports interdisciplinary research to characterize the mechanisms that link biodiversity and human health and to use this knowledge to develop integrative tools and approaches for quantifying and predicting these relationships. Research on these links can have an important impact on our view of biodiversity and how we manage resources to protect human and ecosystem health."
4727,Emerging Infectious Diseases and the Socio-ecological Dimension,
4728,1(st) International One Health Congress Abstracts: Plenary Abstracts,
4729,Wildlife Trade: Threat to Global Health,
4730,A Fall From Grace To… Virulence?,
4731,All Hands on Deck: Transdisciplinary Approaches to Emerging Infectious Disease,"The increasing burden of emerging infectious diseases worldwide confronts us with numerous challenges, including the imperative to design research and responses that are commensurate to understanding the complex social and ecological contexts in which infectious diseases occur. A diverse group of scientists met in Hawaii in March 2005 to discuss the linked social and ecological contexts in which infectious diseases emerge. A subset of the meeting was a group that focused on “transdisciplinary approaches” to integrating knowledge across and beyond academic disciplines in order to improve prevention and control of emerging infections. This article is based on the discussions of that group. Here, we outline the epidemiological legacy that has dominated infectious disease research and control up until now, and introduce the role of new, transdisciplinary and systems-based approaches to emerging infectious diseases. We describe four cases of transboundary health issues and use them to discuss the potential benefits, as well as the inherent difficulties, in understanding the social–ecological contexts in which infectious diseases occur and of using transdisciplinary approaches to deal with them."
4732,JIC Award 2008,
4733,Wildlife Trade and the Emergence of Infectious Diseases,"Most recent emerging infectious diseases have been zoonotic in origin. It is our contention that one of the factors responsible for such emergence is the trade in wildlife and bushmeat in particular. This article considers the effect of increasing diversity in the species hunted on the probability of global epidemics such as SARS. In particular, we develop a mathematical model of the probability of such an outbreak in terms of the number of species hunted, the number of susceptibles, and the rate of contact. Hence, we postulate that local biodiversity loss and increasing rates of animal trafficking, and trade and transportation of animals to large cities—where there is a greater potential for person-to-person transmission—may increase the probability of such outbreaks dramatically."
4734,Restriction site maps of a new type of bovine herpesvirus 1,
4735,Marketing in Heterozygous Advantage,"As the rapidly advancing possibilities of biotechnology have outstripped the adaptive capacity of current legal and ethical institutions, a vigorous debate has arisen that considers the boundaries of appropriate use of this technology, particularly when applied to humans. This article examines ethical concerns surrounding the development of markets in a particular form of human genetic engineering in which heterozygotes are fitter than both homozygotes, a condition known as heterozygous advantage. To begin, we present a generalized model of the condition, illuminated by the application to sickle-cell anemia. Next, we propose a typology of related markets, some of which are currently functioning with available products and services, and others that are widely viewed as imminent. We suggest the manner in which perverse incentives may arise for firms that market genetic intervention in circumstances where heterozygous advantage is possible. Finally, we propose that this misalignment of incentives with social welfare has arisen from both ill-conceived market intervention where markets are capable of achieving efficient outcomes and the lack of market intervention where markets have failed. We offer specific legal and regulatory approaches for reform."
4736,Label-free microcantilever-based immunosensors for highly sensitive determination of avian influenza virus H9,"We report on label-free immunosensors for the highly sensitive detection of avian influenza virus. The method makes use of the microcantilevers of an atomic force microscope onto which monoclonal antibodies against avian influenza virus were covalently immobilized. The factors influencing the performance of the resulting immunosensors were optimized by measuring the deflections of the cantilever via optical reflection, and this resulted in low detection limits and a wide analytical range. The differential deflection signals revealed specific antigen binding and their intensity is proportional to the logarithm of the concentrations of the virus in solution. Under optimal conditions, the immunosensors exhibit a linear response in the 7.6 ng mL(−1) to 76 μg mL(−1) concentration range of avian influenza virus, and the detection limit is 1.9 ng mL(−1). [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-013-1129-x) contains supplementary material, which is available to authorized users."
4737,Book Review,
4738,Evaluating viral agents in marmoset colitis,
4739,"Anthropogenic Environmental Change, Mosquito-borne Diseases and Human Health in New Zealand","Anthropogenic environmental change is acknowledged as a primary factor in the emergence of diseases. New Zealand’s history since human occupation has been characterized by extensive anthropogenic disturbance and the establishment of numerous exotic species. As a result, highly modified habitats have been created, which, in conjunction with introduced organisms, provide suitable conditions for the establishment of exotic systems likely to lead to outbreaks of mosquito-borne disease. The interactions among some disturbance factors in the New Zealand environment are discussed, and the potential public health implications."
4740,An improved method for detection of Edwardsiella tarda by loop-mediated isothermal amplification by targeting the EsrB gene,"Edwardsiella tarda is a major pathogen in aquatic environments that can cause heavy economic losses. An improved method for quick and accurate detection of E. tarda by loop-mediated isothermal amplification (LAMP) with two additional loop primers was developed by targeting the EsrB gene (EsrB — LAMP). In this method, the Mg(2+) concentration, reaction temperature, and reaction time were optimized to 8 mmol/L, 61°C, and 40 min, respectively. The detection limit with the EsrB gene was as low as 10 copies, which is 100 times more sensitive than that of conventional polymerase chain reaction (PCR). The EsrB-LAMP assay was shown more sensitive and rapid than previously reported LAMP assays targeting the hemolysin gene ( hemolysin -LAMP) for detection of E. tarda. The EsrB -LAMP was also highly specific to E. tarda and had no cross-reaction with 13 other strains of bacteria. The assay can be carried out in a simple heating device and the EsrB-LAMP products can be visually detected by adding fluorescent dye to the reaction mixture. Taken together, the improved EsrB-LAMP diagnostic protocol has the potential for detection of E. tarda from indoor and outdoor samples."
4741,Regulation of the promoters in SV40 chromosomes and construction of a substituted SV40 containing aDrosophila hsp70 promoter,
4742,Incubus,
4743,"N′-[4-[(Substituted imino)methyl]benzylidene]-substituted benzohydrazides: synthesis, antimicrobial, antiviral, and anticancer evaluation, and QSAR studies","ABSTRACT: A variety of N′-[4-[(substituted imino)methyl]benzylidene]-substituted benzohydrazides have been synthesized and evaluated for antimicrobial and anticancer potential. Results from testing of antimicrobial activity indicated the most potent antimicrobial agents had pMIC (am) = 1.51. The synthesized compounds were bacteriostatic and fungistatic in action. Results from evaluation of antiviral activity indicated that none of the synthesized hydrazide derivatives inhibited viral replication at sub-toxic concentrations. Results from anti-HIV screening against HIV-2 strain ROD indicated that one compound was more potent (IC (50) ≥ 1 μg/cm(3)) than the standard drug nevirapine (IC (50) ≥ 4 μg/cm(3)) and another was equipotent (IC (50) ≥ 4 μg/cm(3)). The most effective anticancer agent against both HCT116 and MCF7 cancer cell lines had IC (50) = 19 and 18 μg/cm(3), respectively. QSAR analysis indicated the importance of Wiener index (W) and energy of the lowest unoccupied molecular orbital (LUMO) in describing the antimicrobial activity of the synthesized compounds. GRAPHICAL ABSTRACT: [Image: see text]"
4744,Book reviews,
4745,News from the Internet,
4746,Genetic structure of mountain lion (Puma concolor) populations in California,"Analysis of 12 microsatellite loci from431 mountain lions (Puma concolor)revealed distinct genetic subdivision that wasassociated with geographic barriers andisolation by distance in California. Levels ofgenetic variation differed among geographicregions, and mountain lions that inhabitedcoastal areas exhibited less heterozygositythan those sampled inland. The San FranciscoBay and Sacramento-San Joaquin River Delta, theCentral Valley, and the Los Angeles Basinappeared to be substantial barriers to geneflow, and allele frequencies of populationsseparated by those features differedsubstantially. A partial barrier to gene flowappeared to exist along the crest of the SierraNevada. Estimated gene flow was high amongmountain lions inhabiting the Modoc Plateau,the western Sierra Nevada, and northern sectionof the eastern Sierra Nevada. SouthernCalifornia mountain lion populations mayfunction as a metapopulation; however, humandevelopments threaten to eliminate habitat andmovement corridors. While north-south geneflow along the western Sierra Nevada wasestimated to be very high, projected loss andfragmentation of foothill habitat may reducegene flow and subdivide populations. Preservation of existing movement corridorsamong regions could prevent population declinesand loss of genetic variation. This studyshows that mountain lion management andconservation efforts should be individualizedaccording to region and incorporatelandscape-level considerations to protecthabitat connectivity."
4747,"Phospholipids, cerebroside, and cerebroside sulfate levels in the CNS of mice withacute experimental viral demyelination",
4748,IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (JCBN) and Nomenclature Committee of IUBMB (NC-IUBMB) Newsletter 1996,
4749,"Gerald L. Mandell, John E. Bennett, Raphael Dolin (eds): Principles and Practice of Infectious Diseases, 6th edn: Elsevier, Philadelphia, 2005; two volumes + CD-ROM, hardbound, pp 3661 + XXXVIII; €314.90, US$329, GBP 201.13; ISBN 0-443-06643-4",
4750,Ecology of Increasing Diseases: Population Growth and Environmental Degradation,"The World Health Organization (WHO) and other organizations report that the prevalence of human diseases during the past decade is rapidly increasing. Population growth and the pollution of water, air, and soil are contributing to the increasing number of human diseases worldwide. Currently an estimated 40% of world deaths are due to environmental degradation. The ecology of increasing diseases has complex factors of environmental degradation, population growth, and the current malnutrition of about 3.7 billion people in the world."
4751,"Book Review: DECEIT AND DENIAL. THE DEADLY POLITICS OF INDUSTRIAL POLLUTION. By Gerald Markowitz and David Rosner, Berkeley: University of California Press/The Millbank Memorial Fund, 2003, 408 pp., illustrated, $34.95 (hardcover)",
4752,"Health of Antarctic birds: a review of their parasites, pathogens and diseases","Antarctic birds are not beyond the effects of parasites or pathogens. However, potential ecological consequences of wide-spread infections for bird populations in Antarctica have received little attention. In this paper, we review the information published about disease and parasites, and their effects on Antarctic birds. The information on host species, parasites and pathogens, and geographic regions is incomplete and data on ecological effects on the populations, including how birds respond to pathogens and parasites, are almost inexistent. We conclude that more research is needed to establish general patterns of spatial and temporal variation in pathogens and parasites, and to determine how such patterns could influence hosts. This information is crucial to limit the spread of outbreaks and may aid in the decision-making process should they occur."
4753,Pandemic simulation of antivirals + school closures: buying time until strain-specific vaccine is available,"A strain-specific vaccine is unlikely to be available in the early phases of a potential H5N1 avian influenza pandemic. It could be months and at the current production rate may not provide timely protection to the population. Intervention strategies that control the spread of infection will be necessary in this situation, such as the use of the US stockpile of antiviral medication coupled with a 6-month school closure. The agent-based simulation model, EpiSimS, was used to assess the impact of this intervention strategy followed by three different vaccine approaches: (1) 2-dose, 80% effective, (2) 1-dose, 30% effective, and (3) 1 dose, 80% effective. Simulations show that the combination of antivirals, school closures, and a strain-specific vaccine can reduce morbidity and mortality while in effect. A significant second infection wave can occur with current vaccine technology once school closures are relaxed, though an ideal vaccine is able to contain it. In our simulations, worker absenteeism increases in all cases mostly attributed to household adults staying home with children due to the school closures."
4754,Abstracts of papers submitted to the American Motility Society,
4755,"Human biochemistry and disease: by Gerald Litwack, Elsevier, Amsterdam-Boston-Heidelberg-London-New-York-Oxford-Paris, 2008, 1254 p., $199.95",
4756,Carbon nanotag based visual detection of influenza A virus by a lateral flow immunoassay,"The authors report on a rapid and direct visual test for the detection of influenza A virus using a carbon nanotag based lateral flow assay. Carbon nanoparticles in the form of nanostrings are acting as reporters. As carbon nanotags accumulate in the test zone due to formation of an antibody-antigen-carbon nanotag antibody complex, and this allows for the direct visualization of the analytical signal. Under optimal conditions, influenza A virus can be determined in allantoic fluid inoculated with the virus with a limit of detection of 350 TCID(50).mL(−1) (i.e., the 50% tissue culture infectious dose). No interference is found for several other tested proteins, and for closely related viruses. Cell lysates containing different seasonal strains of influenza A viruses (including the H1N1 and H3N2 strains) collected from clinical samples were analyzed. It is demonstrated that the method can detect both influenza A viruses without interference by biological matrices. In our perception, this method has a wide potential in that it may be extended to a generally applicable platform for rapid diagnosis influenza A viruses. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-017-2191-6) contains supplementary material, which is available to authorized users."
4757,Micro-flow analysis by molecular tagging velocimetry and planar Raman-scattering,"The two dimensional molecular tagging velocimetry (2D-MTV) has been used to measure velocity fields of the flow in a micro mixer. Instead of commonly used micro particles an optical tagging of the flow has been performed by using a caged dye. The pattern generation is done by imaging a mask for the first time. This allows to generate nearly any imaginable pattern. The flow induces a deformation of the optically written pattern that can be tracked by laser induced fluorescence. The series of raw images acquired in this way were analyzed quantitatively with a novel optical flow based technique. The reference measurements have been carried out allowing to draw conclusions about the accuracy of this procedure. A comparison to the standard technique of μPIV has also been conducted. Apart from measuring flow velocities in microfluidic mixing processes, the spatial distribution of concentration fields for different species has also been measured. To this end, a new technique has been developed that allows spatial measurements from Planar Spontaneous Raman Scattering (PSRS). The Raman stray light of the relevant species has been spectrally selected by a narrow bandpass filter and thus detected unaffectedly by the Raman stray light of other species. The successful operation of this measurement procedure in micro flows will be demonstrated exemplary for a mixing process of water and ethanol."
4758,Simulating influenza pandemic dynamics with public risk communication and individual responsive behavior,"Individual responsive behavior to an influenza pandemic has significant impacts on the spread dynamics of this epidemic. Current influenza modeling efforts considering responsive behavior either oversimplify the process and may underestimate pandemic impacts, or make other problematic assumptions and are therefore constrained in utility. This study develops an agent-based model for pandemic simulation, and incorporates individual responsive behavior in the model based on public risk communication literature. The resultant model captures the stochastic nature of epidemic spread process, and constructs a realistic picture of individual reaction process and responsive behavior to pandemic situations. The model is then applied to simulate the spread dynamics of 2009 H1N1 influenza in a medium-size community in Arizona. Simulation results illustrate and compare the spread timeline and scale of this pandemic influenza, without and with the presence of pubic risk communication and individual responsive behavior. Sensitivity analysis sheds some lights on the influence of different communication strategies on pandemic impacts. Those findings contribute to effective pandemic planning and containment, particularly at the beginning of an outbreak."
4759,Detection of the antigen-antibody reaction by light scattering spectroscopy,"The possibility of recording the results of serologic reactions not yielding visible phenomena by means of light scattering spectroscopy (LSS) was studied. Influenza virus andMycoplasma pneumoniae antigens and the corresponding antisera were used as the test objects. It was shown that, in principle, LSS can be used to detect the antigen-antibody complex in serologic reactions not yielding viible phenomena."
4760,What’s New?,
4761,"Issues in infectious diseases, Vol. 4. Emerging viral diseases of Southeast Asia. Lal Sunil K (ed): Karger, Basel, 2007, ISBN 3-8055-8175-0, € 123",
4762,Detection of viral aerosols by use of real-time quantitative PCR,"PCR quantification is regarded as one of the most promising techniques for real-time identification of bio-aerosols. We have, therefore, validated a QPCR assay for quantification of a viral aerosol sample using the double-stranded DNA-binding dye SYBR green I, an economical alternative for quantification of target microorganisms. To achieve this objective we used mycobacteriophage D29 as model organism. Phage D29 aerosol was produced in an aerosol cabinet and then collected by use of an AGI liquid sampler. A standard curve was created by use of purified genomic DNA from the phage in liquid culture of known concentration measured by titration. To prevent false-positive results caused by formation of primer–dimers, an additional data-acquisition step was added to the three-step QPCR procedure; the new technique was called four-step QPCR. The standard curve was then used to quantify the total amount of phage D29 in liquid culture and aerosol samples. For liquid culture samples there was no significant difference (P > 0.05) between results from quantification of the virus using double-agar culture and QPCR. For aerosol samples, however, the result determined by the QPCR method was significantly (P < 0.05) higher than that from the double-agar culture method. The four-step SYBR green I QPCR method is a quick quantitative method for mycobacteriophage D29 aerosol. We believe that QPCR using SYBR green I dye will be an economical method for detection of airborne bio-aerosols."
4763,Advances in molecular phytodiagnostics – new solutions for old problems,"In the last decade, developments in molecular (nucleic acid-based) diagnostic methods have made significant improvements in the detection of plant pathogens. By using methods such as the polymerase chain reaction (PCR), the range of targets that can now be reliably diagnosed has grown to the extent that there are now extremely few, known pathogens that cannot be identified accurately by using laboratory-based diagnostics. However, while the detection of pathogens in individual, infected samples is becoming simpler, there are still many scenarios that present a major challenge to diagnosticians and plant pathologists. Amongst these are the detection of pathogens in soil or viruses in their vectors, high throughput testing and the development of generic methods, that allow samples to be simultaneously screened for large numbers of pathogens. Another major challenge is to develop robust technologies that avoid the reliance on well-equipped central laboratories and making reliable diagnostics available to pathologists in the field or in less-developed countries. In recent years, much of the research carried out on phytodiagnostics has focussed in these areas and as a result many novel, routine diagnostic tests are becoming available. This has been possible due to the introduction of new molecular technologies such real-time PCR and microarrays. These advances have been complemented by the development of new nucleic acid extraction methods, increased automation, reliable internal controls, assay multiplexing and generic amplification methods. With developments in new hardware, field-portable real-time PCR is now also a reality and offers the prospect of ultra-rapid, on-site molecular diagnostics for the first time. In this paper, the development and implementation of new diagnostic methods based upon novel molecular techniques is presented, with specific examples given to demonstrate how these new methods can be used to overcome some long-standing problems."
4764,Ecological Studies of Diseases: Promise and Praxis,
4765,Announcements,
4766,Morphological and biochemical changes in brain cells of mice infected with influenza virus,
4767,Oral session 17: Infection of the nervous system,
4768,"19th European Congress of Pathology, Ljubljana, Slovenia, September 6-11, 2003",
4769,News,
4770,Simultaneous detection of multiple viruses in their co-infected cells using multicolour imaging with self-assembled quantum dot probes,"The simultaneous detection and evaluation of the coinfection of a cell by multiple viruses or even multiple subtypes still is a difficult challenge. The authors introduce a method for simultaneous imaging, detection and quantitative evaluation of multiple viruses in single cells by using multicolor quantum dot (QD) probes and in a single staining cycle. The multicolor QD probes were fabricated via interaction between QDs conjugated to Staph. aureus protein A (SpA-QDs) and virus-specific antibodies. A cocktail of differently colored QD-SpA-MAbs probes were loaded into the same cells containing multiple viruses, and this enabled the different viruses to be fluorescently imaged and analyzed simultaneously. Specifically, influenza A viruses of type H1N1, H3N2, and H9N2, as well as human adenovirus species B type 3 (HAdV-B3) were imaged and detected in virus-infected cells or in their co-infected cells. In our perception, the method provides a flexible platform for simultaneous detection of multiple viruses in co-infected cells. Hence, it offers new opportunities for the molecular diagnosis of virus coinfection and for studies on virus-cell interactions. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00604-017-2300-6) contains supplementary material, which is available to authorized users."
4771,"Key word index Volume 31, 2005",
4772,Emerging and Reemerging Infectious Diseases: Biocomplexity as an Interdisciplinary Paradigm,"Understanding factors responsible for reemergence of diseases believed to have been controlled and outbreaks of previously unknown infectious diseases is one of the most difficult scientific problems facing society today. Significant knowledge gaps exist for even the most studied emerging infectious diseases. Coupled with failures in the response to the resurgence of infectious diseases, this lack of information is embedded in a simplistic view of pathogens and disconnected from a social and ecological context, and assumes a linear response of pathogens to environmental change. In fact, the natural reservoirs and transmission rates of most emerging infectious diseases primarily are affected by environmental factors, such as seasonality or meteorological events, typically producing nonlinear responses that are inherently unpredictable. A more realistic view of emerging infectious diseases requires a holistic perspective that incorporates social as well as physical, chemical, and biological dimensions of our planet’s systems. The notion of biocomplexity captures this depth and richness, and most importantly, the interactions of human and natural systems. This article provides a brief review and a synthesis of interdisciplinary approaches and insights employing the biocomplexity paradigm and offers a social–ecological approach for addressing and garnering an improved understanding of emerging infectious diseases. Drawing on findings from studies of cholera and other examples of emerging waterborne, zoonotic, and vectorborne diseases, a “blueprint” for the proposed interdisciplinary research framework is offered which integrates biological processes from the molecular level to that of communities and regional systems, incorporating public health infrastructure and climate aspects."
4773,Announcements,
4774,The Role of Ecotones in Emerging Infectious Diseases,"Recognition of the significance of the boundary between ecological systems, often referred to as the ecotone, has a long history in the ecological sciences and in zoonotic disease research. More recent research in landscape ecology has produced an expanded view of ecotones and elaboration of their characteristics and functions in ecosystems. Parallel research on emerging infectious diseases (EIDs) and the causes of increased rates of pathogen transmission, spread, and adaptation suggests a correspondence between ecotonal processes and the ecological and evolutionary processes responsible for zoonotic and vector-borne emerging infections. A review of the literature suggests that ecotones play a role in a number of the most important EIDs. Yet these are the only diseases for which specific landscape ecological information exists in the literature or disease reports. However, the similar disease ecologies of these with about half of the approximately 130 zoonotic EIDs suggests ecotones, particularly their anthropogenic origination or modification, may be generally associated with ecotones and the global trend of increasing EIDs."
4775,Book reviews,
4776,Cognitive-Behavioral Treatment of Health Anxiety Disorders,
4777,Keyword Index to Volume 22,
4778,Pneumonien bei immunsupprimierten Patienten,"Pneumonia occurs frequently in immunocompromised patients and often shows a complicated course of disease when compared to immunocompetent persons. The type of pathogen involved is directly associated with the type of immunosuppression and includes a wide variety of pathogens. Congenital and primary immunodeficiencies often appear during childhood. Acquired immunodeficiencies are most commonly caused by immunosuppressive medication. The concept of immunosuppression can be extended to patients with COPD or elderly patients because the variety of pathogens and specific features regarding frequency and course of the disease are similar to immunosuppressed patients. Computed tomography can provide an indication of the pathogen and is superior to the chest x‑ray in this respect. Blood cultures, antigen and PCR tests are non-invasive diagnostic tools for pathogen diagnostics. Invasive tests include fiberoptic bronchoscopy and complete the diagnostic methods of identifying the causative pathogen."
4779,"Selected Abstracts of the Institut Pasteur Euroconference on Angiogenesis, Paris, France 8–9 March 2001",
4780,"Book Review: AMERICA'S FORGOTTEN PANDEMIC. THE INFLUENZA OF 1918. Second Edition. By Alfred W. Crosby, Cambridge: Cambridge University Press, 2003, 337 pp., $60.00 (hardcover), $22.00 (softcover)",
4781,Avian Influenza (H5N1) and the Evolutionary and Social Ecology of Infectious Disease Emergence,
4782,News in Brief,
4783,Das neue Verständnis pulmonaler Infektionen,"Epidemiological data on the distribution of mostly bacterial pathogens are still the basis for empirical treatment recommendations on respiratory infections. Because of the dynamic technological developments in molecular multiplexing and sequencing procedures, the spectrum of potential pathogens is increased and challenges the current dogma of virulence and pathogenicity of certain pathogens. Classical pathogens of the lungs are thereby not questioned but are increasingly placed in a context that reflects co-infections with viruses and changes of the local microbiome in more depth. Recent data indicate that integration of this novel information is required for a better understanding of the seasonal differences in the frequency of particular lung infections and to find new approaches to risk stratification of patients. This becomes most obvious in the subgroup of immunosuppressed patients who are at risk of severe courses of diseases with higher morbidity and mortality from infections with viruses and facultative pathogens, such as nontuberculous mycobacteria (NTM). Based on the fundamental knowledge on the spectrum of pathogens of community-acquired and nosocomial lung infections, novel approaches in pathogen diagnostics and lung microbiome analytics are discussed and the applicability with respect to the current clinical routine is questioned."
4784,"2(nd) World Congress on Women’s Mental Health March 17–20, 2004, Washington, DC",
4785,"Vesicular membrane transfer between endoplasmic reticulum and golgi apparatus of a green alga,Micrasterias americana: A 16°C block and reconstitution in a cell-free system","Transfer of membranes between endoplasmic reticulum and Golgi apparatus of the unicellular green alga,Micrasterias americana, is facilitated by 50–70 nm vesicles that form from part-rough. part-smooth transitional regions of the endoplasmic reticulum. In growing cells, the vesicles are present at the normal growth temperature of 23°C. However, at 16°C, vesicle accumulations occur. Golgi apparatus of non-growing cells exhibited both larger numbers of vesicles and larger dictyosomes at all temperatures. In non-growing cells, vesicle numbers also were increased at 16°C. The 16°C block was reconstituted in a cell-free system using Golgi apparatus-and endoplasmic reticulum-enriched fractions prepared from suspension cultures. When incubated in the presence of ATP and cytosol, transitional endoplasmic reticulum fragments ofMicrasterias responded by formation of membrane blebs and vesicles resembling those seen in situ. When prepared from cells metabolically labeled with [(3)H]leucine, the isolated transition elements supported the transfer of radioactivity of Golgi apparatus preparations immobilized on nitrocellulose strips. The transfer was time-and temperaturedependent and stimulated by ATP. The ATP-dependent component of transfer expressed at 23°C was reduced or absent at temperatures of 16°C or below. This suggested that membrane transfer mediated by transition vesicles was the same rate-limiting step in endoplasmic reticulum to Golgi apparatus membrane trafficking both in situ and in the cell-free system. Growth, as evidenced by a progressively alteredMicrasterias morphology, was slowed at low temperatures but showed no abrupt temperature transition as seen with the vesicular traffic between the endoplasmic reticulum and the Golgi appatus."
4786,"Effect of insulin on Na, K-ATP-ase activity in rat brain microsomes",
4787,Feuchter Husten und protrahierte bakterielle Bronchitis bei Kindern und Jugendlichen,"Persistent cough is one of the most common reasons patients present to outpatient practices. Especially in children, chronic cough (>4 weeks) is a significant burden on the child and family. While in the past, the lower airways were considered sterile, the concept of a physiologic microbiome of the lower respiratory tract has increasingly emerged. Of the differential diagnoses of chronic cough, protracted bacterial bronchitis (PBB) is more common in otherwise (pulmonary) healthy children under 6 years of age. Tracheomalacia may primarily exist or be the result of mechanically straining coughing, whereas apart from a reduced alveolar phagocytosis, there is usually no systemic or local immune weakness. Instead, an activated innate immunity with increased gene expression of the interleukin-1β signaling pathway can be immunologically detected. Here too, it is difficult to differentiate between cause and effect of chronic inflammatory events. Today, PBB and non-CF bronchiectasis, i.e., bronchiectasis not caused by cystic fibrosis (CF), are two sides of a disease spectrum of suppurative lung diseases, thus, making consequent therapy and long-term pediatric pneumological support of children with chronic productive cough necessary."
4788,"Three-step research strategies for ARDS: new target molecules—ACE2, HMGB1, and HSP47",
4789,"Book Review: THE HUMAN IMMUNODEFICIENCY VIRUS. BIOLOGY, IMMMUNOLOGY, AND THERAPY. Edited by Emilio A. Emini, Princeton: Princeton University Press, 2003, 532 pp., $80.00 (hardcover)",
4790,What’s New?,
4791,Low temperature compartment formation in feline immunodeficiency virus-infected and uninfected feline kidney cells,"This study was to determine if feline immunodeficiency virus (FIV)-infected and uninfected Crandall feline kidney (CRFK) cells exhibited a low temperature (16°C) block in membrane trafficking between transitional endoplasmic reticulum and Golgi apparatus represented by intermediate compartment formation. Cells were cultured at different temperatures and membrane changes involving the Golgi apparatus and Golgi apparatus-associated membrane structures were monitored by electron microscopy and quantitated. With 30 min of incubation, membranes of the Golgi apparatus stack increased in amount at temperatures of 16°C and below compared to temperatures above 18°C. The increase was greatest along the major polarity axis as evidenced by an increased stack height. Neither the number of cisternae per stack nor the average stack diameter (width) was affected by temperature. The response was maximal between 15 and 30 min of low temperature treatment of the cells. Results with cells infected and uninfected with feline immunodeficiency virus were similar. The increase in stack height was due primarily to an increase of membranes at the cis face (cis Golgi apparatus network). At 18°C, membranes of the trans Golgi apparatus network accumulated suggesting that import from the cis Golgi network could proceed at this temperature, whereas exit from the trans Golgi network was still at least partially blocked. Also increased at 16°C and below were numbers of transition vesicles in the space between the Golgi apparatus and the transitional endoplasmic reticulum associated with the cis Golgi apparatus face. The results suggested interruption of the orderly flux of membranes into the Golgi apparatus at 16°C and below. Moreover, the block appeared to be reversible. Upon transfer from 16°C to 37°C, there was a time-dependent decrease in the accumulations of cis compartment membrane accompanied by a corresponding equivalent increase in the membranes of the trans Golgi apparatus compartment."
4792,Acute abdominal emergencies associated with cytomegalovirus infection in the young infant,"Gastrointestinal signs and symptoms have rarely been reported in association with cytomegalovirus (CMV) infection in young infants. However, in 1981 clear pathologic evidence was presented implicating this virus as a cause of hypoganglionosis and bowel dysmotility. We report our experience with four infants with CMV infection in whom gastrointestinal dysfunction was the reason for emergency abdominal operation. Since the association was made retrospectively, we were unable to demonstrate hypoganglionosis, but our experience underscores the need to include CMV intestinal infection in the differential diagnosis of the acute surgical abdomen in young infants."
4793,2. Metalloproteins,
4794,Structural Analogs of Umifenovir. 1. Synthesis and Biological Activity of Ethyl 5-Hydroxy-1-Methyl-2-(Trans-2-Phenylcyclopropyl)-1H-Indole-3-Carboxylate,Ethyl 5-hydroxy-1-methyl-2-(trans-2-phenylcyclopropyl)-1H-indole-3-carboxylate is the first prototype of conformationally restricted analogs of umifenovir. It has been prepared using a one-pot method and has undergone an antiviral study.
4795,Virus hepatitis a in lower old-world monkeys (possible model for vaccine testing),
4796,Contents to Volume 27(2005),
4797,Ecology of Infectious Disease: Forging an Alliance,"The Ecology of Infectious Diseases (EID) program is a joint National Science Foundation–National Institutes of Health initiative to produce predictive understanding of disease dynamics, with a focus on diseases with an environmental component. The interdisciplinary research projects funded by this program take advantage of the wide range of theoretical and methodological advances developed over the past 30 years. The challenge for disease ecology is to unravel these systems, discover how complex they truly are, and to determine if they can be predicted and controlled using targeted environmental, public health, or medical interventions. Between 1999 and 2005, a total of 42 research awards were made under the EID program. EID projects have had affects on policy in two areas: adoption of novel interventions on a local scale and use of models by government agencies for the purpose of allocating public health resources. The past 6 years have been an exciting time for the field of disease ecology; we expect the coming years to be even more exciting and productive."
4798,What’s New?,
4799,How to Frame Mobility?,
4800,Predicting social response to infectious disease outbreaks from internet-based news streams,"Infectious disease outbreaks often have consequences beyond human health, including concern among the population, economic instability, and sometimes violence. A warning system capable of anticipating social disruptions resulting from disease outbreaks is urgently needed to help decision makers prepare appropriately. We designed a system that operates in near real-time to identify and predict social response. Over 150,000 Internet-based news articles related to outbreaks of 16 diseases in 72 countries and territories were provided by HealthMap. These articles were automatically tagged with indicators of the disease activity and population reaction. An anomaly detection algorithm was implemented on the population reaction indicators to identify periods of unusually severe social response. Then a model was developed to predict the probability of these periods of unusually severe social response occurring in the coming week, 2 and 3 weeks. This model exhibited remarkably strong performance for diseases with substantial media coverage. For country-disease pairs with a median of 20 or more articles per year, the onset of social response in the next week was correctly predicted over 60% of the time, and 87% of weeks were correctly predicted. Performance was weaker for diseases with little media coverage, and, for these diseases, the main utility of our system is in identifying social response when it occurs, rather than predicting when it will happen in the future. Overall, the developed near real-time prediction approach is a promising step toward developing predictive models to inform responders of the likely social consequences of disease spread. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10479-017-2480-9) contains supplementary material, which is available to authorized users."
4801,Biomedical vignette,
4802,Syndromic Surveillance and Patients as Victims and Vectors,"Syndromic surveillance uses new ways of gathering data to identify possible disease outbreaks. Because syndromic surveillance can be implemented to detect patterns before diseases are even identified, it poses novel problems for informed consent, patient privacy and confidentiality, and risks of stigmatization. This paper analyzes these ethical issues from the viewpoint of the patient as victim and vector. It concludes by pointing out that the new International Health Regulations fail to take full account of the ethical challenges raised by syndromic surveillance."
4803,Web alert,
4804,Surface display of recombinant protein on the cell surface of Bacillus subtilis by the CotB anchor protein,"We developed a novel surface display system based on the CotB anchoring motif in order to express foreign protein on the surface of vegetative Bacillus subtilis cells. CotB is a protein in the B. subtilis spore coat. In this system, three repeats of the immunodominant ovalbumin T-cell epitope (OVA(323–339)) were linked with the cholera toxin B subunit (CTB) to construct a fusion protein, CTB-OVA epi, which was then fused to the C-terminal of the CotB protein so that CTB-OVA epi was expressed in vegetatively-growing B. subtilis. The expression and localization of the CTB-OVA epi protein was confirmed by western blotting, immunofluorescence microscopy, and flow cytometry. The results indicated that a CotB-based surface display system was successfully used to express the CTB-OVA epi protein on the surface of vegetative B. subtilis cells."
4805,Cloning and expression of the membrane protein gene of TGEV HB06 strain,"The membrane protein gene(M) of transmissible gastroenteritis virus (TGEV) strain HB06, isolated from the feces of piglets infected with TGEVon a pig farm in Hebei province, was amplified by reverse transcriptase-polymerase chain reaction (RT-PCR). The amplified PCR products of TGEV HB06 were cloned, sequenced, and compared with other TGEV strains genes selected from the GenBank. Then, the recombinant fragment in pMD18-T was subcloned into corresponding sites of prokaryotic expression vector pGEX-6P-1 after digestion with EcoRI and XhoI to construct a recombinant fusion expression vector pGEX-6P-M. Then, the verified recombinant plasmid was transformed into Escherichia coli Rossetta (DE3), and the expression of M fusion protein was induced by using isopropylthio-beta-D-galactoside (IPTG) as inducer. The results showed that the gene fragment of M at a length of 789 bp was amplified and cloned into the vector pMD18-T successfully, and sequence comparison with that reported in GenBank revealed that the M gene complete sequence shares more than 94% homology in nucleotide. The result of SDS-PAGE showed that the recombinant membrane protein had a molecular mass of approximately 56 kDa, which was the same as the expected results. It was proven by Western blotting that the recombinant membrane protein had strong positive reactions with TGEV-specific antibody. Therefore, the expressed fusion protein has a good antigenicity. This work established a good foundation for further studies on the production of anti-TGEV vaccines."
4806,Annual Meeting Abstracts,
4807,Data Decision and Transmission Based on Mobile Data Health Records on Sensor Devices in Wireless Networks,"The contradiction between a large population and limited and unevenly distributed medical resources is a serious problem in many developing countries. This problem not only affects human health but also leads to the occurrence of serious infection if treatment is delayed. With the development of wireless communication network technology, patients can acquire real-time medical information through wireless network equipment. Patients can have the opportunity to obtain timely medical treatment, which may alleviate the shortage of medical resources in developing countries. This study establishes a new method that can decide and transmit effective data based on sensor device mobile health in wireless networks. History data, collection data, and doctor-analyzed data could be computed and transmitted to patients using sensor devices. According to probability analysis, patients and doctors may confirm the possibility of certain diseases."
4808,"Chandra Wickramasinghe, A Journey with Fred Hoyle: The Search for Cosmic Life. Edited by Kamala Wickramasinghe: World Scientific Publishing, Singapore, 2005, US$ 33.00, ISBN-10 981-238-912-1",
4809,Clinical characteristics of 42 SARS patients and their treatment of integrative Chinese and western medicine,"Objective: To understand the clinical manifestation of severe acute respiratory syndrome (SARS) and explore its effective treatment with integrative Chinese and western medicine (ICWM).Methods: The data of patients, whose diagnosis of SARS had been confirmed were summarized and analyzed, and clinical observation was conducted when the patients were treated with ICWM.Results: In the early stage of the 42 patients, the symptoms revealed were fever in 100% of SARS patients, headache in 92. 9%, aversion to cold in 76. 2%, chest stuffiness in 76. 2%, cough in 73. 8% and myalgia in 88. 1%; pulmonary lesion involves ≥3 lobes in 42. 9%, 2 lobes in 47. 6% and 1 lobe in 9. 5%; 61. 9% of them showed liver function abnormality (increase of ALT or AST), 47. 6% showed elevated myocardial enzyme (CK or CK-MB), 0. 48% showed an inclination of renal function (higher of BUN or Cr); in their T lymphocyte subsets, 91. 2% (31/34 patients) had lowered CD(3) and 76. 5% (26/34 patients) lowered CD(4)/CD(8) ratio. In the mid-late stage, the symptoms were lassitude and weakness in 85. 7%, scare in 81. 0%, short of breath or chest stuffiness in 71. 4%, loss of appetite in 64. 3%; light dark tongue proper in 52.4%, yellow and white tongue coating in 45. 2%, and yellow thick coating on the middle-root part of the tongue in 21. 4%. Most of them were asymptomatic when discharged from hospital, with 92. 8% of their pulmonary lesion, according to chest film, completely absorbed and liver function, myocardial enzyme and renal function all normalized. However, of the 30 patients who had CD(3) reexamination, 70% of the CD(3) showed lower than normal range and 36. 7% showed their CD(4)/CD(8) inclined to lower margin, follow-up should be done for these patients. Of the 42 patients, who received western medicine (WM) alone in the early stage and ICWM in the mid-late stage, 10 were severe cases and 3 critical cases, but none of them died. The mean defervescent time was 3. 52±0. 85 days, the time for complete absorption of pulmonary lesion judged by chest X-ray film was 26. 82±5. 98 days, and the mean hospitalization time was 33. 60±4. 37 days.Conclusion: The manifestation of SARS is multifarious, showing that there were damage in multiple organs. The T lymphocyte count percentage and its subsets, CD(3) and CD(4) /CD(8) ratio, are valuable for early diagnosis and follow-up in the rehabilitation stage. Majority of the patients could be clinically cured. Combined treatment of WM and TCM according to syndrome differentiation and psychiatric intervention are beneficial to remit partial symptoms and promote rehabilitation."
4810,The vignette for V13N3 issue,
4811,Optimization of transfection methods for Huh-7 and Vero cells: A comparative study,"Availability of an efficient transfection protocol is the first determinant in success of gene transferring studies in mammalian cells which is accomplished experimentally for every single cell type. Herein, we provide data of a comparative study on optimization of transfection condition by electroporation and chemical methods for Huh-7 and Vero cells. Different cell confluencies, DNA/reagent ratios and total transfection volumes were optimized for two chemical reagents including jetPEI™ and Lipofectamine™ 2000. Besides, the effects of electric field strength and pulse length were investigated to improve electroporation efficiency. Transfection of cells by pEGFP-N1 vector and tracking the expression of GFP by FACS and Fluorescence Microscopy analysis were the employed methods to evaluate transfection efficiencies. Optimized electroporation protocols yielded 63.73 ± 2.36 and 73.9 ± 1.6% of transfection in Huh-7 and Vero cells respectively, while maximum achieved level of transfection by jetPEI™ was 14.2 ± 0.69 and 28 ± 1.11% Huh-7 and Vero cells, respectively. Post transfectional chilling of the cells did not improve electrotransfection efficiency of Huh-7 cells. Compared to chemical based reagents, electroporation showed superior levels of transfection in both cell lines. The presented protocols should satisfy most of the experimental applications requiring high transfection efficiencies of these two cell lines."
4812,Literature alert,
4813,Prophylactic and therapeutic effects of egg yolk immunoglobulin against porcine transmissible gastroenteritis virus in piglets,"Porcine transmissible gastroenteritis virus (TGEV) is the causative agent of acute diarrhea of newborn piglets that provokes high mortality rates in affected farms. In this study, specific immunoglobulin from egg yolk against TGEV was produced by immunization of White leghorn hens. Enzyme-linked immunosorbent assay (ELISA) and virus neutralization (VN) test revealed that the specific antibody titer started to increase on the tenth day post-immunization, reached its peak on the eighth week, and remained at a high level until the last week that we tested. The prophylactic and therapeutic effects of egg yolk immunoglobulin (IgY) was investigated in piglets. IgY was found effective to increase piglets survival rate significantly after challenge exposures in prophylactic efficacy analysis. The therapeutic effects test revealed that the mortality was dramatically reduced by orally administered IgY. All these results in our study indicated that IgY specific to TGEV could be an alternative prophylactic method like colostral antibodies against TGEV in piglets."
4814,Detection and analysis system for hybridization images of lab-in-a-tube microarray,"A lab-in-a-tube microarray system is developed for sample inspection and signal detection by fabricating a flat transparent window cap of the Eppendorf tube. The oligonucleotide microarray is immobilized on the inner surface of the cap. A small vessel is placed in an Eppendorf tube for storing hybridization solutions. With the microarray system, the full biochemical processes, including gene fragment amplification, fluorescence labeling, hybridization, and fluorescence detection, have been performed in the sealed tube without opening the cap. The images are obtained from a fluorescence microscope and captured by a CCD, and the data are transported to a computer through the universal serial bus (USB). After noise reduction, signal intensity is determined from hybridization image and the presence of gene fragments is identified. The final data output includes sample information, process steps, and hybridization results. A lab-in-a-tube microarray system for detecting ten respiratory viruses at a single detection is designed. High detection throughput and accuracy have been demonstrated with the system."
4815,The vignette for V15 N3 issue,
4816,Virus rejection with two model human enteric viruses in membrane bioreactor system,"A membrane bioreactor (MBR) with gravity drain was tested for virus rejection with two coliphages, T4 and f2, which were used as surrogates for human enteric viruses. Virus rejection was investigated by PVDF and PP membrane modules, with the pore sizes of 0.22 and 0.1 μm, respectively. In tap water system, 2.1 lg rejection of coliphage T4 could be achieved by PVDF membrane compared with complete rejection by PP membrane, while for coliphage f2 with smaller diameter, 0.3–0.5 lg rejection of the influent virus was removed by the two membranes. In domestic wastewater system, cake layer and gel layer on the membrane surface changed the cut-off size of the membrane so that there was no significant difference between PP and PVDF for each coliphage. The removal ratios of coliphage T4 and f2 in the MBR were more than 5.5 and 3.0 lg, respectively. Compared with 5.5 lg removal for virus T4 in the MBR system, only 2.1 lg (96.8%–99.9%) removal rate was observed in the conventional activated sludge system with the influent virus concentration fluctuating from 1830 to 57000 PFU/mL. Only 0.8%–22% virus removal was the effect of adsorption to activated sludge, which showed a decreasing tendency with the retention time, while 75%–98% was the effect of virus inactivation by microbial activity. It indicated that the major mechanism of virus removal was not the transfer of viruses from the water phase to the sludge phase but inactivation in the biological treatment process."
4817,Learn to fight from the war,
4818,Biomedical Vignette,
4819,Reducing Energy Consumption and Overhead Based on Mobile Health in Big Data Opportunistic Networks,"A great number of people and non-equalizing medical resources, in developing countries, have become a serious contradiction. Not only does it affects the person’s life, but also causes serious epidemic contagious, because patients can not get help with hospital on time. With the development of wireless communication network, patient may get medical information by wireless network device. It can alleviate contradictions between patients and medical resources. But in developing countries, population quantity is a big data. How to solve data packets in wireless communication network is a big problem when researchers face huge population. In order to solve some problems in big data communication, this paper founds availability data transmission routing algorithm. This algorithm can reduce energy consumption and overhead, then improve deliver ratio in big data communication. Compare with Spray and Wait algorithm, Binary spray and wait algorithm in opportunistic networks, this algorithm acquires good results by reduce energy consumption, overhead and deliver ratio."
4820,Experimental study on effect of Compound Biejia Ruangan prescription on high-resolution computerized tomographic images in bleomycin induced pulmonary fibrosis rats,"Objective: To study the therapeutic effect of Compound Biejia Ruangan prescription (CBRP) on rat model with pulmonary fibrosis induced by bleomycin.Methods: Fifty-four male Sprague-Dawley rats were randomly divided into 6 groups (9 rats in each group). From the first day to the 28th day of the experiment, except to those in the sham-model control group that were treated with normal saline, the same amount of bleomycin injection as the normal saline given to the control group was given through endotracheal instillation to all the rats in all the other groups. From the 29th day of the modeling, CBRP solution of different dosages was respectively injected into the rats in the high, moderate and low CBRP dose group, while equal volume of normal saline was given to those in the sham-model control group and the model control group, and an equal volume of prednisone solution was given to rats in the prednisone group. On the 80th day, the high-resolution computerized tomographic (HRCT) images were observed on an equal footing, and HRCT-pathology was correlatively studied.Results: Different HRCT pathological changes were shown in the rats with pulmonary fibrosis, such as lung consolidation, thickening of interlobular septum and interlobular mesenchyma as well as lobular deformation, nodule shadow, abnormal brochiovascular tract, thickened pleura with irregular junction and polished glass-like dense shadows. Honeycomb lung was observed in some cases. Pathological sections showed fibrotic proliferation of lung tissues and noticeable pulmonary interstitial fibrosis. CBRP could improve HRCT images of rats with pulmonary fibrosis, and lower fibrotic proliferation of the lung tissue.Conclusion: CBRP plays its therapeutic role possibly through its effect on the structure of the lung in rats with pulmonary fibrosis."
4821,Dynamics of HIV/AIDS in Turkey from 1985 to 2016,"In this paper, we formulated a mathematical model that studies the dynamics of HIV/AIDS in Turkey from 1985 to 2016. We find two equilibrium points, disease free equilibrium and endemic equilibrium. Global stability analysis of the equilibria was conducted using Lyapunov function which depends on the basic reproduction ratio R (0). If R (0) < 1, the disease free equilibrium point is globally asymptotically stable, and if R (0) ≥ 1 the endemic equilibrium point is globally asymptotically stable. We computed and predicted the basic reproduction ratios across all the years. It was found out that there were flaws in the exact values of R (0) which is related to the poor registration system of HIV/AIDS in Turkey. Hence, there is need for the government to improve the system in order to cover the actual cases of the disease. The increase of the basic reproduction ratio over the years also shows the need for the relevant authorities to adopt appropriate control measures in combating the disease."
4822,Therapeutic effect of integrative traditional Chinese and western medicine on 51 SARS patients and its influence on their T lymphocyte subsets,"Objective: To observe the clinical effect of integrative Chinese and western medicine (IC-WM) in treatment of patients with severe acute respiratory syndrome (SARS) and its influence on their T-lymphocyte subsets.Methods: Fifty-one patients with SARS of severe type were observed with synchronous non-randomized controlled method. They were divided into the ICWM group (29 patients) and the western medicine (WM) group (22 patients). Western medical treatment was applied to both groups, but to the ICWM group, Chinese medicine was given additionally. The therapeutic course was 2–3 weeks for both groups. Clinical effect and changes of T-lymphocyte subsets (CD4(+)) after treatment were observed.Results: In the ICWM group, 26 patients (89. 66%) were cured and 3 (10. 34%) died, while in the WM group, 12 (54. 55%) cured and 10 (45. 45%) died, thus comparison of the cure rate between the two groups showing significant difference (P <0.01). The score of clinical symptoms in the ICWM group was decreased from 7.14±5.20 scores before treatment to 1.82±3.75 scores after treatment, while in the WM group, it lowered from 7. 36±3.84 scores before treatment to517±417 scores after treatment, significant difference shown in the comparison of the values between the two groups after treatment (P < 0.01). Immunological function test showed that CD4(+) T-lymphocyte in the ICWM group rose from 361 ± 278 cells/mm(3) before treatment to 630 ± 454 cells/mm(3) after treatment, showing significant difference (P < 001); but in the WM group, it merely rose from 288±186 cells/mm(3) to 376±285 cells/mm(3) in the corresponding period (P > 0.05).Conclusion: ICWM could improve the clinical symptoms of SARS patients markedly, enhance their T-lymphocyte immune function, and reduce their mortality."
4823,Biomedical and Environmental Ethics Alliance: Common Causes and Grounds,"In the late 1960s Van Rensselaer Potter, a biochemist and cancer researcher, thought that our survival was threatened by the domination of military policy makers and producers of material goods ignorant of biology. He called for a new field of Bioethics—“a science of survival.” Bioethics did develop, but with a narrower focus on medical ethics. Recently there have been attempts to broaden that focus to bring biomedical ethics together with environmental ethics. Though the two have many differences—in habits of thought, scope of concern, and value commitments—in this paper we argue that they often share common cause and we identify common ground through an examination of two case studies, one addressing drug development, the other food production."
4824,Effective use of a Limited Antiviral Stockpile for Pandemic Influenza,"Just allocation of resources for control of infectious diseases can be profoundly influenced by the dynamics of those diseases. In this paper we discuss the use of antiviral drugs for treatment of pandemic influenza. While the primary effect of such drugs is to alleviate and shorten the duration of symptoms for treated individuals, they can have a secondary effect of reducing transmission in the community. However, existing stockpiles may be insufficient for all clinical cases. Here we use simple mathematical models to present scenarios where the optimum policies to minimise morbidity and mortality, with a limited drug stockpile, are not always the most intuitively obvious and may conflict with theories of justice. We discuss ethical implications of these findings."
4825,Control of acute virus diseases of calves in the Federal Republic of Germany,"The most important acute viral diseases of calves in the Federal Republic of Germany (FRG) are: 1. Enzootic bronchopneumonia. 2. Bovine viral diarrhoea — mucosal disease (BVD-MD). 3. Infectious bovine rhinotracheitis — infectious pustular vulvovaginitis (IBR-IPV). 4. Rota- and Coronavirus infections. The incidence, diagnosis and control of these infections in the FRG are discussed. Stomatitis papulosa and malignant catarrhal fever are also briefly mentioned."
4826,Organization and regulation of nucleocytoplasmic transport,"Separation of DNA replication and transcription, which occur in the nucleus, from protein synthesis, which occurs in the cytoplasm, allows a more precise regulation of these processes. Selective exchange of macromolecules between the two compartments is mediated by proteins of the nuclear pore complex (NPC). Receptor proteins of the karyopherin family interact with NPC components and transfer their cargos between the nucleus and cytoplasm. Nucleocytoplasmic transport pathways are regulated at multiple levels by modulating the expression or function of individual cargoes, transport receptors, or the transport channel. The regulatory levels have increasingly broad effects on the transport pathways and affect a wide range of processes from gene expression to development and differentiation."
4827,Emerging research fronts in science and technology: patterns of new knowledge development,"Research fronts represent the most dynamic areas of science and technology and the areas that attract the most scientific interest. We construct a methodology to identify these fronts, and we use quantitative and qualitative methodology to analyze and describe them. Our methodology is able to identify these fronts as they form—with potential use by firms, venture capitalists, researchers, and governments looking to identify emerging high-impact technologies. We also examine how science and technology absorbs the knowledge developed in these fronts and find that fronts which maximize impact have very different characteristics than fronts which maximize growth, with consequences for the way science develops over time."
4828,Targeting and expression of antigenic proteins in transgenic plants for production of edible oral vaccines,"Exploiting plants as biological bioreactors for production and delivery of edible oral subunit vaccines is a promising application of biotechnology. Efforts to enhance expression levels of transgenes coding for antigenic proteins by exploiting promoters, targeting sequences, and enhancer elements have produced rather low quantities of the antigen in plant tissues, but enough to induce immune responses in feeding studies. This review will cover components of various gene constructs used in developing plant-based vaccines against a myriad of viral and bacterial diseases. Specifically, it will focus on sequences that are involved in targeting the antigen to mucosal tissues of the intestinal tract, thus enhancing the immunogenicity of the plant-based vaccine as well as those components that result in higher accumulation of the protein within the plant."
4829,Enterotoxins from gram-negative bacteria relevant for veterinary medicine,"The chemistry, mechanism of action, assay methods, pharmacology, and prevention and treatment of diarrhoea due to toxins of gram-negative microbes are discussed. Other virulence factors are mentioned briefly. Special emphasis is placed on non-specific treatment by oral rehydration."
4830,In situ airborne virus inactivation by microwave irradiation,"Infectious diseases cause tremendous costs of both human and economy annually. Previously, we have studied the bacterial, fungal, and allergen aerosol inactivation by direct microwave irradiation. Here, we further investigated its effects on airborne viruses. MS2 coliphage used as a human model virus was aerosolized and exposed to the direct microwave irradiation for ~2 min at three different power levels (700, 385, and 119 W). In addition to the survival rate, the viral genes before and after the microwave treatments were also examined using PCR and gel electrophoresis. Direct exposure of airborne MS2 viruses to the microwave irradiation at 700 W for less than 2 min was shown to result in more than 90 % inactivation efficiency, about 65 % at medium power level (385 W), and 50 % at the lowest level (119 W). The aerosol inactivation rate followed a linear relationship with the microwave exposure time (R (2) = 0.9889). Scanning electron images revealed visible damages to the viral surface after the exposure. Damages were also observed to the viral RNA genes coding for coat proteins, among which the A protein gene was completely destroyed. This study demonstrated that even without the filtration the direct microwave irradiation could also achieve rapid inactivation of viral aerosols. The information obtained can provide useful guidance on the development of microwave-based viral threat mitigation solutions in a closed or semi-closed space."
4831,Search for the new potential RNA thermometers in the genome of Salmonella enterica,"Currently, a number of structurally and functionally different temperature-sensitive elements such as RNA thermometers which control a variety of biological processes in bacteria, including virulence, are known. Based on computer and thermodynamic analysis of completely sequenced genomes of 25 Salmonella enterica isolates, the algorithm and criteria for the search of potential RNA thermometers were developed. It will make it possible to carry out the search for potential riboswitches in the genome of other socially important pathogens. For S. enterica, apart from the known 4U RNA thermometer, four hairpin-loop structures were identified which may probably act as additional RNA thermometers. They satisfy the necessary and sufficient conditions for formation of RNA thermometers and are highly conservative uncanonical structures, since these highly conservative structures were found in the genome of all 25 isolates of S. enterica. The hairpins forming a cruciform structure in the supercoiled pUC8 DNA were visualized by atomic force microscopy."
4832,Transgenic plants for animal health: plant-made vaccine antigens for animal infectious disease control,"A variety of plant species have been genetically modified to accumulate vaccine antigens for human and animal health and the first vaccine candidates are approaching the market. The regulatory burden for animal vaccines is less than that for human use and this has attracted the attention of researchers and companies, and investment in plant-made vaccines for animal infectious disease control is increasing. The dosage cost of vaccines for animal infectious diseases must be kept to a minimum, especially for non-lethal diseases that diminish animal welfare and growth, so efficient and economic production, storage and delivery are critical for commercialization. It has become clear that transgenic plants are an economic and efficient alternative to fermentation for large-scale production of vaccine antigens. The oral delivery of plant-made vaccines is particularly attractive since the expensive purification step can be avoided further reducing the cost per dose. This review covers the current status of plant-produced vaccines for the prevention of disease in animals and focuses on barriers to the development of such products and methods to overcome them."
4833,Clinical controlled study of integrative Chinese and western medicine in treating 49 cases of SARS,"Objective: To evaluate the efficacy of integrative Chinese and western medicine (ICWM) in treating severe acute respiratory syndrome (SARS) patients.Methods: Through parallel control design, 49 SARS patients were observed. Used as control, there were in the western medicine (WM) group 29 patients, who were treated with Ribavirin, Levofloxacin, Thymopentin, Azithromycin, methylprednisolone, etc., on the basis of “Recommended Protocol for Infectious Atypical Pneumonia” (abbreviated as “Recommended Protocol”) issueed by Ministry of Health. As the treated group, there were in the ICWM 20 cases. The protocol for treatment of SARS in “Special Science and Technological Action to Prevent and Treat SARS” (abbreviated as “Special S-T Action”), issued by Ministry of Science and Technology, together with the same WM as those for the control group.Results: (1) Time from the disease onset to the symptom improvement were 5.10±2. 83 days and 7. 62±2. 27 days in ICWM and WM group respectively,P < 0.05; (2) As to corticosteroid (CS) amount and days before reducing dosage, 2 groups showed no significant difference,P > 0.05; (3) There was no significant difference in the time from disease onset to the body temperature normalization and the total amount of CS and the duration of using CS before reducing it to 80 mg between the ICWM group and the WM group; (4) The days and amounts for use CS after reducing between the ICWM group and the WM group were significantly different (P < 0. 05).Conclusion: There were obvious advantages in ICWM to treat SARS, compared with that of WM alone, especially in improving the clinical symptoms, promoting the recovery of immune function, promoting the absorption of pulmonary inflammation and reducing the dosage and duration of CS treatment."
4834,Animal Symposia,
4835,Role of siRNAs and miRNAs in the processes of RNA-mediated gene silencing during viral infections,"Phenomenon of RNA-induced gene silencing is a highly conservative mechanism among eukaryotic organisms. Several classes of small RNAs (siRNAs and miRNAs) 21–25 nt in length, which play a significant role in the processes of development of an organism, occurred important components of antiviral defence in animals and plants. This review shortly describes the main stages of gene silencing mechanism, features of antiviral RNA silencing in plants, invertebrates, mammals, ways of suppression of RNA-interference by viruses, as well as possible approaches of utilization of abovementioned phenomenon for struggling against viral infections."
4836,Recognition for avian influenza virus proteins based on support vector machine and linear discriminant analysis,"Total 200 properties related to structural characteristics were employed to represent structures of 400 HA coded proteins of influenza virus as training samples. Some recognition models for HA proteins of avian influenza virus (AIV) were developed using support vector machine (SVM) and linear discriminant analysis (LDA). The results obtained from LDA are as follows: the identification accuracy (R (ia)) for training samples is 99.8% and R (ia) by leave one out cross validation is 99.5%. Both R (ia) of 99.8% for training samples and R (ia) of 99.3% by leave one out cross validation are obtained using SVM model, respectively. External 200 HA proteins of influenza virus were used to validate the external predictive power of the resulting model. The external R (ia) for them is 95.5% by LDA and 96.5% by SVM, respectively, which shows that HA proteins of AIVs are preferably recognized by SVM and LDA, and the performances by SVM are superior to those by LDA."
4837,"Synthesis, Biological Evaluation and Ligand Based Pharmacophore Modeling of New Aromatic Thiosemicarbazones as Potential Anticancer Agents","Two series of new aromatic thiosemicarbazone derivatives were synthesized by condensation of N-(4-cyanophenyl)hydrazine carbothioamide (I) and N-(4-methylsulfanylphenyl)hydrazine carbothioamide (II) with appropriate aromatic aldehydes in order to investigate their antiviral and cytostatic potency. The chemical structures of all compounds were fully characterized by elemental analysis and spectroscopic techniques. The results of the bioassays indicated that compounds Id, Ie, If and IIf proved inhibitory against influenza virus A (EC(50) = 13 – 27 μg/mL for strain H1N1 and 9.3 – 18 μg/mL for strain H3N2). Compounds Ig and IIg were the most cytostatic compounds with inhibition of HeLa cell proliferation at an IC(50) = 0.3 μg/mL for Ig and 1.9 μg/mL for IIg. Especially, compound Ig showed the highest cytostatic activity with IC(50) of 0.30, 0.70 and 2.50 μg/mL against HeLa, CEM and L1210 cell lines, respectively. This inhibition range was within the same order of magnitude as that for cisplatin. Furthermore, molecular modeling was carried out to examine the cytostatic activity and determine the best pharmacophore model as a guide for the design and development of potential prodrugs in future studies."
4838,Biomedical vignette,
4839,Applying integrative Chinese and western medicine in fighting SARS,
4840,Erratum to: Candidate Genes Associated with Susceptibility for SARS-Coronavirus,
4841,Potential thermosensitive riboswitches in the genome of Salmonella,"Currently, a number of structurally and functionally different thermosensitive elements, such as structurally and functionally different RNA thermometers, for controlling a variety of biological processes in bacteria, including virulence are known. These well-known RNA thermometers are structures, whether matched or mismatched, which are represented by either a single stretched hairpin structure or a few hairpins. Based on computer and thermodynamic analyses of 25 isolates of Salmonella enterica with complete genome, we have developed an algorithm and criteria to search for potential RNA thermometers, which will enable us to undertake a future search for potential riboswitches in the genomes of other socially significant pathogens. In addition to the well-known 4U RNA thermometer, another four hairpin-loop structures have been identified in S. enterica as new potential RNA thermometers and two of them are localized in 5′-UTR of virulence regulators gltB and yaeQ. They are highly conserved noncanonical structures and correspond to the necessary and sufficient conditions for forming RNA thermometers, since they are found in each of the 25 S. enterica genome isolates. We analyzed the thermosensitive motif in the pXO1 plasmid of Bacillus anthracis—an anthrax-causative pathogen—and visualized matched hairpins that form a cruciform structure in pUC8 supercoiled plasmid by atomic force microscopy."
4842,Evaluation of Total Proteins and Serum Protein Fractions in Cats Naturally Infected by Leishmania infantum–A Preliminary Study,
4843,Preparation and physicochemical property of chicken yolk immunoglobulin (IgY) against porcine transmissible gastroenteritis virus (TGEV),"Oral administration of immunoglobulin prepared from the egg yolk of hens immunized with porcine transmissible gastroenteritis virus (TGEV) has been demonstrated to reduce piglets mortality significantly in our previous studies. In the present study, we investigated the stability of chicken yolk immunoglobulin (IgY) specific to TGEV by measuring the remaining activity by ELISA. The results showed that the IgY was stable between pH 4 and pH 11. In the incubation with pepsin at pH 4 and pH 6, about 90% and 100% of the IgY activity remained, respectively. IgY activity could remain approximately 80% at 60°C for 30 min, suggesting that pasteurization can be applied to sterilizing the product. The stability of IgY at 25°C and freezing-thawing treatment indicated that the IgY was easy to be conserved. These results highlight the attractive potential application of IgY as the antibodies of oral administration for treatment of TGEV infections."
4844,The effect of adjuvants on vaccine-induced antibody response against influenza in aged mice,"While influenza remains a major threat to public health, researchers continue to search for a universal solution to improving the efficacy of the influenza vaccine. Even though influenza affects people of all different ages, it can be extremely hazardous to people of 65 years of age or older since that is the population that makes up the high majority of the death toll caused by influenza-related diseases. Elderly individuals suffer the effects of immunosenescence as they age, which is the diminishing of the overall immune response. Immunosenescence occurs by specifically affecting the adaptive immune response which controls the establishment of immunity after vaccination or infection. There are many studies under way that are trying to find a resolution to the problem of the influenza vaccine not providing enough protection in the elderly population. One of the possible strategies is to seek the use of an optimal adjuvant, an immunological agent that can enhance immune responses, with the current vaccine formulation. Here, we used the murine model to review the effects of adjuvants on the antibody response to influenza vaccines in aged mice. Since adjuvants can enhance the production of important inflammatory cytokines and activation of dendritic cells, the stimulation of these cells are boosted to increase the effectiveness of the influenza vaccine in aged mice which would hopefully translate to the elderly."
4845,Population-genetic study of Balkan endemic nephropathy in Serbia,"The study of Balkan endemic nephropathy (BEN) in the affected localities of southern Serbia shows population-genetic difference between samples of BEN affected individuals and control group consisting of non-affected individuals from the same localities. Detailed population-genetic study in village Chepure, which includes 20 large families where BEN is present in 646 (from first to fourth degree) relatives of probands, shows a familial character of disease as well as significant genetic influences in expression of the illness. Our study of genetic homozygosity degree includes an analysis of the presence, distribution and individual combination of 20 to 30 selected genetically controlled morphophysiological traits in the sample of BEN patients and in the control-healthy group. Assuming that BEN is genetically controlled disease, we made a hypothesis that an increased homozygosity level, as well as the changed variability among the patients, could be populationgenetic parameter for the prediction of the illness. Taking into consideration our experience, as well as the experience of numerous scientists who studied the nature of the inheritance of mono-and oligo-genically controlled qualitative traits, we applied a methodology to estimate the proportion of such homozygously recessive characters (HRC-test). This population-genetic study did not only show statistically significant difference of the mean values of genetic homozygosity (BEN: 8.7 ± 0.3; control: 7.6 ± 0.3), but of the differences in the type of distribution too, as well as the differences in the presence of certain individual combinations of such traits."
4846,"Infection and immunity in farm animals: R. Pandey (ed). Progress in veterinary microbiology and immunology, vol. 1, S. Karger, Basel, Switzerland, 1985. 225 pp, US$98.25, ISBN 3 8055 3925 8",
4847,"Evolution of virulence, environmental change, and the threat posed by emerging and chronic diseases","Assessments of future threats posed by infection have focused largely on zoonotic, acute disease, under the rubric “emerging diseases.” Evolutionary and epidemiological studies indicate, however, that particular aspects of infrastructure, such as protected water supplies, vector-proof housing, and health care facilities, protect against the emergence of zoonotic, acute infectious diseases. While attention in the global health community has focused on emerging diseases, there has been a concurrent, growing recognition that important chronic diseases, such as cancer, are often caused by infectious agents that are already widespread in human populations. For economically prosperous countries, the immediacy of this threat contrasts with their infrastructural protection from severe acute infectious disease. This reasoning leads to the conclusion that chronic infectious diseases pose a more significant threat to economically prosperous countries than zoonotic, acute infectious diseases. Research efforts directed at threats posed by infection may therefore be more effective overall if increased efforts are directed toward understanding and preventing infectious causes of chronic diseases across the spectrum of economic prosperity, as well as toward specific infrastructural improvements in less prosperous countries to protect against virulent, acute infectious diseases."
4848,Laboratory diagnosis methods for bovine respiratory syncytial virus,"Laboratory diagnosis of bovine respiratory syncytial (BRS) virus no longer poses a problem. Clinical diagnosis, based on signs of pulmonary emphysema manifest in autumn, should be confirmed by laboratory techniques. Direct isolation of the BRS virus from field samples in cell cultures is often unsuccessful, whereas detection of the viral antigens by staining ultra-thin tissue sections with fluorescein isothiocyanate antibody conjugates is highly effective. Complement fixation and especially indirect immunofluorescence tests are still very useful for the detection of BRS specific antibodies in serum and nasal mucus."
4849,Book Reviews,
4850,Screening efficient siRNAs in vitro as the candidate genes for chicken anti-avian influenza virus H5N1 breeding,"The frequent disease outbreaks caused by avian influenza virus (AIV) not only affect the poultry industry but also pose a threat to human safety. To address the problem, RNA interference (RNAi) has recently been widely used as a potential antiviral approach. Transgenesis, in combination with RNAi to specifically inhibit AIV gene expression, has been proposed to make chickens resistant to avian influenza. For the transgenic breeding, screening the efficient siRNAs in vitro as the candidate genes is one of the most important tasks. Here, we combined an online search tool and a series of bioinformatics programs with a set of rules for designing the siRNAs targeting different mRNA regions of AIV H5N1 subtype. By this method we chose five rational siRNAs, constructed five U6 promoter-driven shRNA expression plasmids contained the siRNA genes, and used these to produce stably transfected Madin-Darby canine kidney (MDCK) cells. Data from virus titration, IFA, PUI-stained flow cytometry, real-time quantitative RT-PCR and DAS-ELISA analyses showed that all five stably transfected cell lines were effectively resistant to viral replication when exposed to 100 CCID50 of AIV, and we finally chose the most effective plasmids (pSi-604i and pSi-1597i) as the candidates for making the transgenic chickens. These findings provide baseline information for breeding transgenic chickens resistant to AIV in combination with RNAi."
4851,The spreading frontiers of avian-human influenza described by the free boundary,"In this paper, a reaction-diffusion system is proposed to investigate avian-human influenza. Two free boundaries are introduced to describe the spreading frontiers of the avian influenza. The basic reproduction numbers r (0)(F) (t) and R (0)(F)(t) are defined for the bird with the avian influenza and for the human with the mutant avian influenza of the free boundary problem, respectively. Properties of these two time-dependent basic reproduction numbers are obtained. Sufficient conditions both for spreading and for vanishing of the avian influenza are given. It is shown that if r (0)(F) (0) < 1 and the initial number of the infected birds is small, the avian influenza vanishes in the bird world. Furthermore, if r (0)(F) (0) < 1 and R (0)(F)(0) < 1, the avian influenza vanishes in the bird and human worlds. In the case that r (0)(F) (0) < 1 and R (0)(F)(0) > 1, spreading of the mutant avian influenza in the human world is possible. It is also shown that if r (0)(F) (t (0)) ⩾ 1 for any t (0) ⩾ 0, the avian influenza spreads in the bird world."
4852,The characteristics and dynamic changes of X-ray chest film in 50 patients with severe acute respiratory syndrome,
4853,The bedford-stuyvesant healthy homes initiative: A comprehensive approach to residential hazard assessment and control,
4854,Effects of integrative Chinese and Western medicine on arterial oxygen saturation in patients with severe acute respiratory syndrome,"Objective: To evaluate the effects of treatment of integrative Chinese and Western medicine (ICWM) on arterial oxygen saturation (SaO(2)) in patients with severe acute respiratory syndrome (SARS).Methods:The non-randomized, controlled trial was conducted on 447 SARS patients treated synchronously with western conventional treatment (WM group,n = 171) alone and ICWM (ICWM group,n = 276). The changes of the cases with normal level (≥95%) or abnormal level (<95%) SaO(2) were observed dynamically.Results: In the 3rd-14th day of the therapeutic course, the percentage of patients with normal SaO(2 ) in the ICWM group was higher than that in the WM group (OR = 0. 5178,P = 0.0038), and this tendency was more evident in patients of the severe type (OR = 0.18,P = 0.0001). However, the statistical significance of difference was only shown in patients for whom the ICWM treatment started in the early period after the onset (<-7 days after it, OR = 0.3803,P = 0.006), but not shown in those who received ICWM treatment later in the mid-late period of SARS (P>0.05).Conclusion: ICWM treatment, particularly when it is used for intervention in the early stage, is beneficial for maintaining normal SaO(2) in SARS patients."
4855,Identification of indoor contaminant source location by a single concentration sensor,"Methods of maximum correlation coefficient (MCC) and the minimum discrete degree (MDD) are developed to identify the location of indoor contaminant source. These two methods are simple, effective, and economic due to the need of only one sensor. The methods are validated by a three-dimensional case study. The effects of the sampling time, the sampling interval, and the sensor response time and measurement error on the location identification of the contaminant source are analyzed. The results indicate that the identification performance of the MDD method is better than that of the MCC method; however, the MDD requires a fast response and high-accuracy sensor. MCC method not only has smaller effects of response time and measurement error compared with the MDD method but it also does not require high-performance (accuracy) sensor and it is not suitable for fast identification in a short time. For source location identification, the two methods need to properly choose sampling time, sampling interval, and response time."
4856,Analysis and comparison of the tongue picture of 34 patients with severe acute respiratory syndrome,"Objective: To explore the changes of tongue pictures in the developing process of disease in patients with severe acute respiratory syndrome (SARS), and to compare the tongue pictures of SARS patients with those of suspected SARS patients.Methods: Materials of tongue picture were dynamically collected from 34 SARS patients and 35 suspected SARS patients, and the difference and similarity between them were analyzed. Meanwhile, the changes in clinic symptoms and tongue picture after integrative medicinal treatment were observed.Results: Characteristics of tongue picture in SARS patients were changed along with the progress of the disease, showing that there existed a tendency of the pathogen invading from exterior to interior, from surface to the deep. Also the tongue pictures were varied due to the coexistence of dampness pathogen; the time of the early stage was generally 1–1.5 days, shorter than that of other stages. While in the patients with suspected SARS, the tongue picture was mostly red with thin white or yellow coating, comparatively steady and showing no obvious change along with the development of the disease.Conclusion: Observing the tongue picture and its changes in different stages can be helpful to understanding the property of pathogenic evil and its developing rules, thus offering a basis for clinical treatment."
4857,Vignette for V13N1 issue,
4858,Immune responses of a designed HIV-1 DNA vaccine on rhesus monkeys,"An effective HIV-1 vaccine will be the ultimate solution for the prevention of HIV/AIDS, though HAART plays important roles in treating the disease. In this study, a large-scale recombinant DNA plasmid containing a designed HIV-1 multi-epitope-p24 chimeric gene was prepared and purified. Rhesus monkeys were then inoculated muscularly with the plasmid for four times in week 0, 4, 8 and 18. Whole blood was collected two weeks after the third and fourth inoculation, followed by serum and peripheral blood mononuclear cell (PBMC) separation. The CTL activity and proliferation of PBMCs stimulated by macaque MHC-I-restricted HIV-1 CTL epitope peptide were analyzed by MTT and LDH release assay, respectively. Th1 cytokines in supernatant of cultured PBMC stimulated by HIV-1 CTL epitope peptide and anti-HIV-1 antibody in serum were assayed by ELISA. The results showed that increased CTL target-killing activity, higher secretion of Th1 cytokines (IFN-γ and IL-2) and promoted proliferative reaction of monkey PBMCs stimulated by HIV-1 CTL epitope peptide were detected in the immunization group inoculated by the recombinant DNA vaccine for three times, which were further enhanced by the fourth inoculation. At the same time, HIV-1 specific antibody in serum of immunized monkeys was higher than that in controls. We concluded that the designed HIV-1 DNA vaccine may induce HIV-1 specific cellular and humoral immunity on monkeys."
4859,"Preparation, identification, and clinical application of anti-HBs monoclonal antibody that binds both wild-type and immune escape mutant HBsAgs","Using a standard cellular fusion technique and indirect enzyme-linked immunosorbent assay (ELISA), a hybridoma cell line strain secreting anti-HBs monoclonal antibody (mAb) (defined G6 mAb) was obtained. The cells grew and secreted mAb stably. Antibody titers in the culture supernatant and ascites were 2.048×10(6) and 4.096×10(6), respectively. By applying the anti-HBs G6 mAb and horseradish peroxidase (HRP)-labeled goat anti-HBs antibody, we developed a sandwich ELISA (defined G6m ELISA) for detecting both wild-type and immune escape mutant HBsAgs (IEM HBsAg). The assay was performed to detect 17 species of genome recombinant expression HBsAg, including two wild-type species and 15 IEM HBsAg species, which varied in the “a” determinant, in a group of patients infected with hepatitis B virus (HBV). The patients previously had a lower ELISA detection signal [(absorbance of patients/absorbance of normal people (P/N): 1.0–4.5)]. The results demonstrated that the sensitivity of this assay to wild-type HBsAg was no less than 0.125 μg/L; 12 of 15 IEM HBsAg species (P/N⩾2.5) were positive for G6 mAb. Of the positive IEM HBsAg species, two had a low absorbance value at 450 nm (A (450)), one had an intermediate A450 value and nine had a high A (450) value, which was 7.55%(mean), 59.4%and 92.1%–109.4% of the wild-type A (450) value, respectively. The two species with low A (450) value and the three negative species mutated at the bases 120–124 in the first loop of the HBV “a” determinant. Using the G6 ELISA and two commercial ELISA kits (A and B), 177 patients were tested. The G6 ELISA had a significantly higher detection rate than either commercial ELISAs (19.21% vs 14.89% and 6.21%, respectively; P<0.01, P<0.05, respectively)."
4860,Stochastic dynamic model of SARS spreading,"Based upon the simulation of the stochastic process of infection, onset and spreading of each SARS patient, a system dynamic model of SRAS spreading is constructed. Data from Vietnam is taken as an example for Monte Carlo test. The preliminary results indicate that the time-dependent infection rate is the most inportant control factor for SARS spreading. The model can be applied to prediction of the course with fluctuations of the epidemics, if the previous history of the epidemics and the future infection rate under control measures are known."
4861,Biomedical Vignette,
4862,Homelessness and housing,
4863,"Construction of a CaHPO(4)-PGUS1 hybrid nanoflower through protein-inorganic self-assembly, and its application in glycyrrhetinic acid 3-O-mono-β-d-glucuronide preparation","Glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG), an important pharmaceutical intermediate and functional sweetener, has broad applications in the food and medical industries. A green and cost-effective method for its preparation is highly desired. Using site-directed mutagenesis, we previously obtained a variant of β-glucuronidase from Aspergillus oryzae Li-3 (PGUS1), which can specifically transform glycyrrhizin (GL) into GAMG. In this study, a facile method was established to prepare a CaHPO(4)-PGUS1 hybrid nanoflower for enzyme immobilization, based on protein-inorganic hybrid self-assembly. Under optimal conditions, 1.2 mg of a CaHPO(4)-PGUS1 hybrid nanoflower precipitate with 71.2% immobilization efficiency, 35.60 mg·g(−1) loading capacity, and 118% relative activity was obtained. Confocal laser scanning microscope and scanning electron microscope results showed that the enzyme was encapsulated in the CaHPO(4)-PGUS1 hybrid nanoflower. Moreover, the thermostability of the CaHPO(4)-PGUS1 hybrid nanoflower at 55°C was improved, and its half-life increased by 1.3 folds. Additionally, the CaHPO(4)-PGUS1 hybrid nanoflower was used for the preparation of GAMG through GL hydrolysis, with the conversion rate of 92% in 8 h, and after eight consecutive runs, it had 60% of its original activity."
4864,Review on supermolecules as chemical drugs,"Supramolecular medicinal chemistry field has been a quite rapidly developing, increasingly active and newly rising interdiscipline which is the new expansion of supramolecular chemistry in pharmaceutical sciences, and is gradually becoming a relatively independent scientific area. Supramolecular drugs could be defined as medicinal supermolecules formed by two or more molecules through non-covalent bonds. So far a lot of supermolecules as chemical drugs have been widely used in clinics. Supermolecules as chemical drugs, i.e. supramolecular chemical drugs or supramolecular drugs, which might have the excellences of lower cost, shorter period, higher potential as clinical drugs for their successful research and development, may possess higher bioavailability, better biocompatibility and drug-targeting, fewer multidrug-resistances, lower toxicity, less adverse effect, and better curative effects as well as safety, and therefore exhibit wide potential application. These overwhelming advantages have drawn enormous special attention. This paper gives the definition of supramolecular drugs, proposes the concept of supramolecular chemical drugs, and systematically reviews the recent advances in the research and development of supermolecules, including organic and inorganic complex ones as chemical drugs in the area of antitumor, anti-inflammatory, analgesic, antimalarial, antibacterial, antifungal, antivirus, anti-epileptic, cardiovascular agents and magnetic resonance imaging agents and so on. The perspectives of the foreseeable future and potential application of supramolecules as chemical drugs are also presented."
4865,Meeting Report and Abstracts of the 2005 UC Davis Transgenic Animal Research Conference V,
4866,Modified Atmosphere Packaging Technology of Fresh and Fresh-cut Produce and the Microbial Consequences—A Review,"Modified atmosphere packaging (MAP) technology offers the possibility to retard the respiration rate and extend the shelf life of fresh produce, and is increasingly used globally as value adding in the fresh and fresh-cut food industry. However, the outbreaks of foodborne diseases and emergence of resistant foodborne pathogens in MAP have heightened public interest on the effects of MAP technology on the survival and growth of pathogenic organisms. This paper critically reviews the effects of MAP on the microbiological safety of fresh or fresh-cut produce, including the role of innovative tools such as the use of pressurised inert/noble gases, predictive microbiology and intelligent packaging in the advancement of MAP safety. The integration of Hazard Analysis and Critical Control Points-based programs to ensure fresh food quality and microbial safety in packaging technology is highlighted."
4867,Recent developments in the use of transgenic plants for the production of human therapeutics and biopharmaceuticals,"In recent years there has been a dramatic increase in the application of plant biotechnology for the production of a variety of commercially valuable simple and complex biological molecules (biologics) for use in human and animal healthcare. Transgenic whole plants and plant cell culture systems have been developed that have the capacity to economically produce large-scale quantities of antibodies and antibody fragments, antigens and/or vaccine epitopes, metabolic enzymes, hormones, (neuro)peptides and a variety of biologically active complexes and secondary metabolites for direct use as therapeutic agents or diagnostic tools in the medical healthcare industry. As the products of genetically modified plants make their way from concept to commercialization the associated risks and acceptance by the public has been become a focal point. In this paper, we summarize the recent advances made in the use of transgenic plants and plant cell cultures as biological factories for the production of human therapeutics and biopharmaceuticals and discuss the long-term potential of `molecular farming' as a low-cost, efficient method for the production of biological materials with demonstrated utility to the pharmaceutical industry or medical community."
4868,"Molecular cloning, genomic structure, polymorphism and expression analysis of major histocompatibility complex class IIA gene of swamp eel Monopterus albus","Major histocompatibility complex (MHC) class II molecules play an important role in the immune response of vertebrates. In this paper, full-length MHC IIA cDNA was isolated from swamp eel (Monopterus albus) by rapid amplification of cDNA ends PCR. The genomic structure, molecular polymorphism, tissue distribution, and immune response of the MHC IIA gene to bacterial challenge were investigated. The full-length cDNA (GenBank accession No.: KC616308) is 1,509 bp in length including an 83 bp-long 5′ untranslated region (UTR) and a 709 bp-long 3′ UTR, which encoded a 238 amino acids protein. In the 2,339 bp-long MHC IIA genomic DNA, four exons and three introns were identified. Sequence comparison exhibited that the deduced amino acid sequence shared 27.1–66.3% identity with those of other species. Seven alleles were identified from five healthy individuals. Number of alleles per individual diversified from two to five. Five different 5′ UTR sequences and two different 3′ UTR sequences from one individual may infer the existence of five loci at least. Real-time quantitative PCR demonstrated that swamp eel MHC IIA transcripts were ubiquitously expressed in ten tissues, but the expression level was distinctly different. Significant changes were observed in liver, spleen, kidney and intestine after challenged with pathogenic bacteria Aeromonas hydrophilia."
4869,CT manifestations of lung changes and complications in patients with severe acute respiratory syndrome,"Objective: To investigate the role of CT scanning in diagnosing severe acute respiratory syndrome (SARS).Methods: One hundred and twelve times of spiral CT scanning, 106 times on the chest with standard pulmonary and mediastinal window, 5 on the brain and once on the abdomen, were performed in 82 patients (37 males and 45 females) of SARS.Results: Bilateral shadows showed in 66 patients (80.48%) and unilateral shadow in 16 (19.52%). The lung CT findings were sub-pleural focal consolidation in 26 patients (31.70%), flaky cloudy opacity in 53 (64.63%), large area consolidation in 9 (10.97%), ground-glass blurry shadow in 31 (37.80%), alveolar substantive shadow in 14 (17.07%) and interstitial changes in 16 (19.51%). The pulmonary CT signs of SARS were relatively characterized by: (1) The lesions tending to multiply occur, mostly to be bilaterally distributed and commonly involved in the lower lung field. (2) The lung shadows mostly showed as sub-pleural focal consolidation, flaky cloudy shadow, large area consolidation, ground-glass blurry shadow, and often accompanied with signs of broncho-inflation. (3) Having opacified nodular shadows in the alveolar cavities. (4) Rapid progressions or changes on the size, amount, and distribution of the lesions likely to be found in dynamic observation of chest X-ray and CT scanning, i.e., markedly dynamic changes found within 24 to 48 hrs. Lesions with these characteristics may be recognized as pulmonary changes possibly induced by SARS. Complications were found in 6 patients (7.31%), including tuberculosis of lung and brain accompanied with pneumomediastinum in one patient, secondary infection of lung in 2, pneumothorax in 1, pulmonary fungus in 1, and pyothorax in 1.Conclusion: CT scanning is a sensitive method for diagnosis of SARS, by which more accurate assessment of the abnormal changes of lung and occurrence of complications in SARS patients can be made."
4870,Effect of acupuncture on uncoupling protein 1 gene expression for brown adipose tissue of obese rats,"Objective; To explore the effects of acupuncture on the expression of uncoupling protein 1 (UCP(1)) gene of brown adipose tissue (BAT) in obese rats.Methods: The expression of UCP(1) gene of BAT was determined with RT-PCR technique. The changes of body weight, Lee’s index, body fat, and the expression of UCP(1) gene of BAT in obese rats were observed before and after acupuncture.Results: The body weight, Lee’s index, body fat in obese rats were all markedly higher than those in normal rats, but the expression of UCP(1) gene of BAT in obese rats was all lower than that in normal rats. There were negative correlation between the obesity index and the expression of UCP(1) gene in BAT. After acupuncture the marked effect of weight loss was achieved while the expression of UCP(1) gene of BAT obviously increased in obese rats.Conclusion: The abnormal reduction for expression of UCP(1) gene of BAT might be an important cause for the obesity. To promote the expression of UCP(1) in obese organism might be an important cellular and molecular mechanism in anti-obesity effect by acupuncture."
4871,Therapeutic effects of integrated traditional Chinese medicine and western medicine in treating severe acute respiratory syndrome,"Objective: To improve the effects of treatment of severe acute respiratory syndrome (SARS) and to explore the clinical significance of integrated traditional Chinese medicine and western medicine (ICWM) in the treatment of SARS and its influence on the chief indexes in the process of the disease.Methods: The clinical study involving observation of 135 patients of SARS was conducted in the randomized, synchronously controlled and open way. The patients were divided into two groups, 68 in the ICWM group and 67 in the control group, all of whom were treated with the same basic treatment of western medicine, but to the ICWM group, Chinese drugs for clearing Heat, detoxifying and removing Dampness were given additionally. The comprehensive effect on relieving fever, cell-mediated immunity, pulmonary inflammation and secondary infection was compared between the two groups.Results: The therapeutic effect in the ICWM group was better than that in the control group in such aspects as steadily lowering body temperature, alleviating general symptoms, accelerating the absorption of pulmonary infiltration and easing cellular immunity suppression.Conclusion: The therapeutic effect of ICWM is better in treating SARS than that of western medicine alone."
4872,Dynamics of a novel nonlinear SIR model with double epidemic hypothesis and impulsive effects,"In this paper, the propagation of a nonlinear delay SIR epidemic using the double epidemic hypothesis is modeled. In the model, a system of impulsive functional differential equations is studied and the sufficient conditions for the global attractivity of the semi-trivial periodic solution are drawn. By use of new computational techniques for impulsive differential equations with delay, we prove that the system is permanent under appropriate conditions. The results show that time delay, pulse vaccination, and nonlinear incidence have significant effects on the dynamics behaviors of the model. The conditions for the control of the infection caused by viruses A and B are given."
4873,Exploration on the effect and mechanism of Shenfu injection on resuscitation from general anesthesia,
4874,Effect of water deficit on biomass production and accumulation of secondary metabolites in roots of Glycyrrhiza uralensis,"Two-year-old seedlings of licorice plant (Glycyrrhiza uralensis Fisch) were exposed to three degrees of water deficit, namely weak (60–70%), moderate (40–50%), and strong (20–30%) relative water content in soil, whereas control plants were grown in soil with 80–90% water content. Moderate and strong water deficit decreased the net photosynthetic rate, stomatal conductance, and biomass production. Water use efficiency and the root-to-shoot ratio increased significantly in response to water deficit, indicating a high tolerance to drought. Weak water deficit did not decrease root biomass production, but significantly increased the production of glycyrrhizic acid (by 89%) and liquiritin (by 125%) in the roots. Therefore, a weak water deficit can increase the yield of root medical compounds without negative effect on root growth."
4875,State of research in the field of the creation of plant vaccines for veterinary use,"Transgenic plants as an alternative of costly systems of recombinant immunogenic protein expression are the source for the production of cheap and highly efficient biotherapeuticals of new generation, including plant vaccines. In the present review, possibilities of plant system application for the production of recombinant proteins for veterinary use are considered, the history of the “edible vaccine” concept is briefly summarized, advantages and disadvantages of various plant systems for the expression of recombinant immunogenic proteins are discussed. The list of recombinant plant vaccines for veterinary use, which are at different stages of clinical trials, is presented."
4876,Structure and function of the signal recognition particle (SRP),
4877,The 20th Conference of the Asian Pacific Association for the Study of the Liver Poster Presentation,
4878,Application of building simulation tools for studying airborne infection and its control,
4879,Control of Viral Contamination of Food and Environment,"Viruses are often transmitted via food and the environment. Contamination may be controlled either by preventing its occurrence or by inactivating the contaminating virus. The majority of agents transmitted in this way are human enteric viruses, produced either in the intestines or the liver. They are shed in human feces (noroviruses also in vomitus) in a broad range of circumstances, and they are relatively stable outside the host. Non-enteric viruses are less often transmitted via foods and are generally less environmentally stable. Insofar as vaccines are available, they are able to prevent fecal shedding. Viruses shed in feces via the water-carriage toilet may be eliminated by proper treatment and disinfection of the wastewater. In the foods context, the most effective antiviral measures are cooking and hand washing. Detection methods are most useful after the fact, in investigating outbreaks and devising preventive measures."
4880,Immune responses and histopathological changes in rabbits immunized with inactivated SARS coronavirus,"To evaluate the immunogenicity of inactivated SARS coronavirus (SARS-CoV), three groups of rabbits were immunized three times at 2-week intervals with inactivated vaccine + adjuvant, adjuvant, and normal saline respectively. Eight batchs of serum were sampled from the auricular vein at day 7 to day 51, and specific IgG antibody titers and neutralizing antibody titers were detected by indirect ELISA and micro-cytopathic effect neutralizing test. Antibody specificity was identified by proteinchip assay. Histopathological changes were detected by H&E staining. The results showed that, rabbits in the experimental group immunized with inactivated SARS-CoV all generated specific IgG antibodies with neutralizing activity, which suggested the inactivated SARS-CoV could preserve its antigenicity well and elicit an effective humoral immune responses. The peak titer value of specific IgG antibody and neutralizing antibody reached 1:40960 and 1:2560 respectively. In the experimental group, no obvious histopathological changes was detected in the H&E stained slides of heart, spleen, kidney and testis samples, but the livers had slight histopathological changes, and the lungs presented remarkable histopathological changes. These findings are of importance for SARS-CoV inactivated vaccine development."
4881,Modeling transient particle transport by fast fluid dynamics with the Markov chain method,"Fast simulation tools for the prediction of transient particle transport are critical in designing the air distribution indoors to reduce the exposure to indoor particles and associated health risks. This investigation proposed a combined fast fluid dynamics (FFD) and Markov chain model for fast predicting transient particle transport indoors. The solver for FFD-Markov-chain model was programmed in OpenFOAM, an open-source CFD toolbox. This study used two cases from the literature to validate the developed model and found well agreement between the transient particle concentrations predicted by the FFD-Markov-chain model and the experimental data. This investigation further compared the FFD-Markov-chain model with the CFD-Eulerian model and CFD-Lagrangian model in terms of accuracy and efficiency. The accuracy of the FFD-Markov-chain model was similar to that of the other two models. For the two studied cases, the FFD-Markovchain model was 4.7 and 6.8 times faster, respectively, than the CFD-Eulerian model, and it was 137.4 and 53.3 times faster than the CFD-Lagrangian model in predicting the steady-state airflow and transient particle transport. Therefore, the FFD-Markov-chain model is able to greatly reduce the computing cost for predicting transient particle transport in indoor environments."
4882,Trends and Perspectives of Biosensors for Food and Environmental Virology,"Food and environmental virology has become a very important and interesting area of research because of food safety and public health concerns. During the last few decades, increasing foodborne diseases and environmental generated illnesses are considered to be highly challenging issues. Biosensor technology holds great promise for the healthcare market, and the security sector. Similar to clinical diagnostic tools, biosensors are being developed for the rapid, reliable, yet inexpensive identification and enumeration of pathogenic viruses which are adulterating environment, food and feed commodities. In this modern era, bio-and nano-technologies play a pivotal role in virological diagnostics of food industry, environmental and veterinary samples. This review covers the recent advances and future prospects of nanotechnology-based bioanalytical microsystems for food and environmental virology."
4883,Minimum Infective Dose of the Major Human Respiratory and Enteric Viruses Transmitted Through Food and the Environment,"Viruses are a significant cause of morbidity and mortality around the world. Determining the minimum dose of virus particles that can initiate infection, termed the minimum infective dose (MID), is important for the development of risk assessment models in the fields of food and water treatment and the implementation of appropriate infection control strategies in healthcare settings. Both respiratory and enteric viruses can be shed at high titers from infected individuals even when the infection is asymptomatic. Presence of pre-existing antibodies has been shown to affect the infectious dose and to be protective against reinfection for many, but not all viruses. Most respiratory viruses appear to be as infective in humans as in tissue culture. Doses of <1 TCID(50) of influenza virus, rhinovirus, and adenovirus were reported to infect 50% of the tested population. Similarly, low doses of the enteric viruses, norovirus, rotavirus, echovirus, poliovirus, and hepatitis A virus, caused infection in at least some of the volunteers tested. A number of factors may influence viruses’ infectivity in experimentally infected human volunteers. These include host and pathogen factors as well as the experimental methodology. As a result, the reported infective doses of human viruses have to be interpreted with caution."
4884,Molecular epidemiology and sequencing of the G-L intergenic region of rabies viruses isolated in China,"A group of 25 rabies viruses (RABVs), recovered from 24 dogs and one human case, were collected from various areas in China between 2004 and 2006. Genetic and phylogenetic analyses of the G-L intergenic region were carried out in 25 street RABV isolates and CTN vaccine strains of 7 generations. The study was based on the comparison of a 519 bp nucleotide sequence, encompassing the G-L intergenic region. The nucleotide sequence homologies of Chinese street strains were from 95.5% to 100%. The phylogenetic analysis showed that all Chinese isolates clearly supported the placement of all Chinese viruses in Lyssavirus genotype 1 and they were distributed according to their geographical origins. All of the Chinese strains were closely related but they could still be divided into two groups: group of street strains and group of CTN strains. This study presents details about the molecular epidemiology of rabies viruses based on the sequences of the G-L Intergenic region."
4885,Killing two birds with one stone: How do Plant Viruses Break Down Plant Defenses and Manipulate Cellular Processes to Replicate Themselves?,"As simple organisms with a parasite nature, viruses have become masters in manipulating and subvert cellular components, including host proteins and organelles, to improve viral replication. Therefore, the understanding of viral strategies to manipulate cell function disrupting plant defenses and enhancing viral infection cycles is fundamental to the production of virus-resistant plant lines. After invading susceptible plants, viruses create conditions that favor local and systemic infections by suppressing multiple layers of innate host defenses while use cellular machinery to own benefit. Viral interference in interlinked essential cellular functions results in phenotypic changes and disease symptoms, which debilitates plants favoring infection establishment. Herein in this review, the novelty it will be the discussion about the strategies used by (+) single strand RNA viruses to affect cellular processes and components to improve viral replication, in parallel to overcome plant defenses, favoring disease establishment by applying in one action using the same viral protein to coordinate viral replication and breaking down plant defense. This focus on plant-virus interaction was never done before, and this knowledge has the potential to help in the development of new strategies to produce resistant plants."
4886,Abstractbook of the Joint Conference 2017 of the DGHM & VAAM: Microbiology and Infection,
4887,P19 of tomato bushy stunt virus suppresses RNA silencing induced by short hairpin RNA in mammal cells,"To counteract the immune system in parasitic hosts, some viruses encode proteins to suppress the RNA interference (RNAi) effect. In this report, we established two RNAi systems to be easily observed with strong and obvious effect. The function of the P19 of tomato bushy stunt virus, which suppresses RNAi in mammal cells, was then studied using these two systems. Short hairpin RNAs targeting green fluorescence protein (pshRNA-GFP) and firefly luciferase (pshRNA-luc) were designed and inserted into a eukaryotic transcriptional vector pTZU6+1, respectively. The shRNA expressing vectors were co-transfected with plasmids containing the target gene with or without P19. The GFP expression level was assayed by fluorescence microscopy, Western blotting and RT-PCR. The luciferase expression level was analyzed by the dual-luciferase assay system. pshRNA designed in this study down-regulated the target gene specifically and efficiently, with a decrease of expression of both genes of about 70%, respectively. When P19 was introduced into the RNAi systems, the expression of both GFP and the luciferase were mostly recovered compared with the control groups. The RNAi systems of GFP and luciferase were constructed successfully, demonstrating that P19 of tomato bushy stunt virus has the ability to counteract the RNAi effect induced by shRNA in mammal cells."
4888,The influence of envelope features on interunit dispersion around a naturally ventilated multi-story building,"This study examines the influence of building envelope features on interunit dispersion around multi-story buildings, when the presence of an upstream interfering building is also considered. Validated CFD methods in the steady-state RANS framework are employed. In general, the reentry ratios of pollutant from a source unit to adjacent units are mostly in the order of 0.1%, but there are still many cases being in the order of 1%. The influence of envelope features is dependent strongly on the interaction between local wind direction and envelope feature. In a downward dominated near-facade flow field, the presence of vertical envelope features forms dispersion channels to intensify the unidirectional spread. Horizontal envelope features help induce the dilution of pollutant to the main stream and weakens largely the vertical interunit dispersion. The large influences caused by the presence of envelope features extend the existing understanding of interunit dispersion based on flat-facade buildings."
4889,An improved culture system for virus isolation and detection,"Cell culture plays an important role in virology. It provides a platform for the detection and isolation of viruses as well as for the biochemistry and molecular biology based studies of viruses. In the present work, a new system that could permits multiple (different) cell lines to be simultaneously cultured in one dish was developed. In the system, each cell line was cultured in an isolated zone in the same dish or well and the system is therefore called an isolated co-culture system. The usefulness of this novel approach for virus isolation was demonstrated using a model system based on adenovirus."
4890,Research proposals on diarrhoeal diseases,
4891,Temperature sensing using red fluorescent protein,"Genetically encoded fluorescent proteins are extensively utilized for labeling and imaging proteins, organelles, cell tissues, and whole organisms. In this study, we explored the feasibility of mRFP1 and its variants for measuring intracellular temperature. A linear relationship was observed between the temperature and fluorescence intensity of mRFP1 and its variants. Temperature sensitivities of E. coli expressing mRFP1, mRFP-P63A and mRFP-P63A[(4R)-FP] were −1.27%, −1.26% and −0.77%/°C, respectively. Finally, we demonstrated the potentiality of mRFP1 and its variants as an in vivo temperature sensor."
4892,Indirect Enzyme-Linked Immunosorbent Assay based on the nucleocapsid protein of SARS-like coronaviruses,"The nucleocapsid protein (N) is a major structural protein of coronaviruses. The N protein of bat SARS-like coronavirus (SL-CoV) has a high similarity with that of SARS-CoV. In this study, the SL-CoV N protein was expressed in Escherichia coli, purified and used as antigen. An Indirect Enzyme-Linked Immunosorbent Assay (indirect ELISA) was developed for detection of SARS- or SL-CoV infections in bat populations. The detection of 573 bat sera with this indirect ELISA demonstrated that SL-CoVs consistently circulate in Rhinilophus species, further supporting the proposal that bats are natural reservoirs of SL-CoVs. This method uses 1–2 μl of serum sample and can be used for preliminary screening of infections by SARS- or SL-CoV with a small amount of serum sample."
4893,Air infiltration induced inter-unit dispersion and infectious risk assessment in a high-rise residential building,"Identifying possible airborne transmission routes and assessing the associated infectious risks are essential for implementing effective control measures. This study focuses on the infiltration-induced inter-unit pollutant dispersion in a high-rise residential (HRR) building. The outdoor wind pressure distribution on the building facades was obtained from the wind tunnel experiments. And the inter-household infiltration and tracer gas transmission were simulated using multi-zone model. The risk levels along building height and under different wind directions were examined, and influence of component leakage area was analysed. It is found that, the cross-infection risk can be over 20% because of the low air infiltration rate below 0.7 ACH, which is significantly higher than the risk of 9% obtained in our previous on-site measurement with air change rate over 3 ACH. As the air infiltration rate increases along building height, cross-infection risk is generally higher on the lower floors. The effect of wind direction on inter-unit dispersion level is significant, and the presence of a contaminant source in the windward side results in the highest cross-infection risks in other adjacent units on the same floor. Properly improving internal components tightness and increasing air change via external components are beneficial to the control of internal inter-unit transmission induced by infiltration. However, this approach may increase the cross-infection via the external transmission, and effective control measures should be further explored considering multiple transmission routes."
4894,Biological effects of HBV X protein on hepatocellular carcinogenesis in association with cellular factors,"The X protein (HBx) of Human hepatitis B virus (HBV) acts as an indirect transcriptional transactivator to regulate the expression of many viral and cellular genes, as well as playing a critical role in pathogenesis and the development of Hepatocellular carcinoma (HCC). Here we described the biological effects of HBx in association with four cellular factors, including inflammatory factors (COX-2 and iNOS), oncoprotein (Ras), and a newly identified tumor suppressor (YueF). The characteristics of these effectors, which might be associated with hepatocellular carcinoma, are also discussed."
4895,Anti-cariogenic Characteristics of Rubusoside,"Streptococcus mutans plays an important role in the development of dental caries in humans by synthesizing adhesive insoluble glucans from sucrose by mutansucrase activity. To explore the anti-cariogenic characteristics of rubusoside (Ru), a natural sweetener component in Rubus suavissimus S. Lee (Rosaceae), we investigated the inhibitory effect of Ru against the activity of mutansucrase and the growth of Streptococcus mutans. Ru (50 mM) showed 97% inhibitory activity against 0.1 U/mL mutansucrase of S. mutans with 500 mM sucrose. It showed competitive inhibition with a K(i) value of 1.1 ± 0.2 mM and IC(50) of 2.3 mM. Its inhibition activity was due to hydrophobic and hydrogen bonding interactions based on molecular docking analysis. Ru inhibited the growth of S. mutans as a bacteriostatic agent, with MIC and MBC values of 6 mM and 8 mM, respectively. In addition, Ru showed synergistic anti-bacterial activity when it was combined with curcumin. Therefore, Ru is a natural anti-cariogenic agent with anti-mutansucrase activity and antimicrobial activity against S. mutans. ELECTRONIC SUPPLEMENTARY MATERIAL (ESM): The online version of this article (doi: 10.1007/s12257-018-0408-0) contains supplementary material, which is available to authorized users."
4896,Book reviews,
4897,The functional motif of SARS-CoV S protein involved in the interaction with ACE2,"SARS-CoV is a newly discovery pathogen causing severe acute respiratory problems. It has been established that the S protein in this pathogen plays an important rule in the adsorption and penetration of SARS-CoV into the host cell by interaction with the ACE2 receptor. To determinant which functional motif of the S protein was involved in the interaction with ACE2, seven truncated S proteins deleted from the N or C terminal were obtained by an E.coli expression system and purified by column chromatography to homogeneity. Each truncated S protein was fixed on to the well of an ELISA plate and an interaction was initiated with the ACE2 protein. The adsorption were quantified by ELISA, and the results indicated that amino acids from 388 to 496 of the S protein was responsible for the interaction with the ACE2 receptor, and the interaction could be completely disrupted by an antibody specific to these amino acids. Deletions adjacent to this domain did not appear to have a significant impact on the interaction with ACE2, suggesting that the S protein of SARS-CoV could be developed as a vaccine to prevent the spread of SARS-CoV."
4898,Evaluation of sensitivities and specificities of SARS-CoV detection by real-time quantitative reverse transcription-PCR assays,"The etiological agent of severe acute respiratory syndrome (SARS) was identified as a new coronavirus, termed SARS-CoV. Establishment of an efficient and sensitive diagnostic system of SARS-CoV genetic materials is crucial for SARS control. In this study, we quantified SARS-CoV mRNAs in both infected cell culture lysate and in supernatant by using Real-time quantitative revere transcription-PCR based on EvaGreen™ dye and Taqman-MGB probes. For extensive evaluation of sensitivities and specificities, 13 pairs of primers and 4 probes were designed based on different genes of SARS-CoV. Glyceraldehydes-3-phosphate dehydrogenase (GAPDH) was selected as the internal control gene. Results showed that S-gene-specific PCR was the most sensitive for detection, but because of its sequence variability in the different viral strains, primers and a probe based on the N gene were suitable substitutions. Meanwhile, we found the mRNA concentrations in cell culture lysates were much higher than in cell supernatant and facilited more sensitive detection of the SARS-CoV."
4899,"Simultaneous extraction and separation of liquiritin, glycyrrhizic acid, and glabridin from licorice root with analytical and preparative chromatography","Simultaneous extraction and separation of liquiritin, glycyrrhizic acid, and glabridin from licorice were developed by liquidliquid extraction with liquid chromatography separation. By utilizing different extraction solvents, procedures, and times, the optimum extraction conditions were established. The extracts of licorice were separated and determined using a C(18) column with a mobile phase consisting of acetonitrile-water (containing 1.0% acetic acid) with a gradient elution of 0∼10 min from 20:80 to 60:40 (v/v). Preparative columns with different packing sizes were investigated to isolate the three compounds from the extracts of licorice. The 12 μm chromatographic column showed better separation for the three compounds from licorice. 0.29 mg/g for liquiritin, 1.43 mg/g for glycyrrhizic acid, and 0.07 mg/g for glabridin were obtained and the recoveries were 80.8, 89.7, and 72.5%, respectively."
4900,Issues Concerning Survival of Viruses on Surfaces,"Viruses are the causative agents of an estimated 60% of human infections worldwide. The most common viral illnesses are produced by enteric and respiratory viruses. Transmission of these viruses from an infected person or animal to a new host can occur via several routes. Existing studies strongly suggest that contaminated fomites or surfaces play an important role in the spreading of viral diseases. The potential of viral spreading via contaminated surfaces depends particularly on the ability of the virus to maintain infectivity whilst it is in the environment. This is affected by a combination of biological, physical and chemical factors. This review summarises current knowledge about the influence of environmental factors on the survival and spread of viruses via contaminated surfaces."
4901,AIDS research and its role in China’s AIDS prevention and control policies,"By the end of 2005, the estimated number of HIV infected people in China was 650,000. The seriousness of the epidemic calls for effective control measures to tackle the problems in order to avoid the tragedy in Africa from happening in China. “Prevention First” is the cornerstone of the country’s health policy. On 2003 World AIDS Day, Premier Jiabao Wen announced a new national AIDS control policy, “Four Frees and One Care”. This policy clearly shows that the Chinese government has once again taken full responsibility to solve public health problems and has profound impact far beyond the AIDS field. In early 2006, the central government put scientific and technology innovation as a national priority and set the target to build an innovative China by year 2020. Since then, the government has been increasing investment in science and technology with major emphasis on both infectious diseases control and new drug research and development. For the first time, development of 100 new drugs and control of major infectious diseases (AIDS, HBV, TB and other emerging infectious diseases) have been selected as national key scientific projects. China’s best minds in related fields will be pooled to work together in order to remove the technical barriers blocking efficient control of the major infectious disease in China. Knowledge on molecular epidemiology, immunology, pathogenesis, HAART, as well as HIVDR strains will certainly provide urgently needed scientific information for China’s AIDS control program. Only evidence-based strategy from good research will provide long-term effective control of AIDS."
4902,Human papillomavirus type 16 mutant E7 protein induces oncogenic transformation via up-regulation of cyclin A and cdc25A,"A new mutant human papillomavirus type 16 E7 gene, termed HPV16 HBE7, was isolated from cervical carcinoma biopsy samples from patients in an area with high incidence of cervical cancer (Hubei province, China). A previous study showed that the HPV16 HBE7 protein was primarily cytoplasmic while wild-type HPV16 E7 protein, termed HPV16 WE7, was concentrated in the nucleus. With the aim of studying the biological functions of HPV16 HBE7, the transforming potential of HPV16 HBE7 in NIH/3T3 cells was detected through observation of cell morphology, cell prolieration assay and anchorage-independent growth assay. The effect of HPV16 HBE7 on cell cycle was examined by flow cytometry. Dual-luciferase reporter assay and RT-PCR were used to investigate the influence of HPV16 HBE7 protein on the expression of regulation factors associated with G1/S checkpoint. The results showed that HPV16 HBE7 protein, as well as HPV16 WE7 protein, held transformation activity. NIH/3T3 cells expressing HPV16 HBE7 could easily transition from G1 phase into S phase and expressed high level of cyclin A and cdc25A. These results indicated HPV16 mutant E7 protein, located in the cytoplasm, induces oncogenic transformation of NIH/3T3 cells via up-regulation of cyclin A and cdc25A"
4903,Production of a heat-labile enterotoxin B subunit-porcine epidemic diarrhea virus-neutralizing epitope fusion protein in transgenic lettuce (Lactuca sativa),"Plant-based vaccines have been produced in transgenic plants including tobacco, potatoes, corn, and rice. However, these plants are not suitable for administration without cooking. To overcome this obstacle, a fusion gene encoding the synthetic enterotoxigenic Escherichia coli heat-labile enterotoxin B subunit genetically fused with a synthetic neutralizing epitope of porcine epidemic diarrhea virus (sLTB-sCOE) was introduced into lettuce cells (Lactuca sativa) by Agrobacterium-mediated transformation methods. The integration and expression of the sLTB-sCOE fusion gene was confirmed in transgenic lettuce by genomic DNA PCR amplification and Northern blot analysis, respectively. Synthesis and assembly of the LTB-COE fusion protein into oligomeric structures with pentamer size were observed in transgenic plant extracts by Western blot analysis with anti-LTB or anti-COE antibodies. The binding of plantproduced LTB-COE to intestinal epithelial cell membrane glycolipid receptors was confirmed by G(M1)-ganglioside enzyme-linked immunosorbent assay (G(M1)-ELISA). Based on the ELISA results, LTB-COE fusion protein made up about 0.026∼0.048% of the total soluble protein in the transgenic lettuce leaf tissues. The synthesis and assembly of LTB-COE monomers into biologically active oligomers in transgenic lettuce leaf tissues demonstrates the feasibility of using uncooked edible plant-based vaccines for mucosal immunization."
4904,Bats and viruses: a brief review,"Bats, probably the most abundant, diverse and geographically dispersed vertebrates on earth, have recently been shown to be the reservoir hosts of a number of emerging viruses responsible for severe human and livestock disease outbreaks. Flying foxes have been demonstrated to be the natural reservoir for Hendra and Nipah viruses. Evidence supporting the possibility of bats as potential reservoirs for SARS coronavirus (SARS-CoV) and Ebola virus has also been reported. The recent discovery of these viruses and other viruses occurring naturally in the bat population provides a unique insight into a diverse pool of potentially emergent and pathogenic viruses. The factors which influence the ability of zoonotic viruses to effectively cross the species barrier from bats to other animal populations are poorly understood. A brief review is provided here on the recently emerged bat viruses and on current and future strategies for research in this area."
4905,Inhibitory effects of epigallocatechin gallate and its glucoside on the human intestinal maltase inhibition,"Human intestinal maltase (HMA) is an α-glucosidase responsible for the hydrolysis of α-1,4-linkages from the non-reducing end of malto-oligosaccharides. HMA has become an important target in the treatment of type-2 diabetes. In this study, epigallocatechin gallate (EGCG) and EGCG glucoside (EGCG-G1) were identified as inhibitors of HMA by an in vitro assay with IC(50) of 20 ± 1.0 and 31.5 ± 1.0 μM, respectively. A Lineweaver-Burk plot confirmed that EGCG and EGCG-G1 were competitive inhibitors of maltose substrate against HMA and inhibition kinetic constants (K (i)) calculated from a Dixon plot were 5.93 ± 0.26 and 7.88 ± 0.57 μM, respectively. Both EGCG and EGCG-G1 bound to the active site of HMA with numerous hydrophobic and hydrogen bond interactions."
4906,Cloning the structure genes and expression the N gene of porcine epidemic diarrhea virus DX,"The structure genes spike (S), nucleocapsid (N), membrane (M), small membrane (sM) of a porcine epidemic diarrhea virus (PEDV) strain DX isolated in Gansu province, North-west of China, were cloned, sequenced and compared with published sequences of PEDV strains. The nucleotide sequences encoding the entire S, sM, M and N genes open reading frame (ORF) of DX were 4 152, 231, 681 and 1 326 bases long respectively. There were transcription regulatory sequences (TRSs) upstream of the initiator ATG of the S, N and M genes. The amino acids sequences of S, M and N contained 30, 3 and 7 potential asparagine (N)-linked glycosylation sites. Homologous analysis and phylogenetic trees showed that DX had the closest relationship with strains LJB/06, JS-2004-2Z and CH/HLJH/06 that were also isolated from China and indicated the prevalence of some PEDV isolates in China were widespread since the JS-2004-2Z strain originated from the south of the China, and LJB/06 and CH/HLJH/06 were isolated from northeast China. The N gene was cloned using two primers which contained Nco I and BamH I restriction enzyme sites and subcloned into expression vector pET30a. The recombinant plasmid was then transformed into E.coli Rossta. SDS-PAGE showed there was a protein of about 55kDa as expected and Western blot indicated the N protein had biological activity."
4907,Investigation of seasonal frequency and pathogens in febrile neutropenia,"BACKGROUND: In patients with hematological malignancies, febrile neutropenia (FEN) is the most frequent complication and the most important cause of mortality. Various risk factors have been identified for severe infection in neutropenic patients. However, to the best of our knowledge, it is not defined whether there is a change in the risk of febrile neutropenia according to seasons. The first aim of study was to determine the difference in frequency of febrile neutropenic episodes (FNEs) according to months and seasons. The second aim was to document isolated pathogens, as well as demographical and clinical characteristics of patients. METHODS: In the study, 194 FNEs of 105 patients who have been followed with hematological malignancies between June 2013 and May 2014 were evaluated retrospectively. RESULTS: Although the number of FNEs increased in autumn, there was no significant difference in frequency of FNEs between months (p = 0.564) and seasons (p = 0.345). There was no isolated pathogen in 54.6% of FNEs. In 45.4% of 194 FNEs, pathogens were isolated. Of all pathogens, 50.4% were gram negative bacteria, 29.2% were gram positive bacteria, 13.3% were viruses, 5.3% were fungi, and 1.8% were parasites. CONCLUSİONS: The frequency of FEN does not change according to months or seasons. Also, the relative proportions of different pathogens in the cause of FEN do not vary according to seasons."
4908,Novel coronaviruses and astroviruses in bats,"Zoonotic transmissions of emerging pathogens from wildlife to human have shaped the history of mankind. These events have also highlighted our poor understanding of microorganisms circulated in wild animals. Coronaviruses and astroviruses, which can be found from a wide range of mammals, were recently detected in bats. Strikingly, these bat viruses are genetically highly diverse and these interesting findings might help to better understand the evolution and ecology of these viruses. The discoveries of these novel bats viruses not only suggested that bats are important hosts for these virus families, but also reiterated the role of bats as a reservoir of viruses that might pose a zoonotic threat to human health."
4909,Inhibition effect of flavonoid compounds against neuraminidase expressed in Pichia pastoris,"Neuraminidase (NA) is one of the two glycoproteins on the surface of influenza virus, which cleaves terminal sialic acid residues and facilitates the release of virions from infected cells. The recombinant NA from H5N1 influenza virus strain A/Vietnam/1203/04 was expressed in Pichia pastoris X33 as a 45 kDa protein that displayed a K (m) of 9.96 ± 1.26 μM with fluorogenic substrate, 2′-(4-methylumbelliferyl)-α-D-N-acetyl neuraminic acid. Partially purified NA was used for the inhibition and kinetic assays with eight flavonoid compounds and gallic acid. Among them, gallocatechin gallate (GCG) showed the best inhibition against NA with the IC(50) of 8.98 ± 0.46 μM and showed a competitive inhibition pattern with K (i) value of 8.34 ± 0.25 μM. In molecular docking experiments, GCG displayed a binding energy of −13.71 kcal/mol to the active site of NA and the galloyl moiety was required for NA inhibition activity."
4910,Person to person droplets transmission characteristics in unidirectional ventilated protective isolation room: The impact of initial droplet size,"Person to person droplets/particles or contaminant cross transmission is an important issue in ventilated environment, especially in the unidirectional ventilated protective isolation room (UVPIR) where the patient’s immune system is extremely low and easily infected. We simulated the dispersion process of the droplets with initial diameter of 100 μm, 10 μm and gaseous contaminant in unidirectional ventilated protective isolation room and studied the droplets dispersion and cross transmission with different sizes. The droplets with initial size of 100 μm settle out of the coughing jet quickly after coming out from mouth and cannot be carried by the coughing jet to the human thermal plume affecting (HTPA) zone of the susceptible manikin. Hence, the larger droplets disperse mainly in the HTPA zone of the source manikin, and the droplets cross transmission between source manikin and susceptible manikin is very small. The droplets with initial size of 10 μm and gaseous contaminant have similar dispersion but different removal process in the UVPIR. Part of the droplets with initial size of 10 μm and gaseous contaminant that are carried by the higher velocity coughing airflow can enter the HTPA zone of the susceptible manikin and disperse around it. The other part cannot spread to the susceptible manikin’s HTPA zone and mainly spread in the source manikin’s HTPA zone. The results from this study would be useful for UVPIR usage and operation in order to minimize the risk of cross infection."
4911,Evolution of large-scale flow structures and traces of marked fluid particles within a single-aisle cabin mock-up,"Over the past several decades, rapidly growing popularity of airline transportation has pushed many passengers and crew to focus on potential risk of contaminant transmission during commercial air travel. Understanding airflow dynamics and transport property within an aircraft cabin is critical to creating a healthy cabin environment and improving control of epidemics. This work reveals the temporal and spatial evolution process of large-scale flow structures around the aisle region and evaluates impact of airflow’s large-scale flow structures (swing motion around the aisle region and large-scale vortices) on transport property by calculating traces of marked fluid particles (MFPs) passing through passengers’ exhalation area within a Boeing 737-200 cabin mock-up. The Peixoto theorem has been used to interpret temporal and spatial evolution process of large-scale flow structures around the aisle region. Transport property within this single-aisle aircraft cabin is a mixed effect of the airflow’s swing motion, large-scale vortices and longitudinal airflow. Airflow’s swing motion around the aisle region tends to carry MFPs nearby across the aisle region and invade the large-scale vortex in the opposite side. The large-scale vortices try to control MFPs in its each separated zone. The airflow’s swing motion and large-scale vortices dominate MFPs’ latitudinal transmission, while longitudinal airflow dominates MFPs’ longitudinal transmission."
4912,Expression of prothrombinase/fibroleukin gene fg12 in lung impairment in a murine severe acute respiratory syndrome model,"To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage."
4913,Plasmonic molecular assays: Recent advances and applications for mobile health,"Plasmonics-based biosensing assays have been extensively employed for biomedical applications. Significant advancements in use of plasmonic assays for the construction of point-of-care (POC) diagnostic methods have been made to provide effective and urgent health care of patients, especially in resourcelimited settings. This rapidly progressive research area, centered on the unique surface plasmon resonance (SPR) properties of metallic nanostructures with exceptional absorption and scattering abilities, has greatly facilitated the development of cost-effective, sensitive, and rapid strategies for disease diagnostics and improving patient healthcare in both developed and developing worlds. This review highlights the recent advances and applications of plasmonic technologies for highly sensitive protein and nucleic acid biomarker detection. In particular, we focus on the implementation and penetration of various plasmonic technologies in conventional molecular diagnostic assays, and discuss how such modification has resulted in simpler, faster, and more sensitive alternatives that are suited for point-of-use. Finally, integration of plasmonic molecular assays with various portable POC platforms for mobile health applications are highlighted."
4914,Assessment of the Antiviral Properties of Zeolites Containing Metal Ions,"The antiviral properties of zeolite (sodium aluminosilicate) powders amended with metal ions were assessed using human coronavirus 229E, feline infectious peritonitis virus (FIPV), and feline calicivirus F-9. Zeolites containing silver and silver/copper caused significant reductions of coronavirus 229E after 1 h in suspension. The silver/copper combination yielded a >5.13-log(10) reduction within 24 h. It was also the most effective (>3.18-log(10)) against FIPV after 4 h. Other formulations were ineffective against FIPV. On plastic coupons with incorporated silver/copper-zeolites, >1.7-log(10) and >3.8-log(10) reductions were achieved for coronavirus 229E and feline calicivirus within 24 h, respectively. Silver/copper zeolite reduced titers of all viruses tested, suggesting that it may be effective against related pathogens of interest [i.e., SARS coronavirus, other coronaviruses, human norovirus (calicivirus)]. Of note, it was effective against both enveloped and nonenveloped viruses. Metal-zeolites could therefore possibly be used in applications to reduce virus contamination of fomites and thus the spread of viral diseases."
4915,Oral presentations,
4916,The Prevalence of Human Parainfluenza Virus 1 on Indoor Office Fomites,"The objective of this study was to evaluate the potential role of fomites in human parainfluenza virus 1 (HPIV1) transmission by assessing the occurrence of HPIV1 on surfaces in an adult setting (office). In 2004, a total of 328 fomites from 12 different office buildings in five different cities were evaluated for HPIV1 viral RNA. HPIV1 was isolated using reverse transcriptase–polymerase chain reaction (RT–PCR) and detected on 37% of all office fomites. HPIV1 RNA was frequently isolated on desk tops (47%), and infrequently isolated on light switches (19%). Data revealed a statistically significant difference between the percentage of HPIV1 positive fomites in office cubicles and conference rooms (Chi-square P < 0.011, Fisher’s Exact P = 0.054). A statistically significant difference was also found among positive fomites in different buildings (Chi-square P < 0.011). HPIV1 was consistently isolated on various indoor fomites in the 12 office buildings assessed during 2004, a low HPIV incident year."
4917,Survival of Coronaviruses in Water and Wastewater,"The advent of severe acute respiratory syndrome and its potential environmental transmission indicates the need for more information on the survival of coronavirus in water and wastewater. The survival of representative coronaviruses, feline infectious peritonitis virus, and human coronavirus 229E was determined in filtered and unfiltered tap water (4 and 23°C) and wastewater (23°C). This was compared to poliovirus 1 under the same test conditions. Inactivation of coronaviruses in the test water was highly dependent on temperature, level of organic matter, and presence of antagonistic bacteria. The time required for the virus titer to decrease 99.9% (T(99.9)) shows that in tap water, coronaviruses are inactivated faster in water at 23°C (10 days) than in water at 4°C (>100 days). Coronaviruses die off rapidly in wastewater, with T(99.9) values of between 2 and 4 days. Poliovirus survived longer than coronaviruses in all test waters, except the 4°C tap water."
4918,"Eleventh annual meeting of the Czechoslovak Society for Microbiology Špindlerův Mlýn-Bedřichov, May 14–16, 1974",
4919,Medical virology in Malaysia,"Virology is a branch of biological science dealing with the study of viruses, and medical virology focuses on the study and control of diseases due to viruses that is of medical importance. The development of medical virology in Malaysia has its beginning in the Institute for Medical Research (IMR), following the establishment of the Division of Medical Zoology and Virus Research in the institute on 23 March 1953. The second institution in the country to establish diagnostic and research work in medical virology was Department of Medical Microbiology, Faculty of Medicine, University Malaya. This was followed by University Kebangsaan Malaysia, University Sains Malaysia and University of Sarawak Malaysia. The National Public Health Laboratory (NPHL) is the latest institution to establish a laboratory in 2003 for virus isolation and services to support country surveillance and outbreak investigation of infectious diseases due to viruses. In the field of medical virology, Malaysia contributed substantially in the areas of virus diagnostic services, development and research ranging from survey and documentation on the existence and prevalence of viruses causing diseases in Malaysia, clinical presentation and epidemiological features of virus diseases, evaluation of new diagnostic tests to pathogenesis of viral diseases. Malaysia contributed to the discoveries of at least 12 new viruses in the world. ASEAN plus Three (China, Japan, Republic of Korea) Emerging Infectious Programme was established to overcome the challenges and impact of emerging and re-emerging infectious diseases in this region. Malaysia as the co-ordinator of the laboratory component of the programme, contributed to strengthen the regional laboratory capability, capacity, laboratory-based surveillance and networking. The future of medical virology in Malaysia in terms of integration of diagnostic, reference and research to support the country’s need will be enhanced and strengthened with the on-going development of the National Centre for Disease Control and Prevention (CDC Malaysia) which also incorporates a futuristic Special Diagnostic and Reference Laboratory."
4920,Genetic variation analyses of nsp2 gene of PRRSV in Ningxia Hui Autonomous Region of China,"To gain a better understanding of the genetic diversity and evolution of PRRSV in the Ningxia Hui Nationality Autonomous Region (Ningxia) of China, the nsp2 genes from a series of PRRSV strains collected from the region in 2007 were partially sequenced. These sequences were then analyzed along with the classical strain (ch-1a) and two other epidemic strains SD (3) and SD2006. Comparison of the nucleotide sequence with ch-1a indicated that nsp2 genes of seventeen Ningxia isolates (NX strain) have deletions of 87 nucleotides. Sequence analysis indicated that homology between the Ningxia strain and ch-1a was 60.3%–79.9% in the nucleotide sequence, and homology between the NX strains and SD strains was 80.3%–98.8% in the nucleotide sequence. The nsp2 genes of the seventeen isolates had 74.9%–100% nucleotide sequence identities with each other. This study was undertaken to assess the regional variation of prevalent PRRSV and to establish a sequence database for PRRSV molecular epidemiological studies."
4921,Essentials of microbiology for dental students,
4922,"Infection control and management of hazardous materials for the dental team, 5th edition",
4923,Paediatric diseases,
4924,Reviews,
4925,"Prematurity, a significant predictor for worse outcome in viral bronchiolitis: a comparative study in infancy","BACKGROUND: The rate of admissions to hospital with bronchiolitis has increased over the past years. The reasons for this are likely to be multifactorial including improved survival of preterm infants. AIM: To assess the severity of viral bronchiolitis in preterm compared to term infants admitted at a tertiary hospital in Cairo, Egypt, based on the outcome. PATIENTS AND METHODS: This prospective study was conducted throughout a 3-year period from September 2011 to October 2014. It included 153 infants, 74 healthy preterm, and 79 healthy term infants admitted with clinical diagnosis of bronchiolitis at a tertiary hospital in Cairo, Egypt. Bronchiolitis severity score (BSS) was recorded, and nasopharyngeal swabs were obtained from each patient at the time of presentation. Viruses were identified using reverse transcription polymerase chain reaction (RT-PCR). The clinical course and patient’s outcome were recorded. RESULTS: This study recorded a significantly more severe BSS for preterm compared to term infants. The preterm group had an increased mean length of hospital stay and oxygen therapy and was more likely to need intensive care unit admission and mechanical ventilation (MV) compared to the term group. The mean (± SD) BSS for infections with h-MPV, RSV, and para-influenza 3 was more significantly severe in preterm compared to term infants. Bacterial co-infection was significantly correlated with severity scoring in both groups. CONCLUSION: Prematurity significantly affects the severity of bronchiolitis, and this underscores the importance of early categorization as a high-risk group on their first visit. The physician should be aware that their illness runs a more severe course, even if they have no underlying disorders."
4926,Short summaries,
4927,Publication only: EBMT 2010,
4928,17. Cytokines and Gene Therapy,
4929,Proteinous nanotubes,Viruses and bacteria team up to build protein-based biological nanotubes.
4930,Physicians Poster Abstracts: EBMT 2010,
4931,A unique subpopulation of lung cells which function as pulmonary stem cells and as preferential target for SARS and H5N1 virus,
4932,Publication Only,
4933,News updates,
4934,Physicians Poster Sessions,
4935,Physicians Poster Sessions,
4936,Paediatric issues 1,
4937,Physicians Poster Sessions,
4938,KEYWORD INDEX,
4939,Infectious diseases other than CMV (1st Section),
4940,Oral Sessions,
4941,Physicians Poster Abstracts: EBMT 2011,
4942,5. Autoimmune Disease,
4943,Keyword index to Volume 21,
4944,Cell therapy,
4945,New Products,
4946,Physicians Poster Abstracts,
4947,Publication only,
4948,Poster Session Nurses Group,
4949,Physicians Poster Sessions,
4950,Publication only,
4951,The 44(th) Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians Oral Session,Sponsorship Statement: Publication of this supplement is sponsored by the European Society for Blood and Marrow Transplantation. Copyright: Modified and published with permission from http://www.ebmt2018.org/
4952,Assessing the risks of introduced chickens and their pathogens to native birds in the Galápagos Archipelago,"Poultry production is an important economic activity on inhabited islands of the Galápagos archipelago. There has been a recent surge in both small-scale backyard chickens and larger scale broiler production associated with growth in the human population and the tourist industry. With increased poultry production, concerns have been expressed about the increasing risk of transfer of disease from chickens to native Galápagos bird species that may have little resistance to introduced pathogens [Wikelski, M., Foufopoulos, J., Vargas, H., Snell, H., 2004. Galápagos birds and diseases: invasive pathogens as threats for island species. Ecology and Society 9(5). Available from: URL:http://www.ecologyandsociety.org/vol9/iss1/art5]. This study evaluates risks posed by chicken disease to endemic and native Galápagos bird species, based on empirical evidence of pathogens present in chickens on the islands and a literature review of effects of these pathogens in wild species. Pathogens identified in domestic chicken populations of immediate avian conservation concern are Newcastle disease, Mycoplasma gallisepticum, and the proventricular parasite Dispharynx sp. Newcastle disease (avian paramyxovirus-1) poses an imminent threat to Galápagos penguins (Spheniscus mendiculus), flightless cormorants (Phalacrocorax harrisi), and lava gulls (Larus fuliginosus), species with very small population sizes (less than 1500 animals each). Additionally, litter from broiler farms could affect ecological processes in local ecosystems. Improved poultry biosecurity measures are urgently needed on the Galápagos Islands for avian disease management, yet developing these strategies presents political, social, and economic challenges."
4953,Erratum to “Potent and selective inhibition of SARS coronavirus replication by aurintricarboxylic acid” [Biochem. Biophys. Res. Commun. 320 (2004) 1199–1203],
4954,Nomogram for the Individualized Prediction of Survival Among Patients with H7N9 Infection,"BACKGROUND: Until recently, almost all of these studies have identified multiple risk factors but did not offer practical instruments for routine use in predicting individualized survival in human H7N9 infection cases. The objective of this study is to create a practical instrument for use in predicting an individualized survival probability of H7N9 patients. METHODS: A matched case–control study (1:2 ratios) was performed in Zhejiang Province between 2013 and 2019. We reviewed specific factors and outcomes regarding patients with H7N9 virus infection (VI) to determine relationships and developed a nomogram to calculate individualized survival probability. This tool was used to predict each individual patient’s probability of survival based on results obtained from the multivariable Cox proportional hazard regression analysis. RESULTS: We examined 227 patients with H7N9 VI enrolled in our study. Stepwise selection was applied to the data, which resulted in a final model with 8 independent predictors [including initial PaO(2)/FiO(2) ratio ≤300 mmHg, age ≥60 years, chronic diseases, poor hand hygiene, time from illness onset to the first medical visit, incubation period ≤5 days, peak C-reactive protein ≥120 mg/L], and initial bilateral lung infection. The concordance index of this nomogram was 0.802 [95% confidence interval (CI): 0.694–0.901] and 0.793 (95% CI: 0.611–0.952) for the training and validation sets, respectively, which indicates adequate discriminatory power. The calibration curves for the survival showed optimal agreement between nomogram prediction and actual observation in the training and validation sets, respectively. CONCLUSION: We established and validated a novel nomogram that can accurately predict the survival probability of patients with H7N9 VI. This nomogram can serve an important role in counseling patients with H7N9 VI and guide treatment decisions."
4955,Ambulatory surgery center infection control coordinator,
4956,Management of Adenoviral Keratoconjunctivitis: Challenges and Solutions,"Human adenovirus (HAdV) is the most common cause of infectious conjunctivitis, accounting for up to 75% of all conjunctivitis cases and affecting people of all ages and demographics. In addition to ocular complications, it can cause systemic infections in the form of gastroenteritis, respiratory disease, and dissemination in immunocompromised individuals. HAdV causes lytic infection of the mucoepithelial cells of the conjunctiva and cornea, as well as latent infection of lymphoid and adenoid cells. Epidemic keratoconjunctivitis (EKC) is the most severe ocular manifestation of HAdV infection, in which the presence of subepithelial infiltrates (SEIs) in the cornea is a hallmark feature of corneal involvement. SEIs have the tendency to recur and may lead to long-term visual disability. HAdV persistence and dissemination are linked to sporadic outbreaks of adenoviral keratoconjunctivitis. There is no FDA-approved antiviral for treating adenoviral keratoconjunctivitis, and as such, solutions should be proffered to handle the challenges associated with viral persistence and dissemination. Several treatment modalities have been investigated, both systemically and locally, to not only mitigate symptoms but reduce the course of the infection and prevent the risk of long-term complications. These options include systemic and topical antivirals, in-office povidone-iodine irrigation (PVI), immunoglobulin-based therapy, anti-inflammatory therapy, and immunotherapy. More recently, combination PVI/dexamethasone ophthalmic formulations have shown favorable outcomes and were well tolerated in clinical trials for the treatment of EKC. Possible, future treatment considerations include sialic acid analogs, cold atmospheric plasma, N-chlorotaurine, and benzalkonium chloride. Continued investigation and evaluation of treatment are warranted to reduce the economic burden and potential long-term visual debilitation in affected patients. This review will focus on how persistence and dissemination of HAdV pose a significant challenge to the management of adenoviral keratoconjunctivitis. Furthermore, current and future trends in prophylactic and therapeutic modalities for adenoviral keratoconjunctivitis will be discussed."
4957,Viral respiratory infections in elderly patients and patients with chronic obstructive pulmonary disease(),"Patients with chronic obstructive pulmonary disease (COPD) and elderly individuals are prone to the development of significant lower respiratory tract symptoms from colds caused by viral respiratory pathogens. Longitudinal surveillance studies conducted to assess the impact of viral respiratory tract pathogens on morbidity and mortality in each of these at-risk populations demonstrate that there is a substantial burden of disease from viral respiratory infection (VRI), including rhinovirus infections, with respect to utilization of health-care resources. Despite a similar rate of occurrence of VRI among subjects with COPD and the control group, a cohort with moderate to severe COPD had a 2-fold increase in medical resource utilization, including clinician visits, emergency center visits, and hospitalizations. In surveillance studies of respiratory viruses in the elderly, regular seasonal infections with rhinoviruses cause substantial morbidity, which has been largely underappreciated and underreported."
4958,References,
4959,News in brief,
4960,Research highlights,
4961,OP 0364-0412,
4962,Oral Presentations 001 - 053,
4963,"Abstracts Survival under Critical Life Conditions: Rome, October 4–6, 1989",
4964,News in brief,
4965,Queen's University of Belfast,
4966,Spotlight on Osaka,
4967,Posters_Wednesday_14 October 2009,
4968,Highlight:Austria,
4969,Timely tale of avian flu,"A gripping account of the spread of the bird flu virus across southeast Asia holds lessons for the global management of pandemics such as swine flu, explains Ab Osterhaus."
4970,Posters_Monday_12 October 2009,
4971,Books Received,
4972,Fast vaccine offers hope in battle with Ebola,Similar vaccines could form part of future emergency strategy.
4973,All I want for 2005 is...,
4974,Caution raised over SARS vaccine,Jab against one strain might worsen infection with others.
4975,Charaterization of H9 subtype influenza viruses from the ducks of southern China: a candidate for the next influenza pandemic in humans?,Poultry market sequence survey highlights pandemic potential.
4976,FASEB in Las Vegas,"Next week, over 16,000 scientists will travel to Las Vegas, Nevada for the annual meetings of the Federation of American Societies for Experimental Biology and the American Society for Biological Chemistry and Molecular Biology. Selections from the more than 450 companies with exhibit booths are described below."
4977,Oral Sessions_Wednesday_14 October 2009,
4978,Nasal solution joins SARS race,Vaccine against fatal virus works in monkeys.
4979,Was the fuss overblown?,"To the friends and relatives of the 800-plus people slain by severe acute respiratory syndrome (SARS), this might seem like a callous question. But SARS barely registers a blip in the annual body count caused by infectious disease. Influenza is likely to kill up to half-a-million people in 2003, whereas the death tolls from malaria, tuberculosis and AIDS will each run to seven figures. So, when the outbreak is put into perspective, was the panic over SARS really warranted?"
4980,SARS may be here to stay,Vaccines and tracking could benefit from slow mutation of killer virus genome.
4981,Mysterious disease spreads in China,Unexplained deaths of farmers await diagnosis.
4982,Spotlight on Guangzhou,
4983,How and who does SARS kill?,
4984,Living with viruses,
4985,Extra-terrestrial research goes on,Closed astrobiology centre to be reborn as private company.
4986,Virology: Potent tiny packages,"Carl Zimmer's primer on viruses entertains, but reveals little about their basic traits, says Robin Weiss."
4987,Technological advances behind the anthrax investigation,Machines can quickly compare strains and pinpoint origin.
4988,PS 0035-0363,
4989,"A fatal case of seronegative, late-onset systemic lupus erythematosus presenting with motor sensory axonal polyneuropathy","Systemic lupus erythematosus is a multisystemic, autoimmune, inflammatory disorder predominantly affecting young females. Its onset may be abrupt or insidious, presenting with a broad range of clinical and immunological features. We report an unusual case of elderly-onset systemic lupus erythematosus in a woman initially diagnosed with discoid lupus, and subsequently admitted to hospital due to a progressive psycho-motor deficit. Electrophysiological measurements suggested a diagnosis of acute motor sensory axonal neuropathy. Unusual clinical features and negative serology led to diagnostic uncertainty. This case report offers information on the course of the disease through the entire chain of the health care delivery (from primary to tertiary). Despite the efforts of the hospital staff, it was not possible to save the life of the woman."
4990,Gazetteer,
4991,Poster Presentations,
4992,Ionicity in silica,
4993,News in brief,
4994,SARS hits hard,"Death rates higher than expected, but control measures seem to be working."
4995,"Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches",
4996,The flu pandemic: were we ready?,"Welcome to my weblog. I'm Sally O'Reilly, a freelance journalist based in Washington DC. I've been researching a book on pandemic preparedness. But now the time for preparation has run out."
4997,Hard water,
4998,ESICM 2010 WEDNESDAY SESSIONS 13 October 2010,
4999,On the origin of Triton and Pluto,"Lyttleton hypothesized long ago that Triton and Pluto originated as adjacent prograde satellites of Neptune(1). With the presently accepted masses of Triton and Pluto–Charon(2,3), however, the momentum and energy exchange that would be required to set Triton on a retrograde trajectory is impossible. The mass of Triton has probably been seriously overestimated(4,5), but not by enough to relax this restriction. It is implausible that the present angular momentum state of Pluto–Charon has been significantly influenced by Neptune(6). It could not acquire such angular momentum during an ejection event unless a physical collision was involved, which is quite unlikely. The simplest hypothesis is that Triton and Pluto are independent representatives of large outer Solar System planetesimals. Triton is simply captured, with potentially spectacular consequences that include runaway melting of interior ices and release to the surface of clathrated CH(4), CO and N(2) (ref. 7). Condensed remnants of this proto-atmosphere could account for features in Triton's unique spectrum(8–11)."
5000,Poster Sessions 602-806,
5001,Highlight: Francophone,
5002,Nitric oxide,
5003,Russia's secret weapons,
5004,Politics and disease,
5005,News in brief,
5006,Poster Sessions 054-249,
5007,Spotlight on Immunology,
5008,ESICM 2010 TUESDAY SESSIONS 12 October 2010,
5009,News in brief,
5010,Transplantation/Digestive tract,
5011,Free posters A,
5012,SARS may not be alone,Antibodies to a SARS-like virus hint at repeated infections.
5013,Is the SARS virus mutating?,"Viruses such as HIV and those that cause influenza have often been described as 'wily' because they mutate rapidly, a trait that helps them to evade drugs or the human immune system. But so far, the SARS virus seems remarkably invariant: the genome sequences of 14 isolates from patients in Singapore, Toronto, China and Hong Kong have not revealed any changes of real consequence(17)."
5014,Viral infections & autoimmune disease,
5015,Opportunities: The National Institutes of Health,
5016,Preparing for pandemics,"More deadly than the First World War, the global outbreak of influenza in 1918 terrified populations and tested governments. But would we fare any better today, asks Michael Sargent?"
5017,Sound of silence,
5018,Acute/Chronic respiratory failure,
5019,SARS spreads in China,Investigation launched into lab safety.
5020,Endoscope decontamination; wearing rings under gloves; effects of Chinese herbal medicines; anesthetic adverse events,
5021,Be a part of the process of establishing standards,
5022,Bacteria bound to cloth; glucoprotamin; toluidine blue O; surgical helmets versus filtering masks,
5023,"Synergy, energy, and teamwork",
5024,"7th European Congress on Intensive Care Medicine Innsbruck, June 14–17, 1994 East and West—A Common Future",
5025,"Abstracts of the 4th European Congress on Intensive Care Medicine, Baveno-Stresa, Italy, June 14–18, 1988",
5026,Viral neuroimmunology/Viral neuropathogenesis I,
5027,Opportunities: The National Institutes of Health,
5028,Solar oscillations,
5029,Spotlight on Immunology,
5030,OP 262-338,
5031,Deadly virus effortlessly hops species,Genetic engineering helps reveal origin of deadly 'flu
5032,Opportunities: The National Institutes of Health,
5033,Summer books,"With the yearly exodus from labs and lecture theatres imminent, Nature's regular reviewers and editors share some tempting holiday reads."
5034,Worlds Apart Together,Science has advanced enormously over the past 25 years. Yet progress has been limited to a few countries. What can be done in developing countries to ensure that knowledge and development are shared by all?
5035,"Editor’s picks, 2011–2012: fifteen articles in open access in Intensive Care Medicine",
5036,Bird flu 2005: the ongoing story,"News@nature.com keeps tabs on the situation, day-to-day."
5037,Drug may help treat SARS,Interferon helps infected monkeys breathe more easily.
5038,Reproductive and genetic consequences of founding isolated lion populations,"Species survival is critically dependent on reproductive performance, a complex physiological process under rigorous genetic control. Classical studies of inbreeding in laboratory animals and livestock have shown that increased homozygosity can adversely affect spermatogenesis, ovulation and perinatal mortality and morbidity(1–3). For wild populations, the consequences of inbreeding depression have not been examined intensively, although our recent studies of the African cheetah revealed a striking degree of genetic uniformity(4,5) combined with an extremely high incidence of structurally abnormal spermatozoa (>70%) in captive(6) as well as free-ranging(7) males. In this study, we report definitive evidence that the reproductive function of free-ranging mammals can be impaired as a result of demographic contraction followed by inbreeding. In an examination of three distinct lion populations (two from the Serengeti ecosystem in East Africa and a third descended from lions in the Gir Forest of western India), a direct correlation was observed between genetic variability and two physiological traits, incidence of abnormal sperm and circulating testosterone, a critical hormone for spermatogenesis."
5039,Bacteriology: Pathogens in perspective,"Andrew Jermy travels with Hugh Pennington on the arc of humanity's long, troubled relationship with microorganisms."
5040,Earth science: Suspect terranes,
5041,Towards the Absolute Zero,"Low Temperature Physics Four Lectures. By F. E. Simon, N. Kurti, J. F. Allen, K. Mendelssohn. Pp. vi + 132. (London: Pergamon Press, Ltd., 1952.) 21s."
5042,"Pittsburgh Award of the Pittsburgh Section, American Chemical Society: Dr. W. A. Gruse",
5043,SARS vaccine trial spotlights continued peril,Vigilance remains but other infectious diseases loom large.
5044,"ACMT 2020 Annual Scientific Meeting Abstracts – New York, NY",
5045,Unorthodox epidemiology,
5046,Fears of the return of SARS,Quarantines and animal culls in China aim to stop the disease.
5047,2002 Pioneer in NeuroVirology lecture,
5048,Bird flu spreads to China,The World Health Organization warns that a safe cull of birds is needed.
5049,News in brief,
5050,Acute lung injury/Airway,
5051,Spotlight on Wuhan,
5052,PS 0446-0765,
5053,Emerging virus evolves in camels,
5054,SARS linked to sweat,Could you catch the disease from a handshake?
5055,West Africans at risk from bat epidemics,Ecologists hope to avert public-health disaster without a cull.
5056,Poster Sessions 323-461,
5057,Disease monitors 'looking in the wrong places',Health leaders need global strategy for spotting disease threats.
5058,Oral Presentations 208–237,
5059,Bird flu data languish in Chinese journals,Untranslated reports noted in January that pigs had been infected by avian virus.
5060,SARS vaccines speed towards clinic,Researchers urge caution to avoid jabs pitfall.
5061,Highlight: British Columbia,
5062,Part-time Work in Chemical Engineering,
5063,SARS threatens reappearance in China,Authorities respond swiftly to suspected cases.
5064,PS 339-563,
5065,West Nile Virus may have felled Alexander the Great,Conservation and medicine collide in the jungle.
5066,Poster Sessions 91-226,
5067,Reviews in neurovirolgy: An introduction,
5068,Gossip mongers push for national networks,Surveillance of disease rumours looks set to expand.
5069,Antibodies for Middle East virus,
5070,Molecular lines in the red,
5071,PS 0849-1170,
5072,Spotlight on Osaka,
5073,Portrait of a probable killer,Viral double act implicated in 'killer flu' epidemic.
5074,Zoos help track spread of pandemics,Avian flu will be monitored in American zoos but no plans yet for swine flu.
5075,The constraints of history,"The Most Solitary of Afflictions: Madness and Society in Britain, 1700–1900. By Andrew Scull. Yale University Press: 1993. Pp. 448. $45, £29.95."
5076,Pigs test positive for bird flu,Unconfirmed report suggests fatal strain of virus has managed to infect swine.
5077,SARS database ramps up,Coronavirus website collates viral vitals.
5078,Poster Sessions 499–563,
5079,Research highlights,
5080,SARS may be mammal-bird merger,Genetic shuffle might have allowed human infection.
5081,Express delivery,
5082,Infectious disease: Chronicles of a killer virus,"Just over 30 years after HIV/AIDS was first recognized, three accounts of its ravages intrigue Robin Weiss."
5083,Poster Sessions 555 - 719,
5084,SARS sources widen,Labs brace for disease comeback.
5085,"Prognosis, classification, organisation",
5086,SARS' Achilles' heel revealed,Drugs to treat common cold may be effective against the virus.
5087,German virologist's race for swine flu test,Christian Drosten talks to Nature about tackling the threat of a pandemic.
5088,Books Received,
5089,Poster Sessions 292 - 465,
5090,Spotlight on Israeli science products,"As an accompaniment to this week's special feature on Science in Israel, the spotlight falls on a collection of Israeli diagnostics, drugs, research reagents, and medical products."
5091,Living with the Neanderthals,
5092,News in brief,
5093,Identity of mystery pneumonia bug sharpens,Questions raised over readiness for lethal SARS epidemic.
5094,Opportunities: The National Institutes of Health,
5095,Procalcitonin for differential diagnosis of graft rejection and infection in patients with heart and/or lung grafts,"Objectives: Investigation of the reliability of Procalcitonin (PCT) for differential diagnosis of acute rejections and non-viral infections in heart and lung transplanted patients.¶Design: Retrospective study.¶Setting: Transplant intensive care unit (ICU) at a university hospital.¶Patients: 57 heart, 18 lung and 3 heart-lung transplant patients.¶Measurements: PCT was measured in plasma samples of heart and lung transplanted patients using a commercial immuno-luminescence assay and was compared with values of C-reactive protein (CRP) and leukocytes (WBC).¶Results: PCT was elevated in patients suffering from bacterial and fungal infections. The magnitude of values was clearly associated with the severity of the infection. Rejections and viral infections did not interfere with the PCT release.¶Conclusion: PCT is a reliable predictor with discriminating power for non-viral systemic infections in patients after heart and/or lung transplantation. PCT allows an early differential diagnosis between rejection (AR) and bacterial/fungal infection (IF) and thus a rapid and focused therapeutic intervention. It avoids unnecessary antibiotic treatment which could be toxic for the graft itself in patients with rejection only. PCT provides vital information early to clinicians and allows them to improve the management of bacterial/fungal infections in immunocompromized transplant patients. PCT thus facilitates and improves the outcome of survival rate and the quality of life in the postoperative period of patients with heart and/or lung grafts."
5096,Labs crack killer's code,Sequence shows that animal spawned SARS virus.
5097,Liquorice may tackle SARS,After trying all sorts of compounds researchers say root extract looks promising.
5098,"Abstracts of the Annual Meeting of the “Societé de Réanimation de Langue Française”, Paris, 26–29 November 1981: Acute pulmonary failure and artificial ventilation",
5099,US politics and the test ban,
5100,PS 0036-0344,
5101,Abstracts DGPPN 2007,
5102,Einzelreferate und Buchbesprechungen,
5103,Abstracts der 45. Gemeinsamen Jahrestagung der DGIIN und ÖGIAIN,
5104,Mitteilungen der DGIM,
5105,Die Hypokotylfarbe als Markierungsfaktor von Genomstufen der Zuckerrübe,"In zunehmendem Maße werden anisoploideBeta-Rübensorten angebaut, deren zytologische Kontrolle zwecks Feststellung der Genomstufenprozentanteile recht arbeitszeitaufwendig ist. Übereinstimmend mit polnischen Autoren wurde festgestellt, daß die Hypokotylfarbe ein geeigneter Markierungsfaktor für die einzelnen Genomstufen darstellt. Kreuzt man tetraploide Pflanzen, die ein grünes Hypokotyl besitzen, mit diploiden Pflanzen, die ein rosa Hypokotyl aufweisen, so erhält man von dem tetraploiden Partner tetraploide “grüne” und triploide “hellbraune”, von dem diploiden Partner diploide “rosa” und triploide “hellbraune” Nachkommenschaften. Die in bezug auf die Hypokotylfarbe heterozygoten Pflanzen kann man demnach von den homozygot “grünen” und homozygot “rosa” Individuen unterscheiden. Die Kreuzung diploid grünxtetraploid rosa ist für diese Zwecke nicht brauchbar, da sich die triploiden Heterozygoten mit einem “grünen” und zwei “rosa” Allelen in der Hypokotylfarbe nicht deutlich von den homozygoten “rosa” Pflanzen abheben. Auf die Bedeutung dieser Markierungsmöglichkeit für bestimmte Forschungsprobleme, die Züchtung und die Saatgutkontrolle wird hingewiesen."
5106,Union of Swiss Societies of Experimental Biology: Abstracts of the 16(th) Annual Meeting,
5107,New from NPG,
5108,Abstracts der Jahrestagung,
5109,Mitteilungen der DGIM,
5110,News In Brief,
5111,How epidemics happen,
5112,Gentransfer mit adenoviralen Vektoren,"Adenoviral vectors are promising vectors for somatic gene therapy in a number of inherited and acquired disorders. In this contribution, the current scientific knowledge as it relates to production and function of adenoviral vectors is summarized. The different types of adenoviral vectors are described and their respective advantages and disadvantages are delineated. Current problems with adenoviral vectors, and implications as they derive from the fatality observed in the Philadelphia gene therapy trial are discussed."
5113,Atemwegsinfektionen bei immunsupprimierten Personen,"Pulmonary infections in immunocompromised patients remain a diagnostic and therapeutic challenge.New methods for the early detection of fungal and viral diseases might allow an immediate and specific therapy, thereby lowering the high mortality associated with such infections.The development of new drugs will hopefully lead to more effective treatment while decreasing the incidence of adverse effects. Interdisciplinary team work between internal medicine, radiology, surgery, microbiology, and virology is essential for the successful management of these patients."
5114,Biomedical briefing,
5115,Hope and hype,
5116,Biomedical briefing,
5117,Notable advances 2012,"From the microbiome to the microenvironment, certain areas of biomedicine saw fast-paced discovery this year. Here's a rundown of the papers that helped these fields advance quickly in 2012."
5118,Einzelreferate und Buchbesprechungen,
5119,"2003: The good, the bad and the unexpected",
5120,Mitteilungen der DGIM,
5121,Oral Communications and Posters,
5122,News In Brief,
5123,Biomedical briefing,
5124,Abstracts des Kongresses für Kinder- und Jugendmedizin 2019,
5125,Abstracts der 110. Jahrestagung der Deutschen Gesellschaft für Kinder- und Jugendmedizin e.V. (DGKJ),
5126,News in brief,Timeline of events...a brief history of the important news stories this month
5127,Timeline of events: A brief history of what made news this year,"Biomedical research in 2013 saw some dramatic developments, with unprecedented government action in the US ranging from the budget sequester in the spring to a dramatic government shutdown in autumn. But throughout the year, bright spots in science around the globe continued to dazzle, including multimillion-dollar partnerships to advance drug discovery and the go-ahead for highly anticipated trials of regenerative medicine."
5128,News in brief,Timeline of events...a brief history of the important news stories this month
5129,News In Brief,
5130,Abstractband zum 119. Kongress der DGIM 2013,
5131,Biomedical briefing,
5132,Abstracts der 46. Gemeinsamen Jahrestagung der DGIIN und ÖGIAIN,
5133,Falldefinitionen des Robert Koch-Instituts zur Übermittlung von Erkrankungs- oder Todesfällen und Nachweisen von Krankheitserregern § 4 (2) des Gesetzes zur Verhütung und Bekämpfung von Infektionskrankheiten beim Menschen (Infektionsschutzgesetz – IfSG): § 4 (2) des Gesetzes zur Verhütung und Bekämpfung von Infektionskrankheiten beim Menschen (Infektionsschutzgesetz – IfSG),
5134,Abstracts des Kongresses für Kinder- und Jugendmedizin 2018,
5135,Abstracts der 51. Gemeinsamen Jahrestagung der DGIIN und ÖGIAIN,
5136,"Abstracts der 48. Gemeinsamen Jahrestagung der DGIIN und ÖGIAIN. Der Mensch – ein anspruchsvoller Arbeitsplatz. 8.-10. Juni 2016 in Berlin, Estrel Berlin",
5137,Abstracts der 44. Jahrestagung der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin (GNPI): Gemeinsam mit der 26. Jahrestagung der Arbeitsgemeinschaft Neonatologie Mecklenburg-Vorpommern e. V.,
5138,News In Brief,
5139,Emerging infectious diseases,
5140,U. R. Fölsch,
5141,Mitteilungsseiten der DGIM,
5142,Plagues and people meet the microbe hunters,
5143,Mitteilungen der DGKJ und ÖGKJHK,
5144,64. wissenschaftliche Jahrestagung der GPOH,
5145,Hämovigilanz von Blutkomponenten Meldungen an das Paul-Ehrlich-Institut vom 1.1.1995 bis zum 15.11.1998: Meldungen an das Paul-Ehrlich-Institut vom 1.1.1995 bis zum 15.11.1998,"In Germany cellular blood products are a licensed medicinal product. In the following we would like to present the reporting procedure, analysis and evaluation of suspected cases from spontaneously recorded data. During the time period from 1.1.95 until 1.1. 98 a total of 1488 suspected adverse events were reported in connection with cellular blood products and fresh plasma. In 1270 (85.34%) of these case reports viral transmissions were implicated, in 187 (12.56%) immunological transfusion reactions and in 31 (2.06%) bacterial infections. The case reports concerning viral transmission were further evaluated in a look-back-procedure according to the guidelines of the „Arbeitskreis Blut”, a working party on acute issues arising in the transfusion medicine area. In 864 (68%) of the 1270 cases the causality of the blood product could be excluded by re-testing the donor. In 118 cases (9.3%) infectious donors were subsequently identified; 21 were HIV-, 81 HCV- and 16 HBV transmissions. The reports were decoded according to year of treatment to differentiate those cases that occurred before the introduction of mandatory donor screening from those that occurred afterwards. 51 transmissions arose from the time prior to screening for viral antibodies. A total of 67 cases (3 HIV, 48 HCV, 16 HBV) can be traced back to the diagnostic window of each infection. In Germany transfusion reactions are most likely to be underreported compared to France or theUnited Kingdom. The frequency of infections that arose from cellular blood products is comparable to the remaining risk described in scientific literature."
5146,Abstracts der 41. Jahrestagung der Gesellschaft für Neonatologie und Pädiatrische Intensivmedizin,
5147,Einzelreferate Und Buchbesprechungen,
5148,Buchbesprechungen,
5149,Reviews and comment from the nature publishing group,
5150,Plavix fzzranchise in jeopardy,
5151,A comparison of oligonucleotide-based microarray and real-time PCR for the detection of sexually transmitted infections,"Many diagnostic methods for sexually transmitted infections (STIs) have been developed. Because various infection agents are associated with STIs, and because infected persons sometimes show no symptoms, the diagnosis of STIs using nucleic acid amplification tests(NAATs) has required not only simultaneous multi-targeting, but also sensitive detection. Here, we compare microarray and real-time PCR for the detection of three common STIs agents, Ureaplasma urealyticum, Mycoplasma genitalium, and Chlamydia trachomatis, using human urine samples. The detection results showed that microarray and real-time PCR technology are both effective tools for the detection of STI agents. In conclusion, real-time PCR detection offers more sensitivity and specificity than microarray, because of the quantitative method employed. But, microarray offers better performance, in terms of high-throughput and simultaneous multi-targeting."
5152,Reviews and comment from the nature publishing group,
5153,Bovine Respiratory Disease in Finland,
5154,Cause of SARS still uncertain,
5155,SARS escaped Beijing lab twice,
5156,In the news,
5157,Latest SARS evidence,
5158,SARS-CoV ancestor found in Chinese bats,
5159,Reviews and comment from the nature publishing group,
5160,News in brief,
5161,Wednesday posters,
5162,Glucocorticoid contribution to lymphopaenia and immunpathology in patients with SARS,
5163,IN BRIEF,
5164,Genetics hits the headlines,
5165,Research Highlights,
5166,Thursday posters,
5167,In the News,
5168,Bat immunology takes off,
5169,News in Brief,
5170,In the news,
5171,Anthony Fauci,
5172,In the News,
5173,In Brief,
5174,In vitro estimation of metal-induced disturbance in chicken gut-oviduct chemokine circuit,"BACKGROUNDS: Heavy metals affect various processes in the embryonic development. Embryonic fibroblasts (EFs) play key roles in the innate recognition and wound healing in reproductive tissues. METHODS: Based on the relative toxicities of different inorganic metals and inorganic nonmetallic compounds against murine and chicken EF cells, mechanistic estimations were performed based on transcriptomic analyses. RESULTS: Lead (II) acetate induced preferential injuries in the chicken EF and mechanistic analyses using transcriptome revealed that chemokine receptor-associated events are potently involved in metal-induced adverse actions. As an early sentinel of metal exposure, the precision-cut intestine slices (PCIS) induced the expression of chemokines including CXCLi1 or CXCLi2, which were potent gut-derived factors that activate chemokine receptors in reproductive organs after circulation. CONCLUSION: EF-selective metals can be estimated to trigger the chemokine circuit in the gut-reproductive axis of chickens. This in vitro methodology using PCIS-EF culture could be used as a promising alternate platform for the reproductive immunotoxicological assessment."
5175,Small scares,
5176,Erratum: Emerging regulation and functions of autophagy,
5177,T cells calm the storm,
5178,In Brief,
5179,"3rd Winfocus Italian Congress, Bologna, Italy, 28–30 November 2009",
5180,In the News,
5181,"Dix-huitième réunion du Comité local de la SPE à La Réunion, 15 mars 2011",
5182,Faster drugs for unknown bugs,
5183,Infections and perinatal diseases – a comparative overview,
5184,In the news,
5185,Novel coronavirus spreads,
5186,In the News,
5187,SARS unanswered questions,
5188,Reviews and comment from the nature publishing group,
5189,In the news,"Our monthly round up of infectious diseases news, which this month includes inhibiting autophagy to target H5N1 influenza, how MRSA gained resistance down on the farm and 're-education' for the boy who cried outbreak."
5190,Research Highlights,
5191,In Brief,
5192,Structural genomics in the spotlight,"Structural genomics efforts have spurred the continuing development of new methods and technologies, benefiting a broad community."
5193,Expanding role for the apelin/APJ system in physiopathology,"Apelin is a bioactive peptide known as the ligand of the G protein-coupled receptor APJ. Diverse active apelin peptides exist under the form of 13, 17 or 36 amino acids, originated from a common 77-amino-acid precursor. Both apelin and APJ mRNA are widely expressed in several rodent and human tissues and have functional effects in both the central nervous system and peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular functions, fluid homeostasis, vessel formation and cell proliferation. More recently, apelin has been described as an adipocyte-secreted factor (adipokine), up-regulated in obesity. By acting as circulating hormone or paracrine factor, adipokines are involved in physiological regulations (fat depot development, energy storage, metabolism or eating behavior) or in the promotion of obesity-associated disorders (type 2 diabetes and cardiovascular dysfunctions). In this regard, expression of apelin gene in adipose tissue is increased by insulin and TNFα. This review will consider the main roles of apelin in physiopathology with particular attention on its role in energy balance regulation and in obesity-associated disorders."
5194,Prediction for Target Sites of Small Interfering RNA Duplexes in SARS Coronavirus,RNA interference is used for SARS-related pharmaceutical research and development. Following bioinformatic method twenty seven 21~25 base-long sequence segments in SARS-CoV genome are predicted as the optimal target sites of small interfering RNA duplexes.
5195,Safety first,"With a potential influenza pandemic looming, how practical is it to conduct vital experiments on emergent and often lethal pathogens?"
5196,Three decades of antiviral drugs,"Thirty years ago, just three drugs were available for the treatment of viral infections, but now more than forty have been approved. What have been the guiding principles in these achievements and what might the future hold for antiviral drug development? SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd2485) contains supplementary material, which is available to authorized users."
5197,Glucocorticoid treatment of patients with SARS: implications for mechanisms of immunopathology,
5198,"Günter Witzany (ed): Viruses: essential agents of life: Springer, 2012, ISBN 978-94-007-4898-9",
5199,Abstracts of the EPSM-ABEC 2008 conference,
5200,In Brief,
5201,Preemptive SARS patents,
5202,In the news,
5203,Living and dying with viruses,
5204,Articles selected by Faculty of1000: identifying antigens involved in autoimmune response; statistics in genomics; mouse full-length cDNA encylopedia; screen for Drosophila neural development genes; proteome of SARS-coronavirus,"A selection of evaluations from Faculty of 1000 covering the identification of antigens involved in an autoimmune reseponse, the difference between false positive and false discovery rate, a mouse full-length cDNA encylopedia, analysis of bristle number in Drosophila mutants to identify neural development genes and an analysis of the proteome of SARS-coronavirus."
5205,Quick custom flu vaccines,
5206,In the news,
5207,Direct buffer composition of blood pre-process for nucleic acid based diagnostics,"Recently, a variety of methods, so called “direct buffer”, have been developed to utilize nucleic acid in the blood for the measurement of infectious bacteria and virus without any equipment in the field. In here, we first investigated the individual and combinatory effects of candidate chemicals which might be composed of the direct buffer on the PCR inhibition reduction of main compositions in whole blood. The long and short PEGs, Na(2)SO(4) and GuSCN were selected as representative kosmotropic and chaotropic salts, respectively. MgCl(2) were chosen as divalent cation source and NaOH was used to control blood pH. The effect of common non-ionic biological detergent was tested with Triton X-100 and SDS (Sodium Dodecyl sulfate) was chosen as anionic detergent. These results could provide a foundation for the development of sample preparation solution in nucleic acid based diagnostic field. As a result, the direct buffer developed in this study was able to detect viruses with a concentration of 10(2) pfu/100 μL of whole blood by a very simple method."
5208,A microbial decade,"In celebration of our tenth anniversary, we revisit selected topics from the first few issues of the journal and assess the progress that has been made over the past decade."
5209,Functional analysis of the receptor binding domain of SARS coronavirus S1 region and its monoclonal antibody,"Severe acute respiratory syndrome (SARS) is caused by the SARS coronavirus (CoV). The spike protein of SARS-CoV consists of S1 and S2 domains, which are responsible for virus binding and fusion, respectively. The receptor-binding domain (RBD) positioned in S1 can specifically bind to angiotensin-converting enzyme 2 (ACE2) on target cells, and ACE2 regulates the balance between vasoconstrictors and vasodilators within the heart and kidneys. Here, a recombinant fusion protein containing 193-amino acid RBD (residues 318–510) and glutathione S-transferase were prepared for binding to target cells. Additionally, monoclonal RBD antibodies were prepared to confirm RBD binding to target cells through ACE2. We first confirmed that ACE2 was expressed in various mouse cells such as heart, lungs, spleen, liver, intestine, and kidneys using a commercial ACE2 polyclonal antibody. We also confirmed that the mouse fibroblast (NIH3T3) and human embryonic kidney cell lines (HEK293) expressed ACE2. We finally demonstrated that recombinant RBD bound to ACE2 on these cells using a cellular enzyme-linked immunosorbent assay and immunoassay. These results can be applied for future research to treat ACE2-related diseases and SARS."
5210,Death by viroporin,
5211,Structure Watch,
5212,Targeting SARS,
5213,WHO says coronavirus causes SARS,
5214,Conference conundrum,Does the popularity of a recent online photonics conference signify a growing appetite for a change in scientific interaction?
5215,In the News,
5216,"Vingt-quatrième réunion du comité local de la Société de pathologie exotique, 18 mars 2014",
5217,In this issue,
5218,A common cure for SARS?,
5219,News review of 2003,A month-by-month rundown and follow-up of this year's news highlights in drug discovery
5220,Reply to “Lack of support for an association between CLEC4M homozygosity and protection against SARS coronavirus infection”,
5221,In Brief,
5222,Unravelling SARS lethality,
5223,In the news,
5224,Some recent patent applications in the area of protease inhibitors,
5225,Awareness and outreach,
5226,SARS resource,
5227,Risikomanagement besonderer Infektionssituationen,"The WHO considers that there is considerable danger of an influenza pandemic. One result of globalisation is that other highly contagious infectious diseases, such as SARS or Ebola, which are potentially endemic, can also be brought into Germany. Bioterorrism must also be considered. As well as all other medical disciplines, hospital surgical departments must be armed against this now. National pandemic planning will be taken as an example to illustrate the planning needed in hospitals to prepare for emergencies arising from infections in such specific situations."
5228,C-X-C Motif Chemokine 10 Contributes to the Development of Neuropathic Pain by Increasing the Permeability of the Blood–Spinal Cord Barrier,"Neuropathic pain is among the most debilitating forms of chronic pain. Studies have suggested that chronic pain pathogenesis involves neuroimmune interactions and blood–spinal cord barrier (BSCB) disruption. However, the underlying mechanisms are poorly understood. We modeled neuropathic pain in rats by inducing chronic constriction injury (CCI) of the sciatic nerve and analyzed the effects on C-X-C motif chemokine 10 (CXCL10)/CXCR3 activation, BSCB permeability, and immune cell migration from the circulation into the spinal cord. We detected CXCR3 expression in spinal neurons and observed that CCI induced CXCL10/CXCR3 activation, BSCB disruption, and mechanical hyperalgesia. CCI-induced BSCB disruption enabled circulating T cells to migrate into the spinal parenchyma. Intrathecal administration of an anti-CXCL10 antibody not only attenuated CCI-induced hyperalgesia, but also reduced BSCB permeability, suggesting that CXCL10 acts as a key regulator of BSCB integrity. Moreover, T cell migration may play a critical role in the neuroimmune interactions involved in the pathogenesis of CCI-induced neuropathic pain. Our results highlight CXCL10 as a new potential drug target for the treatment of nerve injury–induced neuropathic pain."
5229,Managing the social amplification of risk: a simulation of interacting actors,"A central problem in managing risk is dealing with social processes that either exaggerate or understate it. A longstanding approach to understanding such processes has been the social amplification of risk framework. But this implies that some true level of risk becomes distorted in social actors’ perceptions. Many risk events are characterised by such uncertainties, disagreements and changes in scientific knowledge that it becomes unreasonable to speak of a true level of risk. The most we can often say in such cases is that different groups believe each other to be either amplifying or attenuating a risk. This inherent subjectivity raises the question as to whether risk managers can expect any particular kinds of outcome to emerge. This question is the basis for a case study of zoonotic disease outbreaks using systems dynamics as a modelling medium. The model shows that processes suggested in the social amplification of risk framework produce polarised risk responses among different actors, but that the subjectivity magnifies this polarisation considerably. As this subjectivity takes more complex forms it leaves problematic residues at the end of a disease outbreak, such as an indefinite drop in economic activity and an indefinite increase in anxiety."
5230,Pathology Elsewhere,
5231,Book Review,
5232,The Great Influenza: The Epic Story of the Deadliest Plague in History,
5233,Multisensory processes,
5234,Protein Crystallography in Drug Discovery,
5235,"Disinfection, Sterilization, and Control of Hospital Waste",
5236,Liver Disease Associated With Systemic Viral Infection,
5237,Inside Lab Invest,
5238,"Pandemic Influenza — Prevention and Treatment: Past, Present and Future",
5239,Book Review,
5240,The social ecology of infectious diseases by Kenneth H. Mayer and H.F. Pizer,
5241,MURINE CYTOMEGALOVIRUS INFECTION OF PHAGOCYTIC LEUKOCYTES,"Cytomegalovirus (CMV) infections have been associated with altered host defense and increased susceptibility to secondary infection. In previous experiments, we observed impaired migratory and chemotactic activity of neutrophils harvested from mice during sublethal murine CMV (MCMV) infection. To investigate further the effects of CMV infection upon phagocytic leukocytes, we incubated murine leukocyte suspensions (95% neutrophils) in vitro with MCMV derived either from tissue culture passage or salivary gland homogenate. Neutrophils incubated with salivary gland MCMV had depressed chemotactic activity at 2 and 4 h. For example, at 4 h the mean chemotactic index of neutrophils incubated with MCMV was 0.92 vs 2.56 in controls (p<0.01). Phagocytic activity at 4 h was also reduced (mean of 1.53 latex particles/cell in MCMV-incubated vs 2.39 in controls, p<0.01). In contrast, tissue culture-passed MCMV did not alter leukocyte function. Adherence of MCMV to phagocytic leukocytes was comparable to adherence of virus to mouse embryo fibroblast cells (2 to 3 log plaque forming units of MCMV/10(6) cells). Transmission electron microscopy at 4 h demonstrated occasional intracytoplasmic virions. These results indicate that impaired chemotactic and phagocytic activity of phagocytic leukocytes occurs after in vitro incubation with salivary gland-derived MCMV but not with tissue culture-passed virus. These differences may be attributable to altered virulence of MCMV or to the presence of soluble factors in salivary gland MCMV pools"
5242,Management of SARS relies on supportive measures and preventing the spread of infection,
5243,Single Dose Treatments in Tropical Infectious Diarrhoea: The Place of Secnidazole,"Single dose treatments have the important advantages of simple administration, excellent compliance, short-lived side effects (if any) and short period of drug pressure. However, drugs used for single dose treatments must possess important characteristics, namely, long half-life, effective concentration in tissues over a long period, and low toxicity. In tropical medicine, such drugs are an important advance in the treatment of malaria (mefloquine and halofantrine), schistosomiasis (praziquantel and metrifonate), filariasis (ivermectin), and genitourinary tract and intestinal infections. Intestinal infections are one of the most frequent problems in tropical medicine. While a large number of cases of diarrhoea are of viral (rotavirus) or bacterial (Salmonella, Escherichia coli) origin, necessitating only oral rehydration, some are of parasitological origin (Giardia, Entamoeba histolytica, Strongyloides, Trichuris, Schistosoma) and can be cured by a single dose treatment (tinidazole, secnidazole, ivermectin, albendazole, praziquantel). Secnidazole is the nitroimidazole with the longest half-life and is, therefore, used in single dose treatments for Giardia, acute intestinal amoebiasis and E. histolytica cyst carriers. Single dose treatments of most intestinal parasites will be a major advance in the management of tropical infectious diarrhoea. In the next decade, opportunistic intestinal infections (Cryptosporidium, Isospora, Enterocytozoon) in AIDS patients that are refractory to treatment could be the major problem."
5244,Extracorporeal membrane oxygenation (ECMO) for pulmonary parenchymal disease in older children,"Extracorporeal membrane oxygenation (ECMO) for the support of children outside the newborn period who have pulmonary failure is only recently becoming accepted. It is again being applied, after earlier failures, because well-trained teams and improved equipment and techniques are available following the success of neonatal ECMO. In addition, in Europe extracorporeal CO(2) removal (ECCO(2)R) in adults has been more successful. The use of ECMO for pulmonary failure in children does not have fixed indications and has had considerably less success than neonatal ECMO. Patients who require inspired oxygen fractions of over 0.5 and positive end-expiratory pressures of over 6 cm H(2)O for more than 12 h after being treated for more than 48 h should be considered candidates, given the high mortality of children with ARDS (70%). Survival averages 50% to 60%. Circuits and patient management techniques are very similar to those for newborn ECMO, but patients usually require longer times on ECMO. There are many more options for cannulation for both venoarterial and venovenous techniques than in neonatal and cardiac ECMO. The improving results indicate that ECMO will play a part in treating children with pulmonary failure. Further studies will be required to determine which patients can benefit from ECMO as well as the exact application in each case."
5245,"49th Annual Meeting of the Austrian Society of Surgery, Innsbruck, May 21–23, 2008 (Guest Editors: Beate Neuhauser, Dietmar Öfner, Elfriede Ruttmann-Ulmer, and Anton Schwabegger)",
5246,THE PREVALENCE OF CYTOMEGALOVIRUS (CMV) VIRURIA AMONG HOSPITALIZED CHILDREN AND THE RISK OF CMV ACQUISITION BY NURSES,"In 17 months 2198 children had admission urines cultured for CMV. 4.7% had CMV viruria (105 positive cultures), but significant age differences were observed. In the intensive care nursery the prevalence of CMV viruria (congenital and acquired infections) was 3.3% (18 of 551 newborns with viruria). On the nursing units for children ages 0 to 2 yrs, the prevalence of CMV viruria was 6.8% (32 of 544 positive, P<0.01, Chi square=7.3, when compared to newborns). The prevalence of CMV viruria on a nursing unit for children ages 2 to 5 yrs was 7.2% (27 of 382), similar to that for children 0 to 2 yrs (P>0.5 Chi square=0.004). On a nursing unit for children ages 5 to 12 yrs the prevalence of CMV viruria decreased to 4.2% (20 of 476, P=0.01, Chi square=6.6 when compared to children 2 to 5 yrs). For 12 to 18 year olds the prevalence of CMV viruria was only 1.2% (3 of 245, P<.001, Chi square=9.2, when compared to children 5 to 12 yrs). Among 72 seronegative nurses with daily patient contact, none acquired CMV but only 20 worked with the high prevalence age group (0 to 5 yrs). These results suggest that in spite of constant exposure CMV transmission occurs infrequently."
5247,"39th ESCP European symposium on clinical pharmacy & 13th SFPC congress: clinical pharmacy at the front line of innovations. 21–23 October 2010, Lyon, France",
5248,Chondrogenic differentiation and three dimensional chondrogenesis of human adipose-derived stem cells induced by engineered cartilage-derived conditional media,"Due to lack of optimal inductive protocols, how to effectively improve chondrogenesis of adiposederived stem cells (ASCs) is still a great challenge. Our previous studies demonstrated that the culture media derived from chondrocyte-scaffold constructs (conditional media) contained various soluble chondrogenic factors and were effective for directing chondrogenic differentiation of bone marrow stem cells. Nevertheless, it remains unclear whether the conditional media can induce ASCs towards chondrogenic differentiation, especially for three-dimensional (3D) cartilage formation in a preshaped scaffold. In this study, it demonstrated that the conditional media derived from chondrocyte-scaffold constructs could promote ASCs to differentiate into chondrocyte-like cells, with similar expression of type II collagen to those induced by chondrogenic growth factors. Moreover, the expression level of chondrocyte-specific genes, such as SOX9, type II collagen, and COMP, was even higher in conditional medium group (CM) than that in optimized chondrogenic growth factor group (GF), indicating that the conditional media can serve as an effective inducer for chondrogenic differentiation of ASCs. Most importantly, the conditional media could also induce ASC-scaffold constructs to form 3D cartilage-like tissue with typical lacunae structures and positive expression of cartilage specific matrices, even higher contents of GAG and type II collagen were achieved in CM group compared to GF group. The current study establishes a simple, but stable, efficient, and economical method for directing 3D cartilage formation of ASCs, a strategy that may be more closely applicable for repairing cartilage defects."
5249,Autopsy,
5250,Techniques,
5251,"Special Issue: Abstracts of the 9(th) International Conference on Environmental Health Science, 2-3 November 2016, Incheon, Republic of Korea: Global Issues in Marine Environmental Conservation and Health Diagnosis November 2 (Wed) – 3 (Thu), 2016 Ghent University Songdo Global Campus Incheon, Republic of Korea",
5252,Pflegepolitik in 5 Minuten,
5253,Es gibt auch noch etwas Anderes,
5254,Mitteilungen der DGIM,
5255,Role of Viral Infection in the Aetiology of Multiple Sclerosis: Status of Current Knowledge and Therapeutic Implications,"Multiple sclerosis (MS) is a chronic disease of the CNS that typically begins in late adolescence or early adulthood. It is highly variable in its expression and severity. The cause of MS is unknown, but both genetic and environmental factors have been implicated in its pathogenesis. It is known that viruses can induce chronic neurological disease, but the pathogenetic process in unclear. A viral cause for MS has been postulated, but to date no single virus has been confirmed to be associated with the disease. Although most viral candidates are no longer considered as possible aetiological agents in MS, a few are still being investigated."
5256,Sustaining Hospital Readiness for Ebola,
5257,Literature in pediatric radiology,
5258,"European Society of Pediatric Radiology 32nd Congress Utrecht, The Netherlands, May 18–20,1995 Abstracts of Oral Presentations and Poster Presentations",
5259,Posters,
5260,Book review,
5261,Differentially expressed genes in human gingival fibroblasts cultured on microgrooved titanium substrata: A pilot study,"The purpose of this study was to determine the differentially expressed genes in human gingival fibroblasts (HGFs) cultured on titanium (Ti) substrata with topographies presenting microgrooves and acid-etched roughness. Microgrooves were fabricated with a truncated V-shape in cross-section at 15/3.5, 30/10, and 60/10 μm (width/depth) by photolithography. Subsequent acid etching was applied to the entire surface of the fabricated Ti substratum to generate etched microgrooves and ridges (designated as E15/3.5, E30/10, and E60/10). Both smooth and acidetched-only Ti were used as controls (designated as NE0 and E0). Large-scale gene expression analyses were performed using differential display PCR, and the results were confirmed using RT-PCR and quantitative real-time PCR. Of the 21 genes with altered expression determined by differential display PCR and sequencing, we verified through RT-PCR that MTDH and TIMP1 were up-regulated and TGF-β1, TPM1, and VIM were down-regulated in the HGFs cultured on E60/10 versus NE0. We also confirmed, by quantitative real-time PCR, that MTDH and TIMP1 expression in HGFs on E60/10 was significantly up-regulated compared to HGFs on the other Ti substrata. This study indicates that acid-etched ridges and microgrooves on Ti with a width and depth of 60 and 10 μm (E60/10) induce alterations in the expression of genes involved in cell adhesion, proliferation, and regulation of the cytoskeleton in HGFs."
5262,"Canicules, La Santé Publique en Question",
5263,Book review,
5264,Book review,
5265,Mixed and blended emotional reactions to 2014 Ebola outbreak,
5266,CMV reactivation caused by methylprednisolone therapy for ARDS after esophagectomy,"BACKGROUND: Cytomegalovirus (CMV) infection is endemic worldwide. Although CMV reactivation often becomes a serious problem in immunocompromised patients, the prevalence of CMV reactivation caused by methylprednisolone therapy for ARDS after esophagectomy has yet to be determined. METHOD: Among 175 consecutive patients with thoracic squamous cell esophageal cancer who underwent esophagectomy with extensive lymph node dissection at Akita University Hospital between 2007 and 2010, 11 patients (6.3 %) diagnosed with ARDS during the acute phase of esophagectomy were enrolled and treated with steroid pulse therapy, high-dose (15–20 mg/kg/day) administration and tapering in this retrospective study. RESULTS: Seven of the 11 patients (63.6 %) were diagnosed with CMV reactivation based on CMV antigenemia assayed 19.1 days after the start of methylprednisolone administration and were treated with ganciclovir for 39.6 days. Six of the 7 patients (85.7 %) diagnosed with CMV reactivation were administered a total methylprednisolone dose of more than 4,000 mg. Though there was no significant difference between patients with and without CMV reactivation, there was a tendency that patients with CMV reactivation showed a lower minimum number of lymphocytes during the acute phase of esophagectomy (p = 0.051, Student’s t test, average 223.3 and 298.0/μl, respectively). CONCLUSION: Though the number of study patients is small, the prevalence of CMV reactivation caused by high-dose methylprednisolone therapy for ARDS after esophagectomy is remarkably high. This result strikes a note of warning concerning the management of these patients and suggests the importance of screenings for CMV reactivation so as to make an accurate diagnosis and initiate treatment in a timely manner."
5267,Abstracts of the 35th annual meeting of the GTH,
5268,43. Jahrestagung der Österreichischen Gesellschaft für Pneumologie. 3. Jahrestagung der Österreichischen Gesellschaft für Thoraxchirurgie,
5269,Inside the USCAP Journals,
5270,"25. Jahrestagung der Deutschen Gesellschaft für Hämatologie und Onkologie gemeinsam mit der Österreichischen Gesellschaft für Hämatologie und Onkologie: Kongreß 1980, Homburg/Saar, 5. bis 8. Oktober 1980 Referate 1–32, Freie Vorträge 33–140",
5271,XVI meeting of the European Association for Haematopathology 2012 Abstracts,
5272,"Selected Abstracts from the National Congress of the Italian Society of Hypertension (SIIA 2009): 2009 October 1–4, Rome, Italy",
5273,"Abstracts presented at the 13th International Congress on Amino acids, peptides and proteins",
5274,Stomata and plasmodesmata,"In developing epidermal tissue ofPhaseolus vulgare L. complete plasmodesmatal connections occurred between guard cells and epidermal cells and between sister guard cells of a stoma but they were not seen in fully differentiated tissue. However, incomplete, aborted plasmodesmata were occasionally seen in the common guard/epidermal cell wall, usually connected to the epidermal cell protoplast, in mature tissue. Plasmodesmatal connections between neighbouring epidermal cells were commonly observed in tissue at all stages of development. In all locations, the plasmodesmata were usually unbranched occurring singly or in small pit fields; very rarely branched, incomplete plasmodesmata were also seen in the wall between mature guard and epidermal cells. The significance of these findings were related to stomatal functioning and to the development of plasmodesmata in general."
5275,"PP4 - Displayed on Wednesday, September 12",
5276,Abstracts of papers and posters advanced activities in pharmaceutical care 24th European Symposium on Clinical Pharmacy,
5277,Hinweise auf Artikel in dieser Ausgabe,
5278,"Abstract of the 68th Meeting (Spring Meeting) 6–9 March 1990, Heidelberg",
5279,BHS Abstracts,
5280,"Abstracts for the IPNA Congress, 30 August - 3 September 2013, Shanghai, China",
5281,The pathogenesis of inflammatory disease: Surgical shock and multiple system organ failure,"Chronic inflammatory disease, embracing rheumatoid arthritis (RA), inflammatory bowel disease (IBD), hepatitis, asthma, atherosclerosis, multiple system organ failure (MSOF), etc., is mediated by reactive oxygen species (ROS). These ROS originate from activated neutrophils in infections and in immune and autoimmune reactions, from tissue deposits of ferritin, and from futile cycling of cytochrome P450 (CYP) following exposure to persistent chemicals, and may be perpetuated by the actions of complement, cytokines and eicosanoids. Acute inflammation is normally arrested by removal of ROS by tissue glutathione (GSH) and the antioxidant vitamins, A, C and E, all of which are regenerated by NADH and NADPH. Failure of this antioxidant defence system can lead to oxidative stress and to chronic inflammatory disease, including surgical shock and MSOF. The roles of oxidative stress and microcirculatory arrest in promoting MSOF, and of GSH, the antioxidant defence system, and fibronectin in preventing this, are reviewed in the light of recent experimental studies of surgical shock, including fasting, anaesthesia, hepatic ischaemia and reperfusion."
5282,43. Jahrestagung der Österreichischen Gesellschaft für Innere Medizin,
5283,Kardiopulmonale Reanimation „oben ohne“. Mode oder Wissenschaft,
5284,AUTHOR INDEX,
5285,Abstracts of the 37th annual meeting of the GTH (Gesellschaft für Thrombose- und Hämostase-forschung),
5286,"Transgenesis and genome analysis, Nantes, France, June 6th 2011",
5287,Subject Index to Volume 35,
5288,Traumatologie II,
5289,Viruseinschlüsse in der Zellwand und in Protoplasten vonin vitro kultiviertenArmoracia-Geweben,"Root explants ofArmoracia rusticana were cultivatedin vitro on theMurashige, andSkoog 1962 nutrient medium with addition of 2,4 D (2,4-Dichlorophenoxyacetic acid). Under such conditions callus tissue containing several apical meristems developed. Without 2,4 D the explants were growing to aseptic small plants; when further cultivated in soil they developed into big plants showing leaves with different deformations. These leaves, aseptically cultivated plants and callus tissue were examined by light and electron microscopy. There occured two types of inclusions consisting of isometric and elongated particles, respectively. Those of the isometric type were observed in the cytoplasm of meristematic cells of the callus; the isometric particles had a diameter of about 20–22 nm and were arranged hexagonally or in curvilinear arrays. In all other tissues that were examined such aggregates were to be seen only in vacuoles. Isometric particles were also found in plasmodesmata of all tissues examined. They lay in a tubulus which protrudes into the cytoplasm on one side of the cell wall. Desmotubuli appeared only in particle-free plasmodesmata. Protrusions of the cell wall into the cytoplasm containing tubuli and isometric particles within were observed only in callus tissue and in epidermic cells of leaves. In the cell wall of callus cells, conspicuous cavities connected with the cytoplasm by plasmodesmata contained many particles which were arranged in hexagonal structures. It seemed as if they had been put away into the cell walls or into the vacuoles. The occurence of fibrillar inclusions together with those consisting of isometric particles in the same cell was extremely rare. The fibrillar inclusions were observed in the cytoplasm and in the nucleus. The diameter of one fibril is about 12 nm. The thylacoids in well differentiated chloroplasts in callus and in cells of leaves are curved; single swelled thylacoids lie as vesicles in peripheral stroma. As tissues ofArmoracia rusticana plants from different localities do not contain such inclusions we assume that the root segment examined was infected with two different viruses. The isolation of the viruses has not yet been possible."
5290,"Irish thoracic society: Proceedings of Meeting held November, 1691 in Belfast",
5291,"Author and Subject Indexes—Volume 27, 2003",
5292,"Abstracts, IAP'98 8th Meeting of the International Association of Pancreatology July 13–15, 1988 Tokyo, Japan",
5293,Inside the USCAP Journals,
5294,Jahrestagung 2011 der Österreichischen Gesellschaft für Pneumologie,
5295,Book review,
5296,"35th Annual Meeting of the Arbeitsgemeinschaft für Pädiatrische Nephrologie, 18 - 20 March 2004, Mainz, Germany",
5297,Inaugural national scientific medical meeting,
5298,Scientific Programme,
5299,Abstracts of the contributed papers,
5300,"Abstracts of the 9th Congress of the International Pediatric Nephrology Association, August 30–September 4, 1992, Jerusalem, Israel",
5301,"Neuroimmunomodulation: Stress and immune function: The Lovelace Institutes, Albuquerque, New Mexico 7–9 October 1994",
5302,Hinweise auf Artikel in dieser Ausgabe,
5303,Joint Esctaic – Sfimar Meeting,
5304,Biomedical vignette,
5305,Book reviews,
5306,Nierenerkrankungen undihre Beziehungen zu Infektherden im Hals-Nasen-Ohrengebiet und an den Zähnen,
5307,"15(th) Congress of the International Pediatric Nephrology Association: 29 August – 2 September, 2010 New York, NY, USA",
5308,"ESCP 36th European Symposium on Clinical Pharmacy ‘Implementing Clinical Pharmacy in Community and Hospital Settings: Sharing the Experience’, Istanbul, Turkey 25–27 October 2007; Abstracts",
5309,Irish Society of Gastroenterology: Proceedings for summer meeting – 26th/27th May 1995 in Galway,
5310,Successive changes in the ultrastructure ofOryza sativa L. cells during growth and aging,"The ultrastructure ofOryza sativa L. cells in suspension was determined as cells developed, matured and senesced at 3, 10, and 17 days, respectively, after transfer to fresh medium. Although cultures of 3-day-old cells contained some senescent cells, the symptoms of cell aging were very conspicuous at 10 days and were most pronounced at 17 days. The amount of cytoplasm decreased as the number of lytic areas, myelin figures and vesicle bodies increased. Other noticeable subcellular changes observed were ultrastructural modifications of mitochondria, proplastids, amyloplasts, and nuclei. Such changes were associated with a general deterioration of the lipoprotein complex of the cell during its growth. A fibrous structure without an external membrane was observed and its reported for the first time for cells grown in suspension culture."
5311,"Abstract 7th International Symposium Supportive Care in Cancer, Luxembourg, 20–23 September 1995",
5312,The ultrastructure of plasmodesmata,"It is suggested that the central strand which traverses plasmodesmata is in open continuity with the endoplasmic reticulum of adjacent cells, and that this strand (desmotubule) represents a modulation of a normal ER membrane so that it comprises solely spherical protein subunits. This concept is used to illustrate how plasmodesmata could form a median nodule or anastomosing central strands. The implications of this model in relation to current theories of symplasmic transport are discussed, and the possibility for further experimental work is outlined."
5313,"Seventeenth Sir Peter Freyer memorial lecture and surgical symposium: September 23rd & 24th, 1993",
5314,31st Workshop for Pediatric Research: held at the Kinderklinik of the Georg-August-Universität Göttingen 16–17 February 1995,
5315,Irish Society of Gastroenterology: Proceedings of winter meeting held in Dublin on 25th/26th November 1994.,
5316,"Abstracts of the 64th Annual Conference of IACTS, February 2018",
5317,"Strongyloidiasis: Epidemiology, clinical manifestations and new methods for diagnosis and treatment","Strongyloidosis is a parasitic disease of the intestines, seen mainly in tropical areas. It is quite likely that, because its manifestations are milder than those of other tropical diseases, it may be overlooked in regions where parasitic diseases such as hookworms and roundworms are endemic. With future improvements in hygiene and the resulting decreases in parasitic diseases, increasing attention will be focused on strongyloidiasis in tropical regions — a phenomenon currently being observed in Okinawa. Studies on the diagnosis and treatment of apparently healthy Strongyloides carriers have only just started. These studies can be expected to play a major role in improving the near-future health and welfare of people in tropical regions of the world. Parasitic diseases in Japan have a strong local character; a long-term eradication program, with due consideration to HTLV-1 infection, must be instituted."
5318,"Abstracts Jahrestagung 2015 der Österreichischen Gesellschaft für Pneumologie: Graz, 15.–17. Oktober 2015",
5319,2012 CIS Annual Meeting: Primary Immune Deficiency Diseases North American Conference,
5320,"Abstracts of the European Association of Nuclear Medicine Congress: 20–24 May, 1990 Amsterdam, The Netherlands",
5321,"10th Asian Congress of Pediatric Nephrology 2008 (ACPN 2008) Innovation in Prevention and Therapeutic Strategies August 28–30, 2008 Centara Grand & Bangkok Convention Centre at Central World, Bangkok, Thailand",
5322,Abstract,
5323,20th ECP,
5324,Beijing's Hard and Soft Repression in Hong Kong,"Hong Kong's new Police Commissioner Chris Tang announced in Beijing on December 7, 2019, that he would use “both hard and soft approaches” to end the anti-government protests. This article argues that such “approaches” amount to physical and non-physical repression—hard power, but employed by Hong Kong, rather than mainland, forces, combined with sharp power exercised by both Beijing and the local authorities. These measures are responses to the limits on what Beijing can do under the “one country, two systems” model. As Beijing cannot send the People's Liberation Army (PLA), it has subverted Hong Kong's once-respected civilian police force to act like the mainland's public security. And as Hong Kong's judiciary is relatively autonomous and many of the arrested would not be convicted or sentenced, the police have resorted to a decapacitation campaign to inflict direct violence on protesters. Moreover, as the city's freedom has allowed the public to support protesters in various ways, Beijing has launched a program of dismissal of pro-democracy individuals in both public and private sectors. To zoom in on Beijing's hard and soft repression, this article examines in closer detail the other “frontliners” at protest sites who provide professional services vital to the sustainability of protests: medics, firefighters, lawyers, journalists, and educators."
5325,Les exacerbations sévères de l’asthme : quels sont les acteurs saisonniers ? Les infections virales,
5326,ESPR 2017,
5327,In Kürze,
5328,Abstracts_Poster presentations,
5329,SPR 2013,
5330,Abstract,
5331,Abstracts Scientific Papers Honorary Lectures Categorical Courses Workshops State-of-the-Art Symposia,
5332,Satellite Symposia and Meet-the-Professor Sessions: Satellite Symposium I,
5333,B scientific sessions (SS),
5334,"2001 Scientific Session of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) St. Louis, Missouri, USA, 18–21 April 2001 Poster presentations",
5335,C scientific exhibits (SE),
5336,Posters,
5337,Scientific Programme — Abstracts,
5338,"3rd Central European Congress of Surgery, Norman Barrett Symposium & 5th Croatian Congress of Surgery with International Participation. Dubrovnik, April 28–May 1, 2010. Guest Editor: Božidar Župančić (Zagreb, Croatia)",
5339,"25th Annual Meeting of the Austrian Society of Transplantation, Transfusion and Genetics Graz, October 19–21, 2011",
5340,"8th Annual Meeting of Chinese College of Surgeons and 19th Annual Meeting of the European Society of Surgery: Beijing, May 15—17, 2015",
5341,"34th Seminar of the Austrian Society for Surgical Research. Wagrain, November 11–13, 2010. Guest Editor: H. Cerwenka, Graz, Austria",
5342,"48th Annual Meeting of the Austrian Society of Surgery, Graz, June 7–9, 2007",
5343,"50th Annual Meeting of the Austrian Society of Surgery. Vienna, June 18–20, 2009. Guest Editors: Albert Tuchmann, Erhard Schwanzer, Benedikt Walzel",
5344,"55th Annual Meeting of the Austrian Society of Surgery: Graz, June 25—27, 2014",
5345,Abstracts of the world congresses,
5346,National scientific medical meeting 1996 abstracts,
5347,Review of the proceedings,
5348,"Waterford Surgical October Club Royal Academy of Medicine, Surgical Section proceedings of meeting held 19th October 1996 at Waterford Regional Hospital",
5349,Postgraduate Course: Integrating Basic Science into Clinical Practice,
5350,Potential therapies for coronaviruses,"Coronavirus replication offers several attractive targets for chemotherapy. These include: viral entry (inhibited by chloroquine and peptides); viral RNA (targeted by antisense approaches/RNAi); the main protease 3CLpro (inhibited by peptidic molecules such as HIV-1 protease inhibitors and miscellaneous compounds); the accessory protease(s) PLpro(s) (inhibited by zinc ions); RNA-dependent RNA polymerase (inhibited by aurintricarboxylic acid and antisense approaches); and helicase (inhibited by bananins). Chloroquine and HIV-1 protease inhibitors (with well-known toxicity profiles) should be considered for clinical tests if severe acute respiratory syndrome (SARS) re-emerges; however, there are other attractive compounds. Lessons should be learnt from AIDS research for choosing the best strategies."
5351,Symposium,
5352,Posters,
5353,"10th Congress of International Society of Systemic Auto-Inflammatory Diseases (ISSAID): Genoa, Italy. 31 March - 3 April 2019",
5354,Symposia,
5355,April 2020 People & Events,
5356,Calendar,
5357,Komkommertijd,
5358,Posttraumatic stress disorder in survivors of acute respiratory distress syndrome (ARDS) and septic shock,"Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) define medical conditions of acute respiratory insufficiency deriving from direct and indirect damage of the alveolar parenchyma and often associated with multiorgan dysfunction (MODS). As a rule, intensive care is based on mechanical ventilation often requiring high doses of sedatives and narcotics. Despite major progress in intensive care medicine the rate of mortality is still very high. Whereas in the past the level of medical progress has been rated based on the mortality rate alone, the many negative somatic and psychological sequelae in long-term-survivors of ARDS are only now being appreciated. From a perspective of C/L psychiatry persisting cognitive dysfunctions, anxiety and mood disorders, posttraumatic stress disorders (PTSD) in their negative impact on health-related quality of life are intensively investigated. In the etiopathogenesis of PTSD associated with ALI/ARDS, many influences have to be discussed, e.g., increases in CO(2) triggering panic affects, a mismatch of norepinephric overstimulation and cortisol insufficiency, negative effects of high doses of benzodiazepines resulting in oversedation, prolonged phases of weaning and more frequent states of delirium. Consolidation and retrieval of traumatic memories of the ICU stay are influenced by complex factors. From a clinical point of view prophylactic stress doses of hydrocortisone may reduce the major risk of PTSD associated with ALI / ARDS."
5359,Physicians Poster Sessions,
5360,1345 The Use of Hood Cpap to Improve Compliance with Non-Invasive Ventilation (NIV): A Single Centre Experience,"Background: The Ca-Star CPAP (Continuous Positive Airway pressure) Hood is a relatively novel method of delivering CPAP to infants and children. Aims: To report the experience of a single centre in the application of Hood CPAP for provision of NIV. Methods: We retrospectively analysed all children admitted to a six bedded PCCU for NIV over a 2 year period. Children included in the study were those who had failed conventional mask CPAP yet gone on to tolerate Hood CPAP for >24 hours or until NIV was no longer required. Results: Six patients (4 males) were identified with mean age of 14 months (range 6 months - 3 years). The reasons for failing conventional CPAP were pressure areas on face (1), child intolerance of mask pressing on face (4) and inability to get seal due to facial abnormalities (1). The indications for CPAP included primary Respiratory condition (5) and neuromuscular (1). The underlying co-morbidities were ex pre-maturity (2), Trisomy 21 (2), congenital abnormalities (1) and none (1). Hypothermia was observed as a complication in 2 patients. Conclusions: Intolerance of the mask is a problem in the ‘toddler’ age range, and in our experience the HOOD is an under-utilised but useful interface to provide CPAP in these patient groups. It can be used successfully as an alternative to intubation, for relief of facial pressure areas and to provide an effective seal in case of facial abnormalities."
5361,Scientific Abstracts,
5362,THE EFFECT OF GESTATIONAL AGE AND LABOR UPON INTRACELLULAR SURVIVAL OF HERPES SIMPLEX VIRUS (HSV),"Neonatal HSV infection is often characterized by rapid, life-threatening dissemination. Perinatal immunologic factors examined to date incompletely account for this tendency to disseminate, for the rapid disappearance of this vulnerability early in postnatal life, and for the disproportionate occurrence in prematures. To determine a possible influence of gestational age or perinatal events upon this phenomenon, we studied 29 placental specimens of varying gestational age and mode of delivery. The intracellular survival of type 2 HSV within placental lymphocytes was assessed at 48 hour intervals for 6 days to determine the frequency and magnitude of virus titer changes. Early (0-48hrs) titer increases were significantly (p=0.015) more frequent in specimens with gestational age ≤ 35 wks (3/8) than those with ≥ 36 wks (0/21) gestations. Titer increases from 48 to 96 hours were common (14/29) but bore no relationship to gestational age, labor, or mode of delivery. Most importantly, late (>96 hrs) titer increases were most influenced by the occurrence of labor and unrelated to gestational age. Late titer increases did not occur in specimens from caesarian section without labor(0/12) and were significantly (p=0.023) more frequent in specimens where labor occurred (7/17). These findings are consistent with the hypothesis that early gestational age and the occurrence of labor transiently provide a more permissive intracellular environment for HSV replication and dissemination."
5363,Publication only,
5364,POSTER SESSION I,
5365,President’s Plenary Session,
5366,Scientific Abstracts,
5367,Pathobiology,
5368,Scientific Abstracts,
5369,DETECTION OF DONOR'S LYMPHOCYTES IN THE PERIPHERAL BLOOD OF NEONATES FOLLOWING EXCHANGE-TRANSFUSION,"Twenty preterm and term female neonates were exchange-transfused with males donor fresh blood during their first days of life because of hyperbilirubinaemia or severe septicaemia. In order to study the presence of donor lymphocytes in the neonates peripheral blood, chromosome studies were performed immediately after,12 and 72 hours following the exchange transfusion. We used the fluorescent-binding technique in order to distinguish the donor's cells by the presence of the γ-chromosone or other fluorescent markers in at least 300 mitotic figures in each speciment. We found that in jaundiced babies immediately following exchange transfusion less than 10% of the lymphocytes came from the donor and 12 hours later only 1-2% were still present.However in neonates exchange-transfusion for septicaemia the percentage of donor's lymphocytes immediately following the proceedure sometimes reached 50% and dropped to less than 10% by 12 hours.This shows the inability of the depressed by the infection host defence mechanisms of the newborn to deal with the donor's lymphocytes."
5370,Techniques,
5371,POLYMORPHONUCLEAR LEUKOCYTE SUPEROXIDE ANION GENERATION IN CRITICALLY ILL CHILDREN,"Generation of active oxygen species by activated PMNs plays a paramont role in human immunologic defenses. However, numerous in vitro experiments have demonstrated that inadvertant release of highly reactive oxygen metabolites by the PMN into the surrounding milieu results in autoinjury and is associated with diffuse capillary leak syndromes (septic shock, ARDS). NADPH oxidoreductase, the superoxide anion generating enzyme, is a PMN membrane bound flavoprotein normally dormant but inducible by a variety of agents. We studied the specific activity of this enzyme in critically ill children to determine if detection of its activation might provide an early clue of impending in inflammatory amplification injury. Venous blood specimens from 12 healthy young adult controls reflected an induced enzyme activity of 8.23 ± 2.1 nmoles superoxide/min./10(6) PMNs ± S.D. Similarly the induced activity in a group of 6 pediatric intensive care patients without evidence of capillary leak syndrome was 7.3 ± 2.2 . In constrast the mean induced activity from a group of 6 critically ill children with evidence of capillary leak syndrome was 3.0 ± 1.1 (p<.001). No activity was demonstrated in non-induced PMNs from any group. No differences in induced enzyme activity were appreciated between venous and arterial blood samples. Such findings may demonstrate the phenomena of desensitization of previously in vivo activated neutrophils to additional stimulation, and may represent a host defense which minimizes autoinjury."
5372,Scientific Abstracts,
5373,Bone and Soft Tissue Pathology,
5374,Genitourinary,
5375,Scientific Abstracts,
5376,Pathobiology,
5377,1347 Non Invasive Ventilation in Pediatric Intensive Care Unit,"Objective: The aim of this study was to investigate the benefit of the Non Invasive Ventilation (NIV) in children admitted to the Pediatric Intensive Care Unit (PICU). Methods: We studied 22 children supported by NIV, aged 1 month to 15 years. The duration of the study was 4 years (January 2006- December 2009). The total number of admissions to ICU during this period was 759 (2,9% supported by NIV). The causes of the respiratory failure in these children supported by NIV were: chronic diseases-infection (n=11; 50%), neuromuscular diseases (n=4; 18,18%), renal transplantations-immunosuppression (n=3; 13,63%), leukemias (n=2; 9,09%), respiratory infections (n=2; 9,09%). We selected the Biphasic Ventilation mode (Bi-Vent) by facial mask, because our patients were in severe respiratory distress. The parameters in this mode were as follow: PIP: 10-16 cmH2O and PEEP 6-12 cmH2O. The mean duration of NIV was 4 days (3 hours to 14 days). Results: Facial mask was well tolerated and with no injuries from her use. Results showed that 19 patients (86,36%) recovered and 3 patients (13,63%) died because of their underlying disease and not from the respiratory failure. Two of our patients continued the NIV ventilation as home care treatment. Conclusions: NIV support of respiratory failure is a very useful tool in the pediatric intensivists' hands because it is good alternative to mechanical ventilation. It is well tolerated, reduces the need of sedation and the PICU stay in these patients."
5378,CEFOTAXIME IN THE TREATMENT OF BACTERIAL MENINGITIS,"We evaluated the efficacy of cefotaxime in the treatment of bacterial meningitis and the diffusion of the drug into CSF. Eleven children(9 days to 5 yrs) with meningitis due to H. influenzae (7 cases), S. pneumoniae(2) , group B streptococcus (1) , and Salmonella sp.(1), were treated with 40 mg/kg of IV cefotaxime q6hrs. Cefotaxime levels were determined by HPLC. The mean cefotaxime plasma level 3 hrs after a dose early in the treatment was 14.1 mg/L(range 5.1-42.2 mg/L), and the mean CSF level was 3.9 mg/L(0.7-16.6 mg/L). The mean CSF diffusion rate was 26.4%. At the end of treatment, the mean plasma level was 7.9 mg/L(1.5-13.6 mg/L) and the mean CSF level was 1.23 mg/L(0.5-3.1 mg/L) representing a mean diffusion rate of 21.9%. Cefotaxime MBC for the infecting organisms ranged between 0.015 mg/L and 0.25 mg/L. CSF was bactericidal to the infecting organisms at dilutions between 8 and 256. The CSF diffusion correlated positively with the cefotaxime plasma level (r=0.86), CSF protein (r=0.63), CSF leukocyte count (r=0.61) and negatively with CSF sugar (r=-0.37).All patients responded well to treatment with no apparent sequelae. Serial levels were also determined in 5 infants with ventriculostomies. Following a single dose of 40 mg/kg, the mean cefotaxime CSF levels (and mean plasma levels) were 6.6 mg/L(28.4 mg/L) at 2 hrs, 5.7 mg/L(8.9 mg/L) at 4 hrs, and 4.5 mg/L (1.8 mg/L) at 6 hrs. Cefotaxime diffuses sufficiently and consistently into CSF. Further assessment of its efficacy in the treatment of childhood meningitis is warranted."
5379,Infectious Disease Pathology,
5380,Physicians Poster Abstracts: EBMT 2012,
5381,President’s Plenary Session,
5382,Bone and Soft Tissue Pathology,
5383,1348 Influenza a H1N1 Virus Infection in a Pediactric Intensive Care Unit,"Background: the main form of clinical presentation in critically ill patients with H1N1 infection is rapidly progressive respiratory failure, shock, neurological involvement and renal failure. Children with comorbidity and aged < 2 years are at particular risk. Methods: a descriptive, retrospective study on the clinical presentation and management of patients with H1N1 infection was performed in a Pediatric Intensive Care Unit (PICU). All children admitted in PICU of Coimbra's Pediatrics Hospital (CPH) were described, from July 15(th) to November 30(th) of 2009. Results: during this period, 241 children with laboratory confirmation of H1N1 infection were observed in CPH, of whom 38 (16%) required hospitalization, 4 (1.7%) in PICU-CPH. The age ranged from 4 months to 21 years. Three patients had previous co-morbidities. All met clinical criteria for H1N1 infection and were admitted with respiratory distress (4), rapidly progressive and evolution to ARDS (2), associated with shock (2) and lethargy (2). Three patients required mechanical ventilation (conventional and high-frequency oscillatory ventilation); the duration ranged between 4-12 days. Two patients received intravenous catecholamines support, two developed acute renal failure and two had pancytopenia. There were two bacterial coinfections. All received treatment with oseltamivir. Length of PICU stay ranged from 5-22 days, with a favorable outcome in all cases. Conclusion: in the 1st peak of H1N1 outbreak, 10% of the hospitalized children required PICU admission. Despite severe respiratory disease and multiple organ dysfunction, a good outcome was achieved, with no mortality."
5384,1346 Flutisane Propionate in Prevention of Rhynitis Alergica with Children,"Introduction: In childhood rhynitis alergica is medical and social problem. The nasal mucous membrane first gets in touch with a lot of causes, including causes of allergy. Objective: Improvement of quality of the life with children who are treated with Fluticasone propionate. Material and Methods: We processed the data from medical records of 58 children on the age of 6 and 12 years in the period of 2 years (2008 - 2009), and 43 children from them were put on prevention with Fluticasone propionate. For processing the data we used analytic and descriptive method. Results: We processed 58 cases with rhynitis alergica proved with: skin tests or RIDA screen tests, total IgE, eosinophyles in nose and drainage secretion. 15 children were put only on symptom's therapy, and 43 children were put on therapy with Fluticasone propionate in a period of a few months. With 9 children rhinitis alergica was followed by conjuctivitis alergica and they get antihistaminic medicaments. All children that were put on prevention had minimal symptoms of Rhynitis and they had normal physical activities and attend a school regularly. Conclusion: Suitable and therapy on time allows normal and healthy life and free activity with children who have proved rhynitis alergica."
5385,Scientific Abstracts,
5386,Infectious Disease Pathology,
5387,"Scientific Program & Abstracts: 57™ Annual Meeting March 24–27, 2010",
5388,Scientific Abstracts,
5389,Design and application of the method for isolating magnetotactic bacteria,"A simple apparatus was designed to effectively isolate magnetotactic bacteria from soils or sediments based on their magnetotaxis. Through a series of processes including sample incubation, MTB harvesting, isolation, purification and identification, several strains of bacteria were isolated from the samples successfully. By Transmission Electron Microscopy (TEM) and Energy-Dispersive X-ray Analysis (EDXA), these bacteria were certificated to be magnetotactic bacteria. The phylogenetic relationship between the isolated magnetic strains and some known magnetotactic bacteria was inferred by the construction of phylogenetic tree based on 16SrDNA sequences. This apparatus has been proven to have the advantages of being inexpensive, simple to assemble, easy to perform and highly efficient to isolate novel magnetotactic bacteria. The research indicated that the combined approach of harvesting MTB by home-made apparatus and the method of plate colony isolation could purify and isolate magnetotactic bacteria effectively."
5390,A GMC Oxidoreductase GmcA Is Required for Symbiotic Nitrogen Fixation in Rhizobium leguminosarum bv. viciae,"GmcA is a FAD-containing enzyme belonging to the GMC (glucose-methanol-choline oxidase) family of oxidoreductases. A mutation in the Rhizobium leguminosarum gmcA gene was generated by homologous recombination. The mutation in gmcA did not affect the growth of R. leguminosarum, but it displayed decreased antioxidative capacity at H(2)O(2) conditions higher than 5 mM. The gmcA mutant strain displayed no difference of glutathione reductase activity, but significantly lower level of the glutathione peroxidase activity than the wild type. Although the gmcA mutant was able to induce the formation of nodules, the symbiotic ability was severely impaired, which led to an abnormal nodulation phenotype coupled to a 30% reduction in the nitrogen fixation capacity. The observation on ultrastructure of 4-week pea nodules showed that the mutant bacteroids tended to start senescence earlier and accumulate poly-β-hydroxybutyrate (PHB) granules. In addition, the gmcA mutant was severely impaired in rhizosphere colonization. Real-time quantitative PCR showed that the gmcA gene expression was significantly up-regulated in all the detected stages of nodule development, and statistically significant decreases in the expression of the redoxin genes katG, katE, and ohrB were found in gmcA mutant bacteroids. LC-MS/MS analysis quantitative proteomics techniques were employed to compare differential gmcA mutant root bacteroids in response to the wild type infection. Sixty differentially expressed proteins were identified including 33 up-regulated and 27 down-regulated proteins. By sorting the identified proteins according to metabolic function, 15 proteins were transporter protein, 12 proteins were related to stress response and virulence, and 9 proteins were related to transcription factor activity. Moreover, nine proteins related to amino acid metabolism were over-expressed."
5391,The polymerase chain reaction and pathology practice,"Pathology practice is increasingly augmented with molecular tests for improved diagnostics and patient management. The polymerase chain reaction (PCR) is foremost amongst these techniques. This review explains the principles of PCR and the methodological factors that contribute to a successful assay. Key PCR technique variations, such as reverse transcription (RT)-PCR and quantitative real-time (q) PCR, are described and an overview is provided of how PCR products are analysed. The review includes examples of PCR usage in clinical practice for the detection of infectious and genetic diseases, for tumour diagnostics and in molecular forensic applications such as specimen identity confirmation."
5392,News in Brief,
5393,Rodent Diagnostic Testing,"Clinical medicine is an important part of scientific medicine that is all too often neglected when treating rodents and small mammal pets. As with more traditional pets, a progressive diagnostic regimen should include a thorough history, clinical signs, physical examination, and laboratory findings."
5394,The American Organization of Nurse Executives and Global Citizenship,"Globalization is impacting many aspects of American society, and nursing has especially been impacted over the past few decades. Global issues such as nurse migration, pandemic infections, natural disasters, man-made disasters, and geopolitical unrest have made it clear that no nation can remain isolated and unaffected by world events and trends. With these facts, the American Organization of Nurse Executives' (AONE) leaders and members increasingly understand that leaders along with their communities and health care organizations work in all arenas, from local to national and international."
5395,Paraplegia in a Domestic Ferret (Mustela Putorius Furo) Secondary to Metastatic Adrenocortical Carcinoma with Myxoid Differentiation,"Neurologic disease is a common presentation of domestic ferrets (Mustela putorius furo) with infectious, neoplastic, and traumatic etiologies documented. Adrenocortical neoplasia is also well documented in domestic ferrets, with metastatic lesions rarely described. This case report describes an abnormal presentation of adrenocortical adenocarcinoma with myxoid differentiation and subsequent metastasis to the spinal cord and vertebral bodies, resulting in hind limb paraplegia in an adult spayed female ferret."
5396,Systemic Infection Due to Candida parapsilosis in a Domestic Ferret (Mustela putorius furo),"An 18-month-old castrated male ferret (Mustela putorius furo) was presented to the veterinary hospital for acute collapse but died despite initiation of emergency treatment. The body was submitted for a complete postmortem examination. The pathologist determined the ferret was suffering from severe necrotizing encephalitis, necrogranulomatous mediastinal lymphadenitis, and ulcerative dermatitis attributable to systemic Candida parapsilosis. This is the first report of systemic Candida parapsilosis in a ferret."
5397,Current Approach to Rodents as Patients,"Rodent species are routinely presented to veterinary hospitals for wellness checks and different illnesses. When rodents are presented to the veterinarian for diagnosis and treatment, they deserve the same thorough approach that any other domestic species receives. The purpose of this article is to provide readers a review of the current information regarding examination, diagnosis, and treatment of some of the most common conditions for which rodent patients are presented. This article will cover 5 of the most common rodent species presented to veterinarians: guinea pigs, chinchillas, rats, mice, and hamsters."
5398,Technology confronts SARS,
5399,Respiratory pharmacology: In defense of the lung: innovations to bolster or prevent acute and chronic lung diseases,
5400,Web serves as conduit for SARS information,
5401,Where on the Web,
5402,The hog-badger is not an edentate: systematics and evolution of the genus Arctonyx (Mammalia: Mustelidae),"Hog-badgers (mustelid carnivorans classified in the genus Arctonyx) are distributed throughout East and Southeast Asia, including much of China, the eastern Indian Subcontinent, Indochina and the large continental Asian island of Sumatra. Arctonyx is usually regarded as monotypic, comprising the single species A. collaris F. Cuvier, 1825, but taxonomic boundaries in the genus have never been revised on the basis of sizeable series from throughout this geographical range. Based on a review of most available specimens in world museums, we recognize three distinctive species within the genus, based on craniometric analyses, qualitative craniodental features, external comparisons, and geographical and ecological considerations. Arctonyx albogularis (Blyth, 1853) is a shaggy-coated, medium-sized badger widely distributed in temperate Asia, from Tibet and the Himalayan region to eastern and southern China. Arctonyx collaris F. Cuvier, 1825, is an extremely large, shorter-haired badger, distributed throughout Southeast Asia, from eastern India to Myanmar, Thailand, Vietnam, Cambodia and Laos. The world's largest extant badger, A. collaris co-occurs with A. albogularis in eastern India and probably in southern China, and fossil comparisons indicate that its geographical range may have extended into central China in the middle Pleistocene. The disjunctly distributed species Arctonyx hoevenii (Hubrecht, 1891), originally described within the order ‘Edentata’ by a remarkable misunderstanding, is the smallest and darkest member of the genus and is endemic to the Barisan mountain chain of Sumatra. Apart from A. hoevenii, no other Arctonyx occurs on the Sunda Shelf below peninsular Thailand. The natural history of each species of Arctonyx, so far as is known, is briefly reviewed. No claim to original US Government works."
5403,2001 SPSS & SCAD Abstracts - Subject Index,
5404,Etiology and clinical characteristics of influenza-like illness in healthy adults by hospitalization status,"BACKGROUND: Viral respiratory infections are a common cause of hospitalization for younger, otherwise-healthy populations. In this study, we describe the epidemiology of influenza-like illness in non-elderly adults within the U.S. Military Health System (MHS) by pathogen and hospitalization status. METHODS: The Acute Respiratory Infection Consortium (ARIC) is a prospective cohort of patients with influenza-like illness within the MHS. Participants between 18 and 65 years of age were identified in outpatient settings between 2012 and 2017, and were excluded if pregnant, if reporting chronic cardiac, respiratory, renal, or neurologic disease, or if on long-term aspirin therapy. Demographics, nasopharyngeal swabs and symptom data were collected; swabs were tested for viral pathogens using a target-enriched multiplex PCR panel (TEM-PCR(TM), Diatherix LLC). Data were analyzed to compare clinical features and risks for hospitalization. RESULTS: 397 participants met inclusion criteria. 34 participants required hospitalization; 363 were outpatients. Median length of hospitalization was 2 days. A virus was identified in 58.4% of outpatients (OP) and 55.9% of inpatients (IP); coronaviruses (63/363), enteroviruses (50/363), and influenza A (73/363) predominated in OP, whereas influenza A predominated among IP (35.3%, 12/34). There were no significant differences between OP and IP in terms of age, gender, ethnicity, or tobacco use. IP were more likely to be obese (BMI ≥30, 43.3% vs. 20.5%, P = 0.004) and less likely to have received influenza vaccination (45.5% vs. 16.9%, P > 0.001). IP with influenza did not report more severe symptoms (chills, cough, sore throat, diarrhea, myalgia, or headache) on enrollment but were more likely to have fever (temperature ≥38.0⁰ C) than OP (92.9 vs. 57.1%, P = 0.014). CONCLUSION: Influenza A is the most frequently identified cause of hospitalization among healthy, non-elderly adults with viral respiratory infection. Although age and tobacco use may be risks for viral acquisition, they do not appear to increase the risk of hospitalization in infected patients. Non-obese BMI and influenza vaccination appear protective against hospitalization, even in a relatively healthy cohort. DISCLOSURES: L. Malone, Diatherix Laboratories: Employee, Salary; E. Grigorenko, Diatherix Laboratories: Employee, Salary; D. Stalons, Diatherix Laboratories: Employee, Salary"
5405,"Evaluation of Serum TNF-alpha, IL-6, IL-10, and IFN-gamma Levels in Patients with Crimean–Congo Hemorrhagic Fever","BACKGROUND: Crimean–Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. Cytokines plays an important role in the pathogenesis of viral, bacterial, and immunologic diseases. This study aimed to investigate the role of TNF-alpha, IL-6, IL-10, and IFN-gamma levels in the severity of infection and clinical outcome of patients with CCHF. METHODS: Patients with confirmed CCHF were divided into two groups (severe cases: Patients who exhibited hemorrhage during their hospital stay, and mild/moderate cases: Patients who displayed no hemorrhage during their hospital stay). Demographic characteristics, laboratory tests on admission of all patients with CCHF were investigated, and serum TNF-alpha, IL-6, IL-10, and IFN-gamma levels were measured. RESULTS: A total of 154 patients with confirmed CCHF were investigated. Forty-six (29.9%) of these patients were in the severe group. In patients with severe CCHF, significantly higher serum levels of TNF-alpha (68.2 ± 23.5; P = 0.008) and IL-6 (73.1 ± 41.6; P = 0.003) were detected, compared with cytokine levels in patients who mild/moderate CCHF (Table 1). No differences in serum IL-10 and IFN-gamma levels between patients who severe CCHF and those who mild/moderate CCHF were detected (P > 0.05). CONCLUSION: Cytokines, chemokines, and other inflammatory mediators function in a manner, acting on many different cell types to regulate the host’s immune response. When cytokines present in high concentrations, they might toxic or even lethal effects. In accordance with this view, we have detected increased serum TNF-alpha, IL-6 levels in the patients with severe CCHF. DISCLOSURES: All authors: No reported disclosures."
5406,HRCT imaging features in representative imported cases of 2019 novel coronavirus pneumonia,"With the spread of novel coronavirus (2019-nCoV) pneumonia, chest high-resolution computed tomography (HRCT) has been one of the key diagnostic tools. To achieve early and accurate diagnostics, determining the radiological characteristics of the disease is of great importance. In this small scale research we retrospectively reviewed and selected six cases confirmed with 2019-nCoV infection in West China Hospital and investigated their initial and follow-up HRCT features, along with the clinical characteristics. The 2019-nCoV pneumonia basically showed a multifocal or unifocal involvement of ground-glass opacity (GGO), sometimes with consolidation and fibrosis. No pleural effusion or lymphadenopathy was identified in our presented cases. The follow-up CT generally demonstrated mild to moderate progression of the lesion, with only one case showing remission by the reducing extent and density of the airspace opacification."
5407,PCR Array Profiling of Antiviral Genes in Human Embryonic Kidney Cells Expressing Human Coronavirus OC43 Structural and Accessory Proteins,"BACKGROUND: Human coronavirus OC43 (HCoV-OC43) causes common cold, and is associated with severe respiratory symptoms in infants, elderly and immunocompromised patients. HCoV-OC43 is a member of Betacoronavirus genus that includes also the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS) coronaviruses. Both SARS-CoV and MERS-CoV were shown to express proteins with the potential to evade early innate immune responses. However, the ability of HCoV-OC43 to antagonise the intracellular antiviral defences has not yet been investigated. The objective of this study was to investigate the role of HCoV-OC43 structural (membrane and nucleocapsid) and accessory (ns5a and ns2a) proteins in the modulation of antiviral gene expression profile in human embryonic kidney 293 (HEK-293) cells using PCR array analysis. METHODS: HCoV-OC43 membrane (M), nucleocapsid (N), ns5a and ns2a mRNA were amplified and cloned into the pAcGFP1-N expression vector (Clontech), followed by transfection in HEK-293 cells. Expression of M, N, ns5a and ns2a proteins were confirmed by indirect immunofluorescence test. Three days post-transfection, the cells were challenged by Sendai virus. The Human Antiviral Response PCR array system (Qiagen) was used to profile the antiviral gene expression in HEK-293 cells, using the fold regulation comparison and the manual normalisation methods. RESULTS: Around 50–60 genes were downregulated by HCoV-OC43 proteins, the most prominent genes being those critical for the activation of transcription factors involved in the antiviral response like interferon regulatory factors (IRFs) and activator protein 1 (AP-1). Among the most important downregulated genes were those coding for Interferons (IFNs) mitogen-activated protein kinases (MAPKs), pro-apoptotic and pyroptotic proteins (Caspases, cathepsins, tumour necrosis factor), pro-inflammatory cytokines (Interleukins), pattern recognition receptors (PRRs; toll-like receptors and NOD-like receptors) and their signaling transduction proteins (TICAM1, MAVS). CONCLUSION: This study shows for the first time that similarly to SARS-CoV and MERS-CoV, HCoV-OC43 has the ability to downregulate the transcription of genes critical for the activation of different antiviral signaling pathways. DISCLOSURES: All authors: No reported disclosures."
5408,"Subject Index of Original Papers, Volume 87, 2008",
5409,Quantitative Assessment of the Bioburden of High-Touch Environmental Surfaces in Pediatric Operating Rooms,"BACKGROUND: Previous studies have linked healthcare-associated infections to bacterial pathogens in the operating room (OR) environment. The purpose of this study was to determine the bioburden on OR surfaces to guide future quality improvement efforts and optimize OR cleanliness. METHODS: This study was performed in the pediatric ORs of a 200-bed, academically affiliated, children’s hospital with ~6000 general and subspecialty surgical procedures annually. Immediately after cases were finished, but prior to cleaning, the 3M Clean-Trace Clinical Hygiene Monitoring System was used to quantify bioburden (in surface ATP concentration) on 24 surfaces in each of 8 ORs. These 24 surfaces were previously identified by the Association of periOperative Registered Nurses as high-touch surfaces and various disciplines are responsible for their cleaning. Each OR was sampled 1–4 times. A surface passed the test of cleanliness if the result was <250 relative light units (RLUs). RESULTS: In all, 364 surfaces were tested. The median RLUs were <250, 250–850, and >850 RLUs for 7, 11, and 6 surfaces, respectively. Of the 24 surfaces tested, all demonstrated bioburden ≥250 at least once. Median RLUs for each surface ranged from 39-2282 and median RLUs for each OR ranged from 196 to 1534. The highest bioburden occurred following cardiac surgery (median 1534, range 24-13275 RLU) and the lowest bioburden occurred after neurosurgery (median 196, range 23-2475 RLU). The surfaces with the highest bioburden were the anesthesia keyboards (median 2282, range 347-38376 RLU) and core door handles (median 1471, range 140–6788 RLU) and those with the lowest bioburden were the Mayo stand (median 39, range 19-765 RLU) and back table (median 39, range 17-406 RLU). CONCLUSION: ATP testing demonstrated that most OR surfaces were contaminated with organic material. While OR surfaces prior to cleaning are expected to be contaminated, these data highlight the importance of cleaning/disinfection. These findings are being used to develop educational tools and interventions for the interdisciplinary OR team, which will focus on delineation of cleaning responsibilities, the use of appropriate cleaning products, and audits of end-of-case cleaning and terminal cleaning. DISCLOSURES: All authors: No reported disclosures."
5410,Coronavirus Infection in Hematopoietic Stem Cell Transplant Recipients,"BACKGROUND: Hematopoietic stem cell transplants (HSCT) recipients are at increased risk of respiratory viral infections and their associated complications. Although the epidemiology of many respiratory viruses has been well characterized in this population, little is known about the epidemiology of human coronavirus (HoCV) infection. METHODS: We identified HSCT recipients with symptoms of a respiratory tract infection who tested positive for HoCV by nasopharyngeal (NP) swab from January 2013 to December 2016 at our hospital. NP swabs were analyzed by the FilmArray® Respiratory Panel, which detects 17 respiratory viruses, including 4 coronavirus serotypes. We reviewed the demographics, transplant type, comorbidities, smoking status, respiratory symptoms, co-pathogens, and radiographic findings of infected patients. We then assessed the incidence of developing a lower respiratory tract infection (LRTI), defined as new pulmonary infiltrates or detection of HoCV in bronchoalveolar lavage fluid, within 30 days of initial diagnosis. RESULTS: We identified 58 HSCT recipients who tested positive for HoCV. The median patient age was 54 years, 29 (50%) were men, and 24 (41%) were current or prior smokers. Fifty (86%) patients had received an allogeneic HSCT and 8 (14%) had received an autologous HSCT. The coronavirus serotypes were: OC43 (n = 19, 33%), NL63 (n = 18, 31%), HKU1 (n = 16, 28%), and 229E (n = 5, 9%). The median time from transplant until detection of HoCV infection was 135 days (IQR=256). Seventeen (29%) patients were lymphopenic at the time of diagnosis and 17 (29%) were receiving corticosteroids. The most common initial symptoms were cough (n = 41, 71%), rhinorrhea (n = 31, 53%), and dyspnea (n = 17, 29%), and 19 (33%) and 16 (28%) patients had fever and hypoxia, respectively. Seventeen patients (29%) developed a LRTI within 30 days of diagnosis and 43% harbored a co-pathogen in the blood or respiratory tract. Three patients (5%) were intubated for respiratory failure and 1 (2%) died within 30 days. CONCLUSION: HoCV infection is common in HSCT recipients and is caused by multiple serotypes. Nearly one-third of patients have fever and hypoxia upon initial diagnosis or progress to LRTI. Further research is needed to identify risk factors for HoCV LRTI in this population. DISCLOSURES: All authors: No reported disclosures."
5411,Respiratory Viral Infections in Multiple Myeloma Patients,"BACKGROUND: Multiple myeloma (MM) patients are at increased risk of respiratory viral infections (RVIs) due to disease-related alterations in their immune systems. Data in the literature specific to MM patients is limited. We reviewed four years of multiplex respiratory viral panel (RVP) data in MM patients at our institution to evaluate incidence and seasonality of RVIs. methods. The results from all positive RVPs, obtained via nasopharyngeal swab and as identified by polymerase chain reaction during the years 2013 to 2016, were analyzed. A positive result less than 6 weeks apart was considered a duplicate and removed. All specimens were analyzed in the molecular diagnostics laboratory using the eSensor® Respiratory Viral Panel (GenMark Dx, Carlsbad, CA). This assay is a qualitative nucleic acid multiplex in vitro diagnostic test that provides for the simultaneous detection and identification of 14 respiratory viral nucleic acids. Results. RVIs were reported in every month in all four years. The peak months were January and February, driven by the peak activity of Influenza and respiratory syncytial virus (RSV). Rhinovirus was isolated the most frequently. The least isolated was Adenovirus. A seasonality was observed with Influenza, RSV, human parainfluenza and human metapneumovirus; however, infections with each virus occurred outside of peak months including an outbreak of Influenza in July and August 2013. The total number of viral infections varied each year as did the total number for each virus. The year 2015 had the lowest number of RVIs reported at 427, followed by the year 2016 with the most RVIs reported at 515. However, 2016 was not the peak incidence for each virus; it was the peak incidence for RSV and Rhinovirus. In fact, Influenza had its lowest number of cases in 2016. Conclusion. At our institution, we have shown that RVIs are more common than previously described in MM patients. RVIs occur in every month throughout the year. Although a seasonality is seen with these viral infections, infections do occur outside of the months considered to be peak months for each virus. Infection control policies, therefore, must be enforced year round. More studies, however, are needed to assess the proportion of community vs. healthcare acquired. Two DISCLOSURES: All authors: No reported disclosures."
5412,The Management of Outpatient Cellulitis at The Moncton Hospital before and after the Initiation of a Clinical Treatment Pathway,"BACKGROUND: Antimicrobial Stewardship is a coordinated effort to improve and measure the appropriate use of antimicrobials. Antibiotic resistance is an emerging world health problem and unnecessary prescribing of broad-spectrum antibiotics is a major contributor to this. Skin and soft-tissue infections are a common reason to receive a prescription for antibiotics. Currently there exists a trend for using broad-spectrum intravenous antibiotics for moderate to severe infections when more narrow-spectrum options would be adequate. This study aimed to characterize the choice of antibiotic being prescribed for the management of outpatient cellulitis requiring intravenous antibiotics and evaluate the success of a clinical order set outlining optimal therapy. METHODS: This study was a retrospective chart review looking at antibiotic prescribing through the Emergency Department at The Moncton Hospital, in Moncton, New Brunswick. Charts were reviewed before and after the introduction of a clinical order set outlining optimal antibiotic therapy. The goal was to review charts from the pre- and post-intervention group and compare antibiotic usage, treatment failure rates, and adverse events. RESULTS: Of the 54 patients receiving IV antibiotics in the pre-intervention group, 3 received cefazolin, 50 received ceftriaxone, while 1 received levofloxacin. The median duration of IV therapy was four days. After the introduction of the clinical order set there was an absolute increase of 53.8% (n = 35) in the use of cefazolin and absolute decrease of 53.7% (n = 23) in the use of ceftriaxone in the post-intervention group of 59 patients. Both results were statistically significant (P < 0.001). The median duration of IV therapy in this group was 3.5 days. In eligible patients, the clinical order set was utilized 61.1% of the time. There was no significant difference in rates of treatment failure or adverse events between cefazolin and ceftriaxone. CONCLUSION: The introduction of a clinical order set outlining the preferential use of once-daily cefazolin plus probenecid for the treatment of outpatient cellulitis lead to a statistically significant increase use of cefazolin, and decrease use of ceftriaxone, thus demonstrating a positive stewardship effect at a local level. DISCLOSURES: All authors: No reported disclosures."
5413,Preventing Respiratory Viruses in the Neonatal ICU,"BACKGROUND: Infants in the neonatal ICU can acquire respiratory viruses from ill healthcare personnel (HCP), visitors, or other infants. We describe the epidemiology of respiratory viruses and infection prevention and control interventions aimed to reduce acquisition and transmission of respiratory viruses in our NICU. METHODS: From May 2012 to December 2016, we tracked respiratory viruses detected by a multiplex reverse-transcriptase (RT)-PCR assay (FilmArray, Biofire, Inc.) in our 58-bed level IV NICU (~1,000 annual admissions). Testing was ordered by treating clinicians for symptomatic infants. Infants with positive RT-PCR tests generally remained on contact/ droplet precautions throughout their NICU stay. HCP were instructed not to work sick and report to Workforce Health and Safety if they became ill at work. Ill visitors were not permitted in the NICU, as enforced by written educational materials and signage, but formal screening was not performed. Starting in January 2015, asymptomatic infants exposed to RT-PCR-positive index cases were screened by RT-PCR, put on contact/ droplet precautions for the incubation period (IP) of the index case’s virus, and screened again at IP end. Starting in December 2015, visitors <12 years old were banned year-round. We assessed dyad transmission events (2 infants), clusters (3 infants), and outbreaks (>3 infants); all were defined as detecting geographically related cases within the relevant IP. We determined screened infants who had positive RT-PCR tests. RESULTS: During the 56 month observation period, 79 infants had 83 viruses detected (~1.8% of admissions). Rhino/ enterovirus (RV/EV) were most common (n = 59) and caused 1 outbreak of 7 infants, 4 clusters, and 5 dyad transmissions. Adenovirus caused 1 outbreak of 5 infants. Two dyad transmissions occurred for parainfluenza. Sporadic cases of RSV (n = 5), coronavirus (n = 5), and influenza (n = 2) occurred. Ill household contacts were identified for 10 infants. No HCPs were identified with respiratory illnesses. Since January 2015, 8 screened infants had positive RT-PCR tests. Since December 2015, only 1 transmission dyad (RV/EV) occurred. CONCLUSION: Preliminary data suggest that our interventions have reduced the burden of respiratory viruses in the NICU. DISCLOSURES: All authors: No reported disclosures."
5414,Impact of Timing of Diagnosis of Respiratory Syncytial Virus (RSV) Disease on Hospital Length of Stay (LOS) in Adults: Final Analysis from a Retrospective Chart Review Study,"BACKGROUND: Despite growing clinical awareness of RSV disease in at-risk adult subpopulations, significant gaps remain in knowledge, especially around diagnosis. This analysis aimed to understand the impact of timing of diagnosis on hospital LOS. METHODS: A retrospective review of patient charts was conducted. Data for adults ≥18 years with confirmed RSV (Oct 2014–Oct 2016; USA) were collected. Each physician (n = 132) submitted up to 3 randomly selected patient cases via an online survey. RESULTS: This study comprised 379 patients, collected in 4 groups (Table). >80% of patients received an RT-PCR test; rapid antigen tests were uncommon (≤10%) with an RT-PCR test also performed in 45% of these. Early RSV diagnosis and less severe disease were associated with a shorter mean LOS (Figure 1and2). Patients diagnosed >24h post-admission had a longer mean [SD] LOS (9.8 [8.6] days; n = 29) than patients diagnosed <12h post-admission (6.2 [3.9] days; n = 67; P = 0.006), and patients diagnosed 12–24h post-admission (7.4 [4.2] days; n = 56; P = 0.038). LOS was higher (P = 0.005) in patients diagnosed in the intensive care unit (9.4 days) than the emergency room or hospital ward (both 6.8 days). CONCLUSION: RSV disease in adults was typically diagnosed by PCR. Delayed diagnosis and greater RSV disease severity are associated with longer LOS, but results need to be confirmed by prospective trials. Introduction of diagnostic testing protocols may lead to earlier identification of patients in need of supportive care and reduce mean LOS. DISCLOSURES: E. Walsh, Janssen Pharmaceuticals: Scientific Advisor, Consulting fee; I. Sander, Janssen Pharmaceuticals: Independent Contractor, Licensing agreement or royalty; R. Stolper, Janssen Pharmaceuticals: Independent Contractor, Licensing agreement or royalty; J. Zakar, Janssen: Independent Contractor, Licensing agreement or royalty; G. De La Rosa, Janssen Pharmaceuticals: Employee, Salary; V. Wyffels, Janssen Pharmaceuticals: Employee, Salary; D. Myers, Janssen Pharmaceuticals: Employee, Salary; R. Fleischhackl, Janssen Pharmaceuticals: Employee, Salary"
5415,Impact of Asymptomatic Bacteriuria (ASBU) Overtreatment During a Controlled Trial of Antimicrobial Stewardship (AS),"BACKGROUND: What are the clinical profiles, outcomes, and antimicrobial costs attributed to patients admitted with presumed urinary tract infection (UTI) but deemed to have “no infection” (NI) by infectious diseases (ID) MD reviewers? METHODS: We performed a review of a subset of patients entered into a randomized, controlled, AS trial that began 7.1.2015. Patients with UTI and 3 other ID syndromes were evaluated by ID MDs within 12–24 hours of receiving empirical antimicrobials. The ID MD designated patients as having NI when a patient lacked compatible symptoms, signs, and laboratory evidence to support a diagnosis of UTI. Patients with NI were tracked but not included in the study intervention to identify AS opportunities. RESULTS: Over 21 months 6,402 antimicrobial starts were entered into the AS study; 2,196 (34.3%) were UTI. Of these 564 (25.7%) were designated NI. The initial admission of 104 patients designated NI are the subject of this report. Four had possibly clinically significant UTI and were excluded. Of the remaining 100 the average age was 83.6 years, 80% were female and 50% were admitted with acute or chronic altered mental status (dementia, seizure, or stroke); Sixty-five % of urine cultures were positive. The mean Systemic Inflammatory Response Syndrome (SIRS) score was 0.6; the mean quick Sequential Organ Failure Assessment Score (qSOFA) score was 0.9. A mean 3.7 days of antimicrobials were prescribed during the admission; 3.2 additional days at discharge. Of the 100 NI patients followed (up to 21 months following study entry) 34% have died (all-cause), 49% had a subsequent episode of bacteriuria; the mean number of re-admissions per patient was 2.4(range 0–14) and 9% developed C. difficile infection (CDI). CONCLUSION: AS identified a subset of patients treated for UTI but determined by ID MDs as NI, as an elderly, predominantly female cohort, with a high incidence of new or pre-existing neurological conditions, subsequent bacteriuria, re-admission, and short -term mortality. Low SIRS and qSOFA scores in these patients supported a lack of clinically significant infection. AS programs should focus on early efforts to identify ASBU. Preservation of antimicrobial resources, antibiotic cost savings (estimated over 3 years to be $ 450,000), and avoidance of CDI are among the likely benefits. DISCLOSURES: All authors: No reported disclosures."
5416,"Use of Unannounced “Mystery Patient Drills” to Assess Hospital Emergency Department Preparedness for Communicable Diseases of Public Health Concern in New York City, 2016","BACKGROUND: Recent infectious disease epidemics have highlighted the importance of rapid recognition and isolation of patients with severe infectious diseases. In response, the New York City Department of Health and Mental Hygiene carried out a series of unannounced “Mystery Patient Drills” to assess Emergency Departments (ED) ability to identify and safely respond to patients with communicable diseases of public health concern. METHODS: All 911-receiving hospitals participating in the NYC Hospital Preparedness Program were recruited to participate. Scenarios utilized an actor presenting to an ED describing symptoms and history consistent with measles or MERS-CoV. An exercise evaluation guide captured performance measures to analyze 1) compliance with key infection control measures; 2) association between screening interventions (e.g., travel history) and implementation of infection control measures; 3) times from patient entry to triage, donning a mask, and placement into isolation. Post-drill report narratives were reviewed to identify additional strengths and challenges. RESULTS: Among 50 eligible hospitals, 49 participated in 2 drills (N = 98) during December 2015–May 2016. Three pilot drills were excluded from the analysis. The patient was masked and isolated in 78% of drills; 61% of hospitals completed this process in both drills. Masking and isolation was observed in a higher proportion of drills when travel history was obtained, compared with drills when travel history was not obtained (88% vs. 21%; P < 0.0001). The median time from patient entry to masking was 1 minute and 9 minutes to placement into isolation. Overall, 36% of staff practiced hand hygiene and 77% entered the isolation room wearing Personal Protective Equipment. Identified best practices include the use of triage questionnaires to identify high-risk patients and algorithms to guide masking and isolation procedures. CONCLUSION: ED staff’s ability to identify potentially infectious patients and implement recommended control measures varied. Drill findings were used to inform hospital improvement planning and will guide citywide efforts to improve healthcare system readiness for communicable diseases through addressing identified gaps and supporting implementation of best practice recommendations. DISCLOSURES: All authors: No reported disclosures."
5417,Pharmacokinetics (PK) of Eravacycline in Subjects with Renal or Hepatic Impairment Compared with Healthy Subjects,"BACKGROUND: Eravacycline (ERV) is a fluorocycline being developed for the treatment of serious infections, including those caused by multidrug-resistant pathogens. The PK of ERV in subjects with end stage renal disease (ESRD) or hepatic impairment (HI) were investigated. METHODS: Two multi-center studies were completed; one in subjects with ESRD and one in subjects with mild, moderate or severe HI based upon Child-Pugh scoring. Each included a cohort of healthy subjects (HS) matched by gender, age and BMI. A single IV dose of 1.5 mg/kg ERV was administered. PK parameters were calculated using standard non-compartmental methods and within study comparisons of PK for the ESRD and HI subjects were made with HS. RESULTS: The following comparative AUC(inf) and C(max) values for ERV were observed: CONCLUSION: Following a single IV dose of ERV, the systemic exposures in subjects with ESRD and mild or moderate hepatic impairment were similar to those observed in HS. The 2-fold increase in AUC(inf) observed in subjects with severe HI did not result in increased adverse events. Therefore, no dose adjustment should be required when ERV is given to subjects with either renal or hepatic impairment. Funded in whole or in part with Federal funds from the Biomedical Advanced Research and Development Authority, Office of the Assistant Secretary for Preparedness and Response, Office of the Secretary, Department of Health and Human Services, under Contract No HHSO100201200002C. DISCLOSURES: P. Horn, Tetraphase Pharmaceuticals: Employee, Salary; S. Redican, Tetraphase Pharmaceuticals: Employee, Salary; M. Olesky, Tetraphase Pharmaceuticals: Employee, Salary."
5418,Incidence and Outcomes of Cytomegalovirus (CMV) Infection among Hematopoietic Stem Cell Transplant (HSCT) Recipients,"BACKGROUND: Outcomes of CMV infection among HSCT recipients likely vary by patient population and treatment modality. However, data on these outcomes have been reported by relatively few centers. METHODS: This was a retrospective cohort study of allogenic HSCT recipients age ≥18 years at Oregon Health and Science University Hospital (OHSU) between 2010–2015. During the study period, OHSU standard practice was to preemptively treat CMV-viremic patients (quantitative PCR assay ≥ 200 copies/mL or consecutive PCR assays <200 copies/mL) with first-line valganciclovir or ganciclovir and second line foscarnet if there were contraindications to first-line agents. Study data were collected from an electronic health record repository and local Center for International Blood and Marrow Transplant Research (CIBMTR) database. Primary outcomes were clinical manifestations of CMV disease, death, and cause of death within 1 year of transplant. RESULTS: Among 409 HSCT recipients, mean age was 53 (standard deviation: 13) years and 41% were female. 192 (47%) patients had CMV viremia and the median (interquartile range) time to CMV reactivation was 42 (31–53) days (Figure 1). Patients with acute myeloid leukemia were significantly less likely to have CMV reactivation (39% vs. 55%, P < 0.01) and those with myelodysplastic syndromes had a non-significantly higher risk (24% vs. 17%, P = 0.06). 4 (1%) patients had a documented clinical manifestation of CMV disease (3 pneumonia and 1 pancreatitis). One-year mortality was 36% (148/409); there was no significant difference in mortality (37.5% vs. 35.0%, P = 0.60) or cause of death (P = 0.30) between patients with and without CMV reactivation (Figure 2). The most frequent causes of death among CMV viremic patients were recurrent/persistent disease (35%), acute graft vs. host disease (GVHD) (22%), infection (19%), and chronic GVHD (11%). CMV was documented as the primary cause of death for 2 patients. CONCLUSION: Nearly half of HSCT recipients had CMV reactivation and more than a third died within one year of transplant. However, incidence of CMV disease was rare and reactivation was not associated with increased mortality. Further study is needed to identify risk factors for CMV reactivation, infection and mortality in this population. DISCLOSURES: J. P. Furuno, Merck & Co.: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium. L. Strasfeld, Merck: Independent Contractor, Salary. J. C. McGregor, Merck & Co.: Grant Investigator, Research grant"
5419,Congenital Zika Syndrome (CZS) Phenotype Seen in Older Children,"BACKGROUND: Zika virus (ZIKV) has been documented in Africa since 1947 and Asia since 1969. However, the association of congenital ZIKV infection with microcephaly and serious brain defects was not recognized until a large ZIKV outbreak began in Brazil in 2015. A similar association was retrospectively identified in a 2013–2014 French Polynesian outbreak. In this report, we describe two children, ages 6 (Case 1) and 7 years (Case 2), who display a phenotype consistent with CZS. In both cases, the mothers were residing in Cambodia during their pregnancies (2011 and 2010, respectively); Cambodia has reported ZIKV infections since 2007. METHODS: We review epidemiologic, clinical and laboratory data, and the neurodevelopmental status of these two children. RESULTS: Both mothers reported low-grade fever and erythematous rash during their early second trimesters. The infants were born with severe microcephaly (>3 SD below the mean) with central hypotonia and peripheral spasticity (Figure 1). Both had normal karyotypes, negative TORCH results, and neuroimaging suggestive of CZS with subcortical calcifications, polymicrogyria, abnormal corpus callosum, ex-vacuo ventriculomegaly, and reduced white matter (Figure 2). Case 1 had overlapping cranial sutures and redundant scalp (Figure 3). In 2016, serology immunofluorescence assay, immunoglobulin G, and plaque reduction neutralization test for the mother of Case 1 was positive for Zika. Serology for the mother of Case 2 is pending. Presently, both children have severe developmental delays; neither can sit or hold up their head, and both are nonverbal. Case 1 has bilateral hip contractures and hearing loss. Both are visually impaired and require gastrostomy-tube feedings. Case 2 is tracheostomy dependent. CONCLUSION: Given the maternal febrile rash illness, residence in a ZIKV region during pregnancy, infant features consistent with CZS, and the lack of other identified etiology, CZS should be considered as a possible diagnosis in these cases. It suggests that CZS may have occurred prior to the Brazil and French Polynesia outbreaks. Investigations into neurodevelopmental status of older children with possible CZS can provide insights into the possible long-term effects of CZS. DISCLOSURES: All authors: No reported disclosures."
5420,A Cross-Sectional Surveillance Study of Acute Respiratory Illness (ARI) in Pregnant Women,"BACKGROUND: Among pregnant women, pneumonia is the third-leading cause of death and the most common non-obstetric infection resulting in death. Pregnant women who become infected with influenza have hospitalization rates comparable to non-pregnant women with high-risk medical conditions. Other than influenza, little is known about the consequences of viral-related ARI on the pregnant woman and the fetus. Our objective was to determine the respiratory viruses causing ARI and their clinical outcomes during pregnancy. METHODS: Pregnant women in their second and third trimester were enrolled prospectively at a Houston clinic between October 1, 2015 and April 30, 2016 during their regular prenatal visits. Pregnant women were enrolled if they reported having symptoms of ARI or were healthy within the preceding two weeks. Nasal-pharyngeal secretions were evaluated for respiratory viruses by real time-PCR. Clinical outcomes and complications of illness were obtained at enrollment and two weeks after the initial visit. RESULTS: A total of 155 pregnant women were enrolled. The average age at enrollment was 30.7 years among women with ARI and 29.7 among healthy controls. Average gestational age at enrollment was 26.0 weeks among women with ARI and 26.3 among healthy controls. Among the 91 healthy controls, 10 (11%) tested positive for a respiratory virus, with rhinovirus (n = 6) being the most common of the viruses detected. On the other hand, of the 81 cases of ARI, 51 (63%) tested positive for a virus. The most frequently detected viruses were rhinovirus (n = 22), coronavirus (n = 14), and respiratory syncytial virus (n = 8). Twelve patients reported fever during the course of their ARI. Seventeen ARI patients reported at least one symptom of lower respiratory tract illness (LRTI). Of those patients with LRTI, two reported decreased fetal heart rate and one was hospitalized for her illness. CONCLUSION: Respiratory viruses were frequently detected in pregnant women with ARI. One-third of pregnant women with viral ARI had evidence of LRTI. Hospitalization and non-reassuring fetal heart tones were among the complications reported by pregnant women with LRTI. Viral ARI during pregnancy appears common and is associated with significant morbidity. DISCLOSURES: All authors: No reported disclosures."
5421,Antiviral Activity of Peptide Nucleic Acid against Human Parechovirus Type 3,"BACKGROUND: Human parechovirus (HPeV) type 3 (HPeV3) is an emerging pathogen causing sepsis and meningoencephalitis in neonates and young infants. However, specific treatment for HPeV3 infection is currently unavailable. The application of antisense technology, such as peptide nucleic acids (PNAs), to viral infection has opened a new era of therapeutics. The aim of this study is to develop PNAs inhibiting HPeV3 gene expression in an in vitro model. METHODS: We designed four PNAs that target domains I, J (base and head of domain J structure), and K of an internal ribosomal entry site (IRES) region within the 5’ untranslated region of HPeV3. The IRES region is needed for the cap-independent translation. The PNAs were conjugated to cell-penetrating peptide (RXR)(4)XB (R = L-arginine, X = 6-aminohexanoic acid, B = β-alanine). LLC-MK2 cells were treated with 0.1–10µM of each PNA or water-containing growth medium for 4h. The cells were then infected with HPeV3 at the multiplicity of infection (MOI) of 10 for 1h. The infected cells were incubated for 7 days at 37ºC in 5% CO(2). Extracellular levels of HPeV3 RNA were measured by real-time PCR on days 0 and 7. RESULTS: Without any treatment, an extracellular level of HPeV3 RNA increased to 8.2 × 10(6) copies/µL on day 7. When the cells were treated with 10µM of PNA targeting the domain I of IRES, an extracellular level of HPeV3 RNA was suppressed to 4.7 × 10(4) copies/µL (−99%) on day 7. Using the same PNA with lower concentrations, 1 µM and 0.1 µM of the PNA suppressed 24% and 0% of extracellular levels of HPeV3 RNA, respectively, which demonstrated the effect is dose-dependent. In contrast, 10µM of PNAs targeting domain J (base), J (head), and K suppressed 94%, 92%, and 20% of extracellular levels of HPeV3 RNA, respectively, compared with control. CONCLUSION: The PNA-(RXR)(4)XB targeting the domain I of IRES suppressed extracellular levels of HPeV3 RNA in an in vitro model in a dose-dependent manner. Thus, PNA treatment may be a therapeutic candidate for HPeV3-infected patients. This novel therapy could target other HPeV genotypes given that the target sequence used in this study is identical to those of other clinically significant HPeVs. DISCLOSURES: All authors: No reported disclosures."
5422,Recommended psychological crisis intervention response to the 2019 novel coronavirus pneumonia outbreak in China: a model of West China Hospital,"The novel coronavirus pneumonia (COVID-19) epidemic has brought serious social psychological impact to the Chinese people, especially those quarantined and thus with limited access to face-to-face communication and traditional social psychological interventions. To better deal with the urgent psychological problems of people involved in the COVID-19 epidemic, we developed a new psychological crisis intervention model by utilizing internet technology. This new model, one of West China Hospital, integrates physicians, psychiatrists, psychologists and social workers into Internet platforms to carry out psychological intervention to patients, their families and medical staff. We hope this model will make a sound basis for developing a more comprehensive psychological crisis intervention response system that is applicable for urgent social and psychological problems."
5423,Le contrôle des infections au cabinet du pédiatre,"La transmission des infections au cabinet du pédiatre est de plus en plus préoccupante. Le présent document expose les voies de transmission des infections et les principes sous­jacents aux mesures actuelles pour contrôler les infections. Pour prévenir les infections, il faut bien concevoir le cabi­net et adopter des politiques administratives et de triage convenables, de même que des pratiques de base pour les soins de tous les patients (p. ex., hygiène des mains, port de gants, de masques, de lunettes de protection et d’une blouse d’hôpital pour des interventions précises; nettoyage, désin­fection et stérilisation convenables des surfaces et du matériel, y compris les jouets, et techniques d’asepsie en cas d’interventions effractives) et des précautions addition­nelles en cas d’infections précises. Le personnel doit avoir reçu les vaccins pertinents, et les personnes infectées doivent respecter les politiques de restriction au travail."
5424,Ganciclovir-resistant CMV (GCV-R CMV) Infection Leads to Poor Clinical Outcomes and Economic Burden of Ganciclovir-resistant Cytomegalovirus Infection in Lung Transplant Recipients,"BACKGROUND: GCV-R CMV infection is an emerging cause of morbidity and mortality in lung transplant recipients. The purpose of this study was to evaluate the clinical and economic impact of GCV-R CMV infection in a high-risk population. METHODS: We performed a single-center, retrospective cohort study of lung transplant recipients with genotype confirmed GCV-R CMV and ganciclovir-sensitive (GCV-S) CMV infection, matched (1:3) by year of diagnosis. Clinical outcomes within 1 year following the onset of CMV infection and total hospital costs were assessed. RESULTS: Twenty-eight patients were included in the analysis: 7 with GCV-R CMV infection and 21 with GCV-S CMV infection. Baseline demographics (Table 1) were similar in the two groups. CMV load at diagnosis was numerically higher (282,932 I.U./mL [IQR, 43,181 IU/mL 3,368,931 I.U./mL] vs. 44,604 IU/mL [IQR, 6,314 I.U./mL 88,797 IU/mL], P = 0.10) and days to CMV infection following discontinuation of antiviral prophylaxis was numerically lower (20 [IQR, 0–137] vs. 175 [IQR, 123–190], P = 0.07) in the GCV-R CMV group. All-cause mortality (71.4% vs. 19.0%, P = 0.02) and total hospital days due to CMV infection (63 [IQR, 34–76] vs. 6 [IQR, 2–9], P < 0.01) were significantly higher in the GCV-R CMV cohort. There were no differences in allograft rejection and hospital readmission between the two groups. Total hospital costs were significantly higher amongst patients with GCV-R CMV infection ($208,924 [IQR, $114,555-$253,191] vs. $20,419 [IQR, $12,438-$27,892], P < 0.01). CONCLUSION: GCV-R CMV infection is associated with poor outcomes and considerable healthcare costs. Novel prophylaxis and treatment strategies are needed to combat CMV infection in lung transplant recipients. DISCLOSURES: T. Patel, Merck: Grant Investigator, Research grant. K. Gregg, Merck: Grant Investigator, Research grant"
5425,Transmission Dynamics of Respiratory Viruses in a Congregated Military Population: Prospective Cohort Study,"BACKGROUND: Human coronaviruses (HCoVs), rhinoviruses, and non-polio enteroviruses (NPEVs) are leading causes of seasonal acute respiratory infections among children and adults, posing significant health and economic burden annually. Despite this, little is known about their epidemiological dynamics, including the role of asymptomatic shedding in transmission; the durations of virus incubation and shedding; and the effect of immune responses on risk for re-infection during the same season. We studied respiratory virus shedding in military recruits, and used mathematical models to measure pathogen-specific transmission rates and durations of incubation, shedding, and immune protection. METHODS: We tested for shedding of HCoVs, rhinoviruses, and NPEVs in nasal samples collected from 78 military recruits entering basic training and then at staggered, biweekly visits over 65 days during winter 2017. We developed a continuous-time Markov chain model for virus acquisition and clearance, and used Bayesian methods to estimate model parameters for each of HCoV-229E, HCoV-OC43, rhinoviruses, and NPEVs. RESULTS: We observed widespread transmission of HCoV-229E, rhinoviruses, and NPEVs within the first week after entry into basic training, and a subsequent phase of transmission predominantly involving HCoV-OC43 during the second month (Figure). We estimated pre-epidemic reproductive numbers ranging from 1.97 (95% credible interval: 1.49, 2.60) for HCoV-OC43 to 5.69 (3.92, 7.98) for HCoV-229E (Table). Subjects re-acquired HCoV-229E, rhinoviruses, and NPEVs despite previous exposure; for these pathogens, we estimated reversion to pre-infection susceptibility to occur, on average, 28.5 (15.8, 49.7) days, 52.2 (22.3, 151.1), and 144.7 (61.3, 812.5) days, respectively, following clearance of viral shedding. CONCLUSION: Asymptomatic shedding is a source of transmission of common respiratory viruses in the close-contact basic training environment. Protection against re-acquisition is short-lived, and may be inadequate to prevent re-infection by rhinoviruses and NPEVs within a season. Estimated durations of shedding and incubation periods provide a basis for modeling pathogen spread and informing isolation protocols. DISCLOSURES: J. Lewnard, Pfier: Grant Investigator, Research grant. E. Grigorenko, Diatherix Laboratories: Employee, Salary. D. M. Weinberger, Pfizer, Merck, Affinivax: Consultant and Grant Investigator, Consulting fee and Research grant."
5426,Predictors of Clinical Respiratory Virus Testing Among Adults Hospitalized with Acute Respiratory Illness (ARI) (2015–2016),"BACKGROUND: Vaccine effectiveness (VE) studies require an accurate indicator of influenza infection, often obtained through research testing independent of clinical (physician-ordered) testing. Clinical testing could be used to detect influenza in these studies if factors associated with clinical testing for influenza were better understood. METHODS: Adults hospitalized with ARI at three study sites during the study period were enrolled in CDC’s 2015–16 Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study and tested for influenza by RT-PCR. Clinical testing information, presenting symptoms, and patient characteristics were collected from medical records and patient interview. Logistic regression was used to estimate odds of receiving a clinical test based on age, vaccination status, comorbidities, presentation with influenza-like illness (ILI; defined as fever and cough or sore throat) and other factors. RESULTS: Of 895 enrollees, 571 (64%) patients meeting study inclusion criteria received physician-ordered testing. Of these, 53% had a multipathogen panel, 13% had a rapid antigen test, 7% had singleplex PCR, <1% had viral culture, and 27% had multiple tests; influenza infection was detected in 55 (6%) patients. Of 150 influenza cases identified by study testing, 25 (17%) were not tested clinically. Enrollees who did not receive clinical testing were older, had longer time to admission, and were less likely to present with ILI. Immunosuppressive disorders (aOR=2.05), non-COPD lung conditions (aOR=1.68), presentation with ILI (aOR=4.03), and admission ≤2 days from symptom onset (aOR=1.89) were positively associated with receiving a clinical test (P < 0.01 for all; Figure 1). After adjusting for these factors, enrollees with influenza vaccination were 37% less likely (aOR=0.63) to receive a clinical test (P < 0.01). CONCLUSION: Patients with ARI who were clinically tested for influenza differed from those not tested. A lower likelihood of testing among influenza positive vaccinees could potentially bias VE estimates upward and requires further evaluation. Clinical testing alone may fail to detect a substantial proportion of influenza cases. DISCLOSURES: All authors: No reported disclosures."
5427,BK Polyoma Virus Nephropathy in Hematopoietic Cell Transplant Recipients with Renal Dysfunction,"BACKGROUND: BK polyoma virus (BKV) nephropathy (BKVN) is a well-established cause of allograft loss after kidney transplantation. In contrast BKVN is rarely been reported in hematopoietic cell transplant (HCT) recipients. Renal dysfunction after HCT is common and often attributed to total body irradiation, drug toxicity, hypertension or microangiopathy. As kidney biopsies are rarely performed after HCT, BKVN may be underdiagnosed. We report a Single-center experience of BKVN in HCT recipients. METHODS: Retrospective chart review of HCT recipients from January 1, 2016 through March 31, 2017. Only cases of BKVN confirmed by immunohistochemical stain on renal biopsy are included. Urine and blood BKV PCR was performed at Viracor Eurofins (Lee’s Summit, MO). Glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: From 2016 to 2017, 320 patients received HCT and 6 patients underwent kidney biopsy and 4 had BKVN. Patient characteristics are shown in Table 1. Three patients (75%) received ex vivo T-cell depleted (CD34+ selected) peripheral blood (PB) HCT and did not receive pharmacologic GVHD prophylaxis; one patient received cord blood allograft. All patients had BKV viruria with a median BKV viral load of 9.3 log(10) copies/mL (range, 8.6–10.0) and median onset 18 days (range 6–41) post HCT. BKVN was diagnosed at a median of 275.5 days post-HCT (range, 141–637). All patients presented with decreased GFR (median 47.5% reduction, range 16–75%) from GFR at transplant. One patient had proteinuria (3 g over 24 hours); one patient had hydronephrosis. At BKVN diagnosis plasma BKV viral load was a median of 6.2 log(10) copies/mL; range, 6.0–6.3), absolute lymphocyte count median 1027 (range 335–2,536) and CD4+ lymphocyte count median 145 (range 64–172). CONCLUSION: (1) BKVN should be considered in HCT recipients with worsening renal function and high BKV viremia. (2) Early, noninvasive predictors of BKVN could aid in identifying high-risk patients for early intervention prior to irreversible loss of kidney function. (3) Reduction of immunosuppression is often not feasible in HCT. The role of preemptive antiviral therapy and/or adoptive cell therapy for BKV viremia in HCT should be evaluated in clinical trials. DISCLOSURES: G. Papanicolaou, Chimerix: Consultant, Grant Investigator and Investigator, Consulting fee, Grant recipient and Research grant"
5428,Intranasal Administration of Integrase Defective Lentiviral Vectors Expressing mAbs Protects from H5 Influenza Virus Challenge In Vivo,"BACKGROUND: Despite medical advances, we are often unable to rapidly protect non-immune populations from infectious agents. Passive immunotherapy is a fast method of protection, but large-scale administration of monoclonal antibodies (mAbs) in unpractical. The delivery of mAbs using a viral vector can be an attractive alternative to direct mAbs injection. Integrase-defective lentiviral vectors (IDLV) have several advantages including the absence of pre-existing anti-vector immunity and the safety features of non-integration and non-replication. IDLV are maintained in non-dividing cells, and can express steady levels of functional proteins in vivo. We engineered IDLV to express mAbs against the influenza A virus (IAV) hemagglutinin, and tested their ability to protect from IAV in vivo. METHODS: IDLV were produced by co-transfection of transfer, packaging, and envelope plasmids in 293T cells and purification on sucrose gradients. IDLV were normalized using a colorimetric reverse transcriptase assay. Plasmid expressing mAb VN04-2 was provided by B. Hanson. mAb in the supernatant of transduced cells were detected by western blot and quantified by the Easy-Titer Human IgG Assay Kit. For in vivo studies, groups of 6–8 weeks old mice received IDLV either by intranasal (in) or intramuscular (im) route. mAb production was detected by western blot and ELISA. Mice were challenged using the recombinant IAV VNH5N1-PR8/CDC-RG derived from IAV A/Vietnam/1203/2004. RESULTS: We engineered IDLV producing the humanized mAb VN04-2 (IDLV-VN4-2), which is broadly neutralizing against H5 IAV. We found that after transduction of 293T cell with different dosages IDLV-VN4-2, the production of mAb was time and dose dependent. mAb were also functional, and bind specifically H5 HA but not other IAV proteins. We also measured VN04-2 production in the serum of mice 3, 6, 9, 14, 21 and 30 days after in or im administration of IDLV-VN4-2. We found that levels of mAb were sustained. In separate experiments 5/5 mice receiving IDLV-VN4-2 by the in route and 2/5 mice receiving it by the im route were protected from lethal IAV challenge. CONCLUSION: Our data suggest that IDLV may represent an attractive candidate for vector-mediated immunization against infectious disease. DISCLOSURES: All authors: No reported disclosures."
5429,Burden of Community-Acquired Pneumonia due to PCV-13 Streptococcus pneumoniae Serotypes Among Hospitalized Adults in the United States,"BACKGROUND: The burden of disease for US adult patients hospitalized with community-acquired pneumonia (CAP) due to S. pneumoniae (Sp) PCV13 vaccine types (VT) is not known. The objective of this study was to determine the incidence, patients’ characteristics, length of stay and mortality for US adults hospitalized with CAP due to Sp-PCV13VT. METHODS: This was a prospective observational study of adults hospitalized between October 7, 2013 and September 30, 2016 with radiographically confirmed CAP in 19 centers in the US. Patients were included if the following 5 criteria were met: 1) Age 18 years and older; 2) Presence of two or more of the following: fever, hypothermia, chills or rigors, pleuritic chest pain, cough, sputum production, dyspnea, tachypnea, malaise, and abnormal auscultatory findings suggestive of pneumonia; 3) Radiographic finding consistent with pneumonia; 4) Able to provide urine sample; 5) Signed informed consent. The presence of Sp-PCV13VT was investigated using a Luminex-based urinary antigen detection (UAD) assay or serotyping from a positive Sp isolate. Data on patients’ characteristics, length of stay (LOS) and in-hospital mortality (IHM) were collected. RESULTS: From a total of 12,055 hospitalized patients with CAP, VT Sp-PCV13 was detected in 552 patients via UAD or culture (4.6%). Among patients hospitalized with CAP due to Sp-PCV13VT, median age was 64 years, and the most common comorbidities were chronic obstructive pulmonary disease (46.2%) and diabetes (27.3%). Median LOS was 6 days, and IHM was 5.4%. There were no clinically significant differences when this population was compared with the population of patients with non-PCV13 VT Sp-CAP. CONCLUSION: In approximately 5% of US adults hospitalized with CAP, the etiologic agent is VT Sp-PCV13. Clinical characteristics and outcomes in this population were similar when compared with the general population of hospitalized patients with CAP. In conclusion, this study indicates a persistent burden of disease for adult patients hospitalized with CAP due to vaccine preventable Sp serotypes. DISCLOSURES: All authors: No reported disclosures."
5430,A Varicella Outbreak Among Preschool Children Despite One-dose Vaccination,"BACKGROUND: In Turkey, a single-dose varicella vaccine was introduced into the National Immunization Program in 2013. Before this implementation, varicella vaccine had been available in the private sector since 2000. However, varicella outbreaks continued to occur in preschools and elementary schools. We investigated a varicella outbreak to estimate the effectiveness of 1-dose varicella vaccine and to evaluate potential risk factors for breakthrough disease. METHODS: This study was carried out during a varicella outbreak in 3 preschools in İzmir, Turkey, in April 2016. Using questionnaires, data including children’s medical and vaccination history were collected from their parents. Vaccination status of children was also verified with immunization records. Attack rates in vaccinated and unvaccinated children were calculated and the analysis of vaccine effectiveness and of risk factors for breakthrough disease were conducted. Vaccine effectiveness was calculated using the equation: (attack rates in unvaccinated children-attack rates in vaccinated children/ attack rates in unvaccinated children) × 100%. RESULTS: A total of 124 children were enrolled in the study. Of the 124 children, 77 (62%) had received 1-dose varicella vaccine before the outbreak. Varicella developed in 34 of 124 children during the outbreak, and 18 of them (53%) had breakthrough varicella. The attack rate was 23.4% among vaccinated children and 34% among unvaccinated children. The effectiveness of single-dose varicella vaccine was 33.6% against varicella disease of any severity and 82.5% against moderate or severe varicella. Children vaccinated 5 or more years before the outbreak had 3.5 times the risk of disease than those who had been vaccinated more recently (OR 3.5 [95% CI, 1.08–11.5]); P = 0.046). Age at vaccination (<15 months vs.≥15 months) and the brands of varicella vaccine were not associated with the increased risk of breakthrough varicella. CONCLUSION: One-dose of varicella vaccine is not sufficient to prevent school outbreaks. For this reason, varicella outbreaks continued to occur in schools and kindergartens among healthy vaccinated children in Turkey. A 2-dose varicella vaccination program may help to prevent varicella outbreaks and achieve effective control of the disease. DISCLOSURES: All authors: No reported disclosures."
5431,Assessment of a Healthcare-Associated Pneumonia (HCAP) Risk Stratification and Empiric Treatment Guideline: A New Antimicrobial Stewardship Initiative,"BACKGROUND: Risk stratification of HCAP patients is a possible Antimicrobial Stewardship (AST) intervention for the treatment of multidrug resistant (MDR) Gram-negative (GN) vs. community-acquired pneumonia (CAP) pathogens. This study assessed the impact of a risk stratification guideline for empiric antimicrobial selection relative to acceptance rates and clinical outcomes. METHODS: In 2017, a guideline for inpatients with HCAP was launched. High risk (HR) of MDR GN was defined as patients admitted to the intensive care unit (ICU), or with >1 risk factor including: receipt of any antimicrobial within 30 days or broad spectrum antimicrobials within 90 days, hemodialysis dependence, or immunocompromised. HR patients were recommended to receive antimicrobials covering MDR GN and low-risk patients to narrower CAP regimens. Patients treated for HCAP post guideline implementation were compared with a historic 2014 cohort for guideline concordance, antimicrobial selection, and clinical outcomes. AST interventions were also assessed. RESULTS: Overall, 105 patients in the post-implementation period were compared with 309 historic patients. Guideline-concordant risk-stratified therapy increased 13% [95% CI (3%, 24%)] overall. Clinical failure rates were similar with 11% vs 10% (P = 0.608) in the pre- and post-implementation periods, with an 84% AST acceptance rate (Figure 1). Treatment length decreased [8.1 to 6.6 days (P < 0.001)] and de-escalation increased [31% to 72% (P < 0.001)] as seen in Table 1. CONCLUSION: Introduction of a risk stratified guideline through AST intervention changed practice by matching MDR risk with empiric HCAP therapy. Failure rates were comparable. Secondary benefits included: decreased treatment duration and hospital stay, increased de-escalation rates and decreased MDR GN antimicrobial use in low-risk patients. DISCLOSURES: All authors: No reported disclosures."
5432,Epidemiology of Polymyxin Use in a Tertiary Care Setting of South India,"BACKGROUND: Polymyxin B(PB) and Colistin (PE) use have increased in India due to emergence of resistant Gram-negative organisms. The Indian Council of Medical Research has identified carbapenems, polymyxins (PE and PB) as key antimicrobials which require restriction in hospitals. We describe epidemiology of PB and PE use following implementation of an Antibiotic Stewardship Program (ASP) in a 1300-bed, private, tertiary-care center in Southern India. METHODS: An ASP was established at Amrita Hospital in Feb 2016 consisting of an administrative champion, hospitalist, microbiologist, intensivist and 5 pharmacists. Institutional guidelines for polymyxins were established and disseminated. The ASP team performed daily post-prescriptive reviews, evaluated and tracked appropriateness of PB and PE use, including administration of a loading dose (LD), maintenance dose (MD), frequency, route and duration of therapy. ASP recommendations and compliance were recorded. RESULTS: During the 12-month study period (Feb ‘16-Jan ‘17), 348 patients received 295 PE and 94 PB courses. Mean age was 50 yrs and 73% were male. Patients on Medicine and Hematology/Oncology teams accounted for 42% of all prescriptions. The most common infections were bacteremia (34%), pneumonia (29%) and UTI (23%). Pathogens were recovered in 69% (269/389) of cases, Klebsiella pneumoniae 23% (90/389) and Acinetobacter baumanii11 % (45/389) were most common. 290 (75%) of polymyxin course were judged to be inappropriate (78% of PE and 22% of PB). The most frequent reasons for inappropriate therapy included incorrect frequency of administration (64% for PB and 58% for PE), inappropriate MD (60% for PB and 48% for PE) and wrong duration of therapy (54% for PE and 48% for PB). 95% of incorrect MD for both PE and PB were too low. The reasons for inappropriateness were similar for both polymyxins.While all inappropriate LD episodes for PB (n = 22 %) were due to lack of a LD, errors for PE (n = 34%) involved either omission of LD or administration of LD that was too low.ASP recommendations were made in 190 instances with 58% provider compliance. CONCLUSION: Review of PB and PE use in our hospital indicates a high percentage of inappropriate use and highlights stewardship opportunities for improving care of patients with resistant infections. DISCLOSURES: K. S. Kaye, Xellia: Consultant, Consulting fee; Merck: Consultant and Grant Investigator, Consulting fee and Research support; The Medicines Company: Consultant and Grant Investigator, Consulting fee and Research support"
5433,Impact of CMV Blips in Transplant Recipients,"BACKGROUND: Management of CMV infection in solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT) recipients mainly relies on screening of emerging CMV DNA in plasma or whole blood by PCR. However, a first positive CMV PCR may not be reproducible, but constitute a CMV blip (single positive CMV PCR measurements). Such blips are known from monitoring of other viral infections using PCR technology, and may either constitute a false positive read due to assay variability or reflect transient low-level viral replication. We investigated the impact of CMV blips in a cohort of SOT and HSCT recipients. METHODS: SOT and HSCT recipients transplanted between 2010 and 2015, who had a known donor (D)/recipient (R) CMV IgG serostatus (D+/R+, D+/R- or D-/R+), and with ≥3 CMV PCRs fulfilling the CMV PCR triplicate criteria (Figure 1) were included (N = 851). Odds ratio (OR) for factors associated with a triplicate being a blip was estimated by binomial regression adjusted for repeated measurements. Whether blips affected the hazard ratio (HR) for subsequent CMV infection was determined with a Cox model. RESULTS: 851 transplant recipients generated 3883 CMV PCR triplicates (104 blips, 307 infections, 3472 negatives, Figure 1). In the 411 positive triplicates, the OR of a triplicate being a blip decreased with increasing CMV viral load of the second measurement ([vs. = 273 IU/mL]; >273–910 IU/mL: OR 0.2 [95% CI 0.1–0.4], >910 IU/mL: OR 0.07 [95% CI 0.03–0.2], P < 0.0001) and was elevated in recipients with intermediary/low-risk CMV IgG serostatus ([vs. those with high] OR 2.2 [95% CI 1.3–3.6] P = 0.003). If the cumulative exposure to viremia in the CMV blips was >910 IU/mL, there was a higher risk of subsequent CMV infection (HR 4.6 [95% CI 1.2–17.2] P = 0.02) (Figure 2). CONCLUSION: CMV blips are frequent while screening transplant recipients with CMV PCR. CMV blips >910 IU/mL is a risk factor for subsequent infection, indicating that CMV blips at least partly reflect transient low-level CMV infection in transplant recipients. These observations suggest that first positive CMV PCR results should be confirmed before initiation of anti-CMV treatment, especially if the viral load of the first positive PCR is <910 IU/mL, or if the patient has intermediary/low-risk serostatus. DISCLOSURES: All authors: No reported disclosures."
5434,Frailty Hinders Recovery From Acute Respiratory Illness in Older Adults,"BACKGROUND: Influenza vaccination programs aim to prevent serious outcomes. Given that frailty may impact recovery from influenza, we examined frailty as a predictor of recovery in older adults hospitalized with acute respiratory illness. METHODS: Data came from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network during the 2011/12, 2012/13, and 2013/14 influenza seasons; all patients were aged 65+. Frailty was measured using a previously validated Frailty Index (FI) of health and functional deficits; baseline frailty was categorized using published cutoffs (0-.1 non-frail, >.1-.21 pre-frail, >.21-.45 frail, >.45 most frail). Recovery was operationalized as being alive 30 days post-discharge with less than two additional health/functional deficits (<=0.06 FI increase). Logistic regression was used to examine the change in odds of recovery for every 0.1 increase in baseline FI, controlling for age, sex, season, lab-confirmed influenza status, and seasonal influenza vaccination status. RESULTS: Of 5125 hospitalized older adults, 15% were non-frail, 39% pre-frail, 40% frail, and 6% most frail. 11% died, and poor recovery was experienced by 520/4544=11% of survivors. Poor recovery was inversely associated with baseline frailty (11% non-frail, 17% pre-frail, 28% frail, 38% most frail; P < .001). Frailty was associated with lower odds of recovery in all three seasons [2011/12 (OR=0.71; 95% CI 0.60–0.85), 2012/13 (OR=0.72; 0.66–0.78), 2013/14 (OR=0.76; 0.70–0.82)] though results varied by season, influenza status, and vaccination status. In 2011/12, frailty was associated with poor recovery in unvaccinated (OR=0.46. 95% CI=0.32–0.67) but not vaccinated older patients (OR=0.83, 95% CI=0.68–1.02). CONCLUSION: Increasing frailty was consistently associated with lower odds of recovery in older adults admitted with influenza and other acute respiratory illnesses; depending on seasonal factors, vaccination may offer some buffering of this impact. Understanding frailty and functional status is important, both because frailty is predictive of poor recovery and because persistence of new health/functional deficits is an adverse outcome with important implications for patients, families and health systems. DISCLOSURES: M. K. Andrew, GSK: Grant Investigator, Research grant; Pfizer: Grant Investigator, Research grant; Sanofi-Pasteur: Grant Investigator, Research grant; J. McElhaney, GSK Vaccines: Scientific Advisor, Speaker honorarium; M. Elsherif, Canadian Institutes of Health Research: Investigator, Research grant; Public Health Agency of Canada: Investigator, Research grant; GSK: Investigator, Research grant; S. A. Halperin, GSK: Scientific Advisor, Consulting fee; GSK: Grant Investigator, Research grant; T. Hatchette, GSK: Grant Investigator, Grant recipient; Pfizer: Grant Investigator, Grant recipient; Abbvie: Speaker for a talk on biologics and risk of TB reactivation, Speaker honorarium; J. M. Langley, GSK: Investigator, Research grant; Canadian Institutes of Health Research: Investigator, Research grant; A. Mcgeer, Hoffman La Roche: Investigator, Research grant; GSK: Investigator, Research grant; sanofi pasteur: Investigator, Research grant; J. Powis, Merck: Grant Investigator, Research grant; GSK: Grant Investigator, Research grant; Roche: Grant Investigator, Research grant; Synthetic Biologicals: Investigator, Research grant; M. Semret, GSK: Investigator, Research grant; Pfizer: Investigator, Research grant; S. Trottier, Canadian Institutes of Health Research: Investigator, Research grant; L. Valiquette, GSK: Investigator, Research grant; S. McNeil, GSK: Contract Clinical Trials and Grant Investigator, Research grant; Merck: Contract Clinical Trials and Speaker’s Bureau, Speaker honorarium; Novartis: Contract Clinical Trials, No personal renumeration; sanofi pasteur: Contract Clinical Trials, No personal renumeration"
5435,Improving Patient and Employee Safety through Implementation of an Infection Risk Screening Process for International Patients at Boston Children’s Hospital—The “AIRSHIP” Protocol,"BACKGROUND: Vaccine-preventable diseases and multi-drug-resistant organisms (MDROs) are common outside of the US, and multiple infectious outbreaks have been linked to travelers. Boston Children’s Hospital cared for 2796 international patients in 2016 but lacked an infection risk screening process for these patients, placing patients and staff at risk. We developed the Assessing Infection Risks for Safe Healthcare of International Patients (AIRSHIP) protocol to identify risks to guide infection prevention and control (IPC) measures. METHODS: A multidisciplinary team of IPC, infectious diseases, and International Health Services (IHS) experts assessed current IHS intake procedures and stakeholder engagement. We then developed AIRSHIP, devising standardized processes and forms to (1) assess underimmunization, MDRO and tuberculosis history, recent exposures, and current symptoms and (2) triage cases for catch-up immunization, urgent healthcare evaluation, and/or IPC intervention (Figure 1). We piloted incorporation of AIRSHIP into existing intake procedures. We tracked process, outcome, and balancing measures to evaluate feasibility, effectiveness, and acceptability to families (Figure 2) and made iterative improvements through Plan-Do-Study-Act (PDSA) cycles. RESULTS: For our first 13 cases, we completed pre-arrival family and referring provider interviews in 5 cases and on-arrival family interviews in 8 cases (in no cases were both pre-arrival and on-arrival interviews feasible). We were able to assign a risk category in all cases, identifying 5 patients with infection risks (38%) and 4 who were undervaccinated (30%). In 7 of 8 cases (88%) in which on-arrival interviews were performed, the interview and referring provider records yielded complete and reliable data. The average duration of family interviews was 18 minutes. All 13 families reported being “very satisfied” with AIRSHIP. CONCLUSION: International patients often present with active infections and are commonly undervaccinated. A feasible and effective strategy for infection risk screening of international patients is review of records pre-arrival, together with on-arrival family interview to gather additional data and identify acute symptoms and exposures. DISCLOSURES: All authors: No reported disclosures."
5436,Evaluating Symptom Severity of Influenza Viral Infection Using the Influenza Patient-reported Outcomes Instrument (FLU-PRO) in a Healthy Human Challenge Model,"BACKGROUND: To apply the validated FLU-PRO scoring method to assess influenza symptom severity in a healthy human challenge model. METHODS: Healthy adults admitted to the NIH Clinical Center (Day -1) underwent a 9 day inpatient quarantine after intranasal challenge with H1N1pdm (Day 0). Participants completed the 32 item FLU-PRO diary twice daily for 14 days to assess presence and severity of symptoms across six body systems. Secondary analyses included descriptive statistics to examine FLU-PRO scores over the course of illness and analysis of variance to compare severity scores on Day 3 post-challenge by viral shedding, and pre-challenge hemagglutinin and neuraminidase inhibition (HAI and NAI) titers. RESULTS: 61 of 65 subjects reported symptoms (Days: Median 5, Mean 6 ± 7), of which 37 (61%) had viral shedding. Pre-challenge, 39 (64%) and 10 (16%) subjects had low (<40) HAI and NAI titers, respectively. Mean daily FLU-PRO symptom severity domain and total scores are shown in Figure 1. Symptoms were present across all FLU-PRO domains from Day 1 post-challenge. Nose, throat, body, and GI symptoms reached peak severity at Day 3, followed by chest and eye symptoms at Day 4. Subjects with viral shedding had significantly higher mean FLU-PRO scores compared with those without, except for Eye and GI domains (P < .05); mean FLU-PRO scores were significantly higher for subjects with low NAI titer (P < .05) across all domains. No significant differences were observed between HAI titer groups. FLU-PRO scores of the low HAI-low NAI group (n = 10) were significantly higher (more severe) than the other two groups (P < .05) ((high HAI-low NAI (n = 22), low HAI-high NAI (n = 29)). CONCLUSION: The FLU-PRO can be used to track symptom onset, severity, and recovery from influenza infection in clinical research. In this challenge study, scores were responsive to change even in mild disease and distinguished known clinical subgroups. The use of NAI as an independent predictor of influenza disease severity was also supported. Funded by NCI Contract No. HHSN261200800001E and in part by the Intramural Research Program of the NIH, NIAID DISCLOSURES: J. L. Poon, Evidera: Employee, Salary; R. Yu, Evidera: Employee, Salary; N. K. Leidy, Evidera: Employee, Salary"
5437,A Cloud Based Epidemiology Network to Investigate Geographical Dynamics of Respiratory Disease,"BACKGROUND: Real-time data collection of respiratory disease is important for understanding the spatiotemporal dynamics of disease transmission in the US. Healthcare professionals use tools such as FluView to help identify local pathogen circulation; however, these tools are limited to syndromic surveillance, and track a limited set of pathogens. Understanding respiratory disease dynamics requires 1) a large, pathogen rich data set 2) geographically dispersed data sources, and 3) fine temporal resolution. Here we utilize FilmArray® Trend, a research epidemiology system containing exported data from FilmArray® Respiratory Panel (RP) tests, to investigate geographic patterns of 20 common pathogens. METHODS: Over 6,000,000 individual pathogen assays from 19 clinical sites were exported to the Trend database from 2013 to present. Trend data were smoothed and normalized to produce the time series of pathogen incidence. A cross-correlation analysis was performed to compare sites to one another and determine offset of pathogen incidence. The results were plotted on a map of the US with visual indicators of correlation strength and directional movement as defined by cross-correlation lag values. RESULTS: The respiratory pathogens detected by the FilmArray RP test show a diverse set of spatial and temporal behaviors Most striking was the spread of the virus Coronavirus OC43, and Respiratory Syncytial Virus (RSV), with RSV traveling from east coast sites to west coast sites across the US over 20 days. In contrast Parainfluenza virus 3 (PIV3) shows a small cross-correlation lag across all of the Trend sites during the regular summer season, indicating near simultaneous onset of detection nationwide. A localized cluster of PIV3 in the winter of 2016 was observed in the midwest and west, identifying the significance of localized regional trends. CONCLUSION: FilmArray Trend shows great promise in deciphering spatiotemporal dynamics of these common respiratory pathogens. This system can identify localized outbreaks and directional movement of pathogens over time. Future work with finer geographic distribution of contributing sites will aide in making conclusions regarding spatial dynamics of all 20 RP pathogens. Other pathogen transmission models may also be explored using this data set. DISCLOSURES: C. Cook, BioFire Diagnostics: Employee, Salary. A. Wallin, BioFire Defense: Employee, Salary. A. Faucett, BioFire Diagnostics: Employee, Salary. L. Meyers, BioFire Diagnostics: Employee, Salary"
5438,"Infectious Complications of Intravenous Drug Use: A Single-Center Review of Hospitalized Patients in Massachusetts, 2012-2015","BACKGROUND: The national opioid epidemic has been accompanied by precipitous increases in overdose deaths and hospitalizations for infectious complications of injection drug use (IDU). Despite this, there is scant literature addressing the topic. We aimed to describe demographic characteristics, type of infection, healthcare utilization, disposition and outcomes among patients hospitalized for IDU-related infection over a multi-year period at a large tertiary care referral center in Boston, MA. METHODS: We conducted a retrospective chart review of patients hospitalized for IDU-related infection from 1/1/2012-9/30/2015. 901 charts were initially identified using administrative codes; 234 met the following inclusion criteria: 1) hospitalization within the study period for treatment of ≥1 of 6 selected infections and 2) IDU within 6-months preceding qualifying hospitalization. During the study period, 234 patients had 488 cumulative admissions. Admissions for IDU-related infection and ≤30-day readmission, all-cause, underwent detailed abstraction (N = 338; 69%). RESULTS: Of 234 patients, over half were male (57%; N = 134), 78% white (N = 183), 17% homeless (N = 37), 88% had public insurance (N = 210); 53% had a history of Hepatitis C infection (N = 124), most with untreated or unknown infection status (86%; N = 107). Average age was 38 (range 18-75). Fifty-eight percent (N = 136) of patients had one admission during the study period, the remainder had between 2-13 (mean = 3.6). Sentinel admission infection types were 1) skin and soft tissue (SSTI) N = 111 (42%), 2) endocarditis N = 70 (30%), 3) bone and joint N = 26 (10%), 4) pyogenic spinal N = 39 (15%), 5) isolated bacteremia N = 9 (3%) 6) and acute viral hepatitis N = 8 (3%). Of 338 admissions, 57% (N = 192) included infectious disease consultation; 50% resulted in discharge to another facility and 82% (excluding isolated SSTI) required multi-week intravenous antibiotics on discharge. By 15-months following the study period, 12% were deceased (N = 28); 5 died during hospitalization. CONCLUSION: Our study describes the characteristics of patients hospitalized with IDU-related infection over a multi-year period in a region highly impacted by the opioid epidemic. High rates of hospital readmission, prolonged antibiotic therapy and out-of- hospital death were common in this young cohort. DISCLOSURES: All authors: No reported disclosures."
5439,New evidence-based clinical practice guideline timely supports hospital infection control of coronavirus disease 2019,
5440,Hand hygiene: Knowledge and Practices of Clinical Teachers in Selected Teaching Hospitals in Kenya,"BACKGROUND: Healthcare-associated infections lead to substantial morbidity and mortality worldwide, and adequate hand hygiene (HH) in the clinical setting is essential for prevention. Clinical teachers are central to the training of healthcare workers (HCW) as they teach and model safe practices in the clinical environment. However, there is limited research on the knowledge and practices of clinical teachers related to HH in teaching hospitals, particularly in African settings. We describe the knowledge and practices of HH amongst clinical teachers in selected teaching hospitals in Kenya. METHODS: Data were collected through self-administered standardized questionnaires with basic demographic, knowledge and practices about HH from clinical teachers employed at two teaching hospitals. Participating clinical teachers were anonymously audited for HH practices using an adapted World Health Organization tool. The audits consisted of 20–30 minutes observations in each ward RESULTS: Among 57 participants overall, 42 (73.7%) were nurses, 8 (14.0%) clinicians, and 5 (8.8%) therapists. Twenty-one (36.8%) of the participants had knowledge regarding the minimum time needed to practice HH using alcohol based hand rub, 14 (24.6%) knew that hand washing and hand rubbing should be performed in sequence. The combined knowledge score for each individual ranged from 0% to 94.1% with a mean of 50.1% (SD=20.1, Cl 95% 44.7- 55.4%). Hand hygiene compliance significantly varied by clinical instructor’s type; nurses (42.7%) and therapists (38.0%) had the highest adherence and clinicians had the lowest 33.7% (P = 0.0001). CONCLUSION: Clinical teachers in this study demonstrated knowledge gaps and poor practices related to HH. Since they serve as role models for future generations of healthcare workers, clinical teachers must recognize the importance of HH in preventing hospital-acquired infections, including when and how HH should be performed while following recommended practices. DISCLOSURES: All authors: No reported disclosures."
5441,"Mumps Outbreak—Colorado, 2017","BACKGROUND: During 2016, an unusually high number (>5,000) of mumps cases were reported in the United States. On January 20, 2017, we identified a mumps outbreak in the Denver metropolitan area among a Marshallese community. We performed active surveillance to assess outbreak magnitude and guide implementation of control measures. METHODS: On January 22, local and state health departments initiated active case surveillance by using a church-based community roster. Each household was contacted by telephone ≥3 times to identify mumps cases, according to the 2012 CDC/Council of State and Territorial Epidemiologists case definition, and risk factors (e.g., household size). Measles, mumps, and rubella (MMR) vaccination status was reviewed in the Colorado Immunization Information System (CIIS). Four church-based vaccination clinics were held to bring participants up-to-date for MMR vaccination. Targeted messaging about mumps, MMR vaccine, and vaccination clinics was distributed through social media, churches, and Marshallese-language radio. RESULTS: Of the 21 households on the church roster, 17 were successfully contacted, 13 of which (76%) provided data for 85 persons (median household size: 6 persons; range: 5–12). Through household interviews and laboratory reporting, we identified 47 mumps cases (17 confirmed; 30 probable). Median patient age was 20 years (range: 3 months–44 years), 24 (51%) were male, and 34 (72%) reported no or unknown prior mumps vaccination and had no MMR vaccination documented in CIIS. During vaccination clinics, 118 (80%) of 148 presenting Marshallese persons were eligible for and received MMR vaccine; of those vaccinated, median age was 21 years (range: 1–55 years) and 104 (88%) had no prior MMR vaccine documentation. CONCLUSION: Active surveillance, facilitated through culturally appropriate communication with church leaders, helped identify cases, disseminate materials, and promote MMR vaccination. Household interviews provided timely data to define outbreak magnitude and need for urgent MMR vaccination. DISCLOSURES: All authors: No reported disclosures. sdsdsdsd"
5442,"Clinical Features and Outcomes of Immunocompromised Adults Hospitalized with Laboratory-confirmed Influenza in the USA, 2011–2015","BACKGROUND: Data on immunocompromised (IC) adults with influenza are limited but suggest they may present differently and have worse outcomes than non-IC adults. Using a national surveillance system, we describe the epidemiology of IC adults hospitalized with influenza. METHODS: We analyzed data on adults (aged ≥18 years) hospitalized with laboratory-confirmed influenza during the 2011–2012 through 2014–2015 seasons and reported to CDC’s Influenza Hospitalization Surveillance Network (FluSurv-NET). We defined IC patients as having ≥1 of the following: HIV, AIDS, cancer, stem cell or organ transplantation, non-steroid immunosuppressive therapy, immunoglobulin deficiency, asplenia, and other rare conditions. We compared IC and non-IC patients using χ(2) or Fisher’s exact tests and t-tests or Mann–Whitney U tests. RESULTS: Among 35,348 adults hospitalized over four seasons, 3,633 (10%) were IC. The most common IC conditions were cancer (44%), non-steroid immunosuppressive therapy (44%), and HIV (17%). IC patients were younger than non-IC patients (mean 61 ± 17 vs. 67 ± 20 years; P < 0.01). IC patients were more likely to have underlying renal disease (27% vs. 18%) and liver disease (7% vs. 3%) and less likely to have most other chronic underlying conditions including obesity (18% vs. 23%), cardiovascular disease (40% vs. 47%), and chronic lung disease (35% vs. 41%; P < 0.01 for all). IC patients were more likely to have received influenza vaccination (53% vs. 46%; P < 0.01). Among cases with symptom data (2014–2015), IC patients were more likely to present with fever (68% vs. 61%; P < 0.01) but respiratory distress was similar (53% vs. 54%; P = 0.3). Overall, the majority of IC and non-IC patients received antivirals (87% vs. 85%; P < 0.01). IC patients had a longer duration of hospitalization (median (IQR) 4 (2–6) vs. 3 (2–6) days; P < 0.01) and were more likely to be diagnosed with pneumonia (34 vs. 31%; P < 0.01) and to require intensive care (18% vs. 16%; P = 0.01). Death during hospitalization occurred in 135 (3.7%) IC and 945 (3.0%) non-IC patients (P = 0.01). CONCLUSION: Among adults hospitalized with influenza, IC patients had worse outcomes including a longer duration of hospitalization and higher probability of pneumonia and intensive care unit admission, and increased all-cause mortality, although these results are not adjusted for potential confounders. DISCLOSURES: W. Schaffner, Pfizer: Scientific Advisor, Consulting fee. Merck: Scientific Advisor, Consulting fee. Novavax: Consultant, Consulting fee. Dynavax: Consultant, Consulting fee. Sanofi-pasteur: Consultant, Consulting fee. GSK: Consultant, Consulting fee. Seqirus: Consultant, Consulting fee. E. J. Anderson, AbbVie: Consultant, Consulting fee. NovaVax: Research Contractor, Research support. Regeneron: Research Contractor, Research grant. MedImmune: Research Contractor, Research grant and Research support"
5443,The Impact of Respiratory Viral Testing in Hospitalized Adult Patients at a Tertiary Care Facility,"BACKGROUND: The use of multiplex nucleic acid amplification assays to detect respiratory viruses is increasing. However, these tests are expensive, and the clinical significance of a positive result is often unclear. Positive viral results have the potential to decrease antibiotic use and length of stay, but their actual impact is unknown. METHODS: We completed a retrospective review of all adult patients with positive respiratory viral panel (RVP; GenMark) and/or rapid RSV/influenza PCR tests (Cepheid Xpert) collected within 48 hours of admission to the general inpatient or stepdown units of an academic tertiary care hospital between September 1, 2015 and March 15, 2016. Data collected included demographics, comorbidities, clinical presentation, time of test collection and result, additional diagnostic evaluation, and antibiotic use. RESULTS: A total of 221 positive respiratory viral tests were collected on 215 patients during the study period. The median age at time of testing was 56.8 years; 48% were female. Respiratory symptoms were documented in 92.8% of cases. COPD was the most common respiratory co-morbidity (20.2%), while 30% of patients had cancer, and 3.2% were HIV-infected. Respiratory support on admission was common (51.6%). A rapid PCR and RVP were performed in 58.8% of cases, while 28.5% had only an RVP and 12.7% had only a rapid PCR. Of the patients who had a positive rapid PCR, 17.6% also had an RVP done. Antibiotics were started within 24 hours of presentation in 87.4% of all cases and 70.6% of patients who had a positive rapid PCR. Rhinovirus was the most frequently isolated pathogen (44.6% of positive tests) followed by metapneumovirus (14%), respiratory syncytial virus (13.5%), and coronavirus (13.5%). Median time from specimen collection to result was 38.8 hours for RVP, and 15.3% were resulted after patient discharge. For those who had a rapid PCR alone, median time from collection to result was 1.5 hours. CONCLUSION: In this non-critically ill cohort, most patients with positive viral assays received antibiotics, and a substantial number of RVPs were resulted after discharge. This suggests that there are many lost opportunities to impact clinical management with respiratory viral testing. DISCLOSURES: M. Miller, GenMark Diagnostics: Grant Investigator, Research support and Salary; R. Jhaveri, GenMark: Investigator, Grant recipient"
5444,Long-term Respiratory Complication in Patients with Middle East Respiratory Syndrome: 1-year Follow-up After the 2015 Outbreak in South Korea,"BACKGROUND: There are few data about long-term respiratory complications following Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection. This study aimed to evaluate respiratory functions and radiologic sequelae according to the severity of infection one year after the patients experienced MERS-CoV infection. METHODS: A total of 73 patients undergoing MERS-CoV infection during the 2015 MERS outbreak in South Korea were enrolled in this prospective multicenter study. Pulmonary function tests and 6-minute walking tests were performed 1 year after infection. Radiologic sequelae was defined as fibrosis or atelectasis on chest computer tomography and severe pneumonia was defined as that requiring oxygen therapy. Multivariate linear regression tests were used to evaluate the effect of infection severity on respiratory function. RESULTS: At the time of MERS-CoV infection, 18 patients had no pneumonia, 35 experienced mild pneumonia, and 20 did severe pneumonia. The median age was not different between groups (P = 0.942). Forced vital capacity (FVC) was 102.6%, 94.9%, and 88.7% in the no, mild, and severe pneumonia group, respectively (P = 0.010) and forced expiratory volume in 1 second was 105.3%, 95.7%, and 91.7% (P = 0.057). Diffusing capacity (DLCO) was significantly lower in the severe pneumonia group than in the no or mild pneumonia group (78.3% vs. 89.4% or 88.6%, P = 0.035). In multivariate analyses, FVC and DLCO were significantly correlated with infection severity after adjustment with age, sex, underlying lung disease, and smoking. There was no difference in the walking distance of 6 minute tests between groups. Radiologic sequelae were shown in 18.8%, 65.6%, and 100% in the no, mild, and severe pneumonia group, respectively (P < 0.001). CONCLUSION: The patients with more severe pneumonia by MERS-CoV had more impaired respiratory function in one year follow-up, which was compatible with radiologic sequelae. DISCLOSURES: All authors: No reported disclosures."
5445,Use of Oral Ribavirin for the Treatment of RSV Infections in Hematopoietic Cell Transplant (HCT) Recipients,"BACKGROUND: The benefit of aerosolized ribavirin (AR) in reducing the risk of progression of RSV infections and RSV-associated mortality in HCT recipients has been recognized, yet there is a paucity of data assessing the use of oral ribavirin (OR) in this patient population. We evaluated outcomes associated with the use of OR compared with AR in HCT recipients. METHODS: Retrospective review of all HCT recipients with RSV infection treated with OR or AR during three RSV seasons (September 2014 – February 2017). An established immunodeficiency Scoring Index (ISI) was applied to identify patients at high risk for progression and death based on host risk factors. Mortality, progression to lower respiratory infection (LRI), and need for ICU admission was compared among recipients of AR and OR. RESULTS: A total of 107 patients were treated with OR (n = 42, 39%) or AR (n = 65, 61%). Recipients of AR and OR were equally likely to be high-risk by ISI scoring (11% vs. 10%, P = 1.00). Fifty-three patients (50%) presented with upper respiratory infection (URI) of whom 13 (25%) progressed to LRI. There was no difference in the rate of progression to LRI between patients who received AR and OR (28% vs. 19%, P = 0.53). No difference was found in 30-day mortality rates based on treatment strategy (8% AR vs. 5% OR, P = 0.70). Interestingly, 90-day mortality was found to be significantly lower among patients who received OR vs. AR (20% vs. 5%, P = 0.04). No differences in rates of ICU admission and requirement for mechanical ventilation were found between the two groups. For the 99 inpatients at time of diagnosis, median (interquartile range) length of stay was 7 (5 – 19) days, and was similar for patients on either treatment modality. Eight patients were treated for RSV on an outpatient basis and all received OR. CONCLUSION: HCT patients with RSV had similar outcomes when treated with AR and OR. OR may be a safe and effective alternative to AR for prevention and treatment of RSV in HCT patients with significantly reduced cost. DISCLOSURES: R. Chemaly, Gilead: Consultant and Investigator, Consulting fee and Research grant. Ansun: Investigator, Research grant. GSK: Investigator, Research grant."
5446,The Association of Physicians of Great Britain and Ireland 1994: Eighty-Eighth Annual General Meeting,
5447,Impact of formaldehyde addition to spray-dried plasma on functional parameters and animal performance(),"Experimental objectives of this study were to determine effects of formaldehyde treatment on the chemical composition of spray-dried plasma (SDP) and to test the hypothesis that growth performance of pigs fed formaldehyde-treated diets containing SDP or diets containing formaldehyde-treated SDP is not reduced compared with pigs fed untreated control diets. Sal CURB ASF liquid antimicrobial and CURB RM Extra liquid mold inhibitor (Kemin Industries, Des Moines, IA) were applied on SDP at 0.1% or 0.3% to determine effects of the products on chemical and functional properties of SDP. Regardless of product, there were no changes in SDP for analyzed protein, ash, pH, or moisture concentration, but IgG concentration in SDP was decreased 8% and 24%, respectively, for 0.1% and 0.3% inclusion of Sal CURB or CURB RM. Two feeding studies using weaned pigs were conducted to determine effects of formaldehyde applied at 0.3% to SDP (experiment 1) or 0.3% to a complete diet containing 5% SDP (experiment 2). Experiment 1 pigs (n = 265) were weaned at 20 ± 2 d of age and allotted to five treatment groups. Experiment 2 pigs (n = 135) were weaned in two groups at 20 ± 2 d of age and allotted to three treatments groups. In experiment 1, the untreated control diet contained soy protein concentrate (SPC) and test diets contained 2.5% or 5.0% SDP without or with formaldehyde treatment. In experiment 2, formaldehyde was applied to a diet containing 5% SDP and an untreated SPC control diet and an untreated diet containing 5% SDP were also included in the experiment. In experiment 1, linear increases (P < 0.05) in average daily gain (ADG), average daily feed intake (ADFI), and gain-to-feed ratio (G:F) were observed as SDP was included in the diets and the relative bioavailability of formaldehyde-treated SDP was 62% (P = 0.018) if calculations were based on ADG and 15% (P = 0.031) if calculations were based on ADFI. In experiment 2, pigs fed the SDP diet untreated or treated with formaldehyde had increased (P < 0.05) final body weight, ADG, ADFI, and G:F compared with pigs fed the control diet. However, formaldehyde treatment of the plasma-containing diet did not affect pig growth performance compared with pigs fed the untreated SDP diet. In conclusion, formaldehyde treatment applied directly on SDP affects analyzed concentrations of IgG and reduces growth rate of pigs. Treating a complete diet containing 5% SDP with formaldehyde did not affect pig growth performance, and pigs fed diets containing SDP had improved growth performance than those fed the control diet without SDP."
5448,Twenty-First Century Plague. The Story of SARS,
5449,Viral Infections and the Development of Disinfection: 100 Years of Progress at I&ECR,
5450,"Viruses in Ixodes Uriae (Acari: Ixodidae) from Seabird Colonies at RøSt Islands, Lofoten, Norway1","A total of 1929 Ixodes uriae collected from Røst Islands, Lofoten, Norway, in July 1974, was divided into 204 pools and inoculated into suckling mice and chick embryo cell cultures for virus isolation. Virus was detected in 6.6% of the laboratory-molted female ticks, 5.4% of the males and 1.8% of the nymphs. No isolates were obtained from 149 unengorged adult ticks. Of 50 viral strains recovered, 30 belonged to the Uukuniemi group, 13 to the Kemerovo group, and I was a strain of Tyuleniy of Group B. Of 6 untyped strains, I was orbiviruslike and I resembled a coronavirus in a negative-staining electron microscopy. The infection rates of I. uria in Lofoten were similar to those reported in the Murmansk area in the northern USSR."
5451,"Managing SARS Amidst Uncertainty Wenzel RP, Edmond MB The New England Journal Of Medicine. 2003;348:1947–1948",
5452,Selected Bibliography,
5453,Veterinary Medicine (902),
5454,Emerging Infectious Disease in Transfusion Medicine,
5455,A Large Variation in the Rates of Synonymous Substitution for RNA Viruses and Its Relationship to a Diversity of Viral Infection and Transmission Modes,
5456,Probability Sampling by Connecting Space with Households Using GIS/GPS Technologies,"Sampling methods for survey studies are challenged by the replacement of landline telephones with mobile phones, the lack of timely census data, and the growing need for studies to address new health challenges. GIS/GPS-assisted methods provide a promising alternative, but these methods need further improvement. We established a stratified 3-stage GIS/GPS-assisted sampling method in which residential areas of a target population are divided into mutually exclusive cells – geographic units (geounits) as the primary sampling frame (PSF). Geounits with residential households were randomly selected from the PSF with a semi-automatic algorithm implemented in R. Novel methods were used to sample households and participants. Simulations and application studies indicated adequate feasibility, efficiency and validity of the method in sampling rural-to-urban migrants from a large city with complex residential arrangements. With this method, researchers can determine sample size and number of geounits, households and participants to be sampled; optimally allocate geounits; determine area size of sampled geounits and estimate sample weights; and complete sampling for field data collection in a short period. Our method adds an integrative approach for GIS/GPS-assisted random sampling with a de facto population assumption. Additional evaluation studies are needed to assess the utility of this method in different settings."
5457,Veterinary Immunology and Serology: Clinical Laboratory Diagnostics,"Methods used in clinical laboratory diagnosis in the veterinary laboratory closely parallel the common techniques used in the human laboratory. Immunology procedures include immunohematology, autoimmune testing, and assays for detection of immune deficiencies and infectious diseases. Veterinary immunohematology procedures deal with immune-mediated hemolysis, as well as blood typing, cross matching, and transfusion. Diseases of the immune system in animals include rheumatoid arthritis, systemic lupus erythematosus (SLE), and immunodeficiency disorders. The number of infectious diseases that can be diagnosed in a veterinary laboratory is almost limitless, but perhaps two of the most prevalent and significant are heartworm disease and feline infectious peritonitis (FIP)."
5458,Emerging Pathogens: What Are the Sources and How Can They Be Spotted Quickly?,
5459,Matrix Issues Associated With Analysis of Veterinary Specimens,"Accurate analysis and interpretation of veterinary samples may be hampered by differences in sample matrix, compared with human samples. In addition to differences in sample collection methods, abnormal findings include lipemia, hemolysis, icterus, higher protein concentrations, and different therapeutic drug concentrations. Although many of these findings are similar to those in human sample testing, significant differences are present that affect several areas of the laboratory."
5460,News,
5461,Chronic Bacterial and Viral Infections in Neurodegenerative and Neurobehavioral Diseases,"Often, patients with neurodegenerative or neurobehavioral diseases have chronic, neuropathic infections that could be important in disease inception, disease progression, or increasing the types or severities of signs and symptoms. Although controversial, the majority of patients with various neurodegenerative or neurobehavioral conditions, such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and autistic spectrum disorders, show evidence of central nervous system or systemic bacterial and viral infections. For example, using serology or polymerase chain reaction evidence of Chlamydia pneumoniae, Borrelia burgdorferi, Mycoplasma species, human herpesvirus-1 and -6, and other bacterial and viral infections revealed high infection rates that were not found in control subjects. Although chronic infections were not found in some studies, and the specific role of chronic infections in neurological disease pathogenesis has not been determined or is inconclusive, the data suggest that chronic bacterial or viral infections could be common features of progressive neurodegenerative and neurobehavioral diseases."
5462,Severe Acute Respiratory Syndrome Epidemiology and Control,
5463,Book Reviews,
5464,MP647 OUTCOMES OF HEMODIALYSIS PATIENTS WITH MERS-COV EXPOSURE IN KOREA,
5465,Elevated levels of plasma cytokines in COVID-19 reflect viral load and lung injury,This article was published early due to publisher error and has been temporarily removed. The publisher apologizes for the error.
5466,MP722 POSTTRAUMATIC STRESS DISORDER OF HEMODIALYSIS PATIENTS WITH MERS-COV EXPOSURE,
5467,In the Literature,
5468,In the Literature,
5469,Moral imperative for the immediate release of 2019-nCoV sequence data,
5470,1122 Increase in Influenza-Like Illness in the Spring of 2014 Associated with Human Metapneumovirus,
5471,15 October News,
5472,129 Acute Respiratory Viral Infection among Outpatient Healthcare Personnel,
5473,"Bennett & Brachman's Hospital Infections Edited by William R. Jarvis Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins, 2007. 832 pp., Illustrated. $210.00 (hardcover)",
5474,"DIALYSIS. EPIDEMIOLOGY, OUTCOME RESEARCH, HEALTH SERVICES 1",
5475,In the Literature,
5476,1 January News,
5477,On the origin and continuing evolution of SARS-CoV-2,"The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19)."
5478,Editors' selection of papers from China's academic journals,
5479,1 December News,
5480,1 February News,
5481,1 November News,
5482,Reply,
5483,In the Literature,
5484,Cyclosporin,
5485,"Infectious Diseases: Hot Topics Edited by Vincent Lo Re, III Philadelphia: Hanley and Belfus, 2004. 395 pp. $29.95 (cloth)",
5486,SP675 CIRCULATING CELL FREE DNA AND MITOCHONDRIAL DNA IN THE PATIENTS ON HEMODIALYSIS AND MEDICAL STAFFS DURING ISOLATION BY MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS IN KOREA,
5487,"Reemergence of Established Pathogens in the 21st Century Edited by I. W. Fong and Karla Drlica New York: Kluwer Academic/Plenum Publishers, 2003. 367pp., illustrated. $139.50 (cloth)",
5488,"Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 6th Edition Edited by Gerald L. Mandell, John E. Bennett, and Raphael Dolin Philadelphia: Elsevier Churchill Livingstone, 2005. 3661 pp., illustrated. $329 (cloth)",
5489,MP747 EFFECTS OF ISOLATION ON HEMODIALYSIS PATIENTS WITH MERS-COV EXPOSURE IN KOREA: A COHORT STUDY,
5490,In the Literature,
5491,1 October News,
5492,1 May News,
5493,In the Literature,
5494,"Beasts of the Earth: Animals, Humans, and Disease E. Fuller Torrey and Robert H. Yolken New Brunswick, NJ: Rutgers University Press, 2005. 191 pp. $23.95 (cloth)",
5495,1403 Evaluation of Diatherix Laboratories TEM-PCR: a novel multiplex diagnostic panel for detection of bacterial and viral respiratory pathogens,
5496,"Clinical Virology, 3rd Edition Edited by D. D. Richman, R. J. Whitley, and F. G. Hayden Washington, DC: ASM Press, 2009. 1408 pp, Illustrated. $259.59 (hardcover)",
5497,1 September News,
5498,Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients,
5499,In the Literature,
5500,1 June News,
5501,A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes,"Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions."
5502,15 November News,
5503,Imported Infectious Diseases: The Impact in Developed Countries,
5504,In the Literature,
5505,Viruses and the Lung: Infections and Non-Infectious Viral-Linked Lung Disorders,
5506,15 August News,
5507,Emerging Infectious Diseases: Clinical Case Studies,
5508,15 November News,
5509,1 January News,
5510,1 April News,
5511,1 August News,
5512,15 December News,
5513,Genetics and Evolution of Infectious Diseases,
5514,News,
5515,ACCENT® Continuing Education Credit for Readers of Clinical Chemistry,
5516,In the Literature,
5517,Correction,
5518,How viruses use cells,
5519,Molecular diagnostic techniques,"Clinical microbiology laboratories increasingly rely on molecular diagnostic techniques. The various formats of nucleic acid amplification are the most frequently used molecular tests in the diagnosis of infectious diseases. In many clinical settings, polymerase chain reaction (PCR) is clearly the method of choice due to its exquisite sensitivity and specificity. Today, many conventional PCR methods are being replaced by real-time PCR, which allows more rapid detection and quantification of the PCR product, as well as detection of different strains of the pathogen by melting curve analysis. The ability to measure the quantity of microbe by quantitative PCR has become increasingly important, providing information on the progression and prognosis of disease, and effectiveness of treatment. Other widely used molecular diagnostic techniques are isothermal amplification methods and nucleic acid hybridization techniques. Microarray is a technique which holds promise and has an exceptional sensitivity and the capacity to detect several pathogens simultaneously. However, microarrays are currently too expensive to be adapted for routine diagnostics, and their diagnostic use requires broad-based nucleic acid amplification prior to analysis which is not well established. Several molecular methods can be used for genotyping, which allows the identification of different subtypes of the pathogen; genotyping plays a role in the risk assessment and management of infections. Clinicians need to recognize the enhanced accuracy and speed of the molecular diagnostic techniques for the diagnosis of infections, but also to understand their limitations. Laboratory results should always be interpreted in the context of the clinical presentation of the patient, and appropriate site, quality, and timing of specimen collection are required for reliable test results."
5520,Invasive and non-invasive mechanical ventilation,"Early recognition of patients who might potentially require ventilatory support is a key goal of critical care outreach programmes and an important skill for all hospital medical staff. Decisions about the initiation and timing of invasive ventilation can be difficult, and early discussion with critical care colleagues is essential. Appropriateness of invasive ventilatory support can also require advanced discussion with patients and families. In the past 10–15 years, the role of non-invasive ventilation (NIV) has expanded, not least in an attempt to minimize the complications inherent in invasive ventilation. Indeed, NIV is now considered first-line therapy in some conditions (chronic obstructive pulmonary disease, pulmonary oedema, mild to moderate hypoxaemic respiratory failure in immunocompromised patients), and a ‘trial of NIV’ is often considered in respiratory failure resulting from an increasingly wide range of causes. With NIV, the importance of the environment (setting, monitoring, experience of staff) and forward planning cannot be overemphasized. When used for other than the standard indications, NIV should be employed in a high-dependency or intensive care setting in patients for whom invasive ventilation would be considered."
5521,Acute exacerbations of chronic obstructive pulmonary disease: treatment and prevention,"An acute exacerbation of chronic obstructive pulmonary disease (COPD) is sustained worsening of dyspnoea and sputum production in patients with COPD. They may be managed in the community with oral steroids and antibiotics but hospital referral is required where there is doubt about the diagnosis or if there are features of severity such as confusion, respiratory distress or haemodynamic instability. Regular review is required as failure to improve should prompt consideration of another diagnosis. In the emergency department, nebulized β(2)–agonists and anticholinergic bronchodilators should be given and arterial blood gases assessed. Patients with an arterial pH of 7.35 or less should be assessed for non-invasive ventilation. Patients who are stable and are not in type 2 respiratory failure should be considered for discharge if there is adequate home support. Warded patients should be discharged if they are stable for 24 hours and if both patient and doctor are confident that they can manage at home with outpatient follow-up at 4 to 6 weeks. About 25% of COPD patients may not have recovered to baseline lung function at this time."
5522,Invasive and non-invasive mechanical ventilation,"Early recognition of patients who might potentially require ventilatory support is a key goal of critical care outreach programs and an important skill for all hospital medical staff. Decisions about the initiation and timing of invasive ventilation can be difficult and early discussion with critical care colleagues is essential. Appropriateness of invasive ventilatory support may also be an issue requiring advanced discussion with patients and their families. In the past 10–15 years, the role of non-invasive ventilation (NIV) has expanded, not least in an attempt to minimize the complications inherent with invasive ventilation. As such, NIV is now considered first-line therapy in some conditions (chronic obstructive pulmonary disease, pulmonary oedema, mild-to-moderate hypoxaemic respiratory failure in immunocompromised patients), and a ‘trial of NIV’ is often considered in respiratory failure resulting from an increasingly wide range of causes. When using NIV, the importance of the environment (setting, monitoring and experience of staff) and forward planning cannot be overemphasized. When used for other than the standard indications, NIV should be employed in a high-dependency/intensive care setting only in patients for whom invasive ventilation would be considered."
5523,"Methods in Molecular Medicine: Microarrays in Clinical Diagnostics. Thomas O. Joos and Paolo Fortina, editors. Totowa, NJ: Humana Press, 2005, 288 pp., $121.50, hardcover. ISBN 1-58829-394-7.",
5524,The next pandemic: on the front lines against humankind's gravest dangers,
5525,Program and Abstracts for the 2007 Meeting of the Society for Glycobiology,
5526,China vs the WHO: a behavioural norm conflict in the SARS crisis,"This article studies a conflict over two competing norms in which the actors demonstrated incompatible positions not through arguments, but through actions. During the SARS crisis, China and the World Health Organization (WHO) entered a norm conflict over the precedence of sovereignty or global health security. Both resorted to behavioural, not discursive contestation: while the WHO practically but not rhetorically challenged the sovereignty norm by acting according to the norm of global health security, China—without openly acknowledging it—contravened the basic principles of global health security by acting according to the overlapping sovereignty norm. Why and with what consequences do actors choose to contest norms through actions rather than words? The article accounts for the resort to behavioural contestation by pointing to the strategic advantages it offers for furthering a contentious norm understanding without facing the social costs of making it explicit. It furthermore highlights that behavioural contestation may feed back into and change the odds of discursive contestation as its practical effects provide rhetorical resources to (de-)legitimate one or the other position. The propositions are illustrated in the interactions of China and the WHO during the SARS crisis and the subsequent norm development. This article forms part of the special section of the May 2019 issue of International Affairs on ‘The dynamics of dissent’, guest-edited by Anette Stimmer and Lea Wisken."
5527,"The New Global Threat. Severe Acute Respiratory Syndrome and Its Impacts. Tommy Koh, Aileen Plant, Eng Hin Lee. Singapore: World Scientific Publishing Company, 2004, pp. 356, $17.00 (PB) ISBN: 9812386688",
5528,IN THIS ISSUE,
5529,Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Outbreak and National and Hospital Response in Korea,
5530,171 Molecular breeding value prediction of pregnancy rate in Holstein dairy cows managed in a heat-stressed environment using candidate gene SNP,"Reproductive performance in Holstein dairy cattle managed during summer in southern Sonora is a challenge because of high ambient temperature and relative humidity. Both of these factors contribute to heat stress, which influences cow behavior. The physiological response of cows to heat stress is one component of a system-wide gene network. Within this environment, a superior cow's ability to get pregnant early during postpartum is favorable as to reduce the trait days open and to increase productive life. Recently, many reproductive specialists have recommended using pregnancy rate as a measure of reproductive success, after converting this trait into a quantitative value using a linear formula. In comparison to the traditional measure of days open, pregnancy rate calculation includes more easily cows that do not become pregnant; furthermore, the output variable indicates that larger values are more desirable, and therefore, more understandable by dairy producers. The objective herein was to predict pregnancy rate in lactating Holstein cows using molecular markers associated with fertility in Holstein cows under a heat-stressed environment. This study included 500 cows from three dairy herds located in the Yaqui Valley of Sonora. A blood sample was collected from every cow and spotted onto FTA cards. The DNA was extracted from each card and used to genotype 179 tag SNP within 43 genes in the prolactin and GH-IGF1 pathways. Five SNP within the genes IGFBP7, IGFBP2, PAPPA1, SSTR2, and STAT6 were associated with pregnancy rate using a mixed effects model. The genotype term was later included in this model to calculate allele substitution effects. Molecular breeding values of the individual cows were calculated by summing the additive genotype effect for each SNP that showed a significant independent association with pregnancy rate, and the average MBV was 0.46 ± 0.01%. Two statistical regression models were used to predict the variable pregnancy rate: a full model that included effects of days and number of lactations, contemporary group (e.g., farm management group), health status, and MBV and a reduced model that only included MBV. Coefficients of determination were 37.61% and 3.07% for full and reduced models, respectively (P < 0.01). These results indicate that five SNP explained only a small proportion of the additive genetic variance for pregnancy rate. Additional research is needed to understand if these results are due to low heritability/repeatability of a fertility and (or) if these results are also influenced by heat stress."
5531,0177 Bovine macrophage phenotype influences inflammatory response to lipopolysaccharide,"Severe inflammation during gram negative bacterial disease is common in periparturient dairy cows and increases the severity of diseases such as Escherichia coli mastitis. Tissue inflammation is partly orchestrated by macrophage responses to bacterial infection. Studies in monogastric species showed classical phenotype macrophages have proinflammatory responses and alternative phenotype macrophages have protective and restorative responses during disease. However, responses of diverse bovine macrophage phenotypes to lipopolysaccharide are unclear. The objective of this research was to compare the lipopolysaccharide-induced inflammatory response in several phenotypes of bovine primary monocyte-derived macrophages. Peripheral blood mononuclear cells were isolated from whole blood using Ficoll (n = 8 cows). Monocytes were identified using mouse anti-bovine CD172α monoclonal antibody and separated from lymphocytes using magnetic assisted cell sorting. Monocytes were cultured with interferon-γ or interleukins (IL) 4 and 13 to induce a classical or alternative macrophage phenotype, respectively, then stimulated with lipopolysaccharide. Macrophage mRNA was quantified in adipose using qPCR. Fold changes in mRNA concentration were calculated by 2(-ΔΔCt), using the untreated cells as calibrator and three endogenous control mRNA. Treatment differences in mRNA expression were identified using Fisher pairwise comparisons and ANOVA (P ≤ 0.05). Flow cytometry showed magnetic assisted cell sorting increased CD172α(+) cells from 22.3 ± 1.9 to 81.6 ± 2.8%. After 48 h in vitro, CD68 expression increased and CD172α(+) was 95.2 ± 0.4%. Lipopolysaccharide increased IL6, IL10, TNF, and CCL2 expression. Lipopolysaccharide stimulated IL6 and IL10 expression was decreased in alternative macrophages, whereas lipopolysaccharide stimulated TNF expression was increased in classical macrophages. Lipopolysaccharide stimulated CCL2 expression was not different between macrophage types. Together these results show an exacerbated proinflammatory cytokine profile in a model of classical bovine macrophages during gram negative bacterial disease. Results suggest that macrophage phenotype could be involved with severe inflammatory responses seen during dairy cow periparturient periods characterized by prolonged and exacerbated lipolysis and increased disease susceptibility. Ongoing research will describe macrophage phenotype during bovine disease and identify factors contributing to phenotype change. Such factors could ultimately be manipulated to control the bovine macrophage inflammatory response."
5532,Lessons from lesions: the effects of olfactory bulbectomy,"Olfactory bulb removal has been used to examine a wide-ranging number of topics. The present review outlines the categories of studies employing the technique, discusses some problems with the methodology and with previous interpretations of observed results, and suggests some potential avenues of investigation."
5533,SARS Bulletin from Hong Kong: What Might We Have Done Better?,
5534,Reply to van der Hoek and Berkhout,
5535,Workshop on Coronaviruses,
5536,Reply to Tso et al,
5537,SARS Bulletin from Hong Kong,
5538,SARS Bulletin from Hong Kong: 30 March—4 April 2003,
5539,Infectious Diseases Subdue Serengeti Lions,
5540,Verification of a Novel Multiplex PCR Respiratory Virus Panel in a US Biocontainment Unit,"Emerging infectious diseases carry unique logistical, financial, and clinical ramifications. Rapid diagnostic testing methods can alleviate some of these challenges by providing definitive diagnoses earlier in the clinical course, leading to appropriate targeted therapy, cost savings, and improved patient outcomes. The BioFire FilmArray Respiratory Panel 2 plus (RP2plus; bioMérieux, Marcy l’Etoile, France) is a multiplexed nucleic acid test for detection of Middle East respiratory syndrome coronavirus (MERS-CoV) and 14 common viral and 4 bacterial respiratory pathogens in nasopharyngeal swabs obtained from those meeting MERS-CoV epidemiological criteria. The aim of this study was to verify the FilmArray RP2plus for use in our biocontainment unit. Of note, the RP2plus is FDA approved but not currently available for sale in the United States. Eight patient samples were tested with known results (GenMark Respiratory Virus Panel [RVP] or Cepheid Xpert Flu/RSV). We had concordant results between the platforms for samples containing influenza A, respiratory syncytial virus (RSV), parainfluenza virus 2, rhinovirus, and a negative sample. We evaluated two influenza B samples from two different patients. The FilmArray RP2plus did not detect influenza B in one of the patient samples. The sample was exhausted and repeat testing could not be performed. A second rhinovirus sample was not detected by the RP2plus, but Coronavirus 229E was detected in this sample, a virus not detected by the RVP. The sample was repeated and again did not detect rhinovirus. Further investigation into this discrepancy revealed that rhinovirus was originally detected by RVP at a signal of 34.4 nA (repeat of 46.9 nA). The concordant rhinovirus sample had a signal of 226.7 nA by RVP, which was much higher than the discrepant sample. Because of the low signal by RVP in the discrepant sample, perhaps the viral load was below the limit of detection of the RP2plus. All other quality control sample pools passed verification testing, including day-to-day and operator variance. It is not uncommon for a person under investigation (PUI) for a highly communicable disease to be evaluated in our facility. The performance of the RP2plus test on clinical samples showed acceptable concordance with our current means of testing for respiratory pathogens. The RP2plus will eliminate challenges implicated in storing and transporting specimens to an off-site lab, facilitate quicker turnaround time, and streamline the often cumbersome, complex protocols and practices required to work up a serious communicable disease."
5541,"Conservation Medicine on the Galápagos Islands: Partnerships Among Behavioral, Population, and Veterinary Scientists",
5542,Animal Reservoirs: Harboring the Next Pandemic,Recent studies of emerging infectious diseases show most are zoonoses transmitted to humans from domesticated animals and wildlife.
5543,"Abstracts from the 45(th) Annual Meeting of Japanese Association for the Stusy of Taste and Smell (JASTS 2011), Kanazawa, Japan, October 5-7(th), 2011 (The president of the meeting was Dr. Takaki Miwa, Kanazawa Medical University)",
5544,NOTICES OF RECENT PUBLICATIONS,
5545,0175 The effect of various parameters measured at farrowing on subsequent pig performance,"The objective of this study was to evaluate birth weight, gender, stall conditions at birth, umbilical diameter, ratio of umbilical diameter to birth weight (as a potential indicator of placental efficiency), and umbilical antiseptic treatment as predictors of pre-weaning mortality, incidence of umbilical hernias, and 150 d weight of pigs in a commercial facility. A total of 466 mixed gender commercial piglets from a breed-to-wean sow farm were enrolled. Piglets were alternately assigned by birth order within a litter to four umbilical treatment groups; iodine (2%), Zurex umbilical dip, a dry dip created using an antibacterial peptide (nisin) mixed with talc (formulation concentration = 3.105 g nisin/100 g talc on a wt/wt basis), and no treatment. At birth, stall conditions (wet/dry and clean/dirty) were evaluated on a 3 point scale (3 = most dirty or most wet and 1 = dry or clean). Before treatment, diameter of the umbilical cords were determined using digital calipers. All data were analyzed using mixed model methods. Models included the fixed effects of birth weight, umbilical diameter at birth, gender, stall conditions and treatment. Pre-weaning mortality was significantly affected by umbilical treatment (p < 0.05) and by ratio of umbilical diameter to birth weight (p < 0.001). Piglets treated with 2% iodine had a higher mortality rate than piglets treated with other antiseptics or those that were untreated. Piglets with the lowest umbilical cord diameter to birth weight ratio had the highest survival rate. Stall conditions at birth (p < 0.005) and the ratio of umbilical diameter to birth weight (p < 0.05) affected the incidence of umbilical hernias. Piglets born in wet stall conditions or those with a high umbilical cord to birth weight ratio had a higher incidence of umbilical hernias in the growing phase. Final 150 d weight of pigs was affected by the ratio of umbilical diameter to birth weight (p < 0.0001) and gender (p < 0.0001), and tended to be affected by stall conditions at birth (p = 0.06). Male pigs weighed 93.5 kg, while female pigs weighed 86.5 kg. Piglets with the highest ratio of umbilical cord diameter to birth weight and those born in wet stall conditions weighed less. In conclusion, measuring the umbilical cord to birth weight ratio was a much better predictor of pre-weaning mortality, incidence of umbilical hernias, and 150 d weight than birth weight alone."
5546,0106 Evaluating preweaned calf housing and its impact on calf respiratory parameters on New York dairy farms,"The objectives of this project were to (1) evaluate environmental and air quality parameters across different types of calf housing facilities; (2) evaluate rates of respiratory illness in preweaned calves; and (3) determine the impact of environmental factors, air quality, and housing type on calf health. This was an observational study in which calf facilities were evaluated on a single visit during June 2015. Housing included hutches (n = 9), individual pens in a barn (n = 11), and group pens in a barn (n = 9). Facility and calf pen evaluations included wind speed, temperature, relative humidity, heat stress index, bedding type, bedding composite sample for bacteria counts, nesting score of calf pens, calf health scoring, and airborne bacteria. Data were analyzed using SAS 9.3 to determine the impact of housing type, environmental, and air quality variables on calf respiratory score. A total of 29 facilities and 437 preweaned calves were evaluated. Calf facility temperature averaged 24.2°C (range 15.5 to 30.6°C) with a relative humidity of 21.5% (range 10 to 78%) and a heat index of 21.5°C (range 6 to 30.9°C). Temperature and airborne bacterial counts were greater in hutches as compared with individual and group pens (P < 0.01). Humidity was similar for hutches and group pens, but greater than individual pens. Gram negative airborne bacterial counts were lowest in individual pens. No difference in heat index was observed across housing type. Mean calf respiratory scores was 2.5 (range of 0 to 9) on a 12 point scale; 13.33% of calves evaluated scored greater than 5, indicating a respiratory challenge. Prevalence of respiratory illness in preweaned calves ranged from 0 to 50% of calves on a per farm basis (mean = 11.05% of calves/farm), with 44.82% of farms having no respiratory illness and 10.32% of farms having 30 to 50% of evaluated calves exhibiting signs of respiratory illness. There was a negative correlation between respiratory score and pen temperature (R(2) = 0.90). There was no influence on respiratory score by housing system, bedding type, ventilation system, relative humidity, airflow, or airborne bacterial counts. Data collected from this study suggests that respiratory illness continues to be a challenge, even when weather is temperate. Additional research is needed to evaluate rates of respiratory illness during cold stress and transitional weather, as well as to evaluate management factors that increase the risk of infection."
5547,Deadly Outbreaks,
5548,Hepatitis Workshops of the National Institute of Allergy and Infectious Diseases,
5549,"0105 Serum and colostrum antibody titers in Holstein cows, and the relationship between these titers and serum antibody titers in their calves","Vaccination of cows in late gestation is sometimes used to improve maternal antibody titers in their calves. However, scant published research has reported the relationship between serum antibody titers to specific infectious agents in vaccinated cows, the colostrum of these cows, and the serum of calves consuming their colostrum. As part of a larger study, the relationship between cow serum and colostrum antibody titers and calf titers was evaluated. Fifty-four multiparous Jersey and Jersey-cross cows were vaccinated between dry-off and calving with commercially available vaccines containing bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), rotavirus, coronavirus, E. coli J-5, and Salmonella siderophore receptor and porin (SRP); blood was collected at dry off, mid-dry, and at calving. Calves born to enrolled cows were fed colostrum from only their dams; calf serum was collected at 7 and 30 d of life. Antibody titers against agents in the vaccine were measured in serum and colostrum of cows by standard neutralizing techniques or ELISA, and correlations between cow serum antibodies at 30 d before calving, cow colostrum, and calf serum antibodies at 7 d of life were evaluated. Correlations between cow serum antibodies and colostrum antibodies for different agents were significant (P < 0.05) but only moderately strong (Pearson correlation coefficient [PCC] range: 0.32–0.7), and varied for different agents. Similarly, correlations between cow colostrum antibodies and calf serum antibodies were usually significant, but only moderate (PCC range: 0.36–0.77). The R(2) value for the correlation between colostrum antibodies and calf antibodies ranged from 0.11–0.59, indicating that for most agents, the colostrum antibody titer to a given agent did not explain a majority of variation in the calf serum antibody titer to that agent. Antibody titers to specific agents in cows are significantly, but not strongly, correlated with their colostrum antibody titers, and colostrum antibody titers are significantly but not strongly, related to antibody titers in calves. These data suggest that, in addition to maternal antibody concentration, other factors have an important impact on serum antibody titers to specific infectious agents in young dairy calves."
5550,"0176 Environmental persistence of porcine epidemic diarrhea virus, porcine delta corona virus, and transmissible gastroenteritis in feed ingredients","Porcine epidemic diarrhea virus (PEDV), porcine delta corona virus (PDCoV), and transmissible gastroenteritis (TGEV) are major threats to swine production. Investigations of recent outbreaks confirmed that contaminated feed plays a role in virus transmission. This risk makes it necessary to evaluate the survival of such viruses in various feed ingredients. The objective of our experiment was to characterize the inactivation of PEDV, PDCoV, and TGEV in various feed and ingredient matrices. To determine differences in virus survival, 5-g samples of complete feed, spray-dried porcine plasma, meat meal, meat and bone meal, blood meal, corn, soybean meal, and low, medium, and high oil dried distillers grains with solubles were weighed into separate scintillation vials. These samples were inoculated with 1 mL of PEDV, PDCoV, or TGEV and incubated at room temperature for up to 56 d. At each time point, surviving virus was eluted and the supernatant was inoculated into vero-81 cells for PEDV, or swine testicular cells for PDCoV and TGEV. Cells were observed daily for 10 d for cytopathic effects, and this information was used to calculate a median tissue culture infectious dose (TCID(50)) using the Karber method. Inactivation kinetics were determined using the Weibull model. A delta value was estimated from the model, indicating the time necessary to reduce virus concentration by 1 log. This delta value was then compared across ingredients using the mixed procedure of SAS, and correlations between ingredient proximate analysis data and delta values were determined. Results showed that soybean meal had the greatest delta value (7.50 d) for PEDV compared with other ingredients (P < 0.06). Likewise, PDCoV (42.04 d) and TGEV (42.00 d) delta values were highest in soybean meal (P < 0.001). There was a moderate positive correlation between moisture and the delta value for PDCoV (r = 0.49, P = 0.01) and TGEV (r = 0.41, P = 0.02). There was also a moderate negative correlation between lipid content and the delta value for TGEV (r = −0.51, P = 0.01), suggesting that TGEV is less stable in ingredients with greater lipid content compared with ingredients with less lipid content. In conclusion, these results indicate that the first log reduction of PDCoV and TGEV takes the greatest amount of time in soybean meal and it appears to be the result of greater moisture content."
5551,Young Investigator Awards Program Abstracts,
5552,1 December News,
5553,News,
5554,"Reply to van der Hoek and Berkhout, Ebihara et al., and Belay et al",
5555,15 July News,
5556,15 June News,
5557,Coronavirus Infection in Acute Lower Respiratory Tract Disease of Infants,"A serologic surveillance of lower respiratory tract disease in 417 hospitalized children under 18 months of age revealed infection with coronviruses (strains OC43 and/ or 229E) in 34 (8.2%). During the same interval, one of 13 control infants was infected. There were two distinct periods lasting six and 14 weeks, respectively, during which the incidence rose to as high as 18.9 % of patients with lower respiratory tract disease. The incidence of coronavirus infection in patients with pneumonia and bronchiolitis was higher than the incidences of adenoviruses, influenza, parainfluenza viruses types 1 and 2, and rhinoviruses, and lower only than the incidences of parainfluenza virus type 3 and respiratory syncytial virus. Coronoviruses serologically similar or identical to strain 229E were recovered from frozen nasal washes obtained during the acute phase of pneumonia in two children."
5558,170 Genetic parameters of incidence and timing of respiratory disease in cattle,"Respiratory disease is a complex phenotype and the diagnostic can be attributed to multiple causes including viral infection (e.g., respiratory coronavirus, bovine respiratory syncytial virus), bacterial infection (e.g., pneumonic spp.; lungworm), and vena caval thrombosis. Moreover, the impact of respiratory disease in cows varies with the stage of lactation when the disease is detected. In general, intense management practices facilitate the detection of respiratory disorders in dairy cattle herds relative to beef cattle herds. Thus, we propose that study of respiratory disease incidence in a large dairy cattle data set as paradigm to advance the knowledge on the factors influencing the incidence of this disease across cattle types. Respiratory disease information on 6,283 Holstein cows across four U.S. states and nine herds were evaluated. Two descriptors of respiratory disease were evaluated: days in milk to respiratory disease detection and the binary detection of respiratory disease. Survival analysis was used to study the days in milk-to-disease. The binary variable respiratory disease detection was analyzed using a binary logistic model. Lactation number, season, region, farm, body condition score, and milk yield level (3 levels) were included in the model as fixed explanatory effects whereas sire was considered a random effect. Incidence of respiratory disease was lower in summer relative to winter, and there was a nonsignificant trend on lactation number. Body condition score had a significant effect, with higher body condition score associated with lower incidence of respiratory disease. Farm, body condition score, and milk yield level had significant effect on the time when respiratory disease was identified. The heritability estimate for incidence of respiratory disease was 0.4, suggesting that despite the high number of potential causative agents, selection for less susceptible cattle can be an effective strategy to reduce the impact of this disease. The heritability estimate of the days in milk-to-disease was 0.13, showing that non-genetic components may play an important role on the stage of the lactation when the disease is detected. These findings contribute to an animal health project (USDA-NIFA-ILLU-538909) and a multistate project database (USDA-NIFA-AFRI-003542) for direct measures of health and fertility in cattle."
5559,SARS Bulletin from Hong Kong: 30 March—4 April 2003,
5560,The Cost of Growing Older: Challenges for European Pension Systems,
5561,coronanieuws,
5562,Parallel Session 28 – Infectious Diseases,
5563,"Fifth symposium on coronaviruses: Chantilly, France, 14–18 September 1992",
5564,An improved method for the routine identification of faecal viruses using ammonium sulphate precipitation,
5565,HCoV-NL63 and HCoV-HKU1 Rates of Infection in Chicago: Winter 2011,
5566,"Molecular organization of positive-strand RNA viruses: 24-26 June, 1985 Cambridge, England",
5567,Morphological and intracellular alterations induced by cytotoxin VT2y produced by Escherichia coli isolated from chickens with swollen head syndrome,"Recently, a novel verocytotoxin named VT2y was described which belongs to the STx family and is produced by Escherichia coli isolated from domestic poultry with swollen head syndrome (SHS). The VT2y toxin induced apoptosis in Vero, HeLa, CHO, CEF (primary chicken embryo fibroblast) and PCK (primary chicken kidney) cell lines. Morphological evidence (nuclear shrinkage, chromatin condensation and blebbing of the plasma membrane) of apoptosis could be distinguished in 15 min and was maximal at 1 h after treatment with VT2y. This was confirmed by the terminal dUTP nick-end-labeling (TUNEL) method."
5568,Foodborne viruses,"Foodborne and waterborne viral infections are increasingly recognized as causes of illness in humans. This increase is partly explained by changes in food processing and consumption patterns that lead to the worldwide availability of high-risk food. As a result, vast outbreaks may occur due to contamination of food by a single foodhandler or at a single source. Although there are numerous fecal–orally transmitted viruses, most reports of foodborne transmission describe infections with Norwalk-like caliciviruses (NLV) and hepatitis A virus (HAV), suggesting that these viruses are associated with the greatest risk of foodborne transmission. NLV and HAV can be transmitted from person to person, or indirectly via food, water, or fomites contaminated with virus-containing feces or vomit. People can be infected without showing symptoms. The high frequency of secondary cases of NLV illness and – to a lesser extent – of hepatitis A following a foodborne outbreak results in amplification of the problem. The burden of illness is highest in the elderly, and therefore is likely to increase due to the aging population. For HAV, the burden of illness may increase following hygienic control measures, due to a decreasing population of naturally immune individuals and a concurrent increase in the population at risk. Recent advances in the research of NLV and HAV have led to the development of molecular methods which can be used for molecular tracing of virus strains. These methods can be and have been used for the detection of common source outbreaks. While traditionally certain foods have been implicated in virus outbreaks, it is clear that almost any food item can be involved, provided it has been handled by an infected person. There are no established methods for detection of viruses in foods other than shellfish. Little information is available on disinfection and preventive measures specifically for these viruses. Studies addressing this issue are hampered by the lack of culture systems. As currently available routine monitoring systems exclusively focus on bacterial pathogens, efforts should be made to combine epidemiological and virological information for a combined laboratory-based rapid detection system for foodborne viruses. With better surveillance, including typing information, outbreaks of foodborne infections could be reported faster to prevent further spread."
5569,Preliminary studies on the isolation of coronavirus 229E nucleocapsids,
5570,FEMS SYMPOSIA,
5571,Structural studies on the Ebola virus matrix protein VP40 indicate that matrix proteins of enveloped RNA viruses are analogues but not homologues,"Matrix proteins are the driving force of assembly of enveloped viruses. Their main function is to interact with and polymerize at cellular membranes and link other viral components to the matrix–membrane complex resulting in individual particle shapes and ensuring the integrity of the viral particle. Although matrix proteins of different virus families show functional analogy, they share no sequence or structural homology. Their diversity is also evident in that they use a variety of late domain motifs to commit the cellular vacuolar protein sorting machinery to virus budding. Here, we discuss the structural and functional aspects of the filovirus matrix protein VP40 and compare them to other known matrix protein structures from vesicular stomatitis virus, influenza virus and retroviral matrix proteins."
5572,Status report on porcine epidemic diarrhea virus in the United States,"On 16 May 2013, the USDA Animal and Plant Health Inspection Service, National Veterinary Services Laboratories reported the detection of porcine epidemic diarrhea virus in the United States for the first time. This virus causes severe diarrhea and vomiting in young pigs. Porcine epidemic diarrhea virus does not infect humans and is not a food safety risk. This virus is already found in many countries around the world, and there is no US official regulation of the virus and no export restrictions to other countries."
5573,"Fifth symposium on coronaviruses: Chantilly, France, 14–18 September 1992",
5574,Mini-transposons in microbial ecology and environmental biotechnology,"Mini-transposon is the generic name given to the members of a collection of genetic assets derived from transposons Tn10 and Tn5, in which the naturally occurring functional segments of DNA have been rearranged artificially to originate shorter mobile elements. In the most widespread design (that known as the pUT system), any heterologous DNA segment can be conveniently cloned within the boundaries of a mini-Tn5 vector and finally inserted into the chromosome of target Gram-negative bacteria after a few simple genetic manipulations. The large variety of antibiotic, non-antibiotic and excisable selection markers available has been combined at ease with DNA fragments encoding one or more phenotypes of interest for ecological or biotechnological applications. These include the tagging of specific strains in a community with selectable and/or optical marker genes, the production of stable gene fusions for monitoring transcriptional regulation in single cells, the metabolic engineering of strains destined for bioremediation, the non-disruptive monitoring of gene transfer and the assembly of gene containment and strain containment circuits for genetically manipulated microorganisms."
5575,"Characterisation of the bovine enteric calici-like virus, Newbury agent 1","The bovine enteric calici-like virus, Newbury agent 1 (NA1) was characterised to determine if it is a member of the Caliciviridae and to establish its antigenic relationship to the established bovine enteric calicivirus Newbury agent 2 (NA2). Solid phase immune electron microscopy (SPIEM) allowed quantification of NA1 virions and identification of faecal samples with optimal virus levels. NA1 particles were 36.6 nm in diameter, had an indefinite surface structure resembling that of human small round structured viruses (SRSVs), and a buoyant density of 1.34 g ml(−1). A single capsid protein of 49.4 kDa was detected by Western blotting in purified NA1 preparations prepared from post-infection but not pre-infection faecal samples and with post- but not pre-infection sera. NA1 was antigenically unrelated to the bovine enteric calicivirus NA2 by SPIEM. These properties were consistent with classification of NA1 within the Caliciviridae but demonstrated heterogeneity in the capsid composition of bovine enteric caliciviruses."
5576,"Molecular biology of microbial pathogenicity: Adhesion, invasion and receptors: 17-20 June 1985 Umeå, Sweden",
5577,Syncytium production by human coronavirus 229E group viruses,
5578,"Pertussis: 22-24 April 1985 Potsdam, GDR, Postponed",
5579,Immune response of mice immunized with mouse hepatitis virus strain 3,
5580,Translation of infectious bronchitis virus RNA,
5581,Invasive Species: The Search for Solutions,
5582,Global Zoonotic Disease Surveillance: An Emerging Public Health and Biosecurity Imperative,
5583,Stressful Times,
5584,News Briefs,
5585,"Earn valuable contact hours by attending education sessions and viewing posters at AORN Congress: Saturday, March 20, to Thursday, March 25, 2004",
5586,News Briefs,
5587,Infectious disease: Inextricable linkages between human and ecosystem health,
5588,Membrane Proteins - II,
5589,The SARS-CoV Fusion Peptide Forms an Extended Bipartite Fusion Platform that Perturbs Membrane Order in a Calcium-Dependent Manner,
5590,Opportunities From the Center for Perioperative Education,
5591,"Thirty-eighth Annual Meeting March 6-10, 1994 New Orleans Convention Center New Orleans, Louisiana. Wednesday Symposia and Posters, Part I",
5592,Systematic Biophysical Insights into the Interaction of Anti MERS-CoV Drug Ribavirin with Major Transport Protein in Human Serum: In-Vitro Studies and Implications in Diabetes and Uremia,
5593,Virus Structure & Assembly,
5594,"Structures, Dynamics, and Functions of Viral Membrane Proteins by NMR",
5595,News Briefs,
5596,SRAS – Syndrome Respiratoire Aigu Sévère,
5597,Highlights from the Current Issue – Audiovisual Summary,
5598,Foot & mouth disease,
5599,Subject index volumes 251–350,
5600,Fluorescence cross-correlation spectroscopy using single wavelength laser,"In this paper, we first introduced the basic principle of fluorescence cross-correlation spectroscopy (FCCS) and then established an FCCS setup using a single wavelength laser. We systematically optimized the setup, and the detection volume reached about 0.7 fL. The homebuilt setup was successfully applied for the study of the binding reaction of human immunoglobulin G with goat antihuman immunoglobulin G. Using quantum dots (745 nm emission wavelength) and Rhodamine B (580 nm emission wavelength) as labeling probes and 532 nm laser beam as an excitation source, the cross-talk effect was almost completely suppressed. The molecule numbers in a highly focused volume, the concentration, and the diffusion time and hydrodynamic radii of the reaction products can be determined by FCCS system."
5601,P1.3 Pathologies et risques infectieux,
5602,Effect of down-regulating VEGF on proliferation of colon carcinoma cell HT-29,"We designed specific small interfering RNA (siRNA) targeting vascular endothelial growth factor (VEGF) mRNA and synthesized oligo fragments, then siRNA was obtained by in vitro transcription and transfected into cultured human colon carcinoma cell line HT-29 with lipofectamine. We also analyzed the effect of the siRNA on proliferation of HT-29 cells by methyl thiazolyl tetrazolium (MTT) assay and expression level of VEGF mRNA of transfected cells by RT-PCR as well as amounts of secreted VEGF protein in the supernatant by enzyme linked immunosorbent assay (ELISA). Two groups of siRNA targeting human VEGF effectively inhibited proliferation of HT-29 cells after transfection. The secretion of VEGF protein also notably decreased, but the control scramble siRNA showed no effect."
5603,Virus,Rond het begin van de twintigste eeuw heerste er een algemeen optimisme de mens van alle ernstige infectieziekten voor altijd te zullen kunnen bevrijden. Er bleek helaas een klasse pathogenen te zijn – die nog niemand ooit gezien had – die deze hoop ondermijnde.
5604,Infecties en immunisatie: Een gewaarschuwd mens …,"De nieuwe WIP-richtlijn heeft al veel stof doen opwaaien. Binnen alle discussies over de nieuwe richtlijn wordt echter nauwelijks gesproken over hoofdstuk 5: ‘Infecties en immunisatie’. Dit is enorm uitgebreid ten opzichte van de vorige versie en bevat wel degelijke relevante aanbevelingen. Wanneer is een medewerker bijvoorbeeld daadwerkelijk beschermd tegen hepatitis B? En hoe dient een praktijk de behandeling van een MRSA-patiënt uit te voeren? Of mag je deze eigenlijk helemaal niet behandelen? Vragen die – zoals blijkt uit onze ervaring – binnen praktijken nauwelijks aan bod komen, maar wel degelijk bijdragen aan infectiepreventie."
5605,Epidemic Spread on One-Way Circular-Coupled Networks,"Real epidemic spreading networks are often composed of several kinds of complex networks interconnected with each other, such as Lyme disease, and the interrelated networks may have different topologies and epidemic dynamics. Moreover, most human infectious diseases are derived from animals, and zoonotic infections always spread on directed interconnected networks. So, in this article, we consider the epidemic dynamics of zoonotic infections on a unidirectional circular-coupled network. Here, we construct two unidirectional three-layer circular interactive networks, one model has direct contact between interactive networks, the other model describes diseases transmitted through vectors between interactive networks, which are established by introducing the heterogeneous mean-field approach method. Then we obtain the basic reproduction numbers and stability of equilibria of the two models. Through mathematical analysis and numerical simulations, it is found that basic reproduction numbers of the models depend on the infection rates, infection periods, average degrees, and degree ratios. Numerical simulations illustrate and expand these theoretical results very well."
5606,Heterocycle-Fused Acridines,
5607,NMR spectroscopy of basic/aromatic amino acid clusters in membrane proteins,
5608,Contents Page,
5609,Contents Page,
5610,New CLEM Method to Reveal Ultrastructural Reorganization in the Host Cell during Coronavirus Infection,
5611,Erratum,"In the 1 May 2006 issue of the Journal in the article by Poccia et al. (Poccia F, Agrati C, Castilletti C, et al. Anti–severe acute respiratory syndrome coronavirus immune responses: the role played by Vγ9Vδ2 T cells. J Infect Dis 2006; 193:1244–9), there was a deficiency in the “Financial support” footnote, at the bottom of the left-hand column of the title page (page 1244); the sources of support listed in this footnote should have included the European Commission EPISARS (contract NSP22-CT-2004-511063). The authors regret this error"
5612,Seligman (2007; 195:609),"In the 15 February 2007 issue of the Journal, in the letter by Seligman (Seligman SJ. Evidence for quasi species in severe acute respiratory syndrome—associated coronavirus deletion mutants. J Infect Dis 2007; 195:609), it should be noted that, in accordance with Journal style, “quasi species” has been spelled as 2 words, whereas many other publications use the single-word form, “quasispecies”; readers doing a search for the term are advised to take this variant treatment into account."
5613,Security Issues,"Cyber Terrorism, attacks on the integrity of travel documents, the use of full body scanners and issues flowing therefrom, civil unrest as they threaten the security of airports and unlawful interference with civil aviation are issues that draw the attention of the aviation community in general and the air transport industry in particular."
5614,"Clinical Virology in NICU, PICU and AICU","Viruses are significant causes of nosocomial infections, particularly in intensive care unit (ICU) where seriously ill and vulnerable patients are being cared for. Four major routes of nosocomial virus transmission in the ICU are identified, viz. respiratory, faecal–oral, exposure to blood and body fluid and direct contact with infected patients or through fomites. Different infection control measures are available according to the natural history, biology, pathogenesis, epidemiology and mode of transmission of each virus. In this chapter, we discuss some of the important viruses that could be associated with nosocomial infections in the ICU. Intensivists should work closely with microbiologists, virologists and the laboratory to diagnose such infection early, work proactively to prevent outbreaks and manage viral infections using appropriate strategies."
5615,Climate Change,"The battle lines that have been drawn between climate change believers and deniers could not be more distinct. However, outside of the halls of power and beyond diplomatic chatter there is a subtle, if imperceptible shift heralding a potentially more impactful climate awakening. Those favoring grandiose solutions to the very real challenges posed by climate change will find no victory with the advent of true market-based solutions to climate risk. These shifts in the market are brought forth without presidential decree and signing ceremonies. Rather, they are brought about the same way each economic revolution occurs—with the inexorable drive among entrepreneurs, engineers, planners and risk managers tackling the immediacy of problems, with practical solutions for which the market is willing to pay."
5616,Distribution of Graph-Distances in Boltzmann Ensembles of RNA Secondary Structures,"Large RNA molecules often carry multiple functional domains whose spatial arrangement is an important determinant of their function. Pre-mRNA splicing, furthermore, relies on the spatial proximity of the splice junctions that can be separated by very long introns. Similar effects appear in the processing of RNA virus genomes. Albeit a crude measure, the distribution of spatial distances in thermodynamic equilibrium therefore provides useful information on the overall shape of the molecule can provide insights into the interplay of its functional domains. Spatial distance can be approximated by the graph-distance in RNA secondary structure. We show here that the equilibrium distribution of graph-distances between arbitrary nucleotides can be computed in polynomial time by means of dynamic programming. A naive implementation would yield recursions with a very high time complexity of O(n (11)). Although we were able to reduce this to O(n (6)) for many practical applications a further reduction seems difficult. We conclude, therefore, that sampling approaches, which are much easier to implement, are also theoretically favorable for most real-life applications, in particular since these primarily concern long-range interactions in very large RNA molecules."
5617,Cleavage Site Analysis Using Rule Extraction from Neural Networks,"In this paper, we demonstrate that the machine learning approach of rule extraction from a trained neural network can be successfully applied to SARS-coronavirus cleavage site analysis. The extracted rules predict cleavage sites better than consensus patterns. Empirical experiments are also shown."
5618,Electrophoresis in Microfluidic Systems,"Many chemical and biochemical analysis methods involve performing a sequence of processes that can be broadly classified in terms of sample preparation, reactions, and product analysis. Since the reaction products often contain mixtures of multiple chemical species, subsequent analytical steps must be capable of separating and identifying the individual components. Electrophoresis, which relies on inducing detectable differences in migration behavior between charged species under the influence of an applied electric field, has proven to be a highly versatile analytical technique owing to a favorable combination of characteristics including relatively simple hardware design and compatibility with a wide range of analytes including biological macromolecules (e.g., DNA, proteins). More recently, there has been considerable interest in adapting electrophoresis technology to miniaturized microfluidic formats with the aim of producing portable low-cost versions of conventional benchtop-scale instrumentation. Ultimately, it is envisioned that these efforts will enable electrophoresis to become an integral component of self-contained “lab-on-a-chip” devices capable of putting the power to perform a variety of sophisticated chemical, biological, and biomedical assays directly in the hands of those who need the information most."
5619,Antibacterial Activity of Chitosan-Based Systems,"Chitosan and its derivatives can be called environmental purification functional materials as they can effectively control the growth and reproduction of hazardous bacteria and also control toxic pollutants. From the basic science to the latest developments and innovations, starting with the history of the material, this chapter presents a facile way to understand the antibacterial activity of the chitosan, together with other materials, to the reader. This chapter also summarizes the general developments in the study of antimicrobial applications. In the light of the current situation of the research and the progress in the related fields, this chapter discusses the differences among influencing factors in detail and compares the antimicrobial activity between different physical states of chitosan. Also, this chaper discusses the more recent processes and applications."
5620,Global Strategies and Response Measures to the Influenza A (H1N1) Pandemic,"As an infectious respiratory disease, influenza is prone to cause pandemics for its fast mutation, easy dissemination, susceptibility to humans, and its elusive nature in terms of treatment. Three influenza pandemics occurred in the 20th century which caused huge losses worldwide."
5621,The Practice of Advanced Mathematics Teaching Quality Evaluation System,"To integrate the mathematical history and the idea of mathematical modeling into the teaching of mathematics timely, so that students can get deeper understanding of how to get and apply the mathematics concepts and theories to real life. In order to prove the feasibility, the advanced mathematics teaching quality evaluation system is designed. And, the effectiveness of the implementation of the advanced mathematics teaching quality evaluation system in our university is verified."
5622,Age-associated T-cell Clonal Expansions (TCE) in vivo—Implications for Pathogen Resistance,"Age-related T-cell clonal expansions (TCE) are an incompletely understood disturbance in T-cell homeostasis found frequently in old humans and experimental animals. These accumulations of CD8 T-cells have the potential to distort T-cell population balance and reduce T-cell repertoire diversity above and beyond the changes seen in the aging of T-cell pool in the absence of TCE. This chapter discusses our current knowledge of the role of these expansions in health and disease, with a special focus on their influence upon immune defense against infectious diseases."
5623,Viruses,"Viral infections are an important and often unrecognized component of disease in immunocompromised patients. The diagnosis and management of viral infections have expanded largely because of new quantitative molecular diagnostic assays. Well-recognized pathogens such as herpes simplex virus (HSV), cytomegalovirus (CMV), and respiratory viruses have been joined by newly recognized pathogens such as BK virus, human herpesvirus-6 (HHV-6), and human metapneumovirus in this highly susceptible patient population. The role of Epstein-Barr virus (EBV) and Human herpesvirus-8 (HHV-8) in lymphoproliferative diseases also continue to be clarified. As a result, the management of viral infections in patients with hematologic malignancies continues to be a growing challenge for the clinician."
5624,Emergency Preparedness,"Outbreaks of infectious diseases during peacetime or in disaster/war-related conditions, may most often need an effective crisis management in the hospital. The emergency preparedness in hospitals may vary within, and between countries, dependent on endemic and epidemic conditions, capacity, knowledge and economy. Lack of preparedness may result in a high risk of disease burden and death and cause a high economic impact on the health care."
5625,Social Disparities in the Evolution of an Epidemiological Profile: Transition Processes in Mortality Between 1971 and 2008 in an Industrialized Middle Income Country: The Case of Hungary,"The present paper seeks to understand the transformation of mortality patterns in Hungary, by which mortality inequalities by education began to appear in the early 1980s, continued to grow in the following 25 years, and now seem to be stabilising. The first part of this paper overviews the theoretical innovations of the last decades regarding the interpretation of cause-specific mortality dynamics, often referred to as epidemiological transition theories, and their relevance for the analysis of mortality inequalities. The paper then analyses the cause-specific trends of mortality for two educational classes between 1971 and 2008. The trends were corrected for changes in the coding system and divided into linear (stagnating, increasing or decreasing) periods. Causes of death were grouped according to the relationship between the sequences of these periods for the two educational classes. The 57 causes of death were finally clustered into six groups. One group, which is dominated by nutrition-related and cardiovascular diseases, is largely responsible for the onset of mortality inequalities in 1980. The results imply that the quality of nutrition has diverged for the educational classes since 1980, and this fact has left its footprint on the pattern of mortality. The history of food production and availability seems to be in line with nutrition-related mortality, and it is argued that nutrition transition theory provides a very plausible explanatory framework for the growth of mortality inequalities."
5626,Emerging Zoonotic and Vector-Borne Viral Diseases,"Many vector-borne and zoonotic diseases are considered to be emerging; since they are either newly reported to cause human disease, or are causing disease in geographical locations or species not previously documented. In the past 15 years, significant outbreaks of Severe Acute Respiratory Syndrome (or SARS) and Middle Eastern Respiratory Syndrome (or MERS), Nipah and Hendra, Ebola virus disease and Zika fever and others have been reported. In this chapter the clinical characteristics, epidemiological aspects, treatment and prevention and information related to the laboratory investigation of important zoonotic and vector-borne diseases that have emerged in the past 10 years, and how this affects children, will be discussed. Furthermore rabies, considered a neglected viral disease with the majority of victims in Africa being children, will also be addressed."
5627,International Organizations and Their Approaches to Fostering Development,"Multilateral agencies define and operationalized health and development in a variety of ways. The World Health Organization (WHO) and the World Bank are two dominant actors in health and development. Each espouses a different ideal of health as it relates to the process of development. The WHO defines health as a human right, and focuses on health outcomes as inputs to and the result of development. The World Bank’s approach to development focuses largely on macro-economic growth as input to human capabilities. The World Bank became a leading actor in international health policy in the 1990s when it operationalized health as an outcome of financial and health care systems. This chapter looks at programming efforts by the WHO and the World Bank to foster development via investment in health or through macro-economic adjustment. Results are mixed. Efforts to improve primary care were successful in improving health outcomes of children under five, but made little impact on maternal mortality. Structural adjustment programs achieved moderate success with medium- to long-term economic growth but increased health inequities. These mixed achievements resulted in an effort by the United Nations to foster a multi-sectoral approach to development espoused in the Millennium Development Goals and Sustainable Development Goals."
5628,Bioorganometallic Chemistry and Malaria,"This chapter summarizes recent developments in the design, synthesis, and structure–activity relationship studies of organometallic antimalarials. It begins with a general introduction to malaria and the biology of the parasite Plasmodium falciparum, with a focus on the heme detoxification system. Then, a number of metal complexes from the literature are reported for their antiplasmodial activity. The second half of the chapter deals with the serendipitous discovery of ferroquine, its mechanism(s) of action, and the failure to induce a resistance. Last, but not least, we suggest that the bioorganometallic approach offers the potential for the design of novel therapeutic agents."
5629,Article 14 Prevention of Spread of Disease,"Each contracting State agrees to take effective measures to prevent the spread by means of air navigation of cholera, typhus (epidemic), smallpox, yellow fever, plague, and such other communicable diseases as the contracting States shall from time to time decide to designate, and to that end contracting States will keep in close consultation with the agencies concerned with international regulations relating to sanitary measures applicable to aircraft. Such consultation shall be without prejudice to the application of any existing international convention on this subject to which the contracting States may be parties."
5630,Integration of Instance-Based Learning and Text Mining for Identification of Potential Virus/Bacterium as Bio-terrorism Weapons,"There are some viruses and bacteria that have been identified as bioterrorism weapons. However, there are a lot other viruses and bacteria that can be potential bioterrorism weapons. A system that can automatically suggest potential bioterrorism weapons will help laypeople to discover these suspicious viruses and bacteria. In this paper we apply instance-based learning & text mining approach to identify candidate viruses and bacteria as potential bio-terrorism weapons from biomedical literature. We first take text mining approach to identify topical terms of existed viruses (bacteria) from PubMed separately. Then, we use the term lists as instances to build matrices with the remaining viruses (bacteria) to discover how much the term lists describe the remaining viruses (bacteria). Next, we build a algorithm to rank all remaining viruses (bacteria). We suspect that the higher the ranking of the virus (bacterium) is, the more suspicious they will be potential bio-terrorism weapon. Our findings are intended as a guide to the virus and bacterium literature to support further studies that might then lead to appropriate defense and public health measures."
5631,Modeling the Impact of Behavior Changes on the Spread of Pandemic Influenza,"We use mathematical models to assess the impact of behavioral changes in response to an emerging epidemic. Evaluating the quantitative and qualitative impact of public health interventions on the spread of infectious diseases is a crucial public health objective. The recent avian influenza (H5N1) outbreaks and the 2009 H1N1 pandemic have raised significant global concerns about the emergence of a deadly influenza virus causing a pandemic of catastrophic proportions. Mitigation strategies based on behavior changes are some of the only options available in the early stages of an emerging epidemic when vaccines are unlikely to be available and there are only limited stockpiles of antiviral medications. Mathematical models that capture these behavior changes can quantify the relative impact of different mitigation strategies, such as closing schools, in slowing the spread of an infectious disease. Including behavior changes in mathematical models increases complexity and is often left out of the analysis. We present a simple differential equation model which allows for people changing their behavior to decrease their probability of infection. We also describe a large-scale agent-based model that can be used to analyze the impact of isolation scenarios such as school closures and fear-based home isolation during a pandemic. The agent-based model captures realistic individual-level mixing patterns and coordinated reactive changes in human behavior in order to better predict the transmission dynamics of an epidemic. Both models confirm that changes in behavior can be effective in reducing the spread of disease. For example, our model predicts that if school closures are implemented for the duration of the pandemic, the clinical attack rate could be reduced by more than 50%. We also verify that when interventions are stopped too soon, a second wave of infection can occur."
5632,"Ear, Nose, and Throat Disorders","This chapter reviews Otolaryngology conditions most commonly seen by pediatricians. Included are issues involving the ears, nose and nasopharynx, sinuses, throat, mouth and oropharynx, and the neck. The most common surgical Otolaryngological procedures will also be discussed. Many of the disease discussed can be effectively identified, diagnosed, and treated by primary care physicians. However, for certain conditions, prompt identification and timely referral to Otolaryngology are required."
5633,Nanomaterials-Based (Bio)Sensing Systems for Safety and Security Applications,"The development of new nanomaterials and nanotechnologies has ­provided many new opportunities for (bio)sensing systems. The introduction of nanomaterials, such as magnetic nanoparticles, gold nanoparticles, graphene, quantum dots, etc. is bringing advantages in terms of improving the selectivity and sensitivity of these systems. These nanomaterials also offer advantages in biosensors owing to their nanometric size, shape, composition, physical properties, ability to manipulate their surface chemistry and the property that they have in terms of adsorbing biological molecules and the change of their physical properties. In recent years, several ­bacterial pathogens, toxins, viruses, parasites and explosives have been considered as potential threats for bioterrorism, among which can find Escherichia coli, Salmonella, Bacillus anthracis, Clostridium botulinum, Botulinum Neurotoxin, Vaccinia, Plasmodium falciparum, Trinitrotoluene, etc. Bioterrorism is extremely complex to tackle but the science and technology are fundamental ­elements to reduce its threat. For this reason, monitoring systems for quick identification of biomolecules are the core of much of the basic research activities in combating bioterrorism. In this chapter we discuss the research efforts by using nanobiotechnologies with the aim of developing accurate, easy, cheap, portable and ultrasensitive assays for agents that pose a biologic threat. Some ­nanomaterial-based (bio)sensing systems used to detect agents related with bioterrorism for safety and security applications in agriculture, food, forensic, biomedical are also given."
5634,Plant-Based Vaccines as a Global Vaccination Approach: Current Perspectives,"This chapter provides a perspective on the evolution of the field of plant-based vaccine from the limitations identified in initial developments as to how this biotechnological approach has become sophisticated via the development of new technologies and has gained industry interest. Perspectives for the field at both the basic research and the industrial level are emphasized. Perspectives considered of relevance in terms of basic research include (1) advancing the development of oral formulations, (2) expanding the modalities of expression of immunogens, (3) diversifying production platforms, particularly those performed under full containment, and (4) targeting a broader number of diseases. These goals are expected to multiply the expectations for benefits derived from plant-based vaccine-production technology. On the other hand, technology transfer and regulatory issues represent a critical hurdle to this technology becoming a reality. It is also critical to achieve social acceptance as well as implement initiatives for the exploitation of the technology for humanitarian purposes and for the benefit of poor countries. This overview predicts considerable potential for plant-based vaccines to positively impact the field of vaccinology in the near future."
5635,Application of Support Vector Machines in Viral Biology,"Novel experimental and sequencing techniques have led to an exponential explosion and spiraling of data in viral genomics. To analyse such data, rapidly gain information, and transform this information to knowledge, interdisciplinary approaches involving several different types of expertise are necessary. Machine learning has been in the forefront of providing models with increasing accuracy due to development of newer paradigms with strong fundamental bases. Support Vector Machines (SVM) is one such robust tool, based rigorously on statistical learning theory. SVM provides very high quality and robust solutions to classification and regression problems. Several studies in virology employ high performance tools including SVM for identification of potentially important gene and protein functions. This is mainly due to the highly beneficial aspects of SVM. In this chapter we briefly provide lucid and easy to understand details of SVM algorithms along with applications in virology."
5636,An Introduction to Ecoimmunology,"Ecoimmunology is the study of the causes and consequences of variation in immunity. This integrative field builds on and complements comparative immunology by evaluating immunity across levels of biological organization using an evolutionary and ecological framework. One major accomplishment of ecoimmunology has been to demonstrate that immune defenses have costs, and these costs can be context-dependent. As a result, researchers assess immunity not only in terms of specific immune pathways but also as functional, emergent traits, such as resistance against and tolerance of parasites. Ecoimmunology also highlights the importance of integration across physiological systems, including the immune, endocrine, and nervous systems, in the production of immune defenses. The field has demonstrated the importance of genetics, developmental environment, and current conditions to individual variation in immune function and emphasized the traits of species, such as body size, that could be integral to immune phenotypes. Furthermore, ecoimmunological studies have shown that heterogeneity in immunity at the individual and species levels can have important consequences for disease dynamics within populations and communities as well as population cycling. Herein we discuss these key research areas in ecoimmunology as they relate to three central themes: (1) immunity in the context of the whole organism, (2) heterogeneity in immunity, and (3) the broad consequences of individual variation in immunity. We conclude by reviewing future directions for ecoimmunology, focusing on those that could have important implications for public health, conservation, and wildlife management."
5637,"Newer Insights into the Biochemical Physiology of the Renin–Angiotensin System: Role of Angiotensin-(1-7), Angiotensin Converting Enzyme 2, and Angiotensin-(1-12)","Knowledge of the mechanisms by which the rennin–angiotensin system contributes to cardiovascular pathology continues to advance at a rapid pace as newer methods and therapies uncover the nature of this complex system and its fundamental role in the regulation of blood pressure and tissue function. The characterization of the biochemical pathways and functions mediated by angiotensin-(1-7) [Ang-(1-7)], angiotensin converting enzyme 2 (ACE2), and the mas receptor has revealed a vasodepressor and antiproliferative axis that within the rennin–angiotensin system opposes the biological actions of angiotensin II (Ang II). In addition, new research expands on this knowledge by demonstrating additional mechanisms for the formation of Ang II and Ang-(1-7) through the existence of an alternate form of the angiotensinogen substrate [angiotensin-(1-12)] which generates Ang II and even Ang-(1-7) through a non-renin dependent action. Altogether, this research paves the way for a better understanding of the intracellular mechanisms involved in the synthesis of angiotensin peptides and its consequences in terms of cell function in both physiology and pathology."
5638,"Preventive, Diagnostic and Therapeutic Applications of Baculovirus Expression Vector System","Different strategies are being worked out for engineering the original baculovirus expression vector (BEV) system to produce cost-effective clinical biologics at commercial scale. To date, thousands of highly variable molecules in the form of heterologous proteins, virus-like particles, surface display proteins/antigen carriers, heterologous viral vectors and gene delivery vehicles have been produced using this system. These products are being used in vaccine production, tissue engineering, stem cell transduction, viral vector production, gene therapy, cancer treatment and development of biosensors. Recombinant proteins that are expressed and post-translationally modified using this system are also suitable for functional, crystallographic studies, microarray and drug discovery-based applications. Till now, four BEV-based commercial products (Cervarix(®), Provenge(®), Glybera(®) and Flublok(®)) have been approved for humans, and myriad of others are in different stages of preclinical or clinical trials. Five products (Porcilis(®) Pesti, BAYOVAC CSF E2(®), Circumvent(®) PCV, Ingelvac CircoFLEX(®) and Porcilis(®) PCV) got approval for veterinary use, and many more are in the pipeline. In the present chapter, we have emphasized on both approved and other baculovirus-based products produced in insect cells or larvae that are important from clinical perspective and are being developed as preventive, diagnostic or therapeutic agents. Further, the potential of recombinant adeno-associated virus (rAAV) as gene delivery vector has been described. This system, due to its relatively extended gene expression, lack of pathogenicity and the ability to transduce a wide variety of cells, gained extensive popularity just after the approval of first AAV-based gene therapy drug alipogene tiparvovec (Glybera(®)). Numerous products based on AAV which are presently in different clinical trials have also been highlighted."
5639,Cells and Viruses,"Cells are the smallest structural component of all known living organisms capable of self-maintenance and reproduction. Although cells vary greatly in their appearance or size, their structure is basically similar. Even the plant and animal cells show a significant degree of similarity in their overall organization. There are two types of cells: eukaryotic and prokaryotic. The main difference between them is the method of genetic material storage: in eukaryotic cells — in an isolated nucleus, in prokaryotic cells — directly in the cytoplasm (there is no nucleus). Prokaryotic cells are usually independent (unicellular), while eukaryotic cells are often found in multicellular organisms."
5640,Gene therapy for cystic fibrosis lung disease,"Cystic fibrosis (CF) is characterised by respiratory and pancreatic deficiencies that stem from the loss of fully functional CFTR (CF transmembrane conductance regulator) at the membrane of epithelial cells. Current treatment modalities aim to delay the deterioration in lung function, Which is mostly responsible for the relatively short life expectancy of CF sufferers; however none have so far successfully dealt with the underlying molecular defect. Novel pharmacological approaches to ameliorate the lack of active CFTR in respiratory epithelial cells are beginning to address more of the pathophysiological defects caused by CFTR mutations. However, CFTR gene replacement by gene therapy remains the most likely option for addressing the basic defects, including ion transport and inflammatory functions of CFTR. In this chapter, We will review the latest preclinical and clinical advances in pharmacotherapy and gene therapy for CF lung disease."
5641,Trends and National Needs of China’s Public Health,"It is widely recognized among governments and public in the world that the public health has a direct influence upon economic development and social progress of countries, and it is an important base for constructing a harmonic society. Rapid development of science and technology has exerted unprecedented influences in the field of the public health, including the life span and the quality of life, the mechanism of the human body and combat against diseases. Current status and characteristic of the public health are described below."
5642,Incidental Findings in TMJ Imaging,"For years, the conventional imaging modalities are generally used in dental practice routine. They provide precious information about dentomaxillofacial region; they also have some limitations such as superimpositions, magnifications, distortions, and low-image quality. Because of these limitations, some pathologies, calcifications, and anatomical variations may be missed. Any findings on a radiographic image which are not related to the research areas of interest could be a description of “incidental findings.” Calcifications are one of these incidental findings. They are asymptomatic and also common in TMJ images. Although most of the calcifications require no treatment, correct identification will reduce further diagnostic assessments. Incidental findings on TMJ images were rare, while examining images for temporomandibular disorders and associated issues, it is important not only to examine the TMJ structures but also to look at the nearby anatomical features to check for evidence of incidental findings pathologies that may have mimicked signs and symptoms of TMJ disorders."
5643,Avida: A Software Platform for Research in Computational Evolutionary Biology,"Avida(1) is a software platform for experiments with self-replicating and evolving computer programs. It provides detailed control over experimental settings and protocols, a large array of measurement tools, and sophisticated methods to analyze and post-process experimental data. This chapter explains the general principles on which Avida is built, its main components and their interactions, and gives an overview of some prior research."
5644,High-Throughput Carbohydrate Microarray Technology,"One of our long-term interests is to explore the immunogenic sugar moieties that are important for “self-” and “nonself” discrimination and host immune responses. We have established a highthroughput platform of carbohydrate microarrays to facilitate these investigations. Using this technology, carbohydrate-containing macromolecules of distinct structural configurations, including polysaccharides, natural glycoconjugates, and mono- and oligosaccharides coupled to lipid, polyacrylamide, and protein carriers, have been tested for microarray construction without further chemical modification. Here, we discuss issues related to the establishment of this technology and areas that are highly promising for its application. We also provide an example to illustrate that the carbohydrate microarray is a discovery tool; it is particularly useful for identifying immunological sugar moieties, including differentially expressed complex carbohydrates of cancer cells and stem cells as well as sugar signatures of previously unrecognized microbial pathogens."
5645,Gastrointestinal Emergencies,"Oropharyngeal: Neurological motility disorder: stroke; movement disorders (Parkinson’s disease, progressive supranuclear palsy); amyotrophic lateral sclerosis; multiple sclerosis; bulbar palsy; brainstem tumour; pseudobulbar palsy. Striated muscle disease: myasthenia gravis; myotonic dystrophy; polymyositis; dermatomyositis; inflammatory myopathy; muscular dystrophy. Reduced salivary flow leading to dry mouth (xerostomia): Sjogren’s syndrome; anticholinergics; antihistamines; ACE inhibitors; alpha-adrenergic blockers. Structural lesions: inflammatory: pharyngitis, tonsillar abscess; head and neck tumours; pharyngeal diverticula; ulcerative stomatitis; painful glossitis; anterior marginal cervical osteophytes (especially with diffuse idiopathic skeletal hyperostosis). Metabolic: hypothyroidism; hyperthyroidism; steroid myopathy."
5646,Global Variations and Changes in Patterns of Infectious Uveitis,"Before 1940, most uveitis cases were supposed to be due to infectious agents, mainly syphilis or tuberculosis [1]. Progress in the understanding of intraocular inflammation led to the discovery that uveitis can be of infectious and noninfectious origin and that many pathogens can cause infectious uveitis. Theoretically, Koch postulates must be fulfilled, in order to formerly demonstrate that a disease is due to an infectious agent. However, in infectious uveitis, most often, serological evidence, molecular or histological demonstration, and treatment response are usually the only available elements to suggest the infectious origin of the uveitis. Using those evidences, a large number of infectious organisms have been demonstrated to cause infectious uveitis. Some have a global importance around the world, while others have more limited niches. Many of them have been considered as emerging pathogens."
5647,RNA Interference Mechanisms and Therapeutic Applications,"RNA interference (RNAi) is a technology developed after the recent discovery of well-conserved cellular processes that induce posttranscriptional gene silencing triggered by small fragments of double-stranded RNA. This technique is rapidly developing into a promising tool used for functional genetics and therapeutic applications. We focus here on the aspects concerning RNAi mechanism, applications in mammals, and construct design and delivery. We summarize some therapeutic applications in general and speculate on the relevance in cardiovascular medicine."
5648,Infectious Mechanisms Regulating Susceptibility to Acute Exacerbations of COPD,"Acute exacerbations of COPD (AECOPD) are defined by clinical criteria, outlined in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines [1]. These include an acute increase in one or more of the following cardinal symptoms, beyond day to day variability: dyspnea, increased frequency or severity of cough and increased volume or change in character of sputum, which represent an acute increase in airway inflammation. The role of infection in the pathogenesis of COPD, acute exacerbation and disease progression has been a clinical and research question for many years, and the pendulum has swung from infection as a major cause of acute exacerbation and COPD (British Hypothesis) [2], to infection as an unrelated epiphomenon in acute exacerbation [3–5], and back again to infection as integral in the development of AECOPD and likely an important contributor to COPD progression [6–19]. Upwards of 80 % of AECOPD are driven by infectious stimuli, with 40–50 % associated with bacterial infection and 30–50 % associated with acute viral infection, with some exacerbations having dual bacterial and viral causation [20]. Much of the advancement in our understanding of the role of infection is AECOPD is due to the advancement of clinical and research tools that have allowed researchers to accurately characterize the microbial pathogens, and better understand the host-pathogen interactions (Table 1)."
5649,What Next?,
5650,Assessing the Threat: Public Health,"This chapter describes three methods for assessing the impact of transfusion-transmitted infections on public health. In order of increasing precision and labor intensity, these tools are: 1. A blueprint for a structured, qualitative inventory and report, describing the relevant characteristics of the emerging agent, which helps to make ad hoc decisions and which identifies gaps in our knowledge. 2. Two more sophisticated “off the shelf” methods for the quantitative analysis of threats to blood safety are mentioned: the Biggerstaff-Petersen model and the European Up-Front Risk Assessment Tool (EUFRAT). The Biggerstaff-Petersen model estimates the number of potentially infectious donations, while EUFRAT also takes into account the components prepared from donations and the efficacy of various mitigating interventions. 3. Finally examples of quantitative studies of specific agents are mentioned: a donor-recipient transmission study and a cost-benefit modeling study. For this kind of analysis, no standardized recipe is available."
5651,Nanomechanical Cantilever Array Sensors,"Microfabricated cantilever sensors have attracted much interest in recent years as devices for the fast and reliable detection of small concentrations of molecules in air and solution. In addition to application of such sensors for gas and chemical-vapor sensing, for example as an artificial nose, they have also been employed to measure physical properties of tiny amounts of materials in miniaturized versions of conventional standard techniques such as calorimetry, thermogravimetry, weighing, photothermal spectroscopy, as well as for monitoring chemical reactions such as catalysis on small surfaces. In the past few years, the cantilever-sensor concept has been extended to biochemical applications and as an analytical device for measurements of biomaterials. Because of the label-free detection principle of cantilever sensors, their small size and scalability, this kind of device is advantageous for diagnostic applications and disease monitoring, as well as for genomics or proteomics purposes. The use of microcantilever arrays enables detection of several analytes simultaneously and solves the inherent problem of thermal drift often present when using single microcantilever sensors, as some of the cantilevers can be used as sensor cantilevers for detection, and other cantilevers serve as passivated reference cantilevers that do not exhibit affinity to the molecules to be detected."
5652,"Chitin/Chitosan: Versatile Ecological, Industrial, and Biomedical Applications","Chitin is a linear polysaccharide of N-acetylglucosamine, which is highly abundant in nature and mainly produced by marine crustaceans. Chitosan is obtained by hydrolytic deacetylation. Both polysaccharides are renewable resources, simply and cost-effectively extracted from waste material of fish industry, mainly crab and shrimp shells. Research over the past five decades has revealed that chitosan, in particular, possesses unique and useful characteristics such as chemical versatility, polyelectrolyte properties, gel- and film-forming ability, high adsorption capacity, antimicrobial and antioxidative properties, low toxicity, and biocompatibility and biodegradability features. A plethora of chemical chitosan derivatives have been synthesized yielding improved materials with suggested or effective applications in water treatment, biosensor engineering, agriculture, food processing and storage, textile additives, cosmetics fabrication, and in veterinary and human medicine. The number of studies in this research field has exploded particularly during the last two decades. Here, we review recent advances in utilizing chitosan and chitosan derivatives in different technical, agricultural, and biomedical fields."
5653,"Viral pathogens and epidemiology, detection, therapy and resistance","Worldwide community-acquired pneumonia (CAP) is one of the most frequent infectious diseases and a leading cause of death. Several studies have shown that a pathogen could be identified only in 50 to 60% of all patients, although in children < 6 month infectious agents can be detected in about 90%. Viral infections are most frequent in children < 2 years (80%), whereas bacterial infections increase with age. RSV, influenzaviruses, rhinoviruses, parainfluenzaviruses and adenoviruses are the most common viruses associated with CAP in children. Among adenoviruses a predominance of adenovirus 7 has been reported in several countries with emergence of highly pathogenic variants with significant lethality in young children. Many childhood respiratory infections are caused by more than one pathogen and up to 30% mixed viral / bacterial infections can be observed. CAP in immunocompetent adults is rare, whereas persons with underlaying diseases have an increased incidence of CAP. In the elderly, RSV, influenzaviruses, parainfluenzaviruses and less frequent adenoviruses are predominant viruses causing pneumonia. Less frequently associated with CAP are the newly discovered human metapneumovirus and the coronaviruses NL63 and HKU1. Hantaviruses, involved in the hantavirus pulmonary syndrome, belong to the emerging pathogens to date in North, Middle and South America. For optimum diagnosis the whole spectrum of potential respiratory viral agents should be included and multiple diagnostic techniques have to be used. In view of the high relevance of influenzavirus for CAP influenza vaccination is highly advisable for prevention of CAP, especially in high-risk groups."
5654,Common Viral Pneumonia,"Common respiratory viruses are now recognised as true opportunistic respiratory pathogens in patients with haematological malignancies. The epidemiology of these viruses has not been extensively studied in immunocompromised hosts, but is probably closely related to viral activity in immunocompetent hosts, who constitute the virus reservoir for immunocompromised patients. In these patients, common respiratory viruses may cause severe infections with higher rates of progression to pneumonia and mortality compared to immunocompetent individuals. Prolonged high-titre viral shedding is common in patients with haematological malignancies and may enhance not only viral transmission, but also the selection of resistant strains. Influenza and respiratory syncytial virus (RSV) infections have been particularly well studied. They are associated with pneumonia rates of about one-third for influenza and 30–40% for RSV. Both viruses are responsible for mortality rates ranging from 15% to 30%. The exact mechanisms of pneumonia related to these viruses remains unknown, but bacterial and fungal co-infections are frequent and must be carefully investigated. Parainfluenza viruses (PIV) and RSV have also been linked to late airflow obstruction in haematopoietic stem cell transplant recipients. Neuraminidase inhibitor therapy has been suggested for influenza, ribavirin for RSV, and cidofovir for adenovirus infections. However, there is no evidence supporting the use of these drugs, and randomised controlled trials are urgently needed to better define the optimal management of common viral pneumonia in patients with haematological malignancies. The absence of proven effective treatments highlights the critical importance of prevention. Viral transmission may be interrupted by contact isolation with droplet precautions for infected patients and by having patients and health care workers with suspected infection, and their relatives, refrain from visits and work. Immunisation remains the cornerstone of influenza prevention and is recommended for patients with haematological malignancies, their relatives, and health care workers."
5655,Implications of Results,"While the pursued customer network-centric valuation approach contains a variety of implications, this chapter summarizes the most relevant issues with respect to the outlined target group. First, findings relevant to managers of companies operating in software markets are presented, before implications for financial sponsors are depicted. Then, the consequences for various streams of research conclude this chapter. In this first section the most relevant implications for managers are investigated. All in all, managers should note that the outlined approach supports decision making in software markets based on a better understanding of customer networks, their topologies and their dynamics. This has implications on various aspects of management, such as strategic management, marketing and turnaround management. It is important to note that the following categories are not mutually exclusive and collectively exhaustive as some of the following implications are relevant to more than one cluster."
5656,Global Health Security Innovation,"Heyman et al. (Global health security: the wider lessons from the west African Ebola virus disease epidemic, vol 385. May 9, 2015 www.thelancet.com, 2015:1888) argues that, “the world is ill-prepared” to handle any “sustained and threatening public-health emergency”. Disease outbreaks such as Ebola SARS, and H1N1 challenged national and global response mechanisms. The emergence of these disease outbreaks and their influence globally has sparked a renewed attention to global health security. In the Chatham House report ‘Preparing for High Impact, Low Probability Events’, Lee et al. (Preparing for high-impact, low-probability events: lessons from Eyjafjallajökull. Chatham House Report, January 2012:vii) ‘…found that governments and businesses remain unprepared for such events … the frequency of ‘high-impact, low-probability’ (HILP) events in the last decade signals the emergence of a new ‘normal’. This calls for innovation on an unprecedented level to manage such global health threats as they represent a global health security challenge. This chapter explores the foundations of the innovation space as it applies to global health security. The wicked nature of global health security points to how innovation and complexity framing go hand in hand in dealing with such global issues."
5657,Molecular Diagnostics,"Effective and early management of diseases requires record of the history, behavioral parameters, and travel information. These are helpful for the diagnosis, prevention, and control of the disease. There have been several advancements in the methods for diagnosing infectious diseases. The wide spectrum of tests such as biochemical evaluation, microbiological tools, immunological and molecular biology techniques, etc., is available. Each type of diagnostic technique is strong and reliable in its own sense but poses certain limitations. These limitations may be complemented by using a combination of tests. Older techniques such as microscopy and culturing of organisms from clinical specimens are error-free but are very labor intensive and extremely time consuming. There is a need to develop rapid and sensitive tests that can be used in both high- and low-resource settings. Molecular diagnostics such as Western blot, ELISA, PCR, DNA, and protein microarrays are revolutionizing the clinical practice of infectious diseases. Their effects are significant in acute-care settings where timely and accurate diagnostic tools are critical for patient treatment decisions and outcomes."
5658,Pharmacogenomic Biomarkers in Neuropsychiatry: The Path to Personalized Medicine in Mental Disorders,"Neuropsychiatric disorders and dementia represent a major cause of disability and high cost in developed societies. Most disorders of the central nervous system (CNS) share some common features, such as a genomic background in which hundreds of genes might be involved, genome-environment interactions, complex pathogenic pathways, poor therapeutic outcomes, and chronic disability. Recent advances in genomic medicine can contribute to accelerate our understanding on the pathogenesis of CNS disorders, improve diagnostic accuracy with the introduction of novel biomarkers, and personalize therapeutics with the incorporation of pharmacogenetic and pharmacogenomic procedures to drug development and clinical practice. The pharmacological treatment of CNS disorders, in general, accounts for 10–20% of direct costs, and less than 30–40% of the patients are moderate responders to conventional drugs, some of which may cause important adverse drugs reactions (ADRs). Pharmacogenetic and pharmacogenomic factors may account for 60–90% of drug variability in drug disposition and pharmacodynamics. Approximately 60–80% of CNS drugs are metabolized via enzymes of the CYP gene superfamily; 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are major substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are major substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. About 10–20% of Caucasians are carriers of defective CYP2D6 polymorphic variants that alter the metabolism of many psychotropic agents. Other 100 genes participate in the efficacy and safety of psychotropic drugs. The incorporation of pharmacogenetic/ pharmacogenomic protocols to CNS research and clinical practice can foster therapeutics optimization by helping to develop cost-effective pharmaceuticals and improving drug efficacy and safety. To achieve this goal several measures have to be taken, including: (a) educate physicians and the public on the use of genetic/ genomic screening in the daily clinical practice; (b) standardize genetic testing for major categories of drugs; (c) validate pharmacogenetic and pharmacogenomic procedures according to drug category and pathology; (d) regulate ethical, social, and economic issues; and (e) incorporate pharmacogenetic and pharmacogenomic procedures to both drugs in development and drugs in the market to optimize therapeutics."
5659,The Role of DUOX Isozymes in the Respiratory Tract Epithelium,"Increasingly, reactive oxygen species such as superoxide and hydrogen peroxide are recognized to be intentionally generated intracellularly to serve important cellular functions. A key protein family responsible for the regulated generation of reactive oxygen species in multiple cell types is the NOX/DUOX enzyme family. Two family members, DUOX1 and DUOX2, appear to be highly expressed in tissues of endodermal origin including the thyroid, respiratory tract, and gastrointestinal tract. In this chapter, we will focus our review on DUOX proteins in the respiratory tract. We will discuss a brief history of the discovery of the DUOX isoforms, the estimated hydrogen peroxide-generating capacity of DUOX in respiratory tract epithelium, putative functions of the DUOX enzymes, and some regulatory factors responsible for DUOX gene expression and oxidase activity."
5660,Viral Diagnostics,"This chapter discusses recent developments in diagnostics for cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK virus (BKV), community respiratory viruses (CRVs), parvovirus, hepatitis viruses, HIV, and other viral agents of importance in solid organ and hematopoietic stem cell transplantation."
5661,Advances in Transfusion Safety,"Although transfusion is now extremely safe, the tools of molecular biology are continually being harnessed to improve diagnosis and therapy. Viral genome testing has been introduced in the developed world for HIV and HCV, to detect donors in the infectious “window period” before sero-conversion. Pathogen inactivated fresh frozen plasma and platelets are already available, but alloimmunization has halted trials of pathogen-inactivated red cells. Development of synthetic oxygen carriers has included perflurocarbons, and crosslinked, polymerized or mutated human or bovine hemoglobin, either free or encapsulated. No perfect replacement for the human red cell is yet on the horizon."
5662,Soft Computing Based Epidemical Crisis Prediction,"Epidemical crisis prediction is one of the most challenging examples of decision making with uncertain information. As in many other types of crises, epidemic outbreaks may pose various degrees of surprise as well as various degrees of “derivatives” of the surprise (i.e., the speed and acceleration of the surprise). Often, crises such as epidemic outbreaks are accompanied by a secondary set of crises, which might pose a more challenging prediction problem. One of the unique features of epidemic crises is the amount of fuzzy data related to the outbreak that spreads through numerous communication channels, including media and social networks. Hence, the key for improving epidemic crises prediction capabilities is in employing sound techniques for data collection, information processing, and decision making under uncertainty and exploiting the modalities and media of the spread of the fuzzy information related to the outbreak. Fuzzy logic-based techniques are some of the most promising approaches for crisis management. Furthermore, complex fuzzy graphs can be used to formalize the techniques and methods used for the data mining. Another advantage of the fuzzy-based approach is that it enables keeping account of events with perceived low possibility of occurrence via low fuzzy membership/truth-values and updating these values as information is accumulated or changed. In this chapter we introduce several soft computing based methods and tools for epidemic crises prediction. In addition to classical fuzzy techniques, the use of complex fuzzy graphs as well as incremental fuzzy clustering in the context of complex and high order fuzzy logic system is presented."
5663,New concepts in anti-HIV therapies,
5664,Reticulate Evolution Everywhere,"Reticulation is a recurring evolutionary pattern found in phylogenetic reconstructions of life. The pattern results from how species interact and evolve by mechanisms and processes including symbiosis; symbiogenesis; lateral gene transfer (that occurs via bacterial conjugation, transformation, transduction, Gene Transfer Agents, or the movements of transposons, retrotransposons, and other mobile genetic elements); hybridization or divergence with gene flow; and infectious heredity (induced either directly by bacteria, bacteriophages, viruses, prions, protozoa and fungi, or via vectors that transmit these pathogens). Research on reticulate evolution today takes on inter- and transdisciplinary proportions and is able to unite distinct research fields ranging from microbiology and molecular genetics to evolutionary biology and the biomedical sciences. This chapter summarizes the main principles of the diverse reticulate evolutionary mechanisms and situates them into the chapters that make up this volume."
5665,Anti-Histidine Antibodies as Tools for Reversible Capturing of His-Tagged Fusion Proteins for Subsequent Binding Analysis,"The hexahistidine tag is one of most commonly used fusion tags in affinity purification of recombinantly expressed proteins. Real-time binding analysis using Biacore technology allows in-depth characterization of respective association and dissociation patterns of potential binders. Here we tested four commercially available anti-His antibodies for reversible capturing of His-tagged proteins as a basis for a subsequent interaction analysis with non-His-tagged proteins. Anti-penta-, anti-hexa- and anti-RGS-(His)4 antibodies from different distributors were covalently coupled to Biacore sensor chips. Parallel binding studies of 12 heterogeneously sized RGS-(His)6-tagged (Arg-Gly-Ser-(His)6) proteins revealed that the slowest dissociation rate was obtained when using an anti-RGS-(His)4 antibody. Thus in a sandwich binding assay the anti-RGS-(His)4 antibody can be utilized as an appropriate tool for stable yet reversible capturing of RGS-(His)6-tagged proteins with a non-His-tagged protein."
5666,Human Security in East Asia: Beyond Crises,"In this globalized world, we face multiple threats to human security, a powerful supplement to national security. The introduction to this book provides both a history and a definition of human security. Enhanced connectivity in East Asia not only gives rise to serious threats but also provides the means for ensuring people’s security and opportunities for mutual learning. After explaining the three research questions that are aimed at evaluating the practice of human security—sovereignty, coordination and empowerment—the introductory chapter goes on to provide summaries of the following chapters."
5667,"Influenza-Associated Pediatric Mortality and the Application of Multiplex Testing to Detect Respiratory Virus Coinfection—Wisconsin, October 4, 2014–February 7, 2015",
5668,Comparative Evaluation of Diatherix Target Enriched Multiplex Polymerase Chain Reaction and BioFire FilmArray in the Detection of Viral and Bacterial Respiratory Pathogens,
5669,Crystal Structure of Human Coronavirus NL63 Main Protease in Complex With an Inhibitor,
5670,Modelling of potentially promising SARS protease inhibitors,"In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation."
5671,Beyond SumBasic: Task-focused summarization with sentence simplification and lexical expansion,"In recent years, there has been increased interest in topic-focused multi-document summarization. In this task, automatic summaries are produced in response to a specific information request, or topic, stated by the user. The system we have designed to accomplish this task comprises four main components: a generic extractive summarization system, a topic-focusing component, sentence simplification, and lexical expansion of topic words. This paper details each of these components, together with experiments designed to quantify their individual contributions. We include an analysis of our results on two large datasets commonly used to evaluate task-focused summarization, the DUC2005 and DUC2006 datasets, using automatic metrics. Additionally, we include an analysis of our results on the DUC2006 task according to human evaluation metrics. In the human evaluation of system summaries compared to human summaries, i.e., the Pyramid method, our system ranked first out of 22 systems in terms of overall mean Pyramid score; and in the human evaluation of summary responsiveness to the topic, our system ranked third out of 35 systems."
5672,Papel de los receptores toll-like en las enfermedades respiratorias,"There has been growing interest in the last 10 years in the study of innate immunity, in particular because of the possible role that toll-like receptors (TLR) may play in the pathogenesis of some respiratory disease such as for example, asthma, chronic obstructive pulmonary disease, and infections. TLR are a family of type 1 transmembrane proteins, responsible for recognizing molecular patterns associated with pathogens (PAMP, pathogen-associated molecular patterns), and expressed by a broad spectrum of infectious agents. This recognition leads to quick production of cytokines and chemokines which provides a long-lasting adaptive response to the pathogen. Currently, it is considered that the administration of drugs which modulate the activity of these receptors upwards or downwards may represent major therapeutic progress for handling these diseases. The aim of this review is to describe the different TLS, define their possible role in the pathogenesis of the main respiratory diseases and finally, speculate over the therapeutic possibilities which their modulation, agonist or antagonist, offers as possible therapeutic targets."
5673,Agudización de la EPOC,
5674,Wichtige Zoonosen: Neuartige Coronaviren,
5675,Neuartiges Coronavirus (SARS-CoV-2),
5676,Neuartiges Coronavirus (SARS-CoV-2),
5677,Clinical and Molecular Epidemiology of Respiratory Viruses in a Tertiary Care Center During the 2009–2014 Consecutive Winter Seasons,
5678,Screening for Respiratory Viruses in Healthcare Workers During the Influenza Season,
5679,Etiology Unknown: Are Less Recognized Respiratory Pathogens Associated With a Milder Course of Illness?,
5680,Epidemiology of Respiratory Viral Infections in Pediatric Solid Organ Transplant or Hematopoietic Stem Cell Transplant Recipients,
5681,Patterns of Viral and Bacterial Co-detection Among Otherwise Healthy Adults With Influenza-Like Illness: Utilization of a Multiplex Respiratory Pathogen Panel,
5682,Impact of Enterovirus D68 in Children With Asthma and Other Complex Medical Conditions,
5683,Cross-protection studies between feline infectious peritonitis and porcine transmissible gastroenteritis viruses,"Cross-protection studies between the feline infectious peritonitis (FIP) and the porcine transmissible gastroenteritis (TGE) viruses were conducted in cats, pigs and pregnant gilts. Cats vaccinated with TGE virus developed neutralizing antibodies against TGE virus and low titer antibody against FIP virus detected by an indirect fluorescent antibody technique but were not protected against a virulent FIP virus challenge. Baby pigs and pregnant gilts vaccinated with FIP virus did not develop detectable antibodies to TGE virus. Nevertheless, it appeared that vaccination of swine with FIP virus conferred some immunity against TGE virus infection. Seventeen-day-old pigs vaccinated with two doses of FIP virus had a 67% survival rate following a virulent TGE virus challenge, and 75% of the 3-day-old pigs suckling either FIP or TGE-virus-vaccinated gilts survived virulent TGE virus infection in contrast to 0% survival of baby pigs suckling unvaccinated gilts."
5684,"Contents of veterinary microbiology, volume 28",
5685,Clinical Differences Between Respiratory Viral and Bacterial Mono- and Dual-Pathogens Detected Among Singapore Military Servicemen With Febrile Respiratory Illness,
5686,Early Detection and Timely Reporting of Non-Mumps Etiologies of Parotitis: An Example in Developing Clinical and Public Health Partnerships,
5687,"In Vivo and In Vitro Characterization of Provodine, a Long Acting, Alcohol-Free Professional Antiseptic, Against Ebola Virus and Other Serious Viral, Bacterial and Fungal Pathogens",
5688,Effects of ambient temperatures on clinical and immune responses of pigs infected with transmissible gastro-enteritis virus,"Two- to three-months-old pigs infected with transmissible gastroenteritis (TGE) virus showed no clinical response when housed at 30°C, but comparable infected pigs exposed to temperature changes from 30°C to 4°C following infection showed typical signs of TGE. Development of TGE-specific immune responses, as measured by blastogenic response of tissue lymphocytes, occurred at 3 days post-inoculation (DPI) in pigs held at 30°C, but not until 7 DPI in infected pigs held under the adverse conditions. Immunosuppression with corticosteroids resulted in a fall in circulatory T cells, lowering of non-specific blastogenic response of circulatory lymphocytes, and clinical signs of disease when immunosuppressed pigs were infected with TGE virus and held at 30°C. It is suggested that clinical responses to TGE virus infection may be affected by the influence of ambient temperatures on the immune responses of pigs."
5689,"Subject Index, Volumes 98-104",
5690,Keyword index — volumes 43–47 (1995),
5691,"Contents of veterinary microbiology, volume 31",
5692,"Author index, volumes 48–53",
5693,"Veterinary Immunology: Bruce N. Wilkie and Patricia E. Shewen (Editors) Elsevier Science Publishers, Amsterdam, 1988. 518 pp., price US$ 126.25/ Dfl. 240.00, ISBN 0-444-42917-4.",
5694,"Contents of veterinary microbiology, volume 21",
5695,"New aspects of positive-strand RNA viruses: Edited by M.A. Brinton and F.X. Heinz (1990). American Society for Microbiology, Washington, D.C. 405 pp, US$75, ISBN 1-5581-022-S.",
5696,"Proceedings of minisymposium on neonatal diarrhea in calves and pigs: Saskatoon, Sask., 3–4 May 1976. Veterinary Infectious Diseae Organization (VIDO), University of Saskatchewan, Saskatoon, University Publications Office, 1976, 155pp., $5.00, ISBN 0-88880-004-5",
5697,"Author index : Veterinary Microbiology, volumes 26–50, 1991–1996",
5698,"Contents of Veterinary Microbiology, Volume 115",
5699,Detection of rotavirus infection by immunodiffusion,"Three precipitin reactions associated with bovine rotavirus infection were demonstrable by immunodiffusion. One of the reactions has been utilized in a diagnostic test for the detection of rotavirus in faeces, or specific antibody to rotavirus group antigen in serum or faeces. The test, based on bovine materials, appeared to be group-specific and effective in demonstrating rotaviral antigen or antibody in other species of animals, including human beings. The procedure was as efficient as electron microscopy in detecting evidence of rotavirus in faeces of calves and a range of other species."
5700,Volume contents,
5701,"Subject index, volumes 48–53",
5702,"Virus infections of rodents and lagomorphs: edited by A.D.M.E. Osterhaus, Elsevier, 1994, 432 pp, ISBN 0-444-81909-6, US$ 225.75, Dfl. 395.00",
5703,"Virus infections of ruminants: Z. Dinter and B. Morein (Editors). Elsevier Science Publishers, 1990, 572 pp., hardcover, Dfl 380/$194.75, ISBN 0-444-87312-0",
5704,"Contents of veterinary microbiol, volume 48",
5705,"Contents of veterinary microbiology, volume 20",
5706,"Contents of veterinary microbiology, volume 58",
5707,"Contents of veterinary microbiology, volume 22",
5708,"Author Index, Volumes 98-104",
5709,Volume contents,
5710,"Contents of Veterinary microbiology, volume 19",
5711,Volume contents,
5712,"Contents of veterinary microbiology, volume 26",
5713,"Virus infections of porcines: 283 pp, Price US$ 142/Dfl.270, Elsevier Science Publishers, 1989. ISBN 0-444-42909-3",
5714,"Microbiology of animals and animal products: Edited by J.B. Woolcock, 1991, Elsevier Science Publishers, 278 pp., hardcover, Dfl 275/$157.25, ISBN 0-444-43010-5.",
5715,"Contents Vol. 42, 1994",
5716,Antigenicity of structural components from porcine transmissible gastroenteritis virus,"Pregnant sows were inoculated with inactivated transmissible gastroenteritis virus and with preparations of virus surface projections and subviral particles derived by detergent treatment of the virus. Neutralising antibody was demonstrated in serum and colostrum from animals that received whole virus or preparations of surface projections whereas subviral particles failed to stimulate neutralising antibody formation. Similar results were obtained with serum from rabbits inoculated with whole virus and structural components. All three preparations stimulated the formation of agglutinating antibodies, as demonstrated by sedimentation analysis and filtration studies with radiolabelled virus. The immunoglobulin classes responsible for neutralising antibody activity in sows inoculated by the intramammary route were examined. In each case where the immunoglobulin class was determined, IgG was found. One sow that received surface projections also had IgA with neutralising activity in her colostrum. In contrast, infection of sows with live whole virus resulted in neutralising antibody of the IgG, IgM and IgA classes."
5717,"Contents of veterinary microbiology, volume 37",
5718,Hematologic and Biochemical Changes in Hospitalized Patients With Middle East Respiratory Syndrome-Coronavirus,
5719,"Prevalence of Respiratory Viruses, Including Influenza, Among Nursing Home Residents and High-Touch Room Surfaces",
5720,Comparison of the Reproductive Numbers of Middle East Respiratory Syndrome Coronavirus Nosocomial Outbreaks in Saudi Arabia and Korea,
5721,A Prospective Study Comparing Self-Collected Nasal Swabs to Oral Washes for Monitoring Viral Load Kinetics in Lung Transplant Recipients With Respiratory Virus Infection,
5722,Differences in Self-Reported Severity of Symptoms Between Women and Men Experiencing Influenza-Like Illness,
5723,Role of Respiratory Virus Panels in Antimicrobial Stewardship in Immunocompromised Patients,
5724,Neutrophil Activation in Infants Hospitalized With Severe Respiratory Viral Infection,
5725,Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplantation Recipients and Hematologic Malignancy Patients,
5726,Quality of Life Among Survivors of Middle East Respiratory Syndrome Corona Virus,
5727,Laboratory-Confirmed Human Coronavirus Infections Among Children: Does Type Matter?,
5728,"Prevalence of Respiratory Viral Pathogen Testing and Co-Detections Among Patients Hospitalized With Influenza, 2012–2015",
5729,Acute Respiratory Infections (ARIs) Among Outpatient Healthcare Personnel (HCP),
5730,Low Co-infection Rate in Children With Community-Acquired Pneumonia in Spain,
5731,Drug repurposing strategies for COVID-19,"COVID-19 has now been declared a pandemic and new treatments are urgently needed as we enter a phase beyond containment. Developing new drugs from scratch is a lengthy process, thus impractical to face the immediate global challenge. Drug repurposing is an emerging strategy where existing medicines, having already been tested safe in humans, are redeployed to combat difficult-to-treat diseases. While using such repurposed drugs individually may ultimately not yield a significant clinical benefit, carefully combined cocktails could be very effective, as was for HIV in the 1990s; the urgent question now being which combination."
5732,Congenital malaria: rare but potentially fatal,"Congenital malaria is rare and usually indolent but can be fatal. Mortality risk is high in newborns with Plasmodium falciparum born to nonimmune women, who typically present at birth or soon thereafter. Semi-immune women are less likely to transmit malaria, and their children often become ill weeks after delivery with less severe symptoms. Cases in the USA usually trace to semi-immune immigrant mothers whose last exposure to malaria may have preceded the pregnancy, leading to misdiagnoses. Congenital malaria may be under-recognized in malaria-endemic areas since parasitemia occurring after the first week of life is usually attributed to mosquito transmission. Malaria prophylaxis and the absence of fever during pregnancy do not preclude congenital malaria in a newborn. Quinine plus clindamycin is commonly used to treat P. falciparum congenital malaria, and chloroquine is used to treat other malaria parasites, such as Plasmodium vivax. Severe cases should be managed with intravenous quinine (available as its enantiomer quinidine in the USA) or with intravenous artesunate, which was recently approved for investigational use by the US FDA. Primaquine is not required for infants with congenital P. vivax or Plasmodium ovale, but should be offered to their mothers after excluding G6PD deficiency."
5733,855 Double Blind Placebo Controlled Food Challenge Useful to Disconfirm Over Estimated Diagnosis of Cmpa in Children,"Background and aims: The incidence of CMPA in infancy seems to be approximately 3%. In Italy diagnosis of CMPA is often over estimated. The double-blind, placebo controlled food challenge(DBPCFC) is widely considered as the “gold standard” for the diagnosis of food allergy. Methods: 14 patients, (12 months-12 yrs) previously diagnosed as having CMPA, underwent our diagnostic algorithm in order to confirm or to exclude diagnosis. Diagnostic algorithm includes: total blood cell count, serum IgE assay, RAST, betalactotest, Prick by prick with fresh milk, chemical examination and eosinophilic cell count of the stools. DBPCFC was performed with extensively hydrolyzed formula (as placebo) VS a lactose-free, cow milk derived formula. At discharge a post challenge form was given to parents to record delayed symptoms that might occur at home. Results: 12 out of 14 patients had positive results for skin prick test (prick by prick) and four out of them also presented specific IgE against CMPs. 13 patients showed tolerance to CMP during and after DBPCFC and had no symptoms also in the next 72h. Only one patient, aged 30 months, had to keep CMP avoidance. Conclusion: In our survey DBPCFC demonstrated tolerance to CMP for all but one patients. DBPCFC is effective also to disconfirm diagnosis of CMPA. Skin prick tests and serological specific IgE do not always correlate with oral tolerance test. Subjects with positive skin prick test and high serological specific IgE against CMP but tolerant at DBPCFC may reintroduce cow milk proteins in to their dietary meals."
5734,856 Etiology of Bronchiolitis in a Hospitalized Pediatric Population: Prospective Multicenter Study,"Background and aims: In 2006, bronchiolitis due to adenovirus nosocomial infections resulted in the closure of a pediatric department in northern Portugal. Objectives: To determine the etiology of bronchiolitis in northern Portugal. Methods: It was a prospective multicenter study on the etiology of bronchiolitis during the respiratory syncytial virus (RSV) season (November-April). Children ≤24 months of age admitted for a first wheezing episode were included. Nasopharyngeal specimens were analyzed by an indirect immunofluorescentantibody assay (IFA) for RSV, adenovirus (HAdV), parainfluenza (PIV) 1-3 and influenza (IV)Aand B and by polymerase chain reaction (PCR) or reverse transcription-PCR for the same viruses and for human metapneumovirus (hMPV), bocavirus (HBoV), rhinovirus (HRV), coronaviruses (229/E; NL63; OC43; HKU1) and enterovirus. Results: During this period, 253 children were included, 249 IFA analyses and 207 PCRs were performed. IFA detected RSV in 58.1%; PCR increased it to 66.7%. IFA detected HAdV in 3.2%, PCR 10.0%. PCR detected IV A in 5; IV B in 2; PIV 1 in 6, PIV 2 in 4 and PIV 3 in 11 cases. HBoV, as single agent in 2 cases, and HRV were positive in 8 samples and hMPV in 11. With this virus panel, 19.7% remained without etiology. Conclusions: The most frequent agent was RSV, followed by HAdV. PCR can be cost-effective and more accurate than IFA, which is crucial for HAdV that may be associated with significant mortality (IFA alone did not detect 2/3 of the cases)."
5735,Infections diverses,
5736,"Ebola et autres, ces virus venus d’ailleurs","In the last decade, we faced a large number of emerging pathogens. As a consequence we had to adapt our medical practice as well as our health system. This review summarizes the main features of the recent emerging pathogens with a particular focus on the recent and ongoing Ebola outbreak, we tried to evaluate the consequences on our national health management."
5737,Quels prélèvements aux urgences pour le diagnostic microbiologique d’une infection pulmonaire communautaire grave du sujet immunocompétent ?,"Current diagnostic methods allow microbial identification in 50% of patients admitted with severe community-acquired pneumonia (CAP). Guidelines derived from epidemiological data help physicians to start empirical antimicrobial therapy. Definitive microbial diagnosis is useful to guide further pathogen-directed therapy. Blood cultures, cultures of respiratory specimens and urine antigen tests are recommended to determine the causative bacterial pathogen. Positive blood cultures range from 15 to 25% of CAP patients according to severity. Whether sputum specimens represent or not lower respiratory secretions determines its accuracy in CAP microbial diagnosis. In intubated patients, endotracheal aspirates are often of interest. Detection of positive pneumococcal or legionella urinary antigen is often associated with CAP severity. The sensitivity of this test is not decreased in patients who have received antibiotics prior to sampling. Viral pneumonia account for 10 to 40% of severe CAP. Nasal swabs are recommended for influenza identification using polymerase chain reaction (PCR) in order to deliver oseltamivir treatment. In the emergency department, atypical pneumonia serology is less useful than respiratory specimens obtained using fiberoptic bronchoscopy. Serum PCR to diagnose bacterial CAP is not superior to the other usual methods."
5738,La modulation de la signature transcriptomique de l’hôte infecté : une nouvelle stratégie thérapeutique dans les viroses graves ? Exemple de la grippe,"During the last decades, emergence and reemergence of viruses were responsible for epidemic and pandemic infectious diseases, with variable degrees of severity. Current preventive strategies are not sufficient at all, and available therapeutic drugs are very limited. Indeed, genetic variations of viruses can impair the efficacy of antiviral compounds by the apparition of resistance. Moreover, current delay needed for de novo development of drugs does not allow a rapid response in case of important epidemic or pandemic events. In this context, new therapeutic approaches are necessary. An innovative concept is to repurpose already marketed compounds that can reverse the host cellular transcriptomic response to the infection. By targeting the host, these molecules exhibit a broad-spectrum activity and are potentially effective even against new emergent strains. This strategy implements the characterization of specific host gene expression profiles, the in silico screening of drugs, and their validation in in vitro and in vivo models, until their evaluation in clinical trials. Here, we will present this approach, with the example of the flu."
5739,Diagnostics en pathologie infectieuse,
5740,Infections respiratoires virales à herpesviridae en réanimation,"Herpesviridae, including herpes simplex virus (HSV) and cytomegalovirus (CMV), are commonly detected in the respiratory tract of non-immunocompromised patients receiving mechanical ventilation. Although their detection usually involves viral reactivation without the involvement of pulmonary tissue, viral lung disease may occur in a particular population of patients. Although histological examination for specific cytopathic effects forms the basis of diagnosis, the use of modern virological tests (amplification using real-time polymerase chain reaction to estimate the vial load) should replace the histological tests in the near future. HSV bronchopneumonitis is associated with the reactivation of HSV in oropharyngeal and oral-labial lesions. It seems to clearly affect patients’ outcome due to prolonged mechanical ventilation and length of stay in the intensive care unit (ICU). However, only interventional studies will be able to determine its real impact. To date, use of acyclovir in these patients remains to be assessed. Although CMV reactivation in the blood is frequent in ICU patients, CMV pneumonia is difficult to diagnose because of the cumbersomeness of the procedure (open lung biopsies). Its true prognosis remains uncertain. The use of ganciclovir in this subset of patients also remains to be assessed."
5741,Place des micro-organismes atypiques et des virus dans les pneumonies aiguës communautaires sévères,"Usually, intensivists do not focus on atypical bacteria and viruses in severe community-acquired pneumonia (CAP). Only Legionella pneumophila and influenza virus, following the recent H1N1 influenza pandemic, are routinely suggested as responsible agents. However, CAP due to atypical bacteria may represent up to 44% of all CAP. Viral CAP is considered less severe than the usual bacterial ones, although 25% of them warrant hospitalization and 15% result in severe sepsis. Even though L. pneumophila is the most frequently atypical pathogen involved in severe cases, Mycoplasma pneumoniae may be responsible for multiorgan failure. To date, tools including detection of Legionella antigen in urine and Mycoplasma using polymerase chain reaction (PCR) allow rapid and accurate diagnosis. The treatment is based on macrolides and fluoroquinolones that can be associated in severe Legionnaire diseases. The presence of virus in CAP, either alone or in association with bacteria, has been demonstrated using molecular biology tests. These techniques also allowed the identification of several new viruses in CAP. However, the exact role of these detected viruses in CAP as well as the efficiency of antiviral therapy still represent major unsolved concerns."
5742,Grippe A (H1N1),
5743,Grippe A (H1N1) en réanimation,
5744,Grippe A (H1N1): donn’ees des r’eseaux,
5745,ECMO veinoveineuse,
5746,Insuffisance respiratoire aiguë : terrains particuliers,
5747,"Postępy w rozpoznawaniu, diagnostyce laboratoryjnej i leczeniu chorób zakaźnych w ciągu stulecia 1908–2008()",
5748,"The prevention and control of nosocomial infections: it is time for renewed emphasis and efforts: Proceedings of the 7th international BODE hygiene days, 15–17 May 2003, Tarragona (Barcelona), Spain",
5749,Emergency department dental care,
5750,LB-S&T-36 RECOVERY FROM NEUROLOGIC IMPAIRMENT IN MURINE MODEL OF CORONAVIRUS-INDUCED DEMYELINATION DOES NOT DIRECTLY CORRELATE WITH IMPROVEMENT OF NEUROGENIC BLADDER DYSFUNCTION: LONG-TERM FOLLOW UP STUDY,
5751,Self assessment/CPD answers,
5752,Effects of viral respiratory infections on lung development and childhood asthma,
5753,Role of Src in VEGF mediating the activation of rabbit osteoclasts in vitro,
5754,Staphylococcal and streptococcal infections,
5755,Community Acquired Respiratory Viral Infections (CARV) in Patients with Acute Leukemia and Hematopoietic Stem Cell Transplant (HSCT) Recipients,
5756,OR.18. VLA-4-Dependent Recruitment of Effector Memory CD8+T Lymphocytes into the Central Nervous System,
5757,Emerging infections and their causative agents,
5758,The role of the nervous system in rhinitis,
5759,The improvement of porcine epidemic diarrhea vaccine production by stimulating agents,
5760,Infectious complications following Venetoclax-Proteasome Inhibitor based regimens in relapsed myeloma: a single center retrospective analysis,
5761,"Travel Medicine, Check Program of Self Assessment Unit 387, Vol. 2; Bruce Short (Ed.), 1st ed.; The Royal Australian College of General Practitioners, South Melbourne, May 2004, 33 pages, Paperback, ISSN 0812-9630",
5762,An Informal Discussion of Emergency Nurses' Current Clinical Practice: What's New and What Works,
5763,An informal discussion ofemergency nurses' current clinical practice: What's new and what works()()(),
5764,One-Teaming:: Gaining a Competitive Edge through Rapid Team Formation and Deployment,
5765,Beyond Our Pages,
5766,The diagnostic and prognostic significance of relative lymphopenia in adult patients with influenza A,
5767,This Month in AJP,The following highlights summarize research articles that are published in the current issue of The American Journal of Pathology.
5768,"SUBJECT INDEX: VOLUME 134, 2003",
5769,"AUTHOR INDEX, volumes 123-130",
5770,J. Virol. Methods: Erratum to “Detection of human coronavirus 229E-specific antibodies using recombinant fusion proteins” [55 (1995) 175],
5771,Human adenoidal organ culture: A model to study nontypable haemophilus influenzae (NTHI) and other bacterial interactions with nasopharyngeal mucosa—implications in otitis media : Bernstein J.M.; Hard R.; Cui Z.D.; Nobuo S.; Fisher J.; Ogra P.L.OTolaryngol. Head Neck Surg. (1990) 103/5 I (784–791),
5772,T-lymphocyte subset abnormalities in the Guillain-Barré syndrome,
5773,"Cumulative Contents, volumes 123-130",
5774,Antigen presentation by human autoreactive PLP specific T-cell clones,
5775,"AAVI/ACVM Symposium—Mucosal Infection and Immunity: Sunday November 13, 1994 (1 p.m. to 5 p.m.) Gold Room, Ramanda Congress Hotel Chicago, IL, USA",
5776,Cytokines,
5777,Phenotypic and functional properties of CD8(+) T-lymphocytes from the CNS of rats with coronavirus-induced encephalomyelitis,
5778,Author index (vol. 12),
5779,Mucosal immunity,
5780,Corrigendum to “Concentration and detection of SARS coronavirus in sewage from Xiao Tang Shan Hospital and the 309th Hospital” [J. Virol. Methods 128 (2005) 156–161],
5781,"Microglia reaction on the neurotoxic effect of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in the nigrostriatal pathway in mice",
5782,Alterations of macrophage functions during acute murine cytomegalovirus infection,
5783,Neutrophil induced T-cell apoptosis during a viral infection,
5784,"Subject index : Veterinary Immunology and Immunopathology, volumes 26–50, 1990–1996",
5785,Astrocyte-derived TGF β is secreted during persistent coronovirus infection,
5786,Immunology of viral infection,
5787,Interleukin-4 enhances in vitro T-cell recruitment in glioblastoma-bearing patients,
5788,IL-2 and IL-4 gene expression in human peripheral blood and intestinal biopsies,
5789,Volume 127 - Contents,
5790,Virus-induced type-1 cytokine response in IL-12 deficient mice,
5791,Influence of MHC class I and class II (mis)matching between donor and recipient on the cytomegalovirus induced accelerated graft arterioscierosis in a rat aorta transplant model,
5792,Lymphoid architecture and distribution of HIV-1 in chronic HIV-1 infected chimpanzees,
5793,Mitogenetic effect of saliva to peripheral lymphocytes in patients with oral cancer and chronic nasopharyngeal infections,
5794,CTLA4-Ig treatment prevents murine experimental autoimmune encephalomyelitis,
5795,Cytokine gene expression in mucosal T lymphocyte populations,
5796,A functional interleukin-1 type 1 receptor on rat brain endothelial cells,
5797,Attenuated recombinant Bordetella pertussis as live vaccines for the protection against homologous and heterologous diseases,
5798,TGEV-specific IgA at different mucosae following infection of pigs with transmissible gastroenteritis virus or the antigenically related porcine respiratory coronavirus(),
5799,The signal sequence of lymphocytic choriomeningitis virus contains an immuno-dominant CD8(+) cytotoxic T cell epitope that is restricted by both H-2D(b) and H-2K(b) molecules,
5800,Alterations in RSV induced pulmonary illness due to mutations in the attachment protein G,
5801,"ISNI 2010 Abstracts: Tuesday October 26(th), 2010 10th Course of the European School of Neuroimmunology",
5802,Enteroviral infections and idiopathic dilated cardiomyopathy: is there a causal relationship?,
5803,Erkrankungen der Atemwege und der Lunge,"Der italienische Arzt Girolamo Cardano (1501–1576), der zu seiner Zeit als einer der größten Gelehrten und Ärzte in ganz Europa galt, wurde im Jahre 1552 von John Hamilton, dem Erzbischof von St. Andrews in Edinburgh, zur Konsultation eingeladen. Hamilton, der Bruder des Regenten von Schottland, litt seit mehreren Jahren an Husten, Dyspnoe und Expektoration, die nach Ansicht der königlichen Leibärzte von einem kalten und feuchten Hirn herrührten, in dem sich durch Destillation Phlegma anhäufte, das anschließend durch die Luftröhre in die Lunge absank."
5804,NHG-Standaard Influenzapandemie,"Deze standaard is opgesteld op verzoek van het ministerie van Volksgezondheid, Welzijn en Sport. Zij geeft huisartsen richtlijnen voor een vooralsnog hypothetische situatie waarin een voor mensen nieuw influenzavirus zich wereldwijd verspreidt. Omdat deze richtlijnen volledig worden bepaald door de fase waarin een influenzapandemie zich bevindt, heeft deze standaard een andere opbouw dan gebruikelijk. De paragraaf ‘Achtergronden’ is relatief uitgebreid en geeft uitleg over het ontstaan en de mogelijke gevolgen van een influenzapandemie. Daarna wordt het beleid uiteengezet in drie delen. Eerst worden de algemene principes besproken: de virusverspreiding in de populatie indammen en de gevolgen voor de individuele patiënt beperken. De daaropvolgende onderdelen beschrijven het beleid (inclusief diagnostiek) in twee verschillende situaties: een dreigende pandemie en een manifeste pandemie. Voor de uitvoerbaarheid van het geadviseerde beleid is het van groot belang dat de huisartsgeneeskundige zorg goed georganiseerd is en dat huisartsen tijdens een influenzapandemie samenwerken met andere disciplines. Het NHG heeft implementatiemateriaal ontwikkeld waarin deze aspecten aan de orde komen. Het is onvoorspelbaar hoe een nieuwe influenzapandemie zich zal ontwikkelen en wat de aard zal zijn van een nieuw pandemisch influenzavirus. Er kunnen zich ontwikkelingen voordoen die aanpassing van het geadviseerde beleid nodig maken. Deze NHGStandaard zal daarom regelmatig geactualiseerd worden op de website van het NHG (http://www.nhg.org). Voor de meest recente informatie wordt verwezen naar overheidsrichtlijnen waarop deze standaard is gebaseerd.(49)"
5805,Civil Society Involvement in National HIV/AIDS Programs,"Globally, the AIDS response relies on active participation of nongovernmental organizations (NGOs) and civil society. In China, the government is the main provider of health and social services, and the role of NGOs is more limited than in other countries. Despite this, China has opened the door for NGO participation in its AIDS response, initially because of donor pressure but increasingly due to official acknowledgment of the important role these groups play in controlling the epidemic. Since the first AIDS NGOs were established in China in the 1990s, Chinese AIDS NGOs have made unique contributions to China’s AIDS response in critical areas like access to drugs, support for treatment compliance, outreach to marginalized at-risk groups, and efforts to reduce stigma among marginalized populations. However, there has been a substantial drop-off in donor funding in recent years, and although the Chinese government has filled the funding gap, demonstrating its commitment to the sector, recent policy moves toward greater control over the work and funding of NGOs threatens their survival. Thus far, China’s AIDS response has been noteworthy, but these new NGO funding and regulatory developments pose significant challenges to the next phase of outreach, prevention, treatment, and care."
5806,Pharmacology and Pharmacotherapy,
5807,Structure and Organization of Virus Genomes,"This chapter provides an in depth study on the structure, composition, and organization of viral genomes, their classification into double stranded and single stranded DNA viruses, positive and negative stranded RNA viruses with and their genome diversity. Segmentation and re-assortment of viral genomes have been discussed along with the multipartite virus genomes. Genome details of 13 different viruses have been provided as type studies for better understanding of these topics. Concepts of viral genome evolution have also been discussed."
5808,Human Coronaviruses,"Human Coronaviruses (HCoVs) are recognised to be an important cause of the common cold. In 1962 HCoV-229E and HCoV-OC43 where first recognised, more recently HCoV-NL63 and HCoV-HKU-1 have been discovered in respiratory specimens from children and adults [3]. This protocol describes two real-time reverse-transcriptase polymerase chain reaction (RT-PCR) methods, a single target and triplex RT-PCR that identifies and differentiates HCoV infection."
5809,"Thinking like a Virus: Contagion, Postmodernist Epistemology, and the Ethics of Belief","This chapter explores how postmodernism and its rejection of grand narratives inform current epistemological theory, emerging from the study of contagion as a fluid and transgressive phenomenon. Donner proposes a drastic re-centering of epistemology around the notion of belief as well as the abandonment of truth and knowledge as possible objects of enquiry. By embracing the idea that the foundations of every belief cannot but themselves be the unjustified and unjustifiable products of an epistemic act, the result of an arbitrary cultural or individual decision, this chapter suggests a new approach to epistemology. Re-framing belief as akin to an insidious form of viral programming, lurking endemically in every belief and act, this new theory signals the invariably performative dimension of every belief and, ultimately, the necessary ethical responsibility revealed by applying epidemiological thinking to epistemological problems."
5810,Idiopathic Pulmonary Fibrosis,"Idiopathic pulmonary fibrosis (IPF) is a specific clinicopathologic ­syndrome presenting in older adults with the predominant features: dyspnea, dry cough, restrictive defect on pulmonary function tests (PFTs), hypoxemia, characteristic abnormalities on high-resolution thin section computed tomographic (HRCT) scans, usual interstitial pneumonitis (UIP) pattern on lung biopsy. Surgical lung biopsy is the gold standard of diagnosis, but the diagnosis can be established in some cases by HRCT, provided the clinical features are consistent. The cause of IPF is unknown. However, IPF is more common in adults >60 years old, smokers (current or ex), and patients with specific occupational or noxious exposures. Familial IPF, associated with several distinct genetic mutations, accounts for 1.5–3% of cases. Unfortunately, the prognosis is poor, and most patients die of respiratory failure within 3–6 years of diagnosis. However, the course is highly variable. In some patients, the disease is fulminant, progressing to lethal respiratory failure within months, whereas the course may be indolent, spanning >5 years in some patients. Therapy has not been proven to alter the course of the disease or influence mortality, but recent studies with pirfenidone and tyrosine kinase inhibitors are promising. Lung transplantation is the best therapeutic option, but is limited to selected patients with severe, life-threatening disease and no contraindications to transplant."
5811,Respiratory Tract Diseases That May Be Mistaken for Infection,"The differential diagnosis of lung infiltrates in transplant patients includes non-infectious processes that may mimic pneumonia. Hydrostatic and non-cardiogenic pulmonary edema, as well as transfusion-related lung injury, may cause bilateral airspace opacification that may be confused with an infectious process. Chemotherapeutic agents, whether administered for treatment of an underlying hematologic malignancy, for induction prior to transplant, or for the treatment of GVHD or graft rejection after transplant, may cause lung injury that in some cases may not become apparent until years later. Radiation-induced lung injury may cause a distinct pattern of lung injury, which may present months after exposure. In hematopoietic stem cell transplant patients, pulmonary diagnoses such as engraftment syndrome, idiopathic pneumonia syndrome, and diffuse alveolar hemorrhage can mimic pneumonia. After lung transplantation, infiltrates may be seen as a consequence of primary graft dysfunction or allograft rejection. Organizing pneumonia may be seen both in recipients of solid organ and hematopoietic stem cell transplants. Organizing pneumonia may be cryptogenic or associated with the use of the mTOR inhibitor sirolimus. Failure to accurately diagnose non-infectious infiltrates may lead to unnecessary antibiotic treatment and failure to address the underlying pathophysiologic process."
5812,Laboratory Test for Diagnosis of Parasitic Diseases,"Parasitic diseases generally develop chronically, and most patients experience non-specific symptoms and show unobvious physical signs. Except medical history and physical examination, the diagnosis is mainly based on the laboratory tests. The commonly applied laboratory tests for the diagnosis of parasitic diseases include etiological examination, immunological assay and molecular biological examination."
5813,Bio-Microfluidics: Overview: Coupling Biology and Fluid Physics at the Scale of Microconfinement,"With a view to establish unique interfacial synergistic interactions between two seemingly distant fields of microfluidics and biology, Bio-microfluidics has become a progressive arena of research in recent times. Bio-microfluidic tools in the format of lab-on-a-chip devices have been extensively utilized to uncouth hitherto un-illuminated regions of cellular-molecular biology, biotechnology and biomedical engineering. This chapter elaborately delineates the linking between the fundamental microscale physics and biologically relevant physico-chemical events and how, in practice, these relations are exploited in microfluidic devices. Finally, potential directions of future biomicrofluidic research are also discussed."
5814,Animal Models in Virology,"The knowledge we have gained from the study of many diseases that affect humans comes from the study of disease processes in different animal species, and this has enhanced our understanding of the pathogenesis of the disease in humans. The American Medical Association says almost every advance in medical science in the twentieth century, from antibiotics and vaccines to antidepressant drugs and organ transplants, has been achieved either directly or indirectly through the use of animals as models of disease. In this chapter a brief overview of the uses of animal models for research on human viral diseases is presented."
5815,Inflammatory Diseases of the Meninges,"Neuroimaging is of major importance in all cases of suspected infectious meningitis in order to get quick information about the extent of the disease, typical lesion patterns, and potential complications, such as hydrocephalus, involvement of the underlying brain parenchyma, or vasculitis. In bacterial meningitis, abnormal and asymmetrical enhancement of the leptomeninges and the subarachnoid space is typical. Initial neuroimaging has to rule out infectious foci of the skull base such as purulent sinusitis or mastoiditis. In patients with focal deficits or seizures, MRI is the tool of choice to diagnose vascular or septic complications. Neoplastic, viral, or fungal infections of the CNS may present with similar changes of the meninges; however, fungal meningitis normally causes a thicker and more nodular enhancement. In case of basal accentuation of the leptomeningeal contrast enhancement and conspicuous signal changes in the basal cisterns, one has to consider tuberculous meningitis for differential diagnosis, especially in patients with HIV infection. Non-infectious causes of meningeal enhancement comprise several primary and secondary tumors (e.g., CNS lymphoma, medulloblastoma, or breast cancer), granulomatous diseases, and post-operative changes."
5816,Neonatologie,"Noch vor 10 Jahren war die häufigste Todesursache Frühgeborener das akute Lungenversagen. Die sensationellen Ergebnisse von Mary Ellen Avery ebneten dann den Weg für eine kausale Therapie des Atemnotsyndroms. M.E. Avery beobachtete, dass die Lungen eines verstorbenen Frühgeborenen luftleer und „schwer“ waren und kein „schäumendes Material“ („foam“)enthielten. Wiesie durch Experimente belegen konnte, fehlte diesen Lungen in der Tat eine Substanz, die die Oberflächenspannung in den Alveolen vermindert: das pulmonale Surfactant. Die 1959 publizierten Ergebnisse ihrer Untersuchungen fanden zunächst nicht die ihnen gebührende Aufmerksamkeit. Um die weitere Resonanz auf ihre Entdeckung zu beschreiben, verweist M.E. Avery gerne auf den deutschen Philosophen Schopenhauer. Dieser hatte erkannt, dass sich neues Wissen in 3 Phasen verbreitet: Die 1. Phase, in der neue Ergebnisse bekannt gegeben werden, wird meist ignoriert. In der 2. Phase rufen die inzwischen von anderen nicht mehr zu leugnenden Ergebnisse Feindseligkeiten hervor, in der 3. und letzten Phase besteht eine generelle Übereinstimmung darüber, dass man schon immervon dieser Tatsacheausgegangen sei.(CPS)"
5817,Revolutionary Struggle for Existence: Introduction to Four Intriguing Puzzles in Virus Research,"Cellular life is immersed into an ocean of viruses. Virosphere forms the shadow of this cell-based tree of life: completely dependent on the tree for existence, yet, the tree is equally unable to escape its ever evolving companion. How important role has the shadow played in the evolution of life? Is it a mere ethereal partner or a constitutive factor? In this chapter four puzzles in virus research are taken under the scope in order to probe some of the intriguing ways by which viruses can help us understand life on Earth. These puzzles consider the origin of genetic information in viruses, viruses as symbiotic partners, the structural diversity of viruses and the role of viruses in the origin of cellular life. More than providing answers, this introduction exemplifies how viruses can be approached from various angles and how each of the angles can open up new ways to appreciate their potential contributions to life."
5818,Viroporins,"Virus encoded ion channels, termed viroporins, are expressed by a diverse set of viruses and have been found to target nearly every host cell membrane and compartment, including endocytic/exocytic vesicles, ER, mitochondria, Golgi, and the plasma membrane. Viroporins are generally very small (<100 amino acids) integral membrane proteins that share common structure motifs (conserved cluster of basic residues adjacent to an amphipathic alpha-helix) but only limited sequence homology between viruses. Ion channel activity of viroporins is either required for replication or greatly enhances replication and pathogenesis. Channel characteristics have been investigated using standard electrophysiological techniques, including planar lipid bilayer, liposome patch clamp or whole-cell voltage clamp. In general, viroporins are voltage-independent non-specific monovalent cation channels, with the exception of the influenza A virus M2 channel that forms a highly specific proton channel due to a conserved HXXXW motif. Viroporin channel currents range between highly variable (‘burst-like’) fluctuations to well resolved unitary (‘square-top’) transitions, and emerging data indicates the quality of channel activity is influenced by many factors, including viroporin synthesis/solubilization, the lipid environment and the ionic composition of the buffers, as well as intrinsic differences between the viroporins themselves. Compounds that block viroporin channel activity are effective antiviral drugs both in vitro and in vivo. Surprisingly distinct viroporins are inhibited by the same compounds (e.g., amantadines and amiloride derivatives), despite wide sequence divergence, raising the possibility of broadly acting antiviral drugs that target viroporins. Electrophysiology of viroporins will continue to play a critical role in elucidating the functional roles viroporins play in pathogenesis and to develop new drugs to combat viroporin-encoding pathogens."
5819,Special Considerations in Preschool Age,"The diagnosis of asthma can be particularly difficult in young children, in whom wheezing is not always synonym with asthma. It is also difficult to predict which preschool children with wheeze will go on to be true asthmatics. In this chapter, we will characterize preschool wheezing and asthma and discuss early risk factors for the development of severe asthma. We will also review risk factors for severe acute wheezing in young children. Finally, we will describe the natural history and prognosis of wheezing and some of the attempts at early identification of children who will develop severe asthma."
5820,Interpretation and Relevance of Advanced Technique Results,"Advanced techniques in the field of diagnostic microbiology have made amazing progress over the past two decades due largely to a technological revolution in the molecular aspects of microbiology [1, 2]. In particular, rapid molecular methods for nucleic acid amplification and characterization combined with automation and user-friendly software have significantly broadened the diagnostic capabilities of modern clinical microbiology laboratories. Molecular methods such as nucleic acid amplification tests (NAATs) rapidly are being developed and introduced in the clinical laboratory setting. Indeed, every section of the clinical microbiology laboratory, including bacteriology, mycology, mycobacteriology, parasitology, and virology, have benefited from these advanced techniques. Because of the rapid development and adaptation of these molecular techniques, the interpretation and relevance of the results produced by such molecular methods has lagged somewhat behind. The purpose of this chapter is to review and discuss the interpretation and relevance of results produced by these advanced molecular techniques. Moreover, this chapter will address the “myths” of NAATs, as these myths can markedly influence the interpretation and relevance of these results."
5821,Swine and Avian Influenza Outbreaks in Recent Times,"Influenza A is a zoonotic virus and wild waterfowls are the main reservoir of avian influenza viruses, which are precursors of human influenza A viruses. Through mutations and gene reassortment, some strains of avian influenza viruses establish stable lineages in poultry species, pigs, horses, and humans. The first zoonotic influenza pandemic of the twenty-first century, the swine H1N1 pandemic of 2009, originated from Mexico, and fortunately the virus was only of modest virulence. However, lessons have been learned on the shortcomings of the global preparedness for influenza pandemic, and this should be considered as a valuable experience for the preparation of the next major outbreak. Of more concern is the emergence of the highly pathogenic avian influenza A [H5N1], ongoing since 1996, and the low pathogenic avian influenza A [H7N9], since 2013, which have crossed the species barrier to humans in China. Risks of a H5N1 pandemic appear to be receding with declining human cases, and the H7N9 influenza virus is now the leading candidate as the next pandemic influenza virus. However, influenza pandemics are unpredictable in their timing, specific strain of virus, and origin. Most experts predict that the next influenza pandemic will arise from Asia, especially China, and will be directly of avian origin. Continued influenza surveillance in animals and humans globally with prompt reporting to the WHO and the World Animal Health Organization with sharing of data promptly between countries is essential. Long-term solutions to prevent cross-species transmission of zoonotic influenza viruses to humans and development of more effective, longer-lasting vaccines against emerging avian influenza viruses are needed. Currently there is no evidence of an impending zoonotic or avian influenza pandemic, and the viruses of interest, H5N1 and H7N9 avian influenza A viruses, have not mutated to allow for easy transmission to humans nor human to human."
5822,Alveolar Hemorrhage,Diffuse alveolar hemorrhage (DAH) is a clinical syndrome characterized by generalized intra-alveolar bleeding originating from the pulmonary microcirculation. The finding of DAH carries an extended differential diagnosis and may be associated with a number of histopathologic patterns. The prompt recognition and diagnosis of DAH is of critical importance to the practicing clinician as accurate diagnosis and prompt initiation of therapy may dramatically improve patient outcomes. This chapter reviews the diagnosis and management of diffuse alveolar hemorrhage.
5823,Multidetektor-CT-Diagnostik der infektiösen Lungenerkrankungen,Die Thorax-Übersichtsaufnahme ist aufgrund der VerfÜgbarkeit und der exzellenten Kosten-Nutzen-Relation die häufigste verwendete Untersuchungsmethode in der Diagnostik der infektiösen Lungenerkrankungen. Allerdings ist ihre Zuverlässigkeit durch eine große Interobserver-Variabilität in der radiologischen Interpretation limitiert [1]. Die Rolle der Computertomographie und der High-Resolution-CT (HRCT) ist aufgrund der Überlegenen Detektion und Charakterisation pulmonaler Infiltrate gut etabliert.
5824,Eukaryote Genomes,"General overviews of eukaryote genomes are first discussed, including organelle genomes, introns, and junk DNAs. We then discuss the evolutionary features of eukaryote genomes, such as genome duplication, C-value paradox, and the relationship between genome size and mutation rates. Genomes of multicellular organisms, plants, fungi, and animals are then briefly discussed."
5825,Weibliche und männliche Fertilitätsstörungen und Risiken der assistierten Fertilisation,Ca. 10–15% der Paare im reproduktionsfähigen Alter bleiben ungewollt kinderlos. Der Anteil steigt tendentiell durch den zunehmend „späten Kinderwunsch“. Das durchschnittliche Alter der Erstgebärenden hat sich u.a. aus Gründen der Ausbildungszeit und Berufstätigkeit der Frau zwischen 1970 und 2000 vom 24. auf das 30. Lebensjahr verschoben. Eine gewollte Kinderlosigkeit kommt in ca. 10% der Ehen vor.
5826,Litigation in Infections of Obstetrics and Gynecology,"A 28-year-old female Native American Indian, in her third trimester of pregnancy (34 weeks), presented to an isolated, stand-alone medical center serving the local community (Indian Reservation) at 6 p.m. on a Sunday evening. This center serves the dual purpose of medical clinic and emergency facility. Available teleconsultation and transportation to a tertiary care center via air ambulance were accessible 24 h/day. Normally, air ambulance transfer to a distant tertiary care hospital can be accomplished within 3–4 h after notification by phone."
5827,Corticosteroidi,"I corticosteroidi sono ormoni secreti dalla porzione corticale del surrene in seguito a stimolazione ipofisaria mediata dall’ormone adrenocorticotropo (ACTH). Sapendo che la surrenale è l’organo per eccellenza che controlla l’omeostasi dell’organismo, si evince come gli effetti dei cortisonici siano importanti e numerosi. Essi influenzano il metabolismo glucidico, lipidico e proteico, il sistema immunitario, il bilancio idroelettrolitico, le funzioni del sistema cardiovascolare, del rene, del sistema nervoso e del tessuto muscolare. Inoltre rendono l’organismo capace di resistere a numerosi stimoli nocivi, ai cambiamenti ambientali e agli eventi stressanti. Il cortisolo rappresenta il glucocorticoide fisiologico, ma alcune modificazioni della sua struttura hanno portato alla sintesi di molte molecole, che possiedono effetti farmacologici e durata di azione diversificati rispetto al composto di base."
5828,Risks and Disasters,
5829,Mechanism-based Screening for Cancer Therapeutics with Examples from the Discovery of Marine Natural Product-based HIF-1 Inhibitors,"Recent advances in cancer genetics combined with an increasing number of new methods in molecular and cell biology provide exciting new antitumor drug targets and a wide array of means to design bioassay systems for the discovery of novel cancer chemotherapeutics. Marine natural products continue to play a vital role in molecular-targeted antitumor drug discovery. Although most recognize the critical and expanding role mechanism-based antitumor bioassays play in modern anticancer drug discovery, few natural products chemists have specific training in bioassay technology. Critical bioassay development factors are outlined and introduced at a level intended to provide a basic understanding to a general audience. These include molecular target identification, antitumor target validation, selection of assayable biochemical processes, data acquisition methods, experimental controls, bioassay validation and statistical methods, experimental artifacts, active compound identification, and the dereplication of nuisance compounds. Marine natural products have been identified that inhibit the activation of the anticancer drug target hypoxia-inducible factor-1 (HIF-1). Bioassay systems and recent results from marine HIF-1 inhibitor discovery programs are used to illustrate important factors that must be considered when using molecular-targeted antitumor bioassay methods."
5830,Evolution in Lateral Flow–Based Immunoassay Systems,
5831,"Coronavirus, humanpathogenes","Humanes Coronavirus, Gruppe 1 Coronavirus"
5832,Myokarditis,
5833,Local Angiotensin Generation and AT(2) Receptor Activation,
5834,Neurologic Implications of Critical Illness and Organ Dysfunction,"Critical illness has consequences for the nervous system. Patients experiencing critical illness are at risk for common global neurologic disturbances, such as delirium, long-term cognitive dysfunction, ICU-acquired weakness, sleep disturbances, recurrent seizures, and coma. In addition, complications related to specific organ dysfunction may be anticipated. Cardiovascular disease presents the possibility for CNS injury after cardiac arrest, sequelae of endocarditis, aberrancies of blood flow autoregulation, and malperfusion. Respiratory disease is known to cause short-term effects of hypoxia and long-term effects after ARDS. Sepsis encephalopathy and sickness behavior syndrome are early signs of infection in patients. In addition, commonly encountered organ dysfunction including uremia, hepatic failure, endocrine, and metabolic disturbances present with neurologic findings which may manifest in the critically ill patient as well."
5835,The Realization Path of Network Security Technology Under Big Data and Cloud Computing,"This paper studies the cloud and big data technology based on the characters of network security, including virus invasion, data storage, system vulnerabilities, network management etc. It analyzes some key network security problems in the current cloud and big data network. Above all, this paper puts forward technical ways of achieving network security. Cloud computing is a service that based on the increased usage and delivery of the internet related services, it promotes the rapidly development of the big data information processing technology, improves the processing and management abilities of big data information. With tie rapid development of computer technology, big data technology brings not only huge economic benefits, but the evolution of social productivity. However, serials of safety problems appeared. How to increase network security has been become the key point. This paper analyzes and discusses the technical ways of achieving network security."
5836,Modeling Evolutionary Dynamics of HIV Infection,"We have modelled the within-patient evolutionary process during HIV infection. We have studied viral evolution at population level (competition on the same receptor) and at species level (competitions on different receptors). During the HIV infection, several mutants of the virus arise, which are able to use different chemokine receptors, in particular the CCR5 and CXCR4 coreceptors (termed R5 and X4 phenotypes, respectively). Phylogenetic inference of chemokine receptors suggests that virus mutational pathways may generate R5 variants able to interact with a wide range of chemokine receptors different from CXCR4. Using the chemokine tree topology as conceptual framework for HIV viral speciation, we present a model of viral phenotypic mutations from R5 to X4 strains which reflect HIV late infection dynamics. Our model investigates the action of Tumor Necrosis Factor in AIDS progression and makes suggestions on better design of HAART therapy."
5837,Analysis of Infectious Disease Data Based on Evolutionary Computation,"An international cooperative research project on intelligence and security informatics (ISI) was initialized in 2005 with funding support by the Chinese Academy of Sciences. This abstract summarizes an ongoing study on ISI data analysis using evolutionary computation methods, conducted by the Chinese team of this international project."
5838,"Urbanization and Infectious Diseases: General Principles, Historical Perspectives, and Contemporary Challenges","In 2009, a major demographic line was crossed: for the first time in history, the majority of the world population lived in cities rather than in towns and countryside (Fig. 4.1). This shift has been occurring over the past 100 years, with the most rapid rate of urban growth occurring over in the latter half of the twentieth century. Urban centers in the more developed regions of the world (i.e., North America, Australia, New Zealand, and Europe) experienced earlier growth in the 1920s–1950s, and since then, the rapid rate of urban growth has been concentrated in the cities and towns of developing nations [1]."
5839,"Detection, Occurence And Isolation","Lectins are ubiquitous in nature, and are found in all classes of organism. They are easy to detect and often to isolate. In addition, many are available from commercial suppliers. They are now obtainable also by recombinant techniques. The classic, and still simplest, way to detect the presence of a lectin in a biological material is to prepare an extract from the material and examine its ability to agglutinate erythrocytes (Fig. 3.1) (Rüdiger, 1993). A more refined screening procedure is based on the ability of these proteins to precipitate polysaccharides (Goldstein, 1976) (Fig. 3.2) or glycoproteins. If a positive result is obtained, it is essential to show that the agglutination or precipitation is specifically inhibited by mono- or oligosaccharides, i.e., it is sugar specific (Fig. 3.1). Hemagglutination is commonly assayed by the serial dilution technique using erythrocytes from humans or rabbits. Occasionally erythrocytes that have been treated with trypsin or sialidase are employed, since such cells are often more sensitive to agglutination than the untreated cells (Fig. 3.3). Hemagglutination also serves to monitor and quantify the activity of lectins in the course of purification. Because of the wide use of the agglutination reaction, it deserves some comments (Lis & Sharon, 1986). For agglutination to occur, the lectin must bind to the cells and form cross-bridges between them. There is however no simple relation between the amount of lectin bound and agglutination. Cases are even known where considerable amounts of lectin are bound to cells, without causing agglutination. This is because agglutination is affected by many factors, among them accessibility of receptor sites, membrane fluidity and metabolic state of the cells. It is also influenced by external conditions of the assay, such as temperature, cell concentration, mixing and so on. The relative contribution of the different factors depends on both the lectin and the cells examined. When agglutination does occur and it is inhibited by monoor oligosaccharides, it serves as an indication that carbohydrate structures for which the lectin is specific are present on the surface of the cell. Additional information on the nature of the receptors may be obtained with erythrocytes pretreated with enzymes, in particular glycosidases, or with sugar-modifying reagents, such as periodate. Agglutination with lectins is also of use in following changes on cell surfaces during physiological and pathological processes."
5840,Membrane Transport,Every living cell has to exchange molecules across the membrane for cellular functions. The hydrophobic or lipophilic molecules do not require energy for crossing the membrane. They can diffuse freely from higher to lower concentration till equilibrium is established. This process is called passive transport or diffusion.
5841,Event Relationship Analysis for Temporal Event Search,"There are many news articles about events reported on the Web daily, and people are getting more and more used to reading news articles online to know and understand what events happened. For an event, (which may consist of several component events, i.e., episodes), people are often interested in the whole picture of its evolution and development along a time line. This calls for modeling the dependent relationships between component events. Further, people may also be interested in component events which play important roles in the event evolution or development. To satisfy the user needs in finding and understanding the whole picture of an event effectively and efficiently, we formalize in this paper the problem of temporal event search and propose a framework of event relationship analysis for search events based on user queries. We define three kinds of event relationships which are temporal relationship, content dependence relationship, and event reference relationship for identifying to what an extent a component event is dependent on another component event in the evolution of a target event (i.e., query event). Experiments conducted on a real data set show that our method outperforms a number of baseline methods."
5842,The Future of Mesothelioma Research: Basic Science Research,"Our current understanding of mesothelioma in terms of disease induction, development, and treatment is underpinned by decades of basic laboratory science. In this chapter, we discuss the tools that have been developed to aid our understanding of mesothelioma such as cell lines and animal models. We then go on to detail the current use and understanding of conventional therapies for mesothelioma, e.g. chemotherapy, surgery, and radiotherapy, plus their mechanisms of action, and why they may be ineffective. Finally, we discuss a range of newer treatments that are either undergoing clinical trials or are still in the earlier stages of preclinical investigation. These include a growing number of immunotherapies (e.g. checkpoint inhibitors), plus targeted therapies, the search for clinical biomarkers to predict whether patients with mesothelioma might respond to particular treatments, and combined therapies where conventional treatments may be added to newer drugs. The strategy of repositioning existing drugs, approved for other diseases, to treat mesothelioma is also discussed."
5843,A Cognitive-Behavioral Perspective,
5844,Antibody-Dependent Enhancement of Viral Infections,"Antiviral antibodies constitute an important component of the host immune response against viral infections and serve to neutralize and reduce infectivity of the virus. However, these antibodies, intended to protect the host, may sometimes prove beneficial to the virus, by facilitating viral entry and replication in the target cell. This phenomenon, known as antibody-dependent enhancement (ADE) of infection, is a result of interaction of virus–antibody immune complexes with Fcγ and/or complement receptors on certain types of host cells and promotes viral entry into the host cells. The internalized immune complexes then modulate host immune response so as to enhance viral replication and aggravate disease severity. The possibility of induction of ADE remains a concern in the development and implementation of viral vaccines and immunotherapeutics."
5845,Treatment of Crimean-Congo Hemorrhagic Fever,"Ribavirin is a synthetic purine nucleoside analog with a modified base and D-ribose sugar, also known as virazol, first synthesized by Sidwell and colleagues in 1972 [43, 49] (Fig. 19-1). It is of particular interest, because it was the first synthetic nucleoside to exhibit broad spectrum antiviral activity, and it is one of few antiviral drugs in clinical use effective against agents other than HIV and herpesviruses [43]. It inhibits the replication of a wide range of RNA and DNA viruses in vitro, including orthomyxo, paramyxo, arena, bunya, flavi, herpes, adeno, pox, and retroviruses [49]. In current clinical practice, ribavirin is commonly used for certain viral infections (Table 19-1). Most notably, it is used in combination with interferon-α for treatment of HCV infection [66]. Ribavirin aerosol is used for treatment of pediatric infection by respiratory syncytial virus [19]. It is the only antiviral drug that could be also used in viral hemorrhagic fever syndromes. Besides Crimean- Congo hemorrhagic fever (CCHF), it is used in Lassa fever [70]. Viruses in the Bunyaviridae family are generally sensitive to ribavirin [92]. A prospective, randomized, double-blind, placebo-controlled trial of 242 patients with serologically confirmed Hantaan virus in the People’s Republic of China found a sevenfold decrease in mortality among ribavirin-treated patients [54], other studies did not confirm these benefits. Ribavirin was found to be effective against CCHF virus (CCHFV) in vitro [99, 104]."
5846,Nucleotide sugar transporters of the Golgi apparatus,"The Golgi apparatus is the major site of protein, lipid and proteoglycan glycosylation. The glycosylation enzymes, as well as kinases and sulfatases that catalyze phosphorylation and sulfation, are localized within the Golgi cisternae in characteristic distributions that frequently reflect their order in a particular pathway (Kornfeld and Kornfeld 1985; Colley 1997). The glycosyl-transferases, sulfotransferases and kinases are “transferases” that require activated donor molecules for the reactions they catalyze. For eukaryotic, fungal and protozoan glycosyltransferases these are the nucleotide sugars UDP-N-acetylglucosamine (UDP-GlcNAc), UDP-galactose (UDP-Gal), GDP-fucose (GDP-Fuc), CMP-sialicacid (CMP-Sia), UDP-glucuronicacid (UDP-GlcA), GDP-mannose (GDP-Man), and UDP-xylose (UDP-Xyl) (Hirschberg et al. 1998). For the kinases, ATP functions as the donor, while for the sulfotransferases, adenosine 3′-phosphate 5′-phosphate (PAPS) acts as the donor (Hirschberg et al. 1998). The active sites of all these enzymes are oriented towards the lumen of the Golgi cisternae. This necessitates the translocation of their donors from the cytosol into the lumenal Golgi compartments. In this chapter we will focus on the structure, function and localization of the Golgi nucleotide sugar transporters (NSTs), and highlight the diseases and developmental defects associated with defective transporters. We direct the reader to several excellent reviews on Golgi transporters for additional details and references (Hirschberg et al. 1998; Berninsone and Hirschberg 2000; Gerardy-Schahn et al. 2001; Handford et al. 2006; Caffaro and Hirschberg 2006)."
5847,Pneumonia,"Despite antibiotic therapy, pneumonia remains a significant worldwide cause of morbidity and mortality. The term pneumonia covers several distinct clinical entities, and correct classification is vital as the aetiology, infective organism, antibiotic management and outcome are determined by how and where pneumonia was contracted. Early recog-nition and appropriate treatment improve outcome. Critical care physicians must be familiar with all aspects of pneumonia, as they will be expected to advise on and manage severe community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP) and opportunistic pneumonias in immuno-compromised patients in the wards, high depend-ency units (HDUs) and intensive care units (ICUs). Differences in the recently published antibiotic guidelines between the British and American Tho-racic Societies are highlighted in this chapter."
5848,Fundamentals of Vaccine Delivery in Infectious Diseases,"Infectious diseases continue to be the major causes of illness, disability, and death. Moreover, in recent years, new infectious agents and diseases are being identified, and some diseases that were previously considered under control have reemerged. Furthermore, antimicrobial resistance has grown rapidly in a variety of hospital as well as community acquired infections. Thus, humanity still faces big challenges in the prevention and control of infectious diseases. Vaccination, generally considered to be the most effective method of preventing infectious diseases, works by presenting a foreign antigen to the immune system to evoke an immune response. The administered antigen can either be a live, but weakened, form of a pathogen (bacteria or virus), a killed or inactivated form of the pathogen, or a purified material such as a protein. However, no vaccine is completely safe; therefore, vaccine safety research and monitoring are necessary to minimize vaccine related harms. From the formulation point of view, the goal continues to be to improve the quality and global availability of vaccine delivery systems. This chapter provides an introduction to vaccine formulation, describes the delivery routes that are utilized, and discusses the factors that affect the safety and stability of a vaccine formulation."
5849,Veterinary Immunologists Meet,
5850,8 Plotselinge uitbraken,"Er is sprake van een plotselinge uitbraak van ziekte als het aantal nieuwe ziektegevallen dat men in een bepaalde situatie en in een relatief korte tijd waarneemt aanzienlijk groter is dan men zou verwachten. Eigenlijk is dit ook de definitie van een epidemie, maar toch prefereren veel epidemiologen die term voor meer grootschalige en geografisch meer uitgebreide stijgingen van de ziekte-incidentie."
5851,Progress of Research in Neonatal Sepsis,"Neonatal sepsis remains a significant global problem with little progress made despite major efforts. At present, there is a lack of an accepted international consensus on the definition, diagnosis, and treatment of neonatal sepsis; the unclear understanding of the pathogenesis of neonatal sepsis leads to blindness in treatment, which will result in an unsatisfactory therapeutic outcome. In addition, some serious diseases caused by noninfectious factors, such as trauma, stress, asphyxia, and so on, have very similar pathophysiological results with neonatal sepsis. In this review we synthesize the recent advances in definition, incidence, causative agents, risk factors, pathophysiology, clinical manifestations, and diagnosis and treatment of neonatal sepsis. Of course, there are still many challenges to neonatal sepsis in many ways."
5852,Occupational and Public Health Risks,"Symptoms reported by passengers and crewmembers on commercial aircraft are described according to individual air quality-related sources, including: (1) elevated levels of bioeffluents; (2) infectious agents; (3) extreme temperatures; (4) exhaust fumes, deicing fluid, fuel fumes, and cleaning products; (5) heated engine oil and hydraulic fluid; (6) reduced oxygen supply; (7) ozone gas; and (8) insecticides. A brief overview of the aircraft regulatory environment and available sources of data on the hazards and associated health effects is also provided."
5853,The Chemistry of Marine Sponges(∗),"Marine sponges continue to attract wide attention from marine natural product chemists and pharmacologists alike due to their remarkable diversity of bioactive compounds. Since the early days of marine natural products research in the 1960s, sponges have notoriously yielded the largest number of new metabolites reported per year compared to any other plant or animal phylum known from the marine environment. This not only reflects the remarkable productivity of sponges with regard to biosynthesis and accumulation of structurally diverse compounds but also highlights the continued interest of marine natural product researchers in this fascinating group of marine invertebrates. Among the numerous classes of natural products reported from marine sponges over the years, alkaloids, peptides, and terpenoids have attracted particularly wide attention due to their unprecedented structural features as well as their pronounced pharmacological activities which make several of these metabolites interesting candidates for drug discovery. This chapter consequently highlights several important groups of sponge-derived alkaloids, peptides, and terpenoids and describes their biological and/or pharmacological properties."
5854,Important Databases Related to Genomes,"Genome databases are the locations, which permits storing, sharing, retrieving and comparison of the information related to the genomes of various individuals and organisms. Traditionally the databases were confined to the updated information of certain vital model organisms. Rapid development of technology and high speed internet facilities have created an explosion of databases resulting in the development of specific databases of almost all model organisms and a group of organisms with a common specificity. In the present chapter, details of the databases related to the genomes of viruses, archaea, bacteria, cell organelle, invertebrates, vertebrates, plants, and human beings are provided in a table format which provides an instant information, about different databases and their URLs."
5855,An Introduction to Biotechnology,"Biotechnology is multidisciplinary field which has major impact on our lives. The technology is known since years which involves working with cells or cell-derived molecules for various applications. It has wide range of uses and is termed “technology of hope” which impact human health, well being of other life forms and our environment. It has revolutionized diagnostics and therapeutics; however, the major challenges to the human beings have been threats posed by deadly virus infections as avian flu, Chikungunya, Ebola, Influenza A, SARS, West Nile, and the latest Zika virus. Personalized medicine is increasingly recognized in healthcare system. In this chapter, the readers would understand the applications of biotechnology in human health care system. It has also impacted the environment which is loaded by toxic compounds due to human industrialization and urbanization. Bioremediation process utilizes use of natural or recombinant organisms for the cleanup of environmental toxic pollutants. The development of insect and pest resistant crops and herbicide tolerant crops has greatly reduced the environmental load of toxic insecticides and pesticides. The increase in crop productivity for solving world food and feed problem is addressed in agricultural biotechnology. The technological advancements have focused on development of alternate, renewable, and sustainable energy sources for production of biofuels. Marine biotechnology explores the products which can be obtained from aquatic organisms. As with every research area, the field of biotechnology is associated with many ethical issues and unseen fears. These are important in defining laws governing the feasibility and approval for the conduct of particular research."
5856,Diagnosis and Assessment of Microbial Infections with Host and Microbial MicroRNA Profiles,MicroRNAs (miRNAs) encoded by viral genome or host have been found participating in host-microbe interactions. Differential expression profiles of miRNAs were shown linking to specific disease pathologies which indicated its potency as diagnostic/prognostic biomarkers of infectious disease. This was emphasized by the discovery of circulating miRNAs which were found to be remarkably stable in mammalian biofluids. Standardized methods of miRNA quantification including RNA isolation should be established before they will be ready for use in clinical practice.
5857,"Acute Kidney Injury in the Tropics: Epidemiology, Presentation, Etiology, Specific Diseases, and Treatment","The characteristics of AKI are significantly influenced by the setting in which it develops. The unique characteristics in the tropical ecosystem along with the prevailing socioeconomic circumstances in the region make AKI in the tropics different regarding etiology, clinical characteristics, and outcomes. Community-acquired AKI caused by infections; animal, plant, or chemical toxins; and obstetric complications are common in the tropics, compared to predominantly hospital-acquired AKI from sepsis and diagnostic and therapeutic interventions elsewhere. It is possible to discern certain distinct “AKI syndromes” in the tropics, like febrile illness with AKI, envenomation-related AKI, and obstetric AKI, where the patients develop AKI along with a typical constellation of clinical features, allowing more specific and quick diagnostic and therapeutic approach. Changes in disease epidemiology and ongoing socioeconomic transitions in the tropics are reflected in changing epidemiology of tropical AKI. While the incidence of obstetric AKI has shown a steady decline, HIV-associated AKI emerged as a significant entity in regions where HIV was endemic in the past few decades. There is better recognition of scrub typhus as a significant contributor to AKI with availability of better diagnostic techniques, and it is well recognized that the epidemiology of AKI associated with post-infectious glomerulonephritis is different in the tropics. Rapid urbanization has made large swaths of population susceptible to emerging infections like dengue fever, with increased incidence of AKI. Climate change and scarcity of potable water are expected to pose significant challenges to kidney health in the tropics in the future. However, community-acquired AKI in the tropics also presents a unique opportunity for prevention of AKI, and attendant morbidity and mortality as most of the contributing factors can be addressed by public health interventions and innovative strategies to deliver healthcare."
5858,Current Practices for Infection Prevention in the Hospital Settings,"The principles and practices aimed at prevention and control of hospital-acquired infections are directed at various links in the chain of transmission. They include the following: (1) to contain or eliminate the reservoirs of agents and/or to curtail the persistence of agents in a specific setting, (2) to protect the host against disease caused by microorganisms, and (3) to interrupt the transmission of infection. Interventions to modify environmental reservoirs are aimed at interrupting the transmission for these inanimate environmental sources. The barriers, e.g., masks, were used to keep the smells and “contagion” away even before the germ theory of disease was conceived. The appropriate barriers now include gloves, gowns, and eye protection for blood/body fluid–borne infections and high-filtration masks for infections transmitted by droplet nuclei. The most important and effective nosocomial infection control intervention remains the routine washing of hands before, between, and after patient contact in healthcare settings. This chapter focuses on the interruption of transmission of infectious agents in the hospital setting by Standard Precautions recommended for all patients and “isolation” of patients using precautions based on known methods of transmission."
5859,Modified ELISPOT: Modifications of the Elispot Assay for T Cell Monitoring in Cancer Vaccine Trials,"The use of the IFN-γ ELISPOT assay to evaluate cellular immune responses has gained increasing popularity, especially as a surrogate measure for CTL responses. We developed and validated some modifications of the IFN-γ ELISPOT assay to optimize immunological monitoring of various cancer vaccine trials. Taking into consideration that the main mechanism of cell-mediated cytotoxicity is the release of cytolytic granules that contain, among others, cytolytic protein Granzyme B (GrB), we developed the GrB ELISPOT assay. Extensive studies demonstrated that the GrB ELISPOT assay is specific, accurately measures the rapid release of GrB, is more sensitive than the 51Cr-release assay, and that it may be successfully applied to measuring CTL precursory frequency in PBMC from cancer patients. Assuming that immunological assays that demonstrate recognition of native tumor cells (tumor-specific) may be more clinically relevant than assays that demonstrate recognition of tumor protein or peptide (antigen-specific), we developed and validated the Autologous Tumor IFN-γ ELISPOT assay using PBMC from idiotype vaccinated lymphoma patients as effectors and autologous B cell lymphoma tumor cells as targets. The precursor frequency of tumor-reactive T cells was significantly higher in the postvaccine PBMC, compared with prevaccine samples in all patients tested. Furthermore, the specificity of these T cells was established by the lack of reactivity against autologous normal B cells. These results demonstrate the feasibility of evaluating tumor-specific T cell responses when autologous, primary tumor cells are available as targets. Modifications of ELISPOT assay described in this chapter allow more comprehensive assessment of low frequency tumor-specific CTL and their specific effector functions and can provide valuable insight with regards to immune responses in cancer vaccine trials."
5860,Airway Disease,"There are few conditions in emergency medicine as potentially challenging and high risk as the acute airway obstruction. Time is often limited, the patient’s condition may be critical, and a failed airway has the potential for significant morbidity or death. Chest radiography (CXR) is useful in diagnosing and evaluating the progression of atelectasis, aspiration, pulmonary edema, pneumonia, and pleural fluid collections. Lung ultrasonography (LUS) is an excellent complementary diagnostic tool in emergency diagnosis. For patients who can tolerate lying flat for the study, thin-section multidetector computed tomography (MDCT) provides the anatomic detail that permits planning of therapy and is useful when the clinical and radiologic presentations are discrepant and the patient is not responding to therapy or in further defining a radiographic abnormality. Imaging plays a key role in the diagnosis and monitoring of bronchiectasis and the management of complications. Exacerbation of bronchiectasis can confer substantial potential morbidity, usually secondary to recurrent infection. In severe cases of bronchiectasis, massive hemoptysis can lead to death. CXR is useful as an initial screening tool and during acute exacerbations, but has limited sensitivity and specificity. Thin-section MDCT is the reference standard for diagnosis and quantification of bronchiectasis, providing detailed morphological informations. Radiologists must know various causes of bronchiectasis, including common causes, such as recurrent infection or aspiration, and uncommon causes, such as congenital immunodeficiencies and disorders of cartilage development. In industrialized countries, inhalational exposures to various toxicants are commonplace. Most acute toxic inhalations come from industries, home, and recreational sources. In addition to individual susceptibility, the characteristics of inhaled substances such as water solubility, size of substances, and chemical properties may affect disease severity as well as its location. A detailed history becomes even more important in such a patient and may help make a difference in the often chaotic setting of the emergency department. Laboratory evaluation, arterial blood gas analysis, and supportive measures, including the ABCs (airway, breathing, and circulation), may be required. Unfortunately, the varied presentations result in a nonspecific clinical syndrome and make diagnosis somewhat difficult. Despite substantial limitations, imaging can help in showing diffuse interstitial, alveolar, or mixed infiltrates, segmental consolidation, hyperinflation, pneumothorax, and pleural effusion. Thin-section MDCT can be used to further characterize lung abnormalities and continues to demonstrate previously unidentified characteristics that shape our understanding of noxious inhaled toxicant injury."
5861,RNA-Cleaving DNA Enzymes and Their Potential Therapeutic Applications as Antibacterial and Antiviral Agents,"DNA catalysts are synthetic single-stranded DNA molecules that have been identified by in vitro selection from random sequence DNA pools. The most prominent representatives of DNA catalysts (also known as DNA enzymes, deoxyribozymes, or DNAzymes) catalyze the site-specific cleavage of RNA substrates. Two distinct groups of RNA-cleaving DNA enzymes are the 10-23 and 8-17 enzymes. A typical RNA-cleaving DNA enzyme consists of a catalytic core and two short binding arms which form Watson–Crick base pairs with the RNA targets. RNA cleavage is usually achieved with the assistance of metal ions such as Mg(2+), Ca(2+), Mn(2+), Pb(2+), or Zn(2+), but several chemically modified DNA enzymes can cleave RNA in the absence of divalent metal ions. A number of studies have shown the use of 10-23 DNA enzymes for modest downregulation of therapeutically relevant RNA targets in cultured cells and in whole mammals. Here we focus on mechanistic aspects of RNA-cleaving DNA enzymes and their potential to silence therapeutically appealing viral and bacterial gene targets. We also discuss delivery options and challenges involved in DNA enzyme-based therapeutic strategies."
5862,Laboratory Test for Diagnosis of Influenza,"Laboratory tests for diagnosis of influenza include 4 aspects of examinations, virus culture and isolation, serological test, immunoassay, and molecular biological examination."
5863,Extracorporeal Membrane Oxygenation for Acute Pediatric Respiratory Failure,"The use of extracorporeal membrane oxygenation (ECMO) to support children with acute respiratory failure has steadily increased over the past several decades, with major advancements having been made in the care of these children. There are, however, many controversies regarding indications for initiating ECMO in this setting and the appropriate management strategies thereafter. Broad indications for ECMO include hypoxia, hypercarbia, and severe air leak syndrome, with hypoxia being the most common. There are many disease-specific considerations when evaluating children for ECMO, but there are currently very few, if any, absolute contraindications. Venovenous rather than veno-arterial ECMO cannulation is the preferred configuration for ECMO support of acute respiratory failure due to its superior side-effect profile. The approach to lung management on ECMO is variable and should be individualized to the patient, with the main goal of reducing the risk of VILI. ECMO is a relatively rare intervention, and there are likely a minimum number of cases per year at a given center to maintain competency. Patients who have prolonged ECMO runs (i.e., greater than 21 days) are less likely to survive, though no absolute duration of ECMO that would mandate withdrawal of ECMO support can be currently recommended."
5864,Neuromyopathies in the Critically Ill,"After studying this chapter, you should be able to: Be aware of the different neuromuscular disorders that are encountered in the ICU. Know the effects of neuromuscular dysfunction on the respiratory system. Know the proper initial evaluation and management of patients with neuromuscular dysfunction and respiratory failure. Be aware of the various therapies used to treat neuromuscular disorders that are most commonly encountered in the ICU."
5865,"Pseudoknot-Dependent Programmed —1 Ribosomal Frameshifting: Structures, Mechanisms and Models","Programmed —1 ribosomal frameshifting is a translational recoding strategy that takes place during the elongation phase of protein biosynthesis. Frameshifting occurs in response to specific signals in the mRNA; a slippery sequence, where the ribosome changes frame, and a stimulatory RNA secondary structure, usually a pseudoknot, located immediately downstream. During the frameshift the ribosome slips backwards by a single nucleotide (in the 5′-wards/—1 direction) and continues translation in the new, overlapping reading frame, generating a fusion protein composed of the products of both the original and the —1 frame coding regions. In eukaryotes, frameshifting is largely a phenomenon of virus gene expression and associated predominantly with the expression of viral replicases. Research on frameshifting impacts upon diverse topics, including the ribosomal elongation cycle, RNA structure and function, tRNA modification, virus replication, antiviral intervention, evolution and bioinformatics. This chapter focuses on the structure and function of frameshift-stimulatory RNA pseudoknots and mechanistic aspects of ribosomal frameshifting. A variety of models of the frameshifting process are discussed in the light of recent advances in our understanding of ribosome structure and the elongation cycle."
5866,Systematic Survey of Zoonotic and Sapronotic Microbial Agents,"Viruses, bacteria, fungi, protozoa, and metazoa (parasitic worms and arthropods) are among the aetiological agents of zoonoses and sapronoses. Our survey only concerns the agents of microbial diseases (i.e., not the metazoan invasions and infestations), and is arranged according to systematic position. In addition, a new zoonotic disease caused by prions – variant of Creutzfeld-Jakob disease – is included."
5867,"Viral Disease, Air Pollutants, Nanoparticles, and Asthma","Health care providers who treat patients with respiratory disease are often asked by their patients, “What caused my asthma? And what causes my asthma suddenly to become worse?” These questions have always been difficult to answer, and moving directly to a discussion of the management of asthma is a much easier road to take. In recent years, though, enough information has accumulated about the causes of asthma that one can weave a story containing useful advice that may help patients participate in the management of their disease. And there are also recent studies that can provide answers to the questions posed by physicians who have watched in puzzlement as their previously well-controlled asthma patients have spiraled rapidly out of control. This story has been growing increasingly complex, with an ever-expanding cast of players that sometimes creates a tangled web of interactions."
5868,Viral Dynamics and Mathematical Models,"Mathematical tools have been widely applied in understanding the dynamics and control of viral infections. Here we present some fundamental aspects of infection dynamics, starting with acute immunising infections as a case study for herd immunity and other important factors in the spread and control of infection. We then discuss the dynamics of infections with more complex life histories, including chronic infections, and those showing evolution for immune escape. We conclude with a discussion of important gaps in our current understanding of viral dynamics, along with future research needs."
5869,Multidrug Resistant Gram-Negative Bacteria in Community-Acquired Pneumonia,"Community-acquired pneumonia (CAP) is associated with high morbidity and mortality worldwide [1]. Although several different bacteria and respiratory viruses can be responsible for CAP, Streptococcus pneumoniae (pneumococcus) remains the most common causative pathogen. A small proportion of CAP cases are caused by Gram-negative bacteria, especially Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and Stenotrophomona maltophilia [2, 3]. The main problem concerning the treatment of Gram-negative bacterial infections is their related antibiotic resistance, reported as multidrug resistant (MDR = resistant to at least one agent in three or more groups of antibiotics), extensively drug resistant (XDR = resistant to at least one agent in all but two or fewer groups of antibiotics) and pan-drug resistant (PDR = resistant to all groups of antibiotics) [4]. This makes the clinical management of pneumonia caused by such pathogens a challenge for physicians. Taking into account the clinical severity that may be associated with CAP caused by Gram-negative bacteria (respiratory failure, bacteremia, shock, acute respiratory distress syndrome [ARDS]) the magnitude of the global health problem is tremendous."
5870,The Many Roads to an Ideal Paper-based Device,"The recent Zika and Ebola virus outbreaks highlight the need for low-cost diagnostics that can be rapidly deployed and used outside of established clinical infrastructure. This demand for robust point-of-care (POC) diagnostics is further driven by the increasing burden of drug-resistant diseases, concern for food and water safety, and bioterrorism. As has been discussed in previous chapters, paper-based tests provide a simple and compelling solution to such needs."
5871,Ethical and Legal Issues Impacting Migrant Health,
5872,Other Allergic Skin Disorders,"In this chapter we discuss allergic skin disorders other than atopic dermatitis (AD): the urticaria-angioedema syndrome, allergic contact dermatitis (ACD), protein contact dermatitis (PCD), phytodermatitis, allergic photodermatitis and allergic vasculitis."
5873,Rare and Emerging Viral Infections in the Transplant Population,"Viral infections account for a large proportion of emerging infectious diseases, and the agents included in this group consist of recently identified viruses as well as previously identified viruses with an apparent increase in disease incidence. In transplant recipients, this group can include viruses with no recognized pathogenicity in immunocompetent patients and those that result in atypical or more severe disease presentations in the immunocompromised host. In this chapter, we begin by discussing viral diagnostics and techniques used for viral discovery, specifically as they apply to emerging and rare infections in this patient population. Focus then shifts to specific emerging and re-emerging viruses in the transplant population, including human T-cell leukemia virus 1, rabies, lymphocytic choriomeningitis virus, human bocavirus, parvovirus 4, measles, mumps, orf, and dengue. We have also included a brief discussion on emerging viruses and virus families with few or no reported cases in transplant recipients: monkeypox, nipah and hendra, chikungunya and other alphaviruses, hantavirus and the Bunyaviridae, and filoviruses. Finally, concerns regarding infectious disease complications in xenotransplantation and the reporting of rare viral infections are addressed. With the marked increase in the number of solid organ and hematopoietic stem cell transplants performed worldwide, we expect a corresponding rise in the reports of emerging viral infections in transplant hosts, both from known viruses and those yet to be identified."
5874,Viral-associated Ventilator-associated Pneumonia,"Nosocomial pneumonia is the most commonly acquired infection in intensive care units (ICUs). Its frequency is approximately 10 cases/1000 admissions; however, the incidence may increase to 20 times that number in patients undergoing invasive mechanical ventilation [1–3]. The overall incidence of ventilator-associated pneumonia (VAP) may range between 15 % to 20 % [2–6]. This complication prolongs the length of hospital stay, increases healthcare costs and may increase mortality [4, 5, 7, 8]."
5875,Immunosenescence Modulation by Vaccination,"A decline in immune function is a hallmark of aging that leads to complicated illness from a variety of infectious diseases, cancer and other immune-mediated disorders, and may limit the ability to appropriately respond to vaccination. How vaccines might alter the senescent immune response and what are the immune correlates of protection will be addressed from the perspective of 1) stimulating a previously primed response as in the case of vaccines for seasonal influenza and herpes zoster, 2) priming the response to novel antigens such as pandemic influenza or other viruses, 3) vaccination against bacterial pathogens such as pneumococcus, and 4) altering the immune response to an endogenous protein as in the case of a vaccine against Alzheimer’s disease. In spite of the often limited efficacy of vaccines for older adults, influenza vaccination remains the only cost-saving medical intervention in this population. Thus, considerable opportunity exists to improve current vaccines and develop new vaccines as a preventive approach to a variety of diseases in older adults. Strategies for selecting appropriate immunologic targets for new vaccine development and evaluating how vaccines may alter the senescent immune response in terms of potential benefits and risks in the preclinical and clinical trial phases of vaccine development will be discussed."
5876,A Brief Comparison Between In Vivo DNA Replication and In Vitro PCR Amplification,"In principle, PCR generates large quantities of DNA from a minute amount of nucleic acid starting material using a methodology similar to (but much simpler than) that seen in living cells. For living cells, in vivo DNA synthesis is dependent upon a well defined but complex set of enzymes and co-factors, which have evolved to act in a concerted fashion during the synthetic phase (S-phase) of the cell cycle. In comparison, PCR facilitates in vitro DNA synthesis in a much simpler fashion, making use of a smaller set of defined ingredients and reaction conditions involving relatively high temperatures. The range of factors contributing to successful PCR amplification is reviewed below."
5877,Lung Defenses,"We breathe to live, but the air we breathe carries many potentially harmful agents. To protect us against these constant challenges, our lungs have defenses that are remarkably effective, biologically complex, and scientifically fascinating. It is not hyperbole to say that the pathogenesis of most lung disease begins with a breach of these defenses. This chapter surveys these normal lung defense systems. Just as this text assumes familiarity with general pathology, we also assume knowledge of basic immunology. This chapter emphasizes the lung’s variations on themes of innate and adaptive immunity, and discusses the special role of granulomatous inflammation in lung defenses."
5878,Therapy of Ebola and Marburg virus infections,
5879,Infection,"Community-Acquired Pneumonia (CAP) is the first leading cause of death due to infection worldwide.Many gram-positive, gram-negative bacteria, funguses and viruses can cause the infectious pulmonary disease, and the severity of pneumonia depends on the balance between the microorganism charge, the body immunity defenses and the quality of the underlying pulmonary tissue. The microorganisms may reach the lower respiratory tract from inhaled air or from infected oropharyngeal secretions. The same organism may produce several different patterns that depend on the balance between the microorganism charge and the body immunity defenses.CAP is classified into three main groups: lobar pneumonia, bronchopneumonia and interstitial pneumonia.Lobar pneumonia is characterized by the filling of alveolar spaces by edema full of white and inflammatory cells. Necrotizing pneumonia consists of a fulminant process associated with focal areas of necrosis that results in abscesses. Bronchopneumonia or lobular pneumonia, is characterized by a peribronchiolar inflammation with thickening of peripheral bronchial wall, the diffusion of inflammation to the centrilobular alveolar spaces and development of nodules.The interstitial pneumonia represents with the destruction and esfoliation of the respiratory ciliated and mucous cells. The interstitial septa, the bronchial and bronchiolar walls become thickened for the inflammation process and lymphocytes interstitial infiltrates.Chest radiography represents an important initial examination in all patients suspected of having pulmonary infection and for monitoring response to therapy.Its role is to identify the pulmonary opacities, their internal characteristics and distribution, pleural effusion and presence of other complications as abscesses and pneumothorax.High spatial CT resolution allows accurate assessment of air space inflammation.The CT findings include nodules, interlobular septal thickening, intralobular reticular opacities, ground-glass opacities, tree-in-bud pattern, lobar-segmental consolidation, lobular consolidation, abscesses, pneumatocele, pleural effusion, pericardial effusion, mediastinal and hilar lymphoadenopaties, airway dilatation and emphysema."
5880,Design Points for Negative Pressure Isolation Ward,"According to “Law of the People’s Republic of China on the Prevention and Control of Infectious Diseases” issued on December 1st in 2004, infectious diseases can be classified as the first class, the second class and the third class."
5881,Erkrankungen des Pankreas,"Leitsymptom der Pankreaserkrankungen ist der gürteiförmige Oberbauchschmerz mit Ausstrahlung in den Rücken, häufig mit Übelkeit und Erbrechen, bei chronischem Verlauf mit den Zeichen des progredienten Funktionsverlustes."
5882,Pulmonary Infections,"Pneumonia is a lung infection involving the alveoli and can be caused by a variety of microbes including bacteria, viruses, and fungi. It is the leading infectious cause of hospitalization and death in the United States [1]. In 2010, in the United States, pneumonia resulted in 1.1 million discharges from the hospital with an average length of stay of 5.2 days. Pneumonia accounted for 3.4 % of hospital deaths in 2006. In 2013 it accounted for 16.9 deaths per 100,000 population [2]. Pneumonia continues to be the leading killer of young children around the world, causing 14 % of all deaths in children ages 1 month to 5 years [3]."
5883,Considerations for the Development of Nasal Dosage Forms,"The anatomy and physiology of the nasal cavity provide unique advantages for accessing targets for local, systemic, and potentially central nervous system drug delivery. This chapter discusses these advantages and the challenges that must be overcome to reach these targets. The chapter then comprehensively reviews nasal dosage forms, analytical testing, and regulatory requirements in the context of existing nasal spray products. Since nasal sprays are moving towards being preservative-free, the chapter covers specialized methods of achieving a sterile product, namely, formulation strategies, manufacturing strategies, and the device landscape that support this upcoming platform. Finally, the chapter reviews various pathways for regulatory approval around the world, for brand and generic, with particular emphasis on the growing acceptance of in vitro data for locally acting nasal spray products."
5884,The Interaction Between Nutrition and Inflammatory Stress Throughout the Life Cycle,"The human race inhabits a world in which it is surrounded by a myriad of different microorganisms—yeasts, bacteria, protozoa, and viruses. Most of these are benign, and some, such as the normal gut flora, play an important part in promoting health via the synthesis of vitamins and stimulation of normal function of gut epithelia. Approximately 0.1% of microbes in our environment have catastrophic effects if they penetrate the epithelial surfaces of the body (Bryson, 2003). History reveals many instances in which armies have been defeated and civilizations have collapsed because of encounters between humans and such microorganisms (Diamond, 1999)."
5885,Lung Disease in Older Patients with HIV,"Successful treatment of HIV with combination antiretroviral therapy (ART) has resulted in an aging HIV-infected population. As HIV-infected patients are living longer, noninfectious pulmonary diseases are becoming increasingly prevalent with a proportional decline in the incidence of opportunistic infections (OIs). Pulmonary OIs such as Pneumocystis jirovecii pneumonia (PCP) and tuberculosis are still responsible for a significant proportion of pulmonary diseases in HIV-infected patients. However, bacterial pneumonia (BP) and noninfectious pulmonary diseases such as chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary arterial hypertension (PAH), and interstitial lung disease (ILD) account for a growing number of pulmonary diseases in aging HIV-infected patients. The purpose of this chapter is to discuss the spectrum and management of pulmonary diseases in aging HIV-infected patients, although limited data exists to guide management of many noninfectious pulmonary diseases in HIV-infected patients. In the absence of such data, treatment of lung diseases in HIV-infected patients should generally follow guidelines for management established in HIV-uninfected patients."
5886,Infectious Diseases,"Livelihoods play a role in the infectious diseases that a population can be exposed to and the risk attached to it. Poor living conditions, lack of income and other basic amenities such as safe drinking water and toilets, poor healthcare facilities and low literacy levels have contributed to the spread of infectious diseases in rural communities. Depending on the mode of transmission these diseases can spread from one person, to communities, to a country, across borders and a whole region. This makes infectious diseases one of the most dangerous threats to the global population. There are still millions of people affected by infectious diseases worldwide, most of which live in poor rural regions of developing countries. These rural communities, which depend on livelihoods such as farming, fishing, livestock rearing, hunting and so on, are vulnerable to infectious diseases and their livelihoods are affected by the impact of these diseases."
5887,Multiple Sklerose — eine neuroimmunendokrine Erkrankung,"Die Multiple Sklerose (MS) ist eine chronische, entzündlich-demyelinisierende Erkrankung des Zentralnervensystems (ZNS), betrifft also Gehirn und Rückenmark, wobei heute eine autoimmune Ätiologie allgemein angenommen wird. Sie ist die häufigste Entmarkungserkrankung des ZNS in Nordeuropa und Nordamerika (Prävalenz 1:1000) und die häufigste chronisch-neurologische Erkrankung, die bei jungen Erwachsenen zu bleibender Behinderung führt."
5888,Infections in Liver Transplantation,"Liver transplantation has become an important treatment modality for patients with end-stage liver disease/cirrhosis, acute liver failure, and hepatocellular carcinoma. Although surgical techniques and immunosuppressive regimens for liver transplantation have improved significantly over the past 20 years, infectious complications continue to contribute to the morbidity and mortality in this patient population. The use of standardized screening protocols for both donors and recipients, coupled with targeted prophylaxis against specific pathogens, has helped to mitigate the risk of infection in liver transplant recipients. Patients with chronic liver disease and cirrhosis have immunological deficits that place them at increased risk for infection while awaiting liver transplantation. The patient undergoing liver transplantation is prone to develop healthcare-acquired infections due to multidrug-resistant organisms that could potentially affect patient outcomes after transplantation. The complex nature of liver transplant surgery that involves multiple vascular and hepatobiliary anastomoses further increases the risk of infection after liver transplantation. During the early post-transplantation period, healthcare-acquired bacterial and fungal infections are the most common types of infection encountered in liver transplant recipients. The period of maximal immunosuppression that occurs at 1–6 months after transplantation can be complicated by opportunistic infections due to both primary infection and reactivation of latent infection. Severe community-acquired infections can complicate the course of liver transplantation beyond 12 months after transplant surgery. This chapter provides an overview of liver transplantation including indications, donor-recipient selection criteria, surgical procedures, and immunosuppressive therapies. A focus on infections in patients with chronic liver disease/cirrhosis and an overview of the specific infectious complications in liver transplant recipients are presented."
5889,Human Adenovirus Type 12: Crossing Species Barriers to Immortalize the Viral Genome,"When viruses cross species barriers, they often change their biological and pathogenetic properties. In the author's laboratory the nonproductive interaction of Syrian hamster cells with human adenovirus type 12 (Ad12) has been studied. Ad12 induces undifferentiated tumors in newborn hamsters (Mesocricetus auratus) at high frequency. Ad12 inefficiently enters hamster (BHK21) cells, and only small amounts of viral DNA reach the nucleus. Viral DNA replication and late transcription are blocked. In Ad12-induced tumor cells, multiple copies of viral DNA are chromosomally integrated. The integrated viral DNA becomes de novo methylated. Cellular DNA methylation and transcription patterns in Ad12-transformed cells and in Ad12- induced tumor cells are altered. These changes may be related to the oncogenic potential of Ad12 in hamsters. In this chapter, concepts and techniques for the study of the Ad12-hamster cell system are summarized."
5890,"Uncharakteristisches Fieber (UF), afebrile Allgemeinreaktion (AFAR), Luftwegekatatthe, Tonsillitis","uncharakteristisches Fieber (UF), gleichartige, jedoch afebrile Verläufe (afebrile Allgemeinreaktion/AFAR), Angina tonsillaris (die häufig genug das Symptom einer viralen Allgemeinerkrankung darstellt), sowie; verschiedene fieberfreie Katarrhe der Luftwege (◘ Tabelle 1.1)."
5891,The Role of Immunity and Inflammation in IPF Pathogenesis,"IPF is thought to be a consequence of repetitive micro-injury to ageing alveolar epithelium by factors including tobacco smoke, environmental exposures, microbial colonisation/infection, microaspiration, endoplasmic reticulum stress and oxidative stress, with resultant aberrant wound healing. Though partially effective antifibrotic therapies have focused attention away from older inflammation-based hypotheses for IPF pathogenesis, innate and adaptive immune cells and processes may play roles potentially in initiation and/or disease progression in IPF and/or in IPF acute exacerbations, based on multiple lines of evidence. Members of the Toll-like family of innate immune receptors have been implicated in IPF pathogenesis, including a potential modulatory role for the lung microbiome. A variety of chemokines are associated with the presence of IPF, and an imbalance of angiogenic chemokines has been linked to vascular remodelling in the disease. Subsets of circulating monocytes, including fibrocytes and segregated-nucleus-containing atypical monocytes (SatM), have been identified that may facilitate progression of fibrosis, and apoptosis-resistant pulmonary macrophages have been shown to demonstrate pro-fibrotic potential. Inflammatory cells that have been somewhat dismissed as irrelevant to IPF pathogenesis are being re-evaluated in light of new mechanistic data, such as activated neutrophils which release their chromatin in a process termed NETosis, which appears to mediate age-related murine lung fibrosis. A greater understanding is needed of the role of lymphoid aggregates, a histologic feature of IPF lungs found in close proximity to fibroblastic foci and highly suggestive of the presence of chronic immune responses in IPF, as are well-characterised activated circulating T lymphocytes and distinct autoantibodies that have been observed in IPF. There is a pressing need to discern whether or not the indisputably present immune dysregulation of IPF constitutes cause or effect in the ongoing search for more effective therapeutic strategies."
5892,The Role of Neuropeptide Endopeptidases in Cutaneous Immunity,"Proteolytic processing and degradation plays an important role in modulating the generation and bioactivity of neuroendocrine peptide mediators, a class of key molecules in cutaneous biology. Accordingly, the cellular localization and expression, and the molecular biology and structural properties of selected intracellular prohormone convertases and ectopically expressed zinc-binding metalloendoproteases are discussed. A special reference will be made to the physiologic and pathophysiologic significance of these endopeptidases in cutaneous immunobiology. Because of the number of pathologically relevant changes in inflammation and tumor progression that can be directly attributed to neprilysin and angiotensin-converting enzyme, a particular focus will be on the role of these enzymes in modulating innate and adaptive immune responses in the skin."
5893,Emerging Plant Viruses: a Diversity of Mechanisms and Opportunities,"Although emerging plant viruses receive much less publicity than their animal- or human-infecting cousins, they pose a serious threat to worldwide agricultural production. These viruses can be new (i.e., not previously known) or already known; however, they share the common characteristic of occupying and spreading within new niches. Factors driving the emergence of plant viruses include genetic variability in the virus, changes in agricultural practices, increases in the population and/or distribution of insect vectors and long-distance transport of plant materials. In recent years, individual as well as entire groups of viruses have emerged, and this has involved a variety of mechanism(s), depending on the virus and the environment. Here, we will discuss some of these viruses, and highlight the mechanisms that have mediated their emergence. Special emphasis is placed upon the whiteflytransmitted geminiviruses (begomoviruses) and the thrips-transmitted tosposviruses, which have emerged as major threats to crop production throughout the world. Other examples include the recent emergence of novel viruslike agents, the acquisition and role of satellite DNA or RNA molecules in emergence of plant viruses, and cases where emerging viruses have had only a transient impact. It seems clear that global movement of plant materials, expansion of agriculture and large-scale monoculture will continue to favor emergence of plant viruses. However, improved diagnostics should allow for rapid identification of emerging viruses and better understanding of viral biology. This information can be used in the development of effective management strategies, which will hopefully minimize impact on agricultural production."
5894,Using Rough Set to Find the Factors That Negate the Typical Dependency of a Decision Attribute on Some Condition Attributes,"In real world, there are a lot of knowledge such as the following: most human beings that are infected by a kind of virus suffer from a corresponding disease, but a small number human beings do not. Which are the factors that negate the effects of the virus? Standard rough set method can induce simplified rules for classification, but cannot generate this kind of knowledge directly. In this paper, we propose two algorithms to find the factors. In the first algorithm, the typical rough set method is used to generate all the variable precision rules firstly; secondly reduce attributes and generate all the non-variable precision rules; lastly compare the variable precision rules and non-variable precision rules to generate the factors that negate the variable precision rules. In the second algorithm, firstly, induce all the variable precision rules; secondly, select the examples corresponding to the variable precision rules to build decernibility matrixes; thirdly, generate the factors that negate the variable precision rules. Three experimental results show that using the two algorithms can get the same results and the computational complexity of the second algorithm is largely less than the firs one."
5895,Immunology of Norovirus Infection,"Noroviruses are the leading cause of epidemic non-bacterial gastroenteritis worldwide. Despite their discovery over three decades ago, little is known about the host immune response to norovirus infection. The purpose of this chapter is to review the field of norovirus immunology and discuss the contributions of outbreak investigations, human and animal challenge studies and population-based studies. This chapter will survey both humoral and cellular immunity as well as recent advances in norovirus vaccine development."
5896,Infection in the Hematopoietic Stem Cell Transplant Recipient,
5897,Medicinal Applications of Plant Lectins,"Plant lectins are a unique group of proteins and glycoproteins with potent biological activity and have received widespread attention for many years. They can be found in wheat, corn, tomatoes, peanuts, kidney beans, bananas, peas, lentils, soybeans, mushrooms, tubers, seeds, mistletoe and potatoes among many others. Due to their ability to bind reversibly with specific carbohydrate structures and their abundant availability, plant lectins have commonly been used as a molecular tool in various disciplines of biology and medicine. Whilst once thought of being a dietary toxin, the focus on plant lectins has since shifted to understanding the useful properties of these lectins and utilizing them in medicinal applications to advance human health. This chapter reviews the current and potential applications of plant lectins in various areas of medically related research."
5898,Ventilatory Strategy Used for Management of Acute Respiratory Failure Due to Novel Influenza A(H1N1) Infection,"The first cases of the novel influenza A(H1N1) virus were reported in April 2009, especially in Mexico and the United States [1, 2]. The disease spread rapidly, becoming a pandemic by June 2009. On August 21, 2009, a total of 177 reported cases of novel influenza 182.166 A(H1N1) infection, of which 1,799 were fatal [2]. It has been observed in animal studies that the novel influenza virus A has a high replication rate in lung tissue, with a great capacity to invade the lower respiratory tract in humans, causing especially acute fulminant respiratory failure."
5899,Viral Interactions with Glycans,"The cell surface of mammalian cells is covered with complex glycans or polysaccharides. Several viruses attach to cells via glycans present on the host cell surface. These cell surface glycans such as heparan sulfate proteoglycan enhance the infectivity of host cells. Cell surface glycans also serve as cellular receptors involved in the transmission of endocytosis-inducing signals or in the induction of fusion between viral envelope and cellular membrane for some other viruses. In contrast, viruses can use host cell functions to glycosylate viral proteins, which affects viral glycoprotein stability and function during host cell entry. Glycosylation of viral glycoproteins is also involved in viral antigenicity responsible for immune evasion by viruses. In this review, functions of glycan-mediated interactions between host cells and viruses are discussed."
5900,A Gesture-Based Door Control Using Capacitive Sensors,"In public places sanitary conditions are always of concern, particularly of surfaces that are touched by a multitude of persons, such as door handles in rest rooms. Similar issues also arise in medical facilities. Doors that open based on presence are common in environments such as shopping malls; however they are not suited for sensitive areas, such as toilet stalls. Capacitive proximity sensors detect the presence of the human body over a distance and can be unobtrusively applied in order to enable hidden gesture-based interfaces that work without touch. In this paper we present a concept for a gesture controlled automated door based on this sensor technology. We introduce the underlying technology and present the concept and electronic components used in detail. Novel interaction patterns and data processing methods allow to open, close, lock and unlock the door using simple gestures. A prototype device has been created and evaluated in a user study."
5901,Construction and Development of Ecological Aesthetics,"If we begin from the mid-20th century, the proposition of Ecological Aesthetics has been 50 years so far. All along, there have been different views on the formulation and development of ecological aesthetics."
5902,Selecting the Appropriate Funding Mechanism,
5903,Influenza A (H1N1),"In March 2009, an outbreak of human infected swine influenza, first name by WHO, occurred in Mexico that rapidly spread worldwide. On Apr 30, 2009, the WHO, the United Nations Food and Agriculture Organization and the World Organization for Animal Health agreed to use the name of influenza A (H1N1), which was then used in bulletins issued by Ministry of Health in China."
5904,Hemophagocytic Lymphohistiocytosis and Other Culture Negative Sepsis-Like Syndromes in the ICU,"There are many sepsis-like inflammatory syndromes that may be encountered by critical care practitioners. Clinically, these syndromes may imitate sepsis and are often identified after an extensive, but unrevealing evaluation for infection. In some instances, these syndromes are anticipated complications of advanced therapies for malignancy. It is vitally important to identify these disorders and treat them with specific chemotherapeutic or immunomodulating therapies. This chapter will focus on hemophagocytic lympho-histiocytosis (HLH), a rare disorder of pathologic immune system activation that presents as a sepsis-like illness in the critically ill. While treatment of HLH with chemotherapy and immunosuppression should be guided by an expert hematologist, the diagnosis is often made by the critical care medicine practitioner. We present a case illustrating the challenges of defining this syndrome in a patient with recurrent critical illness, and review the evidence underlying diagnostic and prognostic criteria for this protean syndrome. We also review several of the more common sepsis-like inflammatory syndromes that are encountered in the critical care unit along with their specific treatments."
5905,Aspetti infettivologici e rischio di trasmissione,"Il trapianto d’organo a scopo terapeutico è una pratica ormai consolidata e rappresenta l’ultima fase di un processo integrato, complesso e multidisciplinare."
5906,Intensive Care Management of the Neuromuscular Patient,"Neuromuscular emergencies are a distinct group of acute neurological diseases with distinct characteristic presentations. Patients who suffer from this group of diseases are at immediate risk of losing protection of their native airway as well as aspirating orogastric contents. This is secondary to weakness of the muscles of the oropharynx and respiratory muscles. Although some neuromuscular emergencies such as myasthenia gravis or Guillain-Barré syndrome are well understood, others such as critical illness myopathy and neuropathy are less well characterized. In this chapter, we have discussed the pathophysiology, diagnostic evaluation, and management options in patients who are admitted to the intensive care unit. We have also emphasized the importance of a thorough understanding of the use of pharmacological anesthetic agents in this patient population."
5907,"1 Micro-organismen, de mens en het ontstaan van infectieziekten: algemene principes",Infectieziekten zijn te beschouwen als een aparte groep ziekten van de mens. Steeds gaat het om ziekten die het gevolg zijn van een interactie tussen de mens en een ander biologisch agens: een micro-organisme.
5908,Real-Time RT-PCR Detection of Equine Coronavirus,"Equine coronavirus (ECoV) is a recently identified equine virus, involved mainly in enteric infections. Since the ECoV discovery in 1999, only two real-time RT-PCRs have been developed for viral identification. In this chapter we describe a one-step real-time RT-PCR that has been routinely used in our laboratory for ECoV detection from fecal and respiratory samples."
5909,The Genetics of Autism,"This chapter is written to make the fast-paced, expanding field of the genetics of autism accessible to those practitioners who help children with autism. New genetic knowledge and technology have quickly developed over the past 30 years, particularly within the past decade, and have made many optimistic about our ability to explain autism. Among these advances include the sequencing of the human genome (Lander et al., 2001) and the identification of common genetic variants via the HapMap project (International HapMap Consortium, 2005), and the development of cost-efficient genotyping and analysis technologies (Losh, Sullivan, Trembath, & Piven, 2008). Improvement in technology has led to improved visualization of chromosomal abnormality down to the molecular level. The four most common syndromes associated with autism include fragile X syndrome, tuberous sclerosis, 15q duplications, and untreated phenylketonuria (PKU; Costa e Silva, 2008). FXS and 15q duplications are discussed within the context of cytogenetics. TSC is illustrated within the description of linkage analysis."
5910,"SUBJECT INDEX, volumes 123-130",
5911,"Substanzprofile: Zytostatika, Hormone, Zytokine1",
5912,When Does Transaminitis Become Acute Hepatic Failure? What Is the Management of Transaminitis and Acute Hepatic Failure?,"The non-toxicological causes for elevated transaminases include infection, ischemia, metabolic derangements, malignancy, autoimmune disease, and primary graft failure after transplant. Acute liver failure is a common pathway for many conditions and insults, leading to massive hepatic necrosis or loss of normal hepatic function. Acute liver failure can be described in different subgroups by acuity of encephalopathy onset. Tools exist to aid in the prognostication of acute liver failure. Treatment of transaminitis and disposition of the patient are guided by the underlying diagnosis."
5913,Aandoeningen van de farynx,"Inspectie van de nasofarynx kan geschieden door een klein (0,4-1 cm) licht verwarmd spiegeltje achter de vrije rand van het gehemelte te brengen (figuur 17.1). Om voldoende ruimte te krijgen moet de tongbasis met een tongspatel naar beneden worden gedrukt. De afstand tussen de vrije rand van het gehemelte en de farynxachterwand is het grootst als de patiënt rustig door de neus ademt. Het spiegelonderzoek van de nasofarynx is echter niet bij iedereen goed mogelijk, onder meer door het optreden van wurgreflexen. Inspectie van de nasofarynx gebeurt meestal direct met behulp van via de neus ingebrachte dunne starre of flexibele scopen. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-313-9807-2_17) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers."
5914,Use of Nanomaterials in Food Science,"The current global population is nearly 6 billion; due to this rapid population growth, there is a need to produce food in a more efficient, safe, and sustainable way, and it should be safe from the adverse effects of pathogenic organisms. A large proportion of population living in developing countries face daily food shortages as a result of environmental impacts or some other reasons like political instability, etc., while in the developed countries, food is surplus. For developing countries, the objective is to develop drought- and pest-resistant crops, with maximized yield. In developed countries, the food industry depends on consumer’s demand for fresher and healthier foodstuffs. The present chapter describes the use of nanoparticles in food science."
5915,Molecular Techniques for Blood and Blood Product Screening,"Blood product safety is a high priority for manufacturing industries, hospitals, and regulatory agencies. An important step in ensuring safety is the screening of donated blood for infectious diseases. Molecular technologies for screening infectious diseases have improved remarkably over the years. Molecular biological assay significantly reduced the risk of transfusion-transmitted infections. Unlike previous methods, molecular technologies for screening infectious diseases are specific, efficient, easy to use, and economical. A new era in molecular biology is coming to the field of blood safety."
5916,"Sickle Cell Disease and Acute Chest Syndrome: Epidemiology, Diagnosis, Management, Outcomes","Sickle cell disease (SCD) is one of the most common monogenetic diseases worldwide and is attributable to significant morbidity and mortality. Mutations causing abnormal hemoglobin formation in this disease lead to structural abnormalities and cumulative damage to the cellular membrane of sickled erythrocytes. Polymerization and aggregation of these cells within the microvasculature results in severe vaso-occlusive pain crisis, chronic hemolytic anemia, and multiorgan pathology in patients. Pulmonary manifestations of SCD, including the acute chest syndrome (ACS), are a leading cause of hospitalization and mortality. ACS is a severe type of acute lung injury, defined as the development of a new pulmonary infiltrate, involving at least one complete lung segment, that is accompanied by fever, chest pain, tachypnea, wheezing, or cough in a patient with SCD. The etiology of ACS is multifactorial, with the most common mechanisms including infection, fat and bone marrow embolism, and direct microvascular vaso-occlusion. Despite recent advances in our understanding of the pathogenesis and clinical management of ACS in SCD, patient outcomes remain unacceptably poor. This chapter reviews the epidemiology, diagnosis, management, and outcomes of ACS in SCD. Proper screening, a high index of clinical suspicion, and immediate clinical care for this condition are pivotal for improving patient outcomes."
5917,The Genesis of Supply Chain Risk,"Supply chain officers may feel with Edward Smith. After years of uneventful supply chain management and after years of striving after more efficient processes, unexpected and sometimes even devastating events have derogated supply chains. A series of major disruptions like Hurricane Katrina, piracy attacks offshore Somalia, global financial crisis, flooding in Thailand, European ash-cloud, Japanese earthquake and tsunami among others have revealed a missing preparedness within today’s supply and distribution networks [248]. Thus, the management of so-called supply chain risks became an issue."
5918,The Role of the Media in Bioterrorism,
5919,Metaphors and Risk Cognition in the Discourse on Food-Borne Diseases,"The aim of this contribution is to discuss the most important issues connected with communicating food-borne diseases. The investigation focuses on the role of symbolic language in informing stakeholders about food-borne crisis situations. To narrow the scope of the research, the study concentrates on metaphors and their role in risk cognition, especially in the face of information overload. This approach allows the author to study the metaphorical dimension of risk cognition as well as its dynamics connected with the necessity of a constant response to changing internal and external conditions. Theoretical investigations on metaphors in food, health and risk discourse are often supported by empirical analyses on the use of metaphors in communicating food-borne diseases. This study encompasses selected materials on food-borne diseases gathered from Italian online sources and covers the corpus of investigated verbal metaphors. The aim of this chapter is to show whether metaphors strengthen or weaken risk cognition, and how far they determine the risk communication of food-borne diseases."
5920,Research Advances in Biomarker for Sepsis,Sepsis is one of the most common causes of death in severely injured patients worldwide. The early detection of sepsis still has to be solved in clinical practice. The delayed diagnosis often contributes to inappropriate antimicrobial treatment and subsequent high mortality. Sepsis biomarkers are produced during the host response to infection. Traditional biomarkers are polypeptides and/or proteins derived from this response. Omics-based biomarkers are screening out from all kinds of molecules of host response while high-throughout omics technologies are emerging. This review describes traditional and potential omics-based sepsis biomarkers from currently available literatures. The combination of these biomarkers would refine the identification of sepsis for further clinical and experimental sepsis studies.
5921,Emerging Respiratory Pandemics,"Since the identity of the respiratory pathogen is not known at the time of admission, emergency department personnel and intensive care staff are at the highest risk of exposure while handling such patients."
5922,Ziekten van de tractus respiratorius,De aandoeningen van de luchtwegen worden onderscheiden naar lokalisatie. Als grens tussen bovenste en onderste luchtwegen wordt het strottenhoofd aangehouden: tot en met de larynx worden ziekten en klachten toegerekend aan de bovenste luchtwegen. Het aandeel van ziekten van de luchtwegen in de totale incidentie bedraagt rond de 30%. Deze komen daarmee in de rangorde van frequentie van voorkomen op de eerste plaats. Veel van de aandoeningen van de bovenste luchtwegen vormen dan ook dagelijkse kost voor de huisarts.
5923,Disaster Planning for Cosmic Impacts: Progress and Weaknesses,"On the evening of June 18, 1178, several witnesses near Canterbury, England saw a spectacular night sky event (Ingram 1999). These observers reported directly to a monk who was keeping detailed records of events occurring in or around Christ Church Cathedral. Fortunately, this diary, the Chronicles of Gervase has survived and provides a detailed description of the strange events of 1178: This year, on the Sunday before the Birth of Saint John the Baptist, after sunset when the moon had first become visible, a marvellous phenomenon appeared to five or more men while sitting facing it. Now there was a bright new moon, and as usual the horns protruded to the east; and lo, suddenly, the upper horn split in two. From the middle of this division a firebrand burst forth, throwing over a considerable distance fire, hot coals and sparks. Meanwhile the body of the moon which was lower [than this] writhed as if troubled, and in the words of those who told this to me and who saw it with their own eyes, the moon throbbed as a beaten snake. It then returned to its former state. This phenomenon was repeated twelve times and more, the flame assuming various twisting shapes at random then returning to normal. And after these vibrations it became semi-dark from horn to horn, that is, throughout its length. Those men who saw this with their own eyes reported these things to me who writes them; [they are] prepared to give their word or oath that they have added nothing false to the above."
5924,Nanotechnology for Detection of Small Mass Difference,"Mostly, mass of a macroscopic object is determined by comparing the gravitational forces experienced by the object and the body of known mass. Relative uncertainty in 1kg is pretty small say one part in 10(9). However, gravitational force of an object of molecular scale is too feeble to detect. Hence, normal method of using a balance will not do for mass measurement on the microscopic scale. Measurement of mass at the microscopic scale is very vital as it serves powerful tool that can provide information about the molecular and atomic composition of an object, detection, prevention and treatment of various diseases. Mechanical balances with electronic devices can detect only up to 0.1μg. An alternate method to measure the mass of an object is to consider mass as quantification of inertia. This principle is used in mass spectroscopy. In this the trajectory of an ionised particle in a strong electromagnetic field provides a precise measure of the inertia of the particle and hence a measure of its mass. Mass spectroscopy is able to distinguish ionised particles that differ by a single atomic mass unit. One atomic mass unit is equal to 1.66 ×10(−27)kg. However, mass spectroscopy is restricted to ionised particles so it cannot be applied to all microscopic objects, which are neither in charged state nor can be charged. So for smaller masses, one has to depend upon certain other phenomenon."
5925,Role of Microglia and Macrophages in Eae,"Microglia and macrophages are related cell types that play an important role in the pathogenesis of MS and EAE. This chapters reviews the role of these cells in the normal brain and their contribution to inflammatory demyelinating disease, including their role in antigen presentation, co-stimulation, and production of cytokines and other inflammatory mediators"
5926,Biologically Active Metabolites from Sponges and Their Activities,"Sponges are mostly marine found distributed right from the intertidal region to the deeper waters of the oceans. Its spatial and temporal distribution is found ubiquitous. Though the sponges have simple morphology and anatomy, they show symbiotic association with several microorganisms, which are the main source of secondary metabolites and are capable of producing many biologically active compounds. So there is a good debate going on among the researchers that the source of such biologically active compounds/substances is either the sponge itself or the microorganism residing in the sponges. But unfortunately most of these symbiotic microorganisms are non-culturable. Anyhow the sponges as a whole are the good source of several substances covering the polyketides, alkaloids, terpenes, etc. This chapter deals with the variety of such chemical substances present in the sponges and their biological activities."
5927,Metodologie per il trasferimento genico,"L’esito di qualsiasi approccio di terapia genica, sia che esso preveda l’inoculazione del materiale genetico direttamente in vivo sia che venga effettuato ex vivo nelle cellule prelevate dal paziente, dipende strettamente dall’efficienza con cui gli acidi nucleici con funzione terapeutica vengono internalizzati dalle cellule bersaglio. Di fatto, l’efficienza del trasferimento genico probabilmente rappresenta a tutt’oggi il parametro più importante che ancora limita le applicazioni di terapia genica, o comunque ne condiziona il successo."
5928,"Infektionskrankheiten weltweit: Epidemiologie, Erfassung, Surveillance","Nach aktueller WHO-Statistik (2005) liegen Infektionskrankheiten mit 41 % der Todesfälle weltweit als häufigste Todesursache deutlich vor den Herz-Kreislauf-Erkrankungen (20 %), den Krebserkrankungen (18 %) und den zerebrovaskulären Erkrankungen (13 %). Bezüglich der Reihenfolge in der Häufigkeit haben dabei Pneumonien vor Tuberkulose, Gastroenteritiden, Malaria, AIDS und Hepatitis B einen deutlich überwiegenden Anteil."
5929,Identification of an immunodominant neutralising and protective epitope from measles virus fusion protein using acute post-infection human sera,
5930,Acute levensbedreigende aandoeningen,"Hoewel in principe elke ziekte op de kinderleeftijd een levensbedreigend beloop kan krijgen, is er een aantal aandoeningen dat men vanwege het spoedeisende karakter van hun onderkenning en behandeling kan aanduiden als levensbedreigende aandoeningen."
5931,Acute Pancreatitis (AP),"All of these conditions can be associated with acute pancreatitis, except ?"
5932,Globalizzazione in medicina: l’emergenza HIV,"L’ottimismo generato dalle migliori condizioni di vita (cibo e acqua più sani, migliori sistemi di raccolta rifiuti e di discarica, nuove conoscenze nella biologia e nella medicina capaci di consentire lo sviluppo e l’uso diffuso di vaccini, la produzione di antinfettivi e di antiparassitari più sicuri ed efficaci) che avevano portato nel mondo occidentale all’allungamento dell’aspettativa di vita da una media di 46,5 anni nel 1950 a 65 anni nel 2002 (51 anni per i redditi bassi, 78 per gli alti), negli anni Ottanta si era già esaurito per l’emergenza di agenti infettivi “nuovi” (non riconosciuti prima) e per la riemergenza di altri già noti, a causa sia di fattori determinati dall’agente infettante stesso, quali l’acquisizione della capacità di salto di specie o la formazione di varianti farmacoresistenti, che di fattori determinati dall’ospite, quali: 1) manovre invasive iatrogene responsabili di infezioni ospedaliere; 2) cambiamenti climatici capaci di favorire il diffondersi di parassiti vettori di infezione e alterazioni degli ecosistemi (con prevalenza incontrollata di predatori o di prede); 3) esplosione demografica con ripercussioni importanti sulle tecnologie industriali di produzione alimentare, sullo sviluppo economico-urbanistico tumultuoso, sulle migrazioni di rifugiati; 4) promiscuità sessuale e turismo sessuale; 5) tossicodipendenza, e infine 6) spostamenti delle persone e delle merci che sono sempre stati fonte di diffusione degli agenti infettivi, ma che avevano raggiunto livelli di quantità e frequenza impensabili precedentemente [1] (vedi anche i Capitoli pubblicati altrove in questo volume)."
5933,Reproductive Epidemiology,"In writing this chapter we assumed that the reader is familiar with the basic concepts in epidemiology. You will not find any overview of different designs, measure of disease occurrence, standardisations, other ways of adjusting for confounders, or any general discussion on bias, confounding or on measuring effects. If you are not familiar with these topics you should start by reading other parts of the book or turn to one of the many fine available textbooks."
5934,Diffuse Lung Disease,"Diffuse lung disease (DLD) comprises a diverse group of disorders characterized by widespread pulmonary parenchymal pathology and impaired gas exchange. While many of these disorders are categorized under the rubric of interstitial lung disease (ILD), some of these disorders involve the airspaces or peripheral airways in addition to, or rather than, the interstitium. Some of these disorders are present primarily in infancy or early childhood, while others that are prevalent in adulthood rarely occur in childhood. This chapter will review the classification of pediatric DLD and the characteristic imaging findings of specific disorders to facilitate accurate diagnosis and guide appropriate treatment of children with these disorders."
5935,Ebola in West Africa: Biosocial and Biomedical Reflections,"The West Africa ebola epidemic, which killed more than 11,000 people, is fading from urgency and memory. Technical biomedical lessons-learned are being applied in drug and vaccine development, for example in response to Zika. But biosocial issues that arose may not have been directly confronted, or sometimes even noticed, despite their overall importance in the eventual control and ending of the epidemic."
5936,Acute Frontal Sinusitis,
5937,Respiratory Hygiene and Cough Etiquette,"Respiratory infections are a leading cause of illness, morbidity, and mortality around the globe. Easily transmitted between people, respiratory pathogens are a leading cause of widespread illness but can be prevented. With the use of standard precautions, appropriate respiratory and hand hygiene, and appropriate patient precautions at the onset of symptoms, respiratory infections can be managed and maintained. There are several key pathogens that contribute to the burden of respiratory disease across the globe, among them are Mycobacterium tuberculosis and Haemophilus influenzae. Some respiratory infections are self-limiting and require symptomatic treatment, while some require specific treatments and antibiotics. This chapter will review protocols to limit the spread of respiratory infections, respiratory hygiene methods, as well as common and virulent respiratory infections and methods of management and treatment."
5938,Obstetrical and Gynecological-Related Infections,"The vast majority of pregnancies occur amongst a generally healthy patient population, i.e. females from the teenage years in to the 40s. In most cases, the pregnancy is uneventful and where infections do arise, these are often relatively minor and easily treatable, e.g. urinary tract infection and vaginal thrush. However, sepsis is now the leading cause of maternal deaths in the UK accounting for 26 deaths between 2006 and 2008 and there has been an increase in death due to community-acquired Group A streptococcal (GAS) (also known as Streptococcus pyogenes) disease [1]. A literature review of 55 pregnancies with symptomatic Groups A streptococcal infection since 1966 recorded early onset septic shock in 91 % with a maternal mortality rate of 58 % but the mortality has improved to 32 % in recent years [2]. Furthermore, when toxic shock syndrome due to Group A streptococci (can also be caused by Staphylococcus aureus) occurs during pregnant, it can have devasting consequences with multi-organ failure and a mortality of over 50 % in reported cases [3]. A recent review from the UK covers many of the important issues associated with GAS in the obstetrical setting including the its diverse manifestations, the need to manage puerperal sepsis caused by GAS quickly, suggested initial antibiotic therapy (e.g. cefuroxime and metronidazole until confirmed), and issues such as prophylaxis for contacts and the possible role of intravenous immunoglobulins [4]."
5939,Bioprospecting of Endophytes for Agricultural and Environmental Sustainability,"The term endophytes refers to a group of endosymbionts usually bacterium, fungus or interactive bacterium-fungal species residing asymptomatically and grows within plants for at least a part of their life cycle intra- and intercelullarly in the tissues of higher plants without causing any visible manifestation of disease. The endophytes represent a potential source of novel natural and ecofriendly products for medicinal, agricultural and industrial uses with least adverse effect on the environment. The enormous biological diversity coupled with their capability to biosynthesize bioactive secondary metabolites has provided the momentum for the researchers working on endophytes. The present review was undertaken to highlight the biotechnological processes and bioprospection of endophytes as potential antimicrobial agents, secondary metabolites, antibiotics, antagonists against disease causing phytopathogens, cytotoxic, anticancer, insecticidal, antioxidant antiviral compounds andisolation and production of bioactive compounds with potent enzymatic activities. Endophyte enhances biodegradation and hydrolysis processes significantly important against pathogenic infection, biotransformation studies and production of compounds with immense industrial applications. The interaction of the endophytic microbiota with the plants are more protected and can withstand the adverse environmental conditions and contribute to plant growth, productivity, carbon sequestration, enhanced phytoremediation efficiencies and amelioration of metal induced toxicity. The strategies governed by the endophytes for efficient production of novel bioactive phytocompounds was comprehensively discussed. The review envisaged the biodiversity, transmission of endophytes, plant endophyte interactions for the production of bioactive compounds for therapeutic, environmental and agricultural sustainability."
5940,Strategies for the Nonclinical Safety Assessment of Vaccines,"Over the past century, vaccines have made a large impact on public health. Prophylactic vaccines prevent disability and disease, saving millions of dollars in potential health-care spending. Since prophylactic vaccines are administered to healthy individuals, including infants and children, it is important to demonstrate the safety of vaccines preclinically prior to testing the vaccine in clinical studies. A benefit-to-risk profile is considered for each individual vaccine and depends on many factors including preclinical and clinical toxicities that are observed, frequency of administration and intended target population. For prophylactic vaccines, in particular, the concerns about potential risks often outweigh the perception of benefit [1]. Therefore, over the past decade, there has been an increased focus on nonclinical safety assessment of vaccines, including toxicity testing."
5941,"Epidemic Models: Their Spread, Analysis and Invasions in Scale-Free Networks","The mission of this chapter is to introduce the concept of epidemic outbursts in network structures, especially in case of scale-free networks. The invasion phenomena of epidemics have been of tremendous interest among the scientific community over many years, due to its large scale implementation in real world networks. This chapter seeks to make readers understand the critical issues involved in epidemics such as propagation, spread and their combat which can be further used to design synthetic and robust network architectures. The primary concern in this chapter focuses on the concept of Susceptible-Infectious-Recovered (SIR) and Susceptible-Infectious-Susceptible (SIS) models with their implementation in scale-free networks, followed by developing strategies for identifying the damage caused in the network. The relevance of this chapter can be understood when methods discussed in this chapter could be related to contemporary networks for improving their performance in terms of robustness. The patterns by which epidemics spread through groups are determined by the properties of the pathogen carrying it, length of its infectious period, its severity as well as by network structures within the population. Thus, accurately modeling the underlying network is crucial to understand the spread as well as prevention of an epidemic. Moreover, implementing immunization strategies helps control and terminate theses epidemics."
5942,Intrabody Expression in Mammalian Cells,"The intracellular expression of antibodies or antibody fragments (intrabodies) in different compartments of mammalian cells allows to block or modulate the function of endogenous molecules. Intrabodies can alter protein folding, protein-protein, protein-DNA, protein-RNA interactions and protein modification. They can induce a phenotypic knockout and work as neutralizing agents by direct binding to the target antigen, by diverting its intracellular traffic or by inhibiting its association with binding partners. They have been largely employed as research tools and are emerging as therapeutic molecules for the treatment of human diseases as viral pathologies, cancer and misfolding diseases. The fast growing bio-market of recombinant antibodies provides intrabodies with enhanced binding specificity, stability and solubility, together with lower immunogenicity, for their use in therapy. This chapter describes the crucial aspects required to express intrabodies in different intracellular compartments of mammalian cells, their various modes of action and gives an update on the applications of intrabodies in human diseases."
5943,Oxidative Stress Mechanisms in the Pathogenesis of Environmental Lung Diseases,"Globally, respiratory diseases are major cause of disability and mortality, and more alarmingly, it disproportionately affects developing countries, which is largely attributed to poor quality of air. Tobacco smoke and emissions from combustion of fossil fuel and biomass fuel are the major airborne pollutants affecting human lung health. Oxidative stress is the dominant driving force by which the airborne pollutants exert their toxicity in lungs and cause respiratory diseases. Most airborne pollutants are associated with intrinsic oxidative potential and, additionally, stimulate endogenous production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Elevated ROS and RNS in lungs modulate redox signals and cause irreversible damage to critical biomolecules (lipids, proteins and DNA) and initiate various pathogenic cellular process. This chapter provides an insight into oxidative stress-linked pathogenic cellular process such as lipid peroxidation, inflammation, cell death, mitochondrial dysfunction, endoplasmic reticulum stress, epigenetic changes, profibrotic signals and mucus hypersecretion, which drive the development and progression of lung diseases. Lungs are associated with robust enzymatic and non-enzymatic (GSH, ascorbic acid, uric acid, vitamin E) antioxidant defences. However, sustained production of free radicals due to continuous exposures to airborne pollutants overwhelms lung antioxidant defences and causes oxidative injury. Preclinical studies have demonstrated the critical roles and therapeutic potential of upregulating lung antioxidants for intervention of respiratory diseases; however, so far clinical benefits in antioxidant supplementation trials have been minimal and conflicting. Antioxidants alone may not be effective in treatment of respiratory diseases; however it could be a promising adjunctive therapy."
5944,Hematological and Oncological Emergencies,
5945,Virus Specific T-Cell Responses,"CD8+ and CD4+ T-cells play a key role in the maintenance of our immunity against viruses. Recent technological developments, such as the use of MHC-peptide tetrameric complexes, have permitted significant improvements in the study of these cells. It is now possible to assess precisely frequencies as well as phenotypic and functional features of virus specific T-cells from the onset of many viral infections onwards. Different virus specific T-cell populations exhibit distinct functional characteristics and can be positioned at different stages of a process of post-thymic development, which we are drawing near to understanding the significance. Still, further work is needed before consensus is reached as regards what defines and how to induce the optimal virus specific T-cell response which will confer long lasting immunological protection in humans."
5946,A Probabilistic Beam Search Approach to the Shortest Common Supersequence Problem,"The Shortest Common Supersequence Problem (SCSP) is a well-known hard combinatorial optimization problem that formalizes many real world problems. This paper presents a novel randomized search strategy, called probabilistic beam search (PBS), based on the hybridization between beam search and greedy constructive heuristics. PBS is competitive (and sometimes better than) previous state-of-the-art algorithms for solving the SCSP. The paper describes PBS and provides an experimental analysis (including comparisons with previous approaches) that demonstrate its usefulness."
5947,Opvang bij acute problemen,"Onder een acute buik verstaat men een plotselinge abdominale crisis ten gevolge van peritoneale prikkeling, waarbij zo spoedig mogelijk een werkdiagnose moet worden gesteld om al dan niet tot operatieve behandeling over te gaan."
5948,Scientific Literacy Revisited,"In recent decades, the notion of scientific literacy has become increasingly prominent in international debate about science education, a trend mirrored by a similarly expanding interest in technological literacy and environmental literacy1. Although a number of writers have traced the history and evolving definition of scientific literacy (Gräber & Bolte, 1997; Laugksch, 2000; De Boer, 2001; Ryder, 2001; McEneaney, 2003; Roberts, 2007; Dillon, 2009), there is some value in revisiting that history and development here, albeit very briefly."
5949,2 Beeldvormende diagnostiek,De radiologie is een vakgebied waarin de opleiding en de expertise van radiologen naar orgaansysteem zijn georganiseerd. In dit hoofdstuk wordt de radiologie echter om praktische redenen besproken per beeldvormende techniek.
5950,Forensic Lung Pathology,"Sudden and unexpected natural deaths and nonnatural deaths may result from various pulmonary conditions. Additionally, several nonpulmonary conditions of forensic significance may be complicated by the development of respiratory lesions. Certain situations with pulmonary pathology are particularly likely to be critically scrutinized and may form the basis of allegations of medical negligence, other personal injury liability, or wrongful death.1"
5951,Pulmonary Medicine,"• oropharynx—enlarged tonsils, retropharyngeal abscess, obesity, post-nasal drip • larynx—laryngeal edema, laryngostenosis, laryngocele, epiglottitis, anaphylaxis, severe laryngopharyngeal reflux, and laryngospasm • vocal cords—vocal cord dysfunction, paralysis, hematoma, tumor, cricoarytenoid arthritis"
5952,Behandlung von Patienten mit HIV-Infektion auf der Intensivstation,"HIV-infizierte Patienten können aus einer Reihe von Indikationen heraus der Intensivbehandlung bedürfen (·Abb. 66.1; [7, 17, 19, 33, 41, 44, 51]). In 50–75% der Fälle stellt akutes respiratorisches Versagen die Indikation für die Behandlung HIV-Infizierter auf der Intensivstation dar [7, 17, 19, 33, 41, 44, 51]. Bei 55–90% dieser Patienten mit intensiv behandlungsbedürftigem respiratorischen Versagen stellt Pneumocystis carinii das für die Erkrankung verantwortliche Pathogen dar [7, 33, 44]."
5953,Model and Dynamic Behavior of Malware Propagation over Wireless Sensor Networks,"Based on the inherent characteristics of wireless sensor networks (WSN), the dynamic behavior of malware propagation in flat WSN is analyzed and investigated. A new model is proposed using 2-D cellular automata (CA), which extends the traditional definition of CA and establishes whole transition rules for malware propagation in WSN. Meanwhile, the validations of the model are proved through theoretical analysis and simulations. The theoretical analysis yields closed-form expressions which show good agreement with the simulation results of the proposed model. It is shown that the malware propaga-tion in WSN unfolds neighborhood saturation, which dominates the effects of increasing infectivity and limits the spread of the malware. MAC mechanism of wireless sensor networks greatly slows down the speed of malware propagation and reduces the risk of large-scale malware prevalence in these networks. The proposed model can describe accurately the dynamic behavior of malware propagation over WSN, which can be applied in developing robust and efficient defense system on WSN."
5954,Hematology,"SPURIOUS—stress (Geisböck’s syndrome), decrease intravascular volume PRIMARY—polycythemia rubra vera"
5955,Field Epidemiology and One Health: Thailand’s Experience,"Field epidemiology has become a major principle in public health and animal health service. Field epidemiologists are the primary group of professionals responding to outbreaks and other health emergencies who provide evidence-based recommendations for decision makers. In outbreak investigations, their duties are to identify the disease etiology, risk factors or source of an outbreak, and to contain the spread of the disease. Field epidemiology training programs (FETP) recruit professionals with training in medical, veterinary medical and other related health sciences to deal with real-life outbreaks and health problems. Joint training in surveillance and outbreak investigation has led to improved surveillance and control of zoonotic diseases by young professionals from human health and animal health sectors. Field epidemiology training programs for veterinarians (FETPV) is a living branch of a mature FETP which could support the development of wildlife and ecosystem needs under a broad One Health canopy. FETP can be a practical means of actualizing the One Health approach based upon shared needs and mutual benefit. One such model for sustainable, joint capacity development in field epidemiology under a One Health approach has been initiated in Thailand and is being adopted in other Asian countries. The Field Epidemiology Training Network of FETP in Southeast Asia is a useful platform for further strengthening regional disease surveillance and improving response to both public and animal health problems of international concern."
5956,Die Eigenschaften der Online-Kommunikation,Lesen Sie in diesem Kapitel: Welche spezifischen Vor- und Nachteile die Eigenschaften der Online-Medien mit sich bringen; welche unterschiedlichen Aufgaben Text und Bilder in der Online-Kommunikation haben; warum im Online-Dialog ein erhöhtes Potenzial für Missverständnisse besteht und wie man damit umgehen kann; wie sich Online-Kommunikation auf bestehende Hierarchien auswirkt und was dies für Führungskräfte bedeutet und; was man im Online-Kontakt mit anderen Kulturen beachten sollte.
5957,Computer Network Vulnerabilities,
5958,The Biosecurity Threat Environment,"This chapter surveys how the biosecurity threat environment has changed since 9/11 and examines in detail a range of technological, psycho-social and policy drivers that will influence how our intelligence communities understand emerging bio-threats and risks. It argues that the emerging threat environment remains contentious though the intelligence enterprise must still come to grips with understanding the various drivers influencing bio-threats and risks."
5959,"Keel-, neus-, oorziekten","Hypertrofie van het lymfoïde weefsel in de nasofarynx. Een van de meest voorkomende aandoeningen op de kleuterleeftijd. Vanaf de schoolleeftijd minder frequent door involutie van het adenoïd. Aet. Recidiverende infectie. Sympt. 1. Neussymptomen a. Belemmerde neusademhaling, waardoor open mond, snurken, onrustig slapen, kwijlen, vaak slechte eetlust en gesloten neusspraak."
5960,"Flavonoids in Cancer Prevention and Therapy: Chemistry, Pharmacology, Mechanisms of Action, and Perspectives for Cancer Drug Discovery","Among the numerous products available from plants, the flavonoid superfamily plays a central role by its large number of molecules (over 6000) and also by the role these products occupy in the normal physiology of plants. Flavonoids are secondary plant metabolites involved in several biological processes (e.g., germination, UV protection, insecticides) and are also involved in the attraction of pollinating agents via the vivid colors of the anthocyanin pigments found in flowers (e.g., blue, purple, yellow, orange, and red) [1–3]. Flavonoids are found in the normal human diet composed of green vegetables, onions, fruits (apples, grapes, strawberries, etc.), beverages (coffee, tea, beer, red wine) [4, 5], and isoflavonoids are mainly found in soya bean-derived products [6]."
5961,The Economics of HIV/AIDS,"Economics is inextricably linked with HIV/AIDS. Economic conditions affect HIV/AIDS and, in turn, HIV/AIDS affects an economy at both the macro and micro levels. Thus, the link works in both directions. In this chapter, we examine the relationships between HIV/AIDS and poverty, inequality and social capital, and consider whether economic differences between countries explain differences in HIV prevalence. As we have noted in Chap. 3, HIV/AIDS disproportionately affects people of working age. In this chapter, we examine the potential economic impact of HIV/AIDS, using a macroeconomic model. This is followed by a review of microeconomic and epidemiological models that try to answer questions about the behavioral response of people who are either at risk of or actually living with HIV/AIDS. Such studies provide a useful mechanism for determining the effectiveness of HIV/AIDS prevention strategies (a topic we explore further in Chap. 9). Economics plays a significant role in the propagation of HIV/AIDS in high incidence countries. The economics of HIV/AIDS also shows us the likely economic returns on different strategies to prevent HIV infections."
5962,Postoperative Care of the Liver Transplant Recipient,"Liver transplantation for both acute and chronic liver failure results in excellent outcomes. Perhaps more than with any other surgical program, graft and patient outcomes for liver transplantation reflect the combined efforts of several specialties. The success stems from a multidisciplinary approach with close involvement of gastroenterologists, anesthesiologists, surgeons, and intensivists. This chapter will review topics related to the immediate care of the liver transplant patient in the intensive care unit (ICU). Existing evidence on hemodynamic monitoring, respiratory failure, neurologic management, electrolyte and glucose correction, coagulation management, systemic immunosuppression, graft function and rejection, and technical problems will be reviewed. The chapter will conclude with brief mention of long-term complications related to recurrence of disease that may lead to future ICU admissions."
5963,Sistemi di sorveglianza e di allarme rapido,"Come per tutti gli interventi di politica sanitaria, anche le scelte in tema di sorveglianza, prevenzione e controllo delle zoonosi non possono prescindere da valutazioni sull’impatto sanitario, sociale ed economico delle diverse possibili strategie. Questo impatto varia a seconda delle caratteristiche della specifica patologia: incidenza, prevalenza e gravità nell’uomo e nell’animale, rischio di contagio interumano, velocità di diffusione, possibile evoluzione dell’agente patogeno, dimensione delle popolazioni a rischio, area geografica interessata, costi della prevenzione, disponibilità e costi di profilassi e terapie, costo della sorveglianza epidemiologica e altri costi sociali ed economici."
5964,Good Arguments During the BSE Inquiry,"At this stage of discussion, we have all the raw materials in place to construct a model of scientific reasoning that is adapted to contexts of uncertainty. At the conceptual heart of this model is presumption. Through its unique features of defeasibility, context sensitivity and much else besides, presumption, it was argued, is equipped to handle the full range of demands that uncertainty imposes on investigators during scientific inquiry. But presumption could not act alone in this endeavour. Several argument forms that have traditionally been characterized as fallacies became the vehicle through which presumption was given effect in a model of reasoning. These argument forms, it was contended, served to facilitate scientific inquiry when widespread uncertainty threatened to halt inquiry in its tracks. The purpose of this chapter will be to demonstrate in quite specific ways how certain of the fallacies achieved this facilitation in the case of scientific inquiry into BSE. The presumptive analyses of fallacies that have been advanced to date have certainly served to reveal rational features of the fallacies. These features have been largely obscured from view under traditionally dominant deductive and inductive conceptions of argument. To this extent, these analyses have helped to move the fallacies a bit further along the road towards full integration within cognitive rationality. But there are lingering suspicions amongst theorists that these argument forms, despite their demonstrated practical and other benefits in inquiry, may still not somehow fully warrant the type of rational legitimacy that routinely attends deductive and inductive modes of reasoning. In this chapter, I aim to dispel those suspicions once and for all by arguing in support of a clear role for the fallacies within cognitive rationality."
5965,CUSUM Residual Charts for Monitoring Enterovirus Infections,"We consider the syndromic surveillance problem for enterovirus (EV) like cases. The data used in this study are the daily counts of EV-like cases sampled from the National Health Insurance Research Database in Taiwan. To apply the CUSUM procedure for syndromic surveillance, a regression model with time-series error-term is used. Our results show that the CUSUM chart is helpful to detect abnormal increases of the visit frequency."
5966,"The development of antimicrobial agents, past, present and future",
5967,Disaster Medicine,
5968,Neutropenic Fever,"Neutropenia is defined as an abnormally low absolute neutrophil count (ANC) and can be further delineated as severe or profound (see below). Recipients of chemotherapy will often have a decreased ANC leading to an increased risk of infections specifically from bacterial sources. Neutropenia traditionally is risk stratified based on duration and depth of neutropenia. Recipients of chemotherapy for acute myelogenous leukemia (AML) and stem cell transplants (SCTs) often are deemed as having high risk neutropenia due to significant depth and duration of neutropenia. The mortality associated with febrile neutropenia is up to 11%, and can be as high as 50% in the setting of severe sepsis or septic shock. By risk stratifying neutropenia and the resultant neutropenic fever, the goal is to decrease the resultant morbidity and mortality (Taplitz et al., J Clin Oncol 36:3043–3054)."
5969,A Health Policy Simulation Model of Smallpox and Ebola Haemorrhagic Fever,"This study proposes a simulation model of a new type of infectious disease based on smallpox, Ebola haemorrhagic fever and a health policy Game. SIR (Susceptible, Infected, Recovered) model has been widely used to analyse infectious diseases such as influenza, smallpox, bioterrorism, to name a few. On the other hand, Agent-based model or Individual-based model begins to spread in recent years. The model enables to represent behaviour of each person in the computer. It also reveals the spread of an infection by simulation of the contact process among people in the model. The study designs a model based on Epstein’s model in which several health policies are decided such as vaccine stocks, antiviral medicine stocks, the number of medical staff to infection control measures and so on. Furthermore, infectious simulation of Ebola haemorrhagic fever, which has not yet any effective vaccine, is also implemented in the model. As results of experiments using the model, it has been found that preventive vaccine, antiviral medicine stocks and the number of medical staff are crucial factors to prevent the spread. In addition, a health policy game against a new type of infectious disease is designed as a serious game."
5970,6 Preventie en publieke gezondheidszorg,"Preventie betreft zorg zowel voor gezonde mensen als voor niet meer gezonde mensen, die echter zonder klachten zijn of die de klachten (nog) niet zodanig ervaren dat ze een huisarts raadplegen (zie paragraaf 2.1 en figuur , en paragraaf 5.1 en schema 5.2)."
5971,"FAO/IAEA International Symposium on Application of Gene-Based Technologies for Improving Animal Production and Health in Developing Countries: Summary, conclusions and recommendations",
5972,Human-Wildlife Contact and Emerging Infectious Diseases,"The majority of all emerging pathogens in humans are zoonotic (nonhuman animal) in origin. Population, ecological, and behavioral changes that increase contact with wildlife exacerbate emergence of these pathogens. Anthropogenic modification of the physical environment has altered not only our risk of zoonotic infection from wildlife but also the likelihood of pathogen transmission from human to nonhuman animal populations. This is particularly the case for primates that share a number of common infections with humans. In this chapter, I use a series of case studies involving SARS, HIV, Nipah virus, Lyme disease, malaria, and Ebola to exemplify how various anthropogenic factors have facilitated pathogen transmission between human and nonhuman animal populations. The costs and benefits of primate-based ecotourism are also reviewed to better illustrate how human-wildlife contact can affect both populations. Responsible health monitoring of human-wildlife interactions is a necessary prerequisite for prevention of the transmission of future emerging infectious diseases."
5973,Detection of Viral RNA Splicing in Diagnostic Virology,"Diagnostic virology is to identify the etiologic cause of infection from patient’s samples. In the past the diagnostic virology relied on three classical techniques to make a diagnosis of viral infection: (a) virus isolation by direct virus cultivation, (b) viral antigen detection, (c) indirect detection of virus-specific antibodies. While being important tools in the diagnostic virology today, these techniques are time-consuming and require specific tools such as cultivation media, cell or tissue cultures, antibodies, purified antigens. In the past decade the number of new molecular-based methods grew rapidly and gained more popularity in diagnostic labs. The core of these techniques constitutes of techniques based on nucleic acid detection by specific amplification, hybridization, and/or sequencing (reviewed in ref. [1]). The most nucleic acid-based diagnostic methods are simple, speed, sensitive and specific and thus meet the gold four-S-standard for their application in any diagnostic laboratories. The methods are simple and speed because only a specific primer pair and a PCR machine are needed in a lab setting and identification of a viral pathogen takes within few hours. They are sensitive and specific and require only a small amount of patients’ materials to detect a specific nucleotide sequence region. In general, these techniques can be used to detect almost all types of viral pathogens and even to identify multiple viral pathogens or their variants at the same time. In this chapter we focus on detection of viral RNA splicing as a new tool for diagnostic virology."
5974,Porcine Circovirus,"Porcine circovirus (PCV) infections associated with post-weaning multisystemic wasting syndrome (PMWS) are characterized by weight loss, respiratory distress, jaundice, etc. Although PCV2 infection is ubiquitous, the prevalence of clinical disease is lower and the most common form is PCV2 subclinical infection. Recently, a novel porcine circovirus (PCV3) has been identified in pigs in the USA that is associated with porcine dermatitis nephropathy syndrome, acute myocarditis and multisystemic inflammation, etc. Genetic heterogeneity of PCV2 has been studied in Indian pig population. Different genotypes like PCV2a-2D, PCV2b-1C, PCV2d and recombinant strain between PCV2a-2C and PCV2b-1C are reported from different studies. PCV2 has been discovered in human faeces, human vaccines and beef. But its pathogenicity in humans is not clear. PCV detection is based on common golden standard techniques including nucleic acid and antigen detection in the tissues, in situ hybridization (ISH) and immunohistochemistry (IHC) using monoclonal or polyclonal antibody against PCV2, respectively. The commercial vaccines available are effective in reducing the severity of clinical diseases and improving production parameters. Recently, antiviral compounds have also shown promising results against PCV2. This chapter summarizes aetiology, epidemiology, transmission, immunopathobiology, diagnosis, prevention and control of porcine circovirus."
5975,"Strategies of Gene Transfer and Silencing, and Technical Considerations","Cancer gene therapy is a relatively new modality that might ultimately revolutionize oncology. The basic principle is to alter the tumor genetically to enhance more traditional chemo- and radiation therapy schema. The last decade has seen tremendous progress and development of new technologies in the areas of vector delivery, tumor targeting, and numerous clever ways to increase tumor killing, including early attempts to modulate tumor gene expression by RNA interference. In recent years, attempts to image affected cells have also been part of these efforts. Many studies have proceeded to the preclinical stage and a fair number to early clinical testing with some showing encouraging results. However, real impact on patient survival remains to be seen. One major problem still to be overcome is the quantitative delivery of the vector into the tumor mass. The next decade is expected to resolve many of these technical issues and improve the treatment of patients. This chapter will discuss new technologies and provide a brief overview of the field."
5976,"Infectious Diseases, Climate Change Effects on","Infectious diseases of humans continue to present a significant burden to our health, disproportionately so in the developing world. Infectious diseases of livestock affect their health and welfare, are themselves important causes of human disease and, exceptionally, can threaten our food security. Wildlife infections again present a zoonotic risk to humans, but additionally, such diseases may threaten vulnerable populations and be a cause of extinction and biodiversity loss. Wild populations are inherently more susceptible to environmental change, largely lacking any human protective influence that domesticated species and human populations may benefit from."
5977,A Framework of Web GIS Based Unified Public Health Information Visualization Platform,"The GIS plays a vital role in public health information visualization for public health information management, broadcasting, data management, statistical analysis, and decision supporting. This paper described the elementary requirement and the essential technology for public health information visualization and proposed a framework of the unified public health information visualization platform based on the Web GIS and visualization technology. The system framework adopted multi-tier system infrastructure that consist the sever tier and the front tier. In the server tier, the J2EE based architecture was adopted to construct a distrusted system infrastructure. In the front tier, the GIS map java applet is used to show the public health information with spatial graphical map, and the web based graphics figures such as curves, bars, maps and multi-dimensional visualization technology are used to visualize the public health information. The public health information contained the geo-referenced data, such as specific location, area code, latitude and longitude, street address, and geopolitical boundaries can be visualized with GIS distribution maps. The system infrastructure, functions, system integration, and some key technology were discussed in this paper. It would have the important practical value for constructing the visible public health information system."
5978,Virale Infektionen,"Adenoviren verursachen im Kindesalter Krankheiten der Atemwege und des Darms, aber auch Krankheiten der Harnwege, der Lymphorgane und kardiologische und neurologische Manifestationen werden beobachtet. Einige typische Krankheitsbilder können klinisch diagnostiziert werden."
5979,A Review of Hendra Virus and Nipah Virus Infections in Man and Other Animals,"Hendra virus (HeV) and Nipah virus (NiV) emerged in the last decade of the twentieth century. They were the cause of a number of outbreaks of respiratory and neurological disease infecting horses and pigs respectively. Transmission from infected domestic animal species resulted in human infections as well, with high case fatality rates a feature. Today they continue to cause outbreaks of human and animal disease. NiV causes yearly disease outbreaks in humans in Bangladesh, and HeV causes sporadic disease outbreaks in horses in north eastern Australia. Due to their zoonotic nature, they have been ideal candidates for collaborative projects in the One Health space, bringing public health and animal health professionals together. This has lead to insightful epidemiological studies, which has resulted in practical disease prevention solutions including a horse vaccine for HeV and NiV spill-over prevention interventions in the field. As more surveillance is undertaken, their known distributions have expanded, as has the range of reservoir host species. The majority of bat species for which there is evidence of henipavirus infection belong to the group known as the Old World family of fruit and nectar feeding bats (Family Pteropodidae, Suborder Megachiroptera). This review of the bat borne henipaviruses discusses the epidemiology, pathology, transmission and disease symptoms in these closely related viruses which belong to the Genus Henipavirus, Family Paramyxoviridae."
5980,Dengue and chikungunya virus infection in Southeast Asia: active governmental intervention in Republic of Singapore,"This paper discusses countermeasures of Republic of Singapore towards mosquito-borne infectious diseases, particularly, dengue and chikungunya virus infection to identify an essential factor in controlling emergence of infectious diseases. In spite of expanding areas affected by and upsurge of these diseases in the region, the tropical urban country is known to have sustained an effective vector control, which often resulted in moderate prevalence and/or quick control of domestic outbreaks. This research has adopted an inter-disciplinary review of previous studies combined with field studies: interviewing at the Ministry of Health, Singapore and the National Environment Agency, Singapore; visiting a laboratory and hospitals; and observing on-site vector mosquito surveillance operations conducted by the agency. The findings have pointed out the national vector surveillance and control system implemented by 1970s, followed by improved countermeasures like vector and virus surveillance which have incorporated science and technology especially in the last two decades. The analysis produces an influential role of a government in promoting and supporting public health measures, which have been typically demonstrated through inter-ministry collaboration, public-private cooperation, and community involvement. In light of increasing transnational nature of emerging infectious diseases, Singapore’s contribution in the region like sharing its knowledge of and experiences in dengue and chikungunya virus infection is illustrated. The resilient model of Singapore’s vector control and governmental action warrants a further study to investigate transferability in other parts of the region."
5981,Virus Neutralization Assay for Turkey Coronavirus Infection,Turkey coronavirus (TCoV) infection induces the production of protective antibodies against the sequent exposure of TCoV. Serological tests to determine TCoV-specific antibodies are critical to evaluate previous exposure to TCoV in the turkey flocks and differentiate serotypes from different isolates or strains. A specific virus neutralization assay using embryonated turkey eggs and immunofluorescent antibody assay for determining TCoV-specific neutralizing antibodies is described in this chapter. Virus neutralization titer of turkey serum from turkeys infected with TCoV is the dilution of serum that can inhibit TCoV infection in 50 % of embryonated turkey eggs. Virus neutralization assay for TCoV is useful to monitor the immune status of turkey flocks infected with TCoV for the control of the disease.
5982,Thymus Transplantation,"Thymus transplantation was first attempted in the 1960s and 1970s using fetal thymus tissue [1, 2]. The results overall were disappointing [3–6]. In part the poor outcomes related to the lack of reagents needed to characterize and identify the patients into those who were truly athymic (complete DiGeorge anomaly) and those who had bone marrow stem cell problems (severe combined immunodeficiency). It is also possible that the fetal thymus tissue was too small to reconstitute a human infant [7]. The use of fetal thymus carried the risk of fatal graft versus host disease since mature T-cells can be found in the human thymus by the end of the first trimester [3]. By 1986, in a review of 26 infants treated with fetal thymus transplantation, 22 had died; the other 4 patients had achieved a 3-year survival [6]."
5983,Respiratory,"Lung disease rivals the position for the top cause of death worldwide. Causes and pathology of the myriad lung diseases are varied, yet nutrition can either affect the outcome or support treatment in the majority of cases. This chapter explores the modifiable risk factors, from lifestyle changes to dietary intake to specific nutrients, anti-nutrients, and toxins helpful for the nutritionist or dietitian working with lung disease patients. General lung health is discussed, and three major disease states are explored in detail, including alpha-1 antitrypsin deficiency, asthma, and idiopathic pulmonary fibrosis. Although all lung diseases have diverse causes, many integrative and functional medical nutrition therapies are available and are not being utilized in practice today. This chapter begins the path toward better nutrition education for the integrative and functional medicine professional."
5984,Vasculitis,"Vasculitis, characterized by inflammation and necrosis, manifests a wide spectrum of presentation by involving a vasculature of various sizes and locations. A definitive diagnosis of vasculitis invariably requires histologic confirmation since there are no diagnostic clinical, imaging, or laboratory findings. The most widely adopted vasculitis classification is the Chapel Hill Consensus Conference (CHCC) nomenclature of systemic vasculitis which integrated clinical symptoms, histopathologic features, and laboratory findings. This classification accounts for the size of the involved vessels. This chapter outlines the clinical and histologic features of the small-vessel vasculitis including the immune complex vasculitis and antineutrophil cytoplasmic antibody-associated vasculitis; medium-vessel vasculitis such as polyarteritis nodosa and Kawasaki disease; large-vessel vasculitis, namely, giant cell arteritis and Takayasu arteritis; variable-vessel vasculitis such as Behcet disease and Cogan syndrome; and vasculitis associated with systemic diseases including rheumatoid arthritis, lupus vasculitis, and sarcoid vasculitis. Vasculitis can also be secondary to drugs, infection, underlying systemic disease, or trauma. Therefore, a diagnosis of vasculitis cannot be based on histologic ground alone. Clinical pathologic correlation is necessary."
5985,Evaluation and Management of Bacterial and Fungal Infections Occurring in Patients with a Hematological Malignancy: A 2011 Update,"Patients with a hematological malignancy are a heterogeneous patient population who are afflicted with diseases that range from rapidly fatal acute leukemia to indolent lymphoma or chronic leukemia. Treatment options for these patients range from observation to hematopoietic stem cell transplantation (HSCT), but all patients are more susceptible to infection. The problem of infection is dynamic with continued shifts in pathogenic organisms and microbial susceptibilities, new treatment regimens that further diminish immune function, and patients receiving treatment who are now older and frailer. The classic patterns of immunodeficiency for patients with a hematological malignancy include: periods of profound neutropenia, increased iatrogenic risks (i.e., central vascular catheters), and cellular immune suppression that affects HSCT recipients, patients with lymphoid malignancies, and those receiving treatment with corticosteroids or agents like alemtuzumab [1–4]. Recent advances in antimicrobial drug development, new technology, clinical trial results, and further clinical experience have enhanced the database on which to make infection prophylaxis and treatment decisions. However, the practicing clinician must remember that the majority of basic infection management principles for patients who are neutropenic remain unchanged."
5986,Infectieziekten,"Infectie ontstaat bij een stoornis in de interactie(s) tussen gastheer en microorganisme (zie fig. 10.1). Bij gezonde personen is er evenwicht tussen de gastheer en de micro-organismen op huid en slijmvliezen en in het omringende milieu. Dit evenwicht kan worden verstoord: 1. doordat de gastheer in contact komt met micro-organismen die nieuw voor hem zijn en waartegen hij zich (nog) niet voldoende kan verweren, 2. doordat het aantal micro-organismen is toegenomen en 3. doordat de weerstand van de gastheer is verminderd. Infectie kan men dus definiëren als het samenspel van de reacties van de gastheer op micro-organismen."
5987,Transmissible Spongiforme Enzephalopathie (TSE),
5988,Regulation of Air Cargo,"Annex 9 to the Chicago Convention in its Chapter 4 has several provisions pertaining to cargo which comes under the purview of ICAO. With a view to facilitating and expediting the release and clearance of goods carried by air, Contracting States are required to adopt regulations and procedures appropriate to air cargo operations and shall apply them in such a manner as to prevent unnecessary delays. Standards and Recommended Practices on Facilitation were first adopted by the Council on 25 March 1949, pursuant to the provisions of Article 37 of the Convention on International Civil Aviation (Chicago, 1944), and designated as Annex 9 to the Convention with the title “Standards and Recommended Practices — Facilitation”. They became effective on 1 September 1949. To begin with, States are advised that with respect to cargo moving by both air and surface transport under an air waybill, Contracting States should apply the same regulations and procedures and in the same manner as they are applied to cargo moving solely by air. When introducing or amending regulations and procedures for the release and clearance of goods carried by air, Contracting States are required to l consult with aircraft operators and other parties concerned, with the aim of accomplishing the actions set forth in the Annex. Furthermore, Contracting States are required to develop procedures for the pre-arrival and pre-departure lodgement of an import and export goods declaration to enable expeditious release/clearance of the goods. Where the nature of a consignment could attract the attention of different public authorities, e.g. the customs, veterinary or sanitary controllers, Contracting States shall endeavour to delegate authority for release/clearance to customs or one of the other agencies or, where that is not feasible, take all necessary steps to ensure that release/clearance is coordinated and, if possible, carried out simultaneously and with a minimum of delay. Contracting States are not normally expected to require the physical examination of cargo to be imported or exported and are required to use risk management to determine which goods shall be examined and the extent of that examination. Where practicable, and with a view to improving efficiency, modern screening or examination techniques are required to be used to facilitate the physical examination of goods to be imported or exported."
5989,Enhancing the Literature Review Using Author-Topic Profiling,"In this paper, we utilize bibliographic data for identifying author-topic relations which can be used to enhance the traditional literature review. When writing a research paper, researchers often cite on the order of tens of references which do not provide the complete coverage of the research context especially when the targeted research is multidisciplinary. Author-topic profiling can help researchers discover a broader picture of their topic of interest including topical relationships and research community. We apply the Latent Dirichlet Allocation (LDA) to generate multinomial distributions over words and topics to discover author-topic relations from text collections. As an illustration, we apply the methodology to bibliographic abstracts related to Emerging Infectious Diseases (EIDs) research topic."
5990,Viral Haemorrhagic Fever (VHF) and Other Serious Viral Infections: First contact - how to act and protect,"Viral haemorrhagic fever—VHF—virus and a number of other special viruses are considered to cause the world’s most dangerous infections with very high mortality, lack of therapeutic possibilities and often absence of effective vaccines. Such viruses are identified as “biohazard-level 4” agents and are treated at the highest level of infection protection with strict isolation measures. At least 14 patients with Ebola disease were transported to Europe and the United States (11 patients) for hospital treatment during the African epidemic in 2014. There were no secondary spread of VHF import cases in Europe and the United States from 1999 until the Ebola outbreak in 2014. Then there were three cases of nosocomial spread to personnel in hospitals, two in the United States and one in Spain, despite alleged use of strict containment routines. This indicates a high risk of spread of infection through intensive treatment and handling of very sick persons with VHF like Ebola. In most cases vaccines are not available or specific antiviral drugs. Therefore, infection control must be based on a proper infection protection. This chapter is focused on practical means to handle and treat patients with suspect VHF or other dangerous agents to avoid spread to personnel and environment"
5991,Eating Cultures,
5992,Schwarze Haarknötchenkrankheit,
5993,Reconfiguring Species for Immunitary Hybridity,"Like blood, transplantation is a singularly defining expression of the contemporary biopolitics of immunity. This chapter focuses on the contentious clinical and research domain of transpecies transplantation, or xenotransplantation. Where the previous chapter was primarily concerned with the biopolitics of immunitary circuits between humans, this discussion turns towards our changing biotechnological relationship to other species, other immunitary animals. Whilst the approach may well offer a therapeutically life-saving solution for transplant patients, it potentially provides a means of transferring contagious diseases across species barriers. The chapter explores, with reference to Derrida and Sloterdijk, the tendency of immunitary purification and protection to recoil back upon their original designs. The chapter asks what might it mean to place trust in, or have confidence in, biosecurity measures that make the realisation of a threat (pandemics, xenozoonotic disease outbreaks, etc) more possible, not less so."
5994,Respiratory Pathogens,"Respiratory tract infections are among the most common presenting complaints of patients in both hospital and community settings. They are a considerable burden in terms of both patient morbidity and public health interventions. Laboratory diagnosis of respiratory tract infections should provide guidance in therapy and prognosis, as well as useful epidemiological information reflecting trends in the community. Understanding and monitoring such trends facilitates early recognition of new infectious agents in a population. A summary of the common viruses and bacteria causing respiratory tract infections and their clinical relevance is given in Tables 41–1 and 41–2, respectively."
5995,Hemostatic Resuscitation,"Advances in surgical and critical care medicine frequently parallel the course of armed conflict. Indeed, surgery is a specialty born of warfare and will continue to drive advancements as mankind finds new and more lethal methods of combat. As hemorrhage is far and away the leading cause of potentially survivable death on the battlefield, the methods of resuscitation and blood transfusion continue to evolve. The critical role that blood plays in resuscitation of the critically injured patient was first explored during World War I for the treatment of ‘wound shock’. Type O whole blood was collected in sterile glass bottles containing citrate and transfused into patients prior to surgery. During the years following World War I, blood component fractionation became available, blood banking was initiated, and the transfusion of packed red blood cells (RBCs), fresh frozen plasma (FFP) and platelets became a mainstay of the trauma management paradigm. However, in times of war the variable availability of short-lived platelets, FFP, and cryoprecipitate inevitably leads back to the resurrection of fresh whole blood transfusion. Fresh whole blood, though not without some risk, restores the hemostatic mechanism and provides volume and oxygen-carrying capacity."
5996,Researching Migrant Chinese Families in Hong Kong: Changing Perspectives and Methodologies,"This chapter argues that research on Mainland Chinese migrants in Hong Kong has become more diverse, dynamic and complex over the past 25 years. The previously dominant thinking, such as the social adjustment agenda and the human capital-deficit model, has strongly been challenged by three emerging perspectives, such as rights-based citizenship, gender and empowerment, and social capital building. These new perspectives enrich our understanding by deconstructing migrants as many social groups with competing needs and facing constraints. They also demystify migrant families by examining the power dynamics within these families. New research methodologies, such as ethnography and participatory action research, and new methods, such as photovoice and community map drawing, have been experimented with in order to engage and empower the migrants. These changing perspectives are more sensitive to the influence of locality and have brought some impact on social service provision and delivery."
5997,Noninvasive Ventilation in Patients with Acute Respiratory Failure Due to Influenza A(H1N1) Virus Infection,"During the type ‘A’ Influenza epidemic (‘swine flu’), most of the patients admitted to the intensive care unit (ICU) required assisted ventilation because of an acute respiratory failure (ARF). Noninvasive ventilation (NIV) was used in varying proportions in the published series, but it showed a high failure rate. In our series — specifically in a group of hypoxemic patients — NIV was employed successfully in all cases without any hypoxemia-related deaths. Accordingly, we recommend NIV can be applied to healthy young hypoxemic patients before considering invasive mechanical ventilation (IMV)."
5998,Screening for Gastric Cancer in Japan,"Gastric endoscopy has not yet been recommended for organized or population-based cancer screening because at the moment, the sole criterion for evaluating the effectiveness of cancer screening is the reduction in the death rate, and not the mere detection of cancer. Nevertheless, compared with X-ray screening, which has normally been recommended, endoscopic screening is better at finding small lesions, at finding cancer at its earlier stages, making it more easily and economically treatable, and allows on-the-spot biopsies. Opportunistic, individually initiated screening by endoscopy is more and more in demand. Therefore, its excellent efficacy needs to be matched by improved toleration, improved safety, and improved manpower efficiency so that it can be standardized and utilized to its full diagnostic, therapeutic, and quality-of-life potential."
5999,The Role of the Human Bocavirus (HBoV) in Respiratory Infections,"The human bocavirus is one of the most common respiratory viruses and occurs in all age groups. Because Koch’s postulates have been fulfilled unintendedly, it is currently accepted that the virus is a real pathogen associated with upper and lower respiratory tract infections causing clinical symptoms ranging from a mild common cold to life-threatening respiratory diseases. In order to exclude a viremia, serological analysis should be included during laboratory diagnostics, as acute and chronic infections cannot be differentiated by detection of viral nucleic acids in respiratory specimen alone due to prolonged viral shedding. Besides its ability to persist, the virus appears to trigger chronic lung disease and increases clinical symptoms by causing fibrotic lung diseases. Due to the lack of an animal model, clinical trials remain the major method for studying the long-term effects of HBoV infections."
6000,Pseudoknot Identification through Learning TAG(RNA),"Studying the structure of RNA sequences is an important problem that helps in understanding the functional properties of RNA. Pseudoknot is one type of RNA structures that cannot be modeled with Context Free Grammars (CFG) because it exhibits crossing dependencies. Pseudoknot structures have functional importance since they appear, for example, in viral genome RNAs and ribozyme active sites. Tree Adjoining Grammars (TAG) is one example of a grammatical model that is more expressive than CFG and has the capability of dealing with crossing dependencies. In this paper, we describe a new inference algorithm for TAG(RNA,) a sub-model of TAG. We also introduce an RNA structure identification framework, TAG(RNA)Inf, within which the TAG(RNA) inference algorithm constitutes the core of the training phase. We present the results of using the proposed framework for identifying RNA sequences with pseudoknot structures. Our results outperform those reported in [14] for the same problem that employs a different grammatical formalism."
6001,10 Acute bovenbuikpijn,"Op de afdeling spoedeisende hulp wordt ’s nachts een 53-jarige vrouw binnengebracht met pijn in de bovenbuik, die acuut is ontstaan na de maaltijd. De huisarts heeft de patiënte met spoed ingestuurd. Zij is bekend met symptomatisch galsteenlijden (recidiverende kolieken) en staat op de opnamelijst voor een laparoscopische cholecystectomie."
6002,Guide to Terms,
6003,"Sourcing the Fungal Endophytes: A Beneficial Transaction of Biodiversity, Bioactive Natural Products, Plant Protection and Nanotechnology","Endophytes are the group of microorganisms that reside to internal and healthy tissues without causing negative symptoms to their host plant. Endophytes are extremely diverse and range from fungi, bacteria and actinomycetes. Development of drug resistance to pathogenic forms of bacteria, fungi and other microbes, emergence of lethal viruses, the perpetuating epidemics in developing and under developing countries, and multifold fungal infection, enhancement in human population globally, all shows our inability to overcome these biomedical problems. In addition to this, we are also unable to assure people towards enough food security in specific regions of the earth due to infestation of different plant diseases. Since the fungal endophytes are relatively less studied group of microbial flora, but are responsible for several prospects such as biodiversity, ecology, bioactive metabolites (metabolomics) and nanotechnology, may enable us to overcome the above mentioned problems. Fungal endophytes represent a dependable source of specific secondary metabolites and can be manipulated both physicochemically and genetically to increase yield of desired compounds and to produce novel analogues of active metabolites. In this chapter, we have discussed several bioactive compounds and classified them in to different classes as per their properties such as antifungal, antibacterial, antiviral, antimalarial, anticancer, antioxidants, antidiabetic and immunosuppressive agents derived from fungal endophytes with their hosts and made the chemical structures for 73 compounds using chemdraw 3D ultra version 7.0. These bioactive products are related to human health with MIC/EC/IC(50) values less that 50 μg/mL. This article also discusses nematicidal, some antimicrobial volatile compounds (VOCs) that are related to plant protection and faecal disposal. Therefore, this chapter is not very specific and covers almost prospects of fungal endophytes which could be useful in biodiversity, agrochemicals, biotechnology, biomedical and nanotechnology in ecofriendly manner."
6004,Schlachthausfieber,
6005,A Framework for Social Development Assessment,"Behavioural change is probably the single most difficult objective communicators are asked to undertake. In the private sector it is an area which falls under marketing, and in the context of development it could also be called social marketing. Nor is behavioural change communication confined to the developing world. Countries at all levels of development undertake mass awareness campaigns in order to influence behaviours, as does the private sector."
6006,Management of Ventilator-associated Pneumonia,"Pneumonia is the most important respiratory infection in mechanically ventilated patients. It is defined as the presence of microorganisms in the pulmonary parenchyma leading to the development of an inflammatory response by the host, which may be localized in the lung or may extend systemically. Nosocomial pneumonia is an infectious process which develops within 48 hours after admission to the hospital and that was not incubating at the time of hospitalization. Ventilator-associated pneumonia (VAP) is considered as a subgroup of nosocomial pneumonia and is an infectious pulmonary process which develops 48 hours after the presence of an artificial airway and mechanical ventilation. Since a large proportion of the patients who develop nosocomial pneumonia are intubated and receive mechanical ventilation, most epidemiological and clinical studies on nosocomial pneumonia have been focused on critically ill patients and those receiving mechanical ventilation. From a clinical point of view, nosocomial pneumonia is of great importance not only because of the consequences of the important morbidity and mortality but also due to the high costs associated with development of this disease."
6007,Collagen Vascular Diseases and Disorders of Connective Tissue,"The collagen vascular diseases, also referred to as connective tissue diseases, are a diverse group of systemic inflammatory disorders thought to be immunologically mediated. The concept of collagen vascular disease began to take shape in the 1930s, when it was recognized that rheumatic fever and rheumatoid arthritis can affect connective tissues throughout the body.1,2 During the following decade, as conditions such as systemic lupus erythematosus (SLE) and scleroderma came to be viewed as systemic diseases of connective tissue, the terms diffuse connective disease and diffuse collagen disease were proposed.3,4 During the same period, the designation of diffuse vascular disease was proposed for diseases such as scleroderma, polymyositis, SLE, and polyarteritis nodosa, which featured widespread vascular involvement.5 With the realization that many of these entities can exhibit both systemic connective tissue manifestations and vascular abnormalities, the unifying designation of collagen vascular disease was introduced.6"
6008,"Dynamic Light Scattering (DLS): Principles, Perspectives, Applications to Biological Samples","Focus a laser on dissolved particles and analyze the scattered light to reveal their size. This well established principle is used in dynamic light scattering (DLS), or also called photon-correlation spectroscopy, which is a widely popular and highly adaptable analytical method applied in different fields of life and material sciences, as well as in industrial quality control processes."
6009,Ventilazione non invasiva nell’insufficienza respiratoria in età pediatrica,"Il termine ventilazione non invasiva (NIV) identifica una ventilazione sincronizzata a pressione positiva combinata, con l’applicazione di pressione positiva di fine espirazione (PEEP) sulle vie aeree, attraverso un’interfaccia non invasiva e pertanto senza necessità di intubazione endotracheale. Scopi principali della NIV sono l’incremento del volume corrente e della ventilazione alveolare, unitamente alla riduzione del lavoro respiratorio del paziente. La NIV utilizza dunque un’interfaccia esterna, che può essere rappresentata da diversi tipi di cannule nasali, maschere nasali o facciali, oppure da un casco (elmetto), i quali sono connessi a un apposito ventilatore per NIV o comunque a un ventilatore con controllo di pressione."
6010,Amelanchier alnifolia,"This species is native to North America from Alaska, Western Canada and western (southwards to North California, Utah and Colorado) and north central Unites States. In Canada, the species is found in British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec, North West Territories and Nunavut."
6011,Assessment of Age-related Decline of Immunological Function and Possible Methods for Immunological Restoration in Elderly,"The immune system plays an important role in protection against infection and in the maintenance of the internal environment of the body. However, such important immune functions are known to decline with age in many mammals, including humans. It is a matter of clinical importance that the incidence of various age-associated diseases such as infections, cancer and vascular disorders increases with a decrease in immunological vigor. The extent of immunologic decline is variable and exhibits wide inter-individual variations. Thus, it is important to assess the extent of immunologic decline in both patients suffering from various diseases and in healthy people in order to maintain healthy conditions. To this end, we have developed a scoring system that analyzes immune parameters according to a database of known age-associated immune changes obtained from a healthy population. Using this scoring system, we can combine several different immunological parameters and express the immune status of individuals as a simple numeral. After determining immunological vigor for individuals, it is necessary to replenish immune defects and restore them to normalcy for individuals with depressed immunological scores. This chapter provides methods of immunological restoration in animal models and introduces some similar attempts in humans. The effect of any immunological restoration varies with the individual and must therefore verified. Currently, the proposed immune scoring system proposed is useful to determine whether the methods employed are effective for the restoration of immune functions."
6012,Neisseria gonorrhoeae,Gonokokken
6013,Hematologic Disorders,Definition. Anemia is defined as an absolute decrease in the circulating red blood cell (RBC) mass.
6014,Medische aspecten van bloedtransfusie,"Lang werd gedacht dat bloed het wezen van het leven was, het middelpunt van de geest; men geloofde dat het mensen voorzag van fysieke kracht en geestelijke vermogens. Dit leidde tot de veronderstelling dat men door het drinken van bloed sterker en gezonder zou worden. Gladiatoren werden aangemoedigd om in de arena het bloed van de verslagenen te drinken om een deel van hun moed en kracht te verkrijgen. Anderzijds heerste in die tijd ook de gedachte dat een slechte gezondheid, geestelijke ziekten en depressies een gevolg waren van verdorven lichaamssappen of vergiftigd bloed en dat aderlaten om die reden een geneeskracht had voor vele kwalen. Ovidius vertelde in zijn Metamorphosen (43 v.Chr.) het verhaal van de tovenares Medea, die het verdriet van haar geliefde Jason over zijn steeds zwakker wordende oude vader nauwelijks kon verdragen. In een poging de vader weer kracht te geven en te verjongen, sneed ze de keel van de oude man door, liet al het bloed eruit lopen en verving het door een eigen toversap. En ziedaar, het wonder geschiedde: zijn witte haren en baard werden zwart, zijn rimpels verdwenen en hij verrees krachtig van lijf en leden. Ook toen bloedtransfusies tot de mogelijkheden gingen behoren, werden ze gek genoeg niet gebruikt om een voor de hand liggende reden als bloedverlies, maar voor de bestrijding van allerlei geestelijke of emotionele kwalen."
6015,Gentherapie,"Die Gentherapie ist eine junge Wissenschaft, die Nukleinsäuren zur Therapie einsetzt (Hengge u. Bardenheuer 2004). Die somatische Gentherapie befasst sich mit der Behandlung von somatischen (Körper-)Zellen (⧁ Tab. 4.1.1), wobei das therapeutische Gen ein im Organismus benötigtes Protein kodiert."
6016,Noninvasive Mechanical Ventilation Guidelines and Standard Protocols for Noninvasive Mechanical Ventilation in Patients with High-Risk Infections,"Noninvasive ventilation (NIV) is associated with lower rates of endotracheal intubation and decreased mortality in patients with acute respiratory failure. Therefore, NIV should be preferred to invasive ventilation whenever possible [1]. In clinical settings, most of the patients were treated by NIV because of pulmonary edema or exacerbated chronic obstructive lung disease (COPD) [2]. With endemic and high-risk infection, most of the critically ill patients develop acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS). Furthermore, NIV, an “aerosol-producing factor” might be regarded as a high-risk procedure for medical staff [3]."
6017,Risk Management in Global Supply Chain Networks,"In this paper, we develop a framework to classify the Global supply chain risk management problems and present an approach for the solution of these problems. The risk management problems need to be handled at three levels strategic, operational and tactical. In addition, risk within the supply chain might manifest itself in the form of deviations, disruptions and disasters. To handle unforeseen events in the supply chain there are two obvious approaches: (1) to design chains with built in risk-tolerance and (2) to contain the damage once the undesirable event has occurred. Both of these approaches require a clear understanding of undesirable events that may take place in the supply chain and also the associated consequences and impacts from these events. We focus our efforts on mapping out the propagation of events in the supply chain due to supplier non-performance, and employ our insight to develop a mathematical programming based model for strategic level deviation and disruption management. The first model, a simple integer quadratic optimization model, adapted from the Markowitz model, determines optimal partner selection with the objective of minimizing both the operational cost and the variability of total operational cost. This model offers a possible approach to robust supply chain design. Key words: Supply Chain Risk Management; Risk Management; Supply Chain Planning; Supply Chain Design; Mean-Variance Optimization; Cause-Consequence Diagrams; Failure Analysis."
6018,Tropische kindergeneeskunde,"Tropische kindergeneeskunde is een geijkte, maar niet nauwkeurig omschreven term. De ernstige gezondheidsproblemen van kinderen in de tropen en subtropen vinden namelijk hun oorzaak eerder in armoede, ongeletterdheid en oorlogen dan in specifieke tropische condities."
6019,Epidemic-Logistics Network Considering Time Windows and Service Level,"In this chapter, we present two optimization models for optimizing the epidemic-logistics network. In the first one, we formulate the problem of emergency materials distribution with time windows to be a multiple traveling salesman problem. Knowledge of graph theory is used to transform the MTSP to be a TSP, then such TSP route is analyzed and proved to be the optimal Hamilton route theoretically. Besides, a new hybrid genetic algorithm is designed for solving the problem. In the second one, we propose an improved location-allocation model with an emphasis on maximizing the emergency service level. We formulate the problem to be a mixed-integer nonlinear programming model and develop an effective algorithm to solve the model. In this chapter, we present two optimization models for optimizing the epidemic-logistics network. In the first one, we formulate the problem of emergency materials distribution with time windows to be a multiple traveling salesman problem. Knowledge of graph theory is used to transform the MTSP to be a TSP, then such TSP route is analyzed and proved to be the optimal Hamilton route theoretically. Besides, a new hybrid genetic algorithm is designed for solving the problem. In the second one, we propose an improved location-allocation model with an emphasis on maximizing the emergency service level. We formulate the problem to be a mixed-integer nonlinear programming model and develop an effective algorithm to solve the model."
6020,Microbial Contamination in Airplane Cabins:Health Effects and Remediation,"Microorganisms that affect human health are found in all indoor environments, including cabins of commercial aircraft. Those that arise from human sources can be transmitted by direct contact, droplets, or the airborne route. Infections from human sources include Influenza, Rhinovirus, SARS and tuberculosis. Transmission by the airborne route can be reduced by sterilizing the air with ultraviolet germicidal irradiation, or by diluting the contaminated air with outdoor air through ventilation. Microbes arising from environmental sources include bacteria, fungi and other organisms such as protozoa. These usually have very simple requirements for growth – water and a simple substrate such as dust. They cause health effects through direct infection rarely (one example is Legionnella), but more commonly cause immune reactions resulting in hypersensitivity or allergy mediated diseases. Environmental sources of microbial contamination are best prevented, but can be remediated through cleaning, germicidal chemicals, or ultraviolet germicidal irradiation. Airborne microbial substances including toxins, antigens and viable organisms can be removed by outdoor air ventilation or filtration. In aircraft cabins transmission of pathogens from human sources is difficult to control, but airborne transmission can be reduced through increased outdoor air ventilation or filtration. Environmental microbial contamination can, and does occur in aircraft cabins. These microbial sources are best prevented but, if detected, can be removed through cleaning or disinfection. Ultraviolet germicidal irradiation is an under-utilized technology that may be useful for sterilizing air as well as potential environmental sources."
6021,Disease Now and Potential Future Pandemics,"The chapter reviews diseases of humanity, both chronic disease and emergent diseases, that may harp much of humanity over short periods of time. It explains why the chances for pandemics are increasing and how they are inevitable. The threats of biological warfare and bioterrorism are covered, and the ways that we can stop pandemics are brought to the reader’s attention."
6022,Presentation and Diagnosis of Interstitial Lung Diseases,"Diffuse interstitial lung disease is a heterogeneous group of lung pathologies with similar clinical presentations. Radiologists and pathologists attempted to identify precise diagnostic criteria. Often, the pattern and distribution of the disease allow to narrow down the possible diagnoses, but the correlation with the clinical presentation is essential."
6023,Noninvasive Mechanical Ventilation in Patients with Severe Pneumonia,"Community-acquired pneumonia (CAP)—pneumonia occurring within 48 h after hospital admission or more than 2 weeks after discharge—leads to hospitalization rates of 20–35 % in Europe, with figures in Spain being even higher at 22–61 %. A substantial proportion of these cases (10 %) are defined as severe. These patients must be admitted to the intensive care unit (ICU) because of the possible need for ventilatory or hemodynamic support. Their mortality rate can be as high as 40 % [1]. In the rest of Europe the incidence of CAP is 5–11 cases per 1,000 person-years, and in Spain it drops to 1.6–1.8 cases per 1,000 person-years, with men and the elderly most often affected and mostly in winter [1]."
6024,Genotype-Specific Detection of Ferret Coronavirus by Conventional and Real-Time Reverse Transcription Polymerase Chain Reaction,"Ferret coronavirus is associated with two disease presentations in ferrets, namely, epizootic catarrhal enteritis and a feline infectious peritonitis (FIP)-like systemic disease. In this chapter, we describe conventional and real-time one-step reverse transcription polymerase chain reaction assays that are routinely used in our laboratory to detect either genotype 1 or genotype 2 ferret coronavirus in clinical specimens. These assays were designed based upon the conserved spike gene sequence difference found between three strains of ferret systemic coronavirus and three strains of ferret enteric coronavirus. Recent literature evidence indicates that pathotype is not associated with a specific genotype, and therefore, it is important to test for both genotypes either in enteric or systemic disease."
6025,Smallpox and Bioterrorism,
6026,"The 2003 SARS Outbreak In Singapore: Epidemiological and Clinical Features, Containment Measures, and Lessons Learned","On 6 March 2003, the Singapore Ministry of Health was notified of a cluster of atypical pneumonia in three patients with a history of travel to Hong Kong (Hsu et al., 2003). These three female travelers had stayed at the Metropole Hotel on the same floor as a Chinese physician later diagnosed with severe acute respiratory syndrome (SARS) (Hsu et al., 2003; Peiris et al., 2003). After returning to Singapore, one of the travelers (index A) who developed fever on February 25 was hospitalized at Tan Tock Seng Hospital on March 1, and was managed initially for straightforward community-acquired pneumonia. The other two travelers were also admitted with similar symptoms. Shortly thereafter, clusters of cases emerged in three separate wards, all traceable to the first imported case. By the time index A was isolated on March 6, she had already infected 22 persons, comprising ten health care workers, two inpatients, seven visitors, and three family members. One of the infected health care workers (index case B), with onset of symptoms on March 7 and a provisional diagnosis of dengue fever, was later admitted on March 10 to Ward 8A. At the ward she in turn infected 21 persons, including an inpatient with ischemic heart disease and diabetes mellitus, before she was isolated on March 13 (Wilder-Smith et al., 2004b). The inpatient (index case C) had been admitted on March 10 with fever, community-acquired pneumonia, and gramnegative bacteremia. When she developed heart failure on March 12, she was transferred to Ward 6A (the coronary care unit) and mechanically ventilated. However, she was isolated only on March 20 when SARS was suspected. By that time, 21 health care workers and 5 family members had become infected (Wilder- Smith et al., 2004b). A total of 109 cases were epidemiologically linked to index A. Intra-hospital transmission at Tan Tock Seng Hospital was interrupted by April 12, the date of onset of the hospital’s last case. Despite the institution of very rigorous infection control measures at Tan Tock Seng Hospital, SARS spread to four other health care institutions (Singapore General Hospital, National University Hospital, Changi General Hospital, and Orange Nursing Home – the last two are grouped together in Fig. 1 and a vegetable wholesale market (Gopalakrishna et al., 2004) (Fig. 1)."
6027,Economic Aspects of Zoonoses: Impact of Zoonoses on the Food Industry: Impact of Zoonoses on the Food Industry,"The increase of complexity of livestock production and the associated value chains has led to changes in the food systems that feed us, which in turn carry new challenges from zoonotic diseases in particular their impact, and the costs of surveillance, control and prevention. Direct losses to the animal and public health sectors, connected mainly to value losses due to morbidity and mortality in humans and animals, and indirect losses, such as the economic cost caused by the reaction to disease and the limiting of its negative effects, all contribute to this negative impact. Its full assessment can be challenging, but economic tools and frameworks can be used to estimate zoonotic disease impact and the economic efficiency of possible technical ways of dealing with these diseases. In this chapter, we review the impact of zoonoses across sectors, also in the context of an increasingly complex value chain, address the economic concepts behind the balance between losses due to direct costs of disease and expenditures in reaction to disease presence, and identify possible economic tools and frameworks to assess the impact of zoonoses and interventions."
6028,Surveillance,"Health surveillance is the continuous observation, a strategic and systematic collection, analysis and interpretation of health-related data for public health purposes. The data collected from surveillance systems can be stored in databases and can be used for scientific research, proving facts and identifying trends that can be used to make informed decisions. Surveillance systems do provide information that can be used as an early warning system for disease outbreaks and epidemics. Health surveillance, active or passive, provides a window into the health conditions and risks in communities and how these conditions are affecting the populations and their livelihoods. Developing countries should install systems of registration in place in order to track behaviour, traditions, diet and other ways of life that could contribute to infectious disease occurrence. Lack of knowledge has cost many lives especially for the poor communities in developed countries. Promoting the use of information and data in public decision-making is cardinal in managing infectious diseases and controlling disease outbreaks."
6029,Pleiomorphic viruses revealed by cryo tomography: the structure of coronaviruses,"Cryo-electron microscopy has provided in the last decades a wealth of three-dimensional information on viral structures. However, most of this knowledge stems from single particle methods, which rely on averaging and are therefore restricted to viral homogenous structures such as icosahedral capsids [1]. This type of analysis excludes pleiomorphic viruses, that is, viruses that, having defined general architectures, arrange their components into different shapes or sizes. Cryo-electron tomography, which provides three-dimensional reconstructions of unique specimens, is now starting to shed light into the structure of this type of viruses [2]."
6030,Adrenal Insufficiency and CIRCI,"The stress system receives and integrates a diversity of cognitive, emotional, neurosensory, and peripheral somatic signals that are directed to the central nervous system through distinct pathways. The stress response is normally adaptive and time limited and improves the chances of the individual for survival. The stress response is mediated largely by activation of the hypothalamic–pituitary–adrenal (HPA) axis with the release of cortisol. In general, there is a graded cortisol response to the degree of stress, such as the type of surgery. Cortisol levels also correlate with the severity of injury, the Glasgow Coma Scale, and the APACHE score. Cortisol effects the transcription of thousands of genes in every cell of the body. In addition, the cortisol–glucocorticoid receptor complex effects cellular function by non-transcriptional mechanisms. Cortisol has several important physiological actions on metabolism, cardiovascular function, and the immune system. Cortisol increases the synthesis of catecholamines and catecholamine receptors, which are partially responsible for its positive inotropic effects. In addition, cortisol has potent anti-inflammatory actions including the reduction in number and function of various immune cells, such as T and B lymphocytes, monocytes, neutrophils, and eosinophils at sites of inflammation. Cortisol is the most important inhibitor of the transcription of pro-inflammatory mediators (inhibits NF-κB and AP-1 by multiple mechanisms).(1)"
6031,"Severe Malaria: Manifestations, diagnosis, chemotherapy, and management of severe malaria in adults",
6032,Mathematical Modeling of Crimean-Congo Hemorrhagic Fever Transmission,"This chapter is divided into five sections. Section 15.1 discusses the rationale for using mathematical models. Section 15.2 considers the specific areas where models may be useful in studying Crimean-Congo hemorrhagic fever (CCHF). Section 15.3 reviews work on modeling the dynamics of tick-borne diseases and considers the relevance of this work for CCHF. Section 15.4 considers the problem of modeling the nosocomial transmission of CCHF. Section 15.5, lastly, suggests future directions for CCHF modeling work."
6033,Pancreatitis and Pancreatic Pseudocyst,"Pancreatitis which is characterized by inflammation of the pancreas is an uncommon condition in the pediatric age group. Pancreatitis in children represents a diagnostic challenge for clinicians and a high index of suspicion is important for early diagnosis of pancreatitis which is known to be associated with significant morbidity and mortality. The etiology, diagnosis and aspects of management are discussed."
6034,Idiopathic Interstitial Pneumonias,"The idiopathic interstitial pneumonias are a distinct group of clinicopathologic entities. High-resolution computed tomography (HRCT) plays a critical role in the evaluation and management of patients. In the appropriate clinical setting, characteristic HRCT findings may be diagnostic, obviating the need for open lung biopsy. In more challenging or complicated cases, consensus among the clinician, radiologist, and pathologist may be required. This chapter describes and depicts the characteristic HRCT features of usual interstitial pneumonia, nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, respiratory bronchiolitis, respiratory bronchiolitis associated interstitial lung disease, desquamative interstitial pneumonia, and lymphoid interstitial pneumonia."
6035,Selenium in health and disease IV: The immune response and other selenium-related conditions,
6036,Evolutionary epistemology and the origin and evolution of language: Taking symbiogenesis seriously,"Symbiogenesis is a form of horizontal evolution that occurred 2 billion years ago, with the evolution of eukaryotic cells. It will be argued that, just as we can develop universal selection theories based upon a general account of natural selection, we can also develop a universal symbiogenetic principle that can serve as a general framework to study the origin and evolution of language. (1) Horizontal evolution will be compared with and distinguished from vertical evolution. (2) Different examples of intra- and interspecific horizontal evolution will be given to show that horizontal evolution is quantitatively and qualitatively the most commonly occurring form of evolution throughout the history of life. (3) Finally, three examples are given of how a universal symbiogenesis principle can be implemented in the study of language origins and evolution, more specifically within: (a) the study of language variation, (b) language genes and (c) conceptual blending."
6037,Multiple Sclerosis and Other Demyelinating Diseases,"Multiple sclerosis (MS) is the most common idiopathic demyelinating disease of the central nervous system (CNS). Although partially effective treatments are now available, MS represents a major target for research into the development of disease-modifying therapies that specifically focus on the neuroimmune pathways of myelin and tissue damage that currently are incompletely understood. Multiple sclerosis is considered to be an example of development of autoimmunity to self-antigens within the CNS through multiple initiating events that include infections and other environmental factors. The direct or indirect induction of immune responses against CNS antigens includes chemotaxis of T cells, B cells, and monocytes, and production of immunoglobulin responses, each of which can act as an effector of myelin damage that occurs in distinct histological patterns. Because a specific cause for MS has not been identified, much MS research has focused on CNS immune responses triggered by unidentified insults that in turn trigger inflammation-mediated cascades of myelin and cellular damage that are likely relevant to other neurodegenerative diseases. This chapter discusses current the epidemiology, etiology, pathophysiology, animal models, virus models and recent advances in the neuroimmunology of MS from the perspective of the potential for development of newer therapies for MS and other inflammatory CNS diseases."
6038,Schwimmbadgranulom,
6039,Interpretation and Relevance of Advanced Technique Results,"Advanced techniques in the field of diagnostic microbiology have made amazing progress over the past 25 years due largely to a technological revolution in the molecular aspects of microbiology [1, 2]. In particular, rapid molecular methods for nucleic acid amplification and characterization combined with automation in the clinical microbiology laboratory as well as user-friendly software and robust laboratory informatics systems have significantly broadened the diagnostic capabilities of modern clinical microbiology laboratories. Molecular methods such as nucleic acid amplification tests (NAATs) rapidly are being developed and introduced in the clinical laboratory setting [3, 4]. Indeed, every section of the clinical microbiology laboratory, including bacteriology, mycology, mycobacteriology, parasitology, and virology, has benefited from these advanced techniques. Because of the rapid development and adaptation of these molecular techniques, the interpretation and relevance of the results produced by such molecular methods continues to lag behind. The purpose of this chapter is to review, update, and discuss the interpretation and relevance of results produced by these advanced molecular techniques."
6040,Characteristics of Metazoan DNA Replication Origins,"DNA replication in metazoan cells initiates at multiple discrete chromosomal sites called replication origins. Recent genome-wide studies have mapped thousands of origins in animal and plant cells, but without yielding a distinct and universal consensus sequence. However, origin-associated regions with particular base composition features have been identified, such as the G-rich OGRE motif, predicted to form G-quadruplexes. Epigenetic marks such as histone modifications that promote open chromatin also favor origin formation. Before DNA replication can initiate at origins, they need to be “licensed” by the binding of the origin recognition complex (ORC) and other proteins to form pre-replication and pre-initiation complexes. Origin-associated proteins are themselves subject to multilayered regulation, notably by posttranslational modification and proteasomal degradation. Origins are organized into replicons and replicon clusters, whose firing occurs at discrete subnuclear bodies known as replication foci. A still poorly characterized nuclear matrix structure might be involved in the attachment of replication units and the formation of replication foci. Preferential genomic sequences responsible for these attachments have been reported, as well as factors playing roles in their regulation. There appears to be great flexibility in the choice of origins used in each S-phase, being affected by factors including cell identity and replication stresses. Origin selection also changes dramatically during embryogenesis in concert with developmental signaling pathways. Dysregulation of origin positioning and recognition are implicated in human disease, as mutations in origin-binding proteins have been found in developmental disorders, and expansions in repeat-containing genomic regions promote genome instability. This chapter summarizes current understanding about replication origins, the most recent discoveries, and outlines key unanswered questions in this exciting field."
6041,Importziekten,"Importziekten komen voor bij reizigers en migranten die terugkeren van een verblijf in de tropen. Ze zijn een afspiegeling van het ziektepatroon in het land van herkomst en men moet dus rekening houden met ziekten die in Nederland onbekend of vrijwel uitgebannen zijn. Het is van belang de omstandigheden waarin mogelijk een besmetting plaatsvond zo nauwkeurig mogelijk te noteren, daar deze behulpzaam kunnen zijn bij het onderzoek van de patiënt. In dit hoofdstuk worden drie veelvoorkomende uitingen van import- of reizigersziekten besproken: koorts, diarree en huidafwijkingen."
6042,"No More SMS from Jesus: Ubicomp, Religion and Techno-spiritual Practices","Over the last decade, new information and communication technologies have lived a secret life. For individuals and institutions around the world, this constellation of mobile phones, personal computers, the internet, software, games, and other computing objects have supported a complex set of religious and spiritual needs. In this paper, I offer a survey of emerging and emergent techno-spiritual practices, and the anxieties surrounding their uptake. I am interested in particular in the ways in which religious uses of technology represent not only a critique of dominant visions of technology’s futures, but also suggest a very different path(s) for ubiquitous computing’s technology envisioning and development."
6043,Human Group Identity: Language and a Social Mind,
6044,Pneumonia Caused by Emerging Viral Agents,"Emerging viruses that cause pneumonia in humans are agents which normally circulate in the animal population but can move to human hosts under certain circumstances, which determines the occurrence of a new type of disease. The Middle East respiratory syndrome (MERS) is caused by a coronavirus. The disease has a wide symptomatic spectrum that can range from asymptomatic infections to fulminant respiratory failure. Diagnostic confirmation is achieved through viral isolation. Severe acute respiratory syndrome (SARS), also produced by a coronavirus, is capable of producing a serious pulmonary disease outbreak with no reappearance. The clinical presentation includes fever, malaise, cough, and headache followed by diarrhea. Other coronaviruses (HCoV-NL63 and HCoV-HKU1) can cause serious lower respiratory infections in small children, the elderly, and immunosuppressed patients. Influenza virus is widespread in nature, and avian virus may spread to humans, as has been reported with H7N9, H5N1, H10N8, and H6N1. Cardiopulmonary hantavirus syndrome, a feverish disease characterized by respiratory insufficiency and shock, is produced by Andes virus. Other emerging viruses are enterovirus D68 and polyomavirus."
6045,Visualization of DNA Sequence Features Based on Cellular Automata,"Visualization of special patterns in biological sequences can assist revealing important roles in gene regulation and other basic molecular activities of the sequence. The visualization method needs to highlight interesting sequence patterns while suppressing trivial aspects. A biology sequences visualization scheme based on cellular automata is developed in this study. Features such as alleles of a DNA sequence were extracted and mapped into a grid in a two-dimensional plane, creating an initial pattern. Then, two-dimensional cellular automata were iteratively executed according to predefined rules and turned the initial pattern into a two-dimensional pattern, forming the fingerprint of the sequence. This fingerprint can be served as a representation of the sequence and can be used to make sequences comparing."
6046,Viral RNase Involvement in Strategies of Infection,"The overwhelming majority of RNase activity is engaged in catabolic processes. Viruses have no metabolism of their own, but rely completely on host cellular energy and substrate provision to support the biochemical processes necessary for virus replication. It is therefore obvious that RNA hydrolysis does not represent an obligate step in the viral life cycle that would have to be governed by viral proteins. Accordingly, RNases are found only rarely in the viral proteomes and serve special functions. In this chapter, several virus-specific RNases will be described and their role in the viral life cycle discussed. The text will concentrate on RNases of members of the nidoviruses, herpesviruses, pestiviruses, and several viruses with segmented negative-strand RNA genome including influenza virus. These enzymes are involved in specific steps of viral gene expression, viral genome replication, shutoff of host cellular gene expression, and interference with the host’s immune response to virus infection."
6047,Recent Advances in Veterinary Diagnostic Virology: Report from a Collaborating Centre of the World Organization for Animal Health (OIE),"Infectious diseases have a very high impact on animal and human health and welfare today, despite of strong efforts and good results in diagnostics, vaccine developments and control measures, including the early warning systems. There are many reasons, which have to be considered as supporting factors for the spread of infectious diseases, such as the open borders of the European Union, allowing rather free movement of animals over a whole continent, the globalization, the released and accelerated international and national trade and animal transfer. Simultaneously, the emergence and re-emergence of new or already known pathogens is a various serious issue in veterinary and in human medicine. This scenario is clearly illustrated by the regular occurrence of transboundary animal diseases (TADs), such as foot-and-mouth disease (FMD), classical swine fever (CSF), African swine fever (ASF), among others. The recent occurrence of African swine fever in the Caucasus region and the spread afterwards to large territories of Russia clearly illustrates that our health authorities require a very strong preparedness, including prompt and powerful diagnosis, for the successful fight against the novel scenarios."
6048,Molecular Techniques for Blood and Blood Product Screening,"“Blood banking has become a manufacturing industry, an industry that must conform to high standards and quality control requirements comparable to those of pharmaceutical companies or other regulated industries,” said David A. Kessler, M.D., former FDA commissioner (Revelle, 1995). Screening donated blood for infectious diseases that can be transmitted through blood transfusion is very important in ensuring safety. The United States has the safest blood supply in the world (Revelle, 1995), and the Food and Drug Administration (FDA) is striving to keep it safe by decreasing the risk of infectious disease transmission. The regulatory agency is continuously updating its requirements and standards for collecting and processing blood. An important step in ensuring safety is the screening of donated blood for infectious diseases. In the United States, tests for infectious diseases are routinely conducted on each unit of donated blood, and these tests are designed to comply with regulatory requirements (Table 21.1). The field of clinical microbiology and virology is now moving into the focus of molecular technology. Currently, nucleic acid testing techniques have been developed to screen blood and plasma products for evidence of very recent viral infections that could be missed by conventional serologic tests. It is time for all blood safety staffs to use molecular detection techniques. This approach can significantly aid in blood safety to reduce the risk of transmission of serious disease by transfusion. This chapter will review the current antigen/antibody–based technology, molecular biological technology, and published regulatory policy data for blood safety."
6049,Homeless People,
6050,A New Algorithm for Fast All-Against-All Substring Matching,"We present a new and efficient algorithm to solve the ’threshold all vs. all’ problem, which involves searching of two strings (with length N and M respectively) for finding all maximal approximate matches of length at least S and with up to K differences. The algorithm is based on a novel graph model, and it solves the problem in time O(NMK (2))."
6051,"Nucleinsäuren, Genexpression und molekularbiologische Methoden","a. Vergleichen Sie die Wasserstoffbrückenbindungen in der α-helikalen Struktur von Proteinen mit denjenigen in der DNA-Doppelhelix. Berücksichtigen Sie strukturelle Aspekte sowie die Rolle der Wasserstoffbrücken für die Stabilisierung der jeweiligen Struktur. b. Welche Eigenschaft eines DNA-Moleküls lässt sich durch Messung der Viskosität seiner wässrigen Lösung bestimmen? Wie ändert sich die Viskosität dieser Lösung, wenn eine DNase- Behandlung durchgeführt wird?"
6052,"In the Realm of Opportunity: The Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics during World War II, 1938/42–1945","On March 8, 1940, Eugen Fischer wrote a long, confidential letter to Otmar von Verschuer, director of the Institute for Genetic Biology and Race Hygiene at the University of Frankfurt at that time. In this letter Fischer expressed critique — and certainly also self-critique — about the scientific development of his institute since the mid-1930s."
6053,Experiments of Concern,"Human knowledge and understanding of the natural world is, presumably, both desirable in itself and a means to the provision of other human goods, such as health and longevity. Moreover, human freedom, including freedom of intellectual inquiry, is agreed on all hands to be an intrinsic human good. Accordingly, there is a presumption in favour of allowing research in the biological sciences, as there is in other areas of human knowledge. In short, research in the biological sciences is morally permissible, absent special considerations in relation to specific kinds of such research. What, if any, research in the biological sciences is morally impermissible? Research in the biological sciences undertaken for the purpose of weaponising biological agents so that they can be used to kill or cause illness in human populations is presumably morally impermissible, whether the research in question is undertaken by state actors, (non-state) terrorist groups, criminal organisations or malevolent individuals. So much is proclaimed in the Biological Weapons Convention (BWC), notwithstanding the fact that arguments have been used from time to time to justify the use of biological weapons in the context of a just war. It has been argued, for example, that some biological weapons are more “humane” than some conventional weapons. It has also been argued that biological weapons development during peacetime may play an important role in deterrence [79]. It is not within the scope of this report to discuss the moral complexities arising from the use of various forms of weaponry, albeit this is an important and somewhat neglected topic. However, we note that, in so far as biological weapons are a species of weapons of mass destruction (WMD), there is a general moral objection to their development and use, namely, that inevitably they target civilian populations and not merely combatants. As such, they violate the so-called jus in bello condition of just war theory; the condition that, among other things, gives expression to the moral principle of civilian immunity in war."
6054,Benvenuto doctor web,"Come tanti altri“mestieri”, anche la professione del medico, oggi, non è più la stessa che un laureato in medicina svolgeva mezzo secolo fa. Immense sono le riflessioni sul tema già dagli anni della rivoluzione industriale, basti ricordare che già nei più prossimi anni ’50 del XX secolo, alle sensibili trasformazioni della professione e dell’organizzazione medico-assistenziale e ai dilemmi conseguenti, un grande filosofo, Karl Jaspers, aveva dedicato un libro, Il medico nell’età della tecnica, nel quale già si calava il sipario sul medico preistorico“di tipo sacerdotale, il medico ippocratico che cura razionalmente osservando con occhio imparziale il complesso dell’uomo e la sua situazione, il medico medievale aggrappato alle concezioni speculative derivanti dall’autorità”, nel tentativo di ridare centralità al rapporto tra chi cura e chi è curato (1). Una figura di medico è tramontata, ma forse non ne è emersa un’altra altrettanto definita e, allo stesso modo, sono entrate in un campo opinabile anche le definizioni di“malato-paziente”, di“atto medico”, di“malattia”."
6055,Präsentismus,"Auch bezüglich der Begriffsdefinition Präsentismus ist die geläufigste Quelle die Internetplattform Wikipedia. Hier wird Präsentismus wie folgt beschrieben: „Mit Präsentismus […] bezeichnen Arbeitspsychologie und Arbeitsmedizin das Verhalten von Arbeitnehmern, die insbesondere in Zeiten hoher Arbeitslosigkeit […] trotz Krankheit am Arbeitsplatz sind, bzw. die Reduktion der Arbeitsproduktivität durch Leistungseinschränkung von Beschäftigten, die auf gesundheitliche Einschränkungen wie z. B. chronische Erkrankungen zurückzuführen sind.“"
6056,Pharmacological Activities and Phytochemical Constituents,"Glycyrrhiza glabra is one of the most popular medicinal plants and it has been used in traditional herbal remedy since ancient times (Blumenthal et al. in Herbal medicine: expanded commission E monographs. Integrative Medicine Communications, Newton, 2000; Parvaiz et al. in Global J Pharmocol 8(1):8–13, 2014; Altay et al. in J Plant Res 129(6):1021–1032, 2016). Many experimental, pharmacological and clinical studies show that liquorice has antimicrobial, antibacterial, antiviral, antifungal, antihepatotoxic, antioxidant, antiulcer, anti-hemorrhoid antihyperglycemic, antidiuretic, antinephritic, anticarcinogenic, antimutagenic, anticytotoxic, anti-inflammatory, and blood stopper activity."
6057,Introduction: What Is This Volume About?,"In these early years of the twenty-first century, it can often seem that across the globe we are living in a world of crisis. When we began this book, there were bombings at the end of the Boston Marathon of 2013, an army coup in Egypt that overthrew the first democratically elected government, an armed conflict in Syria, the President of North Korea made bellicose threats against South Korea and the USA , and the shrinking of the Arctic ice sheet that was implicated in the extreme winter weather that the UK has faced in 2012–2013. ‘The war on terror’, the age of austerity, global warming and consequent climatic instability, disparities in wealth, and other issues add to the sense that social institutions are unable to cope with the major problems that the world faces. It is certainly the case, on the one hand, that states around the world are under enormous fiscal pressure, in large part brought about by the banking failures of 2008, which heralded the end of a long period of conspicuous consumption and an era of deregulation. On the other hand, the private sector, too, is under pressure, losing once-certain markets to new competitors, and ‘fat cat’ directors facing angry shareholders and governments seeking to curb their excess salaries and the bonus culture of those in charge of large corporations."
6058,Postoperative Care of the Liver-Transplant Patient,"Liver transplantation (LT) is performed to improve life expectancy and quality of life in patients with advanced chronic liver disease (CLD), and to save life in the context of acute liver failure (ALF). These two groups of patients differ significantly in terms of mean age, prior comorbidity, and degree of extra-hepatic organ dysfunction, requiring substantially different approaches to supportive care. Common aspects of care are those directed at the transplanted organ itself, with regard to monitoring and recognition of early dysfunction, initiation of immunosuppression, and management of surgical complications. Close liaison with the multidisciplinary team, which will include the intensivist, transplant surgeon, transplant hepatologist, anesthesiologist, and radiologist, is required."
6059,Inflammatory Bowel Disease at the Intersection of Autophagy and Immunity: Insights from Human Genetics,"Studies using human genetics have identified more than 160 loci that affect the risk of developing inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Several of these genes have been found to play key roles in the process of autophagy, a lysosome-based degradation pathway. Although historically considered to be a relatively nonselective process of degradation of cytosolic contents, autophagy has recently been revealed to have several selective and immune-specific functions that are relevant to the maintenance of intestinal homeostasis, including xenophagy, mitophagy, antigen presentation, secretion, and inflammasome regulation. In this chapter, we review the evidence that links autophagy-related genes, their immune-specific functions, and possible mechanisms of IBD pathogenesis. We summarize the basic molecular events underlying general and selective autophagy, and present evidence suggesting possible pathogenic mechanisms revealed by studies of IBD-associated risk alleles of ATG16L1 and IRGM. Finally, we review chemical biology-based experimental approaches for identifying autophagy regulatory pathways that may have implications for the development of therapeutics."
6060,Pneumonia,"The chapter will begin with an overview of pathological-clinical correlates in pneumonia, and of the principles of diagnosis and treatment that can be broadly applied to all pneumonias. Thereafter, community-acquired pneumonia, hospital-acquired and ventilator-associated pneumonia, and aspiration pneumonia will be considered separately, considering aspects of management specifically relevant to each. The chapter will end by discussing preventive strategies, and with a brief outline of future challenges for the management of pneumonia."
6061,Pathogen Genomics and the Potential for Understanding Diseases in the Developing World,"Approximately 46% and 32% of deaths among children under five globally occur in sub-Saharan Africa and South Asia, respectively. Over 80% of the 4.2 million child deaths in Africa are caused by infectious diseases, sharply contrasted to Europe where 39% of the 0.15 million child deaths are attributable to infectious diseases (Fig. 5.1) (Black et al. 2010). Hence, despite the remarkable public health advancements in hygiene, sanitation, antimicrobial drugs and vaccine strategies of the twenty-first century, the burden of infectious diseases remains unacceptably high in the developing world."
6062,Towards Merging Models of Information Spreading and Dynamic Phenomena in Social Networks,"While the impact of network properties on information spreading is now widely studied, influence of network dynamics is very little known. In this paper, we study how evolution mechanisms traditionally observed within social networks can affect information diffusion. We present an approach that merges two models: model of information diffusion through social networks and model of network evolution. Since epidemics provide a reference in application domains of information spreading, we measure the impact of basic network structure changes on epidemic peak value and timing. Then we investigate observed trends in terms of changes appearing in the network structure. Our results provide promising results on how and why network dynamics is a strong parameter to integrate in requirements for information spreading modelling."
6063,"Lonicera japonica Thunb 金银花 (Jinyinhua, Honey Suckle)","Jinyinhua, a sprawling and twining lianas in the family of Caprifoliaceae, is a popular Chinese herbal medicine used for the treatment of inflammatory diseases and as a well-known dietary supplement that has been used for many centuries."
6064,Factors Involved in Aerosol Transmission of Infection and Control of Ventilation in Healthcare,"Experience with the recent viral pandemics has generated a renewed interest in the study of the transmission modes of respiratory pathogens. It not only provides better understanding of the pathogenesis of the disease but also of the rational design of infectious-control strategies. Hospital-acquired infections still account for many hospitalizations and deaths around the world, with many of these infections being transmitted via aerosolized microorganisms to patients and healthcare workers (HCWs)."
6065,Erreger,"Der mit Abstand wichtigste Erreger der ambulant erworbenen Pneumonie ist Streptococcus pneumoniae. Weitere bedeutende Erreger sind Influenzaviren, die „atypischen“ bakteriellen Erreger Legionella spp. und Mycoplasma pneumoniae sowie Haemophilus influenzae. Nur selten, jedoch aufgrund ihrer Pathogenität wichtig, sind Staphylococcus aureus, Enterobakterien und P. aeruginosa. Weitere seltene Erreger müssen beachtet werden, besonders bei Reiserückkehrern. Risikofaktoren sind für alle Erreger definiert. Epidemien können von Legionellen, Coxiella burnetii, Influenzaviren und „neuen“ Viren ausgehen. Das klinische Bild ist mitunter charakteristisch, jedoch nie spezifisch. Die Kenntnis der Besonderheiten der möglichen Erreger hinsichtlich Mikrobiologie, Übertragung, Risikofaktoren und klinischem Bild ist wertvoll für die angemessene Behandlung der ambulant erworbenen Pneumonie, insbesondere die gezielte antimikrobielle Therapie."
6066,Managing Global Risks: Vietnamese Poultry Farmers and Avian Flu,"This chapter documents the logics underpinning farmers’ management practices of an emerging disease. In the area of our survey, Vietnamese farmers, who are one of the front lines of the fight against H5N1, are called upon to collaborate to the international fight against the virus. Our study highlights that direct (poultry mortality) and indirect impacts (consequence of the measures imposed by the government to contain the virus, fluctuation of consumers’ demand, etc.) tend to be relatively limited when compared to the permanent state of instability which characterises the context of poultry production in the surveyed village. This instability is mainly related to numerous and regular poultry infectious diseases and market fluctuations. If international community considers H5N1 as a zoonotic risk and a pandemic threat which asks for emergency tools, H5N1 is framed by the farmers of our study as an epizootic problem manageable through routinised measures. These measures aim at minimising the economic impact of the disease rather than preventing poultry and Human from the disease. Consequently, local management of the disease cannot fit with the precautionary approach promoted by the international community."
6067,"Isolation: Serious, Infectious Diseases","All persons staying in hospitals should be protected against exposure to infectious agents, and especially to high-risk, dangerous agents - that pose a risk to health and life. It is not acceptable to place a patient with a known high-risk, serious infection in the same hospital room as other patients (WHO). In this chapter, the preparedness of isolation capacity and escalation of hospital beds for patients with dangerous infections are described."
6068,The Experimental Pathology at Ancona: 50 Years of Exciting and Pioneering Research on Human Pathology,"Half century ago, a few academic pioneers founded the laboratories of experimental and ultrastructural pathology in Ancona. From this origin, a new phase of experimental studies developed aimed at translational and clinical research up to the present, when our group is internationally recognized for its fundamental contributions in gerontological research and molecular diagnostic pathology. Since the desire of immortality and of eternal youth seems to be as old as mankind, in the future we plan to focus our scientific research on Regenerative Medicine and Rejuvenation strategies. This is the most ambitious aim in the framework of the world aging population. We do not know whether we would achieve these results by ourselves. We are confident that, as in the past, new generations of scientist of the school of experimental pathology at Ancona will get the baton by the older one and lead the future with the same enthusiasm, love and commitment."
6069,Challenges for Experimentation on Living Beings at the Dawn of the 21(st) Century,"“We can talk endlessly about moral progress, about social progress, about poetic progress, about progress made in happiness; nevertheless, there is a type of progress that defies any discussion, and that is scientific progress, as soon as we judge it within the hierarchy of knowledge, from a specifically intellectual point of view.”"
6070,"Medical, Psychological, and Environmental Issues of Artificial Gravity",
6071,Treatment of Perianal Crohn Disease Fistulae,
6072,Acronyms and Abbreviations,
6073,17 Infecties bij patiënten met gestoorde afweer,"De eerste verdedigingslinie, gevormd door het intacte oppervlak van huid en slijmvliezen, is van eminent belang voor de afweer tegen micro-organismen (tabel 17.1)."
6074,Green Biotechnology: A Brief Update on Plastid Genome Engineering,"Plant genetic engineering has become an inevitable tool in the molecular breeding of crops. Significant progress has been made in the generation of novel plastid transformation vectors and optimized transformation protocols. There are several advantages of plastid genome engineering over conventional nuclear transformation. Some of the advantages include multigene engineering by expression of biosynthetic pathway genes as operons, extremely high-level expression of protein accumulation, lack of transgene silencing, etc. Transgene containment owing to maternal inheritance is another important advantage of plastid genome engineering. Chloroplast genome modification usually results in alteration of several thousand plastid genome copies in a cell. Several therapeutic proteins, edible vaccines, antimicrobial peptides, and industrially important enzymes have been successfully expressed in chloroplasts so far. Here, we critically recapitulate the latest developments in plastid genome engineering. Latest advancements in plastid genome sequencing are briefed. In addition, advancement of extending the toolbox for plastid engineering for selected applications in the area of molecular farming and production of industrially important enzyme is briefed."
6075,Public Health in Canada and Adaptation to Infectious Disease Risks of Climate Change: Are We Planning or Just Keeping Our Fingers Crossed?,"Climate change is expected to increase the health risks for Canadians from infectious diseases from our environment, including vector-borne, water-borne, and food-borne diseases. Adaptation efforts will be important to reduce the impact of these risks. Public health systems are in place in Canada to control many disease risks but there are still knowledge gaps on, and modifications needed to, existing approaches to protecting the population from endemic diseases and new or emerging pathogens. This chapter addresses five key questions on whether public health is on track to helping communities adapt to changing risks. The questions address adaptation to disease risk of climate change by exploring the following: assessments of disease risks, methods for adaptation, responsibility, resources, and public action and societal will. Overall, with these increasing risks to the health of Canadians, all sectors of society will need to participate in the adaptive response, while federal, provincial, and community public health bodies will need to work together to identify and communicate risk and promote and coordinate adaptation responses."
6076,Emerging Animal Coronaviruses: First SARS and Now MERS,"The first major pandemic of the new millennium that arose from southern China in 2002 was of zoonotic origin from wild game animals, called severe acute respiratory syndrome [SARS]. The culprit was determined to be a coronavirus of animal origin [SARS-CoV]. The discovery of the SARS-CoV, which caused an outbreak of >8000 people in >30 countries with fatality of about 10%, resulted in intense search for novel coronaviruses with potentially high pathogenicity. Ten years later after the SARS pandemic, another novel coronavirus crossed the species barrier from bats to humans through an intermediate camel host, to produce a severe lower respiratory infection labeled the Middle East respiratory syndrome [MERS]. A novel coronavirus [MERS-CoV] was first identified in September 2012, from patients who resided or traveled to Saudi Arabia. The MERS-CoV spread through contacts with camel and subsequently from human to human via droplet transmission. MERS cases occurred in several other countries including in Europe and the United States, mainly from residence or travel to the Arabian Peninsula, but was not of pandemic potential. However, in the spring of 2015, a MERS outbreak started in South Korea which was initiated by a returning traveler from Saudi Arabia, and subsequently secondary infection of over 186 local residents occurred. Recent estimate in May 2015 indicates that the MERS-CoV have afflicted 1167 patients with MERS worldwide with 479 deaths [41% fatality]. Thus MERS is more deadly than SARS but appears to be less contagious. However, unlike SARS which has not reappeared since 2002–2003, MERS-CoV have the potential to cause sporadic or local outbreaks for many years as the virus may now be entrenched endemically in dromedary camels of the Middle East."
6077,The Nonhuman Primate as a Model for Biomedical Research,"This chapter provides a brief summary of issues surrounding the utilization of nonhuman primates in biomedical research. Although a relatively small proportion of the total number of animals utilized in biomedical research, nonhuman primates occupy a unique position as the species most closely related to humans, and thus have the potential to provide highly relevant information regarding human health issues. Nonhuman primates are utilized across a wide diversity of research topics and examples are provided including infectious disease, neuroscience, and genomics. Pertinent information relating to ethical issues, species selection, housing, and specific pathogen-free status are provided as an overview of relevant issues associated with selection of nonhuman primate models. Selected references are provided as a reference for more comprehensive information relating to these topics."
6078,Calculation of Air Change Rate,"In order to dilute and effectively remove the bioaerosol in the negative pressure isolation ward, a certain amount of flow rate, i.e., the air change rate, is needed."
6079,Prevention and Psychological Intervention in Depression and Stress-Related Conditions,"This chapter focuses on depression and stress-related conditions to discuss possible strategies for the prevention or early management of such conditions. Health education constitutes the first important strategy, and we outline a school-based educational activity using a case-method approach. We next illustrate the impact of stressful events on psychological health with the results of a survey among Chinese individuals conducted after an unexpected epidemic of severe acute respiratory syndrome in 2003. Communication plays an important role in the assessment and management services provided by medical practitioners to sick individuals, with very diverse backgrounds and levels of medical knowledge, who consult health care providers with concerns about their health. In this context, we introduce a recent advance in patient–doctor communication. Finally, we address the cognitive and behavioral features of those who suffer from depression and psychosocial stress. Based on our recent activities and on evidence pertaining to health promotion and education, we emphasize the importance of health education and communication in the prevention of stress-related diseases and the promotion of physical and psychological health."
6080,Medical Conditions,"An acute hypoxemic respiratory failure (AHRF) has high possibilities to develop acute respiratory distress syndrome (ARDS) and increased death risk. AHRF which represents a common end-point to multiple pathological processes either local or systemic may have many medical conditions as aetiology. The causes may be pulmonary and extrapulmonary. Between pulmonary determinants, pneumonia and bacterial and virus infection diseases are the most frequent disease associated with AHRF. On the other hand, many non-infectious etiologic conditions, such as blunt chest contusion, multiple injuries, aspiration of gastric contents, inhalation burns, pancreatitis, and blood transfusions may cause ARDS."
6081,Bacterial Infections,"In Osier’s time, bacterial pneumonia was a dreaded event, so important that he borrowed John Bunyan’s characterization of tuberculosis and anointed the pneumococcus, as the prime pathogen, “Captain of the men of death.”1 One hundred years later much has changed, but much remains the same. Pneumonia is now the sixth most common cause of death and the most common lethal infection in the United States. Hospital-acquired pneumonia is now the second most common nosocomial infection.2 It was documented as a complication in 0.6% of patients in a national surveillance study,3 and has been reported in as many as 20% of patients in critical care units.4 Furthermore, it is the leading cause of death among nosocomial infections.5 Leu and colleagues6 were able to associate one third of the mortality in patients with nosocomial pneumonia to the infection itself. The increase in hospital stay, which averaged 7 days, was statistically significant. It has been estimated that nosocomial pneumonia produces costs in excess of $500 million each year in the United States, largely related to the increased length of hospital stay."
6082,Next-Generation Sequencing for Porcine Coronaviruses,"The outbreak of porcine epidemic diarrhea virus and the discovery of porcine deltacoronavirus in the USA have led to multiple questions about the evolution of coronaviruses in swine. Coronaviruses are enveloped virus, containing a positive-sense single-stranded RNA genome (26–30 kb) that can cause respiratory or enteric illness in swine. With current technologies, the complete viral genomes can be determined to understand viral diversity and evolution. In this chapter, we describe a method to deep genome sequence porcine coronavirus on the Illumina MiSeq, avoiding the number of contaminating reads associated with the host and other microorganisms."
6083,Outbreaks of Infection in the ICU: What’s up at the Beginning of the Twenty-First Century?,Surveillance cultures are the only cultures that allow the distinction between secondary endogenous and exogenous infections. These types of infection are the two known to cause outbreaks. Secondary endogenous infections can be controlled by enterally administered antimicrobials and should be integrated into the routine infection control measures. Exogenous infections can be controlled by topically applied antimicrobials and hygiene.
6084,Pulmonary Manifestations of Vasculitis,"Respiratory manifestations in patients with a primary systemic vasculitis syndrome need to be separated into those caused by the vasculitis itself, those related to treatment complications, and those caused by unrelated or only indirectly related comorbidities such as obstructive sleep apnea. Respiratory tract involvement is most common in the ANCA-associated vasculitides. Respiratory manifestations are less frequent and less prominent in other forms of systemic vasculitis, but they may nevertheless represent significant management challenges and carry a poor prognosis. This chapter reviews the tracheobronchial and pulmonary parenchymal disease manifestations, their clinical presentation, and differential diagnosis for each of the vasculitis syndromes. A systematic differential diagnostic approach to the patient with diffuse alveolar hemorrhage is also provided."
6085,Rhinology,"Osteomas are the most common benign sinonasal lesion with the frontal sinus the most common location. On sinus MRI, dried secretions show as hyperintense on T1, hypointense on T2, and polyps show hypointense on T1, hyperintense on T2. Rhinoscleroma is caused by Klebsiella rhinoscleromatis with histopathology showing Mikulicz cells (macrophages containing pathogen) and Russell bodies (plasma cells)."
6086,The genetic basis of resistance to antimicrobial drugs,
6087,Modeling Detection of HIV in Cuba,"A nonlinear compartmental model is developed for the HIV detection system in Cuba with different types of detections, some random and others non-random. We analyze the dynamics of this system, compute the reproduction numbers, and use the data from the Cuban HIV/AIDS epidemic between 1986-2008 to fit the model. We obtain estimates for the detection-related parameters during two separate time periods to reflect the timeline of the implementation of various types of searches. The reproduction numbers for each time period are also computed from the sets of values of the parameters. We found that random screening is most important as a mean of surveillance. Moreover, local asymptotic stability for the Disease Free Equilibrium can be achieved if (i) random screening is sufficiently effective and (ii) infection by detected HIV-positive individuals is minimal. Our results highlight the importance of education for the known infectious for the purpose of preventing further infection. Fitting the 1986-2008 HIV data to obtain the model parameter estimates indicates that the HIV epidemic in Cuba is currently approaching an endemic equilibrium. A Genetic Algorithm is used."
6088,Nutrition and Polymyositis and Dermatomyositis,"• Chronic muscle inflammation in polymyositis or dermatomyositis causes muscle weakness and fatigue. • The chronic inflammation could lead to a catabolic state and additional loss of muscle mass. • The chronic muscle inflammation could induce a metabolic myopathy. • Body weight may not be reliable to measure muscle loss, rather measurement of body composition is recommended. •For patients with polymyositis or dermatomyositis it is important to provide the body with the right amount of macronutrients and trace elements for maintenance and improvement of body functions. • One recommendation is supplementation with calcium and vitamin D. • Another recommendation is regular physical exercise that during limited periods can be combined with supplements such as creatine, if done under the care of a physician."
6089,Role of CD14 in Lung Inflammation and Infection,"Toll-like receptors (TLR) on the surface of cells of the respiratory tract play an essential role in sensing the presence of microorganisms in the airways and lungs. These receptors trigger inflammatory responses, activate innate immune responses, and prime adaptive immune responses to eradicate invading microbes [1]. TLR are members of a family of pattern-recognition receptors, which recognize molecular structures of bacteria, viruses, fungi and protozoa (pathogen-associated molecular patterns or PAMPs), as well as endogenous structures and proteins released during inflammation (damage/danger-associated molecular patterns or DAMPs). To date, ten different TLR have been identified in humans and twelve in mice. TLR are expressed on all cells of the immune system, but also on parenchymal cells of many organs and tissues. The binding of a PAMP to a TLR results in cellular activation and initiates a variety of effector functions, including cytokine secretion, proliferation’ co-stimulation or phagocyte maturation. To facilitate microbial recognition and to amplify cellular responses, certain TLR require additional proteins, such as lipopolysaccharide (LPS) binding protein (LBP), CD14, CD36 and high mobility group box-l protein (HMGB-l). In this chapter, the role of CD14 as an accessory receptor for TLR in lung inflammation and infection is discussed. The central role of CD14 in the recognition of various PAMPs and amplification of immune and inflammatory responses in the lung is depicted in Fig. 1."
6090,The Pediatric Asthmatic,"The incidence of allergies and asthma in the Western world has been increasing over the past 30 years. However, more recent data suggests that over the past 5–10 years, the overall global trends of asthma incidence have begun to stabilize (1). Urbanization and industrialization has contributed to the increase in developed countries, but the reasons for this are still unclear. Asthma is estimated to be responsible for 1 in every 250 deaths worldwide. Many of these deaths are preventable, and specific issues have been identified that may contribute to this high mortality rate. Factors that contribute to high ­mortality and morbidity include slow access to care and medications, inadequate environmental control of allergens and irritants, dietary changes, genetic variations, cultural barriers, lack of education amongst patients and providers, insufficient resources, and improper use of health care dollars."
6091,Hong Kong Students’ Decision-Making About Ecological and Health Issues,"Decision-making about socioscientific issues could serve as a means to engage students in multi-perspective thinking, critical reasoning, argumentation, and value judgment, which are regarded as increasingly important goals of school education in general and science education in particular. This chapter draws on four studies that examine Hong Kong secondary students’ informal reasoning for decision-making about socioscientific issues in the areas of health and ecology. While some of these studies involved decision-making about issues within the context of Hong Kong, others engaged students in reasoning on regional or global issues with due consideration to the decision of their counterparts in other contexts or cultures. Three distinctive patterns of reasoning among Hong Kong students emerge from this review. These include their general ability to reason from multiple perspectives, insufficient use of scientific evidence to inform decision-making, and the tendency to change their decision through interactions with peers. Furthermore, the use of a decision-making framework to guide students’ decision-making and the impacts of interpersonal exchanges both within and across contextual or cultural groups on students’ decisions were discussed."
6092,Ecological effects of aviation,
6093,Epidemic Thresholds in SIR and SIIR Models Applying an Algorithmic Method,"Epidemic thresholds were deduced and simulated from SIR models of Susceptible – Infected – Recovered individuals, through local stability analysis of the disease free and endemic equilibrium, with an algorithmic method. One and two types of infected individuals were modeled, considering the influence of sub clinical, undiagnosed or unrecognized infected cases in disease transmission."
6094,Chai Jing: The Power of Vulnerability,"In the past seventeen years Chai Jing has risen from China’s official media to become a recognized investigative journalist, public intellectual, author, and more recently, an independent filmmaker and environmental activist. Her experience and work reflect how China’s news apparatus has reformed to adapt to the drastic societal changes with emotion being used to open up new ways of news communication. Her documentary Under the Dome further shows how the internet has transformed the ecology of media and provided innovative platforms for social engagement. Chai’s embracing her own feelings of vulnerability, which dominated the beginning of her career, and using it to channel public feelings and drive news reporting has made her a distinctively controversial media personality. Her leaving the CCTV can be viewed as a self-marginalization that helps her sustain that vulnerability, through which she gains resilience and critical power. The use of maternal voice in Under the Dome exemplifies her use of the power of vulnerability in its most mature form. The controversiality about that voice signals that post-socialist China remains a space where environmental and gender discourses are contested and negotiated."
6095,7 Importziekten,De besmetting met Entamoeba histolytica komt overal ter wereld maar vooral in de tropen voor. Ook de apathogene Entamoeba dispar komt kosmopolitisch voor.
6096,The Infectious Disease Physician and Microbial Bioterrorism,"On the morning of September 11, 2001, and later in the weeks that chronicled the spread of anthrax through the U.S. mail, our global consciousness of the terrorist threat was altered. We had awakened to a nightmare. Microbes are a perfect metaphor for our fears: our world seemed infected with terrorists, unlimited in virulence, waiting to emerge from dormancy. The metaphor had become real. Although the atmosphere evokes cold-war fears, the world of this century is more complex than that of the McCarthy-era. The infectious disease physician's role in bioterrorism response must be framed in this context."
6097,Human-Specific Changes in Sialic Acid Biology,"Sialic acids are components of cell-surface glycans and play important roles in cell–cell communication and host–pathogen interaction. More than 55 genes, encoding receptors, enzymes, and transporters, are known to be involved in sialic acid biology. Nearly 10 years of research have revealed that several of these genes show human-specific changes in genome structure, expression, or function. In this chapter, we introduce these human-specific changes and their possible impact on the human evolution. Also, we give an overview of the evolution of sialic acid biology in primates. The discovery of human-specific changes in sialic acid biology is one step toward explaining the genetic basis of human uniqueness, one of the major activities in primatology, contributing to answering a transdisciplinary question: What makes us human?"
6098,Pulmonary Manifestations of Hematological Malignancies: Focus on Pulmonary Chronic Graft-Versus Host Disease,"Advances in the management of patients in terms of the diagnosis and treatment of hematologic malignancies and treatment-related complications, especially infectious complications, have increased survival time. However, more than half of the patients treated for hematologic malignancies will develop a pulmonary complication during their follow-up, infectious pneumonia remaining the most common diagnosis that should be considered first in regard to its potential severity. Otherwise, new complications that may involve different organs, including the lungs, have been increasingly reported. Currently, over a quarter of lung infiltrates occurring in the context of hematological diseases are due to noninfectious causes. Thus, lung physicians may be increasingly confronted with these lung disorders. Various noninfectious pulmonary complications have been described in the different hematological malignancies; however, these complications are most often studied in the context of allogeneic hematopoietic stem cell transplantation (HSCT). In this chapter, we will briefly review the lung diseases associated with various hematological malignancies before focusing on noninfectious pulmonary complications following allogeneic HSCT."
6099,Pulmonary Arterial Hypertension in Intensive Care Unit,"For the intensive care unit (ICU) physician, the diagnosis of pulmonary arterial hypertension (PAH) is difficult as it can easily be confounded with other forms of pulmonary hypertension (PH). The key issue is that PAH is a form of PH. On the opposite, PH does not automatically imply PAH. Pulmonary arterial hypertension must be differentiated from other causes of PH that are frequently seen in ICU. It was recently emphasized that pulmonary veno-occlusive disease (PVOD) must be differentiated from PH and PAH. The prognosis of PAH was consistently improved in the ten past years by introduction of selective pulmonary vasodilators and management by highly specialized medical teams. In ICU patients, PAH remains a severe disease with a high mortality rate. When PAH is suspected, a systematic diagnosis approach is of particular importance in order to rapidly eliminate left cardiac, thromboembolic and pulmonary causes of PH. Left cardiac disease is the most common cause of PH. Early recognition of PAH allows a rapid introduction of selective pulmonary vasodilators that can improve outcome. Idiopathic PAH is the most frequent cause but it can also be associated with scleroderma, HIV infection, anorexigen toxicity, thyroid disease, cirrhosis. Pulmonary vasodilators should be only a part of a general management including treatment of triggering factors, optimization of fluid balance, decrease of RV afterload by using pulmonary vasodilators while maintaining cardiac output and mean arterial pressure. The early contact of PH referral center or specialized physician is of particular importance."
6100,Advanced In Silico Tools for Designing of Antigenic Epitope as Potential Vaccine Candidates Against Coronavirus,"Vaccines are the most economical and potent substitute of available medicines to cure various bacterial and viral diseases. Earlier, killed or attenuated pathogens were employed for vaccine development. But in present era, the peptide vaccines are in much trend and are favoured over whole vaccines because of their superiority over conventional vaccines. These vaccines are either based on single proteins or on synthetic peptides including several B-cell and T-cell epitopes. However, the overall mechanism of action remains the same and works by prompting the immune system to activate the specific B-cell- and T-cell-mediated responses against the pathogen. Rino Rappuoli and others have contributed in this field by plotting the design of the most potent and fully computational approach for discovery of potential vaccine candidates which is popular as reverse vaccinology. This is quite an unambiguous advance for vaccine evolution where one begins with the genome information of the pathogen and ends up with the list of certain epitopes after application of multiple bioinformatics tools. This book chapter is an effort to bring this approach of reverse vaccinology into notice of readers using example of coronavirus."
6101,"Sepsis: Clinical Approach, Evidence-Based at the Bedside","Sepsis is a common disease in intensive care medicine representing almost one third of patient admissions. Its incidence has substantially increased over the past decades and overall mortality has declined during this period of time. It was reported that sepsis incidence increased from 82.7 to 240.4 per 100,000 population between 1979–2000. At the same time, sepsis global mortality decreased from 27.8 to 17.9% [1–3]. However, the absolute number of deaths significantly increased from 21.9 to 43.9 per 100,000 population. Male gender, some chronic diseases like diabetes, immunosuppressive states, human immunodeficiency virus infections, and malignancies are factors that increase the risk for sepsis. Some particular conditions like progressive number of organ dysfunctions, in-hospital-acquired infections and increasing age are associated with higher risk of death [1,4]. On the other hand, septic shock mortality only diminished from 61.6 to 53.1% [5]. This slight decline in mortality observed during recent decades could be attributable to improvements in supportive care and/or avoidance of iatrogenic complications. For example, the instrumentation of early goal resuscitation protocols not aiming at supranormal targets for cardiac output and oxygen delivery, and the use of lung protective strategies could explain at least in part this favorable change. Other strategies directed to treat the pathophysiological mechanisms involved in the septic process like recombinant human-activated protein-C (rhAPC), have also contributed to improve survival. However, mortality remains unacceptably high and further improvement in sepsis management is needed."
6102,"Holistic Trinity of Services Sciences: Management, Social, and Engineering Sciences","Services industries comprise about 75% of the economy of developed nations. To design and operate services systems for today and tomorrow, we need to educate a new type of engineer who focuses not on manufacturing but on services. Such an engineer must be able to integrate 3 sciences-management, social and engineering — into her analysis of services systems. Within the context of a new research center at MIT — CESF (Center for Engineering Systems Fundamentals) — we show how newly emerging services systems require such a 3-way holistic analysis. We deliberately select some non-standard services, as many business services such as supply chains have been studied extensively."
6103,Infectious Diseases,"This list is not exclusive, but highlights some important causes of FUO after the common causes of fever have been excluded:"
6104,Nutritional Supplements and Upper Respiratory Tract Illnesses in Young Children in the United States,"KEY POINTS: In the United States, children have lower blood levels than adults of eicosapentaenoic acid (EPA), an important ω-3 fatty acid that helps decrease inflammation; vitamin A, the “anti-infective” vitamin; and selenium (Se), a trace metal that is an intrinsic part of glutathione peroxidase, an important free-radical scavenging enzyme. EPA, vitamin A, and Se are important in controlling inflammation and can be supplied by oral nutritional supplements. Cod liver oil contains EPA (and other important ω-3 fatty acids), and vitamin A as well as vitamin D. Fish oil contains ω-3 fatty acids (including EPA) but no vitamins. Our clinical research demonstrates that daily supplementation with a flavored cod liver oil (which meets European purity standards) and a children’s multivitamin-mineral with trace metals, including Se, can decrease morbidity from upper respiratory tract illnesses, otitis media, and sinusitis in young children living in the United States. These supplements can be used by practitioners on an individual basis, when clinically indicated; the supplements can be purchased in the United States without a prescription. Socioeconomically disadvantaged children are at risk for micronutrient deficiencies. However, their families may not be able to afford to purchase these supplements, which are not available through Medicaid, The Special Supplemental Nutrition Program for Women, Infants and Children, or the Food Stamp Program. If our results are confirmed in larger studies, a system change will be needed to provide these supplements to nutritionally vulnerable, socioeconomically disadvantaged children living in the United States."
6105,The Genera Staphylococcus and Macrococcus,
6106,Defining Natural Hazards – Large Scale Hazards,"The natural forces at work on planet Earth have been an integral part of life since the dawn of mankind. The impacts of hazards of natural origin can range from affecting infrastructure, personal possessions, and ecosystems to negatively affecting individuals’ psychosocial wellbeing. Disasters are the aftermath of hazards caused by natural phenomena, set off by shifts in tectonic plates or atmospheric interactions in populated areas. The extant literature offers a variety of ways to classify natural hazards. For example, they can be categorized by their origin – geological, hydrometeorological or biophysical; by their nature and speed – permanent, ephemeral or episodic; or on the basis of their size or scale – large, medium or small. Adopting the last of the three classification schemes, this chapter presents large scale hazards, which are more likely to occur on the North American continent, in alphabetical order. The list of hazards includes biophysical hazards, droughts, earthquakes, extreme weather, floods, forest fires, ice storms and hurricanes. To help readers follow the material, the chapter draws heavily on recent examples."
6107,Therapie und Prophylaxe von Infektionen bei Neutropeniee,Die zytostatische Chemotherapie bösartiger Erkrankungen führt häufig zum Abfall der neutrophilen Granulozyten und zur mehrtägigen Granulozytopenie bzw. Neutropenie. Das Risiko einer Infektion nimmt unterhalb von 1000/μl neutrophilen Granulozyten signifikant zu. Ausmaβ und Dauer der Neutropenie beeinflussen ebenfalls die Wahrscheinlichkeit von Infektionen. Patienten mit einer länger als 10 Tage anhaltenden schweren Neutropenie (<100/μl) entwickeln in mehr als 80% der Fülle Infektionen.
6108,Summary and Results: Facing Global Environmental Change and Sectorialization of Security,The previous 99 chapters contain diverse theoretical and conceptual approaches and empirical results that are briefly summarized below following the ten parts of the book.
6109,Postoperative Management of Composite Tissue Graft Transplantation,"Composite tissue allotransplantation (CTA) is the transplantation of body structures such as the limbs, larynx, abdominal wall, tendons, and face. This chapter discusses the general and specific postoperative management of patients following CTA."
6110,Airplanes and Infectious Disease,"Air travel is associated with crowded conditions that can facilitate the transmission of airborne infectious diseases. The risk of contracting such diseases depends on the presence of an infected person who is shedding infectious particles and sufficient exposure of a sensitive person to achieve an adequate dose to cause disease. Proximity to the infectious person and the length of time spent near the person are the most important risks for contracting a disease. Ventilation patterns play a lesser role in disease transmission. Well-documented outbreaks of influenza, severe acute respiratory syndrome (SARS), and tuberculosis have occurred. Other common respiratory illnesses have probably also been spread via aircraft, but outbreaks remain unrecognized. Research on the spread of infectious disease in aircraft has focused on sampling for microorganisms in air (which has little relevance), and on the development of models to predict the risks for specific diseases."
6111,"Enhancing Students’ Understanding of the Nature of Science and the Interconnection Between Science, Technology and Society Through Innovative Teaching and Learning Activities","Understanding the nature of science (NOS) and the interconnection between science, technology and society (STS) has been a prominent objective of science curricula worldwide (e.g. American Association for the Advancement of Science, 1993; Council of Ministers of Education, 1997; Millar & Osborne, 1998). Research confirms the contention that sound knowledge of the NOS and STS will enhance students’ learning of science content, interest in science, and ability to make informed decisions based on evidence (Driver, Leach, Miller, & Scott, 1996; McComas, Clough, & Almazroa, 1998; Aikenhead, 1994)."
6112,Economic Importance,"The beneficial effects of liquorice in treating chills, colds, and coughs have been fully discussed in Ayurveda, as well as in the texts of ancient Egyptians, Greeks, and Romans. The plant has been prescribed for dropsy during the period of famous Hippocrates. The reason being that it was quite helpful as thirst-quenching drugs (Biondi et al. in J Nat Prod 68:1099–1102, 2005; Mamedov and Egamberdieva in Herbals and human health-phytochemistry. Springer Nature Publishers, 41 pp, 2017). No doubt, the clinical use of liquorice in modern medicine started around 1930; Pedanios Dioscorides of Anazarba (Adana), first century AD-Father of Pharmacists, mentions that it is highly effective in the treatment of stomach and intestinal ulcers. In Ayurveda, people in ancient Hindu culture have used it for improving sexual vigor."
6113,Sind wir gefährdet?: Krisenkommunikation für ein Bundesinstitut auf dem Gebiet des Gesundheitsschutzes,"Freitag, 24. April 2009, kurz nach 9 Uhr. Eine Nachrichtenagentur meldet, dass Mexiko wegen eines „tödlichen Grippevirus“ mit „mindestens 20 Toten“ alle Schulen und Universitäten in Teilen des Landes schließt (AFP 2009a). Um 15 Uhr wird gemeldet: „die Erreger breiteten sich bis in den Südwesten der USA aus, wo sich die Gesundheitsbehörden ´äußerst besorgt` zeigten“ (AFP 2009b). Die Weltgesundheitsorganisation (WHO) weist darauf hin, dass die am meisten betroffene Altersgruppe junge Erwachsene sind, und Influenzaviren normalerweise diese Gruppe nicht besonders betreffen (vgl. WHO 2009). Schnell etabliert sich der Begriff Schweinegrippe, der bleibt, obwohl Behörden und Wissenschaftler den Erreger später weltweit umbenennen in Neues Influenzavirus und danach in (Pandemische) Influenza H1N1 2009."
6114,Safeguards,"The multiplicity of threats and vulnerabilities associated with AmI will require a multiplicity of safeguards to respond to the risks and problems posed by the emerging technological systems and their applications. In some instances, a single safeguard might be sufficient to address a specified threat or vulnerability. More typically, however, a combination of safeguards will be necessary to address each threat and vulnerability. In still other instances, one safeguard might apply to numerous treats and vulnerabilities. One could depict these combinations in a matrix or on a spreadsheet, but the spreadsheet would quickly become rather large and, perhaps, would be slightly misleading. Just as the AmI world will be dynamic, constantly changing, the applicability of safeguards should also be regarded as subject to a dynamic, i.e., different and new safeguards may need to be introduced in order to cope with changes in the threats and vulnerabilities."
6115,From Medical Geography to Computational Epidemiology – Dynamics of Tuberculosis Transmission in Enclosed Spaces,"Medical geographers study the geographic distribution of health and health-related phenomena such as diseases, and health care facilities. Seeking to understand who is getting what diseases or health services where and why, they examine spatial disparities in access to health care services, and the geographic distribution of health risks. Medical geographers apply tools of geographic enquiry such as disease mapping and geographical correlation studies to health-related issues (Elliot et al., 2000; Pickle, 2002). Some have called this research endeavor spatial epidemiology (Cromley, 2003; Rushton, 2003a)."
6116,"Acute Lung Injury: The Injured Lung Endothelium, Therapeutic Strategies for Barrier Protection, and Vascular Biomarkers","The vascular endothelium can be considered as an organ/tissue which comprises a monolayer of endothelial cells which serve as a semipermeable cellular barrier separating the inner space of blood vessels from its surrounding tissue and to control the exchange of fluids and cells between the two compartments. Since the pulmonary circulation receives the entire cardiac output, the large surface area of the lung microvasculature is well suited for sensing mechanical, chemical, and cellular injury by inhaled or circulating substances. This endothelial barrier is dynamically regulated through exposure to these various stimuli of physiological and pathological origin and serves to regulate multiple key biological processes (including lung fluid balance and solute transport between vascular compartments). For example, an increase in vascular permeability is a necessary feature of the body’s defense mechanism to provide injured tissues with access to leucocytes, resulting in tissue edema due to fluid extravasation. However, during conditions of intense lung inflammation such as observed in acute lung injury or its severer form of acute respiratory distress syndrome, the large surface area becomes a liability and provides the opportunity for profound vascular permeability resulting in massive fluid accumulation in the alveolar space and progressively leading to pulmonary failure. Alterations in vascular permeability occur not only in acute inflammatory lung disorders primarily caused by sepsis, pneumonia, and trauma which result in high rates of patient morbidity and mortality, but are an attractive target for therapeutic intervention in subacute lung inflammatory disorders such as ischemia–reperfusion injury, radiation lung injury, and asthma. Thus, understanding the mechanisms of endothelial barrier dysfunction is vital for the management and treatment of key and enigmatic pulmonary disorders."
6117,PET-CT Imaging of Lymphoma,"PET-CT is now the mainstay for imaging lymphoma patients. The complimentary nature of the metabolic and anatomic information provided by a PET-CT examination has become an essential component of patient management, complimenting clinical and laboratory criteria used in staging, restaging, and therapy monitoring. The nature of a particular lymphoma subtype and the patient’s clinical presentation will determine the extent PET-CT imaging is best employed in a particular patient’s management."
6118,Novel Molecular Diagnostics and Therapeutic Tools for Livestock Diseases,"Recent novelties in diverse diagnostics and therapeutic tools in animal health sector have paved a brighter and clearer way ahead. These are proved to be better in detection, management, control and eradication of animal sufferings caused by various infectious and non-infectious diseases. These innovations have potential impact that extends beyond the animal health and welfare. The advancements have significantly contributed towards improvement in the economy of the country as well as food security. In the present competitive era of evolution, the organisms have inculcated a number of new strategies for survival and spread. Therefore, science needs to continuously evolve more sensitive, specific and high-throughput tools to overcome pathogen cleverness to escape from host immune surveillance. For visible or remarkable changes, it is necessary to use full potential of these advanced molecular techniques into current animal health standards and practices. Under ‘One Health’ concept, the health of animals and humans has to be taken care simultaneously. At present, these advanced molecular diagnostic methods play a significant role in the detection of new and emerging pathogens of livestock. The acquired information also helps to study the interrelationships of pathogens, their hosts and their surroundings. Additionally new vaccines bridging human and animal health development may be discovered. Latest developments in the field of diagnostics and vaccine design through genomics approach have also laid the foundation to enhance the diagnosis and surveillance and in turn helped in the control of infectious diseases. Latest high-throughput DNA sequencing platforms are currently being used for identification and detailed analysis of both disease pathogen and host genomes. The high-throughput data generated using these platforms need to be analysed adopting the bioinformatics and computational genomics that have taken a very high pace nowadays. In the context of animal health, the data analysis may provide some key opportunities for the development of better diagnostic and therapeutic tools for emerging or re-emerging diseases. Such novel and potent technologies put forward a significantly new scenario of disease knowledge, which enables more accurate predictions leading to faster and greater management responses to combat potentially devastating disease crises."
6119,The Ligands of C-Type Lectins,"In this chapter, a comprehensive overview of the known ligands for the C-type lectins (CTLs) is provided. Emphasis has been placed on the chemical structure of the glycans that bind to the different CTLs and the amount of structural variation (or overlap) that each CTL can tolerate. In this way, both the synthetic carbohydrate chemist and the immunologist can more readily gain insight into the existing structure-activity space for the CTL ligands and, ideally, see areas of synergy that will help identify and refine the ligands for these receptors."
6120,Artificial Intelligence Technology and Social Problem Solving,"Modern societal issues occur in a broad spectrum with very high levels of complexity and challenges, many of which are becoming increasingly difficult to address without the aid of cutting-edge technology. To alleviate these social problems, the Korean government recently announced the implementation of mega-projects to solve low employment, population aging, low birth rate and social safety net problems by utilizing AI and ICBM (IoT, Cloud Computing, Big Data, Mobile) technologies. In this letter, we will present the views on how AI and ICT technologies can be applied to ease or solve social problems by sharing examples of research results from studies of social anxiety, environmental noise, mobility of the disabled, and problems in social safety. We will also describe how all these technologies, big data, methodologies and knowledge can be combined onto an open social informatics platform."
6121,Risk Assessment and Contingency Planning for Exotic Disease Introductions,"Globalisation has greatly enhanced opportunities for the spread of infectious diseases throughout the world, giving rise to serious threats to human and animal health. This is illustrated by the recent introduction and subsequent spread of West Nile virus in the USA, and outbreaks of Severe Acute Respiratory Syndrome (SARS) in South-East Asia. It is therefore becoming increasingly important that national (and potentially regional) governments should not only have robust systems in place to reduce the risk of disease introductions, but that they need to also consider how to identify and deal with outbreaks of pathogens in wild and domestic animals. In this chapter we will discuss the roles of risk assessment and contingency planning in the management of exotic disease risks involving wild mammals. The principal purpose of contingency planning is to ensure that a State of preparedness exists in the event of a disease introduction. This requires that the most likely risks of pathogen introduction are identified, that there are adequate means of detecting the pathogen's presence, and that a set of instructions exists describing the best available methods for its rapid and cost-effective containment and control. Contingency planning will involve some of the approaches to disease surveillance (Chapter 10) and management (Chapters 6–8) discussed in other chapters, and so will entail many of the associated challenges, costs and benefits. However, as the aim of a contingency plan is likely to be the rapid containment and subsequent elimination of a pathogen (that is either exotic or endemic but emergent) within a restricted area, the methods of management should reflect this urgency. This may mean that it is appropriate to deploy more severe or costly measures over a short period than would be considered for the sustained control of an endemic pathogen."
6122,The University-Driven LISs,"Theoretical conceptions of the role of universities in local innovation systems have evolved over the past 20 years, from an initial approach that stressed the importance of knowledge spillovers from university educational and research activities into their regional knowledge spaces, towards a new emphasis on the “third role” of universities, as animators of regional economic and social development. However the typical conception is that universities and research centres in developing countries take little part in stimulating the formation of LISs, with this mission instead being substituted by the state or large companies. This chapter analyses the role and the mechanisms through which universities can contribute to creation of LISs, first from a theoretical point of view. The theoretical arguments are then supported by an analysis of the role of the National University of Singapore, in driving the development of the “Biopolis” biotech LIS."
6123,AIDS Patients in the ICU,"At the beginning of the AIDS epidemic, there were higher mortality rates in patients requiring admission to an intensive care unit (ICU) most likely due to acute respiratory failure. Whereas the use of prophylaxis and corticosteroids for Pneumocystis jiroveci pneumonia and highly active antiretroviral therapy has changed this outcome and has improved survival rate. However, respiratory failure has remained the most common indication for an ICU admission. When HIV-infected patients are admitted to the ICU, intensivists need to be knowledgeable about the manifestations of common diseases and the new manifestations related to antiretroviral therapy. Much HIV mortality has been linked directly to late diagnosis and late initiation of appropriate antiviral therapy. This l, the most important cause of ICU admission for AIDS patients. We analyzed the characteristics of P. jiroveci pneumonia, bacterial pneumonia, cytomegalovirus pneumonia, mycobacterial infections, pulmonary invasive fungal infections, Kaposi’s sarcoma, and the immune reconstitution inflammatory syndrome."
6124,Anaplasmose und Ehrlichiose,"Die humane Anaplasmose und die humane Ehrlichiose werden durch Zeckenstich auf den Menschen übertragen. Es handelt sich um unspezifische akut fieberhafte Erkrankungen. An Laborveränderungen werden am häufigsten eine Leukopenie, eine Thrombozytopenie und erhöhte Transaminasen gefunden. Hautmanifestationen sind bei der humanen Anaplasmose selten. Bei der humanen Ehrlichiose können makulopapulöse Exantheme und Petechien auftreten. Die Therapie besteht bei beiden Erkrankungen in der Gabe von Doxycyclin."
6125,Acute Pneumonia and Importance of Atypical Bacteria,"The term and concept of atypical pneumonia appeared in the 1940s following observations of penicillin-resistant pneumonia [1]. Despite the identification of a large number of microorganisms, the challenge of isolating so-called ‘atypical’ bacteria is the principal cause of failure of the etiologic diagnosis of pneumonia. These pathogenic agents in the tracheobronchial tree include a large variety of bacteria, viruses and even protozoa. Among atypical bacteria, Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumoniae, Bordetella pertussis, and Coxiella burnetii are the most widespread. Numerous other bacteria are emerging pathogenic species whose virulence is currently being evaluated. Clinical examination only provides a diagnostic orientation in a restricted number of cases. The availability of rapid and specific microbiologic examination improves the diagnostic performance for this type of pneumonia (Table 1) [2]. Since most of these bacteria are intracellular, diagnosis is based principally on serology."
6126,Acute Chest Infections in Children,"Radiation dose is a contentious issue in pediatrics, as it is well-established that the lifetime cancer mortality risks attributable to CT examinations are considerably higher than for adults. As proposed by the ALARA principle ‘as low as reasonably achievable’, the selection of appropriate scanning parameters focuses on the optimization of image quality whilst delivering the lowest possible radiation dose and shifting the risk-benefit balance towards benefit."
6127,Blood Transfusion-Associated Infections in the Twenty-First Century: New Challenges,"Blood transfusions are vital components of modern medical treatment to which there is no viable alternative despite efforts to create artificial blood. Each year thousands of lives are saved by blood transfusions in every country of the world. However, blood and blood products can result in significant adverse events including immunologic reactions, infections, inefficacy, and others which can sometimes result in death and severe disability. Thus, the sustainability of safe blood systems and costs are considered to be at crisis level. In industrialized countries, the risk of transfusion-transmitted infections such as HIV, syphilis, hepatitis viruses B and C are very low [generally [<1 in a million units], but in developing countries [especially in Africa] blood safety is still not assured. Compounding the problem of blood/product safety with respect to infectious agents are new emerging infectious microbes that are not being routinely tested for in blood that are donated. This chapter reviews the infectious risk of blood transfusions, types, mode and geographic variation, and the methods being used by blood services to attenuate and prevent these risks."
6128,Meaning of dangerous goods,"The parties to a contract for the carriage of goods by sea, whether this is embodied in a bill of lading or one of the standard charterparty forms, customarily negotiate its terms against a background of both commercial and legal considerations. The parties’ respective liability for risks to which the vessel and its cargo might be exposed during the course of the contracted voyage will be of paramount importance. Should they arise, the potential risks might expose the parties, through their insurance, to expensive damage claims. Therefore, the description of the cargo for shipment is one of the crucially important components of the negotiations between the parties to any shipping contract.(1) This requirement becomes especially relevant when it has been estimated that more than 50% of the cargoes transported by sea today may be regarded as dangerous, hazardous, and/or harmful and need to be handled with special care. As a result, a shipper does not have unlimited freedom as to what he may transport by sea. Restrictions on goods which a charterer or shipper may ship are imposed by law, the terms of the contract and statutes. These restrictions are commonly elided into a general proposition that a person sending goods by sea must not ship dangerous goods. Yet it is the case that dangerous goods are often shipped and legitimately so; and the carrier should discharge his normal duties in respect of whatever cargo he has agreed to carry. The real issues, therefore, are to identify what risks are involved in the carriage of the cargo in question, how these risks are allocated between the parties and what the consequences of shipping dangerous goods are.(2)"
6129,Metabolic Engineering of Fungal Strains for Efficient Production of Cellulolytic Enzymes,"Filamentous fungi are widely used for production of cellulase and other cellulolytic enzymes. Metabolic engineering of filamentous fungal strains has been applied to improve enzyme production, and rapid progress has been made in the recent years. In this chapter, genetic tools and methods to develop superior enzyme producers are summarized, which includes establishment of genetic modification systems, selection and redesign of promoters, and metabolic engineering using either native transcription factors or artificial ones. In addition, enhancement of cellulase production through morphology engineering was also discussed. Emerging tools including CRISPR-Cas9-based genome editing and synthetic biology are highlighted, which are speeding up mechanisms elucidation and strain development, and will further facilitate economic cellulolytic enzyme production."
6130,Prospects of brassinosteroids in medicinal applications,"Steroids are an imperative group of hormones which play a key role in the transmission of signals that mediate growth and physiological responses in most pluricellular organisms. Brassinosteroids (BRs), a class of plant-specific steroid hormones, control many of the developmental and physiological processes like their animal counterparts, including regulation of gene expression, cell division and expansion, differentiation, programmed cell death, and homeostasis. Recent studies have indicated that these hormones have antiviral, antifungal, antiproliferative, antibacterial, neuroprotective and immunomodulatory properties in animal system. BRs analogues have been reported to have antiviral activity against herpes simplex virus type 1 (HSV-1), arenaviruses as well as against replication of vesicular stomatitis virus (VSV) in Vero cells. Also, antiherpetic activities both in a human conjunctive cell line (IOBA-NHC) and murine herpetic stromal keratitis (HSK) experimental models have been reported. In human cells, anticancer structure-activity relationship of natural BRs revealed their high cytotoxic activity. Since, BRs and their analogues are reported to inhibit cell growth in cancer cell lines, they may be considered as promising phytohormones for potential anticancer drugs. The use of pollens in folk medicine also indicates scope of steroids of plant pollens in medicines. An attempt has been made in this paper to document the information available on the prospects of BRs in therapeutics."
6131,CT Imaging of Interstitial Lung Diseases,"Until today, computed tomography (CT) is the most important and valuable radiological modality to detect, analyze, and diagnose diffuse interstitial lung diseases (DILD), based on the unsurpassed morphological detail provided by high-resolution CT technique. In the past decade, there has been a shift from an isolated histopathological diagnosis to a multidisciplinary acquired diagnosis consensus that is nowadays regarded to provide the highest level of diagnostic accuracy in patients with diffuse interstitial lung diseases. The 2002 ATS/ERS statement on classification of idiopathic interstitial pneumonias assigned a central role to high-resolution CT (HRCT) in the diagnostic workup of idiopathic interstitial pneumonias (ATS/ERS consensus classification 2002). The more recent 2013 ERS/ATS statement reinforced that combined clinical data (presentation, exposures, smoking status, associated diseases, lung function, and laboratory findings) and radiological findings are essential for a multidisciplinary diagnosis (Travis et al., Am J Respir Crit Care Med 188(6):733–748, 2013). The traditional HRCT consisted of discontinuous 1 mm high-resolution axial slices. The primary focus was on visual pattern analysis demanding for the highest possible spatial resolution. Because of the intrinsic high structural contrast of the lung, it has been possible to substantially reduce dose without losing diagnostic information. This development has been supported by new detection and reconstruction techniques. Not only detection of subtle disease and visual comparison of disease stage but also disease classification and quantification nowadays take advantage of continuous volumetric data acquisition provided by multidetector row (MD) CT technique. The following book chapter will focus on acquisition technique with special emphasis on dose and reconstruction, advantages, and new diagnostic options of volumetric MDCT technique for interstitial lung diseases. Based on evidence from the literature, certain diseases will be covered more specifically, but it has to be noted that for the pattern analysis of the various interstitial lung diseases, the plethora of other publications and books is recommended."
6132,Functionalised Nanoliposomes for Construction of Recombinant Vaccines: Lyme Disease as an Example,"Liposomes (phospholipid bilayer vesicles) represent an almost ideal carrier system for the preparation of synthetic vaccines due to their biodegradability and capacity to protect and transport molecules of different physicochemical properties (including size, hydrophilicity, hydrophobicity, and charge). Liposomal carriers can be applied by invasive (e.g. i.m., s.c., i.d.) as well as non-invasive (transdermal and mucosal) routes. In the last 15 years, liposome vaccine technology has matured and several vaccines containing liposome-based adjuvants have been approved for human and veterinary use or have reached late stages of clinical evaluation. Given the intensifying interest in liposome-based vaccines, it is important to understand precisely how liposomes interact with the immune system and how they stimulate immunity. It has become clear that the physicochemical properties of liposomal vaccines – method of antigen attachment, lipid composition, bilayer fluidity, particle charge, and other properties – exert strong effects on the resulting immune response. In this chapter we will discuss some aspects of liposomal vaccines including the effect of novel and emerging immunomodulator incorporation. The application of metallochelating nanoliposomes for development of recombinant vaccine against Lyme disease will be presented as a suitable example."
6133,Life-Threatening Complications of Biological Therapies,"The last decade was characterized by the successive introduction of several biological agents for the treatment of autoimmune rheumatic diseases (ARD). Randomized controlled trials (RCT) proved them to have globally acceptable safety and tolerability profiles. However, life-threatening complications are rare events and RCT are underpowered to detect them. As these drugs became more widely prescribed in clinical practice, and particularly, having the information from multiple national biologics registries available, serious adverse events became perceptible. Infection remains the major concern, but other serious and life-threatening complications have emerged, such as malignancies, congestive heart failure, demyelinating disorders, and drug-induced autoimmune syndromes. Several of these are correlated with either the underlying disease or concomitant immunosuppressive medication. Most of them can be avoided by the adoption of preventive measures and an early proper management might significantly change the outcome. Awareness of the possible serious side effects is of utmost importance for a safer use of biological agents. In this chapter, we aim to describe the most commonly reported life-threatening complications of biological therapies in the literature – including those with antitumor necrosis factor agents, rituximab, abatacept, tocilizumab, and anakinra. Risk groups are identified and strategies for the prevention and initial management are included."
6134,"Bird Flu, SARS and Beyond","In the politically sensitive year of 1997, Hong Kong experienced an outbreak of avian flu when the deadly H5N1 virus unprecedentedly jumped the species barrier from chickens and infected human beings. Hong Kong decided to slaughter over a million chickens, and the virus was stopped in its tracks. In 2003, Hong Kong was the epicenter of the SARS pandemic, which originated in Guangdong province. The Faculty of Medicine played key roles in both instances, with its Microbiology Department successfully identifying a novel coronavirus as being responsible for SARS. Hong Kong learned from its experience and took action to combat the emergence of new infectious diseases. Such vigilance paid off in 2009, when swine flu swept the world, and in 2013, when a novel avian flu H7N9 emerged in China."
6135,Bridging the Gap Between Conservation and Health,"Health is frequently in the news, whether it is the “bird flu” headlines or woven into the core of climate change reports. And in these articles, health is the common thread that connects humans, animals, and the environment; however, this underlying link is often undervalued, leaving a “gap” that challenges our ability to prevent and mitigate major global catastrophes. The Ebola virus disease has ravaged West Africa, leaving a swath of devastation and unanswered questions in its wake, but it highlights the alarming potential of a zoonotic disease, one of hundreds that pass between animals and humans. Climate change continues to fuel controversy, but it is undeniable that our exploitation of the Earth is impacting the fundamental resources that form the foundation of our existence. The state of our ecosystems is integral to the conservation and sustainable management of our wildlife and natural resources. The health of the environment cannot be segregated from our own health; thus, we need to examine health from a global stance. Our traditional perspectives of “health” and “disease” are outdated, and it is prime time for us to reevaluate our approaches to engage a comprehensive audience as well as holistic strategies to address these issues as “One Health.”"
6136,The Impact of Infectious Diseases on the Development of Africa,"Despite the success of vaccination programs for polio and some childhood diseases, other diseases like HIV/AIDS, malaria, tuberculosis, acute respiratory infections and diarrheal disease are causing high mortality rates in Africa. However, mortality figures give only a partial measure of the toll asked by infectious diseases, and the global burden includes also health impact measured by disabilities, deformities, loss of productivity, care and treatment caused by a multitude of diseases like lymphatic filariasis, leishmaniasis, schistosomiasis, sleeping sickness and others. The impact of infectious diseases can be traced according to economic performance of African countries, showing that 34 out of 53 countries are classified as low-income economies. The disease burden is, however, more devastating since it affects all components of human development, including income, health and education. The impact of infectious diseases on African countries is no longer a crisis only for the healthcare sector, but presents a challenge to all sectors. It has the potential to reverse those gains made in human development in the last few years. Consequently, beyond health issues, these diseases should and must globally be seen as a development concern, affecting education and knowledge acquisition, income and social status, productivity and economic growth and other direct and indirect components of human development such as gender equality and human rights. For health strategies to be successful, international solidarity and public-private partnerships are needed to tackle the problems of shortage and lack of treatments, resistance and the need for new drugs, vaccines and diagnostic procedures. However, the output of international initiatives will remain limited without the national and local implication."
6137,Acronyms and Abbreviations,
6138,Trophoblast Cells as Immune Regulators,"Medawar, in the early 1950s, recognized for the first time, the unique immunology of the maternal-fetal interface and its potential relevance for transplantation. In his original work, he described the “fetal allograft analogy” whereby the fetus may be viewed as a semi-allogeneic conceptus that has evaded rejection by the maternal immune system. Although numerous hypotheses have been proposed to prove this observation, none have demonstrated that the maternal immune system is antagonist to the invading trophoblast. In the present manuscript we have reviewed recent studies demonstrating the expression and function of TLRs in trophoblast cells and based on this data we propose an alternative view for maternal-fetal immune interactions."
6139,Infectious Diseases of the Nervous System,"In this chapter infectious diseases of the nervous system are discussed. These include bacterial, viral, fungal, spirochetal, and parasitic infections. Although the central nervous system (CNS) is protected from bacterial invasion by the intact blood-brain barrier, bacterial invasion is enhanced by the special surface properties of bacteria as well as host immune deficiencies. Similar to any type of infection of the nervous system, bacteria may involve any of the nervous system compartments: the epidural space (epidural abscess); the dura (pachymeningitis); the subdural space (subdural empyema); the leptomeninges and the subarachnoid space containing cerebrospinal fluid (meningitis or leptomeningitis); and the brain parenchyma (brain abscess). The clinical manifestations, pathogenesis, pathology, etiology, epidemiology, diagnosis, differential diagnosis, and treatment of these syndromes are presented."
6140,Viral Diseases of the Liver,"Viruses other than the classic hepatotropic viruses, hepatitis A through E, may cause hepatic injury [1]. Among these are Epstein–Barr virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV), varicella zoster virus (VZV), human herpes viruses (HHV) 6, 7, and 8, human parvovirus B19, and adenoviruses (Table 11.1). The clinical presentation of infections with these viruses may be indistinguishable from that associated with infection with classic hepatotropic viruses. The presentation ranges from mild and transient elevation of aminotransferases to acute hepatitis and can also lead to acute liver failure [1]. These viruses should be considered as possible etiologic agents in patients who have acute liver injury and whose serologic markers for the classic hepatotropic viruses are not indicative of an active infection [1]. In the present chapter, we review the clinical manifestations and the potential for immune-mediated liver injury associated with several of these viruses (see summary Table 11.2)."
6141,Kulturgeschichte der Angst,"Man kann eine »Kulturgeschichte der Angst« kaum epochal ordnen. Bildet die Sattelzeit um 1800 hinsichtlich der Angst wirklich einen Epocheneinschnitt? Wird dies bejaht, so folgt man Parametern, die mit der Geschichte der Modernisierung verbunden sind: Werden die traditionalen von funktional differenzierten Gesellschaften systemisch unterschieden, dann ist 1800 ein Epochendatum, das auch für die Geschichte der Angst gelten muss. Wir werden zeigen, dass diese Annahme berechtigt ist. Dennoch ist dieser von Niklas Luhmann inspirierte Ansatz hinsichtlich der Geschichte von Gefühlen nur bedingt ein probater Weg; und er ist aussichtsreich eher für die Liebe als für die Angst, eher für die Sympathie als für die Wut. Sofern sich in der Moderne neue Felder der Angst und vielleicht auch neue Angsttypen ausmachen lassen, so gilt dennoch das, was eine der großen Entdeckungen Sigmund Freuds war, nämlich der Erhaltungssatz psychischer Energien."
6142,Pathogenesis of Fever,"#x203A; Although infection is the most common cause of fever, fever is also a common finding in hypersensitivity reaction, autoimmune diseases, and malignancy. › Febrile response is mediated by endogenous pyrogens (cytokines) in response to invading exogenous pyrogens, primarily microorganisms or their direct products (toxins). › These endogenous pyrogens act on thermosensitive neurons in the hypothalamus, which ultimately upgrade the set point via prostaglandins. › The body reacts by increasing the heat production and decreasing the heat loss until the body temperature reaches this elevated set point. › Fever, in contrast to hyperthermia, will not climb up relentlessly because of an effective central control of the hypothalamic center. › Cytokines play a pivotal role in the immune response by activation of the B cells and T lymphocytes. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favor of the protective role of fever. › The protective processes of the immune response are optimal at high temperature (around 39.5°C). › Not all effects resulting from fever generation benefit the host; some are harmful and even lethal. This occurs mainly by overproduction of the cytokines or imbalance between cytokines and their inhibitors, such as severe and fulminate infections and septic shock."
6143,La ventiloterapia non invasiva nel trattamento dell’insufficienza respiratoria acuta: indicazioni controverse,"La polmonite che richiede il ricorso alla ventilazione, sia essa invasiva o NIV, è sempre un evento grave associato a una elevata mortalità, soprattutto nell’anziano, nonostante questa patologia venga dai media spesso considerata come malattia di “facile” risoluzione."
6144,Rabbit Coronavirus-like Viruses(‡): Coronaviridae,
6145,Smallpox as a Weapon for Bioterrorism,"Smallpox, the only disease ever eradicated, is one of the six pathogens considered a serious threat for biological terrorism (Henderson et al., 1999; Mahy, 2003; Whitley, 2003). Smallpox has several attributes that make it a potential threat. It can be grown in large amounts. It spreads via the respiratory route. It has a 30% mortality rate. The potential for an attack using smallpox motivated President Bush to call for phased vaccination of a substantial number of American health care and public health workers (Grabenstein and Winkenwerder, 2003; Stevenson and Stolberg, 2002). Following September 11, 2001, the United States rebuilt its supplies of vaccine and Vaccinia Immune Globulin (VIG), expanded the network of laboratories capable of testing for variola virus, and engaged in a broad education campaign to help health care workers and the general public understand the disease (Centers for Disease Control and Prevention, 2003a). This chapter summarizes the scientific and theoretical bases for use of smallpox as a bioweapon and options for preparation for defense against it."
6146,"Introduction to the Economic, Financial, Political and Legal Implications of Global Pandemics","In this chapter, we begin with an assessment of the risks posed by fast-moving global pandemics. We then examine the origin and nature of the slow-moving global HIV/AIDS pandemic. The remainder of this chapter summarizes the topics that will be covered in the subsequent chapters of this book."
6147,Pulmonary Disorders in Pregnancy,"Pregnancy is associated with some profound changes in the cardiovascular, respiratory, immune, and hematologic systems that impact the clinical presentation of respiratory disorders, their implications in pregnancy, and the decisions to treat. In addition, concerns for fetal well-being and safety of various interventions complicate the management of these disorders. In many circumstances, especially life-threatening ones, decisions are based upon a careful assessment of the risk benefit ratio rather than absolute safety of drugs and interventions. In this chapter, we review some of the common respiratory disorders that internists or obstetricians may be called upon to manage."
6148,Types of Human Disease by Source of the Infectious Agent,"In general, the source of infection for human beings is another human, or an animal, or the environment (extra-animal substrate). In line with this we can distinguish human infectious diseases as anthroponoses, zoonoses and sapronoses, respectively."
6149,Critical Illness Stress-induced Immune Suppression,"Despite the use of Centers for Disease Control and Prevention (CDC) recommended practices to minimize infection risk, nosocomial sepsis and multiple organ failure (MOF) remain a leading cause of morbidity and mortality in critically ill patients. It is well documented that the use of immunosuppressant therapies dramatically increases this risk in patients with cancer, transplantation, and immunologic disease. Although immune monitoring has yet to be universally embraced, withdrawal of immunosuppressant therapies and use of immune restoration therapies is the standard of care when these patients develop sepsis. Critical illness stress can also induce a level of immunosuppression which is as life-threatening as is seen in the purposefully immunosuppressed patient. This chapter reviews the role of critical illness stress-induced immunosuppression in the development of nosocomial sepsis and MOF, and outlines clinical strategies which can be employed to maintain and restore immune function, and reduce morbidity and mortality in critically ill patients."
6150,Potential of Tree Endophytes as Sources for New Drug Compounds,"The novel or designer metabolites produced by fungal endophytes are increasingly recognized by natural chemists due to their diverse structures and as candidates for drug discovery and development. Many of the metabolites belong to different classes i.e. alkaloids, benzopyranones, coumarins, chromones, cytochalasines, enniatines, isocoumarin derivatives, quinones, peptides, phenols, phenolic acids, semiquinones, steroids, terpenoids, xanthones and lactones. One of the most widely studied endophytic genera is Pestalotiopsis, from which more than 140 metabolites are reported with antimicrobial, antioxidant and antitumor activities. Besides reviewing the advances made in identifying bioactive metabolites with drug development potential from endophytic fungi, this chapter discusses possibilities and bottlenecks involved in employment of endophytic fungi and their products by the pharmaceutical industry. Furthermore, issues involved in anti-infective discovery and timeline of drug development are discussed in the view of developing new drug compounds from endophytic products."
6151,Emergency Triage of Highly Infectious Diseases and Bioterrorism,"Emergency medical services are a key element in health systems for the evaluation and treatment of patients exposed to highly infectious diseases or bioterrorism agents. Triage and early identification at any point of care can have a significant impact on the prevention and management of these diseases. This chapter reviews triage practices, including early isolation and decontamination, of highly infectious diseases and bioterrorism agents at different health system levels."
6152,An Oral Vaccine for TGEV Immunization of Pigs,"Transmissible gastroenteritis virus (TGEV) is a commercially important pathogen of hog farms and causes contagious, lethal diarrhea in piglets. While orally and parenterally administered vaccines made from inactivated or attenuated TGEV are commercially available, they require individual administration to piglets, which is time and labor intensive, and run the risk of reversion to pathogenicity. Also, parenteral vaccines produce neutralizing serum antibodies which may be less effective against an orally transmitted pathogen, compared to an oral vaccine that would induce the production of mucosal antibodies. There has been an effort to produce subunit vaccines in an edible form in plants for convenient administration through feed. These efforts towards the expression of the S-antigen of TGEV in maize seed, its effectiveness at inducing neutralizing antibody production in the colostrum of gilts, and its efficacy in protecting piglets against challenge by virulent TGEV are summarized here."
6153,Real-Time Reverse Transcription-Polymerase Chain Reaction for Detection and Quantitation of Turkey Coronavirus RNA in Feces and Intestine Tissues,"Turkey coronavirus (TCoV) infection causes acute atrophic enteritis in turkey poults, leading to significant economic loss in the turkey industry. Rapid detection, differentiation, and quantitation of TCoV are critical to the diagnosis and control of the disease. A specific one-step real-time reverse transcription-polymerase chain reaction (RT-PCR) assay using TCoV-specific primers and dual-labeled fluorescent probe for detection and quantitation of TCoV in feces and intestine tissues is described in this chapter. The fluorogenic probe labeled with a reporter dye (FAM, 6-carboxytetramethylrhodamine) and a quencher dye (Absolute Quencher™) was designed to bind to a 186 base-pair fragment flanked by the two PCR primers targeting the 3′ end of spike gene (S2) of TCoV. The assay is highly specific and sensitive and can quantitate between 10(2) and 10(10) copies/mL of viral genome. It is useful in monitoring the progression of TCoV-induced atrophic enteritis in the turkey flocks."
6154,Demand for Tourism in Malaysia by UK and US Tourists: A Cointegration and Error Correction Model Approach,
6155,Non-vaccine-Preventable Infections,"There are many potentially serious infections that may pose a risk to travellers for which no vaccines are available. Following discussions on vaccines, malaria prevention and travellers’ diarrhoea at the consultation, the travel-medicine practitioner should identify other infectious risks that may apply to the traveller, whether because of destination/s and duration of travel, occupational or other activities, or individual susceptibility. Information should be provided about these infections, their relevance, modes of transmission and methods of prevention, or the traveller should be referred to an authoritative source of information. In this chapter, advice will be given on both destination- and activity-related infections. The risk, distribution, clinical features and methods of prevention of a number of specific infections for which no vaccines are available are then outlined. This includes information on emerging viral infections such as Zika, MERS, Ebola and Chikungunya."
6156,Conclusion: Contributions of Multiple Representations to Biological Education,"Our book project began in 2009 with the intent to bring together international biology educators and biology education researchers who are involved in improving biological education from the perspective of multiple representations. It was also our goal that this volume would be able to address how biological education could meet the challenges of the twenty-first century, in which the breakthroughs in biological research would necessitate the integration of research and education with global economics and human social structures (Kress & Barrett, 2001)."
6157,Scopulariopsis brevicaulis,"Scopulariopsis hominis, Scopulariopsis rufulus, Penicillium brevicaulis"
6158,Pulmonary Infections: Imaging with CT,"Computed tomography (CT) plays a key role in various kinds of pulmonary infections especially in immunocompromised patients, owing to its much higher sensitivity and specificity than the traditionally performed chest X-ray. CT permits the detection of the main infectious pattern and associated findings with high confidence and allows for the precise assessment of all involved structures, to potentially guide a bronchoalveolar lavage or another diagnostic procedure, and to ensure a reliable follow-up. It may be performed at a carefully chosen dose, which may nearly reach that of a chest X-ray in specific situations. The importance of post-processing tools is undeniable in some conditions, in particular for the evaluation of micronodules in the immunocompromised population. The wide spectrum of features of specific organisms according to the immune status, such as in aspergillosis or tuberculosis, must be known, as well as the potential of atypical presentations in case of Pneumocystis jirovecii (PCP) pneumonia when occurring in non-HIV immunocompromised patients. In all cases, underlying disorders must be considered as well as all the differential diagnoses. Overall, CT definitely helps clinicians to diagnose pulmonary infections and to make treatment decisions, especially in vulnerable patients."
6159,A New Approach to Ventilator-associated Pneumonia Based on the PIRO System,"Several new scoring systems have been developed over recent years to assess the degree of organ failure (e.g., Acute Physiology and Chronic Health Evaluation [APACHE] II, APACHE III, Sequential Organ Failure Assessment [SOFA], Simplified Acute Physiology Score [SAPS] II, and Multiple Organ Dysfunction Score [MODS]). Most of these were models generated based on the concepts of sepsis, severe sepsis and septic shock. In 2001, an International Sepsis Definition Conference updated these terms in order to facilitate standardized enrolment into clinical trials, but due to their simplicity and easy use physicians rapidly adopted them for daily clinical practice [1]."
6160,Viruses,
6161,The Challenge of Emerging Infections and Progressive Antibiotic Resistance,
6162,"Hospital Wastewater Treatments Adopted in Asia, Africa, and Australia","This chapter provides an overview of the current management and treatment of hospital wastewater in Asia, Africa, and Australia. Twenty peer reviewed papers from different countries have been analyzed, highlighting the rationale behind each study and the efficacy of the investigated treatment in terms of macro- and micro-pollutants. Hospital wastewaters are subjected to different treatment scenarios in the studied countries (specific treatment, co-treatment, and direct disposal into the environment). Different technologies have been adopted acting as primary, secondary, and tertiary steps, the most widely applied technology being conventional activated sludge (CAS), followed by membrane bioreactor (MBR). Other types of technology were also investigated. Referring to the removal efficiency of macro- and micro-pollutants, the collected data demonstrates good removal efficiency of macro-pollutants using the current adopted technologies, while the removal of micro-pollutants (pharmaceutical substances) varies from low to high removal and release of some compounds was also observed. In general, there is no single practice which could be considered a solution to the problem of managing HWWs – in many cases a number of sequences are used in combination."
6163,Notfall- und Intensivmedizin bei speziellen Krankheitsbildern,"Ein 63-jähriger Mann bricht beim Tennisspielen zusammen und bleibt reglos liegen. Die anwesenden Personen können keine Atmung feststellen und beginnen mit der Herz-Lungen-Wiederbelebung. Die sofort alarmierte Rettung trifft 12 min nach dem Kollaps ein und setzt die Reanimationsmaßnahmen fort. Der EKG-Monitor zeigt Kammerflimmern, der Patient wird sofort defibrilliert und die Reanimation fortgesetzt. Kurz darauf ist ein Puls tastbar, das EKG zeigt einen Sinusrhythmus mit zahlreichen ventrikulären Extrasystolen. Der Patient wird daraufh in intubiert und analgosediert. Der angeforderte Notarzthubschrauber transportiert den Patienten ins Krankenhaus. Dort wird ein ausgedehnter Vorderwandinfarkt festgestellt; der Patient erhält sofort eine PTCA mit Stentimplantation und wird für weitere 24 h auf 33 °C gekühlt. Wenige Tage nach dem Ereignis kann er ohne neurologisches Defi zit die Rehabi litation antreten."
6164,Malaria,"Malaria is a significant cause of morbidity and mortality throughout the world, and environmental changes are likely to increase its importance in the coming years. Diagnosing this disease is difficult and requires a high index of suspicion, especially in non-endemic countries. Critical care providers play a major role in treating severe malaria and its complications, which has management particularities that might not be readily apparent. Fluid resuscitation should be carefully tailored to avoid complications, and dysperfusion seems more related to degree of parasitemia than hypovolemia. Antimalarial agents are effective, but resistance is growing. Complications can be found in nearly every organ, including cerebral malaria, acute respiratory distress syndrome, and acute kidney injury. As such, a critical care unit is frequently required for organ support when they appear. Superimposed infections are not infrequent. Despite all of this, mortality is encouragingly low with a timely diagnosis and access to appropriate treatment."
6165,Migration in Saudi Arabia: Present and Prospects,"As compared with other Gulf Cooperation Council (GCC) countries, Saudi Arabia has distinct demographic features. This leads the Saudi government to take measures to revisit its existing policies and schemes concerned with population. With this brief outline, migration data used in this article are pitched to understand five dimensions: (1) to look at the Saudi citizens’ migration trends within the Kingdom, (2) to analyse the impact of migration on the Kingdom’s population growth and also on the neighbouring GCC countries, (3) to look at the changes taking place annually in the Kingdom’s migration trends and in the other GCC countries, (4) to examine the migrants, looking at their origin place and (5) to analyse the variation between immigrants and Saudi Arabia citizens in terms of demographic parameters like population growth, sex ratio, broad age groups and age-sex distribution. Various databases available at both national and international levels were taken to address the five dimensions. The findings showed that push and pull factors and infrastructure differentials are taken into consideration while Saudi population internally migrate. All the GCC countries, including Saudi Arabia, experience international migration streams subject to the labour requirements and governmental regulations for both Arabs and non-Arabs. Immigrant demographics are characterized by Saudi Arabia’s labour demand controlled by adult males from other countries."
6166,Mo-Buzz: Socially-Mediated Collaborative Platform for Ubiquitous Location Based Service,"This paper describes a middleware platform for user-generated multimedia contents which facilitates visualization and communication of vector-borne diseases (dengue, malaria, etc.). It acts as a community platform, where diverse users from geographically distributed locations can collaborate to seek and contribute multimedia contents of such diseases and related issues (breeding sites, etc.). Some of the essential services supported by the system are display of live hotspots, timeline, multimedia and Twitter-feed visualization, and location based services for both users and authorities. As a proof-of-concept, dengue disease was selected to build services using this platform to observe its capabilities."
6167,Immunologie,"Die Mechanismen der Immunabwehr, mit denen ein Organismus Virusinfektionen bekämpft, können in zwei Gruppen eingeteilt werden. Zum einen gibt es die unspezifischen, nichtadaptativen Immunreaktionen, die eindringende Erreger als fremd erkennen und eliminieren. Diese sogenannte natürliche oder angeborene Immunabwehr wird als erste aktiv, nachdem ein Virus die äußeren physikalischen Schutzschranken des Körpers (Haut, Schleimhaut) überwunden hat. Sie besteht aus bestimmten Zellen, nämlich aus den dendritischen Zellen, den Granulocyten, den Monocyten und Makrophagen sowie den natürlichen Killerzellen. Diese verfügen über Proteine, die als Rezeptoren (beispielsweise toll-like-Rezeptoren, Komplementrezeptoren) für bestimmte Erregerstrukturen und für die löslichen Produkte des unspezifischen Immunsystems (Akutphaseproteine, die Faktoren des Komplementsystems, Cytokine, Chemokine und Interferone) dienen. Auf die Wirkung und Funktion der Cytokine, Chemokine und Interferone wird in ▸ Kapitel 8 gesondert eingegangen."
6168,Serine Proteases in the Lectin Pathway of the Complement System,"The complement system plays a crucial role in host defense against pathogen infections and in the recognition and removal of damaged or altered self-components. Complement system activation can be initiated by three different pathways—classical, alternative, and lectin pathways—resulting in a proteolytic cascade, which culminates in multiple biological processes including opsonization and phagocytosis of intruders, inflammation, cell lysis, and removal of immune complexes and apoptotic cells. Furthermore, it also functions as a link between the innate and adaptive immune responses. The lectin pathway (LP) activation is mediated by serine proteases, termed mannan-binding lectin (MBL)-associated serine proteases (MASPs), which are associated with the pattern recognition molecules (PRMs) that recognize carbohydrates or acetylated compounds on surfaces of pathogens or apoptotic cells. These result in the proteolysis of complement C2 and C4 generating C3 convertase (C4b2a), which carries forward the activation cascade of complements, culminating in the elimination of foreign molecules. This chapter presents an overview of the complement system focusing on the characterization of MASPs and its genes, as well as its functions in the immune response."
6169,Entwicklung von Arzneistoffen,"Die Entwicklung von Arzneistoffen stellt eine der wichtigsten Schnittstellen zwischen der Biochemie und der Medizin dar. In den meisten Fällen entfalten die Arzneistoffe ihre Wirkung, indem sie an spezifische Rezeptoren oder Enzyme binden und diese inhibieren oder deren Aktivität auf eine andere Weise verändern. Deshalb ist das Wissen über diese Moleküle und die Stoffwechselwege, in die sie eingreifen, von entscheidender Bedeutung für die Arzneistoffentwicklung. Ein effektiver Arzneistoff ist jedoch weit mehr als ein stark wirkender Modulator. Arzneistoffe müssen sich den Patienten einfach verabreichen lassen, vorzugsweise als kleine, oral gegebene Tabletten, und sie müssen im Körper lange genug überdauern, damit sie ihr Ziel erreichen können. Um unerwünschte physiologische Wirkungen zu verhindern, dürfen die Arzneistoffe zudem nicht die Eigenschaften von anderen Biomolekülen verändern, die nicht ihre Zielmoleküle sind. Diese Anforderungen schränken die Anzahl der Verbindungen, die klinisch von Nutzen sein können, enorm ein."
6170,Study on Efficient Complex Network Model,"This paper summarizes the relevant research of the complex network systematically based on Statistical Property, Structural Model, and Dynamical Behavior. Moreover, it emphatically introduces the application of the complex network in the economic system."
6171,The Pharmaceutical Company Approach to Antibiotic Policies,
6172,Metabolic disorders and storage diseases,"Primary metabolic disorders and storage diseases are caused by endogenous factors, usually a gene mutation. Since the congenital defect is predominantly or exclusively located in the liver, the resulting diseases also become manifest in this organ."
6173,Kawasaki Disease,"Kawasaki disease (KD) is a systemic vasculitis mainly affecting children below 5 years of age. Diagnosis is made upon a combination of criteria, including persistent fever; edema, erythema, or desquamation of the extremities; polymorphous exanthema; conjunctival injection; erythema of the lips and oral mucosa; and lymphadenopathies. Many cases do not meet all diagnostic criteria but should also be considered for therapy. IVIG and aspirin are the main therapeutic measures."
6174,Edible Vaccines,"In recent years edible vaccine emerged as a new concept developed by biotechnologists. Edible vaccines are subunit vaccines where the selected genes are introduced into the plants and the transgenic plant is then induced to manufacture the encoded protein. Foods under such application include potato, banana, lettuce, corn, soybean, rice, and legumes. They are easy to administer, easy to store and readily acceptable delivery system for different age group patients yet cost effective. Edible vaccines present exciting possibilities for significantly reducing various diseases such as measles, hepatitis B, cholera, diarrhea, etc., mainly in developing countries. However, various technical and regulatory challenges need to overcome in the path of this emerging vaccine technology to make edible vaccine more efficient and applicable. This chapter attempts to discuss key aspects of edible vaccines like host plants, production, mechanism of action, advantages and limitations, applications, and different regulatory issues concerned to edible vaccines."
6175,Fundamentals of XML and BSML,
6176,Early Warning Systems Defined,"This chapter defines and describes early warning systems (EWS) by examining structures and functions of EWS. The focus of this book is on climate change, but other hazards help to better illustrate and understand EWS in the context of climate change. These include hazards which manifest rapidly, such as tsunamis, as well as creeping hazards which manifest slowly, such as drought. The fundamental tenet is that each EWS needs to be viewed as a social process which often involves technical components embedded in their social context. That leads to a preference for a ‘First Mile’ approach for designing EWS, which involves communities from the beginning of developing an EWS, rather than a ‘Last Mile’ approach, which adds people and communities towards the end of the design process. By keeping people and communities at the centre of an EWS from the beginning, the EWS can contribute to daily life and livelihoods, thereby supporting wider disaster risk reduction and sustainable development endeavours, rather than being a separate system waiting to be triggered only when a hazard appears. Yet any EWS has limitations. Those limitations need to be recognised and overcome through other approaches, with possibilities being to consider ‘medium warning’ and ‘late warning’ systems rather than just early warning."
6177,Rural Livelihood,"In most rural areas of the world, approximately 90 % of the population is involved in farming as a way of earning a living. Small-scale farming, fishing, raising livestock and non-farm activities are some of the common livelihoods that these populations survive on. Rural livelihood poses a great challenge as these populations are often in a state of poverty where they lack the basic necessities for survival. A rural household with diverse sources of income earning activities has better chances of survival financially than a household which has only one source. Delivery of quality education and training in a variety of skills in rural areas is therefore needed to attain sustainable rural livelihoods. In order for a rural population to strive there is need for livelihoods that would sustain and support their households and communities."
6178,Discoveries in Molecular Genetics with the Adenovirus 12 System: Integration of Viral DNA and Epigenetic Consequences,"Starting in the 1960s, the human adenovirus type 12 (Ad12) system has been used in my laboratory to investigate basic mechanisms in molecular biology and viral oncology. Ad12 replicates in human cells but undergoes a completely abortive cycle in Syrian hamster cells. Ad12 induces neuro-ectodermal tumors in newborn hamsters (Mesocricetus auratus). Each tumor cell or Ad12-transformed hamster cell carries multiple copies of integrated Ad12 DNA. Ad12 DNA usually integrates at one chromosomal site which is not specific since Ad12 DNA can integrate at many different locations in the hamster genome. Epigenetic research occupies a prominent role in tumor biology. We have been using the human Ad12 Syrian hamster cell system for the analysis of epigenetic alterations in Ad12-infected cells and in Ad12-induced hamster tumors. Virion or free intracellular Ad12 DNA remains unmethylated at CpG sites, whereas the integrated viral genomes become de novo methylated in specific patterns. Inverse correlations between promoter methylation and activity were described for the first time in this system and initiated active research in the field of DNA methylation and epigenetics. Today, promoter methylation has been recognized as an important factor in long-term genome silencing. We have also discovered that the insertion of foreign (Ad12, bacteriophage lambda, plasmid) DNA into mammalian genomes can lead to genome-wide alterations in methylation and transcription patterns in the recipient genomes. This concept has been verified recently in a pilot study with human cells which had been rendered transgenomic for a 5.6 kbp bacterial plasmid. Currently, we study epigenetic effects on cellular methylation and transcription patterns in Ad12-infected cells and in Ad12-induced hamster tumor cells. These epigenetic alterations are considered crucial elements in (viral) oncogenesis."
6179,Organizing Pneumonias,"Organizing pneumonia is a particular type of inflammatory and reparative reaction of the lung parenchyma characterized by fibroblast proliferation in the distal airspaces with overall preservation of the lung architecture. When microscopic, it is an asymptomatic and nonspecific reaction of little clinical significance accompanying many pathological processes. When macroscopic and affecting large portions of the lung parenchyma, it manifests by restrictive ventilatory defect and gas exchange impairment leading to dyspnea, cough, hypoxemia, alveolar opacities at chest imaging, and symptoms of systemic inflammation such as fever, malaise, and weight loss. This picture constitutes the clinico-pathological syndrome of organizing pneumonia, which has been recognized and characterized as a distinct entity in the past 30 years. Although the classical features of organizing pneumonia are increasingly familiar to chest physicians, and the efficacy of corticosteroid treatment makes it appear at first sight as an easy problem to resolve, atypical clinical presentations, similarities with other diseases, severe forms, histological variants, side effects of therapy, and relapses can make the management more difficult than initially expected. This chapter will address the classical and less common features of organizing pneumonia, and will provide practical clues to the diagnosis and management of this disorder."
6180,Animal Coronaviruses: A Brief Introduction,"Coronaviruses (CoVs) are single-stranded positive-sense enveloped RNA viruses. Among RNA viruses, CoVs have the largest genome. CoVs infect diverse animal species including domestic and wild animals. In this chapter, we provide a brief review on animal CoVs by discussing their receptor, host specificity, reverse genetics, and emerging and re-emerging porcine CoVs."
6181,The Role of Humoral Immunity in Mouse Hepatitis Virus Induced Demyelination,"Pathogenesis induced by mouse hepatitis virus (MHV) infection of rodents is characterized by acute viral encephalomyelitis and demyelination which progresses to a persistent CNS infection associated with ongoing myelin loss, pathologically similar to multiple sclerosis (MS). Although humoral immunity appears redundant for the control of acute virus replication, it is vital in maintaining virus at levels detectable only by RNA analysis. T cell mediated control of acute infection cannot be sustained in antibody (Ab) deficient mice, resulting in virus reactivation. The protective role of Ab during persistence is strongly supported by detection of Ab in the cerebrospinal fluid of MHV infected rodents and maintenance of virus specific Ab secreting cells (ASC) in the CNS long after virus clearance. Ab mediated neutralization constitutes the major mechanism of protection, although fusion inhibition also plays a minor role. Delayed accumulation of ASC, concomitant with a decline in T cell function, assures control of residual virus while minimizing T cell mediated pathology. Although there is little evidence for a detrimental role of Ab in demyelination, an association between Ab mediated protection and remyelination is unclear."
6182,Intensive Patient Treatment,"Intensive care units (ICUs) are treating hospital’s poorest patients that need medical assistance during the most extreme period of their life. Intensive patients are treated with extensive invasive procedures, which may cause a risk of hospital infections in 10–30% of the cases. More than half of these infections can be prevented. The patients are often admitted directly from outside the hospital or from abroad with trauma after accidents, serious heart and lung conditions, sepsis and other life-threatening diseases. Infection or carrier state of microbes is often unknown on arrival and poses a risk of transmission to other patients, personnel and the environment. Patients that are transferred between different healthcare levels and institutions with unknown infection may be a particular risk for other patients. In spite of the serious state of the patients, many ICUs have few resources and are overcrowded and understaffed, with a lack of competent personnel. ICU should have a large enough area and be designed, furnished and staffed for a good, safe and effective infection control. The following chapter is focused on practical measures to reduce the incidence of infections among ICU patients."
6183,Targeting Viral Heart Disease by RNA Interference,"Viral heart disease (VHD) is an important clinical disease entity both in pediatric as well as adult cardiology. Coxsackieviruses (CVBs) are considered an important cause for VHD in both populations. VHD may lead to dilated cardiomyopathy and heart failure which can ultimately require heart transplantation. However, no specific treatment modality is so far available. We and others have shown that coxsackieviral replication and cytotoxicity can be successfully targeted by RNA interference, thus leading to increased cell viability and even prolongation of survival in vivo. However, considerable limitations have to be solved before this novel therapeutic approach may enter the clinical trials arena."
6184,Kratzwürmer,
6185,Highly Pathogenic Avian Influenza,"Highly pathogenic avian influenza is an acute respiratory infectious disease caused by some viral strains of avian influenza virus A. Its severity is highly diverse ranging from common cold-like symptoms to septicemia, shock, multiple organ failure, Reye syndrome, pulmonary hemorrhage, and other complications leading to death. According to the laws, human infection of highly pathogenic avian influenza has been legally listed as class B infectious diseases in China. And it has been stipulated that it should be managed according to class A infectious diseases in China."
6186,Noninvasive Mechanical Ventilation in Patients with High-Risk Infections in Intermediate Respiratory Care Units and on the Pneumology Ward,"Several studies have examined the benefit of noninvasive ventilation (NIV) as first-line therapy in some critically ill patients versus conventional therapy [1]. Currently, NIV is frequently started outside the intensive care unit (ICU)—not only in the emergency department but also in general wards with less-extensive monitoring facilities [2, 3]. Plant et al. [4] showed that it is possible to apply NIV to patients with chronic obstructive pulmonary disease (COPD) and hypercapnic acute respiratory failure (ARF) in the general ward provided the respiratory failure is not severe (assessed by pH>7.30). A European survey of a European Respiratory Society Task Force [5] defined the ICU as a location with a high staff-to-patients ratio and facilities for performing invasive ventilation and monitoring. It defined a respiratory intermediate ICU (RIICU), or a high-dependency unit, as a specific clinical area that has the capability of performing continuous vital sign monitoring and a staff-to-patient ratio somewhere between those for an ICU and a general ward (usually 1:4). Clinical criteria for performing NIV in an RIICU are based on mental status and the presence (or absence) of multi-organ failure [1]."
6187,Reading an uncertain future,assess the limitations of the information available for strategy making; recognize what kind of information is relevant to strategy making; learn how to read the general environment; understand what is involved in forecasting the future; identify the different kinds of risks to which the enterprise is exposed; build different scenarios of the future.
6188,Bis an die Grenzen der Vorstellungskraft? Sicherheitspolitische Bedrohungsanalysen,"Eine Analyse der gegenwärtigen sowie der in der Zukunft zu erwartenden sicherheitspolitischen Bedrohungen bildet die Basis für die Konzipierung nationaler Sicherheits- und Verteidigungspolitik. Konsequenterweise ist die Analyse sicherheitspolitisch relevanter Bedrohungen nicht nur fester Bestandteil entsprechender Grundsatzdokumente und findet sich sowohl im deutschen Weißbuch aus dem Jahr 2006 als auch in Livre Blanc und NSS von 2008 jeweils im vorderen Teil des Dokuments, sondern stellt auch einen grundlegenden Teilbereich nationaler Sicherheits- und Verteidigungspolitik dar."
6189,Transfusion Medicine,"Anemia is common in pediatric intensive care units (PICU). Severe anemia can significantly increase the risk of death. Only a red blood cell (RBC) transfusion can rapidly treat a severe anemia. In stable PICU patients, RBC transfusion is probably not required if the hemoglobin concentration is above 7 g/dL, unless the patient has a cyanotic cardiac condition. The trigger or goal that should be used to direct RBC transfusion therapy in unstable critically ill children remains undetermined, although some data suggest that RBC transfusion may help in the early treatment of unstable patients with sepsis if their ScvO(2) is below 70 % after mechanical ventilation, fluid challenge, and inotropes/vasopressors perfusions have been initiated. Plasma and platelets are used to prevent or to treat hemorrhage attributable to a coagulopathy, thrombocytopenia or platelet dysfunction. The risks and benefits of plasma and platelet concentrates in PICU patients are discussed. There is almost no evidence at the present time that might permit a strong recommendation with regard to the use of plasma and platelets in PICU. Good knowledge of transfusion reactions is required in order to appropriately estimate the cost/benefit ratio of transfusion. Nowadays, non-infectious serious hazards of transfusion (NISHOT) are more frequent and more challenging for pediatric intensivists than transfusion-transmitted infectious diseases. The decision to prescribe a transfusion must be tailored to individual needs and repeated clinical evaluation of each critically ill child."
6190,Vascular Lung Diseases,"Here we will discuss infarct and thromboembolic disease, vasculitis, vascular malformations, and pulmonary hypertension. Vascular tumors have already been discussed."
6191,Hoe zoekt PubMed? (vervolg),Hier volgt een korte opsomming van de diverse mogelijkheden om in PubMed te zoeken. Er is een aantal eenvoudige en tevens snelle varianten die heel bruikbaar zijn voor bepaalde vragen. Ook de gecompliceerdere mogelijkheden van de MeSH worden behandeld.
6192,Trait-Mediated Effects of Parasites on Invader-Native Interactions,"Parasites have a variety of behavioural effects on their hosts, which can in turn affect species with which the host interacts. Here we review how these trait-mediated indirect effects of parasites can alter the outcomes of invader-native interactions, illustrating with examples from the literature and with particular regard to the invader-native crustacean systems studied in our laboratories. Parasites may potentially inhibit or exacerbate invasions via their effects on host behaviour, in addition to their direct virulence effects on hosts. In several crustacean systems, we have found that parasites influence both host predation rates on intra- and inter-guild prey and host vulnerability to being preyed upon. These trait effects can theoretically alter invasion impact and patterns of coexistence, as they indirectly affect interactions between predators and prey with the potential for further ramifications to other species in the food web. The fitness consequences of parasite-induced trait-mediated effects are rarely considered in traditional parasitological contexts, but demand attention in the context of ecological communities. We can regard these trait effects as a form of cryptic virulence that only becomes apparent when hosts are examined in the context of the other species with which they interact."
6193,The Usual Suspects: Chemokines and Microbial Infection of the Central Nervous System,"For many years, the central nervous system (CNS) was considered an “immunologically privileged site” — a perspective based on limited immune surveillance when compared to peripheral tissue, muted expression of MHC molecules in the context of an apparent lack of professional antigen presenting cells, and the absence of a classical lymphatic drainage system. Together, these observations supported the notion that the CNS was unable to mount and/or support an immune response. However, over time this view evolved and it is now clear that CNS tissue is neither immunologically inert nor privileged, rather, its immune response is exquisitely sensitive to antigenic challenge. Indeed, overwhelming evidence now indicates that upon microbial infection of the CNS there is often a dynamic and orchestrated localized immune response that culminates with infiltration of antigen-specific lymphocytes, usually resulting in control and elimination of the invading pathogen. It is important to note that not all effective immune responses originating in the CNS are completely beneficial to the host; alternatively, there are instances where immune cell infiltration following infection is associated with severe neuropathology resulting in death or chronic neurodegenerative disease."
6194,Critical Care Pandemic Preparedness Primer,"The first half decade of the 21(st) century has brought with it infectious outbreaks such as severe acute respiratory syndrome (SARS) [1], bioterrorism attacks with anthrax [2], and the spread of H5N1 influenza A in birds across Asia and Europe [3, 4] sparking concerns reminiscent of the days of the Black Plague. These events, in the context of an instantaneous global-media world, have placed an unprecedented emphasis on preparing for a human influenza pandemic [5, 6]. Although some argue that the media have exaggerated the threat, the warnings of an impending pandemic are not without foundation given the history of past influenza pandemics [7], incidence of H5N1 infections among humans [8], and the potential impact of a pandemic. Reports of the 1918 pandemic vary, but most suggested that approximately one third of the world’s population was infected with 50 to 100 million deaths [9]. Computer modeling of a moderate pandemic, less severe then in 1918, in the province of Ontario, Canada predicts 73,252 admissions of influenza patients to hospitals over a 6-week period utilizing 72% of the hospital capacity, 171% of intensive care unit (ICU) capacity, and 118% of current ventilator capacity. Pandemic modeling by the Australian and New Zealand Intensive Care Society also showed that critical care resources would be overwhelmed by even a moderate pandemic [10]. This chapter will provide intensivists with a review of the basic scientific and clinical aspects of influenza as well as an introduction to pandemic preparedness."
6195,Interleukin-22: A Bridge Between Epithelial Innate Host Defense and Immune Cells,"Interleukin-22 (IL-22), an IL-10 family cytokine, is produced by various leukocytes. The receptor of IL-22, however, is preferentially detected on peripheral tissue epithelial cells. IL-22 functions as a unique messenger from immune system to tissue epithelial cells and to regulate homeostasis of epithelia. IL-22 is able to directly enhance antimicrobial defense mechanisms in epithelial cells and to facilitate epithelial barrier repair and wound healing process. It, therefore, possesses an irreplaceable role in host defense against certain pathogens that specifically invade epithelial cells. In addition, IL-22 can help to preserve the integrity and homeostasis of various epithelial organs during infection or inflammation. The importance of its tissue-protective function is manifested in many inflammatory situations such as inflammatory bowel diseases (IBD) and hepatitis. On the other hand, as a cytokine, IL-22 is capable of induction of proinflammatory responses, especially in synergy with other cytokines. Consequently, IL-22 contributes to pathogenesis of certain inflammatory diseases for example psoriasis."
6196,Lessening the Impacts from Non-Tectonic (Natural) Hazards and Triggered Events,"Floods are a global problem. They are predictable to some degree by weather forecasting but to a greater degree and with more accuracy when drainage basin monitoring equipment is in place. This includes stream gauges that telemeter the elevation of stream/river surface in a channel and the rate of water flow to a central computing station. The computed data from the telemetered sites plus the input of stream/river channel cross-sections data allow prediction of where flooding will be a problem, when the flooding will reach an area, and to what level out of a channel (magnitude) the flood is estimated to reach. This gives the populations at risk of the flooding early warnings (hours, days) and time to prepare for the floodwaters or to gather important documents and evacuate to safe higher ground."
6197,Strict Isolation,"Strict isolation: suspected highly infectious and transmissible virulent and pathogenic microbes, highly resistant bacterial strains and agents that are not accepted in any form of distribution in the society or in the environment. Examples are completely resistant Mycobacterium tuberculosis, viral haemorrhagic fevers like Ebola and Lassa, pandemic severe influenza and coronavirus like SARS, MERS, etc. In most countries, strict isolation is a rarely used isolation regime but should be a part of the national preparedness plan. For instance, in Norway, strict isolation has not been used for the last 50–60 years, except for one case of imported Ebola infection in 2014. Patients in need of strict isolation should be placed in a separate isolation ward or building. Infection spread by contact, droplet and airborne infection, aerosols, re-aerosols, airborne microbe-carrying particles, skin cells, dust, droplets and droplet nuclei. At the same time, it is always contact transmission (contaminated environment, equipment, textiles and waste). The source of infection is usually a patient but may also be a symptomless carrier or a zoonotic disease."
6198,Community-Acquired Pneumonia,"Community-acquired pneumonia is an infection of the small airways and pulmonary parenchyma that develops in the outpatient setting. Despite the development of new antibiotics and vaccines, pneumonia is still a disease that occurs frequently in children under 5 years of age and is one of the main causes of mortality, especially in developing countries. The biggest challenge in treating pneumonia is to determine the agent, which depends on age, disease severity, immunological condition, geographic location, epidemiological situation, and immunizations. The classic clinical picture presents with fever, coughing, and difficulty in breathing. The physical examination shows tachypnea, reduced breath sounds, and fine crackles. Wheezing may be present in infants with viral pneumonia. The chest X-ray is considered an important tool to confirm the disease diagnosis and may guide specific treatment. Acute-phase reactants have a low sensitivity and specificity to distinguish between virus and bacteria. Microbiological identification does not have a clinical impact for most children with community-acquired pneumonia. Bronchoalveolar lavage may be considered for immunocompromised patients. Antibiotic treatment is empirical based on the best possible etiology, depending on the patient’s age and epidemiological timing. Amoxicillin is the treatment of choice for Streptococcus pneumoniae, and azithromycin is preferred for Mycoplasma pneumoniae."
6199,Novel Blue- and Red-Shifted Internally Quenched Fluorogenic Substrates for Continuous Monitoring of SARS-CoV 3CL(pro),
6200,"12 Intersectionality, Structural Vulnerability, and Access to Sexual and Reproductive Health Services: Filipina Domestic Workers in Hong Kong, Singapore, and Qatar","In this chapter the experiences of Filipina domestic workers in Hong Kong, Singapore, and Qatar are examined in the framework of their structural vulnerability to health problems. The chapter shows how their poor state of Sexual and Reproductive Health (SRH) can be the outcome of a combination of forms of institutional discrimination that are interconnected and should be investigated in respect of: (a) the worth of their ‘identity’ (migrant, female, the work they do); (b) the distinct aspects of discourse on sexuality and normativity which specifically relate to their presence in the destination countries; and (c) ideational and material realities constraining their own agency in finding adequate care. The chapter shows how variations in the potential for access may be explained by the types and degree of their structural vulnerability regarding labour rights, their relationship with employers and migrants’ associations, and their personal SRH awareness–together with what emerges from cooperation between those government officials and civil society organizations who work with migrant domestic workers. Attentiveness to the particular combination of forms of institutional discrimination in a given cultural and institutional context, especially the ways in which the Sexual and Reproductive Health of Filipina domestic workers are linked to the ways in which labour migration are organized, should be helpful for effective SRH advocacy."
6201,Design and Study of Novel Peptide Inhibitors against the SARS-Coronavirus Spike Protein,
6202,Lung Transplantation and Precision Medicine,"Lung transplantation is an accepted therapeutic option for end-stage lung diseases. Its history starts in the 1940s, initially hampered by early deaths due to perioperative problems and acute rejection. Improvement of surgical techniques and the introduction of immunosuppressive drugs resulted in longer survival. Chronic lung allograft dysfunction (CLAD), a new complication appeared and remains the most serious complication today. CLAD, the main reason why survival after lung transplantation is impaired compared to other solid-organ transplantations is characterized by a gradually increasing shortness of breath, reflected in a deterioration of pulmonary function status, respiratory insufficiency and possibly death."
6203,New Human Astroviruses,"The first human astrovirus was discovered in 1975 by Madeley and Cosgrove through visualization of viral particles in stool using electron microscopy. Over the course of the next ∼20 years, an additional seven serotypes of human astroviruses were discovered. In the last decade, new technological advances in microarrays and sequencing strategies enabled more sophisticated methods for detecting viruses in clinical and environmental specimens. These methods led to the discovery of many novel viruses from a variety of virus families. They also brought about a dramatic realization that more astroviruses can be found in humans than previously recognized. In fact, the number of astroviruses associated with humans has nearly doubled within the last few years. Furthermore, the discovery of novel astroviruses in human specimens revealed that there is more diversity amongst them than was assumed based on the high level of similarity between human astroviruses 1 and 8. This chapter will describe the discovery and early characterization of the five novel astroviruses initially identified in human stool samples in 2008 and 2009."
6204,Surface Disinfection,"The patient-care areas in a dental setting become contaminated with bacterial and viral pathogens during patient treatment. Incorporating standard precautions set forth by CDC and OSHA guidelines will reduce the risk of disease transmission. Contaminated environmental surfaces, including clinical contact and housekeeping surfaces, become a reservoir of infectious material with the potential to spread an infection to health-care personnel and patients. Transmission of pathogens can occur by direct or indirect contact of clinical contact surfaces and the hands of health-care personnel. Proper infection control protocol of these surfaces includes cleaning, disinfecting, and the use of barriers to prevent the spread of infectious pathogens. This chapter will provide an overview of the disinfection protocol of environmental surfaces in the dental setting. The topics include the various chemical formulations of hospital disinfectants and their proper use, as well as physical barriers that aim to reduce the degree of contamination in the dental treatment area thus decreasing the probability of cross-infection and disease transmission."
6205,Global Health Security: The WHO Response to Outbreaks Past and Future,"During the first years of the 21(st) century, concern about the threat of infectious diseases has rapidly escalated after three dramatic events: a bioterrorist attack, the emergence and international spread of a severe new disease, and the looming threat of an influenza pandemic."
6206,High-Risk Infections: Influence of Down-Regulation and Up-Regulation of Cough Using Airway Reflexes and Breathing Maneuvers,"Coughing is a watchdog of the lungs. It represents the most important airway defensive reflex and one of the main symptoms of respiratory disease. During coughing and sneezing, particles of mucus can be expelled for a distance of up to 9 m [1]. Various pathogens, if present, may therefore, infect nearby people and animals, contributing to massive dissemination of airborne infections. In addition to using various protective measures, down-regulation of coughing plays a substantial role in preventing dissemination of respiratory infections. For example, about 80 % of passengers on a 3-h airplane trip may be infected by the cough of an individual carrying the flu virus. These newly infected passengers then disseminate the viral infection at their destinations worldwide."
6207,Staff Uniforms and Uniform Policy,"Personnel in contact with patients or equipment and textiles should always use the hospital’s work attire. It includes anyone handling food, medicines, textile, waste or cleaning tools. By caring, treating, examining and transporting patients, there will be direct contact between own work clothes and the patient’s cloths/bedding or skin. The same is true when working with used patient equipment such as bedpans, toilet chairs, beds and other aids and working in patient rooms, toilets and bathrooms or when handling bedding and bandages, giving physiotherapy, etc. The work uniform is particularly exposed to organic matter and microbes, for example, in ambulances, in emergency services, in restless and anxious patients and children, during sampling and examination/treatment, etc. In acute wards, the staff is often exposed to splashes from patients, especially blood but also vomit, sputum, pus, faeces and urine. This chapter is focused on practical measures to prevent transmission of infections via contaminated staff uniforms."
6208,"Was ist denn „Molekularbiologie“, bitteschön?","In diesen Zeiten Molekularbiologie zu betreiben ist aufregend. Es bedeutet „Gentechnik“ und „Klonieren“ und hat etwas Göttliches. Beim einen Teil der Bevölkerung wird man, wenn man verrät, womit man seinen lieben langen Arbeitstag verbringt, grenzenlose Bewunderung hervorrufen, beim anderen grenzenlose Ablehnung — man sollte sich daher genauestens überlegen, mit wem man es gerade zu tun hat, bevor man den Mund aufmacht. Am besten, man erwähnt keiner der Gruppen gegenüber, mit wieviel Problemen und Frust man in Wahrheit täglich kämpft, weil der erste Teil dann desillusioniert wäre und der zweite, vielleicht zurecht, unweigerlich die Frage stellen würde: “Wozu machst du das dann überhaupt?”"
6209,Lung,"Experiments with animals in the 1940 and 1950s demonstrated that lung transplantation was technically possible [33]. In 1963, Dr. James Hardy performed the first human lung transplantation. The recipient survived 18 days, ultimately succumbing to renal failure and malnutrition [58]. From 1963 through 1978, multiple attempts at lung transplantation failed because of rejection and complications at the bronchial anastomosis. In the 1980s, improvements in immunosuppression, especially the introduction of cyclosporin A, and enhanced surgical techniques led to renewed interest in organ transplantation. In 1981, a 45-year-old-woman received the first successful heart–lung transplantation for idiopathic pulmonary arterial hypertension (IPAH) [106]. She survived 5 years after the procedure. Two years later the first successful single lung transplantation for idiopathic pulmonary fibrosis (IPF) [128] was reported, and in 1986 the first double lung transplantation for emphysema [25] was performed."
6210,Fungal Infections,"The incidence of invasive fungal infections has increased dramatically over the past two decades, mostly due to an increase in the number of immunocompromised patients.1–4 Patients who undergo chemotherapy for a variety of diseases, patients with organ transplants, and patients with the acquired immune deficiency syndrome have contributed most to the increase in fungal infections.5 The actual incidence of invasive fungal infections in transplant patients ranges from 15% to 25% in bone marrow transplant recipients to 5% to 42% in solid organ transplant recipients.6,7 The most frequently encountered are Aspergillus species, followed by Cryptococcus and Candida species. Fungal infections are also associated with a higher mortality than either bacterial or viral infections in these patient populations. This is because of the limited number of available therapies, dose-limiting toxicities of the antifungal drugs, fewer symptoms due to lack of inflammatory response, and the lack of sensitive tests to aid in the diagnosis of invasive fungal infections.1 A study of patients with fungal infections admitted to a university-affiliated hospital indicated that community-acquired infections are becoming a serious problem; 67% of the 140 patients had community-acquired fungal pneumonia.8"
6211,Infectious Diseases,"Pulmonary infections are caused by a wide range of pathogenic microorganisms, including bacteria, viruses, fungi, and parasites. The most common lung infections in immunocompetent hosts are caused by pyogenic bacteria (e.g., Streptococcus pneumoniae), common respiratory viruses, and mycoplasma. These infections are usually diagnosed by clinical and microbiologic studies, including cultures and serology tests. Lung biopsy is rarely used in these diagnoses. Patients with life-threatening pneumonia, especially those who are immunocompromised, are more likely to undergo lung biopsy to rule out unusual infections not easily diagnosed using conventional microbiologic methods and for which treatment strategies may be different. Pathogens more likely to be diagnosed using lung biopsy for which there are characteristic pathologic changes are highlighted in this chapter and listed in Table 4.1."
6212,An Infectious Disease Outbreak Simulator Based on the Cellular Automata Paradigm,"In this paper, we propose the use of Cellular Automata paradigm to simulate an infectious disease outbreak. The simulator facilitates the study of dynamics of epidemics of different infectious diseases, and has been applied to study the effects of spread vaccination and ring vaccination strategies. Fundamentally the simulator loosely simulates SIR (Susceptible Infected Removed) and SEIR (Susceptible Exposed Infected Removed). The Geo-spatial model with global interaction and our approach of global stochastic cellular automata are also discussed. The global stochastic cellular automata takes into account the demography, culture of a region. The simulator can be used to study the dynamics of disease epidemics over large geographic regions. We analyze the effects of distances and interaction on the spread of various diseases."
6213,Emerging Infectious Diseases,Emerging infectious diseases (EIDs) including novel avian influenza viruses or even recently reported Zika virus (ZIKV) have drawn great attentions globally. The application of modern diagnostic technologies is expected to increase. Imaging plays a key role on diagnosis and prognosis assessment in patients with EID.
6214,Working Towards A Healthier Brunei,"Brunei Darussalam is a small equatorial country of 5,765 square kilometers that lies on the north-west coast of the island of Borneo. An affluent nation, its economy is based mostly on oil and gas. Brunei’s GDP per capita of US$50,117 places the country fifth highest on this index internationally (International Monetary Fund, 2010). The population of Brunei is about 398,000, with Malays, who are Muslims, forming the majority (just under 67% of the country’s people) (Prime Minister’s Office, 2008). The annual population growth rate is just over 2.0%; life expectancy is 75 years (Central Intelligence Agency, 2010)."
6215,Post-Newborn: A New Concept of Period in Early Life,"Post-newborn infants refer to infants from >28 days to <100 days after birth. During this period, infants are still completely dependent on breast milk or/and formula milk for feeding. Up to now, the concept of post-newborn has not been mentioned in classic textbooks. With the development of perinatal medicine, mortality rate of diseases in neonates such as premature infants, asphyxia, infectious diseases have decreased significantly, and consequently, issues of the quality of life for these survivors have aroused widespread concerns. The post-newborn infants have some important characteristics differing from both newborn infants and infants after the period: (1) different fatal diseases and mortality rate; (2) the diseases inherited from newborn period requiring early and prompt treatments; (3) some peculiar diseases during this period requiring much attention; (4) either similar or different immune function; (5) rapid growth and uneven development of organ systems. Establishment of the new concept of post-newborn will further reveal the nature of life, reduce the mortality rate of infants, and improve the quality of life."
6216,Pneumonia,"Most patients suffering from community acquired pneumonia do not appear at a radiology department since diagnosis is made on a clinical basis. In severe or unclear situations, a chest X-ray is done and analysis is frequently done by interns. Radiologists frequently see those patients that suffer from recurrent, nosocomial pneumonia, or an additional predisposing disease. The appropriate investigational technique, frequently targeted differential diagnosis, and the special needs of these patients need to be understood by radiologists. Early detection of a focus of infection is the major goal in immunocompromised patients. As pneumonia is the most common focus, chest imaging is to be done at the beginning. The sensitivity of chest X-rays, especially in the supine position, is known to be low. Therefore the very sensitive high-resolution CT (HRCT) became the gold standard in neutropenic hosts and is widely replaced by thin-section multi-detector-row-CT (MDCT). Underlying diseases such as pulmonary embolism or bronchial carcinoma might also be depicted. Furthermore, the costs of CT are low in comparison to antibiotics. The infiltrate needs to be localised, so that a physician can utilise this information as a guidance for invasive procedures for further microbiological work-up. The radiological characterisation of infiltrates gives a first and rapid hint to differentiate between different sorts of infectious (typical bacterial, atypical bacterial, fungal) and non-infectious aetiologies. Follow-up investigations need careful interpretation according to disease and concomitant treatment. Temporary exclusion of infectious involvement of the lung with high accuracy is, besides of pneumonia management, a hot topic for clinicians."
6217,Precision Medicine in Critical Illness: Sepsis and Acute Respiratory Distress Syndrome,"Sepsis and the acute respiratory distress syndrome (ARDS) each cause substantial morbidity and mortality. In contrast to other lung diseases, the entire course of disease in these syndromes is measured in days to weeks rather than months to years, which raises unique challenges in achieving precision medicine. We review advances in sepsis and ARDS resulting from omics studies, including those involving genome-wide association, gene expression, targeted proteomics, and metabolomics approaches. We focus on promising evidence of biological subtypes in both sepsis and ARDS that consistently display high risk for death. In sepsis, a gene expression signature with dysregulated adaptive immune signaling has evidence for a differential response to systemic steroid therapy, whereas in ARDS, a hyperinflammatory pattern identified in plasma using targeted proteomics responded more favorably to randomized interventions including high positive end-expiratory pressure, volume conservative fluid therapy, and simvastatin therapy. These early examples suggest heterogeneous biology that may be challenging to detect by clinical factors alone and speak to the promise of a precision approach that targets the right treatment at the right time to the right patient."
6218,Viral Infection and Multiple Sclerosis,
6219,Gastrointestinal Disorders,A.Classification 1.Upper gastrointestinal (GI) bleeding is above the ligament of Treitz.2.Lower GI bleeding is below the ligament of Treitz.
6220,History of the Thermometer,"The temperature of the human body has been used as a diagnostic sign since the earliest days of clinical medicine. The earliest thermal instruments were developed during the sixteenth and seventeenth centuries. In 1665, it was suggested that the melting point of ice and the boiling point of water should be the standard. The most common scales today are the Fahrenheit, Centigrade, and the Kelvin scales. Since the earliest days of medicine, physicians have recognized that the human body can exhibit an abnormal rise in temperature, usually defined as fever, as an obvious symptom of illnesses. In 1868, Wunderlich established that the temperature in a healthy person is constant and that variation of temperature occurs in disease. The Allbutt thermometer was the first practical device to become commercially available. The technology has then improved to provide highly accurate devices, for example, thermal imaging; its use is still growing in medicine."
6221,Epidemiology and Etiology of Mesothelioma,"Unequivocally the history of mesothelioma parallels that of asbestos exposure. The estimation that the asbestos cancer epidemic will cause 10 million deaths past and present renders the need to reach urgently a global ban on asbestos an issue of highest priority, so that the asbestos cancer epidemic will not become more devastating and will not continue indefinitely."
6222,Extracorporeal Membrane Oxygenation,"Extracorporeal Membrane Oxygenation (ECMO) is a life-saving technology that uses partial heart and lung bypass for extended periods. It is not a therapeutic modality, but rather a supportive tool that provides suf-fi cient gas exchange and perfusion for patients with acute, reversible cardiac or respiratory failure. This affords the patient's cardiopulmonary system time to rest, sparing them from the deleterious effects of traumatic mechanical ventilation and perfusion impairment. The Extracorporeal Life Support Organization (ELSO) was formed in 1989 by a collaboration of physicians, nurses, perfusionists, and scientists with an interest in ECMO. The group provides an international registry that collects data from almost all ECMO centers in the United States and throughout the world. At the end of 2005, ELSO registered nearly 30,000 neonatal and pediatric patients treated with ECMO for a variety of cardiopulmonary disorders with an overall survival rate of 66%."
6223,Predicting Palmitoylation Sites Using a Regularised Bio-basis Function Neural Network,"Palmitoylation is one of the most important post-translational modifications involving molecular signalling activities. Two simple methods have been developed very recently for predicting palmitoylation sites, but the sensitivity (the prediction accuracy of palmitoylation sites) of both methods is low (< 65%). A regularised bio-basis function neural network is implemented in this paper aiming to improve the sensitivity. A set of protein sequences with experimentally determined palmitoylation sites are downloaded from NCBI for the study. The protein-oriented cross-validation strategy is used for proper model construction. The experiments show that the regularised bio-basis function neural network significantly outperforms the two existing methods as well as the support vector machine and the radial basis function neural network. Specifically the sensitivity has been significantly improved with a slightly improved specificity (the prediction accuracy of non-palmitoylation sites)."
6224,Surveillance for Hepatitis C,"Hepatitis C is a global public health problem. Globally, an estimated 170 million persons (3 % of the world’s population) have been infected with the hepatitis C virus, and an estimated 350,000 persons die annually from complications of chronic hepatitis C. Furthermore, an increasing trend in hepatitis C mortality in the USA was observed over the last decade; in 2007, mortality associated with hepatitis C surpassed mortality associated with HIV. As the hepatitis C epidemic continues, it is increasingly important to accurately measure hepatitis C-related morbidity and mortality in order to inform public health programs and policies and prioritize and evaluate prevention efforts. This chapter provides an overview of hepatitis C surveillance and methods used in the USA with some examples from other countries."
6225,Epidemic Alert & Response Framework and Technology Based on Spreading Dynamics Simulation,"There have been many research works on epidemic spreading by mathematical or simulation methods. However, to make it practical as a decision support tool for policy maker, it should be combined with business operation of epidemic control. Thus, an alert and response framework covering outbreak detection, policy analysis and policy execution is proposed in this paper. Key technologies for such a framework at modeling, analysis and data collection aspects are discussed. Sensitivity analysis is proposed for model verification and confidence analysis. Critical point identification is another important topic for control policy making by network topology analysis. The importance and feasibility of these technologies are illustrated by the experiment on Beijing SARS (Severe Acute Respiratory Syndrome) data in 2003."
6226,Teilgebiete der Biomathematik und ihre Bezüge zur Menschheitsgeschichte,"Die Demographie befasst sich ganz allgemein mit der menschlichen Bevölkerung, ihrer Struktur und ihren Bewegungen. Kenngrößen, die in der Demographie häufig verwendet werden, sind z. B. die Geburten- und die Sterberate. Dabei ist natürlich darauf zu achten, dass diese Größen in unterschiedlichen Altersgruppen auch unterschiedlicheWerte annehmen. Ebenso wie die Fertilität, also die mittlere Anzahl an Nachkommen pro Zeiteinheit und Frau. Und nicht nur vom Alter, auch von der geographischen Lage hängen diese Größen und damit auch die durchschnittliche Lebenserwartung bzw. die Gesamtzahl an Nachkommen pro Jahrgang ab. So genannte Alterspyramiden, also Darstellungen der Bevölkerungsstruktur nach Altersklassen, sehen demnach in unterschiedlichen Teilen der Welt auch qualitativ sehr verschieden aus."
6227,Mathematical Models of Infectious Diseases in Livestock: Concepts and Application to the Spread of Highly Pathogenic Avian Influenza Virus Strain Type H5N1,"Animal health governance faces new challenges as the ecology of infectious livestock diseases is changing (Tomley and Shirley 2009). Environmental and climate changes, intensification of livestock production, modification in land-use and agricultural practices, globalization of human travel, the development of the trade of livestock and livestock products have created conditions for an increase in the emergence and re-emergence of infectious agents in the last decades (Weiss and McMichael 2004; Randolph and Rogers 2010; Jones et al. 2008; Gibbs 2005). The frequency of emergence of new highly pathogenic avian influenza viruses (HPAIV) has increased over the past 20 years, as well as the economic impact of associated outbreaks (Alexander and Brown 2009). Bluetongue virus serotypes have continuously increased their spatial distribution, specifically in a northern direction. Treatment-resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), have appeared. Numerous infectious diseases such as foot-and-mouth disease (FMD) are endemic in many parts of the world, and may have a high impact on animal health and farmer livelihood. Moreover, they constrain the ability of affected countries to trade livestock and livestock-derived products. Production systems in developed countries are also vulnerable. For example, outbreaks of FMD in United Kingdom in 2001, classical swine fever in Holland in 1997/1998, and highly pathogenic avian influenza H7N7 in Holland in 2003 resulted in the loss of millions of animals, mainly as a result of culling of affected and exposed animals. Finally, infectious livestock diseases are a threat for public health: about 75% of human infectious agents that emerged in the last 25 years had an animal origin (King et al. 2006)."
6228,Alignment-Free Z-Curve Genomic Cepstral Coefficients and Machine Learning for Classification of Viruses,"Accurate detection of pathogenic viruses has become highly imperative. This is because viral diseases constitute a huge threat to human health and wellbeing on a global scale. However, both traditional and recent techniques for viral detection suffer from various setbacks. In codicil, some of the existing alignment-free methods are also limited with respect to viral detection accuracy. In this paper, we present the development of an alignment-free, digital signal processing based method for pathogenic viral detection named Z-Curve Genomic Cesptral Coefficients (ZCGCC). To evaluate the method, ZCGCC were computed from twenty six pathogenic viral strains extracted from the ViPR corpus. Naïve Bayesian classifier, which is a popular machine learning method was experimentally trained and validated using the extracted ZCGCC and other alignment-free methods in the literature. Comparative results show that the proposed ZCGCC gives good accuracy (93.0385%) and improved performance to existing alignment-free methods."
6229,14 Intravasale infecties en sepsis,Infecties in het hart en de bloedbaan worden intravasale of endovasculaire infecties genoemd. De circulatie van bloed door het hart is essentieel voor de aanvoer van zuurstof en voedingstoffen naar weefsel en organen en voor de afvoer van afvalstoffen.
6230,The Migrant Monsters of Multiculturalism in Andrew Currie’s Fido,"On June 9, 2008, the Canadian House of Commons passed an amendment to the Immigrant and Refugee Protection Act. Titled Bill C-50, the amendment shifts discretionary powers from Parliament to current and future immigration and citizenship ministers. Touted by the Conservative Party as an expedient remedy to the 900,000-applicant backlog and an estimated labour shortage of 300,000, Bill C- 50 raised immediate concerns within immigrant and activist communities (CBC News, 2008). Critics contend that the bill caters to the interests of Canadian employers and business lobbyists in its provision of “disposable” and inexpensive labour, while “family” and “refugee” applications may be deferred indefinitely and without recourse. In some ways, the changes under Bill C-50 are redolent of the Live-in Caregiver Program in Canada as well as the Bracero Program (1942-1964), Guest Worker legislation and H-2A initiatives in the US, all of which offered temporary visas to migrant workers but resembled what Gilbert Gonzalez calls “an imperialist schema of colonial labour” (2006, p. 2). Whereas government policies in North America continue to reduce migrants to economic figures, other conservative discourses depict migrants as self-identical foreigners who flood the economy with cheap labour, deplete welfare resources reserved for “native”citizens and present a possible threat of terror in the “post-9/11” era. If “the socalled invasion of immigrants is the exaggerated rhetoric” of political pundits, however, “the increase in global migration within and from Third World countries is real” (Bakan and Stasiulis, 1997b, p. 30)."
6231,Surfattante polmonare,"La respirazione normale include circa 12 atti respiratori al minuto, ognuno dei quali di circa 0,500 l. Pertanto il volume di aria che transita nei polmoni al minuto (ventilazione minuto) è di circa: 12 × 0,500 = 6 l min. A sua volta, il volume inspirato è uguale all’incirca a quello espirato (volume corrente). Poiché, in tal caso, il flusso inspiratorio è uguale a − 0,5 l sec(−1) e quello espiratorio a + 0.5 l sec(−1), il flusso definitivo di un ciclo completo è pari a zero."
6232,Acronimi ed abbreviazioni,"“The patient went from the ER to the OR and then to the ICU”. Indubbiamente il lessico dei medici è ricco di abbreviazioni, tanto che gli operatori della sanità di lingua italiana e inglese adoperano perlomeno dieci abbreviazioni per minuto (questa è una statistica fatta in casa, per favore non citatela). Questa alta prevalenza ci ha spinto a considerare le abbreviazioni in medicina come una dilagante epidemia."
6233,Besmettingsbronnen,Aan de GGD worden twee gevallen van hepatitis A (besmettelijke geelzucht) op een kinderdagverblijf gemeld. Al een maand eerder was via melding door het laboratorium een geval van hepatitis A bekend geworden in dezelfde woonwijk. In de dagen daarna kwamen nog meer meldingen binnen. Uiteindelijk raken binnen vier maanden 41 personen (23 kinderen en 18 adolescenten en volwassenen) besmet met het hepatitis A-virus. Het primaire geval betrof een driejarige peuter van Marokkaanse ouders die vóór zijn ziekte ongevaccineerd op vakantie naar Marokko was geweest en daar waarschijnlijk besmet was geraakt. Via het gezin werd hepatitis A op een kinderdagverblijf en een basisschool geïntroduceerd. Het voortduren van de epidemie wordt gestopt door gezinnen en kinderen op het kinderdagverblijf en de basisschool uit voorzorg te immuniseren tegen hepatitis A. Daarmee werd het optreden van nieuwe gevallen en het verder verspreiden van de infectieziekte voorkomen.
6234,Bakterielle Infektionen,"Vor der Einführung von Antibiotika führten schwere bakterielle Infektionen wie Sepsis, Diphtherie und Meningitis fast zwangsläufig zum Tod. Heute meist folgenlose Erkrankungen wie Typhus, Scharlach oder bakterielle Gelenksinfektionen führten zu Tod oder schweren Behinderungen. Gefahren gehen heute v.a. durch Resistenzentwicklungen gegen Antibiotika (z.B. bei der Tuberkulose) und durch mangelnde Impffreudigkeit (z. B. bei Diphtherie) aus. So sind bakterielle Infektionen weiterhin nicht zu verharmlosen."
6235,Profiling and Searching for RNA Pseudoknot Structures in Genomes,We developed a new method that can profile and efficiently search for pseudoknot structures in noncoding RNA genes. It profiles interleaving stems in pseudoknot structures with independent Covariance Model (CM) components. The statistical alignment score for searching is obtained by combining the alignment scores from all CM components. Our experiments show that the model can achieve excellent accuracy on both random and biological data. The efficiency achieved by the method makes it possible to search for structures that contain pseudoknot in genomes of a variety of organisms.
6236,Longziekten,"In het eerste deel van dit hoofdstuk worden de ziektebeelden op het gebied van de longziekten op een beknopte, heldere wijze behandeld door een vakexpert, huisarts en apotheker; de beste combinatie om de klinische relevantie voor de huisartsenpraktijk te waarborgen. De volgorde van de paragrafen is alfabetisch. In het tweede deel volgt een bespreking van de belangrijkste verschijnselen/ klachten in de pulmonologie, die bij verschillende ziekten kunnen horen, zoals hemoptoë, hoesten, hyperventilatie, piepen, snurken."
6237,Viren mit einzelsträngigem RNA-Genom in Plusstrangorientierung,"Heute sind acht Virusfamilien bekannt, deren Vertreter eine einzelsträngige RNA in Plusstrangorientierung besitzen: Die Picornaviridae, Caliciviridae, Astroviridae und Hepeviren verfügen über Capside, die keine Hüllmembran aufweisen, wohingegen die Flaviviridae, Togaviridae, Arteriviridae und Coronaviridae durch membranumhüllte Partikel gekennzeichnet sind. Allen gemeinsam ist, dass sie ihre Genome als mRNA verwenden und davon ein oder mehrere Polyproteine synthetisieren, die im weiteren Verlauf durch virale oder auch zelluläre Proteasen in Einzelkomponenten gespalten werden. Die Viren verfügen über eine RNA-abhängige RNA-Polymerase, welche die Plusstrang-RNA sowie die als Zwischenprodukte der Replikation auftretenden Negativstränge übersetzt; dabei gehen die neuen genomischen RNA-Moleküle aus dem zweiten Transkriptionsschritt hervor. Die Einteilung in die unterschiedlichen Familien richtet sich nach Zahl, Größe, Lage und Orientierung der Virusgene auf der RNA, nach der Anzahl der unterschiedlichen Polyproteine, die während der Infektion synthetisiert werden, und nach dem Vorhandensein einer Hüllmembran als Teil der Virionen."
6238,Systemic consequences of intestinal inflammation,
6239,Article 13 Entry and Clearance Regulations,"The laws and regulations of a contracting State as to the admission to or departure from its territory of passengers, crew or cargo of aircraft, such as regulations relating to entry, clearance, immigration, passports, customs, and quarantine shall be complied with by or on behalf of such passengers, crew or cargo upon entrance into or departure from, or while within the territory of that State."
6240,Pneumonia in the Pregnant Patient,"Community acquired pneumonia is a common illness, and pneumonia and influenza serve as the seventh leading cause of death in the United States. In the pregnant patient, pneumonia is the most common cause of fatal non-obstetric infection (1–3). Pneumonia can have adverse consequences for both the mother and her fetus, with certain infections (particularly viral and fungal) assuming greater virulence and mortality than in non-pregnant women of similar age (2, 3). Pneumonia is a relatively common cause of respiratory failure in pregnant patients, but in contrast to older studies, newer data suggest that not all pneumonias are more common or more serious in pregnant women than in other populations. However, because pneumonia can impact both the mother and fetus, it may lead to an increased likelihood of complicated preterm delivery, compared to pregnancies in which infection is absent. The pathogens responsible for community-acquired pneumonia (CAP) are similar in pregnant and non-pregnant patients, with Streptococcus pneumoniae, Hemophilus influenzae, Mycoplasma pneumoniae, Legionella spp., Chlamydophila pneumoniae, and influenza A accounting for the majority of cases (2–4). However, reduction in cell-mediated immunity associated with pregnancy (especially during the third trimester) places women at an increased risk of more severe forms of pneumonia and disseminated diseases from pathogens normally contained by this type of immune response, including herpes virus, influenza, varicella, and coccidioidomycosis (3, 5–7)."
6241,Viral Infections in Hematopoietic Stem Cell Transplant Recipients,"Viral infections are important as causes of morbidity and mortality after allogeneic stem cell transplantation (SCT). Severe viral infections are more common after unrelated and mismatched donor SCT and in particular after haploidentical SCT. B-cell function and specific antibodies are the main defense mechanisms against infection with exogenous viruses, thus reducing the risk for reinfection in already seropositive individuals. On the other hand, T-cell function in particular cytotoxic T-cell function is the main mechanism for preventing severe viral disease and also for the control of viruses such as herpesviruses that can cause latency and thus reactivate in an immunocompromised individual. The immune defects in SCT-patients are frequently complex with defects in cytotoxic T-lymphocyte, helper T-lymphocyte, NK-cell, and B-lymphocyte functions. T-cell dysfunction is usually most important early after SCT while deficient B-cell reconstitution can remain for many years after SCT. Furthermore, since loss of specific antibodies occurs frequently over time after allogeneic SCT, this will also increase the risk for reinfections with previously encountered viruses such as measles or varicella-zoster virus (VZV) and allow reactivation of viruses controlled by antibodies such as hepatitis B virus (HBV) [1, 2]."
6242,Plant Edible Vaccines: A Revolution in Vaccination,"Plants have been used as a source for many pharmaceutical since long. However, utilization of plant systems for production of edible vaccines has been a comparatively recent phenomenon. There are several potential advantages of plant derived vaccines over other conventional systems of vaccine production such as mammalian or avian cell culture. The cost of vaccines is one factor preventing further use of vaccination, leaving hundreds of thousands of children susceptible to preventable diseases. Especially for developing world this novel technique proved to be a boon for its low cost of production, convenient administration, easy storage and negligible chances of infection whereas the conventional system of vaccine production limits the applicability of vaccines in many parts of the world. These vaccines are prepared by introducing selected desired genes into plants and inducing these genetically modified plants to manufacture the encoded proteins. Transgenic plants may provide an ideal expression system, in which transgenic plant material can be fed directly as oral dose of recombinant vaccines. Expression of vaccines in plant tissue eliminates the risk of contamination with animal pathogen, provides a heat stable environment and enables oral delivery thus eliminating infection related hazards. Identification of transgenic material, containment of the transgenes and control of recombinant protein may be potential problems for large scale production of vaccines in plants. Factors like scaling up production as well as distribution and handling of transgenic plant material must comprise the future consideration in this field."
6243,Mechanisms of Hypersensitivity,"Allergic reactions to drugs are not always the result of the drug’s protein-binding capacity, biotransformation, or degradation. Mediator release may occur via cross-linking of cell-bound IgE by di-(multi-) valent free drug. Physiological and pharmacological effects of histamine are mediated through four receptors, H(1), H(2), H(3), and H(4.) The H(3) receptor has a regulatory role in the release of neurotransmitters such as serotonin and dopamine; the H(4) receptor exerts a chemotactic effect on several cell types associated with allergy and asthma. Cysteinyl leukotrienes and PAF are powerful mediators of anaphylaxis, asthma, and shock. Sphingosine-1-phosphate, elevated in the lungs of asthmatics, regulates pulmonary epithelium permeability and contributes to the pathogenesis of anaphylaxis. Urticaria is a heterogeneous disease with many subtypes. Both ACE inhibitors and angiotensin II receptor blockers may cause angioedema. Abacavir changes the shape of the HLA antigen-binding cleft producing an alteration in the repertoire of self-peptides that bind HLA-B*57:01 and a T cell response to self-proteins. Drug-induced delayed-type cutaneous hypersensitivity reactions are mediated by CD4+ and CD8+ CD3+ T cells in the dermis and epidermis. Granulysin appears to be a key molecule for keratinocyte killing in TEN/SJS. Drugs provide good examples of types II (immune hemolytic anemia, drug-induced thrombocytopenia) and III (serum sickness-like) hypersensitivities."
6244,A Comparative Analysis of Models for West Nile Virus,"This chapter describes the steps needed to formulate, analyze and apply epidemiological models to vector-borne diseases. Our models focus on West Nile (WN) virus, an emerging infectious disease in North America, first identified in Africa. We begin by introducing a minimalist model for WN dynamics to illustrate the processes of model formulation, analysis, and application. We then revisit the question of model formulation to examine how two major biological assumptions affect the model structure and therefore its predictions. Next, we briefly compare these different model structures in an introductory exercise of model parameterization, validation, and comparison. Finally, we address model applications in more detail with two examples of how the model output can usefully be connected to public health applications."
6245,"Modernities, Sciences, and Democracy","The “modern” in “modern science” is a relatively uninterrogated and untheorized concept within the sciences and in the philosophy, sociology, and history of science. This is so today at a time when other aspects of Western sciences have been fruitfully explored in critical and illuminating ways (see Christensen and Hansen, Chap. 13; and Skovsmose, Chap. 15). In particular, the exceptionalism and triumphalism characteristic of Western attitudes toward our sciences have been explicitly criticized and purportedly abandoned by many of the scholars working in science studies fields. By exceptionalism is meant the belief that Western sciences alone among all human knowledge systems are capable of grasping reality in its own terms—that these alone have the resources to escape the human tendency to project onto nature cultural assumptions, fears, and desires. By triumphalism is meant the assumption that the history of science consists of a history of achievements — that this history has no significant downsides. According to this view, Hiroshima, environmental destruction, the alienation of labour, escalating global militarism, the increasing gap between the “haves” and the ”have nots,” gender, race, and class inequalities — these and other undesirable social situations are all entirely consequences of social and political projects, to which the history of Western sciences makes no contribution. Such conventional Euro centric assumptions can no longer gather the support either in the West or elsewhere that they could once claim In recent decades a huge amount of literature on modernity has emerged from the social sciences and humanities. Stimulated by the massive shifts in local and global social formations during the last half of the Twentieth Century, and by the post-modern response to such changes, social theorists, literary and other cultural critics, and, especially, historians have debated the uneven and complex origins, nature, and desirable futures of modernity, modernization, and modernism. Such controversies about modernity are first and foremost about a culture's relation to its past and its possible futures. They arise as ways of asking what went wrong, and what needs to be corrected. The last half a century has witnessed the global decline and fall of belief in the unquestionably legitimate authority of the white, bourgeois, male. Contributing to the epistemological, economic, political, and cultural rubble left by his demise — or, at least, deflation — have been compelling and influential counter-histories of social relations between the races, classes, genders, and within colonial and imperial eras"
6246,Development of Highly Active Titanium Oxide Photocatalysts Anchored on Silica Sheets and their Applications for Air Purification Systems,"The purpose of this study is to develop highly active titanium oxide photocatalysts that can be anchored onto a substrate. We have, thus, prepared a titanium oxide photocatalyst using a wet or dry process and the results of this study have led to the successful development of highly active rectangular column-structured titanium oxide photocatalysts, which can be anchored onto silica sheets. These highly active photocatalysts were then applied to develop an effective air purification system."
6247,Pregnancy-Associated Kidney Injury,"A 23-year-old G1P0000 without prior past medical history is 31 weeks pregnant with prenatal care presents with complaints of worsening leg and face swelling for the past 2 days now seeks care because of headache, diarrhea, nausea, and vomiting. On exam she is found to have a blood pressure of 120/86, edema, and brisk deep tendon reflexes. Laboratory testing revealed hemoglobin 11.3 g/dl, platelet count 141,000/μl white blood count 18,000/μl, creatinine 1.1 mg/dl, aspartate aminotransferases (AST) 65 U/l, lactate dehydrogenase (LDH) 400 U/l, total bilirubin 1.1 mg/dl, prothrombin time (PT) 14.7 s, ammonia of 90 mcg/dl, blood glucose 139 mg/dl, calcium 7.3 mg/dl, and uric acid of 6.0 mg/dl. The urinalysis demonstrated WBC’s 3–5/hpf, RBC’s 3–5/hpf—non-dysmorphic, renal tubular epithelial cells were seen and a urine protein to creatinine ratio of 2. One day after hospitalization the patient’s blood pressure was 145/87 with a similar blood pressure 6 h later."
6248,Pneumonien,"Pneumonien sind wichtige Verursacher kindlicher Morbidität und in den Entwicklungsländern eine führende Todesursache. Die ätiologische Diagnostik bakterieller Infektionen ist unbefriedigend, die therapeutischen Möglichkeiten bei viralen Pneumonien sehr beschränkt. Klare Möglichkeiten zur Differenzierung der einzelnen Pneumonien fehlen. Für die Behandlung ambulant erworbener Pneumonien orientiert man sich am besten an den zu erwartenden Erregern, die ein gewisse Altersabhängigkeit aufweisen. Amoxicillin und Makrolide stellen die besten, weil zielorientiertesten, Antibiotika für ambulante Pneumonien dar. Angesichts noch relativ günstiger Empfindlichkeitsverhältnisse in mitteleuropäischen Ländern ist nicht primär mit Therapieversagern zu rechnen. Besondere Probleme ergeben sich bei neonatalen Pneumonien sowie bei Pneumonien als Folge von Immunsuppression. Allergisch bedingte Pneumonien müssen gesondert untersucht werden."
6249,Alphabetisches Verzeichnis der Professoren,Alphabetisches Verzeichnis der Professoren
6250,Ventilator-Associated Pneumonia,"Ventilator-associated pneumonia occurs in patients who have been intubated for at least 2–3 days with significant exposure to hospital-acquired organisms. Treatment should be initiated rapidly and cover Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, and methicillin-resistant Staphylococcus aureus(MRSA). Within 72 h or with the availability of culture results, antibiotics should be narrowed. Active research is on-going to identify patients at risk for ventilator-associated complications and to minimize the likelihood of infection in these patients."
6251,"Bioterrorismus, infektiologische Aspekte","Infektionskrankheiten sind ständige Begleiter und gefürchtete Geißeln der Menschheit. Pest und Pocken versetzen als todbringende Seuchen die Menschen nicht erst seit dem Altertum in Schrecken (lat.: terror). Archaische Ängste und eine hohe Medienaufmerksamkeit sorgen mitunter bis in die Gegenwart noch für Panik und irrationale Reaktionen, wie die Massenflucht während eines ungewöhnlichen Lungenpestausbruchs in Surat im Herbst 1994 und daraus resultierende drastische Flug- und Handelsbeschränkungen mit Indien beweisen."
6252,Hong Kong Paradox: Appearance and Disappearance in Western Cinema,"This chapter investigates what I call “the paradox of appearance and disappearance of Hong Kong” in Western cinema over the past two decades. The city has in recent years appeared in a number of big-budget Hollywood productions (e.g. The Dark Knight, Transformers, Doctor Strange, Pacific Rim), attesting to its continuing visual and “exotic” appeal to Western audiences, reminding one of the role pre-handover Hong Kong played in the conception and design of Blade Runner. However, the real Hong Kong is often displaced in these films and supplanted by a recycled and stereotyped impression of the city’s skyline and urban landscape. The chapter looks at instances of Hong Kong being otherworlded and the implications for the Hong Kong identity in the global cinematic gaze."
6253,Pharmacogenomics of Viral Diseases,"Viral diseases are leading cause of deaths worldwide as WHO report suggests that hepatitis A virus (HAV) infects more than 80 % of the population of many developing countries. Viral hepatitis B (HBV) affects an estimated 360 million people, whereas hepatitis C affects 123 million people worldwide, and last but not least, at current, India has an HIV/AIDS population of approximately 2.4 million people and more than 30 million in whole world and now it has become a reason for 1.8 million death globally; thus, millions of people still struggle for their lives. The progress in medical science has made it possible in overcoming the various fatal diseases such as small pox, chicken pox, dengue, etc., but human immunodeficiency viruses, influenza, and hepatitis virus have renewed challenge surprisingly. The obstacles and challenges in therapy include existence of antibiotic resistance strains of common organisms due to overuse of antibiotics, lack of vaccines, adverse drug reaction, and last but not least the susceptibility concerns. Emergence of pharmacogenomics and pharmacogenetics has shown some promises to take challenges. The discovery of human genome project has opened new vistas to understand the behaviors of genetic makeup in development and progression of diseases and treatment in various viral diseases. Current and previous decade have been engaged in making repositories of polymorphisms (SNPs) of various genes including drug-metabolizing enzymes, receptors, inflammatory cells related with immunity, and antigen-presenting cells, along with the prediction of risks. The genetic makeup alone is most likely an adequate way to handle the therapeutic decision-making process for previous regimen failure. With the introduction of new antiviral therapeutic agents, a significant improvement in progression and overall survival has been achieved, but these drugs have shown several adverse responses in some individuals, so the success is not up to the expectations. Research and acquisition of new knowledge of pharmacogenomics may help in overcoming the prevailing burden of viral diseases. So it will definitely help in selecting the most effective therapeutic agents, effective doses, and drug response for the individuals. Thus, it will be able to transform the laboratory research into the clinical bench side and will also help in understanding the pathogenesis of viral diseases with drug action, so the patients will be managed more properly and finally become able to fulfill the promise of the future."
6254,"Pleura: Anatomy, Physiology, and Disorders","Disorders of the pleura and pleural space reflect some of the oldest diseases encountered in surgical history. Hippocrates described the symptoms of empyema 2400 years ago: “Empyema may be recognized by the following symptoms: In the first place the fever is constant, less during the day and greater at night, and copious sweats supervene. There is a desire to cough and the patient expectorates nothing worth mentioning.” He also described an open drainage procedure: “When the fifteenth day after rupture has appeared, prepare a warm bath, set him upon a stool, which is not wobbly, someone should hold his hands, then shake him by the shoulders and listen to see on which side a noise is heard. And right at this place, preferably on the left, make an incision, then it produces death more rarely.”1,2 Beyond providing less-wobbly stools, few advances were made for more than 2000 years that allowed surgeons to routinely enter the pleural cavity, the fear being a potentially fatal pneumothorax. With the advent of positive pressure ventilation in the early 1900s, pneumothorax was no longer a prohibitive risk, and the era of surgical intervention in the pleural cavity had begun.3"
6255,Human Immunodeficiency Virus Infection: Spectrum of Rheumatic Manifestations,"Emerging and reemerging viral infections have been a characteristic feature of the past several decades, with HIV infection being the most important example of an emergent viral infection. To date, the status of a considerable proportion of HIV/AIDS patients has changed from a near-fatal disorder secondary to opportunistic infections to a chronic disease in which a variety of co-morbid conditions have become prevalent and relevant. Arthralgia and myalgias are the most common symptoms. The rate of spondyloarthritis varies according to the geographic area, genetic and mode of transmission. Most RA and SLE patients might go into remission after the development of AIDS, but also there are patients that continue with active disease. Prevalence of DILS is highest among African Americans in less advanced stages. PAN is clinically less aggressive and peripheral neuropathy is the most common clinical manifestation. Anti-phospholipid syndrome (APS), systemic sclerosis and poly-dermatomyositis are uncommon. After the introduction of combination antiretroviral therapy (cART), a decline of spondyloarthritis disorders and of DILS and development of new syndromes such as IRIS, osteoporosis and avascular bone necrosis have occurred. The treatment of patients with rheumatic diseases and HIV infection remains a challenge."
6256,The Impact of ASEAN FTA: Regional Level Analysis,", ASEAN India FTA and ASEAN Australia New Zealand FTA. These three considerations have significantly changed the major factors that affect FDI inflows in ASEAN region other than ASEAN FTA as such. Given its time-series framework, this chapter takes the founding members of ASEAN and in particular Indonesia, Malaysia, Thailand, and Philippines as the observation countries."
6257,Clinical Aspects and Principles of Management of Tuberculosis,"Tuberculosis over the ages, has killed more people than any other infection has. Notwithstanding the advances in modern science, clinical diagnosis sometimes remains elusive, owing principally to the frequent paucibacillary occurrence of the disease and the slow doubling time of the organism; empiric treatment is often fraught with risks in the era of increasing drug resistance. This chapter attempts to provide an overview of the disease, beginning with the pathogenesis and its protean clinical presentations. It also discusses the recent evolution of molecular methods that have lately provided an impetus to early diagnosis with a clear opportunity to unmask drug resistance before initiating “blind”, potentially ineffective, and sometimes harmful treatment with standard therapy. The chapter also provides insight into tuberculosis in special situations, and discusses briefly the treatments in uncomplicated cases as well as in special situations, and in instances of drug resistance. Preventive methods including current and upcoming vaccines are mentioned. Finally, a short discussion of the sequelae of tuberculosis—which have the potential to be confused with active disease—is presented."
6258,Chemokine Receptors in Allergic Lung Disease,"This chapter is an attempt to integrate recent studies concerning the role of chemokine receptors in the initiation, development, and maintenance of allergic lung diseases collectively referred to as asthma. The pathogenesis of asthma involves the coordinated trafficking of inflammatory cells to the lungs and draining lymph nodes, as well as the activation of these inflammatory cells. Chemokine receptors and their ligands play a prominent role in directing the inflammation associated with allergic lung disease. T lymphocyte-mediated immune responses can be broadly categorized as being type 1 or type 2, based on the cell types present and the associated cytokines produced. Allergic lung disease is a predominately type 2-mediated disease. The chemokine receptors CCR4, CCR6, and CCR8 serve to promote the recruitment of type 2 T (T helper 2; Th2) cells, whereas CXCR3 antagonizes type 2 and promotes type 1 T (T helper 1; Th1) cells. The pathophysiologic manifestations of asthma, including excessive mucus production, eosinophilia, and airway hyperreactivity, are dependent upon the trafficking and activation of eosinophils, mast cells, and goblet cells. Roles for chemokine receptors, including CCR4, CCR2, and CXCR4, in the trafficking and activation of these cell types during allergic lung disease are discussed. Finally, the incidence of allergic lung disease is increasing, and the costs associated with it are substantial. Chemokine receptor expression and use by inflammatory cells during allergic lung disease makes chemokine receptors an attractive therapeutic target. Implications for drug development are discussed in the context of experimental results."
6259,Challenges to the European Exception: What Can S&T Do?,
6260,Geschichte der nosokomialen Pneumonie,"Nosokomiale Pneumonien sind ein Problem, das sich erst in der Folge des zivilisatorischen und medizinischen Fortschritts ergeben hat. Ihre Geschichte hängt eng zusammen mit der regelhaften Etablierung von Krankenhäusern und Intensivstationen sowie mit der Entwicklung der Beatmungsmedizin. In der Nachkriegszeit bis zum Ende der achtziger Jahre bildet sich die nosokomiale Pneumonie als Entität aus. Johanson Jr und seine Arbeitsgruppe legten den Grundstein in der Forschung der Pneumonie unter invasiver Beatmung (VAP). Jean-Yves Fagon und Jean Chastre sowie Antoni Torres gebührt das Verdienst, bis Anfang der neunziger Jahre auf der Basis der Arbeiten der Johanson-Gruppe neue und wichtige Impulse im Verständnis dieser Pneumonie-Entität sowie speziell hinsichtlich der Diagnostik gesetzt zu haben. Die Konsensus-Konferenz 1992 war ein Meilenstein der weiteren Entwicklung, indem sie zudem eine Reihe anderer Arbeitsgruppen zu methodisch komplexen Untersuchungen stimulieren konnte, deren Ertrag das Verständnis der nosokomialen Pneumonie heute noch prägt. Die Einführung der nichtinvasiven Beatmung auf der einen sowie der lungenprotektiven invasiven Beatmung auf der anderen Seite hat die Charakteristik der beatmeten Patienten grundlegend verändert. Eine hohe Aufmerksamkeit auf die Prävention der nosokomialen Pneumonie, bis hin zum Ziel der „Zero VAP“, sowie die Herausforderungen durch steigende Prävalenzen von multiresistenten Erregern prägen die Praxis und Forschungslandschaft der Gegenwart."
6261,Longziekten,"Deze aandoeningen, die soms met ‘verkoudheid’ of ‘griep’ betiteld worden, doen zich regelmatig – en vaak epidemisch – voor; bij kinderen (drie- tot viermaal per jaar) vaker dan bij volwassenen (een- tot tweemaal per jaar). Bij verkoudheid of griep is er vrijwel uitsluitend sprake van een virusinfectie. Slechts een deel van de verwekkers is bekend: influenzavirussen, para-influenzavirussen, adenovirussen en rinovirussen. Zo veroorzaken rinovirusinfecties vooral ontstekingsverschijnselen van het neusslijmvlies. Zij geven meestal weinig algemene ziekteverschijnselen. Adenovirusinfecties beginnen met keelpijn en neusirritatie en worden vaak vergezeld van bronchitis, terwijl koorts en algemene malaise als regel vanaf het begin aanwezig zijn. Infecties door influenzavirus uiten zich meestal door ernstige algemene symptomen (koorts, spierpijn, ‘doodziek’), terwijl lokale ziekteverschijnselen (keelpijn, hoest) op de achtergrond staan of zelfs achterwege kunnen blijven. Virale luchtweginfecties doen zich vooral voor in het najaar (vanaf september) en in het voorjaar (tot april). Zowel meteorologische (temperatuurwisselingen) als sociale (schoolgaan) omstandigheden lijken een rol te spelen."
6262,"Influenza: Biology, Infection, and Control","The growth of the human population has profoundly affected the global ecosystem, influencing the animal population balance, the availability of fresh water, arable land, biotic production, and atmospheric gases. The human ecological impact has significantly accelerated the evolutionary change of numerous organisms. For example, the production of human medicine and food has resulted in the rapid evolution of drug-resistant pathogenic organisms as well as plants and insects resistant to pesticides (Palumbi, 2001). Recently, the nutritional support of the human population has relied on the vast monoculture of domestic mammals and birds, which has facilitated the emergence of pathogenic enzootic organisms that infect both animals and humans. This chapter will focus on the global threat to human health represented by the highly contagious enzootic virus influenza. It will also discuss current efforts and future improvements to protect humans from global influenza epidemics and pandemics."
6263,Antimicrobials,"This chapter introduces the reader to the treatment of infections with antimicrobial drugs. In doing so, an ecological and evolutionary approach is taken that sees humans as just one part of the biosphere, which is the totality of life on earth. Our interaction with microorganisms is constant and ever changing, and it is this dynamic relationship between evolving organisms that makes the treatment of infectious diseases so challenging. Early in the chapter, this ecological approach is introduced, followed by the key to treating infectious diseases, which is the concept of selective toxicity. After that the key groups of organisms and their treatment are discussed, most notably bacteria, viruses and fungi, but also protozoa and helminths. More general topics of identification, testing and resistance are then discussed and before the chapter ends with consideration of opportunistic infections and pharmacological approaches to prevention."
6264,Hematology and Hemostasis,
6265,Propinquity,"One defining attributes of the city is propinquity. Propinquity, defined as the state of physical proximity to another individual, can also develop into relational propinquity by design. Through environmental design, individuals who are brought close together in propinquity can be regarded as neighbors, while those outside this circle are usually marked as strangers. In turn, and at least by the ethics of proximity, how neighbors and strangers are treated is likely to be different. This difference is morally significant and impinges on any city with cosmopolitan aspirations. What then is an ethic of proximity that can commensurate with the cosmopolitan aspirations in cities today? This chapter then relies on the story of the Good Samaritan as an intuition pump to initiate thinking on this question."
6266,Drivers of Emerging Zoonotic Infectious Diseases,"This chapter discusses drivers of emerging infectious diseases (EID) of humans that have an origin in other vertebrate animals (zoonoses). This is a broad topic, worthy of a book in its own right. This chapter will therefore provide only an overview of key concepts of drivers of the emergence of zoonotic diseases, and particularly infectious diseases with a major disease burden in humans. As the authors mainly work in Asia, the focus of this chapter is Asia, but many of the lessons learned in this region are likely to apply elsewhere. More than 60 % of the world population live in Asia, a region with some of the fastest developing economies in the world. Yet, despite tremendous advances, infectious diseases still remain a major burden for the human population in Asia. Of the estimated 2.1 million deaths in children aged less than 5 years in Southeast Asia in 2010, 47 % are attributable to infectious causes (Liu et al., Lancet 379:2151–2161, 2012). As such, Asia is both vulnerable to imported EIDs and a global focus of major social and environmental change that may facilitate the emergence and dissemination of new pathogens. However, it would be too simplistic to present the extensive changes in Asia as inevitably increasing the risk of EIDs. Some aspects of socio-economic change might serve to reduce the overall risk of infectious disease emergence, but all ecosystem changes have the potential to provide new opportunities for microorganisms to spill-over into human populations."
6267,The flowering of the age of Biotechnology 1990–2000,
6268,Surveillance and Epidemiology of Infectious Diseases using Spatial and Temporal Lustering Methods,"In the control of infectious diseases, epidemiologic information and useful clustering algorithms can be integrated to garner key indicators from huge amounts of daily surveillance information for the need of early intervention. This chapter first introduces the temporal, spatial and spatio-temporal clustering algorithms commonly used in surveillance systems–the key concepts behind the algorithms and the criteria for appropriate use. This description is followed by an introduction to different statistical methods that can be used to analyze the clustering patterns which occur in different epidemics and epidemic stages. Research methods such as flexible analysis of irregular spatial and temporal clusters, adjustment of personal risk factors, and Bayesian approaches to disease mapping and better prediction all will be needed to understand the epidemiologic characteristics of infectious diseases in the future."
6269,Arctic health problems and environmental challenges in Greenland,
6270,Ethics and Terror Medicine,"The field of medicine has long been defined not only by diagnostic and treatment techniques but also by standards of behavior. The Hippocratic Oath was introduced about the same time as the concept of case histories and prognosis, in ancient Greece, fifth century BCE. Despite vast changes in medicine through the ages, the oath’s core message continues to resonate: that a physician has a special responsibility to perform honorably. Forms of the Hippocratic Oath are still recited during graduation ceremonies at medical schools, many in the United States, though the classical version has been altered to suit contemporary values.(1) For example, passages in the early oath that prohibited the practice of abortion or euthanasia now are commonly omitted. The shifting text is a reflection of attempts to accommodate medical ethics to new findings, experiences, and values."
6271,Oncologic Emergencies,"It has been estimated that genitourinary malignancies will account for 25% of new cancer diagnoses in the United States in 2005 (Jemal et al. 2005). While the incidence of many of these malignancies has increased over the past two decades, the mortality rates appear to be decreasing. Early cancer detection combined with improvements in surgical and nonsurgical oncologic therapy account for these trends. Although not common, newly diagnosed cancer patients occasionally present in an emergent, life-threatening manner that warrants immediate medical or surgical intervention. As the prevalence of genitourinary malignancies continues to expand, additional patients can be expected to develop disease or treatment-related complications. This chapter will serve to review the diagnosis and management of oncologic emergencies as they pertain to the urologist."
6272,Intergenerational Cities Embracing Diversity and Social Justice,"Concentration and diversity of people and activities are invaluable assets for cities, colorful beehives and schools for respecting difference and learning how to live in society. This chapter sheds light on the evolving social capital of cities and their capacity for intergenerational and intracity equity, social justice, and solidarity. Urban social capital is of increasing importance in cities that face new forms of poverty and exclusion, where more than three generations coexist, and immigrants come looking for better living and working conditions. Citizens can play a major role in shaping vital urban spaces and forging bonds out of degraded spaces and estranged relationships. Distressed urban areas, the backstage of urban dramas where underprivileged and excluded citizens come together, can be transformed into innovative neighborhoods and vibrant inclusive communities acting as extended families for the disadvantaged. The participation of youth and women in projects can further extend opportunities, and education is always the most decisive productive investment towards a skill-intensive economy."
6273,Pulmonary Complications of Malignancies and Blood and Marrow Transplantation,"Advances in childhood cancer therapies and blood and marrow transplantation (BMT) have dramatically improved survival in the past decade, with 5-year survival now approaching 85% (Australian Institute of Health and Welfare, Cancer in Australia: an overview 2014. Cancer series no 90 Cat no CAN 88 Canberra, AIHW2014). Pulmonary complications however remain an important cause of short- and long-term morbidity and mortality in childhood malignancies (Meyer et al., Pediatr Hematol Oncol 21(2):175–195, 2004; Jenney, Paediatr Respir Rev 1(3):279–286, 2000). The development of acute respiratory complications should prompt consideration of a wide range of differentials as appropriate management can be a major predictor of survival, especially in children undergoing BMT (Meyer et al., Pediatr Hematol Oncol 21(2):175–195, 2004; McCahon, Paediatr Respir Rev 7(3):191–196, 2006; Krowka et al., Chest 87(2):237–246, 1985). In childhood cancer survivors, permanent and late-onset respiratory dysfunction have been found in up to 45% of patients and continue to have important impacts on quality of life and premature mortality (Mertens et al., Cancer 95(11):2431–2441, 2002; Versluys and Bresters, Paediatr Respir Rev 17:63–70, 2015; Huang et al., Chest 140(4):881–901, 2011; Mulder et al., Thorax 66(12):1065–1071, 2011). This chapter provides an overview of respiratory complications of childhood cancer and BMT, with a focus on mechanisms of injury."
6274,Biomarkers of Pulmonary Diseases,"Lungs and airways are affected by several pathologies, the most important of which are inflammation, infection and cancer. Some of the biomarkers of these pathologies are similar to those found in involvement of other organs. This chapter will briefly discuss general issues of biomarkers of pulmonary disorders listed in Table 16.1. Biomarkers of lung cancer are described in Chapter 13."
6275,Elderly Transplant Recipients,"While the total number of organs transplanted in this country has increased over the years, there is still an ever-widening gap between the need for organs and our capacity to meet that need as the overall waiting list continues to grow. This is due in part to significant advances in transplant techniques and outcomes such that Americans with organ failure now seek transplants in greater numbers. Additionally, life-expectancy gains in the United States are creating an aging population who are more likely to suffer organ failure than younger Americans. The national transplant waiting list has continued to shift toward older candidates. The Scientific Registry of Transplant Recipients (SRTR) reported that at the end of 2007, 59.7% of all 97,248 candidates on the waiting list for all organs were 50 years old or older, and 14.9% were 65 years or older. These percentages are substantially higher than they were in 1998 (41.5 and 8.1%, respectively) [1]."
6276,Tracheobronchitis in the Intensive Care Unit,"Tracheobronchitis can be broadly defined as inflammation of the airways between the larynx and the bronchioles. Clinically, this syndrome is recognized by an increase in the volume and purulence of the lower respiratory tract secretions and is frequently associated with signs of variable airflow obstruction. In the intensive care unit (ICU), tracheobronchitis is a relatively common problem with an incidence as high as 10.6% [1]. Although tracheobronchitis is associated with a significantly longer length of ICU stay and a prolonged need for mechanical ventilation, it has not been shown to increase mortality. These outcomes can be improved through the use of antimicrobial agents [1]."
6277,Supply Chain Risk Management,"Recognizing various natural and man-made disasters have caused major supply chain disruptions over the last two decades, this chapter illustrates the vulnerability of many global supply chains and provides justifications for companies to develop a systemic approach to managing supply chain risks. Viewing supply chain risk management as comprising four steps—identifying risks, accessing risks, mitigating risks, and responding to risks—this chapter highlights the overall structure and key objectives of the book."
6278,Microarrays as Research Tools and Diagnostic Devices,"Molecular diagnostics comprises a main analytical division in clinical laboratory diagnostics. The analysis of RNA or DNA helps to diagnose infectious diseases and identify genetic determined disorders or even cancer. Starting from mono-parametric tests within the last years, technologies have evolved that allow for the detection of many parameters in parallel, e.g., by using multiplex nucleic acid amplification techniques, microarrays, or next-generation sequencing technologies. The introduction of closed-tube systems as well as lab-on-a-chip devices further resulted in a higher automation degree with a reduced contamination risk. These applications complement or even stepwise replace classical methods in clinical microbiology like virus cultures, resistance determination, microscopic and metabolic analyses, as well as biochemical or immunohistochemical assays. In addition, novel diagnostic markers appear, like noncoding RNAs and miRNAs providing additional room for novel biomarkers. This article provides an overview of microarrays as diagnostics devices and research tools. Introduced in 1995 for transcription analysis, microarrays are used today to detect several different biomolecules like DNA, RNA, miRNA, and proteins among others. Mainly used in research, some microarrays also found their way to clinical diagnostics. Further, closed lab-on-a-chip devices that use DNA microarrays as detection tools are discussed, and additionally, an outlook toward applications of next-generation sequencing tools in diagnostics will be given."
6279,New Emerging Risks,"In earlier chapters, mention has been made to some new emerging risks in the changing world of work. Here we give a short list of new risks (Section 5.1), combined with a description of strategies and methods on how to deal with those risks within the Risk Management and Risk Governance process, focussing on the “precautionary principle” (Section 5.2)."
6280,Nodular Diseases,
6281,Alveolar Diseases,
6282,Neonatal Emergencies,Newborns may present with vague signs and symptoms that result from a large variety of aetiologies.
6283,"Antivirals: Past, Present and Future","The uses of antiviral agents are increasing in the new era along with the development of vaccines for the effective control of viral diseases. The main aims of antiviral agents are to minimize harm to the host system and eradicate deadly viral diseases. However, the replications of viruses in host system represent a massive therapeutic challenge than bacteria and fungi. Antiviral drugs not just penetrate to disrupt the virus’ cellular divisions but also have a negative impact on normal physiological pathways in the host. Due to these issues, antiviral agents have a narrow therapeutic index than antibacterial drugs. Nephrotoxicity is the main adverse reaction of antiviral drugs in human and animals. In this chapter, we summarize the antiviral agents’ past, present and future perspectives with the main focus on the brief history of antiviral in animals, miscellaneous drugs, natural products, herbal and repurposing drugs."
6284,Explaining the Neolithic Demographic Transition,"Three main questions are raised in this chapter. 1. The part of the signal of the NDT which is demographically identifiable, based on the proportion of the immature skeletons in cemeteries, shows that a baby-boom occurred and, beyond that, with the onset of the change in the economic system, a fertility transition towards high values also occurred. What was the biodemographic cause of this fertility explosion, beyond the proxy variable represented by sedentarism? The cause is a major shift in the maternal energetics of farming communities relative to mobile foragers. In the energy balance there was (i) on the intake side, an underlying trend towards a reduction in low-calorie food from hunting and fishing, and a correlative increase in high-calorie food from agriculture, (ii) on the expenditure side, a reduction in the physical energy devoted to mobility and the maternal stress of child transportation. 2. The NDT is detectable from a signal representing a fertility transition, but the transition relating to mortality is missing and must be inferred. If, during the fertility transition, mortality had remained the same as in the preceding forager period, then the population would have grown infinitely. The assumption of unchanged mortality during the entire fertility transition is therefore not realistic. Mortality, in its turn, must have begun to rise well before the end of the fertility transition. But when? Why? One of the answers consists of a model where, except at the start of the process, birth and mortality rates rise more or less simultaneously, bringing about a typical rate of increase for pre-industrial populations of slightly above zero. 3. According to the level and speed of the population growth, what should we expect in terms of population structure? What are the expected effects of this growth, not only on the population in numbers but also on age distribution, the distribution and structure of families, the distribution of households and on family systems?"
6285,Epidemic Dynamics Modeling and Analysis,"Disastrous epidemic such as SARS, H1N1, or smallpox released by some terrorists can significantly affect people’s life. The outbreak of infections in Europe in 2011 is another example. The infection, from a strain of Escherichia coli, can lead to kidney failure and death and is difficult to treat with antibiotics. A recent example of epidemic outbreak was the 2014–2015 Ebola pandemic in West Africa, which infected approximately 28,610 individuals and approximately 11,300 lives were lost in Guinea, Liberia, and Sierra Leone. It is now widely recognized that a large-scale epidemic diffusion can conceivably cause many deaths and more people of permanent sequela, which presents a severe challenge to the local or regional health-care systems."
6286,Introduction of Emerging Infectious Diseases,"Emerging infectious diseases (EIDs) refer to contagious diseases newly appeared, or with drug resistance, whose incidences have been rapidly increasing and are likely to further rise in the future. EIDs are usually discovered in three ways. Firstly, some existing diseases are ascertained as EIDs due to the recent discovery of pathogens. Secondly, previously considered noninfectious diseases are identified contagious as a result of new etiological findings. Thirdly, new infectious diseases are incurred by various complicated reasons such as evolution of pathogens. Due to their uncertainty and unpredictability, EIDs could result in high mortality and great impacts on social stability and economic development as people are unable to react immediately and take specific preventive or control measures. Therefore, EIDs have become a major public health problem worldwide. Cases in point are the epidemics of SARS in 2003 and H7N9 avian influenza around 2006, which have eloquently demonstrated their great threats to human health, society, and economy. In the coming twenty-first century, contagious diseases are expected to remain as a crucial public health concern for countries around the world."
6287,Advances in Lentiviral Vector-based Cell Therapy with Mesenchymal Stem Cells,"The field of possible application of mesenchymal stem cells in medicine and research expanded tremendously with the advent of improved Lentiviral-vectors capable of inserting stable copies of genes of interest and expressing proteins or biologically active RNA species ad libitum, performing delicate gene editing or active gene silencing or serving as advanced drug delivery systems utilized in ex vivo cell therapy. The combination of these two fields has created a number of new areas of research in the landscape of modern medicine which are now extensively studied and discussed here. These areas include tissue engineering, tissue repair, wound healing and tissue implants, anticancer therapies, angiogenesis, myocardial infarction and repair as well as understanding and treating acute lung damage and injury. In addition, genetically modified, tagged MSCs are being intensively deployed in research and therapeutic attempts of the various ailments of the central nervous system including Parkinson’s disease, Alzheimer’s disease, various phases of acute ischemia and trauma. The emergence of new and important data for type II diabetes research is being followed with treatment suggestions and studies of senescence to find novel applications for genetically engineered MSCs. We find in ­general that genetically modified MSCs are at the cusp of breaking through from basic research into the next phase of clinical trials."
6288,Disinfection Agents and Antiseptics,"Germicidal agents are nonspecific antimicrobial agents that are too toxic to be administered internally but are safe and effective when used topically. When applied to living tissue (e.g., the skin), they are termed antiseptics. When applied to inanimate objects (e.g., environmental surfaces or instruments used to perform medical procedures), they are termed disinfectants. All of these agents work at least by damaging microbial surfaces, often by alkylation, oxidation, or reaction with proteins. Products capable of destroying all forms of microbial life, including bacterial spores, are termed sterilizing agents."
6289,Pulmonary Infections – Pneumonia,"The different appearances of pneumonia such as ill-defined nodules, ground-glass opacities, and consolidations can be easily detected and differentiated with MRI. Since very small nodules and calcifications are extremely challenging due to rather thick slices and loss of signal, MRI is highly recommended as a follow-up tool, to avoid repetitive investigations using ionizing radiation. With the sensitivity of T2-weighted sequences and the potential of contrast-enhanced T1-weighted sequences important differential diagnostic considerations can be provided. Additionally, developing complications, such as pericardial or pleural effusions, empyema or lung abscess, are easily recognized. Current and future studies are to demonstrate that MRI is well suited as a monitoring and follow-up tool during and after therapy and compares favorably with CT or other imaging methods regarding sensitivity and specificity."
6290,"'Hallo, ik ben June' maar niet aanraken",
6291,Respiratory Infections,"Pneumonia is defined as the presence of a new pulmonary infiltrate on radiologic imaging in the patient with appropriate clinical symptoms such as fever, cough, production of purulent sputum, shortness of breath and/or hypoxia, in the absence of pulmonary edema [1, 2]."
6292,Estimating Phylogenies from Molecular Data,"Phylogenetic estimation from aligned DNA, RNA or amino acid sequences has attracted more and more attention in recent years due to its importance in analysis of many fine-scale genetic data. Nowadays, its application fields range from medical research to drug discovery, to epidemiology, to systematics and population dynamics. Estimating phylogenies involves solving an optimization problem, called the phylogenetic estimation problem (PEP), whose versions depend on the criterion used to select a phylogeny among plausible alternatives. This chapter offers an overview of PEP and discuss the most important versions that occur in the literature."
6293,SARS (Schweres Akutes Respiratorisches Syndrom),
6294,Protein Microarray Technologies for Detection and Identification of Bacterial and Protein Analytes,"Protein-based microarrays is a novel, rapidly evolving proteomic technology with great potential for analysis of complex biological samples. The technology will provide miniaturized set-ups enabling us to perform multiplexed profiling of minute amounts of biological samples in a highly specific, selective, and sensitive manner. In this review, we describe the potential and specific use of protein microarray technology, including both functional protein microarrays and affinity protein microarrays, for the detection and identification of bacteria, bacterial proteins as well as bacterial diseases. To date, the first generations of a variety of set-ups, ranging from small-scale focused biosensors to large-scale semi-dense array layouts for multiplex profiling have been designed. This work has clearly outlined the potential of the technology for a broad range of applications, such as serotyping of bacteria, detection of bacteria and/or toxins, and detection of tentative diagnostic biomarkers. The use of the protein microarray technology for detection and identification of bacterial and protein analytes is likely to increase significantly in the coming years."
6295,Infectieziekten,"In dit hoofdstuk wordt beoogd de belangrijkste nieuwe ontwikkelingen waarvan de huisarts moet kennisnemen, te bespreken. Voor specifieke therapie wordt verwezen naar hoofdstuk 25 Antimicrobiële therapie waaraan wij ook hebben bijgedragen."
6296,Foreign Aid and Humanitarian Assistance,"Together the US and EU provide two-thirds of global humanitarian assistance for the alleviation of emergencies arising from natural and man-made disasters and 80% of global foreign aid for longer-term development assistance programs. It is therefore vital that they continue their close partnership to ensure their dollars and euros are spent as effectively as possible in an era of increasingly tight budgetary constraints. The outbreak of Ebola in West Africa in 2014 is a good example of how the US and the EU successfully addressed (albeit belatedly) a major health crisis that could have turned into a global pandemic. In many areas in Africa, they are collaborating closely on the foundation of shared priorities, including on food security, resilience, and electrification. They are also among the largest donors to the Global Fund to fight HIV/AIDS, tuberculosis, and malaria and to the Global Alliance for Vaccines and Immunisation."
6297,Wireless Network Security Fundamentals,
6298,General Infectious Disease Question and Answer Items,"An overview of the general pediatric infectious disease topics necessary for ward knowledge, clinical acumen in practice, and board examination preparation is presented in an easy-to-study question & answer format."
6299,3 Medische microbiologie,"De microbiologie is de wetenschap die zich bezighoudt met de bestudering van micro-organismen. Dit zijn kleine organismen die niet met het blote oog waarneembaar zijn. Micro-organismen zijn essentieel voor alle levensprocessen, ze zijn dan ook alom vertegenwoordigd op aarde. Zo spelen ze onder meer een belangrijke rol bij het vruchtbaar houden van de aardbodem, de recirculatie van afvalstoffen en de vorming van voedingsbronnen."
6300,COrona-rap,
6301,Hospital Environments and Epidemiology of Healthcare-Associated Infections,"Today, hospitals are facing difficult challenges: increasing proportion of immunologically vulnerable patients often affected by diseases requiring high complex level of healthcare; rapidly evolving medical technologies and healthcare models; and budget restrictions. All these features interfere with healthcare and can modify the risk of acquiring healthcare-associated infections (HCAIs). Therefore, HCAI prevention is a high priority for healthcare systems. Authors describe human and environmental origin of HCAIs, focusing on the modality of transmission of those airborne pathogens, including the new insight derived from the recent acquisitions about SARS and Ebola epidemiology. They also describe the state of the art about microorganism concentration (infective dose) required to determine a HCAI and the role played by other virulence factors. Finally, the effective control measures used for the prevention of airborne pathogen transmission are described, focusing mainly on the risk assessment and infection control."
6302,Defining Drug Interactions with the Viral Membrane Protein Vpu from HIV-1,"The replication of HIV-1 is strongly enhanced by a small membrane protein called virus protein U (Vpu). Vpu achieves its task by (a) interacting with CD4, the HIV-1 receptor, and (b) by amplifying particle release at the site of the plasma membrane. While the first role is due to interactions of the cytoplasmic site of Vpu with CD4, the second role may be due to ion channel activity caused by the self-assembly of the protein. Recently, a blocker has been proposed which abolishes channel activity. In this chapter, the mechanism of blocking is described using computational methods, including a brief overview of other viral ion channel blockers."
6303,Cysteine Proteases,
6304,Pulmonary Infections,"The lungs are a frequent site of infectious diseases. Pleuropulmonary infections include bronchitis and bronchiolitis, pneumonia, lung abscess, cavity formation, allergic bronchopulmonary reaction, as well as pleural effusion and empyema. An accurate diagnosis of infection by means of cytology can be lifesaving. Sputum, lung FNA, bronchoscopic brushing, washing, and BAL are useful procedures that can help provide a fast, cost-effective, and noninvasive diagnosis of pulmonary infection. This chapter covers a wide variety of viral, bacterial, fungal, and parasitic infections that involve the lower respiratory system."
6305,Modeling the Spread and Outbreak Dynamics of Avian Influenza (H5N1) Virus and Its Possible Control,"Avian Influenza, commonly known as Bird Flu, is an epidemic caused by H5N1 Virus, that primarily affects birds such as chickens, wild water birds, ducks, and swans etc. On rare occasions, pigs and humans will also be affected with this virus In recent years this epidemic has emerged as a major global health concern. The present chapter is aimed at developing mathematical models that predict the spread and outbreak diversity of low pathogenic avian influenza virus. Essentially, we present (1) a deterministic mathematical model which deals with the dynamics of human infection by avian influenza both in birds and in human, (2) a discrete dynamical model for the spread of H5N1, and (3) the statistical transmission model of bird flu taking into account the factors that affect the epidemic transmission such as source of infection and social and natural factors."
6306,Critical Care,"This chapter contains 16 tables on critical care principles. It features tables on the management of sepsis/septic shock, PAD guidelines, neuromuscular blocker use and reversal, management of malignant hyperthermia, use of red blood cell transfusions, drug-induced fever, stress-related mucosal damage prophylaxis, therapeutic drug monitoring, and select antidotes."
6307,Co-evolutionary Models for Reconstructing Ancestral Genomic Sequences: Computational Issues and Biological Examples,"The inference of ancestral genomes is a fundamental problem in molecular evolution. Due to the statistical nature of this problem, the most likely or the most parsimonious ancestral genomes usually include considerable error rates. In general, these errors cannot be abolished by utilizing more exhaustive computational approaches, by using longer genomic sequences, or by analyzing more taxa. In recent studies we showed that co-evolution is an important force that can be used for significantly improving the inference of ancestral genome content. In this work we formally define a computational problem for the inference of ancestral genome content by co-evolution. We show that this problem is NP-hard and present both a Fixed Parameter Tractable (FPT) algorithm, and heuristic approximation algorithms for solving it. The running time of these algorithms on simulated inputs with hundreds of protein families and hundreds of co-evolutionary relations was fast (up to four minutes) and it achieved an approximation ratio < 1.3. We use our approach to study the ancestral genome content of the Fungi. To this end, we implement our approach on a dataset of 33,931 protein families and 20,317 co-evolutionary relations. Our algorithm added and removed hundreds of proteins from the ancestral genomes inferred by maximum likelihood (ML) or maximum parsimony (MP) while slightly affecting the likelihood/parsimony score of the results. A biological analysis revealed various pieces of evidence that support the biological plausibility of the new solutions."
6308,From Influenza-Induced Acute Lung Injury to Multiorgan Failure,"Influenza viruses are among the most common causes of human respiratory infection, causing high morbidity and mortality. In the United States, influenza results in approximately 200,000 hospitalizations and 36,000 deaths during a seasonal epidemic [1]. During a pandemic, up to 50% of the population can be infected by influenza, increasing the number of deaths [2]. In 1918, the worst influenza pandemic recorded in history caused up to 50 million deaths worldwide, with elderly, infants, and people with underlying illness having the highest risk of fatality [3]."
6309,Regulation of Cardiovascular Control Mechanisms by Angiotensin-(1–7) and Angiotensin-Converting Enzyme 2,"Among the molecular forms of angiotensin peptides generated by the action of renin on angiotensinogen (Aogen), both angiotensin II (Ang II) and the amino terminal heptapeptide angiotensin-(1–7) [Ang-(1–7)] are critically involved in the long-term control of tissue perfusion, cell-cell communication, development, and growth. Whereas an impressive body of literature continues to uncover pleiotropic effects of Ang II in the regulation of cell function, research on Ang-(1–7) has a shorter history as it was only 16 yr ago that a biological function for this heptapeptide was first demonstrated in the isolated rat neuro-hypophysial explant preparation (1). On the contrary, the synthesis of angiotonin/ hypertensin (now Ang II) was first obtained in 1957 (2), three decades ahead of the discovery of Ang-(1–7) biological properties."
6310,Astrovirus Structure and Assembly,"Recent structural studies on the astrovirus virion and viral proteins have yielded exciting new insights into the molecular mechanisms of the astrovirus life cycle. The 25 Å-resolution cryo-electron microscopy (Cryo-EM) reconstructions of the astrovirus virion reveal a solid capsid shell studded with spikes. Proteolytic maturation of the virus particle results in capsid conformational changes, most prominently at the spikes. High-resolution crystal structures of the human and avian astrovirus capsid spike domains have shed light on potential host receptors and species specificity. Together, both the structural studies on the astrovirus virion and capsid spike domains have revealed similarities to hepatitis E virus, suggesting an evolutionary relationship. The only other structural information on astrovirus is from the high-resolution crystal structure of the protease that is involved in nonstructural polyprotein processing. Overall, these structural studies have led a better understanding of the astrovirus life cycle, including astrovirus assembly, virus release, maturation, receptor binding, antibody neutralization, and nonstructural polyprotein processing."
6311,HIV Coreceptors and Their Roles in Leukocyte Trafficking During Neuroinflammatory Diseases,"Due to the increasing resistance of HIV-1 to antiretroviral therapies, there has been much emphasis on the discovery and development of alternative therapeutics for HIV-1-infected individuals. The chemokine receptors CXCR4 (Bleul et al. 1996a; Feng et al. 1996; Nagasawa et al. 1996; Oberlin et al. 1996) and CCR5 (Alkhatib et al. 1996; Deng et al. 1996; Dragic et al. 1996) were identified as target molecules from the time their role as coreceptors for HIV-1 entry into leukocytes was first discovered 10 years ago. Initial studies focused on the use of the chemokine ligands, or altered derivatives, of CXCR4 and CCR5 to prevent the entrance of HIV-1 into immune cells (Schols 2006). While these studies showed some initial promise, there was evidence of significant caveats to their use, including selection of alternative coreceptor utilizing strains (Marechal et al. 1999; Mosier et al. 1999) and the potential to cause inflammatory side effects. These data prompted the development and study of small molecule inhibitors of CXCR4 and CCR5, which have also been used to examine the roles of these molecules in a variety of inflammatory and infectious diseases."
6312,The Impact of Population Growth on the Epidemiology and Evolution of Infectious Diseases,"It is generally expected that in developing countries the epidemiological transition, with improved health and lower mortality rates, will eventually lead to a demographic transition with lower fertility rates. The reductions in mortality characterising the epidemiological transition are often associated with controlling the infectious diseases within populations, which leaves the chronic diseases associated with old age, cancer and heart disease dominating the causes of death. However, if the demographic transition does not occur quickly, populations can grow rapidly, creating an increased potential for spread of infectious disease. These infectious diseases could, in turn, increase death rates amongst young people and reverse the epidemiological transition. The relationship between population growth, size and infection depends upon the changes in contact pattern associated with there being more people. If facilities can keep pace with growth, then the increase in contact rates can be kept to a minimum, and the potential reversal in the epidemic transition prevented. This makes development a crucial adjunct to population growth if the global community is not to be increasingly exposed to pandemics of infectious disease. Here we review the epidemiological and demographic theory which relates population growth and infectious disease."
6313,Epidemiology of Respiratory Infections,"The study of respiratory infections using epidemiologic tools allow the clinician to better understand the most frequently involved agents—viruses and bacteria, which usually originate in humans. Many strategies have been implemented to track the epidemic season of pathogenic agents to improve recognition at a local level, especially for virus detection. A surveillance program implemented a decade ago has allow pediatricians to improve the diagnostic yield on a regular basis."
6314,Infectieziekten,"De mens wordt belaagd door talloze micro-organismen. Sommige daarvan kunnen een infectieziekte veroorzaken. Op een infectie volgt een ontstekingsreactie die het lichaam helpt om de infectie te bestrijden, maar soms is die ontstekingsreactie onvoldoende. In dat geval zijn er geneesmiddelen nodig om de infectie te behandelen. In dit hoofdstuk gaan we nader in op de veroorzakers van infectieziekten, zoals bacteriën, schimmels, virussen, protozoa en wormen, luizen en mijten. Voor elke ziekteverwekker zullen we geneesmiddelen bespreken die voor de behandeling worden gebruikt."
6315,Interactions of Piriformospora indica with Medicinal Plants,"The microbial world exerts a negative as well a positive impact on living plants and animals, and forms an association either pathogenic or symbiotic with the other partners of the living world. Mycorrhiza refers to an association or symbiosis between plants and fungi that colonize the roots during periods of active plant growth. The intimate symbiotic relationships developed between mycorrhizal fungi and plants, since the colonization of land by the latter, have led to interdependence between these organisms for many basic processes. The fungi require plants to accomplish their life cycle. Plants depend heavily on mycorrhizal fungi for many different functions, such as mineral nutrition and abiotic and biotic stress resistance. Substantial evidence has accumulated in the recent past about how the use of the microsymbiont could significantly contribute in decreasing use of fertilizers and pesticides in agriculture, forestry and flori-hortriculture, especially if combined with other beneficial soil microorganisms. The most common and prevalent arbuscular mycorrhizal fungi play an indispensable role in upgrading plant growth, vigor and survival by a positive impact on the nutritional and hydratic status of the plant and on soil health, by increasing the reproductive potential, improving root performance, and providing a natural defence against invaders, including pests and pathogens. The described species of arbuscular mycorrhizal fungi mainly belong to Zygomycetes placed in the order Glomerales. However, the growing of arbuscular mycorrhizae in pure culture in the absence of living host roots is a matter of global concern. Unfortunately, their biotechnological applications cannot be exploited to the level they deserve due to their axenically unculturable nature."
6316,Psittacosis,"Psittacosis, also known as ornithosis, is an acute infectious disease caused by Chlamydia psittaci (Cps) and commonly prevails in poultry and other species of bird. Humans infected by Chlamydia psittaci may suffer from unapparent subclinical infection, with symptoms ranging from mild flulike illness to severe SARS. As a typical animal-based infectious disease, psittacosis rarely has pulmonary signs but a long illness course, despite its clinical manifestation characterized by severe pulmonary lesions. Repeated onsets of psittacosis may lead to chronic diseases."
6317,Interferon-Induced Effector Proteins and Hepatitis C Virus Replication,"Hepatitis C virus (HCV) is a small, enveloped RNA virus that is often capable of establishing a persistent infection, which may lead to chronic liver disease, cirrhosis, hepatocellular carcinoma, and eventually death. For more than 20 years, hepatitis C patients have been treated with interferon-alpha (IFN-α). Current treatment usually consists of polyethylene glycol-conjugated IFN-α that is combined with ribavirin, but even the most advanced IFN-based therapies are still ineffective in eliminating the virus from a large proportion of individuals. Therefore, a better understanding of the IFN-induced innate immune response is urgently needed. By using selectable self-replicating RNAs (replicons) and, more recently, recombinant full-length genomes, many groups have tried to elucidate the mechanism(s) by which IFNs inhibit HCV replication. This chapter attempts to summarize the current state of knowledge in this interesting field of HCV research."
6318,Infections: Viruses,"Viruses can cause meningitis, encephalitis, myelitis, arteritis when affecting the nervous system. Viruses are classified as DNA viruses and RNA viruses. Imaging of viral encephalitis is often nonspecific showing focal or diffuse edema (acute infection) or focal atrophy (chronic infection). Location of the lesion depends on causative agent, thus, HSV encephalitis displays an almost pathognomonic involvement of the limbic system. The various steps in the pathogenesis include entry into the body, delivery of the virus to the target tissue, interaction of virus with target tissue, cytopathogenesis, host responses, immunopathology, virus production in a tissue with release of the virus to other people (contagion), and transmission of viruses. Treatment consists of administration of antiviral drugs which aim at altering virion disruption, attachment, penetration and uncoating, RNA synthesis, genome replication, virion assembly and release. Clinical outcome depends on age of infection, nature of disease, severity of disease, and progression of viral disease. Human immunodeficiency virus (HIV)-1 infection is a serious health problem worldwide as 33 million adults and 2 million children are infected with HIV-1. The brain is often involved which leads to the HIV-associated neurocognitive disorders (HAND) of which asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD) represent various stages. The neuropathologic changes in HIV-1 induced lesions, i.e. HIV-1 encephalitis (characterized by multiple disseminated foci composed of microglia, macrophages, and multinucleated giant cells (MGCs) predominantly located in the cortex, deep gray matter, and the white matter), HIV-1 leukoencephalopathy (diffuse damage to the white matter), lymphocytic meningitis (LM), perivascular lymphocytic infiltration (PLI), vacuolar myelopathy (VM), vacuolar leukoencephalopathy (VL) are described. Therapy might lead to the immune restituiton inflammatory syndrome (IRIS). The sequelae of HIV-1 infection of the nervous system include changes in neuronal number, neuronal size, synapses, dendrites, nerve fibers, astroglia, oligodendroglia, microglia/macrophages, vessels, vascular endothelial cells, and capillaries. Pathogenetic mechanisms deal with the mode of entrance of HIV-1 into the brain, target cells of HIV-1, mechanisms of brain lesions, and interactions between the blood–brain-barrier (BBB) and HIV. Cytomegalovirus infection (CMV), progressive multifocal leukoencephalopathy (PML), Herpes Simplex Virus (HSV) encephalitis, and Tick-borne encephalitis are further described."
6319,Plague as a Biological Weapon,"Three well-documented plague pandemics have occurred in the past two millennia, resulting in more than 200 million deaths and great social and economic chaos (Perry and Fetherston, 1997; Pollitzer, 1954). The Justinian pandemic arose in northern Africa in the mid-6th century, and by the 7th century had spread throughout the Mediterranean and near-eastern regions—severely impacting both the Roman and Byzantine empires. The second pandemic, the Black Death or great pestilence, originated in Central Asia, was carried to Sicily in 1347 via ships from the Crimea, and rapidly swept through medieval Europe. By 1352, it had killed 30% or more of afflicted populations, slowly playing itself out in successive epidemics, including the Great Plague of London in 1665 (Perry and Fetherston, 1997). The third (Modern) pandemic began in southwestern China in the mid-19th, struck Hong Kong in 1894, and was soon carried by rat-infested steamships to port cities on all inhabited continents, including several in the United States (US) (Link, 1955; Pollitzer, 1954). By 1930, the third pandemic had caused more than 26 million cases and 12 million deaths. Plague in these three pandemics was predominantly the bubonic form, emanating from Yersinia pestis-infected rats and fleas, although terrifying outbreaks of the more virulent person-to-person spreading pneumonic form were recorded during the course of each. The explosive contagiousness and severity of pneumonic plague was most completely documented in Manchurian epidemics in the early 20th century, which involved tens of thousands of cases, virtually all of them fatal (Wu, 1926)."
6320,Assessment of sustainability effects in the context of specific applications,"In an initial investigation possible nanotechnology application contexts were considered and qualitatively evaluated. Also studies to life cycle aspects of nanotechnology were analyzed. So far, only a handful of life cycle assessments (LCAs) on nanotechnologies have been completed. A summary of studies of life cycle aspects identified are provided."
6321,Transiente aplastische Krise (TAC),
6322,Role of the Renin-Angiotensin System in ARDS,"The renin-angiotensin system (RAS) is a powerful biological system that plays an important role in regulation of systemic blood pressure through the maintenance of fluid and salt homeostasis. It is a multifactorial system since it includes different components (Fig. 1): The first, renin, was discovered in 1898 [1], whereas the discovery of the last component, angiotensin-converting enzyme 2 (ACE 2), is relatively recent, from 2000 [2, 3]. Three kinds of RAS are known: A) circulating, B) local, and C) intracellular."
6323,Erkrankungen der oberen Atemwege,"Eine akute Rhinitis ist meist Folge einer Tröpfcheninfektion durch respiratorische Viren (⊡ Übersicht). Durch akute viral bedingte zytopathische Schleimhautveränderungen wird der Boden für Abflussbehinderungen der Nasennebenhöhlen und für eine bakterielle Infektion bereitet. Bei einer bakteriellen Superinfektion spielen Streptococcus pneumoniae (Pneumokokken) und andere typische Pathogene der Atemwege die Hauptrolle. Eine Sinusitis, die aufgrund der anatomischen Verhältnisse bei Kindern in bis zu 5% bei akuter Rhinitis auftritt, folgt auf die entzündliche Blockade des Sinusostiums. Auch sie ist überwiegend primär viral bedingt. Bakterielle Superinfektionen folgen gelegentlich. Anatomische Varianten (Septumdeviation, Nasenmuschelhyperplasie, Conchae bullosae, Adeno-ide) wirken dabei begünstigend. Bei Sinusitis maxilla-ris muss eine dentogene Genese bedacht werden, die Infektion ist in diesem Fall bakterieller Natur."
6324,The Elderly Patient and the Intensive Care Unit,"At least 20–50 % of all ICU admissions occur in patients older than 65 years of age, and geriatric patients account for almost 60 % of all ICU days. Unfortunately, many older patients’ final days are spent in the ICU; 40 % of Medicare patients who die are admitted to an ICU during their terminal illness, accounting for 25 % of all Medicare expenditures. Additionally, of those who survive, many are discharged to a subacute facility with persistent organ failure where they will eventually die. Furthermore, those discharged to a subacute care facility have a higher mortality rate compared to those discharged home (31 vs. 17 %). The decision to admit an elderly patient to an ICU should be based not only on their comorbidities, acuity of illness, and prehospital functional status, including quality of life, but also on their preference for the use of life-sustaining treatments if it is known. The underlying disease process is not altered despite the use of invasive procedures in terminally ill patients, and potential harm or discomfort can occur if invasive procedures are used inappropriately. To avoid such unintended consequences and enhance optimal end-of-life decision making, healthcare providers need to identify, explain, and negotiate consensus therapeutic goals."
6325,Zorgvuldig en verantwoord handelen in de basiszorg,"Basisverpleegkunde of basiszorg is de meest omvangrijke vorm van zorgverlening in de gezondheidszorg. Verpleegkundigen, verzorgenden, helpenden en mantelzorgers helpen dagelijks mensen met hun lichamelijke verzorging, hun toiletgang, het verschonen van hun kleding en het opruimen en schoonmaken van hun omgeving. Hun aandacht gaat daarbij ook uit naar het psychisch welzijn van degenen die zij helpen, in de vorm van een gesprek, een troostend of opbeurend woord of een aardig gebaar. Het een hoeft niet belangrijker te zijn dan het ander, afhankelijk van welke gewoonten en wensen de patiënt zelf heeft voor zijn verzorging. Zo wil de een elke dag twee keer onder de douche en een ander wil zichzelf liever elke dag aan de wastafel wassen."
6326,The Post-Modern Era: Chronic Disease and the Onslaught of a Sedentary Lifestyle,"New technologies have speeded research in many areas of Exercise Science during the Post-Modern Era. Political interest in physical fitness and sport remains spasmodic, but the U.S. has finally introduced a scheme of universal health insurance. The cardiovascular disease epidemic is partially contained, but obesity and diabetes show a growing prevalence. Consensus conferences have underlined both the safety and the health benefits of physical activity and disease, and Universities offer an increasing range of doctoral programmes in Exercise Sciences and Kinesiology. However, optimal evidence-based exercise prescriptions have yet to be defined for many conditions. Health and fitness landmarks over the past 50 years include the standardization of test methodology, development of tools for population screening and testing, completion of representative National Health and Fitness surveys, quasi-experimental evaluations of school and employee fitness programmes, definition of minimum occupational fitness needs, demonstration of the beneficial effects of exercise on the aging process, and documentation of the high fitness levels associated with a hunter-gatherer lifestyle. Attempts to increase physical activity in the general population have as yet had only modest success. In Public Schools, the emphasis of Physical Educators is shifting from the training of sports teams to the teaching of life-long exercise skills. International sports programmes have received ever growing support from governments and commercial sponsors, with a multiplication of the corresponding professional associations. Olympic and Masters Games now cater to women, athletes with disability and the elderly, but athletic competition has lost much of its earlier idealism, and any positive impact upon population health and fitness is limited."
6327,Disease Management in Endangered Mammals,"One quarter of all mammal species are considered threatened with extinction (IUCN 2007). The rate of loss of biodiversity is accelerating because increasing pressure from an expanding human population is shrinking natural habitat and over-exploiting wild animal populations. Although processes such as habitat loss and over-harvesting are usually identified as the major drivers of extinction, recent evidence suggests that disease can also be a significant threat to endangered species (Lyles and Dobson 1993; Daszak and Cunningham 1999; Daszak et al. 2000b; de Castro and Bolker 2004; Choisy and Rohani 2006; Lips et al. 2006; Smith et al. 2006). Disease has already been documented as a cause of extinction of a land snail (Partula turgida) (Cunningham and Dazsak 1998), and several amphibian species (Schloegel et al. 2006; Skerrat et al. 2007). Diseases are also known to cause significant population declines, as illustrated by the impact of canine distemper virus in black-footed ferrets (Mustela nigripes) (Williams et al. 1988) and lions (Panthera leo) (Roelke-Parker et al. 1996), rabies virus in African wild dogs (Lycaon pictus) (Woodroffe and Ginsberg 1999), Ebola virus in apes (Leroy et al. 2004), squirrelpox virus in red squirrels (Sciurus vulgaris) (Rushton et al. 2006) and transmissible facial tumour disease in Tasmanian devils (Sarcophilus harrisii) (Pearse and Swift 2006)."
6328,Imaging of Parasitic Diseases of the Thorax,"A broad spectrum of parasitic infections frequently affects the lungs, mediastinum, and thoracic wall, manifesting with abnormal imaging findings that often make diagnosis challenging. Although most of these infections result in nonspecific abnormalities, familiarity with their imaging features and the diagnostic pathways help the radiologist to formulate an adequate differential diagnosis and to guide diagnosticians in reaching a definitive diagnosis."
6329,Molecular Determinants of Coronavirus Mhv- Induced Demyelination,"Mouse hepatitis virus (MHV) is a member of the coronavirus family of the nidovirales order. MHV is an enveloped virus with single-stranded, positive genomic RNA of about 31kb. Infection of susceptible strains of mice with the MHV-JHM and A59 strains results in acute encephalomyelitis and chronic demyelinating disease with features similar to the human demyelination disease multiple sclerosis (MS). Because the mechanism of demyelination in MS is not completely understood, various experimental models, including MHV infection in mice, have been used to study the pathogenesis of inflammatory autoimmune demyelination. The spike (S) glycoprotein of MHV has been implicated as the most critical genomic determinant of MHV pathogenesis and demyelination. However, other genes and proteins are likely to contribute to MHV pathogenesis as well."
6330,Asthma,"Asthma has been recognized as a disease since the earliest times. In the Corpus Hippocraticum, Hippocrates used the term “ασθμα” to indicate any form of breathing difficulty manifesting itself by panting. Aretaeus of Cappadocia, a well-known Greek physician (second century A.D.), is credited with providing the first detailed description of an asthma attack [13], and to Celsus it was a disease with wheezing and noisy, violent breathing. In the history of Rome, we find many members of the Julio-Claudian family affected with probable atopic respiratory disorders: Caesar Augustus suffered from bronchoconstriction, seasonal rhinitis as well as a highly pruritic skin disease. Claudius suffered from rhinoconjunctivitis and Britannicus was allergic to horse dander [529]. Maimonides (1136–1204) warned that to neglect treatment of asthma could prove fatal, whereas until the 19th century, European scholars defined it as “nervous asthma,” a term that was given to mean a defect of conductivity of the ninth pair of cranial nerves."
6331,"The Social and Political Dimensions of the Ebola Response: Global Inequality, Climate Change, and Infectious Disease","The 2014 Ebola crisis has highlighted public-health vulnerabilities in Liberia, Sierra Leone, and Guinea—countries ravaged by extreme poverty, deforestation and mining-related disruption of livelihoods and ecosystems, and bloody civil wars in the cases of Liberia and Sierra Leone. Ebola’s emergence and impact are grounded in the legacy of colonialism and its creation of enduring inequalities within African nations and globally, via neoliberalism and the Washington Consensus. Recent experiences with new and emerging diseases such as SARS and various strains of HN influenzas have demonstrated the effectiveness of a coordinated local and global public health and education-oriented response to contain epidemics. To what extent is international assistance to fight Ebola strengthening local public health and medical capacity in a sustainable way, so that other emerging disease threats, which are accelerating with climate change, may be met successfully? This chapter considers the wide-ranging socio-political, medical, legal and environmental factors that have contributed to the rapid spread of Ebola, with particular emphasis on the politics of the global and public health response and the role of gender, social inequality, colonialism and racism as they relate to the mobilization and establishment of the public health infrastructure required to combat Ebola and other emerging diseases in times of climate change."
6332,Respiratorische Erkrankungen,"Dieses Kapitel gibt kurz und knapp einen Überblick über respiratorische Erkrankungen, insbesondere Dyspnoe, Apnoen, Krupp-Syndrom, Epiglottitis, Tracheitis und Fremdkörperaspiration. Ebenso werden Informationen zum akuten Asthmaanfall sowie dem Status asthmaticus, der bronchopulmonale Dysplasie, Bronchiolitis, Schocklunge und den Pneumonien gegeben."
6333,The Human Antibody Response Against WNV,"Experimental evidence has shown that antibody responses to West Nile virus (WNV) are critical for protection from WNV-mediated disease. Antibody responses are also an important immune correlate of protection for the clinical evaluation of WNV vaccines. However, little direct study has been carried out on the characteristics of the human antibody response to natural WNV infection. Preliminary evidence suggests that there are important differences in the way humans and experimental animals mount humoral responses to WNV. In humans, IgM is remarkably persistent in the serum and specific IgG is slow to appear. In addition, mapping of the IgG response to the functionally relevant E-protein suggests that it directed away from critical protective epitopes and towards weakly neutralizing immunodominant epitopes. These findings have important implications for vaccine design and testing."
6334,Aircraft Cabin Air Quality Trends Relative to Ground Level Standards,"Aircraft cabin air quality has attracted much attention, summarized recently by a detailed examination and commentary by a U.S. National Academy of Sciences Committee. Ventilation of aircraft has several significant variables that require control measures that are seldom of concern for occupied space at ground level. The principal of these special requirements are the need to compensate for the substantial difference between cabin and outside pressures, the much lower available space per occupant in aircraft cabins, and the need for coping with more extreme external temperatures than are common at ground level. The breadth of these concerns is of interest in the policies and regulatory aspects of a number of agencies which are briefly described, and their roles and areas of potential interest outlined. Types of possible contaminants are listed, and the limits which have been set by several of these agencies for many of these potential contaminants are tabulated. In addition recent measured aircraft cabin concentrations of several key contaminants are listed. This chapter provides an overview of the general air quality variables affecting enclosed space to enable these to be related to the special needs of some of the less common enclosed spaces described in the following chapters."
6335,A Multiagent-Based Model for Epidemic Disease Monitoring in DR Congo,"Any infectious diseases have been reported in sub-Saharan countries over the past decade due to the inefficiency of health structures to anticipate outbreaks. In a poorly-infrastructure country such as the Democratic Republic of Congo (DRC), with inadequate health staff and laboratories, it is difficult to respond rapidly to an epidemic, especially in rural areas. As the DRC’s health system has three levels (peripheral, regional and national), from the production of health data at the peripheral level to the national level that makes the decision, meantime the disease can spread to many people. Lack of communication between health centres of the same health zone and Health zones of the same Health Provincial Division does not contribute to the regional response. This article, an extended version of [1], proposes a well elaborated solution track to deal with this problem by using an agent-centric approach to study by simulation how to improve the process. A new experiment is described by arranging twenty-eight health zones of Kinshasa to show how their collaboration can provide unique health data source for all stakeholders and help reducing disease propagation. It concerns also 47 health centres, 1 medical laboratory, 1 Provincial Health Division and 4 Rapid Riposte Teams. The simulation data, provided by Provincial Health Division of Kinshasa, concerned cholera outbreak from January to December 2017. The interaction between these agents demonstrated that Health Zone Agent can automatically alert his neighbours whenever he encountered a confirmed case of an outbreak. This action can reduce disease propagation as population will be provided with prevention measures. These interactions between agents have provided models to propose to the current system in order to find out the best that can help reducing decision time."
6336,Antiviral and Antimicrobial Evaluation of Some Heterocyclic Compounds from Turkish Plants,"Antibiotic resistance has become a problem since the discovery of antibiotics. Not long after the introduction of penicillin, Staphylococcus aureus, which can be also transmitted to humans via milk and milk products, began developing penicillin-resistant strains. Therefore, one approach that has been used for the discovery of new antimicrobial agents from natural sources is based on the evaluation of traditional plant extracts. Natural products have played a pivotal role in antibiotic drug innovation and include aminoglycosides, cephalosporins, macrolides, cycloserine, novobiocin, and lipoproteins. However, only a few antiviral agents are available on the market. To this purpose, we have screened a great number of herbal extracts along with some pure natural substances and obtained interesting findings. This chapter covers the results of our rigorous search for new antiviral and antimicrobial alternative compounds from a number of Turkish plants."
6337,Pulmonary Interstitium,"The first step in the radiographic evaluation of interstitial lung disease begins with a fundamental knowledge of the anatomy of the pulmonary interstitium and the different patterns of disruption. The anatomy of the pulmonary interstitium as demonstrated on CT of the chest with high resolution cuts is largely essential to establish the various radiological patterns that define interstitial lung disease such as the tree-in-bud, ground-glass opacity, crazy -paving, etc."
6338,"The Domestic Cat, Felis catus, as a Model of Hereditary and Infectious Disease","The domestic cat, currently the most frequent of companion animals, has enjoyed a medical surveillance, as a nonprimate species, second only to the dog. With over 200 hereditary disease pathologies reported in the cat, the clinical and physiological study of these feline hereditary diseases provides a strong comparative medicine opportunity for prevention, diagnostics, and treatment studies in a laboratory setting. Causal mutations have been characterized in 19 felid genes, with the largest representation from lysosomal storage enzyme disorders. Corrective therapeutic strategies for several disorders have been proposed and examined in the cat, including enzyme replacement, heterologous bone marrow transplantation, and substrate reduction therapy. Genomics tools developed in the cat, including the recent completion of the 2-fold whole genome sequence of the cat and genome browser, radiation hybrid map of 1793 integrated coding and microsatellite loci, a 5-cM genetic linkage map, arrayed BAC libraries, and flow sorted chromosomes, are providing resources that are being utilized in mapping and characterization of genes of interest. A recent report of the mapping and characterization of a novel causative gene for feline spinal muscular atrophy marked the first identification of a disease gene purely from positional reasoning. With the development of genomic resources in the cat and the application of complementary comparative tools developed in other species, the domestic cat is emerging as a promising resource of phenotypically defined genetic variation of biomedical significance. Additionally, the cat has provided several useful models for infectious disease. These include feline leukemia and feline sarcoma virus, feline coronavirus, and Type C retroviruses that interact with cellular oncogenes to induce leukemia, lymphoma, and sarcoma."
6339,Tracing the Diffusion of Infectious Diseases in the Transport Sector,
6340,"Microbiology of Acute, Subacute, and Chronic Rhinosinusitis in Children","Acute, subacute, and chronic rhinosinusitis may involve an infectious etiology. Knowledge of the microbiology of sinusitis is necessary because it impacts the choice of antibiotic therapy. The sinus aspirate is the most reliable source of microbiological data in sinusitis in children. However, sinus aspirates are rarely done in cases of patients with rhinosinusitis; the last time one was done in a child was in 1984. When they are done, sinus aspirate studies of children showed the presence of Streptococcus pneumoniae (S. pneumoniae), Haemophilus influenzae, and Moraxella catarrhalis (M. catarrhalis). Unlike sinus aspirates, nasopharyngeal and middle meatal cultures are not reliable in determining the bacteriology of children with acute sinusitis. The observation of an increase in the proportion of cases of acute otitis media caused by H. influenzae may reflect that in acute sinusitis as well. Staphylococcus aureus does not play a significant role in uncomplicated acute bacterial sinusitis. The microbiology of acute otitis media can be used as a surrogate for that of acute bacterial sinusitis in children. In contrast to bacteria, the contribution of viruses to the pathogenesis of acute bacterial sinusitis has not been studied systematically. The pathogenesis of chronic sinusitis may be related to bacterial biofilms as a stimulant of chronic inflammation."
6341,Airborne/Droplet Infection Isolation,"Airborne/droplet infection is caused by infected agents in the air around a person. Microbial pathogenic agents that are mainly transmitted airborne are aerosols, re-aerosols, microbe-carrying particles, huge amounts of bacteria-carrying airborne skin cells, dust, droplets and droplet nuclei. At the same time, there is always a contact transmission from contaminated environment, equipment, textiles and waste. Droplet nuclei are small evaporated droplet residues (<5 μm) produced by coughing, sneezing, shouting, singing and speaking very distinct—especially the consonants. Droplet nuclei remain for many hours in the air and may be carried by normal air currents in long distances outside the room. Therefore, “droplet isolation and droplet precaution” is included in the airborne isolation regime. The source of infection is usually a patient but may also be a healthy carrier. The patient should be placed in isolate dedicated for airborne infections."
6342,Part II Acronyms and Abbreviations,
6343,Human Infected H5N1 Avian Influenza,"Avian influenza is an infectious disease caused by avian influenza virus, which is also known as avian plague or European avian plague."
6344,Human Pathogenic Viruses in the Marine Environment,"Indigenous marine virus strains outnumber any form of life in the sea, usually occurring in billion amounts per liter (Danovaro et al., 2001; Fuhrman, 1999). However, although transspecific propagation of viruses may take place, the virus—host relationship tends to be quite constrained, and consequently human viruses are the only viral agents of public health concern in the marine environment."
6345,Vaccines,"Vaccines continue to offer the key line of protection against a range of infectious diseases; however, the range of vaccines currently available is limited. One key consideration in the development of a vaccine is risk-versus-benefit, and in an environment of perceived low risk, the benefit of vaccination may not be recognised. To address this, there has been a move towards the use of subunit-based vaccines, which offer low side-effect profiles but are generally weakly immunogenic. This can be compensated for by the development of effective adjuvants. Nanotechnology offers key attributes in this field through the ability of nanoparticulates to incorporate and protect antigens from rapid degradation, combined with their potential to effectively deliver the antigens to appropriate cells within the immune system. These characteristics can be exploited in the development of new adjuvants. This chapter will outline the applications of nanosystems in vaccine formulations and consider the mechanisms of action behind a range of formulations."
6346,Postoperative Care of the Cardiac Surgical Patient,"The subspecialty of interventional cardiology began in 1977. Since then, the discipline of interventional cardiology has matured rapidly, particularly with regards to ischemic heart disease. As a result, more patients are undergoing percutaneous catheter interventional therapy for ischemic heart disease and fewer patients are undergoing surgical myocardial revascularization. Those patients referred for surgical revascularization are generally older and have more complex problems. Furthermore, as the population ages more patients are referred to surgery for valvular heart disease. The result of these changes is a population of surgical patients older and sicker than previously treated."
6347,Housing And Welfare,
6348,Human Infected H7N9 Avian Influenza,"Human infected H7N9 avian influenza is an acute respiratory infectious disease caused by subtype H7N9 of avian influenza virus. Since the first case was reported in Yangzi River Delta of China in Feb. 2013, the total cases with definitive diagnosis had been up to 451 cases, including 176 cases of death, by Dec. 31, 2014, with a mortality rate of roughly 39 %."
6349,Antimicrobial Use in Surgical Intensive Care,"Intensive care has evolved over its 50-year history to yield previously unimaginable recovery from major trauma, multi-organ system failure, and extensive surgery, including organ transplantation. Antimicrobial therapy plays an essential role in combating invasive infections in the intensive care population that are often the ultimate causes of death. However, a parallel evolution of antimicrobial compensation has occurred, engendering resistance and virulence mechanisms to circumvent each new antimicrobial agent. The surgical intensive care unit provides the ultimate microcosm of antimicrobial resistance selection, combining complex and severe underlying illness with invasive devices, bypassed defenses, compromised tissues, and proximity to other high-risk patients, all in one intimate environment. New resistance mechanisms may be introduced from referring institutions or can emerge in response to treatments, and then may spread to others within or outside the ICU. Multidrug-resistant organisms have become a dominant issue in modern health care; a strategic response is essential to short- and long-term success."
6350,Apoptosis in MHV-Induced Demyelination,"Mouse hepatitis virus (MHV) induced encephalitis, hepatitis and chronic demyelinating disease involves inflammatory and parenchymal cell death. TUNEL assays and electron microscopy reveal that brain parenchymal cells such as neurons, astrocytes, microglia/macrophages and oligodendrocytes are undergoing apoptosis during acute and chronic infection with a neurotropic strain MHV-A59. Although apoptosis is a normal phenomenon in helping the turnover of inflammatory cells, apoptosis of brain parenchymal cells may have significant implications for the pathogenesis of viral-induced demyelination."
6351,Polmoniti,"Non è semplice ordinare una materia così articolata come la patologia infettiva respiratoria. La gestione delle polmoniti si presenta complessa per le problematiche ad esse connesse (aspetti epidemiologici, microbiologici, farmacoeconomici, ecc.) per cui è necessario confrontare costantemente le conoscenze di quanti hanno dimestichezza in questo settore per proporre e condividere linee strategiche che tengano in considerazione da un lato i suggerimenti contenuti nelle linee guida più accreditate e dall’altro le esperienze prodotte dalla pratica quotidiana al fine di migliorare potenzialità e metodi di cura e razionalizzare i percorsi diagnostico-terapeutici più idonei a fronteggiarle. L’incremento costante delle infezioni respiratorie sostenute dai patogeni emergenti e interessate dal fenomeno delle resistenze batteriche è oggi un elemento preoccupante che rischia, tra l’altro, di vanificare, in carenza di un adeguamento costante, tutti gli schemi, le linee guida e i protocolli diagnostico-terapeutici elaborati in questi ultimi anni per un razionale trattamento delle patologie pneumoinfettivologiche. Il trattamento delle polmoniti acquisite in comunità (CAP) rappresenta uno degli argomenti più dibattuti in pneumologia negli ultimi anni, sottoposto a continue revisioni, aggiornamenti, precisazioni dottrinarie."
6352,News Timeline Generation: Accounting for Structural Aspects and Temporal Nature of News Stream,"The number of news articles that are published daily is larger than any person can afford to study. Correct summarization of the information allows for an easy search for the event of interest. This research was designed to address the issue of constructing annotations of news story. Standard multi-document summarization approaches are not able to extract all information relevant to the event. This is due to the fact that such approaches do not take into account the variability of the event context in time. We have implemented a system that automatically builds timeline summary. We investigated impact of three factors: query extension, accounting for temporal nature and structure of news article in form of inverted pyramid. The annotations that we generate are composed of sentences sorted in chronological order, which together contain the main details of the news story. The paper shows that taking into account the described factors positively affects the quality of the annotations created."
6353,"Plant,Animal, and Microbe Invasive Species in the United States and World","Approximately 50,000 plant, animal, and microbe invasive species are present in the United States, and an estimated 500,000 plant, animal, and microbe invasive species have invaded other nations of the world. Immediately, it should be pointed out that the US and world agriculture depend on introduced food crops and livestock.Approximately 99 % of all crops and livestock in all nations are intentionally introduced plants, animals, and microbes (Pimentel 2002). Worldwide, the value of agriculture (including beneficial non-indigenous species) is estimated to total $ 30 trillion per year. Other exotic species have been introduced for landscape restoration, biological pest control, sport, and food processing, also contributing significant benefits. Calculating the negative economic impacts associated with the invasion of exotic species is difficult.For a few species, there are sufficient data to estimate some impacts on agriculture, forestry, fisheries, public health, and the natural ecosystem in the US and worldwide. In this article, we estimate the magnitude of the economic benefits, and environmental and economic costs associated with a variety of invasive species that exist in the United States and elsewhere in the world."
6354,Learning the Lessons of the BSE Crisis,"By any standard, the BSE crisis was a most difficult period in the public health of the UK. This period saw a previously unknown TSE emerge in cattle and then transmit to humans, a scenario which by August 2009 had cost 164 people their lives in the UK and which has resulted in an unknown number of other people incubating variant CJD (vCJD). The economic damage caused by this disease has been considerable. In April 2000, the government estimated that by the end of the 2001/2002 financial year, the total net cost of the BSE crisis to the Exchequer would be £3.7 billion (BSE Inquiry Report, Volume 10: 1). Less quantifiable consequences have also stemmed from this crisis. Chief amongst them has been significant damage to the public’s ability to trust the pronouncements of government on matters of food safety and risk. The scientific community has suffered inestimable damage to its expertise and to its capacity to provide objective, consistent scientific advice to the public. With such serious consequences emanating from the BSE affair, it is incumbent on all those who were involved in this tragic episode to reflect on the events that took place and to consider how things could have been done better. Such a reflective exercise has, of course, been conducted by Lord Phillips and his inquiry team who examined all the events that took place during the BSE epidemic and drew a wide-ranging set of lessons from these events. A reflective purpose is also a central motivation of the current chapter. However, the focus of this reflection – scientific reasoning in contexts of uncertainty – is altogether narrower than that undertaken during the public inquiry into BSE. Moreover, the question of reasoning in contexts of uncertainty was omitted from Lord Phillips’ inquiry into BSE and has also been overlooked within the vast literature that has been written on the topic of BSE both before and after this inquiry was conducted."
6355,Acronimi ed abbreviazioni,"“The patient went from the ER to the OR and then to the ICU”. Indubbiamente il lessico dei medici è ricco di abbreviazioni, tanto che gli operatori della sanità in generale ed i radiologi in particolare adoperano perlomeno dieci abbreviazioni per minuto (questa è una statistica fatta in casa, per favore non citatela)."
6356,Environmental Pathology,"Humans are constantly exposed to hazardous pollutants in the environment—for example, in the air, water, soil, rocks, diet, or workplace. Trace metals are important in environmental pathology because of the wide range of toxic reactions and their potential adverse effects on the physiological function of organ systems. Exposures to toxic trace metals have been the subject of numerous environmental and geochemical investigations, and many studies have been published on the acute and/or chronic effects of high-level exposures to these types of agents; however, much fewer data are available concerning the health effects of low-dose chronic exposure to many trace metals. Chronic low-dose exposures to toxic elements such as cadmium and arsenic have been shown to cause these metals to accumulate in tissues over time, leading to multiple adverse effects in exposed individuals."
6357,Dynamic Chromatin Loops and the Regulation of Gene Expression,"Although we have a draft sequence of the human genome, little is known about how the chromatin fiber is packed in three-dimensional (3D) space, or how packing affects function (Jackson 2003). We know packing plays a major role; the rate of transcription of a typical gene can vary over eight orders of magnitude (Ivarie et al. 1983), but deleting local elements like promoters and enhancers reduces expression by less than 5000-fold in transient transfection assays where the 3D “context” is missing. Common sense suggests the fiber cannot be packed randomly, but elucidating what any underlying order might be has proved difficult. First, the foldings of the chromatin fiber have dimensions below the resolution (≈200 nm) of the light microscope (LM) and so can only be seen by electron microscopy (EM), but then the fixation required can distort structure. Second, DNA is so long and packed so tightly it breaks and/or aggregates easily on isolation. Third, chromatin is poised in a metastable state so small charge alterations trigger changes in structure and function, and replacing the natural environment with our buffers often promotes aggregation."
6358,"Specific Serum Markers of IPF: What Is the Significance of KL-6, SP-A, and SP-D?","Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause. It is characterized by the progressive worsening of lung function and has a poor prognosis (median survival is approximately 3 years). However, the clinical course of disease shows considerable individual variability. Therefore, it is important to monitor the clinical course and to predict prognosis for optimal therapy. Serum biomarkers are both less invasive and reproducible diagnostic tools. Useful biomarkers for patients with IPF are strongly coveted; however, to date, there are no biomarkers that are globally known. In Japan, surfactant protein (SP)-A, SP-D, and KL-6 are commonly used as serum markers of interstitial pneumonia, including IPF, in the clinical setting, and empirical data has been accumulated over 10 years. SP-A and SP-D are hydrophilic proteins and members of the collectin family. These collectins have been shown to function as host defense lectins in the lung. KL-6 is a high molecular weight glycoprotein and now classified as a human MUC1 mucin protein. These three proteins are mainly synthesized by alveolar type II cells. The mechanisms of increase for these protein levels in sera of patients with IPF are probably a combination of a loss of epithelial integrity due to injury and an increased mass of type II cells due to hyperplasia. It has been revealed that those proteins are useful for monitoring the clinical course and predicting prognosis as well as for the diagnosis of IPF. In this review article, the molecular structures and biological functions of these biomarkers are outlined, and we discuss the clinical application of these biomarkers for patients with IPF."
6359,Issue Framing: Making Your Concerns a Global Priority,"One of the challenges stakeholders in global public health negotiations face is how to focus media, public and policy-maker attention on a specific public health concern in a way that motivates action. Whether the issue is the threat posed by a new virus (e.g., HIV/AIDS, SARS, H5N1/avian flu, H1N1/swine flu), the impact of the WTO’s TRIPS agreement on the access to essential medicines, or the marketing of unhealthy foods to children, defining the issue in a compelling manner is a key first step in any negotiating process."
6360,Economic Assessment of the Damages Caused by Global Warming,"Damages avoided – the principal benefit of mitigating climate change – are investigated in this chapter, particularly the potential adverse impacts on the primary sectors, biodiversity and human health. A review of studies indicates that climate change is unlikely to have much impact on agriculture and forestry; projected climate change will increase productivity in some regions while reducing it in others, leading to a redistribution of land rents with little impact on overall output. When CO(2) fertilization is taken into account, there might even be an overall increase in primary sector productivity that results in more undisturbed land, thus protecting biodiversity. Other findings in this chapter also run counter to current shibboleths: The biggest threat to polar bears is hunting, not climate change; current trends in Arctic ice extent are not without historical precedent; sea level rise is not an imminent threat; extreme weather events are not increasing; malaria is not only a tropical disease; and human health is a function of income, not climate, with bottom-up models using UN data predicting that death rates from almost all causes will be lower with projected global warming than without it. Meanwhile, integrated assessment models (IAMs) simply assume damages are an arbitrary function of temperature; upon balancing discounted costs and benefits, IAMs can be used to find an optimal path (usually of a carbon tax or emissions cap) for mitigating climate change. It is shown that different assumptions regarding damages, the discount rate, and/or the probability of catastrophic damage can be used to justify completely different policies for addressing global warming. Therefore, a carbon tax that is contingent on the temperature in the troposphere above the tropics – where the earliest indication of global warming is predicted to occur – is considered to be the preferred policy strategy as it should appeal to global warming proponents and skeptics alike. Finally, the Kaya identity is used to demonstrate the policy dilemma that decision makers face in reducing CO(2) emissions."
6361,A Brief History of Advances Toward Health,"Three major discoveries determined the health and history of the human species. The first occurred almost a million years ago, when our hominid precursors discovered how to use fire to cook the meat they had hunted. They found that cooked meat tasted better, it didn’t go bad so quickly, and eating it was less likely to make them ill. Our understanding of nutrition, a basic tenet of public health science, and the art of cooking have been improving ever since."
6362,Diffuse Alveolar Hemorrhage,"Diffuse alveolar hemorrhage[DAH] is a serious condition that can be life threatening. It can be caused by a constellation of disorders which presents with hemoptysis, anemia, and diffuse alveolar infiltrates. Respiratory failure from DAH can be so severe that it has been called an ARDS mimic/imitator. Early recognition is crucial because prompt diagnosis and treatment are required for survival. DAH should be distinguished from other causes of pulmonary hemorrhage caused by localized pulmonary abnormalities and the bronchial circulation. Early bronchoscopy with bronchoalveolar lavage (BAL) is generally required to confirm the diagnosis of DAH and rule out infection. Progressively bloody bronchoalveolar lavage samples can distinguish DAH. Systemic vasculitis is one of the most common causes of DAH and can be pathologically defined by the presence of cellular inflammation, vessel destruction, tissue necrosis, and eventually, organ dysfunction. Corticosteroids and immunosuppressive agents remain the gold standard for the treatment. The following case illustrates a patient who was dependent on dialysis, then presented with hemoptysis. Bronchoscopy demonstrated progressively bloody bronchoalveolar lavage samples consistent with diffuse alveolar hemorrhage. Serologic testing was consistent with microscopic polyangiitis. The patient experienced a clinical remission with cyclophosphamide and corticosteroids."
6363,Prologue,"All living things are associated with a boundary defined ecological niche. Steady state conditions are rarely constant but evolutionary adaptation is too slow to adapt to daily threats so a surrogate variation mechanism is necessary. The genome defines the most basic instructions for life so that a molecular biology perspective provides the foundation for understanding resilience. Variations in the expression of RNA offers rapid variation and this book proposes this is the basis of resilience. This book attempts to illuminate mechanisms of resilience beginning with elaborating threats leading to disruption in steady state conditions. Recognition of threats and defense systems are described followed by adaptive changes in gene expression that refine responses. Finally, environmental conditions are discussed that serve to dampen the adaptive response oscillator to disruptive threats at the level of RNA expression. This prologue is intended to acquaint the reader with my background and the genesis of optimism for an idea that the benefit of transcriptome plasticity is resilience. I grew up in several National Parks, remote regions of the United States that are set aside to preserve natural environments. I attended 12 schools by the time I graduated from high school, a fact that forced me to develop personal resilience. My career path as a scientist followed a path from ecologist to pharmacologist to molecular biologist. I was a professor that transitioned to biotechnology ensuring research subjects involving very diverse in subject matter so I appreciate the value of plasticity."
6364,Viral Integration and Consequences on Host Gene Expression,"Upon cell infection, some viruses integrate their genome into the host chromosome, either as part of their life cycle (such as retroviruses), or incidentally. While possibly promoting long-term persistence of the virus into the cell, viral genome integration may also lead to drastic consequences for the host cell, including gene disruption, insertional mutagenesis and cell death, as well as contributing to species evolution. This review summarizes the current knowledge on viruses integrating their genome into the host genome and the consequences for the host cell."
6365,Emergency Logistics Distribution Optimization Model and Algorithm in Disaster Chain,"Emergency logistics distribution of disasters and accidents is an effective means to reduce the loss of lives and property. On the condition of meeting the timeliness requirement of emergency logistics, the study of emergency logistics distribution can rationally schedule vehicle, substantially reduce the vehicle allocation time and the logistical cost. Through the analysis of the characteristics of rescue emergency logistics, the system structure of emergency logistics distribution is proposed. After the material distribution optimization model for emergency logistics is established, an improved genetic algorithm is designed to solve this problem. In improved genetic algorithm, the best individual reservations, roulette selection, blend crossover, and blend mutation have been adopted to avoid premature convergence and enhance the process efficiency. A numeric example is presented to validate the feasibility and effectiveness of the model and its algorithm."
6366,Respiratory Syncytial Virus and Other Pediatric Respiratory Virus Infections,"Infants and young children undergoing their primary infection with common human respiratory viruses are at risk of serious, even life-threatening, lower respiratory tract infection, A multiplicity of viruses infect the human respiratory tract but a relatively small number are responsible for the majority of significant illness. Of these the most commonly diagnosed in the pediatric population is respiratory syncytial virus (RSV), which infects essentially all children in their first or second year of life, bringing approx 1% into the hospital with bronchiolitis or pneumonia (1). Children with underlying cardiac or pulmonary disease, or born prematurely are particularly at risk. The virus also causes problems in the immunosuppressed and mortality rates are alarmingly high for RSV pneumonia after bone marrow transplantation (2). The availability of therapy with ribavirin (3) or high titer anti-RSV γ-globulin (4), which may be of benefit in these at risk groups, places a premium on rapid and accurate, but cost effective, diagnosis."
6367,Interleukin-35: A Novel Mediator of Peripheral Tolerance,"Interleukin-35 is a potent suppressive cytokine of the IL-12 family. Although other members of the IL-12 family are produced mainly by antigen-presenting cells (APCs), IL-35 is produced by regulatory T (Treg) cells and suppresses cell proliferation. It has been shown to play an important role in many disease models and has been recently shown to have additional functions aside from inhibition of proliferation, including inducing its own expression in non-Treg cells. In this chapter, we discuss the history and current status of IL-35 biology, as well as suggest where the field might move in the future."
6368,Edible Rabies Vaccines,"Rabies has been one of the most feared diseases throughout history. Human rabies remains an important public health problem in many developing countries. The WHO reports that more than 55,000 people die of this disease every year. Most of these cases occur in developing countries. In most Latin American countries, the major reservoirs of rabies are the dog and the hematophagous bat (Desmodus rotundus), which is present in the tropical and subtropical areas from Northern Mexico to Northern Argentina and Chile and transmits the disease to cattle. One of the better options for controlling rabies is vaccination. The expression of rabies virus G protein in different plant systems for developing an oral rabies vaccine could reduce costs of production and distribution and would be convenient for developing countries where the disease is endemic."
6369,Diagnosis and Assessment of Microbial Infections with Host and Microbial microRNA Profiles,"Biomarkers are continuously being sought in the field of diagnostic microbiology for the laboratory diagnosis and assessment of microbial infections. A set of clinical and laboratory criteria necessary for an ideal diagnostic marker of infection have previously been proposed by Ng and his colleagues [1]. According these criteria, an ideal biomarker should possess at a minimum the following characteristics: (a) biochemically, a biomarker should be stable and remain significantly deregulated in the body fluid compartment for at least 12–24 h even after commencement of appropriate treatment that may allow an adequate time window for specimen collection or storage without significant decomposition of the active compound until laboratory processing; (b) its concentration should be determined quantitatively and the method of measurement should be automatic, rapid, easy, and inexpensive; (c) the collection of a specimen should be minimally invasive and require a small volume (e.g., <0.5 mL blood). Numerous biomarkers have been found and tested in clinical practice. Currently, microRNA (miRNA) molecules are without a doubt the biomarkers with the greatest potential capacities in the diagnostic microbiology field."
6370,Probe Selection with Fault Tolerance,"Microarray techniques play an important role for testing some reactions of diseases which are caused by viruses. Probes in microarray are one kind of the most important materials. Usually, scientists use a unique probe for marking a special target sequence. Thus, for identifying n different viruses, we need n different probes. Recently, some researchers study non-unique probes to identify viruses by using less number of probes. In this case, a virus can be identified by a combination of some probes. In this paper, we study the problem of finding a set of probes that can identify all the given targets. We consider the k-fault tolerance selection of probes. That is, if any k probes fail, then we still can identify each target. We propose a practical algorithm for this k-fault tolerance probe selection problem. Some experiments are studied on SARS, H5N1, and so on."
6371,Gli antagonisti dei recettori AT1,"Nella storia del SRA, la sintesi degli antagonisti dei recettori AT1 può essere considerata nello stesso tempo come un punto di arrivo ed un punto di partenza, perché essa ha sicuramente contribuito a rendere più efficace e razionale il trattamento di numerose patologie, ma - proprio per i risultati ottenuti, spesso inaspettati - ha dato anche il via a nuove ricerche, necessarie per chiarire il meccanismo con cui funzionano realmente questi antagonisti: essi infatti si sono dimostrati efficaci non solo nella IA e nello scompenso cardiaco (cioè in condizioni in cui è sicuramente coinvolto il SRA) (Pitt 2002; Ruddy e Kostis 2005), ma anche in altre patologie, che non appaiono legate in via primitiva ad un disordine di questo sistema, come lo stroke, l’aterosclerosi, la nefropatia diabetica, il decadimento delle funzioni cognitive e perfino di quelle sessuali (Koh e coll. 2003; Sierra e de la Sierra 2005)."
6372,A Model for Characterizing Annual Flu Cases,"Influenza outbreaks occur seasonally and peak during winter season in temperate zones of the Northern and Southern hemisphere. The occurrence and recurrence of flu epidemics has been alluded to variability in mechanisms such temperature, climate, host contact and traveling patterns [4]. This work promotes a Gaussian–type regression model to study flu outbreak trends and predict new cases based on influenza–like–illness data for France (1985–2005). We show that the proposed models are appropriate descriptors of these outbreaks and can improve the surveillance of diseases such as flu. Our results show that limited data reduces our ability to predict unobserved cases. Based on laboratory surveillance data, we prototype each season according to the dominating virus (H3N2, H1N1, B) and show that high intensity outbreaks are correlated with early peak times. These findings are in accordance with the dynamics observed for influenza outbreaks in the US."
6373,Accelerating Dock6’s Amber Scoring with Graphic Processing Unit,"In the drug discovery field, solving the problem of virtual screening is a long term-goal. The scoring functionality which evaluates the fitness of the docking result is one of the major challenges in virtual screening. In general, scoring functionality in docking requires large amount of floating-point calculations and usually takes several weeks or even months to be finished. This time-consuming disadvantage is unacceptable especially when highly fatal and infectious virus arises such as SARS and H1N1. This paper presents how to leverage the computational power of GPU to accelerate Dock6 [1]’s Amber [2] scoring with NVIDIA CUDA [3] platform. We also discuss many factors that will greatly influence the performance after porting the Amber scoring to GPU, including thread management, data transfer and divergence hidden. Our GPU implementation shows a 6.5x speedup with respect to the original version running on AMD dual-core CPU for the same problem size."
6374,The Aerobiology Pathway,
6375,Population Mobility and the Geography of Microbial Threats,
6376,TCR Analyses: T-cell receptor CDR3 analysis: Molecular fingerprinting of the T-cell receptor repertoire,"T-cells play a crucial role in immune surveillance against transformed cells and intracellular infections; they are involved in auto-immune reactions. They recognize their targets, i.e. MHC / peptide complexes, trough the T-cell receptor. TCR usage determines the molecular interaction of the immune system with biologically relevant MHC/peptide molecules. The TCR coding genes (variable, diversity and junctional) determine the molecular composition of the TCR alpha and beta heterodimer. The random association of the VDJ genes constitutes the complementarity determining region 3 (CDR3) responsible for antigen recognition and TCR specificity. The molecular composition of a T-cell population can be objectively defined by measuring the CDR3 region. Qualitative and quantitative comparisons of the TCR composition in different anatomic compartments, or longitudinally over time, allow to asses the entire TCR repertoire. This methodology can be supplemented with functional T-cell based assays and aids to objectively describe any alteration in the T-cell pool. TCR CDR3 analysis is useful in immunomonitoring, e.g. examining patients after BMT or solid organ transplantation, patients with HAART therapy, or patients receiving molecularly defined vaccines."
6377,Implications of Human Microbiome Research for the Developing World,"The human microbiome refers to all of the species that inhabit the human body, residing both on and in it. Over the past several years, there has been a significantly increased interest directed to the understanding of the microorganisms that reside on and in the human body. These studies of the human microbiome promise to reveal all these species and increase our understanding of the normal inhabitants, those that trigger disease and those that vary in response to disease conditions. It is anticipated that these directed research efforts, coupled with new technological advances, will ultimately allow one to gain a greater understanding of the relationships of these species with their human hosts. The various chapters in this book present a range of aspects of human microbiome research, explain the scientific and technological rationale, and highlight the significant potential that the results from these studies hold. In this chapter, we begin to address the potential and long-term implications of the knowledge gained from human microbiome research (which currently is centered in the developed world) for the developing world, which has often lagged behind in the benefits of these new technologies and their implications to new research areas."
6378,Early Outbreak Detection Using an Automated Data Feed of Test Orders from a Veterinary Diagnostic Laboratory,"Disease surveillance in animals remains inadequate to detect outbreaks resulting from novel pathogens and potential bioweapons. Mostly relying on confirmed diagnoses, another shortcoming of these systems is their ability to detect outbreaks in a timely manner. We investigated the feasibility of using veterinary laboratory test orders in a prospective system to detect outbreaks of disease earlier compared to traditional reporting methods. IDEXX Laboratories, Inc. automatically transferred daily records of laboratory test orders submitted from veterinary providers in Ohio via a secure file transfer protocol. Test products were classified to appropriate syndromic category using their unique identifying number. Counts of each category by county were analyzed to identify unexpected increases using a cumulative sums method. The results indicated that disease events can be detected through the prospective analysis of laboratory test orders and may provide indications of similar disease events in humans before traditional disease reporting."
6379,Impact of Disasters and Disaster Risk Management in Singapore: A Case Study of Singapore’s Experience in Fighting the SARS Epidemic,"Singapore is vulnerable to both natural and man-made disasters alongside its remarkable economic growth. One of the most significant disasters in recent history was the Severe Acute Respiratory Syndrome (SARS) epidemic in 2003. The SARS outbreak was eventually contained through a series of risk mitigating measures introduced by the Singapore government. This would not be possible without the engagement and responsiveness of the general public. This chapter begins with a description of Singapore’s historical disaster profiles, the policy and legal framework in the all-hazard management approach. We use a case study to highlight the disaster impacts and insights drawn from Singapore’s risk management experience with specific references to the SARS epidemic. The implications from the SARS focus on four areas: staying vigilant at the community level, remaining flexible in a national command structure, the demand for surge capacity, and collaborative governance at regional level. This chapter concludes with a presence of the flexible command structure on both the way and the extent it was utilized."
6380,The 2003 SARS Outbreaks in Taiwan,"Severe acute respiratory syndrome (SARS) is caused by SARS-associated coronaviruses (SARS-CoVs) (Drosten et al., 2003; Fouchier et al., 2003; Peiris et al., 2003b; Ksiazek et al., 2003). The first known outbreak of SARS occurred in China’s Guangdong province in November, 2002 (Chinese SARS Molecular Epidemiology Consortium, 2004). By August 7 of the following year, SARS had spread to more than 30 countries, affecting 8,096 people and resulting in 774 deaths worldwide (World Health Organization, 2004). In 2003, Taiwan experienced a series of SARS outbreaks and the Municipal Hoping Hospital (referred to hereafter as HP) in Taipei City suffered the first and the most serious outbreak of SARS-CoV nosocomial infections: 137 probable cases and 26 deaths (Division of Surveillance and Investigation, Center for Disease Control, Taiwan, 2003; Lan et al., 2005b). According to the Center for Disease Control (CDC) in Taiwan, 364 of the 664 probable Taiwanese SARS cases reported to the World Health Organization were confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) and/or neutralizing antibody tests (Center for Disease Control, 2003a). In this chapter, we will discuss the molecular and clinical epidemiology of SARS infection in Taiwan during 2003."
6381,Animals and Mechanisms of Disease Transmission,"More than 60% of human infectious diseases are shared with domestic or wild animals, with over a billion illnesses in the global population and millions of deaths each year. It is estimated that 75% of emerging infectious diseases are zoonoses. There is a great diversity of animals, terrestrial and marine vertebrates, which can directly or indirectly transmit a wide variety of microbial pathogens to humans. This chapter reviews the means of transmission by different groups of animals [pets, farm animals, and wildlife] that can result in zoonoses. The diverse range of infectious agents encompasses the gamut of microbes that can affect humans: bacteria [including rickettsiae and mycobacteria], viruses, fungi, parasites [protozoa, metazoan, and helminths], and prions. Infectious agents can be transmitted by animals by several different mechanisms: fecal-oral route with foodborne zoonoses or accidentally through contamination of drinking water or the unwashed hands, direct contact with or without bites or scratches, indirectly through various vectors [mosquitos, sandflies, fleas, and ticks], and incidentally by environmental contamination with animal pathogens, including aerosol of dried infected animal excrements."
6382,Community Acquired Pneumonia,"Early identification of patients with severe community-acquired pneumonia (SCAP) who require ICU care is important as delayed transfer is associated with increased mortality. In such patients, aggressive diagnostic testing is warranted given the increased probability of detecting a pathogen resistant to usual empirical therapy. Despite aggressive culture and other routine diagnostic testing, the majority of cases of SCAP remain without a definitive etiology. Early coverage of S. pneumoniae, methicillin-susceptible S. aureus, and L. pneumophila is crucial and adequate in the absence of risk factors for drug-resistant pathogens. Combination antibiotics with a beta-lactam and either a macrolide or fluoroquinolone are strongly recommended. When methicillin-resistant Staphylococcus aureus is suspected, linezolid is superior to vancomycin. Several aspects of managing severe CAP remain without consensus, including risk factors for multidrug resistant pathogens, need for suppression of exotoxin production, the role of procalcitonin, and adjunctive treatment with corticosteroids and extracorporeal membrane oxygenation."
6383,Viral Genomics: Implications for the Understanding and Control of Emerging Viral Diseases,"In recent decades, many infectious diseases have significantly increased in incidence and/or geographic range, in some cases impacting heavily on human, animal or plant populations. Some of these ‘emerging infectious diseases’ are associated with pathogens that have appeared in populations for the first time as a result of cross-species transmission (e.g. human immunodeficiency virus—acquired immunodeficiency syndrome (HIV-AIDS), severe acute respiratory syndrome (SARS)), while others were previously known but are rapidly increasing in incidence or geographic range as a result of underlying epidemiological changes (e.g. multi-drug resistant Staphylococcus aureus (MRSA) infection, dengue, West Nile encephalitis, foot and mouth disease, cassava mosaic disease). The latter include prominent diseases as tuberculosis, malaria and yellow fever that were once on the decline but are now ‘re-emerging diseases’."
6384,Exposure,
6385,Risk Assessment for Airworthiness Security,"The era of digital avionics is opening a fabulous opportunity to improve aircraft operational functions, airline dispatch and service continuity. But arising vulnerabilities could be an open door to malicious attacks. Necessity for security protection on airborne systems has been officially recognized and new standards are actually under construction. In order to provide development assurance and countermeasures effectiveness evidence to certification authorities, security objectives and specifications must be clearly identified thanks to a security risk assessment process. This paper gives main characteristics for a security risk assessment methodology to be integrated in the early design of airborne systems development and compliant with airworthiness security standards."
6386,Multiorganinfektionen — komplexe klinisch infektiologische Krankheiten,"Wir verfügen über ein hochwirksames Arsenal an Antibiotika, wir können auf der Suche nach einem Fokus mit bildgebenden, diagnostischen Verfahren jeden Bereich des menschlichen Körpers darstellen und ggf. punktieren, und doch sind unsere therapeutischen Erfolge bei der Sepsis nach wie vor enttäuschend. Die Letalität der schweren Sepsis und des septischen Schocks liegt unverändert hoch bei 40–70%."
6387,Adult-Onset Still’s Disease,"Adult-onset Still’s disease (AOSD) is a rare systemic, autoinflammatory disorder that often presents in adolescence and early adulthood with fever, rash, and polyarthritis. There are significant genetic and clinical similarities with systemic juvenile idiopathic arthritis (sJIA) with a different chronological disease onset. The disease can have many protean characteristics leading to delays in diagnosis. Treatment includes corticosteroids; traditional immunomodulators, such as methotrexate; and targeted biologic treatments that include IL-1 and IL-6 inhibitors."
6388,Infektionskrankheiten,"Virale Infektionen zählen immer noch weltweit, besonders in den Entwicklungsländern, zu den häufigsten Todesursachen. Durch internationale systematische Impfkampagnen der WHO ist die Welt pockenfrei geworden. Die Inzidenz der Infektionen, die durch eine Immunprophylaxe verhindert werden können, wurde drastisch gesenkt (Poliomyelitis, Tollwut). In den 80er Jahren trat eine neue Tierseuche beim Rind auf, die bovine spongyforme Enzephalopathie (BSE), die mit der neuen Variante der Creutzfeldt-Jakob-Krankheit (vCJK) in Zusammenhang steht (Nahrungskette). Im selben Zeitraum begann die explosionsartige weltweite Verbreitung eines neuen Retrovirus, des HIV. Trotz intensiver Aufklärungskampagnen und neuen therapeutischen Möglichkeiten (hochaktive antiretrovirale Therapie, HAART) ist es nicht gelungen, die weitere Ausbreitung der HIV-Infektion zu verhindern."
6389,Two Critical Issues in Quantitative Modeling of Communicable Diseases: Inference of Unobservables and Dependent Happening,"In this chapter, we discuss two critical issues which must be remembered whenever we examine epidemiologic data of directly transmitted infectious diseases. Firstly, we would like the readers to recognize the difference between observable and unobservable events in infectious disease epidemiology. Since both infection event and acquisition of infectiousness are generally not directly observable, the total number of infected individuals could not be counted at a point of time, unless very rigorous contact tracing and microbiological examinations were performed. Directly observable intrinsic parameters, such as the incubation period and serial interval, play key roles in translating observable to unobservable information. Secondly, the concept of dependent happening must be remembered to identify a risk of an infectious disease or to assess vaccine efficacy. Observation of a single infected individual is not independent of observing other individuals. A simple solution for dependent happening is to employ the transmission probability which is conditioned on an exposure to infection."
6390,Pathophysiology of Acute Respiratory Failure in Children with Bronchiolitis and Effect of CPAP,"Acute bronchiolitis is the most common lower respiratory tract infection (LRTI) during the first year of life. Respiratory syncytial virus (RSV) infection is the most prevalent virus found in these children, accounting for 60–80 % of cases. The rate of hospitalization is less than 2 %. Up to 8 % of those hospitalized require ventilatory support [1, 2]."
6391,Quantitative Real-Time PCR,"Changes in mRNA expression levels occur during physiological and pathological processes in the cardiovascular system. An increase inDNAtranscription results in increasedmRNAlevels and will subsequently result in increased protein levels that regulate processes inside and outside the cell. To determine alterations in mRNA levels, traditional methods such as Northern blot and ribonuclease protection assay can be used; however, large amounts of RNA are necessary and the methods are very labor intensive. In this chapter, we focus on the newest advancements in reverse transcription polymerase chain reaction (rt-pcr) technology, the real-time PCR or quantitative PCR, using small amounts of RNA to determine expression levels.We discuss the technique in general and describe two different approaches."
6392,Viral Genome Packaging Machines: An Overview,
6393,Production of Recombinant Pharmaceutical Proteins,"The proteins produced in the body control and mediate the metabolic processes and help in its routine functioning. Any kind of impairment in protein production, such as production of mutated protein, or misfolded protein, leads to disruption of the pathway controlled by that protein. This may manifest in the form of the disease. However, these diseases can be treated, by supplying the protein from outside or exogenously. The supply of active exogenous protein requires its production on large scale to fulfill the growing demand. The process is complex, requiring higher protein expression, purification, and processing. Each product needs unique settings or standardizations for large-scale production and purification. As only large-scale production can fulfill the growing demand, thus it needs to be cost-effective. The tools of genetic engineering are utilized to produce the proteins of human origin in bacteria, fungi, insect, or mammalian host. Usage of recombinant DNA technology for large-scale production of proteins requires ample amount of time, labor, and resources, but it also offers many opportunities for economic growth. After reading this chapter, readers would be able to understand the basics about production of recombinant proteins in various hosts along with the advantages and limitations of each host system and properties and production of some of the important pharmaceutical compounds and growth factors."
6394,Telencephalon: Neocortex,"The neocortex is an ultracomplex, six-layered structure that develops from the dorsal palliai sector of the telencephalic hemispheres (Figs. 2.24, 2.25, 11.1). All mammals, including monotremes and marsupials, possess a neocortex, but in reptiles, i.e. the ancestors of mammals, only a three-layered neocortical primordium is present [509, 511]. The term neocortex refers to its late phylogenetic appearance, in comparison to the “palaeocortical” olfactory cortex and the “archicortical” hippocampal cortex, both of which are present in all amniotes [509]."
6395,Pathogen Detection in the Genomic Era,"In the 21st century, one of the greatest challenges to public health and clinical microbiologists is the rapid detection and identification of emerging and reemerging pathogens. Complex factors such as genetic variation in the host and pathogen, environmental changes, population pressures, and global travel can all influence the emergence of infectious diseases. The SARS epidemic of 2003 highlighted the potential of an emerging pathogen to spread globally in a very short time frame (Peruski and Peruski, 2003). The diagnostics of such infectious diseases has been greatly affected in the past 20 years. No longer is cultivation and microscopy the only means of detecting infectious agents. With the introduction of molecular diagnostics, the ability to detect minute amounts of microbial nucleic acids in clinical specimens has revolutionized clinical microbiology. In particular, the utility of PCR allows the detection and quantitation of specific agents in a matter of hours. PCR sequencing of specific segments of nucleic acid allows for the determination of specific drug resistance that now aids in guiding viral therapies."
6396,Ademhaling,"Dyspneu is een subjectieve sensatie van inefficiënte ventilatie. Het betreft een van de meest voorkomende klachten waarmee patiënten zich op een SEH melden. De opname-indicaties zijn zeer divers. De behandeling is vooral gericht op onderliggende pathofysiologische mechanismen. Tracheobronchitis is een van de meest gestelde diagnoses; verder worden toegelicht: pneumonie, pneumothorax, longembolie, asthma bronchiale, ARDS, longoedeem, pleura-effusie en hemoptoë. Een patiënt met een acute bovensteluchtwegobstructie krijgt, zolang op gespecialiseerde hulp wordt gewacht, een zo hoog mogelijke concentratie zuurstof toegediend en er moet een noodtracheostomieset klaarstaan. Met niet-invasieve monitoring kan men de ingestelde behandeling evalueren; voor diagnosticering blijven de anamnese en het lichamelijk onderzoek van belang. Indien onverwacht een moeilijke intubatie vereist is, moeten alternatieve plannen beschikbaar zijn. Er kan een reanimatiesituatie ontstaan waarbij artsen én verpleegkundigen gerechtigd zijn alle benodigde maatregelen te nemen. Idealiter beschikt elke SEH over een algoritme/protocol dat men volgt bij patiënten met een ‘moeilijke luchtweg’."
6397,Planning and Managing Mass Prophylaxis Clinic Operations,"Along with their federal, tribal, and state counterparts, local health departments, as part of the public health system, are on the front lines to assist the community to prepare, respond, and recover from public health emergencies. Local health departments have many roles during a public health emergency; one important role is to create a successful mass prophylaxis operation for the public using points of dispensing (PODs). This chapter outlines the specific functions necessary for a successful and efficient POD operation. A step-by-step process is described and can be used both for emergency and everyday planning of POD operations. In addition, researchers continue to work to solve many of the complex challenges facing local health departments attempting to prevent morbidity and mortality during a biological disaster. A discussion of some of these challenges and opportunities for future research is outlined in this chapter."
6398,Acute and chronic liver insufficiency,
6399,Novel Natural Products From Rainforest Endophytes,"Endophytic microorganisms are found in virtually every higher plant on earth. These organisms reside in the living tissues of the host plant and do so in a variety of relationships, ranging from symbiotic to pathogenic. Endophytes may contribute to their host plant by producing a plethora of substances that provide protection and survival value to the plant. Ultimately, these compounds, once isolated and characterized, may also have potential for use in modern medicine. Novel antibiotics, antimycotics, immunosuppressants, and anticancer compounds are only a few examples of what has been found after the isolation and culturing of individual endophytes followed by purification and characterization of some of their natural products. The potential of finding new drugs that may be effective candidates for treating newly developing diseases in humans is great."
6400,The Role of the Environment and Colonization in Healthcare-Associated Infections,"Healthcare-associated infections (HAIs) can be caused by endogenous host microbial flora or by exogenous microbes, including those found in the hospital environment. Efforts to decrease endogenous pathogens via decolonization and skin antisepsis may decrease the risk of infection in some settings. Controlling the spread of potential pathogens from the environment requires meticulous attention to cleaning and disinfection practices. In addition to selection of the appropriate cleaning agent, use of tools that assess the adequacy of cleaning and addition of no-touch cleaning technology may decrease environmental contamination. Hand hygiene is also a critical component of preventing transmission of pathogens from the environment to patients via healthcare worker hands."
6401,Kryptosporidien,"Cryptosporidium parvum, Cryptosporidium hominis"
6402,Pulmonary Vascular Disease,"The pulmonary vasculature is an anatomic compartment that is frequently overlooked in the histologic review of lung biopsy samples, other than those obtained specifically to assess pulmonary vascular disease.1 Though often of a nonspecific nature, the histologic pattern of vascular remodeling may at times suggest its underlying pathogenesis and provide clues to the cause of pulmonary hypertension.2 Disproportionately severe vascular pathology may further indicate alternate disease processes, such as congestive heart failure or thromboemboli, contributing to the patient’s overall respiratory condition."
6403,"Primates, Pathogens, and Evolution: A Context for Understanding Emerging Disease","The world is rife with potential pathogens. Of those that infect humans, it is estimated that roughly 20 % are of nonhuman primate origin. The same ease characterizes pathogen transmission in the other direction, from humans to nonhuman primates. This latter problem has increasingly serious ramifications for conservation efforts, as growing numbers of ecotourists and researchers serve as potential vectors of disease. Here, we present an analysis of major cross-species transmission events between human and nonhuman primates. In particular, we consider HIV and malaria as case studies in which nonhuman primate pathogens emerged and became permanent fixtures in human populations. The human practices that facilitate such events are considered, as well as the evolutionary consequences of these events. In addition, we describe human-to-nonhuman primate transmission events and discuss the potential of human pathogens to adapt to nonhuman primate hosts. The topic of emerging infections is addressed, in both human and nonhuman species, in light of changing patterns of contact and novel adaptations on the part of pathogens and hosts."
6404,Bengalisches Fieber,"Ein 43-jähriger in Deutschland lebender Bengale wird am Wochenende im Februar 2004 mit dem Rettungstransportdienst in die Notaufnahme des Krankenhauses gebracht. Seit 3 Tagen leidet er unter zunehmendem Husten, Auswurf, Luftnot, Fieber und atemabhängigen Thoraxschmerzen. Der Hausarzt hatte bereits Roxithromycin verordnet, hierunter verschlechterte sich die Luftnot jedoch weiter. Nach Angaben der Ehefrau war der Patient 14 Tage zuvor von einem mehrwöchigen Aufenthalt in Dhaka/Bangladesh mit einem Zwischenstop in Dubai/Vereinigte Arabische Emirate zurückgekommen."
6405,Kretafieber,
6406,"Imports, Exports and Foreign Businesses in Japan","This chapter discusses imports, exports, and foreign firms’ investments in Japan. Imports to Japan total to about US$ 812 billion and exports from Japan total to about US$ 697 billion in the year of 2013. Japan consists of two economically vivid areas, Kanto consisting of Tokyo, Saitama, Kawasaki and Yokohama; and the Kansai area consisting of Osaka, Kyoto and Kobe. Both areas are discussed separately. It will be shown that Chinese trade has a bigger impact on Kansai than on Kanto area. In the next part, information about foreign affiliated firms doing business in Japan will be demonstrated by expanding on Japanese External Trade Organization data. Kansai will also be discussed separately here. At the end of the chapter, some examples of success stories will be given of foreign affiliated firms located in the Kansai region."
6407,Agent-Based Simulation Tools in Computational Epidemiology,"An agent-based approach is evaluated for its applicability as a new modeling technology in the emerging area of Computational Epidemiology, a research domain that attempts to synergistically unite the fields of Computer Science and Epidemiology. A primary concern of epidemiologists is investigating the spread of infectious diseases. Computer Scientists can provide powerful tools for epidemiologists to study such diseases. The existing simulation approaches available to epidemiologists are fast becoming obsolete, with data being stored in newer formats like GIS formats. There is an urgent need for developing computationally powerful, user-friendly tools that can be used by epidemiologists to study the dynamics of disease spread. We present a survey of the state-of-the-art in agent-based modeling and discuss the unique features of our chosen technique. Our agent-based approach effectively models the dynamics of the spread of infectious diseases in spatially-delineated environments by using agents to model the interaction between people and pathogens. We present preliminary results of modeling an actual tuberculosis disease outbreak in a local shelter. This model is an important step in the development of user-friendly tools for epidemiologists."
6408,Thorax,"■ The respiratory system (Fig. 16.1) arises as an out-pouching from the primitive lung bud at the 3rd week of embryonic life. Between the 6th and 16th weeks of gestation, rapid bronchial division beyond the subsegmental level occurs ■ Alveoli begin to develop at the 24th week of gestation by out-pouching, so that by 8 years of age the adult number of approximately 300 million alveoli is attained ■ Each lung is divided into 10 segments (Fig. 16.2). For certain localized lesions segmental and subsegmental resections rather than lobectomy should be performed ■ The pulmonary lymph nodes are located at points of division of segmental bronchi or at the bifurcations of the pulmonary artery. The hilar nodes are allocated along the main bronchi. The interlobar nodes are situated in the angles of the main bronchi into the lobar bronchi ■ The child’s thorax is more flexible than that of adults"
6409,A History of Zoonoses and Sapronoses and Research into Them,The history of these diseases and of their study is given in a brief chronological review of the most important events (important epidemics) and milestones of their study (relevant microbiological discoveries). In some historical data it is difficult to differentiate between the year of discovery and the year of its publication.
6410,Introduction to Drugs and Drug Targets,"This chapter lays out some formal definitions of a drug or medicine and introduces the concept of a drug target. It then describes the wide range of drug types that are being produced by the biopharmaceutical industry. These include orally available drugs, proteins, nucleic acids, vaccines and stem cells. Some background on all of these different types of molecule is provided to create a foundation for the remainder of the book."
6411,Using Geographic Information for Disease Surveillance at Mass Gatherings,"Mass gatherings present the medical community with an excellent window of opportunity to study infectious diseases that can be transmitted over long distances. This is because the venue of a mass gathering usually does not change year-to-year. As a result, special attention can be given to the public health risks that are introduced by travelers from around the world into these mass gatherings. Travelers can also be infected with diseases that are endemic in the host country and transport the locally acquired infectious diseases to their home environments. Therefore, mass gatherings can be thought of as global-to-local-to-global events because of the initial convergence of global populations and the subsequent divergence of populations throughout the world. This chapter discusses three active areas of geographic research that have emerged from our understanding of disease surveillance at mass gatherings: the role of transportation and population geographies in disease surveillance; the spatial and temporal dimensions of environmental geography in the spread of disease; and the advances in GIScience that provide real-world surveillance and monitoring of disease and injuries at mass gatherings."
6412,Molecular Differential Diagnoses of Infectious Diseases: Is the Future Now?,"The clinical presentations for most infectious agents are often not specific enough to allow for a definitive diagnosis. Coughing and fever, for example, are symptoms that may be caused by many different bacterial or viral infections. Thus, for better treatment and disease control, a molecular differential diagnostic (MDD) assay that can identify, differentiate, and pinpoint the offending pathogen associated with a clinical syndrome (Fig. 27.1) is needed. MDDs are essential tools for effective infectious disease surveillance, biodefense, and personalized medicine."
6413,No Lasting Stability,"In as much as the main reason for the establishment of the 1986 Public Health Enquiry was the identification of problems concerned with the control of communicable disease, it was important to ensure that its recommendations were being implemented. By a curious set of coincidences, I found myself almost immediately deeply involved in many of the activities flowing from the Government’s acceptance of the recommendations. Having indicated my intention to take premature retirement from Coventry Health Authority in 1990 in order to develop my teaching activities at Warwick University, where I had been a visiting senior lecturer in community medicine for 10 years, I found that the fact that I was immediately available for part-time work led to a number of interesting invitations from a variety of organisations all of which were focused on one or other aspect of implementing the Acheson recommendations."
6414,An Evaluation of Gene Set Analysis for Biomarker Discovery with Applications to Myeloma Research,"In this paper, we evaluate 15 methods for gene set analysis in microarray classification problems. We employ four datasets from myeloma research and three types of biological gene sets, encompassing a total of 12 scenarios. Taking a two-step approach, we first identify important genes within gene sets to create summary gene set scores, we then construct predictive models using the gene set scores as predictors. We propose two powerful linear methods in addition to the well-known SuperPC method for calculating scores. By comparing the 15 gene set methods with methods used in individual-gene analysis, we conclude that, overall, the gene set analysis approach provided more accurate predictions than the individual-gene analysis."
6415,15 Vlekjesziekten,"Infecties die met exantheem gepaard gaan, behoren tot de meest voorkomende ziekten op de kinderleeftijd. Historisch gezien worden deze ziekten onderverdeeld in de eerste tot en met de zesde ziekte, in de volgorde waarin ze zijn ontdekt. Zo is mazelen (morbilli) de ‘eerste ziekte’, roodvonk de ‘tweede ziekte’ en rodehond (rubella) de ‘derde ziekte’."
6416,Transition Feasibility and Implications for Stakeholders,
6417,Interesting case histories,"No crisis is ever exactly the same as any other. There are always variations and different factors to be taken into consideration, even in incidents which appear to be identical. But much can be learned from case histories. The details of those which follow have been culled from published information or personal experience. Some have been selected as interesting examples of how a problem has been tackled or even exploited. Others have been chosen because, in the view of the author, they have been watersheds in establishing guiding principles in the way in which crises should be handled. Some of the content may even be hearsay, but this is felt to be important to convey the atmosphere at the time."
6418,Radiofrequency Biology: In vivo,
6419,Viral Infections in ICU Patients,
6420,Nonneoplastic Pleural Disease,"This chapter discusses the etiology, epidemiology, and laboratory features of pleural effusions, and the pathologic features of selected pleural diseases."
6421,Nosokomiale Pneumonie – Antibiotikatherapie und hygienische Interventionsstrategien,Die Pneumonie ist auch in unserer Zeit eine schwere Infektionskrankheit. Sie ist eine der häufigsten infektiösen Todesursachen der westlichen Industrieländer und steht an 3. Stelle unter den Infektionskrankheiten. Jede 4. ärztlich diagnostizierte Pneumonie ist nosokomial erworben. Nosokomiale Pneumonien führen neben einer verlängerten Morbidität und erhöhten Letalität zu einer Verlängerung der Krankenhausverweildauer und zu erheblichen Kosten.
6422,Protein-protein interactions: analysis and prediction,"Proteins represent the tools and appliances of the cell — they assemble into larger structural elements, catalyze the biochemical reactions of metabolism, transmit signals, move cargo across membrane boundaries and carry out many other tasks. For most of these functions proteins cannot act in isolation but require close cooperation with other proteins to accomplish their task. Often, this collaborative action implies physical interaction of the proteins involved. Accordingly, experimental detection, in silico prediction and computational analysis of protein-protein interactions (PPI) have attracted great attention in the quest for discovering functional links among proteins and deciphering the complex networks of the cell."
6423,"Aandoeningen van ademhalingsstelsel, mediastinum en thoraxwand","Aet. Holtevorming in een ontstekingsproces dat met verettering gepaard gaat en dat o.a. ontstaat na bacteriële infecties (stafylokokken) eventueel in aansluiting op infecties met influenzavirus (grieppneumonie), bij patiënten met een geringe weerstand tegen infecties (klebsiellapneumonie), bij slechte mondhygiëne, na verslikken met aspiratie, bij verdrinking, verminderd bewustzijn, longinfarct en septische embolen, maar ook in een obstructiepneumonie achter een bronchusobstructie (bijv. bronchuscarcinoom of corpus alienum) of zonder bekende oorzaak. Geen voorkeurlokalisatie, behalve bij verslikken: dan in de dorsobasale segmenten, voornamelijk rechts."
6424,Management of Severe Malaria,"Imported malaria is the principal, preventable, life-threatening infection among US travelers. Using a case scenario, we discuss the most recent information on the management and treatment of Severe Malaria."
6425,"Influenza, Measles, SARS, MERS, and Smallpox","Influenza, measles, SARS, MERS, and smallpox illnesses are caused by highly infectious viral pathogens that induce critical illness. These biologically diverse viruses enter and replicate within host cells triggering viral- and host-mediated damage that results in pneumonia and multiorgan failure in severe cases. Early case identification and strict infection control limit healthcare transmission. Vaccination allowed smallpox eradication and limits global measles and seasonal influenza mortality. While SARS-coronavirus (CoV) is no longer circulating, MERS-CoV and zoonotic influenza viruses, with pandemic potential, remain persistent threats. Supportive critical care is the mainstay of treatment for severe disease due to these viral infections."
6426,"Gold salts, D-penicillamine and allopurinol","Gold salts have been used in the treatment of patients with rheumatoid arthritis since 1927 [1]. After a controlled study, the Empire Rheumatism Council [2], confirmed the effectiveness of gold salts for the treatment of rheumatoid arthritis. Even today, chrysotherapy has remained one of the major therapeutic modalities in the second line treatment of progressive rheumatoid arthritis. Gold salts are also used in the treatment of pemphigus vulgaris [3] and bronchial asthma [4]. Before the introduction of an orally administered gold compound, auranofin (triethylphosphine gold tetra-acetyl glycopyranoside), to clinical use [5-7], parenterally administered gold salts, such as sodium aurothiomalate and gold thioglucose comprised chrysotherapy. The frequency and severity of the side effects for patients treated with parenteral gold versus those given oral gold preparations are significantly different [8-10]. With introduction of newer parental DMARDs, toxicity has been reduced using combination therapy [10a, 10b]."
6427,Afwijkingen van het respiratoire systeem,"Respiratoire afwijkingen komen zeer frequent voor als primaire aandoening of secundair aan een maligniteit, infectie of systeemziekte. Zoals voor veel inwendige aandoeningen geldt, is een goede anamnese en lichamelijk onderzoek onontbeerlijk bij de analyse van pulmonale aandoeningen. De eerste paragrafen van dit hoofdstuk zullen hier dieper op ingaan. Helaas zijn de klachten vaak weinig specifiek en noodzaken dikwijls tot verder beeldvormend onderzoek. De X-thorax is vaak het beginpunt van een dergelijk diagnostisch traject. In de latere paragrafen zullen specifieke bevindingen op de X-thorax verder worden uitgediept. In veel gevallen is naast laboratoriumonderzoek ook functieonderzoek en computertomografie van de thorax noodzakelijk om de differentiële diagnose verder te versmallen. Het verkrijgen van weefsel is bij interstitiële longaandoeningen, tuberculose en maligniteit vaak het sluitstuk van de diagnostiek. Nieuwe endoscopische echogeleide technieken komen steeds meer in de plaats van invasief onderzoek zoals mediastinoscopie of thoracotomie. Ook kan met behulp van PCR-technieken sneller en meer specifiek een juiste diagnose worden verkregen."
6428,Interview Marc Faber,"Marc Faber ist meistens anderer Meinung als die Mehrheit der Börsenexperten. Da der Schweizer erst über Risiken spricht, bevor er die Chancen an der Börse würdigt, wird er auch “Dr. Doom” genannt. Sein Börsenbrief, mit dem er die Anleger immer wieder konfrontiert, heißt “Gloom, Boom & Doom Report”. Mit 24 Jahren promovierte Faber im Fach Wirtschaftswissenschaft. Früh zog es ihn nach Asien. Faber erläutert die Grenzen von Börsenprognosen und bezeichnet die wachsende Börsenspekulation als gefährlich. „Sie ist ein Indiz vergangener Prosperität.“"
6429,Hoofdstuk 3 Afwijkingen van het respiratoire systeem,"Onder dyspnoe wordt gewoonlijk verstaan de subjectieve beleving van een bemoeilijkte ademhaling. Dit ontstaat als er sprake is van een excessieve stimulatie van de respiratoire motoneuronen, vooral als deze toegenomen activiteit niet leidt tot een adequate toename van de ventilatie. Men spreekt van orthopnoe indien de kortademigheid toeneemt in liggende houding en van platypnoe indien deze in staande houding toeneemt."
6430,Avian Astroviruses,"Avian astroviruses comprise a diverse group of viruses affecting many avian species and causing enteritis, hepatitis, and nephritis. To date, six different astroviruses have been identified in avian species based on the species of origin and viral genome characteristics: two turkey-origin astroviruses [Turkey Astrovirus type 1 (TAstV-1) and type 2 (TAstV-2)]; two chicken-origin astroviruses [Avian Nephritis Virus (ANV) and Chicken Astrovirus (CAstV)]; and two duck-origin astrovirus [Duck Astrovirus type 1 (DAstV-1) and type 2 (DAstV-2)]. ANV has also been detected in turkeys, ducklings, pigeons, and guinea fowl; and TAstrovirus-2-like viruses have also been found in guinea fowl. Astroviruses are commonly associated with enteric disease syndromes in poultry including runting-stunting syndrome of broilers (RSS), poult enteritis complex or syndrome (PEC or PES), poult enteritis mortality syndrome (PEMS), and enteritis in guinea fowl. The molecular characterization of the different avian astroviruses shows great genetic variability among each type, and this variability influences the ability to detect these viruses by molecular and serological techniques. In this chapter, we review the different aspects related to avian astroviruses, including molecular biology, pathogenesis, diagnosis, and control."
6431,A Young Lady with AVN after SARS,"Section I consists of a total of 39 clinical cases ranging from the very common case scenarios orthopedic surgeons and generalists see literally every day in their clinics (like issues regarding glucosamine, knee osteo-arthritis, bone health, foot problems associated with the wearing of high heels) to the introduction of new emerging rehabilitation techniques and concepts. Examples include concepts of home-based rehabilitation, the use of smart materials now popular in the field of engineering applied to orthopedics, the response of our skeleton to hyper-gravity stimulation and to micro-gravity environments as in space travel. Orthopedic conditions in which rehabilitation can be very challenging like hamstring injuries will also be touched upon."
6432,Acronimi e abbreviazioni,"“The patient went from the ER to the OR and then to the ICU”. Indubbiamente il lessico dei medici è ricco di abbreviazioni, tanto che gli operatori della sanità in generale e i cardiologi in particolare adoperano perlomeno dieci abbreviazioni per minuto (questa è una statistica fatta in casa, non citatela)."
6433,Parsing NCBI XML in Perl,
6434,Colchicine,"Colchicine is an alkaloid which was originally extracted from bulbs of a plant called Colchicum autumnale (meadow saffron). Its active pharmacological component was isolated in 1820 and in 1833 the active ingredient was purified and named colchicine. It consists of three hexameric rings termed A, B, and C. It was first recommended for the treatment of gout by Alexander of Tralles in the sixth century AD. Later it has been employed for suggested and approved indications including primary biliary cirrhosis (PBC), alcohol induced hepatitis, psoriasis, Behçet disease, Sweet syndrome, scleroderma, sarcoidosis and amyloidosis. Perhaps the most effective results have been obtained in the prophylaxis of familial Mediterranean fever (FMF). Colchicine is absorbed in the jejunum and ileum and is trapped in the body tissues. It is metabolized in the liver and the intestine by cytochrome P (CYP) 450 3A4 and P-glycoprotein (PGY) 1. Colchicine is excreted mainly by the biliary system, intestines and the kidneys. It has a narrow therapeutic range, but with normal liver and kidney functions is relatively safe and can be used during pregnancy, nursing and in infants. The main mechanism of action of colchicine is probably through interaction with microtubules affecting leukocyte chemotaxis, thereby suppressing inflammation. The blood level of colchicine may be affected by concomitant drug administration and therefore, caution should be exercised when such medications are added."
6435,Sinusitis in Multiple Sclerosis and Acinetobacter,Previous studies have shown that the onset of multiple sclerosis had been associated with the presence of upper respiratory tract infections involving both viral and bacterial agents. The relevance of these reports requires further consideration.
6436,Gezondheid van de Nederlandse bevolking,"Na 1970: hernieuwde sterftedaling in Europa en Noord-Amerika: vierde fase van de epidemiologische transitie. Het tijdperk van delayed degenerativediseases, d.w.z. geen uitschakeling ziekten maar uitstel naar hogere leeftijden (zie paragraaf 3.2.1). Daling sterfte hart- en vaatziekten door afname roken, daling serumcholesterol, betere opsporing hypertensie, betere medische zorg. Daling verkeersongevallen door verkeersveiligheid (zie paragraaf 3.2.1). Ischemische hartziekte werd van managersziekte een 'volksziekte' (zie paragraaf 3.2.1). Terugkeer infectieziekten na 1970 door resistentie micro-organismen tegen antibiotica en nieuwe infectieziekten zoals hiv/aids, SARS (zie paragraaf 3.2.1). Levensverwachting Nederlanders neemt toe, maar minder snel dan andere Europese landen (zie paragraaf 3.2.1). In de twintigste eeuw vijf tot acht jaar winst in levensverwachting door verbeteringen gezondheidszorg (o.a. antibiotica, vaccinaties, combinatiechemotherapie, verbeteringen chirurgie) (zie paragraaf 3.2.2). infecties bovenste luchtwegen; nek- en rugklachten; acute urineweginfecties; privéongevallen; contacteczeem. nek- en rugklachten; contacteczeem; artrose; diabetes mellitus; coronaire hartziekten. Kwaliteit van leven: 11% van Nederlanders van 12 jaar en ouder heeft een of meer ernstige functionele beperkingen (zie paragraaf 3.3.1). Top-5 aandoeningen met grootste verlies kwaliteit van leven is ander rijtje dan top-5 aandoeningen met hoogste prevalentie. Angststoornissen en depressie staan hoog in rangorde want beperkt sociaal functioneren (zie paragraaf 3.3.1). Sterfte belangrijkste indicator volksgezondheid. Sterftegegevens betrouwbaar en registratie over het algemeen volledig (zie paragraaf 3.3.1). Door toename levensverwachting is het relatieve belang van sterfte als indicator volksgezondheid verminderd (zie paragraaf 3.3.1). Belangrijkste doodsoorzaken Nederland. Mannen: kanker. Vrouwen: hart- en vaatziekten (zie paragraaf 3.3.1). Levensverwachting wordt berekend met behulp van overlevingstafel en geboortecohort (zie paragraaf 3.3.1). gezonde levensverwachting; health-adjusted life expectancy; disability-adjusted life years (DALY's). : Anticonceptie en vruchtbaarheidsproblemen. Geboorteregeling in Nederland nagenoeg perfect. Keerzijde: uitstellen zwangerschappen. Perinatale sterfte en zuigelingensterfte. Sinds jaren tachtig verloopt daling in Nederland minder snel dan bijvoorbeeld Zweden en Finland, door o.a. meerlingzwangerschappen (door ivf), roken, allochtone herkomst zwangeren, verschillen in zorg. Barkerhypothese: groeivertraging foetus heeft langetermijngevolgen voor gezondheid. Foetale programmering: aanpassingen van metabole en endocriene systeem van foetus onder invloed van tekort aan voedingsstoffen zijn schadelijk op latere leven. Ongevallen, suïcide(poging) en geweld: ongevallen in de privésfeer zorgen voor meeste aantal gewonden en overledenen. Moord en doodslag in Nederland vrij zeldzaam. Alcoholgebruik speelt bij verschillende categorieën een rol (zie paragraaf 3.3.3). : Depressie. Prevalentie 5%. Kwetsbaarheid en uitlokkende factoren spelen rol. Schizofrenie. Prevalentie 7 gevallen per 1.000 personen. Openbaart zich vaak op jonge leeftijd, tussen 16 en 24 jaar. Combinatie kwetsbaarheid en omgevingsfactoren. Komt meer voor bij Marokkanen en Surinamers, waarschijnlijk door migratie-ervaringen en/of discriminatie. . Thuisloosheid: vaak oorzaak ernstige psychische problemen. : Ischemische hartziekte. Hoge incidentie komt o.a. door toegenomen welvaart en roken, hoge bloeddruk en hoog serumcholesterol. Beroerte. Een derde toe te schrijven aan verhoogde bloeddruk. Ook verhoogd serumcholesterol, roken, overmatig alcoholgebruik en lichamelijke activiteit. Westerse ziekte en gevolg van modern voedingspatroon (met veel zout). Kanker. Strijd tegen kanker geen succesverhaal. Vroegere opsporing, dus overlevingsverbetering is deels artificieel. Longkanker heeft hoogste sterfte. Huidkanker komt het meest voor. Borstkanker komt na longkanker het meest voor bij vrouwen. Bevolkingsonderzoek leidt tot verbetering opsporing en daling sterfte. : Vergrijzing. Beperkingen: chronische ziekten, mobiliteit, slechthorendheid, dementie. Ontwikkelingen van (gezonde) levensverwachtingen: meningen zijn verdeeld. Evolutiebiologen denken dat bovengrens misschien bereikt is. Euthanasie: vormt uiterste puntje op heel scala aan medische beslissingen rond levenseinde, zoals intensivering pijnbestrijding en palliatieve sedatie. Relatief risico (RR): de verhouding van de incidentie van een ziekte bij personen met en zonder blootstelling aan een bepaalde determinant (zie paragraaf 3.4.1). Populatieattributieve fractie (PAF): de proportie van de totale incidentie van een ziekte binnen de bevolking die toe te schrijven is aan de blootstelling aan een bepaalde determinant (zie paragraaf 3.4.1). Voor de berekening van PAF hoeft de incidentie van de ziekte niet bekend te zijn. Kan met behulp van RR. Voor formules voor berekening RR en PAF, zie paragraaf 3.4.1. : Infectieziekten. Omgekeerde samenhang tussen ernst infectie en besmettelijkheid. Verspreidingswegen. Meldingsplicht bij ziekten als bacillaire dysenterie, kinkhoest, legionellose, malaria en tuberculose. Maag-darminfecties. Voedselvergiftiging komt op grote schaal voor. Hepatitis. A: verspreiding langs fecaal-orale weg. B: via bloed en andere lichaamsvloeistoffen, C: via bloed en veel gezien onder hemofiliepatiënten. Vectorgebonden infectieziekten: Malaria (importziekte). Ziekte van Lyme (via tekenbeten, wel in Nederland). Klimaatverandering verhoogt risico's op vectorgebonden infectieziekten. Zoönosen: infectieziekten van dier op mens. Creutzfeldt-Jakob, hondsdolheid, ornithose/psittacose, Q-koorts, SARS, vogelgriep. Risico is vermoedelijk toegenomen door verstoring ecosystemen en klimaatverandering. Soa's: ook in Nederland neemt frequentie toe, vermoedelijk door toename onveilig vrijen. Komt ook door besef dat behandeling hiv/aids is verbeterd. : Omgevingstemperatuur: verhoging sterfte met hittegolven en koude wintermaanden. Vooral bij kwetsbare groepen. Lawaai. Op werk of thuis. Stress en slaapverstoring kan tot hoge bloeddruk leiden. Veel jongvolwassenen gehoorschade door popconcerten. Ultraviolette straling. Veroorzaakt huidkanker. Neemt erg toe laatste jaren door verandering gedrag bevolking en dunner worden ozonlaag. Chemische stoffen. Asbest, metalen, oplosmiddelen. Geen grote bron gezondheidsschade in Nederland. Luchtverontreiniging. 'Fijn stof' zorgt vermoedelijk voor flink aantal extra sterfgevallen, maar nog niet duidelijk waarop dat effect berust. EU-norm wordt in grote delen van Nederland overschreden. Klimaatverandering. Gevolgen grotendeels onbekend. . : Psychosociale stress. Life events en arbeidssituatie kan invloed hebben. Sociale steun heeft gunstig effect op psychosociale stress. Roken. Verhoogd risico hart- en vaatziekten, kanker en COPD. Tabakswet van 2002 is mijlpaal in antirookbeleid. Rokers in Nederland onder 30%. Middenmoter in Europa. Alcohol en drugs. Veel lichamelijke en psychische problemen en oorzaak huiselijk geweld en zinloos geweld. Comazuipen onder jongeren in Nederland probleem. Ecstasygebruik ook hoog. Voeding. Nederlanders eten te vet en te weinig fruit en groenten, wat risico hart- en vaatziekten vergroot. Lichaamsbeweging. Helpt beschermen tegen hart- en vaatziekten, diabetes, depressie, borst- en dikkedarmkanker. Helft van de Nederlanders beweegt te weinig. . Energiebalans en overgewicht. Obesitas in Nederland 11% onder volwassenen en neemt toe. : Genen versus omgeving en gedrag. Genen belangrijk bij gezondheid individuen, niet zozeer bij volksgezondheid. Genen en ziekte. Rol genetische factoren bij ontstaan ziekte varieert sterk. . Belang van preventie. Belangrijk om meer inzicht te krijgen in genetische determinanten van multifactoriële aandoeningen. Gezondheidsverschillen naar geslacht (zie paragraaf 3.5.1): vrouwen worden ouder maar groter aantal jaren met minder goede gezondheid. Gezondheidsverschillen naar burgerlijke staat (zie paragraaf 3.5.1): gehuwden leven langer. : Arbeidsmarktpositie. Werkenden gezonder dan werklozen en arbeidsongeschikten. Sociaaleconomisch. Mensen met een lagere sociaaleconomische positie zijn vaker ziek. : Regionale verschillen. Verstedelijkte gebieden en aantal regio's in noordoosten hogere sterfte- en ziektecijfers. Brabant en Limburg hebben achterstand. Urbanisatiegraad. In grote steden sterfte hoger. Komt door veranderde bevolkingssamenstelling (gezonde bewoners vertrekken naar elders), niet door slechte levensomstandigheden."
6437,Introduction to Efficiency and Competitiveness of International Airlines,"This chapter provides the background on the significance of an efficiency analysis of airline industry in terms of its performance, motivation, and main objectives. This introductory chapter reviews the market size and economic contributions of the aviation industry to the global economy and briefly discusses the key issues in the industry in recent decades. It also provides an outline of the research questions, methodologies used, and the structure of the chapters in this volume."
6438,"Health Inequalities, General Trends in Mortality and Morbidity, and Associated Factors","All measures of health status are ultimately derived from observations of individuals. At the field level we have such measures as self-assessed health status, report of a specific disease, record of a particular death, or an individual’s test on a biomarker, such as blood pressure or serum cholesterol. The observations for individuals are combined and summarized to represent subnational geographic areas, demographic or socioeconomic groups within countries, or national populations. The summary measures, whether they are percentages, averages, or rates, apply to groups. A problem arises when the measures that are based on groups are assumed to represent individuals. The analysis becomes especially problematic when the units analyzed are geographic areas and inferences are being made about individuals from the analysis for these geographic areas."
6439,Webgestützter Organisationsaufbau,"Junge Firmen oder neue Unternehmensbereiche müssen von Beginn an kosteneffizient arbeiten und problemlos wachsen können. Dies kann durch neue Internet-Tools maß geblich unterstützt werden, wenn sie beherrschbar und wirklich effizienzstiftend sind. Junge Teams haben dabei die Chance, die neuen Internet-Tools und die damit einhergehende, offene Kommunikation und Projektarbeit auch gleich in ihrer Arbeitskultur zu verankern."
6440,Cysteine/Glutathione Deficiency: A Significant and Treatable Corollary of Disease,"Glutathione (GSH) deficiency may play a pivotal role in a variety of apparently unrelated clinical conditions and diseases. Orally administered N-acetylcysteine (NAC), which replenishes the cysteine required for GSH synthesis, has been tested in a large number of randomized placebo-controlled trials involving these diseases and conditions. This chapter focused on developing a base of evidence suggesting that NAC administration improves disease by increasing cysteine and/or GSH in a variety of diseases, thereby implying a significant role for GSH deficiency in the clinical basis of many diseases. To develop this base of evidence, we systematically selected studies which considered the hypothesis that the therapeutic efficacy for NAC is an indication that cysteine and/or GSH deficiency is a pathophysiological part of the diseases studied. In this manner we focus this chapter on explaining the biological mechanisms of NAC therapy in a wide variety of disorders and demonstrate its ubiquitous role in improving disease that involves disrupted GSH and/or cysteine metabolism. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/978-981-10-5311-5_20) contains supplementary material, which is available to authorized users."
6441,Mapping and Modeling Disease Risk Among Mobile Populations,
6442,Die Gesellschaft Deutscher Neurologen und Psychiater im Zweiten Weltkrieg,"Mit Beginn des Zweiten Weltkriegs kam es – als Folge der Einberufung wichtiger Protagonisten – zu einer deutlichen Beeinträchtigung der Organisationsstrukturen der Gesellschaft Deutscher Neurologen und Psychiater. Im Verlauf des Krieges lösten sich die formalen Strukturen weiter auf, während das informelle Netzwerk, das die Fachgesellschaft zusammenhielt, weitgehend intakt blieb und es an der Schnittstelle von Wissenschaft und Politik zu neuen Konstellationen und Kooperationen kam."
6443,Bronchiolitis,"Bronchiolitis produces significant morbidity and mortality worldwide every year. Approximately 3–10 % of all infants hospitalized with bronchiolitis develop acute respiratory failure and require admission to a pediatric intensive care unit. The vast majority of cases are caused by Respiratory Syncytial Virus (RSV), though other viruses (human metapneumovirus, parainfluenza, influenza, adenovirus, rhinovirus, coronavirus and bocavirus) may also cause bronchiolitis. Bronchiolitis is not merely a single organ disease (i.e. lung), but impacts on extrapulmonary organ systems. Basic supportive management remains the cornerstone. There is a paucity of established therapeutic options, with supplementary oxygen, continuous positive airway pressure (CPAP), humidified high-flow nasal oxygen, mechanical ventilation being the mainstay of respiratory support."
6444,RNA Pseudoknot Folding through Inference and Identification Using TAG(RNA),"Studying the structure of RNA sequences is an important problem that helps in understanding the functional properties of RNA. After being ignored for a long time due to the high computational complexity it requires, pseudoknot is one type of RNA structures that has been given a lot of attention lately. Pseudoknot structures have functional importance since they appear, for example, in viral genome RNAs and ribozyme active sites. In this paper, we present a folding framework, TAG(RNA)Inf, for RNA structures that support pseudoknots. Our approach is based on learning TAG(RNA) grammars from training data with structural information. The inferred grammars are used to indentify sequences with structures analogous to those in the training set and generate a folding for these sequences. We present experimental results and comparisons with other known pseudoknot folding approaches."
6445,"Taxonomy, Physiology, and Ecology of Aquatic Microorganisms","The principles behind the taxonomy of the microorganisms, especially the ­molecular approach (using the sequence of the 16S RNA in the small subunit of the ribosome) in the identification of bacteria, are discussed. The detailed taxonomy of bacteria, fungi, algae, protozoa, and viruses (including bacteriophages) is discussed, and emphasis is laid on those microorganisms which are aquatic. The chapter includes information on some of the smaller macroorganisms found in water such as nematodes and rotifers. The activities of aquatic microorganisms in photosynthesis, and the global cycling of nitrogen and sulfur is discussed."
6446,Health Research Behind Bars: A Brief Guide to Research in Jails and Prisons,"While most people make staying out of jail and prison a priority, a growing number of researchers are eager to get into correctional facilities in order to study the criminal justice system, the causes and consequences of incarceration, and the role of corrections in our society. For health researchers and their collaborators, the audience for this chapter, correctional facilities offer several unique advantages: a population at high risk of many health problems including infectious and chronic diseases, substance abuse, and mental health problems; social and physical environments that can enhance or impede well-being; a setting that is a focal point for the class, racial/ethnic, and gender differences that divide the United States; a site where health and mental health services and prevention programs are offered and can be evaluated; a controlled environment for administration of treatments such as directly observed therapy for tuberculosis; and a stopping point in the cycle of incarceration and reentry that so profoundly affects community well-being."
6447,Acronyms and Abbreviations,“The patient went from the ER to the OR and then to the ICU.” It is an irrefutable fact that doctor’s speech is full of abbreviations. Health-care professionals in general and cardiologists in particular use many abbreviations. This high prevalence has led us to consider medical abbreviations as a challenging pandemic.
6448,Sickle Cell Disease,"Sickle cell disease is characterized by vaso-occlusive and hemolysis events that may occur in a variable range of clinical presentations. Patients with this disease, particularly with acute chest syndrome, suffer acute episodes of chest pain caused by vaso-occlusive crisis, that tend to repeat, especially under the influence of lower respiratory infections, dehydration, and any cause of hypoxemia. Children and adolescents with sickle cell disease must be periodically evaluated through oximetry, lung function tests, sleep study, and echocardiograms to detect obstructive and restrictive diseases that frequently worsens the lung condition. Asthma and sleep disorders contribute to morbidity and must be controlled."
6449,Anti-viral approaches against influenza viruses,
6450,Management of the Rheumatoid Arthritis Patient with Interstitial Lung Disease,"The treatment of rheumatoid arthritis (RA) has undergone considerable changes over the last 15–20 years. With an expansion in the armamentarium of therapies available for RA comes a wider choice in selecting the best treatment in terms of comparative safety in the presence of comorbidities. Clinicians frequently encounter patients with RA-associated interstitial lung disease with uncontrolled joint disease and have to make decisions about the safest treatments in this context with the eventual goal of joint remission. In this chapter, available evidence is reviewed on the comparative pulmonary safety of non-biologic disease-modifying antirheumatic drugs (nbDMARDs), biologic DMARDs, biosimilars and targeted synthetic DMARDs in RA-ILD. In addition, the potential role for additional immunosuppression in RA-ILD is reviewed as well as overarching recommendations proposed for patient assessment to guide treatment decisions and management."
6451,Molecular farming for antigen (vaccine) production in plants,"Genomic and proteomic approaches to the study of fundamental cell mechanisms are rapidly contributing to broaden our knowledge on metabolic pathways for the optimal exploitation of the cell as a factory. In the last few years this knowledge has led to important advances in the large scale production of diagnostic and therapeutic proteins in heterologous hosts (bacteria, yeasts, mammalian and insect cells or transgenic animals and plants), allowing the comparison of the most efficient methods in terms of costs, product quality and safety."
6452,Cytopenias in Transplant Patients,"Anemia, leukopenia, thrombocytopenia, as well as pancytopenias can be seen following solid organ transplant. Varying patterns of cytopenia can be seen based on the drugs used in the posttransplant period, infections encountered by the individual, as well as the individual’s immune response and bone marrow function. The chapter discusses the main causes of anemia, leukopenia/neutropenia, and thrombocytopenia. The differential diagnosis for anemia after solid organ transplant includes hemolysis, drug toxicities, iron deficiency, infection, posttransplant lymphoproliferative disorder, graft-vs.-host disease, and hemophagocytic syndrome. Etiologies for leukopenia and neutropenia include drug toxicities and infection, and etiologies for thrombocytopenia include drug toxicities, infections, autoimmune events such as immune thrombocytopenic purpura, and underlying causes such as persistent portal hypertension and splenomegaly."
6453,Astrovirus Infections in Animal Mammalian Species,"The first reports of astroviruses in animals date back to the end of the 1970s, when infections in mammals such as lambs and calves suffering from diarrhea were reported for the first time. Since then, several mammalian species have been shown to be susceptible to astroviruses which appear to be genetically diverse and to have acquired host-specificity. To date, astroviruses have been detected in 16 different orders or species of mammals in addition to humans, and signs of infection range from unapparent infection or very mild disease to diarrhea, lethargy, and anorexia, mainly observed in young individuals. This chapter describes those astroviruses detected in nonhuman mammalian species worldwide, as well as their molecular and phenotypic characteristics and their role in diseases. The capacity of these viruses to cross-species barriers and their subsequent adaptation to novel hosts is also highlighted."
6454,Diabetes Mellitus: New Challenges and Innovative Therapies,"Diabetes is a common chronic disease affecting an estimated 285 million adults worldwide. The rising incidence of diabetes, metabolic syndrome, and subsequent vascular diseases is a major public health problem in industrialized countries. This chapter summarizes current pharmacological approaches to treat diabetes mellitus and focuses on novel therapies for diabetes mellitus that are under development. There is great potential for developing a new generation of therapeutics that offer better control of diabetes, its co-morbidities and its complications. Preclinical results are discussed for new approaches including AMPK activation, the FGF21 target, cell therapy approaches, adiponectin mimetics and novel insulin formulations. Gene-based therapies are among the most promising emerging alternatives to conventional treatments. Therapies based on gene silencing using vector systems to deliver interference RNA to cells (i.e. against VEGF in diabetic retinopathy) are also a promising therapeutic option for the treatment of several diabetic complications. In conclusion, treatment of diabetes faces now a new era that is characterized by a variety of innovative therapeutic approaches that will improve quality of life in the near future."
6455,Metalloproteases and Proteolytic Processing,"Proteolytic enzymes constitute around 2% of the human genome and are involved in all stages of cell and organism development from fertilization through to cell death. In the human genome the major classes of peptidases are represented by cysteine-, serine- and metalloenzymes, which possess a wide spectrum of substrate specificity and physiological functions. The identification of many novel peptidases from genome sequencing programmes has suggested potential new therapeutic targets. In addition, several well characterised peptidases were recently shown to possess new and unexpected biological roles in neuroinflammation, cancer and angiogenesis, cardiovascular diseases and neurodegeneration. This chapter will briefly characterize the main classes of metallopeptidases and their roles in health and disease. Particular attention will be paid to the angiotensin-converting enzyme (ACE), neprilysin (NEP) and adamalysin (ADAM) families of proteases and their pathophysiological roles with a particular emphasis on cancer and neurodegeneration. The roles and mechanisms of protein shedding which primarily involve the ADAMs family of metallopeptidases will be explained using amyloid protein precursor (APP) processing cascades as a well characterized example. The therapeutic significance of modulating (activating or inhibiting) metallopeptidase activity will be a particular focus of this chapter."
6456,Axons and Neurons in Corona Virus-Induced Demyelination,"Infection of mice with the coronavirus mouse hepatitis virus induces primary demyelination in susceptible strains of rodents. Although demyelination is the primary pathological process detected in the central nervous system of infected mice, axonal dysfunction and damage also occur concomitantly with demyelination. This process is T cell mediated, with either CD4 or CDS T cells sufficient for MHV-induced axonal damage. A striking feature is that axonal damage occurs early in the disease process, at nearly the same time as demyelination is first observed. Axonal damage in MHV-infected mice has many similarities with the parallel process in humans with multiple sclerosis."
6457,Xenotransplantation,"The above statement was made by Guido Persijn, former Medical Director of the Eurotransplant Foundation, an international organisation that coordinates organ donation and transplantation. Xenotransplantation is the transplantation of organs, tissues or cells from one species of animal to another. This chapter will look at transplantations between animal and humans. Xenotransplantation is one possible solution for the organ donor shortage in the area of transplant medicine(77). However, there is still a ban on this type of procedure because of the lack of clarity about the sort of risks entailed. The natural rejection responses to cross–species components still create insurmountable problems. The transfer of viral DNA with, as yet, unpredictable consequences is also another matter that requires due attention. The various facets of this topic will be discussed in this chapter, as will the question of whether or not xenotransplantation is ethically responsible. We’ll begin with the history of xenotransplantation, which has its origins in a dark past."
6458,Respiratoire aandoeningen,"De incidentie van community-acquired pneumonie (cap, pneumonie begonnen thuis of binnen 48 uur na ziekenhuisopname) bedraagt 0,5-i,5%. Zij is hoger bij jonge kinderen en ouderen en stijgt tijdens een influenza-epidemie. Slechts 10-20% van de patiënten moet worden opgenomen vanwege de ernst van de pneumonie of een belangrijke bijkomende aandoening. De mortaliteit van deze patiënten bedraagt 5-15%; pneumonie is dus de frequentste infectieuze doodsoorzaak."
6459,The Global Threats from Naturally Occurring Infectious Diseases,"Biological risk relates to a broad spectrum of possible scenarios, that can be classified in three categories: natural occurring, unintended and deliberate. The prevention and management of such events require dedicated measures at national and international level, in terms of biosafety and biosecurity: an optimized intervention can minimize the probability of occurrence, but also adverse short-term (i.e.: number of casualties, population reaction…) and long-term (i.e.: chronic illnesses, ecological changes, trades drop…) consequences. Natural scenarios include common, emerging/re-emerging and chronic infectious diseases: they are caused by biological agents, which can be normally present in the communities, as acute or chronic pathologies, or suddenly appear, causing new or uncommon syndromes. In particular, a lot of environmental and human factors can influence emerging and re-emerging diseases: for example, urbanization and people mobility facilitate microorganisms spread, while climate changes are likely to induce a relocation of pathogens vectors. Unintended events are usually due to research and diagnostic activities: laboratories are the places where biological agents are handled and a lack in Biosafety measures or negligence can result in accidental release; the so called Laboratory Acquired Infections represent the main consequence, since they cause pathologies in the laboratory workers, but could be also transmitted in the population. Deliberate use of biological agents is strictly related to terroristic activities: microorganisms are very suitable for this purpose, since they are hidden and can easily spread. The present chapter summarizes the main characteristics of biological agents related events, taking in account their origin and the principal consequences on the community."
6460,"Health, Disease, and Illness as Conceptual Tools","There is no absolute consensus on the definitions of health, disease, and illness, even though these concepts are central not only in medicine but also in the health social sciences. A definition of each of the concepts is imperative because they constitute part of the analytical tools in medical sociology. This chapter presents definitions of these concepts, noting that each of them is multidimensional, complex, and sometimes elusive. The WHO’s definition of health is critically examined with respects to its components, criticisms, and alternative definitions of health. This chapter proceeds to discuss the features of a disease and the specific realities of illness by showing the difference between the two concepts. Disease and illness categories (acute, chronic, accidents/injuries, and mental disease/illness) are discussed. The chapter concludes with a strong emphasis on the cultural beliefs regarding illness causation among lay populations, especially in the African context. The natural, supernatural, mystical, and hereditary/genetic causations are discussed based on cultural realities but are sometimes divergent from biomedical models of disease causation."
6461,4 Infectieziekten,In het vorige hoofdstuk hebben we gezien dat de mens zich tegen velerlei soorten prikkels kan beschermen door middel van ontstekings- of immuunreacties. In dit hoofdstuk wordt besproken welke veranderingen in het lichaam plaatshebben indien de noxe bestaat uit micro-organismen.
6462,Infektionsimmunologie8,"Im Laufe der Entwicklung der Lebewesen traten die Organismen gegeneinander in Konkurrenz und entdeckten andere Spezies als eigene Lebensgrundlage oder Nahrung. Bei höheren Lebewesen sehen wir dies als selbstverständlich an und teilen Sie in Fleisch- und Pflanzenfresser ein. Bei niederen Lebewesen bezeichnen wir dies jedoch als pathogene Eigenschaft oder als parasitäre Lebensweise, wenn wir ihnen als Nahrungsgrundlage dienen. Zur Abwehr der Krankheitserreger entwickelten alle höheren Lebewesen ein Immunsystem, um das Fortbestehen der Spezies zu garantieren. Je weiter sich die Lebewesen entwickelt haben, desto höher hat sich auch das Immunsystem in einer Coevolution in Konkurrenz zu den Erregern entwickelt. Da das Immunsystem in der Evolution zur Infektionsabwehr entstanden ist, leiten sich seine übrigen physiologischen und pathophysiologischen Mechanismen von denen der Infektionsabwehr ab. Die Tumorabwehr entspricht der Abwehr von Viren und die Allergie der Abwehr von „nicht vorhandenen Parasiten“. Damit ist die Infektionsimmunologie der zentrale Punkt der Immunologie. Während wirbellose Tiere nur eine angeborene Immunität besitzen, hat sich bei den Wirbeltieren zusätzlich die spezifische (adaptive) Immunität entwickelt. Die Komplexität des Immunsystems steht dabei mit der Lebensdauer der Organismen und der Rate an Nachkommen im Einklang, d. h., je länger die Lebensdauer und je geringer die Anzahl der Nachkommen, desto komplexer muss das Immunsystem aufgebaut sein, um das Überleben der Art zu gewährleisten. Somit haben sich im Laufe der Evolution die in den vorherigen Kapiteln beschriebenen Abwehrsysteme entwickelt, die für die Abwehr von Infektionen koordiniert zusammenarbeiten müssen. Wichtig ist dabei, dass das Immunsystem den richtigen Reaktionsweg einschlägt, der den Erreger spezifisch bekämpfen kann, da sonst die Immunreaktion ins Leere läuft und der Erreger sich trotzdem weitervermehrt und den Körper schädigt."
6463,Contrast-Enhanced MRI and Micro-CT Adopted for Evaluation of a Lipid-Lowering and Anticoagulant Herbal Epimedium-Derived Phytoestrogenic Extract for Prevention of Steroid-Associated Osteonecrosis,"We developed an alternative steroid-associated osteonecrosis (ON) rabbit model using a combination of a single injection of low-dose lipopolysaccharide (LPS) and three subsequent injections of pulsed high-dose methylprednisolone (MPS).The usefulness of this experimental ON model was evaluated using both conventional and advanced bio-imaging techniques, including contrast-enhanced dynamic MRI and a high-resolution micro-CT. Details on establishment of methodology are described, which were adopted into an efficacy study on a herbal Epimedium-derived phytoestrogenic extract (HEPE) developed for prevention of steroid-associated ON using an established rabbit model. The underlying mechanisms of HEPE for prevention of steroid-associated ON were found to be associated with inhibition of both intravascular thrombosis and extravascular bone marrow lipid deposition, the two known mechanistic pathways in pathogenesis of ON. Our experimental results provide for potential clinical trials or applications of HEPE in the prevention of ON among hig-hrisk patients undergoing steroid treatment."
6464,Ambient Temperature and Major Infectious Diseases in China,"Infectious diseases are a group of diseases which have complex transmission ways and various influencing factors. Clarifying the correlation between ambient temperature and major infectious diseases in China is a crucial step toward the successful control of infectious diseases including vector-borne diseases, water-borne diseases, food-borne diseases, respiratory infectious diseases, etc. and the implementations of climate change adaption strategy and measures in China. However, no study has systematically reviewed the available evidences on the impact of ambient temperature on the incidence of major infectious diseases, and such information is essential for policymakers and stakeholders to take specific actions to control infectious diseases and protect the vulnerable population in the future. In order to fill this gap, we systematically review the current evidence for the effect of ambient temperature on major infectious diseases in China. The findings could provide explicit information for the scientific prevention and control of infectious diseases in China."
6465,Nasal Cavity and Paranasal Sinuses,
6466,La terapia antimicrobica nella pratica clinica,"In questa sezione vengono riportate le informazioni utili per un uso adeguato degli antimicrobici. Lo schema di presentazione ricalca il percorso clinico abituale: prima un approccio empirico, poi una terapia mirata nella quale è noto il patogeno e infine una classificazione che si concentra sul singolo principio attivo."
6467,The Impact and Control of Emerging and Re-Emerging Viral Diseases in the Environment: An African Perspective,"Emerging viral infections (EVI), and re-emergent variants of existing ones, are a growing threat to public health worldwide with outbreaks occurring sporadically especially in Africa associated with significant adverse ecological, socioeconomic and public health implications. These pathogens have devised evolved environmental adaptations, including the possession of genomic resistance mutations. Haemorrhagic fever viruses like Ebola, Marburg and Lassa fever viruses and respiratory pathogens like the avian and human influenza severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) viruses, most from zoonotic reservoirs, may significantly increase morbidity and mortality in the human population in the nearest future. Likewise, vector-borne zoonotic viral diseases including Rift Valley fever, yellow fever, dengue, chikungunya and West Nile, transmitted by arthropods from animal reservoirs, occur frequently in the tropics, exhibiting previously unseen patterns of infection and spread. These patterns are facilitated by many intrinsic factors like mutated sites in the viral genome, and external factors including urbanization, displacement, human migration and climate change. Emerging viruses can easily cross boundaries and pose severe threats to the human populations in new geographical areas. Here, we outline the features of common emergent viruses and factors facilitating their emergence, effects, control and sustained management in the environment."
6468,Guangdong Province: Trade Liberalization and HIV,"The Guangdong experience is interesting as a case study, given its role as an economic hub, having attracted both domestic migrant workers, as well as people from abroad ever since the economic reforms of the late 1970s. The first Special Economic Zones were set up in Guangdong, due to its proximity to Hong Kong, most famously in the city of Shenzhen. The region has a prospering manufacturing industry, where both labor-intensive manufacturing products, as well as high-end technology products, are produced and assembled. Trade liberalization and rapid economic growth have also created a booming commercial sex industry and a situation where many economically-marginalized workers are migrating to the region. Here, we document the development of Guangdong’s HIV epidemic, which has grown dramatically from 1997 to 2017, and we describe epidemic response efforts in Guangdong over the same period."
6469,Geschichtlicher Überblick,"Für die Krankheiten, die wir heute als Viruserkrankungen kennen, sah man ursprünglich „Gifte“ als Ursache an. Mit den damals üblichen Methoden ließen sich keine (krankheitserzeugenden) pathogenen Organismen wie Bakterien oder Protozoen in den „giftigen Materialien“ nachweisen. Erst gegen Ende des 19. Jahrhunderts legten Tierversuche, die von Louis Pasteur durchgeführt wurden und bei denen sich auch nach mehreren Passagen keine Ausverdünnung der giftigen Eigenschaften einstellte, nahe, dass das krankheitsauslösende Agens in der Lage war, sich im Organismus zu vermehren. Man sprach deshalb von einem in lebenden Organismen, später auch von einem in Zellen vermehrungsfähigen „Virus“ (lateinisch für „Gift“ oder „Schleim“). Im Jahre 1892 konnte Dimitri I. Iwanowski in St. Petersburg zeigen, dass die Mosaikkrankheit der Tabakpflanzen durch ein „ultrafiltrierbares“ und damit deutlich unter Bakteriengröße liegendes Agens verursacht wird: das Tabakmosaikvirus."
6470,Erkrankungen der Trachea und der Bronchien,
6471,Lung,"In the present chapter, we review and summarize current advances on the role of angiotensin-(1-7) [Ang-(1-7)] in the pathophysiology of main lung diseases: pulmonary hypertension (PH), acute respiratory distress syndrome (ARDS), asthma, and pulmonary fibrosis. Understanding the involvement of renin angiotensin system (RAS) in pulmonary inflammation may open new therapeutic possibilities for the treatment of respiratory diseases. Studies to date showed that Ang-(1-7) presents anti-inflammatory, antifibrotic activities and reduces pulmonary remodeling. These actions support the development of new pharmacological therapies based on the increase in Ang-(1-7) in the lungs to improve the treatment of inflammatory diseases."
6472,Issues in Community-Acquired Pneumonia,"Pneumonia is one of the most commonly diagnosed infectious diseases and is the third most frequent cause of death worldwide. Accurate statistics of community-acquired pneumonia incidence globally or in countries of various regions are lacking. Although the clinical diagnosis of pneumonia is not difficult, the etiology diagnosis to guide targeted specific antimicrobial therapy still poses a challenge even with novel molecular methods. This has led to different approaches and guidelines for the empiric treatment of community-acquired pneumonia, often with broad-spectrum antimicrobial agents which may play a role in fostering the worldwide development of antibiotic resistant bacteria. Severe community-acquired pneumonia, seen mainly at the extremes of age and in persons with chronic underlying diseases, is associated with high mortality of 20–40%. Pneumonia severity tools, such as CURB-65, have been developed over the past decade to assist emergency department physicians to recognize, admit, and implement rapid antimicrobial therapy in severely ill patients. The evidence for the beneficial effects of these tools will be reviewed in this chapter. Issues in the management of severe community-acquired pneumonia that are discussed include: combination with newer macrolides [irrespective of microbial etiology], value of adjunctive therapy such as corticosteroids and statins."
6473,Rhinoviruses,"Picornaviruses, which include the human rhinoviruses (HRVs) and enteroviruses (EVs), are the most frequent cause of acute human illness worldwide. HRVs are the most prevalent cause of acute respiratory tract illnesses (ARIs) which usually commence in the upper respiratory tract (URT). ARIs are the leading cause of morbidity in children under 5 years and occur in all seasons. ARIs linked to HRV infections are associated with excessive and perhaps inappropriate antibiotic prescribing and with significant direct and indirect healthcare expenditure. ARI incidence is highest in the first 2 years of life, with up to thirteen episodes per year including up to six positive for an HRV, and it is not uncommon to average one infection per child-month."
6474,The Baboon in Xenotransplant Research,"If cross-species transplantation is ever to become a reasonable therapeutic modality for human beings, it will be because the potential for success has been demonstrated in a nonhuman primate model. The imperative has always been to select a primate research subject from a species that is plentiful, is not endangered, readily procreates in a managed environment, and mimics the human response (immunologic homology) to both organ transplantation and potential transfer of infectious disease. Several Papio subspecies of baboons, including Papio hamadryas anubis (olive baboon), meet these important criteria. These animals remain ubiquitous throughout sub-Saharan Africa and have adapted well to the managed environments of major primate centers worldwide. A list of United States-based primate centers housing breeding colonies of baboons can be found in Table 19.1. The Surgical Research Laboratory at Loma Linda University, for instance, has maintained a salutary relationship with the Southwest National Primate Research Center in San Antonio, Texas, for the procurement of juvenile baboon research subjects."
6475,Medicinal Plant Active Compounds Produced by UV-B Exposure,"Ultraviolet (UV) radiation is a part of the sunlight reaching Earth surface. The UV spectrum of solar radiation is by convention divided into three parts: UV-A: 310–400 nm, UV-B: 280–310 nm and UV-C: less than 280 nm. UV-B is the most energetic component reaching Earth surface because the stratospheric ozone layer effectively absorbs completely wavelengths below 290 nm. UV-B is an increasing threat due to increasing UV-B levels on Earth surface as a consequence of depletion of stratospheric O(3). In general, the effects of atmospheric UV-B radiation are negative for biological life. Enhanced levels of UV-B radiation can indeed negatively change plant physiological processes, growth and productivity. However, while studying UV-B effects on medicinal plants, some interesting phenomena have been discovered. For example, basil plants respond positively to UV-B radiation by increasing oil yield (Chang et al. J Horticult For 1:27–31, 2009). In other studies medicinal plants show beneficial aspects in term of increase in volatile oil yield and secondary metabolite production (Kumari et al. Ecotoxicol Environ Safety 72:2013–2019, 2009c, 2010). Medicinal herbs have great market value in India and worldwide. The medicinal value of plants depends upon phenolics, antioxidants and volatile yield. Therefore further UV-B experiments increasing the levels of these compounds are needed. Here we review the effect of UV-B exposure on metabolites, volatiles, and antioxidants potential in medicinal plants. This chapter reports: (1) aspects of the global market for medicinal and aromatic plants in India in order to assist the medicinal plant industry to make informed decisions. (2) The biodiversity loss due to wild harvesting of plants, and as an alternative the cultivation strategy of medicinal plants. (3) Main medicinal plant species having rich antioxidant potential. (4) Main secondary metabolites of plant origin such as phenylpropanoids, terpenes, alkaloids, and volatile oil, and other important metabolites containing high antioxidant level used in human diet and health. (5) UV-B factors that enhance the quality of medicinal plant by increasing the content of secondary bioactive products. (6) Secondary metabolic pathways involving regulation of key enzymes, chalcone synthase, and phenylalanine ammonia lyase. Understanding of UV-B responses on secondary plant metabolites expand new opportunities for plant enriched in medicinal active compounds."
6476,Venous Thrombus,"Venous thromboembolism (VTE) includes pulmonary thromboembolism (PE) and deep venous thrombosis (DVT). Both belonging to thrombus, acute arterial thrombus is white thrombus, while acute venous thrombus is red thrombus. What does the pathological difference mean? Venous thrombosis can autolyze, while arterial thrombosis cannot. For VTE patients, oral anticoagulants are usually recommended for 3, 6, or 12 months and occasionally lifelong, but the course cannot be determined. Furthermore, even with standard anticoagulation therapy and INR, some patients still develop chronic thromboembolic pulmonary hypertension (CTEPH). Thus, the physicians are extremely puzzled about anticoagulant usage. Proposed risk factors for VTE include advanced age, infection, malignancy, autoimmune disease, surgery, trauma, pregnancy, long trip syndrome, family history, AMI, heart failure, and so on. Relevant risk factors are increasing over time. Risk factors are derived from the summary of evidence-based medicine. Although these factors are found to be associated with venous thrombosis, the intrinsic factors have not been well elucidated."
6477,Optimal Control of Multi-strain Epidemic Processes in Complex Networks,"The emergence of new diseases, such as HIV/AIDS, SARS, and Ebola, represent serious problems for the public health and medical science research to address. Despite the rapid development of vaccines and drugs, one challenge in disease control is the fact that one pathogen sometimes generates many strains with different spreading features. Hence it is of critical importance to investigate multi-strain epidemic dynamics and its associated epidemic control strategies. In this paper, we investigate two controlled multi-strain epidemic models for heterogeneous populations over a large complex network and obtain the structure of optimal control policies for both models. Numerical examples are used to corroborate the analytical results."
6478,Challenges in modelling complexity of fungal entomopathogens in semi-natural populations of insects,"The use of fungal entomopathogens as microbial control agents has driven studies into their ecology in crop ecosystems. Yet, there is still a lack of understanding of the ecology of these insect pathogens in semi-natural habitats and communities. We review the literature on prevalence of fungal entomopathogens in insect populations and highlight the difficulties in making such measurements. We then describe the theoretical host-pathogen models available to examine the role that fungal entomopathogens could play in regulating insect populations in semi-natural habitats, much of the inspiration for which has been drawn from managed systems, particularly forests. We further emphasise the need to consider the complexity, and particularly the heterogeneity, of semi-natural habitats within the context of theoretical models and as a framework for empirical studies. We acknowledge that fundamental gaps in understanding fungal entomopathogens from an ecological perspective coupled with a lack of empirical data to test theoretical predictions is impeding progress. There is an increasing need, especially under current rapid environmental change, to improve our understanding of the role of fungi in insect population dynamics beyond the context of forestry and agriculture."
6479,Damage Control Resuscitation,"Damage control resuscitation is a resuscitation modality that integrates permissive hypotension, hemostatic resuscitation, and damage control surgery, initially addressing all three components of the “lethal triad”: coagulopathy, acidosis, and hypothermia. Trauma patients predicted to require massive transfusion, administration of fresh frozen plasma, packed red blood cells, and platelets in a 1:1:1 ratio (of individual units) are associated with improved survival and less need for innumerous transfusions. In addition, the evidence so far indicates that the incorporation of these principles into a MTP will also contribute to less transfused units by minimizing variability of transfusion practices. Importantly, fewer units transfused will contribute to fewer complications associated with transfusions. These conclusions will need to be verified, especially with regard to the effect of MTPs incorporating higher ratios of FFP:PRBC:platelets effect on varying mechanism of injury, the timing of transfusions, and the number of units actually transfused. Also recombinant factor VIIa, cryoprecipitate, and tranexamic acid can be considered adjunctive treatments for coagulopathy. Lastly, damage control surgery is a surgical strategy aimed at restoring normal physiology rather than anatomical integrity; however, this component of damage control resuscitation should not be applied in isolation."
6480,Health Issues in Returned Travellers,"Travellers are more than ever choosing to visit adventurous destinations, sometimes in remote places. In addition, the ease of international travel makes it possible for travellers with underlying medical conditions, such as immunosuppression, the elderly, pregnant women and children to travel to destinations that may place them at risk of a range of exotic infections. It is therefore important for the travel medicine practitioner to have a firm understanding of the spectrum of infections that travellers may acquire according to their travel destination. This chapter provides an overview of the spectrum of infections travellers may encounter and provides an approach to the diagnosis and management of ill returned travellers."
6481,1.2 The Health System,"There are several factors (or determinants 1. Biology: the age and sex of the person; the genetic makeup including heritable diseases. At the current time, biological factors are the hardest to change, although many are hopeful that genetic engineering may change this at some point. For this reason, most public-sector investment in public health aims to affect the behavioral, social, environmental and medical access determinants. . 2. Behaviors: alcohol, tobacco, substance abuse; risk-prone lifestyles, such as working as a miner or prostitute. . 3. Social: discrimination, income disparities, socioeconomic status, education, occupation, class, social support. Poorer people often lack time and opportunity to exercise. Food for a healthier diet tends to be more expensive and takes longer to prepare. A strong and consistent finding of epidemiological research is that there are health differences among socioeconomic groups. Lower mortality, morbidity, and disability rates among socioeconomically advantaged people have been observed for hundreds of years. . 4. Environment (or total ecology): where a person lives, sanitary and crowding conditions, air and water quality, lead exposure, and the design of neighborhoods. Some of the most dramatic improvements in population health during the twentieth century include: improved water, food, and milk sanitation, reduced physical crowding, improved nutrition, and central heating with cleaner fuels. Most Americans live in urban areas, which are often associated with harmful health behaviors, such as exercise, diet, sexual behavior, alcohol and substance abuse. Cities also have higher levels of air pollution, which may cause cardiovascular and respiratory disease. Crowded buildings may increase the risk of lead exposure as well as asthma. Those that live in rural areas have other risks, such as exposure to pesticides. . 5. Medical care: access to quality health care; having insurance. For example, the availability of Medicaid (health insurance for the poor) was expanded greatly with the passage of the Affordable Care Act. This resulted in greater access to medical care for a previously underserved population. Similarly, the nationwide shift to high-deductible insurance plans has actually reduced accessibility to affordable healthcare for many. ;"
6482,"Vaccines: Biotechnology Market, Coverage, and Regulatory Challenges for Achieving Sustainable Development Goals","This chapter provides an overview, from bioeconomic and global sustainability perspectives, of the main constraints to the current global vaccine innovation system for achieving Sustainable Development Goals – SDGs. Biotechnology market trends, gaps in vaccine coverage against emerging and neglected diseases, and patent protection and regulation are discussed. A structured long-term “public-return-driven” innovation model to overcome vaccine market failure is proposed."
6483,Towards Automated TEM for Virus Diagnostics: Segmentation of Grid Squares and Detection of Regions of Interest,"When searching for viruses in an electron microscope the sample grid constitutes an enormous search area. Here, we present methods for automating the image acquisition process for an automatic virus diagnostic application. The methods constitute a multi resolution approach where we first identify the grid squares and rate individual grid squares based on content in a grid overview image and then detect regions of interest in higher resolution images of good grid squares. Our methods are designed to mimic the actions of a virus TEM expert manually navigating the microscope and they are also compared to the expert’s performance. Integrating the proposed methods with the microscope would reduce the search area by more than 99.99 % and it would also remove the need for an expert to perform the virus search by the microscope."
6484,Understanding and Exploring HIV/AIDS and Discrimination,"This chapter outlines the main theories of discrimination and stigma and the methodology of the research. Both qualitative and quantitative techniques were used in collecting and analyzing the data. Research on refugees is a complex undertaking, and there is no tested method for studying both refugees and HIV/AIDS. This results in the enhanced challenge of conducting research in precarious conditions where refugees reside, owing to displacement of refugees caused by myriad of factors that we have to take into consideration. In this way, it addresses the vacuum in scholarship and prepares the ground for designing research based on geographical and political settings, and proposes new alternatives for addressing them. This will be an important contribution to the methodological underpinning in refugee research. Ethical issues pose a significant challenge as this research involves human subjects and deals with delicate and sensitive issues. This chapter also explains the process for handling confidential research material, developing intersectional analyses and answering specific questions related to multi-strategy research design that are crucial in researching refugees."
6485,Krim-Kongo-Virus,
6486,Leberversagen,"Das Leberversagen ist eine schwere Leberfunktionseinschränkung mit Auftreten einer hepatischen Enzepha-lopathie infolge einer akuten oder chronischen Lebererkrankung. Ob es reversibel oder irreversibel ist, hängt von der Grunderkrankung, dem Lebensalter, einer Vorschädigung der Leber und dem Auftreten von Komplikationen ab."
6487,Disinfection Room: Cleaning Room,"The disinfection room is central to all operations and is a multifunctional room. Here, all contaminants and organic materials are taken care of and removed. Contaminated textiles are sorted and ordinary waste from infectious waste. Used syringes and other stabbing/cutting waste, glass, etc. are collected as hazardous waste. Used wheelchairs and other major patient aids are usually washed here. The bedpan, urine bottles, etc. are disinfected in the decontaminator. The room has a large load of dirt and microbial agents where the personnel may perform many space-demanding tasks. A large and efficient area with good separation between clean and unclean work tasks, good ventilation and negative pressure ventilation and good methods for cleaning and disinfection are necessary. The following chapter is focused on areal and outfit of the disinfection room to avoid transmittance of infections between patients, personal and environment."
6488,Interstitial Lung Diseases,"The term interstitial lung disease (ILD) comprises a diverse group of diseases that lead to inflammation and fibrosis of the alveoli, distal airways, and septal interstitium of the lungs. The ILDs consist of disorders of known cause (e.g., collagen vascular diseases, drug-related diseases) as well as disorders of unknown etiology. The latter include idiopathic interstitial pneumonias (IIPs), sarcoidosis and a group of miscellaneous, rare, but nonetheless interesting, diseases. In patients with ILD, MDCT enriches the diagnostic armamentarium by allowing volumetric high resolution scanning, i.e., continuous data acquisition with thin collimation and a high spatial frequency reconstruction algorithm. CT is a key method in the identification and management of patients with ILD. It not only improves the detection and characterization of parenchymal abnormalities, but also increases the accuracy of diagnosis. The spectrum of morphologic characteristics that are indicative of interstitial lung disease is relatively limited and includes a reticular pattern (with or without traction bronchiectasis), thickening of interlobular septa, honeycombing, nodules, and ground-glass opacities. In the correct clinical context, some patterns or combination of patterns, together with the anatomic distribution of the abnormality, i.e., from the lung apex to the base, or peripheral subpleural versus central bronchovascular, can lead the interpreter to a specific diagnosis. However, due to an overlap of the CT morphology between the various entities, complementary lung biopsy is recommended in virtually all cases of ILDs."
6489,Understanding the Impact of Face Mask Usage Through Epidemic Simulation of Large Social Networks,"Evidence from the 2003 SARS epidemic and 2009 H1N1 pandemic shows that face masks can be an effective non-pharmaceutical intervention in minimizing the spread of airborne viruses. Recent studies have shown that using face masks is correlated to an individual’s age and gender, where females and older adults are more likely to wear a mask than males or youths. There are only a few studies quantifying the impact of using face masks to slow the spread of an epidemic at the population level, and even fewer studies that model their impact in a population where the use of face masks depends upon the age and gender of the population. We use a state-of-the-art agent-based simulation to model the use of face masks and quantify their impact on three levels of an influenza epidemic and compare different mitigation scenarios. These scenarios involve changing the demographics of mask usage, the adoption of mask usage in relation to a perceived threat level, and the combination of masks with other non-pharmaceutical interventions such as hand washing and social distancing. Our results shows that face masks alone have limited impact on the spread of influenza. However, when face masks are combined with other interventions such as hand sanitizer, they can be more effective. We also observe that monitoring social internet systems can be a useful technique to measure compliance. We conclude that educating the public on the effectiveness of masks to increase compliance can reduce morbidity and mortality."
6490,The Mighty World of Microbes: An Overview,"The world of microbes on our planet is vast and diverse. This includes the normal bacterial flora present on the skin and mucous membranes of humans. The human microbiome project (HMP) was launched by NIH in 2007 as a part of a road map for medical research. The HMP serves as a template for researchers who are studying more than 1,000 microbial genomes with a focus on their role in health and disease. The study samples have been derived from five human body regions that are known to be inhabited by microbial flora. These include the gastrointestinal tract, female urogenital tract, mouth, nose, and skin. The techniques being used include finger printing, sequencing, dynamic range, and comparison of multiple samples. It is now well accepted that there are more microbial cells than human cells in the human body. Just the gastrointestinal tract harbors more than tenfold microbial cells than the number of human cells in the entire body. The understanding of the relationship between microbes and humans is at best rudimentary at this point in time. Similarly, the relationship between humans and microbes in the environment and environmental surfaces is poorly understood except for a few pathogenic microbes."
6491,Financial Services Industry,"Critical infrastructure and services in financial industry are important for our society and the financial industry starts to understand the topic beyond the normal and well maintained Business Continuity Management and Disaster Recovery Plans (BCM & DRP). Today, the international backbone financial infrastructures operate pretty well, but in the infrastructure towards clients, two issues are utmost critical for the banks: Drive By Download and Phishing; both are related to steeling identity and money via e-banking. This is one of the results achieved by the EU project Parsifal (Protection and Trust in Financial Infrastructure (Parsifal-Team, 2010), for compositing a research agenda for the cyber security of the financial industry."
6492,Infections in Transplantation: Introduction and Overview,"Over the last 70 years, a steady growth in population of patients with severe and mostly iatrogenically induced immune suppression while undergoing myeloablative antineoplastic therapy and blood- and marrow-derived stem cell or solid organ transplantation has resulted in a near-explosive growth of opportunistic infections. Furthermore, the advent and now common use of biologic immunosuppressive drugs are given to an increasing number of patients prior to transplantation or for treatment of complications arising during the posttransplant period such as graft-versus-host disease, lymphoproliferative disorders, opportunistic malignancies, cancer recurrences, and rejection of solid organ allograft. These and other recent therapeutic advances in transplantation procedures continue to be fraught with prolonged and often unpredictable period of drug-induced immune dysregulation. The emergence and spread of difficult-to-treat opportunistic bacterial, viral, fungal, and parasitic diseases in transplant population have evolved under the influence of environmental-, host-, disease-, and treatment-specific variance. A diligent diagnostic adjudication is of utmost importance in a population with known proclivity for atypical disease presentation. Inaccurate diagnosis may result in inappropriate and ineffective empiric therapy that may worsen patients’ morbidity and heighten the risk for further complications and death. Advancement in understanding the immunopathogenesis of infectious diseases, hosts’ immunologic vulnerability for infections, emerging molecular diagnostic paradigms, deciphering potential therapeutic impact of immune modulation by existing and new antimicrobial drugs, and active research and development in mitigation strategies to promote immune recovery and immune preservation are encouraging developments in optimizing care for patients in need for lifesaving transplantation procedures."
6493,How Governmental Regulation Can Help or Hinder the Integration of Bt Crops within IPM Programs,"Regulatory risk assessments are an important part of the introduction of insect-resistant genetically modified (GM) crops (e.g., Bacillus thuringiensis [Bt] crops) into the environment to ensure the safe use of such products. In doing so, the regulatory assessment process can be clearly beneficial to integrated pest management (IPM) programs. In general, the regulatory framework for insect-resistant GM crops includes an assessment of the following: effects of the insecticidal trait on non-target organisms, other potential adverse environmental impacts, evolution of resistance to target pests, and environmental and agronomic benefits of the insecticidal trait. Each country’s regulatory system is dependent on the overall environmental risk management goals, relevant and available risk information, scientific capacity, and the available financial resources. A number of regulatory activities can help to ensure that new products such as Bt crops fit well within IPM programs: (1) evaluation of the environmental safety of new products, and their ability to enhance IPM; (2) encouragement of the adoption of new technologies with improved environmental safety profiles; (3) adoption of an expedited regulatory review system; and (4) encouragement and appropriate oversight of sustainable use of such products. Governmental regulation of insect-resistant GM crops can also hinder IPM programs by creating significant barriers to the adoption of such technologies. Such barriers include: (1) absence of functioning regulatory systems in many developing countries; (2) meeting the obligations and understanding the various interpretations of international treaties, e.g., Cartagena Protocol on Biosafety; (3) lack of public sector research to generate data supporting the safety of these crops; and (4) regulatory costs involved in the development and commercialization of novel products for small market sectors. Ways in which regulatory data requirements can be globally harmonized need to be considered to decrease the regulatory barriers for insect-resistant GM crops and comparable technologies. International organizations can play a key role in rationalizing regulatory systems; however, public sector research will also be needed to make sure that the risk assessment process is scientifically sound and transparent."
6494,Aircraft Environmental Control Systems,"The external environment at 41000 ft (12500 m), a typical cruise altitude for modern civil aircraft, is hostile to human life. Aircraft environmental control systems are designed to ensure the survival of the aircraft occupants as well as providing them with a comfortable atmosphere. Major design drivers for the environmental control system are thermal comfort, pressurisation and cabin air quality. However, these parameters cannot be considered independently. They interact between themselves and with other parameters, which may or may not be controllable by the system designer. These interactions occur in a highly complex manner. Research has led to a good understanding of the basic functions to allow safe and comfortable aircraft environmental conditions. Future research efforts will be increasingly focussed on identifying and elaborating the interdependency of factors in order to further enhance the aircraft cabin environment."
6495,Ventilator-Associated Pneumonia and Other Complications,"Ventilator-associated pneumonia occurs in patients who have been intubated for two to three days with significant exposure to hospital-acquired organisms. Treatment should be initiated rapidly and cover P. aeruginosa, Escheriochia coli, Klebsiella pneumonia, and Acinetobacter species as well as methicillin-resistant S. aureus. Within 72 h or with the availability of culture results, antibiotics should be narrowed. Active research is on-going to identify patients at risk for ventilator-associated complications and to minimize the likelihood of infection in these patients."
6496,Diagnosis of Viral Infections,"Accurate diagnosis of viral infections enhances the ability of the clinician to make decisions on appropriate treatment of patients, evaluate disease progression and prevent misuse of antibiotics. Knowledge of the pathogen involved also allow implementation of infection control and monitoring of success of antiviral treatments that may affect the prognosis of patients. Epidemiological data collected through accurate diagnostics play an important role in public health through identification and control of outbreaks, implementation of appropriate diagnostic tests, vaccination programs and treatment but also to recognize common and emerging pathogens in a community. It is key that the clinician have an understanding of appropriate specimens to send to the laboratory and the value of specific nucleic acid and serological testing for different viral pathogens. Molecular techniques have revolutionized viral diagnoses over the past decade and enhanced both the sensitivity and specificity of tests and the speed by which a diagnosis can be made and new tests be developed. The continued use of serology for viruses with a short viremia, or for chronic infections should however complement these tests. This chapter aims to provide an overview of the available tests, the principles of testing and appropriate tests to select for different viruses and syndromes. Also provided is a glimpse of new developments in diagnostics that may further enhance the capacity to make a conclusive diagnosis in the near future."
6497,The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis,"Apoptosis is a fundamental process contributing to tissue homeostasis, immune response, and development. CD95, also called Fas, is a member of the tumor necrosis factor receptor (TNF-R) superfamily. Its ligand, CD95L, was initially detected at the plasma membrane of activated T lymphocytes and natural killer (NK) cells where it contributes to the elimination of transformed and infected cells. Given its implication in immune homeostasis and immune surveillance combined with the fact that various lineages of malignant cells exhibit loss-of-function mutations, CD95 was initially classified as a tumor suppressor gene. Nonetheless, in different pathophysiological contexts, this receptor is able to transmit non-apoptotic signals and promote inflammation and carcinogenesis. Although the different non-apoptotic signaling pathways (NF-κB, MAPK, and PI3K) triggered by CD95 are known, the initial molecular events leading to these signals, the mechanisms by which the receptor switches from an apoptotic function to an inflammatory role, and, more importantly, the biological functions of these signals remain elusive."
6498,Wie katz und Maus,"Die Patientin M.S. ist eine 20-jährige Frau, bei der vor etwa 2 Jahren eine akute lymphoblastische Leukämie festgestellt wurde. Die Erstmanifestation war ein lymphozytäres Chlorom an der rechten Seite des Kopfes. Nach der operativen Entfernung des Chloromes erhielt Frau S. eine kurative Radio- und Chemotherapie. Rund 18 Monate später kam es zu einem Rezidiv, das nach Konditionierung mit Cyclophosphamid, Anti-Thymozyten-Globulin und Ganzkörperbestrahlung mit einer allogenen Stammzelltransplantation behandelt wurde. Die Patientin war seit einem halben Jahr in einer kompletten Remission. Vor einigen Tagen bekam sie plötzlich Fieber bis zu 40°C. Bis zur Aufnahme im Krankenhaus entwickelte sie Dyspnoe, Tachypnoe und etwas unproduktiven Husten."
6499,Krätzmilben (Sarcoptes scabiei und ähnliche),"Acarus scabiei, Sarcoptes scabiei scabiei, itch mite"
6500,"Appropriate Antibiotic Use for Treatment of Nonspecific Upper Respiratory Infections, Rhinosinusitis, and Acute Bronchitis in Adults","Acute sinusitis, bronchitis, pharyngitis, and nonspecific upper respiratory tract infections (URIs) account for the majority of antibiotics prescribed by primary care physicians in the United States. The emergence of antibiotic-resistant bacteria in the community setting is now an issue for individual patients as well as society at large, and it is the responsibility of all clinicians to limit antibiotic treatment to those patients who are most likely to benefit from it. The vast majority of acute respiratory infections are caused by viruses. Antibiotic treatment of patients with these infections selects for resistant nasopharyngeal bacteria, acutely increasing the spread of resistant pathogens through secretions and predisposing the treated patient to more serious bacterial infections in the future. The guidelines summarized in this chapter were designed by a panel of physicians representing family medicine, internal medicine, emergency medicine, and infectious diseases to provide a practical approach to the appropriate diagnosis and treatment of previously healthy adults with nonspecific URI, acute sinusitis, or acute bronchitis in the ambulatory care setting. Recommendations for the diagnosis and treatment of pharyngitis are provided in a separate chapter."
6501,7 Leverfalen,"De lever vervult tal van essentiële functies in het menselijk lichaam, waaronder ontgifting van het bloed en aanmaak van diverse eiwitten en hormonen. Tevens speelt de lever een rol in het afweersysteem. Leverfalen kan omschreven worden als een situatie van onvoldoende werking van de lever bij deze processen. Dit beeld ontstaat wanneer door het verlies van functionele cellen het totale effectieve levervolume beneden een kritische grens komt. In dit hoofdstuk wordt ingegaan op diverse vormen van leverfalen en twee specifieke bij leverfalen voorkomende problemen, namelijk hepatische encefalopathie en verhoogde bloedingsneiging."
6502,Using Emergency Department Data For Biosurveillance: The North Carolina Experience,"Biosurveillance is an emerging field that provides early detection of disease outbreaks by collecting and interpreting data on a variety of public health threats. The public health system and medical care community in the United States have wrestled with developing new and more accurate methods for earlier detection of threats to the health of the public. The benefits and challenges of using Emergency Department data for surveillance are described in this chapter through examples from one biosurveillance system, the North Carolina Disease Event Tracking and Epidemiologic Collection Tool (NC DETECT). ED data are a proven tool for biosurveillance, and the ED data in NC DETECT have proved to be effective for a variety of public health uses, including surveillance, monitoring and investigation. A distinctive feature of ED data for surveillance is their timeliness. With electronic health information systems, these data are available in near real-time, making them particularly useful for surveillance and situational awareness in rapidly developing public health outbreaks or disasters. Challenges to using ED data for biosurveillance include the reliance on free text data (often in chief complaints). Problems with textual data are addressed in a variety of ways, including preprocessing data to clean the text entries and address negation. The use of ED data for public health surveillance can significantly increase the speed of detecting, monitoring and investigating public health events. Biosurveillance systems that are incorporated into hospital and public health practitioner daily work flows are more effective and easily used during a public health emergency. The flexibility of a system such as NC DETECT helps it meet this level of functionality."
6503,Viral Gene Compression: Complexity and Verification,"The smallest known biological organisms are, by far, the viruses. One of the unique adaptations that many viruses have aquired is the compression of the genes in their genomes. In this paper we study a formalized model of gene compression in viruses. Specifically, we define a set of constraints that describe viral gene compression strategies and investigate the properties of these constraints from the point of view of genomes as languages. We pay special attention to the finite case (representing real viral genomes) and describe a metric for measuring the level of compression in a real viral genome. An efficient algorithm for establishing this metric is given along with applications to real genomes including automated classification of viruses and prediction of horizontal gene transfer between host and virus."
6504,"Immunomodulators: interleukins, interferons, and IV immunoglobulin","The outstanding progress in immunology and the development of new technologies have resulted in the introduction of new immunotherapies, the so-called “immunomodulators”, for autoimmune diseases, inflammatory disorders, allograft rejection, and cancer. These immunomodulators comprise recombinant cytokines and specific blocking or depleting antibodies. Many of these therapies achieve their effect by stimulating the release of cytokines. The term cytokines includes interleukins (IL-), chemokines, growth factors, interferons (IFN), colony stimulating factors (CSF), and tumor necrosis factors (TNF). These molecules are involved in inflammation, cell proliferation and apoptosis, tissue injury and repair. These new therapeutic tools can be associated with side effects among which nephrotoxicity. The most common immunomodulators associated with nephrotoxicity are described in Table 1. The nephrotoxic side effects of immunomodulators can be roughly divided into (ischemic) tubular necrosis, thrombotic microangiopathy, serum sickness, and autoimmune disorders."
6505,Designing Medical Facilities to Care for Patients with Highly Hazardous Communicable Diseases,"Certain highly hazardous communicable diseases (HHCD), including viral hemorrhagic fevers, the Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome virus (SARS), have caused nosocomial outbreaks in unprepared facilities. Consequently, biocontainment units have been constructed to protect caregivers, patients, and family members, in addition to providing optimal care of the infected patient. Biocontainment units have adopted many of the design features originally found in biocontainment laboratories and can serve as national referral facilities for the most severe and highly hazardous infections. Although a patient with a HHCD can show up at any healthcare facility unannounced, not every hospital can or should attempt to establish a biocontainment unit. Nevertheless, there are design features or management principles found in biocontainment units that can be adopted in most facilities. Awareness of the potential risk, in addition to adopting structural and policy control measures, can do a lot to prepare a facility for the next unexpected infectious disease outbreak."
6506,High Frequency Oscillatory Ventilation,"Forty years have elapsed since investigators first appreciated that tidal volumes measuring less than the physiologic dead space can produce reliable ventilation when delivered at high frequencies. Of all high frequency ventilation techniques, high frequency oscillatory ventilation (HFOV) is the most well studied and is the most commonly utilized in clinical practice today. In HFOV, small volume oscillatory vibrations are superimposed on continuous distending pressure in a manner that allows efficient CO(2) elimination during continuous alveolar recruitment. By preserving end-expiratory lung volume, minimizing cyclic stretch, and avoiding alveolar overdistension at end-inspiration, HFOV is uniquely capable of providing the ultimate “open lung” strategy of ventilation. Over the past decade, a growing evidence base implicating phasic alveolar stretch in the pathogenesis of acute and chronic lung injury in patients with respiratory failure has driven the iterative refinement of HFOV management protocols for infants, children, and adults. The next step toward applying HFOV in a manner that takes into account the heterogeneity of parenchymal involvement in diseases such as the acute respiratory distress syndrome will require the development of non-invasive bedside technologies capable of identifying regional changes in lung volume and lung mechanics. Electrical impedance tomography (EIT) is a promising technique that could play a supporting role in the conduct of future clinical trials seeking to identify HFOV strategies that are maximally lung protective."
6507,Kardiologie,"Dieses Kapitel gibt einen Überblick über Ätiologie, Häufigkeit und Einteilung angeborener Herzfehler. Die einzelnen Herzfehler werden nach Definition, Einteilung, Klinik, Diagnostik, Therapie und Prognose beschrieben. Gleiches folgt für die erworbenen Herzerkrankungen. Abschließend werden die im Kindesalter typischen Herzrhythmusstörungen betrachtet."
6508,What We Think About When We Think About Triffids: The Monstrous Vegetal in Post-war British Science Fiction,"In the face of continuing post-war reconstruction and the rising tide of urbanization, British science fiction writers such as John Wyndham (a pseudonym for John Beynon Harris) and John Christopher (Sam Youd) portrayed post-apocalyptic scenarios in which the vegetal directly determines the fate of human civilization. By destabilizing the relationship between plant and human, Wyndham and Christopher open up a space to reconsider the vegetal as a distinct life form itself, beyond its instrumental use-value, or as an anthropomorphized reflection of human thought. Although plant life is traditionally defined by its inability to move or to speak, both writers suggest that communication bound to the visual or oral is highly limited (for instance, human sight is confined to a limited spectrum). In Wyndham’s The Day of the Triffids (1951) plants become mobile and seemingly sentient, in the process becoming an invasive presence that exposes and challenges the limits of anthropocentric thought. By contrast, in Christopher’s The Death of Grass (1956), the absence of the vegetal renders manifest the subaltern status of plant life, while suggesting that plants are able to communicate through their materiality and posture. Both texts signal that what is conventionally understood as Other is actually a blank repository that ventriloquizes humans’ unconscious desire. Following the population’s sudden loss of sight in The Day of the Triffids, the characters begin to project their own thoughts and emotions onto the triffids, which highlights the indeterminate limits of anthropomorphic representation. The Death of Grass demonstrates that such anthropocentrism constitutes an act of metaphysical violence that, at the same time, under-imagines plant life and installs specialist terminology and botanical classification as a substitute. Presenting the relationship between plant life and human life as a contested space, these texts manifest the problem of anthropocentric certainties and the absolute alterity of plant-thought."
6509,Infections in Patients with Acute Leukemia,"Patients with acute leukemia are at increased risk of developing infections both as a result of the leukemia and its treatment. Neutropenia is the primary risk factor associated with the development of infection, with the severity and frequency of infection increasing as the absolute neutrophil count drops below 500 cells/mm(3), as initially described by Bodey and colleagues. Other risk factors may be present including impaired cellular or humoral immunity, breakdown of normal barriers such as the skin and mucosal surfaces, and vascular access catheters and other foreign medical devices. Multiple risk factors are often present in the same patient. Additionally, the frequent use of antimicrobial agents for various indications (prophylaxis, empiric therapy, pre-emptive administration, specific or targeted therapy, and occasionally maintenance or suppressive therapy) has an impact on the nature and spectrum of infections, with the emergence/selection of multidrug-resistant (MDR) organisms being of particular concern. Bacterial infections tend to occur early on in a neutropenic episode, with fungal infections being uncommon at this stage. If neutropenia persists, the risk for fungal infections increases. There are periodic changes in the epidemiology/spectrum of infection in patients with leukemia. It is important to conduct periodic epidemiologic and susceptibility/resistance surveys, especially at institutions dealing with large numbers of such patients, in order to detect these shifts and changes in susceptibility/resistance patterns, since empiric therapy is largely based on this information. Such surveys are conducted every 3–5 years at our institution."
6510,"Physical, Social and Cultural, and Global Influences","In Chap. 5, we examined the technological environment of the health care policy-making system. Specifically, we examined the classification, evolution, and diffusion of medical technology; the effects of medical technology on medical training and the practice of medicine; effects on medical costs, quality of care, and quality of life; effects on access to care; the ethical concerns raised by medical technology; and the practice of technology assessment. We concluded the chapter by observing that the growth of technology, as well as other human endeavors, affects other important aspects of our lives, most notably, the air we breathe, the food we eat, the generation of radioactive by-products and toxic chemicals, the manufacture of illicit drugs, and the generation of natural and man-made hazards. In other words, in addition to their effects on the health care system, technology and other human activities affect many other aspects of our lives that are associated with health."
6511,Avian Infectious Bronchitis Virus,"Avian infectious bronchitis (IB) is caused by avian infectious bronchitis virus (IBV) belonging to Coronaviridae family. The disease is prevalent in all countries with almost 100% incidence rate. Chicken and commercially reared pheasant are the natural host for IBV. Virus causes respiratory diseases, poor weight gain, feed efficiency in broiler, damage to oviduct, and abnormal egg production in mature hens resulting in economic losses. IBV also replicates in tracheal and renal epithelial cells leading to prominent tracheal and kidney lesions. Virus undergoes spontaneous mutation leading to continual emergence of new variants. The effectiveness of immunization program is diminished because of poor cross-protection among the serotypes. Identification of circulating serotypes is important in controlling IBV infection. Toll-like receptor 3 (TLR3) and TLR21 are involved in early recognition of virus resulting in induction of inflammatory cytokines. Both humoral and cellular immune responses are important in the control of infection. Humoral immunity plays an important role in recovery and clearance of viral infection. IBV-specific cytotoxic T lymphocytes induce lysis of IBV-infected cells. Effective diagnostic tools are required at field level to identify different IBV variants. Embryonated chicken eggs are effective model for virus isolation. Identification by other specific methods like virus neutralization (VN), hemagglutination inhibition (HI), enzyme linked immunosorbent assay (ELISA), immunohistochemistry, or nucleic acid analysis or by electron microscopy is also indispensable. VN test in tracheal organ culture is the best method for antigenic typing for surveillance purposes. Continuous epidemiological surveillance, strict biosecurity measures, and vaccine effective against various serotypes are necessary for controlling IB in chickens."
6512,Biotechnology Applications of Grapevine Viruses,"Plant virus genomes are engineered as vectors for functional genomics and production of foreign proteins. The application of plant virus vectors is of potential interest to the worldwide, multibillion dollar, grape and wine industries. These applications include grapevine functional genomics, pathogen control, and production of beneficial proteins such as vaccines and enzymes. However, grapevine virus biology exerts certain limitations on the utility of the virus-derived gene expression and RNA interference vectors. As is typical for viruses infecting woody plants, several grapevine viruses exhibit prolonged infection cycles and relatively low overall accumulation levels, mainly because of their phloem-specific pattern of systemic infection. Here we consider the biotechnology potential of grapevine virus vectors with a special emphasis on members of the families Closteroviridae and Betaflexiviridae."
6513,Acute Pancreatitis,Early diagnosis and treatment are crucial in the management of acute pancreatitis to prevent complications and to reduce morbidity and mortality.
6514,Advanced Pathology Techniques for Detecting Emerging Infectious Disease Pathogens,"The control and prevention of infectious diseases remain a fundamental part of public health programs throughout the world. The modern medicine and public health have been challenged by a series of emerging and reemerging infections in the past three decades. These diseases have occurred following a false sense of victory over infectious diseases on a global scale due to effective vaccinations and antibiotic agents against certain microorganisms. Because of the unique circumstances of the modern world, these new infectious diseases are emerging at much faster rates than before, and old ones are returning with formidable strength. These infections have posed severe threats to global public health and have raised serious questions regarding the capability of modern medicine to face their challenges. Therefore, it is crucial to understand the dynamics and impact of these emerging and reemerging infectious diseases. Diagnostic pathology continues to be an essential counterpart of clinical microbiology in dealing with emerging and reemerging infections. Diagnosis with advanced pathology techniques not only helps identify or confirm the novel pathogens causing emerging infections but is also essential for epidemiologic surveillance and studying pathogenesis of these emerging infections."
6515,Beeldvormende diagnostiek,"Radiologie en nucleaire geneeskunde zijn geïntegreerd in de opleiding radiologie. Expertise binnen de radiologie is naar orgaansysteem georganiseerd, maar in dit hoofdstuk wordt de radiologie per beeldvormende techniek besproken, dat wil zeggen conventionele radiologie, computertomografie (CT), echografie, magnetische resonantie imaging (MRI) en de nucleaire geneeskunde. De binnen de interne geneeskunde meest voorkomende indicaties voor de verschillende onderzoeken worden besproken inclusief de risico’s en gevaren van beeldvormende diagnostiek. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1841-4_2) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers."
6516,The Needs of Children in Natural or Manmade Disasters,"Disasters have been described as “events of sufficient scale, asset depletion, or numbers of victims to overwhelm medical resources” [1] or as “a serious disruption of the functioning of a community or a society causing widespread human, material, economic or environmental losses that exceed the ability of the affected community or society to cope using its own resources” [2]. Importantly, that definition goes on to state: “A disaster is a function of the risk process. It results from the combination of hazards, conditions of vulnerability and insufficient capacity or measures to reduce the potential negative consequences of risk.”"
6517,Alcohol-Mediated Zinc Deficiency Within the Alveolar Space: A Potential Fundamental Mechanism Underlying Oxidative Stress and Cellular Dysfunction in the Alcoholic Lung,"Zinc is one of the most abundant trace elements in the human body, and its presence is essential for numerous biological processes including enzymatic activity, immune function, protein synthesis, and wound healing. Given these important roles, zinc has a sophisticated transport system to regulate its homeostasis. Determination of zinc status, however, is difficult to determine as serum levels are closely maintained and are not an accurate reflection of total body zinc or metabolism at the organ level. Fortunately, the discovery of zinc-specific fluorescent dyes has allowed for a much better assessment of zinc status in the respiratory system and has revealed that alcoholism perturbs this highly developed zinc metabolism such that its distribution to the lung and alveolar space is significantly decreased. As a result, this pulmonary zinc deficiency impairs function in the alveolar macrophage, which is the primary host immune cell within the lower airway. Experimental models have demonstrated that correction of this zinc deficiency restores immune function to the alveolar macrophage as best reflected by improved bacterial clearance in response to infection. While the precise mechanisms underlying alcohol-induced zinc deficiency are still under investigation, there is experimental evidence of several important connections with granulocyte–macrophage colony-stimulating factor and oxidative stress, suggesting that alteration of zinc homeostasis may be a fundamental mechanism underlying the cellular pathology seen in the alcohol lung phenotype. This chapter reviews zinc homeostasis and offers insight into our understanding of zinc deficiency in the setting of alcoholism and the potential of zinc as a therapeutic modality in the vulnerable alcoholic host."
6518,Fever in Common Infectious Diseases,"#x203A; Infection of the respiratory tract is the most common reason for seeking medical advice and hospital admission in children. A viral upper respiratory tract infection (URTI) is the most common infection of the respiratory tract. › In developing countries, acute respiratory infection remains a leading cause of childhood mortality, causing an estimated 1.5–2 million deaths annually in children younger than 5 years of age. › In developed countries, viruses are responsible for most upper and lower respiratory tract infections, including pharyngitis and pneumonia. › Although the degree of fever cannot differentiate between viral and bacterial diseases, high fever is associated with a greater incidence of serious bacterial diseases such as pneumonia or meningitis. › Worldwide, diarrheal disease is the leading cause of childhood deaths under 5 years of age. › If the fever does not have an evident source, urinary tract infection (UTI) should be considered, particularly if the fever is greater than 39.0°C and persists for longer than 24–48 h. › Widespread vaccinations against bacteria causing meningitis, such as Hib, and vaccines against meningococci and pneumococci have dramatically reduced the incidence of meningitis. › A child with fever and nonblanching rash should be promptly evaluated to exclude meningococcal diseases. › Young children with malaria may present with irregular fever and not with typical paroxysms of fever, occurring particularly in early falciparum infection or as a consequence of previous chemoprophylaxis, which modifies the typical pattern of fever."
6519,Die Zelle als gengesteuertes System,"Die genetische Information der Pflanzenzelle ist in den DNA-Molekülen des Zellkerns (nucleäres Genom), der Plastiden (plastidäres Genom) und der Mitochondrien (mitochondriales Genom) niedergelegt. Die Genome der Plastiden und Mitochondrien leiten sich von Genomen prokaryotischer Organismen ab, die während der Evolution als Endosymbionten in die Eukaryotenzelle aufgenommen wurden, Endosymbiontentheorie.Diese Organellengenome, und die zugehörigen Mechanismen der Genexpression, zeichnen sich auch heute noch durch viele prokaryotische Merkmale aus."
6520,Editoriale — Polmoniti acquisite in comunità e polmoniti nosocomiali,Per polmonite si intende un’infezione del parenchima polmonare.
6521,Automated Solid Phase Oligosaccharide Synthesis,"Of the three classes of biopolymers—nucleic acids, proteins and glycoconjugates, nucleic acids and proteins have seen the most breakthroughs in understanding their biological role, in part due to their ready availability. The automation of oligonucleotide and peptide synthesis has been fruitful in providing biologists and biochemists with pure, well-defined structures. This work reviews the recent developments in the automated synthesis of oligosaccharides, the third class of biopolymers. Both glycosyl phosphates and glycosyl trichloroacetimidates have been used successfully in the automated assembly of oligosaccharides employing an octenediol-functionalized polystyrene resin. The product was cleaved either by methanolysis of an ester bond or by olefin cross metathesis. Several biologically important carbohydrates have been synthesized by automation, in a fraction of the time needed to synthesize them by traditional methods. For example, the tumor associated antigens Lewis Y, Le(y)-Le(x), were synthesized by automation. A Leishmania cap tetrasaccharide and a malaria toxin vaccine candidate were also assembled."
6522,Deconstructing the Medical Chart,"This chapter provides an overview of the medical chart, and its sections. The neuropsychologist will be provided with detailed information about how to decipher some of the many abbreviations, and we also provide the neuropsychologist, who may not be familiar with common lab values with descriptions of the neurologic examination common grading systems such as motor and sensory functions. In addition, this chapter provides a brief overview of neurologic terms commonly encountered in general medical and more detailed neurological examinations along with figures and illustrations of some of these terms."
6523,Diagnostic Imaging in Sepsis of Pulmonary Origin,"Lung infections (community- or hospital-acquired) represent the most common cause for sepsis. Diagnostic imaging plays a crucial role in the initial evaluation of patients with criteria for sepsis and suspected pulmonary infection. In patients with clinical signs and symptoms of respiratory infection, the chest X-ray allows confirming the diagnosis of pneumonia. On the other hand, the chest X-ray can be useful to assess response to treatment (in some patients), define a pattern suggesting specific germs (particularly TB), identify complications (empyema and ARDS), and propose a differential diagnosis."
6524,Plague as a Biological Weapon,
6525,Construction and Building Applications,"The construction industry is a particularly attractive industry for nanotechnology applications. Since it employs a diversity of building materials, nanomaterials can be employed to enhance the materials’ performances, durability, longevity and sustainability. The construction and building practice is detrimental to the environment in various aspects such as electricity consumption, landfill accumulation, unhealthy aesthetics and neighborhoods. This chapter shows how nanotechnology-based building materials are playing an important role in green architectural design and construction, which has become a growing trend in many countries. Nanomaterials could be integrated with cement, concrete, or windows to conserve energy, minimize electricity bills and sanitize the surrounding atmosphere. Nevertheless, the industry is still facing many hurdles towards the wide application of nanomaterials in a cost effective manner."
6526,Infections in Burns,"Infections remain a leading cause of death in burn patients. This is as a result of loss of the environmental barrier function of the skin predisposing these patients to microbial colonization leading to invasion. Therefore, reconstitution of the environmental barrier by debriding the devitalized tissue and wound closure with application of allograft versus autograft is of optimal importance."
6527,Understanding Objectivity in Research Reported in the Journal Science & Education (Springer),"Based on a website search with the keyword “objectivity,” 131 articles in the 23 year period (1992–2014) referred to some form of objectivity and were classified according to the following criteria: Level I, traditional understanding of objectivity as found in science textbooks and positivist philosophers of science; Level II, a simple mention of objectivity as an academic/literary objective; Level III, problematic nature of objectivity is recognized, however, no mention is made of its changing/evolving nature; Level IV, an approximation to the evolving/changing nature of objectivity based on social and cultural aspects; Level V, a detailed historical reconstruction of the evolving nature of objectivity that recognized the role of the scientific community and its implications for science education. Results obtained showed the following distribution of the 131 articles evaluated: Level I = 5, Level II = 56, Level III = 58, Level IV = 10, and Level V = 2. Only 9% (12 out of 131) of the articles were considered to have an understanding of objectivity that approximated to its historical evolution. Four articles referred to the work of Daston and Galison on objectivity and only one mentioned “trained judgment.” One article based on the work of Longino (explanatory plurality) reconciled the objectivity of science with its social and cultural construction (Level IV)."
6528,Engels-Nederlands,
6529,Pneumonie unter allogener Stammzelltransplantation,"Die allogene Transplantation beinhaltet im Gegensatz zur autologen Transplantation die Übertragung von Knochenmark oder Blutstammzellen eines anderen Spenders. Im Falle einer Pneumonie reflektiert die Phase der Immunsuppression das zu erwartende Erregerspektrum. Im Unterschied zur autologen Stammzelltransplantation umfasst das Risiko für bestimmte Erreger je nach Phase nicht nur das der Neutropenie, sondern auch der zellulären und humoralen Immunsuppression durch die immunsuppressive Medikation bzw. die akute und chronische GvHD. Zudem besteht das Risiko für nichtinfektiöse pulmonale Komplikationen. Das Zytomegalievirus ist einer der wichtigsten Erreger von schweren Infektionen bzw. Pneumonien. Nach Etablierung der präventiven Therapien sind CMV-Pneumonien bis Tag 100 eher selten geworden; ein Problem bleiben weiterhin die späten CMV-Pneumonien durch ihre hohe Letalität. Die Indikation zur Bronchoskopie sollte den allgemeinen Prinzipien der Diagnostik von pulmonalen Komplikationen unter Immunsuppression folgen."
6530,Semantic Tracking in Peer-to-Peer Topic Maps Management,"This paper presents a collaborative semantic tracking framework based on topic maps which aims to integrate and organize the data/information resources that spread throughout the Internet in the manner that makes them useful for tracking events such as natural disaster, and disease dispersion. We present the architecture we defined in order to support highly relevant semantic management and to provide adaptive services such as statistical information extraction technique for document summarization. In addition, this paper also carries out a case study on disease dispersion domain using the proposed framework."
6531,Agrochemical Poisoning,"A general increase in the use of chemicals in agriculture has brought about a concomitant increase in the incidence of agrochemical poisoning. Organophosphates are the most common agrochemical poisons followed closely by herbicides. Many agricultural poisons, such as parathion and paraquat are now mixed with a coloring agent such as indigocarmine to prevent their use criminally. In addition, paraquat is fortified with a “stenching” agent. Organo-chlorines have an entirely different mechanism of action. Whereas organophosphates have an anticholinesterase activity, organochlorines act on nerve cells interfering with the transmission of impulses through them. A kerosene-like smell also emanates from death due to organochlorines. The diagnosis lies in the chemical identification of organochlorines in the stomach contents or viscera. Organochlorines also resist putrefaction and can be detected long after death. Paraquat has been involved in suicidal, accidental, and homicidal poisonings. It is mildly corrosive and ulceration around lips and mouth is common in this poisoning. However, the hallmark of paraquat poisoning, especially when the victim has survived a few days, are the profound changes in lungs. Other agrochemicals such as algicides, aphicides, herbicide safeneres, fertilizers, and so on, are less commonly encountered. Governments in most countries have passed legislations to prevent accidental poisonings with these agents. The US government passed the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) in 1962 and the Indian government passed The Insecticides Act in 1968. Among other things, these acts require manufacturers to use signal words on the labels of insecticides, so the public is warned of their toxicity and accompanying danger."
6532,Antiviral Properties of Phytochemicals,"In recent years, significant progress has been achieved for the development of novel anti-viral drugs. These newly developed drugs belong to three groups of compounds, nucleoside analogues, thymidine kinase-dependent nucleotide analogues and specific viral enzyme inhibitors. It has been found that the natural products, like plant-derived compounds (phytochemicals) as well as traditional medicines, like traditional Chinese medicines (TCM), Ayurvedic medicines and so on, are the important sources for potential and novel anti-viral drugs. In this chapter, the history of natural products as antiviral drugs, the approaches to discover potential lead compounds, and the anti-viral properties of phytochemicals with different action mechanisms are discussed. The key conclusion is that natural products are most important sources for novel anti-viral drugs."
6533,Application in Medicine Systems,"Modern pharmacological studies on Danshen have shown that the pharmacologic actions of Danshen mainly include dilating vessels, promoting blood flow, improving microcirculation, changing blood viscosity, increasing myocardial blood and oxygen supplies, reducing myocardial consumption of oxygen, etc. The drug is used to treat diseases of the cardio-cerebrovascular system. In addition, Danshen also has antitumor, antibacterial, and anti-inflammatory functions. Therefore, Danshen has wide clinical application. In recent years, there has been an increase in the number of reports on the clinical application of Danshen extract and Danshen compound preparations. Danshen is seldom used alone; rather, it is usually combined with other drugs to form compound preparations. Various Danshen preparations have been developed, such as Compound Danshen Tablets, Compound Danshen Dropping Pill ( Dantonic™), Compound Danshen Granules, Compound Danshen Capsule, Compound Danshen Oral Liquid, Compound Danshen Aerosol, and Compound Danshen Injection (CDI), etc. The successful development of these preparations has improved product quality, enhanced efficacy, and opened up broader prospects for Danshen’s clinical application."
6534,Structure of an ECMO Network for Respiratory Support,"In adult patients with respiratory failure refractory to conventional treatment, ECMO represents a potentially lifesaving option, and the CESAR trial indeed indicated that significantly more patients with severe ARDS survived without severe disability if they were transferred to a single ECMO center compared with patients who were managed conventionally at remote hospitals. During the 2009 influenza A (H1N1) pandemic, the Italian Ministry of Health instituted a national network of selected ICU centers, the Extracorporeal Membrane Oxygenation Network (ECMOnet). The Italian network was set up to centralize all potentially severe patients in a limited number of tertiary hospitals to provide advanced treatment options including ECMO and identify predictors of mortality in order to define the best timing of ECMO institution. The institution of the Italian ECMO network allowed a high survival rate of patients with severe ARDS due to H1N1 infection treated by ECMO, providing effective and safe centralization and creating an important organization platform to face future possible epidemics with high demand for critical care services and specialized respiratory support."
6535,Pädiatrische Intensivmedizin,"Dieses Kapitel soll einen verständlichen Überblick geben über Besonderheiten der intensivmedizinischen Betreuung des Kindes, insbesondere des Kleinkindes, im Vergleich zur Intensivmedizin beim Erwachsenen. Es werden deshalb nicht alle Aspekte der pädiatrischen Intensivmedizin im Sinne eines eigenständigen Lehrbuchs beleuchtet. In einem ersten Teil (·Kap. 84.2-84.4) werden allgemeine Themen und Aspekte inklusive die kardiopulmonale Reanimation behandelt, in einem zweiten Teil (·Kap. 84.5) werden spezifische pädiatrische Krankheitsbilder und ihre Therapie diskutiert."
6536,Immunisierung,"Wie funktionieren Impfungen? Wir unterscheiden aktive und passive Vakzinierungen. Bei der aktiven Vakzinierung wird Antigen appliziert, das im Organismus eine adaptive Immunantwort auslöst. Dies benötigt Zeit, doch hält die Wirkung lange an, da ein antigenspezifisches Immungedächtnis aufgebaut wird. Bei der passiven Vakzinierung werden immunologische Effektormoleküle oder Immunzellen appliziert, die ihre Wirkung sofort entfalten."
6537,Inference Claims,"A conclusion follows from given premisses if and only if an acceptable counterfactual-supporting covering generalization of the argument rules out, either definitively or with some modal qualification, simultaneous acceptability of the premisses and non-acceptability of the conclusion, even though it does not rule out acceptability of the premisses and does not require acceptability of the conclusion independently of the premisses. Hence the reiterative associated conditional of an argument is true if and only it has such a covering generalization, and a supposed unexpressed premiss supplied to make an argument formally valid should be a covering generalization."
6538,Online Monitoring Technologies For Drinking Water Systems Security,"More stringent constraints placed nowadays on water companies to provide high quality drinking water, increasing water resources scarcity in many areas of the planet, forcing water companies to work on marginal water bodies for supply, and the threat of hostile actions by political extremists and terrorist groups, that may willingly and deliberately cause contamination of an otherwise safe supply, are recent issues that have spurred demand for more efficient and comprehensive online water monitoring technologies. Traditionally, quality parameters associated with drinking water provision were monitored using routine grab samples followed by laboratory analysis. This approach only allowed to capture small data sets, mostly unrepresentative of the true variance at the source, and allowed potentially important events to occur undetected. This paper examines state-of-the-art technologies for online monitoring of water quality in supply water systems, and reports some recent application examples."
6539,Genetic Models,"Genetically altered rat and mouse models have been instrumental in the functional analysis of genes in a physiological context. In particular, studies on the renin-angiotensin system (RAS) have profited from this technology in the past. In this review, we summarize the existing animal models for the protective axis of the RAS consisting of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7)(Ang-(1-7), and its receptor Mas. With the help of models with altered expression of the components of this axis in the brain and cardiovascular organs, its physiological and pathophysiological functions have been elucidated. Thus, novel opportunities for therapeutic interventions in cardiovascular diseases were revealed targeting ACE2 or Mas."
6540,Application of UPT-POCT in Public Health Emergencies,"Rapid and reliable detection of infectious agents on site is essential for timely initiation of medical treatment and post-exposure prophylactic measures when public health emergencies occur. However, the referee standard for confirmation of infectious agents remains laboratory diagnosis, which is time-consuming and not available in the field. UPT-POCT technology is a versatile tool that requires limited resources and can realize rapid detection of infectious agents on site, providing timely information for the quick response to public health emergencies."
6541,"Management of Gram-Positive Bacterial Disease: Staphylococcus aureus, Streptococcal, Pneumococcal and Enterococcal Infections","Gram-positive bacteria are a diverse group of organisms that are a major source of morbidity and mortality in patients with cancer. The increasing use of long-term indwelling central catheters and cytotoxic chemotherapies has contributed to the emergence of Gram-positive bacteria as the leading cause of bacteremia in cancer patients. These organisms are also among the foremost causes of pneumonia, skin and soft-tissue infections, osteomyelitis, and central nervous system infections in cancer patients. Gram-positive organisms have a remarkable ability to develop resistance to many of the currently available antimicrobials, but the predilection to become antimicrobial resistant varies substantially for particular organisms and for individual antimicrobial agents. Therefore physicians treating cancer patients need to be familiar with the common clinical manifestations, complications, and treatment options for a wide variety of diseases caused by Gram-positive bacteria."
6542,Bacterial Infections,"Bacterial infections are the most significant infectious source of morbidity and mortality in cirrhotic patients. Bacteria infections result is both acute decompensation in chronic liver disease and mortality in patients with decompensated cirrhosis. Spontaneous bacterial peritonitis (SBP), bacteremia, pneumonia, urinary tract infections (UTI) and skin and soft tissue infection (SSTI) are the most significant sources of infection in cirrhosis. Bacterial infections can precipitate renal failure and worsening hepatic encephalopathy, and patients with sepsis and liver disease have higher rates of acute respiratory distress syndrome (ARDS) and coagulopathy."
6543,Schwindsucht,
6544,Evolution of HIV/AIDS Policy,"The HIV/AIDS-related policy framework in China has come a long way from initially attempting to prevent HIV from entering the country in the early stages of the epidemic to facilitating comprehensive national HIV response of today. Each step of the way, policymakers in China have strived to ensure that HIV-related policies were pragmatic, tailored to the Chinese context, aligned with international best practices, and based upon the best available information at the time. Although there have been a great many policy actions since HIV was first discovered on the mainland, a few key policies were foundational, had a major impact on the epidemic, and marked an important shift China’s HIV response, for example, the Blood Donation Law (1998), the first Five-Year Action Plan for the Containment and Control of HIV/AIDS (2001), and the “Four Frees and One Care” policy (2003). These and other key policies are highlighted here. Going forward, as China’s HIV epidemic increases in size and complexity, policymakers need to remain grounded in evidence but also be open to alternative and innovative approaches."
6545,Market Area Delineation for Airports to Predict the Spread of Infectious Disease,"Air travel facilitates the international spread of infectious disease. While global air travel data represent the volume of travel between airports, identifying which airport an infected individual might use, or where a disease might spread after an infected passenger deplanes, remains a largely unexplored area of research and public health practice. This gap can be addressed by estimating airport catchment areas. This research aims to determine how existing market area delineation techniques estimate airport catchments differently, and which techniques are best suited to anticipate where infectious diseases may spread. Multiple techniques were tested for airports in the Province of Ontario, Canada: circular buffers, drive-time buffers, Thiessen polygons, and the Huff model, with multiple variations tested for some techniques. The results were compared qualitatively and quantitatively based on spatial patterns as well as area and population of each catchment area. There were notable differences, specifically between deterministic and probabilistic approaches. Deterministic techniques may only be suitable if all airports in a study area are similar in terms of attractiveness. The probabilistic Huff model appeared to produce more realistic results because it accounted for variation in airport attractiveness. Additionally, the Huff model requires few inputs and therefore would be efficient to execute in situations where time, resources, and data are limited."
6546,Endemic mycosis,
6547,Molecular Virology of Enteric Viruses (with Emphasis on Caliciviruses),
6548,Spezielle Therapieformen,"Jede Sauerstoffgabe, die länger als 15 h/Tag über mehr als 3 Monate indiziert ist, bezeichnet man als Langzeitsauerstofftherapie (»long term oxygen therapy«, LTOT)."
6549,Therapeutic and Medicinal Uses of Terpenes,"Terpenes, also known as terpenoids are the largest and most diverse group of naturally occurring compounds. Based on the number of isoprene units they have, they are classified as mono, di, tri, tetra, and sesquiterpenes. They are mostly found in plants and form the major constituent of essential oils from plants. Among the natural products that provide medical benefits for an organism, terpenes play a major and variety of roles. The common plant sources of terpenes are tea, thyme, cannabis, Spanish sage, and citrus fruits (e.g., lemon, orange, mandarin). Terpenes have a wide range of medicinal uses among which antiplasmodial activity is notable as its mechanism of action is similar to the popular antimalarial drug in use—chloroquine. Monoterpenes specifically are widely studied for their antiviral property. With growing incidents of cancer and diabetes in modern world, terpenes also have the potential to serve as anticancer and antidiabetic reagents. Along with these properties, terpenes also allow for flexibility in route of administration and suppression of side effects. Certain terpenes were widely used in natural folk medicine. One such terpene is curcumin which holds anti-inflammatory, antioxidant, anticancer, antiseptic, antiplasmodial, astringent, digestive, diuretic, and many other properties. Curcumin has also become a recent trend in healthy foods and open doors for several medical researches. This chapter summarizes the various terpenes, their sources, medicinal properties, mechanism of action, and the recent studies that are underway for designing terpenes as a lead molecule in the modern medicine."
6550,Mining Candidate Viruses as Potential Bio-terrorism Weapons from Biomedical Literature,"In this paper we present a semantic-based data mining approach to identify candidate viruses as potential bio-terrorism weapons from biomedical literature. We first identify all the possible properties of viruses as search key words based on Geissler’s 13 criteria; the identified properties are then defined using MeSH terms. Then, we assign each property an importance weight based on domain experts’ judgment. After generating all the possible valid combinations of the properties, we search the biomedical literature, retrieving all the relevant documents. Next our method extracts virus names from the downloaded documents for each search keyword and identifies the novel connection of the virus according to these 4 properties. If a virus is found in the different document sets obtained by several search keywords, the virus should be considered as suspicious and treated as candidate viruses for bio-terrorism. Our findings are intended as a guide to the virus literature to support further studies that might then lead to appropriate defense and public health measures."
6551,The Clinical Application of Ozonetherapy,
6552,Viral RNA Targets and Their Small Molecule Ligands,"RNA genomes and transcripts of viruses contain conserved structured motifs which are attractive targets for small molecule inhibitors of viral replication. Ligand binding affects conformational states, stability, and interactions of these viral RNA targets which play key roles in the infection process. Inhibition of viral RNA function by small molecule ligands has been extensively studied for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) which provide valuable insight for the future exploration of RNA targets in other viral pathogens including severe respiratory syndrome coronavirus (SARS CoV), influenza A, and insect-borne flaviviruses (Dengue, Zika, and West Nile) as well as filoviruses (Ebola and Marburg). Here, I will review recent progress on the discovery and design of small molecule ligands targeting structured viral RNA motifs."
6553,Respiratory Viral Infections in Transplant Recipients,"Respiratory viral infections (RVIs) are common among the general population; however, these often mild viral illnesses can lead to serious morbidity and mortality among recipients of hematopoietic stem cell and solid organ transplantation. The disease spectrum ranges from asymptomatic or mild infections to life-threatening lower respiratory tract infection or long-term airflow obstruction syndromes. Progression to lower respiratory tract infection or to respiratory failure is determined by the intrinsic virulence of the specific viral pathogen as well as various host factors, including the type of transplantation, status of the host’s immune dysfunction, the underlying disease, and other comorbidities. This chapter focuses on the epidemiology, clinical manifestations, diagnosis, and management of RVIs in this susceptible population and includes respiratory syncytial virus, parainfluenza virus, human metapneumovirus, influenza virus, human coronavirus, and human rhinovirus. The optimal management of these infections is limited by the overall paucity of available treatment, highlighting the need for new antiviral drug or immunotherapies."
6554,Hemorrhage and Transfusions in the Surgical Patient,"Hemorrhage remains the leading cause of intra-operative deaths and those in the first 24 h. Many cardiovascular and hepatobiliary procedures result in massive hemorrhage and postpartum hemorrhage events in labor and delivery place the patient at a high risk for mortality. Both upper and lower gastrointestinal bleeding (e.g., diverticulosis, esophageal and gastric varices, and peptic ulcer disease) can also result in significant blood loss requiring massive transfusion and resuscitation from hemorrhagic shock. Therefore, safe, timely, and effective transfusion of blood products is critical. The aim of this chapter is to provide clinicians with a discussion of the current literature on the various blood component products, their indications, and unique hemostatic conditions in the surgical patient. While the majority of data concerning optimal management of acquired coagulopathy and hemorrhagic shock resuscitation is based on trauma patients, many of the principles can and should be applied to the surgical patient (or likely any patient) with profound hemorrhage."
6555,Immunoinformatics and Computational Vaccinology: A Brief Introduction,"Immunoinformatics has recently emerged as a buoyant and dynamic sub-discipline within the wider field of bioinformatics. Immunoinformatics is the application of bioinformatic methods to the unique problems of immunology and vaccinology. Immunoinformatics, as a principal component of incipient immunomic technologies, is beginning to foment important changes within immunology, as this key discipline tries to free itself from the empirical straight jacket that has characterised its development and attempts to grapple with the post-genomic revolution. Immunoinformatics is, importantly, also beginning to establish itself as a pivotal tool within vaccine discovery."
6556,Allergic Diseases (and Differential Diagnoses),
6557,Diagnostic Techniques,"The chapter describes diagnostic techniques adapted by avian veterinarians encompassing the procedure, pros and cons of anamnesis, physical examination, collection and processing of clinical specimens, laboratory examination, radiography, USG, CT, MRI, myelography, echocardiography, electrocardiography and endoscopy."
6558,Land Use Change and Human Health,"Human activity is rapidly transforming our planet. The most pervasive changes to the landscape include deforestation, extension and intensification of agriculture, and livestock management, the construction of dams, irrigation projects, and roads, and rapidly spreading urbanization. In addition to the well-known environmental costs of these changes, each also has important health implications that are often less recognized. However, a growing number of studies that combine ecology and human health are demonstrating how these activities impact the emergence of new infectious diseases and alter the distribution of already recognized diseases."
6559,Opportunistic Infections,"Evolution in paediatric HIV management has changed the incidence and prevalence of opportunistic infections and a major reduction has been shown for most opportunistic infections with antiretroviral therapy use in lower and middle-income countries, especially in the first year of treatment. However, the high prevalence of disease still requires adequate management of opportunistic infections, to improve patient quality of life and the impact on burden of disease. Lower CD4 counts were associated with chronic infection and increased risk of opportunistic infections in patients, but some studies have shown that even children with high CD4 counts may have opportunistic infections. This chapter reviews common opportunistic infections that may infect HIV positive children and adolescents, particularly in sub Saharan Africa."
6560,Noninvasive Mechanical Ventilation in Patients with Acute Respiratory Failure Due to Pandemic Influenza A(H1N1) Virus,Pandemic influenza A (PA-H1N1) is a new strain of influenza virus that was first identified in Mexico and United States during the early part of 2009. The PA-H1N1 virus originated from the swine influenza (H1) virus circulating in North American pigs.
6561,Tropische ziekten,"Aet. De verwekker is het retrovirus hiv(1). In West-Afrika is ook hiv(2) geïsoleerd. Freq. Aids komt thans overal ter wereld voor maar er zijn belangrijke regionale verschillen. Aids in de tropen onderscheidt zich van aids elders in de wereld onder meer door verschillende epidemiologische en klinische karakteristieken. De meeste van de nieuwe aidsgevallen doen zich momenteel voor in Sub-Sahara-Afrika, India en Zuidoost-Azië. Ook in Latijns-Amerika neemt de incidentie toe. Sub-Sahara-Afrika is thans de meest getroffen regio ter wereld. Meer dan 70% van het totale geschatte aantal aidsgevallen (sinds het begin van de aidsepidemie) doet zich voor in Afrika. Daar kan in endemische gebieden 30% en meer van de jonge mannen en vrouwen geïnfecteerd zijn, met hogere frequentie bij prostitué(e)s, hun cliënten en bij patiënten met tuberculose. Er zijn belangrijke verschillen tussen stad (hogere frequentie) en platteland. De verhouding man: vrouw is 1:1. De transmissie vindt bij 80% plaats door heteroseksueel contact, daarnaast door parenterale besmetting (bloedtransfusie, besmette spuiten en naalden) en ‘verticaal’ van hiv-positieve moeders naar 25-30% van de pasgeborenen, ook via borstvoeding."
6562,Informatics for Infectious Disease Research and Control,"The goal of infectious disease informatics is to optimize the clinical and public health management of infectious diseases through improvements in the development and use of antimicrobials, the design of more effective vaccines, the identification of biomarkers for life-threatening infections, a better understanding of host-pathogen interactions, and biosurveillance and clinical decision support. Infectious disease informatics can lead to more targeted and effective approaches for the prevention, diagnosis and treatment of infections through a comprehensive review of the genetic repertoire and metabolic profiles of a pathogen. The developments in informatics have been critical in boosting the translational science and in supporting both reductionist and integrative research paradigms."
6563,"Astrovirology, Astrobiology, Artificial Intelligence: Extra-Solar System Investigations","This chapter attempts to encompass and tackle a large problem in Astrovirology and Astrobiology. There is a huge anthropomorphic prejudice that although life is unlikely, the just-right Goldilocks terrestrial conditions mean that the just-right balance of minerals and basic small molecules inevitably result in life as we know it throughout our solar system, galaxy, and the rest of the universe. Moreover, when such conditions on planets such as ours may not be quite right for the origin of life, it is popularly opined that asteroids and comets magically produce life or at the very least, the important, if not crucial components of terrestrial life so that life then blooms, when their fragments cruise the solar system, stars, and galaxies, and plummet onto appropriately bedecked planets and moons. It is no longer extraordinary to detect extraterrestrial solar systems. Moreover, since extra-solar system space exploration has commenced, this provides the problem of detecting life with enhanced achievability. Small organisms, which replicate outside of a living cell or host, would not be catalogued as viruses. How about viruses that cohabit with life? On the Earth, viruses are a major, if underestimated, condition of life – will that be the case elsewhere? Detection of extra-solar system viruses, if they exist, requires finding life, since viruses necessitate life to replicate. (It should be noted, though, that viruses could be detected through various types of portable ultra-microscopes, including Electron Microscopes (EM) (scanning and transmission) as well as Atomic Force Microscopes (AFM).) However, extra-solar system detection of life does not oblige that viruses exist ubiquitously. Viruses are important potential components of biospheres because of their multiple interactions and influence on evolution, although viruses are small and obligatory parasitic. In addition, nanotechnology – living or replicating nano-synthetic machine organisms might also be present out there, and require consideration as well. An imposing caveat is that, if found, could some extraterrestrial viruses and synthetic nanotechnological microorganisms infect humans? Possibly, intelligence and cognition may at times be contemporaneous with life. Concomitantly, life and viruses that may be detected, could well be impacted upon by intelligences existing on such exoplanets (and vice versa). Coming to an understanding of the plurality of extraterrestrial intelligence is an optimal objective, in order to avoid causing harm on exoplanets, as well as avoiding conflict and possible human devastation. This is especially the case if we encounter greatly advanced galactic-level civilizations, compared to terrestrial civilizations. Their machine and bionic technologies on the Dyson engineering civilization scale may be prominently superior to ours; their biological expertise may be similarly critically radical. For example, they may use viruses for purposes for which we are barely aware, and which could be utterly deadly for humans. A series of steps is being taken in space exploration. Scientists hypothesize and claim that types of life may be near the Earth, in the solar system, and outside the solar system, similar to ours in the sense that only such conditions, Goldilocks conditions, are key sine qua non requirements, based on our terrestrial chemistry and biochemistry. If detected within the solar system, will life or its remnants resemble terrestrial life? Outside the solar system a similar chauvinism exists, although the likelihood for life, in any event, remains probably low, according to more cautious approaches to the problem. The study of our solar system includes planets, asteroids, comets, and other planetesimals that have been in overall contiguity during several billion years; anthropomorphisms claims life consequently has been developing along terrestrial-type mechanisms. However, a non-anthropomorphic view would surmise, probably not, especially for extra-solar system locales. The prime warning and admonition in all these deliberations is the contamination and damage, which current and past practice and procedures has caused and continues, due to insufficient biocontainment concepts and technology to date. Advances in the development of robotics, artificial intelligence (AI), and high capacity ultrafast quantum computers (QC) greatly enhance the sophisticated control and logical development of extra-solar system studies. Consequently, future long-range manned space exploration seems unwarranted. Clearly, reduced dangers to human health and safety, will result from the use of intelligent machine-based investigations and besides, with increased cost-effectiveness. Space exploration comes at great cost to humanity as a whole and utilizes global resources. Consequently, appropriate organizational measures and planning/cooperation need to be in place. Moreover, the bottom line is that despite all the slogans and claims, there have been next to no financial benefits to our planet as a whole. Such financial and heedless difficulties need to be addressed, the sooner the better. In addition, prior to exposure to exoplanetary life, deep understanding of the problems of infectious diseases and immune dysfunction risks are needed. In addition, global efforts should avoid serendipity and stochasticity as this work should be directed with long-term organization, commitment, scientific, and technological methodology. This chapter briefly reviews such questions assuming a new paradigm for oversight of extrasolar system viral investigations including intelligence and life. Finances are included as an essential adjunct."
6564,Host Factors Promoting Viral RNA Replication,"Plus-stranded RNA viruses, the largest group among eukaryotic viruses, are capable of reprogramming host cells by subverting host proteins and membranes, by co-opting and modulating protein and ribonucleoprotein complexes, and by altering cellular pathways during infection. To achieve robust replication, plus-stranded RNA viruses interact with numerous cellular molecules via protein–protein, RNA–protein, and protein–lipid interactions using molecular mimicry and other means. These interactions lead to the transformation of the host cells into viral “factories"" that can produce 10,000–1,000,000 progeny RNAs per infected cell. This chapter presents the progress that was made largely in the last 15 years in understanding virus–host interactions during RNA virus replication. The most commonly employed approaches to identify host factors that affect plus-stranded RNA virus replication are described. In addition, we discuss many of the identified host factors and their proposed roles in RNA virus replication. Altogether, host factors are key determinants of the host range of a given virus and affect virus pathology, host–virus interactions, as well as virus evolution. Studies on host factors also contribute insights into their normal cellular functions, thus promoting understanding of the basic biology of the host cell. The knowledge obtained in this fast-progressing area will likely stimulate the development of new antiviral methods as well as novel strategies that could make plus-stranded RNA viruses useful in bio- and nanotechnology."
6565,Engineered Viruses as Vaccine Platforms,"Many viruses have been investigated for the development of genetic vaccines and the ideal ones must be endowed with many properties, such as the quality and the quantity of the immunological response induced against the encoded antigens, safety and production on a large scale basis. Viral based vaccines must also deal with the potential problem of the pre-existing antivector immunity. Several viral vaccine vectors have emerged to date, all of them having relative advantages and limits depending on the proposed application. Recent successes reflect diverse improvements such as development of new adenovirus serotypes and prime-boost regimes. This chapter describes the features of four viral vector systems based on poxviruses, adenoviruses, alphaviruses and lentiviruses and recent results following their use with a particular emphasis on clinical research, highlighting the challenges and successes."
6566,Who Cares About Wildlife?,
6567,Food as a New Human and Livelihood Security Challenge,"As a result of a process of “regressive globalization” (Kaldor/Anheier/Glasius 2003; Oswald 2008b) and of an increasing concentration of wealth in few hands, the economic gap has widened between North and South and within the countries between rich and poor, which has often affected the survival of social groups."
6568,Identification of Candidate Vaccine Antigens In Silico,"The identification of immunogenic whole-protein antigens is fundamental to the successful discovery of candidate subunit vaccines and their rapid, effective, and efficient transformation into clinically useful, commercially successful vaccine formulations. In the wider context of the experimental discovery of vaccine antigens, with particular reference to reverse vaccinology, this chapter adumbrates the principal computational approaches currently deployed in the hunt for novel antigens: genome-level prediction of antigens, antigen identification through the use of protein sequence alignment-based approaches, antigen detection through the use of subcellular location prediction, and the use of alignment-independent approaches to antigen discovery. Reference is also made to the recent emergence of various expert systems for protein antigen identification."
6569,Bead-Based Suspension Arrays for the Detection and Identification of Respiratory Viruses,"The clinical signs and symptoms associated with many infectious diseases are often too nonspecific to discriminate between causative agents, and thus, definitive diagnosis requires specific laboratory tests for all of the suspected pathogens. In particular, respiratory tract infections can be caused by numerous different viral, bacterial, and fungal pathogens that are indistinguishable by clinical diagnosis. Respiratory tract infections are also among the most common infections in humans, with approximately 6−9 episodes per year in children and 2−4 episodes per year in adults [1]. These infections cause considerable morbidity and mortality as well as high healthcare costs associated with doctor visits, hospitalizations, treatment, and absences from work and school. Early diagnosis of the etiological agent in a respiratory infection permits effective antimicrobial therapy and appropriate management of the disease."
6570,"Epiglottitis, Acute Laryngitis, and Croup","Epiglottitis, acute laryngitis, and croup (acute laryngotracheobronchitis) are infections of the upper airway, affecting the epiglottis, larynx, and larynx and trachea, respectively. Epiglottitis is a bacterial infection, while viruses cause nearly all cases of acute laryngitis and croup. Acute laryngitis in adults is usually self-limited. Epiglottitis, which used to be prevalent in children under age 5, is now seen more often in adults than in children. This decline in childhood epiglottitis is due to the Haemophilus influenzae type b (Hib) vaccine. Streptococci, including Streptococcus pneumoniae, are now important causes of epiglottitis. Croup is a viral infection, usually due to parainfluenza virus, that primarily affects children ages 6 months to 3 years old. Epiglottitis and croup can cause life-threatening loss of the airway, and misdiagnosis or mismanagement can result in fatalities. This chapter reviews the clinical features and treatment of these three upper respiratory tract infections."
6571,White Paper on Risk Governance: Toward an Integrative Framework,"This document aims to guide the work of the International Risk Governance Council and its various bodies in devising comprehensive and transparent approaches to ‘govern’ a variety of globally relevant risks. Globally relevant risks include trans-boundary risks, i.e. those that originate in one country and affect other countries (such as air pollution), international risks, i.e. those that originate in many countries simultaneously and lead to global impacts (such as carbon dioxide emissions for climate change) and ubiquitous risks, i.e. those that occur in each country in similar forms and may necessitate a co-ordinated international response (such as car accidents or airline safety). To this end the document and the framework it describes provide a common analytic structure for investigating and supporting the treatment of risk issues by the relevant actors in society. In doing so, the focus is not restricted to how governmental or supranational authorities deal with risk but equal importance is given to the roles of the corporate sector, science, other stakeholders as well as civil society — and their interplay. The analytic structure will, it is hoped, facilitate terminological and conceptual clarity, consistency and transparency in the daily operations of IRGC and assure the feasibility of comparative approaches in the governance of risks across a broad range of hazardous events and activities. In particular, this document is meant to assist members of IRGC in their tasks to provide scientifically sound, economically feasible, legally and ethically justifiable and politically acceptable advice to IRGC's targeted audiences. It is also to support IRGC in its effort to combine the best available expertise in the respective field with practical guidance for both risk managers and stakeholders."
6572,Infectieziekten,Aan het eind van dit hoofdstuk weet je: welke verschillende ziekteverwekkers infectieziekten kunnen veroorzaken; welke geneesmiddelen worden gebruikt bij de behandeling van infectieziekten; welk gevolg onoordeelkundig gebruik van deze geneesmiddelen kan hebben; welke gebruiksadviezen je moet geven bij de verschillende middelen tegen infectieziekten.
6573,Nederlands-Engels,
6574,Healthcare Emergencies in Africa: The Case of Ebola in Nigeria,"The Ebola crisis in Africa presented a case study in both hope and despair. There were severe casualties in the weak and unprepared system of Liberia and Sierra Leone, but hope for a developing system in Nigeria, which managed to prevent a mass outbreak. This chapter takes a closer look at the Ebola crisis of 2014 in Africa and examines Nigeria as a model of political will and voluntary preparedness to tackle this national and continental health emergency. This chapter looks at risk and crisis communication in particular, and explores the concepts of ethics in the case of the Ebola outbreak."
6575,Analysis of Microorganisms in Hospital Environments and Potential Risks,"This report provides information on indoor air quality and on associated potential risks in hospitals. Spread and persistence of microbial communities in hospital environments are of huge interest to public health. Hospitals are characterized by high infective risk, firstly cause of the compromised immunologic conditions of the patients that make them vulnerable to bacterial, viral, parasitological and fungal opportunistic infections. Evidence suggests that microbial agents spread through air, surfaces, aerosol and hands. If surfaces may act as a reservoir for some pathogens, hands are an important transmission route. Airborne and aerosolized waterborne microorganisms are taken into consideration, and their presence into the hospital environments is reviewed."
6576,Diffusion in Dynamic Social Networks: Application in Epidemiology,"Structure and evolution of networks have been areas of growing interest in recent years, especially with the emergence of Social Network Analysis (SNA) and its application in numerous fields. Researches on diffusion are focusing on network modeling for studying spreading phenomena. While the impact of network properties on spreading is now widely studied, involvement of network dynamicity is very little known. In this paper, we address the epidemiology context and study the consequences of network evolutions on spread of diseases. Experiments are conducted by comparing incidence curves obtained by evolution strategies applied on two generated and two real networks. Results are then analyzed by investigating network properties and discussed in order to explain how network evolution influences the spread. We present the MIDEN framework, an approach to measure impact of basic changes in network structure, and DynSpread, a 2D simulation tool designed to replay infections scenarios on evolving networks."
6577,The Role of Phosphoinositide 3-Kinase-Akt Signaling in Virus Infection,"Successful virus infection of host cells requires efficient viral replication, production of virus progeny and spread of newly synthesized virus particles. This success, however also depends on the evasion of a multitude of antiviral signaling mechanisms. Many viruses are capable of averting antiviral signals through modulation of host cell signaling pathways. Apoptotic inhibition, for example, is a universal intracellular antiviral response, which prolongs cellular survival and allows viruses to complete their life cycle. Ongoing apoptotic inhibition contributes to the establishment of latent and chronic infections, and has been implicated in viral oncogenesis. The phosphoinositide 3-kinase (PI3K)-Akt pathway has become recognized as being pivotal to the inhibition of apoptosis and cellular survival. Thus, modulation of this pathway provides viruses with a mechanism whereby they can increase their survival, in addition to other established mechanisms such as expression of viral onco-genes and direct inhibition of proapoptotic proteins. Recent research has revealed that this pathway is up-regulated by a number of viruses during both short-term acute infections and long-term latent or chronic infections. During acute infections PI3K-Akt signaling helps to create an environment favorable for virus replication and virion assembly. In the case of long-term infections, modulation of PI3K-Akt signaling by specific viral products is believed to help create a favorable environment for virus persistence, and contribute to virus-mediated cellular transformation."
6578,The Epidemiology of Alcohol Abuse and Pneumonia,"The association between alcohol abuse and pneumonia has been recognized for more than two centuries and represents an enormous health burden worldwide. The first published notation of alcohol as a clinical risk factor for the development of pneumonia is now over 200 years old, and since then there have been over a 1,000 references in the medical literature confirming these observations. Even in this modern era of medicine pneumonia remains a common infection that afflicts over 450 million persons worldwide annually and causes 7 % of all deaths. When one considers that alcohol is the most commonly abused substance in the world, the enormous excessive burden that alcohol contributes to the morbidity and mortality of pneumonia represents a major public health consideration. In this chapter we review the foundational literature that has chronicled the evolution of our understanding of the association between pneumonia and alcohol abuse over the past century. In addition, we discuss some of the specific pathogens that are particularly associated with serious lung infections in individuals with alcohol use disorders. Finally, we consider some of the specific guidelines for the treatment and prevention of pneumonia in the setting of alcohol abuse."
6579,Schweinefinnenbandwurm,
6580,Pneumonia in the Cancer Patient,"Lower respiratory tract infections result in ­unacceptably high mortality among cancer patients. Pneu­monias cause death in this population both directly through impairment of gas exchange and progression to system infection/sepsis, as well as indirectly by precluding delivery of necessary, antineoplastic therapies. Malignancy and treatment-related impairments of host immune responses and the emergence of ­multidrug-resistant organisms associated with recurrent exposures to hospital environments may not only enhance the risks of mortality, but also exacerbate the difficulty of diagnosing pneumonia in the cancer setting. As a consequence of disordered inflammatory responses, the typical clinical observations of pneumonia, including purulent respiratory secretions and early radiographic findings, may be inapparent or absent. A comprehensive review of etiology, clinical ­presentation, diagnosis, and management of pulmonary infections is presented in this chapter."
6581,Sewage Disposal and Wildlife Health in Antarctica,"Sewage and its microbiology, treatment and disposal are important to the topic of Antarctic wildlife health because disposal of untreated sewage effluent into the Antarctic marine environment is both allowed and commonplace. Human sewage contains enteric bacteria as normal flora, and has the potential to contain parasites, bacteria and viruses which may prove pathogenic to Antarctic wildlife. Treatment can reduce levels of micro-organisms in sewage effluent, but is not a requirement of the Environmental Protocol to the Antarctic Treaty (the Madrid Protocol). In contrast, the deliberate release of non-native organisms for any other reason is prohibited. Hence, disposal of sewage effluent to the marine environment is the only activity routinely undertaken in Antarctica knowing that it will likely result in the release of large numbers of potentially non-native species. When the Madrid Protocol was negotiated, the decision to allow release of untreated sewage effluent was considered the only pragmatic option, as a prohibition would have been costly, and may not have been achievable by many Antarctic operators. In addition, at that time the potential for transmission of pathogens to wildlife from sewage was not emphasised as a significant potential risk. Since then, the transmission of disease-causing agents between species is more widely recognised and it is now timely to consider the risks of continued discharge of sewage effluent in Antarctica and whether there are practical alternatives."
6582,Whole-Genome Sequencing of Porcine Epidemic Diarrhea Virus by Illumina MiSeq Platform,"Porcine epidemic diarrhea virus (PEDV) belongs to the genus Alphacoronavirus of the family Coronaviridae. PEDV was identified as an emerging pathogen in US pig populations in 2013. Since then, this virus has been detected in at least 31 states in the USA and has caused significant economic loss to the swine industry. Active surveillance and characterization of PEDV are essential for monitoring the virus. Obtaining comprehensive information about the PEDV genome can improve our understanding of the evolution of PEDV viruses, and the emergence of new strains, and can enhance vaccine designs. In this chapter, both a targeted amplification method and a random-priming method are described to amplify the complete genome of PEDV for sequencing using the MiSeq platform. Overall, this protocol provides a useful two-pronged approach to complete whole-genome sequences of PEDV depending on the amount of virus in the clinical samples."
6583,Reducing Spreading Processes on Networks to Markov Population Models,"Stochastic processes on complex networks, where each node is in one of several compartments, and neighboring nodes interact with each other, can be used to describe a variety of real-world spreading phenomena. However, computational analysis of such processes is hindered by the enormous size of their underlying state space. In this work, we demonstrate that lumping can be used to reduce any epidemic model to a Markov Population Model (MPM). Therefore, we propose a novel lumping scheme based on a partitioning of the nodes. By imposing different types of counting abstractions, we obtain coarse-grained Markov models with a natural MPM representation that approximate the original systems. This makes it possible to transfer the rich pool of approximation techniques developed for MPMs to the computational analysis of complex networks’ dynamics. We present numerical examples to investigate the relationship between the accuracy of the MPMs, the size of the lumped state space, and the type of counting abstraction."
6584,Laboratories,"Patient test samples are taken and examined at outpatient clinics, in bed posts and at policlinic consultations and treatment units. They are collected and transported to central laboratories or examined by smaller laboratory units, adapted to the patient group. Samples are sent in pipes or transported by defined methods to the laboratory. A large number of samples are also sent to other hospitals, laboratories or diverse private laboratories. The following chapter is focused on laboratory safety for patients and personnel to avoid spread of infections between patients, personnel and environment."
6585,"DATA, DATA, AND MORE DATA",
6586,"Interstitial Lung Disease in Infants and Children: New Classification System with Emphasis on Clinical, Imaging, and Pathological Correlation","Interstitial lung diseases in infants and children comprise a rare heterogeneous group of parenchymal lung disorders, with clinical syndromes characterized by dyspnea, tachypnea, crackles, and hypoxemia. They arise from a wide spectrum of developmental, genetic, inflammatory, infectious, and reactive disorders. In the past, there has been a paucity of information and limited understanding regarding their pathogenesis, natural history, imaging findings, and histopathologic features, which often resulted in enormous diagnostic challenges and confusion. In recent years, there has been a substantial improvement in the understanding of interstitial lung disease in the pediatric patient, due to the development of a structured classification system based on etiology of the lung disease, established pathologic criteria for consistent diagnosis, and improvement of thoracoscopic techniques for lung biopsy. Imaging plays an important role in evaluating interstitial lung diseases in infants and children by confirming and characterizing the disorder, generating differential diagnoses, and providing localization for lung biopsy for pathological diagnosis. In this chapter, the authors present epidemiology, challenges and uncertainties of diagnosis, and amplify a recently developed classification system for interstitial lung disease in infants and children with clinical, imaging, and pathological correlation."
6587,Care of the Postoperative Pulmonary Resection Patient,"Patients undergoing pulmonary resection all exhibit, to some degree, a level of pulmonary dysfunction. This is due to the physiologic stress of the procedure performed, the patient’s comorbidities, and preexisting cardiopulmonary reserve. Although prognostic factors for intensive care requirement exist, to date, there is no consensus for postoperative admission. Institutional practices vary across the country, with patients often admitted to intensive care for surveillance. Guidelines published from the American Thoracic Society in 1999 emphasize that admission to the ICU be reserved for those patients requiring care and monitoring for severe physiologic instability. Admissions following pulmonary resection are typically due to respiratory complications and are an independent predictor of mortality. The following chapter will review the indications for admission to the ICU and common issues encountered following pulmonary resection and conclude with a discussion of the management of patients undergoing pulmonary transplantation."
6588,Infections in the Long-Term Care Setting,"In the long-term care setting The diagnosis of infection is primarily based from the clinical assessment. Infection is a common cause of fever, when present, and acute change in functional status. Infection can often present atypically; usual symptoms, physical findings, and diagnostic abnormalities may be lacking. Evaluation of fever and suspected infection should initially focus on the most common clinical syndromes. Treatment should initially focus on the most common organisms that are present at the most likely suspect site of infection."
6589,Virus Evolution in the Face of the Host Response,"Microbial infections are highly dynamic. Viruses have evolved two main strategies against the host response: interaction or evasion. Interaction is typical of complex DNA viruses. Their genomes encode a number of proteins that exert modulatory functions that alter the immune response of the host. Evasion strategy is used mainly by RNA viruses, and is based on high mutation rates and quasispecies dynamics. The complexity of viral populations demands research on new antiviral strategies that take into consideration the adaptive potential of viruses, in particular RNA viruses."
6590,Learning About Nature of Science Through Listening to Scientists’ Stories of Scientific Enquiry,"This chapter first reviews a series of curricular reforms of science education in Hong Kong that started at the turn of the 21st Century. It moves on to share the decade of efforts in promoting teachers’ learning and their subsequent teaching of the nature of science (NOS). Among these efforts, two teacher professional development programmes received overwhelmingly positive views from teachers in terms of developing their understanding about NOS and scientists. Both programmes provided teachers with special encounters with world-renowned local scientists."
6591,Airway Pathology in Lung Transplants,"The histologic diagnosis of lung transplant rejection is based on the assessment of perivascular mononuclear cell inflammation, airway inflammation and fibrosis, and vasculopathic changes. This chapter describes the pathologic features of acute and chronic rejection of the small airways (i.e., lymphocytic and obliterative bronchiolitis). As transbronchial lung biopsy is the mainstay for the assessment of rejection, a brief discussion of some of the limitations of this technique is provided from the pathologist’s perspective. Several important and common entities that can mimic airway rejection are described with practical guidance for distinguishing these potential confounders on transbronchial biopsy. The non-rejection findings that are discussed include the normal biopsy, nonspecific forms of chronic bronchiolitis, cytomegalovirus and pneumocystis pneumonia, bronchiolitis obliterans-organizing pneumonia, and aspiration pneumonia."
6592,Venues of Counter-Hegemonic Visuality; Days of Contention,"This chapter introduces and describes how, as the arguable center of the Hong Kong Special Administrative Region’s protest culture and tradition, Hong Kong, and especially Hong Kong Island, contains a number of venues where demonstrations, rallies, and protests are prepared, deployed from, or held. The chapter, and the associated repertoire of images, begins the visual exploration of how the city has been visually re-imagined, transformed, and utilized by its subalterns to reproduce their aspirations and demands for greater democracy and social justice while subversively contesting and resisting hegemonic pressures to accept mainland Chinese cultural, economic, and political domination. The co-optation by anti-hegemonic Hongkongers of key cultural, economic, social, and political venues within the city during its many demonstrations, processions, rallies, and protests can be seen as visual resistance and as an effort to create a rich countervisuality by giving “voice to the visual.” Similarly, the conflation of special days (January 1st, May 4th, June 4th, July 1st, October 1st) with identifiable protests in Hong Kong—“Days of Contention”—suggest a similar impetus."
6593,Targeting Oncoproteins for Molecular Cancer Therapy,"Cancer and efforts to treat cancer are described in Ancient Egyptian documents dating back to 1600B.C. The first successful cancer treatments were arsenic-based therapies for leukemias, with the first reported application to cancer in the nineteenth century. However, nitrogen mustards are often accredited as the first modern chemotherapy. Originally intended as a chemical warfare agent in World War I, nitrogen mustard was stockpiled by several countries. During World War II, Axis bombers sunk a ship containing large quantities of nitrogen mustard and killed numerous Allied sailors. This observation birthed the hypothesis that nitrogen mustards might prevent the rapid division of cancer cells, one of the few properties of cancer understood at that time. Today, the hallmarks of cancer as recently redefined by Hanahan and Weinberg include several complex and connected cellular properties that allow for this phenotype: resistance to cell death, sustained angiogenesis, limitless ability to replicate, self-sufficiency in growth factor signaling, unresponsiveness to anti-growth factor signaling, genomic instability and mutation, deregulating cellular energetics, evading immune-mediated destruction, oncogenic inflammation, and invasiveness and metastasis. The identification and understanding of these hallmarks is a direct result of our molecular understanding of cancer that has surfaced relatively recently. Each of these hallmarks is determined by a host of molecules that together represent distinct therapeutic opportunities to target molecules that give rise to these defining properties of cancer."
6594,Health Care Workers’ Obligations in CBRNE Crises,"Health care workers (HCWs) often suffer the brunt of injuries during chemical, biological radiological, nuclear and explosive (CBRNE) events. Throughout history, those caring for the injured, dying and dead put themselves at risk of harm, infection or contamination. Recent events include the 2014–2016 infectious outbreak of Ebola virus disease in West Africa and the targeting of health facilities in the conflict in Syria. Decisions by HCWs to care for others in the face of such risks have been lauded as heroic whether undertaken for personal moral reasons or in response to an ethical duty to care. However, some have questioned whether such a duty to care is ethically obligatory in the face of some CBRNE events. Ethical analysis of the SARS outbreak found that additional ethical reflection was needed on HCWs’ obligations during CBRNE events. The ethical arguments used to justify the duty to care are reviewed in this chapter. However, other duties exist for HCWs which may conflict with the duty to care. The World Health Organization’s guidance on ethics in pandemics notes that the duty to provide care in pandemics is not unlimited, and that employers and governments have reciprocal obligations to provide training and protective equipment to HCWs during CBRNE. Empirical research raises questions about whether health care organisations are adequately prepared for CBRNE, particularly for the ethical decision-making that will be required. Rather than taking a regulatory or legal approach to this issue, this chapter will argue that the ethical virtues of courage and volunteerism should be fostered in HCW training. In keeping with a virtue ethics approach, leadership takes on an important role in ethical decision-making, as well as praising those who respond to CBRNE by caring for others in spite of the personal risks and their conflicting obligations."
6595,"Respiratory Tract Infections: Sinusitis, Bronchitis, and Pneumonia","Solid organ and hematopoietic stem cell transplant recipients are at increased risk of upper and lower respiratory tract infections. While these infections are frequently encountered in the general population, the spectrum of their clinical presentation including morbidity and mortality is increased in patients undergoing transplantation procedures. Impaired innate and adaptive immunity, potential anatomical abnormalities resulting from extensive surgical procedures, presences of indwelling medical devices, and increased healthcare exposure put transplant recipients at particularly high risk for respiratory tract disease. Infections of the respiratory tract can be divided into those affecting the paranasal sinuses, the upper airways such as bronchitis and tracheobronchitis, and the lower airways like pneumonia. Each of these clinical syndromes can further be classified based on their chronicity, acute vs. chronic; their setting, community vs. nosocomial; and the etiology such as bacteria, viruses, fungi, and rarely parasites. It is also important to realize that such immunologically vulnerable patients are at risk for polymicrobial infection that may present concurrently or in a sequential, consecutive fashion. This chapter reviews the common respiratory tract infections affecting transplant recipients with particular attention directed toward epidemiological risk factors, clinical presentations, diagnostic strategies, and common pathogens. Specific causes of opportunistic pneumonias are also reviewed."
6596,Characteristics of the Dynamic of Mobile Networks,"We propose in this paper a novel framework for the study of dynamic mobility networks. We address the characterization of dynamics by proposing an in-depth description and analysis of two real-world data sets. We show in particular that links creation and deletion processes are independent of other graph properties and that such networks exhibit a large number of possible configurations, from sparse to dense. From those observations, we propose simple yet very accurate models that allow to generate random mobility graphs with similar temporal behavior as the one observed in experimental data."
6597,Future Applications of GMOs,
6598,Prediction and Prevention: Interventions to Enhance Blood Safety,"The transmission of infectious disease by blood transfusion has been a major problem since the middle of the twentieth century. Since about 1960, there has been a concerted and prolonged effort to reduce or eliminate this outcome; the efforts have been successful, but new challenges continue to appear, mostly in the form of emerging infectious diseases. This chapter reviews two relevant issues: the possibility of predicting microbial threats to blood safety and the interventions that may be used to reduce the risks of transfusion transmission. While there are only limited opportunities to predict relevant infections, there are effective measures to enhance blood safety. These involve appropriate selection of donors, implementation of effective tests, and development and implementation of pathogen reduction."
6599,Die Evolution der Viren,"Viren sind aufgrund ihrer kurzen Generationszeit, der großen Zahl von Nachkommen, die sie im Infektionsverlauf produzieren, und nicht zuletzt aufgrund ihrer einfachen Struktur ideale Objekte zum Studium von Evolutionsprozessen. Viren müssen sich ständig den Bedingungen ihres Wirtes oder ihrer Wirtspopulationen anpassen, sodass Mechanismen der Selektion experimentellen Ansätzen zugänglich sind. Dabei spielen unterschiedliche Kriterien, wie die antigene Diversität, das Ausmaß der Virusausscheidung, der Grad der Virulenz und viele andere Faktoren eine wichtige Rolle. Die vollständige Adaptation eines Virus an seinen Wirt, welche in eine möglichst geringe Virulenz des Infektionserregers mündet, ist die für beide erstrebenswerte Konsequenz: ein problemloses Zusammen- und Überleben. So scheinen die Hepatitis-G-Viren, die zwar erstmals aus Patienten mit einer Leberentzündung isoliert wurden, ähnlich wie die TT-Viren in vielen Menschen zu persistieren, ohne dass sie dabei Erkrankungen verursachen (▸Abschnitte 14.5 und 20.2)."
6600,Asthma and Microbes: A New Paradigm,"Asthma is worldwide at pandemic levels for the past 30 years but is increasing at a greater rate in more affluent societies. It is a heterogeneous disorder caused by interaction between genetic predisposition, atopy, and environmental factors, including allergens, air pollution, and respiratory infections. The pathological aspects and pathophysiological mechanisms are reviewed in this chapter. Allergens or infectious agents may stimulate Th-2 inflammation which causes activation of IL-13, eosinophils, and increase IgE levels, subsequently leading to bronchial smooth muscle hypercontraction. Respiratory viral infections are well-known causes of precipitation of acute asthma exacerbations in 50–60 % of attacks. There is also increasing evidence that bacterial infections, Chlamydia pneumoniae, and Mycoplasma pneumoniae, may contribute to the onset and course of asthma. The two main hypothesis of microbial genesis of asthma that has arisen in the past 20–30 years appears to be incongruous, but are not, are the hygiene hypothesis of asthma, and the virus-related asthma, early onset of viral bronchiolitis in the susceptible hosts being responsible for later development of asthma. The clinical and experimental evidences to support these contentions are reviewed and critiqued."
6601,Diagnostic Knowledge in the Genetic Economy and Commerce,"On 5 December 2002 the Australian Senate passed the Research Involving Embryos and Prohibition of Human Cloning Bill 2002, which regulates stem cell research. The bill introduces some restrictions with regard to the use of stored frozen embryos, which are not destined to be implanted. The bill states that only frozen embryos created before April 2002 can be used for research purposes, provided that the individuals whom these embryos relate to give their consent. The alternative to this restriction would have been no research at all, and this would have happened if the law had been stopped. The Australian scientists regarded the new law as a compromise that would undoubtedly slow down research, but not entirely stop it."
6602,High Capacity Vectors,"Since the construction of the first generation of general cloning vectors in the early 1970s, a large number of cloning vectors have been developed. Despite the bewildering choice of commercial and other available vectors, the selection of cloning vector to be used can be decided by applying a small number of criteria: insert size, copy number, incompatibility, selectable marker cloning sites, and specialized vector functions. Several of these criteria are dependent on each other. Most general cloning plasmids can carry a DNA insert up to around 15 kb in size. Several types of vectors are available for cloning large fragments of DNA too. This chapter presents a consolidated account of some new generation of high-capacity vectors such as cosmid, yeast artificial chromosome (YAC) , bacterial artificial chromosome (BAC), P1 phage artificial chromosome (PAC), and human artificial chromosome (HAC)."
6603,Vector-based antiviral therapy,
6604,Heparan Sulfate Proteoglycans in Infection,"To cause infections, microbial pathogens elaborate a multitude of factors that interact with host components. Using these host–pathogen interactions to their advantage, pathogens attach, invade, disseminate, and evade host defense mechanisms to promote their survival in the hostile host environment. Many viruses, bacteria, and parasites express adhesins that bind to cell surface heparan sulfate proteoglycans (HSPGs) to facilitate their initial attachment and subsequent cellular entry. Some pathogens also secrete virulence factors that modify HSPG expression. HSPGs are ubiquitously expressed on the cell surface of adherent cells and in the extracellular matrix. HSPGs are composed of one or several heparan sulfate (HS) glycosaminoglycan chains attached covalently to specific core proteins. For most intracellular pathogens, cell surface HSPGs serve as a scaffold that facilitates the interaction of microbes with secondary receptors that mediate host cell entry. Consistent with this mechanism, addition of HS or its pharmaceutical functional mimic, heparin, inhibits microbial attachment and entry into cultured host cells, and HS-binding pathogens can no longer attach or enter cultured host cells whose HS expression has been reduced by enzymatic treatment or chemical mutagenesis. In pathogens where the specific HS adhesin has been identified, mutant strains lacking HS adhesins are viable and show normal growth rates, suggesting that the capacity to interact with HSPGs is strictly a virulence activity. The goal of this chapter is to provide a mechanistic overview of our current understanding of how certain microbial pathogens subvert HSPGs to promote their infection, using specific HSPG–pathogen interactions as representative examples."
6605,"Angiotensin-(1-7), Angiotensin-Converting Enzyme 2, and New Components of the Renin Angiotensin System","The discovery of angiotensin-(1-7) [Ang-(1-7)] in 1988 represented the first deviation from the traditional biochemical cascade of forming bioactive angiotensin peptides. Prior to that time, the biological actions of angiotensin II (Ang II) were being investigated as it relates to cardiovascular function, including hypertension, cardiac hypertrophy and failure, as well as biological actions in the brain and kidney. We now know that Ang II elicits a whole host of actions both within and outside of the cardiovascular system. Furthermore, the discovery of Ang-(1-7) by our laboratory was also the first indication of a biologically active angiotensin peptide that further studies revealed served to counter-balance the actions of Ang II. This chapter reviews the data demonstrating the role of the vasodepressor axis of the renin angiotensin system in the regulation of cardiovascular function and the new data that shows the existence of angiotensin-(1-12) as a novel alternate substrate for the production of angiotensin peptides. The ultimate role of this discovery, as well as the continuing elucidation of mechanisms pertaining to RAS physiology, will likely be clarified in the coming years, in hopes of improving the treatment of cardiovascular disease."
6606,Epidemiologie und Prävention von nosokomialen Infektionen,"Eine nosokomiale Infektion (griechisch: nosokomeion = Krankenhaus) ist laut Infektionsschutzgesetz definiert als eine „Infektion mit lokalen oder systemischen Infektionszeichen als Reaktion auf das Vorhandensein von Erregern oder ihrer Toxine, die im zeitlichen Zusammenhang mit einer stationären oder einer ambulanten medizinischen Maßnahme steht, soweit die Infektion nicht bereits vorher bestand“. Das Risiko, eine Infektion zu entwickeln, ist für Patienten im Krankenhaus höher als für Menschen außerhalb des Krankenhauses. Grund dafür ist, dass bei vielen Patienten durch ihre Grunderkrankung eine Schwächung des Immunsystems besteht und/oder invasive Maßnahmen durchgeführt werden, die das Eindringen von Erregern in das Körperinnere und das Entstehen einer Infektion erleichtern. Besonders gefährdet sind deshalb im Bereich der Pädiatrie Frühoder Mangelgeborene, pädiatrische Intensivpatienten, Patienten mit chronischen Erkrankungen wie der zystischen Fibröse oder Dialysepflicht und onkologisch-pädiatrische Patienten. Dabei können auch fakultativ pathogene Mikroorganismen zu einer Infektion führen. Außerdem kommt es im Krankenhaus durch häufige durchgeführte Antibiotikatherapien zu einer Selektion von Keimen mit problematischem Resistenzspektrum, was die Therapie erschwert und die Übertragung dieser Keime erleichtert."
6607,Spezielle Erreger und Infektionen,"Durch das konsequente Einhalten und Anwenden der Standardhygienemaßnahmen lassen sich die meisten Transmissionen zwischen Patienten, aber auch Übertragungen auf das Personal vermeiden. Das folgende Kapitel widmet sich den Besonderheiten einzelner Erreger und Infektionskrankheiten und den ggf. erforderlichen zusätzlichen Schutzmaßnahmen. Es hilft bei der individuellen Risikoanalyse hinsichtlich Erregertyp, Übertragungsweg, Streupotenzial und exponierter Personen. Eine erregerspezifische Übersicht zum Nachschlagen ermöglicht eine schnelle Orientierung."
6608,The Global Threat of Emergent/Re-emergent Vector-Borne Diseases,"The past 30 years has witnessed a dramatic re-emergence of epidemic vector-borne diseases throughout much of the world. Factors contributing to this are many, but the principal drivers have been complacency and de-emphasis of infectious diseases in pubic health policy, increased population growth, uncontrolled urbanization without concomitant attention to water and waste management, increased globalization and the ease with which modern air transport can quickly spread pathogens and their vectors. The re-emergence of parasitic, bacterial and viral vector-borne pathogens is described. This re-emergence increases the current and future need for preventative measures to contain disease outbreaks and for international cooperation and collaboration to constantly monitor the outbreak of these debilitating and deadly diseases."
6609,Virus-Like Particles-Based Mucosal Nanovaccines,"Virus-like particles (VLPs) are protein complexes that resemble a virus and constitute highly immunogenic entities as they mimic the pathogen at an important degree. Among nanovaccines, those based on VLPs are the most successful thus far with some formulations already commercialized (e.g., those against hepatitis B and E viruses and human papillomavirus). This chapter highlights the advantages of VLPs-based vaccines, describing approaches for their design and transmittance of the state of the art for mucosal VLPs-based vaccines development. Several candidates have been produced in insect cells, plants, and E. coli and mammalian cells; they have been mainly evaluated in i.n. and oral immunization schemes. i.n. vaccines against the influenza virus and the Norwalk virus are the most advanced applications. For the latter, i.n. formulations are under clinical evaluation. Perspectives for the field comprise the expansion of the use of low-cost platforms such as plants and bacteria, the development of multiepitopic/multivalent vaccines, and computationally designed VLPs. Mucosal VLPs-based vaccines stand as a major promising approach in vaccinology and the initiation of more clinical trials is envisaged in a short time."
6610,Managing the Negotiation Process,"In global public health negotiations, the stakes are usually high and often time is of the essence. The outbreak of the SARS epidemic in late 2002, for example, illustrated how rapidly crises can occur and how immediate action may be required. Negotiations on immediate and short-term issues such as SARS, and even on long-term policies not triggered by a crisis, can be made all the more complex by diverse interests, conflicting understandings of underlying facts and linkages among the multitude of issues. Specific obstacles to joint problem-solving may include disagreement on the existence, certainty or severity of the problem; on the best way to tackle the problem or the likelihood of success; or on who bears responsibility to act, who will pay costs and who will manage the response. In the health sector, national leaders in key countries may be reluctant to acknowledge the urgent need to address the spread of a disease, either because they question the facts or because they fear that taking action will have negative impacts on their international image and/or domestic political support."
6611,Imaging of Pulmonary Infections,"Pulmonary infections have always been a cause of high morbidity and mortality, particularly in the pediatric and geriatric population and in immunocompromised hosts [1]. Pulmonary infections have various etiologies and have variegated patterns on radiographs and computed tomography (CT). Imaging plays an important role in the initial diagnosis and follow-up of various lung infections. Radiographs can be normal or non-specific during the initial evaluation, and CT findings may be more definitive. CT not only helps with the diagnosis but can also aid in management by guiding the diagnostic and therapeutic procedure. The pulmonary infections spread by direct or indirect contact with the infected host, droplet transmission, or an airborne spread. In rare cases, some infections can also be transmitted by vectors, namely, insect or animal hosts, and rarely by direct invasion from nearby infected organs. Pulmonary infections may have typical imaging patterns and distribution based on the mode of spread. There are a number of well-described imaging patterns of alveolar infections. The localization and morphological features on imaging may help in the diagnosis of infection and identification of mode of infection and, in certain cases, the microorganism responsible for the infection."
6612,Porcine Epidemic Diarrhea Virus,"Porcine epidemic diarrhea virus (PEDv) causes disease and mortality to piglets worldwide. Most vaccines used to combat the disease have been ineffective live attenuated virus vaccines. Research has emerged showing both the spike (S) and membrane (M) proteins of the virus have potential for use as subunit vaccines. This research has been largely undertaken using plants as expression platforms, with some promising candidates having emerged."
6613,Summary of Infection Control in the Dental Office: A Global Prospective,"During the delivery of dental care, there is the potential for the dissemination and/or exposure to blood and other body fluids as well as numerous microorganisms that colonize the mouth and/or oral, nasal, and respiratory fluids/secretions. Dentists, dental staff, and patients can be exposed to a variety of pathogenic microorganisms from these sources within the dental office. Contamination from any of these organisms may result in disease transmission which may occur from direct contact with infected body fluids and tissues, or indirectly by contacting surfaces and/or devices that have been contaminated. This phenomenon can occur anywhere in the world where dental care is provided. The principles of infection control must be employed to ensure that dental care is delivered in as safe a manner as possible for both the dental providers and the patients."
6614,Technical and Clinical Niches for Point of Care Molecular Devices,"A point of care (POC) device is one that is used outside of a central laboratory environment; generally near , or at the site of the patient/client. Point of care testing (POCT) varies from tests performed in physician’s office labs, or “satellite” or “stat” labs, to tests performed on tabletop instruments in a clinic area, to testing performed with hand-held instruments at the bedside. In peripheral lab settings, POCT may be performed by trained laboratory staff, but clinic and bedside POCT is frequently performed by staff who lack specialized laboratory training and whose primary job is something other than doing lab tests."
6615,Science,"Science today studies phenomena lasting less than 10(−21) s and phenomena which occurred more than 13 billion years ago; science also studies phenomena occurring over distances greater than 10(28) cm and shorter than 10(−13) cm; that is, science studies phenomena occurring over times and distances varying by a factor of about 10(40) (Fig. 3.1). In those incomprehensible ranges of time and space, the description of the physical world presented by science is most impressive. Based on what we know today everything in this enormous cosmos everywhere is made up of the same microscopic particles, the atoms and their constituents; their behavior is governed by the same physical laws everywhere."
6616,Asthma,
6617,Virtual Screening and Molecular Design Based on Hierarchical Qsar Technology,"This chapter is devoted to the hierarchical QSAR technology (HiT QSAR) based on simplex representation of molecular structure (SiRMS) and its application to different QSAR/QSPR tasks. The essence of this technology is a sequential solution (with the use of the information obtained on the previous steps) of the QSAR paradigm by a series of enhanced models based on molecular structure description (in a specific order from 1D to 4D). Actually, it’s a system of permanently improved solutions. Different approaches for domain applicability estimation are implemented in HiT QSAR. In the SiRMS approach every molecule is represented as a system of different simplexes (tetratomic fragments with fixed composition, structure, chirality, and symmetry). The level of simplex descriptors detailed increases consecutively from the 1D to 4D representation of the molecular structure. The advantages of the approach presented are an ability to solve QSAR/QSPR tasks for mixtures of compounds, the absence of the “molecular alignment” problem, consideration of different physical–chemical properties of atoms (e.g., charge, lipophilicity), and the high adequacy and good interpretability of obtained models and clear ways for molecular design. The efficiency of HiT QSAR was demonstrated by its comparison with the most popular modern QSAR approaches on two representative examination sets. The examples of successful application of the HiT QSAR for various QSAR/QSPR investigations on the different levels (1D–4D) of the molecular structure description are also highlighted. The reliability of developed QSAR models as the predictive virtual screening tools and their ability to serve as the basis of directed drug design was validated by subsequent synthetic, biological, etc. experiments. The HiT QSAR is realized as the suite of computer programs termed the “HiT QSAR” software that so includes powerful statistical capabilities and a number of useful utilities."
6618,Anemia and RBC Transfusion,"Anemia is common in critically ill patients. More than 90% of patients have subnormal hemoglobin by the third day of ICU admission. Despite the fact that blood transfusions have not been shown to improve the outcome of ICU patients (see below) and that the current guidelines recommend blood transfusion only when the hemoglobin falls below 7.0 g/dl, almost half of all patients admitted to an ICU receive a blood transfusion.(1,2) The etiology of anemia of critical illness is multi-factorial and complex. Repeated phlebotomy, gastrointestinal blood loss, and other surgical procedures contribute significantly to the development of anemia. Red cell production in critically ill patients is often abnormal and is involved in the development and maintenance of anemia. The pathophysiology of this anemia includes decreased production of erythropoietin (EPO), impaired bone marrow response to erythropoietin, and reduced red cell survival."
6619,Automatic Question Generation for Learning Evaluation in Medicine,"An approach of automatic question generation from given learning material of medical text is presented in this paper. The main idea is to generate the questions automatically based on question templates which are created by training on many medical articles. In order to provide interesting questions, our research focuses on medical related concepts. This method can be used for evaluation of learner’s comprehension after he/she finished a reading material. Different from traditional learning system the articles and questions are all prepared beforehand; participants can learn whatever new input medical articles with the help of automatic question generation."
6620,"Wich tige Gesetze, Verordnungen und Richtlinien",
6621,Epidemiologia e scenari globali,"L’epidemiologia è lo studio dinamico dello stato di salute delle popolazioni. Naturalmente, la complessità delle malattie e dei fenomeni di diversa natura a esse correlati (biologici, ecologici, antropologici eccetera) richiede un approccio che può essere solo multidisciplinare. Per i medici e i veterinari, lo studio della diffusione e della frequenza delle malattie nelle popolazioni umane e animali rappresenta uno strumento essenziale, sia per la prevenzione e il controllo, sia per la diagnosi e la cura."
6622,Hidden Silent Codes in Viral Genomes,"Viruses are small infectious agents that replicate only inside the living cells of other organisms and comprise approximately 94% of the nucleic acid-containing particles in the oceans. They are believed to play a central role in evolution, are responsible for various human diseases, and have important contributions to biotechnology and nanotechnology. Viruses undergo evolutionary selection for efficient transmission from host to host by exploiting the host’s gene expression machinery (e.g., ribosomes) for the expression of the genes encoded in their genomes. As a result, viral genes tend to be expressed via non-canonical mechanisms that are very rare in living organisms. Many of the gene expression stages and other aspects of the viral life cycle are encoded in the viral transcripts via ‘silent codes’, and are induced by mutations that are synonymous to the viral amino acid content. In a series of studies that included the analyses of dozens of organisms from the three domains of life, it was shown that there are overlapping ‘silent codes’ in the genetic code that are related to all stages of gene expression regulation. The aim of this chapter is to summarize the current knowledge related to the silent codes in viral genomes and the open questions in the field."
6623,Long Non-coding RNA,"Rapid development in genome-wide transcriptional analyses has led to the discovery of a large number of non-coding transcripts, also called long non-coding RNA (lncRNA). LncRNAs harbor biological activities including regulation of protein-coding gene expression at epigenetic, transcriptional and post-transcriptional levels. They also take a part in various physiological and pathological processes, participating in cell development, immunity, disease processes and oncogenesis. Here I discuss and summarize, current knowledge about lncRNA origin, function and involvement in human disease."
6624,Introduction to Human-Environment Interactions Research,"Contemporary theories about the reciprocal interactions of human beings with the environment are only fully intelligible in the light of the historical roots of such theories. In this introduction we provide an overview of the major Western intellectual currents up to those that are commonly used today. Three main themes help organize this broad array of theories and approaches: environmental determinism, cultural determinism, and human-environment interaction concerned with the processual relationships between people and environment as grounded in historical, social, and ecological contexts. This chapter also provides an overview of the four parts of the book and discusses the coverage, diversity, and parallels in themes and approaches across all chapters."
6625,World Health Organization,"The World Health Organization (WHO) is a specialized agency of the United Nations (UN) that is concerned with international public health. It was established on April 7, 1948, with headquarters in Geneva, Switzerland and is a member of the UN Development Group. The membership of the WHP includes 193 countries and 2 associate members. Six regional committees, located in the Americas, Europe, the Eastern Mediterranean, South-East Asia, the Western Pacific, and Africa, focus on regional health concerns."
6626,Viruses and the Nucleolus,"The nucleolus is a dynamic sub-nuclear structure integral to the function of a eukaryotic cell. Some of its major roles involve ribosome subunit biogenesis, RNA processing, cell cycle control and responding to cellular stress, such as infection. Our understanding of the relationship between viruses and the nucleolus has moved from a phenomenological approach describing protein localisation to functional studies involving genetic analysis and proteomic approaches. These advances have provided fundamental insights as to how and why the nucleolus is targeted by many different viruses both to usurp normal functioning and to recruit nucleolar proteins to facilitate virus replication. This knowledge has been exploited for therapeutic strategies involving targeted inhibition of virus replication and live-attenuated recombinant vaccines."
6627,Infections,"Even if heart transplantation is an undisputed source of medical progress, several complications still hamper the outcome of transplanted patients. Among them, infections are associated with significant morbidity, mortality, and economic burden. Depending on clinical and radiological signs and based on the time interval after transplantation, a broad spectrum of microbial pathogens can be responsible for these infections. This microbiological diversity, associated with altered clinical signs due to immunosuppressive drugs, is a cause of delayed diagnosis and treatment. The objective of this overview is to provide a structured procedure to explore fever and specific symptoms that can be suggestive of infection in heart-transplanted patients. Furthermore, main preventive and curative strategies will be described."
6628,Cordylobia spp.,
6629,Strategies of Preparedness Response to Biological Warfare and Bioterrorism Threats,"Risks associated with deliberate use of biological agents against population and the needs for a strong public health system are well recognized. The potential use of biological agents is mounting every day, especially with growing political dissidence as well as social and economical conflicts in several countries. Countries in Eastern Europe have considerable vulnerability because of economical, social and political difficulties they are facing, along with inadequate response capacity and large number of outfits having continuous low intensity conflicts with established administrative system. There are no doubts that preparedness against biological weapons must be integrated in national disaster preparedness plan, as well as strengthen the core competencies of public health and other national and local authorities to respond to biological crisis, along with strong collaboration with other national agencies, like intelligence, defense and police."
6630,Kann das Immunsystem unterwandert werden?,"Infektionserreger haben sich in ihrer Evolution darauf spezialisiert, in einem immunkompetenten Wirt zu leben und ein breites Repertoire origineller Tricks entwickelt, das Immunsystem zu unterwandern. Die Tabelle 20.1 zeigt Beispiele."
6631,Geographic Medicine,"This chapter uses a sub-discipline of medicine, known as geographic medicine, to describe how human movements contribute to the transmission of parasites on spatial scales that exceed the limits of its natural habitat. Traditionally, public health programs have focused on the health of populations, whereas the practice of medicine has focused on the health of individuals. It should be noted, however, that the population health management owes much to the effective delivery of clinical care. This chapter demonstrates how public health is intimately linked to patient care through human movement. Nearly a century ago, people typically did not develop a disease where it is contracted or even close to that place. Today, daily travel is a common way of life in modern metropolitan areas. Large, localized mosquito populations in areas that people visit regularly may be both reservoirs and hubs of infection, even if people only pass through those locations briefly. By examining of the role of human movement across different scales, this chapter examines how public health communities can use information on pathogen transmission to increase the effectiveness of disease prevention programs and clinical care."
6632,Therapieversagen,"Eine allgemein anerkannte Definition des Therapieversagens ist nicht verfügbar. Zu unterscheiden sind klinische Kriterien des Therapieansprechens (Entfieberung, Rückgang inflammatorischer Parameter, Stabilisierung oder Rückgang der Beatmungsintensität, hämodynamische Stabilisierung) sowie der Rückbildung der akuten Pneumonie; erstere können nach 72 h erstmals beurteilt werden, letztere erst innerhalb von 8–10 Tagen. Das Therapieversagen der nosokomialen Pneumonie ist mit annähernd 30 % ein häufiges Ereignis. Es ist mit einer ernsten Prognose verbunden und sollte daher eine umfangreiche Differentialdiagnostik erfahren. Muster des Therapieversagens umfassen die rasche Progredienz innerhalb der ersten 72 h (progressive pneumonia), das fehlende Ansprechen nach 72 h (nonresolving pneumonia) sowie das Therapieversagen nach initialem Ansprechen (sekundäres Therapieversagen). Ursachen können sein eine inadäquate kalkulierte antimikrobielle Therapie, gleichzeitig vorliegende andere Infektionsfoci oder nichtinfektiöse Ursachen sowie Ursachen, die mit der Immunantwort des Wirts in Zusammenhang stehen. Ursächliche Erreger entsprechen weitgehend dem für die jeweilige Behandlungseinheit gegebenen Spektrum; aber auch Fadenpilze und Herpesviren sind mögliche Erreger. Die diagnostische Evaluation sollte primär bronchoskopisch und durch Gewinnung einer bronchoalveolären Lavage (BAL) erfolgen. Transbronchiale Biopsien oder offene Lungenbiopsien können im Einzelfall erwogen werden. Histologisch ergeben sich am häufigsten eine Pneumonitis bzw. Fibrose und ein diffuser Alveolarschaden (DAD)."
6633,Influenza,"Influenza, abbreviated as flu, is an acute respiratory infectious disease caused by influenza virus, which is mainly spread along with droplets with strong infectivity. The influenza virus may cause epidemics or pandemics of influenza and its incidence ranks the first among legally listed infectious diseases. The prevalence of influenza peaks in autumns and winters, with short illness course and self limitation. However, influenza can be complicated by pneumonia or other serious complications that may cause death in populations of infants, young children, the elderly, those with underlying heart and lung disease and those with compromised immunity."
6634,Role of Fibrinolysis in the Nasal System,"In this chapter, we show the presence of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and plasminogen activator inhibitor-1 (PAI-1) in nasal mucosa. It is suggested that t-PA synthesized in mucous cells is promptly secreted and modifies the watery nasal discharge in allergic rhinitis and that u-PA activity may help with the passage of large amounts of rhinorrhea by reducing its viscosity. Furthermore, we clarify the relation between fibrinolytic components and the pathology of allergy, particularly during the development of nasal allergy and nasal tissue changes. Wild-type (WT) mice can develop nasal allergy for ovalbumin (OVA) sensitization, but PAI-1-deficient mice (PAI-1(-/-)) cannot. The production of specific immunoglobulins IgG1 and IgE in the serum and production of interleukins IL-4 and IL-5 in splenocyte culture supernatant increased significantly in WT-OVA mice. In PAI-1(-/-) mice, these reactions were absent, and specific IgG2a in serum and interferon-γ in splenocyte culture medium increased significantly. Histopathologically, there was marked goblet cell hyperplasia and eosinophil infiltration into the nasal mucosa in WT-OVA mice, but these were absent in PAI-1(-/-) mice. These results indicate that the immune response in WT-OVA mice can be classified as a dominant Th2 response, which would promote collagen deposition. In contrast, the Th2 response in PAI-1(-/-) mice was down-regulated and the immune response shifted from Th2-dominant reaction to a Th1-dominant one. Taken together, these findings suggest that PAI-1 plays an important role not only in thrombolysis but also in the immune response."
6635,Predictive Dynamics: Modeling for Virological Surveillance and Clinical Management of Dengue,"Dengue fever is a flu-like illness spread by the bite of an infected mosquito and is fast emerging as a major public health concern. Timely and cost-effective diagnosis would reduce the mortality rates besides providing better grounds for clinical management and disease surveillance. Identifying the clinical features for early diagnosis of dengue would be useful in reducing the virus transmission in a community. In addition to the clinical features, obtaining the influential laboratory attributes and their range would aid in quick identification of disease severity in the suspected individuals. In this chapter a new alternating decision tree methodology which generates more accurate and simplified decision tree structures with simplified classification rules is discussed. This approach helps one to obtain the influential clinical and laboratory features which would aid in identifying the suspected dengue individuals and assess the severity of infection in them."
6636,Infections After High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation,"Infection represents an important cause of morbidity after autologous hematopoietic stem cell transplantation (HSCT). Immunodeficiency is the key risk factor and results from interplay between the underlying disease and its therapy. Various defects in the immune system coexist in HSCT recipients. In the early post-transplant period, neutropenia, oral and gastrointestinal mucositis, and the presence of central venous catheters are the main risk factors. Bacterial infections predominate, and the agents and antibiotic susceptibility profiles vary widely in different regions. Invasive candidiasis is infrequent with fluconazole use, but the incidence of invasive aspergillosis is on the rise, mainly in patients receiving purine analogues or intensive chemotherapy before transplant. In the post-engraftment period, infections are less frequent, but may contribute to significant non-relapse mortality. The dynamics of immune reconstitution drives the risk for infection in this period. The most frequent infections are varicella-zoster virus disease and respiratory tract infections. Assessment of the risk of infection in each period and the identification of patients at higher risk of specific infections are critical to the appropriate management of infectious complications after autologous hematopoietic stem cell transplantation."
6637,Medical Words Linked to Places,"Many medical terms come from places: towns, rivers, islands, forests, mountains, valleys, countries, and continents. These toponymous diseases, syndromes, descriptors, and other entities bring us colorful names that help us recall some of their history. Today we have Zika virus, its name coming from the Zika Forest in Ghana. Caucasian comes from the Caucasus Mountains, lesbian from the island of Lesbos, and Epsom salts from a mineral spring in Epsom, Surrey, England. Chapter 10.1007/978-3-319-50328-8_5 tells the stories behind these place-named diseases and how many of them affect us today."
6638,Social Problems: A Cost-Effective Psychosocial Prevention Paradigm,"This introductory chapter provides a discussion about the need for prevention. As justification for prevention, the chapter highlights the costs of social problems discussed in the book, including academic problems, violence in schools, child maltreatment, HIV/AIDS, and substance abuse."
6639,MHC Class I Expression and CD8 T Cell Function: Towards the Cell Biology of T-APC Interactions in the Infected Brain,"Antigen presentation by major histocompatibility complex class I (MHC-I) and class II (MHC-II) molecules is a prerequisite for T cell engagement during the activation as well as the effector phase. The central nervous system (CNS) is unique in that cells resident in the parenchyma, glia and neurons, do not constitutively (or very sparsely at best) express MHC molecules (Aloisi et al., 2000; Sedgwick and Hickey, 1997; Xiao and Link, 1998), making them invisible to T cells. Additional restrictions on T cell surveillance are imposed by the absence of classical lymphatic drainage, the blood—brain barrier (BBB), and the unique anatomy of the brain microvasculature (Bechmann et al., 2007; Galea et al., 2007; Hickey, 2001; Xiao and Link, 1998; Lowenstein, 2002). Infiltrating cells not only have to cross the vascular wall to penetrate into the perivascular space, but more importantly overcome the barrier formed by the glia limitans to access the CNS parenchyma. While the first step is generally not associated with pathology, penetration from the perivascular space of postcapillary venules into the parenchyma is more restricted and once overcome, associated with clinical consequences (Bechmann et al., 2007). In the resting state, perivascular macrophages are maintained by replacement with circulating monocytes. However the glial limitans is not breached, and thus, these cells are considered to be located outside the confines of the BBB. While diffusion of soluble factors and antibodies is restricted by the BBB, especially by the tight, continuous, unfenestrated capillary epithelium, leukocyte infiltration preferentially occurs at distal sites in postcapillary venules (Bechmann et al., 2007). BBB permeability and leukocyte infiltration are thus not necessarily functionally nor physically linked. The barriers separating CNS parenchyma from the circulation explains the rare presence of T cells in the normal CNS parenchyma, despite the ability of peripherally activated and memory T cells to traffic to non lymphoid tissues independent of antigen presentation (Masopust et al., 2004). Nevertheless, T cells activated during an infection or auto-immune response, are able to enter into, and migrate within the brain parenchyma, even in the presence of an intact, non-inflamed BBB (Cabarrocas et al., 2003; Chen et al., 2005; Evans et al., 1996; Hickey, 2001). However, although entry of activated T cells into the CNS is independent of their antigen specificity, only those T cells that recognize antigen are retained. Thus, barriers limiting T cell surveillance of the brain are rapidly overcome following CNS infections and other inflammatory conditions (Griffin, 2003; Ransohoff et al., 2003). Under such conditions, it is also likely that a number of non-activated, bystander T cells, as well as other leukocytes, including B cells are able to penetrate into the brain parenchyma. Mechanisms propagating protective versus pathogenic potential of T cells in varying disease models are complex and require more in depth exploration. This chapter highlights recent advances relating to antigen presentation functions by resident CNS cells and effects exerted by CD8 T cells in vivo with an emphasis on anti-viral functions."
6640,Human Infected H5N6 Avian Influenza,Human infected H5N6 avian influenza is an acute respiratory infectious disease caused by H5N6 subtype of avian influenza virus.
6641,Lychee Biology and Biotechnology,"Lychee (Litchi chinensis Sonn.) is one of the revered members of the soapberry family Sapindaceae which includes 150 genera and 2000 species. It is a tropical and subtropical fruit tree which is native to Fujian and Guangdong regions of China and is cultivated as an important commercial fruit crop in many parts of the world. It is famous for its fragrant and sugary flavour. After China, India is at the second position in the production of lychee in the world. The varieties with large pulp, small seeds and noteworthy flavour are of great interest among the consumers and farmers. Lychee fruit took tremendous attention of scientists as it contains ample amounts of anti-oxidants, vitamins and fibre. Moreover, the plant parts possess considerable anti-pyretic, anti-inflammatory, anti-cancer, anti-diabetic, anti-tumour and anti-oxidant properties. Propagation of lychee from seeds is difficult and not practicable because of longer juvenile period and non-viable, abortive and genetically diverse nature of the seedlings. However, the techniques such as cell, tissue and organ culture (micropropagation) can overcome the difficulties of lychee propagation. Very limited efforts have been made in its varietal improvement through hybridization and modern breeding techniques. In a nutshell, lychee is an important commercial fruit crop, and there is a need to develop technical research so as to sustain and enhance its yield, postharvest management, medicinal value and marketing. This chapter comprises of botanical description, cultivation, medicinal uses, micropropagation and trading of Litchi chinensis."
6642,Testing the Donor,"The transplantation of tissues from donor to recipient is a fundamental part of medicine today. A range of tissues including bone, skin, tendons, heart valves, corneas etc. are collected from suitable donors and transplanted into those patients for whom tissue transplant would have clinical benefit."
6643,Update in Pediatric Hospital Medicine,"Pediatric Hospital Medicine has significantly developed as a field over the past two decades. With the goal of improving care for hospitalized children, much of the research in this field has focused on reducing unnecessary interventions, optimizing necessary treatments, and reducing variability for common inpatient conditions. While this is far from an exhaustive chapter on the vast diversity and advances in this field, it focuses on the updates for some of the top diagnoses in hospital medicine and the major trends in the field. Updated management of acute viral bronchiolitis, urinary tract infections, neonatal infections, brief resolved unexplained events (formerly, apparent life-threatening events), and osteomyelitis are highlighted with emphasis on major management changes. In addition, and distinct to pediatric hospital medicine, the topics of overuse and high value care are discussed as they have gained momentum in influencing the way hospitalists think and practice."
6644,Intensivtherapie nach Organtransplantation,"Nach langen Diskussionen bietet das Transplantationsgesetz, das seit 01.12.1997 in Kraft ist, Rechtssicherheit. Das Gesetz dient dem Schutz des Spenders und des Empfängers, und es bietet Rechtssicherheit für alle in der Transplantationsmedizin Tätigen. Das Gesetz legt die Rechte und Verpflichtungen der Beteiligten und die Wege der Organspende und -vermittlung fest. Das Gesetz unterscheidet zwischen der Organentnahme bei Lebenden und bei Verstorbenen und legt die Rahmenbedingungen fest. Die Umsetzung der Todesbestimmung soll nach den Erkenntnissen der medizinischen Wissenschaft erfolgen und ist in den Richtlinien der Bundesärztekammer (3. Fortschreibung 1997) festgelegt worden."
6645,Surgical Complications of Childhood Tumors,Most childhood tumors will first present to a physician; some tumors will present in an atypical manner and may mimic a surgical condition. The diagnosis may be missed if the surgeon is not aware of the possibility of cancer. A very great number of rare presentations of childhood cancer have been described in the literature. It is important that the surgeon who is not experienced in the management of childhood cancer is aware that an apparently benign condition could be a manifestation of an underlying malignancy.
6646,Influenza in the Elderly,
6647,Pneumocystis jiroveci Pneumonia,"Pneumocystis pneumonia (PCP) is one of the most common pulmonary infections in persons with impaired cell-mediated immunity, and particularly those infected with human immunodeficiency virus (HIV).1–7 Pneumocystis was first described in the lungs of guinea pigs, during experiments on American trypanosomiasis by Carlos Chagas8 in 1909 and by Antonio Carinii9 in 1910. Both considered the cysts of Pneumocystis as part of the trypanosome’s life cycle. Shortly afterward the Delanoes10 found identical forms in the lungs of rats that had not been infected with trypanosomes and recognized the organism as a separate species. The name Pneumocystis carinii, was given to this organism as a generic name (Greek:pneumon, “lung”; kystis, “cyst”), honoring Carinii.11"
6648,Recombinant IgA Antibodies,"The production of monoclonal antibodies and the development of recombinant antibody technology have made antibodies one of the largest classes of drugs in development for prophylactic, therapeutic and diagnostic purposes. Currently, all of the Food and Drug Administration (FDA)- approved antibodies are immunoglobulin Gs (IgGs). However, more than 95%of the infections are initiated at the mucosal surfaces, where IgA is the primary immune effector antibody."
6649,4 Respiratoire spoedgevallen,"Het gebruik van de term ‘status asthmaticus’ voor een ernstige, levensbedreigende astma-aanval schept veel onduidelijkheid. De ene auteur geeft hiermee een bepaalde ernst van bronchusobstructie aan, de andere verdisconteert in dit begrip de duur van een aanval, eventuele complicaties of een zekere mate van therapieresistentie."
6650,Development of Mucosal Vaccines Based on Lactic Acid Bacteria,"Today, sufficient data are available to support the use of lactic acid bacteria (LAB), notably lactococci and lactobacilli, as delivery vehicles for the development of new mucosal vaccines. These non-pathogenic Gram-positive bacteria have been safely consumed by humans for centuries in fermented foods. They thus constitute an attractive alternative to the attenuated pathogens (most popular live vectors actually studied) which could recover their pathogenic potential and are thus not totally safe for use in humans. This chapter reviews the current research and advances in the use of LAB as live delivery vectors of proteins of interest for the development of new safe mucosal vaccines. The use of LAB as DNA vaccine vehicles to deliver DNA directly to antigen-presenting cells of the immune system is also discussed."
6651,Concepts and Theories of Longevity,"This chapter is concerned with the concepts, statistics, theories, and future levels of human longevity, particularly extreme longevity. The term, extreme longevity or superlongevity, is used here to refer to centenarians, that is, persons with a verified age of 100 years or more. Among these we identify for special attention a subgroup known as supercentenarians, that is, persons with a verified age of 110 years or more. In both popular and scientific reporting, people aged 85 years and over have often been considered as extreme aged, but the rapid increase in the number of people in these older age groups suggests a redefinition of the notion of extreme aged. Persons in the broad age group 85 years and over are also referred to as persons of advanced age and the oldest-old. The former description now seems appropriate but the latter one does not. Preferences vary among demographers and gerontologists as to the choice of designations for these groups."
6652,Virus–Platelet Associations,"Virus–platelet interplay is complex. Diverse virus types have been shown to associate with numerous distinct platelet receptors. This association can benefit the virus or the host, and thus the platelet is somewhat of a renegade. Evidence is accumulating to suggest that viruses are capable of entering platelets. For at least one type of RNA virus (dengue virus), the platelet has the necessary post-translational and packaging machinery required for production of replicative viral progeny. As a facilitator of immunity, the platelet also participates in eradicating the virus by direct and indirect mechanisms involving presentation of the pathogen to the innate and adaptive immune systems, thus enhancing inflammation by release of cytokines and other agonists. Virus-induced thrombocytopenia is caused by tangential imbalance of thrombopoeisis, autoimmunity, and loss of platelet function and integrity."
6653,11 Longziekten,"Deze aandoeningen, die soms met ‘verkoudheid’ of ‘griep’ betiteld worden, doen zich regelmatig – en vaak epidemisch – voor; bij kinderen (drie- tot viermaal per jaar) vaker dan bij volwassenen (een- tot tweemaal per jaar)."
6654,Biomedicines as Adverse Event Inducers,"Biomedicines are new agents with old roots. Products of biological origin, such as vaccines, blood and serum components, human proteins, hormones, and immunoglobulins, are used from long time in human therapy."
6655,Behavioural and Medical Differentials of Cognitive Decline and Dementia in Dogs and Cats,"Cognitive dysfunction syndrome (CDS) is a diagnosis of exclusion given that there is no specific diagnostic test or tool and that medical disorders can cause the same set of signs. The veterinary surgeon must first identify that signs are present, collect a full history and then perform a full physical examination and relevant diagnostic tests to rule out medical causes for the signs including blood and urine analysis, radiographs and diagnostic imaging such as magnetic resonance imaging (MRI) where indicated."
6656,Air Pollution and Disasters,"Many disasters lead to air pollution and vice versa. This chapter elaborates major air pollution issues due to earthquake, tsunami, volcanic eruption, epidemics, extreme temperature, insect infestation, mass movement, wars, and fire accidents."
6657,Mycobacterial Sepsis and Multiorgan Failure Syndrome,"Tuberculosis (TB) is a global disease with high prevalence in developing countries. According to the World Health Organization (WHO) fact sheet 2009, more than 2 billion (equal to one third of world’s population) people are infected with TB bacilli. Of the cases detected, 5 % were cases of multi-drug resistant TB. Admission to a critical care unit is not required in the majority of cases. However, TB sepsis is a rapidly fatal disease that requires intensive care unit (ICU) admission and management and represents a big diagnostic and therapeutic challenge."
6658,Temporal Features in Biological Warfare,"No matter how prepared a population may be, bioterrorism cannot be prevented: the first clues will always be given by ill people. Temporal analysis applied to this type of scenarios could be an additional tool for limiting disruption among civilians allowing for recognizing typical temporal progression and duration of symptoms in first infected people. We propose the application of a fuzzy temporal reasoning system we have developed for biomedical temporal data analysis in different scenarios after a hypothetical attack. The system is able to handle both qualitative and metric temporal knowledge affected by vagueness and uncertainty, taking into account in this way the vagueness of patients reports expressed in natural language."
6659,"Cough, Cold, and Congestion","The common cold is a benign, self-limited, acute viral infection with associated symptoms of sneezing, rhinorrhea, nasal congestion, cough, and malaise. It is the most frequent acute illness in the industrialized world. Adults typically have two to three episodes of illness yearly while children can have up to five. The common cold is typically caused by viruses (including rhinovirus, RSV, coronavirus, and others), and often, no infecting organism is detected. Treatment is usually targeted at symptomatic relief. The differential diagnosis for cough, cold, and congestion is broad: ranging from non-emergent causes such as rhinitis to life-threatening illnesses such as pulmonary embolism. Careful assessment is necessary as misidentification can lead to inappropriate discharge of potentially lethal conditions."
6660,Infection Control Methods,
6661,Ontology Evolution: MEDLINE Case Study,"With the rising importance of knowledge interchange, many industrial and academic applications have adopted ontologies as their conceptual backbone. Business dynamics and changes in the operating environment often give rise to continuous changes in application requirements that may be fulfilled only by changing the underlying ontologies. This is especially true for Semantic Web applications, which are based on heterogeneous and highly distributed information resources and therefore need efficient mechanisms to cope with changes in the environment. In our previous work we have developed the KAON ontology evolution framework that (i) enables handling the required ontology changes; (ii) ensures the consistency of the underlying ontology and all dependent artefacts; (iii) supports the user to manage changes more easily; and (iv) offers advice to the user for continual ontology reengineering. In this paper we apply the proposed approach on the MEDLINE system and discuss its benefits. First, we translated the MeSH/MEDLINE into a set of the ontologies by enriching the MeSH vocabulary with the set of rules and by eliminating some inconsistencies. Second, we showed that ontology evolution ensures the consistency between all related data. Third, we indicated how formal semantics provided by an ontology might be useful to improve the indexing in the existing MEDLINE system."
6662,Immunosenescence Modulation by Vaccination,"A decline in immune function is a hallmark of aging that leads to complicated illness from a variety of infectious diseases, cancer and other immune-mediated disorders, and may limit the ability to appropriately respond to vaccination. How vaccines might alter the senescent immune response and what are the immune correlates of protection will be addressed from the perspective of (1) stimulating a previously primed response as in the case of vaccines for seasonal influenza and herpes zoster, (2) priming the response to novel antigens such as pandemic influenza or West Nile virus, (3) vaccination against bacterial pathogens such as pneumococcus and pertussis, (4) vaccines against bacterial toxins such as tetanus and Clostridium difficile, and (5) vaccine approaches to mitigate effects of cytomegalovirus on immune senescence. New or improved vaccines developed over recent years demonstrate the considerable opportunity to improve current vaccines and develop new vaccines as a preventive approach to a variety of diseases in older adults. Strategies for selecting appropriate immunologic targets for new vaccine development and evaluating how vaccines may alter the senescent immune response in terms of potential benefits and risks in the preclinical and clinical trial phases of vaccine development will be discussed."
6663,Document Re-ranking by Generality in Bio-medical Information Retrieval,"Document ranking is an important process in information retrieval (IR). It presents retrieved documents in an order of their estimated degrees of relevance to query. Traditional document ranking methods are mostly based on the similarity computations between documents and query. In this paper we argue that the similarity-based document ranking is insufficient in some cases. There are two reasons. Firstly it is about the increased information variety. There are far too many different types documents available now for user to search. The second is about the users variety. In many cases user may want to retrieve documents that are not only similar but also general or broad regarding a certain topic. This is particularly the case in some domains such as bio-medical IR. In this paper we propose a novel approach to re-rank the retrieved documents by incorporating the similarity with their generality. By an ontology-based analysis on the semantic cohesion of text, document generality can be quantified. The retrieved documents are then re-ranked by their combined scores of similarity and the closeness of documents’ generality to the query’s. Our experiments have shown an encouraging performance on a large bio-medical document collection, OHSUMED, containing 348,566 medical journal references and 101 test queries."
6664,HIV/AIDS Related Respiratory Diseases,"Lungs are the most commonly involved organ by HIV/AIDS related diseases, and pulmonary infections are the main reasons for the increasing death rate from AIDS. Pathogens of HIV related pulmonary infections include parasites, fungi, mycobacteria, viruses, bacteria and toxoplasma gondii. According to international reports, pathogens have different geographical distribution, which is also closely related to the socioeconomic status of the region to produce varied AIDS related diseases spectra. For instance, in the United States, pneumocystis carnii pneumonia (PCP), tuberculosis and recurrent bacterial pneumonia (at least twice within 1 year) occur frequently in HIV infected patients. An international report published 10 years ago indicated that PCP is the most common and serious pulmonary opportunistic infections in HIV infected patients. Now its incidence has dropped with the application of antiretroviral treatment and preventive measures. PCP will continue to occur initially in patients who are aware of their HIV infection. In addition, HIV related viral and parasitic infections have been reported both domestically and internationally. In this section, the clinical manifestations and imaging findings of HIV related pulmonary infections are analyzed and discussed, which provide effective diagnosis basis, so as to reduce the incidence of HIV-related pulmonary infections."
6665,Immune Tolerance in Autoimmune Central Nervous System Disorders,"Multiple sclerosis (MS) afflicts genetically predisposed individuals and is associated with T lymphocyte-mediated damage to the myelin sheath of neurons in the central nervous system, resulting in severely impaired signal transmission. The mechanisms of the induction and manifestation of MS are not entirely understood. The control of autoimmune disorders is accomplished by both central tolerance in which autoreactive T lymphocytes are eliminated in the thymus and by tolerance mechanisms that operate in the periphery. Among the many mechanisms described, T regulatory (Treg) cells derived from the thymus (tTregs) and induced (iTregs) in the periphery as well as T regulatory type 1 cells (Tr1) are involved in many disease models. However, the precise details of the generation and perpetuation of these various Treg subsets and their relevance to the regulation of autoimmune diseases remain elusive. In this review, we critically analyze the current knowledge of the tolerance mechanisms involved in the regulation of MS and its animal model, experimental autoimmune encephalomyelitis."
6666,Step 3 of EBP: Part 1—Evaluating Research Designs,"Step 3 of the EBP process involves evaluating the quality and client relevance of research results you have located to inform treatment planning. While some useful clinical resources include careful appraisals of research quality, clinicians must critically evaluate the content both included in these summaries and what is excluded or omitted from them. For individual research studies, clinicians must first identify and evaluate the research designs and methods reported. The terminology used to describe research designs in EBM/EBP may not always be consistent with that used in most social work research courses. This chapter provides a review of the key research designs used in EBM and EBP in order to orient clinicians to core terminology found in EBP summaries and reports."
6667,A Comparison of Evolutionary Approaches to the Shortest Common Supersequence Problem,"The Shortest Common Supersequence problem is a hard combinatorial optimization problem with numerous practical applications. Several evolutionary approaches are proposed for this problem, considering the utilization of penalty functions, GRASP-based decoders, or repairing mechanisms. An empirical comparison is conducted, using an extensive benchmark comprising problem instances of different size and structure. The empirical results indicate that there is no single best approach, and that the size of the alphabet, and the structure of strings are crucial factors for determining performance. Nevertheless, the repair-based EA seems to provide the best performance tradeoff."
6668,Prevention and Therapy from Contact Dermatitis (with Special Reference to Occupational Dermatology),
6669,RNA Interference and MicroRNA Modulation for the Treatment of Cardiac Disorders: Status and Challenges,"The current status and challenges of RNA interference (RNAi) and microRNA modulation strategies for the treatment of myocardial disorders are discussed and related to the classical gene therapeutic approaches of the past decade. Section 2 summarizes the key issues of current vector technologies which determine if they may be suitable for clinical translation of experimental RNAi or microRNA therapeutic protocols. We then present and discuss examples dealing with the potential of cardiac RNAi therapy. First, an approach to block a key early step in the pathogenesis of a virus-induced cardiomyopathy by RNAi targeting of a cellular receptor for cardiopathogenic viruses (Section 3). Second, an approach to improve cardiac function by RNAi targeting of late pathway of heart failure pathogenesis common to myocardial disorders of multiple etiologies. This strategy is directed at myocardial Ca(2+) homeostasis which is disturbed in heart failure due to coronary heart disease, heart valve dysfunction, cardiac inflammation, or genetic defects (Section 4). Whereas the first type of strategies (directed at early pathogenesis) need to be tailor-made for each different type of pathomechanism, the second type (targeting late common pathways) has a much broader range of application. This advantage of the second type of approaches is of key importance since enormous efforts need to be undertaken before any regulatory RNA therapy enters the stage of possible clinical translation. If then the number of patients eligible for this protocol is large, the actual transformation of the experimental therapy into a new therapeutic option of clinical importance is far more likely to occur."
6670,Nanomicrobiology,"Microbiology plays an important role in practice of medicine. Nanodiagnostics have refined the detection of infectious diseases and many new nanotechnology-based therapies, particularly of viral diseases, are in development."
6671,Dark scenarios,"In this chapter, we present four “dark scenarios” that highlight the key socio-economic, legal, technological and ethical risks to privacy, identity, trust, security and inclusiveness posed by new AmI technologies. We call them dark scenarios, because they show things that could go wrong in an AmI world, because they present visions of the future that we do not want to become reality. The scenarios expose threats and vulnerabilities as a way to inform policy-makers and planners about issues they need to take into account in developing new policies or updating existing legislation. Before presenting the four scenarios and our analysis of each, we describe the process of how we created the scenarios as well as the elements in our methodology for analysing the scenarios."
6672,Preparation Without Panic: A Comprehensive Social Marketing Approach to Planning for a Potential Pandemic,"In recent times the world has faced several potential pandemics – SARS, avian (bird) flu, swine flu, and most recently Ebola. The risk of a disease pandemic presents an important challenge for social marketing –to this point, health-related social marketing has focused on chronic diseases (such as cancer, asthma, obesity) and their risk factors (such as tobacco use, physical inactivity, and dietary intake). In the communicable disease field, most of the challenges we have addressed have had simple and proven preventive strategies (such as immunisation and the use of condoms). However, emerging pandemic diseases pose new challenges – notably in the global scale of the threat, the rapid nature of transmission, and (often) the absence of a known cure or vaccine. In this context, people’s quality of life has scope to be shaped by immense physical and social influences. This chapter reports on a comprehensive study undertaken to inform government policy and practice in the event of an avian influenza pandemic – specifically how to prepare (but not panic) the general public. The research phases included: a media analysis of coverage of a potential pandemic; extensive qualitative formative research; two population CATI surveys; two airport intercept surveys; message development; and message testing. While this research was undertaken in the context of a specific disease, the findings and recommendations are equally relevant to current and future pandemic threats."
6673,Bacterial Biowarfare Agents,
6674,Theories of Biodiversity Value,"The discussion of the calculus of biodiversity values in Chap. 5 is the final requisite prop for the stage across which this chapter parades accounts of how biodiversity is supposed to be valuable. The selection of these accounts is generous and represents a great majority of discussions on this topic, though it is not all-inclusive. It does include, among other theories, the theory that biodiversity is valuable for “unspecified moral reasons” (Sect. 6.1), that it is valuable as a resource (Sect. 6.2), as a service provider (Sect. 6.3), as a sustainer of human life (Sect. 6.4), as a key to human health, both as pharmacopoeia and as an inoculation against infection (Sect. 6.5), as the progenitor of human biophilic tendencies (Sect. 6.6), as a generator of (more) value (Sect. 6.7), as font of knowledge (Sect. 6.8), as having option (and quasi-option) value (Sect. 6.9), as transformative (Sect. 6.10), as having experiential value (Sect. 6.11), and as an expression of the natural order (Sect. 6.12). The chapter concludes (Sect. 6.13) with some proposals that are not customarily offered as self-contained theories of biodiversity value, but that are often suggested as still heavily influencing evaluation. These include what conservation biologists call “viability” and “endangerment” as well as conservation “efficiency”. Section 6.13 concludes with an extended discussion of the significance for biodiversity’s value of the history of human impingements on the natural world."
6675,Pharmacogenomics and Molecular Diagnostics,"To develop new Polymerase Chain Reaction (PCR)-based assays for nucleic acid detection for infectious diseases. Development of new assays on demand for emerging infectious diseases. For example, no proper nucleic acid-based tests exist for detection of H1N1 influenza virus. My lab, being the parasitology research unit aims to fill this gap by developing this ability."
6676,Molecular Mechanisms of Flaviviral Membrane Fusion,"Enveloped viruses rely on transmembrane fusion proteins to fuse the viral membrane to the host-cell membrane and deliver the viral genome into the cytoplasm for replication. Although the structures and evolutionary origins of viral fusion proteins vary widely, all fusion proteins use the same physical principles and topology to drive membrane fusion. First, exposure of a hydrophobic fusion anchor allows them to insert into the host-cell membrane. Conserved hydrophobic residues in the fusion anchor penetrate part way into the outer bilayer leaflet of the host-cell membrane. The fusion protein then folds back on itself, directing the C-terminal viral transmembrane anchor toward the fusion loop. This fold-back forces the host-cell membrane (held by the fusion loop) and the viral membrane (held by the C-terminal transmembrane anchor) against one another until they fuse. In West Nile virus and other flaviviruses this fold-back in the fusion protein, E, is triggered by the reduced pH of an endosome, is accompanied by the assembly of E monomers into trimers, and occurs by domain rearrangement rather than by an extensive refolding of secondary structure. The rearrangement releases a large amount of energy, which is used to exert a bending force on the apposed viral and cellular membranes, propelling them toward each other and, eventually, causing them to fuse. The conserved regions of E that are responsible for driving membrane fusion are attractive targets for antiviral therapies."
6677,Traumatologie und gewaltsamer Tod,"Vorgeschichte: Eine 39 Jahre alt gewordene, alkoholabhängige Frau habe von ihrem Hausarzt eine Packung Distraneurinkapseln (25 Stück) verschrieben bekommen; sie solle morgens und mittags je 1, abends 2 Kapseln einnehmen. Aus der Apotheke zurück gekehrt, begann sie zu Hause, mit ihrem Ehemann Alkohol zu trinken. Es sei zu einem Streit gekommen, in dessen Verlauf die Frau die Polizei angerufen habe. Der Ehemann sei daraufhin gegen 17.00 Uhr in Gewahrsam genommen und zur Wache verbracht worden. Ein Atemalkoholtest habe einen Atemalkoholwert von 1,29 mg/l ergeben. Gegen 04.00 Uhr morgens sei der Ehemann wieder entlassen worden (!). Er selbst habe angegeben, seine Ehefrau schlafend auf dem Sofa angetroffen zu haben; er habe sie geweckt, sie habe u.a. zu ihm gesagt, dass sie die Distraneurintabletten eingenommen habe. Ihr Zustand habe sich deutlich von dem bei sonstiger Alkoholisierung unterschieden. Gegen 05.30 Uhr habe er den Notarzt verständigt, der nur noch den Tod feststellen konnte."
6678,Infectious Diseases: The Role of the Forensic Physician,"Infections have plagued doctors for centuries, in both the diagnosis of the specific diseases and the identification and subsequent management of the causative agents. There is a constant need for information as new organisms emerge, existing ones develop resistance to current drugs or vaccines, and changes in epidemiology and prevalence occur. In the 21st century, obtaining this information has never been more important. Population migration and the relatively low cost of flying means that unfamiliar infectious diseases may be brought into industrialized countries. An example of this was an outbreak of severe acute respiratory syndrome (SARS), which was first recognized in 2003. Despite modern technology and a huge input of money, it took months for the agent to be identified, a diagnostic test to be produced, and a strategy for disease reporting and isolation to be established. There is no doubt that other new and fascinating diseases will continue to emerge."
6679,(13)C Chemical Shifts in Proteins: A Rich Source of Encoded Structural Information,"Despite the formidable progress in Nuclear Magnetic Resonance (NMR) spectroscopy, quality assessment of NMR-derived structures remains as an important problem. Thus, validation of protein structures is essential for the spectroscopists, since it could enable them to detect structural flaws and potentially guide their efforts in further refinement. Moreover, availability of accurate and efficient validation tools would help molecular biologists and computational chemists to evaluate quality of available experimental structures and to select a protein model which is the most suitable for a given scientific problem. The (13)C(α) nuclei are ubiquitous in proteins, moreover, their shieldings are easily obtainable from NMR experiments and represent a rich source of encoded structural information that makes (13)C(α) chemical shifts an attractive candidate for use in computational methods aimed at determination and validation of protein structures. In this chapter, the basis of a novel methodology of computing, at the quantum chemical level of theory, the (13)C(α) shielding for the amino acid residues in proteins is described. We also identify and examine the main factors affecting the (13)C(α)-shielding computation. Finally, we illustrate how the information encoded in the (13)C chemical shifts can be used for a number of applications, viz., from protein structure prediction of both α-helical and β-sheet conformations, to determination of the fraction of the tautomeric forms of the imidazole ring of histidine in proteins as a function of pH or to accurate detection of structural flaws, at a residue-level, in NMR-determined protein models."
6680,Era of Intelligent Systems in Healthcare,"The aim of this chapter is to prepare the reader for the outstanding trip that she/he embarked when starting reading this book. At first, we shall try to look for answers to some of the most important questions regarding the connection between intelligent systems and healthcare. What are intelligent systems? How can they be used in healthcare? Have they got benefits and prospects? Let us highlight some of the decisive factors for a successful deployment of intelligent systems in healthcare, including intelligent clinical support and intelligent patient management."
6681,Behavioral Epidemiology of Infectious Diseases: An Overview,"The focus of the growing discipline of behavioral epidemiology (BE) of infectious diseases is on individual behavior as a key determinant of infection trajectories. This overview departs from the central, but static, role of human behavior in traditional mathematical models of infection to motivate the importance of including behavior into epidemiological models. Our aim is threefold. First, we attempt to motivate the historical and cultural background underpinning the BE revolution, focusing on the issue of rational opposition to vaccines as a natural endpoint of the changed relation between man and disease in modern industrialized countries. Second, we review those contributions, from both mathematical epidemiology and economics, that forerun the current “epidemic” of studies on BE. Last, we offer a more detailed overview of the current epidemic phase of BE studies and, still motivated by the issue of immunization choices, introduce some baseline ideas and models."
6682,Market Trends in Lateral Flow Immunoassays,
6683,Quantitative Performance Monitoring of China’s HIV Response,"China has made tremendous progress in advancing its national HIV program. Key to this progress was setting targets to motivate implementers to work effectively. Indicators were established using an iterative process with national stakeholders while also meeting international pressures. A plethora of demands may have distracted from ownership of the initial national program but, in the end, strengthened a focus on marginalized groups. China gradually relied less on donors and developed a uniquely Chinese HIV control program. The result was remarkable enlargement of prevention and treatment services that led to a reduction in mortality. Setting targets, and measuring performance against those targets, was vital to gauge continued progress and identify gaps in programing and implementation."
6684,Grundlagen der systemischen Therapie,"Die Möglichkeiten einer systemischen Therapie maligner Erkrankungen - außerhalb der zytostatischen Chemotherapie - sind in den letzten Jahren deutlich erweitert worden. Dazu haben insbesondere neue Erkenntnisse zur molekularen Pathogenese von Tumorerkrankungen beigetragen. Von besonderem Interesse sind Strategien, die in Prozesse der tumorassoziierten Neoangiogenese oder der neoplastischen Wachstumsregulation eingreifen."
6685,Bronchite acuta,"La bronchite acuta è una infiammazione dei bronchi primari e secondari ed è una delle patologie relativamente più frequenti nella pratica clinica, anche se la sua definizione rimane, per certi aspetti, non sempre ben definita. La localizzazione del processo infiammatorio spesso coinvolge tratti respiratori limitrofi (faringe, laringe, trachea, bronchi, bronchioli) determinando un interessamento progressivo dell’albero bronchiale."
6686,Nanomolecular Diagnostics,"Clinical application of molecular technologies to elucidate, diagnose and monitor human diseases is referred to as molecular diagnosis. It is a broader term than DNA (deoxyribonucleic acid) diagnostics and refers to the use of technologies that use DNA, RNA (ribonucleic acid), genes or proteins as bases for diagnostic tests. The scope of the subject is much wider and includes in vivo imaging and diagnosis at single molecule level. A more detailed description of molecular diagnostics is presented elsewhere (Jain 2017a)."
6687,Nanotechnological Approaches for Genetic Immunization,"Genetic immunization is one of the important findings that provide multifaceted immunological response against infectious diseases. With the advent of r-DNA technology, it is possible to construct vector with immunologically active genes against specific pathogens. Nevertheless, site-specific delivery of constructed genetic material is an important contributory factor for eliciting specific cellular and humoral immune response. Nanotechnology has demonstrated immense potential for the site-specific delivery of biomolecules. Several polymeric and lipidic nanocarriers have been utilized for the delivery of genetic materials. These systems seem to have better compatibility, low toxicity, economical and capable to delivering biomolecules to intracellular site for the better expression of desired antigens. Further, surface engineering of nanocarriers and targeting approaches have an ability to offer better presentation of antigenic material to immunological cells. This chapter gives an overview of existing and emerging nanotechnological approaches for the delivery of genetic materials."
6688,"The Successes and Failures of Global Health Organizations: The World Health Organization, UNAIDS, Médicins sans Frontières and PEPFAR","Chapter 7 examined the operations of multilateral, bilateral and private donors in financing the fight against HIV/AIDS. This chapter examines the operations of five organizations that focus more directly on addressing HIV/AIDS health issues on the ground: the World Health Organization; UNAIDS; Médicins sans Frontières (Doctors without Borders); the US President’s Emergency Plan for AIDS Relief (PEPFAR); and the US Centers for Disease Control and Prevention. The first two form part of the United Nations (UN) system, the third is a private, non-profit non-governmental organization that relies on volunteers to deliver medical services and products in developing countries that are facing health crises and the fourth and fifth are a US government program and agency, respectively. The UN has won the Nobel Peace Prize a number of times: UN Middle East mediator (1950); UNHCR, the UN refugee agency (1954); UN Secretary-General (1961); UNICEF (1965); ILO, the UN labor agency (1969); UNHCR, the UN refugee agency (1981); UN peacekeeping (1988); and UN Secretary-General and the UN, jointly (2001). There are several bodies inside the UN that also have won the Nobel Peace Prize, such as the International Atomic Energy Agency (2005) and Director Mohamed El-Baradei and the Intergovernmental Panel on Climate Change (2007). In addition, the prime minister of Canada, Lester Bowles Pearson, won Nobel Peace Prize for his work with the UN (1957). Médicins sans Frontières has won the Nobel Peace Prize once (1999)"
6689,The Impact of Disease on Welfare,"Welfare is usually defined in terms either of an animal’s ability to cope (Broom, 1986) or of health and behavioural needs. Indeed the very word “dis-ease” implies a state lacking “ease” or well-being. We feel it is important to consider disease holistically: that is to consider the animal’s ability to resist stress and the environmental challenges it faces. Whereas the outcome of poor welfare is expressed as disease, the relative contributions of various stressors will vary with each individual. The other chapters consider genetics, nutrition and environment in terms of the welfare of poultry. However, given the same housing, air, feed and water, some birds may become diseased and some remain healthy. Intrinsic biological variation results in a range of nutrient reserves and immune status at hatching, plus differences in genetic make up, social status and behaviour that interact with each other and further factors to provide different outcomes for the individual. In the pragmatic world of farming, flock health status may be frequently chosen as the index of welfare, but it is important not to lose sight of the health and well-being of each individual, even in flocks numbering tens of thousands of birds."
6690,Myzetom,
6691,How Does Biodiversity Influence the Ecology of Infectious Disease?,"Over the past years, biodiversity has been reduced on an unprecedented scale, while new infectious diseases are emerging at an increasing rate. Greater overall biodiversity could lead to a greater diversity of hosts and thus of pathogens. Yet disease regulation – due to the buffering role of host diversity – is considered to be one of the services provided by biodiversity. In this chapter, we ask how biodiversity is linked to infectious disease. First, we investigate the influence of the biodiversity of pathogens. We highlight that the number of pathogen species is not well known but that new findings are facilitated by the rapid expansion of molecular techniques. We show that, although there is a trend to find higher pathogen richness toward the equator, identifying a global pattern between the richness of all pathogen species and their latitudinal distribution is challenging. We emphasize that pathogen intraspecific diversity is a crucial factor in disease emergence and allows pathogens to adapt to the selective pressures they face. In addition, the selective pressure acting on hosts due to parasite, and reinforced by parasite diversity within hosts seems to be a major evolutionary and ecological force shaping hosts biodiversity. Second, we investigate how the diversity of hosts influences infectious disease ecology. For multi-host diseases, a change in host species richness or abundance can modify the dynamics of local infectious diseases by either reducing (“dilution effect”) or increasing (“amplification effect”) the risk of transmission to the targeted host species. The underlying hypothesis is that, the competence of reservoirs varies according to the host species. The dilution effect has been demonstrated mainly through theoretical work and there have been only few case studies. Regarding the genetic diversity of host, an important issue is: to what extent does a reduction of this diversity impact the ability of the host population to response to infectious diseases? Third, we rapidly examine the role of biodiversity in the treatment of infectious diseases. To conclude, we consider that the consequences of the loss of species biodiversity on infectious diseases is still largely unknown, notably due to the lack of knowledge on the dynamics of host-pathogen relationships, especially at the population and at the community level.. We highlight that work on multi-host/ ulti-pathogen systems should be fostered and that new approaches, such as metagenomic investigations that does not require a priori assumptions, are promising to describe a community of pathogens and their interactions."
6692,Performing Interventions: The Politics and Theatre of China’s AIDS Crisis in the Early Twenty-First Century,"Theatrical productions attest to a radical shift in Chinese governmental policy and public awareness of the AIDS epidemic at the dawn of the twenty-first century; state-subsidised theatre worked directly with the government to contain the transmission of HIV. Produced by two of the country’s most elite cultural institutions, the Shanghai Dramatic Arts Center and the Beijing People’s Art Theatre respectively, The Dying Kiss (Shengsi Zhiwen) in 2003 and Student Zhao Ping (Zhao Ping Tongxue) in 2005 represented a sea change in the political response to the epidemic while documenting public perceptions towards people living with HIV and AIDS in China. Marking policy change, they reflect experiences that capture a society transitioning from denial to confrontation at the dawn of the twenty-first century."
6693,The Ubiquitin-Proteasome System (UPS) as a Cancer Drug Target: Emerging Mechanisms and Therapeutics,"The Ubiquitin-Proteasome System (UPS) plays an important role in the setting of the cellular response to multiple stress signals. Although the primary function of ubiquitin was initially associated with proteolysis, it is now considered as a key regulator of protein function controlling, among other functions, signalling cascades, transcription, apoptosis or oncogenesis. Failure at any level of the UPS is associated with the development of multiple pathologies including metabolic problems, immune diseases, inflammation and cancer. The successful use of the proteasome inhibitor Bortezomib (Velcade) in the treatment of multiple myeloma (MM) and mantle cell lymphoma (MCL) revealed the potential of the UPS as pharmacological target. Ten years later, new inhibitors tackling not only the proteasome but also different subsets of enzymes which conjugate or de-conjugate ubiquitin or ubiquitin-like molecules, have been developed. Most of them are excellent tools to characterize better the emerging molecular mechanisms regulating distinct critical cellular processes. Some of them have been launched already while many others are still in pre-clinical development. This chapter updates some of the most successful efforts to develop and characterize inhibitors of the UPS which tackle mechanisms involved in cancer. Particular attention has been dedicated to updating the status of the clinical trials of these inhibitors."
6694,Disruptive Behaviors: Should We Foster or Prevent Resiliency?,
6695,Emerging Issues in Environmental and Occupational Lung Diseases,"Humans continue to introduce new or greatly modified agents and techniques into the workplace and environment. These new agents and altered practices lead to evolving patterns of established diseases as well as entirely novel conditions never experienced before in medical history. Although many of these emerging conditions appear in the literature as case reports or case series, these sentinel cases frequently raise the public awareness that drives social movements or, in some situations, represent a warning sign for subsequent outbreaks. The emerging environmental and occupational lung diseases (EOLD) may be grouped arbitrarily into two categories: (1) conditions caused by novel utilization or routes of exposure to agents known to cause EOLD and (2) conditions caused by novel agents not known to cause specific EOLD in the past. Conditions in the first category may include those caused by new exposure scenarios in nonindustrial settings and thus a large population may be at risk. The second category includes new risk factor(s) that were not known to be associated with a specific EOLD, and thus the association between the agent and the new condition could be easily missed. Clinicians should remain astute and vigilant when evaluating the potential role of environmental risk factors in any lung diseases and especially pay attention to the identification of clusters of cases of disease of unknown etiology."
6696,Sexual Dysfunction,"Female sexual dysfunction or dissatisfaction is a common complaint among obstetric-gynecology patients. These complaints may result from medical treatments and procedures, or may secondarily complicate the management and patient compliance of treatment for other medical issues. Therefore, it is important that clinicians treating females obtain basic information regarding human sexual function and dysfunction. This chapter presents an integration of the clinical research as well as the author’s experience regarding sexual function and the management of sexual problems often presented in an obstetricgynecology practice."
6697,Common Colds and Respiratory Viruses: Impact on Allergy and Asthma,
6698,Acute Respiratory Failure After Hematopoietic Stem Cell Transplantation,"Infectious and noninfectious pulmonary complications are common among HSCT recipients and are the leading cause for respiratory failure requiring mechanical ventilation and ICU admission. Unique pulmonary syndromes include peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, and idiopathic pneumonia syndrome. Respiratory failure requiring mechanical ventilation after HSCT continues to be associated with a poor prognosis."
6699,Engineering Control of Airborne Disease Transmission in Health Care Facilities,"Hospital acquired illness or “nosocomial” illness is of increasing concern to public health administrators, hospitals, physicians and patients. Engineering infection control measures are used to reduce the concentration and prevent the spread of these particles throughout a building in order to decrease exposure to and risk of illness from infectious pathogens. The engineer who attempts to deal with microbial indoor air quality finds that pertinent microbiological information exists in abundance but not in easily digestible forms. This paper will provide a brief review of the problem of controlling airborne disease transmission in healthcare facilities with emphasis on medical microbiology and aerobiology in order to offer some conclusions regarding the potential for engineering control of infectious diseases."
6700,Nutrition and the Gastrointestinal System,"The following chapter will focus on the gastrointestinal system and nutrition. Pertinent questions, answers, and rationale will be reviewed. Answers for this chapter can be found beginning on page 136."
6701,Expert-Based Scenarios for the Logistics Service Industry 2025,"The previous chapter 7 represented the first research part of this thesis. It captured the current state of scenario planning practices in the logistics service industry from an internal and an external perspective. It revealed, in line with the literature review, a backward picture of such planning practices compared to industry sector standard and overall. The need for an exemplary industry focused scenario study in the logistics environment was particularly worked out in the chapters 5.3 (literature review) and 7.3 (conclusion of triangulation research). This chapter 8 presents the research results of research phase II and therefore addresses the identified research gap."
6702,Department of Defense Global Emerging Infections System Programs in Biodefense,"One of the great fallacies of the mid-20th century was that infectious diseases were nearing elimination. In the face of those prognostications, more than 25 new infectious diseases were recognized for the first time between 1975 and 2000. These new scourges included HIV, Ebola, Legionnaire’s Disease, Hantavirus pulmonary syndrome, deadly new strains of influenza, and new forms of drug-resistant bacteria and malaria. Rather than nearing extinction as a broad class of human suffering, infectious diseases remain the leading cause of death worldwide. The ability of microbes to adapt to new pressures, including antibiotic usage coupled with changes in society, technology, and the environment make it likely that the microbial threat will remain a threat to humanity, and even suggests the possibility of regional and global epidemics comparable to the worst in history."
6703,"Nanomaterials-Based siRNA Delivery: Routes of Administration, Hurdles and Role of Nanocarriers","Ribonucleic acid interference (RNAi) is a potential alternative therapeutic approach to knock down the overexpression of genes in several disorders especially cancers with underlying genetic dysfunctions. For silencing of specific genes involved in cell cycle, small/short interfering ribonucleic acids (siRNAs) are being used clinically. The siRNA-based RNAi is more efficient, specific and safe antisense technology than other RNAi approaches. The route of siRNA administration for siRNA therapy depends on the targeted site. However, certain hurdles like poor stability of siRNA, saturation, off-target effect, immunogenicity, anatomical barriers and non-targeted delivery restrict the successful siRNA therapy. Thus, advancement of an effective, secure, and long-term delivery system is prerequisite to the medical utilization of siRNA. Polycationic nanocarriers mediated targeted delivery system is an ideal system to remove these hurdles and to increase the blood retention time and rate of intracellular permeability. In this chapter, we will mainly discuss the different biocompatible, biodegradable, non-toxic (organic, inorganic and hybrid) nanocarriers that encapsulate and shield the siRNA from the different harsh environment and provides the increased systemic siRNA delivery."
6704,Detection of Viral RNA Splicing in Diagnostic Virology,"This chapter is the first one to introduce the detection of viral RNA splicing as a new tool for clinical diagnosis of virus infections. These include various infections caused by influenza viruses, human immunodeficiency viruses (HIV), human T-cell leukemia viruses (HTLV), Torque teno viruses (TTV), parvoviruses, adenoviruses, hepatitis B virus, polyomaviruses, herpesviruses, and papillomaviruses. Detection of viral RNA splicing for active viral gene expression in a clinical sample is a nucleic acid-based detection. The interpretation of the detected viral RNA splicing results is straightforward without concern for carry-over DNA contamination, because the spliced RNA is smaller than its corresponding DNA template. Although many methods can be used, a simple method to detect viral RNA splicing is reverse transcription-polymerase chain reaction (RT-PCR). In principle, the detection of spliced RNA transcripts by RT-PCR depends on amplicon selection and primer design. The most common approach is the amplification over the intron regions by a set of primers in flanking exons. A larger product than the predicted size of smaller, spliced RNA is in general an unspliced RNA or contaminating viral genomic DNA. A spliced mRNA always gives a smaller RT-PCR product than its unspliced RNA due to removal of intron sequences by RNA splicing. The contaminating viral DNA can be determined by a minus RT amplification (PCR). Alternatively, specific amplification of a spliced RNA can be obtained by using an exon-exon junction primer because the sequence at exon-exon junction is not present in the unspliced RNA nor in viral genomic DNA."
6705,Microfluidic Diagnostic Systems for the Rapid Detection and Quantification of Pathogens,
6706,Il lavaggio broncoalveolare nelle pneumopatie infiltrative diffuse,"Le pneumopatie infiltrative diffuse costituiscono un gruppo eterogeneo di malattie caratterizzate, istologicamente, dalla presenza di un danno a carico della parete alveolare che puÒ essere infiltrata da cellule infiammatorie/neoplastiche/fluidi/tessuto connettivo. Si parla di forme “diffuse” per sottolineare l’interessamento non solo dell’interstizio, ma anche delle strutture acinari e bronchiolari."
6707,Global Issues and Health Interactions: Reflexions from the South,"This chapter draws attention to a range of global issues that interact, and aims to provoke thought and research on their impact on health. Initially, it deals with communication, economic issues and physician migration. Then it summarizes a wide field of mechanisms by which global forces affect health, indirectly or directly. Within this classification there has to be some overlap—for example the HIV virus causing AIDS would appear to be a direct health effect, but a shift in lifestyles that has seen an increase in the number of individuals’ sexual partners—a shift that perhaps reflects a breakdown of family and religious value systems—may be the more fundamental, but indirect, cause. The view is primarily from the standpoint of developing countries, the “South,” and does not eschew controversy."
6708,Investigating Protein Adsorption via Spectroscopic Ellipsometry,"In this chapter, the basic concepts behind ellipsometry and spectroscopic ellipsometry are discussed along with some instrument details. Ellipsometry is an optical technique that measures changes in the reflectance and phase difference between the parallel (R (P)) and perpendicular (R (S)) components of a polarized light beam upon reflection from a surface. Aside from providing a simple, sensitive, and nondestructive way to analyze thin films, ellipsometry allows dynamic studies of film growth (thickness and optical constants) with a time resolution that is relevant to biomedical research. The present chapter intends to introduce ellipsometry as an emerging but highly promising technique, that is useful to elucidate the interactions of proteins with solid surfaces. In this regard, particular emphasis is placed on experimental details related to the development of biomedically relevant conjugated surfaces. Results from our group related to adsorption of proteins to nanostructured materials, as well as results published by other research groups, are discussed to illustrate the advantages and limitations of the technique."
6709,Biologics,"Currently, ~28–30 mAbs are approved or under consideration for approval as specific therapies in the USA or European Union, although about 350 new mAbs for therapeutic application in humans are in the commercial pipeline. So far, the number of target antigens for the mAbs is surprisingly small with more than one of the approved antibodies specific for TNF, HER2, CD20, EGFR, or VEGF. Other specificities include EpCAM, glycoprotein IIb/IIIa, CD30, CD52, C5, α-4 integrin, IgE, IL-6R, BLys, IL-1β, and RANK-L. Initial infusion reactions to some mAbs may provoke tumor lysis syndrome, cytokine release syndrome, and systemic inflammatory response syndrome. Systemic and cutaneous reactions also occur to mAbs. Rituximab, for example, may cause serum sickness, vasculitis, cutaneous reactions, interstitial pneumonitis, and ARDS as well as post-infusion reactions. Some patients receiving cetuximab experienced severe immediate hypersensitivity reactions. The antibodies involved are IgE specific for α-d-galactose-(1–3)-β-d-galactose and reactive with this disaccharide present on the Fab portion of the chimeric antibody. The nature of, and main adverse reactions to, etanercept, the synthetic IFNs pegylated IFNα-2a and pegylated IFNα-2b, IL-2, denileukin diftitox, anakinra, aflibercept, anti-thymocyte globulin, epoetins, and recombinant human insulin are discussed."
6710,Recent Experiences in Parameter-Free Data Mining,"Recent results supporting the usefulness of the normalized compression distance for the task to classify genome sequences of virus data are reported. Specifically, the problem to cluster the hemagglutinin (HA) sequences of in uenza virus data for the HA gene in dependence on the host and subtype of the virus, and the classification of dengue virus genome data with respect to their four serotypes are studied. A comparison is made with respect to hierarchical and spectral clustering via the kLine algorithm by Fischer and Poland (2004), respectively, and with respect to the standard compressors bzlip, ppmd, and zlib. Our results are very promising and show that one can obtain an (almost) perfect clustering for all the problems studied."
6711,Flu or a Bug?,"Of late, apart from the four calendar seasons, there is yet another season referred to as the “flu season.” During this time of the year, we routinely hear the phrase “the flu is going around.” I was surprised last week when I heard my 6-year-old son mention to me that there is some bug going around in his class and that his best friend was sick. I asked him to define the bug and he said it causes stuffy nose. The word “bug” is used so callously by adults that it has been registered wrongly in the minds of the little ones."
6712,Virology,"Molecular techniques have become indispensable in viral diagnostics. Current applications include: (1) The detection of (unknown) viral infections in clinical samples. (2) Quantitative monitoring of viral load. (3) Genotyping of viral strains. (4) Detection of mutations in the viral genome that are associated with viral resistance. Proper sample acquisition and sample transport, as well as accurate DNA or RNA isolation are a prerequisite for reliable test results in molecular diagnostics of viral infections. In-house as well as commercial assays can be used for the amplification of viral DNA or RNA for the detection of viral infections and viral load monitoring. Many virus species consist of several subspecies, genotypes or variants. This molecular variation has to be taken into account when applying molecular diagnostics. More complicated diagnostics for genotyping or the detection of mutations related to therapy failure often rely on sequencing, although for some viral targets commercial assays are available. In this chapter, applications are described in which molecular methods have become the most important form of viral diagnostics. Molecular test results have a direct impact on patient management and as such, results have to be reliable, standardized and reproducible. Therefore, quality control and standardization are important issues!"
6713,Great Plagues of the Past and Remaining Questions,"Due to the difficulty of obtaining tissue samples from victims of the ancient plagues, it is not always possible to utilise palaeomicrobiology techniques to determine the etiology of ancient infection. Therefore, it is often necessary to utilise other means to arrive at a likely diagnosis. The most helpful of these is the literary description of the disease. While this is often the best evidence available, working with such documents can prove difficult. Three great plagues of the ancient world, the Plague of Athens, the Antonine Plague, and the Justiniac Plague are described in either Latin or ancient Greek. The difficulties encountered when translating any ancient foreign language are compounded by the fact that so many words in these languages have a variety of meanings. This chapter reviews the three great plagues of antiquity from a clinical perspective."
6714,"Multiplex PCR in Molecular Differential Diagnosis of Microbial Infections: Methods, Utility, and Platforms","We are entering the age of personalized medicine where treatments are designed to target specific causes, rather than a group of patients with similar symptoms. However, personalized medicine is impossible without a personalized diagnosis that considers all the possible causes of a person’s disease. Traditional molecular diagnostic methods, such as PCR and qPCR, cannot provide the necessary information to practice personalized medicine, because they cannot be multiplexed, allowing the detection of only one or a few (no more than 3) targets at a time in one sample. Practicing personalized medicine, therefore, requires multiplex PCR (mPCR), which can evaluate many molecular targets at once, in one reaction, from one sample."
6715,Physiologie und Pathophysiologie der Zelle,"Die Kenntnis des Aufbaues einer Zelle ist wichtig, um biochemischen Veränderungen funktionelle Störungen auf zellulärem Niveau zuordnen zu können (Bruce et al., 2004). Von Bedeutung sind die Membranen, deren Funktionen im Wesentlichen durch Membranproteine vermittelt werden, die intrazellulären Organellen als Räume spezifischer Reaktionen und das Zytoskelett, welches Stabilität, Motilität und den intrazellulären Transport von zellulären Strukturen und Vesikeln ermöglicht."
6716,Cardiovascular Anatomy and Pharmacology,"This chapter reviews the cardiovascular anatomy, the effects of medications on the cardiovascular system, and current guidelines. Patients in the perioperative period often receive agents that affect hemodynamic variables such as heart rhythm and rate, blood pressure, or cardiac output."
6717,"Efficacy, Safety and Targets in Topical and Transdermal Active and Excipient Delivery","A key requirement for topical and transdermal active delivery is the effective delivery of an active to a desired target site, to achieve both safe and efficacious outcomes. This chapter seeks to explore the importance of the pharmacological, toxicological and therapeutic properties of actives and excipients, as well as the site of action as complementary components in percutaneous absorption. This is crucial for optimized topical and transdermal product design."
6718,Noninvasive Mechanical Ventilation: Models to Assess Air and Particle Dispersion,"Respiratory failure is a major complication of viral infections such as severe acute respiratory syndrome (SARS) [1], avian influenza H5N1 infection [2], and the 2009 pandemic influenza (H1N1) infection [3]. The course may progress rapidly to acute respiratory distress syndrome (ARDS) and multi-organ failure, requiring intensive care. Noninvasive ventilation (NIV) may play a supportive role in patients with severe viral pneumonia and early ARDS/acute lung injury. It can act as a bridge to invasive mechanical ventilation, although it is contraindicated in critically ill patients with hemodynamic instability and multi-organ dysfunction syndrome [4]. Transmission of some of these viral infections can convert from droplets to airborne during respiratory therapy."
6719,Bioinformatics and Translation Elongation,"Codon usage depends on mutation bias, tRNA-mediated selection, and the need for high efficiency and accuracy in translation. One codon in a synonymous codon family is often strongly over-used, especially in highly expressed genes, which often leads to a high dN/dS ratio because dS is very small. Many different codon usage indices have been proposed to measure codon usage and codon adaptation. Sense codon could be misread by release factors and stop codons misread by tRNAs, which also contribute to codon usage in rare cases. This chapter outlines the conceptual framework on codon evolution, illustrates codon-specific and gene-specific codon usage indices, and presents their applications. A new index for codon adaptation that accounts for background mutation bias (Index of Translation Elongation) is presented and contrasted with codon adaptation index (CAI) which does not consider background mutation bias. They are used to re-analyze data from a recent paper claiming that translation elongation efficiency matters little in protein production. The reanalysis disproves the claim."
6720,"Viren mit einzelsträngigem, segmentierten RNA-Genom in Negativstrangorientierung","Bis heute sind drei Virusfamilien bekannt, deren Vertreter ein RNA-Genom mit negativer Orientierung besitzen, das in den infektiösen Viruspartikeln nicht als ein kontinuierliches Molekül, sondern in mehreren Segmenten vorliegt. Es handelt sich um die Arenaviridae, die Bunyaviridae und die Orthomyxoviridae. Ähnlich wie die Mononegavirales (▸ Kapitel 15) benötigen auch sie für die Synthese der mRNA und für die Replikation ein spezielles Enzym, das zusammen mit weiteren Virus-komponenten bei der Infektion in die Zelle gelangt: die RNA-abhängige RNA-Polymerase. Ein in Segmenten vorliegendes Genom ermöglicht den Viren die Bildung von Reassortanten. Hier werden die RNA-Moleküle bei Doppelinfektionen von Zellen mit unterschiedlichen Virus-typen während der Replikation und der Morphogenese gemischt. Die Nachkommenviren können so Neukombinationen der RNA-Segmente und damit neue Eigenschaften erhalten. Besonders häufig und gut untersucht ist dieser Mechanismus, der als antigenic shift bezeichnet wird, bei den Influenza-A-Viren, den Erregern der Virus-influenza oder echten Grippe (▸ Abschnitt 16.3)."
6721,Detection of Bovine Coronavirus by Conventional Reverse Transcription Polymerase Chain Reaction,"Bovine coronavirus (BCoV) is an economically significant cause of enteric and respiratory diseases in cattle throughout the world. BCoV is a known cause of neonatal calf diarrhea, winter dysentery in adult cattle, and respiratory disorders in cattle of all ages. In this chapter, we describe a simple and efficient protocol for total nucleic acids extraction to be used in conventional RT-PCR assay. This is a technique used routinely in our virology laboratory to detect BCoV from stool and nasopharyngeal samples of cattle."
6722,Drug Development Research,"Infectious diseases are significant causes of human mortality, morbidity, and economic loss. Although effective antimicrobial agents are available for treating bacterial infections, as are limited agents for viral, fungal, and parasitic infections, many diseases are still very difficult to treat effectively and may present serious health concerns. The emergence of drug resistance among common pathogens continues to render ineffective many previously frontline therapies, and the use of many drugs is often limited by toxicity concerns. Emergence of diseases caused by new or drug-resistant pathogens demands more effective drugs. However, current advances in chemistry, bioinformatics, and structural biology should make it possible to discover or design novel anti-infective agents that target specific functions required for pathogen growth and pathogenesis (http://www3.niaid.nih.gov/about/organization/dmid/overview.htm)."
6723,Mitochondria and Antiviral Immunity,"Mitochondria are unique dynamic organelles that evolved from free-living bacteria into endosymbionts of mammalian hosts (Sagan 1967; Hatefi 1985). They have a distinct ~16.6 kb closed circular DNA genome coding for 13 polypeptides (Taanman 1999). In addition, a majority of the ~1500 mitochondrial proteins are encoded in the nucleus and transported to the mitochondria (Bonawitz et al. 2006). Mitochondria have two membranes: an outer smooth membrane and a highly folded inner membrane called cristae, which encompasses the matrix that houses the enzymes of the tricarboxylic acid (TCA) cycle and lipid metabolism. The inner mitochondrial membrane houses the protein complexes comprising the electron transport chain (ETC) (Hatefi 1985)."
6724,Advocating Global Health Security,"For the last two decades, a recurring strategy employed by health professionals, scientists, and diplomats has been to play the ‘health security card’ to achieve particular trade, diplomatic, strategic, and development goals. The presumption has been that the securitisation of health will harness global political leadership and resources. This marriage of health issues to security logic has been met with a mix of applause, caution, and critique. In particular, there have been growing claims that the successful global health initiatives such as, the Global Fund for AIDS, TB, and Malaria (Global Fund) and the Global Alliance for Vaccine Immunization (GAVI) were achieved without asserting their necessity on security considerations. Thus, what difference does the association of security to health make for the success and longevity of global health initiatives? In this chapter, I answer this question through comparing a case where the security logic was deliberately deployed to frame the ‘health emergency’ (Framework Convention on Tobacco Control), against a case where human rights logic was used to advocate for its creation (the GAVI). I critically explore the conditions under which linking securitisation with an international health initiative captures and maintains political leadership and resources."
6725,"DNA, RNA und IHRE Amplifikation","DNA heißt die magische Helix des Lebens — der materielle Träger der Erbsubstanz, die Desoxyribonucleinsäure (DNA, deoxyribonucleic acid) (siehe Box 6.1)."
6726,Alcohol and HIV: Experimental and Clinical Evidence of Combined Impact on the Lung,"Despite antiretroviral therapy, lung disease is a leading cause of death in individuals infected with human immunodeficiency virus type 1 (HIV). Individuals infected with HIV are susceptible to serious bacterial and viral infections, such as pneumococcus and influenza, which are particularly problematic for lung health, resulting in lung injury. Additionally, HIV-infected individuals are susceptible to a number of pulmonary diseases for unknown reasons. Alcohol, the most commonly abused drug in the world, continues to exact an enormous toll on morbidity and mortality in individuals living with HIV. Chronic alcohol abuse has been shown to affect lung immunity, resulting in significant lung injury. There is a paucity of literature on the additive effects of HIV and alcohol, two diseases of immune senescence, in the lung. This chapter begins by discussing the latest literature evaluating the epidemiology of HIV, alcohol use, and lung health focusing on two prevalent infections, tuberculosis and pneumococcal pneumonia. In parallel, we discuss the interactions of alcohol and HIV on the risk for acute lung injury and subsequent morbidity and mortality. We then discuss the pathophysiology of how these two diseases of immune dysfunction affect the lung, with a focus on the oxidative stress, alveolar macrophage host immune capacity, and immunomodulatory role of zinc in the airway. Finally, we review the latest literature on how HIV and alcohol affect other pulmonary disorders including chronic obstructive pulmonary disease, pulmonary hypertension, and lung cancer."
6727,Schlafkrankheitserreger,
6728,Gastroenteric Viruses,"In recent years, viruses have been recognized increasingly as an important cause of foodborne infections. More than 160 enteric viruses are excreted in the feces of infected individuals, and some may also be present in the vomitus. Food and water are directly contaminated with fecal material, through the use of sewage sludge in agriculture, sewage pollution of shellfish culture beds, or may be contaminated by infected food-handlers."
6729,The Discovery Process of SFTS in China,"Heightened surveillance of acute febrile illness in China since 2004 led to the identification of a severe fever with thrombocytopenia syndrome (SFTS) with unknown etiology. Sporadic patients hospitalized with SFTS in 2009 and 2010 were identified and serum samples were collected. Sequence from a novel species of phlebovirus was identified by sequence independent single primer amplification (SISPA) from the serum of a patient with SFTS. The virus was isolated in Vero cell culture and its complete genome sequence was determined, only distantly related to other known phleboviruses. Electron microscopic analysis revealed a virion morphologically characteristic of phleboviruses. The virus was named as SFTS virus. The viral RNA and/or specific antibodies were detected from the blood of patients with SFTS. Serological assays demonstrated a virus-specific immune response in pairs of sera collected from patients at acute and convalescent phases. The pathogenic mechanisms of thrombocytopenia in human SFTS disease was resembled in a mouse model. The results had been collected to demonstrate that SFTS virus was etiologically associated with an acute and novel infectious disease, SFTS in humans."
6730,Social Network Analysis for Contact Tracing,"Contact tracing is an important control measure in the fight against infectious disease. Healthcare workers deduce potential disease pathways and propose corresponding containment strategies from collecting and reviewing patients’ contact history. Social Network Analysis (SNA) provides healthcare workers with a network approach for integrating and analyzing all collected contact records via a simple network graph, called a contact network. Through SNA, they are able to identify prominent individuals in disease pathways as well as study the dynamics of disease transmission. In this chapter, we review the role of SNA in supplementing contact tracing and present a case study of the Taiwan SARS outbreak in 2003 to demonstrate the usefulness of geographical contacts to disease investigation."
6731,Acute and chronic liver insufficiency,"The term “liver insufficiency” denotes a break down in the functions of the liver. The syndrome of functional liver failure covers a wide spectrum of clinical, biochemical and neurophysiological changes. In principle, liver insufficiency can occur without previous liver damage as well as with already existing liver disease. It is characterized by a deterioration in the synthesizing, regulatory and detoxifying function of the liver. This final stage of liver disease terminates in hepatic coma."
6732,Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis,"Erythema multiforme in its most extreme form has traditionally been divided between toxic epidermal necrolysis and Stevens-Johnson Syndrome. These two life-threatening skin diseases are now considered part of the same spectrum of disease. They can be differentiated by clinical and histological criteria. We can also now predict which patients are apt to have the most guarded prognosis. Treatment by multiple agents is imperfect, but offers a better chance of a good outcome than ever before."
6733,Computational Vaccinology,"In this chapter we shall review recent developments in computational vaccinology, highlighting work in the area of epitope and antigen identification, and the discovery of delivery vectors and adjuvants. These diverse activities all have the potential to reduce significantly the laboratory resource needed for efficient vaccine discovery. We discuss how computational analysis of pathogenic genomes by epitope mapping and reverse vaccinology can provide viable vaccine targets."
6734,Primordial and Primary Levels of Biothreat and Bioterrorism Prevention,"There is still an abundance of preventive and solving measures against biological attacks that makes confusion and dezorientation among experts and health policy-makers. Our pyramidal model of adversaries, and spherical system of prevention help us to solve this problem. They make clearly to us, which measures should be applied at any of four levels of prevention without robust spending. Primordial level of prevention should be focused to stop entering perpetrator/source of infection/reservoir of pathogen and biological agent/pathogen on defended territory. This is the first line of biodefense, deeply and multiply linked with the strategies of intelligence and deterrence. The primary prevention of biological attack is focused on monitoring and surveillance of potential internal sources of biological agents and bioterrorists. We elaborate three types of surveillance: clinical (syndromic), laboratory and environmental. Both levels of prevention were detailed analyzed, according to the next issues: Perpetrator/source of infection/reservoir of pathogen (Sophistication, Motivation, Intention, Intelligence, Secrecy, Number of perpetrators, Number of sources of infection/reservoirs, Accessibility to sources of agent/pathogen, Accessibility to targets/population at risk), Biological agent/pathogen (A category, B category, C category, Emerging pathogens, Amount of the available agent/pathogen), Means/media of delivery/factors of transmission (Air, Water, Food, Fomites, Vectors, Biological ammunition, Delivery systems, Dispersion systems mechanism of release), Target/susceptible population at risk (Intelligence, Secrecy, Personal control, Control of means/media of delivery/factors of transmission, Physical protection, Protection by chemoprophylaxis, Protection by immunoprophilaxis, Number of people in a target/population at risk, Importance of target/population at risk, Location of target/population, Distribution of people in a target/population at risk), and for each issue a whole spectrum of cheap, simple and effective preventive measures were proposed."
6735,Immunosenescence and Respiratory Infections Among Nursing Home Residents,"Residents of nursing homes are at high risk of infectious complications due to respiratory infection. The nursing home setting places residents at high risk given the frequent contact among residents and by staff along with the possibility for continuous introduction of respiratory viruses from the community. Nursing home residents are among the most frail members of society. They have multiple comorbidities that can increase their risk of infection. Immunosenescence plays an important role in not only rendering these seniors susceptible in infection, particularly viral respiratory infection, but also interferes with protection. That is, the ability to mount a robust immune response to influenza and pneumococcal vaccine increase the risk. There have been a number of T cell deficits described in this population. CD4+ T cells, in particular T-regs and CMV-reactive CD4+ T cells, have been shown to be predictive of respiratory viral infection in this population. Although evidence exists that T cell subsets may correlate better with response to vaccine and protection, antibody responses to influenza vaccine remains an important correlate in this population. Large-scale epidemiologic studies are needed to establish better correlation between biomarkers for protection and respiratory and other pathogens that circulate in nursing homes."
6736,Public Education About Science in Singapore: The Role of Science Journalism via Newspapers,"This chapter explores the role of science journalism in contributing towards public education about science in Singapore, an aspect which is under-explored in the literature. Though the key platforms for promoting public understanding of science are spearheaded mainly by institutions that promote informal science learning as well as by learned societies, the contribution from newspapers is also important. Content analysis of one continuous week of a national newspaper was undertaken, and the results show that coverage of science and technology was modest and predominantly news driven. For news stories set locally, there was a pronounced emphasis on the use of institutional actors in the text as well as quotations. Articles on health/medicine and earth science elicited the most coverage in the press. Some suggestions for using newspaper science to introduce inquiry in the science classroom are discussed."
6737,Prevention and Control of Influenza Viruses,"The 2003–2004 outbreaks of highly pathogenic avian influenza (HPAI) have proven to be disastrous to the regional poultry industry in Asia, and have raised serious worldwide public health apprehension regarding the steps that should be taken to urgently control HPAI. Control measures must be taken based on the principles of biosecurity and disease management and at the same time making public aware of the precautionary measures at the verge of outbreak. Creation of protection and surveillance zones, various vaccination strategies viz. routine, preventive, emergency, mass and targeted vaccination programmes using live, inactivated and recombinant vaccines are the common strategies adopted in different parts of the globe. The new generation vaccines include recombinant vaccines and recombinant fusion vaccine. The pro-poor disease control programmes, giving compensation and subsidies to the farmers along with effective and efficient Veterinary Services forms integral part of control of HPAI. Following biosecurity principles and vaccination forms integral part of control programme against swine and equine influenza as well. Use of neuraminidase (NA) inhibitors (Zanamivir and Oseltamivir) for the treatment of human influenza has been widely accepted worldwide. The threat of increasing resistance of the flu viruses to these antivirals has evoked interest in the development of novel antiviral drugs for influenza virus such as inhibitors of cellular factors and host signalling cascades, cellular miRNAs, siRNA and innate immune peptides (defensins and cathelicidins). Commercial licensed inactivated vaccines for humans against influenza A and B viruses are available consisting of three influenza viruses: influenza type A subtype H3N2, influenza type A subtype H1N1 (seasonal) virus strain and influenza type B virus strain. As per WHO, use of tetravaccine consisting of antigens of influenza virus serotypes H3N2, H1N1, B and H5 is the most promising method to control influenza pandemic. All healthy children in many countries are required to be vaccinated between 6 and 59 months of age. The seasonal vaccines currently used in humans induce strain-specific humoral immunity as the antibodies. Universal influenza virus vaccines containing the relatively conserved ectodomain of M2 (M2e), M1, HA fusion peptide and stalk domains, NA, NP alone or in combination have been developed which have been shown to induce cross-protection. The T cell-based vaccines are another recent experimental approach that has been shown to elicit broad-spectrum heterosubtypic immunity in the host. As far as HPAI is concerned, various pandemic preparedness strategies have been documented."
6738,The Effect of Turbulence on the Spreading of Infectious Airborne Droplets in Hospitals,"The dispersion of droplets plays an important role in the transmission of disease in a hospital environment. The challenge is that as they move, their properties change due to evaporation, the Wells (Am. J. Hyg. 20:611–618, 1934) droplet-nuclei hypothesis. In this paper we examine the effect of evaporation on their movement within a homogeneous turbulent environment. The effect of turbulence is to significantly increase the transmission distance and spread. These numerical results demonstrate that by reducing the level of turbulence, the potential for spreading diseases is reduced. This is in accordance with available experimental/in situ measurements."
6739,Exacerbation of Bronchiectasis,Please check the hierarchy of the sections and correct if necessary.
6740,Older Human B Cells and Antibodies,"B cells have a number of different roles in the immune response. Their excellent antigen presentation potential can contribute to the activation of other cells of the immune system, and evidence is emerging that specialized subsets of these cells, that may be increased with age, can influence the cell-mediated immune system in antitumor responses. They can also regulate immune responses, to avoid autoreactivity and excessive inflammation. Deficiencies in regulatory B cells may be beneficial in cancer but will only exacerbate the inflammatory environment that is a hallmark of aging. The B cell role as antibody producers is particularly important, since antibodies perform numerous different functions in different environments. Although studying tissue responses in humans is not as easy as in mice, we do know that certain classes of antibodies are more suited to protecting the mucosal tissues (IgA) or responding to T-independent bacterial polysaccharide antigens (IgG(2)) so we can make some inference with respect to tissue-specific immunity from a study of peripheral blood. We can also make inferences about changes in B cell development with age by looking at the repertoire of different B cell populations to see how age affects the selection events that would normally occur to avoid autoreactivity, or increase specificity, to antigen."
6741,Modeling Approaches Toward Understanding Infectious Disease Transmission,"Long-standing neglected diseases continue to challenge our global health infrastructure, and emerging pathogens pose new threats worldwide. To inform prevention and response efforts, mathematical models of infectious disease dynamics are being increasingly applied. Here we explain how models can be developed to enhance our understanding and predictive power over population-level disease trends, by capturing both fundamental aspects of transmission and also the effects of medical and behavioral interventions. We review advances in transdisciplinary approaches of disease modeling and illustrate these advances with applications including community-based initiatives undertaken during the Ebola epidemic in West Africa and age-targeting of influenza vaccination in the USA. We further discuss how modern statistical inference facilitates the incorporation of data from behavioral sciences and epidemiology into models, highlighting how data-driven models can constitute powerful tools to inform and improve public health strategies."
6742,Oligonucleotide Therapeutics,"The idea of sequence-specific gene silencing by synthetic oligonucleotides targeting mRNA is at least 40 years old, but it was only in the mid-1980s when technical advances made the chemical synthesis of oligonucleotides possible that practical steps could be taken toward its implementation. The result was a deluge of experimental data in a variety of systems [1], most of which employed the phosphorothioate (PS) backbone modification, and much of which was ultimately, and unfortunately, uninterpretable."
6743,Kutane Lymphome,"Kutane Lymphome (cutaneous lymphomas: CL) umfassen die Gruppe der kutanen T-Zell-Lymphome (cutaneous T-cell lymphomas: CTCL), kutanen B-Zell-Lymphome (cutaneous B-cell lymphomas: CBCL) und die sog. hämatodermischen Neoplasien (HN). CL gehören zur Gruppe der Non-Hodgkin-Lymphome (NHL) und stellen in der Subgruppe der extranodalen NHL die zweithäufigste Gruppe hinter den gastrointestinalen Lymphomen dar (Jaffe et al. 2009). Man unterscheidet zwischen primären und sekundären CL. Primäre CL haben ihren Ursprung in der Haut und bleiben in der Regel darauf auch längere Zeit beschränkt, während sekundäre CL kutane Manifestationen von primär nodalen oder extranodalen Lymphomen darstellen (Willemze 2005). Die primären CL unterscheiden sich hinsichtlich klinischem Verlauf, Therapieoptionen und Prognose erheblich von nodalen und extrakutanen Lymphomen. So zeigen z. B. die primär kutanen CD30+-T-Zell-Lymphome einen gutartigen Verlauf, wogegen die nodalen Varianten als aggressiv eingestuft werden. Da die CL zumeist weniger aggressiv sind, werden sie auch weniger aggressiv behandelt."
6744,The Contribution of Tertiary Education: Theory vs. Reality,"Participation in education is not an end in itself. What matters for people and for our economies are the skills acquired through education. It is the competence and character qualities that are developed through schooling, rather than the qualifications and credentials gained, that make people successful and resilient in their professional and private lives. They are also key in determining individual well-being and the prosperity of societies."
6745,Case Study – Germany,"Public health structures in Germany reflect the federal system: health care in general lies within the responsibility of the 16 constituent states and the federal government only acts if a state asks for assistance. There were no bioterror-related intentional releases of biological agents in Germany in recent years. The potentially devastating effects of such an incident require sound public health preparedness planning. The Basic Constitutional Law (Grundgesetz) does not allow the deployment of armed forces within Germany with some rare exceptions. However, there is a well-established civil-military cooperation. The Federal Armed Forces (Bundeswehr) are deployed in humanitarian and multinational UN or NATO crisis containment missions abroad, requiring adequate protection from pathogens and diseases endemic or enzootic to those regions. Both, the military and the civil public health system are complex structures that contain administrative, care giving, medical investigation, and research capabilities in order to cope with natural, accidental or intentional biological incidents."
6746,Terror-Related Trauma,"In our current era, terrorist attacks have become a part of our daily life experience almost worldwide. New terrorist groups are emerging and the number of terrorist attacks is constantly rising."
6747,Strategien der Distanzierung. Die späten Raumerkundungen,"Der Anspruch ist dick unterstrichen: “Noch einmal anfangen: ganz unten, mit Fakten.”(1) Rolf Dieter Brinkmanns nach 1970 geschriebene Texte sind das Dokument einer Umorientierung, die freilich nur den immer schon vorherrschenden empirischen Aspekt des Schreibens ins Extrem treibt. Mit den Collage-Bänden Rom, Blicke (1972/73 entstanden und 1979 veröffentlicht), Erkundungen zur Präzisierung des Gefühls für einen Aufstand (1971 und im Mai 1973 entstanden, 1987 veröffentlicht) und schließlich Schnitte (März 1973 bis Juni 73 entstanden und erst 1988, 13 Jahre nach dem Tod des Autors, zur Veröffentlichung freigegeben) fand Brinkmann zu einer Form, die jegliche Rücksichtnahme darauf, wie ein ’literarischer’ Text auszusehen hat, hinter ein striktes Ziel zurückstellte: Materialien zu einer “Grundlagenforschung der Gegenwart”(2) beizutragen."
6748,7 Longaandoeningen,"Om ziekteprocessen die zich afspelen in de longen, luchtwegen en longvliezen (pleurae) te kunnen begrijpen en de gevolgen ervan voor het functioneren van het lichaam te kunnen inschatten, is kennis nodig van de normale anatomie van de thoraxinhoud en de fysiologie van het functioneren van de long. Deze is te vinden in het boek Algemene ziekteleer uit de reeks Basiswerk, waarnaar wordt verwezen. Alleen waar nodig zal er in het kort op worden ingegaan."
6749,Grid Services Complemented by Domain Ontology Supporting Biomedical Community,"This paper describes the increasing role of ontologies in the context of Grid computing for obtaining, comparing and analyzing distributed heterogeneous scientific data. In the communities of people committed to a common goal, the management of resources and services becomes very important. We chose the application domain of human disease research and control. A characteristic of the domain is that trusted databases exist but their schemas are often poorly or not documented. The network of biomedical databases forms a loose federation of autonomous, distributed, heterogeneous data repositories ripe for information integration. Grid services will provide a dynamic way to use resources in such a large distributed scientific environment while the use of ontology enables the system to carryout reasoning at 3 levels: a) available information in all Bio-Databases (Grid nodes) worldwide, b) reasoning about the retrievable information from each node, c) reasoning about the retrieved information and presenting it in a meaningful format for users. We adopted the ontology design methodology of DOGMA and developed Generic Human Disease Ontology (GenDO) that contains common general information regarding human diseases. The information is represented in 4 “dimensions”: (a) disease types, (b) causes (c) symptoms and (d) treatments. We illustrate how this GenDO helps to produce Specific Human Disease Ontologies (SpeDO) on request. We show how the combination of two different but complementary techniques, namely Grid computing and ontology, results in a dynamic and intelligent information system. The two approaches together, being complementary, enable the system as a whole."
6750,Biological Agents and Terror Medicine,"In the last decade, terror has become an increasingly global problem. More people have become radicalized, the know-how to use weapons of mass destruction (WMD) is easily accessible by Internet and electronic media, and precursors and basic ingredients are easily purchased. Terrorists are innovative and we now face a new era of nonconventional terrorism: chemical, biological, radiological, nuclear (CBRN), as well as cyber terrorism. The deliberate use of (WMD–CBRN) by hostile states or terrorists and of naturally emerging infectious diseases that have a potential to cause illness on a massive scale could pose a national security threat.1 Resulting panic and economic damage could paralyze a country."
6751,Survey on the Likely Behavioural Changes of the General Public in Four European Countries During the 2009/2010 Pandemic,"In order to assess the likely impact of public health interventions, it is important to predict the acceptance of control measures, as well as the behavioural changes that may occur among the general public in response to epidemics, in particular lethal ones. The emergence of 2009 pandemic allowed us to assess the general public’s behaviour during the pandemic, via two surveys: one at the beginning and one after the first wave of the 2009 pandemic, in four European countries.Results showed some differences between participating countries in previous behaviours relating to seasonal flu and in beliefs and knowledge about 2009 pandemic influenza. No substantial differences were detected among the four countries in the first survey with respect to the intended behaviours in anticipation of the spread of the pandemic virus. However, results from the second survey showed differences within and among the four participating countries. The two surveys were useful in showing differences between behavioural intentions and actual actions related to the 2009 pandemic influenza. To our knowledge this is the first study investigating the actual behaviour of the population in four EU countries and provides crucial descriptions of pandemic impact on social-network dynamics parameters which can be included in mathematical models."
6752,"The Role of Astrocytes, Microglia, and Endothelial Cells in Coronavirus-Induced Demyelination: Induction of cytokines and other signaling mechanisms","Infection of neurotropic strains of coronaviruses in susceptible animals results in acute encephalomyelitis followed by a chronic demyelinating disease, similar to multiple sclerosis (MS). Although the mechanism of chronic coronavirus-induced demyelination is not entirely clear, studies show that it is mostly immune-mediated. Astrocytes, microglia and endothelial cells play an important role in normal functions as well as in immunologic and pathologic processes in the central nervous system (CNS). The interaction between coronaviruses and these cells induces various inflammatory mediators including cytokines, chemokines, MHC and NO, which acting in concert are involved in the pathogenesis of demyelination."
6753,Mucosal Delivery of RNAi Therapeutics,"The effectiveness of RNA interference-based drugs is dependent on accumulation at the target site in therapeutically relevant amounts. Local administration to the mucosal surfaces lining the respiratory, gastrointestinal and genitourinary tracts allows access into diseased areas without the necessity to overcome serum nuclease degradation, rapid renal and hepatic clearance and non-specific tissue accumulation associated with systemic delivery. This work describes RNAi therapeutics focused on pulmonary, oral, rectal and intravaginal routes of administration. Mucosal barrier components including site variations and delivery considerations are addressed in order to design an effective mucosal delivery strategy."
6754,Air Purification Technology by Means of Cluster Ions Generated by Plasma Discharge at Atmospheric Pressure,"The increased density of our living environment coupled with pollution of the atmosphere has led to a growing need for the removal of harmful molecules in the air (1). As a result research into applying a plasma discharge into the atmosphere and creating ozone and radicals of strong chemical reactivity to purify the air environment has gathered momentum. The removal of airborne particles, such as bacteria, allow for an improvement in indoor air quality so that our environment is healthy and pleasant. Within the medical field, illnesses caused by viruses such as influenza and SARS (2), hospital infections caused by airborne bacteria, fungi and allergic bronchial tube asthma (3), Japanese cedar hay fever caused by inhaling cedar pollen (4) are becoming large social concerns. In this research article, we discuss how we have applied our novel plasma discharge technology to produce positive and negative “cluster” ions. This iongenerating device operates at a normal atmospheric pressure. Subsequent investigations have permitted characterization of the resultant cluster ions. We have performed a series of experiments to prove the air purification effects of cluster ions, paying close attention to airborne harmful microbes and cedar pollen allergens."
6755,Postinfectious Hemolytic Uremic Syndrome,"Post-infectious hemolytic uremic syndrome (HUS) is caused by specific pathogens in patients with no identifiable HUS-associated genetic mutation or autoantibody. The majority of episodes is due to infections by Shiga toxin (Stx) producing Escherichia coli (STEC). This chapter reviews the epidemiology and pathogenesis of STEC-HUS, including bacterial-derived factors and host responses. STEC disease is characterized by hematological (microangiopathic hemolytic anemia), renal (acute kidney injury) and extrarenal organ involvement. Clinicians should always strive for an etiological diagnosis through the microbiological or molecular identification of Stx-producing bacteria and Stx or, if negative, serological assays. Treatment of STEC-HUS is supportive; more investigations are needed to evaluate the efficacy of putative preventive and therapeutic measures, such as non-phage-inducing antibiotics, volume expansion and anti-complement agents. The outcome of STEC-HUS is generally favorable, but chronic kidney disease, permanent extrarenal, mainly cerebral complication and death (in less than 5 %) occur and long-term follow-up is recommended. The remainder of this chapter highlights rarer forms of (post-infectious) HUS due to S. dysenteriae, S. pneumoniae, influenza A and HIV and discusses potential interactions between these pathogens and the complement system."
6756,"Diseases from Animals, Poultry, and Fish",
6757,Early Interventions in Allergic Diseases,"Atopy has been defined as the genetic predisposition to develop IgE antibody responses to a variety of common environmental allergens. Clinically, atopy is expressed by asthma, allergic rhinoconjunctivitis and atopic dermatitis. It has been recognized that the “atopic march” evolves from food allergy and atopic dermatitis in the first 2 years of life, followed by asthma and allergic rhinitis. Over the past 30 years, the prevalence of allergies and asthma has increased significantly in developed countries, and asthma is one of the most common chronic diseases in children. Evidence indicates that environmental factors acting early in life, including respiratory viral infections, exposure to pets and microbial products, day-care attendance, breast feeding, and exposure to allergens, tobacco smoke and other pollutants, are key events for establishment of sensitization and development of chronic, persistent symptoms of allergic diseases [1]. It is thought that gene—environment interactions play a crucial role in these processes. Therefore, attempts to successfully prevent development of allergic diseases should be a priority. At present, there are no genetic markers for atopy or asthma which could be used routinely in clinical practice and family history of atopy has been used to identify children genetically at-risk of developing allergic diseases. These children from high-risk families have been the focus of most of the intervention studies."
6758,Comparative Considerations and Conclusions,"The noteworthy success of a small embargoed island in scientific development, and in particular in a typically US-dominated and capital-intensive sector like biotechnology, has attracted considerable interest and discussion among the analysts and specialists, since it shows features that are unique in the panorama of developing countries. Cuba’s achievements in science and technology seem an exception with respect to what usually happens in other underdeveloped countries, excluded probably the biggest and richest ones. Even more exceptional is the development of biotechnology in Cuba. Some concepts are summarized, inspired form the most competent specialists in the field."
6759,Infectieziekten,"In dit hoofdstuk komen kliniek, diagnostiek en behandeling van de belangrijkste infectieziekten bij kinderen aan de orde."
6760,Sarkosporidiose,
6761,Gene Therapy for Lung Diseases,"Gene therapy is under development for a variety of lung disease, both those caused by single gene defects, such as cystic fibrosis and α(1)-antitrypsin deficiency, and multifactorial diseases such as cancer, asthma, lung fibrosis, and ARDS. Both viral and nonviral approaches have been explored, the major limitation to the former being the inability to repeatedly administer, which renders this approach perhaps more applicable to conditions requiring single administration, such as cancer. Progress in development and clinical trials in each of these diseases is reviewed, together with some potential newer approaches for the future."
6762,Efficient Parameterized Algorithm for Biopolymer Structure-Sequence Alignment,"Computational alignment of a biopolymer sequence (e.g., an RNA or a protein) to a structure is an effective approach to predict and search for the structure of new sequences. To identify the structure of remote homologs, the structure-sequence alignment has to consider not only sequence similarity but also spatially conserved conformations caused by residue interactions, and consequently is computationally intractable. It is difficult to cope with the inefficiency without compromising alignment accuracy, especially for structure search in genomes or large databases. This paper introduces a novel method and a parameterized algorithm for structure-sequence alignment. Both the structure and the sequence are represented as graphs, where in general the graph for a biopolymer structure has a naturally small tree width. The algorithm constructs an optimal alignment by finding in the sequence graph the maximum valued subgraph isomorphic to the structure graph. It has the computational time complexity O(k (t) N (2)) for the structure of N residues and its tree decomposition of width t. The parameter k, small in nature, is determined by a statistical cutoff for the correspondence between the structure and the sequence. The paper demonstrates a successful application of the algorithm to developing a fast program for RNA structural homology search."
6763,Noninvasive Ventilation in Patients with Severe Acute Respiratory Syndrome,"Severe acute respiratory syndrome first emerged in Guangdong, China in November 2002 and then spread rapidly to many countries through Hong Kong in 2003 [1–4]. A 64-year-old physician from southern China, who had visited Hong Kong on February 21, 2003 and died 10 days later of severe pneumonia, is believed to have been the source of infection causing subsequent outbreaks of severe acute respiratory syndrome (SARS) in Hong Kong, Vietnam, Singapore, and Canada [1–4]. By the end of the epidemic in July 2003, there had been 8,096 cases reported in 29 countries and regions, with a mortality incidence of 774 (9.6 %) [5]. Among the 8,096 cases, 1,706 were health care workers (HCWs). A novel coronavirus (CoV) was responsible for SARS [6]. Bats are likely the natural reservoirs of SARS-like CoV [7, 8]."
6764,Imaging of Lung Transplantation,"Lung transplantation has become a viable treatment option for end-stage lung disease. Common indications for lung transplantation are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, cystic fibrosis, alpha-1 antitrypsin deficiency, and pulmonary arterial hypertension. Either single or bilateral lung transplantation can be performed, but bilateral lung recipients appear to have a better median survival than single lung recipients. Complications after lung transplantation are common and may have nonspecific clinical and radiologic manifestations. The time point at which these complications occur relative to the date of transplant is crucial in formulating a differential diagnosis and recognizing them accurately. Significant advances in imaging techniques and recognition of air trapping in exhalation images and other patterns /distribution of parenchymal abnormalities have led to routine use of HRCT for diagnostic evaluation in patients manifesting respiratory decline in the lung transplant recipient."
6765,3 Infecties van de onderste luchtwegen en tuberculose,"Tot de onderste luchtwegen behoren alle onderdelen van de luchtwegen en longen onder de stembanden (trachea, bronchi en bronchioli)."
6766,Infections: The Emergency of the New Millennium,"The New Millennium opened with alarming data on infections and antimicrobial resistance. Viral infections (SARS, MERS-CoV, Zika, Chikungunya, West Nile, Ebola virus infection, etc.) emerged or re-emerged with threatening outbreaks. However, viral emerging infections in some instances represented marginally a concern for developed countries that were just lapped by them. Currently, the new emergency is represented by antimicrobial resistance in bacterial infections, that is, a matter of extreme importance in developed and developing countries, where this issue has become a top priority for global policy makers and public health authorities. New mechanisms of resistance continue to emerge and spread globally, threatening our ability to treat common infections. The overuse and misuse of antimicrobials both in the human and animal field, and their dispersion in the environment pose a risk for selection of mechanisms of resistance of germs. Some settings, like the healthcare facilities, where the use of antimicrobials is obviously intense and infection prevention and control can be poor, represent the reservoir for multidrug-resistant organisms and, sometimes, the melting pot for pan-resistant strains."
6767,Hematologic Complications,"Critically ill patients are at high risk of developing various hematologic complications that may be present on admission or occur during their stay in the Intensive Care Unit (ICU). Often times the etiology of specific hematologic abnormalities is unclear and the diagnosis may be challenging due to the complexity of critically ill patients. This chapter will focus on diagnosis and management of the most commonly encountered hematologic problems in the critically ill such as anemia, neutropenia, thrombocytopenia, coagulopathy and thrombotic complications, with specific focus on diagnosis and management of these conditions."
6768,Molecular Virology,Traditional viral isolation by cell culture assays and conventional serological methods have been previously used to detect and identify various virus infections
6769,Schützengrabenfieber,
6770,Advanced Immunotechnological Methods for Detection and Diagnosis of Viral Infections: Current Applications and Future Challenges,"Diagnosis and identification of viruses is an important component of diagnostic virology laboratory. Although various modes of diagnostic methods are now available at disposal, a vast majority of the diseases across the globe remain undiagnosed. This is largely due to the overlapping undifferentiated set of symptoms across myriad set of RNA and DNA viral diseases. As such, it becomes critical to take into consideration several factors for viral diagnosis ranging from the type and quality of specimen collected, time of specimen collection, mode of transport, accuracy, specificity, sensitivity, and the type of diagnostic method used. This chapter broadly emphasizes various methods on diagnostic virology ranging from the classical methods of diagnosis to the most recently developed molecular methods of detection of virus."
6771,"Il versamento pleurico: aspetti eziologici, diagnostici e clinici","Il coinvolgimento della pleura puÒ comparire nel corso di molteplici e differenti patologie. Le cause che sottendono un versamento pleurico possono essere intra-toraciche o sistemiche e, se in alcuni casi queste appaiono facilmente individuabili grazie a segni clinici patognomonici, in altri casi l’inquadramento nosografico di un versamento puÒ risultare complesso, dovendosi basare su elementi clinici e reperti laboratoristico-strumentali spesso aspecifici."
6772,Bioinformatics Applications in Advancing Animal Virus Research,"Viruses serve as infectious agents for all living entities. There have been various research groups that focus on understanding the viruses in terms of their host-viral relationships, pathogenesis and immune evasion. However, with the current advances in the field of science, now the research field has widened up at the ‘omics’ level. Apparently, generation of viral sequence data has been increasing. There are numerous bioinformatics tools available that not only aid in analysing such sequence data but also aid in deducing useful information that can be exploited in developing preventive and therapeutic measures. This chapter elaborates on bioinformatics tools that are specifically designed for animal viruses as well as other generic tools that can be exploited to study animal viruses. The chapter further provides information on the tools that can be used to study viral epidemiology, phylogenetic analysis, structural modelling of proteins, epitope recognition and open reading frame (ORF) recognition and tools that enable to analyse host-viral interactions, gene prediction in the viral genome, etc. Various databases that organize information on animal and human viruses have also been described. The chapter will converse on overview of the current advances, online and downloadable tools and databases in the field of bioinformatics that will enable the researchers to study animal viruses at gene level."
6773,Current Capabilities of First Responders in Different Countries,
6774,"25 Keel-, neus- en oorheelkunde","Bovensteluchtweginfecties, recidiverende middenoorontstekingen en tonsillitiden behoren tot de meest frequent voorkomende ziektebeelden bij kinderen. Mede door het veranderde beloop, de verminderde morbiditeit en vernieuwde inzichten zijn de behandelstrategieën de afgelopen jaren veranderd. Een afwachtend beleid, watchful waiting, lijkt nu veelal aangewezen."
6775,Recent Advances in Real-time Mass Spectrometry Detection of Bacteria,"The analysis of bio-aerosols poses a technology challenge, particularly when sampling and analysis are done in situ. Mass spectrometry laboratory technology has been modified to achieve quick bacteria typing of aerosols in the field. Initially, aerosol material was collected and subjected off-line to minimum sample treatment and mass spectrometry analysis. More recently, sampling and analysis were combined in a single process for the real-time analysis of bio-aerosols in the field. This chapter discusses the development of technology for the mass spectrometry of bio-aerosols, with a focus on bacteria aerosols. Merits and drawbacks of the various technologies and their typing signatures are discussed. The chapter concludes with a brief view of future developments in bio-aerosol mass spectrometry."
6776,Pneumonia,"The lung is constantly exposed to airborne infectious agents due to the large surface area of approximately 100 m(2). Therefore pneumonia is one of the most common lung diseases. Understanding infection requires understanding the routes of infections, the way invading organisms infect epithelial cells, as well as defense mechanisms of the lung tissue acquired during evolution. Different variants of infectious and non-infectious pneumonias are discussed; special types of pneumonias such as granulomatous and fibrosing pneumonias are presented under separate sections. Causing organisms and other causes of pneumonias are included, and their mode of action is included as far as understood."
6777,Acute Exacerbation of COPD,"Acute exacerbations of COPD involve increased symptoms such as cough, dyspnea and sputum production. These exacerbations are associated with increased mortality as well as decline in lung function. Non-invasive positive-pressure ventilation (NIPPV) is the preferred method of ventilatory support in respiratory failure secondary to AECOPD. NIPPV reduces work of breathing, improves oxygenation and ventilation and decreases both mortality and the risk of invasive ventilation. Other therapies for AECOPD include inhaled bronchodilators and systemic glucocorticoids. Antibiotics are recommended for severe exacerbations. Future areas of interest in treatment for AECOPD include utilization of biomarkers and extracorporeal carbon dioxide removal."
6778,Tuberculosis in the Intensive Care Unit: The North American Perspective,
6779,Infectious Complications of Cancer Therapy,"Advances in the management of cancer, particularly the development of new chemotherapeutic agents, have greatly improved the survival and outcome of patients with hematologic malignancies and solid tumors; overall 5-year survival rates in cancer patients have improved from 39% in the 1960s to 60% in the 1990s.1 However, infection, caused by both the underlying malignancy and cancer chemotherapy, particularly myelosuppressive chemotherapy, remains a persistent challenge."
6780,"Globalisation and its Effects on Educational Leadership, Higher Education and Educational Policy",
6781,Sarcoptes scabiei,
6782,The Origin and Evolution of Viruses,"The lecture covers three main topics: (i) Viruses: properties, place in the living world, and possible origin; (ii) Molecular basis of viral variability and evolution; and (iii) Evolution of viral pathogenicity and emerging viral infections."
6783,Quasispecies Dynamics of RNA Viruses,"RNA viruses, such as human immunodeficiency virus, hepatitis C virus, influenza virus, and poliovirus replicate with very high mutation rates and exhibit very high genetic diversity. The extremely high genetic diversity of RNA virus populations originates that they replicate as complex mutant spectra known as viral quasispecies. The quasispecies dynamics of RNA viruses are closely related to viral pathogenesis and disease, and antiviral treatment strategies. Over the past several decades, the quasispecies concept has been expanded to provide an adequate framework to explain complex behavior of RNA virus populations. Recently, the quasispecies concept has been used to study other complex biological systems, such as tumor cells, bacteria, and prions. Here, we focus on some questions regarding viral and theoretical quasispecies concepts, as well as more practical aspects connected to pathogenesis and resistance to antiviral treatments. A better knowledge of virus diversification and evolution may be critical in preventing and treating the spread of pathogenic viruses."
6784,"Ungewissheit, Uneindeutigkeit, Unsicherheit – Braucht die Theorie reflexiver Modernisierung eine neue Handlungstheorie?","Moderne Zeiten sind unsichere Zeiten – so lautet der Befund soziologischer Gegenwartsdiagnosen. Die Theorie reflexiver Modernisierung hat diesen Befund weiter zugespitzt. Sie diagnostiziert, dass die Gesellschaft, in der wir leben – die Zweite Moderne – durch Ungewissheit, Uneindeutigkeit und Unsicherheit gekennzeichnet ist: Entscheidungen beruhen nicht mehr auf gesichertem Wissen, soziale Lagen lösen sich auf und vertraute Institutionen wie der Nationalstaat oder die Erwerbsarbeit verlieren ihre Konturen. Während Institutionen, Organisationen und Individuen mehr denn je dazu gezwungen sind, Entscheidungen zu treffen, wird dies gleichzeitig immer schwieriger, denn institutionalisierte Entscheidungskonventionen produzieren Nebenfolgen, die die Basisinstitutionen moderner Gesellschaften bedrohen. „Die Turbulenzen, die … auf allen Handlungsebenen und in allen Handlungskontexten entstehen, bilden das Schlüsselproblem für Gegenwart und Zukunft der Zweiten Moderne und das zentrale Thema ihrer Erforschung“ (Beck/Bonß/Lau 2004: 15)."
6785,Systemic Syndromes with Biomedicines,"Since the introduction of biomedicines in human therapy, a number of systemic reactions have been more frequently reported as important adverse events following treatment. Some monoclonal antibodies, interleukins, receptor inhibitors, and growth factors may preferably induce acute, violent, early events with an overall low frequency, but with serious and life-threatening capacity. ."
6786,Pandemic Risk Modelling,"This chapter will explore the nature of communicable diseases, a brief history of pandemics, and will introduce the mathematical models used to evaluate the risk pandemics pose to human populations. Such modelling is used in a public health context, where modelling past and current events provides insight in how to respond most effectively to a new outbreak. It is also used in the context of risk mutualisation and transfer. As recently as 2013, a survey of 30,000 insurance executives placed global pandemic as the biggest extreme risk facing insurers (Towers Watson. 2013. Insurers Rate Global Pandemic as the Major Extreme Risk. 3 December). The chapter will introduce the principles used to model these events in the insurance industry and will conclude with a review of the way these models are applied in an unconventional risk transfer context."
6787,Management of Malignant Pleural Effusions,
6788,Clinical Application of Stem/Stromal Cells in COPD,"Chronic obstructive pulmonary disease (COPD) is a progressive life-threatening disease that is significantly increasing in prevalence and is predicted to become the third leading cause of death worldwide by 2030. At present, there are no true curative treatments that can stop the progression of the disease, and new therapeutic strategies are desperately needed. Advances in cell-based therapies provide a platform for the development of new therapeutic approaches in severe lung diseases such as COPD. At present, a lot of focus is on mesenchymal stem (stromal) cell (MSC)-based therapies, mainly due to their immunomodulatory properties. Despite increasing number of preclinical studies demonstrating that systemic MSC administration can prevent or treat experimental COPD and emphysema, clinical studies have not been able to reproduce the preclinical results and to date no efficacy or significantly improved lung function or quality of life has been observed in COPD patients. Importantly, the completed appropriately conducted clinical trials uniformly demonstrate that MSC treatment in COPD patients is well tolerated and no toxicities have been observed. All clinical trials performed so far, have been phase I/II studies, underpowered for the detection of potential efficacy. There are several challenges ahead for this field such as standardized isolation and culture procedures to obtain a cell product with high quality and reproducibility, administration strategies, improvement of methods to measure outcomes, and development of potency assays. Moreover, COPD is a complex pathology with a diverse spectrum of clinical phenotypes, and therefore it is essential to develop methods to select the subpopulation of patients that is most likely to potentially respond to MSC administration. In this chapter, we will discuss the current state of the art of MSC-based cell therapy for COPD and the hurdles that need to be overcome."
6789,"Transfusion and Acute Respiratory Distress Syndrome: Clinical Epidemiology, Diagnosis, Management, and Outcomes","Transfusion related acute lung injury (TRALI) is a life-threatening complication of blood product transfusion. It is the leading cause of blood product transfusion related death in the USA. The syndrome is defined by hypoxemic respiratory failure with bilateral infiltrates on chest X-ray in the setting of a blood transfusion and absence of cardiac failure. The exact incidence of TRALI is unknown, but the incidence is higher in the critically ill patient population. Multiple patient and donor related risk factors for TRALI exist, including critically illness, alcohol use, and receiving transfusions with high plasma volumes. Practitioners should have a low index of suspicion for the diagnosis of TRALI, and blood bank reporting is vital to aid in diagnosis and future prevention. Management is primarily supportive care, with supplemental oxygen as the mainstay for therapy. Despite the transient course of TRALI, its morbidity is severe with the majority of patients requiring mechanical ventilation and treatment in the intensive care unit. For patients that survive TRALI, outcomes are promising without residual pulmonary deficits. Prevention strategies over the past 10 years have helped to decrease the incidence of TRALI and have led to increased awareness of this condition in the medical field."
6790,The RPE Cell and the Immune System,"The RPE cell plays a pivotal role in retinal immunity. In fact, the RPE cell orchestrates both innate and adaptive immunity and contains a plethora of factors to regulate the immune response. Many immunoregulatory activities of the RPE cell are accomplished through cytokine production, toll-like receptor (TLR) activation, complement regulation and antigen presentation. The RPE cells immune regulatory network plays an essential role in retinal immunity and autoimmunity, retinal infections and in a variety of retinal degenerative disorders. Understanding the immune regulatory properties of this cell may provide additional clues to disease mechanisms that may lead to future treatments for many human retinal diseases."
6791,Fibrinogen (FI),"Das Hauptsubstrat der Gerinnung ist Fibrinogen (FI). Bei akuter Blutung ist es zumeist der erste Gerinnungsfaktor, der kritische Grenzwerte erreicht (150–200 mg/dl). FI kann hervorragend mittels point-of-care-tauglicher viskoelastischer Methoden (Thrombelstographie oder Thrombelastometrie) monitiert werden. Die Substitution kann mittels Frischplasma, Cryopräzipitat oder Fibrinogenkonzentrat erfolgen. Frischplasma ist nicht besonders effektiv, mit einer erhöhten Morbidität, insbesondere bei kritisch Kranken, sowie mit Volumenbelastung assoziiert. Cryopräzipitat wird in einigen europäischen Ländern nicht angeboten. Die Gabe von Fibrinogenkonzentrat wird in verschiedenen Leitlinien empfohlen. Als Akut-Phase-Protein kann FI physiologischerweise bei Entzündungsprozessen, schweren Verletzungen sowie nach großen Operationen in kurzer Zeit auf über 1000 mg/dl ansteigen; wobei hier Fibrinogenspaltprodukte anti-inflammatorische und sogar antibakterielle Eigenschaften haben."
6792,Healthy Cities: Old and New Solutions,"Cities have had historically higher mortality and morbidity rates than rural areas. These spiked dramatically after the Industrial Revolution, which led to the first health of cities movement that stimulated the adoption of new public health measures to improve the built-environment in the developed countries. Together with such additional factors as increasing prosperity, hygiene and especially medical advances, the old health disadvantages of cities was reversed. But a new set of medical challenges threatening to reverse previous progress has emerged. These include such problems as bacterial resistances to many of the drugs that reduced communicative diseases, to the effects of indoor living and aging, all of which require urgent attention. In addition, a review of the various health determinants that contribute to ill-health shows that since many of these factors are not within the prevue of current medical practice, they must be addressed if the health and well-being of people in cities are to be improved. A series of other problems that were previously overlooked are being tackled by the new Healthy Cities movement, such as the need for more political and citizen involvement in planning and delivering health care, better ways of promoting health rather than just curing ill-health with a new emphasis on wellness, as well as more effective measures to reduce the persistent pockets of ill-health in many cities."
6793,A New Method of Differentiation Between a Biological Attack and Other Epidemics,"The main obstacle in identifying a biological attack (BA), while preventing false alarms, epidemics of panic and unnecessary expenditures is the insufficient data on which to rely. Тhis new method of outbreak analysis is based on our original model of bioterrorism risk assessment. The intention was to develop a model of quick and accurate evaluation of an unusual epidemiologic event (UEE) that would save time, money, human and material resources and reduce confusion and panic. This UEE analysis is a subtle and detailed differentiation through assessment of BA feasibility in comparison with three other types of outbreak scenarios. There are two types of differences between these four scenarios: qualitative and quantitative. Qualitative and quantitative differences are defined with 23 and 10 indicators, respectively. Both types of indicators can have three different values: N/A, 0 or 1. We have carried out a feasibility analysis for subtle and detailed differentiation among four outbreak scenarios. As a tool for feasibility analysis we have introduced a “system of elimination”. System elimination is applied if one component contains all indicators scored with 0 or as N/A – the related scenario is then eliminated from further consideration. The system was applied to four UEEs: (1) an intentional attack by a deliberate use of a biological agent (Amerithrax), (2) a spontaneous outbreak of a new or re-emerging disease (“swine flu”), (3) a spontaneous outbreak by an accidental release of a pathogen (Sverdlovsk anthrax), and (4) a spontaneous natural outbreak of a known endemic disease that may mimic bioterrorism or biowarfare (Kosovo tularemia). It was found that “agent” was the most important and the most informative UEE component of the new scoring system. This system might be helpful in the analysis of unusual epidemic events and a quick differentiation between biological attacks and other epidemics."
6794,Metabolische Störungen,"Bei fortgeschrittenem Organversagen von Niere, Herz, Leber oder Lunge stellt eine Organtransplantation meist das einzige kurative Therapieverfahren dar. Auch eine Knochenmarktransplantation wird bei sonst unheilbaren Leukämien oder Lymphomen eingesetzt. Nach Organtransplantation treten bei 30–60% der Patienten neurologische Komplikationen auf. Differenzialdiagnostisch müssen vorbestehende, durch die Grunderkrankung bedingte, Störungen von intraoperativen Komplikationen, von metabolisch bedingten neurologischen Störungen und von Nebenwirkungen der notwendigen immunsuppressiven Medikation abgegrenzt werden. Immunsuppressiva können dabei sowohl eine direkte Neurotoxizität als auch indirekt vermehrt Infektionen des Zentralnervensystems (ZNS) und sekundäre ZNS-Malignome verursachen. Während metabolische Enzephalopathien oder opportunistische ZNS-Infektionen bei allen Patienten nach Transplantation etwa gleich häufig auftreten können, sind andere neurologische Syndrome für bestimmte Organtransplantationen typisch."
6795,Infectious Diseases,"This chapter contains four tables on infectious diseases. It features tables on common causes of fever in the ICU, prevention and management of hospital-acquired and ventilator-associated pneumonias."
6796,"Mykobakterien, nichttuberkulöse (NTM)","Atypische, ubiquitäre, Umwelt-Mykobakterien, „Mycobacteria other than Mycobacterium tuberculosis“ MOTT"
6797,"Molecular Epidemiology, Genomics, and Phylogeny of Crimean-Congo Hemorrhagic Fever Virus","Crimean-Congo hemorrhagic fever virus (CCHFV) constitutes a group of viruses of the genus Nairovirus (family Bunyaviridae). Like all members of the Bunyaviridae, the genome of CCHFV is composed of tripartite single-stranded RNA. These segments, designated small (S), medium (M), and large (L), minimally encode the nucleocapsid (N), envelope glycoproteins (Gn and Gc), and RNA-dependent RNA polymerase (RdRp), respectively [38]."
6798,Infektionen des Respirationstrakts,Infektionen des Respirationstrakts sind die meistverbreiteten Infektionserkrankungen des Menschen. Vor allem eine Erkältungserkrankung stellt sicherlich eine der häufigsten Ursachen für eine ärztliche Konsultation dar.
6799,Glocal English in Singapore? A Re-exploration of the Localization of English,"This chapter re-considers the notion of ‘glocal English’ or ‘glocalism’ in discussing the use of English in Singapore. As a global language, English has developed in interesting ways via social media and the Internet all over the world. However, it is only in special polities such as Singapore where it is used as the ‘working language’ of the country for a multilingual population base, that English has developed into a phenomenon that has to be studied, better understood and perhaps given a label such as ‘glocal English.’ The chapter will contribute to the ongoing discussions of what it means for English to be a global language and how it adapts as ‘a communicative tool of immense political, ideological, and economic power’(Kachru, Kontalinguistik, 1996, pp. 906–913) in global-local tensions (e.g. commerce, trade, finance, industry, science and technology versus intra-ethnic and inter-ethnic communication within Singapore). In the shifting perspectives of what English is (really global or truly local?), what it does (for and in education), and how it is used in this country (globally and/or locally), the paper hopes to elucidate the dimensions of teaching and learning English in the Singapore context and perhaps more widely in an Asia-Pacific context."
6800,Old and New Pestilences,"a. “Any fatal epidemic disease, affecting man or beast, and destroying many victims.” The Oxford Universal Dictionary, 3(rd) edition, 1955, Oxford Press, 2515 pp. b. “A contagious or infectious epidemic disease that is virulent and devastating.” Webster’s Seventh New Collegiate Dictionary, 1965. G. & C. Merriam Co., Springfield, Mass., 1221 pp. Accordingly, a pestilence should be an infectious disease, devastating (killing) a large number of people (or animals)."
6801,"On Viruses, Bats and Men: A Natural History of Food-Borne Viral Infections","In this chapter, cross-species infections from bats to humans are reviewed that do or do not use intermediate animal amplification hosts and that lead to human-human transmissions with various efficiencies. Rabies infections, Hendra virus infections in Australia, Nipah virus infections in Malaysia and Bangladesh and SARS coronavirus infection in China are explored from the public health perspective. Factors of bat biology are discussed which make them ideal virus reservoirs for emerging diseases. In line with the book theme, it is asked whether even in these epidemic conditions, viruses can be seen as essential agents of life where host species use their viruses to defend their ecological position against intruders. It is asked whether another essential function of animal viral infections could be the “killing the winning population” phenomenon known from phage biology which would stabilize species diversity in nature."
6802,Importziekten,"In dit hoofdstuk worden de ziektebeelden op het gebied van de importziekten op een beknopte, heldere wijze behandeld. Het zijn allemaal infectieziekten die in eigen land (= inheems) niet voorkomen, maar tijdens een verblijf in het buitenland (= uitheems) zijn opgelopen. De volgorde van de paragrafen is alfabetisch."
6803,"Bilateral and Multilateral Financing of HIV/AIDS Programs: The World Bank, the International Monetary Fund, the Global Fund, Bilateral Donors and the Private Sector","This chapter examines the operations of the World Bank (a multilateral development institution), the International Monetary Fund (a multilateral financial institution) and the Global Fund to Fight AIDS, Tuberculosis and Malaria (a multilateral fundraising and financing institution) to fight HIV/AIDS. We also examine the role of bilateral donors and the private sector in financing the fight against HIV/AIDS. We examine the relationships among bilateral donors and international organizations, what distinguishes their roles in the global HIV/AIDS pandemic and the extent to which their activities overlap. In addition, we consider how funding strategies and parameters may affect the effectiveness of AIDS funding in preventing transmission and providing treatment."
6804,"Risk Perception, Heuristics and Epidemic Spread","During an outbreak of an infectious disease, people often change their behaviour to reduce their risk of infection. In a given population, the levels of perceived risk of infection vary greatly among individuals. The difference in perception could be due to a number of different factors including varying levels of information regarding the pathogen, quality of local healthcare, availability of preventive measures, individual and group usage of heuristics in the decision-making process. First we discuss the rigorous assessment of the risk, then we describe how our brain assesses the risk through the use of heuristics that are still rooted in animal evolution. Then we discuss the impact and the role of mass media and social networks in modulating risk perception. Next, we show how mathematical modelling is challenged by multi-scale epidemiological problems where the risk perception level is coupled with all the other microscopic and macroscopic levels. Finally, we draw future scenarios of personal risk evaluation through self-monitoring devices and personal genomics. The aim of this chapter is to discuss the importance of risk perception related to the spreading of a disease and to present a variety of ideas that could be fruitfully explored through modelling."
6805,Alignment-Free Analyses of Nucleic Acid Sequences Using Graphical Representation (with Special Reference to Pandemic Bird Flu and Swine Flu),"The exponential growth in database of bio-molecular sequences have spawned many approaches towards storage, retrieval, classification and analyses requirements. Alignment-free techniques such as graphical representations and numerical characterisation (GRANCH) methods have enabled some detailed analyses of large sequences and found a number of different applications in the eukaryotic and prokaryotic domain. In particular, recalling the history of pandemic influenza in brief, we have followed the progress of viral infections such as bird flu of 1997 onwards and determined that the virus can spread conserved over space and time, that influenza virus can undergo fairly conspicuous recombination-like events in segmented genes, that certain segments of the neuraminidase and hemagglutinin surface proteins remain conserved and can be targeted for peptide vaccines. We recount in some detail a few of the representative GRANCH techniques to provide a glimpse of how these methods are used in formulating quantitative sequence descriptors to analyse DNA, RNA and protein sequences to derive meaningful results. Finally, we survey the surveillance techniques with a special reference to how the GRANCH techniques can be used for the purpose and recount the forecasts made of possible metamorphosis of pandemic bird flu to pandemic human infecting agents."
6806,Respiratory Diseases,"Upper respiratory tract infections are the most common type of infectious diseases and a leading cause of outpatient illness (1,2)."
6807,Disaster Studies at 50: Time to Wear Bifocals?,"Other writers have cataloged the many contributions to understanding and practice that disaster studies have produced over the years, many of them, and the earliest, coming from sociology. The Disaster Research Center at the University of Delaware was founded in 1963 by, and is still inhabited by sociologists, but has embraced an interdisciplinary approach over time, including core and affiliated faculty from English, history, political science, civil engineering, and environmental policy). My thoughts in this essay are not confined to the DRC’s corpus of work, but ‘disaster studies’ more broadly defined below. This said, the roots of disaster studies in sociology are deep, the classic Ur-source being an unpublished PhD study of the 1917 explosion in Halifax, Nova Scotia. This disaster continues to be a source of continuing research that provide lessons for our time. My own essay will mention some of these contributions, and they are truly something to celebrate; however, the central theme I will emphasize is what has been missed and could be added to the research agenda over the next decade or so. I employ an optical metaphor that has as much to do with philosophy of science (‘vision’ and Mao’s famous question, ‘Where do ideas come from?’) as it does with optics, optometry and the detailed application of methods at micro and macro scale. The lens is a remarkable human invention. Glass shaped and polished in one way opened up the microscopic world. Treated in another, the lens gave us the telescope. I will argue that politics – the creation, use and maintenance of power to influence other people and to control space and resources – has been a largely missing raw material, like glass, from which disaster studies could shape lenses for its own tools of inquiry. Consideration of power has not been totally missing. Yet lenses fashioned from an understanding of power have not been used sufficiently in a number of critical areas of research."
6808,Potentiality of DNA Sensors in Activating Immune System in Emerging Viral Infectious Diseases,"Viruses are obligatory intracellular parasites and hijack the host cell machinery to make more identical copies of it and continue self-propagation. They attach and replicate in the susceptible and permissive hosts and host derived cell lines. They enter the cells either through direct attachment, receptor-mediated endocytosis, or phagocytosis. Hence, to thwart the invasion by viruses, hosts have developed immunity in ascending stages—intrinsic, innate and adaptive immunity. A robust intrinsic and innate immune response governs an effective adaptive immune response, should that be needed. Both enveloped as well as non-enveloped viruses are subject to distinct types of DNA sensors, subject to their site of replication. DNA sensors of viral PAMPs can be classified into three types, based on the location of their PAMPs in the host cellular compartment viz. cell surface, cytoplasmic and nuclear. The host cell membrane both, surface as well as intra cellular, is continuously monitored for the non-host, pathogenic components or PAMPs. Among the intracellular sensors of the viral genome, there are two types—essentially due to the two types of major viral genomes i.e. RNA and DNA sensors. The cytosolic DNA sensors include AIM2, IFI16, cGAS, RNA Pol III, DNA-PK, DDX9, DHX36, DDX41, DDX60, DAI, LRRFIP1, HMGB, ABCF1 and MRE11. PYHIN family of sensors include AIM2, IFI16, IFIX and MNDA. Another recently discovered family of sensor called stimulator of interferon (IFN) genes (STING), specifically houses on the endoplasmic reticulum (ER) and functions in association with its upstream sensor, cGAS. Some DNA sensors shuttle between the cytosol and nucleus pre- and post-extraneous DNA binding. These include IFI16, IFIX, RNA Pol III, etc. There is no exclusive nuclear DNA sensor. Many enzymes known to be present in the cells for their obvious primary functions also additionally function as DNA sensors. The DNAse family of sensors include DNAse II and TREX1, which are ubiquitously present in the cell for their housekeeping functions. The RNAse family of sensor includes one member—RNA Pol III. Additionally, DNA-PK also functions to cater to viral DNA sensing. The endosomal DNA sensors include TLR7 and TLR9, which belong to the Toll-like receptor (TLR) family. The DExD/H-box helicase family include the putative DNA sensors recently discovered including DDX9, DHX36, DDX41 and DDX60. Several other sensors remain to be characterised or are less classified viz. DAI, LRRFIP1, HMGB, ABCF1, MRE11. In general, response to a viral RNA or DNA produces three types of responses, namely, production of antiviral cytokines including Types I and III IFNs, release of pro-inflammatory and inflammatory cytokines and chemotactic factors. This chapter discusses the structure, function and mechanism of action of the viral DNA sensors explored till date."
6809,Life-Threatening Diseases of the Upper Respiratory Tract,"Acute airway obstruction is one of the most common causes of acute respiratory failure in children. Left untreated, it can rapidly progress to cardiopulmonary arrest and death. There are several important anatomical differences between pediatric and adult patients that render children more susceptible to acute airway obstruction. In addition, there are several diseases that can cause life-threatening acute airway compromise. An understanding of the developmental anatomy and physiology, as well as the myriad diseases that can cause airway compromise in children is therefore essential for all healthcare personnel that provide care for critically ill children."
6810,Nuclear Proliferation and Terrorism,"In a dramatic moment before the United Nations, Bernard Baruch described the American plan to internationalize and control the atom. He described in biblical fashion the choice between “the quick from the dead” (taken from the Apostle’s Creed) resulting from the global spread of nuclear weapons. This prediction came to fruition 15 years later when presidential candidate John F. Kennedy gave a warning in the third debate with Vice President Richard Nixon:"
6811,Emergencies/Resuscitation,"This chapter discusses neonatal infection, the different causes of shock, hypoglycemia, acid-base balance, and resuscitation. The etiology, signs, investigations, and treatment of these items are addressed. A large number of Tables are added for clinical use to list signs, normal values and treatment guides. Resuscitation is subdivided into clinical assessment of neonates, clinical assessement of children and infants, airway management, ventilation, circulatory resuscitation, and defibrillation. Advices of Advanced Paediatric Life Support (APLS) are the basis of the guide lines for resuscitation in this chapter. Next to ventilatory support without equipment, various types of mechanical ventilation with advantages and disadvantages listed. A large number of figures and drawings visualise the techniques for airway management, ventilation and cardiac compression so that the clinical application of described techniques becomes clear with one glance."
6812,FIV as a Model for HIV: An Overview,"Animal models for human immunodeficiency virus (HIV) infection play a key role in understanding the pathogenesis of AIDS and the development of therapeutic agents and vaccines. As the only lentivirus that causes an immunodeficiency resembling that of HIV infection, in its natural host, feline immunodeficiency virus (FIV) has been a unique and powerful model for AIDS research. FIV was first described in 1987 by Niels Pedersen and co-workers as the causative agent for a fatal immunodeficiency syndrome observed in cats housed in a cattery in Petaluma, California. Since this landmark observation, multiple studies have shown that natural and experimental infection of cats with biological isolates of FIV produces an AIDS syndrome very similar in pathogenesis to that observed for human AIDS. FIV infection induces an acute viremia associated with Tcell alterations including depressed CD4 :CD8 T-cell ratios and CD4 T-cell depletion, peripheral lymphadenopathy, and neutropenia. In later stages of FIV infection, the host suffers from chronic persistent infections that are typically self-limiting in an immunocompetent host, as well as opportunistic infections, chronic diarrhea and wasting, blood dyscracias, significant CD4 T-cell depletion, neurologic disorders, and B-cell lymphomas. Importantly, chronic FIV infection induces a progressive lymphoid and CD4 T-cell depletion in the infected cat. The primary mode of natural FIV transmission appears to be blood-borne facilitated by fighting and biting. However, experimental infection through transmucosal routes (rectal and vaginal mucosa and perinatal) have been well documented for specific FIV isolates. Accordingly, FIV disease pathogenesis exhibits striking similarities to that described for HIV-1 infection."
6813,Intellectual Property and Human Security,"This chapter discusses the interrelatedness between intellectual property and human security. There are two sides of this interrelationship. In the first place, IP issues are closely related to the hard security of nations. In the second place, the application of the regime of international intellectual property laws can help promote economic and social development and, at the same time, can result in major hardships when it comes to protection of the right to life and realization of the rights to health, food, and education. In the pages that follow, different aspects of these issues are explored."
6814,Minimizing the Impact of Complex Emergencies on Nutrition and Geriatric Health: Planning for Prevention is Key,"Complex emergencies (CEs) can occur anywhere and are defined as crisis situations that greatly elevate the risk to nutrition and overall health (morbidity and mortality) of older individuals in the affected area. In urban areas with high population densities and heavy reliance on power-driven devices for day-to-day survival, CEs can precipitate a rapid deterioration of basic services that threatens nutritionally and medically vulnerable older adults. The major underlying threats to nutritional status for older adults during CEs are food insecurity, inadequate social support, and lack of access to health services. The most effective strategy for coping with CEs is to have detailed, individualized pre-event preparations. When a CE occurs, the immediate relief efforts focus on establishing access to food, safe water, and essential medical services."
6815,Mining Semantic Descriptions of Bioinformatics Web Resources from the Literature,"A number of projects (myGrid, BioMOBY, etc.) have recently been initiated in order to organise emerging bioinformatics Web Services and provide their semantic descriptions. They typically rely on manual curation efforts. In this paper we focus on a semi-automated approach to mine semantic descriptions from the bioinformatics literature. The method combines terminological processing and dependency parsing of journal articles, and applies information extraction techniques to profile Web services using informative textual passages, related ontological annotations and service descriptors. Service descriptors are terminological phrases reflecting related concepts (e.g. tasks, approaches, data) and/or specific roles (e.g. input/output parameters, etc.) of the associated resource classes (e.g. algorithms, databases, etc.). They can be used to facilitate subsequent manual description of services, but also for providing a semantic synopsis of a service that can be used to locate related services. We present a case-study involving full text articles from the BMC Bioinformatics journal. We illustrate the potential of natural language processing not only for mining descriptions of known services, but also for discovering new services that have been described in the literature."
6816,Multidimensional Analysis of the News Consumption of Different Demographic Groups on a Nationwide Scale,"Examining 103,133 news articles that are the most popular for different demographic groups in Daum News (the second most popular news portal in South Korea) during the whole year of 2015, we provided multi-level analyses of gender and age differences in news consumption. We measured such differences in four different levels: (1) by actual news items, (2) by section, (3) by topic, and (4) by subtopic. We characterized the news items at the four levels by using the computational techniques, which are topic modeling and the vector representation of words and news items. We found that differences in news reading behavior across different demographic groups are the most noticeable in subtopic level but neither section nor topic levels."
6817,Severe Acute Respiratory Syndrome,"Early in 2003, an outbreak of the until then unknown severe acute respiratory syndrome (SARS) was reported in southeastern People’s Republic of China. The outbreak was thought to have first emerged in the Guangdong province in November 2002. Subsequently, the infections spread to Hong Kong (February 2003) and other countries of Southeast Asia, including Vietnam, Taiwan, and Singapore, as well as to Canada and the United States (http://www.fda.gov/oc/opacom/hottopics/sars/)."
6818,Noninvasive Mechanical Ventilation in Patients with High-Risk Infections and Mass Casualties in Acute Respiratory Failure: Pediatric Perspective,"Respiratory problems are common symptoms in children and common reason for visits to the pediatric emergency department (PED) and admission to the pediatric intensive care unit (PICU). Although the great majority of cases are benign and self-limited, requiring no intervention, some patients need respiratory support. Invasive mechanical ventilation (IMV) is a critical intervention in many cases of acute respiratory failure (ARF), but there are absolute risks associated with endotracheal intubation (ETI). On the other hand, noninvasive ventilation (NIV) is an extremely valuable alternative to IMV. A major reason for the increasing use of NIV has been the desire to avoid the complications of IMV. It is generally much safer than IMV and has been shown to decrease resource utilization. Its use also avoids the complications and side effects associated with ETI, including upper airway trauma, laryngeal swelling, postextubation vocal cord dysfunction, nosocomial infections, and ventilator-associated pneumonia. There are a number of advantages of NIV including leaving the upper airway intact, preserving the natural defense mechanisms of the upper airways, decreasing the need for sedation, maintaining the ability to talk while undergoing NIV, and reducing the length of hospitalization and its associated costs [1–3]."
6819,What the Intensivist Needs to Know About Hematopoietic Stem Cell Transplantation?,"Hematopoietic stem cell transplantation (HSCT) is a potential curative therapy for some patients with hematologic conditions. There are two main types of HSCT. This includes autologous HSCT, for which the stem cells are obtained from the patient, and allogeneic HSCT, for which the stem cells are obtained from a related or unrelated donor. The most common indications for autologous stem cell transplant are multiple myeloma and relapsed/refractory lymphoma, whereas leukemia and bone marrow failure syndromes remain the most common indications for allogeneic stem cell transplant. This chapter will review the different types, indications, processes, and main complications of HSCT. This chapter will also discuss end-of-life issues that patients and providers face when transplant patients are admitted for the intensive care unit."
6820,Research and Application on Key Technologies of J2EE-Oriented Urban Emergency Response System,"With experience of Emergency Response System implement, the exist problem and research status in china is analyzed. Based on these conclusions, the Emergency Response System is constructed which used the J2EE tool, faced to small and medium-size cities, moreover, the research on key technologies related in this architecture are introduced in detail."
6821,Optimization of Ligand Surface Concentration for Biosensor based on Imaging Ellipsometry,"the biosensor based on imaging ellipsometry for bio-molecular interactions has been developed for more than ten years and used to several biological applications successfully, such as detection of five markers of Hepatitis B, tumor markers and virus infection. Ligand surface concentration which might be related with its spatial configuration and bioactivity is an important factor to affect the biosensor sensitivity and dynamic range. In this investigation, IgG and its corresponding antibody are selected as a couple of model molecules for the optimization of ligand surface concentration. The optimization result of ligand surface concentration is achieved by analyzing the surface concentration increase of antigenantibody complex on sensing surface with various ligand surface concentrations."
6822,Walging: ‘Het went nooit helemaal’,"‘Toen ik verzorgingsassistente werd, moest ik erg wennen aan al die onaangename geuren. Maar na een poosje raakte ik er meer mee vertrouwd. De poep van sommige patiënten vond ik stinken, maar van de uitwerpselen van anderen had ik weer geen enkele last. Dat was te vergelijken met de poep-en pieslucht van mijn kinderen toen die nog klein waren.’"
6823,Chikungunya Virus and Zika Virus Expansion: An Imitation of Dengue Virus,"Dengue viruses are the most important arboviral pathogens in the world, which have adapted to human transmission and replication over several hundred years and were initially recognized to cause outbreaks of clinical disease in tropical and subtropical countries by Aedes aegypti mosquitoes. Subsequent global expansion of dengue infection outbreaks has occurred, with millions of cases yearly, probably from a combination of factors including proliferation of international travel and trade, possibly global climate changes, adaptation of the vectors to new environment, and emergence of a new mosquito vector, Aedes albopictus. Chikungunya virus, also transmitted by Aedes mosquitoes, causes a very similar clinical disease but with more prominent arthralgia or arthritis and was originally described in Africa in the 1960s. After a quiescent period of several decades, it reemerged in Africa in 2004 and rapidly spread across the Indian Ocean to involve Asian countries and parts of Europe. However, the past 2 years have seen the emergence of chikungunya virus in the western hemisphere with major outbreaks in the Caribbean and the Americas. Similar to dengue virus, chikungunya virus has adapted to Ae. albopictus mosquitoes which can transmit the disease. Although dengue infection is a more deadly disease especially in young children, chikungunya infection can cause prolonged severe disability and occasionally rare fatalities from encephalitis. No specific treatment is available for either diseases, but development of an effective vaccine for dengue infection is in progress. Until 2007, Zika virus [also transmitted by Aedes species] was associated with only sporadic mild infections in Africa and Asia. In 2007, Zika virus for the first time caused an outbreak beyond Africa and Asia to the Yap Island in the Federated States of Micronesia. Since then Zika virus has spread to French Polynesia, New Caledonia, Cook Islands, and Easter Island in the southeastern Pacific Ocean [Chile] in 2014 and by 2015 to Brazil. By January 2016, it became evident that Zika virus had caused an explosive outbreak in the Americas and the Caribbean with over 30 countries affected. On February 1, 2016, the World Health Organization declared Zika outbreak a global public health emergency. Zika virus infection is most commonly asymptomatic, and 20% of patients may develop a mild viral disease, but of major concern is the reported association of microcephaly in infected pregnant women in Brazil. This chapter explores the history, epidemiology, pathogenesis, clinical features, treatment, and prevention of these rapidly emerging zoonoses."
6824,Impacts and Challenges of Advanced Diagnostic Assays for Transplant Infectious Diseases,"The advanced technologies described in this chapter should allow for full inventories to be made of bacterial genes, their time- and place-dependent expression, and the resulting proteins as well as their outcome metabolites. The evolution of these molecular technologies will continue, not only in the microbial pathogens but also in the context of host-pathogen interactions targeting human genomics and transcriptomics. Their performance characteristics and limitations must be clearly understood by both laboratory personnel and clinicians to ensure proper utilization and interpretation."
6825,Adsorption of Proteins at Solid Surfaces,"Ellipsometry has a very high thin film sensitivity and can resolve sub-nm changes in the thickness of a protein film on a solid substrates. Being a technique based on photons in and photons out it can also be applied at solid-liquid interfaces. Ellipsometry has therefore found many in situ applications on protein layer dynamics but studies of protein layer structure are also frequent. Numerous ex situ applications on detection and quantification of protein layers are found and several biosensing concepts have been proposed. In this chapter, the use of ellipsometry in the above mentioned areas is reviewed and experimental methodology including cell design is briefly discussed. The classical ellipsometric challenge to determine both thickness and refractive index of a thin film is addressed and an overview of strategies to determine surface mass density is given. Included is also a discussion about spectral representations of optical properties of a protein layer in terms of a model dielectric function concept and its use for analysis of protein layer structure."
6826,Case Study – Bulgaria,"The aim of this paper is to map the current situation in Bulgaria’s public healthcare system with regard to bioterrorism response. It explores the main public health threats and focuses specifically on the changing perception of bioterrorism as a potential threat to the country. Furthermore, it explains how this perception is reflected in the existing legal framework and administrative structures. The paper makes the case for the further development of an integrated, flexible and sustainable national management system to respond effectively to emergencies and presents the major challenges for the country in this field. It makes a comparison between military and civilian agencies in their preparedness to respond to naturally occurring emergencies and threats of biological attack. This review points out the higher but still limited capacity of the military medical facilities in Bulgaria. The overall evaluation underlines the need for further strengthening of the relationship between military and civil capabilities and between public healthcare and security and law enforcement structures. As a result the authors make the case for stronger cooperation between military and civil medical facilities as well as for inter-institutional and interdisciplinary dialogue on the expert and political level on biopreparedness in Bulgaria."
6827,Cisplatin Derivatives as Antiviral Agents,"The use of polymeric derivatives of cisplatin as antiviral drugs is reviewed. Some of these drugs inhibit a wide variety of both RNA and DNA viruses including those responsible for herpes, common colds, chickenpox, and smallpox. The desirability of polymeric drugs is described as is the mode(s) of action of cisplatin itself. A description of viruses and methods of combating viruses is presented. Included is a review of current antiviral agents as well as modes of action of these antiviral agents."
6828,Relevante Nebenerkrankungen zu Notfallindikationen und Notfalloperationen in der Viszeral- und Allgemeinchirurgie,"Die Adipositas ist eine über das Normalmaß hinausgehende Vermehrung des Körperfetts und wird über den Body-Mass- Index (BMI = kg/m) bestimmt. Ab einem BMI von 30 kg/m liegt definitionsgemäß eine Adipositas vor. Der Krankheitswert ergibt sich aus der Assoziation von Folgeerkrankungen, deren Risiko mit der Prävalenzdauer und dem Schweregrad der Adipositas ansteigt (Tab. 28.1). Dabei korreliert das kardiovaskuläre Risiko besonders mit dem Vorliegen einer viszeralen Adipositas (>88/102 cm Taillenumfang bei Frauen/ Männern). Die Prävalenz der Adipositas steigt in Deutschland kontinuierlich an. Derzeit ist knapp ein Viertel der deutschen Bevölkerung als adipös einzustufen."
6829,Pesticides,
6830,Predicting RNA Secondary Structures: One-grammar-fits-all Solution,"RNA secondary structures are known to be important in many biological processes. Many available programs have been developed for RNA secondary structure prediction. Based on our knowledge, however, there still exist secondary structures of known RNA sequences which cannot be covered by these algorithms. In this paper, we provide an efficient algorithm that can handle all RNA secondary structures found in Rfam database. We designed a new stochastic context-free grammar named Rectangle Tree Grammar (RTG) which significantly expands the classes of structures that can be modelled. Our algorithm runs in O(n (6)) time and the accuracy is reasonably high, with average PPV and sensitivity over 75%. In addition, the structures that RTG predicts are very similar to the real ones."
6831,Infectious Complications of Transplantation,"Post-transplant infection is a common cause of graft deterioration, morbidity and mortality. It is also responsible for delayed discharge, multiple, often prolonged admissions and thus a significant clinical challenge. Infections can be donor derived, pre-existing in the recipient, nosocomial and opportunistic. For each of these categories, it is often possible to significantly reduce hazard and thus the adverse consequences by first identifying patients at high risk. As always, clinical vigilance is vital, but equally important is the establishment of robust clinical systems for prevention, screening and rapid treatment."
6832,Immunohistochemical Staining for Detection of Porcine Epidemic Diarrhea Virus in Tissues,"Porcine epidemic diarrhea virus (PEDV), a member of the genus Alphacoronavirus, has resulted in significant economic losses in the European, Asian, and North American swine industries in previous years. PEDV infection causes acute diarrhea/vomiting, dehydration, and high morbidity and mortality in seronegative neonatal piglets. In this chapter, materials and methods for performing immunohistochemistry (IHC) for the detection of PEDV antigens in frozen or formalin-fixed, paraffin-embedded (FFPE) tissues are provided. In IHC of frozen tissues where viral antigens are well preserved, the use of specific antibodies labeled with fluorescence dyes provides excellent advantages and convenience, resulting in high sensitivity and specificity of IHC and reduction of operation time. In IHC of FFPE tissues where tissue or cell morphology is well preserved, the use of specific antibodies labeled with enzymes, such as alkaline phosphatase, also gives rise to significant advantages in defining the correlation of viral antigens with histopathologic lesions. PEDV antigens in frozen tissues are visualized as green staining in the cytoplasm of infected cells by fluorescent dyes conjugated with antibodies when activated by exciting light of a specific wavelength under a fluorescence microscope. In FFPE tissues, PEDV antigens are visualized as red staining in the cytoplasm of infected cells by the deposition of the substrate chromogen, Fast Red."
6833,Systemic and Systematic Risk,"The main goal of any risk management practice is to be able to insure an acceptable level of predictability in order to gain a lead-time to mitigate a possible risk. However, until new risk management approaches are employed to fill the gap between the known and unknown, most crises will continue to come as a surprise. Risk is latent until an external event or an internal process will reveal its existence. Predictive analysis is an indispensable tool that can help decision makers preemptively test all possible or even some perceived impossible operational scenarios before a risk transforms into crisis or disaster. To be prepared is a better position than to discover the risk too late for business continuity or disaster recovery measures. In this way, predictive emulation becomes necessary for appropriate risk mitigation."
6834,Diseases with Limited Research of Plant-Based Vaccines,"There are a number of diseases which are important globally in terms of the effect they have on livestock but for which the development of recombinant plant-produced vaccines is preliminary. For many of these diseases such as bovine viral diarrhoea (BVD), bovine rotavirus (BRV), bovine herpes (BoH), transmissible gastroenteritis (TGE) in pigs, infectious bronchitis (IB) in chickens, bluetongue (BT) in sheep, Rift Valley fever (RVF) in sheep and coccidiosis in chickens, commercially available live-attenuated or killed vaccines are available. Although most are effective to varying degrees, there are numerous issues with manufacture and potential reassortment of the vaccine strains. For some diseases such as bovine papillomavirus (BPV) infections and Crimean-Congo haemorrhagic fever (CCHF), there are no commercially available vaccines, and limited studies have been conducted on their development. This chapter discusses some of the research developments in plant-produced vaccine candidates which have potential for further development towards commercialisation."
6835,IDENTIFICATION AND CHARACTERIZATION OF BIOLOGICAL RISKS FOR WATER,"Life on this planet is dependent on water but our health is greatly impacted by the quality of that water. The global water crisis is clear, one only needs to quote the statistics on the billions of people without access to safe water, sanitation and the global estimates of the burden of waterborne disease. The greatest sources of biological contaminants associated with this disease burden in water remains human and animal feces. There is a critical need to develop a science-based program to address both water quantity and quality of water, water uses and discharges. Recommendations to achieve better access to scientific information for decision making include: 1) develop watershed approaches for determining the source and the behaviour of water-borne biological contaminants which can be used within Water Safety Plans, 2) utilize new tools and technologies for measuring the hazards and the exposure within a risk assessment framework and 3) develop a global data base and goals for biological contaminant loading for achieving safe water."
6836,Viral bioinformatics,"Pathogens have presented a major challenge to individuals and populations of living organisms, probably as long as there has been life on earth. They are a prime object of study for at least three reasons: (1) Understanding the way of pathogens affords the basis for preventing and treating the diseases they cause. (2) The interactions of pathogens with their hosts afford valuable insights into the working of the hosts’ cells, in general, and of the host’s immune system, in particular. (3) The co-evolution of pathogens and their hosts allows for transferring knowledge across the two interacting species and affords valuable insights into how evolution works, in general. In the past decade computational biology has started to contribute to the understanding of host-pathogen interaction in at least three ways which are summarized in the subsequent sections of this chapter."
6837,History of Influenza Pandemics,"Influenza pandemics have been amongst the largest and the deadliest epidemics in the history of man, and were observed already in ancient times. For example, records from the fifth century B.C. suggest that influenza pandemics were observed in ancient Greece. In Europe, during the Middle Ages and the Renaissance, numerous concordant reports from different countries describe epidemics of respiratory infections that resemble influenza pandemics. However, it is not possible to be certain that these epidemics were due to influenza. In the twentieth century, three influenza pandemics have occurred, including the deadly Spanish flu pandemic. Modern virology has unravelled the mechanisms of emergence of pandemic viruses, and considerable knowledge on influenza viruses has been accumulated. The picture is now clear: influenza A is a zoonotic virus whose reservoir is in wild birds. In rare cases, these avian viruses are introduced into man and, eventually, become pandemic viruses. Although these mechanisms are now understood, the time frame required for adaptation of the avian virus to its new host remains unknown. Maybe the next pandemic will show us how rapid this adaptation can be."
6838,Environmental Toxicology: Children at Risk,"Children today live in a world that is vastly different from a few generations ago. While industrialization has maximized (for many) children’s opportunities to survive, develop and enjoy high levels of health, education, recreation, and fulfillment, it has also added significant challenges to their development."
6839,Viral Infections of the Central Nervous System,"Viral-mediated central nervous system (CNS) disease is a complex spectrum of clinical syndromes that result from viral tropism and individual immune responses and genetic susceptibility of patients. The epidemiology of the pathogens is constantly influenced by the availability, or non-availability, of health care services; preventative strategies; and the process of globalization, with rapid movement of people, animals and products. It is further complicated by natural disasters, wars and changes in lifestyle. The effects of the neurotropic viruses are discussed against the background of the epidemiology. The pathogenesis is a chain of events with the point of departure when the virus enters the body to spread and reach the different sites of the CNS. The blood-brain barrier and blood-cerebrospinal fluid barrier are then overcome by captivating mechanisms. Once the different viruses have settled at the preferred site or sites, and have sidestepped the initial immune surveillance, the phases of injury commence. The cytopathic effect of the viruses elicits a para- and post-infectious inflammatory response and a vicious circle of continued damage, viral entry and inflammation results in a process not merely of inflammation, but of intense inflammation. The different clinical syndromes are then identifiable and should be interpreted against their own specific and appropriate epidemiological backgrounds. Clinicians face the challenge of problematic management decisions while awaiting results on gravely ill patients and differential diagnostic considerations have to be taken into account. Establishing a diagnosis is a two-tier process: first it requires the integration of cerebrospinal fluid findings, imaging results, electrophysiological studies, serology and ancillary blood tests, for example full blood count, liver function tests and other appropriate microbiological investigations, and then these should be correlated with the clinical condition of the patient. Treatment should be initiated as soon as possible. General treatment principles for stabilizing and maintaining vital functions are crucial and empiric treatment should be initiated as soon as possible. This usually includes a broad-spectrum antibiotic, such as third-generation cephalosporin and acyclovir. As soon as specific etiologies have been excluded antibiotics can be stopped. The use of acyclovir is discussed. In the last section of the chapter specific characteristics of the neurotropic viral families are summarized."
6840,Infectious Diseases and the Kidney in Children,"The kidney is involved in a wide range of bacterial, viral, fungal, and parasitic diseases. In most systemic infections, renal involvement is a minor component of the illness, but in some, renal failure may be the presenting feature and the major problem in management. Although individual infectious processes may have a predilection to involve the renal vasculature, glomeruli, interstitium, or collecting systems, a purely anatomic approach to the classification of infectious diseases affecting the kidney is rarely helpful because most infections may involve several different aspects of renal function. In this chapter, a microbiological classification of the organisms affecting the kidney is adopted. Although they are important causes of renal dysfunction in infectious diseases, urinary tract infections and hemolytic uremic syndrome (HUS) are not discussed in detail because they are considered separately in chapters XX and XX, respectively."
6841,Oligonucleotide and DNA Microarrays: Versatile Tools for Rapid Bacterial Diagnostics,"The rapid and unambiguous detection and identification of microorganisms, historically a major challenge of clinical microbiology, gained additional importance in the fields of public health and biodefence. These requirements cannot be well addressed by classical culture-based approaches. Therefore, a wide range of molecular approaches has been suggested. Microarrays are molecular tools that can be used for simultaneous identification of microorganisms in clinical and environmental samples. Main advantages of microarrays are high throughput, parallelism and miniaturization of the detection system. Furthermore, they allow for both high specificity and high sensitivity of the detection. Microarrays consist of set of probes immobilized on a solid surface. Even though the first application of the microarrays can be seen as relatively recent (Schena et al. 1995), the technology developed rapidly reaching the milestone of 5,000 published papers in 2004 (Holzman and Kolker 2004). This development encompasses both the successful transfer of various technological aspects as well as the expansion of the application scope. The most important technological elements of custom-made platforms as well as the characteristics of the commercially available formats are reviewed in this chapter. Furthermore, application potential is presented together with considerations about quality control."
6842,"Industrial Production of Therapeutic Proteins: Cell Lines, Cell Culture, and Purification","A central pillar of the biotechnology and pharmaceutical industries continues to be the development of biological drug products manufactured from engineered mammalian cell lines. Since the hugely successful launch of human tissue plasminogen activator in 1987 and erythropoietin in 1988, the biopharmaceutical market has grown immensely. In 2014, biotherapeutics made up a significant portion of global drug sales as 7 of the top 10 and 21 of top 50 selling pharmaceuticals in the world were biologics with over US$100 billion in global sales (Table 1, [1])."
6843,The Lung and Its Transplantation and Artificial Replacement,"The human thoracic cavity houses a pair of lungs, the left lung and the right lung. The left lung is slightly smaller (since the heart is placed a bit to the left in the body) and has two lobes, and the right lung is bigger, with three lobes. They are spongy and elastic organs that are broad at the bottom and taper at the top. They consist of air sacs, the alveoli. Many alveoli group together and open into a common space. From this space arise the alveolar ducts, which join together to form bronchioles. The bronchioles connect them to the respiratory tract. The lungs also have blood vessels, the branches of the pulmonary artery and veins (Fig. 15.1)."
6844,Angiotensin II Signaling in Vascular Physiology and Pathophysiology,"Initially recognized as a physiologic regulator of blood pressure and body fluid homeostasis, angiotensin (Ang) II has now been shown in innumerable experiments and clinical studies to contribute to the development and maintenance of cardiovascular disease. Dissection of its signaling mechanisms over the past decades has led to the discovery of several novel concepts, such as tissue-specific metabolism of Ang peptides. Identification and cloning of the various receptors through which Ang II acts on almost all tissues has led to the development of specific pharmacologic inhibitors with proven clinical benefit in patients with cardiovascular disorders. Work on the G-protein-coupled Ang II Type 1 receptor has demonstrated that different receptors interact through oligomerization, compartmentalization, and transactivation, and may explain how Ang II can activate G-protein-independent pathways. Unraveling the downstream effects of Ang II in specific cell types corroborates the importance of the cellular redox state on certain signaling pathways. Finally, the effects of Ang II on cell function and phenotype, such as the expression of inflammatory cytokines and receptors promoting the recruitment of inflammatory cells into vascular tissues, have indicated its role in local inflammation as a general pathogenetic basis of cardiovascular disease. The recognition of Ang II as a contributor to such fundamental pathophysiologic mechanisms, which are believed to be a common pathway for diverse cardiovascular risk factors like hypertension and diabetes, has greatly advanced our knowledge of pathologic signaling in vascular tissues and may help to eventually define novel targets for pharmacologic interventions."
6845,Hemorrhage and Transfusions in the Surgical Patient,"Hemorrhage is the leading cause of intraoperative deaths. Many cardiovascular and hepatobiliary procedures result in massive hemorrhage and postpartum hemorrhage events in labor and delivery place the patient at a high risk for mortality. Gastrointestinal bleeding from diverticulosis, varices, and ulcer disease can result in significant blood loss requiring massive transfusion and resuscitation from hemorrhagic shock. Timely and effective transfusion of blood products is of critical in these scenarios. The frequency in which blood component products are transfused in surgical patients begs for a greater understanding of them. The aim of this chapter is to provide clinicians with a discussion of the current literature on the various blood component products, their indications, and unique hemostatic conditions in the surgical patient. While the majority of data concerning optimal management of acquired coagulopathy and hemorrhagic shock resuscitation is based on trauma patients, many of the principles can and should be applied to the surgical patient (or likely any patient) with profound hemorrhage."
6846,Blood Products Transfusion,"Transfusion of blood products may be required during the perioperative period. Despite a well-established safety record, transfusion of blood and its components is not risk free. Indication for each of the blood components needs to be established based on the laboratory investigation and/or clinical picture. In general terms, when there is a clinical evidence of a deficiency in oxygen-carrying capacity, red cell transfusion should be considered; and in the situations of clinically significant coagulopathy, hemostatic blood products (frozen plasma, platelets, cryoprecipitate, factor concentrates) transfusion should be considered. Complications of blood administration range from rare but severe reactions (hemolytic transfusion reactions) to more common, and also associated with significant morbidity and mortality, such as transfusion-related acute lung injury (TRALI), transfusion-related circulatory overload (TACO), and changes in immune system (transfusion related immunomodulation [TRIM])."
6847,Medical Management of Acute Liver Failure,"Pediatric acute liver failure is a rapidly progressive, life-threatening, and devastating illness in children without preexisting liver disease. Due to the rarity and heterogeneity of this syndrome, there is a significant lack of data to guide evaluation and management of this disease. Most of our practice is extrapolated from adult literature and guidelines. This leads to significant controversies in medical management of acute liver failure in children. With advances in critical care, there has been a tremendous improvement in outcomes with decreased morbidity and mortality; however, there is a dire need for more research in this field. This chapter discusses challenges as well as controversies in diagnostic evaluation and management of this rare but potentially fatal disease. Latest developments in supportive care of liver failure, including advances in the area of liver support systems, are also discussed."
6848,Corynebacterium diphtheriae,Diphtheriebakterium
6849,Medical Classifications and Terminologies,"This chapter presents the different medical classifications and terminologies as ICD diagnosis codes, SNOMED CT, MeSH, UMLS, ATC etc."
6850,Replication Cycle of Astroviruses,"Astrovirus infections cause gastroenteritis in mammals and have been identified as causative agents of diverse pathologies in birds such as hepatitis in ducks and poult enteritis mortality syndrome (PEMS), which causes enteritis and thymic and bursal atrophy in turkeys. Human astroviruses are recognized as the second leading cause of childhood viral gastroenteritis worldwide. Eight traditional astrovirus serotypes have been identified in humans, but recently novel astrovirus strains isolated from humans have been associated with diseases other than gastroenteritis. Herein we summarize our current knowledge of the astrovirus life cycle. Though there are gaps in our understanding of astrovirus replication, similarities can be drawn from Picornaviridae and Caliciviridae virus families. There are, however, unique characteristics of the astrovirus life cycle, including intracellular proteolytic processing of viral particles by cellular caspases, which has been shown to be required for the maturation and exit of viral progeny."
6851,1 Inleiding,"In augustus 2011 wijdde de Journal of the American Medical Association (JAMA) een redactioneel commentaar aan het groeiende probleem van morbide obese kinderen: kinderen die aan een dusdanig ernstige obesitas lijden dat hun gezondheid er direct door wordt bedreigd. In toenemende mate wordt bij deze kinderen zogenoemde bariatrische chirurgie toegepast, waarbij een maagband of een maagbypass wordt aangebracht om de voedselopname te verminderen. In het redactionele commentaar werd de vraag opgeworpen of voor deze kinderen niet een alternatieve benadering moet worden overwogen, namelijk het uit de ouderlijke macht ontzetten van hun ouders. In de Verenigde Staten is dit al een aantal malen daadwerkelijk gebeurd, zoals bij het 4 jaar oude en 138 pond wegende meisje Cory Andis."
6852,RNA Interference: RNAid for Future Therapeutics?,"RNA interference (RNAi) is an evolutionarily conserved phenomenon of double-stranded (ds)RNA-mediated mRNA degradation that leads to the posttranscriptional silencing of the corresponding gene. First reports on RNAi emerged in 1998, and since then, it has become one of the most fascinating fields of molecular biology. RNAi has provided important insights about the diversity of RNA molecules and their implication in many biological processes such as the regulation of developmental genes in eukaryotic organisms. Furthermore, RNAi has rapidly developed into a powerful instrument with a great potential for functional genomics and therapeutic applications by silencing normal and disease-related gene functions. To date, the use of RNAi for genetic-based therapies is widely studied, especially in viral infections, cancers, and inherited genetic disorders. Despite the many unanswered questions on how this technology can be efficiently applied to humans, the development of novel approaches, such as vaccines or novel delivery agents, is certainly one of the major goals in RNAi research."
6853,Advancements in Parasite Diagnosis and Challenges in the Management of Parasitic Infections: A Mini Review,"Intestinal parasitic infections (IPIs) remain a widespread public health concern causing severe implications in both developed and developing countries. Globally, numerous studies have been carried out ranging from various communities to schoolchildren as well as indigenous communities. The infections are commonly caused by helminths (e.g. Ascaris lumbricoides, Trichuris trichiura and hookworm) and protozoa (e.g. Blastocystis hominis, Cryptosporidium sp., Entamoeba histolytica and Giardia duodenalis). Poor sanitation and poverty are some of the factors associated with IPIs. With the ever-increasing impact of IPIs, newer detection approaches have been developed and studied. The efficacy of diagnostic method is crucial to give an accurate identification of these parasites. Recent developments of diagnostic tools such as serology- and molecular-based assays are assisting the conventional method of microscopy in detecting and further confirming current or past infections and the specific species of parasites. Ongoing investigations in parasitic infections using these advanced tools will provide useful information that will enable the evaluation of the effectiveness of the current control program and thus, assist future planning for improved strategies in eradicating these parasitic infections."
6854,22 Levertransplantatie,"In 1963 verrichtte Thomas Starzl in Denver de eerste levertransplantatie bij de mens. In 1966 werden in Nederland de eerste twee (auxiliaire, zie par. 22.3.6) levertransplantaties verricht in Leiden en Arnhem, in 1968 startte Cambridge. Helaas resulteerden de eerste levertransplantaties niet in langetermijnoverleving als gevolg van niet-optimale operatietechniek, matige immuunsuppressie en onbekendheid met complicaties."
6855,Bronchitis and Pneumonia,"The incidence, morbidity, and mortality of both bronchitis and pneumonia are high in older adults and increase with age. The clinical manifestations of bronchitis and pneumonia in older adults may not be typical (e.g., cough, fever, dyspnea). Many older adults, particularly nursing home residents, may present with altered mental status and with or without fever. Obtaining a chest X-ray is often critical to make the distinction between the two clinical entities. Unique risk factors for pneumonia in older adults include multiple comorbidities (e.g., COPD, DM, CHF), poor oral hygiene, lack of vaccinations (e.g., S. pneumoniae, influenza), and swallowing difficulty. Empirical treatment decisions for pneumonia should be based on site of care. Recent information suggests that in-home therapy for community dwellers and therapy within the nursing home for long-term care residents is feasible with good outcomes in selected patients. Prevention strategies for pneumonia should be targeted towards providing vaccinations, improving oral hygiene, and improving swallowing difficulty."
6856,Viruses Present Indoors and Analyses Approaches,"Through human history viruses have shown enormous epidemiological and pandemic potential as the occurrence and spread of viruses in pandemic dimensions poses a threat to the health and lives of seven billion people worldwide. Scientific evidence has associated harmful health effects to indoor air hazards recognizing the existence of a vital concern in public health sector. Thus the assessment of human exposure to biological aerosols and droplets indoor became an imperative requirement of investigation. Environmental bioburden assessment of viruses relies in both culture-dependent approaches that comprise classical methodologies, still prominent and vital in the field of modern biotechnology, and culture-independent approaches based on nucleic acid amplification techniques, which are considered the gold standard in clinical virology. The main factor influencing indoor microbiology is the human being and their activities. Indoor environments to be considered are those regularly occupied by humans: residences, offices, schools, industrial buildings, health care facilities, farming activities and other settings occupied all the time, or in which occupant density is high. It’s well known that approximately 60% of total human respiratory and gastrointestinal infections are acquired indoor, since viruses have a rapid spread in the community and can be transmitted easily, especially in crowded and poorly ventilated environments, causing high morbidity and decline in quality of life and productivity. Studies have shown that respiratory syncytial virus, rhinovirus, metapneumovirus, influenza and parainfluenza virus, and human enterovirus infections may be associated with virus-induced asthma, leading to diseases such as pneumonia. Gastroenteritis infectious (about 30±40% of cases) is attributable to viruses. Rotavirus, Astrovirus, Norwalk-like viruses and other caliciviruses are responsible for 48% of all reported outbreaks of infectious intestinal disease. Safe working conditions are essential for healthy living, that’s why the programmes conceived as a result of strategic and preventive policy maintenance, in refrigeration and ventilation systems, are the determining factor for the control of biological pollutants. Moreover, the development of highly sensitive and specific detection and identification methodologies with capacity to be used in diverse applications, such as diagnosis, public health risk assessment, research and for the implementation of preventive measures and protocols are imperative."
6857,Diagnosis and Monitoring of Infections,"As molecular techniques for identifying and detecting microorganisms in the clinical microbiology laboratory have become routine, questions about the cost of these techniques and their contribution to patient care need to be addressed. Molecular diagnosis is most appropriate for infectious agents that are difficult to detect, identify, or test for susceptibility in a timely fashion with conventional methods. During the last 10 years, the detection of infectious disease agents has begun to include the use of nucleic acid-based technologies. Diagnosis of infection caused by parasitic organisms is the last field of clinical microbiology to incorporate these techniques and molecular techniques (e.g., PCR and hybridization assays) have recently been developed for the detection, species differentiation, and phylogenetic analysis."
6858,Management of Burns and Anesthetic Implications,Burn injuries are highly complex and affect almost every major organ system in the body. The treatment of burn patients requires the presence of a well-organized team of caregivers who understand the multifaceted consequences of burn injuries and who are adept at coordinating care. An understanding of the multitude of abnormalities that must be addressed helps to guide therapy in these patients. Careful anesthetic and perioperative management of these patients carries special importance in this fragile patient population as a part of their often lengthy recovery and rehabilitation.
6859,Case Study – Italy,"After the peak of interest in 2001, the threat of bioterrorism is now considered just one of the diverse risks Italy’s society faces endangering public health. Without major investments, the effort has been to integrate existing resources, to implement tight links among national and supranational agencies and to make plans for their most efficient involvement in case of need. The mainstay for the response to a biological attack is represented by the public health system, entrusted to Italy’s national health service, centrally coordinated but put into action by the Regions. The emerging threat of emerging infectious diseases and of bioterrorism has shown the need for a change in the education curricula of sanitary professions and for specific training of first line operators. Specific courses have been activated by universities and other bodies, but attendance has been limited by the lack of ad hoc funds."
6860,Viren überlisten: Globale Virusinfektionen werden beherrschbar – aber neue Gefahren drohen,"Infektionen begleiten und beschäftigen die Menschheit seit vielen Jahrhunderten. Derzeit zählen allein fünf von den zehn häufigsten Todesursachen weltweit zu den Infektionskrankheiten. Oft ausbruchsartig haben besonders Viruserkrankungen seit dem Beginn aufgezeichneter Historie viele Todesopfer gefordert, so zum Beispiel die „Spanische Grippe“ 1918 (Influenzavirus), AIDS (Human Immunodeficiency Virus) und erst vor Kurzem in bisher nie gesehenem Ausmaß das Ebolavirus. Warum besonders virale Erreger für die Wissenschaft ein große Herausforderung darstellen und wie virale Erreger das menschliche Immunsystem überlisten, zeigen die folgenden Überlegungen. Das Kapitel beschreibt darüber hinaus an konkreten Beispielen erfolgreiche Gegenmaßnahmen im Kampf gegen Viren."
6861,Population and Public Health,"The role of public health is to contribute to the health of the public through assessment of health and health needs, policy formulation, and assurance of the availability of services. While the scope of a medical manager’s work and training is different from that of a public health physician, most will often find that their work overlaps quite significantly, especially when the manager’s influence starts to go beyond his or her own organisation. It is thus important for medical managers who contribute to the development of health systems, to understand key public health issues that face Australia in the coming years."
6862,5 Koorts bij volwassenen,"Koorts wordt bij niet-immuungecompromitteerde volwassenen in de eerste lijn zonder recent verblijf in het buitenland meestal veroorzaakt door een luchtweginfectie. Bij ouderen vormen urineweginfecties een relatief frequente oorzaak van koorts. Bij ontbreken van richtinggevende voorgeschiedenis, klachten of verschijnselen volstaat men in eerste instantie met lichamelijk onderzoek van KNO-gebied en longen. Bij negatieve bevindingen volgt urineonderzoek. Wanneer geen afwijkingen gevonden worden, gaat men uit van een onschuldige virale oorzaak. Bij een ernstig zieke indruk of verminderd bewustzijn is het lichamelijk onderzoek allereerst gericht op eventuele stoornissen in de vitale functies, omdat deze onmiddellijke therapeutische implicaties hebben. Als de koorts een week aanhoudt of eerder bij verandering van het beeld, dient een uitgebreide anamnese en algemeen lichamelijk onderzoek plaats te vinden om diagnostische aanknopingspunten op te sporen. Ook kan de arts dan aanvullend onderzoek laten verrichten: in eerste instantie bloed-, urine- en fecesonderzoek en een X-thorax, eventueel gevolgd door X-sinussen en een mantouxreactie. Medicatie wordt zoveel mogelijk gestaakt om een allergie aan te tonen of uit te sluiten. Na enkele dagen herhaalt men anamnese en lichamelijk onderzoek. Twee weken onbegrepen koorts is reden voor verdere (poli)klinische evaluatie. Concrete aanwijzingen op grond van steeds herhaalde anamnese en lichamelijk onderzoek zijn richtinggevend voor de inzet van complex aanvullend onderzoek. Dit bestaat onder meer uit bloedkweken, uitgebreider bloedonderzoek, leverbiopsie, beenmergpunctie en CT-scan buik en thorax. Bij patiënten ouder dan 55 jaar met koorts en een verhoogde bezinking is een biopsie van de arteria temporalis zinvol."
6863,Identity Health,"Identity health has especially specific meanings for social relationships in contemporary digital age. First, computerized digital communication makes many citizens in severe maladaptation. The WHO often warns mental addictions of internet usages and online gaming among the youth. The advent of social media and online networking has endangered them in ambiguous situations which are not stabilizing in those basic grounds for human relationships. Further, because social networking sites and social gaming frequently enforce each member to interconnect with the others, many of participating members often hold harder mental debts to respond and maintain their interconnections. In this situation, in other words, it can say that all of users simultaneously might share common conditions under mental illness."
6864,The Role of T Cells in Corona-Virus-Induced Demyelination,"Mice infected with neurotropic strains of coronavirus develop acute encephalomyelitis and eliminate infectious virus. However, control of acute infection is incomplete resulting in persistence of viral RNA in the central nervous system (CNS) associated with ongoing primary demyelination. A high prevalence of virus specific CD8 and CD4 T cells within the CNS correlates with ex vivo cytolytic activity and IFN-γ secretion, which are both required for virus reduction during the acute infection. Although most infected cell types are susceptible to perforin mediated clearance, IFN-γ is required for controlling infection of oligodendrocytes. Furthermore, by enhancing class I expression and inducing class II expression within resident CNS cells IFN-γ optimizes T cell receptor dependent functions. In addition to its direct anti viral activity, these multifactorial effects make IFN-γ more essential than perforin for viral control. CD4 T cells enhance CD8 T cell expansion, survival and effectiveness. Although both CD8 and CD4 T cells are retained within the CNS during persistence, they cannot control viral recrudescence in the absence of humoral immunity. Demyelination can be mediated by either CD8 or CD4 T cells; however, although a variety of effector molecules have been excluded, a dominant common denominator remains elusive. Thus concerted efforts to control infection coincide with a variety of potential mechanisms causing chronic demyelinating disease."
6865,Apoptosis in Critical Illness: A Primer for the Intensivist,"The complexities of the cell cycle have occupied a prominent place in the history of cellular biology. Recognition of the process of mitosis dates back over a century, when Fol, Butschli, and Strasburger identified a network of intracellular points and lines, then called the karyokinetic figure, and today known as the mitotic apparatus. This discovery, dating to 1873, laid the foundation for the discovery of chromosomes and, later, the fundamental biologic processes of mitosis and meiosis [1]. But, while cellular growth and proliferation were understood to be essential to the emergence of multicellular organisms, the corollary — that controlled cell death must be part of this calculus of cellular homeostasis — was not appreciated until quite recently. Although cell death was first described in 1859 by Virchow, it took more than a century to appreciate the importance of programmed cell death as a physiological process that eliminated unwanted cells [2]. The term ‘apoptosis’ was coined in 1972 by Kerr, Wyllie, and Currie to describe a distinct type of cell death characterized by the degradation of cellular constituents into membrane-bound apoptotic bodies [3]. Since then, recognition of the importance of apoptosis in health and disease, and an understanding of its cellular mechanisms, has increased exponentially."
6866,"The Genetics of Sepsis: The Promise, the Progress and the Pitfalls","Physicians are used to taking a family history of cardiovascular disease because of the known significant hereditary risk; yet the familial risk of dying from infection is even greater than that for atherosclerotic disease (Sorensen et al. 1988). There is certainly no doubt that genetic differences impact on the risk of developing or dying from infection. Obvious but rare examples include selective immunoglobulin deficiencies, complement deficiencies, and neutrophil function abnormalities. Genetic factors may also be protective, such as with sickle cell trait and malaria or mutations conferring resistance to human immunodeficiency virus infection. Much more subtle differences in immune responses are now being described, usually as the result of one or more single nucleotide polymorphisms (SNP) in a gene. Rather than causing the failure of production of a protein or the production of a nonfunctional protein, SNPs are usually associated with changes in the rate of transcription, producing a much less severe phenotype than the classical examples of genetic defects mentioned above. It is now being appreciated that for many complex diseases, such as sepsis, the ultimate phenotype is the result of the interaction of genetic differences across many loci, not the dominant effect of a few key mutations. As seen in Fig. 3.1, since the mid 1990s, an increasing body of literature has focused on the role that gene polymorphisms in key inflammatory genes play in sepsis. Indeed, with advances in knowledge of the human genome, greater understanding of the inflammatory response, and the development of high throughput genotyping technologies, so many genetic associations have been described that discussion of each one is well beyond the scope of this chapter. I will however summarize those findings that have been reported by multiple groups, as well as give an overview of the major groups of genes that have been implicated in genetic predisposition to sepsis and its adverse outcomes."
6867,Lung Transplantation for Idiopathic Pulmonary Fibrosis,"Despite advances in the development of novel pharmaceutical agents to treat idiopathic pulmonary fibrosis (IPF), there are no medical therapies known to resolve fibrosis or improve lung function in IPF. Therefore, lung transplantation remains the only life-saving therapy available to treat patients with IPF. However, a shortage of suitable donor organs limits the number of affected individuals who can undergo this procedure, and this shortage highlights the need to allocate donor lungs to those who are in the greatest need of a life-saving therapy yet ensure that those who undergo transplantation will have a reasonable expectation of long-term survival. Still, outcomes remain relatively poor for many patients after lung transplantation, although a sizable minority of patients can enjoy long-term survival after lung transplantation."
6868,Severe Sepsis and Septic Shock,"This chapter reviews the remarkable recent advances in the understanding of the molecular basis that underlies the pathophysiology of sepsis. This knowledge has improved diagnostic techniques and introduced new therapeutic agents into the standard management of patients with severe sepsis/septic shock. The current treatment regimens for sepsis are discussed, and the evidence to support each major treatment strategy is outlined in detail. Research priorities to further the optimal management of septic shock in the future are highlighted."
6869,Mechanisms of Acute Liver Failure,"Acute liver failure is characterized by the sudden onset of liver failure in a patient without evidence of chronic liver disease. This definition is important, as it differentiates patients with acute liver failure from patients who suffer from liver failure owing to end-stage chronic liver disease."
6870,Vitamin D: Photobiological and Ecological Aspects,"Vitamin D was discovered as a result of its ability to cure rickets, but recently a wide range of other functions for it in the human body has been suggested. Vitamin D is not a vitamin in the strict sense as it can be synthesised in the human body following exposure of the skin to ultraviolet radiation. Provitamin D (7-dehydrocholesterol) is converted to previtamin D which is further modified by a series of reactions to the active form, 1,25-dihydroxyvitamin D. This Chapter summarises the discovery of vitamin D and reviews the chemistry and photochemistry of its precursors, transformations and metabolites. The production of vitamin D in various human populations is described, and how to assess vitamin D status. The skeletal and non-skeletal effects of vitamin D are discussed, particularly its role in immunomodulation with consequences for protection against a variety of human diseases. The Chapter concludes with evolutionary aspects, the occurrence and role of vitamin D in the plant kingdom, biogeographical considerations, and the nonphotochemical production of vitamin D in certain plants."
6871,Preventing Airborne Disease Transmission: Implications for Patients During Mechanical Ventilation,"The organisms causing respiratory infections such as influenza are spread in droplets or aerosols or by direct or indirect contact with contaminated surfaces. Certain medical procedures have been termed aerosol generating because they are associated with high or augmented inspiratory and expiratory flows, which can increase microbial dissemination. Invasive ventilation maneuvers and noninvasive ventilation (NIV) fall into that category. We discuss the risk of transmitting these procedures and the strategies for mechanical ventilation in future airborne epidemics with special consideration given to the issue of protecting health care workers (HCWs)."
6872,Infections Diseases in the Context of Terrorist Threat,"From the great number of pathogenic and conventionally pathogenic for human beings microorganisms, only some of them can be used for terroristic purposes, since they should meet a lot of the relevant properties. Today priority is given to those biological agents, which have undergone successful tests, and are characterized by high index of morbidity, pathogenicity, low lethal doses, high contagiousness with short incubation period, and which result in high social and economic costs."
6873,Otitis Media and Sinusitis,"Otitis media (OM) and sinusitis are common and costly maladies that are often preceded by the development of a viral upper respiratory infection (vURI). Although antibiotics have been shown to be somewhat effective in the treatment of these disorders, increasing concern over the emergence of pathogen resistence to these agents underscores the need for the development of other treatment options, including agents to treat and/or prevent vURIs. Earlier research implicated roles for cytopathology, cellular infiltration, and inflammatory mediators such as bradykinin, in the pathogenesis of vURIs and its complications, including OM and sinusitis, but these factors are now recognized as late events with specific and limited contributions to disease expression. Current therapies are relatively ineffective and aimed at reducing symptoms rather than moderating underlying mechanisms. Nasal elevations of proinflammatory cytokines and leukotrienes track symptom expression during vURIs, and it is hypothesized that these chemicals orchestrate a common response to infection with many different viruses causing vURIs. Moreover, recent evidence demonstrates that specific cytokine gene polymorphisms may modulate the severity of illness and incidence of complications during episodes of vURI. Additionally, other evidence supports a role for neurogenic inflammation in the development of complications. Future studies should dissect the role of proinflammatory cytokines, leukotrienes, and neuropeptides in the expression of symptoms, signs, pathophysiologies, and complications of vURIs."
6874,Virological Synapse for Cell-Cell Spread of Viruses,"Cell-to-cell spread of retroviruses via virological synapse (VS) contributes to overall progression of disease. VS are specialized pathogen-induced cellular structures that facilitate cell-to-cell transfer of HIV-1 and HTLV-1. VS provide a mechanistic explanation for cell-associated retroviral replication. While VS share some common features with neurological or immunological synapses, they also exhibit important differences. The role of VS might not be limited to human retroviruses and the emerging role of a plant synapse suggests that VS might well be conserved structures for cell-cell spreading of both animal and plant viruses. Dissection of the VS is just at its beginning, but already offers ample information and fascinating insights into mechanisms of viral replication and cell-to-cell communication."
6875,"Chemical, Biological, Radiological and Nuclear (CBRN) Casualty Management Principles","Chemical, biological, radiological or nuclear (CBRN) weapons have been used since antiquity. Examples of their recent use include war fighting, ethnic conflict, terrorism and assassination. In addition, CBRN incidents have also included accidental releases during peace time operations, and many of the principles for CBRN incident response can be applied to other hazardous material (HAZMAT) incidents. The impact of such weapons may have a range of implications for medical personnel both military and civilian."
6876,Acute Disseminated Encephalomyelitis,"Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disease of central nervous system (CNS). ADEM is most commonly seen in children, although adults can also be affected. The disease typically starts with an abrupt onset within day to weeks after a viral infection or immunization. Presenting features include an acute encephalopathy with multifocal neurologic signs and fever. ADEM generally has a monophasic course, although recurrent ADEM has also been described and is defined as multiphasic ADEM. MRI shows widespread lesions located in both brain and spinal cord. An involvement of basal ganglia and thalami has also been described. Analysis of cerebrospinal fluid (CSF) may reveal mild lymphocytic pleocytosis and increased proteins, whereas oligoclonal bands are usually negative. In the absence of specific biologic markers, ADEM remains a diagnosis of exclusion and it is still based on clinical manifestations, imaging, and laboratory features. Therapy is based on steroid administration and the prognosis is usually favorable."
6877,The Efficacy of Vaccines to Prevent Infectious Diseases in the Elderly,"Infectious diseases still represent a major challenge to human progress and survival. Especially elderly persons are more frequently and severely affected by infectious diseases and they display distinct features with respect to clinical presentation and treatment. Although vaccinations are considered a vital medical procedure for preventing morbidity and mortality caused by infectious diseases, the protective effect of vaccinations is abrogated in elderly persons. This is due to a decline in the functions of the immune system referred to as immunosenescence. The first part of this chapter will therefore summarize the status quo of the efficacy of vaccines in preventing morbidity and mortality caused by typical infectious diseases in the elderly, such as influenza, pneumonia and tuberculosis. The second part will then elucidate the underlying age-related mechanisms which may contribute to the decreased efficacy of vaccines. Based on the complex mechanisms involved in immunosenescence, strategies will be outlined which may be succesfful in enhancing protective immune responses following vaccination in elderly persons."
6878,The Role of the Renin-Angiotensin System in Hepatic Fibrosis,
6879,Risk Communication and the Community Response to a Bioterrorist Attack: the Role of an Internet-Based early warning system A.K.A “The Informal Sector”,
6880,Modification of Bone Marrow Stem Cells for Homing and Survival During Cerebral Ischemia,"Over the last decade, major advances have been made in stem cell-based therapy for ischemic stroke, which is one of the leading causes of death and disability worldwide. Various stem cells from bone marrow, such as mesenchymal stem cells (MSCs), hematopoietic stem cells (HSCs), and endothelial progenitor cells (EPCs), have shown therapeutic potential for stroke. Concomitant with these exciting findings are some fundamental bottlenecks that must be overcome in order to accelerate their clinical translation, including the low survival and engraftment caused by the harsh microenvironment after transplantation. In this chapter, strategies such as gene modification, hypoxia/growth factor preconditioning, and biomaterial-based methods to improve cell survival and homing are summarized, and the potential strategies for their future application are also discussed."
6881,Toxic Shock Syndromes,"Staphylococcal toxic shock syndrome (TSS) was first described in seven children aged 8–17 years by Todd et al. in 1978 [1]. It shortly thereafter became well known as an illness of menstruating women who used tampons [2, 3]. The syndrome is characterized by rapid onset of fever, hypotension, and multisystem failure with desquamating rash occurring in convalescence [4]. The majority of early cases reported were menstrually associated (MTSS) but this has been changing with an increasing proportion of cases non-menstrually associated (NMTSS) [5]."
6882,Gefährderkonzepte im Bereich des Terrorismus,"Die Terrorismusbekämpfung ist der Bereich, anhand dem sich die in dieser Studie erforschte Strategie zur Prävention von schwerer Gewalt am besten schildern lässt. Die gezielte Sicherheit gegen die Drohung von Terroranschlägen hat zu einer kontinuierlichen Einführung von gesetzlichen Vorschriften und der Entwicklung von Praktiken der Sicherheitsbehörden geführt."
6883,Vegetables,"The conscious promotion of health by an appropriate, balanced diet has become an important social request. Vegetable thereby possesses a special importance due to its high vitamin, mineral and dietary fibre content. Major progress has been made over the past few years in the transformation of vegetables. The expression of several genes has been inhibited by sense gene suppression, and new traits caused by new gene constructs are stably inherited. This chapter reviews advances in various traits such as disease resistance, abiotic stress tolerance, quality improvement, pharmaceutical and industrial application. Results are presented from most important vegetable families, like Solanaceae, Brassicaceae, Fabaceae, Cucurbitaceae, Asteraceae, Apiaceae, Chenopodiaceae and Liliaceae. Although many research trends in this report are positive, only a few transgenic vegetables have been released from confined into precommercial testing or into use."
6884,The SARS Coronavirus receptor ACE 2 A potential target for antiviral therapy,
6885,Adenovirus-Based Vectors for the Development of Prophylactic and Therapeutic Vaccines,"Emerging and reemerging infectious diseases as well as cancer pose great global health impacts on the society. Vaccines have emerged as effective treatments to prevent or reduce the burdens of already developed diseases. This is achieved by means of activating various components of the immune system to generate systemic inflammatory reactions targeting infectious agents or diseased cells for control/elimination. DNA virus-based genetic vaccines gained significant attention in the past decades owing to the development of DNA manipulation technologies, which allowed engineering of recombinant viral vectors encoding sequences for foreign antigens or their immunogenic epitopes as well as various immunomodulatory molecules. Despite tremendous progress in the past 50 years, many hurdles still remain for achieving the full clinical potential of viral-vectored vaccines. This chapter will present the evolution of vaccines from “live” or “attenuated” first-generation agents to recombinant DNA and viral-vectored vaccines. Particular emphasis will be given to human adenovirus (Ad) for the development of prophylactic and therapeutic vaccines. Ad biological properties related to vaccine development will be highlighted along with their advantages and potential hurdles to be overcome. In particular, we will discuss (1) genetic modifications in the Ad capsid protein to reduce the intrinsic viral immunogenicity, (2) antigen capsid incorporation for effective presentation of foreign antigens to the immune system, (3) modification of the hexon and fiber capsid proteins for Ad liver de-targeting and selective retargeting to cancer cells, (4) Ad-based vaccines carrying “arming” transgenes with immunostimulatory functions as immune adjuvants, and (5) oncolytic Ad vectors as a new therapeutic approach against cancer. Finally, the combination of adenoviral vectors with other non-adenoviral vector systems, the prime/boost strategy of immunization, clinical trials involving Ad-based vaccines, and the perspectives for the field development will be discussed."
6886,Strategic Actionable Net-Centric Biological Defense System,"Technologies required for strategic actionable net-centric biological defense systems consist of : 1) multiplexed multi-array sensors for threat agents and for signatures of the host response to infection; 2) novel vaccines and restricted access antivirals/bacterials to reduce emergence of drug resistant strains pre- and post-event; 3) telemedicine capabilities to deliver post-event care to 20,000 victims of a biological strike; and 4) communication systems with intelligent software for resource allocation and redundant pathways that survive catastrophic attack. The integrated system must detect all threat agents with minimal false positive/negative events, a seamless integrated broad-band communications capability that enables conversion of data to actionable information, and novel pre- and post-event treatments. The development of multiplexed multi-array sensors, appropriate vaccines and antibiotics, and integrated communication capabilities are critical to sustaining normal health, commerce, and international activities."
6887,Streptococcal Infections,"The streptococci are a large heterogeneous group of gram-positive spherically shaped bacteria widely distributed in nature. They include some of the most important agents of human disease as well as members of the normal human flora. Some streptococci have been associated mainly with disease in animals, while others have been domesticated and used for the culture of buttermilk, yogurt, and certain cheeses. Those known to cause human disease comprise two broad categories: First are the pyogenic streptococci, including the familiar β-hemolytic streptococci and the pneumococcus. These organisms are not generally part of the normal flora but cause acute, often severe, infections in normal hosts. Second are the more diverse enteric and oral streptococci, which are nearly always part of the normal flora and which are more frequently associated with opportunistic infections."
6888,Reverse Genetics of Mononegavirales: The Rabies Virus Paradigm,"The neurotropic rabies virus (RABV) is a prototype member of the Mononegavirales order of viruses and is the most significant human pathogen of the Rhabdoviridae family. A reverse genetics system for RABV was established almost 20 years ago, providing a paradigm for other Mononegavirales members as well. The availability of engineered recombinant viruses opened a new era to study common aspects of Mononegavirales biology and specific aspects of the unique lifestyle and pathogenesis of individual members. Above all, the knowledge gained has allowed engineering of beneficial biomedical tools such as viral vectors, vaccines, and tracers. In this chapter, the development of the classical rabies virus reverse genetics approach is described, and some of the most exciting biomedical applications for recombinant RABV and other Mononegavirales are briefly addressed."
6889,Extracorporeal Circulation Membrane Oxygenation Therapy for Acute Respiratory Diseases,"Extracorporeal circulation membrane oxygenation provides pulmonary and/or cardiac support over a limited period of time for severe reversible cardio pulmonary diseases. It is an invasive technique with large risks associated but an improved survival rate of around 80%. It has strict selection criteria for neonatal and pediatric patients. The main complications are hemorrhage, stroke, convulsions, cardiac failure, kidney failure, arterial hypertension, and hemolysis. Extracorporeal circulation membrane oxygenation must be implemented only in high-complexity neonatal and pediatric centers with trained personnel."
6890,Infections of the Liver,"The portal vein carries blood from the gastrointestinal tract to the liver and in so doing carries microbes as well. The liver may therefore be involved in infections with a myriad number of microbial organisms. While some of these infections most commonly occur in the immunocompromised host, others affect the immune competence. Hepatic infections may be primary in nature or secondary, as part of systemic or contagious disease. The purpose of this chapter is to provide a brief overview of the various infections of the liver in the pediatric patient."
6891,Lungenerkrankungen,
6892,Economic Migrants and Health Vulnerability,
6893,GIS in Health and Human Services,"The chapter begins with a general overview of how GIS has evolved in the health and human services over the last several decades providing readers with important definitions and descriptions (Sects. 29.1, 29.2). Sections 29.3, 29.4 uncovers how GIS became an important tool for epidemiologists in the work of tracking infectious diseases and perfecting the study of population health. Readers will also learn that GIS adoption by hospital marketers and planners in the United States accelerated rapidly after the 1970, when US Census data became relatively freely available in digital form. The importance of the legendary work of the Dartmouth Health Care Atlas Project and its founder Jack Wennberg. In areas where high GIS adoption rates occurred, such as in public health, we feature key applications such as immunization management, disease tracking, outbreak analysis, disease surveillance, syndromic surveillance, emergency preparedness and response, community health assessment, environmental health, chronic disease prevention, and animal and veterinary health. The final Sect. 29.5 describes how GIS education has expanded across the academic fields of public health, healthcare administration, and social services. It is pointed out that the material presented in this chapter is not intended to be an exhaustive examination of the history of GIS, but rather, a brief introduction and overview which will generate further interest and self-discovery."
6894,Acute Chest Diseases: Infection and Trauma,"Acute chest diseases include clinical situations with infectious and traumatic etiology. Pulmonary infection is the most common indication for performing chest radiography. Radiological imaging often confirms the diagnosis and allows the evaluation of the location and extent of infection. Chest radiography is the primary imaging procedure and the starting point for the evaluation of all children with acute chest disease. Accurate interpretation of pediatric chest films also requires a basic understanding of the physiologic and anatomic differences among adults, neonates, and infants and their most important differences will be referred. Characterization of pulmonary infiltrates is important, because patterns of abnormality suggest specific organisms and aetiologies. Although providing evidence suggestive of the causative agent, the chest radiograph cannot confirm viral infection, confirm or exclude bacterial etiology. In fact, in infancy, pneumonia usually produces a combination of alterations of the airspace and interstitium. However, some aspects may be useful in distinguishing between viral and bacterial pneumonia. Close attention to CT technique is crucial for imaging evaluation of pneumonia in pediatric patients, namely those with persistent symptoms and/or progressive symptoms despite medical or surgical therapy, or in immunocompromised patients. CT with low radiation dose technique should be carefully performed in these cases. CT examination with IV contrast is very useful for the evaluation of complications of chest infection. Thoracic trauma in children is rare, only 4–6 % of children are hospitalized following severe trauma. Only a small number of children with trauma have thoracic injury (14 %), but the injuries tend to be of serious nature. About 25–50 % of thoracic trauma cases occur in combination with other trauma locations. Pulmonary contusion and lacerations, tracheobronchial injuries, pneumothorax, and esophageal rupture are referred as the main consequences of trauma. The decision for the appropriate use of imaging techniques must consider the specific case under review. Chest radiography should be the initial screening method. The decision to use CT is determined by the nature of the trauma, the clinical circumstances, and the prediction of future revaluation, always taking into account the radiation dose applied to the child."
6895,Risiko-Akteur-Netzwerke,"Einen Monat nach dem globalen Ausbruch einer bisher unbekannten, jedoch hochgradig ansteckenden und lebensbedrohlichen atypischen „Lungenkrankheit“ – die Rede ist von SARS, einer Krankheit, die zum ersten Mal im Februar 2003 in einer südchinesischen Provinz beobachtet wurde – beschreibt David L. Heymann, Leiter der Abteilung Emerging and other Communicable Diseasesder World Health Organization(WHO), das spezifische Risiko- und Gefahrenpotential des Severe Acute Respiratory Syndrom: „SARS is emerging in ways that suggest great potential for rapid international spread under the favorable conditions created by a highly mobile, closely interconnected world. Anecdotal data indicate an incubation period of 2 to 10 days (average 2 to 7 days), allowing the infectious agent to be transported, unsuspected und undetected, in a symptomless air traveler from one city in the world to any other city having an international airport. Person-to-person transmission through close contact with respiratory secretions has been demonstrated. The initial symptoms are nonspecific and common. The concentration of cases in previously healthy staff and the proportion of patients requiring intensive care are particularly alarming. The „21 century“ disease could have other consequences as well. Should SARS continue to spread, the global economic consequences – already estimated at around US $ 30 billion – could be great in a closely interconnected and interdependent world.“ (WHO 2003: 5)"
6896,The Zincins: Collagen Fiber Processing and Degradation,"This chapter discusses the zinc-containing metalloendoproteinases. These enzymes remodel the stroma during development and around tissues that have been injured or stressed. Section 1 describes the three major classes of metalloproteases, their metal ion cofactors, their functions in biology, and the metzincin catalytic mechanism in procollagen and stromal protein processing. Section 2 describes the astacin and adamalysin metzincin subclasses and how they process procollagen to tropocollagen. Section 3 describes the matrilysin metzincin subclass and their roles in collagen and stromal tissue degradation and in enamel synthesis."
6897,Noninvasive Respiratory Support in Pediatrics,"The conventional management of acute respiratory failure (ARF) consists of endotracheal intubation; this carries potential risks, including ventilator-associated pneumonia and laryngeal-tracheal damage [1,2]. Noninvasive respiratory support (NRS) is an alternative form of respiratory treatment which incorporates various techniques aimed at improving alveolar ventilation, oxygenation, and unloading of the respiratory muscles without the need for an invasive tracheal device. Because of its safety and effectiveness, the use of NRS has been adopted throughout the world. During the last 25 years, NRS techniques have increasingly been used in the treatment of both chronic respiratory failure and ARF in adult patients in several pathological conditions. NRS applied to adults in the acute setting has been found to improve outcome, reduce the rate of intubation, and decrease the rate of complications [3]."
6898,"Coronaviruses and Neuroantigens: myelin proteins, myelin genes","Multiple sclerosis (MS) is an autoimmune disease in which autoreactive T cells specific to central nervous system (CNS) myelin antigens are activated. Although disease etiology remains unknown, coronaviruses are suspected to be involved in MS pathology. Molecular mimicry, the recognition of two antigens by a single immune cell, could be the mechanism explaining the link between a viral infection and MS through activation of myelin-reactive T cells by a virus infection in a genetically predisposed individual. Evidence supporting this hypothesis in humans has been accumulated in our laboratory. Human coronavirus (HCoV) — myelin cross-reactive T-cell lines (TCL) were predominantly found in MS patients compared to patients with other neurological or inflammatory diseases, or healthy controls. Moreover, virus-myelin T cell cross-reactivity was confirmed at the clonal level. Molecular mimicry between infectious pathogens such as the ubiquitous human respiratory coronaviruses could, in genetically susceptible individuals, play a role leading to the development of MS. Together with other possible mechanisms such as bystander effects, epitope spreading or even superantigenic activities, this pathogen-associated immune induction could play a role in maintaining and broadening the autoimmune response associated with MS pathology."
6899,Ziektebeelden van importziekten,"In dit hoofdstuk worden de ziektebeelden op het gebied van de importziekten op een beknopte, heldere wijze behandeld. Het zijn allemaal infectieziekten die in eigen land (= inheems) niet voorkomen, maar tijdens een verblijf in het buitenland (= uitheems) zijn opgelopen. De volgorde van de paragrafen is alfabetisch."
6900,A Social Network Model Based on Topology Vision,"There are many researchers proposed social network models in recent years, and most of them focus on clustering coefficient property of a small-world network and power law degree distribution of a scale-free property. In social network topology, we observed the network is consisted of many nodes with small connectivity and a few high-degree nodes. In the small connectivity part, there are many nodes which have only one degree. Most of past social network models can not generate this part. In this paper, we proposed a social network model based on topology vision and with tunable high hub connectivity. At the same time, we suggested a new characteristic of social network, condensed clustering coefficient, to replace the original clustering coefficient. Finally, this study also includes the analysis of real social network data."
6901,Assessment of Age-Related Decline of Immunological Function and Possible Methods for Immunological Restoration in Elderly,"The immune system plays an important role in protection against infection and cancer, and in the maintenance of the internal environment of the body. However, such important immune functions are known to decline with age in many mammals, including humans. It is a matter of clinical importance that the incidence of various age-associated diseases such as infections, cancer, and vascular disorders increases with a decrease in immunological vigor. The extent of immunologic decline is variable and exhibits wide interindividual variations. Thus, it is important to assess the extent of immunologic decline in both patients suffering from various diseases and in healthy people in order to maintain healthy conditions. To this end, we have developed a scoring system that analyzes immune parameters according to a database of known age-associated immune changes obtained from a healthy population. Using this scoring system, we can combine several different immunological parameters and express the immune status of individuals as a simple numeral. Several methods of immunological restoration were introduced and the magnitude of restoration was evaluated by the quantitative assessment of immunological level."
6902,Inflammation During Virus Infection: Swings and Roundabouts,"Inflammation constitutes a concerted series of cellular and molecular responses that follow disturbance of systemic homeostasis, by either toxins or infectious organisms. Leukocytes modulate inflammation through production of secretory mediators, like cytokines and chemokines, which work in an autocrine and/or paracrine manner. These mediators can either promote or attenuate the inflammatory response and depending on differential temporal and spatial expression play a crucial role in the outcome of infection. Even though the objective is clearance of the pathogen with minimum damage to host, the pathogenesis of multiple human pathogenic viruses has been suggested to emanate from a dysregulation of the inflammatory response, sometimes with fatal consequences. This review discusses the nature and the outcome of inflammatory response, which is triggered in the human host subsequent to infection by single-sense plus-strand RNA viruses. In view of such harmful effects of a dysregulated inflammatory response, an exogenous regulation of these reactions by either interference or supplementation of critical regulators has been suggested. Currently multiple such factors are being tested for their beneficial and adverse effects. A successful use of such an approach in diseases of viral etiology can potentially protect the affected individual without directly affecting the virus life cycle. Further, such approaches whenever applicable would be useful in mitigating death and/or debility that is caused by the infection of those viruses which have proven particularly difficult to control by either prophylactic vaccines and/or therapeutic strategies using specific antiviral drugs."
6903,Imaging of Pulmonary Infections,"Pneumonia is one of the most frequent causes of morbidity and mortality throughout the world. It is the most prevalent community-acquired infection and the second most common nosocomial infectious disorder. Infections may occur in healthy people or individuals with concomitant intrapulmonary or extrathoracic diseases. Pneumonia may develop into a life-threatening condition, especially in immunocompromised patients, in children, and in the elderly."
6904,Infectious Disease Modeling,"Infectious disease models are mathematical descriptions of the spread of infection. The majority of infectious disease models consider the spread of infection from one host to another and are sometimes grouped together as “mathematical epidemiology.” A growing body of work considers the spread of infection within an individual, often with a particular focus on interactions between the infectious agent and the host’s immune responses. Such models are sometimes grouped together as “within-host models.” Most recently, new models have been developed that consider host–pathogen interactions at two levels simultaneously: both within-host dynamics and between-host transmissions. Infectious disease models vary widely in their complexity, in their attempts to refer to data from real-life infections and in their focus on problems of an applied or more fundamental nature. This entry will focus on simpler models tightly tied to data and aimed at addressing well-defined practical problems."
6905,"Allergie, Pathomechanismen, Krankheitsbilder","Etwa ein Fünftel der Bevölkerung industrialisierter Länder leidet an mindestens einer Erkrankung aus dem allergischen Formenkreis. Hierzu gehören neben Manifestationen der Haut und des Gastrointestinaltrakts insbesondere die allergischen Erkrankungen der oberen und unteren Atemwege. Aufgrund der hohen und weiter steigenden Prävalenz von Allergien und den sich hieraus ableitenden volkswirtschaftlichen Belastungen ist die Allergologie in den letzten Jahren mehr und mehr in den Mittelpunkt des allgemeinen Interesses gerückt. Zudem haben neue wissenschaftliche Erkenntnisse zu einer Erweiterung des pathogenetischen Verständnisses insbesondere allergischer Atemwegserkrankungen geführt, die zunehmend auch die therapeutischen Möglichkeiten erweitern."
6906,Specific Adoptive T-Cell Therapy for Viral and Fungal Infections,"Despite advances in anti-infective agents, viral and fungal infections after hematopoietic stem cell transplantation (HSCT) continue to cause life-threatening complications that limit the success of HSCT. Early adoptive T-cell immunotherapy studies showed that administration of allogeneic virus-specific cytotoxic T lymphocytes (vCTL) can prevent and control viral infections and reconstitute antiviral immunity to cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Advances in immunobiology, in vitro culture technology, and current good manufacturing practice (cGMP) have provided opportunities for advancing adoptive cell therapy for viral infections: (1) T cells have been expanded targeting multiple pathogens; (2) vCTL production no longer requires viral infection or viral vector transduction of antigen-presenting cells (APCs); (3) the source of lymphocytes is no longer restricted to donors who are immune to the pathogens; (4) naive T cells have been redirected with chimeric antigen receptor T cells (CARTs) or armed with bispecific antibody-armed T cells (BATs) to mediate vCTL activity; (5) these technologies could be combined to targeted multiple viral or fungal pathogens; and (6) pathogen-specific T-cell products manufactured from third parties and banked for “off-the-shelf” use post-HSCT may soon become a reality."
6907,Devil Facial Tumour Disease (DFTD): Using Genetics and Genomics to Investigate Infectious Disease in an Endangered Marsupial,"The Tasmanian devil (Sarcophilus harrisii), so named for its blood-curdling, nocturnal shrieks and snarls, is the largest of the carnivorous marsupials. Although once widely persecuted, concerted efforts are now being made to save the devil from extinction following the emergence of a fatal transmissible malignancy known as devil facial tumour disease (DFTD). DFTD is unusual in that the infectious agent is the cancer cell itself. This chapter discusses the aetiology and pathogenesis of DFTD as well as the profound impact the spread of DFTD has had on the devil’s conservation status. Strategies for managing DFTD and conserving the devil will be explored and the contribution of new sequencing technology to the field of conservation genetics and genomics will be examined with regard to the Tasmanian devil and DFTD."
6908,The Respiratory Tract,"Cytological investigation of the pulmonary tract is one of the most useful diagnostic tests available to the clinician. A wide range of samples can be provided to the laboratory from a variety of sampling techniques. In many cases, the cytologist can provide a clear diagnosis of malignancy, infection, or other specific disease. Even if a diagnosis cannot be offered, the sample frequently aids the clinician with future management by providing reassurance that tumor is unlikely to be present (in the appropriate clinical and radiological setting). This chapter outlines the various samples that the cytopathologist may be faced with and provides a description of the microscopic features that aid diagnosis."
6909,"Dysbiosis, Probiotics, and Prebiotics: In Diseases and Health","The microbiome like any other components of the body undergoes numerous challenges during the life-span of a human being. These complications may involve injuries, aggression by pathogens, pollution, hormonal variations, genetic pre-disposition, unbalanced nutrition and onset of diseases. Although the microbial reconfiguration provoked by these stressors are not immediately evident as in the case of an afflicted visible organ where the abnormality is readily observable, the biological perturbations induced manifest themselves in form of various illnesses. The disruption of a working microbiome is referred to as dysbiosis and is a condition whereby the fine balance between the microbial communities and the host is distressed. Diseases such as cancer, irritable bowel syndrome, rheumatoid arthritis, acne, gastric ulcers, obesity and hypertension can ensue. The pathogeneses of some pulmonary disorders, digestive complications and neurological abnormalities can be traced to the imbalance in the constituents of the microbiome. However, rebiosis, the re-establishment of the native microbiota is proving to be an excellent remedy against this condition. Probiotics, prebiotics, and synbiotics are potent therapeutic tools designed to rectify this situation. Probiotics such as Lactobacillus spp are more or less like stem cells utilized to replenish and rejuvenate the microbiome while prebiotics like fructose oligosaccharides (FOS) are microbiome fertilizers akin to mineral supplements or energy nutrients aimed at promoting the proliferation of select microbes in the invisible organ. Synbiotics is a combination of both probiotics and prebiotics in a proper dosage aimed at remedying dysbiosis. The molecular understanding of dysbiosis and rebiosis will offer a very effective non-invasive means in preventing and curing diseases with probiotics and prebiotics. This will have a dramatic impact on our well-being."
6910,Procedure diagnostiche invasive nelle malattie infiltrative diffuse del polmone,"Le malattie polmonari che, già all’esordio clinico e/o nel loro decorso, coinvolgono più di un lobo e caratterizzate dall’accumulo od infiltrazione nel lobulo polmonare secondario di sostanze o cellule non normalmente presenti in tale sede o presenti, comunque, in quantità anomala, possono essere definite con il termine di pneumopatie infiltrative diffuse (PID) [1]."
6911,6 Infectieziekten,Infectieziekten (synoniem: infecties) zijn ziekten veroorzaakt door levende micro-organismen. Niet alle ziekmakende micro-organismen kunnen van de ene op de andere mens worden overgedragen; in dat geval zijn de patiënten niet besmettelijk.
6912,Collagen Fabrication for the Cell-based Implants in Regenerative Medicine,"Though transplantation of cells, tissue or organ has been regarded as an ideal approach, scarcity of donor is a practical barrier in clinics. Current progresses in cell engineering has opened a new era, providing tools for host-regeneration by implanting manipulated cells in forms of cell therapy, which includes delivery of single cells or multicellular structural support of hybridized cells, as a representative individualized treatment method. This chapter mainly concerns on the cellbased implant made of cells and collagen, the main structural protein in extracellular matrix in mammalian tissue, as it has been regarded as a promising method for manufacturing a biologically mimicked artificial tissues."
6913,Kindergeneeskunde,"Ieder kind maakt tijdens zijn of haar groei en ontwikkeling ziekten door. Veelal betreft het onschuldige aandoeningen, vaak van infectieuze aard. Meestal zijn deze aandoeningen ‘self-limiting’ en horen ze bij een normale ontwikkeling. De toediening van medicijnen heeft zin als onderdeel van een gerichte behandeling. Het voorschrijven van geneesmiddelen aan kinderen is helaas (nog steeds) zelden onderbouwd door goed wetenschappelijk onderzoek naar de effectiviteit en veiligheid ervan bij kinderen. Veelal zijn het soort en de dosering van geneesmiddelen afgeleid van bekende toepassingen en doseringen bij volwassenen. Een dosering wordt daarbij veelal omgerekend op grond van het lichaamsgewicht. Hoewel dit bij jonge kinderen over het algemeen een goed uitgangspunt is voor het berekenen van de juiste dosering, moet er bij oudere kinderen (globaal boven de acht jaar) rekening worden gehouden met de maximale dosering voor volwassenen, omdat men deze onbedoeld kan overschrijden bij het berekenen van de dosering per kg lichaamsgewicht bij deze (oudere) leeftijdsgroep. Voor pasgeborenen en zuigelingen bestaan vaak aparte doseringsvoorschriften. Het therapeutisch effect en bijwerkingen van veel medicamenten zijn bij zuigelingen vaak anders dan bij kinderen en volwassenen."
6914,Working Group II: The Threat from Armed Conflict and Terrorism,"Both terrorism and armed conflict can be threats to water security, either directly or indirectly. Both forms of violence have used disruption or poisoning of water supplies as a weapon, and both may cause collateral damage to water supplies. The distinction between war and terrorism can be arguable. Special Operations forces may use some tactics similar to terrorists, with similar repercussions for water systems, but the main practical distinction is between formal military actions and more informal, smaller scale guerrilla-style activities that may be directed more at civilian personnel and designed to engender fear and panic as much as specific damage."
6915,CD4 T-Cell Immunity in the Lung,"T helper cells are a distinct lineage of T-cells that can differentiate into the well-characterized subsets, Th1 and Th2 and a newer subset called Th17 cells. Data to date suggest that these cells play specific roles in host defense in the lung and thus, these subsets can also be targeted for vaccine-induced immunity. Here we summarize recent progress in our understanding of these specific T-cell subsets, their effector cytokines, and how these cells regulate host defense against pulmonary infection."
6916,Proteasome inhibitors as complementary or alternative antiviral therapeutics,
6917,Engineering Plants for the Future: Farming with Value-Added Harvest,"Plants and their rich variety of natural compounds are used to maintain and to improve health since the earliest stages of civilization. Despite great advances in synthetic organic chemistry, one fourth of present-day drugs have still a botanical origin, and we are currently living a revival of interest in new pharmaceuticals from plant sources. Modern biotechnology has defined the potential of plants to be systems able to manufacture not only molecules naturally occurring in plants but also newly engineered compounds, from small to complex protein molecules, which may originate even from non-plant sources. Among these compounds, pharmaceuticals such as vaccines, antibodies and other therapeutic or prophylactic entities can be listed. For this technology, the term plant molecular farming has been coined with reference to agricultural applications due to the use of crops as biofactories for the production of high-added value molecules. In this perspective, edible plants have also been thought as a tool to deliver by the oral route recombinant compounds of medical significance for new therapeutic strategies. Despite many hurdles in establishing regulatory paths for this “novel” biotechnology, plants as bioreactors deserve more attention when considering their intrinsic advantages, such as the quality and safety of the recombinant molecules that can be produced and their potential for large-scale and low-cost production, despite worrying issues (e.g. amplification and diffusion of transgenes) that are mainly addressed by regulations, if not already tackled by the plant-made products already commercialized. The huge benefits generated by these valuable products, synthesized through one of the safest, cheapest and most efficient method, speak for themselves. Milestone for plant-based recombinant protein production for human health use was the approval in 2012 by the US Food and Drug Administration of plant-made taliglucerase alfa, a therapeutic enzyme for the treatment of Gaucher’s disease, synthesized in carrot suspension cultures by Protalix BioTherapeutics. In this review, we will go through the various approaches and results for plant-based production of proteins and recent progress in the development of plant-made pharmaceuticals (PMPs) for the prevention and treatment of human diseases. An analysis on acceptance of these products by public opinion is also tempted."
6918,Structural Alignment of Pseudoknotted RNA,"In this paper, we address the problem of discovering novel non-coding RNA (ncRNA) using primary sequence, and secondary structure conservation, focusing on ncRNA families with pseudo-knotted structures. Our main technical result is an efficient algorithm for computing an optimum structural alignment of an RNA sequence against a genomic substring. This algorithm finds two applications. First, by scanning a genome, we can identify novel (homologous) pseudoknotted ncRNA, and second, we can infer the secondary structure of the target aligned sequence. We test an implementation of our algorithm (Pal), and show that it has near-perfect behavior for predicting the structure of many known pseudoknots. Additionally, it can detect the true homologs with high sensitivity and specificity in controlled tests. We also use Pal to search entire viral genome and mouse genome for novel homologs of some viral, and eukaryotic pseudoknots respectively. In each case, we have found strong support for novel homologs."
6919,Insect RNAi: Integrating a New Tool in the Crop Protection Toolkit,"Protecting crops against insect pests is a major focus area in crop protection. Over the past two decades, biotechnological interventions, especially Bt proteins, have been successfully implemented across the world and have had major impacts on reducing chemical pesticide applications. As insects continue to adapt to insecticides, both chemical and protein-based, new methods, molecules, and modes of action are necessary to provide sustainable solutions. RNA interference (RNAi) has emerged as a significant tool to knock down or alter gene expression profiles in a species-specific manner. In the past decade, there has been intense research on RNAi applications in crop protection. This chapter looks at the current state of knowledge in the field and outlines the methodology, delivery methods, and precautions required in designing targets. Assessing the targeting of specific gene expression is also an important part of a successful RNAi strategy. The current literature on the use of RNAi in major orders of insect pests is reviewed, along with a perspective on the regulatory aspects of the approach. Risk assessment of RNAi would focus on molecular characterization, food/feed risk assessment, and environmental risk assessment. As more RNAi-based products come through regulatory systems, either via direct application or plant expression based, the impact of this approach on crop protection will become clearer."
6920,Introducing Ebola (EVD): An Unnecessary Surprise,"Chapter 4 tackles the Ebola (Ebola Virus Disease, EVD) pandemic of 2014/2015. It notes that coming in the wake of the ongoing HIV pandemic, the rights of those infected with Ebola to be identified and treated were largely uncontested. The questions of who would be treated, by whom, with what, remained however extremely contentious. The international response to the pandemic also saw, for the first time, not only non-state actors involved in mediating and mitigating a health crisis, but also military intervention. This chapter lays out both the uses and the dilemmas of military response. It explores the impact of these interventions in this Ebola pandemic, with a view towards possible future military deployments against health threats, and offers an initial analysis of the consequences thereof on the relationship between individual and state rights and responsibilities."
6921,Interstitial Lung Diseases,"The term interstitial lung diseases (ILD) comprises a diverse group of diseases that lead to inflammation and fibrosis of the alveoli, distal airways, and septal interstitium of the lungs. The ILD consist of disorders of known cause (e.g., collagen vascular diseases, drug-related diseases) as well as disorders of unknown etiology. The latter include idiopathic interstitial pneumonias (IIPs), and a group of miscellaneous, rare, but nonetheless interesting, diseases. In patients with ILD, MDCT enriches the diagnostic armamentarium by allowing volumetric high-resolution scanning, i.e., continuous data acquisition with thin collimation and a high spatial frequency reconstruction algorithm. CT is a key method in the identification and management of patients with ILD. It not only improves the detection and characterization of parenchymal abnormalities, but also increases the accuracy of diagnosis. The spectrum of morphologic characteristics that are indicative of interstitial lung disease is relatively limited and includes the linear and reticular pattern, the nodular pattern, the increased attenuation pattern (such as ground-glass opacities and consolidation), and the low attenuation pattern (such as emphysema and cystic lung diseases). In the correct clinical context, some patterns or combination of patterns, together with the anatomic distribution of the abnormality, i.e., from the lung apex to the base, or peripheral subpleural versus central bronchovascular, can lead the interpreter to a specific diagnosis. However, due to an overlap of the CT morphology between the various entities, the final diagnosis of many ILD requires close cooperation between clinicians and radiologists and complementary lung biopsy is recommended in many cases."
6922,The Scientific Challenge,"In the last chapter, I described how a number of argument forms that had traditionally been characterized by philosophers as weak or fallacious modes of reasoning could be shown to facilitate scientific inquiry into BSE when little was known about this new brain disease in cattle. The point was made that these argument forms have relevance to the epidemiologists and public health scientists whose task it was to identify and respond to this emerging infectious disease. However, this point requires some explanatory work if it is to have more than a very general application to the work of these public health professionals. For these professionals might ask with some justification why they should treat seriously argument forms that have been deemed to be logically inadequate by generations of philosophers. They might also wonder if philosophical discussion of reasoning has anything but the most abstract lessons for scientists who are charged with containing infectious diseases. In this chapter, I undertake this explanatory work by arguing that philosophical contributions on reasoning and argument are not only relevant to epidemiology, but that they also represent the very best prospect for investigators of addressing some of the criticisms of epidemiology that have been raised in recent years. These criticisms have been expressed most clearly by Christakos et al. (2005), although other theorists have also added their voices to the exchange."
6923,Protein-Based Bioproducts,"Plant proteins can be used for the production of a variety of bioproducts, including films and coatings, adhesives, fibres and pharmaceuticals. Proteins derived from plant production systems have many advantages: they are safe, low-cost and rapidly deployable, allow for simple product storage and result in proteins that are properly folded, assembled and post-translationally modified. While plant-derived protein-based products are natural, renewable, biodegradable and environmentally friendly, they tend to be lower in strength and elasticity than their corresponding synthetic products. Current research in this area is focused on overcoming challenges in plant production platforms related to yield, purification, regulatory approval and customer acceptance."
6924,The History and Formation of East Asian Sports Leagues,"This chapter considers the creation and growth of professional sport leagues throughout East Asia. In this, the different leagues and sport are examined, and noted for their hybrid use of both North American and European methods of business and regulation of sport leagues. Notably, prominent Japanese, Chinese, South Korean, and Taiwanese sport organizations are covered in their emergence as the top sport businesses within the region. The creation of these leagues varies from the old (Japanese baseball) to the new (Chinese football). As the dynamics of political and economic power has shifted in East Asia in the last several decades, so has the popularity and importance of many of the sport leagues in the region. At the same time, as these leagues have grown, many of the top stars have begun to leave for more popular and competitive leagues in North America and Europe. This chapter concludes in considering the future potential of sport leagues in Asia, and whether the teams and leagues will be able to continue to survive in their current formats."
6925,"Errors, Uncertainty, and Ethical Issues","Various medical giants have admonished us to “do no harm,” and yet as we swim in waters of uncertainty, errors do happen. Physician author Lewis Thomas praises restraint in health care, and Arthur Bloomfield reminds us that in our quest to help some, there are no patients we cannot harm."
6926,Biomarkers of Infectious Diseases,Infection is defined as a pathologic process caused by the invasion of normally sterile tissue or fluid or body cavity by pathogenic or potentially pathogenic microorganisms. Sepsis is defined as the presence of organ dysfunction occurring as the result of a dysregulated host response to an infection.
6927,Artikel von A bis Z,"Nach frühem Tod der Eltern Erziehung in Genf; 1843–1848 Studium in Genf und Berlin, dort Bekanntwerden mit der deutschen Philosophie; Reisen in Frankreich und Italien; 1849 Professur für Ästhetik in Genf; 1854 Professur für Philosophie; Wegbereiter des späten deutschen Idealismus in der frankophonen Welt; wenige Veröffentlichungen (Gedichte und Essays) zu Lebzeiten; Verfasser eines postum veröffentlichten Tagebuchs, das für den Ich-Kult des späteren 19. Jh.s von großer Bedeutung war."
6928,Animal Models of Multiple Sclerosis,"To determine whether an immunological or pharmaceutical product has potential for therapy in treating multiple sclerosis (MS), detailed animal models are required. To date many animal models for human MS have been described in mice, rats, rabbits, guinea pigs, marmosets, and rhesus monkeys. The most comprehensive studies have involved murine experimental allergic (or autoimmune) encephalomyelitis (EAE), Semliki Forest virus (SFV), mouse hepatitis virus (MHV), and Theiler’s murine encephalomyelitis virus (TMEV). Here, we describe in detail multispecies animal models of human MS, namely EAE, SFV, MHV, and TMEV, in addition to chemically induced demyelination. The validity and applicability of each of these models are critically evaluated."
6929,Adenosine Receptors in the Lungs,"The ubiquitous adenine nucleoside adenosine (Ado), which plays an important role in cellular energetics, is released from cells under physiologic and pathophysiologic conditions. Another source of extracellular Ado is rapid degradation of extracellular adenosine 5′-triphosphate (ATP) by ectoenzymes. Extracellular Ado acts as an autocrine and paracrine agent by the activation of G protein-coupled cell surface receptors (GPCRs), designated as A(1), A(2A), A(2B), and A(3). Almost four decades ago, published data have indicated that Ado could play a role in immune-mediated histamine release from pulmonary mast cells. Since then, numerous studies have indicated that Ado’s signal transductions are involved in various pulmonary pathologies including asthma and COPD. This chapter is a succinct review of recent studies in this field."
6930,Rethinking Sepsis: New Insights from Gene Expression Profiling Studies,"Critically ill patients encompass an enormously heterogeneous population and, as such, therapeutic interventions, including drug therapy, can produce multiple outcomes in different patient subgroups. For example, researchers not only look for an ‘average effect’ of a drug on a typical patient, but also seek to understand individual variability. The presence of variability impacts significantly on the success of clinical trials and failure to identify this variability can result in the clinical trial being under-powdered to detect a treatment effect. For clinicians, failure to recognize variability can result in unintended toxicity or excessive harm in certain patients. Hence, understanding variability is critically important in both research and clinical practice."
6931,Promoting an Inclusive Approach to Benefit Sharing: Expanding the Scope of the CBD?,"The Convention on Biological Diversity (CBD) is a major international agreement to ensure the conservation of biological diversity, the sustainable use of various components of biological diversity, and fair and equitable access and benefit sharing of advances arising from the use of related genetic resources. The CBD excludes human genetic resources. In light of the rapid advances in biotechnology, genetic resources are increasingly being utilised by different types of users and in different industries. This usage is not confined to plants, animals or micro-organisms but includes human genetic resources and sometimes a mix of such resources. In the absence of any international agreement, various national governments are framing their own rules and guidelines. This patchwork of regulation may eventually impede global research efforts. This chapter argues that the CBD is qualified to be the central agency at the global level for the advance of broader benefit sharing frameworks. By implication, the scope of the CBD should be expanded to include human genetic resources."
6932,Lung,"The lungs are particularly sensitive to RT, and are often the primary dose-limiting structure during thoracic therapy. The alveolar/capillary units and pneumocytes within the alveoli appear to be particularly sensitive to RT. Hypoxia may be important in the underlying physiology of RT-associated lung injury. The cytokine transforming growth factor-beta (TGF-β), plays an important role in the development of RT-induced fibrosis. The histopathological changes observed in the lung after RT are broadly characterized as diffuse alveolar damage. The interaction between pre-treatment PFTs and the risk of symptomatic lung injury is complex. Similarly, the link between changes in PFTs and the development of symptoms is uncertain. The incidence of symptomatic lung injury increases with increase in most dosimetric parameters. The mean lung dose (MLD) and V20 have been the most-often considered parameters. MLD might be a preferable metric since it considers the entire 3D dose distribution. Radiation to the lower lobes appears to be more often associated with clinical symptoms than is radiation to the upper lobes. This might be related to incidental cardiac irradiation. In pre-clinical models, there appears to be a complex interaction between lung and heart irradiation. TGF-β has been suggested in several studies to predict for RT-induced lung injury, but the data are still somewhat inconsistent. Oral prednisone (Salinas and Winterbauer 1995), typically 40–60 mg daily for 1–2 weeks with a slow taper, is usually effective in treating pneumonitis. There are no widely accepted treatments for fibrosis. A number of chemotherapeutic agents have been suggested to be associated with a range of pulmonary toxicities."
6933,Cibotium barometz,Cibotium barometz plant habit
6934,Fetal and Neonatal Illnesses Caused or Influenced by Maternal Transplacental IgG and/or Therapeutic Antibodies Applied During Pregnancy,"The human fetus is protected by the mother’s antibodies. At the end of the pregnancy, the concentration of maternal antibodies is higher in the cord blood, than in the maternal circulation. Simultaneously, the immune system of the fetus begins to work and from the second trimester, fetal IgM is produced by the fetal immune system specific to microorganisms and antigens passing the maternal-fetal barrier. The same time the fetal immune system has to cope and develop tolerance and T(REG) cells to the maternal microchimeric cells, latent virus-carrier maternal cells and microorganisms transported through the maternal-fetal barrier. The maternal phenotypic inheritance may hide risks for the newborn, too. Antibody mediated enhancement results in dengue shock syndrome in the first 8 month of age of the baby. A series of pathologic maternal antibodies may elicit neonatal illnesses upon birth usually recovering during the first months of the life of the offspring. Certain antibodies, however, may impair the fetal or neonatal tissues or organs resulting prolonged recovery or initiating prolonged pathological processes of the children. The importance of maternal anti-idiotypic antibodies are believed to prime the fetal immune system with epitopes of etiologic agents infected the mother during her whole life before pregnancy and delivery. The chemotherapeutical and biological substances used for the therapy of the mother will be transcytosed into the fetal body during the last two trimesters of pregnancy. The long series of the therapeutic monoclonal antibodies and conjugates has not been tested systematically yet. The available data are summarised in this chapter. The innate immunity plays an important role in fetal defence. The concentration of interferon is relative high in the placenta. This is probably one reason, why the therapeutic interferon treatment of the mother does not impair the fetal development."
6935,The Dynamic World View in Action,"The dynamical system is a mathematical concept motivated first by Newtonian mechanics. The state of the system is generally denoted by a point in an appropriately defined geometrical space. A dynamical system operates in time. Typically, we take the time set T to be the real line R (a continuous-time system) or the set of integers Z (a discrete-time system). We then formalize an autonomous system as a ordered pair (Q, g), where Q is the state space, and g : T × Q → Q is a function that assigns to each initial state x(0) ∈ Q the state x = g(t, x(0)), in which the system will be after a time interval t if it started in state x(0). A fundamental property of g, then, is the validity of the identity g(t + s, x(0)) ≡ g(s, g(t, x(0))) (4.1) for all states x, and times t, s. Loosely speaking g is a fixed rule which governs the motion of the system."
6936,Microbiology,"In order to render an accurate diagnosis, and correctly identify clinically important microorganisms, a good understanding and knowledge of microbiology is essential. This chapter provides a broad overview of microbiology that is relevant to the practicing cytologist. Virology addresses the cytopathic effects caused by viruses and discusses many key infections. Bacteriology covers important bacterial causes of infection including those due to mycobacteria and filamentous bacteria. Mycology deals with common fungi as well as deep mycoses, particularly those caused by invasive and dimorphic fungal organisms. Parasitology highlights the protozoa, apicomplexans, and helminths likely to be seen in cytology samples. Algae are also briefly mentioned."
6937,The Crowded Cytosol,"While, given the expansion of the world population, it cannot be guaranteed that it will always be so, currently one accepts as a temporary discomfort short periods of crowding, as in a crowded elevator or subway train. However, if, like most intracellular macromolecules, one were both blind and deaf, the need to communicate by touch might make crowding an option of choice. It seems likely that the first cells to evolve soon discovered the advantage of intracellular crowding, which persists to this day [2]. Indeed, the physiological environment of enzymes is very different from the environment we can normally create in the test-tube."
6938,Infecties van de luchtwegen en cystische fibrose,"Sereuze of mucopurulente neusuitvloed, passagebelemmering, minimale algemene verschijnselen; meestal geen koorts."
6939,"Human Mobility, Networks and Disease Dynamics on a Global Scale","Disease dynamics is a complex phenomenon and in order to address these questions expertises from many disciplines need to be integrated. One method that has become particularly important during the past few years is the development of computational models and computer simulations that help addressing these questions. In the focus of this chapter are emergent infectious diseases that bear the potential of spreading across the globe, exemplifying how connectivity in a globalized world has changed the way human-mediated processes evolve in the 21st century. The examples of most successful predictions of disease dynamics given in the chapter illustrate that just feeding better and faster computers with more and more data may not necessarily help understanding the relevant phenomena. It might rather be much more useful to change the conventional way of looking at the patterns and to assume a correspondingly modified viewpoint—as most impressively shown with the examples given in this chapter."
6940,"Immune response in human pathology: infections caused by bacteria, viruses, fungi, and parasites","Despite the introduction of effective health measurements, vaccination and antimicrobial therapy infectious diseases continue to threaten human life. The reasons are numerous and diverse: antibiotic resistance, hospital-invading pathogens, new emerging infectious diseases, bioterrorism, biological warfare. This chapter is an introduction to several aspects of infectious diseases viewed from the host as well as from the pathogen (bacterium, virus and parasite). Furthermore the basic principles of INNATE and ADAPTIVE IMMUNE RESPONSES, especially in debilitated patients, are described. Detailed information is given on the pathogenesis of septic shock, AIDS and vaccination strategies."
6941,"Bronchitis, Bronchiolitis und Lungenemphysem","Die Bronchitis wird in die akute und die chronische Erkrankungsform eingeteilt. Bei der chronischen Form müssen zusätzlich das Vorhandensein einer zusätzlichen Atemwegsobstruktion und Sekundärveränderungen, insbesondere das Lungenemphysem, berücksichtigt werden."
6942,Mediator-Based Architecture for Integrated Access to Biological Databases,"The amount of biological information accessible via the internet is growing at a tremendous rate. The biologists often encounter problems in accessing huge amount of widely spread data due to disparate formats, remotely dispersed and varying implementation on different platforms and data models. Besides that, the custom browsing and querying mechanism implemented in different data sources requires the users to uniquely query each individual database. Instead of having different custom interfaces to these public bioinformatics databases, an intuitive common integrated data access method is proposed to provide uniform transparent access to disparate biological databases. The proposed mediator-based architecture consists of three conceptual layers namely Query Formulation, Query Transformation and Query Execution."
6943,"Neurotische, Belastungs- und somatoforme Störungen (F40–F48)","Epidemiologischen Studien zufolge beträgt die durchschnittliche Lebenszeitprävalenz der Zwangsstörung bei Erwachsenen der Allgemeinbevölkerung ca. 2,5 %. Die Punktprävalenz liegt bei etwa 1,5 %. Bei der Zwangsstörung finden sich keine Geschlechterunterschiede in den Häufigkeitsraten."
6944,Unmet Medical Needs and the Role of Pharmaceutical Companies,"Rising health care costs have been prioritized in the budget planning of all Western countries. Rising R&D costs of up to $800 million per marketed new pharmaceutical have dramatically reduced the approval of new chemical entities (NCEs). Globalization of diseases like AIDS and SARS has had a definite impact on the economic situation not only in the Western world, but also in developing countries, especially for AIDS in Africa and SARS in Asia. The World Health Organization (WHO) is calling for free anti-tuberculosis (TB) drugs to be made available to people living with human immunodeficiency virus (HIV). The spread between unmet medical need in large indications (e.g. Alzheimer's disease) and in niche indications (e.g. Huntington disease) and the economic burden to create a blockbuster ($1 billion sales within one year after launch) has created a marketing-driven clinical development of new chemical entities. A paradigm shift has occurred by which developing a new innovative drug by documenting shortterm efficacy, quality and safety rather than long-term efficacy and emphasizing pharma-covilliglance including considerations of health economy within the medical environment a shift that has fundamentally changed and challenged the pharmaceutical industry."
6945,The Golgi apparatus and main discoveries in the field of intracellular transport,"In this chapter, we summarize important findings in the field of intracellular transport, which have considerably contributed to the understanding of the function and organization of the Golgi apparatus (GA). It is not possible to mention all authors in this huge field. We apologize for gaps and incompleteness, and are thankful for suggestions and corrections."
6946,Respiratory Failure in a Patient with Idiopathic Pulmonary Fibrosis,"Idiopathic pulmonary fibrosis, in its advanced stages, commonly causes chronic respiratory failure. Additionally, patients with fibrotic lung disease can develop acute respiratory failure due to a myriad of causes, though one of the most common and most deadly is an acute exacerbation of idiopathic pulmonary fibrosis. In this chapter we review the differential diagnosis for patients with idiopathic pulmonary fibrosis who present with acute respiratory failure. Furthermore, we review the available evidence pertinent to the intensivist when these patients are cared for in the intensive care unit. Lastly, we explore treatment controversies (Extracorporeal Life Support, corticosteroids, non-invasive ventilation strategies) that are employed by some centers, but with limited evidence."
6947,Respiratory Diseases of Pregnancy,"Respiratory complaints in the gravid patient are often difficult to identify as a disease state, expected physiologic changes of pregnancy or both. Understanding the underlying pulmonary physiologic changes that come with pregnancy as well as those conditions which are unique to the pregnant patient will help arrive at the correct diagnosis and management. Recognizing that the gravid patient has other physiologic changes that contribute to decreased respiratory reserve, increased risk of aspiration, infection, and difficult airway can help in managing these patients acutely."
6948,Aminopeptidases,
6949,Respiratory Emergencies in Children,Focused clinical observation is the key in the initial recognition of respiratory distress in an acutely ill child.
6950,Pädiatrische Transfusionsmedizin,"Die Indikation zur Transfusion von Blutprodukten wird in den letzten Jahren zurückhaltender gestellt. Dazu trägt die Sorge vor möglichen übertragbaren Infektionen ebenso bei wie eine verbesserte Kenntnis der Gewebeoxygenierung. Prinzipiell sollten nur die fehlenden Blutkomponenten verabreicht werden, die der Patient benötigt, und alle unnötigen und möglicherweise gefährlichen Bestandteile vermieden werden („Hämotherapie nach Maß“). In der Intensivmedizin erlaubt z.B. die Messung der zerebralen Sauerstoffausschöpfung eine auf die individuelle Oxygenierung des Patienten abgestimmte Entscheidung zur Erythrozytensubstitution; vorgegebene starre Transfusionsgrenzen verlieren dadurch an Bedeutung."
6951,Relative Lempel-Ziv Compression of Genomes for Large-Scale Storage and Retrieval,"Self-indexes – data structures that simultaneously provide fast search of and access to compressed text – are promising for genomic data but in their usual form are not able to exploit the high level of replication present in a collection of related genomes. Our ‘RLZ’ approach is to store a self-index for a base sequence and then compress every other sequence as an LZ77 encoding relative to the base. For a collection of r sequences totaling N bases, with a total of s point mutations from a base sequence of length n, this representation requires just [Formula: see text] bits. At the cost of negligible extra space, access to ℓ consecutive symbols requires [Formula: see text] time. Our experiments show that, for example, RLZ can represent individual human genomes in around 0.1 bits per base while supporting rapid access and using relatively little memory."
6952,Ventilator-Associated Pneumonia,"A 50-year-old diabetic male patient was admitted to the hospital with ischemic stroke (GCS = E1V1M3). He was put on invasive positive-pressure ventilation support. On the fourth day of ICU stay, he developed fever (38.6 °C), a rise in total leukocyte count (156,000, N 93%), and heterogeneous, ill-defined shadows in the right lower zone in the chest X-ray. Chest auscultation revealed bronchial breathing in the right infra-axillary area, and the nurse reported an increase in amount and purulence of secretions requiring frequent suctioning. The patient needed 5 mcg/min noradrenaline to maintain systolic blood pressure of more than 100 mmHg."
6953,Koorts en koortssyndromen,"Ongeveer 25–40 % van de kinderen zoeken acute kindergeneeskundige hulp in verband met koorts. In dit hoofdstuk behandelen de auteurs: (1) alarmsymptomen en beleid van een ernstige of specifieke infectie (bijv. pneumonie en urineweginfectie); (2) febris e causa ignota (koorts e.c.i.), die zich kenmerkt door aanhoudende of recidiverende koorts; (3) kinderen met een tropische infectieziekte (waaronder malaria en dengue); dit is zeldzaam, maar er zijn veel mogelijke oorzaken van koorts na tropenbezoek. Een systematische benadering is van belang om de aandoeningen te identificeren die bedreigend, behandelbaar en/of besmettelijk zijn."
6954,5 Zorgvuldig en verantwoord werken,"Verzorgenden in verpleeg- en verzorgingshuizen willen meer scholing over handelingen die de vrijheid van zorgvragers beperken. Ook is er te weinig toezicht op bewoners en zorgvragers. Verzorgenden beperken wekelijks de vrijheid van zorgvragers, maar zijn zich daar niet altijd van bewust. Dat blijkt uit onderzoek onder het Panel Verpleegkundigen & Verzorgenden (TvV, april 2007)."
6955,16 Longziekten,Longziekten komen zeer frequent voor. De meeste longaandoeningen ontstaan in de luchtwegen; voorbeelden hiervan zijn astma en COPD (chronic obstructive pulmonary disease).
6956,Litigations for Unexpected Adverse Events,"A 53-year-old Iranian female who immigrated to Canada about 3.5 years before was referred to an internist for a positive Mantoux skin test (11 mm in diameter). The subject was previously well with no symptoms indicative or suggestive of active tuberculosis. A routine tuberculosis skin test was performed because the patient had applied to be a volunteer at a local hospital. She had no significant past illness or known allergies, and she was never diagnosed with nor had known contact with anyone with active tuberculosis. The subject never ingested alcohol and was not known to have hepatitis or be a carrier of any hepatitis virus. Baseline investigations performed by the internist included routine complete blood count, routine biochemical tests (liver enzymes, creatinine, and glucose), serum ferritin, and thyroid-stimulating hormone – all of which were normal. A chest radiograph was reported to be normal."
6957,Investigation of Animal Reservoir(s) of SARS-CoV,"Severe acute respiratory syndrome (SARS) is a novel infectious disease in the new millennium. It has been ascertained that a new coronavirus, SARS-CoV, is the etiological agent of SARS. While the extraordinarily rapid isolation and full genome sequencing of SARS-CoV constituted a remarkable scientific achievement, identification of the actual animal reservoir(s) of SARS-CoV is more difficult. Initial evidences indicated that the masked palm civet (Paguma larvata) was the primary suspect of the animal origin of SARS (Guan et al., 2003; Song et al., 2005). Recent studies suggested that horseshoe bat is one of the real reservoirs (Lau et al., 2005; Li et al., 2005) and masked palm civet may have only served as an intermediate amplification host for SARS-CoV and fulfilled efficient interspecies transmission (Lau et al., 2005). This chapter will summarize the studies on the animal reservoir(s) of SARS-CoV."
6958,Rhinosinusitis and Tonsillopharyngitis,"Sinusitis is characterized by mucosal inflammation of the sinuses which is almost always accompanied by inflammation of the nasal passages. Since nasal mucosa is contiguous with paranasal sinus mucosa, the term sinusitis is often used interchangeably with [1]; the latter term will be used in this chapter. Rhinosinusitis can be acute (less than 4 weeks’ duration), subacute (4–12 weeks), or chronic (greater than 12 weeks) [2]."
6959,A Graph Cellular Automata Model to Study the Spreading of an Infectious Disease,"A mathematical model based on cellular automata on graphs to simulate a general epidemic spreading is presented in this paper. Specifically, it is a SIR-type model where the population is divided into susceptible, infected and recovered individuals."
6960,Die Vielfalt des Fachjournalismus,"Als zusammenfassendes Verständnis von Fachjournalismus lässt sich bis an diese Stelle aus der theoretischen Analyse heraus formulieren: Fachjournalismus ist Journalismus. In diesem Sinne ist Fachjournalismus ein Sub- und Leistungssystem des publizistischen Systems Journalismus. Er hat sich in viele Richtungen aus-differenziert aufgrund der Komplexität seiner Beobachtungsobjekte. Ebenso wenig wie es den einen Journalismus gibt, existiert nur ein Fachjournalismus. Der Singular bezeichnet das System, die Pluralform muss angewendet werden bei der Beschreibung der empirischen Vielfalt."
6961,Mykobakteriose (pulmonale),
6962,Current Issues in Ventilator-Associated Pneumonia,"Infections in critically ill patients account for a major proportion of the mortality, morbidity, and cost associated with their care. Infection rate in critically ill patients are about 40% and may be 50–60% in those remaining in the intensive care unit (ICU) for more then 5 days.(1,2) Pneumonia acquired in the ICU (after 48 h intuba tion) ranges from 10% to 65%,(3,4) and respiratory infections account for 30–60% of all infections acquired in the ICU(.5,6) Mortality rates of ventilator-associated pneumonia (VAP) have been very high (30–70%) and may account for 15% of all deaths in the ICU. (7–9) When controlled for severity of underlying disease and other factors the attributable mortality of VAP range from 0% to 50% absolute increase, and prolonged length of ICU stay (range 5–13 days).(10) In a recent review of the clinical and economic consequences of VAP from analysis of studies published after 1990, the findings were: 10–20% of ICU-ventilated patients will develop VAP, and are twice as likely to die compared to patients without VAP, with 6 extra days in the ICU and an additional US$10019 hospital cost per case.(11) Empiric broad-spectrum antimicrobials in the ICU for presumed pneumonia has contributed substantially to the worldwide increase in antibiotic-resistant bacteria in hospitals. This has compounded the problem of increasing morbidity, mortality, and cost because of the challenge posed by these difficult-to-treat microorganisms, particularly the use of expensive drugs and need for isolation."
6963,Small Scale Academic Web Archiving: DACHS,
6964,Viral Infections of the Lung,"The lungs are among the most vulnerable to microbial assault of all organs in the body. From a contemporary vantage, lower respiratory tract infections are the greatest cause of infection-related mortality in the United States, and rank seventh among all causes of deaths in the United States.2,3 From a global and historic perspective, the scope and scale of lower respiratory tract infection is greater than any other infectious syndrome, and viral pneumonias have proven to be some of the most lethal and dramatic of human diseases. The 1918–1919 influenza pandemic, perhaps the most devastating infectious disease pandemic in recorded history, resulted in an estimated 40 million deaths worldwide, including 700,000 deaths in the U.S.4 The global outbreak of severe acute respiratory syndrome (SARS) during 2003, although considerably smaller in scale, resulted in 8098 cases and 774 deaths5 and is a dramatic contemporary example of the ability of viral pneumonias to rapidly disseminate and cause severe disease in human populations."
6965,The Physiology of Brain Death and Organ Donor Management,"Brain death is associated with complex physiologic changes that may impact the management of the potential organ donor. Medical management is critical to actualizing the individual or family’s intent to donate and maximizing the benefit of that intent. This interval of care in the PICU begins with brain death and consent to donation and culminates with surgical organ procurement. During this phase, risks for hemodynamic instability and compromise of end organ function are high. The brain dead organ donor is in a distinct and challenging pathophysiologic condition that culminates in multifactorial shock. The potential benefits of aggressive medical management of the organ donor may include increased number of donors providing transplantable organs and increased number of organs transplanted per donor. This may improve graft function, graft survival, and patient survival in those transplanted. In this chapter, pathophysiologic changes occurring after brain death are reviewed. General and organ specific donor management strategies and logistic considerations are discussed. There is a significant opportunity for enhancing donor multi-organ function and improving organ utilization with appropriate PICU management."
6966,Aandoeningen van de luchtwegen,Luchtwegaandoeningen vormen een van de meest frequente oorzaken van morbiditeit bij kinderen. Alleen al luchtweginfecties maken meer dan de helft uit van alle ziekteperioden bij kinderen en zijn verantwoordelijk voor ongeveer eenderde van alle schoolverzuim.
6967,Chromatin and Aging,"Recent studies from a number of model organisms have indicated chromatin structure and its remodeling as a major contributory agent for aging. Few recent experiments also demonstrate that modulation in the chromatin modifying agents also affect the life span of an organism and even in some cases the change is inherited epigenetically to subsequent generations. Hence, in the present report we discuss the chromatin organization and its changes during aging."
6968,Schnupfenviren,
6969,The Past and Present Threat of Avian Influenza in Thailand,"Avian influenza H5N1 infection was first identified in Thailand in January 2004. Since then, there have been three major outbreaks in the cold season of 2003–2004 and in the rainy and cold seasons of 2004–2005 and 2005–2006. More than 62 million birds died or were culled. The burden shifted from large industrial farming in the first outbreak to small farms, backyard chickens, and free-grazing ducks. Up to November 2005, there were 20 confirmed cases of human H5N1 infection. Thirteen of these died. Most of the confirmed cases were solitary ones except for three persons in a single family, and epidemiological evidence indicated that person-to-person transmission may have been involved in this cluster. However, sequence analysis of the virus in the cluster did not suggest any changes that might enhance the viral ability to get transmitted among humans. H5N1 viruses in Thailand and Vietnam belong to a single lineage genetically and are antigenically distinguishable from the viruses of the same genotype Z from southern China and Indonesia. Despite the seemingly subsiding epidemic in Thailand, the problem is far from resolved. H5N1 viruses are still sporadically isolated from domestic poultry as well as from wildlife. More important, isolates were also found in asymptomatic animals. Natural selection may have adapted the virus to a less aggressive form. This would make the virus more elusive and difficult to control. A threat of a pandemic strain emerging from the H5N1 virus is still imminent. A national strategic plan for avian influenza control and influenza pandemic preparedness has been implemented. The plan aims at effective control of avian influenza spread in animals as well as in humans for a three-year period and at efficient pandemic preparedness within one year. Nevertheless, more regional and international collaboration is needed. With proper collective preparedness, there is a hope that the threatening influenza pandemic can be prevented by confining and eliminating a potential pandemic strain at its origin. In December 2003, poultry farms in the eastern, central, and northern regions of Thailand experienced large-scale die-offs. The outbreak started from the eastern region of the country. The disease caused rapid death, with a very high attack rate. At that time, H5N1 outbreaks had been reported in South Korea, Vietnam, and Japan (OIE, 2005). A few humans with pneumonia were suspected to originate from contact with sick or dead poultry. Final diagnosis in these patients was not done as clinical samples were not available at the time when proper diagnostic testing became available. On 23 January 2004, the first case of human H5N1 infection in Thailand was reported. It was a boy from Kanchanaburi, a province about 100 km west of Bangkok. He was admitted to Siriraj Hospital in Bangkok and was diagnosed to have severe progressive pneumonia. The patient was initially treated with broad spectrum antibiotics, and respiratory samples were tested for influenza virus. The laboratory result showed that the patient harbored influenza virus, and sequencing of the viral RNA indicated that the virus belonged to the H5 subtype (Chokephaibulkit et al., 2005; Puthavathana et al., 2005). When this result was reported to the Ministry of Public Health, the government announced that there was a highly pathogenic avian influenza (AI) outbreak in Thailand. The Department of Livestock Development (DLD) confirmed the presence of H5N1 viruses in poultry on the same day. Subsequent analysis of the virus from patients and animals confirmed that it was H5N1 AI virus of genotype Z and was closely related to the virus from Vietnam (Viseshakul et al., 2004; Puthavathana et al., 2005)."
6970,P-Type Lectins: Cation-Dependent Mannose-6-Phosphate Receptor,"In eukaryotic cells, post-translational modification of secreted proteins and intracellular protein transport between organelles are ubiquitous features. One of the most studied systems is the N-linked glycosylation pathway in the synthesis of secreted glycoproteins (Schrag et al. 2003). The N-linked glycoproteins are subjected to diverse modifications and are transported through ER and Golgi apparatus to their final destinations in- and outside the cell. Incorporation of cargo glycoproteins into transport vesicles is mediated by transmembrane cargo receptors, which have been identified as intracellular lectins. For example, mannose 6-phosphate receptors (Ghosh et al. 2003) function as a cargo receptor for lysosomal proteins in the trans-Golgi network, whereas ERGIC-53 (Zhang et al. 2003) and its yeast orthologs Emp46/47p (Sato and Nakano 2002) are transport lectins for glycoproteins that are transported out of ER."
6971,Pharyngitis,
6972,Nierentransplantation,"Die Nierentransplantation ist die effektivste Behandlungsmethode der chronischen terminalen Niereninsuffizienz. Seit den 1960er Jahren entwickelte sie sich zu einer Standardtherapie. Wichtige Voraussetzungen waren die Entdeckung des HLA-Systems, die Entwicklung der Immunsuppressiva sowie die technische Perfektionierung des Organerhaltes außerhalb eines lebenden Körpers. Die 5-Jahres-Überlebensrate für Allotransplantate beträgt etwa 65%, diejenige von Lebendspenden 79%."
6973,International Flight Considerations,"Combined with the rising number of passengers, and increased capacity of larger airplanes with more long-distance domestic and international flights, with long-haul aircrafts—such as the Airbus A380 and Boeing 777 LR now capable of extending flight times to 18–20 h—it is likely that the incidence of in-flight medical emergencies will continue to increase in the coming years. International air travel in particular combines long-haul, extended flight times with unique exposures and an even more austere, secluded environment for passengers with acute and/or chronic illnesses, and suggests unique medical challenges for recognition, stabilization, treatment, diagnosis, and disposition."
6974,Disabled defences,
6975,Anti-infective activity of immunomodulators,"The availability of a vast array of recombinant and synthetic IMMUNOMODULATORS is a significant milestone toward the development of effective therapies for infectious diseases. This is evinced by licensing of several recombinant human CYTOKINES, including COLONY-STIMULATING FACTORS, INTERLEUKINS, INTERFERONS and erythropoietin, for clinical use in patients. Diverse combinations with INTERFERONS and other CYTOKINES for the treatment of various infections have been proposed. Others, including various CHEMOKINES, synthetic CpG oligodeoxynucleotides and glucans, are extensively being investigated in clinical and preclinical studies. Considerable advances have been made on compounds exhibiting CYTOKINE inhibitory properties useful for new treatments of infectious and inflammatory diseases. Many of the major developments and current trends are highlighted in this review. Novel strategies based on the engineering of CYTOKINES and inhibitors are poised to revolutionize therapeutic options contingent upon scientific evidence rather than dictates of discursive empiricism in the coming decades."
6976,Use of IgY Antibodies in Human and Veterinary Medicine,
6977,Numerical Simulation of Urban Coastal Zones,
6978,Pattern Recognition Receptors in CNS Disease,"Pattern recognition receptors (PRRs) are germline encoded receptors utilized by cells of the innate immune system for pathogen recognition. PRRs are classically activated by pathogen-associated molecular patterns (PAMPs) present in whole classes of pathogens, but not in mammalian cells, termed the “infectious nonself model” (Medzhitov and Janeway, 2002). It has also been recent appreciated that there are self-derived products released upon tissue injury or necrotic cell death that can activate PRRs (Morgan et al., 2005). PRR activation leads to opsonization, activation of complement and coagulation cascades, phagocytosis, activation of proinflammatory signaling pathways, and the induction of apoptosis (Janeway and Medzhitov, 2002; Matzinger, 2002). Additionally, activation of the innate immune system is crucial for the induction of adaptive immune responses and the eventual clearance of pathogens (Janeway and Medzhitov, 2002)."
6979,Don’t Toss Your Turtle! Seizures and Fever in an Infant,"A 10-month-old male presented with new-onset seizure activity, a 6-week fever of unknown origin, and a left-sided frontoparietal subdural fluid collection. The child’s mother reported tonic-clonic movements that lasted for about 15 min and that resolved with one dose of lorazepam. At 9 months of age, the infant’s pediatrician had noted an increase in the patient’s head circumference."
6980,Scientific Models in the Severe Acute Respiratory Syndrome (SARS) Research and in the Biology Curriculum,"An in-depth case study of the authentic scientific research during the severe acute respiratory syndrome (SARS) crisis revealed a rich list of features of nature of science (NOS). Among these features, model building stands as a prominent activity of scientists for understanding, explaining, and making sense of some of puzzling observations. In this chapter, we present a detailed analysis of four key episodes of the scientific inquiries during the SARS epidemic, namely, (1) the identification of the transmission mode, (2) the hunt for the causative agent of SARS, (3) the search for the natural host of the SARS-related coronavirus, and (4) the explanation of the mysterious infection pattern in the tragic outbreak at Amoy Gardens (a residential complex), to highlight the important roles and characteristics of models, modeling, and multiple levels of representations of science. We also describe how these scientific models developed were intricately related to social, cultural, and political environments. We then review the roles and nature of scientific models emphasized in the most recent biology curriculum implemented in Hong Kong and critique on its inadequacies in fully reflecting the important function of models and modeling in the authentic scientific inquiries."
6981,Role of Epithelial Cells in Chronic Inflammatory Lung Disease,"Airborne pathogens entering the lungs first encounter the mucus layer overlaying epithelial cells as a first line of host defense [1, 2]. In addition to serving as the physical barrier to these toxic agents, intact epithelia also are major sources of various macromolecules including antimicrobial agents, antioxidants and antiproteases [3, 4] as well as proinflammatory cytokines and chemokines that initiate and amplify host defensive responses to these toxic agents [5]. Airway epithelial cells can be categorized as either ciliated or secretory [6]. Secretory cells, such as goblet cells and Clara cells, are responsible for the production and secretion of mucus along the apical epithelial surface and, in conjunction with ciliated cells, for the regulation of airway surface liquid viscosity. In addition, submucosal mucus glands connect to the airway lumen through a ciliated duct that propels mucins outward. These glands are present in the larger airways between bands of smooth muscle and cartilage. See Fig. 1."
6982,Emerging Disease and the Evolution of Virulence: The Case of the 1918–1919 Influenza Pandemic,"“Why do parasites harm their host?” is a recurrent question in evolutionary biology and ecology, and has several implications for the biomedical sciences, particularly public health and epidemiology. Contrasting the meaning(s) of the concept of “virulence” in molecular pathology and evolutionary ecology, we review different explanations proposed as to why, and under what conditions, parasites cause harm to their host: whereas the former uses molecular techniques and concepts to explain changes and the nature of virulence seen as a categorical trait, the latter conceptualizes virulence as a phenotypic quantitative trait (usually related to a reduction in the host’s fitness). After describing the biology of emerging influenza viruses we illustrate how the ecological and the molecular approaches provide distinct (but incomplete) explanations of the 1918–19 influenza pandemic. We suggest that an evolutionary approach is necessary to understand the dynamics of disease transmission but that a broader understanding of virulence will ultimately benefit from articulating and integrating the ecological dynamics with cellular mechanisms of virulence. Both ecological and functional perspectives on host-pathogens’ interactions are required to answer the opening question but also to devise appropriate health-care measures in order to prevent (and predict?) future influenza pandemics and other emerging threats. Finally, the difficult co-existence of distinct explanatory frameworks reflects the fact that scientists can work on a same problem using various methodologies but it also highlights the enduring tension between two scientific styles of practice in biomedicine."
6983,Emerging Infectious Diseases in Camelids,"Growing interest in camelids presents a unique challenge to scientists and veterinarians engaged in diagnosing infectious diseases of this species. It is estimated that 65 % of fatalities in Old World camels (OWC, i.e., Camelus dromedarius and C. bactrianus) and 50 % in New World camelids/South American camelids (NWC/SAC, i.e., the domestic alpaca (Vicugna pacos) and llama (Lama glama)) are caused by infectious diseases. Factors that contribute to disease emergence in camelids involve climate change and increased demand for camel products resulting in the intensification of production and expanding camel contacts with other animal species and humans. In this chapter, the most important emerging diseases of camelids are described and discussed. The most notable emerging viral infections in OWC include camelpox, Rift Valley fever (RVF), peste des petits ruminants (PPR), and Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Brucellosis, Johne’s disease (JD), and dermatophilosis are the emerging bacterial diseases in OWC. Emerging diseases of NWC include infections with bovine viral diarrhea virus (BVDV), bluetongue (BT), and coronavirus. Parasitic emerging infections in NWCs include the small liver fluke (Dicrocoelium dendriticum) and meningeal worm (Parelaphostrongylus tenuis)."
6984,An Ensemble Trajectory Method for Real-Time Modeling and Prediction of Unfolding Epidemics: Analysis of the 2005 Marburg Fever Outbreak in Angola,"We propose a new methodology for the modeling and real time prediction of the course of unfolding epidemic outbreaks. The method posits a class of standard epidemic models and explores uncertainty in empirical data to set up a family of possible outbreak trajectories that span the probability distribution of models parameters and initial conditions. A genetic algorithm is used to estimate likely trajectories consistent with the data and reconstruct the probability distribution of model parameters. In this way the ensemble of trajectories allows for temporal extrapolation to produce estimates of future cases and deaths, with quantified levels of uncertainty. We apply this methodology to an outbreak of Marburg hemorrhagic fever in Angola during 2005 in order to estimate disease epidemiological parameters and assess the effects of interventions. Data for cases and deaths was compiled from World Health Organization as the epidemic unfolded. We describe the outbreak through a standard epidemic model used in the past for Ebola, a closely related viral pathogen. The application of our method allows us to make quantitative prognostics as the outbreak unfolds for the expected time to the end of the epidemic and final numbers of cases and fatalities, which were eventually confirmed. We provided a real time analysis of the effects of intervention and possible under reporting and place bounds on population movements necessary to guarantee that the epidemic did not regain momentum."
6985,The Angiotensin-(1-7) Axis: Formation and Metabolism Pathways,"The renin-angiotensin system (RAS) constitutes a key hormonal system in the physiological regulation of blood pressure via peripheral and central mechanisms. Dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies and pharmacologic blockade of this system by the inhibition of angiotensin-converting enzyme (ACE) or antagonism of the angiotensin type 1 receptor (AT(1)R) is an effective therapeutic regimen. The RAS is now defined as a more complex system composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS comprises the ACE-Ang II-AT(1)R axis that promotes vasoconstriction, water intake, sodium retention and increased oxidative stress, fibrosis, cellular growth, and inflammation. The non-classical or alternative RAS is composed primarily of the ACE2-Ang-(1-7)-AT(7)R pathway that opposes many actions of the Ang II-AT(1)R axis. In lieu of the complexity of this system, the chapter discusses the current evidence on the enzymatic cascade of the Ang-(1-7) axis of the RAS regarding the peptidases that contribute to the formation and degradation of the peptide in the circulation and various tissues."
6986,Infectious Diseases and the Kidney,"The kidney is involved in a wide range of bacterial, viral, fungal, and parasitic diseases. In most systemic infections, renal involvement is a minor component of the illness, but in some, renal failure may be the presenting feature and the major problem in management. Although individual infectious processes may have a predilection to involve the renal vasculature, glomeruli, interstitium, or collecting systems, a purely anatomic approach to the classification of infectious diseases affecting the kidney is rarely helpful because most infections may involve several different aspects of renal function."
6987,Genetic Diversity of Microbial Endophytes and Their Biotechnical Applications,"The need for new and useful compounds and biological processes to provide assistance and relief in all aspects of the human condition is ever growing. Drug resistance in bacteria, the appearance of life-threatening viruses, and a tremendous increase in the incidence of fungal and drug-resistant bacterial infections in the world’s population, each only underscores our inadequacy to cope with these medical problems. Added to this are enormous difficulties in raising enough food on certain areas of the earth to support local human populations. Environmental degradation, loss of biodiversity, and spoilage of land and water also add to problems facing mankind. In addition, there is the need for bio-derived fuels to supplant the ever-growing demand for petroleum and petroleum products."
6988,Tracheobronchitis und Bronchiolitis,"Definition. Bronchitis im Kindesalter ist eine durch Infektionserreger ausgelöste entzündliche Krankheit der Bronchien, bei der durch den gleichen Erreger häufig auch weitere Teile der Luftwege mitbefallen sind. Die chronische Bronchitis ist im Kindesalter nicht definiert und kommt entsprechend der Definition für Erwachsene (3 oder mehr Monate mit produktivem Husten über 2 oder mehrere aufeinanderfolgende Jahre) nicht vor. Kinder mit häufigen Bronchitiden (mehr als 6 pro Jahr) werden jedoch häufig gesehen."
6989,Governance of Food Security in the 21(st) Century,"Governance is broadly defined as the exercise of power in an institutional context with the main aim of directing, controlling, and regulating activities concerned with the public interest."
6990,"Aspiration, Bronchial Obstruction, Bronchiectasis, and Related Disorders","The conducting airways play a pivotal role in the spectrum of pulmonary pathology, not only as conduits for injurious agents to enter the lung, but also as an anatomic compartment that is affected by a diverse array of primary or secondary bronchocentric diseases. This chapter discusses aspiration and bronchial obstruction in detail, with emphasis on the aspiration of toxic, infective, or particulate matter. Lung abscess, a frequent complication of obstruction or aspiration, is also reviewed. Both aspiration and lung abscess are reconsidered within the context of pulmonary infectious disease mainly in Chapter 8 on bacterial infections, and to some extent in the chapters on mycobacterial (Chapter 9), fungal (Chapter 10), and parasitic diseases (Chapter 14)."
6991,The Sixth Mass Extinction,"After the five mass extinctions on Earth that were caused by meteorite impacts, volcanism and large-scale climate change, several scientists predict that we are currently at the beginning of a sixth mass extinction. In this scenario, it is humankind that is causing the mass extinction with the illegal trade in wildlife as one of the most important hazards to wildlife species. This chapter presents an analysis of the causes and consequences of the global defaunation in the context of technological innovation and industrialisation of the wildlife trade. The complexity of the current decline of biodiversity and the effect of defaunation will be demonstrated by the sensibility of ecological interaction between animals and plants. The exploitation of natural resources has become a part of the social, political and economic dynamics."
6992,Farming human pathogens,"Here we examine examples of the farming of coevolutionary systems, focusing on the mutually amplifying roles of large-scale psychosocial stress, economic structure, and reductionist interventions in the ecology and evolution of highly adaptive disease organisms. We find, in general, that population-level socioeconomic and other stressors, in synergism with reductionist interventions, are precisely suited to trigger mesoscale resonance coevolutionary resilience domain shifts affecting rapidly evolving pathogens."
6993,Pre-primary and Primary Prophylaxis of Variceal Hemorrhage,"Variceal hemorrhage is a life-threatening complication of portal hypertension. Thus, prevention of variceal formation (pre-primary prophylaxis) or at least prevention of variceal bleeding are important goals to improve life quality and—if possible—survival of patients with liver cirrhosis. Interruption of the underlying cause of liver disease is the most successful approach, which, however, often fails. For this situation interruption or modulation of different pathophysiological mechanisms leading to fibrosis, hyperdynamic circulation and portal hypertension have been shown effective in animal models. But few could be translated to humans. By contrast, different steps to prevent first bleeding from varices have proven successful in many clinical trials. These applied mainly drugs to lower portal pressure, such as nonselective β-blockers, or endoscopic obliteration of varices, while prophylactic shunt procedures are not advised."
6994,Cardiovascular Emergencies,"A good focused history is essential to the adequate assessment of chest pain. It is important to rapidly exclude potentially life-threatening causes of chest pain to avoid adverse clinical outcomes.This should be preceded by an ABCD (airway, breathing, circulation, disability) assessment. Once cardiac chest pain is determined to be likely, early risk stratification should be achieved in order to guide choice of further management."
6995,Common Infections Following Lung Transplantation,"The lungs are the only transplanted organ in direct contact with the ‘outside world’. Infection is a significant cause of morbidity and mortality in lung transplantation. Early accurate diagnosis and optimal management is essential to prevent short and long term complications. Bacteria, including Mycobacteria and Nocardia, viruses and fungi are common pathogens. Organisms may be present in the recipient prior to transplantation, transmitted with the donor lungs or acquired after transplantation. The degree of immunosuppression and the routine use of antimicrobial prophylaxis alters the pattern of post-transplant infections."
6996,An RT-PCR Assay for Detection of Infectious Bronchitis Coronavirus Serotypes,"Avian infectious bronchitis virus (IBV), a chicken Gammacoronavirus, is a major poultry pathogen, and is probably endemic in all regions with intensive poultry production. Since IBV was first described in 1936, many serotypes and variants of IBV have been isolated worldwide. IBV isolates are capable of infecting a large range of epithelial surfaces of the chicken, involving the respiratory, renal, and reproductive systems; however, the clinical signs are usually not specific for differential diagnoses. Virus isolation is commonly used for diagnosis of IBV infection, which was achieved through passage of clinical materials via the allantoic route of embryos. Currently, more sensitive molecular approaches for the detection of avian pathogens have been developed, including reverse-transcriptase polymerase chain reaction (RT-PCR) and real-time RT-PCR, which are more suitable for use in diagnostic laboratories. In this chapter, we describe a one-step RT-PCR which can be used for detecting most of IBV serotypes in the IBV-infected allantoic fluid and has been used routinely in our laboratories for detection of IBVs."
6997,Human and Animal Viruses in Food (Including Taxonomy of Enteric Viruses),
6998,The welfare of laboratory rabbits,
6999,The US CDC Global AIDS Program in China,"The China-US Cooperation-Global AIDS Program (GAP) was a strategic technical collaboration program jointly implemented by the US Centers for Disease Control and Prevention and the Chinese Center for Disease Control and Prevention. This program developed, piloted, launched, and evaluated a broad range of projects supporting national and local HIV prevention and control programs; evidence-based decision-making; strengthening systems and capacity at national, provincial, and local levels; prioritizing high-risk geographic areas and populations; developing innovative approaches for scale-up; answering important scientific questions that can be most effectively answered in China but also with global implications for the HIV response; and increasing China’s engagement with the global public health community and sharing critical lessons learned. A productive working relationship with well-conceived models, a results-based activity implementation plan, and proper linkage to the domestic policy process has made a significant contribution to HIV control and prevention in China."
7000,State Capacity and Leadership in ASEAN and the EU,"This chapter examines state capacity as an explanatory factor in order to reconceptualise political leadership in a regional context. This chapter argues that state capacity is crucial in the provision of political leadership in a regional context as it helps to sustain the benefits of regional community-building, and to continually, over time, build and strengthen regional community-building through policy implementation and policy continuation. This chapter compares the role, and the implications of, the Franco-German alliance in steering the development of the EU, with the more circumspect role of Indonesia as the de facto leader in ASEAN, whether in providing sole leadership, or through a coalition with other countries. It also examines and compares both the potential and challenges for smaller member states such as Singapore in ASEAN and the Benelux countries in the EU, to exert increased influence in their regional community-building efforts."
7001,Bioterrorism,"This final section examines a mode of attack which has been repeatedly connected with nuclear terrorism in the debate over security. The weapons, usually phials or bottles, are so small that they easily avoid detection and with this kind of attack there is of course no moment of detonation, only a gradual increase in casualties. And the human carriers can themselves function as human weapons. This fiction repeatedly plays on different meanings to “cell”, relating the fate of individuals to that of the body politic. Once again the conspirators might be Middle Eastern or domestic, the latter frequently lone wolves as happens in Richard Preston’s The Cobra Event, which reportedly shaped the policy of the Clinton administration."
7002,Complications and Toxicities Associated with Cancer Therapies in the Intensive Care Unit,"Advances in the management of hematologic malignancies and solid tumors have given rise to diverse modalities to treat cancer other than cytotoxic chemotherapy, including targeted therapies, immunotherapies, and cellular therapies. Currently, there are over 175 FDA-approved antineoplastic agents in the United States, many with a diverse and profound toxicity profile. Complications of antineoplastic therapy may result in the need for intensive care unit (ICU) admission to provide acute symptom management. Accordingly, ICU providers caring for cancer patients should have a working knowledge of the toxicities and complications associated with antineoplastic therapy."
7003,Obliterative Bronchiolitis,"Obliterative bronchiolitis (OB) is a condition characterized by inflammation and fibrosis of the bronchiolar walls resulting in narrowing or obliteration of the bronchiolar lumen. The most common causes are childhood lower respiratory tract infection, hematopoietic stem cell or lung and heart-lung transplantation, and toxic fume inhalation. The most frequent clinical manifestations are progressive dyspnea and dry cough. Pulmonary function tests demonstrate airflow obstruction and air trapping. Radiographic manifestations include reduction of the peripheral vascular markings, increased lung lucency, and overinflation. The chest radiograph, however, is often normal. High-resolution CT is currently the imaging modality of choice in the assessment of patients with suspected or proven OB. The characteristic findings on high-resolution CT consist of areas of decreased attenuation and vascularity (mosaic perfusion pattern) on inspiratory scans and air trapping on expiratory scans. Other CT findings of OB include bronchiectasis and bronchiolectasis, bronchial wall thickening, small centrilobular nodules, and three-in-bud opacities. Recent studies suggest that hyperpolarized (3)He-enhanced magnetic resonance imaging may allow earlier recognition of obstructive airway disease and therefore may be useful in the diagnosis and follow-up of patients with OB."
7004,"Infections in Heart, Lung, and Heart-Lung Transplantation","Half a century has passed since the first orthotopic heart transplant took place. Surgical innovations allowed for heart, lung, and heart-lung transplantation to save lives of patients with incurable chronic cardiopulmonary conditions. The complexity of the surgical interventions, chronic host health conditions, and antirejection immunosuppressive medications makes infectious complications common. Infections have remained one of the main barriers for successful transplantation and a source of significant morbidity and mortality. Recognition of infections and its management in this setting require outstanding clinical skills since transplant recipients may not exhibit classic signs or symptoms of disease, and laboratory work has some pitfalls. The prevention, identification, and management of infectious diseases complications in this population are a priority to undertake to improve the medical outcomes of transplantation. Herein, we reviewed the historical aspects, epidemiology, and prophylaxis of infections in heart, lung, and heart-lung transplantation. We also discuss the most prevalent organisms affecting the host and the organ systems involved."
7005,Basics of Magnetic Resonance Imaging and Magnetic Resonance Spectroscopy,"In this chapter, the basic principles of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) (Sects. 2.2, 2.3, and 2.4), the technical components of the MRI scanner (Sect. 2.5), and the basics of contrast agents and the application thereof (Sect. 2.6) are described. Furthermore, flow phenomena and MR angiography (Sect. 2.7) as well as diffusion and tensor imaging (Sect. 2.7) are elucidated."
7006,Environmental Determinants of Health,"Several modifiable environmental factors—such as outdoor air pollution, household air pollution, drinking water contamination, occupational exposure to hazardous materials, lead exposure, and built environments that discourage physical activity—influence the risk and experience of chronic disease. The World Health Organization estimates that 21.2% of global deaths and 16.3% of global disability-adjusted life years lost are attributable to these risk factors. There are several approaches for estimating the number of deaths and chronic illnesses attributable to these factors. Managing and mitigating environmentally related chronic illness begins with the administration of an environmental health history."
7007,Entwicklung von Arzneistoffen,
7008,Boyhood,"In those years, even in the most intellectual families, it was not customary and actually considered counterproductive to teach children to read before starting school (“the child would be bored in class”). But my mother was sure that her “treasure” devouring one thick volume after another would be a straight “A” student and infected me with this confidence too. Alas, the first days at school turned out to be a real shock to me. The fact that I could read fluently did not help me at all. Having just one time relished my virtuosic ability to read, the teacher Nina Vasilyevna Smirnova did not call on me any more, concentrating on teaching the overwhelming majority “Russian oral skills”. There were exactly 40 students in the class."
7009,Improving the Human Well-Being of All Africans,"Integrated organic growth must prioritise the interests of the African people by creating equal economic opportunities, generating social and cultural wealth and capital, to a broad spectrum of the population in each country. Human development seeks to enable people to lead full, productive and meaningful lives by raising their incomes and improving their standards of living, which include life expectancy, health, education, security and personal liberty and freedom of choice—unfortunately, Africa fares poorly in this regard if one considers the Human Development Index or the World Happiness Report. China is particularly active in interventions in Africa that aim to improve food security, social development, medical care and public health, poverty eradication, education, environmental protection, security, immigration, law enforcement and international cooperation. One example is China’s significant intervention during the Ebola outbreak crisis in West Africa which saved countless lives. Concerns do, however, remain regarding possible human rights abuses and lack of community engagement by Chinese investors in Africa."
7010,A Woman with a History of a 2-Year Stay in Gabon and Onset of a Cyclical Fever More Than 1 Year Later,"A 23-year-old woman with no significant past medical history presented with fever every other day for 1 week. After graduating from college, she had spent a year as in Gabon, West Africa, before starting medical school. She was healthy until 1 week prior to presentation. At that time, she developed fever up to 102.5 °F, as well as chills and sweats, with symptoms occurring every other day. She also noted myalgia, headache, profuse sweats with defervescence of the fever, and intense fatigue."
7011,Epidemiology of Respiratory Allergies and Asthma,"Asthma has puzzled and confused physicians from the time of Hippocrates to the present day. The word “asthma” comes from a Greek word meaning “panting” (Keeney 1964), but reference to asthma can also be found in ancient Egyptian, Hebrew, and Indian medical writings (Ellul-Micallef 1976; Unger and Harris 1974). There were clear observations of patients experiencing attacks of asthma in the second century and evidence of disordered anatomy in the lung as far back as the seventeenth century (Dring et al. 1689)."
7012,HIV/AIDS: Lessons from a New Disease Pandemic,"The acquired immunodeficiency syndrome (AIDS) was first recognized about 25 years ago (Gottlieb et al., 1981; Masur et al., 1981; Siegal et al., 1981). The best available evidence suggests that HIV newly infected the human species about 50–100 years ago (Korber et al., 2000). It did not originate in Asia. It apparently moved to people from sub-human primates in Africa (Keele et al., 2006; Kanki, 1997). Because of different clinical presentations in different populations of people, and a long incubation period, it was more difficult to diagnose than SARS or avian influenza. As a new epidemic that originated in the era of modern medicine, it taught us many lessons about the difficulties that a new infectious disease can present. Already claiming at least 60–80 million victims, AIDS seems destined to continue as a pandemic for the foreseeable future. Drugs that control HIV replication and reverse disease progression have been developed, but none eliminate the virus from the body. Sexual transmission can be prevented by abstinence or condoms, but such measures, which prevent procreation, provide only limited value. Approaches for making a vaccine using conventional techniques have failed. Most experts believe that an effective vaccine will be made eventually, but not for at least 10–20 years. We need to learn more about the immunobiology of acute HIV infection, and about potentially protective immunoepitopes, such as conformational intermediates of the virus envelope. Until a vaccine is available, there is little or no chance that HIV can be eliminated, or even drastically reduced in prevalence. AIDS has presented scientists, political leaders, and health policy experts with unprecedented challenges."
7013,Uncoordinated Human Responses During Epidemic Outbreaks,"Uncoordinated human behavioral responses triggered by risk perception can alter the evolution of an epidemic outbreak further and beyond control measures imposed by public authorities. In fact, spontaneous behavioral changes could develop as a defensive response during the spread of an epidemic, thereby impacting the epidemic dynamics and affecting timing and overall number of cases. In this chapter, a model coupling the classic SIR disease transmission model with an imitation dynamics process is introduced which accounts for the diffusion of different behaviors in the population as a response to the epidemic threat. A detailed analysis of the model identifies the main determinants leading to remarkable alterations in infection dynamics in both risk perception and diffusion of human behavioral patterns. Empirical evidence points to the need of incorporating human behavior in prediction models informing public health decisions."
7014,Skin Infections,"Cutaneous infections are common in immunocompromised patients. Neutropenia predisposes patients to fungal, bacterial and viral infections. Antibacterial antifungal and antiviral prophylaxis have caused a significant reduction in some of these infections. There are two main types of cutaneous infections : primary cutaneous infections and cutaneous manifestations of a disseminated infection. In the latter, skin lesions may be the window to disseminated bloodstream infection and the first and only evidence of a disseminated life threatening infection. The diagnosis may be at your fingertips; therefore a thorough skin exam is the clue. However, it’s also important to know the characteristic lesions associated with different infections. It will help expedite diagnosis so appropriate treatment is initiated promptly in neutropenic patients, which can be lifesaving. In a retrospective study of 43 neutropenic febrile patients with cutaneous lesions, fungal infections were the most frequent, and nodular lesions on the lower extremities were the most prevalent (Naorungroj and Aiempanakit, J Am Acad Dermatol 74:AB166, 2016). Skin biopsy for pathological study and culture remains the gold standard and should be obtained early to confirm the suspected diagnosis. In these immunocompromised patients the inflammatory response is altered by either the primary disease or its treatment. Therefore, routine pathogens may present in an atypical fashion, with diminished or absent induration, erythema, or pustulation in response to bacterial resulting cutaneous infection without typical cellulitis (Urabe, Clin Infect Dis 39:S53–S55, 2004). Skin lesions are evaluated not only by morphology, but also in the context of the clinical setting and biopsy result. The skin biopsy is inexpensive, relatively noninvasive and without contraindication, and may avoid the need for more invasive procedures such an open lung biopsy (Grossman, et al., Cutaneous manifestations of infection in the immunocompromised host. Springer Science+Business Media, LLC, New York, 2012). In addition to antimicrobial therapy, surgery should not be postponed in the face of progressive skin and soft tissue infection in this population (Brzozowski and Ross, J Hand Surg Br 22:679–680, 1997)."
7015,Fluorine-Containing Diazines in Medicinal Chemistry and Agrochemistry,"The combination of a fluorine atom and a diazine ring, which both possess unique structural and chemical features, can generate new relevant building blocks for the discovery of efficient fluorinated biologically active agents. Herein we give a comprehensive review on the biological activity and synthesis of fluorine containing, pyrimidine, pyrazine and pyridazine derivatives with relevance to medicinal and agrochemistry."
7016,HIV: Biology to Treatment,"AIDS is one of the most dreaded diseases of the twenty-first century caused by human immunodeficiency virus (HIV). Recently, there are reports which show decline in new infections due to better access to anti-retroviral drugs. Still on a daily basis, ~2356 new HIV infections are being reported globally. New treatments and anti-HIV drugs are being continuously developed with the aim to control and cure AIDS. The anti-HIV drugs that are in use usually target HIV entry and replication inside the host cells. However, these drugs are only partially effective in slowing the rate of HIV replication. Nevertheless, the virus manages to replicate at much slower rates even when anti-retroviral treatment is ongoing. The HIV seropositives who are on anti-retroviral treatment for long periods of time are now developing different kinds of other complications including neuroAIDS. The latest development in HIV therapy is a novel kind of bone marrow transplantation from donors who have a homozygous mutation in CCR5 gene."
7017,Leidraad algemene diagnostiek/therapie bij cardiale ziektebeelden,Bijzondere vorm van cardiomyopathie met vervanging van normaal rechterventrikelmyocard door vet en fibrotisch weefsel.
7018,Airspace-Occupying Diseases,"Diseases of the air space of the lung share many common findings and presentation that it makes more sense to be grouped together in a differential diagnosis. The common imaging finding is usually as a lung infiltrate or consolidation of some type of distribution or another. Trying to find the putative cause for the imaging pattern is a good first step in narrowing the differential diagnosis and answering the question: what accounts for this pattern on imaging studies? Most of these diseases have an acute or subacute onset and exhibit restrictive pattern on pulmonary function tests. When treated promptly, they resolve completely with little or no residual injury to the lung architecture. On a small biopsy it is important to have a clinical history and imaging results before embarking on a descriptive rather than a definitive diagnosis. The smaller the sample, the more information is needed to complete the picture. Pulmonologists should be advised to target the part of the lung that should provide the most information related to the process under investigation. An endobronchial wall biopsy is not suitable in the setting of investigating a lung infiltrate as part of the alveolated lung has to be included. The category of airspace-occupying diseases of the lung includes: 1. Acute lung infections such as bacterial and viral pneumonias. 2. Acute lung injury pattern which includes bronchiolitis obliterans/organizing pneumonia and diffuse alveolar damage. 3. Intra-alveolar hemorrhage. 4. Pulmonary alveolar proteinosis. 5. Pulmonary edema. 6. Pneumocystis pneumonia. 7. Lymphangitic carcinomatosis. In all of these instances, there are ground-glass opacities obscuring the air space. Most clinicians would describe the imaging as “infiltrate” or “consolidation.” The task for the pathologist is to find the pertinent finding that could account for the imaging."
7019,How Masqueraders Infiltrate a System,"The U.S. and China take cyber surveillance very seriously. Therefore, let the U.S. get on with it. Finally, that’s the only way of becoming a superpower."
7020,"Concepts of Security Threats, Challenges, Vulnerabilities and Risks","The reconceptualization of security has been triggered by the end of the Cold War, by the process of globalization, and by the gradual transition from the Holocene to the Anthropocene phase of earth history (Brauch 2008, 2009, chap. 1 by Brauch/Oswald Spring above). From a philosophical perspective, in the contemporary security discussion the “dual moment of prevention and compensation of genuinely social and technical uncertainties” (Makropoulos 1995: 745–750) becomes decisive."
7021,Acronyms and Abbreviations,"n many fields today abbreviations and acronyms are common. They provide a useful tool for shortening long words or expression in order to save time and space. Some well-known general examples are DVD (digital versatile disc), UNICEF (United Nations International Children’s Emergency Fund), NASA (National Aeronautics and Space Administration), and UN (United Nations). Abbreviations are extensively used in the scientific and medical communities. It is common practice to use abbreviations for long names of many clinical diseases and procedures, and for scientific techniques that have to be repeated many times in medical or scientific papers, posters, and oral presentations. This can cause substantial communication difficulties for individuals who are not familiar with English abbreviations in their field. The example below is meaningless to individuals who are not familiar with the abbreviations used."
7022,"Poverty, Health and Livelihoods","Developing countries, especially those in the tropical regions of the world, are known for poverty and infectious diseases (ID). People in developing countries carry on their day-to-day living amongst these two challenges. Between the years 1940–2004, over 300 emerging human ID have been reported worldwide. Infectious diseases have resulted in high mortality and morbidity in developing countries. Affecting more than 1 billion of the world’s population, neglected tropical diseases (NTD) are a group of infectious diseases that are endemic in the poorest regions of the world. Most of the affected populations live in rural areas with very minimal resources but at high risk of disease due to their livelihood. Non-communicable diseases are also on the increase in developing countries, further exacerbating public health challenges in these regions. With nearly 15 million people dying each year as a result of ID, most of them living in developing countries, there is need to find solutions to prevent and tackle infectious diseases in these communities. This book is devoted to infectious diseases and livelihoods in developing countries."
7023,The Immune Epitope Database and Analysis Resource,"Epitopes are defined as the molecular structures interacting with specific receptors of the immune system such as antibodies, MHC, and T cell receptor molecules. The Immune Epitope Database and Analysis Resource (IEDB, http://www.immuneepitope.org) is a database specifically devoted to immune epitope data. The database is populated with intrinsic and context-dependent epitope data curated from the scientific literature by immunologists, biochemists, and microbiologists. An analysis resource is linked to the database which hosts various bioinformatics tools to analyze epitope data as well as to predict de novo epitopes. The availability of the IEDB will facilitate the exploration of immunity to infectious diseases, allergies, autoimmune diseases, and cancer. The utility of the IEDB was recently demonstrated through a comprehensive analysis of all current information regarding antibody and T cell epitopes derived from influenza A and determining possible cross-reactivity among H5N1 avian flu and human flu viruses."
7024,Diplomacy and Global Health Security,"This chapter discusses the concept of global health security, the key challenges it raises and the role of diplomacy in addressing them. It begins by outlining an expanded understanding of security, describing the concept of health security, including the dual aspects of societal health security and individual, or personal, health security. The political context is also described. Key issues in societal health security are then outlined, including significant threats and current responses. Threats covered include the emergence of infectious diseases that cross the species barrier from animals to humans, climate change, the deliberate use of disease-causing agents and the growing burden of non-communicable diseases. Current approaches to addressing threats to societal health security are discussed, along with the role to be played by international affairs. The chapter then describes key issues in individual health security, including reliable access to medicines and other health-related products and services; and the politically and economically sensitive determinants of access. The chapter then discusses how to ensure stronger global health security in the future."
7025,Airborne Precautions and Personal Protective Equipment: The Powered Air-Purifying Respirator-Only Approach,"Airborne isolation of patients and use of respirators are a foundational strategy to prevent transmission of pathogens like tuberculosis and novel respiratory viruses via airborne route in healthcare settings. Healthcare personnel respiratory protection programs utilize respirators, which may or may not require fit testing for each individual. This chapter reviews the different types of respirators, which include the more common N95 respirator masks and the somewhat less commonly used powered air-purifying respirators, and the levels of protection offered by each type. The chapter also reviews considerations and controversies regarding use of N95 respirators and PAPRs and situations when a PAPR-only approach might work. In each healthcare facility, the epidemiology and risk assessment of the facility, available evidence in published literature, and certain regulatory standards must inform the clinical policies, protocols, and procedures. Key unanswered questions and further areas for research are outlined."
7026,Origins,"When the first warm breezes of April blow in from Buzzard’s Bay, the South End of New Bedford, near the elbow of the Massachusetts coast as it extends eastward out to Cape Cod, changes character entirely. Not that the fast-food places, convenience stores, double-decker tenements, or boarded-up businesses transform magically into some sort of suburban Valhalla, but the change of season at least encourages people to go out on the streets and makes everything seem a little brighter."
7027,"Constructal Pattern Formation in Nature, Pedestrian Motion, and Epidemics Propagation",
7028,Varieties of Corporate Social Responsibility,"This chapter distinguishes among several versions of capitalism that have very different views of corporate social responsibility (CSR): the maximization of $ value shareholder, the balance the interests of stakeholders view, and the sustainability model that is the official position of the European Union (EU). The Chapter then considers CSR in Japan, and in countries like India and China that have a system of “state capitalism.” I argue that the view of corporate social responsibility (CSR) held by the EU sustainability model of corporate social responsibility is morally superior. I also contend that the American finance based model of philanthropic CSR is not economically adequate in the new international economic order."
7029,Viral Upper Respiratory Tract Infections,"The upper respiratory system is one of the most common sites of infection for adults, but even more so for children. Several viruses, from variable families, cause upper respiratory infections which, although generally underestimated due to their typically self-limiting nature, underlie enormous healthcare resource utilization and financial burden. Such, otherwise “benign” infections, can have very significant sequelae both in the form of bringing about local complications but also inducing asthma attacks, thus greatly increasing morbidity. Their enormous prevalence also indicates that rigorous research should be undertaken in order to tackle them, in both the prevention and treatment field."
7030,Prevention of Infections in Patients with Hematological Malignancies,"Infection is a frequent complication and a leading cause of morbidity and mortality in patients with hematological malignancies. Problems associated with the management of infections in these patients include difficulties in early diagnosis because the clinical signs of infection are subtle, the low performance of diagnostic tests, and suboptimal response to treatment because recovery of host defenses is a key factor for resolution of infection. Preventing these infections relies on infection control measures and antimicrobial chemoprophylaxis. While infection control measures are safe (but not always effective), the use of antimicrobial agents for prophylaxis of infection is not devoid of problems. Its wide use may increase the possibility of the development of resistance, select for resistant organisms, and increase toxicity and cost. Therefore, any attempt to administer an antimicrobial agent should be accompanied by a reflection of the potential benefits and risks of prophylaxis."
7031,Memetic Algorithms with Partial Lamarckism for the Shortest Common Supersequence Problem,"The Shortest Common Supersequence problem is a hard combinatorial optimization problem with numerous practical applications. We consider the use of memetic algorithms (MAs) for solving this problem. A specialized local-improvement operator based on character removal and heuristic repairing plays a central role in the MA. The tradeoff between the improvement achieved by this operator and its computational cost is analyzed. Empirical results indicate that strategies based on partial lamarckism (i.e., moderate use of the improvement operator) are slightly superior to full-lamarckism and no-lamarckism."
7032,MARs and MARBPs: Key modulators of gene regulation and disease manifestation,"The DNA in eukaryotic genome is compartmentalized into various domains by a series of loops tethered onto the base of nuclear matrix. Scaffold/ Matrix attachment regions (S/MAR) punctuate these attachment sites and govern the nuclear architecture by establishing chromatin boundaries. In this context, specific proteins that interact with and bind to MAR sequences called MAR binding proteins (MARBPs), are of paramount importance, as these sequences spool the proteins that regulate transcription, replication, repair and recombination. Recent evidences also suggest a role for these cis-acting elements in viral integration, replication and transcription, thereby affecting host immune system. Owing to the complex nature of these nucleotide sequences, less is known about the MARBPs that bind to and bring about diverse effects on chromatin architecture and gene function. Several MARBPs have been identified and characterized so far and the list is growing. The fact that most the MARBPs exist in a co-repressor/ co-activator complex and bring about gene regulation makes them quintessential for cellular processes. This participation in gene regulation means that any perturbation in the regulation and levels of MARBPs could lead to disease conditions, particularly those caused by abnormal cell proliferation, like cancer. In the present chapter, we discuss the role of MARs and MARBPs in eukaryotic gene regulation, recombination, transcription and viral integration by altering the local chromatin structure and their dysregulation in disease manifestation"
7033,Sepsis,"Definition. „Sepsis“ ist eine systemische entzündliche Reaktion des Organismus (auch als SIRS bezeichnet, systemic inflammatory response syndrome) auf eine Infektion mit Bakterien, Viren, Pilzen und Parasiten. Bei der Sepsis ist die Reaktion des Organismus so heftig, dass es zu Temperaturerhöhungen, Tachykardie, Tachypnoe, Hypotension und disseminierter intravasaler Gerinnung kommen kann. Diagnostische Kriterien einer Sepsis im Kindesalter sind nach der International Sepsis Definitions Conference aus dem Jahr 2001: 1. Nachweis oder Verdacht auf eine Infektion, 2. Hyperthermie (>38,5°C) oder Hypothermie (<36,0°C), 3. Tachykardie, 4. Zeichen mindestens einer gestörten Organfunktion: a. Veränderung des mentalen Status, b. Hypoxie, c. erhöhte Laktatspiegel, d. veränderter Pulscharakter."
7034,Stem Cell Transplantation,"Hematopoietic cell transplantation (HCT) is associated with profound compromises in host defenses. The patterns of immune compromise change over time. Infections are an important cause of serious morbidity and pose substantial threats to life. Thus, the challenges of infection facing the transplant clinician are both myriad and dynamic. Early after transplant, neutropenic infections are most important. Later herpesvirus and invasive fungal infections predominate. Even late after transplant, patients with chronic graft versus host disease remain susceptible to encapsulated bacterial, varicella zoster virus, and invasive fungal infections. Over time, with robust engraftment and control of GVHD, the risk of serious infections recedes with immune reconstitution."
7035,TB Matters More,"Tuberculosis (TB) is the second leading infectious cause of mortality worldwide and arguably the most important neglected topic in bioethics. This chapter: (1) explains the ethical importance of TB, (2) documents its neglect in bioethics discourse, (3) maps the terrain of ethical issues associated with TB, and (4) advocates a moderate pluralistic approach to ethical issues associated with TB."
7036,Delivery Systems for Lymphatic Targeting,"The lymphatic system has a critical role in the immune system’s recognition and response to disease, and it is an additional circulatory system throughout the entire body. Most solid cancers primarily spread from the main site via the tumour’s surrounding lymphatics before haematological dissemination. Targeting drugs to lymphatic system is quite complicated because of its intricate physiology. Therefore, it tends to be an important target for developing novel therapeutics. Currently, nanocarriers have encouraged the lymphatic targeting, but still there are challenges of locating drugs and bioactives to specific sites, maintaining desired action and crossing all the physiological barriers. Lymphatic therapy using drug-encapsulated colloidal carriers especially liposomes and solid lipid nanoparticles emerges as a new technology to provide better penetration into the lymphatics where residual disease exists. Optimising the proper procedure, selecting the proper delivery route and target area and making use of surface engineering tool, better carrier for lymphotropic system can be achieved. Thus, new methods of delivering drugs and other carriers to lymph nodes are currently under investigation."
7037,Health Psychology,"The chapter draws parallels and contrasts between the study of health in North American and other industrialized countries and health of people living in developing countries, which comprise 80% of the world’s population. Lessons are provided for three common health problems where psychologists play a major role within multidisciplinary teams. The lessons use published journal articles, web sites of international organizations, and the author’s personal experiences living and working in developing countries. One topic concerns the large number of women who unnecessarily die in childbirth and the non-medical reasons. The second is environmental health, which includes sources of clean water, waste disposal, and personal hygiene. Solving this problem requires behavior change. The third concerns child hunger and its disabling effects on cognitive development. The focus of this chapter is on examining the health problem within context and identifying solutions that work and do not work. Background is provided for the novice, so students learn the larger picture into which these issues fit, and how to apply the same analysis to other health problems."
7038,Transfusiebeleid,"Anesthesiologen en hematologen zijn in Nederland de grootste voorschrijvers van bloedproducten. Omdat het inzicht in de veiligheid en de indicaties voor bloedproducten de laatste jaren sterk is gewijzigd en omdat er nog steeds grote verschillen in voorschrijfgedrag bestaan tussen artsen en tussen ziekenhuizen, is het belangrijk om dit voorschrijfgedrag te harmoniseren. Up-to-date kennis over de ontwikkelingen in de transfusiegeneeskunde is daarom belangrijk."
7039,The Interconnection between the Built Environment Ecology and Health,"The built environment (BE) affects ecosystems, ecosystem services and human health and well being. While, formally, the BE ranges from the smallest hut to the largest city, this chapter focuses upon the health effects of urban areas, which increasingly are the preferred human habitat. Urban areas have many attractive and beneficial influences to human well-being. But at the same time, many effects of urban areas are harmful to well-being, and many are not even recognized as such. Most publications about these topics have described the effects of the BE separately, on either ecosystems or on human health. The interconnectivity between these two effects relative to BE is rarely studied. This paper focuses on the mutual influence and interactions between three related aspects of the BE which can impact ecosystems and human health: transportation, land use, and life style. It also explores some of the links between the BE, human health, and human security."
7040,Respiratorische Erkrankungen,
7041,Terrorists and Social Media Messages: A Critical Analysis of Boko Haram’s Messages and Messaging Techniques,"Post-colonial Nigeria has been plagued with violent conflicts. A bloody civil war in which an estimated 1 million people were killed ravaged the country from 1967 to 1970. Interethnic and intra-communal conflicts have also shaken the foundations of the nation since 1960 when colonial rule ended. Other violent conflicts that have plagued the country are religious conflicts in Kano, Bauchi, Kaduna, Kafanchan, Zaria, Jos, Maiduguri, and many other places. Blood-letting in the name of religion in these and other places in Nigeria has left thousands dead and wounded. Destruction of property in the course of religious violence in Nigeria has also wreaked economic calamity on the country. For instance, wanton destruction of property during the Maitatsene religious uprising in Kano from 1980 to 1985 resulted in the loss of lives and of millions of dollars. Clashes between members of the militant Shi’ite religious sect and the Nigerian army in 2016 led to the demolition of an entire neighborhood in Zaria city Nigeria’s latest bout of violence emanates from a deadly terrorist group, Boko Haram. Since 2009, it has killed over 20,000 people, displaced more than one million people, and contributed to the devastation of Nigeria’s northeast region. Initially, Boko Haram could not be contained by Nigerian security forces. It captured and held on to 14 local government districts and it constantly churned out online propaganda about its invisibility and its certainty that it would impose a radical Islamic government over the entire country. This chapter provides a critical analysis of Boko Haram’s propaganda. It examines the group’s core messages and the stylistic techniques used in delivering them. The chapter notes that Boko Haram deliberately used crude, unvanished imagery to reinforce the brutality of its actions in suicide bombings, drive-by shootings, and direct attacks against military barracks, markets, mosques, and churches. We contend that the effectiveness of Boko Haram’s propaganda began to decline as it suffered military defeats by Nigerian forces."
7042,Biometrics and Knowledge Management Information Systems,Biometrics and knowledge management information systems are two important fields in recent years to attract wider attentions from different social groups. This chapter explores the use of hierarchical construction linking with biometrics applications and knowledge management information systems. The key issues are discussed and a sample case of information acquisition in content-based image retrieval system has been illustrated.
7043,Viral Subversion of the Immune System,"The continuous interactions between host and viruses during their co-evolution have shaped not only the immune system but also the countermeasures used by viruses. Studies in the last decade have described the diverse arrays of pathways and molecular targets that are used by viruses to elude immune detection or destruction, or both. These include targeting of pathways for major histocompatibility complex class I and class II antigen presentation, natural killer cell recognition, apoptosis, cytokine signalling, and complement activation. This paper provides an overview of the viral immune-evasion mechanisms described to date. It highlights the contribution of this field to our understanding of the immune system, and the importance of understanding this aspect of the biology of viral infection to develop efficacious and safe vaccines."
7044,Human Monoclonal Antibodies Against HIV and Emerging Viruses,
7045,Disease and Injury Among Veterinarians,
7046,Multiplex PCR for Detection and Identification of Microbial Pathogens,"Multiplexed nucleic acid-based tests for infectious disease have become a standard part of clinical laboratory practice. These tests provide a comprehensive syndrome-based approach to determine the etiological agent of disease. The technology underlying these different systems is reviewed here with a special focus on the BioFire FilmArray® platform. The literature on the clinical utility and cost-effectiveness of these platforms for respiratory, blood culture, and gastrointestinal infections is discussed. Although there are reports showing a clear benefit to the patient or to the healthcare system from adopting a syndromic molecular approach, it is also apparent that clinical laboratories and healthcare providers are still learning how to take full advantage of the new systems. Finally, some improvements to this technology that should appear in the next few years are discussed. These include automated pathogen-specific surveillance based on aggregating the data from these systems, a move toward point-of-care syndromic testing, and further decreases in time to result of the tests."
7047,Sore Throat,"Approximately 12 million patients present with acute pharyngitis in the USA annually. Most episodes are viral; however, Group A streptococcus (GAS) is an important and treatable infection (Snow V, Mottur-Pilson C, Cooper RJ, et al., Ann Intern Med 2001;134:506). Group A streptococcus (GAS) is the most common bacterial etiology of acute pharyngitis and accounts for 15–30% of pharyngeal infections in children and 5–20% in adults. The goal of treatment is to reduce the duration and severity of symptoms, as well as reduce complications and transmission. Antimicrobial therapy is recommended for patients with a high index of suspicion for GAS pharyngitis or when it is confirmed by culture or rapid antigen detection testing (RADT). Overtreatment of acute pharyngitis is a major cause of inappropriate antibiotic use and can be avoided by using a systematic approach to evaluation and treatment (Snow V, Mottur-Pilson C, Cooper RJ et al., Ann Intern Med 2001;134:506.)."
7048,Indications for Liver Transplantation,"Candidates for OLT must have irreversible acute or chronic end stage liver disease (table 41b.1). Virus or alcohol-induced liver cirrhosis constitute the most common disease indications in adults [1] (fig. 41b.1). In our department 28% of cirrhotic liver transplant recipients are transplanted for hepatitis C virus (HCV)-related liver disease and 26% undergo OLT for alcohol-related liver disease. Other indications include cholestatic liver disorders [primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), biliary atresia], hepatitis B virus (HBV) infection, autoimmune hepatitis, cystic fibrosis, inherited metabolic diseases (Wilson’s disease, hemochromatosis, alpha-1-antitrypsin deficiency), nonalcoholic steatohepatitis, nonmetastatic hepatocellular carcinoma, and acute virally-, toxin-, or drug-induced hepatic failure. The most common indications in children comprise biliary atresia and metabolic liver diseases"
7049,Clustering the Normalized Compression Distance for Influenza Virus Data,"The present paper analyzes the usefulness of the normalized compression distance for the problem to cluster the hemagglutinin (HA) sequences of influenza virus data for the HA gene in dependence on the available compressors. Using the CompLearn Toolkit, the built-in compressors zlib and bzip2 are compared. Moreover, a comparison is made with respect to hierarchical and spectral clustering. For the hierarchical clustering, hclust from the R package is used, and the spectral clustering is done via the kLine algorithm proposed by Fischer and Poland (2004). Our results are very promising and show that one can obtain an (almost) perfect clustering. It turned out that the zlib compressor allowed for better results than the bzip2 compressor and, if all data are concerned, then hierarchical clustering is a bit better than spectral clustering via kLines."
7050,Tuberculosis in the Intensive Care Unit,
7051,"Human Respiratory Syncytial Virus: Biology, Epidemiology, and Control","According to the World Health Organization, acute lower respiratory tract infection (ALRI) is the fourth leading cause of death worldwide, responsible for approximately 3.1 million (5.5%) of the 56 million estimated deaths per year. Human respiratory syncytial virus (RSV) is recognized as the most important cause of ALRI in infants worldwide. It is estimated that every year 33.8 million new cases of RSV-related ALRIs occur and cause approximately 200,000 deaths in children younger than 5 years; of note, 99% of these deaths occur in developing countries. Usually primary infections occur during the first 2 years of life and are symptomatic, causing from mild upper respiratory tract illness to severe ALRI, and in some cases pneumonia and bronchiolitis may occur simultaneously. Recurrent infections throughout life are common but normally cause milder upper respiratory tract illness. Several studies also associated severe RSV infections during infancy with permanent lung function reduction in adulthood, with higher risk of asthma. The seasonality of the virus varies but it is often detected throughout the year. In South America the highest incidence occurs in the months of January to June. Despite the clinical importance and the disease burden associated with RSV, there is neither specific treatment nor vaccines widely accepted and available nowadays."
7052,Food is Just One of Life’s Risks,
7053,Acute Kidney Injury (AKI),"Kidneys perform a multitude of essential functions within the human body. Of these the most important are (1) maintaining pH through regulation of acid/base levels and (2) excreting end products of metabolism. As for most organ-systems, these functions are especially important for healing following trauma and/or surgery and decline with age. Acute Kidney Injury (AKI) is one of the common forms of organ failures seen in the ICU and elderly patients are more prone to it. The causes maybe classified as Prerenal (inadequate perfusion), renal (inherent kidney disease) and post-renal (urinary obstruction). Preventing AKI should be an important concern in all critically ill patients but especially important in the elderly patients since the development of AKI can significantly increase in-hospital mortality. Once AKI has set in a systematic and step-wise approach of diagnosis and management is key to avoiding adverse outcomes."
7054,Physical Environment of Tall Residential Buildings: The Case of Hong Kong,"Increasing urban populations, scarcity of urban land, depletion in resources and severe impact of urban development on sustainability are critical contemporary issues. Such issues have vast implications on the desirability of compact, high-rise high-dense built forms. Yet, the environmental quality and social acceptance of these forms remain barely studied. This chapter reviews some of the critical environmental implications posed by the closely packed high-rise building and high urban densities."
7055,"Pulmonary Hemorrhage, Transient Tachypnea and Neonatal Pneumonia","In newborn infants, pulmonary hemorrhage, often a manifestation of pulmonary edema can range in severity from bloodtinged secretions in the endotracheal tube to life threatening blood loss with hypovolemic shock. It usually presents in the second to fourth day of life and may be associated with lung tissue damage (RDS, infection, and mechanical ventilation with high-inspired oxygen), hypoxia, hypervolemia, hypoproteinemia, congestive heart failure, and coagulation abnormalities. Klukow confirmed an association between pulmonary hemorrhage and a large patent ductus arteriosus with high pulmonary blood flow [1]."
7056,De immuungecompromitteerde patiënt,"patiënten met aangeboren immuundeficiënties; patiënten met een langer bestaande neutropenie; patiënten met een hiv-infectie en een laag CD4-aantal (< 200); patiënten na een allogene hematopoëtische stamceltransplantatie; patiënten die afweerremmende medicatie ontvangen, bijvoorbeeld na een orgaantransplantatie."
7057,The Multifunctional Nucleolar Protein Nucleophosmin/NPM/B23 and the Nucleoplasmin Family of Proteins,"The nucleophosmin (NPM)/nucleoplasmin family of nuclear chaperones has three members: NPM1, NPM2, and NPM3. Nuclear chaperones serve to ensure proper assembly of nucleosomes and proper formation of higher order structures of chromatin. In fact, this family of proteins has such diverse functions in cellular processes such as chromatin remodeling, ribosome biogenesis, genome stability, centrosome replication, cell cycle, transcriptional regulation, apoptosis, and tumor suppression. Of the members of this family, NPM1 is the most studied and is the main focus of this review. NPM2 and NPM3 are less well characterized, and are also discussed wherever appropriate. The structure–function relationship of NPM proteins has largely been worked out. Other than the many processes in which NPM1 takes part, the major interest comes from its involvement in human cancers, particularly acute myeloid leukemia (AML). Its significance stems from the fact that AML with mutated NPM1 accounts for ∼30% of all AML cases and usually has good prognosis. Its clinical importance also comes from its involvement in virus replication, particularly in the era of outbreaks of infectious diseases."
7058,Community-Acquired Pneumonia—Back to Basics,"Lower respiratory tract infections are among the most common infectious diseases worldwide and are caused by the inflammation and consolidation of lung tissue due to an infectious agent.(1) The clinical criteria for the diagnosis include chest pain, cough, auscultatory findings such as rales or evidence of pulmonary consolidation, fever, or leukocytosis."
7059,Modulation of Pre-mRNA Splicing Patterns with Synthetic Chemicals and Their Clinical Applications,"Recent whole genome sequence analyses revealed that a high degree of proteomic complexity is achieved with a limited number of genes. This surprising finding underscores the importance of alternative splicing through which a single gene can generate structurally and functionally distinct protein isoforms [1]. Based on genome-wide analysis, 75% of human genes are thought to encode at least two alternatively spliced isoforms [2, 3]. The regulation of splice site usage provides a versatile mechanism for controlling gene expression and for the generation of proteome diversity, playing essential roles in many biological processes, such as embryonic development, cell growth, and apoptosis. The splice sites are generally recognized by the splicing machinery, a ribonuclear protein complex known as the spliceosome. Spliceosome binding is determined by competing activities of various auxiliary regulatory proteins, such as members of SR protein or heterogeneous nuclear ribonucleoprotein (hnRNP) protein families, which bind specific regulatory sequences and alter the binding of the spliceosome to a particular splice site [1, 4]. Pre-mRNA splicing is regulated in a tissue-specific or developmental stage-specific manner [5]. The selection of splice site can be altered by numerous extracellular stimuli such as hormones, immune response, neuronal depolarization, and cellular stress, through changes in synthesis/degradation, complex formation, and intracellular localization of regulatory proteins. SR proteins are heavily phosphorylated in cells and involved in constitutive and alternative splicing, and the phosphorylation states of SR proteins are altered in response to these extracellular stimuli [6]. Splicing mutations located in either intronic or exonic regions frequently cause hereditary diseases, and more than 15% of mutations that cause genetic disease affect pre-mRNA splicing [7]. Based on a hypothetical idea that we can cure human diseases by regulating the phosphorylation state of SR proteins with synthetic inhibitors of protein kinases, we started our long voyage to challenge the development of new chemical therapeutics."
7060,Art and Heart,"This study explores the perceptions and opinions of children toward the family. The analysis is based primarily on children’s drawings, interviews with children and observations on them, and literature review. The subjects of this study were 16 children from incomplete families, who participated in weekly drawing activities. In addition to the drawings by the children, data in the form of verbal descriptions and non-verbal expressions were collected throughout the drawing sessions via notes-taking, audio-taping, and photo-taking. The data were analysed to provide an understanding of the children’s definitions of the family, the functions of the family, the roles of the parents, what constitutes a “family member” in the minds of the children, the relationships and affection among family members, and the children’s expectations of the family. With such an analysis, it is hoped to explore the children’s perception of their family life, their feelings and emotions, and their outlook for the future. The children had many expectations and hopes concerning their family, home, family members including themselves, and society at large. They also had many dissatisfactions, even complaints. While the children had not discussed much about the functions of the family, they placed much importance on its emotional aspects, and they had expressed emotional needs for parents. In the eyes of the children from incomplete families, “Children’s Home” is a place that satisfies their daily living needs, but it is not family as it lacks affection. In sum, by letting the children speak their minds through their own drawings and interpretations, this study provides a fresh perspective from children on their views of family, family members, as well as the reality and fantasy of life."
7061,Ontology Development for the Immune Epitope Database,"A key challenge in bioinformatics today is ensuring that biological data can be unequivocally communicated between experimentalists and bioinformaticians. Enabling such communication is not trivial, as every scientific field develops its own jargon with implicit understandings that can easily escape an outsider. We describe here our approach to enforce an explicit and exact data representation for the Immune Epitope Database (IEDB Peters et al. 2005) through the use of a formal ontology. Being the first database of its scale in the immune epitope domain, it was necessary for the IEDB to devise an adequate data structure at the outset of the project with the goal that it should be capable of capturing the context of immune recognition. Early on, it became readily apparent that an unambiguous description of the information being captured is imperative for consistent curation across journal articles and among curators. Accordingly, an initial ontology was developed (Sathiamurthy et al. 2005) based upon consultations with domain experts and guidance from expert ontologists. The structure devised from this ontology proved capable of dealing with a great deal of immunological data over time."
7062,Sensitivity of Model-Based Epidemiological Parameter Estimation to Model Assumptions,"Estimation of epidemiological parameters from disease outbreak data often proceeds by fitting a mathematical model to the data set. The resulting parameter estimates are subject to uncertainty that arises from errors (noise) in the data; standard statistical techniques can be used to estimate the magnitude of this uncertainty. The estimates are also dependent on the structure of the model used in the fitting process and so any uncertainty regarding this structure leads to additional uncertainty in the parameter estimates. We argue that if we lack detailed knowledge of the biology of the transmission process, parameter estimation should be accompanied by a structural sensitivity analysis, in addition to the standard statistical uncertainty analysis. Here we focus on the estimation of the basic reproductive number from the initial growth rate of an outbreak as this is a setting in which parameter estimation can be surprisingly sensitive to details of the time course of infection."
7063,Species-Neutral Disease Surveillance: A Foundation of Risk Assessment and Communication,
7064,"Virus-Like Particles, a Versatile Subunit Vaccine Platform","Virus-like particles (VLPs) can be spontaneously formed after expression of self-polymerising viral capsid proteins. VLPs structurally resemble their native source virus, maintaining immunological relevance by retaining formation of immunogenic motifs with natural conformation. The absence of the virus genome renders VLPs safe for administration as a subunit vaccine. VLPs can target both arms of the immune response, with some VLPs initiating production of specific antibodies and others activating cytotoxic T cells. VLPs are also exceptionally versatile, conferring protection against the host virus or acting as a scaffold for antigenic molecules. In addition, VLP can support intraparticulate encapsulation for immunomodulation and gene delivery. VLP vaccines have been developed for prophylactic protection against infectious organisms, and therapeutic treatment of conditions such as Alzheimer’s disease, hypertension, and cancer. With an expanding list of vaccine candidates, VLP vaccines are a promising field with a wide range of applications."
7065,"Catastrophic Anachronisms: The Past, Present and Future of Disaster Medicine","Disasters, particularly earthquakes, volcanoes, floods, war-related complications, famine and infectious epidemics, have been a part of recorded human experience. From Pompeii to the Johnston Flood and World War II and the Black Plague to the Spanish Influenza, there have been catastrophic occurrences that will not long be forgotten by either legend or history books. Nevertheless, those occurrences were relatively few and far-between before the mid-twentieth century. Indeed, the nature of disasters has changed since then. From terrorists taking advantage of ‘new technology’ to weather-related events that cause trillions of dollars worth of damages and economic loss, the world has evolved."
7066,Nierziekten,"Gekenmerkt door hematurie, proteïnurie, hypertensie, oedemen en soms door oligurie en acute nierinsufficiëntie. Dit ziektebeeld verloopt sneller en heeft andere oorzaken dan ‘rapidly progressive’ *glomerulonefritis. Aet. Kan optreden zowel na bacteriële als na virale of parasitaire infecties. Meest bekend is *acute poststreptokokkenglomerulonefritis. Zeldzamere infectieuze oorzaken zijn: stafylokokken, pneumokokken, lues, waterpokken, mazelen, rubella, mononucleosis infectiosa, cytomegalievirus, hantavirus, hepatitis B en malaria. Andere oorzaken zijn *anti-GBM-glomerulonefritis en systeemziekten: *lupus erythematodes disseminatus, henoch-schönlein-nefritis (zie *Anafylactoïde purpura), *polyarteriitis, *granulomatosis van Wegener. Zie ook *Glomerulonefritis."
7067,Emerging Risks Related to Food Technology,"Global food security and safety are threatened by a number of fast-occurring changes, even in the absence of natural disasters or terrorist attacks: overpopulation and urbanisation, environmental pollution, climate changes, intensive animal breeding, international trade and travel, emerging water- and food-borne diseases, antimicrobial-resistant bacteria, increasing food costs, complexity of food supply chains, malnutrition and risky food behaviour. Food safety management tools, including food legislation, national and international standards, quality management systems, risk analysis, risk-based inspections and controls, monitoring and alert systems for food contaminants and food-borne diseases, quantitative microbial risk assessment, nutrition and toxicology studies, and elaborate food processing technologies have brought to consumers in developed countries a wide selection of safe foods. Predictive and early warning and communication systems are being developed to increase the ability to “expect the unexpected” and take prevention measures before food hazards become real risks. The production, processing, transportation, storage and/or distribution stages of modern food supply chains remain exposed to various types of biological or chemical contaminants, as evidenced by recent events or crises. The prion/BSE, dioxin, acrylamide, melamine, bisphenol A cases, and the numerous pathogen outbreaks illustrate this exposure. The melamine story and the international traffic of counterfeited foods and drinks show that profit-motivated fraud and adulteration are rising threats, opening potential paths for terrorist actions. Recent food preservation, processing or packaging technologies and trends, in spite or because of their benefits (mild treatment, extended product shelf-life, “fresher” quality, RTE pre-cooked convenience) also bring safety risks at the consumer level: incomplete microbial inactivation, possible non respect of adequate storage conditions and expiration dates, undercooking, and generation of stress-resistant micro-organisms. Innovative technologies, such as the use of nanoparticules in foods or food contact materials, and the development of active, intelligent or sustainable food packaging entail uncertainties and safety concerns. Natural disasters, droughts, floods, conflicts, and poverty often lead to emergency situations requiring large assistance operations with complex logistics and specific meals ready-to-eat or nutrient-supplemented foods. Containerised food processing units that could be deployed and quickly set to operate in ­production-disrupted areas are being developed by the World Food Programme. Other strategies against food insecurity include insurance policies for crop failures and renting of agricultural lands abroad. Citizen perception of food safety risks and the EU consumers’ “right to informed choice” explain why some technologies elicit rejection: ionising irradiation of foods, hormonal and antibiotic treatment of animals, the use of various “­artificial” food additives, genetically modified crops and ingredients, cloned animals. Perceived benefits responding to consumers’ needs (healthier, more nutritive, higher quality, more convenient, lower cost), “naturalness”, respect of the environment and trusted information are the major factors influencing consumers’ acceptance of innovative food technologies and products. Novel foods and technologies are also subject to strict regulatory pre-market safety assessment and authorisation procedures. While necessary for protection against unexpected risks, some of these rules serve as barriers to innovation and trade, and fodder for strong political debates."
7068,Animal Models for Reye’s Syndrome,"Reye’s Syndrome (RS) was first documented by Douglas Reye and colleagues in 1963 as an “encephalopathy with fatty degeneration of the viscera,” a rare entity, but one that at that time was associated with an 80% mortality rate (Reye et al., 1963). Although the apparent incidence and outcome of the disease have improved, it continues to be one of the major causes of noninflammatory neurologic death after a viral illness in children (Sullivan-Boylai and Corey, 1981; Heubi et al., 1987)."
7069,Are We from Outer Space?: A Critical Review of the Panspermia Hypothesis,"The biological record suggests that life on Earth arose as soon as conditions were favorable, which indicates that life either originated quickly, or arrived from elsewhere to seed Earth. Experimental research under the theme of “astrobiology” has produced data that some view as strong evidence for the second possibility, known as the panspermia hypothesis. While it is not unreasonable to consider the possibility that Earth’s life originated elsewhere and potentially much earlier, we conclude that the current literature offers no definitive evidence to support this hypothesis. Chladni’s view, that they fall from the skies, pronounced in 1795, was ridiculed by the learned men of the times. (Rachel, 1881) Evidence of life on Mars, even if only in the distant past, would finally answer the age-old question of whether living beings on Earth are alone in the universe. The magnitude of such a discovery is illustrated by President Bill Clinton’s appearance at a 1996 press conference to announce that proof had been found at last. A meteorite chipped from the surface of the Red Planet some 15 million years ago appeared to contain the fossil remains of tiny life-forms that indicated life had once existed on Mars. (Young and Martel, 2010)"
7070,Application of UPT-POCT in Anti-bioterrorism and Biosecurity,"With the exception of toxins, bioterrorism agents are mainly microorganisms, many of which cause serious infectious diseases. Up-converting phosphor technology-based point-of-care testing (UPT-POCT) can detect bioterrorism agents from various samples with high sensitivity and specificity, in particular it shows robust performance for complicated samples, such as food, powder, viscera and grains. The tolerance of UPT-POCT to sample is based on the physical and luminescence stability of UCNPs, the stable covalent interaction between UCNPs and antibody, as well as the strong buffering capacity of the detection system. Reliable results can be obtained in a short time period using a portable biosensor by nonprofessionals owing to the simple nature of UPT-POCT operation and sample pre-treatment."
7071,Thrombotic Microangiopathy Syndrome in the ICU,"Since the first descriptions of haemolytic-uremic syndrome (HUS) by Moschowitz and thrombotic thrombocytopenic purpura (TTP) by Gasser, our knowledge about thrombotic microangiopathy (TMA) has grown considerably [1]. TMA now refers to a group of diseases comprising mechanical hemolytic anemia, peripheral thrombocytopenia, and varying degrees of organ failure. The incidence of TMA is increasing in the USA. Considerable progress has recently been made in the understanding of the pathophysiological mechanisms of TMA. These rare diseases, characterized by platelet thrombi in the microcirculation, are responsible for often serious organ dysfunction leading to the admission of these patients to intensive care units (ICUs). The prognosis of TMA was extremely poor prior to plasma therapy and especially plasma exchange. TMA is a serious, life-threatening disease that requires early diagnosis and urgent specialized therapeutic management."
7072,Melanom,"Das Melanom ist der gefährlichste Hautkrebs mit der höchsten Sterblichkeitsrate, der schon bei jungen Menschen auftreten kann und seit Jahrzehnten steigende Inzidenz verzeichnet (Jemal et al. 2007; Little et al. 2012). Jährlich erkranken weltweit etwa 137.000 Menschen am Melanom und 37.000 versterben an der Erkrankung (Boyle et al. 2004). Die Inzidenz liegt weltweit jährlich bei 2,3–2,6/100.000 Einwohner (Pisani et al. 2002). In Deutschland beträgt die Inzidenz 19,2/100.000 Einwohner und es verstarben 2711 Betroffene im Jahre 2010 (Statistisches Bundesamt)."
7073,"Drug Resistance in Infectious Diseases: Modeling, Parameter Estimation and Numerical Simulation","Infectious diseases are drawing our attention again. In recent years, we have been confronted with SARS, bird-flu, swine-flu and many other severe diseases. In addition, pathogens are getting resistant to drugs controlling them. In this paper we establish a new population dynamical system of infectious diseases including drug treatment. We take into account both sensitive and resistant parasites. The unknown model parameters are fitted based on a set of data for malaria from Cisse, Burkina Faso. The fitted model is used to investigate the influence of drug treatment on drug resistance. Based on these investigations, treatment strategies to reduce drug resistance can be elaborated."
7074,Surveillance and Seroepidemiology,"Surveillance has been defined as the systematic collection of data pertaining to the occurrence of diseases, the analysis and interpretation of these data, and the dissemination of consolidated and processed information to contributors, programs, and other interested persons. A wide variety of data sources are used for surveillance purposes. Some data sources were designed for the purpose of surveillance while other data sources are used secondarily for surveillance. To improve the timeliness and quality of surveillance data while simultaneously minimizing cost, surveillance networks and Health Information Exchanges (HIEs) were developed. Surveillance networks allow developing countries to participate in surveillance, establishing early warning of outbreaks. HIEs facilitate access to and retrieval of patient clinical data to support more efficient, timely, effective, equitable, and safe healthcare and to enhance case reporting. Seroepidemiology is the systematic collection and testing of blood samples from a target population to identify current and past experiences with infectious diseases by means of biological markers. Data from serological surveys can reveal total burden of current and past, as well as apparent and inapparetnt infections. Surveillance and seroepidemiology have provided critical epidemiologic information to support public health policy at the local, national, and international levels."
7075,"Introduction: Climate Change, Human Security, and Violent Conflict in the Anthropocene","This book focuses on possible causal linkages among the three scientific research areas of climate change, human security, and violent conflict and asks whether they have posed challenges for societal stability in the past and in the present, and whether climate change might intensify societal instability in the future. It addresses scientific problems that are primarily analysed."
7076,Online Social Networks Flu Trend Tracker: A Novel Sensory Approach to Predict Flu Trends,"Seasonal influenza epidemics cause several million cases of illnesses cases and about 250,000 to 500,000 deaths worldwide each year. Other pandemics like the 1918 “Spanish Flu” may change into devastating event. Reducing the impact of these threats is of paramount importance for health authorities, and studies have shown that effective interventions can be taken to contain the epidemics, if early detection can be made. In this paper, we introduce Social Network Enabled Flu Trends (SNEFT), a continuous data collection framework which monitors flu related messages on online social networks such as Twitter and Facebook and track the emergence and spread of an influenza. We show that text mining significantly enhances the correlation between online social network(OSN) data and the Influenza like Illness (ILI) rates provided by Centers for Disease Control and Prevention (CDC). For accurate prediction, we implemented an auto-regression with exogenous input (ARX) model which uses current OSN data and CDC ILI rates from previous weeks to predict current influenza statistics. Our results show that, while previous ILI data from the CDC offer a true (but delayed) assessment of a flu epidemic, OSN data provides a real-time assessment of the current epidemic condition and can be used to compensate for the lack of current ILI data. We observe that the OSN data is highly correlated with the ILI rates across different regions within USA and can be used to effectively improve the accuracy of our prediction. Therefore, OSN data can act as supplementary indicator to gauge influenza within a population and helps to discover flu trends ahead of CDC."
7077,Origins of the regulated secretory pathway,"Modes of transport of soluble (or luminal) secretory proteins synthesized in the endoplasmic reticulum (ER) could be divided into two groups. The socalled constitutive secretory pathway (CSP) is common to all eukaryotic cells, constantly delivering constitutive soluble secretory proteins (CSSPs) linked to the rate of protein synthesis but largely independent of external stimuli. In regulated secretion, protein is sorted from the Golgi into storage/secretory granules (SGs) whose contents are released when stimuli trigger their final fusion with the plasma membrane (Hannah et al. 1999)."
7078,Prophylaxis of Healthcare Workers in an Influenza Pandemic,"The threat of an imminent influenza pandemic has galvanized global efforts to identify effective preparedness strategies and consider securing health resources. As the nations prepare to meet this threat, public health interventions are being carefully gauged within the context of influenza epidemiology, populations, and healthcare systems. A pandemic will place enormous demands on healthcare systems that include at the center of planning efforts the protection of healthcare workers. During an influenza pandemic, healthcare workers will be on the front lines delivering care to patients and preventing further spread of the disease. Protecting these workers from acquiring or transmitting infection in the hospital ward and outside the workplace is critical to containing a pandemic and limiting morbidity and mortality of the population. Several approaches to protecting healthcare workers include vaccination, antiviral 10.1007/978-0-387-78665-0_6443, use of personal protective equipment, and adherence to other infection control practices. In the absence of vaccination, application of antiviral drugs has been rationalized as the first-line defense against the 10.1007/978-0-387-78665-0_6288. While the treatment of ill individuals is top priority in most national contingency plans, the use of drugs as prophylaxis has been debatable. This chapter attempts to highlight the importance of a competent healthcare system in response to an influenza pandemic, and presents the conflicting issues that are surrounding an antiviral prophylaxis strategy. An overview of potential benefits and limitations, logistical constraints, and clinical and epidemiological consequences of healthcare worker prophylaxis is also provided."
7079,Pulmonary Complications of Obstetric and Gynecologic Conditions,"The respiratory and the female reproductive systems are not embryologically or functionally related. However, the reproductive system can exert significant effects on the respiratory system as a result of the various hormonal changes that occur during a woman’s menstrual cycle and especially during pregnancy. In addition, there are several unique gynecologic and/or obstetric conditions that can directly affect the respiratory system. The following chapter reviews the effects of pregnancy on the respiratory system, as well as the special issues concerning the management of common respiratory conditions (e.g., pneumonia, asthma) during pregnancy. In addition it reviews several gynecologic disorders with unique pulmonary complications."
7080,Schweinebandwurm,
7081,Epidemiology of Acute Respiratory Failure and Mechanical Ventilation,"Acute respiratory failure, and the need for mechanical ventilation, remains one of the most common reasons for admission to the intensive care unit (ICU). The burden of acute respiratory failure is high in terms of mortality and morbidity as well as the cost of its principal treatment, mechanical ventilation. Very few epidemiologic studies have evaluated the prevalence and outcome of acute respiratory failure and mechanical ventilation in general. Most of the published literature has focused on specific forms of acute respiratory failure, particularly acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In this chapter, we provide a brief review of the pathophysiology of acute respiratory failure, its definition and classification, and then present the incidence and outcomes of specific forms of acute respiratory failure from epidemiologic studies."
7082,Network-Based Analysis of Beijing SARS Data,"In this paper, we analyze Beijing SARS data using methods developed from the complex network analysis literature. Three kinds of SARS-related networks were constructed and analyzed, including the patient contact network, the weighted location (district) network, and the weighted occupation network. We demonstrate that a network-based data analysis framework can help evaluate various control strategies. For instance, in the case of SARS, a general randomized immunization control strategy may not be effective. Instead, a strategy that focuses on nodes (e.g., patients, locations, or occupations) with high degree and strength may lead to more effective outbreak control and management."
7083,Counteraction to CBRN Terrorism in Switzerland,"In Switzerland, the planning of security policy measures now increasingly factors in scenarios involving the use of CBRN weapons on Swiss soil. While there have been no terrorist “spectaculars” or dramatic news reports in recent years, this does not mean that the CBRN threat has diminished. In 2003 a project called National NBC Protection was started in order to guarantee efficient coordination of all partners involved in CBRN prevention and incident management at all levels with the aim of improving the NBC protection in Switzerland in the long term. The availability of outstanding expertise in terms of NBC protection therefore remains as important as ever for the Swiss population."
7084,Single-Particle cryo-EM as a Pipeline for Obtaining Atomic Resolution Structures of Druggable Targets in Preclinical Structure-Based Drug Design,"Single-particle cryo-electron microscopy (cryo-EM) and three-dimensional (3D) image processing have gained importance in the last few years to obtain atomic structures of drug targets. Obtaining atomic-resolution 3D structure better than ~2.5 Å is a standard approach in pharma companies to design and optimize therapeutic compounds against drug targets like proteins. Protein crystallography is the main technique in solving the structures of drug targets at atomic resolution. However, this technique requires protein crystals which in turn is a major bottleneck. It was not possible to obtain the structure of proteins better than 2.5 Å resolution by any other methods apart from protein crystallography until 2015. Recent advances in single-particle cryo-EM and 3D image processing have led to a resolution revolution in the field of structural biology that has led to high-resolution protein structures, thus breaking the cryo-EM resolution barriers to facilitate drug discovery. There are 24 structures solved by single-particle cryo-EM with resolution 2.5 Å or better in the EMDataBank (EMDB) till date. Among these, five cryo-EM 3D reconstructions of proteins in the EMDB have their associated coordinates deposited in Protein Data Bank (PDB), with bound inhibitor/ ligand. Thus, for the first time, single-particle cryo-EM was included in the structure-based drug design (SBDD) pipeline for solving protein structures independently or where crystallography has failed to crystallize the protein. Further, this technique can be complementary and supplementary to protein crystallography field in solving 3D structures. Thus, single-particle cryo-EM can become a standard approach in pharmaceutical industry in the design, validation, and optimization of therapeutic compounds targeting therapeutically important protein molecules during preclinical drug discovery research. The present chapter will describe briefly the history and the principles of single-particle cryo-EM and 3D image processing to obtain atomic-resolution structure of proteins and their complex with their drug targets/ligands."
7085,2 Infecties van de bovenste luchtwegen,Luchtweginfecties in het algemeen en infecties van de bovenste luchtwegen in het bijzonder komen wereldwijd zeer veel voor en zijn de voornaamste reden om een arts te consulteren.
7086,Biosafety and Bioethics,"The advancement in technology is likely to tame several life forms present on earth. Microorganisms are posing a big challenge due to difficulties encountered to control the diseases caused by them. Working with deadly disease-causing microorganisms for their characterization, diagnostics or therapeutics and vaccine development purposes are posing increasingly potential biosafety problems for laboratory workers. Thus, an appropriate biosafe working environment may protect workers from laboratory-induced infections. Biotechnology has the ability to solve the upcoming problems of the world’s increasing population. However, there is often reluctance among the public to accept and support biotechnological products in medicine, industry, or agriculture. There are many safety and ethical issues raised for GM crops and human cloning. Raising transgenic animals and plants has fueled ethical concerns, and the scientists have faced a lot of resistance where genetically modified crop plants or reproductive cloning research of human beings is involved. Thus, biosafety and bioethics are continuously being expanded to combine the rationale of ever-increasing scientific knowledge in biotechnology that is often in conflict with the long-standing social and moral value system of our society."
7087,"7 Hoesten, van symptoom tot diagnose","Hoesten behoort, naast klachten van het houdings- en bewegingsapparaat, tot de twee belangrijkste contactredenen voor consultatie van de huisarts. De hoogste incidentie- en prevalentiecijfers voor hoesten worden gevonden in de leeftijdsgroep van 0-4 jaar (respectievelijk 81,2 en 82,4)."
7088,Broncopneumopatia cronica ostruttiva (BPCO),"La broncopneumopatia cronica ostruttiva (BPCO) è una delle maggiori cause di morbilità e mortalità in tutto il mondo. A causa dell’elevata prevalenza e della possibilità di essere una patologia altamente invalidante, i costi della BPCO possono rappresentare un importante impegno economico e sociale per la spesa sanitaria."
7089,Alpha-1 Antitrypsin as a Therapeutic Agent for Conditions not Associated with Alpha-1 Antitrypsin Deficiency,"Alpha-1 antitrypsin is a positive acute phase reactant whose serum level rises in response to inflammatory stress, presumably to balance pro-inflammatory processes. In addition to its serine protease inhibitory action, alpha-1 antitrypsin exhibits broader anti-inflammatory and immunomodulatory activity, and increasing its serum concentration by the administration of exogenous alpha-1 antitrypsin to above-normal levels potentially could be therapeutic in conditions other than alpha-1 antitrypsin deficiency. In vitro observations, studies in animal models and in some instances early human trials suggest that intravenous or inhaled alpha-1 antitrypsin has beneficial effects in type 1 diabetes, viral infections, graft-versus-host disease, cystic fibrosis, and alpha-1 antitrypsin-replete chronic obstructive pulmonary disease among others. While the results of pivotal clinical trials have not been reported to date, new indications for alpha-1 antitrypsin therapy are likely to emerge in the future based on currently available scientific data."
7090,"Enhancement of Medicinally Important Bioactive Compounds in Hairy Root Cultures of Glycyrrhiza, Rauwolfia, and Solanum Through In Vitro Stress Application","Enhancement of secondary metabolites through elicitation in hairy root culture is a very effective method which is broadly used to simulate the stress responses in plants. Elicitors are compounds that induce plants to produce secondary metabolites at elevated levels and reduce the processing time required to achieve high product concentrations. Hairy root cultures are considered as an excellent alternative for the supply of pharmaceutically important secondary metabolites/bioactives, due to their inherent genetic and biochemical stability. Plant-based secondary metabolites are well accepted in India as well as other countries to cure even the serious medical problems. In this chapter, three medicinally important plants are discussed in which stress-based elicitation of secondary metabolites has been achieved in hairy root cultures. These three plants contain important secondary metabolites in their different parts. Glycyrrhizin found in Glycyrrhiza glabra plant is used as antiulcer, immunomodulatory, antiallergic, and anti-inflammatory. Glycyrrhizin is also effective against HIV and severe acute respiratory syndrome (SARS)-like viruses. In Solanum plant, steroidal glycoalkaloids contain pharmaceutically important secondary metabolites. Solasodine, a major alkaloid of Solanum plant, is used as a contraceptive in different parts of the world. Ajmaline and ajmalicine are important root-specific indole alkaloids of Rauwolfia serpentina. Ajmalicine is useful in circulatory disorders, while ajmaline is principally known for its antiarrhythmic and antihypertensive activities. The main objective of this chapter is to provide knowledge in these plants regarding elicitation-based enhancement of valuable secondary metabolites in the form of research studies conducted till date (as per author’s knowledge)."
7091,Acronimi e abbreviazioni in chirurgia e in medicina,"“The patient went from the ER to the OR and then to the ICU”. Indubbiamente il lessico dei medici è ricco di abbreviazioni, tanto che gli operatori della sanità in generale e i chirurghi in particolare adoperano perlomeno dieci abbreviazioni per minuto (questa è una statistica fatta in casa, non citatela)."
7092,Rituximab,"Rituximab (Rituxan(®), MabThera(®), and Genentech/Roche) is a chimeric murine/human monoclonal IgG1k antibody directed against the CD20 antigen located at the surface of normal and malignant B lymphocytes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/978-88-470-5313-7_35) contains supplementary material, which is available to authorized users."
7093,Endodontics in Systemically Compromised Patients,"A substantial number of people in today’s world are elderly and as the incidence of a number of pathologies increases with age, it is predicted to produce millions of individuals with systemic medical conditions that can affect oral health and subsequent dental treatment. The dental management of these medically compromised patients can be sometimes problematic in terms of oral complications, dental therapy, and emergency care. One of the challenges faced by dental specialists today is the assessment and management of these patients. As mentioned in detail in Chap. 12, geriatric patients are much more likely to be at least partially dentulous having a complex medical history and the use of multiple medications."
7094,Social Communications Assisted Epidemic Disease Influence Minimization,"This work explores the use of social communications for epidemic disease control. Since the most infectious diseases spread through human contacts, we focus on modeling the diffusion of diseases by analyzing the social relationship among individuals. In other words, we try to capture the interaction pattern among human beings using the social contact information, and investigate its impact on the spread of diseases. Particularly, we investigate the problem of minimizing the expected number of infected persons by treating a small fraction of the population with vaccines. We prove that this problem is NP-hard, and propose an approximate algorithm representing a preventive disease control strategy based on the social patterns. Simulation results confirm the superiority of our strategy over existing ones."
7095,Building on Experience: Learning Lessons from Past Framework Programmes,
7096,Infectieziekten,"De bespreking van ziektebeelden in dit boek wordt begonnen met infectieziekten, niet zozeer omdat deze een van de belangrijkste categorieën in de huisartspraktijk zouden vormen, maar omdat alle classificatiesystemen van ziekten hiermee beginnen. Op de keper beschouwd bieden de classificatiesystemen onder het hoofdstuk infectieziekten een restgroep van ziekten omdat een aantal infecties niet hier, maar bij orgaansystemen is ondergebracht. Luchtweginfecties bijvoorbeeld, die zo’n groot deel van het werk van de huisarts uitmaken, worden onder de tractus respiratorius geregistreerd (en in dit boek in hoofdstuk 8 besproken). Soms worden nieuwe infectieziekten aan het hoofdstuk infectieziekten toegevoegd (zoals hiv-infectie). Het bekend worden van de rol van een micro-organisme in de etiologie van een aandoening leidt overigens niet altijd tot aanpassingen (bijvoorbeeld Helicobacter pylori-infectie bij ulcus duodeni en ulcus ventriculi)."
7097,Il lavaggio broncoalveolare (BAL) in età pediatrica,"Il lavaggio broncoalveolare o BAL, permettendo di ottenere le cellule ed i soluti presenti sulla superficie epiteliale del tratto respiratorio distale, si è dimostrato una metodica di ricerca essenziale per lo studio dei meccanismi eziopatogenetici delle malattie del polmone profondo, come ad esempio lo studio delle interstiziopatie, su cui esiste una vastissima letteratura di dati ottenuti con il BAL. Oltre a questo aspetto di metodica di ricerca, il BAL rappresenta perè anche una procedura diagnostica insostituibile nella pratica clinica quotidiana."
7098,Fungal Vaccines and Vaccination: Problems and Perspectives,"Vaccines against human pathogenic fungi, a rather neglected medical need until few years ago, are now gaining steps in the public health priority scale. The awareness of the rising medical threat represented by the opportunistic fungal infections among the health care-associated infections, the advances in the knowledge of fungal pathogenicity and immune response and the extraordinary progress of biotechnology have generated enthusiasm and critical new tools for active and passive anti-fungal vaccination. The discovery that antibodies play a critical role for protection against fungal infection has greatly contributed to the advancements in this field, in recognition that almost all useful vaccines against viral and bacterial pathogens owe their protective efficacy to neutralizing, opsonizing or otherwise effective antibodies. Overall, there is more hope now than few years ago about the chances of generating and having approved by the regulatory authorities one or more antifungal vaccines, be active or passive, for use in humans in the next few years. In particular, the possibility of protecting against multiple opportunistic mycoses in immuno-depressed subjects with a single, well-defined glucan-conjugate vaccine eliciting directly anti-fungal antibodies may be an important step to achieve this public health goal"
7099,Analyzing Global Epidemiology of Diseases Using Human-in-the-Loop Bio-Simulations,"Humanity is facing an increasing number of highly virulent and communicable diseases such as influenza. Combating such global diseases requires in-depth knowledge of their epidemiology. The only practical method for discovering global epidemiological knowledge and identifying prophylactic strategies is simulation. However, several interrelated factors, including increasing model complexity, stochastic nature of diseases, and short analysis timeframes render exhaustive analysis an infeasible task. An effective approach to alleviate the aforementioned issues and enable efficient epidemiological analysis is to manually steer bio-simulations to scenarios of interest. Selective steering preserves causality, inter-dependencies, and stochastic characteristics in the model better than “seeding”, i.e., manually setting simulation state. Accordingly, we have developed a novel Eco-modeling and bio-simulation environment called SEARUMS. The bio-simulation infrastructure of SEARUMS permits a human-in-the-loop to steer the simulation to scenarios of interest so that epidemics can be effectively modeled and analyzed. This article discusses mathematical principles underlying SEARUMS along with its software architecture and design. In addition, the article also presents the bio-simulations and multi-faceted case studies conducted using SEARUMS to elucidate its ability to forecast timelines, epicenters, and socio-economic impacts of epidemics. Currently, the primary emphasis of SEARUMS is to ease global epidemiological analysis of avian influenza. However, the methodology is sufficiently generic and it can be adapted for other epidemiological analysis required to effectively combat various diseases."
7100,Lungenversagen,"Das akute Lungenversagen ist eine schwere diffuse entzündliche Erkrankung der Lunge. Nach der „American-European Consensus Conference“ (Bernard et al., 1994) wird zwischen einem ARDS — acute respiratory distress syndrom und einem ALI — acute lung injury unterschieden."
7101,Dangerous Viral Pathogens of Animal Origin: Risk and Biosecurity: Zoonotic Select Agents,"Most of emerging infectious diseases affecting humans are of animal origin and transmitted under natural circumstances from either, wild or domestic vertebrate animals giving the way of zoonotic infection or epidemics. Zoonotic diseases carry a common ancient history between human and animals as a result of pathogen exchanges involving transgression of the species barrier. Nowadays, several agents have been targeted for their potential to be a major risk for human and animal populations and, have been characterized by their potential to be highly pathogenic and/or transmissible, and lacking of any means of protection. Those agents have been listed as “Select Agents” having the potential to pose a severe threat to both human and animal health, as well as to animal and plant products. Several of the most dangerous agents responsible of viral hemorrhagic fever are review in this chapter including: Ebola virus, Marburg virus, Rift valley fever virus, Kyasanur forest virus, Omsk hemorrhagic fever virus, Alkhurma hemorrhagic fever virus."
7102,Concerns and Threats of Contamination on Aquatic Ecosystems,"Aquatic ecosystems are the ultimate sinks for the contaminants. Water contamination is the outcome of human activities such as urbanization, industrialization, and agricultural activities. The overuse of pesticides and fertilizers and sewage from residential and industrial areas ultimately find its way to aquatic environment. Thus results in the degradation of the water quality and leads to the spread of infectious diseases such as dysentery, diarrhea, and jaundice. Contamination in aquatic environs is one of the leading types of pollution which has significant negative health issues and mortality. Water has a natural capacity to neutralize the contamination, but when contamination becomes uncontrolled, water will lose its self-generating capacity. Therefore, there is a need for regular monitoring and controlling of pollutant discharge into the nearby aquatic environs."
7103,Die Diagnose der Sepsis,"Die frühe Diagnostik der Sepsis ist das Nadelöhr für die weitere Senkung der Sepsissterblichkeit. Inzwischen liegen Befunde vor, dass, vergleichbar mit akutem Myokardinfarkt und Schlaganfall, dem Faktor Zeit eine wichtige Rolle zukommt. Demgegenüber gibt es keine allgemein akzeptierte Sepsisdiagnostik, die der Forderung nach früher Diagnose und der Unabhängigkeit vom Erfahrungsstand des jeweiligen Arztes Rechnung tragen könnte."
7104,14 Neusverstopping,"Acute neusverstopping is een frequente aandoening. Meestal is het geen geïsoleerd symptoom, maar treedt zij gecombineerd op met andere klachten van de neus. In overgrote meerderheid is de oorzaak een virale infectie die vanzelf overgaat, en heeft verdere diagnostiek geen consequenties voor de therapie. Bij chronische klachten is verdere diagnostiek wel zinvol; een allergie of hyperreactiviteit is het meest waarschijnlijk. Bij chronische neusverstopping is aandacht voor chronisch gebruik van decongestieve neusdruppels van belang. Persisterende eenzijdige neusverstopping, zeker wanneer dit gepaard gaat met bloederige afscheiding, is een alarmsymptoom."
7105,An Overview of Antimicrobial Properties of Different Classes of Phytochemicals,"Plants produce a great diversity of phytochemicals, the beneficial properties of which have been used by humans for centuries since the advent of human civilization. With the discovery of effective and potent antimicrobial compounds, these synthetic antimicrobial compounds are widely used to prevent and cure microbial diseases. However, the development of antibiotic resistant strains of bacteria, reduced efficacy and safety of antimicrobials and the search of new antimicrobials against emerging incurable diseases by conventional antimicrobial agents have revived to explore phytochemicals as an alternative to synthetic antimicrobial compounds. Although numerous studies have been conducted in vitro and in vivo in the recent years on the efficacy of plant phytochemicals as antimicrobial agents, this chapter provides an overview of the antimicrobial properties of some major group of phytochemicals, namely, different phenolic compounds, alkaloids, saponins, iridoids and secoiridoids, polyacetylenes, glucosinolates, terpenoids, sulfinate, limonoids (tetranortepenoids) and anthranoids against pathogenic bacteria, fungi, viruses and commensal bacteria in the intestinal tracts of humans and animals. This chapter also discusses their antimicrobial mechanisms of action, the efficiency of different groups of phytochemicals against multiple-drug resistant bacteria, the effect of active dietary phytometabolites on the beneficial and pathogenic microbes of the gastrointestinal tracts and the outcomes of combination of phytofactors and drugs interactions."
7106,Disruption of the Blood-Brain Barrier During Neuroinflammatory and Neuroinfectious Diseases,"As the organ of highest metabolic demand, utilizing over 25% of total body glucose utilization via an enormous vasculature with one capillary every 73 μm, the brain evolves a barrier at the capillary and postcapillary venules to prevent toxicity during serum fluctuations in metabolites and hormones, to limit brain swelling during inflammation, and to prevent pathogen invasion. Understanding of neuroprotective barriers has since evolved to incorporate the neurovascular unit (NVU), the blood-cerebrospinal fluid (CSF) barrier, and the presence of CNS lymphatics that allow leukocyte egress. Identification of the cellular and molecular participants in BBB function at the NVU has allowed detailed analyses of mechanisms that contribute to BBB dysfunction in various disease states, which include both autoimmune and infectious etiologies. This chapter will introduce some of the cellular and molecular components that promote barrier function but may be manipulated by inflammatory mediators or pathogens during neuroinflammation or neuroinfectious diseases."
7107,Identifying Major Histocompatibility Complex Supertypes,"Human leukocyte antigen (HLA) recognizes antigenic fragments and presents them to T cells. HLA is polymorphic. There are over 2000 different HLA alleles at present and the number is constantly increasing. However, antigen binding studies are limited to a small proportion of these alleles; the binding specificities of most alleles are unknown. Several research groups have attempted to partition different HLA alleles into groups. In this chapter previous classifications are reviewed and we present two chemometric approaches to classifying class I HLA alleles. The program GRID is used to calculate interaction energy between protein molecules and defined chemical probes. These interaction energy values are imported into another program GOLPE and used for principal component analysis (PCA) calculation, which groups HLA alleles into supertypes. Amino acids that are involved in the classification are displayed in the loading plots of the PCA model. Another method, hierarchical clustering based on comparative molecular similarity indices (CoMSIA) is also applied to classify HLA alleles and the results are compared with those of the PCA models."
7108,Anhang,
7109,Hemophagocytic Lymphohistiocytosis Syndromes,"Hemophagocytic lymphohistiocytosis (HLH) is a non-malignant, life-threatening hyperinflammatory condition resulting from dysregulation of normal innate and adaptive immune responses. Defects in immune effector cell cytotoxic mechanisms have been identified in many HLH syndromes. Infants and children most often present with this condition, but new onset disease may be observed in adults as well. Presenting signs and symptoms include the classic triad of fever, hepatosplenomegaly, and cytopenias, but neurologic impairment, respiratory and cardiovascular embarrassment, liver disease with coagulopathy, diarrhea, and rash may feature prominently. Diagnosis relies upon fulfilling clinical criteria and laboratory assessments including serum ferritin, soluble IL-2 receptor levels, and natural killer (NK) cell function studies. Treatment consists of excellent supportive care for the critically ill. Specific disease modifying therapy employs immunosuppressant medications and often hematopoietic stem cell transplant. HLH syndromes are frequently fatal if untreated. With current interventions survival ranges 60–70 %."
7110,Dependability and Security in Medical Information System,"Medical Information Systems (MIS) help medical practice and health care significantly. Security and dependability are two increasingly important factors for MIS nowadays. In one hand, people would be willing to step into the MIS age only when their privacy and integrity can be protected and guaranteed with MIS systems. On the other hand, only secure and reliable MIS systems would provide safe and solid medical and health care service to people. In this paper, we discuss some new security and reliability technologies which are necessary for and can be integrated with existing MISs and make the systems highly secure and dependable. We also present an implemented Middleware architecture which has been integrated with the existing VISTA/CPRS system in the U.S. Department of Veterans Affairs seamlessly and transparently."
7111,Microbial Forensics: Beyond a Fascination,"Microbiology has seen a great transition from culture-based identification of microbes using various biochemical and microscopic observations to identify and functionally characterize the microbes by just collecting the DNA and sequencing it. This advancement has not only moved in and around microbiology but has found its applications in fields which were earlier considered to be the remote ones. Forensics is one such field, where tracing the leftover evidence on a crime scene can lead to the identification and prosecution of the culprit. When leftover microbes in the biological material or objects used by the culprit or the person in question are used to correlate the identity of the individual, it takes us to the new field of science—“microbial forensics.” Technological advances in the field of forensics, molecular biology, and microbiology have all helped to refine the techniques of collecting and processing of the samples for microbiological identification using DNA-based methods followed by its inference in the form of evidence. Studies have supported the assumption that skin or surface microflora of an individual is somewhat related with the microflora found on the objects used by that individual and efforts are ongoing to see if this is found consistently in various surroundings and with different individuals. Once established, this technique would facilitate accurate identification and differentiation of an individual or suspect to guide investigations along with conventional evidence. Legal investigations are not only the field where microbial forensic could help. Agriculture, defense, public health, tourism, etc. are the fields wherein microbial forensics with different names based on the fields are helping out and have potential to further support other fields."
7112,Adsorption of Proteins at Solid Surfaces,"Ellipsometry has a very high thin film sensitivity and can resolve sub-nm changes in the thickness of a protein film on a solid substrates. Being a technique based on photons in and photons out it can also be applied at solid-liquid interfaces. Ellipsometry has therefore found many in situ applications on protein layer dynamics but studies of protein layer structure are also frequent. Numerous ex situ applications on detection and quantification of protein layers are found and several biosensing concepts have been proposed. In this chapter, the use of ellipsometry in the above mentioned areas is reviewed and experimental methodology including cell design is briefly discussed. The classical ellipsometric challenge to determine both thickness and refractive index of a thin film is addressed and an overview of strategies to determine surface mass density is given. Included is also a discussion about spectral representations of optical properties of a protein layer in terms of a model dielectric function concept and its use for analysis of protein layer structure."
7113,Exons and Introns,"Organisms can he divided into those whose cells do not have a nucleus, the single celled “prckaryotes” (Greek: pro = before; karyon = nucleus), and those whose cells have a nucleus, the single- or multi-celled “eukaryotes” (Greek: eu = good or normal; karyon = nucleus). Prokaryotes include species of bacteria (eubacteria) and archaea (archaebacteria), the latter being a bacteria- like group sometimes found in extreme environments (e.g. hot springs). Eukaryotes (eukarya) include all species of animals and plants, hoth singlecelled (protozoa, protophyta) and multi-celled (metazoa, metaphyta)."
7114,"Protection of Upper Respiratory Tract, Mouth and Eyes","Pathogenic bacteria and viruses may invade via upper and lower respiratory tract and via eye mucosa. When an infected person coughs or sneezes heavily, small, invisible droplets with the infective agent may reach a good distance from the source. By using the right form of protection at the right time, infection and disease are prevented. The present chapter is focused on the protection against airborne infections."
7115,The Clinical Definitions of Asthma,"It is believed that the term “asthma” was coined by Hippocrates around 450 bc. The term literally means “panting,” from the Greek. Descriptions of the clinical presentation of those affected with asthma appear in medical literature throughout history."
7116,What the Intensivists Need to Know About Critically Ill Myeloma Patients,"Multiple myeloma (MM) is a hematological malignancy characterized by an increase in aberrant plasma cells in the bone marrow leading to rising monoclonal protein in serum and urine. With the introduction of novel therapies with manageable side effects, this incurable disease has evolved into a chronic disease with an acceptable quality of life for the majority of patients. Accordingly, management of acute complications is fundamental in reducing the morbidity and mortality in MM. MM emergencies include symptoms and signs related directly to the disease and/or to the treatment; many organs may be involved including, but not limited to, renal, cardiovascular, neurologic, hematologic, and infectious complications. This review will focus on the numerous approaches that are aimed at managing these complications."
7117,Biological Functions of IgA,"Immunoglobulin A (IgA) is the most enigmatic of immunoglobulins. It is by far the most abundant of human Igs, being present in the blood plasma at concentrations approximating 2–3mg/mL, as well as the dominant isotype in most secretions where its output amounts to some 5–8g/day in adults. Furthermore, its evolutionary origins appear to precede the synapsid– diapsid divergence in tetrapod phylogeny (>300 million years ago) because it is present in both mammals and birds and therefore possibly also in reptiles (reviewed in Peppard et al., 2005); an IgA-like molecule has now been identified in a lizard (Deza et al., 2007)."
7118,Nitric Oxide in TMEV,"We and others have previously investigated the role of inducible nitric oxide synthase (iNOS) on early acute and late chronic demyelinating disease induced by Theiler’s Murine Encephalomyelitis Virus (TMEV). Infection of susceptible SJL mice with this virus serves as an excellent model of virus-induced demyelinating disease, such as multiple sclerosis (MS). iNOS transcripts and protein were detected in brains and spinal cords of TMEV-infected SJL mice during early acute disease, which resembles polioencephalomyelitis. Similar level of expression of iNOS has been found in resistant B6 mice, which develop only early acute disease. Weak iNOS staining was detected in reactive astrocytes and in leptomeningeal infiltrates in TMEV-infected SJL mice at 42 days post infection (p.i.), corresponding to early phase of chronic demyelinating disease, but not at 66 and 180 days p.i. corresponding to advanced and terminal stages of the disease, respectively. Results from other laboratories demonstrated that, blocking of NO by treatment of TMEV-infected SJL mice with amino guanidine (AG), a specific inhibitor of NO resulted in delay of late chronic demyelinating disease. However this protective effect of NO inhibitor depended on the temporal phase of the disease, type of cells expressing iNOS and the time of administration of AG. The results from our laboratory suggests that NO expressed during early acute disease is beneficial to the host through induction of apoptosis of infiltrating T cells and resolution of encephalitis, but its role in myelin/oligodendrocytes damage during late chronic demyelinating disease is not clear and it may depend on availability of superoxide and formation of peroxynitrite."
7119,The fading trail of the sleepy wraith,"Encephalitis lethargica was an enigma throughout its one and only epidemic. All those who have concerned themselves with this disease have been impressed, above all, by its strangeness — no fiction author would have had the temerity to invent a disorder of such incredible clinical diversity and puzzling behavior — and then the mystery was deepened, and its solution perhaps rendered inaccessible, by its unexpected disappearance. The influenza pandemic of 1918/19 killed many more people, and polio made an especially terrifying impression as a crippling disorder of childhood, but EL retains a special place in the history of brain disease because of its peculiar acute face, the fascinating horror of its intermediate and chronic stages, and the uncertainty of both its origins and its withdrawal."
7120,Health Information in the Background: Justifying Public Health Surveillance Without Patient Consent,"Often we think of collecting, storing, and using health data without patient consent as unethical and illegal. However, there are situations where the collection of health information without consent is not only ethical and legal, it is essential for community and public health. Public health surveillance – the ongoing, systematic collection, analysis, and interpretation of health-related data with the a priori purpose of preventing or controlling disease or injury, or identifying unusual events of public health importance, followed by the dissemination and use of information for public health action – allows the government to meet its ethical obligation to protect the health of the population. By adhering to public health ethics principles, public health surveillance systems, including pervasive information and computing technology (PICT), can be designed and implemented in ways that both honor individuals and protect communities."
7121,Global Supply Chain Networks and Risk Management: A Multi-Agent Framework,
7122,Role of Zinc and Selenium in Oxidative Stress and Immunosenescence: Implications for Healthy Aging and Longevity,"Aging is a complex process that includes gradual and spontaneous biochemical and physiological changes which contributes to a decline in performance and increased susceptibility to diseases. Zn and Se are essential trace elements that play a pivotal role in immune functions and antioxidant defense and, consequently, are claimed to play also a role in successful aging trajectories. Consistently with their nature of essential trace elements, a plethora of data obtained “in vitro” and “in vivo” (in humans and animal models) support the relevance of Zn and Se for both the innate and adoptive immune response. Moreover, Zn and Se are strictly involved in the synthesis and regulation of activity of proteins and enzymes, e.g., metallothioneins (MT) and glutathione peroxidase (GPX), that are necessary for our endogenous antioxidant response. This is clearly important to protect our cells from oxidative damage and to slow the decline of our immune system with aging. Age-related changes affecting tissue levels of Zn and Se may indicate that the risk of Zn and Se deficiency increases with aging. However, it is still unclear which of these changes can be the consequence of a “real deficiency” and which can be part of our physiological compensatory response to the accumulating damage occurring in aging. Furthermore, the upregulation of antioxidant proteins (Zn and Se dependent) may be a manifestation of self-induced oxidative stress. By the way, Zn and Se dependent proteins are modulated not only by nutritional status, but also by well-known hallmarks of aging that play antagonistic functions, such as the deregulated nutrient sensing pathways and cellular senescence. Thus, it is not an easy task to conduct Zn or Se supplementation in elderly and it is emerging consistent that these kind of supplementation requires an individualized approach. Anyway, there is consistent support that supplementation with Zn using doses around 10 mg/day is generally safe in elderly and may even improve part of immune performances in those subjects with a baseline deficiency. Regarding Se supplementation, it may induce both beneficial and detrimental effects on cellular immunity depending on the form of Se, supplemental dose, and delivery matrix. The nutritional association of supplements based on “Zn plus Se” is hypothesized to provide additional benefits, but this will likely need a more complex individualized approach. The improvement of our knowledge around screening and detection of Zn and Se deficiency in aging could lead to substantial benefits in terms of efficacy of nutritional supplements aimed at ameliorate performance and health in aging."
7123,The Internationalization Challenge: Where to Access Innovation,"Pharma innovation is becoming increasingly global, partly due to the lure of serving new markets, partly because of the need to access early new technology and talent wherever it emerges. Apart from the established centers of innovation in the United States, Europe and Japan, India, China and Singapore are rising attractors for global life science R&D. China as a pharma market and host of pharma R&D is highlighted as a case study, both from the angle of foreign R&D investors and from the perspective of indigenous Chinese players. Given the significant cost pressures in mature markets, reverse innovation in healthcare has drawn considerable attention by local governments."
7124,Pharmaceutical Drug Discovery: Designing the Blockbuster Drug,"Twenty years ago, drug discovery was a somewhat plodding and scholastic endeavor; those days are gone. The intellectual challenges are greater than ever but the pace has changed. Although there are greater opportunities for therapeutic targets than ever before, the costs and risks are great and the increasingly competitive environment makes the pace of pharmaceutical drug hunting range from exciting to overwhelming. These changes are catalyzed by major changes to drug discovery processes through application of rapid parallel synthesis of large chemical libraries and high-throughput screening. These techniques result in huge volumes of data for use in decision making. Besides the size and complex nature of biological and chemical data sets and the many sources of data “noise”, the needs of business produce many, often conflicting, decision criteria and constraints such as time, cost, and patent caveats. The drive is still to find potent and selective molecules but, in recent years, key aspects of drug discovery are being shifted to earlier in the process. Discovery scientists are now concerned with building molecules that have good stability but also reasonable properties of absorption into the bloodstream, distribution and binding to tissues, metabolism and excretion, low toxicity, and reasonable cost of production. These requirements result in a high-dimensional decision problem with conflicting criteria and limited resources. An overview of the broad range of issues and activities involved in pharmaceutical screening is given along with references for further reading."
7125,The Naming of the Faculty,"Ever since its establishment in 1911, The University of Hong Kong has relied on government funding. The Asian financial crisis caused serious government budget deficits and funding for higher education was sharply reduced. Both the government and the university realized that it was crucial to seek external private support. Within the university, many realized that reliance on the government meant survival but not growth. Philanthropists, in particular Li Ka-shing, became the target of fundraisers. In 2005, he made a very generous gift of HK$1 billion to the university; in turn, the university named the medical faculty after him. This stirred up a storm as critics accused the university of selling off its “ancestral shrine.” This controversy subverted the original intent of the gift, but despite this, the philanthropist’s support of the university continued. Today, the university has forged an East-West Alliance consisting of leading global institutions that had benefited from Li’s generosity, and high-level exchanges are conducted on this platform."
7126,Autoimmune Processes in the Central Nervous System,"In this chapter we discuss the factors that contribute to the unique immunological environment of the central nervous system and the mechanisms that may account for the development of autoimmunity within the CNS, including infectious agents as inducers of autoimmune disease. Consideration is given to a variety of human neurological diseases of autoimmune or presumed autoimmune etiology: autism, neuromyelitis optica, neuromyotonia, schizophrenia, lethargic encephalitis and stiff‐man syndrome. Also, we discuss autoimmunity as a possible mediator of CNS repair and examples of the protective effects of bacterial and helminth infections on CNS disease. Multiple sclerosis and models of multiple sclerosis are discussed with special attention given to the Theiler's virus‐induced demyelination model."
7127,DATA MODEL INTEGRATION: THE GLOBAL EPIDEMIC AND MOBILITY FRAMEWORK,
7128,One Health and Food Safety,"Many, if not most, of all important zoonoses relate in some way to animals in the food production chain. Therefore food becomes an important vehicle for many zoonotic pathogens. One of the major issues in food safety over the latest decades has been the lack of cross-sectoral collaboration across the food production chain. Major food safety events have been significantly affected by the lack of collaboration between the animal health, the food control, and the human health sector. One Health formulates clearly both the need for, and the benefit of cross-sectoral collaboration. Here we will focus on the human health risk related to zoonotic microorganisms present both in food animals and food derived from these animals, and typically transmitted to humans through food. Some diseases have global epidemic—or pandemic—potential, resulting in dramatic action from international organizations and national agricultural- and health authorities in most countries, for instance as was the case with avian influenza. Other diseases relate to the industrialized food production chain and have been—in some settings—dealt with efficiently through farm-to-fork preventive action in the animal sector, e.g. Salmonella. Finally, an important group of zoonotic diseases are ‘neglected diseases’ in poor settings, while they have been basically eradicated in affluent economies through vaccination and culling policies in the animal sector, e.g. Brucella. Here we will discuss these three different foodborne disease categories, paying extra attention to the important problem of antimicrobial resistance (AMR). In addition, we present some of the One Health inspired solutions that may help reduce the threat of several of the foodborne diseases discussed."
7129,Virology,"NIAD supports a broad spectrum of both basic and applied research in virology to expand the understanding of the biology, pathogenesis, and the immunology of viral diseases, leading to their prevention, control, and treatment, including research on (i) the viral replication cycle; (ii) the structure and function of the viral components; (iii) host virus interactions, including pathogenesis, immune evasion, and immune enhancement; (iv) viral genetics and evolution; (v) viral interference and defective interfering particles; (vi) virus vector relationships; (vii) epidemiology and natural history; and (viii) preclinical and clinical research to develop vaccines, adjuvants, therapeutics, immunomodulators, and diagnostics (http://www3.niaid.nih.gov/research/topics/viral/introduction.)"
7130,Chargaff’s GC rule,"Evolutionary selective pressures sometimes act to preserve nucleic acid features at the expense of encoded proteins. That this might occur in the case of nucleic acid secondary structure was noted in Chapter 5. That this might also apply to the species-dependent component of the base composition, (G+C)%, was shown by Sueoka in 1961 [2]. The amino acid composition of the proteins of bacteria is influenced, not only by the demands of the environment on the proteins, but also by the (G+C)% of the genome encoding those proteins."
7131,"Acute Respiratory Failure in the Oncologic Patient: New Era, New Issues","Recent decades have seen an increase in the number of patients living with cancer. This trend has resulted in an increase in intensive care unit (ICU) utilization across this population [1]. Acute respiratory failure is the most frequent medical complication leading to critical illness in oncologic patients [2–4]. Historically, there had been a reluctance to admit cancer patients to the ICU given their poor outcomes, particularly in the setting of hematologic malignancy and invasive mechanical ventilation [5]. ICU treatment limitations or refusal of admission was advocated [6]. Major advances in oncologic care, critical care and more meticulous attention to where the conditions overlap, have resulted in marked improvement in short-term survival in this population [1, 7, 8]. Despite these major advances, acute respiratory failure in this population remains complex with unique challenges surrounding diagnosis and management compared to the general ICU population. This chapter provides a comprehensive overview of acute respiratory failure in the oncologic population and highlights specific considerations for the intensivist. We will focus on the important differences between the immunocompromised oncologic patient and general intensive care population, the spectrum of causes of acute respiratory failure with a specific focus on toxicities related to newer cancer therapies, diagnostic approach, management and an up-to-date overview of prognosis."
7132,Recombination in the TYLCV Complex: a Mechanism to Increase Genetic Diversity. Implications for Plant Resistance Development,"Mutation, reassortment, and recombination are the major sources of genetic variation of plant viruses (García-Arenal et al., 2001; Worobey & Holmes, 1999). During mixed infections, viruses can exchange genetic material through recombination or reassortment of segments (when the parental genomes are fragmented) if present in the same cell context of the host plant. Hybrid progeny viruses might then arise, some of them with novel pathogenic characteristics and well adapted in the population that can cause new emerging diseases. Genetic exchange provides organisms with a tool to combine sequences from different origins which might help them to quickly evolve (Crameri et al., 1998). In many DNA and RNA viruses, genetic exchange is achieved through recombination (Froissart et al., 2005; Martin et al., 2005). As increasing numbers of viral sequences become available, recombinant viruses are recognized to be frequent in nature and clear evidence is found for recombination to play a key role in virus evolution (Awadalla, 2003; Chenault & Melcher, 1994; Moonan et al., 2000; Padidam et al., 1999; Revers et al., 1996; García-Arenal et al., 2001; Moreno et al., 2004). Understanding the role of recombination in generating and eliminating variation in viral sequences is thus essential to understand virus evolution and adaptation to changing environments Knowledge about the existence and frequency of recombination in a virus population might help understanding the extent at which genes are exchanged and new virus variants arise. This information is essential, for example, to predict durability of genetic resistance because new recombinant variants might be formed with increased fitness in host-resistant genotypes. Determination of the extent and rate at which genetic rearrangement through recombination does occur in natural populations is also crucial if we use genome and genetic-mapping information to locate genes responsible of important phenotypes such as genes associated with virulence, transmission, or breakdown of resistance. Therefore, better estimates of the rate of recombination will facilitate the development of more robust strategies for virus control (Awadalla, 2003)."
7133,Infectieziekten,"In de vorige eeuw heerste gedurende een korte periode de optimistische opinie dat infectieziekten dankzij vaccinatie en antibiotica overwonnen waren. Al snel werd duidelijk dat dit helemaal niet het geval was. Gedurende de laatste dertig jaar zijn veel nieuwe infectieziekten ontdekt. Humaan immunodeficintievirus, multiresistente Mycobacterium tuberculosis, meticillineresistente Staphylococcus aureus en vancomycineresistente enterokokken hebben zich als nieuwe verwekkers aangediend, terwijl wereldwijd nog altijd velen overlijden aan oude infectieziekten als malaria en darminfecties. De dreiging van wereldwijde epidemien (bijv. influenza) houden de wereld volop bezig."
7134,The Way Forward,"After the March 2004 attacks in Madrid, there can be no doubt that European cities are as likely to be targeted by terrorist activities as their US counterparts. The drafters of the EU constitutional treaty have thus rightly foreseen a solidarity clause providing mutual assistance for EU member states in case of terrorist activities. So far, however, ongoing discussions about improving Europe’s security capabilities have focused primarily on expeditionary tasks while neglecting the provision of homeland security. To overcome this problem, the capabilities of First Responders must receive substantial reinforcement. Here the corporate sector can play a useful role. However, the most substantial reform effort will have to be undertaken by the community of First Responders themselves. By adopting a capabilities-based planning approach, First Responders should jointly identify their capabilities at the international and national levels and set up a capability development mechanism. These actions will help coordinate research, procurement, and training. In doing so, First Responders will be able to assume the much needed role of a credible and capable player to complement NATO’s security and defense policy."
7135,The Molecular Biology and Treatment of Systemic Vasculitis in Children,"Primary systemic vasculitides are rare in childhood but are associated with significant morbidity and mortality. The cause of the majority of vasculitides is unknown, although it is likely that a complex interaction between environmental factors, such as infections and inherited host responses, triggers the disease and determines the vasculitis phenotype. Several genetic polymorphisms in vasculitides have now been described, which may be relevant in terms of disease predisposition or development of disease complications. Treatment regimens continue to improve with the use of different immunosuppressive medications and newer therapeutic approaches such as biologic agents. This chapter reviews recent studies shedding light on the pathogenesis of vasculitis with emphasis on molecular biology where known, and summarizes current treatment strategies. We discuss new emerging challenges particularly with respect to the long-term cardiovascular morbidity for children with systemic vasculitis and emphasize the importance of future international multicenter collaborative studies to further increase and standardize the scientific base investigating and treating childhood vasculitis."
7136,Infectious Disease Informatics and Syndromic Surveillance,"Infectious disease informatics (IDI) is an emerging field that studies data collection, sharing, modeling, and management issues in the domain of infectious diseases. This chapter discusses various technical components of IDI research from an information technology perspective. Syndromic surveillance is used to illustrate these components of IDI research, as it is a widely-adopted approach to detecting and responding to public health and bioterrorism events. Two case studies involving real-world applications and research prototypes are presented to illustrate the application context and relevant system design and data modeling issues."
7137,FIV as a Model for AIDS Vaccine Studies,"Many experimental strategies have been adopted in experiments to protect cats from FIV infection by vaccination, and some have been successful. The interest in developing a vaccine arose both because FIV is a common cause of morbidity and mortality in pet cats and because the feline virus provides a model for its counterpart in man, human immunodeficiency virus (HIV), for which an effective vaccine is urgently required to halt the current tragic pandemic of acquired immunodeficiency syndrome (AIDS). Shortly after the discovery of FIV and its characterization as a lentivirus, attempts were made to produce a vaccine and success was soon achieved with relatively simple inactivated virus or inactivated virus-infected cell vaccines.82 Further development of this approach led to the introduction in 2002 of the first commercial vaccine against FIV.59 With an estimated prevalence of the infection of up to 25% in populations of pet cats, an effective FIV vaccine could have a significant influence on animal welfare. In addition, this success poses the question of whether a similar strategy might produce an effective vaccine against HIV."
7138,Bone Marrow Transplantation,"Hematopoietic transplantation is increasingly being used as treatment for a variety of severe diseases. Data from International Registries indicate that more than 25,000 transplants are performed every year in Europe, and a similar number in the United States (US) (Copelan 2006; Gratwohl et al. 2007). The objectives of this procedure are: (1) to replace hematopoiesis affected by a severe and irreversible disorder, (2) to rescue the patient from intense marrow toxicity induced by high-dose chemotherapy and/or radiation, and (3) to use a fraction of cells contained in the graft as anti-tumor immunotherapy. Of note, one or more of these objectives may be pursued in a particular situation; for example, in a patient with acute leukemia, transplantation aims to replace the neoplastic hematopoiesis by administering high-dose cytotoxic therapy and taking advantage of the graft-versus-leukemia effect of donor T-lymphocytes from the graft. In contrast, in aplastic anemia the only goal of the procedure is to restore an adequate hematopoiesis."
7139,Die Zelle als gengesteuertes System,"Die genetische Information der Pflanzenzelle ist in den DNA-Molekülen des Zellkerns (nucleäres Genom), der Plastiden (plastidäres Genom) und der Mitochondrien (mitochondriales Genom) niedergelegt. Die Genome der Plastiden und Mitochondrien leiten sich von Genomen prokaryotischer Organismen ab, die während der Evolution als Endosymbionten in die Eukaryotenzelle aufgenommen wurden, Endosymbiontentheorie.Diese Organellengenome, und die zugehörigen Mechanismen der Genexpression, zeichnen sich auch heute noch durch viele prokaryotische Merkmale aus. Andererseits unterscheiden sie sich von den heutigen Prokaryotengenomen z. B. dadurch, dass sie viele Gene an den Zellkern verloren haben, der in der Pflanzenzelle die dominierende Rolle bei der Replication und Transkription der genetischen Information übernommen hat und so viele Funktionen der Organellen steuert. Dieses Kapitel gibt einen Überblick über die Organisation der Genome und die komplexen Mechanismen der Informationsverarbeitung in der Pflanzenzelle, sowie die sich während der Evolution etablierten Abhängigkeitsverhältnisse und Kooperationen zwischen ihren drei genetischen Systemen. Unter Genexpression verstehen wir die Abfolge der molekularen Einzelschritte zwischen einem Gen und seinem reifen Genprodukt, z. B. einem funktionsfähigen Enzym. Dieser Begriff schließt also neben der Transkription (RNA-Synthese) auch die Reifungsprozesse auf der RNA-Ebene, die Translation (Proteinsynthese) und die Mechanismen der Proteinmodifikation und —(in)aktivierung ein. Die auf diesen verschiedenen Ebenen angreifende Regulation der Genexpression liefert die mechanistischen Grundlagen für die Steuerung der Zelldifferenzierung im vielzelligen Organismus und ist daher ein zentrales Thema der molekularen Pflanzenphysiologie."
7140,List of Common Abbreviations,List of Common Abbreviations
7141,Functions of Chikungunya Virus Nonstructural Proteins,"The nonstructural proteins (nsPs) of chikungunya virus (CHIKV) are expressed as one or two polyprotein precursors, which are translated directly from the viral genomic RNA. Mature nsPs are generated by precise processing of these polyproteins. Both the precursors and mature nsPs are essential for CHIKV replication. Similar to other alphaviruses, CHIKV nsPs not only perform virus RNA replication but are also crucial for other activities essential for virus infection and pathogenesis. Thus far the best-studied CHIKV ns-protein is nsP2, for which protease, NTPase, RNA triphosphatase, and RNA helicase activities have been demonstrated. In addition, nsP2 is crucial for shut-off of host cell transcription and translation and it counteracts cellular antiviral responses. Compared to their homologues from the well-studied Sindbis and Semliki Forest viruses, CHIKV nsP1, nsP3, and nsP4 have been subjected to only few studies. Nevertheless, there are strong indirect pieces of evidence indicating that these CHIKV proteins have the same enzymatic activities as their counterparts in the other alphaviruses. Information concerning the specific interaction of CHIKV nsPs with host components is beginning to emerge. All the nsPs are involved in the functioning of membrane-bound replication complexes also called spherules, but the finer details of the structure and assembly of these complexes are currently poorly understood."
7142,Ecological impacts of non-native invertebrates and fungi on terrestrial ecosystems,
7143,A Spatial-Temporal Approach to Differentiate Epidemic Risk Patterns,"The purpose of disease mapping is to find spatial clustering and identify risk areas and potential epidemic initiators. Rather than relying on plotting either the case number or incidence rate, this chapter proposes three temporal risk indices: the probability of case occurrence (how often did uneven cases occur), the duration of an epidemic (how long did cases persist), and the intensity of a transmission (were the case of chronological significance). By integrating the three indicators using the local indicator of spatial autocorrelation (LISA) statistic, this chapter intends to develop a novel approach for evaluating spatial-temporal relationships with different risk patterns in the 2002 dengue epidemic, the worst outbreak in the past sixty years. With this approach, not only are hypotheses generated through the mapping processes in furthering investigation, but also procedures provided to identify spatial health risk levels with temporal characteristics."
7144,Vaccines,"Since vaccination was documented by Edward Jenner in 1798, it has become the most successful means of preventing infectious diseases, saving millions of lives every year. However, application of vaccines is currently not limited to the prevention of infectious diseases. Vaccines in the pipeline include anti-drug abuse vaccines (nicotine, cocaine) and vaccines against allergies, cancer, and Alzheimer’s disease."
7145,"Past, Present, and Future of Infectious Diseases","Since the existence of human beings in the world, they have been haunted by various infectious diseases. In fact, the history of mankind is also a history about the human fighting against infectious diseases. Infectious diseases are characterized by acute onset, rapid spread, and high mortality rate, which have killed billions of human lives and cause endless disasters to the fortunes and cultures of human beings. For instance, many brilliant cultures, such as the ancient Roman culture, the Maya culture, the Inca culture, and the Marine Polynesian culture, were ruined by plague in a direct or indirect manner. Therefore, people have been struggling to explore the possible causes, epidemic patterns, and pathogenic mechanisms of infectious diseases. In terms of their diagnosis and treatment, from the experience stage to the experiment stage till the present molecular biology stage, more and more knowledge about infectious diseases have been gained and keep on increasing."
7146,Framing Infectious Diseases: Effective Policy Implementation and United States Public Opinion,"This chapter combines quantitative and qualitative research methods—content analysis of newspaper reports and analysis of health opinion polls to assess impact of media frames in shaping public opinion. Focusing on framing of transnational infectious diseases (HIV/AIDS, SARS, and avian flu) as medical dangers, economic risks, security threats, and human rights concerns, the chapter draws attention to the role of media frames in enlisting active support and engaging public opinion for effective policy implementation to control spread of these infectious diseases. The findings also address the debate on the role and importance of domestic public opinion as a factor in domestic and foreign policy decisions of governments in an increasingly globalized world."
7147,Resilience in Risk Analysis and Risk Assessment,"Resilience is the ability of a system to react to and recover from disturbances with minimal effects on dynamic stability. Resilience is needed as systems and organizations become more complex and interrelated and the consequences of accidents and incidents increase. This paper analyzes the notion of resilience based on a literature survey and an exploration of incidents. In particular, resilience involves the ability of systems to undergo graceful and controlled degradation, the ability to rebound from degradation, the presence of redundancy, the ability to manage margins close to the performance boundaries, the establishment and exploration of common mental models, the presence of flexibility in systems and organizations, and the reduction of complexity and coupling. The paper describes how resilience can be included in system development and operations by considering organizations, technology and human factors. Also, it shows how past strengths and weaknesses can be considered in risk analysis to enhance safety, security and resilience."
7148,Macrosocial Determinants of Population Health in the Context of Globalization,
7149,Replication of Plus-Sense Viral RNA,
7150,Bioterrorism Alert for Health Care Workers,"When the agent used in a biological attack is known, response to such an attack is considerably simplified. The first eight chapters of this text deal with agent-specific concerns and strategies for dealing with infections due to the intentional release of these agents. A larger problem arises when the identity of an agent is not known. In fact, in some cases, an attack may be threatened or suspected, but it may remain unclear as to whether such an attack has actually occurred. Moreover, it may be unclear whether casualties are due to a biological agent, a chemical agent, or even a naturally occurring infectious disease process or toxic exposure. Recent experience with West Nile Virus (Fine and Layton, 2001), Severe Acute Respiratory Syndrome (SARS) (Lampton, 2003), and monkeypox highlight this dilemma. In each of these cases, the possibility of bioterrorism was raised, and rightly so, although each outbreak ultimately proved to have a natural origin. This chapter provides a framework for dealing with outbreaks of unknown origin and etiology. Furthermore, it addresses several related concerns and topics not covered elsewhere in this text."
7151,Septic Shock,"For more than 20 years, sepsis has been defined as symptoms associated with the response to microorganism infection, which was more specifically called systemic inflammatory response syndrome (SIRS). With the evidence of organ failure, it was called severe sepsis, and this could lead to hypotension (septic shock). However, with the deep understanding of the pathophysiology of sepsis, sepsis has been known as both inflammatory and anti-inflammatory. Additionally, the classic use of SIRS could lead to overestimation of sepsis. For example, usual common cold could be identified as sepsis in classic definition. With this background, new sepsis definition, Sepsis 3, was introduced and sepsis was defined as a “life-threatening organ dysfunction caused by a dysregulated host response to infection.” The management of sepsis has been changed dramatically, with the development of Surviving Sepsis Campaign, which substantially increased the survival of sepsis. However, this is not with the help of a new drug, but the implementation of a treatment system. Unfortunately, no specific drug for sepsis has survived in clinical use even though many candidate drugs have been successfully investigated in preclinical setting, and this leads to the new approach to the sepsis."
7152,Allgemeine Notfälle,"In diesem Kapitel werden Fragen zu allgemeinen Notfallsituationen gestellt, beispielsweise zu zerebralen, kardiozirkulatorischen und respiratorischen sowie gastrointestinalen und abdominalen Notfällen, Notfällen bei Kindern sowie bei Schwangeren und Neugeborenen. Auch HNO-, ophtalmologische, urologische und traumatologische Notfälle werden behandelt."
7153,Survival of Viruses in the Marine Environment,"It has been well established that human pathogenic viruses may be transmitted through the marine environment due to the release of sewage by polluted rivers, outfalls, or release from vessels. These wastes contain human enteric viruses, which if ingested, or in some cases inhaled, can cause a wide variety of illnesses. Their ability to be transmitted by this route is because of their capability to remain infectious long enough in the marine environment to come in contact with a susceptible host. Transmission routes may be fairly direct, such as ingested of contaminated seawater by a swimmer, or more complex by prolonged survival in sediments which are later resuspended and accumulated in shellfish during feeding. The virus is then transmitted during consumption of the shellfish. To understand the potential for human enteric virus transmission through the marine environment numerous studies have been conducted on factors which influence their persistence in this environment (Table 6.1). This reviewfocuses on factors that could play a role in the survival of human pathogenic viruses in the marine environment."
7154,Intensive Care Medicine: Where We Are and Where We Want To Go?,"Intensive care medicine can be defined as the science and art of detecting and managing patients with impending or established critical illness, in order to prevent further deterioration and revert the disease process or its consequences, so as to achieve the best possible outcomes."
7155,Component-Based Modelling of RNA Structure Folding,"RNA structure is fundamentally important for many biological processes. In the past decades, diverse structure prediction algorithms and tools were developed but due to missing descriptions in clearly defined modelling formalisms it’s difficult or even impossible to integrate them into larger system models. We present an RNA secondary structure folding model described in ml-Devs, a variant of the Devs formalism, which enables the hierarchical combination with other model components like RNA binding proteins. An example of transcriptional attenuation will be given where model components of RNA polymerase, the folding RNA molecule, and the translating ribosome play together in a composed dynamic model."
7156,Screening and Surveillance for Promoting Population Health,1. Distinguish between screening and surveillance activities. 2. Interpret the accuracy of a screening test. 3. Identify limitations associated with screening for a health problem. 4. Plan a surveillance system based upon known risk factors for a health problem. 5. Identify limitations of a surveillance system.
7157,Prevention of Infections in Patients with Hematological Malignancies,"Infection is a major complication of patients with hematological malignancies. Prophylaxis is a key element in the management of these patients, and is composed by two main components: infection control measures and antimicrobial chemoprophylaxis. Infection control measures are safe, but not always effective. Antimicrobial prophylaxis is usually effective but may increase resistance rates, toxicity, and cost. Therefore, a careful evaluation of the actual risk for infection, the pathogens that predominate in a particular setting, and the periods at risk are important in order to define the most appropriate strategy. In this chapter we review the most important parameters to assess the risk on an individual basis, and the evidences and recommendations supporting infection control measures and antimicrobial prophylaxis against bacteria, fungi, viruses, and parasites."
7158,Primary Immunodeficiencies,"Primary immunodeficiencies (PIDs), once considered to be very rare, are now increasingly recognized because of growing knowledge in the immunological field and the availability of more sophisticated diagnostic techniques and therapeutic modalities [161]. However in a database of >120,000 inpatients of a general hospital for conditions suggestive of ID 59 patients were tested, and an undiagnosed PID was found in 17 (29%) of the subjects tested [107]. The publication of the first case of agammaglobulinemia by Bruton in 1952 [60] demonstrated that the PID diagnosis is first done in the laboratory. However, PIDs require specialized immunological centers for diagnosis and management [33]. A large body of epidemiological evidence supports the hypothesis of the existence of a close etiopathogenetic relation between PID and atopy [73]. In particular, an elevated frequency of asthma, food allergy (FA), atopic dermatitis and enteric pathologies can be found in various PIDs. In addition we will discuss another subject that is certainly of interest: the pseudo-immunodepressed child with recurrent respiratory infections (RRIs), an event that often requires medical intervention and that very often leads to the suspicion that it involves antibody deficiencies [149]."
7159,Nasal Cavity and Paranasal Sinuses,"The nasal cavity and paranasal sinuses occupy the top of the upper respiratory tract and form pneumatic spaces connected with the atmosphere. They are located immediately beneath the base of the cranium, where crucial vital structures are harbored. From this region, very much exposed to airborne agents, arise some of the more complex and rare benign and malignant lesions seen in humans, whose difficulties in interpretation make this remarkable territory one of the most challenging in the practice of surgical pathology. Contents of this chapter cover inflammations and infections, polyps and pseudotumors, fungal and midfacial destructive granulomatous lesions, as well as benign, borderline, and malignant neoplasms. Among the neoplasms, emphasis is made on those entities characteristic or even unique for the sinonasal region, such as Schneiderian papillomas, glomangiopericytoma, intestinal- and non-intestinal-type adenocarcinomas, olfactory neuroblastoma, nasal-type NK-/T-cell lymphoma, and teratocarcinosarcoma. Moreover, recently recognized entities involving this territory, i.e., HPV-related non-keratinizing carcinoma, NUT carcinoma, and SMARCB1-deficient basaloid carcinoma, are also discussed in the light of their specific molecular findings. Furthermore, the text is accompanied by numerous classical and recent references, several tables, and 100 illustrations."
7160,Risk Assessment for Foodborne Viruses,"Risk is an inherent component of human existence, as is our creation of ways to avoid or minimize such risks. The formal process of assessing the likelihood and magnitude of risk, using that information to manage risk, and then communicating the process to others, forms the basis for risk analysis. This chapter provides an overview of the steps of risk analysis with a focus on risk assessment for foodborne viruses, particularly quantitative efforts that model and estimate the risks these viruses pose to human health. Most risk assessments in food and environmental virology performed in the last decade have focused on water, fresh produce, molluscan shellfish, and prepared foods. Recent examples of enteric virus risk modeling efforts are discussed in detail, as are several of the difficulties and intricacies of performing risk assessments for foodborne viruses compared to bacteria and other agents. This is a relatively new area of study, but one that will continue to grow as national and international agencies continue to adopt and require the methodology for food safety and the protection of human health."
7161,Co-Infection with HIV and Tuberculosis,
7162,Free Radicals and Medicine,"EPR has been employed in attempts to understand the basis of specific pathophysiologies in which free radicals have a postulated role. Examples described include pulmonary free radical damage, free radicals and sickle cell disease, free radicals in amyotrophic lateral sclerosis, melanin and free radicals and the potential role of oxidative stress in the induction of cancer. The final section of the chapter describes the use of NMR as the spectroscopic measure of spin-trapped radicals, after they have reacted further to form diamagnetic species."
7163,Il recettore AT2: gli effetti,"La dimostrazione che anche i recettori AT2 producono effetti importanti, ed in linea di massima opposti a quelli prodotti dai recettori AT1, è arrivata solo in questi ultimi anni (de Gasparo e coll. 2000; Stoll e Unger 2001), quando con metodiche di tipo diverso è stato accertato che questi effetti sono molteplici, perché interessano i livelli pressori e l’attività miocardica, i processi proliferativi e l’apoptosi, la funzione renale, alcune funzioni del SNC ed alcuni parametri metabolici, in pratica tutti i fattori dai quali dipende la omeostasi (Unger 1999; Carey e coll. 2005a eb) (Tabella 4). [Figure: see text]"
7164,Krim-Fieber,
7165,Bioinformatics and Microarray-Based Technologies to Viral Genome Sequence Analysis,"Identification of microbial pathogen is an important event which lead to diagnosis, treatment, and control of infections produce by them. The high-throughput technology like microarray and new-generation sequencing machine are able to generate huge amount of nucleotide sequences of viral and bacterial genome of both known and unknown pathogens. Few years ago it was the DNA microarrays which had great potential to screen all the known pathogens and yet to be identified pathogen simultaneously. But after the development of a new generation sequencing, technologies and advance computational approach researchers are looking forward for a complete understanding of microbes and host interactions. The powerful sequencing platform is rapidly transforming the landscape of microbial identification and characterization. As bioinformatics analysis tools and databases are easily available to researchers, the enormous amount of data generated can be meaningfully handled for better understanding of the microbial world. Here in this chapter, we present commentary on how the computational method incorporated with sequencing technique made easy for microbial detection and characterization."
7166,Abdominal Pain,Wide range of pathologies may present with abdominal pain. Key to reach proper diagnosis is adequate history and physical examination along with laboratory tests and imaging. Disposition of patients with abdominal pain is as difficult as its diagnosis. Low threshold should be kept for high-risk patients. Life-threatening diseases should not be missed in emergency.
7167,Epidemiological Interaction at the Wildlife/Livestock/Human Interface: Can We Anticipate Emerging Infectious Diseases in Their Hotspots? A Framework for Understanding Emerging Diseases Processes in Their Hot Spots,"Emerging infectious diseases’ hotspots have been identified as multi-host and multi-pathogen systems often characterized in tropical ecosystems by an extensive wildlife/domestic/human interface. The pathogen communities shared by the wild and domestic populations at this interface reflect the historical epidemiological interactions between them. In a research framework using recent community ecology, evolutionary biology and molecular biology advances, this information can be used to identify potential pathways for future pathogen spill-over initiating the emergence process. In other words, an understanding of the mechanisms of pathogen transmission in a specific ecosystem can provide an interaction network between host populations defined by nodes and edges and characterized by the frequency, intensity and direction of the interactions with a direct input for targeted disease surveillance."
7168,The Socio-economic Context that Ecological Aesthetics Produces,The necessity of the economy and society produced by ecological aesthetics must explain whether the form of human civilization should achieve a new transition from industrial civilization to ecological civilization.
7169,A Health Policy Simulation Model of Ebola Haemorrhagic Fever and Zika Fever,"This study proposes a simulation model of a new type of infectious disease based on Ebola haemorrhagic fever and Zika fever. SIR (Susceptible, Infected, Recovered) model has been widely used to analyse infectious diseases such as influenza, smallpox, bioterrorism, to name a few. On the other hand, Agent-based model begins to spread in recent years. The model enables to represent behaviour of each person in the computer. It also reveals the spread of an infection by simulation of the contact process among people in the model. The study designs a model based on Epstein’s model in which several health policies are decided such as vaccine stocks, antiviral medicine stocks, the number of medical staff to infection control measures and so on. Furthermore, infectious simulation of Ebola haemorrhagic fever and Zika fever, which have not yet any effective vaccine, is also implemented in the model. As results of experiments using the model, it has been found that preventive vaccine, antiviral medicine stocks and the number of medical staff are crucial factors to prevent the spread. In addition, a modern city is vulnerable to Zika fever due to commuting by train."
7170,Immunological Defence Mechanisms Against Biological Agents,A short discussion about attack strategies by microorganisms and immunological defence mechanisms by human body: facts and concepts for preventing disease and biological warfare.
7171,Scenario Discovery Using Nonnegative Tensor Factorization,"In the relatively new field of visual analytics there is a great need for automated approaches to both verify and discover the intentions and schemes of primary actors through time. Data mining and knowledge discovery play critical roles in facilitating the ability to extract meaningful information from large and complex textual-based (digital) collections. In this study, we develop a mathematical strategy based on nonnegative tensor factorization (NTF) to extract and sequence important activities and specific events from sources such as news articles. The ability to automatically reconstruct a plot or confirm involvement in a questionable activity is greatly facilitated by our approach. As a variant of the PARAFAC multidimensional data model, we apply our NTF algorithm to the terrorism-based scenarios of the VAST 2007 Contest data set to demonstrate how term-by-entity associations can be used for scenario/plot discovery and evaluation."
7172,Intensive Care Management of Severe Acute Liver Failure,"Severe acute liver failure is defined as the development of overt liver failure with encephalopathy over eight weeks or less in previously healthy individuals. In hyperacute liver failure, deterioration occurs in less than 14 days. Whilst it is a relatively uncommon reason for admission to the intensive care unit (ICU), acute liver failure is important because it often occurs in previously well young adults and carries a high mortality. Management of these patients presents considerable challenges within the ICU due to the extreme nature of the associated pathophysiological processes, which affect multiple systems. Integrated management strategies have been poorly studied and treatment is often center-specific [1]. Clinical manifestations include a reduced conscious state, jaundice with abnormal liver function tests (especially elevations in amino acid transferase levels more than 25 times the upper limit of normal) and coagulopathy. Further deterioration can involve marked cerebral edema, hypoglycemia and severe shock with lactic acidosis and multiple organ failure. The use of clinical management guidelines may assist in the treatment of these patients by providing an evidence-based framework for care by staff at the bedside, which ensures that all important priorities are adequately addressed. It is possible that a coordinated combination of specific and general therapies may reduce mortality and the need for liver transplantation. Consideration for transfer to a unit with expertise in liver transplantation may be appropriate in order for this option to be available as a life-saving treatment should supportive care fail to arrest deterioration."
7173,"21 Infecties, ziekte en zwangerschap","Chronische ziekten en infecties vormen een belangrijke oorzaak van maternale en foetale morbiditeit en mortaliteit. Een goede voorbereiding op de interactie tussen de zwangerschap en het onderliggend lijden kan dit mogelijk verbeteren. Preconceptionele advisering, multidisciplinaire behandeling en het treffen van goede voorzorgsmaatregelen in het geval van complicaties maken hier een belangrijk onderdeel van uit. Kennis van de fysiologische veranderingen die optreden tijdens de zwangerschap, is hiervoor onontbeerlijk. Infecties vormen tijdens de zwangerschap een reëel gevaar voor de gezondheid van moeder en kind. Preventie en zo mogelijk tijdige behandeling is obligaat."
7174,Is de kans groot dat een verkouden huisarts zijn patiënten aansteekt?,Volwassenen in de leeftijdsgroep vanaf 30 jaar krijgen per jaar per persoon gemiddeld 1-2 acute luchtweginfecties (1). De aard van het beroep van huisarts kan betekenen dat dit aantal voor huisartsen hoger ligt maar daarover is weinig informatie bekend. Ter vergelijking: kinderen van 0-2 jaar krijgen gemiddeld tussen de 5 en 6 acute luchtweginfecties per jaar (1).
7175,Infection and Inflammation: Catalysts of Pulmonary Morbidity in Bronchopulmonary Dysplasia,"Bronchopulmonary dysplasia (BPD) is the most frequent pulmonary morbidity among survivors of prematurity. While the precise cause remains unknown, both antenatal factors, and specifically chorioamnionitis, as well as bacterial sepsis, cytomegalovirus infection, and respiratory viral infections have been associated with the pathogenesis of BPD. This chapter will focus on the impact that inflammation and infection have on the development of BPD in preterm infants and its long-term pulmonary morbidities. Knowledge of the respiratory tract microbiome and virome and their role in the development of BPD constitutes a major knowledge gap in our continuing efforts to decrease the incidence of BPD and its consequences."
7176,Bioactive Marine Alkaloids,"The chapter deals with bioactive marine alkaloids. The chemistry and biological activities of pyridoacridines, pyrroloacridines, indoles, β-carbolines, pyrroles, isoquinolines, and tyrosine derived alkaloids have been discussed and reviewed."
7177,"The OIE Strategy to Address Threats at the Interface Between Humans, Animals and Ecosystems","In our globalised, fast-changing world (deforestation, fast-growing animal protein demand, etc.), animal diseases that have an impact on public health, livelihoods, food security as well as the international trade of products of animal origin are constantly emerging or re-emerging. The complexity of disease emergencies calls for the identification of often collaborative effective strategies, based on both science and proven practical experience, to reduce future threats. The H(5)N(1) avian influenza crisis has shown how crucial it is to address persistent global threats at the interface between humans, animals and ecosystems which requires (i) to strengthen animal and human health institutions and (ii) build strong partnerships among players who may have different perspectives on some issues and different levels of resources. To address the gaps in the animal health sector, OIE seeks to build member countries’ capacities in policy design and good governance in animal health systems and Veterinary Services. At policy level, the OIE helps its members to enhance their credibility, both at the national and international level, by providing them with efficient tools, such as the strategic planning tools of the Performance of Veterinary Services (PVS) Pathway, with the objective to attract more commitment and more resources from their decision makers and partners. At good governance level, it provides science-based guidance that supports members in detecting, preventing and managing serious animal disease outbreaks through improved surveillance systems, strengthened laboratory networks and improved legislation. OIE promotes strong partnerships, notably with FAO and WHO, especially with regard to two topics that are getting currently a great attention and that require a strong multi-sectoral collaboration at all levels because of their social, economical and ecological determinants: rabies in humans that still kills more than 50,000 persons every year, mainly in Asia and mostly youngsters, and that is believed to be totally preventable through effective dog vaccination, and antimicrobial resistance that can hinder the effective treatment and recovery of illnesses in both humans and animals. At regional level and in full collaboration with ASEAN and other partners, the OIE Sub-Regional Representation (OIESRR) for Southeast Asia plays a significant role in regional coordination of animal health and emerging infectious disease management in a region that is often considered as a ‘hotspot’ for emergence. Along the strategic objectives of the OIE Fifth Strategic Plan, the implementation of its activities to achieve the OIE Strategic Objectives is supported by various programmes and projects funded by donors. Its long-standing flagship regional programme, the Southeast Asia and China Foot-and-Mouth Disease (SEACFMD) Campaign which aims at controlling FMD by 2020 through vaccination promotes socio-economical and participatory approaches as well as assessment of the role of wildlife."
7178,Flourishing,"Being part of, or witnessing, a terrible disaster is clearly very distressing. How do we minimize this kind of distress and continue to flourish in the future as we face extreme climate events such as wildfires and flooding? How do we identify and learn from past events lying hidden, unrecognized and unforeseen as failure incubated? What are the global ‘grand challenges’—both natural and man-made? What are the UN Sustainable Development Goals? To achieve them do we need to reverse the fragmentation of the professions into ‘silos’? What is ‘joined-up’ thinking in ‘joined-up’ organisations and nation states and how important is it? Despite all the advances in science, we know less actually than we think we know. Contingency planning that expects surprises must be the new norm. Learn anew how to learn together is the new wisdom. Use the golden rule ‘do not do to others that you would not have them do to you’, whatever you are told to believe, is our tenet. Behaviour is more important than belief—imperfect doing is better than uncertain knowing. But to do all of this collectively requires leadership that we can trust—perhaps the biggest challenge of all?"
7179,A One Health Approach to Wildlife and Food Safety,"Global health problems including the assurance of safe and secure food are becoming more numerous and complex and require sensitive and transdisciplinary problem solving efforts. One Health provides the framework to approach food safety risks from the whole ecosystem of the food system by using a Web of Causation approach instead of an ‘us vs. them’ approach. This whole ecosystem, One Health approach focuses on prevention through the integration of wildlife, environmental, human, and domestic health sectors improving our ability to prevent rather than react to disease events. A true One Health viewpoint understands that all life is connected to its habitat, and the health of the whole sits squarely on a robust and sustainable environment. Safe food and water, thus ecological health, can be ensured using an evidence-based, transdisciplinary, collaborative based approach to the solution of food production and public health."
7180,Infecties van de luchtwegen en cystische fibrose,"Sereuze of mucopurulente neusuitvloed, passagebelemmering, minimale algemene verschijnselen; meestal geen koorts."
7181,Vorbereitung des Einsatzes,"Für den Einsatz eines Bauleiters ist es besonders wichtig, sich auf seine Rolle vorzubereiten, die dazu erforderlichen Vollmachten abzufordern und alle Möglichkeiten der persönlichen Einsatzvorbereitung zu kennen und landesspezifisch zu nutzen. Im Vergleich zum Inlandeinsatz ergeben sich dabei bedeutend höhere Anforderungen für die späteren Aufgaben."
7182,Regulatory Aspects in the Development of Gene Therapies,"Preclinical therapeutics development research is directed toward fulfilling two overlapping sets of goals. A set of scientific goals includes defining the best molecule or biologic construct for the task at hand, and proving the case for its development. The second set of goals addresses regulatory requirements necessary to introduce the agent into human subjects. In the case of “small molecule” drugs, in most cases the identity of the molecule and appropriate safety studies are straightforward. In contrast, the development of biologic agents, including gene therapies discussed here, presents distinct challenges. The nature of the “drug” may be an organism subject to mutation or selection of variants through recombination. Its properties may vary depending on the scale and method of its preparation, purification, and storage. How to test adequately for its safety prior to first introduction in humans may not be straightforward owing to intrinsic differences in response to the agent expected in humans as compared to animals."
7183,Obstetric Medicine,"JOGC 2008 30:3 S1 PREECLAMPSIA—new onset or worsening hypertension, ± proteinuria (≥300 mg/day or ≥30 mg/mmol spot urine protein to creatinine ratio), ± adverse clinical signs or symptoms or abnormal labs. A disease >20 weeks gestation ECLAMPSIA—preeclampsia with generalized tonic clonic seizures"
7184,Interactive Real-time Image Analysis System for Distant Operation,"This paper reports on the development and implementation of an integrated and interactive system for cell analysis featuring remote operation and real-time analysis for generating analytical data from microscopic images. The system consists of a number of image processing modules implemented in a virtual instrumentation environment, combined with novel techniques developed for thinning and local edge-gap filling in the cell image segmentation process. These approaches, integrated with advances in networking, have been initially applied to viral feature analysis in SARS-CoV microscopy. Real-time operation through the user-interface of the proposed system generates quantitative results for remote clients. The rapidity and viability of operation permit the investigation of mutant viral agents on the basis of their morphological cell features."
7185,Personalized Management of Pulmonary Disorders,There are a large number of pulmonary disorders some of which present challenges in management. Role of genetic ancestry in lung function is under investigation. There is still limited information on pharmacogenomics and pharmacogenetics of pulmonary therapeutics. Personalized approaches to some pulmonary diseases will be described briefly as examples in this chapter.
7186,Epidemiologie,"Früher wurde der Begriff Epidemiologie für die Lehre von den großen, menschheitsbedrohenden Seuchen benutzt. Heute versteht man darunter die Wissenschaft von allen übertragbaren und nichtübertragbaren Krankheiten in einer Population, unabhängig davon, ob sie zeitlich oder räumlich gehäuft auftreten. Im Bereich der Mikrobiologie befasst sich die Epidemiologie mit Erkrankungen, die durch übertragbare Agenzien wie Bakterien, Viren oder auch Prionen verursacht werden, und zwar insbesondere mit deren Verbreitung und den Infektionsfolgen. Epidemiologische Untersuchungen besitzen somit eine große Bedeutung für die Gesundheit der Weltbevölkerung und sind die Grundlage für allgemein- und seuchenhygienische Maßnahmen wie Quarantäne oder Impfungen zur Verhinderung oder Eindämmung von Pandemien und Epidemien. Sie ermöglichen außerdem die Entwicklung von Richtlinien und Vorschriften für Impfungen und andere Maßnahmen zur Verhütung von Infektionen."
7187,Infections in Allogeneic Stem Cell Transplantation,"Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has become a widely used modality of therapy for a variety of malignant and nonmalignant diseases. Despite advances in pharmacotherapy and transplantation techniques, infection remains one of the most severe and frequently encountered complications of allo-HSCT. This chapter will address the risk factors for development of infection following allo-HSCT, including those related to the host, the conditioning regimen, and the graft, as well as the timing of opportunistic infections after allo-HSCT. The most common bacterial, viral, fungal, and parasitic infections, as well as issues surrounding their diagnostics and treatment, will be discussed. Finally, this chapter will address vaccination and other preventative strategies to be utilized when caring for patients undergoing allo-HSCT."
7188,Autoimmune Disease and the Human Metagenome,"The prevailing theory of autoimmune disease, that the body creates autoantibodies that attack “self,” was developed during an era when culture-based methods vastly underestimated the number of microbes capable of persisting in and on Homo sapiens. Thanks to the advent of culture-independent tools, the human body is now known to harbor billions of microbes whose collective genomes work in concert with the human genome. Thus, the human genome can no longer be studied in isolation. Some of these microbes persist by slowing the activity of the vitamin D receptor nuclear receptor, affecting the expression of endogenous antimicrobials and other key components of the innate immune system. It seems that bacteria that cause autoimmune disease accumulate over a lifetime, with individuals picking up pathogens with greater ease over time, as the immune response becomes increasingly compromised. Any one autoimmune disease is likely due to many different microbes within the metagenomic microbiota. This helps explain the high levels of comorbidity observed among patients with autoimmune conditions. What are commonly believed to be autoantibodies may instead be created in response to this metagenomic microbiota when the adaptive immune system is forced to deal with disintegration of infected cells. Similarly, haplotypes associated with autoimmune conditions vary widely among individuals and populations. They are more suggestive of a regional infectious model rather than a model in which an illness is caused by inherited variation of HLA haplotypes"
7189,NIV in the Treatment of Acute Respiratory Failure: Controversial Indications,"A case of pneumonia that requires ventilation, whether invasively or non invasively, is always a serious event associated with a high mortality rate, particularly in the elderly, even though it is often considered by the media as an infection that is “easy” to resolve. Why is this a controversial indication for NIV? Because there are observational studies that are absolutely against the use of NIV and a couple of randomized controlled trial in favor, in theory, but not necessarily in all cases of pneumonia or in all patients."
7190,Wildlife Disease Surveillance and Monitoring,"Emerging diseases of human or veterinary importance are a major challenge to human society. As previously discussed, infectious diseases of wild mammal populations can have significant economic impact, may threaten human and livestock health (Artois et al. 2001), and can affect the welfare and conservation of game (Gortazar et al. 2006) and species of high conservation value (Cleaveland et al. 2002). Wild mammals are also implicated as sources of emerging diseases (Daszak et al. 2000a; Cleaveland 2003; Cunningham 2005). Comprehensive epidemiological investigations and disease surveillance of wild mammal populations will enhance our capaCity to detect and control infectious diseases that may emerge in the future in human and domestic animal populations. Given that the majority of diseases that have emerged in the last couple of decades had a wildlife origin (see Chapter 1), surveillance for wildlife diseases may be seen as an essential tool for the protection of human health. For these reasons, the development of effective programmes for the surveillance of disease in wildlife populations is becoming increasingly important. Epidemiological investigations in wildlife are similar in many respects in terms of their objectives, concepts and methodology to those undertaken for domestic animal health surveillance and monitoring. However, there are also substantial differences, owing to the zoological, behavioural and ecological characteristics of wildlife populations. Consequently, definitions, methods and procedures must often be adapted to suit the unique conditions of wildlife disease surveillance."
7191,Self Assessment Questions,
7192,General Measures of Infection Control,"Health-care-associated infections are a common cause of increased morbidity, mortality, and cost of care in ICUs. Infection control and judicious antibiotic use are the mainstay of management of these patients. A systematic and multidisciplinary approach to infection control practices goes a long way in minimizing this problem."
7193,Other Transgenic Animal Models Used in Cardiovascular Studies,"Previous chapters have described a large number of transgenic animal models used to study specific cardiovascular syndromes. This chapter will fill in some gaps. Many of these transgenic animals were developed to study normal and/or abnormal physiological responses in other organ systems, or to study basic biochemical and molecular reactions or pathways. These models were then discovered to also have effects on the cardiovascular system, some of them unanticipated. A word of caution, particularly when highly inbred mouse strains are used to develop transgenic models - not all strains of a particular species are created equal. When cardiovascular parameters of age- and sex-matched A/J and C57BL/6J inbred mice were compared the C57BL/6J mice demonstrated eccentric physiologic ventricular hypertrophy, increased ventricular function, lower heart rates, and increased exercise endurance.(1)"
7194,The Making of a Modern Endemic: An Introduction,"“Why Mass Shootings May Be Contagious, New Study Examines”; “Is there an antidote to Emotional Contagion”; “Gaining weight is socially contagious—so is losing it.” In 2015, these headlines appeared alongside those pertaining to Ebola virus disease (EVD), West Nile virus, and the recently infamous “Giant Frozen Virus Still Infectious After 3000 Years.”"
7195,Other Emerging Markets,"One major sin committed by Wall Street (besides creating a financial crisis that put millions out of work and causing untold suffering) is creating not only the illusion of constant growth in emerging markets, but also convincing investors and, sadly, many world leaders, that the asset class is filled with markets that are somehow exactly alike."
7196,DNA Repair Protein OGG1 in Pulmonary Infection and Other Inflammatory Lung Diseases,"In the last decades, extensive research has uncovered functional roles and underlying mechanisms of DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1) in the pathogenesis of inflammatory response in infection and other diseases in the lung. OGG1 excises 8-oxo-7,8-dihydroguanine (8-oxo-dG) lesion on DNA that is often induced by generation of reactive oxygen species (ROS) and has been linked to mutations, cancer development, and tissue damage. Most, if not all, environmental toxic agents and mammalian cellular metabolites elicit the generation of ROS, either directly, indirectly, or both, which is among the first cellular responses. ROS in combination with other oxidative molecules/moieties are recognized as a major factor for killing invading pathogens but meanwhile can cause tissue damage. ROS potentially modify proteins, lipids, and DNA due to the strong molecular reactivity. While oxidative stress causes increased levels of all types of oxidatively modified DNA bases, accumulation of 8-oxo-dG in the DNA has been singled out to be a main culprit linking to various inflammatory disease processes. Oxidatively damaged DNA bases such as 8-oxo-dG are primarily repaired by the base excision repair (BER) mechanism, in which OGG1, as the lesion recognition enzyme, plays a fundamental role in fixing this DNA damage. In this chapter, we summarize the roles and potential mechanistic analyses of OGG1 in lung infection and other inflammatory diseases."
7197,Medische aspecten bij chronische hemodialyse,"In dit hoofdstuk wordt een aantal medische problemen behandeld die bij nierfunctievervangende behandeling van belang kunnen zijn. Allereerst komen de indicaties voor dialysebehandeling aan de orde. Daarna wordt ingegaan op de meest voorkomende complicatie: hypotensie tijdens en direct na dialyse. Vervolgens wordt een aantal mogelijke complicaties en calamiteiten besproken, zoals disequilibriumsyndroom, luchtembolie enzovoort. Problemen die meer met de chronische nierinsufficiëntie in het algemeen te maken hebben, zoals anemie en stoornissen in de calciumfosfaathuishouding, worden in hoofdstuk 4 besproken."
7198,Evolving Biosecurity Frameworks,"The relationship between infectious disease and security concerns has undergone an evolution since the end of the Cold War. What was previously seen as two separate domains – public health and national security – have, through various events and disease outbreaks in the last 15 years, become intertwined and as a result biosecurity policies now need to address a spectrum of disease threats that encompass natural outbreaks, accidental releases and the deliberate use of disease as weapons."
7199,Human Rights Issues,"Contemporary China is plagued by a wide range of human rights related issues and problems. In addition to those arising in the areas of religious toleration, judicial practice, treatment of labor and forced abortion, which were extensively reported by the media in the past, some newly emerged problems concerning human rights violation are much more alarming, due to the size of population affected and the degree of challenge caused to the public’s psychological endurance and confidence in the social ethnics and administration of the nation. Most of all, these problems concern nearly every Chinese citizen’s well-being and impact on their personal prosperity, as well as the prosperity of the nation as a whole. These problems are mainly associated with failures in environmental protection, food safety, and medical security."
7200,Importance of Negative Pressure Wards,"At the early beginning of the 21st century, the disaster with airborne infectious diseases appeared in China."
7201,Immunocompromised Patients,"The ominous prognosis of cancer patients with or without neutropenia in need of critical care has led to reservations with regard to admission of cancer patients to the ICU. However, significant improvements in ICU and in-hospital survival of cancer patients in ICU have been demonstrated in studies in recent years [1–4]. Risk factors for mortality have shifted from those related to the underlying condition to those related to the severity of acute illness similar to other critically-ill patients. Neutropenia per se and the underlying malignancy (solid and hematological) do not have an impact on the outcome of patients in ICU. Recent chemotherapy is associated rather with improved survival [3, 5–7], while organ dysfunction, severity of disease scores, need for vasopressor treatment, need for mechanical ventilation immediately or after noninvasive ventilation, no definite diagnosis and a non-infectious diagnosis are associated with mortality [1–3, 8]. Invasive aspergillosis is also associated with very high mortality rates in ICU (see below). In several studies, admission to ICU in the early stages of sepsis or other acute event was associated with better survival than admission later, after development of organ dysfunction. Performance status is perhaps the most important and only variable relating to the underlying condition that is correlated with ICU death. The prognosis remains guarded for certain cancer patients, including patients after allogeneic hematopoietic stem cell transplantation (HSCT) with active uncontrolled graft versus host disease, those with relapse of the primary disease after allogeneic HSCT and special cases of solid cancer including pulmonary carcinomatous lymphangitis and carcinomatous meningitis with coma [9]."
7202,Echinacea purpurea,
7203,Radix Scutellariae — Huangqin,
7204,Lung Transplantation,"The first human lung transplantation (LuTX) was performed by Dr James Hardy (Hardy et al. 1963) in June 1960 at the University of Mississippi in a patient with unresectable lung cancer and obstructive pneumonitis. The patient received immunosuppression with azathioprine (Aza) and irradiation, but he died due to renal failure after 17 days."
7205,Technical Advances in Veterinary Diagnostic Microbiology,"Forming a significant part of biomass on earth, microorganisms are renowned for their abundance and diversity. From submicroscopic infectious particles (viruses), small unicellular cells (bacteria and yeasts) to multinucleate and multicellular organisms (filamentous fungi, protozoa, and helminths), microorganisms have found their way into virtually every environmental niche, and show little restrain in making their presence felt. While a majority of microorganisms are free-living and involved in the degradation of plant debris and other organic materials, others lead a symbiotic, mutually beneficial life within their hosts. In addition, some microorganisms have the capacity to take advantage of temporary weaknesses in animal and human hosts, causing notable morbidity and mortality. Because clinical manifestations in animals and humans resulting from infections with various microorganisms are often nonspecific (e.g., general malaise and fever), it is necessary to apply laboratory diagnostic means to identify the culprit organisms for treatment and prevention purposes."
7206,Viral Genome Compression,"Viruses compress their genome to reduce space. One of the main techniques is overlapping genes. We model this process by the shortest common superstring problem, that is, we look for the shortest genome which still contains all genes. We give an algorithm for computing optimal solutions which is slow in the number of strings but fast (linear) in their total length. This algorithm is used for a number of viruses with relatively few genes. When the number of genes is larger, we compute approximate solutions using the greedy algorithm which gives an upper bound for the optimal solution. We give also a lower bound for the shortest common superstring problem. The results obtained are then compared with what happens in nature. Remarkably, the compression obtained by viruses is quite high and also very close to the one achieved by modern computers."
7207,Community-Acquired Respiratory Complications in the Intensive Care Unit: Pneumonia and Acute Exacerbations of COPD,"This chapter will review the two most common lower respiratory tract infections in the intensive care unit (ICU), community-acquired pneumonia (CAP) and acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In addition we will provide an overview of the topics including recommendations for the diagnosis and treatment."
7208,Resurrections,"Several of Edelman’s illustrious interlocutors have had some criticism for him that is similar to mine. De Lauretis (2010: 87), for example, took her distance from the prescriptive meaning of the death drive in No Future. While Dean has maintained that Edelman is conditioned by a restricted and static vision of the symbolic, which impedes him from imagining the kinds of relationality that challenge the Oedipal law of reproductive futurism. In his opinion, Hocquenghem and Bersani have instead shown themselves capable of a larger imaginative force(1) and a greater contact with reality. In fact, in the concreteness of gay existences, the breaking of the Oedipal social tie generally follows the construction of a new relationality, of which barebacking is only one example:"
7209,Promoting Health for Working Women—Communicable Diseases,
7210,Study of Infectious Agents in Respiratory Diseases,"Viruses and bacteria are the main agents that cause respiratory infections in the pediatric population, although, in some circumstances, any pathogenic agent may cause disease. Diagnosis of several pathogens has improved recently. There have been major advances in microbiological diagnosis, particularly in viral detection."
7211,The Science of Wildlife Disease Management,"In its widest sense disease can be regarded as any impairment of normal functions. However, for the purposes of this book we will mostly restrict our discussion to infectious diseases, the agents of which are often described as parasites or pathogens. For convenience, these organisms are often split into two categories that reflect their broad characteristics, and their relative size. The macroparasites are multi-cellular organisms that live in or on the host, such as helminths and arthropods, while microparasites include viruses, bacteria, fungi and protozoa. The main functional differences between the two relate to their generation times, with microparasites exhibiting relatively higher within-host reproductive rates and shorter generation times than macroparasites. As a result microparasites are frequently associated with acute disease, although they can induce long-lived immunity to re-infection in recovered hosts. Macroparasites by contrast are more likely to produce chronic infections often characterised by short-lived immunity in heavily infected hosts, and re-infection. Macroparasites may also have distinct life stages that can survive outside the host (e.g. eggs or larvae) and sometimes require other host species to complete their life cycle. Two important groups of pathogens fall outside this classification: rogue proteins (prions) implicated in transmissible spongiform encephalopathies (TSEs) and infectious cancers, of which Tasmanian devil facial tumour disease is a well known example. However, in broad respects these are most usefully considered as microparasites, often producing acute clinical signs without host immunity. Disease can affect individual hosts by reducing growth rates or fecundity, increasing metabolic requirements, changing patterns of behaviour and ultimately may cause death. Sub-lethal effects of pathogens may also enhance mortality rates by for example, increasing the susceptibility of the infected host to predation. However, the intimate relationships between hosts and parasites have in many instances evolved over time into subtle and potentially complex interactions, such that infection does not in itself necessarily lead to disease. Many parasites have little detrimental effect on their hosts for most of the time, only causing pathological damage if this delicate balance is upset, for example when the parasites become too numerous or when the immunological capability of the host is impaired. This balance could be influenced by many factors including nutrition, concomitant infections and a variety of physiological stressors."
7212,Micro and Nanopatterning for Bacteria- and Virus-Based Biosensing Applications,"Current technologies capable of rapidly and accurately detecting the presence of infectious diseases and toxic compounds in the human body and the environment are inadequate and new, novel techniques are required to ensure the safety of the general population. To develop these technologies, researchers must broaden their scope of interest and investigate scientific areas that have yet to be fully explored. Lithography is a common name given to technologies designed to print materials onto smooth surfaces. More specifically, micropatterning encompasses the selective binding of materials to surfaces in organized microscale arrays. The selective micropatterning of bacteria and viruses is currently an exciting area of research in the field of biomedical engineering and can potentially offer attractive qualities to biosensing applications in terms of increased sensing accuracy and reliability. This chapter focuses on briefly introducing the reader to the fundamentals of bacterial and viral surface interactions and describing several different micropatterning techniques and their advantages and disadvantages in the field of biosensing. The application of these techniques in healthcare and environmental settings is also discussed."
7213,Humanviren,"Die Viren in diesem Abschnitt werden als Humanviren bezeichnet, da man bei ihrer Erforschung von Infektionen des Menschen ausging. Jedoch infizieren Humanviren häufig auch Tiere, und manchmal auch die zugehörigen Vektorinsekten. Bei einigen Viren sind höhere Tiere oder Insekten die primären Wirte und die Infektion von Menschen ist für sie eine „Sackgasse“. Das heißt, sie können nicht von Mensch zu Mensch übertragen werden. Aber auch diese zählen wir zu den Humanviren, da man sie hier am besten kennt."
7214,Noninvasive Mechanical Ventilation for Hypoxemic Respiratory Failure-Related Infectious Diseases,The strict range of applicability of noninvasive ventilation (NIV)—which had been applied only to patients with an exacerbation of chronic obstructive pulmonary disease (COPD) or acute cardiogenic pulmonary edema (ACPO)—has been extended during the last two decades.
7215,Whither the Research Anticommons?,"Fifteen years ago, the “tragedy of the anticommons” article warned that excessive patenting of biotech products and research methods could deter rather than stimulate invention, but little evidence was offered. Here, subsequent changes in patent law, public research support, and surveys of researchers are summarized. Results indicate the anticipated anticommons has not materialized significantly, and while ongoing monitoring is warranted, declining public research funding may necessitate more patenting to stimulate private investment."
7216,The History of Zhongguancun: Building a Park and Establishing a Benchmark,"The Zhongguancun area was formerly an old river way for the Yongding River, which was known to Beijing residents as “Zhong Wan er (or Middle Bay).” As early as the Ming Dynasty, the area’s picturesque scenery attracted palace eunuchs looking for the perfect burial grounds, thus becoming a sought-after eunuch cemetery. As eunuchs were called “Zhong Guan er (or Chinese officials),” the modern-day innovation hub derived its name, dropping the ‘er’ and becoming “Zhong Guan Cun.”"
7217,Molecular Characterization of Canine Coronavirus,"Canine coronavirus (CCoV) is usually the cause of mild gastroenteritis in dogs and is known to have spread worldwide. In the last decade, as a consequence of the extraordinary large RNA genome, novel recombinant variants of CCoV have been found that are closely related to feline and porcine strains. Moreover highly virulent pantropic CCoV strains were recently identified in dogs. The molecular characterization of the CCoV circulating in canine population is essential for understanding viral evolution."
7218,B-Cells and Antibodies in Old Humans,"It has been well established that the efficiency of the immune system declines with increasing age. Immunosenescence causes increased susceptibility to infectious diseases, and infection is, in fact, the third leading cause of mortality in people aged 65 and over [1]. As is clearly apparent from the other chapters of this book, there are many components of the immune system that can change with age, and are crucial to maintaining an effective immune system. The humoral immune system interacts with the other components, both as part of its own development and via its effector mechanisms. The most important function of B-cells is to produce antibodies, the indispensable soluble effectors of many functions. There are a number of different stages of development for B-cells and their antibodies (Fig. 1)."
7219,Kawasaki Disease,"To learn about the epidemiology, aetiopathogenesis, clinical features and differential diagnosis of Kawasaki disease (KD)"
7220,Responses to Natural Disasters in the Greek and Roman World,"Ancient Greek and Roman records contain many references to natural disasters. Analyzing the immediate reactions to the events, as well as the ensuing responses, is only possible where there is dependable evidence. Two case studies offer eyewitness accounts of disaster, as well as archaeological and scientific studies. These are the plague that struck Athens in 430 BCE during the Peloponnesian War, described by Thucydides who witnessed and suffered from it, and the eruption of Vesuvius in 79 CE, recorded in letters by Pliny the Younger, who saw it and fled from it during its height. The victims of these disasters were plunged into confusion and uncertainty about what to do to survive. In many cases, social cohesion dissolved, and individuals broke norms and traditions. Some sought help from the gods, and others felt there were no gods. In the aftermath, leaders responded with measures intended to help people, restore the body politic, and rebuild. Although frustrated by physical and social barriers, they achieved a degree of success."
7221,Barriers of the Human Organism and Their Achilles’ Heels,"The human body is covered by barriers separating it from the external and internal surroundings. The “milieu enterieur” has to be stabilised in spite of the variable external and internal conditions of toxic, osmotic, microbial and climatic environmental circumstances. This first line of barriers is composed of skin and mucous membranes of complicated structures. A second line of barrier system is present in our organisms. Certain organs have to be separated from the immune system and other parts of the body because of evolutionary reasons (eye-bulb and testicles) because of unique proteins “unknown” for the acquired immune system. The blood-brain barrier (BBB) is providing enhanced safety circumstances for the central nervous system. The second line of barriers is represented by the special properties of the capillary endothelial system. The maternal-fetal barrier is the most complex. At the maternal fetal interface two individuals of two different haplotypes has to be live 9 months separated by a very complicated dynamic barrier. The placenta is the organ, which is separating the maternal and fetal tissues. Similar to others the bidirectional transport of gasses, metabolites, cells, proteins, regulatory substances, are transported by active or passive transcellular and intercellular mechanisms. The fetal immune system develops immunotolerance to all maternal cells and antigens transferred transplacentally. The problem is to mitigate the maternal immune system to tolerate the paternal haplotype of the fetus. In the case of normal pregnancy a complex series of physiological modifications can solve the problem without harmful consequences to the mother and fetus. The outermost contact cells of trophoblasts express instead of HLA-class Ia and class II antigens non-variable HLA-C, HLA-E, HLA-F and HLA-G antigens. The first consequence of this is reduction of the activity of maternal natural killer cells and maternal dendritic cells; Progesteron, micro-RNA and mediators influence the development of T effector-cells. The production of soluble HLA-G(5 and 6) and IL-10 supports the differentiation of Th-2 CD4(+) helper cells, reducing the ability of maternal cells to kill fetal cells. Series of receptors and costimulators are expressed by the different lines of semi-allogenic trophoblast cells to bind HLA-G and mitigate maternal immune response; The maternal immunotolerance is further facilitated by the activation of CD4(+)CD25(bright)Foxp3(+) regulatory T (T(REG)) cells. Infections have to be prevented during pregnancy. The cells of placenta express 10 Toll-like receptors a group of pattern recognition receptors responsible for innate immunity. The interferon level is also higher in the placental tissues than in the somatic fetal or maternal cells. The complement system is also adapted to the requirements of the pregnancy and fetal damage is inhibited by the production of “assymmetric IgG antibodies” under hormonal and placental-regulation. These modifications prevent the activation of complement, cytotoxic activity, opsonising ability, antigen clearance and precipitating activity of the molecules. The Achilles’ heels of the different barriers are regularly found by virus infections. Lamina cribrosa of the blood-brain barrier, optical nerve of the eyes, etc. the risk factors of the maternal-fetal barrier has been summarised in Table 1.1."
7222,Alphabetic Listing of Diseases and Conditions,"Part II begins with a list of special histologic stains, their for use and their corresponding references. At the end of this list is a procedure for removal of formalin precipitate from tissue sections."
7223,Seasonal and Pandemic Influenza Surveillance and Disease Severity,"Continuous investments in influenza research, surveillance, and prevention efforts are critical to mitigate the consequences of annual influenza epidemics and pandemics. New influenza viruses emerge due to antigenic drift and antigenic shift evading human immune system and causing annual epidemics and pandemics. Three pandemics with varying disease severity occurred in the last 100 years. The disease burden and determinants of influenza severity depend on circulating viral strains and individual demographic and clinical factors. Surveillance is the most effective strategy for appropriate public health response. Active and passive surveillance methods are utilized to monitor influenza epidemics and emergence of novel viruses. Meaningful use of electronic health records could be a cost-effective approach to improved influenza surveillance"
7224,A Novel Approach to Retrieval of Similar Patterns in Biological Images,"Novel descriptors of keypoints are proposed for matching (primarily) biological images. The descriptors incorporate characteristics of limited-size neighborhoods of keypoints. Descriptors are quantized into small vocabularies representing photometry of images (SIFT words) and geometry of their neighborhoods, so that significant distortions can be tolerated. In order to keep precision at a high level, Harris-Affine and Hessian-Affine detectors are independently applied. The retrieval results are accepted only if confirmed by both techniques. Using several test datasets, we preliminarily show that the method can retrieve semantically meaningful data from unknown and unpredictable images without any training or supervision. Low computational complexity of the method makes it a good candidate for scalable analysis of biological (e.g. zoological or botanical) visual databases."
7225,Asia Federation Report on International Symposium on Grid Computing (ISGC) 2010,"This report provides an overview of developments in the Asia-Pacific region, based on presentations made at the International Symposium on Grid Computing 2010 (ISGC 2010), held 5-12 March at Academia Sinica, Taipei. The document includes a brief overview of the EUAsiaGrid project as well as progress reports by representatives of 13 Asian countries presented at ISGC 2010. In alphabetical order, these are: Australia, China, India, Indonesia, Japan, Malaysia, Pakistan, Philippines, Singapore, South Korea, Taiwan, Thailand and Vietnam."
7226,Pneumonia,"Respiratory diagnoses continue to make up a large number of admissions to the pediatric intensive care unit (PICU), most notably lower respiratory infections including pneumonia. This chapter will focus on pediatric community-acquired pneumonia (CAP), immunocompromised pneumonia, and aspiration pneumonia. The pathogenesis for developing pneumonia varies; it can occur by direct inhalation of infectious particles in the air or aspiration, direct extension from the upper airways, and hematogenous spread. There are multiple levels of defense against pathogen invasion including anatomic barriers, as well as innate and adaptive immunity, which may be compromised in PICU patients. The etiologies of pediatric pneumonia vary depending on age, host condition, and environmental factors like time of year and location. Viruses remain the most common form of lower respiratory tract infection in children, especially in neonates. Community-acquired bacterial pneumonia continues to be most prevalent in younger children as well, most often affecting children less than 5 years of age who are otherwise healthy. Despite immunizations and public health initiatives, the most common bacterial causes of CAP have remained largely unchanged over the last several decades and include: Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae (including non-typable strains) and Moraxella catarrhalis. Pulmonary infection in an immunocompromised host provides a much broader differential and must be aggressively treated without delay. This chapter will also address various imaging modalities and typical findings with pediatric pneumonia. Methods for pathogen identification are broad and range from non-specific markers of illness to invasive techniques for culture. The mainstay of therapy continues to be antibiotics tailored to the patient and presumed etiology; more novel therapies may include corticosteroids or macrolide antibiotics for immune modulation. In those patients with pneumonia with effusion or empyema, drainage therapies with thoracostomy tubes or a VATS procedure may be indicated."
7227,Pediatric Lung Transplantation,"Lung transplantation is considered the last therapeutic resource for children with life threatening end-stage lung disease, but it is also a lifelong commitment to a complex clinical follow-up. The main indications in childhood are pulmonary hypertension in infancy and cystic fibrosis in children and adolescents. Contraindications are absolute and relative and often vary from one to another transplant program. Multi-organ disorders, active malignancy, and specific active infection are general agreed upon contraindications. Only 21% of organ donors had suitable lungs for transplant. Although immunosuppressive regimens vary, most lung transplant centers use induction to avoid early acute rejection. The postoperative period is not only crucial for early detection of complications, such as infections and rejection, but also in the long term when gastrointestinal and neurological complications may compromise up to 50% of the patients. One year survival rate is around 85%, and 3 year survival is around 65%. Long-term survival is determined primarily by the development of bronchiolitis obliterans syndrome (BOS), so it is important to plan better therapeutic regimes to preserve graft function."
7228,Using Spatial Prediction Model to Analyze Driving Forces of the Beijing 2008 HFMD Epidemic,"Based on the spatial units of community, village and town in Beijing, the relationship betweent HFMD morbidity and the potential risk factors has been examined. According to the 6 selected risk factors (namely population density, disposable income of urban residents, the number of medical and health institutions, the number of hospital beds, average annual temperature and average annual relative humidity) significantly related to HFMD morbidity, the prediction performance of Classical Linear Regression Model(CLRM) and Spatial Lag Model(SLM) has been compared. The results showed that SLM achieved better effect and R square reached 0.82. It was showed that spatial effect played the crucial role in the HFMD morbidity prediction and its contribution attained 88%. However, CLRM showed low prediction accuracy and bias estimation. It was demonstrated that including spatial effect item into CLRM could greatly improve the performance of HFMD morbidity prediciton model."
7229,24 Infectieziekten,"Belangrijkste bacteriële verwekkers bij kinderen < 1 maand: Escherichia coli, groep-B-streptokokken en Listeria monocytogenes ; belangrijkste bacteriële verwekkers bij kinderen > 1 maand: meningokokken en pneumokokken. H a emophilus influenzae type B is als gevolg van vaccinatie vrijwel verdwenen; belangrijkste virale verwekkers: enterovirus en herpessimplexvirus (hsv); predisponerende factoren: leeftijd < 5 jaar, patiënten met liquorshunts, afweerstoornissen, schedeltrauma."
7230,Inflammatory Diseases of the Meninges,"Neuroimaging is of major importance in all cases of suspected infectious meningitis in order to get quick information about the extent of the disease, typical lesion patterns, and potential complications, such as hydrocephalus, involvement of the underlying brain parenchyma, or vasculitis. In bacterial meningitis, abnormal and asymmetrical enhancement of the leptomeninges and the subarachnoid space is typical. Initial neuroimaging has to rule out infectious foci of the skull base such as purulent sinusitis or mastoiditis. In patients with focal deficits or seizures, MRI is the tool of choice to diagnose vascular or septic complications. Neoplastic, viral, or fungal infections of the CNS may present with similar changes of the meninges; however, fungal meningitis normally causes a thicker and more nodular enhancement. In case of basal accentuation of the leptomeningeal contrast enhancement and conspicuous signal changes in the basal cisterns, one has to consider tuberculous meningitis for differential diagnosis, especially in patients with HIV infection. Non-infectious causes of meningeal enhancement comprise several primary and secondary tumors (e.g., CNS lymphoma, medulloblastoma, or breast cancer), granulomatous diseases, intracranial hypotension, and post-operative changes."
7231,The Emergence of an Asia-Pacific Diplomacy of Counter-Terrorism in Tackling the Islamic State Threat,"The militaries in the Asia-Pacific region have been largely established to respond to specific threats to national security. While most of the ASEAN countries have been modernising their force structures for conventional conflict since the waning years of the Cold War, many still retain doctrines and equipment geared for internal security needs. The advent of non-traditional security threats ranging from natural disasters to transnational terrorism may challenge this state of affairs. Against this backdrop, how can one analyse and conceptualise the Asia-Pacific’s diplomacy of counter-terrorism in tackling the threat posed by the Islamic State? This chapter will examine the counter-terrorism policies of Asia-Pacific states and analyse how non-traditional threats such as that posed by terrorism have been managed by the armed forces of the region. A short case study of Indonesia will be included."
7232,C-Type Lectin Receptors,"C-type lectins, originally defined as proteins binding carbohydrates in a Ca(2+)-dependent manner, form a large family containing soluble and membrane-bound proteins. Among them, those expressed on phagocytes and working as pathogen pattern-recognition receptors were designated as C-type lectin receptors (CLRs), in accordance with Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I–like receptors (RLRs). Most of the genes for CLRs are clustered in human chromosome 12 close to the natural killer gene complex. Similar to the killer lectin-like receptors whose genes are clustered in this complex, most of the CLRs induce activating or regulatory signal cascades in response to distinct pathogen- or self-derived components, through the immunoreceptor tyrosine-based activating or inhibitory motif, respectively. In this chapter, some representative CLRs are picked up and their structural features leading to the functional consequences are discussed, especially on the signaling cascades and pathogen interactions, including some impacts on cutaneous pathophysiology. These CLRs should provide targets to develop effective vaccination and therapeutics for distinct infectious and autoimmune/inflammatory diseases."
7233,Avvelenamenti da pesticidi,"Il declino degli impollinatori selvatici e, in particolare, la mortalità delle api domestiche registrata negli ultimi anni hanno messo in evidenza il fondamentale ruolo delle api e degli altri insetti pronubi nell’impollinazione delle piante. L’accertamento delle cause di questi fenomeni non è di facile realizzazione, perché i fattori implicati possono variare e combinarsi fra loro. L’esposizione ai pesticidi, insieme alle patologie, ai parassiti, alle pratiche apistiche e alle condizioni nutrizionali, agroambientali e climatiche contribuiscono, secondo la teoria del vaso traboccante (Fig. 11.1), a causare, in proporzioni differenti, l’indebolimento e il successivo collasso degli alveari. I pesticidi, in particolare gli insetticidi, oltre alle mortalità provocate da grossolani errori durante il loro impiego (interventi fitoiatrici eseguiti in fioritura, durante i flussi di melata, in presenza di vento, contaminazione della flora spontanea, ecc.), sono anche sospettati di abbassare, in dosi sub-letali, le difese immunitarie e di indurre alterazioni sul comportamento, sull’orientamento e sull’attività sociale delle api [1, 2]."
7234,Immunological Aspects of Systemic Vasculitis,"Primary vasculitis are commonly multifactorial disorders involving environmental, genetic and immunological factors. Several immune-based effector mechanisms are implicated in the vascular wall damage. These effector mechanisms commonly imply auto-antibodies or immune complexes - mediated cytotoxicity but the contribution of a T-cell mediated immune response has also been described, particularly in large vascular vasculitis. Despite advances in understanding the pathophysiological mechanisms of vasculitis, the triggering events initiating the disease remain largely undefined in most cases. This review highlights the recent advances in the etiopathogenesis of primary vasculitis. A better understanding of the immunological aspects of these disorders may provide insight into the development of novel therapeutical strategies."
7235,Nanowire BioFETs: An Overview,"In this chapter, the biosensing as a key element of nanotechnology and commanding a wide range of applications is discussed, e.g., fast and efficient clinical diagnostics, health care, security, environmental monitoring, etc. The operation and sensing mechanism of BioFETs and ion-sensitive FETs are elaborated on a molecular level, based upon the molecular recognition between target and probe molecules and the input gate voltage and output ON current of the conventional FETs. In particular, the extended roles of the gate electrode of BioFETs as the probing surface are highlighted, in comparison with the conventional gate electrode, together with the physical and biological processes for detecting target molecules. Moreover, the bottom-up syntheses of vertical and horizontal nanowires are presented and the ensuing nanowires are characterized. Also, the top-down and bottom-up approaches for processing nanowires are compared by taking as criteria the process complexity and quality of the nanowires produced. Finally, the future prospects of bio-sensing are presented."
7236,Re-Bordering State Responsibilities and Human Rights,"This chapter explores the relationship between human security and borders, specifically the borders of sovereign States. Seen through the lens of human security, it argues that on the one hand the right of migrants to move across borders is fundamental, and on the other hand, the human rights and human security of both sedentary and migrant populations across borders are paramount to the security of both the States on either side of any border. It asks the questions: Whose rights are met with responsibilities? What options are there? Answering these questions sheds light on the tensions between State-citizen security and (non-)citizen security and human security, all of which are likely to become more acute; accentuated as they are by political instabilities and exacerbated by climate change, among other co-factors."
7237,Online samenwerken in teams,"Wat kunnen sociale media betekenen voor leren en samenwerken in organisaties en teams? Sociale media maken het mogelijk om virtueel samen te werken in een team, met collega’s uit je eigen organisatie maar ook uit andere organisaties; je hoeft niet langer bij elkaar op kantoor te zitten om te ‘overleggen’. Hoe doe je dit? Is het nodig dat je duidelijk afspraken maakt over hoe je tools gebruikt? We zullen in dit hoofdstuk eerst aandacht besteden aan virtuele teams, maar ook aangeven hoe je met webtools het leren en samenwerken in teams die wel op dezelfde locatie zitten kunt ondersteunen. We introduceren de rol van een technology steward en het begrip ‘de grenzeloze facilitator’. We presenteren een stappenplan om tools te introduceren bij teams die op afstand samenwerken. Vervolgens besteden we aandacht aan leren in teams en specifieke interventies om met sociale media het teamwerk te versterken. Wat kun je met sociale media bij teams die niet goed functioneren?"
7238,Ida: A link to human evolution,"Year 2009 is being celebrated as the bicentenary of British naturalist Charles Robert Darwin’s birth as well as 150 years of his book “On the Origin of Species by Means of Natural Selection, or The Preservation of Favored Races in the Struggle for Life” in short “On the Origin of Species”. Darwin is hailed as one of the greatest scientist who put forth the theory of gradual evolution and branching of all life forms. Unfortunately, then fossil records were incomplete to produce evidence of human evolution. For 200 years paleobiologists were looking for any evidence of a transitional fossil to showcase the evolution of monkeys, apes and human. The story of Ida began in 1983 when she was collected from Messel pit in Germany by an unknown collector, and displayed in his home for 20 years before deciding to sell. The fossil Ida was preserved in nature for ages in the Germany’s Messel pit, a crater rich in Eocene Epoch fossils. Ida lived when major changes were taking place on earth, the dinosaurs had become extinct, the Himalayas were forming and a range of mammals thrived in vast jungles all over the world. Prof. Jørn Hurum of the Natural History Museum, University of Oslo, Norway bought the fossil for 1 million USD, assembled top international team of experts, studied the fossil secretly for 2 years, and satisfied themselves as to the genuineness of the fossil. Finally Prof. Jørn Hurum announced the discovery of 47 million years old fossil — a link in the evolution of monkeys, apes and man. He named the fossil “Ida” and her scientific name is Darwinius masillae (named in honor of Charles Darwin’s bicentenary). Ida will remain for long a subject of intense research and discussion almost throughout the world. The fact that all life forms have common ancestors at some point of time is a well established universal reality as unfolded by research on DNA."
7239,Generating Fake but Realistic Headlines Using Deep Neural Networks,"Social media platforms such as Twitter and Facebook implement filters to detect fake news as they foresee their transition from social media platform to primary sources of news. The robustness of such filters lies in the variety and the quality of the data used to train them. There is, therefore, a need for a tool that automatically generates fake but realistic news. In this paper, we propose a deep learning model that automatically generates news headlines. The model is trained with a corpus of existing headlines from different topics. Once trained, the model generates a fake but realistic headline given a seed and a topic. For example, given the seed “Kim Jong Un” and the topic “Business”, the model generates the headline “kim jong un says climate change is already making money”. In order to better capture and leverage the syntactic structure of the headlines for the task of synthetic headline generation, we extend the architecture - Contextual Long Short Term Memory, proposed by Ghosh et al. - to also learn a part-of-speech model. We empirically and comparatively evaluate the performance of the proposed model on a real corpora of headlines. We compare our proposed approach and its variants using Long Short Term Memory and Gated Recurrent Units as the building blocks. We evaluate and compare the topical coherence of the generated headlines using a state-of-the-art classifier. We, also, evaluate the quality of the generated headline using a machine translation quality metric and its novelty using a metric we propose for this purpose. We show that the proposed model is practical and competitively efficient and effective."
7240,In Pursuit of Precision Medicine in the Critically Ill,
7241,Mikrobiologische Diagnostik und Infektiologie,"Die erfolgreiche Therapie von Infektionskrankheiten setzt in vielen Fällen eine sachgerecht durchgeführte mikrobiologische Diagnostik voraus. Dabei werden die diagnostischen Möglichkeiten im klinisch-mikrobiologischen Labor entscheidend von der Präanalytik beeinflusst. Sie wird ergänzt durch die Bestimmung klinisch-chemischer Parameter, die häufig erst den Anlass für eine entsprechende weitere Diagnostik geben. Im Rahmen der Infektionsprävention und zur Dokumentation einer einwandfreien Medizinprodukteaufbereitung werden Untersuchungen von unbelebten Materialien wie Wasser, Luft, Oberflächen oder kontaminierten Prüfkörpern durchgeführt. In allen Fällen sollte auf eine standardisierte Probenentnahme geachtet werden. Dies beginnt mit der Auswahl geeigneter Abstrichtupfer und Transportgefäße, setzt sich fort in der korrekten Entnahme und – falls notwendig – Lagerung des Materials und endet mit dem möglichst raschen Transport in das Labor."
7242,"Mechanical Ventilation in Infection, Sepsis and Organ Failure","Each day thousands of children across the world die as a result of infection. Sepsis, severe sepsis and septic shock represent a continuum of increasing severity for which present definitions are not wholly satisfactory (Levy et al. 2003; Brilli and Goldstein 2005). The term sepsis refers to the presence of an infection caused by a microbe that invades tissue, fluid or a body cavity that is normally sterile, plus the presence of clinical and/or laboratory evidence of the systemic inflammatory response syndrome (SIRS, temperature or leucocyte abnormalities and abnormal vital signs) (Goldstein et al. 2005). When sepsis is complicated by multi-organ failure, it is regarded as severe, while septic shock is diagnosed when sepsis coexists with a state of acute circulatory failure (Levy et al. 2003)."
7243,The Case Study Approach,
7244,"Taking “The Promise” Seriously: Medical Sociology’s Role in Health, Illness, and Healing in a Time of Social Change","In 1959, C.W. Mills published his now famous treatise on what sociology uniquely brings to understanding the world and the people in it. Every sociologist, of whatever ilk, has had at least a brush with the “sociological imagination,” and nearly everyone who has taken a sociology course has encountered some version of it. As Mills argued, the link between the individual and society, between personal troubles and social issues, between biography and history, or between individual crises and institutional contradictions represents the core vision of the discipline of sociology. While reminding ourselves of the “promise” may be a bit trite, its mention raises the critical question: Why do we have to continually remind ourselves of the unique contribution that we, as sociologists, bring to understanding health, illness, and healing?"
7245,The Fear of Ebola: A Tale of Two Cities in China,"Emerging social issues have often led to rumors breeding and propagation in social media in China. Public health-related rumors will harm social stability, and such noise negatively affects the quality of disease outbreak detection and prediction. In this chapter, we use the diffusion of Ebola rumors in social media networks as a case study. The topic of rumors is identified based on latent Dirichlet allocation method, and the diffusion process is explored using the space-time methods. By comparing Ebola rumors in the two cities, the chapter explores the relationship between the spread of rumors, user factors, and contents. The results show that: (1) rumors have a self-verification process; (2) rumors have strong aggregation characteristics, and similar rumors in different regions at the same period of time will lead to a synergistic effect; (3) non-authenticated users are more inclined to believe the rumors, while the official users play a major role in stopping rumors as they pay more attention to the fact; (4) the spread and elimination of rumors largely depend on the users who have more followers and friends; and (5) the topics of rumors are closely related to the local event."
7246,Health Impact of Urban Physicochemical Environment Considering the Mobility of the People,"Most of the current environmental health researches assumes that exposure to the environmental agents occurs either in the residence or workplace, neglecting the mobility of the people due to commuting and daily activities. Mobility of the people varies in terms of spatial and temporal range, that is, from momentary short ones to generation-scale long ones. Focusing on the daily movement of the people, various methods for grasping the mobility, which also range from simple observational methods like time allocation to methods with advanced technology like global navigation satellite systems, will be reviewed. Referring environmental health studies examining the health effects of either air pollution or heat, importance of the mobility of the people is discussed. Assessing the mobility will open a new research avenue for the study of infectious diseases as well as noncommunicable diseases."
7247,Dynamic Pattern Mining: An Incremental Data Clustering Approach,"We propose a mining framework that supports the identification of useful patterns based on incremental data clustering. Given the popularity of Web news services, we focus our attention on news streams mining. News articles are retrieved from Web news services, and processed by data mining tools to produce useful higher-level knowledge, which is stored in a content description database. Instead of interacting with a Web news service directly, by exploiting the knowledge in the database, an information delivery agent can present an answer in response to a user request. A key challenging issue within news repository management is the high rate of document insertion. To address this problem, we present a sophisticated incremental hierarchical document clustering algorithm using a neighborhood search. The novelty of the proposed algorithm is the ability to identify meaningful patterns (e.g., news events, and news topics) while reducing the amount of computations by maintaining cluster structure incrementally. In addition, to overcome the lack of topical relations in conceptual ontologies, we propose a topic ontology learning framework that utilizes the obtained document hierarchy. Experimental results demonstrate that the proposed clustering algorithm produces high-quality clusters, and a topic ontology provides interpretations of news topics at different levels of abstraction."
7248,Schwimmbadamöbiasis,
7249,Kindergeneeskunde,"In het eerste deel van dit hoofdstuk worden de ziektebeelden op het gebied van de kindergeneeskunde op een beknopte, heldere wijze behandeld door een vakexpert, huisarts en apotheker; de beste combinatie om de klinische relevantie voor de huisartsenpraktijk te waarborgen. De volgorde van de paragrafen is alfabetisch. In het tweede deel volgt een bespreking van de belangrijkste verschijnselen/ klachten in de kindergeneeskunde, die bij verschillende ziekten kunnen horen, zoals diarree, hoesten, melaena. In het derde deel worden nog enkele specifieke therapeutische technieken besproken, zoals voeding bij zuigelingen en voorschrijven van geneesmiddelen aan kinderen."
7250,Einführung,"Das Wort „Viren“ lässt uns an einen grausamen Tod denken, der unsichtbar heranfliegt. Man sieht Bilder von überfüllten Krankenstationen, in denen während der Spanischen Grippe reihenweise Patienten starben, von Poliomyelitis-Patienten in der Eisernen Lunge, von medizinischen Helfern, die in Schutz an zügen das tödliche Ebolavirus bekämpfen, oder von Säuglingen mit zu kleinen Köpfen, hervor gerufen durch das Zikavirus. Das alles sind schreckliche Erkrankungen, aber sie bilden nur einen sehr kleinen Teil des Ganzen. Viren infizieren alle Lebensformen – nicht nur Menschen –, und die meisten Viren sind keine Krankheitserreger. Viren gehören zur Geschichte des irdischen Lebens. Welche Rolle sie genau spielen, ist ein Rätsel, das aber langsam gelöst wird."
7251,The Effective Reproduction Number as a Prelude to Statistical Estimation of Time-Dependent Epidemic Trends,"Although the basic reproduction number, R (0), is useful for understanding the transmissibility of a disease and designing various intervention strategies, the classic threshold quantity theoretically assumes that the epidemic first occurs in a fully susceptible population, and hence, R (0) is essentially a mathematically defined quantity. In many instances, it is of practical importance to evaluate time-dependent variations in the transmission potential of infectious diseases. Explanation of the time course of an epidemic can be partly achieved by estimating the effective reproduction number, R(t), defined as the actual average number of secondary cases per primary case at calendar time t (for t >0). R(t) shows time-dependent variation due to the decline in susceptible individuals (intrinsic factors) and the implementation of control measures (extrinsic factors). If R(t)<1, it suggests that the epidemic is in decline and may be regarded as being under control at time t (vice versa, if R(t)>1). This chapter describes the primer of mathematics and statistics of R(t) and discusses other similar markers of transmissibility as a function of time."
7252,Management of Autoimmune Systemic Diseases in the Intensive Care Unit,"The diagnosis of an autoimmune systemic disease (SD) and/or its management in the intensive care unit (ICU) is dependent on dialogue between the intensivist and specialists in these diseases. However, some clinical (syndromic associations) or biological signs should lead the intensivist to suspect these diseases. Several biological or histological investigations can be rapidly performed in the ICU to confirm the diagnosis. Both treatments of a potential flare-up of the suspected disease and a concurrent infectious complication need often to be started simultaneously. While waiting for the effects of these specific treatments, supportive treatment may include the initiation of non-invasive ventilation or, in severe specified cases, invasive mechanical ventilation with extra-corporeal supports like Renal Replacement Therapy (RRT) and extra-corporeal membrane oxygenation (ECMO). Referent centers should be asked for validation of the therapeutic options, especially when some drugs are used off-label for these severe patients. An integrative diagnostic and therapeutic approach is proposed to guide the intensivist in this complex management."
7253,Hybridizations of Metaheuristics With Branch & Bound Derivates,"An important branch of hybrid metaheuristics concerns the hybridization with branch & bound derivatives. In this chapter we present examples for two different types of hybridization. The first one concerns the use of branch & bound features within construction-based metaheuristics in order to increase their efficiancy. The second example deals with the use of a metaheuristic, in our case a memetic algorithm, in order to increase the efficiancy of branch & bound, respectively branch & bound derivatives such as beam search. The quality of the resulting hybrid techniques is demonstrated by means of the application to classical string problems: the longest common subsequence problem and the shortest common supersequence problem."
7254,Multifaceted Antiviral Actions of Interferon-stimulated Gene Products,"Interferons (IFNs) are extremely powerful cytokines for the host defence against viral infections. Binding of IFNs to their receptors activates the JAK/STAT signalling pathway with the Janus kinases JAK1, 2 and TYK2 and the signal transducer and activators of transcription (STAT) 1 and STAT2. Depending on the cellular setting, additional STATs (STAT3-6) and additional signalling pathways are activated. The actions of IFNs on infected cells and the surrounding tissue are mediated by the induction of several hundred IFN-stimulated genes (ISGs). Since the cloning of the first ISGs, considerable progress has been made in describing antiviral effector proteins and their many modes of action. Effector proteins individually target distinct steps in the viral life cycle, including blocking virus entry, inhibition of viral transcription and translation, modification of viral nucleic acids and proteins and, interference with virus assembly and budding. Novel pathways of viral inhibition are constantly being elucidated and, additionally, unanticipated functions of known antiviral effector proteins are discovered. Herein, we outline IFN-induced antiviral pathways and review recent developments in this fascinating area of research."
7255,Hospital Institutional Context and Funding,"This chapter focuses on hospital ownership and supervision. Public hospitals are mostly, but not always, under the supervision of the Health Ministry. There are a certain number of other governing bodies that are directly involved in the management of hospitals. A cross-ministry group was set up in 2006 to facilitate the implementation of hospital reforms. Apart from the organizational structure, the funding of hospitals and its evolution is studied. Between 1979 and 1991, the government introduced a co-payment system in healthcare establishments. In 1992, the Ministry of Health officially granted greater autonomy to public hospitals. They were authorized to deliver paid services and to make profits, but were made responsible for their losses and debts. By 2003, central government funding had fallen to 8% of the hospital budget. As a result, public hospitals in China behave very similarly to for-profit firms, while being governed as any traditional public structure. The next step is the current experiment of a Diagnostics Related Group-based payment in China. Along with the financial autonomy of public hospitals, different reforms have been directed at developing private hospitals, even though many obstacles still remain."
7256,Pneumonia,"Pneumonia is a common cause of hospital admission and community-acquired pneumonia (CAP) is a growing health problem in developed country and worldwide. Elderly patients suffer from more severe disease, require intensive care unit (ICU) admission, and exhibit higher mortality compared with their younger counterparts. The immunological changes that occur with age called “immunosenescence” (decreased efficiency of the adaptive and innate immune systems) are known to be responsible for the increased susceptibility of elderly persons to infectious diseases and for their limited response to vaccines [1]."
7257,Medical Ethics in Disasters,"Disasters frequently create demands that outstrip available existing medical and societal resources. This may be particularly problematic for giving medical care, because disasters may destroy the infrastructures necessary to both provide patients care and keep new health problems from emerging. Disaster may, for example, not only strike care providers and hospital facilities directly; they may decimate communities’ capacities to provide food to the population and carry out critical waste disposal services. All these effects may be most important to policymakers and care providers deciding triage priorities during disasters. Referring to just these two examples, food and waste disposal services, for instance, care providers should treat first not only other care providers, who can, then, take care of others, but food preparers and waste disposal personnel, likewise, to save the most lives. These two examples are just a few among many that warrant priority for this same reason."
7258,Coronavirus-Induced Demyelination and Spontaneous Remyelination: Growth factor expression and function,MHV-A59 coronavirus infection produces a transient episode of demyelination that is followed by spontaneous remyelination. This paradigm provides a complex lesion environment to examine cellular and molecular mechanisms involved in successful CNS remyelination. Our work in this model has focused on the roles of platelet-derived growth factor and fibroblast growth factor 2 in regulating oligodendrocyte progenitor responses required for remyelination.
7259,"Erkrankungen von Bronchien, Lunge, Pleura",
7260,Alternative Distance Metrics for Enhanced Reliability of Spatial Regression Analysis of Health Data,"We present a spatial autoregressive model (SAR) to investigate the relationship between the incidence of heart disease and a pool of selected socio-economic factors in Calgary (Canada). Our goal is to provide decision makers with a reliable model, which can guide locational decisions to address current disease occurrence and mitigate its future occurrence and severity. To this end, the applied model rests on a quantitative definition of neighbourhood relationships in the city of Calgary. Our proposition is that such relationships, usually described by Euclidean distance, can be more effectively described by alternative distance metrics. The use of the most appropriate metric can improve the regression model by reducing the uncertainty of its estimates, ultimately providing a more reliable analytical tool for management and policy decision making."
7261,Survival of Enteric Viruses in the Environment and Food,"Enteric viruses are those human viruses that are primarily transmitted by the fecal-oral route, either by person-to-person contact or by ingestion of contaminated food or water. The importance of viral foodborne diseases is increasingly being recognized, and several international organizations have found that there is an upward trend in their incidence. Thus, in this review, state-of-the-art information regarding virus persistence in food and the environment is compiled."
7262,Epidemiology: Grappling with the Concept,"Public health as a segment of healthcare naturally is healthcare in the public domain, as distinct from healthcare outside of society’s purview; and the care naturally is paramedical care together with medical care – hence the term ‘health,’ rather than ‘medicine,’ in ‘public health.’ Medicine encompasses community medicine in addition to clinical medicine. This segment of medicine inherently is public-health medicine, whereas clinical medicine falls under public health only to the extent that national health insurance has been introduced. Community medicine used to be focused on epidemics of communicable diseases; and a natural term for this segment of medicine thus was epidemiology. As the concerns in community medicine were extended to encompass endemic occurrence of communicable – and also of non-communicable – illnesses, ‘endemology’ could have been introduced as a term for this extension; but instead, the concept of epidemiology was expanded to community medicine in the thus-expanded meaning of it. Epidemiological research naturally is research to advance (the practice of) community medicine – of epidemiology, that is. This research includes ‘bench’ or ‘basic’ research aimed at the development of vaccines, for example; and it falls under various medical sciences instead of constituting a science unto itself. All of this presumably is natural and quite obviously true in the judgements of beginning students of epidemiological research, but it is here said for the troubling reason that concepts of epidemiology and epidemiological research different from these are endemic in today’s epidemiologic academia. The purpose of this chapter is to help the beginning student to find proper orientation in this academia."
7263,Reverse Genetics of Avian Coronavirus Infectious Bronchitis Virus,"We have developed a reverse genetics system for the avian coronavirus infectious bronchitis virus (IBV) in which a full-length cDNA corresponding to the IBV genome is inserted into the vaccinia virus genome under the control of a T7 promoter sequence. Vaccinia virus as a vector for the full-length IBV cDNA has the advantage that modifications can be introduced into the IBV cDNA using homologous recombination, a method frequently used to insert and delete sequences from the vaccinia virus genome. Here, we describe the use of transient dominant selection as a method for introducing modifications into the IBV cDNA; that has been successfully used for the substitution of specific nucleotides, deletion of genomic regions, and the exchange of complete genes. Infectious recombinant IBVs are generated in situ following the transfection of vaccinia virus DNA, containing the modified IBV cDNA, into cells infected with a recombinant fowlpox virus expressing T7 DNA dependant RNA polymerase."
7264,Affordances in Conversational Interactions with Multimodal QA Systems,"Implementation of adequate conversational structures is a key issue in developing successful interactive user interfaces. A way of testing the adequacy of the structures is to prove the correct orientation of each communicative action towards a preceding action. We refer to this orientation leading to a certain response as the affordance of the communicative action. In this paper we present a case study where affordances of implemented conversational structures (including verbal and graphical elements) in a multimodal medical QA system are identified applying Conversation Analysis (CA) tools and tested using the Cognitive Walkthrough (CW) method. The CW method was modified to fit the conversational approach and tested with five expert evaluators. Results showed that the affordance analysis helps detecting inefficient constructions leading to disruptions in the dialog flow, spots unnecessary functions and provides important insights on systems easy-of-use."
7265,Influenza,"Influenza is one of the commonest infections in human populations, and causing substantial morbidity and mortality globally. The influenza virus is divided into different types and subtypes, three of which are currently circulating widely in humans: influenza A(H3N2) and influenza B. The virus undergoes constant evolution, leading to annual seasonal winter epidemics in temperate countries and necessitating annual updates to the vaccine. Rarely, completely new influenza viruses can emerge in human populations, giving rise to influenza pandemics. Children aged <5 years (especially those <2 years) and those with underlying illness such as cardiac, respiratory and severe neurologic disease have an increased risk of severe outcomes associated with influenza. Pregnant women have an increased risk of severe influenza. Complications may involve the respiratory tract (e.g. otitis media or pneumonia) or, less commonly, other organ systems (e.g. encephalitis or myocarditis). Specific antiviral treatment should be offered as soon as possible for hospitalized children with presumed or confirmed influenza and for influenza of any severity for children at high risk of severe complications of influenza without waiting for laboratory confirmation. Antiviral treatment is usually not warranted for uncomplicated influenza as this is usually self-limiting. Annual influenza vaccination should be offered to all individuals at increased risk for complications of influenza. Vaccine cannot be given to children aged <6 months but maternal influenza immunization during pregnancy is recommended and can confer protection to the young infant."
7266,Nanoformulations: A Valuable Tool in the Therapy of Viral Diseases Attacking Humans and Animals,"Various viruses can be considered as one of the most frequent causes of human diseases, from mild illnesses to really serious sicknesses that end fatally. Numerous viruses are also pathogenic to animals and plants, and many of them, mutating, become pathogenic also to humans. Several cases of affecting humans by originally animal viruses have been confirmed. Viral infections cause significant morbidity and mortality in humans, the increase of which is caused by general immunosuppression of the world population, changes in climate, and overall globalization. In spite of the fact that the pharmaceutical industry pays great attention to human viral infections, many of clinically used antivirals demonstrate also increased toxicity against human cells, limited bioavailability, and thus, not entirely suitable therapeutic profile. In addition, due to resistance, a combination of antivirals is needed for life-threatening infections. Thus, the development of new antiviral agents is of great importance for the control of virus spread. On the other hand, the discovery and development of structurally new antivirals represent risks. Therefore, another strategy is being developed, namely the reformulation of existing antivirals into nanoformulations and investigation of various metal and metalloid nanoparticles with respect to their diagnostic, prophylactic, and therapeutic antiviral applications. This chapter is focused on nanoscale materials/formulations with the potential to be used for the treatment or inhibition of the spread of viral diseases caused by human immunodeficiency virus, influenza A viruses (subtypes H3N2 and H1N1), avian influenza and swine influenza viruses, respiratory syncytial virus, herpes simplex virus, hepatitis B and C viruses, Ebola and Marburg viruses, Newcastle disease virus, dengue and Zika viruses, and pseudorabies virus. Effective antiviral long-lasting and target-selective nanoformulations developed for oral, intravenous, intramuscular, intranasal, intrarectal, intravaginal, and intradermal applications are discussed. Benefits of nanoparticle-based vaccination formulations with the potential to secure cross protection against divergent viruses are outlined as well."
7267,Pathology of the Respiratory Tract,"This chapter discusses six common entities of respiratory disease: obstructive and restrictive disorders of gas exchange, infectious and inflammatory diseases, immunologic disorders, vascular diseases of the lung, tumors of the lung and pleura, and miscellaneous other diseases of the respiratory tract."
7268,The Safety and Efficiency of Addressing ARDS Using Stem Cell Therapies in Clinical Trials,"Acute Respiratory Distress Syndrome (ARDS) is a complex and debilitating disease of the lungs, which continues to have a high mortality rate and huge disease burden on patients. Incidence is rising, possibly due to greater awareness leading to more diagnoses rather than a change in the underlying rate. It arises from multiple etiologies, though pathogenic infection, termed pneumonia, is the most prevalent and widely studied. The distinct pathophysiology and rapid evolution of ARDS makes it uniquely challenging with regard to therapeutics development and, to date, no medicines are licensed for specific therapy. Antibiotics, ventilation, and other organ support remain intervention standards."
7269,Pathology of the Gastrointestinal Tract,"This chapter presents representative photographs of common diseases in the esophagus, stomach, small and large intestines, appendix, and rectum. Most of the diseases discussed here are infectious or neoplastic; a few others appear that students should be able to identify. A few microscopic photographs are added to support the understanding of gross lesions."
7270,Particular Treatment Procedures,
7271,Viral Helicases,"Helicases are motor proteins that use the free energy of NTP hydrolysis to catalyze the unwinding of duplex nucleic acids. Helicases participate in almost all processes involving nucleic acids. Their action is critical for replication, recombination, repair, transcription, translation, splicing, mRNA editing, chromatin remodeling, transport, and degradation (Matson and Kaiser-Rogers 1990; Matson et al. 1994; Mendonca et al. 1995; Luking et al. 1998)."
7272,Cleavage of the Glycoprotein of Arenaviruses,"The arenaviruses are a large family of emerging negative-stranded RNA viruses that include several severe human pathogens causing hemorrhagic fevers with high mortality. During the arenavirus life cycle, processing of the viral envelope glycoprotein precursor (GPC) by the cellular subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) is crucial for productive infection. The ability of newly emerging arenaviruses to hijack human SKI-1/S1P is a key factor for zoonotic transmission and human disease potential. Apart from being an essential host factor for arenavirus infection, SKI-1/S1P is involved in the regulation of important physiological processes and linked to major human diseases. This chapter provides an overview of the mechanisms of arenavirus GPC processing by SKI-1/S1P including recent findings. We will highlight to what extent the molecular mechanisms of SKI-1/S1P cleavage of viral GPC differ from processing of SKI-1/S1P’s cellular substrates and discuss the implications for virus-host interaction and coevolution. Moreover, we will show how the use of the viral GPC as a “molecular probe” uncovered novel and unusual aspects of SKI-1/S1P biosynthesis and maturation. The crucial role of SKI-1/S1P in arenavirus infection and other major human diseases combined with its nature as an enzyme makes SKI-1/S1P further an attractive target for therapeutic intervention. In the last part, we will therefore cover past and present efforts to identify specific SKI-1/S1P inhibitors."
7273,"Sinusitis, Rhinitis, Asthma, and the Single Airway Hypothesis","The one airway, one disease hypothesis proposes that the upper and lower airways share the same physiology and histomorphology. Epidemiological clinical studies support a link between rhinosinusitis and asthma. The relationship can occur in both directions, with nasal allergen challenge leading to inflammatory changes in the lower airway and bronchoprovocation studies of the lower airway leading to inflammatory changes in the upper airway. In addition, both similarities and differences exist in the pathogenesis of nasal polyps and asthma. The mechanism for the connection between the upper and lower airways is a matter of great debate. It has been proposed that inflammatory changes in the lower airway may lead to systemic inflammatory effects that play a role in increased bronchial hyperresponsiveness. Similarly, lower airway inflammatory changes may affect nasal airway patency via systemic effects. Moreover, nasopharyngeal-bronchial reflexes may play a non-immunologic role in the interaction between the lower and upper airways. An example of the connection between the upper and lower airways is found in aspirin-exacerbated respiratory disease whereby leukotrienes play a role in the pathology of chronic rhinosinusitis with polyps and asthma. It is also been observed that the treatment of asthma is hindered by untreated rhinosinusitis."
7274,Application of Nanotechnology in Drug Delivery and Targeting,"Lipidic nanoparticulate self-assembled structures are effective carriers for drug delivery. This chapter describes the most famous nanotechnological drug delivery systems that are already used in clinical practice and clinical evaluation or in academic research. Liposomes are nanocolloidal lyotropic liquid crystals that are able to deliver bioactive molecules. Their membrane biophysics and thermodynamic properties reflect to the creation of metastable phases that affect their functionality and physicochemical behavior. Thermo- and pH-responsive liposomes are innovative nanotechnological platforms for drug delivery and targeting. Polymeric micelles and polymersomes are nanostructures that are promising drug carriers, while dendrimeric structures are considered as real nanoparticulate systems that are used in drug delivery and as nonviral vectors as well as in prevention of serious infections leading to diseases. Vaccines based on nanoparticles such as liposomes are an emerging technology and liposomes seem to meet the requirement criteria of adjuvanicity."
7275,Virology and Immunology of Bats,"Bats harbor many pathogens of veterinary and human health concern, including several emerging and reemerging viruses such as lyssaviruses, filoviruses, henipaviruses, and SARS-like coronaviruses. Despite immune responses to these viruses, many bats remain infected without disease and likely shed virus to other bats and mammals. Little is known about bat immune systems or how the immune responses of bats control infections. The recent characterization of genome and transcriptome sequences of several bat species suggests they are similar to other mammals. These data indicate that bats possess orthologous genes, antibodies, and cells involved in innate and adaptive immune responses as do other mammals, but bats likely evolved unique mechanisms for controlling viruses that cause disease in other species. It is unclear how these diseases affect bat ecology, and thus, a greater understanding of immunology and infection is needed to understand health impact on bats."
7276,"ICU Complications of Hematopoietic Stem Cell Transplant, Including Graft vs Host Disease","Hematopoietic stem cell transplant (HSCT) is an essential treatment modality for many malignant and non-malignant hematologic diseases. Advances in HSCT techniques have dramatically decreased peri-transplant morbidity and mortality, but it remains a high-risk procedure, and a significant number of patients will require critical care during the transplant process. Complications of HSCT are both infectious and non-infectious, and the intensivist must be familiar with common infections, the management of neutropenic sepsis and septic shock, the management of respiratory failure in the immunocompromised host, and a plethora of HSCT-specific complications. Survival from critical illness after HSCT is improving, but the mortality rate remains unacceptably high. Continued research and optimization of critical care provision in this population should continue to improve outcomes."
7277,Kindergeneeskunde,"Ieder kind maakt tijdens zijn of haar groei en ontwikkeling ziekten door. Veelal betreft het onschuldige aandoeningen, vaak van infectieuze aard. Meestal zijn deze aandoeningen ‘self-limiting’ en horen ze bij een normale ontwikkeling.De toediening van medicijnen heeft zin als onderdeel van een gerichte behandeling. Het voorschrijven van geneesmiddelen aan kinderen is helaas (nog steeds) zelden onderbouwd door goed wetenschappelijk onderzoek naar de effectiviteit en veiligheid ervan bij kinderen. Veelal zijn het soort en de dosering van geneesmiddelen afgeleid van bekende toepassingen en doseringen bij volwassenen. Een dosering wordt daarbij veelal omgerekend op grond van het lichaamsgewicht. Hoewel dit bij jonge kinderen over het algemeen een goed uitgangspunt is voor het berekenen van de juiste dosering, moet er bij oudere kinderen (globaal boven de acht jaar) rekening worden gehouden met de maximale dosering voor volwassenen, omdat men deze onbedoeld kan overschrijden bij het berekenen van de dosering per kg lichaamsgewicht bij deze (oudere) leeftijdsgroep. Voor pasgeborenen en zuigelingen bestaan vaak aparte doseringsvoorschriften. Het therapeutisch effect en bijwerkingen van veel medicamenten zijn bij zuigelingen vaak anders dan bij kinderen en volwassenen."
7278,Sphingolipid Metabolism in Systemic Inflammation,"The inflammatory response - induced and regulated by a variety of mediators such as cytokines, prostaglandins, and reactive oxygen species (ROS) - is the localized host’s response of the tissue to injury, irritation, or infection. In a very similar and stereotyped sequence, the mediators are thought to induce an acute phase response orchestrated by an array of substances produced locally or near the source or origin of the inflammatory response. Despite its basically protective function, the response can become inappropriate in intensity or duration damaging host tissues or interfering with normal metabolism. Thus, inflammation is the cause and/or consequence of a diversity of diseases and plays a major role in the development of remote organ failure. Better knowledge of the underlying mechanisms of these processes is, therefore, a fundamental pre-requisite fostering the molecular understanding of novel therapeutic targets or diagnostic variables."
7279,Modification of Animal Products for Fat and Other Characteristics,"This chapter includes information about modification of animal products using biotechnology and the importance of different modifications on the natural composition. The species considered for modified products include beef and dairy cattle, sheep, goats, poultry, and a wide variety of fishes. Moreover, the discussion includes the importance of animal food, nongenetically engineered animal modified food products, genetically engineered animal modified food items primarily for meat, milk, or egg and genetically engineered animal food along the transgenic approach for animal welfare. Modern biotechnology can improve productivity, consistency, and quality of alter animal food, fiber, and medical products. The transgenic technology is potentially valuable to alter characters of economic importance in a rapid and precise way. The food safety issue related to genetic engineering is also included in this chapter. The harm of such modified food and transgenic strategy should also be understood by the reader along with its advantages. In this context, transgenic approaches in animal biotechnology are under discussion that ranges from animal food production to their adverse effects."
7280,Imaging of Pulmonary Infections,"Pulmonary infection is one of the most frequent causes of morbidity and mortality throughout the world. Many infections occur in individuals with concomitant intrapulmonary or extrathoracic diseases; however, they commonly develop in otherwise healthy people. In the non-immunocompromised population, pneumonia is the most prevalent community-acquired infection and the second most common nosocomial infectious disorder. In immunocompromised patients, in children, and in the elderly, pneumonia, as well as other pulmonary infections, may develop into a life-threatening condition."
7281,Synopsis,"Akute entzündliche Reaktionen bzw. der akute Infekt mit Restitutio ad integrum laufen in einer perfekt modulierten Kaskade ab, bei dem eine akute inflammatorische Einleitungsphase von einer antiinflammatorischen Phase und einer Entzündungsauflösungsphase abgelöst werden."
7282,We as Food and Feeders,
7283,Selectins and Associated Adhesion Proteins in Inflammatory disorders,"Inflammation is defined as the normal response of living tissue to injury or infection. It is important to emphasize two components of this definition. First, that inflammation is a normal response and, as such, is expected to occur when tissue is damaged. Infact, if injured tissue does not exhibit signs of inflammation this would be considered abnormal and wounds and infections would never heal without inflammation. Secondly, inflammation occurs in living tissue, hence there is need for an adequate blood supply to the tissues in order to exhibit an inflammatory response. The inflammatory response may be triggered by mechanical injury, chemical toxins, and invasion by microorganisms, and hypersensitivity reactions. Three major events occur during the inflammatory response: the blood supply to the affected area is increased substantially, capillary permeability is increased, and leucocytes migrate from the capillary vessels into the surrounding interstitial spaces to the site of inflammation or injury. The inflammatory response represents a complex biological and biochemical process involving cells of the immune system and a plethora of biological mediators. Cell-to-cell communication molecules such as cytokines play an extremely important role in mediating the process of inflammation. Inflammation and platelet activation are critical phenomena in the setting of acute coronary syndromes. An extensive exposition of this complex phenomenon is beyond the scope of this article (Rankin 2004)."
7284,Sindrome acuta da stress respiratorio (ARDS),"L’esatta incidenza dell’ ARDS non è nota, poiché nella maggior parte delle diagnosi non viene impiegata una definizione univoca. Si può, comunque, affermare che sussiste una frequenza di circa 2–8 casi di malattia per 100.000 abitanti."
7285,Preventie,"Het is een oude wijsheid dat voorkomen beter is dan genezen. Artsen hebben zich van oudsher beziggehouden met preventieve activiteiten. De hippocratische geschriften bijvoorbeeld bevatten tal van aanwijzingen voor een gezonde leefwijze. Ook hebben medici zich ingezet om het uitbreken en verspreiden van verwoestende epidemieën, zoals lepra in de vroege middeleeuwen, pest in de veertiende eeuw en cholera in de negentiende eeuw, tegen te gaan. Met name de overheden werden daarbij ingeschakeld. Door straffe maatregelen, zoals quarantaine en isolatie, poogde men het gevaar voor de gemeenschap af te wenden."
7286,Online Public Health Intelligence: Ethical Considerations at the Big Data Era,"Often times terms such as Big Data, increasing digital footprints in the Internet accompanied with advancing analytical techniques, represent a major opportunity to improve public health surveillance and delivery of interventions. However, early adaption of Big Data in other fields revealed ethical challenges that could undermine privacy and autonomy of individuals and cause stigmatization. This chapter aims to identify the benefits and risks associated with the public health application of Big Data through ethical lenses. In doing so, it highlights the need for ethical discussion and framework towards an effective utilization of technologies. We then discuss key strategies to mitigate potentially harmful aspects of Big Data to facilitate its safe and effective implementation."
7287,Acoustic Wave (TSM) Biosensors: Weighing Bacteria,"This chapter is focused on the development and use of acoustic wave biosensor platforms for the detection of bacteria, specifically those based on the thickness shear mode (TSM) resonator. We demonstrated the mechanical and electrical implications of bacterial positioning at the solid-liquid interface of a TSM biosensor and presented a model of the TSM with bacteria attached operating as coupled oscillators. The experiments and model provide an understanding of the nature of the signals produced by acoustic wave devices when they are used for testing bacteria. The paradox of “negative mass” could be a real threat to the interpretation of experimental results related to the detection of bacteria. The knowledge of the true nature of “negative mass” linked to the strength of bacteria attachment will contribute significantly to our understanding of the results of “weighing bacteria.” The results of this work can be used for bacterial detection and control of processes of bacterial settlement, bacterial colonization, biofilm formation, and bacterial infection in which bacterial attachment plays a role."
7288,Novel and Recent Synthesis and Applications of β-Lactams,"In this chapter, a comprehensive overview of the most significant and interesting contributions published from 2000 until now, concerning the preparation of novel β-lactam structures is presented. Among the different synthetic strategies available, either novel or already known but efficient and versatile methodologies are covered. The simple modifications of one or more substituents linked to the nitrogen N-1, the C-3, and the C-4 carbon atoms of the β-lactam nucleus were considered as an alternative synthetic protocol of more complex and polyfunctionalized molecules. Indeed, it is well known and extensively reviewed that the biological activity of this strained four-membered heterocycle is strictly dependent on the nature of the substituent groups that affect the reactivity towards the molecular active sites, increasing or lowering the possibility of interaction with the substrates. Finally, a synthetic survey of the most significant biological and pharmacological applications of the 2-azetidinones is reported."
7289,From Urban Projects to Healthy City Policies,"A definition of projectitis (also known as ‘projectism’) is proposed to describe a key barrier to full deployment of a Healthy City vision and values. This chapter argues that to put health high on local social and political agendas necessarily means to transcend project-based work, and move into lasting programme and policy development. The conditions for such approaches are favourable in Healthy Cities, as a number of glocal (global and local) developments invest and sustain longer term perspectives. These conditions include emphases on policy diffusion, social justice, a better understanding of complex systems, and global commitments to the development and implementation of Health in All Policies. These efforts, in turn, are grounded in renewed and tangible support from Universal Health Coverage and Primary Health Care, asset-based community health development, and better insights into what drives (health) equity and economic development. In describing these elements of policy development for value-based Healthy Cities the chapter also gives a firm argument for a broad range of stakeholders to engage successfully in longer term policy change."
7290,Approaches to Modeling the Concentration Field for Adaptive Sampling of Contaminants during Site Decontamination,
7291,Understanding and Governing Public Health Risks by Modeling,"Increase in the use and development of computational tools to govern public health risks invites us to study their benefits and limitations. To analyze how risk is perceived and expressed through these tools is relevant to risk theory. This chapter clarifies the different concepts of risk, contrasting especially the mathematically expressed ones with culturally informed notions, which address a broader view on risk. I will suggest that a fruitful way to contextualize computational tools, such mathematical models in risk assessment is “analytics of risk,” which ties together the technological, epistemological, and political dimensions of the process of governance of risk. I will clarify the development of mathematical modeling techniques through their use in infectious disease epidemiology. Epidemiological modeling functions as a form of “risk calculation,” which provides predictions of the infectious outbreak in question. These calculations help direct and design preventive actions toward the health outcomes of populations. This chapter analyzes two cases in which modeling methods are used for explanation-based and scenario-building predictions in order to anticipate the risks of infections caused by Haemophilus influenzae type b bacteria and A(H1N1) pandemic influenza virus. I will address an interesting tension that arises when model-based estimates exemplify the population-level reasoning of public health risks but has restricted capacity to address risks on individual level. Analyzing this tension will lead to a fuller account to understand the benefits and limitations of computational tools in the governance of public health risks."
7292,"Data Explosion, Data Nature and Dataology","The essence of computer applications is to store things in the real world into computer systems in the form of data, i.e., it is a process of producing data. Some data are the records related to culture and society, and others are the descriptions of phenomena of universe and life. The large scale of data is rapidly generated and stored in computer systems, which is called data explosion. Data explosion forms data nature in computer systems. To explore data nature, new theories and methods are required. In this paper, we present the concept of data nature and introduce the problems arising from data nature, and then we define a new discipline named dataology (also called data science or science of data), which is an umbrella of theories, methods and technologies for studying data nature. The research issues and framework of dataology are proposed."
7293,DRDO Herbal Technologies: Military and Civil Applications,"The novel herbal technologies developed by India’s Defence Research and Development Organization are discussed with a view to improving the lives of soldiers and civilians. The life sciences laboratories of DRDO are engaged in R&D with the aim to develop processes, products and technologies and effective strategies to protect and enhance the operational efficiency of the Indian Armed Forces. Over the last five decades, the endeavours have resulted in creating specialized human capital through selection and training; enhancing efficiency through customized nutrition; optimizing human efficiency through traditional systems; optimizing performance through human engineering approach; protecting against health hazards like CBRN and vectors; reducing combat stress by counselling, training and resilience building; reinforcing adaptation through acclimatization processes and saving lives through life support systems. Several technologies with holistic and pragmatic applications for defence and civil sector from a herbal perspective are presented."
7294,Epidemiological Perspective in Managing Viral Diseases in Animals,"Since the first report of a viral disease associated with plants, the fascinating field of virology has evolved and aided mankind altogether. Viral infections are known for inflicting colossal economic losses worldwide in food/work/companion animals. During the last few decades, emergence of a number of new viral diseases in animals, humans and plants has been visualized. Animal disease surveillance and monitoring is essential for the sustainability of healthy livestock production systems internationally. Preparedness for combating the emerging, re-emerging, exotic and transboundary diseases requires comprehensive monitoring and precision detection systems that are pliable under the field situations. With collective and concerted scientific interventions, a few of the animal viral diseases have been stamped out globally or regionally. Rinderpest, popularly called cattle plague, was eradicated from India in 2006 and globally in 2011. Notably, India achieved the disease-free status by OIE in 2014 for African horse sickness (peste equine), a deadly viral disease of equines. Likewise, equine infectious anaemia (EIA) and equine influenza (EI) have been controlled to a greater extent in India by adopting surveillance and monitoring along with zoo sanitary measures. Overall, there is a need for developing the ‘One World, One Health’ concept using multidisciplinary, regional and international networking to control major economically important emerging/re-emerging infectious diseases of humans and animals. This chapter describes various strategies for combating viral diseases of livestock."
7295,Modeling and Simulation for the Spread of H1N1 Influenza in School Using Artificial Societies,"According to the outbreak of H1N1 influenza on campus in Langfang city, Hebei province, at north of China in 2009, this paper constructed an artificial society model of the school, and simulated the spread of H1N1 influenza at the fifth floor in dormitory building. Firstly, it built the geographic environment model in accordance with the real dormitory building and a social relationship network model, including classmates, roommates and playmates. Secondly, it designed the behaviors and activities of students during a day, and built role based agent models of student. Each agent student had three roles, which were susceptible, infectious and recovered student. Finally, it conducted simulation experiments to compare the emergency measures of segregating non-classmates and segregating non-roommates."
7296,Respiratory Failure in a Patient with Idiopathic Pulmonary Fibrosis,"The triggers as well as etiologies for Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) are not known. AE-IPF is defined as an “acute, clinically significant respiratory deterioration characterized by evidence of new widespread alveolar abnormality typically less than 1 month’s duration. The underlying pathologic insult is classically described as diffuse alveolar damage. Ideally, infection is excluded by BAL as in the case presentation, but the severity of hypoxemia and the desire to avoid endotracheal intubation may preclude the performance of this procedure. Supportive care is the mainstay of therapy as there are no proven therapies, although corticosteroids, cytotoxic agents and anti-coagulation have all been suggested as possible treatments. The mortality is high, particularly once invasive ventilation has been instituted."
7297,Threats to Bats and Educational Challenges,"Like most animals, bats are threatened by habitat loss and degradation. However, they are also uniquely threatened almost universally by humans. In this chapter, I will emphasize the educational issues I believe will be most important to the next generation of bat conservationists. Though threat levels and possible solutions vary widely, the importance of addressing unfounded fear cannot be ignored. Putting disease concerns in perspective has been essential throughout the history of bat conservation efforts and is currently a resurgent issue that threatens the educational progress that has been made in recent decades."
7298,Balkan nephropathy,"Balkan (or endemic) nephropathy is a chronic tubulointerstitial disease of unknown, presumably exotoxic etiology. It has been shown to exist only in some parts of the southeastern Europe. While there have been many meetings and papers [1, 2] concerning both cause and treatment of Balkan nephropathy, sociopolitical turmoil, including wars, and economical hardship prevented any meaningful research on the problem during the 1990’s. Thus, despite numerous proceedings and a large number of publications on the subject, many features of Balkan nephropathy, its etiology and natural history in particular, remained nearly as mysterious as when described in the mid-fifties. Meetings organized by international organizations [3-7] had a key role in informing the international scientific community on the disease. A recent source of information is a bilingual (in English and Serbian) monograph published in 2000 [8]."
7299,Major Events in the Evolution of Planet Earth: Some Origin Stories,"With billions of years of evolution before the appearance of animals, prokaryotes shaped and continue to shape both the Earth’s biogeochemical landscape and the setting for animal existence (Fig. 2.1) (Knoll 2003)."
7300,Digesting Oneself and Digesting Microbes: Autophagy as a Host Response to Viral Infection,"Although research in this area is still in a stage of infancy, it seems likely that the lysosomal degradation pathway of autophagy plays an evolutionarily conserved role in antiviral immunity. The interferon-inducible, antiviral PKR signaling pathway positively regulates autophagy, and both mammalian and plant autophagy genes restrict viral replication and protect against virus-induced cell death. Given this role of autophagy in innate immunity, it is not surprising that viruses have evolved numerous strategies to inhibit host autophagy. Different viral gene products can either modulate autophagy regulatory signals or directly interact with components of the autophagy execution machinery. Moreover, certain RNA viruses have managed to “co-apt” the autophagy pathway, selectively utilizing certain components of the dynamic membrane rearrangement system to promote their own replication inside the host cytoplasm. In addition to this newly emerging role of autophagy in innate immunity, autophagy plays an important role in many other fundamental biological processes, including tissue homeostasis, differentiation and development, cell growth control, and the prevention of aging. Accordingly, the inhibition of host autophagy by viral gene products has important implications not only for understanding mechanisms of immune evasion, but also for understanding novel mechanisms of viral pathogenesis. It will be interesting to dissect the role of viral inhibition of autophagy in acute, persistent, and latent viral replication, as well as in the pathogenesis of cancer and other medical diseases."
7301,Risk Factors and Etiologies of Pediatric Acute Respiratory Distress Syndrome,"The risk factors for acute respiratory distress syndrome (ARDS) have been a focus for clinicians and researchers from the original description in 1967 to the most recent Pediatric Acute Lung Injury Consensus Conference (PALICC). Indeed, there are many comorbidities and risk factors that predispose a patient to develop pediatric ARDS (PARDS) including, but not limited to, immunodeficiency, weight extremes, genetics, and environmental factors. These are particularly important to investigators because accurate prediction of which patients are at greatest risk of PARDS – both the development of PARDS and worse clinical outcomes after PARDS has been established – is key to identifying the next generation of diagnostic techniques and preventative strategies. In addition to those risk factors, there are specific disease processes that lead to the development of PARDS, often divided into direct or pulmonary insults and indirect or extrapulmonary insults. Finally, beyond the clinically visible risk factors, researchers are attempting to identify novel biomarkers to uncover hidden phenotypes of PARDS and enrich the prognostication and prediction of patient outcomes. This chapter delves into each of these concepts."
7302,Human Immunodeficiency Virus (HIV) Infection,This chapter discusses the unique problems associated with HIV and pregnancy. It discusses organ complications associated with HIV and vertical transmission.
7303,A Conceptual Framework for Analyzing Social-Ecological Models of Emerging Infectious Diseases,"Unraveling mechanisms underlying new and reemerging infectious diseases (EID) requires exploring complex interactions within and among coupled natural and human (CNH) systems. To address this difficult scientific problem, we need to understand how transformations in social-ecological systems caused by multifaceted interactions with anthropogenic environmental changes such as urbanization, agricultural transformations, and natural habitat alterations, produce feedbacks that affect natural communities and ultimately their pathogens, animal host, and human populations. Focusing on the complex interactions among natural and human systems at diverse spatial, temporal, and organizational scales, we describe the development of a framework for analyzing social-ecological models, to understand how these systems function and the processes through which these systems interact with each other to influence disease outbreaks. To address multi-scale issues within the framework, we draw upon multiple social science theories and methods (e.g., environmental economics, geography, decision and risk science, urban and regional development, and spatial information science). We posit that the framework helps to identify potential vulnerabilities of CNH systems to disturbances, describing important elements as a starting point for the development and testing of more general CNH systems. We also posit that transformations in the elements and how they relate to each other are key in determining the robustness of CNH systems. Given the importance and difficulty of research on social-ecological systems, we recommend a carefully considered theoretical rationale and a model-guided methodological approach. We conclude that no single theory or method is sufficient to explain complex phenomena such as EID and the relationships between factors influencing disease outbreaks. Integrated approaches are arguably the best way to provide an in-depth description and analysis of a complex problem."
7304,Acute and Chronic Infection Management in CF,"CFTR protein malfunction results in thick, copious mucus, causes poor mucociliary clearance and, ultimately, structural lung damage such as bronchiectasis. All of these manifestations of cystic fibrosis contribute to a rich milieu for lower respiratory pathogens in patients affected by the disease. CF patients are, therefore, highly susceptible to chronic colonization with many pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa. They are also uniquely prone to acute infections with respiratory pathogens, which tend to persist longer and cause more impairment in lung function than in patients without CF. Tailored strategies for managing infectious complications of CF patients include chronic prophylactic antibiotics, use of systemic as well as inhaled antibiotics, mechanical assistance with mucus clearance, and scrupulous infection control measures."
7305,Infectious Diseases,"The chapter describes bacerial, viral, parasitic and fungal infections commonly detected in pet birds. The chapter includes history, etiology, susceptible hosts, transmission, pathogenesis, clinical symptoms, lesion, diagnosis, zoonosis, Treatment and control strategy of Tuberculosis, Salmonellosis, Chlamydiosis, Campylobacteriosis, Lyme disease, other bacterial infection, Newcastle disease, Avian Influenza infection, West Nile Virus infection, Usutu virus infection, Avian Borna Virus infection, Beak and feather disease, other viral infection, Toxoplasmosis, Giardiasis, Cryptosporidiosis, other parasitic infection, Cryptococcosis, Aspergillosis, Other fungal infections."
7306,Zur Rolle der Marktforschung in der Konsumgesellschaft,"„Nun, sehen Sie, Miss Ford, wir leben in einer komplizierten Gesellschaft, die es vorzieht, dem Wettbewerb alle Risiken zu entziehen. Deshalb gibt es auch mehr Meinungsforschungsinstitute als ein normaler Sterblicher zu zählen vermag. Bevor wir ein Produkt auf den Markt bringen, wollen wir erfahren, wer es kaufen wird, wie oft und was man dafür anlegen will; welche Gründe fur Bekenntnisse maβgebend sind; welche Chancen Gouverneur Stone hat, wieder gewählt zu werden; welche Waren besonders viel verlangt werden; ob Tante Bessie in der nächsten Modesaison blau oder rosa vorzieht.“ (Daniel F. Galouye, Simulacron 3, 1965)"
7307,Infectious Diseases,"The number of infectious complications encountered in the intensive care unit (ICU) continues to increase. Patients who otherwise would have not survived in the past are now improving due to new technical advancements. However, the length of stay, as well as the large number of devices employed for this purpose, predisposes patients to difficult and often fatal infections. Clinical characteristics of patients who are treated in the ICU have evolved in recent years. Those who are immunocompromised, post-transplant, and the geriatric population are now regularly treated in the ICU with the consequent increase in morbidity, mortality, and cost."
7308,"Society, Differentiation and Globalisation","First, theories of globalisation and their implications for the analysis of health issues are discussed. Emphasis is on: (1) globalisation as embodied, something often overlooked by sociologists working outside of the field of health and (2) health vulnerabilities that arise from the heightened mobility and connectivities that characterise globalisation, taking migration and health as an illustration. Second, differentiation is considered by highlighting disparities in health vulnerability and the capacity of social groups to protect their health. This is illustrated by reference to the securitisation of health and the health consequences of violent conflict and the special vulnerabilities of children and of women. Third, the influence of interconnectedness of various national healthcare systems and implications for the delivery of effective healthcare are considered."
7309,Schwärzepilze,
7310,Elektronenmikroskopie in der Erregerdiagnostik,"Visualisierung als diagnostisches Prinzip Mit der Studie „Die Ätiologie der Milzbrand-Krankheit, begründet auf die Entwicklungsgeschichte des Bacillus Anthracis“ legte Robert Koch (1843–1910) 1876 das Fundament der wissenschaftlichen Infektiologie. Unter Anwendung der später als Koch’sche Postulate bezeichneten experimentellen Strategie beschrieben er und seine Schüler in kurzer Folge Bakterien als die Erreger einer Reihe gefürchteter Seuchen (Tuberkulose 1882; Diphtherie Loeffler, 1883; Cholera 1884; Typhus Gaflky, 1884; Tetanus Kitasato, 1889). Die Ätiologie einer Infektion galt als gesichert, wenn ein morphologisch, durch Form und Anfärbbarkeit definierter Keim (1.) konstant im erkrankten Gewebe nachgewiesen wurde, (2.) wenn er in Reinkultur isoliert werden konnte, und wenn (3.), das Isolat im Versuchstier die ursprüngliche Krankheit wieder auslöste. Wesentliche Voraussetzung zur Begründung der ätiologischen Rolle von Bakterien war die Einführung von Nährböden für ihre Anzucht und Isolierung — kombiniert mit einer sehr fortschrittlichen, über Ölimmersion, Mikrophotographie und Temperierkammer verfügenden Lichtmikroskopie und dem Einsatz von Laboratoriumstieren."
7311,PIRO: The Key to Success?,"Sepsis continues to represent a major problem in intensive care units worldwide. Diagnosis and management are often complex due in part to the remarkably diverse nature of the septic patient. Indeed, sepsis can range in severity from mild systemic inflammation of little clinical importance through to a widespread severe inflammatory response with multiple organ failure and a mortality rate in excess of 50%. Sepsis can affect individuals of any age group, with no or multiple co-morbidities, and with many different ongoing diagnoses. It can occur as the result of infection by one or more of a multitude of microbial pathogens impacting on any of numerous different sites within the body. Given the huge complexity of sepsis and the diverse populations of patients it affects, simple definitions are of relatively little use and a more detailed framework which can be used to better characterize patients with sepsis has been proposed, much as the TNM classification (tumor size, nodal spread, metastases) has been successfully used in clinical oncology. In this chapter, we discuss the development of this PIRO system, and suggest how it may be used in the future to aid diagnosis, guide therapy, and improve prognostication."
7312,Selected Disorders of the Respiratory System,"Respiration and gas exchange require coordination between the chest wall, lungs, central nervous system, and pulmonary circulation. A disruption within any one of these systems or a change in the relationship between systems can result in impairments of ventilation, perfusion, or gas exchange. These disruptions can result in debilitating acute and chronic respiratory disorders. This chapter discusses the etiology, epidemiology, clinical presentation, diagnostic criteria, management, and notable public health implications of respiratory system disorders not addressed in prior chapters. Topic areas covered include acute respiratory distress syndrome (ARDS), pulmonary hypertension, pneumothorax, pleural effusion, interstitial lung disease, bronchiectasis, atelectasis, and pulmonary sarcoidosis."
7313,The Role of Autoimmunity in Multiple Sclerosis,
7314,Virologie,"Noch im 20. Jahrhundert verstarben mehr als 300 Millionen Menschen an den Pocken. Nach dem ersten Weltkrieg tötete die Spanische grippe viele Millionen Menschen. Und heute? Heute müssen sich die FachärztInnen für Virologie neuen Herausforderungen stellen, wie etwa HIV, SARS oder der Vogelgrippe. Denn es treten immer neue Viren in Erscheinung - und deren Erforschung und Bekämpfung steht im Mittelpunkt der Arbeit der VirologInnen."
7315,Distribution of present-day biodiversity,"Biodiversity is unevenly distributed across the planet. A range of factors contribute to this distribution, including the global climatic gradient, the current and historical distribution of land masses, and geographical barriers, such as mountains."
7316,Inflammatory Bowel Disease at the Intersection of Autophagy and Immunity: Insights from Human Genetics,"Studies using human genetics have identified more than 160 loci that affect the risk of developing inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Several of these genes have been found to play key roles in the process of autophagy, a lysosome-based degradation pathway. Although historically considered to be a relatively nonselective process of degradation of cytosolic contents, autophagy has recently been revealed to have several selective and immune-specific functions that are relevant to the maintenance of intestinal homeostasis, including xenophagy, mitophagy, antigen presentation, secretion, and inflammasome regulation. In this chapter, we review the evidence that links autophagy-related genes, their immune-specific functions, and possible mechanisms of IBD pathogenesis. We summarize the basic molecular events underlying general and selective autophagy and present evidence suggesting possible pathogenic mechanisms revealed by studies of IBD-associated risk alleles of ATG16L1 and IRGM. Finally, we review chemical biology-based experimental approaches for identifying autophagy regulatory pathways that may have implications for the development of therapeutics."
7317,Algorithm Combination for Improved Performance in Biosurveillance: Univariate Monitoring,"This chapter proposes an enhancement to currently used algorithms for monitoring daily counts of pre-diagnostic data. Rather than use a single algorithm or apply multiple algorithms simultaneously, our approach is based on ensembles of algorithms. The ensembles lead to better performance in terms of higher true alert rates for a given false alert rate. Combinations can be employed at the data preprocessing step and/or at the monitoring step. We discuss the advantages of such an approach and illustrate its usefulness using authentic modern biosurveillance data."
7318,Nutrition Monitoring in the PICU,"The ideal set of variables for nutritional monitoring that may correlate with patient outcomes has not been identified. This is particularly difficult in the PICU patient because many of the standard modes of nutritional monitoring, although well described and available, are fraught with difficulties. Thus, repeated anthropometric and laboratory markers must be jointly analyzed but individually interpreted according to disease and metabolic changes, in order to modify and monitor the nutritional treatment. In addition, isotope techniques are neither clinically feasible nor compatible with the multiple measurements needed to follow progression. On the other hand, indirect alternatives exist but may have pitfalls, of which the clinician must be aware. Risks exist for both overfeeding and underfeeding of PICU patients so that an accurate monitoring of energy expenditure, using targeted indirect calorimetry, is necessary to avoid either extreme. This is very important, since the monitoring of the nutritional status of the critically ill child serves as a guide to early and effective nutritional intervention."
7319,Basic Mechanisms Mediating Cardiomyopathy and Heart Failure in Aging,"Biological aging represents the major risk factor for the development of heart failure (HF), malignancies, and neurodegenerative diseases. While risk factors such as lifestyle patterns, genetic traits, blood lipid levels, and diabetes can contribute to its development, advancing age remains the most determinant predictor of cardiac disease. Several parameters of left ventricular function may be affected with aging, including increased duration of systole, decreased sympathetic stimulation, and increased left ventricle ejection time, while compliance decreases. In addition, changes in cardiac phenotype with diastolic dysfunction, reduced contractility, left ventricular hypertrophy, and HF, all increase in incidence with age. Given the limited capacity that the heart has for regeneration, reversing or slowing the progression of these abnormalities poses a major challenge. In this chapter, we present a discussion on the molecular and cellular mechanisms involved in the pathogenesis of cardiomyopathies and HF in aging and the potential involvement of specific genes identified as primary mediators of these diseases."
7320,Transportation of Patients in a Bioemergency,"Serious recurrent and emerging communicable diseases, such as novel influenza strains, highly pathogenic viral hemorrhagic fevers, and novel coronaviruses in an era of increased globalization and travel, necessitate heightened vigilance and preparedness. Last year over four billion persons traveled by air. Systems and processes need to be in place to not just recognize and treat individuals, who harbor a serious pathogen, but also to manage and transport them safely while minimizing the risk of transmission to healthcare workers and others in the community. In this chapter, environmental and administrative controls, work practices, and personal protective equipment necessary to prevent transmission are described for the management and transportation of patients in both the out-of-hospital and hospital settings."
7321,Diversity of Coronavirus Spikes: Relationship to Pathogen Entry and Dissemination,"Coronaviruses are widespread in the environment, infecting humans, domesticated and wild mammals, and birds. Infections cause a variety of diseases including bronchitis, gastroenteritis, hepatitis, and encephalitis, with symptoms ranging from being nearly undetectable to rapidly fatal. A combination of interacting variables determine the pattern and severity of coronavirus-induced disease, including the infecting virus strain, its transmission strategy, and the age and immune status of the infected host. Coronavirus pathogenesis is best understood by discerning how each of these variables dictates clinical outcomes. This chapter focuses on variabilities amongst the spike (S) proteins of infecting virus strains. Diversity of coronavirus surface proteins likely contributes to epidemic disease, an important and timely topic given the recent emergence of the human SARS coronavirus."
7322,Surface Nano-patterning of Polymers for Mass-Sensitive Biodetection,"The crafting of sensor material of desired features has always remained a challenging task in the field of material designing and predominantly becomes more interesting when analyte belongs to biospecies. Label-free detection of different bioanalytes such as enzymes, viruses, microorganisms, and blood groups through mass-sensitive transducers has gained considerable importance in the development of modern biosensors. Analyte molecules interact with the surface of sensitive layer coated on these devices and as a result of this interaction, the frequency change is determined, which provides quantitative information about the mass of analyte. One of the most vital elements of these detection systems is to design selective sensor coatings through control surface structuring at nanoscale. Molecular imprinting has proven to be a highly suitable technique to generate selective surfaces that are capable of detecting different analytes, quantitatively and qualitatively as well. The tailor-made synthetic antibody cavities are rigid and stable, which are not immediately collapsed upon analyte interaction; moreover, the different bioanalytes do not undergo any phase change and maintain their original identity during analysis. This chapter will discuss the contribution of imprinting methods to design optimized surfaces for mass-sensitive detection of diverse biological species."
7323,Disaster Preparedness and Social Capital,"The first decade of the 21st century has pushed the field of disaster preparedness to the forefront of public health. In a few short years, the world has witnessed the far–ranging ramifications of 9/11 and anthrax (2001), SARS (2003), the Indian Ocean tsunami (2004), Hurricane Katrina (2005) and the looming threat of pandemic influenza. Societies everywhere are responding to these developments with new policies that commit added resources for protection against future disasters."
7324,Monitoring Immune Dysfunction in Septic Patients: Toward Tailored Immunotherapy,"Septic syndromes represent a major although largely under-recognized healthcare problem worldwide accounting for thousands of deaths every year [1–3]. Mortality remains high ranging from 20 % for sepsis to over 50 % for septic shock despite almost 20 years of anti-inflammatory clinical trials [1–3]. The inability of these therapies to mitigate the devastating effects of this condition indicates that the initial hypotheses for sepsis pathophysiology may have been misconstrued or inadequately addressed. Two major explanations have been proposed: 1) Septic patients have mainly been treated as a group despite the extreme heterogeneity characterizing this population [1]; 2) The postulate that death after sepsis is solely due to an overwhelming pro-inflammatory immune response may actually be inaccurate [1, 3]. Indeed, several lines of evidence have now established that death from septic shock is probably due to the effect of distinct mechanisms over time [1–3]. Early in the course of the disease, a massive release of inflammatory mediators (normally designed to trigger an immune response against pathogens) is occurring that may be responsible for organ dysfunction and hypoperfusion [1, 3]. Concomitantly, the body develops compensatory mechanisms to prevent overwhelming inflammation and dampen an overzealous anti-infectious response [1–3]. These negative feedback mechanisms, although having protective effects during the first initial hours, may paradoxically become deleterious as they persist over time leading to immune paralysis (Fig. 1) [1, 3]. Indeed, considerable clinical and experimental evidence indicates that patients rapidly present with numerous compromised immune functions [1, 3]."
7325,Studying Future Disasters and Crises: A Heuristic Approach,"Over time, new types of crises and disasters have emerged. We argue that new types of adversity will continue to emerge. In this chapter, we offer a framework to study and interpret new forms of crises and disasters. This framework is informed by historical insights on societal interpretations of crises and disasters. We are particularly focused here on the rise of transboundary crises – those crises that traverse boundaries between countries and policy systems. We identify the characteristics of these transboundary disruptions, sketch a few scenarios and explore the societal vulnerabilities to this type of threat. We end by discussing some possible implications for planning and preparation practices."
7326,Feline Coronavirus RT-PCR Assays for Feline Infectious Peritonitis Diagnosis,"Feline infectious peritonitis (FIP) is a highly fatal systemic disease in cats, caused by feline coronavirus (FCoV) infection. FCoV usually has little clinical significance; however, a mutation of this avirulent virus (feline enteric coronavirus) to a virulent type (FIP virus) can lead to FIP incidence. It is difficult to diagnose FIP, since the viruses cannot be distinguished using serological or virological methods. Recently, genetic techniques, such as RT-PCR, have been conducted for FIP diagnosis. In this chapter, the reliability of RT-PCR and procedures used to determine FCoV infection as part of antemortem FIP diagnosis is described."
7327,Current and Future Novel Targets of Gene Therapy for Hypertension,"Traditional therapeutic approaches for the treatment and control of hypertension are effective in normalizing blood pressure (BP) in less than a third of patients with hypertension. These pharmacological approaches may have reached a plateau in their effectiveness and newer strategies need to be investigated to not only increase the number of patients achieving BP control, but to find ways to cure the disease instead of just manage it. Since completion of the Human Genome Project and the continuous advancement of gene delivery systems, it is now possible to investigate genetic means for the treatment and possible cure for hypertension. In this review, we discuss potential genetic targeting for treatment of hypertension. There are two generalized gene transfer approaches that have been used successfully for hypertension. One is an induction approach where genes that lower blood pressure are overexpressed. A second method is a reduction approach where products of genes that are known to increase blood pressure are decreased. There are a variety of methods that have been utilized to meet these objectives, such as “knockout” and “ knock-in” animal models, and the use of sense and antisense (AS) technology. This review will focus on the sense and antisense applications, and how this technique is becoming more refined and precise through the targeting of specific tissues, the regulation and induction of components of the system, and use of other newer technologies, such as short interfering RNA (siRNA). Our lab has generally focused on the reduction approach, specifically in the genetic manipulation of components of the renin-angiotensin system (RAS). This system not only modulates BP, but has also been implicated in cardiac hypertrophy and morphology and in insulin resistance, which is highly correlated with hypertension. We will also discuss how new genes can be identified and subsequently serve as targets for the treatment of human hypertension."
7328,Large-Scale Phylogenetic Analysis of Emerging Infectious Diseases,"Microorganisms that cause infectious diseases present critical issues of national security, public health, and economic welfare. For example, in recent years, highly pathogenic strains of avian influenza have emerged in Asia, spread through Eastern Europe, and threaten to become pandemic. As demonstrated by the coordinated response to Severe Acute Respiratory Syndrome (SARS) and influenza, agents of infectious disease are being addressed via large-scale genomic sequencing. The goal of genomic sequencing projects are to rapidly put large amounts of data in the public domain to accelerate research on disease surveillance, treatment, and prevention. However, our ability to derive information from large comparative genomic datasets lags far behind acquisition. Here we review the computational challenges of comparative genomic analyses, specifically sequence alignment and reconstruction of phylogenetic trees. We present novel analytical results on two important infectious diseases, Severe Acute Respiratory Syndrome (SARS) and influenza. SARS and influenza have similarities and important differences both as biological and comparative genomic analysis problems. Influenza viruses (Orthymxyoviridae) are RNA based. Current evidence indicates that influenza viruses originate in aquatic birds from wild populations. Influenza has been studied for decades via well-coordinated international efforts. These efforts center on surveillance via antibody characterization of the hemagglutinin (HA) and neuraminidase (N) proteins of the circulating strains to inform vaccine design. However, we still do not have a clear understanding of (1) various transmission pathways such as the role of intermediate hosts like swine and domestic birds and (2) the key mutation and genomic recombination events that underlie periodic pandemics of influenza. In the past 30 years, sequence data from HA and N loci has become an important data type. In the past year, full genomic data has become prominent. These data present exciting opportunities to address unanswered questions in influenza pandemics. SARS is caused by a previously unrecognized lineage of coronavirus, SARS-CoV, which like influenza has an RNA based genome. Although SARS-CoV is widely believed to have originated in animals, there remains disagreement over the candidate animal source that lead to the original outbreak of SARS. In contrast to the long history of the study of influenza, SARS was only recognized in late 2002 and the virus that causes SARS has been documented primarily by genomic sequencing. In the past, most studies of influenza were performed on a limited number of isolates and genes suited to a particular problem. Major goals in science today are to understand emerging diseases in broad geographic, environmental, societal, biological, and genomic contexts. Synthesizing diverse information brought together by various researchers is important to find out what can be done to prevent future outbreaks [JON03]. Thus comprehensive means to organize and analyze large amounts of diverse information are critical. For example, the relationships of isolates and patterns of genomic change observed in large datasets might not be consistent with hypotheses formed on partial data. Moreover when researchers rely on partial datasets, they restrict the range of possible discoveries. Phylogenetics is well suited to the complex task of understanding emerging infectious disease. Phylogenetic analyses can test many hypotheses by comparing diverse isolates collected from various hosts, environments, and points in time and organizing these data into various evolutionary scenarios. The products of a phylogenetic analysis are a graphical tree of ancestor–descendent relationships and an inferred summary of mutations, recombination events, host shifts, geographic, and temporal spread of the viruses. However, this synthesis comes at a price. The cost of computation of phylogenetic analysis expands combinatorially as the number of isolates considered increases. Thus, large datasets like those currently produced are commonly considered intractable. We address this problem with synergistic development of heuristics tree search strategies and parallel computing."
7329,Role of Heat Shock Proteins in Viral Infection,"One of the most intriguing and less known aspects of the interaction between viruses and their host is the impact of the viral infection on the heat shock response (HSR). While both a positive and a negative role of different heat shock proteins (HSP) in the control of virus replication has been hypothesized, HSP function during the virus replication cycle is still not well understood. This chapter describes different aspects of the interactions between viruses and heat shock proteins during infection of mammalian cells: the first part focuses on the modulation of the heat shock response by human viral pathogens; the second describes the interactions of HSP and other chaperones with viral components, and their function during different steps of the virus replication cycle; the last part summarizes our knowledge on the effect of hyperthermia and HSR modulators on virus replication."
7330,Eosinophilic Pneumonia,"Eosinophilic pneumonia may manifest as chronic or transient infiltrates with mild symptoms, chronic idiopathic eosinophilic pneumonia, or the frequently severe acute eosinophilic pneumonia that may be secondary to a variety of causes (drug intake, new onset of tobacco smoking, infection) and that may necessitate mechanical ventilation. When present, blood eosinophilia greater than 1 × 10(9) eosinophils/L (and preferably greater than 1.5 × 10(9)/L) is of considerable help for suggesting the diagnosis, however it may be absent, as in the early phase of idiopathic acute eosinophilic pneumonia or when patients are already taking corticosteroids. On bronchoalveolar lavage, high eosinophilia (>25 %, and preferably >40 % of differential cell count) is considered diagnostic of eosinophilic pneumonia in a compatible setting, obviating the need of video-assisted thoracic surgical lung biopsy, which is now performed only on very rare occasions with inconsistency between clinical, biological, and imaging features. Inquiry as to drug intake must be meticulous (www.pneumotox.com) and any suspected drug should be withdrawn. Laboratory investigations for parasitic causes must take into account the travel history or residence and the epidemiology of parasites. In patients with associated extrathoracic manifestations, the diagnosis of eosinophilic granulomatosis with polyangiitis or of the hypereosinophilic syndromes should be raised. Presence of airflow obstruction can be found in hypereosinophilic asthma, allergic bronchopulmonary aspergillosis, idiopathic chronic eosinophilic pneumonia, eosinophilic granulomatosis with polyangiitis, or in the recently identified syndrome of hyperosinophilic obliterative bronchiolitis. Corticosteroids remain the cornerstone of symptomatic treatment for eosinophilic pneumonias, with a generally dramatic response. Relapses are common when tapering the doses or after stopping treatment especially in idiopathic chronic eosinophilic pneumonia. Cyclophosphamide is necessary only in patients with eosinophilic granulomatosis with polyangiitis and poor-prognostic factors. Imatinib is very effective in the treatment of the myeloproliferative variant of hypereosinophilic syndromes. Anti-interleukin-5 monoclonal antibodies are promising in the spectrum of eosinophilic disorders."
7331,Application of MultiBac System to Large Complexes,"Multisubunit protein complexes regulate numerous biologically important processes. Elucidation of their functional mechanisms based on their three-dimensional structures allows us to understand biological events at the molecular level. Crystallography and electron microscopy are powerful tools for analyzing the structures of biological macromolecules. However, both techniques require large-scale preparation of pure and structurally homogenous samples, which is usually challenging for large multisubunit complexes, particularly from eukaryotes. In this chapter, we describe the principles and methods of producing multisubunit complexes in insect cells using the MultiBac system."
7332,Single Sign-on(SSO) to Cloud based Services and Legacy Applications “Hitting the IAM wall”,"Single Sign-On (SSO) projects are a special case of Identity and Access Management (IAM) projects. They are usually undertaken with the aim of increasing the user friendliness of Corporate IT systems’ user log-on processes. This should result in abolishing the use of multiple username and password combinations the user has to remember and change at different intervals. The SSO aim should be achieved without jeopardizing information security in any way. Increasing user convenience in such a manner will increase user satisfaction with the IT department along with general productivity levels. Cost control related to IT help desks resetting forgotten passwords should follow. SSO can also help organizations address information security compliance requirements, through the central logging (and audit facilities) of all access attempts and authorization decisions granted in relation to the organization’s restricted information resources. Sometimes compliance objectives are in fact the major business driver for SSO. In the consumer space customer loyalty and retention rates are often cited as an important commercial driver for SSO projects. With the advent of the de-perimeterized organization and increased scepticism around ‘Cloud Security’ is SSO still a viable worthwhile goal for organisations? This paper takes a closer look at special security issues arising when an organization attempts to create an Enterprise Single Sign-On (ESSO) solution that includes both legacy applications hosted within traditional organizational firewalls and a new breed of ‘Cloud Based’ solutions that are following the Software as Service (SaaS) model and therefore can be hosted with any number of Service Providers (SP) ‘in the cloud’."
7333,Evaluating Tests in Medical Diagnosis: Combining Machine Learning with Game-Theoretical Concepts,"In medical diagnosis, information about the health state of a patient can often be obtained through different tests, which may perhaps be combined into an overall decision rule. Practically, this leads to several important questions. For example, which test or which subset of tests should be selected, taking into account the effectiveness of individual tests, synergies and redundancies between them, as well as their cost. How to produce an optimal decision rule on the basis of the data given, which typically consists of test results for patients with or without confirmed health condition. To address questions of this kind, we develop an approach that combines (semi-supervised) machine learning methodology with concepts from (cooperative) game theory. Roughly speaking, while the former is responsible for optimally combining single tests into decision rules, the latter is used to judge the influence and importance of individual tests as well as the interaction between them. Our approach is motivated and illustrated by a concrete case study in veterinary medicine, namely the diagnosis of a disease in cats called feline infectious peritonitis."
7334,Use of MAR Elements to Increase the Production of Recombinant Proteins,"The biopharmaceutical industry continues to face the challenge of producing large amount of recombinant proteins for use as therapeutics, and eighty percent of protein therapeutics in clinical development are produced in mammalian cell systems. Approaches to increase production addressing growth conditions, such as the improvement of media composition and process control, or transcription of the recombinant gene via the use of strong promoters/enhancers and amplification of gene copy number, have increased the yields obtained from mammalian cells considerably over the past decades. However these processes remain laborious, and extensive screening of clones is often required, as stable cell line and/or protein production is not always obtained. Unstable or variable expression is linked to the location of transgene integration site, the regulation of gene expression, the silencing of genes, and the loss of gene copies. Genetic elements that may remodel chromatin to maintain the transgene in an active configuration are now being employed increasingly to improve protein production using mammalian cells. Here we will review how one type of such elements, the MARs, may increase transgene integration into the cell genome and decrease silencing effects to reduce expression variability. We also illustrate how inclusion of these elements in expression vectors leads to increased specific productivities ranging from 20 to 100 picograms per cell and per day (p/c/d), resulting in protein titers above 5 g/l."
7335,Innate Immune Responses in Ventilator-Associated Pneumonia,"Ventilator-associated pneumonia (VAP) is a common complication of mechanical ventilation, resulting in substantial morbidity, mortality, and health care cost. Early upper airway colonization by pathogenic bacteria and microaspiration are the primary pathogenic events leading to VAP. Patients at risk for VAP have defects in structural/mechanical defenses of the respiratory tract. In addition, critical illness, including sepsis, trauma, and postoperative states, is associated with profound defects in both innate and acquired antibacterial immunity, influencing antimicrobial effector functions of both leukocytes and structural/parenchymal cells. Factors present within the lung microenvironment, including alveolar stretch, cyclical atelectasis, changes in oxygen tension, and respiratory tract microbiota, substantially impact antibacterial host responses. Mechanisms accounting for dysregulated immune homeostasis are incompletely understood, but likely involve: (1) alterations in the balance of pro- and anti-inflammatory cytokines; (2) changes in pathogen recognition receptor and G-protein coupled receptor expression and downstream signaling cascades; and (3) dysregulated cell death responses. Antibiotics and preventive strategies are the mainstay of therapy in patients with VAP. However, novel approaches are needed to reverse immunological reprogramming that occurs during critical illness and/or mechanical ventilation, and to identify patients who are most likely to benefit from immunomodulatory therapy."
7336,Nonhuman Primate Models of Immunosenescence,"Due to a dramatic increase in life expectancy, the number of individuals aged 65 and older is rapidly rising. This presents considerable challenges to our health care system since advanced age is associated with a higher susceptibility to infectious diseases due to immune senescence. However, the mechanisms underlying age-associated dysregulated immunity are still incompletely understood. Advancement in our comprehension of mechanisms of immune senescence and development of interventions to improve health span requires animal models that closely recapitulate the physiological changes that occur with aging in humans. Nonhuman primates (NHPs) are invaluable preclinical models to study the underlying causal mechanism of pathogenesis due to their outbred nature, high degree of genetic and physiological similarity to humans, and their susceptibility to human pathogens. In this chapter, we review NHP models available for biogerontology research, advantages and challenges they present, and advances they facilitated. Furthermore, we emphasize the utility of NHPs in characterizing immune senescence, evaluating interventions to reverse aging of the immune system, and development of vaccine strategies that are better suited for this vulnerable population."
7337,Real-Time Reverse Transcription Polymerase Chain Reaction for Rapid Detection of Transmissible Gastroenteritis Virus,Transmissible gastroenteritis (TGE) is a highly contagious disease of pigs caused by the TGE virus (TGEV). Rapid detection of the virus in the affected pigs’ feces is critical for controlling the disease outbreaks. The real-time RT-PCR assay described in this chapter can quickly detect the presence of TGEV in fecal samples with high sensitivity and specificity.
7338,Paramyxoviruses: Respiratory Syncytial Virus and Human Metapneumovirus,"Human respiratory syncytial virus (RSV) and human metapneumovirus (MPV) are members of the family Paramyxoviridae of the Mononegavirales order, comprising the nonsegmented negative-strand RNA viruses. Paramyxoviridae has two subfamilies: Paramyxovirinae, which includes the parainfluenza viruses 1–4 and measles and mumps viruses, and Pneumovirinae, which includes RSV and MPV. Pneumovirinae has two genera: Pneumovirus, which includes human RSV, bovine respiratory syncytial virus, and pneumonia virus of mice, and Metapneumovirus, which includes human MPV and avian metapneumovirus, sometimes called avian pneumovirus."
7339,Intelligence Tasking and Coordination,"This chapter explains the complexities involved in understanding how intelligence is tasked or coordinated by decision-makers in the bio-threat and risk context. It argues that compared to other threat and risk categories (conventional terrorism, cyber and high volume crime), the political leadership of most ‘Five Eyes’ countries do not see bio-threats and risks as high intelligence priorities. This impacts on the intelligence communities in a number of ways that are not helpful to gaining greater understanding of these issues. Nonetheless, the chapter argues that the intelligence communities themselves can play a more proactive role to improve tasking and coordination of bio-threat and risk intelligence."
7340,Return to Play in Asthma and Pulmonary Conditions,"In football (soccer), an athlete’s cardiopulmonary system consistently operates in a sinusoidal manner with numerous episodes of low- and high-intensity surges. This demand requires an athlete to have the most ideal function to perform at a high level. Multiple pulmonary processes can influence an athlete’s ability to perform by interfering with the pulmonary system’s primary function of ventilation and perfusion to try to optimize gas exchange. In this chapter, we will discuss some of the more common pathology that can affect this delicate balance. Some of the more common, but important, conditions such as asthma, exercise-induced bronchoconstriction (EIB), pneumothorax, and pulmonary infections will be addressed, as each are readily seen, by sports medicine teams, caring for the football players. The discussion will begin with how those conditions are diagnosed through history and advanced testing and will be followed by treatment with environmental trigger modification, pharmacologic interventions, and lastly return to play criteria."
7341,Workplace Health Promotion Interventions ConcerningWomenWorkers' Occupational Hazards,
7342,Production of Antibody Fab Fragments in Escherichia coli,"A phage-display library is the most broadly used platform for preparation of recombinant human monoclonal antibody Fab fragments. Panning is effective for the selection of immunoglobulin genes from naïve and immune libraries. However, it is possible to bypass the phage display system if human peripheral lymphocytes are obtained from seropositive patients with infectious diseases as a source of immunoglobulin genes. Direct screening of bacterial colonies producing Fab fragments by colony blotting using filter membranes is practical for the isolation of human Fab fragments to major antigens of pathogens. An oligoclonal culture can also be used, and is a partial application of Epstein-Barr virus transformation of peripheral lymphocytes. Using these procedures, neutralizing antibody Fab fragments to various antigens can be obtained with a sufficient level of cloning efficacy. Chain shuffling and site-directed mutagenesis are also useful ways to improve the quality of the cloned antibody Fab fragments."
7343,Acronyms and Abbreviations,
7344,Liver,"The discovery that renin–angiotensin system (RAS) components are locally expressed in the liver tissue, pointed out to a role for this system in the pathogenesis of hepatic fibrosis and cirrhosis. The RAS counter-regulatory axis composed by the angiotensin converting enzyme 2 (ACE2), angiotensin-(1-7) [Ang-(1-7)] and Mas receptor mediates pro-inflammatory, pro-thrombotic, and pro-fibrotic processes, frequently opposing the classical RAS arm (ACE-Ang II-AT(1) receptor) actions. Therefore, the balance between both RAS axes most likely affects the clinical and histopathological expression of liver diseases. It is worth noticing that liver diseases are major causes of morbidity and mortality worldwide. Without proper treatment, all types of chronic hepatitis will progress to end-stage liver diseases, including cirrhosis, liver failure, and hepatocellular carcinoma, which ultimately lead to death. In this context, to better comprehend the role of RAS components in liver failure might pave the way for the search of potential predictive biomarkers as well as the development of novel therapeutic approaches. Valuable data have been generated from preclinical and clinical studies. Herein, we summarize the current evidence, mainly focusing in the ACE2-Ang-(1-7)-Mas receptor arm, regarding the role of RAS in liver diseases. The therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed."
7345,Healthcare-Associated Viral Infections: Considerations for Nosocomial Transmission and Infection Control,"Nosocomial and healthcare-associated viral infections are major contributors to patient morbidity and mortality, prolonged hospitalization, and increased healthcare costs in all pediatric age groups. Healthcare workers are also at risk of acquiring nosocomial viral infections, affecting their own health, as well as facilitating spread of the infection to other patients, their family, and the community. Healthcare-associated viral infections may occur in a variety of healthcare settings, including clinics, emergency centers, urgent care centers, procedure suites, operating rooms, hospital wards, nurseries, and intensive care units. In addition, non-patient care areas, such as the cafeteria, waiting areas, and playrooms may also be a source of viral infections that can spread in the healthcare setting. These infections may be device-related or transmitted via blood products or organ donation and respiratory droplets, through food including human milk, person to person, or via air ducts, fomites, and surfaces. They most commonly involve the respiratory and gastrointestinal tracts; however, all organ systems may potentially be involved. Both DNA and RNA viruses, either common or exotic, may contribute to healthcare-associated viral infections. Advances in molecular viral diagnostics have enabled rapid detection and routine surveillance for viral infections and now allow early identification of viruses. Prompt identification allows timely containment measures to minimize transmission to other patients or healthcare workers and avoids hospital, community, and global outbreaks."
7346,Antiviral Activity of Phytochemicals: A Current Perspective,"A wide variety of active phytochemicals have been found to have therapeutic ­applications against genetically and functionally diverse viruses. The antiviral mechanism of these agents may be explained on the basis of their ­antioxidant activities, scavenging capacities, the inhibition of DNA, RNA synthesis, or the blocking of viral reproduction, etc. Numerous epidemiological and experimental studies have revealed that a large number of phytochemicals have promising antiviral activities. Especially in the last decade, a number of promising leads have been identified by a combination of in vitro and in vivo studies using diverse biological assays."
7347,Learning Nature of Science Through Socioscientific Issues,"A series of reforms in science education in Hong Kong started at the turn of the twenty-first century. In line with international trends, science education in Hong Kong has undergone considerable changes in the last decade since the implementation of the revised junior secondary science curriculum (grades 7–9) (Curriculum Development Council [CDC], 1998). The new curriculum encourages teachers to conduct scientific investigations in their classes, advocates scientific investigation as a desired means of learning scientific knowledge, and highlights the development of inquiry practices and generic skills such as collaboration and communication. Most importantly, it was the first local science curriculum that embraced understanding of nature of science (NOS), for example, being “able to appreciate and understand the evolutionary nature of scientific knowledge” (CDC, 1998, p. 3) was stated as one of its broad curriculum aims. In the first topic, “What is science?”, teachers are expected to discuss with students some features about science, for example, its scope and limitations, some typical features about scientific investigations, for example, fair testing, control of variables, predictions, hypothesis, inferences, and conclusions. Such an emphasis on NOS was further supported in the revised secondary 4 and 5 (grade 10 and 11) physics, chemistry, and biology curricula (CDC, 2002). Scientific investigation continued to be an important component while the scope of NOS was slightly extended to include recognition of the usefulness and limitations of science as well as the interactions between science, technology, and society (STS)."
7348,Acute Respiratory Failure Before ICU Admission: A Practical Approach,"Acute respiratory failure (ARF) is a common and life-threatening event in cancer patients. It is the leading cause of admission to ICU among the patients with hematologic and solid malignancies and is often associated with poor outcome. Timely identification of the cause of ARF and the initiation of the appropriate therapy may improve the survival. Pulmonary infections represent the leading cause of ARF in those patients, and unless proven otherwise, ARF must be considered as an infectious emergency. Noninfectious causes of ARF include cardiogenic and noncardiogenic pulmonary edema, acute pulmonary embolism, and complications related both to the underlying malignancy and the toxic effects of chemotherapy. This chapter reviews the most common causes of ARF in oncologic patients and discusses the diagnostic and therapeutic approach before ICU admission."
7349,Part I Dictionary,
7350,Pro-resolution of Inflammation: New Hints to Manage Sepsis?,"Sepsis is newly defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. The pathophysiological mechanism of sepsis is highly complex, and the mortality of in-patients suffering from sepsis is more than 10%. Severe unmanaged inflammation and inappropriate immune response characterize sepsis. Anti-inflammation therapies alone are not successful for the reason that disbalance of anti-inflammatory and pro-resolving agents. In the recent researches, the host responses during the course of self-resolving infections are found to have the involvements of specialized pro-resolution mediators (SPMs), namely, lipoxins, resolvins, protectins and maresins. These endogenous lipid metabolites are core signal molecules in the resolution of inflammation, playing a key role in regulating the inflammation and promoting return to homeostasis. Besides, heme oxygenase-1 (HO-1, a sensitive marker for oxidative stress) is also known for upregulation in inflammation profiling. Carbon monoxide, synthesized by HO-1, performs multiple stances of anti-inflammation and pro-resolution along with the SPMs. If the potentially beneficial effects of these mediators would be well evaluated in clinical trials, they present encouraging new hints in managing infectious maladies especially sepsis."
7351,"On Sci-Fi’s Good China, Bad China: Maureen F. McHugh and Chang-Rae Lee","In this chapter, “On Sci-Fi’s Good China, Bad China,” examines China Mountain Zhang (1992) and On Such a Full Sea (2014). In both works, the universal duality of “good cop, bad cop,” utopia and dystopia, sinophilia and sinophobia, is attributed to the rise of China as the world power and the scourge of the world. In Maureen F. McHugh’s and Chang-rae Lee’s sci-fi novels, they trade the police badge of justice and violence for the Chinese face—a countenance of beauty and bastardy, awesome “China Mountain” that somehow infects with the suggestive C-illness in Lee."
7352,Neutral Evolution,"Neutral evolution is the default process of genomic changes. This is because our world is finite, and the randomness, indispensable for neutral evolution, is important when we consider the history of a finite world. The random nature of DNA propagation is discussed using branching process, coalescent process, Markov process, and diffusion process. Expected evolutionary patterns under neutrality are then discussed on fixation probability, rate of evolution, and amount of DNA variation kept in population. We then discuss various features of neutral evolution starting from evolutionary rates, synonymous and nonsynonymous substitutions, junk DNA, and pseudogenes."
7353,Prediction of Transmembrane Proteins from Their Primary Sequence by Support Vector Machine Approach,"Prediction of transmembrane (TM) proteins from their sequence facilitates functional study of genomes and the search of potential membrane-associated therapeutic targets. Computational methods for predicting TM sequences have been developed. These methods achieve high prediction accuracy for many TM proteins but some of these methods are less effective for specific class of TM proteins. Moreover, their performance has been tested by using a relatively small set of TM and non-membrane (NM) proteins. Thus it is useful to evaluate TM protein prediction methods by using a more diverse set of proteins and by testing their performance on specific classes of TM proteins. This work extensively evaluated the capability of support vector machine (SVM) classification systems for the prediction of TM proteins and those of several TM classes. These SVM systems were trained and tested by using 14962 TM and 12168 NM proteins from Pfam protein families. An independent set of 3389 TM and 6063 NM proteins from curated Pfam families were used to further evaluate the performance of these SVM systems. 90.1% and 86.7% of TM and NM proteins were correctly predicted respectively, which are comparable to those from other studies. The prediction accuracies for proteins of specific TM classes are 95.6%, 90.0%, 92.7% and 73.9% for G-protein coupled receptors, envelope proteins, outer membrane proteins, and transporters/channels respectively; and 98.1%, 99.5%, 86.4%, and 98.6% for non-G-protein coupled receptors, non-envelope proteins, non-outer membrane proteins, and non-transporters/non-channels respectively. Tested by using a significantly larger number and more diverse range of proteins than in previous studies, SVM systems appear to be capable of prediction of TM proteins and proteins of specific TM classes at accuracies comparable to those from previous studies. Our SVM systems – SVMProt, can be accessed at http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi."
7354,Asthma and COPD,"Asthma and chronic obstructive pulmonary disease (COPD) are clinically important in older adults because like heart failure, they are common causes of chronic shortness of breath, which reduces the quality of life by limiting an individual’s activity. In developed countries, about 4% of older adults have been diagnosed with asthma and another 4% have been diagnosed with COPD, but the prevalence is doubled for each of these chronic respiratory diseases when objective tests are performed. COPD has become the fourth leading cause of death in some developed countries. COPD onset occurs almost exclusively in older age due to the cumulative effects of cigarette smoking in genetically-susceptible individuals. An upper respiratory viral infection commonly leads to the initial diagnosis of asthma at any age. About half of older adults with asthma have allergic triggers, compared to about 90% of asthmatic children. Exacerbations with dyspnea, wheezing and cough are the major morbidity of asthma and COPD, which limits activity, reduces quality of life and increases health care utilization and costs. In older adults as in younger adults, the most effective prevention for both asthma and COPD is smoking cessation."
7355,Human Health Threats and Implications for Regional Security in Southeast Asia,"Health security issues like infectious diseases, natural and man-made disasters and environmental degradation represent daunting, non-traditional regional and global security challenges. This chapter examines these major threats to human health, individually and as elements of a complex health security system, and relates them to human security in Southeast Asia and to the global security situation. Loss of confidence in government’s ability to protect its citizens makes people vulnerable to extremists who promise near-term solutions, leading to civil unrest and political violence, refugee migrations into neighboring states, insurgencies and disruption of regional security. Case studies are included to show how governmental failure to respond effectively to health challenges can compromise national and regional security. Additional case studies demonstrate best practices in preventing and mitigating negative health effects on human security and regional stability. Finally, this chapter posits that multilateral collaboration and cross-sectoral interagency cooperation are essential for sustainable regional health security solutions."
7356,Pharyngitis,"A 40-year-old woman presents to her primary care physician complaining of fever, malaise, and sore throat for the last 3 days. The patient has a past medical history significant for hypothyroidism. She takes only levothyroxine pills and recent thyroid tests have been normal. The patient denied nausea, vomiting, diarrhea, cough, chest pain, and shortness of breath. She is a nursery school teacher who reports having taken care of multiple children with “colds” in the recent week. She drinks one glass of wine every week and denied smoking or other drug use. The patient is married and lives with her husband, who has not been sick."
7357,Managing Uncertainty Through Participation,"Participation enjoys a very special status in health promotion discourse. Conceptualised both as a process and a valued outcome, it is often viewed as a defining feature and a key principle of health promotion (Robertson & Minkler, 1994; Rootman, Goodstadt, Potvin & Springett, 2001). Taking advantage of an undisputable position as a cardinal value, the role of participation has rarely been critically examined in relation to health promotion practice and its contribution to public health. The questions regarding the role of participation and how, in practice, practitioners can facilitate and support its emergence, have not been given satisfactory answers. Answers to these crucial questions can only result from a theoretical understanding of what participation entails in terms of action in the social situations of health promotion interventions. Theorizing on the role of participation in health promotion and on the social processes at play when it occurs is a prerequisite to reframing participation as a professional practice rather than as an ideology (see Pelikan, Chapter 6), and to develop appropriate procedures that can foster the conditions for effective participation."
7358,Blut und Blutprodukte,"die Blutgruppe richtet sich nach der Antigeneigenschaft der Erythrozyten; die Blutgruppenantigene A und B des AB0-Systems befinden sich an der Ery throzytenoberfläche. Das Antigen 0 gibt es nicht, man spricht allenfalls vom Merkmal H; die Blutgruppe A lässt sich in A(1) und A(2) unterteilen. Der Hauptunterschied zwischen den Untergruppen besteht darin, dass die Agglutination von A(1)-Erythrozyten bei Kontakt mit Anti-A-Serum wesentlich stärker und rascher verläuft. Für die Transfusion ist diese Unterteilung nicht von Bedeutung, da Antigen-Antikörper-Reaktionen zwischen A(1) und A(2) sehr selten auft reten und nur sehr schwach sind (Verteilung: A(1) ≈ 20%, A(2) ≈ 80%);"
7359,Human Subjects Research in Bioemergencies,"Bioemergencies present unique ethical and operational challenges to performing clinical research with human subjects. Patient care, public health protection, and responder safety are paramount in these situations, which often involve high biosafety level pathogens and containment conditions. While working to halt the spread of disease, research is necessary to understand the ongoing outbreak as well as increase response capabilities in the face of future threats. Research in bioemergencies has novel and unexpected challenges that vary greatly depending on the type of studies being conducted and data being collected. This chapter will provide an understanding of basic principles, challenges, and regulatory components of human subjects research during bioemergencies, as well as ongoing practical components of these studies."
7360,Prediction of RNA Secondary Structure Including Kissing Hairpin Motifs,"We present three heuristic strategies for folding RNA sequences into secondary structures including kissing hairpin motifs. The new idea is to construct a kissing hairpin motif from an overlay of two simple canonical pseudoknots. The difficulty is that the overlay does not satisfy Bellman’s Principle of Optimality, and the kissing hairpin cannot simply be built from optimal pseudoknots. Our strategies have time/space complexities of O(n (4)) / O(n (2)), O(n (4)) / O(n (3)), and O(n (5)) / O(n (2)). All strategies have been implemented in the program pKiss and were evaluated against known structures. Surprisingly, our simplest strategy performs best. As it has the same complexity as the previous algorithm for simple pseudoknots, the overlay idea opens a way to construct a variety of practically useful algorithms for pseudoknots of higher topological complexity within O(n (4)) time and O(n (2)) space."
7361,Pneumonie,"nach dem ursächlichem Agens (virale, bakterielle, mykotische oder atypische); nach klinischem Verlauf (akut, chronisch); nach dem Ort, an dem die Infektion erworben wurde: 1. ambulant, außerhalb des Krankenhauses erworbene Pneumonie („community acquired pneumonia“; CAP); 2. nosokomial erworbene Pneumonie („hospital acquired pneumonia“; HAP); hierzu zählen die: beatmungsassoziierte Pneumonie („ventilator associated pneumonia“; VAP ) und die. Pneumonie bei Patienten, welche aus dem Alten- oder Pflegeheim stammen („health care acquired pneumonia“; HCAP): 3. Pneumonien bei immunsupprimierten Patienten; • primäre und sekundäre Pneumonien (als Folge bestimmter Grunderkrankungen, Bronchiektasien, Aspiration, Inhalationsintoxikation, Lungeninfarkt etc.);"
7362,The Importance of Animal Models in the Development of Vaccines,"Efficient translation of basic vaccine research into clinical therapies greatly depends upon the availability of appropriate animal models. Testing novel vaccine candidates in animal models is a critical step in the development of modern vaccines. Animal models are being used to assess the quality and quantity of the immune response, to identify the optimal route of delivery and formulation, to determine protection from infection and disease transmission, and to evaluate the safety and toxicity of the vaccine formulation. Animal models help to make the translation from basic research to clinical application, and they often allow prediction of the vaccine potential, which helps in predicting the financial risks for vaccine manufacturers. Choosing an appropriate animal model has become increasingly important for the field, as each model has its own advantages and disadvantages. In this review, the criteria for selecting the right animal model, the advantages and disadvantages of various animal models, as well as the future needs for animal models are being discussed."
7363,Respiratory System,"The following chapter will focus on the respiratory system. Pertinent questions, answers, and rationale will be reviewed. Answers for this chapter can be found beginning on page 101."
7364,"Glyco3D: A Suite of Interlinked Databases of 3D Structures of Complex Carbohydrates, Lectins, Antibodies, and Glycosyltransferases","Glyco3D is a portal for structural glycobiology of several interlinked databases that is covering the three-dimensional features of monosaccharides, disaccharides, oligosaccharides, polysaccharides, glycosyltransferases, lectins, monoclonal antibodies, and glycosaminoglycan-binding proteins. Collection of annotated NMR data of bioactive oligosaccharides is also available. A common nomenclature has been adopted for the structural encoding of the carbohydrates. Each individual database stands by itself as it covers a particular family of either complex carbohydrates or carbohydrate-binding proteins. A unique search engine is available that scans the full content of all the databases for queries related to sequential information of the carbohydrates. The interconnection of these databases provides a unique opportunity to characterize the three-dimensional features that a given oligosaccharide molecule can take in different environments, i.e., vacuum, crystalline state, or interacting with different proteins having different biological function. The databases, which have been manually curated, were developed with nonproprietary software. They are web-based platform and are freely available to the scientific community at http://glyco3d.cermav.cnrs.fr."
7365,A Novel Efficient Simulated Annealing Algorithm for the RNA Secondary Structure Predicting with Pseudoknots,"The pseudoknot structure of RNA molecular plays an important role in cell function. However, existing algorithms cannot predict pseudoknots structure efficiently. In this paper, we propose a novel simulated annealing algorithm to predict nucleic acid secondary structure with pseudoknots. Firstly, all possible maximum successive complementary base pairs would be identified and maintained. Secondary, the new neighboring state could be generated by choosing one of these successive base pairs randomly. Thirdly, the annealing schedule is selected to systematically decrease the temperature as the algorithm proceeds, the final solution is the structure with minimum free energy. Furthermore, the performance of our algorithm is evaluated by the instances from PseudoBase database, and compared with state-of-the-art algorithms. The comparison results show that our algorithm is more accurate and competitive with higher sensitivity and specificity indicators."
7366,Adjunctive and Supportive Measures for Community-Acquired Pneumonia,"The widespread introduction of penicillin in the 1940s resulted in a substantial reduction in mortality from community-acquired pneumonia (CAP). However, despite significant advances in medical science, only a small improvement has occurred since, particularly in patients with bacteremic pneumococcal pneumonia [1, 2]. Even modern intensive care has only made a small difference to the mortality in patients with severe pneumonia [3, 4]. While the aging population, increased number of patients with severe co-morbid illnesses, and the human immunodeficiency virus (HIV) epidemic have certainly contributed to the persistently high mortality rate [2, 5, 6], apparently healthy, immunocompetent patients continue to die from CAP. Disturbingly, a recent British Thoracic Society study concluded that no available therapy could substantially reduce the mortality rate from severe CAP in young adults [7]."
7367,Acute Myelogenous Leukemia and Febrile Neutropenia,"Aggressive chemotherapy has a deleterious effect on all components of the defense system of the human body. The resulting neutropenia as well as injury to the pulmonary and gastrointestinal mucosa allow pathogenic micro-organisms easy access to the body. The symptoms of an incipient infection are usually subtle and limited to unexplained fever due to the absence of granulocytes. This is the reason why prompt administration of antimicrobial agents while waiting for the results of the blood cultures, the so-called empirical approach, became an undisputed standard of care. Gram-negative pathogens remain the principal concern because their virulence accounts for serious morbidity and a high early mortality rate. Three basic intravenous antibiotic regimens have evolved: initial therapy with a single antipseudomonal β-lactam, the so-called monotherapy; a combination of two drugs: a β-lactam with an aminoglycoside, a second β-lactam or a quinolone; and, thirdly, a glycopeptide in addition to β-lactam monotherapy or combination. As there is no single consistently superior empirical regimen, one should consider the local antibiotic susceptibility of bacterial isolates in the selection of the initial antibiotic regimen. Not all febrile neutropenic patients carry the same risk as those with fever only generally respond rapidly, whereas those with a clinically or microbiologically documented infection show a much slower reaction and less favorable response rate. Once an empirical antibiotic therapy has been started, the patient must be monitored continuously for nonresponse, emergence of secondary infections, adverse effects, and the development of drug-resistant organisms. The averageduration of fever in serious infections in eventually successfully treated neutropenic patients is 4–5 days. Adaptations of an antibiotic regimen in a patient who is clearly not responding is relatively straightforward when a micro-organism has been isolated; the results of the cultures, supplemented by susceptibility testing, will assist in selecting the proper antibiotics. The management of febrile patients with pulmonary infiltrates is complex. Bronchoscopy and a high resolution computer-assisted tomographic scan represent the cornerstones of all diagnostic procedures, supplemented by serological tests for relevant viral pathogens and for aspergillosis. Fungi have been found to be responsible for two thirds of all superinfections that may surface during broad-spectrum antibiotic treatment of neutropenic patients. Antibiotic treatment is usually continued for a minimum of 7 days or until culture results indicate that the causative organism has been eradicated and the patient is free of major signs and symptoms. If a persistently neutropenic patient has no complaints and displays no evidence of infection, early watchful cessation of antibiotic therapy or a change to the oral regimen should be considered."
7368,"Secondary Hemophagocytic Lymphohistiocytosis, Macrophage Activation Syndrome, and Hyperferritinemic Sepsis-Induced Multiple-Organ Dysfunction Syndrome in the Pediatric ICU","Children with secondary hemophagocytic lymphohistiocytosis present diagnostic and therapeutic challenges to the intensivist. Management of this condition can be facilitated with a collaborative approach among a team of intensivists, immunologists, rheumatologists, hematologists, and infectious disease specialists. Controversy over management approach commonly centers on incomplete understanding at the time of clinical presentation regarding individual patient differences in inflammation pathobiology that require different therapies. This review provides the clinician with the rationale for personalizing care for these critically ill children."
7369,2 Secondary assessment,"Een (dreigend) agressieve of gewelddadige patiënt managen is een complexe uitdaging. Diverse factoren spelen een rol: vroege herkenning van een potentieel agressieve patiënt, diagnose en behandeling, interventietechnieken, veiligheid voor patiënt en omgeving, en medicolegale aspecten. Een goede training van het personeel in de omgang met agressieve patiënten is essentieel."
7370,Pädiatrie,"Was wir essen, wie viel, wie, mit wem, wann und wo ist ein Ausdruck von unseren frühesten Erfahrungen und entscheidet wesentlich über unser späteres Leben, unseren Ernährungszustand und unsere Gesundheit. Die Ernährung des Säuglings und Kindes hat zum Ziel, das Kind in den ersten Lebensjahren an eine ausgewogene Kost und den gemeinsamen Familientisch zu bringen. Essen ist dabei nicht nur ein physiologischer Vorgang, sondern wird von verschiedensten Einflussfaktoren (familiäre Strukturen, kulturelle Zusammenhänge, Mythen und Fakten über Nahrungsmittel und deren Zusammensetzung) geprägt, die bei der Wissensbildung über gesundes Essverhalten nicht einfach außer acht gelassen werden dürfen."
7371,Pediatric Otolaryngology,"Otolaryngologic procedures are commonly performed on children. In fact, pressure equalizing tube placement (ear tubes) and adenotonsillectomy are among the most frequent surgical interventions in the pediatric population. Therefore, every anesthesiologist who manages children undergoing otolaryngologic procedures must be familiar with the special implications of sharing the pediatric airway with an otolaryngologist working in the head and neck region. In addition, it is imperative to be skilled in the challenges of compassionately yet safely managing anxious young patients and their parents from the time of preoperative assessment until discharge from the post anesthesia care unit."
7372,Kryptokokkose,
7373,Alcohol and the Alveolar Epithelium,"The distal airways are covered with a heterogeneous layer of cells known as the alveolar epithelium. Alveolar epithelial cells provide the major barrier between the airspace and fluid filled tissue compartments. As such, regulation of the alveolar epithelium is critical to maintain a healthy lung and for optimal gas exchange. In this chapter, we discuss functional roles for alveolar epithelial cells with particular emphasis on intercellular junctions and communication. As a thin layer of cells directly exposed to atmospheric oxygen, alveoli are particularly sensitive to oxidant insults. Alcohol significantly diminishes the normal antioxidant reserves of the alveolar epithelium, thereby rendering it sensitized for an exaggerated damage response to acute and chronic injuries. The effects of alcohol on alveolar epithelia are discussed along with open questions and potential therapeutic targets to prevent the pathophysiology of alcoholic lung disease."
7374,Proteomic Analysis of the Plant Nucleolus,"The nucleolus is a prominent sub-nuclear structure found in all eukaryotes. It is where the ribosomal RNA genes are transcribed and ribosomes are synthesised. However, much evidence has now accumulated that the nucleolus is involved in many other nuclear processes. Nucleoli are of moderate protein complexity, comprising a few hundred proteins, and can be isolated for proteomic analysis. In this chapter we describe the purification and analysis of plant nucleoli by proteomic methods and summarise the current results. We also discuss more specific tagging methods that have been used to analyse individual protein complexes, as well as methods for analysing post-translational modifications of nucleolar proteins. Finally we discuss the assessment of the reliability of such proteomic data, and the presentation and curation of this type of data."
7375,Vlekjes,"Mijn dochtertje (groep I) komt thuis met het bericht dat haar vriendinnetje de ‘vlekjesziekte’ heeft. Navraag bij de schoolleiding brengt mij niet veel verder. Er wordt iets geroepen van de vijfde of zesde ziekte, met daarbij de mededeling dat een aantal kinderen uit de klas hetzelfde heeft. Hoe is dit met de besmettelijkheid? Zijn er voorzorgen voor mijn tandartspraktijk nodig? Ik heb veel ouders met kinderen van school in mijn praktijk."
7376,Case Studies on the Local Coverage Process,"As providers, beneficiaries, device manufacturers, and other stakeholders strive to more fully understand the working parameters of the Medicare local coverage process, there is considerable value in presenting a more global, integrated approach. There are three major defining forces, which provide such a framework, and can be further exemplified by selected recent coverage case studies. These three forces are (1) specific regulatory mandates of the Medicare program, (2) the creation of stakeholder partnerships, and (3) the need to properly use medical evidence. Most coverage policies represent a combination of these forces. In fact, there is only the occasional local coverage scenario, which is characterized by the pure expression of any solitary element."
7377,24 Longaandoeningen,"Longproblemen tijdens of na een verblijf in de tropen kunnen acuut (zoals Legionella-pneumonie) of chronisch van aard zijn (longtuberculose). Reizigers die longklachten hebben, zullen meestal eerst naar de huisarts gaan. Deze kan verwijzen naar een internist of longarts, een kliniek met expertise in tropische ziekten of (voor onderzoek op tuberculose) een GGD in Nederland, of een VRGT-polikliniek in Vlaanderen."
7378,Nasenhöhle und Nasennebenhöhlen,"Die Gesichtsmitte (der Bezirk zwischen Oberlippe und Stirn) entwickelt sich zwischen der 4. und 8. Schwangerschaftswoche. [ 220] Der Stirnfortsatz bildet sich währen der 4. postovulatorischen Woche, aus ihm gehen die oberen und mittleren Anteile des Gesichts hervor. Die Oberkiefer- und Nasenwülste entwickeln sich unterhalb des Stirnfortsatzes. Am Ende der 4. Woche bilden zwei oberflächliche Verdickungen der Nasenwülste die Riechplakoden, die ektodermaler Herkunft sind und aus denen der Epithelbelag der Nasenhöhle und Nasennebenhöhlen hervorgeht. Die Plakoden stülpen sich ein und bilden die Riechgruben, aus denen die vorderen Choanen (Nasenlöcher) und weniger oberflächlich die primitiven hinteren Choanen entstehen. Die medialen Nasen- und Stirnfortsätze bilden das Nasenseptum, die Stirnknochen, Nasenknochen, die Siebbeinzellen- Komplexe und die oberen Schneidezähne. Die lateralen Nasen- und Oberkieferfortsätze vereinigen sich zur Bildung des Philtrum und der Columella. Das knorpelige Nasenskelet bildet sich während der 7. und 8. postovulatorischen Woche tief unterhalb der Nasen- und Stirnbeinknochen aus dem Chondrocranium. Die Nasennebenhöhlen entwickeln sich in der 6. Fetalwoche aus den lateralen Nasenwänden, und ihr Wachstum setzt sich nach der Geburt während des gesamten Kindes- und Jugendalters fort."
7379,Non-infectious Parenchymal Lung Disease,"Acute dyspnea is a common presenting complaint in the emergency room, emergency medicine and intensive care. It may have a cardiovascular or a non-cardiovascular origin, the latter including pulmonary parenchymal diseases. Depending on the cause, it may be associated with fever, cough, hemoptysis, and/or chest pain, with a duration of symptoms that can range from hours to days. Prompt identification of the underlying cause of acute dyspnea is essential in guiding appropriate therapy and management, as patients may rapidly progress to acute respiratory failure. Evaluation with chest radiography is vital for initial assessment and may reveal diffuse parenchymal abnormalities, which may require further assessment with computed tomography (HRCT). Acute non-infectious parenchymal lung diseases are often overlooked and may be under-diagnosed. Their diagnosis requires the evaluation, along with the HRCT pattern, of the clinical and laboratory features and of the bronchoalveolar lavage. Biopsy may be necessary in more complex cases. Although the most frequent cause of diffuse non-infectious parenchymal lung involvement is acute hydrostatic pulmonary edema, there is a wide variety of diseases that may be encountered, including acute drug toxicity, hypersensitivity pneumonitis (HP), acute respiratory distress syndrome (ARDS) and diffuse alveolar hemorrhage (DAH). In trauma patients, fat embolism syndrome (FES) must be taken into account. Acute respiratory failure is an eventuality that can occur during the course of chronic lung diseases (UIP for example), which may have been unknown until then."
7380,Pulmonary Collectins in Diagnosis and Prevention of Lung Diseases,"Pulmonary surfactant is a complex mixture of lipids and proteins, and is synthesized and secreted by alveolar type II epithelial cells and bronchiolar Clara cells. It acts to keep alveoli from collapsing during the expiratory phase of the respiratory cycle. After its secretion, lung surfactant forms a lattice structure on the alveolar surface, known as tubular myelin. Surfactant proteins (SP)-A, B, C and D make up to 10% of the total surfactant. SP-B and SPC are relatively small hydrophobic proteins, and are involved in the reduction of surface-tension at the air-liquid interface. SP-A and SP-D, on the other hand, are large oligomeric, hydrophilic proteins that belong to the collagenous Ca(2+)-dependent C-type lectin family (known as “Collectins”), and play an important role in host defense and in the recycling and transport of lung surfactant (Awasthi 2010) (Fig. 43.1). In particular, there is increasing evidence that surfactant-associated proteins A and -D (SP-A and SP-D, respectively) contribute to the host defense against inhaled microorganisms (see 10.1007/978-3-7091-1065_24 and 10.1007/978-3-7091-1065_25). Based on their ability to recognize pathogens and to regulate the host defense, SP-A and SP-D have been recently categorized as “Secretory Pathogen Recognition Receptors”. While SP-A and SP-D were first identified in the lung; the expression of these proteins has also been observed at other mucosal surfaces, such as lacrimal glands, gastrointestinal mucosa, genitourinary epithelium and periodontal surfaces. SP-A is the most prominent among four proteins in the pulmonary surfactant-system. The expression of SP-A is complexly regulated on the transcriptional and the chromosomal level. SP-A is a major player in the pulmonary cytokine-network and moreover has been described to act in the pulmonary host defense. This chapter gives an overview on the understanding of role of SP-A and SP-D in for human pulmonary disorders and points out the importance for pathology-orientated research to further elucidate the role of these molecules in adult lung diseases. As an outlook, it will become an issue of pulmonary pathology which might provide promising perspectives for applications in research, diagnosis and therapy (Awasthi 2010)."
7381,Introduction: The World of Bats,"Bats are unique flying mammalians that occur worldwide feeding either on insects, fruits or even on blood depending on the species. Since they are active during the night, many myths have been launched during the last 500 years. All these facets are shortly considered here and prepare for a hopefully intense look into their hidden life."
7382,Point-of-Care Diagnostics,"Rapid tests that are low-cost and portable are the first line of defence in healthcare systems. Dipstick and lateral-flow are the two universal assay formats as they are lightweight and compact, and provide qualitative results without external instrumentation. However, existing formats have limitations in the quantification of analyte concentrations. Hence, the demand for sample preparation, improved sensitivity and user-interface has challenged the commercial products. Recently, capabilities, sensors and readout devices were expanded to multiplexable assays platforms, which might transcend the capabilities of existing design format of diagnostic tests. This chapter outlines the evolution of diagnostic devices and current trends in the development of qualitative and quantitative sensing devices for applications in healthcare, veterinary medicine, environmental monitoring and food safety. The chapter also discusses design parameters for diagnostics, their functionalisation to increase the capabilities and the performance, emerging sensing platforms and readout technologies. The factors which limit the emerging rapid diagnostics to become commercial products are also discussed."
7383,Health and Human Security,"This chapter focuses on health and how it can be reimagined through the lens of human security. It builds on Chap. 10.1007/978-3-319-72068-5_5’s exploration of human security, including of health, beyond borders. It delves more deeply into the nuts and bolts of delivering the right to health by reallocating the responsibility for it across State border as well as between States and NSAs. Antecedent to its analysis is the acknowledgment of the tension between the morality of a universal human right to health and the claim to health care conferred by citizenship, focusing on the continued (r)evolution of the human right to health as part and parcel of human security, and of its practical feasibility beyond State borders."
7384,Limiting the Neighborhood: De-Small-World Network for Outbreak Prevention,"In this work, we study a basic and practically important strategy to help prevent and/or delay an outbreak in the context of network: limiting the contact between individuals. In this paper, we introduce the average neighborhood size as a new measure for the degree of being small-world and utilize it to formally define the de-small-world network problem. We also prove the NP-hardness of the general reachable pair cut problem and propose a greedy edge betweenness based approach as the benchmark in selecting the candidate edges for solving our problem. Furthermore, we transform the de-small-world network problem as an OR-AND Boolean function maximization problem, which is also an NP-hardness problem. In addition, we develop a numerical relaxation approach to solve the Boolean function maximization and the de-small-world problem. Also, we introduce the short-betweenness, which measures the edge importance in terms of all short paths with distance no greater than a certain threshold, and utilize it to speed up our numerical relaxation approach. The experimental evaluation demonstrates the effectiveness and efficiency of our approaches."
7385,Infections in Hematology Patients,"Infections are major causes of morbidity and mortality in hematology patients especially those having undergone allogeneic hematopoietic stem cell transplantation. The management relies on early diagnosis and rapid introduction of appropriate antimicrobial drugs frequently before the infectious agent has been identified. The use of broad-spectrum antibacterial drugs has reduced the mortality in febrile neutropenia. However, the increase of multiresistant strains has in several countries become a major threat, and the development of new antibacterial drugs is urgently needed. Infection control strategies are also very important to limit the spread of multiresistant bacteria. Early diagnosis with imaging and tests for antigen or DNA is important for the management of fungal infections. High-risk patients should also receive prophylaxis. Viral infections are important causes of severe disease in patients having undergone allogeneic stem cell transplantation but do occur also in non-transplanted patients. Early diagnosis usually with tests for viral nucleic acids is the key for appropriate management. Prevention and treatment with antiviral drugs are available for some viruses especially herpesviruses."
7386,The Human Lung Microbiome,"The human lower respiratory tract is considered sterile in normal healthy individuals (Flanagan et al., 2007; Speert, 2006) despite the fact that every day we breathe in multiple microorganisms present in the air and aspirate thousands of organisms from the mouth and nasopharynx. This apparent sterility is maintained by numerous interrelated components of the lung physical structures such as the mucociliary elevator and components of the innate and adaptive immune systems (discussed below) (reviewed in (Diamond et al., 2000; Gerritsen, 2000)). However, it is possible that the observed sterility might be a result of the laboratory practices applied to study the flora of the lungs. Historically, researchers faced with a set of diseases characterized by a changing and largely cryptic lung microbiome have lacked tools to study lung ecology as a whole and have concentrated on familiar, cultivatable candidate pathogens."
7387,Selecting and Screening Donors,"Oocyte donation was originally established in 1983 as a treatment option for younger women with premature ovarian failure and for women with severe pelvic disease whose ovaries, as a result, were surgically inaccessible. The indications for donor oocyte in vitro fertilization (IVF) have now expanded to include not only women with hypergonadotropic hypogonadism but also those with advanced reproductive age, diminished ovarian reserve, significant genetic disease risk, poor oocyte or embryo quality, or multiple failures in prior attempts to conceive using conventional assisted reproductive technology (ART). Oocyte donation has also been recently used as an important source of material to promote the study of stem cell research. In these first cases of donation, gametes were obtained primarily from women already undergoing IVF who had excess oocytes at the time of retrieval. Today, most egg donors are not currently pursing infertility treatment themselves but are willing to donate their gametes for altruistic or commercial reasons. Since its initiation, oocyte donation services have spread throughout the USA and to many areas of the world. In the USA, 9,000–10,000 donor oocyte cycles occur annually. Though donor oocyte IVF is available throughout the USA, globally the practice of oocyte donation varies due to legal restrictions in many countries (Chap. 30)."
7388,BioDIFF: An Effective Fast Change Detection Algorithm for Biological Annotations,"Warehousing heterogeneous, dynamic biological data is a key technique for biological data integration as it greatly improves performance. However, it requires complex maintenance procedures to update the warehouse in light of the changes to the sources. Consequently, a key issue to address is how to detect changes to the underlying biological data sources. In this paper, we present an algorithm called BioDiff for detecting exact changes to biological annotations. In our approach we transform heterogeneous biological data to XML format and then detect changes between two versions of XML representation of biological data. Our algorithm extends X-Diff, a published XML change detection algorithm. X-Diff, being designed for any type of XML data, does not exploit the semantics of biological data to reduce the data set of bipartite mapping. We have implemented BioDiff in Java. We have conducted an extensive performance study using data from EMBL, GenBank, SwissProt and PDB. Our experimental results show that BioDiff runs 1.5 to 6 times faster than X-Diff."
7389,The Role of Infections in BOS,"Background: Infectious agents, particularly cytomegalovirus (CMV), have long been considered to be potential triggers for BOS, although the exact magnitude of the role of infections and the mechanisms thereof remain an area of active research. Methods: This chapter will review previous literature and newer results concerning the possible roles of CMV, other herpesviruses, community-acquired respiratory viruses, bacteria (including Pseudomonas, other gram-negative, gram-positive, and atypical organisms), and fungi, including colonization as well as invasive infection. Results: The text reviews and evaluates the body of literature supporting a role for these infectious agents as risk factors for BOS and time to BOS. Changing patterns of infection over time are taken into account, and studies that have shown an association between BOS (or lack thereof) and CMV are reviewed. Strategies for prevention or early treatment of infections are discussed as potential means of preserving allograft function long term. Immunizations, stringent infection-control practices, and antimicrobial treatment including newer therapies will be discussed. Conclusion: In addition to the classic literature that has focused on CMV, an expanding spectrum of infectious organisms has been implicated as possible risk factors for BOS. Increasing knowledge of the impact of long-term antiviral suppression, prophylaxis, and outcomes of early therapy will help guide future recipient management."
7390,Personal Protective Equipment,"Mindfulness may not be a term usually associated with personal protective equipment (PPE), but it is a useful concept for the discussion of putting together, layer by layer, the protective barriers that allow the safe provision of care for patients with highly hazardous communicable diseases. Each piece of the full PPE ensemble will have limitations that must be understood by the wearer. Close and careful attention to behaviors in the patient care environment becomes good PPE etiquette. Donning, or putting on PPE, carefully and fully before attending to a patient’s needs is fundamental but not intuitive. Removing PPE is a high-risk procedure that can be performed safely with practice, coaching, and observation. Mitigating risk depends on awareness to all areas of potential contamination and a mindful approach to delivering safe patient care."
7391,Inhibitors of respiratory viruses,
7392,Kupffer Cells in Health and Disease,"Kupffer cells (KC), the resident macrophages of the liver, represent the largest population of mononuclear phagocytes in the body. Phenotypic, developmental, and functional aspects of these cells in steady state and in different diseases are the focus of this review. Recently it has become evident that KC precursors seed the liver already early in fetal development, and the population can be maintained independently from circulating monocytes. However, inflammatory conditions allow rapid differentiation of monocytes into mature cells that are indistinguishable from genuine KC. KC are located in the lumen of sinusoids that receive blood both from the portal vein, carrying nutrients and microbial products from the gut, and from the hepatic artery. This positions KC ideally for their prime function, namely surveillance and clearance of the circulation. As such, they are important in iron recycling by phagocytosing effete erythrocytes, for instance. The immunophenotype of KC, characterized by a wide variety of endocytic receptors, is indicative of this scavenger function. In maintaining homeostasis, KC have an ambivalent response to exogenous triggers. On the one hand, their surveillance function requires alert responses to potentially hazardous substances. On the other hand, continuous exposure of the cells to the trigger-rich content of blood originating from the gut dampens their responsiveness to further stimuli. This ambivalence is also reflected in their diverse roles in disease pathogenesis. For the latter, we sketch the contribution of KC by giving examples of their role in metabolic disease, infections, and liver injury."
7393,Saponin Synthesis and Function,"Saponins are one of the most numerous and diverse groups of plant natural products. They serve a range of ecological roles including plant defence against disease and herbivores and possibly as allelopathic agents in competitive interactions between plants. Some saponins are also important pharmaceuticals, and the underexplored biodiversity of plant saponins is likely to prove to be a vital resource for future drug discovery. The biological activity of saponins is normally attributed to the amphipathic properties of these molecules, which consist of a hydrophobic triterpene or sterol backbone and a hydrophilic carbohydrate chain, although some saponins are known to have potent biological activities that are dependent on other aspects of their structure. This chapter will focus on the biological activity and the synthesis of some of the best-studied examples of plant saponins and on recent developments in the identification of the genes and enzymes responsible for saponin synthesis."
7394,Neutropenic Fever in the Intensive Care Unit,"Neutropenic fever is a common and potentially life-threatening condition in patients treated for cancer. Rapid initiation of appropriate antimicrobial therapy is necessary to decrease the risk of mortality. Most infections are due to gram-positive organisms, but the mortality rate is higher for gram-negative infections. Multidrug-resistant organisms are an emerging threat to neutropenic patients. Increasing data suggest that the pathophysiology of neutropenic fever and neutropenic sepsis is substantially different from non-neutropenic fever and sepsis. Additional research is needed to both further elucidate the pathogenesis of neutropenic fever and to develop additional effective antimicrobials."
7395,Acute Hepatic Failure,
7396,Diagnosis and Management of Acute Rhinosinusitis,
7397,A Review of Microblogging Marketing Based on the Complex Network Theory,"Microblogging marketing which is based on the online social network with both small-world and scale-free properties can be explained by the complex network theory. Through systematically looking back at the complex network theory in different development stages, this chapter reviews literature from the microblogging marketing angle, then, extracts the analytical method and operational guide of microblogging marketing, finds the differences between microblog and other social network, and points out what the complex network theory cannot explain. In short, it provides a theoretical basis to effectively analyze microblogging marketing by the complex network theory."
7398,Akute Gastroenteritis und postenteritisches Syndrom,"Definition und Häufigkeit. Die akute Gastroenteritis ist im Säuglings und Kleinkindesalter häufig. Die überwiegende Anzahl der Kinder, die an einem Brechdurchfall erkranken, ist jünger als 1 Jahr. Durch den schweren Wasser und Elektrolytverlust kommt es zur Dehydratation. Bei 70% der Patienten tritt eine isotone, bei 10% eine hyponatriämische und bei 20% eine hypertone (hypernatriämische) Dehydratation auf. Der Typ der Dehydratation ist unabhängig vom Erreger. Der Flüssigkeitsverlust kann das 2- bis 3-Fache des zirkulierenden Blutvolumens betragen, nämlich 150–250 ml/kgKG/Tag. Um das Blutvolumen konstant zu halten, entzieht der Körper dem Intrazellularraum Flüssigkeit. Dies führt zur Exsikkose. Das Ausmaß des Flüssigkeitsverlustes wird klinisch beurteilt und nach der WHO in drei Schweregrade eingeteilt (Tab. 106.1)."
7399,14-jähriger Junge mit Atemnot und Halsschmerzen,"Ein 14-jähriger Junge wird mit Verdacht auf Sepsis von einem peripheren Krankenhaus zuverlegt. Der Junge war im Ferienlager in Nordspanien gewesen und dort an einem fieberhaften Atemwegsinfekt erkrankt. Schon vor Abreise ins Ferienlager hatte er über Halsschmerzen geklagt. Im weiteren Verlauf entwickelte er Fieber und Dysphagie. Von einem Arzt vor Ort war unter der Annahme einer Angina tonsillaris ein Makrolid verschrieben worden. Doch als es dem Jungen immer schlechter ging, organisierten die Veranstalter die Rückreise. Bei Aufnahme zeigt sich der Patient tachydyspnoeisch mit Sauerstoffbedarf und kreislaufzentralisiert. Bei pathologischem Röntgenbefund und erhöhten Entzündungszeichen erfolgt die stationäre Aufnahme. Es folgt eine extensive Diagnostik inklusive Bildgebung und Mikrobiologie. Trotz der zügigen Therapie muss der Patient wegen weiterer Verschlechterung auf die Intensivstation verlegt werden."
7400,Sociology and Health,"Many people (including students of sociology) often wonder about the relevance of social sciences (especially sociology) to health issues. In general, it is often a challenge to discuss the nexus between social science and health. Why medical sociology? What does sociology have to do with medicine or health? This chapter aims to answer these questions. It starts with the meaning of sociology and its links to health studies—a definition and brief history of medical sociology and topic description of the discipline. All health problems are conceived as social problems, which are the core focus of sociological studies. This chapter explains the characteristics of social problems with regard to health issues. Health problems are viewed as parts of social pathologies by advancing the sociological dimensions of health problems. The chapter then attempts to re-explain the topical description of medical sociology (first advanced by David Mechanic in 1968) and includes some current issues. The topical descriptions specifically include social aetiology of disease, cultural beliefs and social response to illness, sociology of medical care and hospitals, sociology of psychiatry, social transition and health care, traditional medicine (alternative medicine), sociology of bioethics, health policy and politics, social epidemiology, sociology of dying and death, and medical education."
7401,Hightech im Dienste der Infektiologie,"Jeden Tag sterben weltweit etwa 13 Millionen Menschen an den Folgen viraler, bakterieller oder parasitärer Erkrankungen."
7402,Vitamin D and Chronic Obstructive Pulmonary Disease,"Vitamin D is an important regulator of calcium and bone homeostasis. It is also involved in the regulation of different genes and cellular functions, particularly in the context of inflammation, regeneration and immune control. Conversely, vitamin D deficiency which is often found in chronic, infectious and inflammatory diseases is thought to drive or enhance uncontrolled inflammation. Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation of the airways most often because of cigarette smoking. It has been recognized that repetitive airway infections and systemic consequences or co-morbidities also contribute to the progressive nature of COPD. Vitamin D deficiency is known to sneak in from the early stages of COPD, to become highly prevalent at the more severe stages, and may thereby catalyse airway infection, inflammation and systemic consequences. Undoubtedly, vitamin D deficiency enhances bone resorption and osteoporosis in COPD for which appropriate vitamin D supplementation is recommended. However, conflicting evidence has emerged on the extra-calcemic effects of vitamin D in COPD. A recent intervention trial with high-dose supplementation in COPD was only able to reduce exacerbation frequency in the subgroup of patients with lowest baseline vitamin D levels. It confirms that severe vitamin D deficiency is a health hazard but that more clinical and experimental studies are needed to explore how vitamin D deficiency may affect airway biology and systemic effects in the context of smoke-induced lung diseases."
7403,Vertebrates as Hosts and Reservoirs of Zoonotic Microbial Agents,"This chapter presents a survey of zoonotic microorganisms that have been isolated from vertebrates (Vertebrata), and are potentially transmissible to humans. It is intended as an aid for microbiologists, zoologists and epidemiologists, making possible better orientation among hosts (and reservoirs) of zoonoses. A great number of sources have been used in this compilation, e.g. Davis et al. (1970), Kucheruk (1979, 1989), Karabatsos (1985–1995), Hubálek (1994), etc."
7404,Antioxidant Properties of Surfactant,"Surfactant treatment is one of the milestones of respiratory distress syndrome (RDS) treatment in preterm infants, but it has been also demonstrated to exert consistent antioxidant and anti-inflammatory activities. Exogenous natural surfactant contains antioxidant enzymes, such as catalase (CAT) and superoxide dismutase (SOD), and nonenzymatic antioxidant molecules, such as plasmalogens and polyunsaturated phospholipids (PUPLs). Moreover, surfactant can contribute to the modulation of intra-alveolar inflammatory processes through the regulation effect of the surfactant A (SP-A) and B (SP-B) proteins. Although less extensively investigated, these functions may contribute to the efficacy of exogenous surfactant administration in preterm neonates with RDS."
7405,Molecular Diagnostics in Pulmonary Infections,"Infection of the lung parenchyma, or pneumonia, accounts for over four million deaths per year worldwide (Ferkol and Schraufnagel, Ann Am Thorac Soc 11:404–406, 2014). The condition is common, but also over-diagnosed, in part due to relatively poor laboratory and radiographic diagnostics. Indeed, we continue to rely on antiquated tools such as sputum culture and chest X-ray – the former of which lacks speed and sensitivity, and the latter specificity (Albaum et al. Chest 110:343–50, 1996). The resulting presumptive diagnoses of pneumonia lead to excessive use of empiric broad spectrum antibiotics; indeed, by some estimates, 30–70% of antibiotic prescriptions for lower respiratory tract infection are inappropriate (Kraus, PLoS One 12(3): e0174584, 2017). This approach begets microbial resistance, exposes patients to medication side effects, and puts patients at risk of potentially life-threatening complications including Clostridium difficile colitis. To improve diagnostic certainty in patients with suspected pneumonia, we must begin to consider and implement emerging technologies for efficient and accurate characterization of host responses to infection and identification of pathogens. In this chapter, we will discuss precision diagnostics already in common practice and those poised to be, and how these tools may ultimately enable personalization in the diagnosis of pneumonia."
7406,"TMEV and Neuroantigens: Myelin Genes and Proteins, Molecular Mimicry, Epitope Spreading, and Autoantibody-Mediated Remyelination","The Theiler’s murine encephalomyelitis (TMEV) model has been used to study the interactions of virus, myelin and anti-neuroantigen autoimmunity, TMEV and myelin can interrelate during virus entry and persistence. On virus entry, TMEV might use peripheral myelin P0 protein as a virus receptor. For persistence, TMEV seems to require myelin functional proteins or structural myelin itself. Here, myelin and oligodendrocyte loss and downregulation of myelin genes would lead to demyelination, but might limit virus spread in the central nervous system. Unlike experimental allergic encephalomyelitis (EAE), a pathogenic role of anti-myelin autoimmunity is unclear in TMEV infection. Anti-myelin autoantibodies have been detected in TMEV infection. Among them, only anti-galactocerebroside (GC) antibody is shown to be myelinotoxic, and has molecular mimicry with TMEV. Myelin-specific T cells play no role in initiation or progression of demyelination in the first two to three months after TMEV infection. However, cellular autoimmunity against several myelin antigens (epitope spreading) can be detected during the late chronic stage. Using the TMEV model, epitope spreading and autoantibody-mediated remyelination have been investigated by recombinant TMEV and anti-neuroantigen (natural) antibodies, respectively"
7407,Networks in Agent-Based Social Simulation,"Computational social science and in particular agent-based social simulation continue to gain momentum in the academic community. Social network analysis enjoys even more popularity. They both have much in common. In agent-based models, individual interactions are simulated to generate social patterns of all kinds, including relationships that can then be analyzed by social network analysis. This chapter describes and discusses the role of agent-based modeling in the generative-analytical part of this symbiosis. More precisely, we look at what concepts are used, how they are used (implemented), and what kind of validation procedures can be applied."
7408,Short Peptide Vaccine Design and Development: Promises and Challenges,"Vaccine development for viral diseases is a challenge where subunit vaccines are often ineffective. Therefore, the need for alternative solutions is crucial. Thus, short peptide vaccine candidates promise effective answers under such circumstances. Short peptide vaccine candidates are linear T-cell epitopes (antigenic determinants that are recognized by the immune system) that specifically function by binding human leukocyte antigen (HLA) alleles of different ethnicities (including Black, Caucasian, Oriental, Hispanic, Pacific Islander, American Indian, Australian aboriginal, and mixed ethnicities). The population-specific allele-level HLA sequence data in the public IMGT/HLA database contains approximately 12542 nomenclature defined class I (9437) and class II (3105) HLA alleles as of March 2015 present in several ethnic populations. The bottleneck in short peptide vaccine design and development is HLA polymorphism on the one hand and viral diversity on the other hand. Hence, a crucial step in its design and development is HLA allele-specific binding of short antigen peptides. This is usually combinatorial and computationally labor intensive. Mathematical models utilizing structure-defined pockets are currently available for class I and class II HLA-peptide-binding peptides. Frameworks have been developed to design protocols to identify the most feasible short peptide cocktails as vaccine candidates with superantigen properties among known HLA supertypes. This approach is a promising solution to develop new viral vaccines given the current advancement in T-cell immuno-informatics, yet challenging in terms of prediction efficiency and protocol development."
7409,25 Speeksel als diagnostische vloeistof,"Speekselonderzoek kan worden toegepast als hulpmiddel voor de diagnose van een aantal speekselklieraandoeningen, waaronder auto-immuunziekten zoals het syndroom van Sjögren. Verschillende ziektebeelden hebben ook invloed op speeksel en met geschikte parameters kunnen deze in de loop der tijd worden vervolgd, zoals cystische fibrose en enkele tumoren, onder andere borsttumoren. Screening van antimicrobiële afweersystemen in speeksel geeft een indicatie voor de ontvankelijkheid voor infectieziekten. Steroïdhormonen, zoals cortisol en de geslachtshormonen, kunnen nauwkeurig in speeksel worden bepaald. Van een groot aantal geneesmiddelen kunnen de kinetiek en het serumniveau doelmatig worden bestudeerd in speeksel. Drugsgebruik, het gebruik van doping en het rookgedrag kunnen betrouwbaar in speekselmonsters worden geanalyseerd. Voor forensische diagnostiek is speeksel een eenvoudig en gemakkelijk verkrijgbaar diagnosticum."
7410,Detection of Enteroviruses,"Enteroviruses are members of the Picornaviridae family and represent one of the most important water-transmitted pathogens. Detection of enteroviruses in water sources, or water-contaminated food, is a very valuable tool not only to prevent waterborne diseases but also to track down animal or human environmental viral pollution. Nowadays, molecular biology techniques allow the use of very sensitive and specific reverse-transcription polymerase chain reaction (RT-PCR) procedures to detect enteroviruses. In this chapter, using bovine enterovirus as a model, we describe procedures for enterovirus detection. Detailed descriptions of proper sample collection, storage, and processing, including methods for water concentration and solid sample extraction to obtain viral RNA, are outlined. Next, we describe methods for enterovirus detection based on virus isolation in appropriate cell culture. Finally, protocols for molecular detection of enterovirus are described, including procedures for conventional, nested, and real-time RT-PCR."
7411,"Requirements for Empirical Immunogenicity Trials, Rather than Structure-Based Design, for Developing an Effective HIV Vaccine","The claim that it is possible to rationally design a structure-based HIV-1 vaccine is based on misconceptions regarding the nature of protein epitopes and of immunological specificity. Attempts to use reverse vaccinology to generate an HIV-1 vaccine on the basis of the structure of viral epitopes bound to monoclonal neutralizing antibodies have failed so far because it was not possible to extrapolate from an observed antigenic structure to the immunogenic structure required in a vaccine. Vaccine immunogenicity depends on numerous extrinsic factors such as the host immunoglobulin gene repertoire, the presence of various cellular and regulatory mechanisms in the immunized host and the process of antibody affinity maturation. All these factors played a role in the appearance of the neutralizing antibody used to select the epitope to be investigated as potential vaccine immunogen, but they cannot be expected to be present in identical form in the host to be vaccinated. It is possible to rationally design and optimize an epitope to fit one particular antibody molecule or to improve the paratope binding efficacy of a monoclonal antibody intended for passive immunotherapy. What is not possible is to rationally design an HIV-1 vaccine immunogen that will elicit a protective polyclonal antibody response of predetermined efficacy. An effective vaccine immunogen can only be discovered by investigating experimentally the immunogenicity of a candidate molecule and demonstrating its ability to induce a protective immune response. It cannot be discovered by determining which epitopes of an engineered antigen molecule are recognized by a neutralizing monoclonal antibody. This means that empirical immunogenicity trials rather than structural analyses of antigens offer the best hope of discovering an HIV-1 vaccine."
7412,MBL Deficiency as Risk of Infection and Autoimmunity,"In pathogen recognition by C-type lectins, several levels of complexity can be distinguished; these might modulate the immune response in different ways. Firstly, the pathogen-associated molecular pattern repertoire expressed at the microbial surface determines the interactions with specific receptors (Fig. 42.1). Secondly, each immune cell type possesses a specific set of pathogen-recognition receptors. Thirdly, changes in the cell-surface distribution of C-type lectins regulate carbohydrate binding by modulating receptor affinity for different ligands. Crosstalk between these receptors results in a network of multimolecular complexes, adding a further level of complexity in pathogen recognition (Cambi and Figdor 2005; Thiel et al. 2006) (see 10.1007/978-3-7091-1065-2_23). MBL deficiency is genetically determined and predisposes to recurrent infections and chronic inflammatory diseases. MBL deficiency has been implicated in susceptibility and course of viral, bacterial, fungal, and protozoan infection. More than 10% of the general population may, depending on definition, be classified as MBL deficient, underlining the redundancy of the immune system. MBL-disease association studies have been a fruitful area of research, which implicates a role for MBL in infective, inflammatory and autoimmune disease processes. MBL deficiency predisposes both to infection by extra-cellular pathogens and to autoimmune disease."
7413,Pooling Experiments for Blood Screening and Drug Discovery,"Pooling experiments date as far back as 1915 and were initially used in dilution studies for estimating the density of organisms in some medium. These early uses of pooling were necessitated by scientific and technical limitations. Today, pooling experiments are driven by the potential cost savings and precision gains that can result, and they are making a substantial impact on blood screening and drug discovery. A general review of pooling experiments is given here, with additional details and discussion of issues and methods for two important application areas, namely, blood testing and drug discovery. The blood testing application is very old, from 1943, yet is still used today, especially for HIV antibody screening. In contrast, the drug discovery application is relatively new, with early uses occurring in the period from the late 1980s to early 1990s. Statistical methods for this latter application are still actively being investigated and developed through both the pharmaceutical industries and academic research. The ability of pooling to investigate synergism offers exciting prospects for the discovery of combination therapies."
7414,Bronchiolite e asma,"La letteratura internazionale ha recentemente riconosciuto la mancanza di confini netti fra bronchiolite (BR), wheezing (WH), o respiro sibilante, e asma."
7415,Journalismus und PR als Seismographen und Frühwarnsysteme?,"Wie so oft, klaffen normative Erwartungen und empirische Befunde im Journalismus und in der PR auch in Bezug auf deren Seismographen- und Frühwarnfunktion weit auseinander. Sowohl Journalisten selbst als auch Kommunikationsforscher haben immer wieder die aufklärende Rolle des Journalismus herausgearbeitet und allen Ernstes gehofft, der Journalismus könnte halbwegs verlässlich — oder zumindest verlässlicher als andere gesellschaftliche Subsysteme — vor Gefahren, vor sich anbahnenden Krisen und Katastrophen warnen."
7416,Toxoplasmose,
7417,7 Ademhaling,"Om ziekteprocessen die zich afspelen in de longen, luchtwegen en longvliezen (pleurae) te kunnen begrijpen en de gevolgen ervan voor het functioneren van het lichaam te kunnen inschatten, is kennis nodig van de normale anatomie van de thoraxinhoud en de fysiologie van het functioneren van de long. Deze is te vinden in het boek Fysiologie en Anatomie uit de serie Basiswerken, waarnaar wordt verwezen. Alleen waar nodig zal er in het kort even op worden ingegaan."
7418,"Nonrestorative Sleep, Musculoskeletal Pain, Fatigue in Rheumatic Disorders, and Allied Syndromes: A Historical Perspective","This chapter provides a historical perspective of the notion that the sleeping–waking brain is intimately related to complaints of unrefreshing sleep, widespread musculoskeletal pain, fatigue, and suffering. Such a constellation of symptoms extend from the remote biblical past, and involve various religious and cultural belief systems up to the recent evolution in Western medicine application of scientific methods for classification of illness. The contemporary application of scientific principles is directed to the etiology of diseases and to derive procedures for the management of such ill-understood illnesses. Historically, this constellation of rheumatic pain and fatigue symptoms have been given ever-changing medical and psychiatric labels that have been devoid of satisfactory medical understanding. In this chapter, the hypothesis that the sleeping/waking brain is integral to the somatic and behavioral symptoms of these disabling rheumatic chronic illness, termed fibromyalgia and various allied disorders, that are being examined and treated by a variety of health care professionals. Contemporary advances in mechanisms of how the sleeping–waking brain connects to these somatic and behavioral symptoms are reviewed. Potential avenues for further scientific understanding are described. Advances in such understanding are influencing current pharmacological and behavioral management of these suffering patients."
7419,Surfactant metabolism: factors affecting lipid uptake in vivo and in vitro,
7420,Patterns and Trends in Semantic Predications,"We demonstrate a series of studies of semantic predications from Semantic MEDLINE, including the detection of semantic predications with burstness and in association with conflict, contradictory, or other sources of uncertainties of scientific knowledge. Semantic networks of predications are analyzed within the framework of structural variations. Examples in this chapter represent scientific knowledge at a level of granularity that differs from those studies of scientific knowledge at the level of articles or journals of scholarly communication."
7421,Bio-kernel Self-organizing Map for HIV Drug Resistance Classification,"Kernel self-organizing map has been recently studied by Fyfe and his colleagues [1]. This paper investigates the use of a novel bio-kernel function for the kernel self-organizing map. For verification, the application of the proposed new kernel self-organizing map to HIV drug resistance classification using mutation patterns in protease sequences is presented. The original self-organizing map together with the distributed encoding method was compared. It has been found that the use of the kernel self-organizing map with the novel bio-kernel function leads to better classification and faster convergence rate ..."
7422,"Food Virology: Past, Present, and Future",
7423,Vaccines and Vaccination,"Livestock vaccines aim to increase livestock product and improve the health and welfare of livestock animals in a cost-efficient manner and prevent disease transmission. Successful livestock vaccines have been generated for pathogens including bacterial, viral, protozoan, and multicellular pathogens. These livestock vaccines have a significant effect on animal health and products and on human health through growing safe food procurement and preventing zoonotic diseases. There are successful production of biotechnological-based animal vaccines licensed for use that include virus-like particle vaccines, gene-deleted marker vaccines, subunit vaccines, DIVA vaccines, and DNA vaccines."
7424,Vasculitides: F. Kawasaki’s Disease,"Kawasaki’s disease (KD), once known as mucocutaneous lymph node syndrome, is a systemic inflammatory disorder occurring in children that is accompanied by vasculitis and a risk of coronary artery aneurysms. Other typical features of KD include spiking fevers, cervical lymphadenopathy, conjunctivitis, erythematous changes on the lips and in the oral cavity, dryness and cracking of the lips, a strawberry appearance to the tongue, and a polymorphous rash. Eighty percent of KD cases occur in children less than 5 years of age. Attempts to link KD definitively to some types of infection, particularly ones associated with superantigens, have thus far been unsuccessful. High dose aspirin and intravenous immune globulin (IVIG) are the cornerstones of therapy in KD. IVIG is essential to the prevention of coronary aneurysms. ■ Years after KD has occurred during childhood years, some cases of myocardial infarction caused by thrombosis of coronary aneurysms have been reported."
7425,Livestock husbandry as a tool for carnivore conservation in Africa’s community rangelands: a case–control study,"Conflict between people and wildlife is a major issue in both wildlife conservation and rural development. In African rangelands, species such as African wild dogs (Lycaon pictus), cheetahs (Acinonyx jubatus), lions (Panthera leo), leopards (Panthera pardus), and spotted hyaenas (Crocuta crocuta) may kill livestock and are therefore themselves killed by local pastoralists. Such conflict has led to the extirpation of these species from many areas, and also impacts the livelihoods of local livestock farmers. To investigate the possibilities for coexistence of people, livestock, and large predators in community rangelands, we measured the effectiveness of traditional livestock husbandry in reducing depredation by wild carnivores, using a case–control approach. Different measures were effective against different predator species but, overall, the risk of predator attack by day was lowest for small herds, accompanied by herd dogs as well as human herders, grazing in open habitat. By night, the risk of attack was lowest for herds held in enclosures (‘bomas’) with dense walls, pierced by few gates, where both men and domestic dogs were present. Unexpectedly, the presence of scarecrows increased the risks of attack on bomas. Our findings suggest that improvements to livestock husbandry can contribute to the conservation and recovery of large carnivores in community rangelands, although other measures such as prey conservation and control of domestic dog diseases are also likely to be necessary for some species."
7426,Biological systems: Applications and perspectives,"Viable biological systems occur on a wide scale of dimensions ranging from sizes of 30 meters for mammals (blue whale), and 120 meters for plants (sequoia tree), down to 10(−6) meters for single cellular organisms."
7427,3 Ziektebeelden,Patiënten kunnen zich melden met de zorg dat ze een besmettelijke aandoening opgelopen hebben na een ‘prikaccident’ of onveilig seksueel contact. Denk echter ook aan de mogelijkheid tot overdracht van een infectieziekte na bijvoorbeeld trauma of een bijtwond.
7428,Dermatologic Emergencies,"Prompt diagnosis and treatment of dermatologic emergencies in cancer patients decrease both morbidity and mortality. However the overlapping clinical presentations, complex medical and surgical comorbidities, and numerous medications often complicate diagnosis. Some dermatologic emergencies are primarily reactive and require immunosuppression such as pyoderma gangrenosum (PG) while others are a sign of systemic infection and require antimicrobials, such as staphylococcal scalded skin syndrome. Many primary inflammatory disorders, such as Steven–Johnson syndrome (SJS), can develop secondary infections and further complicate diagnosis and management. This chapter reviews the most common dermatologic emergencies seen in cancer patients, diagnostic dilemmas, and treatment options. Typical cases with photographs are also presented."
7429,Five Years of Increasing Structural Biology Throughput - A Retrospective Analysis,
7430,Respiratory Infection in Immunocompromised Neutropenic Patients,"Neutropenia is increasingly common in the hospital. The rise in incidence is due to proliferation of indications for and centers performing hematopoietic stem cell transplantation, hematologic effects of AIDS, and myelosuppressive side-effects of anti-viral and cancer chemotherapies (Table 39.1). As a result, these neutropenic patients are increasingly common in the intensive care units. These patients are often lymphopenic, anemic, and thrombocytopenic. They are at risk for multiple organ failures and various infections. This chapter will focus on respiratory infections in the neutropenic patient."
7431,Depressive und Angststörungen bei somatischen Krankheiten,"Depressiv-ängstliche Störungen sind bei den unterschiedlichen somatischen Erkrankungen häufig. Sie sind nicht nur als Reaktion auf die Situation der Erkrankung zu verstehen, sondern in ein komplexes Bedingungsgefüge eingebettet. Sie sind besonders häufig bei Erkrankungen, die das Zentralnervensystem oder endokrine Regulationssysteme direkt betreffen. Es besteht ein enger Zusammenhang zur Chronizität, Schwere und Prognose der Erkrankung. Eigenständige Effekte von diversen pharmakologischen Substanzgruppen sind wahrscheinlich."
7432,Safety and Security Regulations Against Biological Threats,"Biological threat agents include bacteria, viruses, fungi, parasites and their associated toxins. They have the ability to harmfully affect human health ranging from an allergic reactions to serious illnesses, even death. Water, soil, air, plants or animals can be a suitable habitat for their live and proliferation. Because biological agents may reproduce rapidly and initially unnoticed, need minimal resources to survive and can infect at very small doses they can be used as biological warfare agent or bioweapon. Genetic modification may enhance their hazardous and lethal properties, or develop resistance to conventional treatments. In effect, to protect people from dangerous biological agents as well as protect biological agents from intentional malicious acts both, biological safety and biological security measures should be implemented and respected. Because of wide scale of risks caused by biological agents, biosafety and biosecurity issues should be interpreted on many fields taking as priority protection of human beings and their surrounding environment. The reader will familiarize with different point of views on biosafety and biosecurity issues in relation to occupational health and safety, public health and disease surveillance, biodiversity protection, genetic modification of microorganisms, transportation of dangerous goods, storage control of biological agents, dual-use technology, education and awareness raising, weapon of mass destruction threats and bioterrorism acts. The main international agreements, the European Union regulations and principles supporting implementation of national legislation concerning biosafety and biosecurity areas are presented. The role of legally and not-legally binding instruments is highlighted, as well."
7433,Inhibitoren für Hydrolasen mit Acylenzym-Zwischenstufe,"Peptidasen und Esterasen sind hydrolysierende Enzyme. Alleine 2–3 % aller Genprodukte werden dieser Gruppe zugeordnet. Daher sind sie eine wichtige Gruppe von Zielproteinen für den Entwurf neuer Arzneistoffe und haben besondere Bedeutung für das strukturbasierte Wirkstoffdesign. Dies zeigt sich nicht alleine dadurch, dass zurzeit etwa 14 % aller bekannten humanen Peptidasen als mögliche Zielstrukturen für eine Arzneimitteltherapie geprüft werden."
7434,Methods for Gene Delivery,"The success of any gene transfer procedure, either through in vivo inoculation of the genetic material or after gene transfer into the patient’s cells ex vivo, strictly depends upon the efficiency of nucleic acid internalization by the target cells. As a matter of fact, making gene transfer more efficient continues to represent the most relevant challenge to the clinical success of gene therapy."
7435,Fungal Infections,"Older adults are at increased risk of developing opportunistic fungal infections because organ transplantation, intensive cancer chemotherapy regimens, and anti-tumor necrosis factor agents are now used more commonly, and because admission to an intensive care unit, which carries many risk factors for fungal infection, has become commonplace in this group. Candida species are the most common cause of opportunistic fungal infections, and bloodstream infections are usually treated with fluconazole or an echinocandin antifungal agent. Invasive mold infections are mostly caused by Aspergillus species; in older adults, they cause primarily pulmonary and sinus infections, and they are associated with a high mortality rate. The endemic fungi, Histoplasma capsulatum, Coccidioides species, and Blastomyces dermatitidis, cause infection when the mold form is dispersed and inhaled from the environment in those specific areas of the country in which these organisms flourish. Amphotericin B is used for initial treatment of severe histoplasmosis, coccidioi­domycosis, and blastomycosis; itraconazole is the therapy of choice for most mild to moderate infections due to these endemic mycoses."
7436,"Bildgebende Verfahren: Röntgen, Ultraschall, CT, Nuklearmedizin","In der Intensivmedizin findet die radiologische Diagnostik überwiegend am Krankenbett statt (»bedside radiology«). Etwa 90% der radiologischen Untersuchungen in der Intensiv- und Notfallmedizin stellen projektionsradiographische Röntgenaufnahmen des Thorax, des Abdomens und des Skelettsystems dar. In zunehmendem Maße werden neben den klassischen Aufnahmen auch die Schnittbildverfahren eingesetzt. Hier kommt der Ultraschalldiagnostik eine führende Rolle zu, gefolgt von der Computertomographie (CT)."
7437,Public Health Surveillance: A Vital Alert and Response Function,"Ungchusak, Heymann and Pollack address the critical global issue of public health surveillance. They describe how epidemiologists collect and use surveillance data to detect unusual events or outbreaks and to guide control programmes. Drawing on their combined international experience, the authors explain the vital role that data play in alerting authorities to respond to outbreaks such as Severe Acute Respiratory Syndrome, Ebola, Zika virus and Avian influenza. They point to the importance of sharing information globally while ensuring equal benefits to providers of data, coordinating surveillance activities across sectors, building capacity for surveillance and coordinating national surveillance activities. The authors emphasise the need for enhanced global cooperation to prepare for future public health emergencies of international concern."
7438,Hematologic Emergencies in the PICU,"The pediatric critical care physician is frequently challenged by hematologic abnormalities in critically ill children admitted to the pediatric intensive care unit (PICU). The challenge is to differentiate between primary hematologic emergencies that require critical care interventions and abnormalities secondary to other disease conditions. It is therefore necessary for the pediatric critical care physician to collaborate with the pediatric hematologist when managing such patients. This chapter summarizes some of the most common hematologic emergencies of red blood cell (RBC), white blood cell (WBC), or platelet disorders observed in critically ill children that may require attention of the pediatric critical care physician."
7439,Preventieve gezondheidszorg,"Voorkomen is beter dan genezen, is een veelgehoorde uitspraak. Preventie heeft als doel ervoor te zorgen dat mensen gezond blijven door enerzijds de gezondheid te bevorderen en anderzijds de gezondheid te beschermen. Dit kan bereikt worden door ziekten en aandoeningen te voorkomen of in een vroeg stadium op te sporen en door complicaties van ziekten te voorkomen. Maar het bevorderen van gezondheid moet ook in de bredere context van de definitie van de World Health Organisation van gezondheid gezien worden: preventie heeft als doel om te bevorderen dat mensen optimaal functioneren, zowel fysiek als mentaal als sociaal. De algehele kwaliteit van leven staat daarbij centraal."
7440,Infectious Lung Diseases and Endogenous Oxidative Stress,"Lower respiratory tract infections, according to the World Health Organization, account for nearly one third of all deaths from infectious diseases. They account for approximately 4 million deaths annually including children and adults and provide a greater disease burden than HIV and malaria. Among the common respiratory diseases, tuberculosis, influenza, and pneumonia are very common and can be life threatening if not treated properly. The causative agent of tuberculosis is the slow-growing bacilli Mycobacterium tuberculosis, while the causative agent of influenza is a segmented genome RNA virus. Pneumonia can be caused by a number of different microorganisms like bacteria, virus, and mycoplasma. In case of the entry of a pathogen in our body, the immune system gets activated, and the phagocytic cells try to eliminate it by generating reactive oxygen and nitrogen species (ROS and RNS) inside the phagosome. These reactive species or respiratory bursts are sufficient to eliminate most of the pathogens, except a few. M. tuberculosis is one such microorganism that has evolved mechanisms to escape this respiratory burst-mediated killing and thus survive and grow inside the macrophages. Infection with M. tuberculosis leads to the destruction of macrophages and release of cytokines, which lead to prolonged immune activation and oxidative stress. In some cases, the bacilli remain dormant inside macrophages for a long time. Flu viruses infect the epithelial cells present in respiratory tract, and the infection site is dependent on the hemagglutinin protein present on their capsid. Destruction of epithelial cells promotes secretion of mucus and activation of immune system leading to the oxidative damage. Community-acquired pneumonia is more serious and difficult to treat. In all these infections, ROS/RNS are developed as a defense mechanism against the pathogen. Persistence of the pathogen for a long time would lead to the uncontrolled production of ROS/RNS which will lead to oxidative stress and tissue damage to the host. Administration of antioxidants along with conventional treatments can be useful in the elimination of the reactive oxygen and nitrogen species."
7441,Molecular Virology,"This chapter describes common viral pathogens in humans with emphasis on the molecular diagnosis. Each section includes molecular characteristics, clinical presentation, and commonly used diagnostic methods (both conventional and molecular). Commercially available molecular diagnostic kits are preferentially described. Recommendations and guidelines (if available) for result interpretation and clinical approach are also included. For detailed methods, please refer to the chapter “Methodology and Instrumentation” in this book."
7442,"War, Refugees, Migration, and Public Health: Do Infectious Diseases Matter?",
7443,"Tick-Borne Bacterial, Rickettsial, Spirochetal, and Protozoal Diseases","Approximately 900 tick species exist worldwide, parasitizing a broad array of mammals, including humans, and thereby playing a significant role in the transmission of infectious diseases (1). In the United States, tick-borne diseases are generally seasonal and geographically distributed. They occur mostly during the spring and summer but can occur throughout the year."
7444,Pathophysiology of Acute Illness and Injury,"The pathophysiology of acute illness and injury recognizes three main effectors: infection, trauma, and ischemia-reperfusion injury. Each of them can act by itself or in combination with the other two in developing a systemic inflammatory reaction syndrome (SIRS) that is a generalized reaction to the morbid event. The time course of SIRS is variable and influenced by the number and severity of subsequent insults (e.g., reparative surgery, acquired hospital infections). It occurs simultaneously with a complex of counter-regulatory mechanisms (compensatory anti-inflammatory response syndrome, CARS) that limit the aggressive effects of SIRS. In adjunct, a progressive dysfunction of the acquired (lymphocytes) immune system develops with increased risk for immunoparalysis and associated infectious complications. Both humoral and cellular effectors participate to the development of SIRS and CARS. The most important humoral mediators are pro-inflammatory (IL-1β, IL-6, IL-8, IL-12) and anti-inflammatory (IL-4, IL-10) cytokines and chemokines, complement, leukotrienes, and PAF. Effector cells include neutrophils, monocytes, macrophages, lymphocytes, and endothelial cells. The endothelium is a key factor for production of remote organ damage as it exerts potent chemo-attracting effects on inflammatory cells, allows for leukocyte trafficking into tissues and organs, and promotes further inflammation by cytokines release. Moreover, the loss of vasoregulatory properties and the increased permeability contribute to the development of hypotension and tissue edema. Finally, the disseminated activation of the coagulation cascade causes the widespread deposition of microthrombi with resulting maldistribution of capillary blood flow and ultimately hypoxic cellular damage. This mechanism together with increased vascular permeability and vasodilation is responsible for the development of the multiple organ dysfunction syndrome (MODS)."
7445,Tracheobronchitis,
7446,Demographic and Epidemiological Perspectives of Human Movement,
7447,Specificity And Affinity,"The hallmark of lectins is the ability to bind carbohydrates specifically and reversibly. Understanding the properties and functions of lectins, as well as using them for diverse purposes, requires knowledge of this specificity, which is the major topic of the present chapter. Several lectins combine also with non-carbohydrate ligands, either at their carbohydrate binding sites or at sites distinct from the latter. A few others possess enzymatic activity unrelated to their carbohydrate specificity. These will be discussed briefly at the end of the chapter."
7448,Cell Regeneration in Lung Injury,"The acute respiratory distress syndrome (ARDS) is a lethal inflammatory disorder of the lung. Its incidence is estimated at 75 cases per 100,000 population and appears to be increasing [1]. Even with optimal treatment, mortality is about 30% [1–3]. As such, ARDS represents a major public health problem. The effects of two recent crises created by unusual viral infections of the respiratory tract — the severe acute respiratory syndrome (SARS) epidemic caused by the novel SARS coronavirus [4, 5] and the bird flu [6] highlight the importance of research into ARDS. Both viruses cause an ARDS-like picture. Because lung repair and regeneration contribute substantially to the pathophysiology of ARDS, understanding these processes is essential [7]. This chapter focuses on specific cell populations and markers involved in cell division and regeneration. In addition, a brief review of two pathways intimately associated with cell division is provided because of their potential for pharmacologic manipulation."
7449,Exploring the Linkages Between Ecosystems and Human Health,"The linkages between human health and ecosystems are complex, dynamic, and political. For millennia ecosystems have provided humans with essential services such as food, water, shelter and medicine. At the same time, they have mediated the transmission of many diseases and posed a number of health risks. The vitality of ecosystem services for human health and well-being is well captured by Bernard Abraham, President of Weskit-Chi Aboriginal Trappers Association, when he commented on the importance of forest ecosystems to Aboriginal people. He observed that many Aboriginal people consider the forest as: “their food bank, drugstore, meat market, bakery, fruit and vegetable stand, building material centre, beverage supply, and the habitat for all of the creator’s creatures.”(1)"
7450,The Role of Influenza Vaccination in Asthmatic Children,"Asthma is the most occurring chronic disease in children. Asthma related genes and environmental factors play a role in the etiology. Nowadays, asthma is regarded as a chronic inflammatory disease of the airways instead of solely a reversible airway obstruction. Asthma is often diagnosed on specific symptoms such as chest tightness, wheezing, dyspnea, and coughing. It is likely that, rather than a single disease entity, asthma consists of related, partially overlapping syndromes. The first symptoms often are experienced before the age of 5. Children with the highest risk have a family history of atopy and/or asthma. Viral infections with symptoms of wheezing acquired in the first year of life may be associated with the risk of developing asthma later on [1]. However, making the diagnosis with a reasonable certainty that is supported by spirometry is only possible from the age of 6 onward. More than 50% of children with a period of wheezing earlier on in life are not diagnosed as having asthma at the age of 6 [2]. The use of rescue and anti-inflammatory medication has largely altered the prospects of asthma patients and has improved their quality of life. Thus, nowadays, most asthma patients lead a normal life without restrictions. Disease control achieved by the asthmatics is an important predictor of the likelihood of complications of the disease [3]. However, asthma exacerbations neither respond to inhaled steroids nor can they substantially be prevented in this way [4, 5]. Only the use of oral corticos-teroids seems to be unmistakably effective in case of exacerbations [6, 7]."
7451,Sudden Death from Pulmonary Causes,"This chapter seeks to survey many of the common pathological entities identified in the lungs at autopsy and the potential role of pulmonary disease in formulating an opinion regarding the cause of death. Appreciation of pulmonary pathology in the medicolegal context is important as it frequently contributes to the immediate or underlying mechanisms of death. The primacy of the lungs in breathing and their coordinated function with the cardiovascular system means that ­pulmonary failure can rapidly compromise tissue oxygenation and body chemistry, leading to an alteration in blood pH, hypoxic damage to downstream tissues and ultimately multiorgan failure and death. Moreover, given that the lungs have direct contact with the environment through inhalation and receive approximately 50% of the cardiac output with each beat of the heart, they may be adversely affected by hazardous agents from the outside world or other pathologic processes not primarily located in the lungs. The range of topics discussed herein is limited by design to deaths due to disease and largely foregoes discussion of more forensically relevant issues relating to toxicology or trauma. Furthermore, the content and format of this chapter is not intended to be encyclopedic, but rather attempts to highlight selected issues regarding pulmonary disease of potential relevance to surgical or forensic pathologists who perform medicolegal postmortem examinations."
7452,Mining Good Sliding Window for Positive Pathogens Prediction in Pathogenic Spectrum Analysis,"Positive pathogens prediction is the basis of pathogenic spectrum analysis, which is a meaningful work in public health. Gene Expression Programming (GEP) can develop the model without predetermined assumptions, so applying GEP to positive pathogens prediction is desirable. However, traditional time-adjacent sliding window may not be suitable for GEP evolving accurate prediction model. The main contributions of this work include: (1) applying GEP-based prediction method to diarrhea syndrome related pathogens prediction, (2) analyzing the disadvantages of traditional time-adjacent sliding window in GEP prediction, (3) proposing a heuristic method to mine good sliding window for generating training set that is used for GEP evolution, (4) proving the problem of training set selection is NP-hard, (5) giving an experimental study on both real-world and simulated data to demonstrate the effectiveness of the proposed method, and discussing some future studies."
7453,Spectators and Victims: Between Denial and Projection,"This chapter goes into the unproductive metamorphosis of fear, and analyses the defence mechanisms that it generates: namely denial and projection. In the case of global risks, fear provokes self-defensive strategies based on denial (in the face of the nuclear challenge) and self-deception (in the face of global warming); and, in the case of the threat of the other, projective and persecutory strategies based on reactivating the dynamic of the ‘scapegoat’. They are two contrasting but specular responses which, at the emotional level, reflect the divarication between (unlimited) individualism and (endogamous) communitarianism. The first, implosive response converts into an absence of fear, attested to above all by the figure of the global spectator, while the second, explosive response converts into an excess of fear (fear of the other, fear of contamination), fuelled by forms of reinventing community. These responses are defined as irrational since in the first case they inhibit the spectator’s capacity to recognize himself as also a potential victim of the threats, thus preventing his mobilization, and in the second case they give rise to dynamics of demonization-dehumanization of the other, which result in a spiral of violence and impede forms of solidarity."
7454,Basics of Molecular Biology,"Molecular biology is the study of biology on molecular level. The field overlaps with areas of biology and chemistry, particularly genetics and biochemistry. Molecular biology chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interactions between DNA (deoxyribonucleic acid), RNA (Ribonucleic acid) and protein biosynthesis as well as learning how these interactions are regulated([1])."
7455,Effectiveness of Vaccination Strategies for Infectious Diseases According to Human Contact Networks,"A ‘contact network’ modeling infection transmission comprises of nodes (or individuals) that are linked when they are in contact that possibly transmits an infection. We here studied infection transmission on contact networks of various degree distributions—scale-free, exponential and constant—under SIRV model assuming susceptible, infected, removed and vaccinated statuses of nodes. Aiming for infectious disease containment within the very early stage of spreading, we computed the minimum transmissibility at which an infectious disease epidemic begins to emerge, and its change according to mass preventive and ring post-outbreak vaccination. In the most degree-heterogeneous scale-free network, the ‘super-spreading’ by the hubs, or high-degree nodes, allowed epidemics even for low transmissibility. In compensation, vaccination was much more efficient for the scale-free network. We also found that basic reproductive number R (0) defines a measurement of epidemic emergence universally applicable to networks of various degree distributions. These results are significant for public health design."
7456,"Zoonotic Infections and Biowarfare Agents in Critical Care: Anthrax, Plague, and Tularemia","Bacterial zoonotic infections are rare in developed countries in the twenty-first century but may cause major morbidity and mortality in developing regions of the world. In addition, their potential use as biological weapons makes early recognition and effective empiric therapy important for the critical care practitioner. Anthrax, plague, and tularemia share overlapping presenting syndromes, including fulminant respiratory infections and less severe but still highly morbid lymphocutaneous infections. Although all three may be transmitted as infectious aerosols, only plague has a risk of direct human-to-human transmission. Diagnostic testing will require special precautions for laboratory staff and most often involvement of regional and national reference laboratories. Empiric therapy with aminoglycosides may be life-saving for plague and tularemia, while the treatment of anthrax is complex and varies depending on the site of infection. In outbreaks or for post-exposure prophylaxis, treatment with doxycycline or a fluoroquinolone is recommended for all three diseases."
7457,Role of Analytics in Viral Safety,"In summary, this chapter reviews the principles of how the current and routine tests detect adventitious agents, and reviews how novel and emerging methods differ in their detection principles. These facets may permit novel methods to emerge to supplement, refine, or replace the routine methods. We have suggested a framework for risk assessment to assure biosafety in vaccines and suggested quantitative modeling to help crystallize thinking about the place of testing, either routine or novel, in this assurance. We assert that testing for adventitious agents should not be the sole basis on which product biosafety is assured. Appropriate sourcing and quality control of raw and starting materials, adherence to principles of Good Manufacturing Practices, including environmental and personnel monitoring and process validation, and finally, testing as verification are the package needed for maximal assurance of biosafety. Thus, a pathway forward to a new paradigm for adventitious agent testing exists in which detection of a broader array of potential adventitious agents might be included in the testing, with adequate sensitivity to provide the needed assurance of verification that there has been no catastrophic breach, in the context of the overall process, design, and adherence to cGMP. Furthermore, it is our hope that we may be able to implement the 3 Rs policy to reduce, replace, and/or refine the use of animals in product safety testing, at the same time that we provide greater assurance of the biosafety of vaccines."
7458,Betaferon® – Ab Ovo,"Es war einmal der Wunsch, die Replikation von Viren besser zu verstehen oder gar zu entschlüsseln, um wirksame Präparate gegen virale Erkrankungen zu entwickeln. Paul Ehrlich hatte bereits 1908 die antibakterielle Wirkung von Arsphenamin und damit das erste Medikament gegen Syphilis, Alexander Fleming 1928 das Penicillin und Gerhard Domagk 1935 die Sulfonamide entdeckt. Alle drei erhielten für ihre Entdeckungen Nobelpreise und retteten mit ihren Entwicklungen wahrscheinlich Millionen von Menschen das Leben."
7459,The Rationality of Science in Relation to its History,"Many philosophers have thought that Kuhn’s claim that there have been paradigm shifts introduced a problem for the rationality of science, because it appears that in such a change nothing can count as a neutral arbiter; even what you observe depends on which theory you already subscribe to. The history of science challenges its rationality in a different way in the pessimistic induction, where failures of our predecessors to come up with true theories about unobservable entities is taken by many to threaten the rationality of confidence in our own theories. The first problem arises from a perception of too much discontinuity, the second from an unfortunate kind of continuity, in the track record of science. I argue that both problems are only apparent, and due to under-description of the history. The continuing appeal of the pessimistic induction in particular is encouraged by narrow focus on a notion of method that Kuhn was eager to resist."
7460,"Cutaneous, Subcutaneous and Systemic Mycology","The first description of dermatophytosis was recorded by Celsus, a Roman encyclopaedist who described a suppurative infection of scalp (‘porrigo’ or ‘kerion of Celsus’) in De Re Medicina (30 A.D.). Throughout the middle ages, several descriptions of dermatophytosis were produced where it is described as ‘tinea’. The keratin-destroying moths which made circular holes in the woollen garments are known as Tinea. Due to similarity in the structure of circular lesion of dermatophytosis on the smooth skin with the circular hole made by moth, Cassius Felix introduced the term ‘tinea’ to describe the lesions. In 1806, Alibert used the term ‘favus’ to describe the honey-like exudate in some scalp infections. However, the fungal aetiology of tinea was first detected by Robert Remak, a Polish physician who first observed the presence of hyphae in the crusts of favus. This detection is also a landmark in medical history because this is the first description of a microbe causing a human disease. He himself did not publish his work, but he permitted the reference of his observations in a dissertation by Xavier Hube in 1837. Remak gave all the credits of his discovery to his mentor Schoenlein who first published the fungal etiological report of favus in 1839. He observed the infectious nature of the favus by autoinoculation into his own hands and also successfully isolated the fungus later (1945) and named Achorion schoenleinii (Trichophyton schoenleinii) in honour of his mentor. In 1844, Gruby described the etiologic agent of tinea endothrix, later became known as Trichophyton tonsurans. The genus Trichophyton was created and described by Malmsten (1845) with its representative species T. tonsurans. Charles Robin identified T. mentagrophytes in 1847 and T. equinum was identified by Matruchot and Dassonville in 1898. Raymond Jacques Adrien Sabouraud (France) first compiled the description of Trichophyton in his book (Les Teignes) in 1910 which was based on his observation in artificial culture. The sexual state of dermatophyte was described by Nannizzi (1927). Emmons (1934) first reported the classification of dermatophytes based on vegetative structures and conidia. Gentles (1958) established the successful treatment of tinea capitis with griseofulvin."
7461,Spatial Analysis of the 2008 Influenza Outbreak of Hong Kong,"The deaths of three children amid a series of recent influenza outbreaks in early March 2008 resulted in the immediate shut down of all kindergartens and primary schools in Hong Kong. While many parents welcome the decision, others queried the judgment given that citizens lack sufficient information to evaluate whether there is an outbreak and must follow actions prescribed by the government. We demonstrated in this paper various techniques to visualize disease distribution and present outbreak data for public consumption. Our analyses made use of affected (case) and non-affected (control) schools with influenza cases in March 2008. A series of maps were created to show disease spread and concentration by means of standard deviational ellipses, grid-based spatial autocorrelation, and kernel density. The generalized data did not permit statistical analysis other than the nearest neighbor distance. We also made suggestions about requirements of additional data and possible directions of disease analysis."
7462,The Neutrophil,"The neutrophil provides a crucial defence against fungal infections. This numerous phagocyte is recruited rapidly to sites of infection, where it detects pathogens through a range of pathogen-recognition receptors. Phagocytosis and the generation of a range of microbicidal molecules neutralises the pathogen, following which neutrophil death by apoptosis triggers an injury-limiting resolution process facilitating the restoration of normal tissue architecture"
7463,Viruses in the Intensive Care Unit (ICU),Whereas viruses are not usually considered to be important causes of ICU admission this review has demonstrated this perception to be incorrect. Viruses and their manifestations differ from continent to continent and hemisphere to hemisphere and it is essential that the intensivist be familiar with diagnosis and management of these ubiquitous organisms.
7464,Bushmeat,"Since Homo erectus, an ancient ancestor of the modern human, was discovered to have evolved from Africa 2 million years ago, animals have been hunted for their skin and meat . Animal meat is a nutritious, a convenient, and an easily accessible source of protein in the diet. However, over the turn of the last century, a sharp increase in widespread human populations, clusters of extreme poverty in areas surrounded by wildlife, and highly profitable trade revenues have exploited bushmeat at an unprecedented level. It is at a point now whereby some species are on the brink of extinction, and others will follow suit unless a drastic change occurs. This case study will focus on the ethical demand for bushmeat, focusing on the UK and European markets, and zoonotic diseases that have caused a major threat to the existence of human and animals alike."
7465,Progettazione e sicurezza del paziente,"Il termine design ha molti significati; più in generale si pensa al disegno di una forma, di una figura o di una struttura. Per i progettisti, tuttavia, il termine implica un significato più ampio: “creare e sviluppare concetti e caratteristiche che ottimizzino la funzione, il valore e l’aspetto di prodotti e sistemi” (Ulrich, Eppinger, 1995). La progettazione di un processo o di una tecnologia clinica implica, dunque, una fondamentale revisione di un prodotto o di un sistema. Più che cercare di apportare qualche miglioramento marginale, un progettista tende a raffigurarsi il prodotto partendo da zero, ricorrendo alla comprensione del modo naturale in cui gli esseri umani lavorano e interagiscono con la tecnologia. Per contro, l’espressione “miglioramento del processo” suggerisce che il processo in questione presenta alcune carenze, ma che è abbastanza robusto e funzionale. È chiaro, tuttavia, che alcuni processi e sistemi sanitari si sono sviluppati in maniera tale che il miglioramento non è più una soluzione sufficiente. È capitato, per esempio, che un team abbia desistito dall’analisi del sistema di gestione dei farmaci in uso nel proprio ospedale perché era talmente complicato che nessuno riusciva a comprenderlo effettivamente."
7466,Ergebnisse,"Nachfolgend werden die Ergebnisse der vier einzelnen Untersuchungen zunächst wertfrei dargelegt, d. h. die Inhalte dieses Kapitels entsprechen den Sichtweisen der Behörden bzw. der Journalisten. Die Bewertung der Ergebnisse erfolgt in Kapitel 9. Zuerst werden die Ergebnisse zur behördlichen Risiko- und Krisenkommunikation (Kap. 8.1, 8.2) ausgeführt, anschließend die zur medialen Logik im Kontext von Risiken und Krisen (Kap. 8.3, 8.4). Die Ergebnisse werden in Anlehnung an die Forschungsfragen der Arbeit und die sich daraus ableitenden Kategoriensysteme dargestellt."
7467,Cytogenetic and Carcinogenic Effects of Exposure to Radiofrequency Radiation,"Radiofrequency radiation (RFR) is a portion of the electromagnetic spectrum with frequencies of 3 kHz–300 GHz. RFR is produced by many man-made sources, including mobile phones and base stations, television and radio broadcasting facilities, radar, medical equipment, microwave ovens, radiofrequency heaters as well as a diverse variety of other electronic devices within our living and working environments. Owing to ongoing public concern and the increasing prevalence of RFR-emitting devices, a great deal of research has been conducted over the past 50 years to evaluate the biological and/or health effects of thermalizing and non-thermalizing RFR exposures. In the absence of decisive epidemiological evidence to support or refute an association between RFR exposure and cancer risk, laboratory studies of possible mechanisms of carcinogenesis by RFR are important. The scientific literature on this subject is full of conflicting results and the question of whether RFR exposure can contribute to cancer risk remains unresolved. This chapter contains a literature review of the evidence for RFR-induced cytogenetic effects, but also a critique of the literature, highlighting deficiencies in the design of some studies that should be taken into account when assessing the health risk of RFR."
7468,Parasitic Diseases of the Lung,"Parasitic infection is a major healthcare problem that affects millions of the world’s population. Immigration and global warming have changed the natural distribution of parasitic diseases far removed from endemic areas. The respiratory system can be affected by a broad spectrum of helminthic and protozoal parasitic diseases. The diagnosis of parasitic infection of the respiratory system may be delayed due to myriad clinical and radiographic presentations of parasitic diseases which make the diagnosis of these entities challenging. Pulmonologists need to be familiar with the epidemiology, clinical presentation, pathophysiology, and bronchoscopic findings of parasitic lung diseases, in order to provide proper management in a timely fashion. This review provides a comprehensive view of both helminthic and protozoal parasitic diseases that affect the respiratory system, especially the central airways."
7469,Connectivity and Competition in Airline Networks: A Study of Lufthansa's Network,"Air transport networks have exhibited a trend towards complex dynamics in recent years. Using Lufthansa's networks as an example, this paper aims to illustrate the relevance of various network indicators — such as connectivity and concentration — for the empirical analysis of airline network configurations. The results highlight the actual strategic choices made by Lufthansa for its own network, as well in combination with its partners in Star Alliance."
7470,"Interactions among human behavior, social networks, and societal infrastructures: A Case Study in Computational Epidemiology","Human behavior, social networks, and the civil infrastructures are closely intertwined. Understanding their co-evolution is critical for designing public policies and decision support for disaster planning. For example, human behaviors and day to day activities of individuals create dense social interactions that are characteristic of modern urban societies. These dense social networks provide a perfect fabric for fast, uncontrolled disease propagation. Conversely, people’s behavior in response to public policies and their perception of how the crisis is unfolding as a result of disease outbreak can dramatically alter the normally stable social interactions. Effective planning and response strategies must take these complicated interactions into account. In this chapter, we describe a computer simulation based approach to study these issues using public health and computational epidemiology as an illustrative example. We also formulate game-theoretic and stochastic optimization problems that capture many of the problems that we study empirically."
7471,Bronchiolitis,"Everyone on the planet is exposed to respiratory syncytial virus (RSV) infection by the age of 2 years. Most infants admitted to the pediatric intensive care unit (PICU) for respiratory support during this infection are previously healthy, but their principal risk for needing PICU treatment is young age. That is, if you are born in October/November in the northern hemisphere, then your first winter exposure to RSV is likely to be when you are less than 4 months of age and vulnerable because of poor respiratory mechanical reserve (Alonso et al. 2007). However, if you are born in May/June, then you will be 7–8 months during your first winter exposure to RSV, much bigger and stronger and have more efficient thoracic and diaphragmatic mechanics. In the PICU, the main predictors of severe outcome in previously well infants appear to be young age, presence of apnea, and pulmonary consolidation on admission chest radiograph (Tasker et al. 2000; Lopez Guinea et al. 2007). Taken together, we can say that more severe RSV bronchiolitis in PICU practice is typically a problem of pulmonary consolidation, poor respiratory mechanics, and poor reserve, in the younger infant."
7472,Acute nierinsufficiëntie en acute dialyse,Acute nierinsufficiëntie komt steeds vaker voor tijdens ziekenhuisopnames en zorgt naast een verlengde opnameduur ook voor een toegenomen sterfterisico.
7473,Mechanism of Action of Opioids and Clinical Effects,
7474,General Measures of Infection Control,"A 72-year-old male patient with non-Hodgkin’s lymphoma was neutropenic after chemotherapy and presented to the ICU with breathlessness and hypotension. He was intubated and kept on a ventilator and received broad-spectrum antibiotics. He had a peripheral, central, and arterial line in place. A Foley’s catheter and a nasogastric tube were also placed."
7475,Resuscitation,"Blast injuries can produce complex patterns of injury and can easily result in hemorrhagic shock. Adequate resuscitation of blast-injured patients is critical, as both under- and over-resuscitation can result in a number of fatal complications. Consideration must be given to the choice of resuscitative fluid, the volume of resuscitation, the timing of resuscitation relative to definitive surgical management, and the determination of endpoints at which resuscitation can be stopped. This chapter explores resuscitation of blast-injured patients, beginning in the prehospital phase with initial choice of fluid and continuing through definitive resuscitation at a higher echelon of care. Particular consideration is given to the effect of resuscitation on the unique physiologic derangements seen following blast injury. Drawing upon the enormous amount of literature on resuscitation from the recent coalition experiences in Iraq and Afghanistan, we advocate for the use of early hemostatic resuscitation with a high ratio of plasma, platelets, and packed red blood cells, with a transition to resuscitation guided by viscoelastic testing or coagulation status immediately following definitive control of hemorrhage."
7476,Transformation und Tumorbildung,"Schon früh erkannte man, dass Viren bei Tieren Tumorerkrankungen hervorrufen können. Bereits 1911 beschrieb Peyton Rous, dass Viren bei Geflügel Sarkome verursachen. Das verantwortliche tumorauslösende Virus wurde später nach ihm Rous-Sarkomvirus benannt. In den folgenden Jahrzehnten entdeckte man eine Vielzahl von Viren, die bei Geflügel und Nagetieren unterschiedliche Krebserkrankungen wie Lymphome, Sarkome und Karzinome auslösen können. Viele von ihnen gehören zur Familie der Retroviridae und wurden den Gattungen der α-, β- und γ-Retroviren zugeordnet. Die Mehrzahl dieser Erreger wurde aus Inzuchtstämmen der jeweiligen Tierarten oder aus Zellkulturen isoliert; unter natürlichen Bedingungen sind sie als Verursacher von Tumorerkrankungen der jeweiligen Tierarten wahrscheinlich ohne Bedeutung. Eine Ausnahme sind die Leukoseviren der Katze (FeLV; ▸Abschnitt 18.1). Das tumorerzeugende Potenzial der onkogenen Retroviren beruht auf transformationsaktiven Proteinen (v-Onc)."
7477,Diagnostic Imaging of Neonatal Pneumonia,"Respiratory infections remain a significant and formidable threat to the health and well being of the neonate despite potent antibiotics, increasingly sophisticated laboratory detection methods and technologically advanced neonatal intensive care nurseries. Although the clinical and radiological definitions of pneumonia are variable throughout medical and governmental literature, quoted incidence rates for neonatal pneumonia range between 1.5–5.0 per 1,000 live births (Keyserling 1997; Webber et el 1990)."
7478,Punica granatum,
7479,Die Rede von der Vertrauenskrise in China,"Im ersten Teil dieser Arbeit wurden die Ergebnisse der ländervergleichenden Umfrageforschung zu Vertrauen thematisiert, wobei insbesondere das hohe gemessene Vertrauensniveau in der VR China im Zentrum des Interesses stand. In Anbetracht dieser Befunde mag es nun zunächst erstaunen, dass chinesische Soziologinnen und Soziologen im Gegensatz dazu von einer „Vertrauenskrise“ (xinren weiji) im gegenwärtigen China sprechen, obwohl die empirischen Befunde eigentlich genau auf das Gegenteil hinweisen. Andererseits ist es angesichts der politischen, wirtschaftlichen und gesellschaftlichen Umwälzungen Chinas im 20. Jahrhundert mit dem Zusammenbruch der letzten Kaiserdynastie 1911, der brutalen Besetzung von Teilen Chinas durch Japan im Zweiten Weltkrieg, dem Bürgerkrieg zwischen Kommunisten und Nationalisten, sowie den diversen Kampagnen und Bewegungen seit der Gründung der Volksrepublik 1949 und dem Übergang von einer Planwirtschaft in eine dezentralisierte, markt- und exportorientierte Wirtschaft neoliberalen Zuschnitts mit gleichzeitiger autokratischer Ein-Partei-Herrschaft seit Beginn der Politik von Reform und Öffnung (gaige kaifang) im Jahr 1978 nicht überraschend, dass das Vertrauen in der chinesischen Gesellschaft – wie in anderen Gesellschaften, die tiefgreifenden Transformationsprozessen unterworfen sind – in eine Krise gerät. Im Folgenden sollen nun die Ursachen für die Entstehung der Vertrauenskrise in China und ihre Manifestationen in der Gesellschaft näher beschrieben werden, ebenso wie die von chinesischer Seite her vorgeschlagenen Maßnahmen zur Wiederherstellung des Vertrauens."
7480,"Alcohol, HIV/AIDS, and Liver Disease","Globally, there are over 33 million persons living with HIV/AIDS resulting in 1.8 million deaths annually. While the rate of HIV transmission is slowing, it is estimated that 2.6 million new infections occur yearly [1]. In the United States, there are approximately 1.2 million living with HIV/AIDS, with 50,000 new HIV infections and 17,000 deaths from the disease annually [2]. For those who can obtain effective antiretroviral therapy (ART), HIV/AIDS has become a chronic disease with life expectancies over 30 years [3]. Research in the last 10 years has revealed the importance of alcohol in the HIV/AIDS epidemic. Alcohol use, in moderate or hazardous amounts, has been associated with increased acquisition of HIV infection, progression of HIV infection, deleterious effects on HIV treatment, and acceleration in the comorbidities of HIV infection [4–9]. Yet alcohol remains the “forgotten drug” of the HIV/AIDS epidemic [10]."
7481,Zika Virus and HIV/AIDS,"The first documented cases of HIV/AIDS in the United States bewildered physicians as they presented an unusual disease spectrum. Two young men were diagnosed with Kaposi sarcoma and Pneumocystis carinii pneumonia, which was inexplicable at that time, as these health outcomes were rare among their age, race/ethnicity, and individuals not living in nursing homes. Subsequently, it was found that after infection with HIV, individuals were asymptomatic up to 4 weeks and if symptoms developed, they appeared as a simple type of flu. The progression and global proliferation of the HIV pandemic is mirrored by the spread of Zika virus (ZikaV). Humans were probably first infected with HIV in the Kinshasa region in the 1940s and ZikaV was first detected in humans in the Zika forest in the 1950s. Aedes aegypti and Aedes albopictus mosquitoes transmit ZikaV, an arbovirus, as well as other related arboviruses. In addition to mosquito transmission, ZikaV transmission occurs through sexual risk and blood transfusions. The latter two risk factors were prominent modes of transmission during the early stages of HIV/AIDS epidemic and sexual transmission risk remains prominent. In addition, injection drug use is a risk factor to become HIV infected. For HIV, blood transfusion risk was reduced after appropriate testing of blood supplies. Unlike HIV, ZikaV does not produce significant symptoms that require medical attention among four-fifths of infected individuals. Indeed, initially considered a relatively benign virus, the unexpected emergence of ZikaV in the Americas since 2015, and continuing as a virulent and pathological virus for children and adults, created a sense of fear and distress. These emotional responses parallel the HIV/AIDS epidemic. Clinicians, epidemiologists, and other scientists are currently increasingly laboring to discern the full spectrum of risk, relative to vector and population behaviors, and as with HIV, to develop vaccines and chemotherapy against ZikaV. NIH and Walter Reed ZikaV vaccines are on the way."
7482,Nuclear Medicine in Acute Care,1. What is the gold standard diagnostic test for cardiac transplant rejection? a. PET; b. (123)I-IPPA. c. MRI. d. Endomyocardial biopsy. 2. All of the following radionuclide imaging methods are examined for the diagnosis of cardiac transplant rejection EXCEPT: a. (99m)Tc-annexin V. b. Radiolabeled somatostatin analog; c. (111)In-antimyosin; d. (11)C-MQNB;
7483,Infectieproblematiek,"De overdracht van micro-organismen kan plaatsvinden van personeel op patiënt, van apparatuur op patiënt en vice versa. Er moeten hoge eisen worden gesteld aan een schone werkomgeving. Hiertoe behoort het schoonmaken van gecontamineerde oppervlakken van onder andere anesthesieapparatuur, vloeren en wanden van de operatiekamer en de operatietafel. Bij iedere wisseling van patiënten en bij eventuele contaminatie dienen de handen te worden gewassen met water en zeep en gedesinfecteerd chloorhexidi-ne-alcohol. Dit dient ook na het uittrekken van beschermende handschoenen te gebeuren."
7484,18 Zoönosen,Een zoönose is een ziekte die van dier op mens kan overgaan of andersom. Mensen komen op diverse manieren in contact met dieren.
7485,The New Dynamics of Global Health Governance,"This chapter considers the impact of globalization on international health policies and the emergence of new approaches to Global Health Governance (GHG). The first part of the chapter describes the changes in institutional structures since the 1990s that have had a fundamental impact on GHG. These structural changes have occurred as the discourse on trans-boundary health has broadened and engaged more public, private and voluntary sector actors in the debate. This has brought greater recognition of the need to mobilize a range of financial and other resources and to adopt a more flexible approach to problem solving. But the proliferation of public and private actors has also brought greater complexity that could inhibit the effective application of these resources and solutions."
7486,Responsible Tourism: A Conservation Tool or Conservation Threat?,
7487,Sicherheitsregelkreis,"Alles fließ (παντα ρει [Heraklit]), d. h. alles verändert sich: Bedrohungen, Angriffsmöglichkeiten, Schutzbedarf, Prozesse, Ressourcen, Technologien, Organisation und last, but not least, das Personal. Dementsprechend unterliegen alle Elemente der Sicherheits- bzw. RiSiKo-Pyramide einer kontinuierlichen Anpassung, Veränderung und Weiterentwicklung."
7488,Liver Transplantation,"The field of liver transplantation has changed since the MELD scoring system became the most widely used donor allocation tool. Due to the MELD-based allocation system, sicker patients with higher MELD scores are being transplanted. Persistent organ donor shortages remain a challenging issue, and as a result, the wait-list mortality is a persistent problem for most of the regions. This chapter focuses on deceased donor and live donor liver transplantation in patients with complications of portal hypertension. Special attention will also be placed on donor-recipient matching, perioperative management of transplant patients, and the impact of hepatic hemodynamics on transplantation."
7489,Disinfection Policies in Hospitals and the Community,
7490,Hidden Cluster Detection for Infectious Disease Control and Quarantine Management,"Infectious diseases that are caused by pathogenic microorganisms can spread fast and far, from one person to another, directly or indirectly. Prompt quarantining of the infected from the rest, coupled with contact tracing, has been an effective measure to encounter outbreaks. However, urban life and international travel make containment difficult. Furthermore, the length of incubation periods of some contagious diseases like SARS enable infected passengers to elude health screenings before first symptoms appear and thus to carry the disease further. Detecting and visualizing contact–tracing networks, and immediately identifying the routes of infection, are thus important. We apply information visualization and hidden cluster detection for finding cliques of potentially infected people during incubation. Preemptive control and early quarantine are hence possible by our method. Our prototype Infectious Disease Detection and Quarantine Management System (IDDQMS), which can identify and trace clusters of infection by mining patients’ history, is introduced in this paper."
7491,Parasites and pest population management,"The presence of macroparasites can affect the pest status of small mammals and the damage they cause. Pest management of small mammal populations can also affect the macroparasite populations, in a positive as well as a negative way. Despite the effects of macroparasites on small mammal fitness, there is little hope for the near future that they can be used for biological control of small mammals, except perhaps for some bio-pesticides. Small mammals and macroparasites interact in complex ways, and the implications for pest management are equally complex."
7492,Nosocomial Infections and Ventilator-Associated Pneumonia in Cancer Patients,"Nosocomial infections or healthcare-acquired infections are a common cause of increased morbidity and mortality among hospitalized patients. Cancer patients are at an increased risk for these infections due to their immunosuppressed states. Considering these adverse effects on and the socioeconomic burden, efforts should be made to minimize the transmission of these infections and make the hospitals a safer environment. These infection rates can be significantly reduced by the implementing and improving compliance with the “care bundles.” This chapter will address the common nosocomial infections such as ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTI), and surgical site infections (SSI), including preventive strategies and care bundles for the same."
7493,A Framework of NLP Based Information Tracking and Related Knowledge Organizing with Topic Maps,"This paper presents a computational framework for information extraction and aggregation which aims to integrate and organize the data/information resources that spread throughout the Internet in the manner that makes them useful for tracking events such as natural disaster, and disease dispersion. We introduce a simple statistical information extraction technique for summarizing the document into a predefined structure. We apply the topic maps approach as a semantic layer in aggregating and organizing the extracted information for smart access. In addition, this paper also carries out a case study on disease dispersion domain using the proposed framework."
7494,Inflammatory Changes and Coagulopathy in Multiply Injured Patients,"Severe tissue trauma leads to an early activation of several danger recognition systems, including the complement and the coagulation system, often resulting in an overwhelming almost synchronic pro- and anti-inflammatory response of the host. Although the immune response is associated with beneficial effects at the site of injury including the elimination of exogenous and endogenous danger molecules as well as the initiation of regenerative processes, an exaggerated systemic inflammatory response significantly contributes to posttraumatic complications such as multiple organ failure (MOF) and early death. Besides pre-existing physical conditions, age, gender, and underlying comorbidities, surgical and anesthesiological management after injury is decisive for outcome. Improvements in surgical intensive care have increased number of patients who survive the initial phase after trauma. However, instead of progressing to normal recovery, patients often pass into persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The characterization and management of PICS will require new strategies for direct monitoring and therapeutic intervention into the patient’s immune function. In this chapter, we describe various factors involved in the inflammatory changes after trauma and aim to understand how these factors interact to progress to systemic inflammation, MOF, and PICS."
7495,Cuff-Induced Neointimal Formation in Mouse Models,"Ischemic heart failure caused by atherosclerosis is a major cause of death worldwide. Although remarkable technological advances have been made in the treatment of coronary heart disease, there is as yet no treatment that can sufficiently suppress the progression of atherosclerosis, including neointimal thickening. Therefore, a precise understanding of the mechanism of neointimal hyperplasia will provide the development of new technologies. Both ApoE-KO and LDLR-KO mice have been employed to generate other relevant mouse models of cardiovascular disease through breeding strategies. Although these mice are effective tools for the investigation of atherosclerosis, development of a progressive atherosclerotic lesion takes a long time, resulting in increase of both the costs and the space needed for the research. Thus, it is necessary to develop simpler tools that would allow easy evaluation of atherosclerosis in mouse models. In this review, we discuss our experience in generating mouse models of cuff-induced injury of the femoral artery and attempt to provide a better understanding of cuff-induced neointimal formation."
7496,Introduction to 3D Immersive and Interactive Learning,"The concept of 3D is not new. But never like today, 3D is rapidly entering our life. Using 3D for education is an innovative yet challenging work. This chapter introduces the concept of 3D Immersive and Interactive Learning, which is also called In-depth Learning. In particular, the enabling technologies and the supporting learning environments behind 3D Immersive and Interactive Learning are discussed. The relationship between In-depth Learning and other Learning Paradigms, such as Visual Learning, Simulation-based Learning, Constructivism Learning, and Engaged Learning, etc., are studied. This chapter also serves as an overall introduction to the whole book which presents several efforts in Singapore using 3D for In-depth Learning. The book covers a wide spectrum of education including Gifted Program, Normal (technical) Stream, and Special Needs Education. The author(s) of each book chapter share their experiences from different angles on 3D In-depth Learning."
7497,Conclusion: Understanding the Elusive Nature of Objectivity,"An evaluation of research reported in this book shows the problematic nature of understanding some of the universal values associated with objectivity such as certainty, value neutral observations, facts, infallibility, and truth of scientific theories and laws. These results provide a detailed account (over a period of almost 25 years) of how the science education research community conceptualizes the difficulties involved in accepting objectivity as an unquestioned epistemic virtue of the scientific enterprise. Analyses of general chemistry textbooks are used to introduce the idea of “transgression of objectivity” and that scientific progress (nanotechnology) is at a crossroads. Given the importance of objectivity/subjectivity dichotomy in science education, it is plausible to suggest that objectivity has become an opiate of the academic. Although, achievement of objectivity in actual scientific practice is a myth, it still remains a powerful and useful idea. It seems that more work needs to be done in order to facilitate a transition toward a more nuanced understanding of objectivity and eventually the dynamics of scientific progress."
7498,Indicators of Waterborne Viruses,"Enteric viruses excreted by humans and animals may reach water resources and cause large outbreaks. Drinking water is one of the essential global life elements for humanity. However, some of our resources are contaminated with viruses and indicators for continuous monitoring have been developed. The classical ones are coliforms and fecal coliforms that are still the iron standard for water indicator monitoring (see Chap. 10.1007/978-94-017-9499-2_34). In the last decades, bacteriophages have been suggested as potential indicators of enteric viruses and many studies showed their potential as such mainly due to their comparable resistance to water processes such as disinfection. In this chapter, the indicator role of bacteriophages in water is critically reviewed and discussed."
7499,Emergency Mass Critical Care,"At any moment regular television programming could be interrupted with news of the emergence of a new strain of infective agent, a major industrial accident, or a terrorist event. Many devastating events are widespread and naturally occurring, like hurricanes, in which we have ample warning time to enact preparation plans; while others, like earthquakes, volcanoes, or tsunamis may kill or injure thousands before the news reports hit the airwaves. Industrial accidents and terrorist events are usually sudden and occur without any warning. Any of these events may have a local or regional effect; some may even have a global impact [1]. Regardless of the cause, after such an event, large amounts of the populace will be seeking medical care, whether from their primary care providers, public health departments, or local hospitals."
7500,Information Quality Case Studies,In this chapter various real-life examples are presented which illustrate means of analyzing and improving information quality in the context of knowledge-intensive processes. The chapter concludes by formulating propositions and conclusions derived from the six case studies.
7501,Biosafety Recommendations on the Handling of Animal Cell Cultures,"The first steps in tissue culture are dating back to the beginning of the nineteenth century when biosafety measures did not yet exist. Later on, animal cell culture became essential for scientific research, diagnosis and biotechnological activities. Along with this development, biosafety concerns have emerged pointing to the risks for human health and in a lesser extent for the environment associated to the handling of animal cell cultures. The management of these risks requires a thorough risk assessment of both the cell cultures and the type of manipulation prior the start of any activity. It involves a case-by-case evaluation of both the intrinsic properties of the cell culture genetically modified or not and the probability that it may inadvertently or intentionally become infected with pathogenic micro-organisms. The latter hazard is predominant when adventitious contaminants are pathogenic or have a better capacity to persist in unfavourable conditions. Consequently, most of the containment measures primarily aim at protecting cells from adventitious contamination. Cell cultures known to harbour an infectious etiologic agent should be manipulated in compliance with containment measures recommended for the etiologic agent itself. The manipulation of cell cultures from human or primate origin necessitates the use of a type II biosafety cabinet. The scope of this chapter is to highlight aspects relevant for the risk assessment and to summarize the main biosafety recommendations and the recent technological advances allowing a mitigation of the risk for the handling of animal cell cultures."
7502,Chest and Mediastinum,"For interpretation of routine posteroanterior (PA) chest radiographs, the anatomy of the trachea, mediastinum, diaphragm, lungs, lung fissures, lung hila, other soft tissue structures and bony structures should be understood (Fig. 19.1). Important anatomic and imaging criteria for each of these structures will be discussed in this chapter. The normal trachea appears in the PA chest radiograph in the midline. The aortic arch causes slight deviation of the trachea to the right side. This shift is more marked in an expiratory film, due to shortening of the trachea. The transparency of the tracheal lumen normally decreases from cranial to caudal. The maximal width of the trachea is 25 mm (for men) and 21 mm (for women). The right tracheal border, where the trachea is in direct contact with lung tissue, can be traced from the clavicle to the right main bronchus. This border is referred to as the right paratracheal stripe or line and is visible in up to 60% of patients. Its width is normally less than 4 mm. A left paratracheal stripe is generally not visible, because the left tracheal border is in direct contact with the large vessels rather than lung tissue."
7503,Carbohydrates as Recognition Receptors in Biosensing Applications,"Carbohydrates are involved in crucial physiological and pathological events. One can take advantage of carbohydrate-based interaction for drug discovery, diagnosis, antibiotics, vaccine, etc. This chapter deals with biosensors and microarrays that take advantage of carbohydrates-based interactions with a special interest in devices that are designed for medical applications. A large overview of glycochemistry, followed by the biological role of carbohydrates, is given. Carbohydrate-based biosensors are then described with special emphasis on surface chemistry and signal transduction. Finally, medically relevant applications illustrate the use of carbohydrates as recognition receptors in biosensing."
7504,Infections in Patients with Cancer: Overview,"Patients with neoplastic disease are often highly susceptible to severe infections. The following factors influence the types, severity, and response to therapy of these infections: (1) Changing epidemiology of infections; (2) cancer- and/or treatment-associated neutropenia; (3) acquired immune deficiency states such as cellular immune defect; (4) recent development of new-generation diagnostic tools including widely available DNA amplification tests; (5) effective intervention for infection prevention; (6) empiric or presumptive therapy during high-risk periods; (7) availability of new classes of highly active antimicrobial drugs; (8) strategies to promote hosts’ immune response; and (9) future measures. This introductory chapter intended for the reader to become familiar with the important historical milestones in the understanding and development in the field of infectious diseases in immunosuppressed patients with an underlying neoplasms and patients undergoing hematopoietic stem cell trans­plantation."
7505,"Scenarios: Serious, Infectious Diseases","Scenarios for serious, infectious diseases are important procedures used to understand the special microbe’s behaviour (clinical illness, spread of infection, etc.) and how to act most rational during special dangerous outbreaks. Furthermore, scenarios describe how to handle patients, personnel and others possibly exposed to infections,- outside and inside the hospital- to stop spread of the infection as soon as possible. Today, it is not acceptable to place a patient with a known high-risk, serious infection in the same hospital room as other patients with not the same disease (WHO). In this chapter, some seldom but realistic scenario is described to better understand how to react and treat patients to stop spread of microbes during the primary phase of dangerous transmittable diseases."
7506,Nosokomiale Pneumonie,"Nosokomiale Infektionen betreffen nach postoperativen Entzündungen von Wunden und Harnwegsinfektion am dritthäufigsten die unteren Atemwege. Die Pneumonie ist dabei die häufigste nosokomiale Atemwegsinfektion. Sie tritt überwiegend bei invasiv beatmeten Patienten auf. Zunehmend werden nosokomiale Infektionen durch multiresistente Keime hervorgerufen, was das Risiko einer inadäquaten initialen antiinfektiven Therapie erhöht. Die antiinfektive Therapie sollte bereits im Verdachtsfall begonnen werden. Die Diagnose ist im Verlauf kritisch zu überprüfen. Bestätigt sich eine nosokomiale Pneumonie nicht, sollte die antiinfektive Therapie vorzeitig beendet werden. Für die beatmungsassoziierte Pneumonie wurden verschiedene präventiv wirksame Maßnahmenbündel untersucht, mit deren Hilfe die Pneumonierate um über 50 % gesenkt werden konnte."
7507,Modular RADAR: An Immune System Inspired Search and Response Strategy for Distributed Systems,"The Natural Immune System (NIS) is a distributed system that solves challenging search and response problems while operating under constraints imposed by physical space and resource availability. Remarkably, NIS search and response times do not scale appreciably with the physical size of the animal in which its search is conducted. Many distributed systems are engineered to solve analogous problems, and the NIS demonstrates how such engineered systems can achieve desirable scalability. We hypothesize that the architecture of the NIS, composed of a hierarchical decentralized detection network of lymph nodes (LN) facilitates efficient search and response. A sub-modular architecture in which LN numbers and size both scale with organism size is shown to efficiently balance tradeoffs between local antigen detection and global antibody production, leading to nearly scale-invariant detection and response. We characterize the tradeoffs as balancing local and global communication and show that similar tradeoffs exist in distributed systems like LN inspired artificial immune system (AIS) applications and peer-to-peer (P2P) systems. Taking inspiration from the architecture of the NIS, we propose a modular RADAR (Robust Adaptive Decentralized search with Automated Response) strategy for distributed systems. We demonstrate how two existing distributed systems (a LN inspired multi-robot control application and a P2P system) can be improved by a modular RADAR strategy. Such a sub-modular architecture is shown to balance the tradeoffs between local communication (within artificial LNs and P2P clusters) and global communication (between artificial LNs and P2P clusters), leading to efficient search and response."
7508,Background Information: Isolation Routines,"The isolation of patients with suspected or documented infections—to not spread to others—has been discussed for hundreds of years. Guidelines are many, methods are different, attitudes show vide variations, routines and procedures are still changing, regulations by law may be absent, and some healthcare professionals may be afraid of adverse outcomes of isolation [1–44]. Microbes that are spread in the environment, on the hands and equipment are invisible. The invisible agent does not call on attention before the infection; clinical disease, hospital infection or nosocomial infection is a factum that can be registered [23, 28, 29, 35–37]. How to stop the transmission is often “to believe and not believe” in infection control."
7509,3 Medische microbiologie,"Microbiologie is de wetenschap die zich bezighoudt met de bestudering van micro-organismen. Dit zijn kleine organismen die niet met het blote oog waarneembaar zijn. Micro-organismen zijn van wezenlijk belang voor alle levensprocessen, ze zijn dan ook overal op aarde te vinden."
7510,Diarrhea Leads to Pneumonia and Hematuria in the Intensive Care Unit,"A 26-year-old man with a history of Crohn’s disease in remission presented to the Medical Intensive Care Unit with diarrhea, hematuria, left-sided pulmonary infiltrates, transaminitis, and rapid-onset respiratory failure with acute kidney injury. The patient was well until 7 days prior to admission, when he developed severe non-bloody diarrhea. Three days prior, he presented to an emergency department and was sent home after rehydration with normal saline with a reportedly normal chest x-ray. Two days prior, he presented to his primary care provider with continued diarrhea and fever to 39.4 °C, and he was sent home with antidiarrheal medications. One day prior, he returned to the emergency department with chest tightness, shortness of breath, and cough productive of dark sputum. He was found to have radiographic findings consistent with pneumonia. He also reported dark urine and anorexia, but he denied nausea, vomiting, abdominal pain, rash, or dysuria."
7511,Biological Agents and Bioterrorism,"For this very stimulating course, I want to share with you some of my studies and even some of my scientific and phylosophical considerations on biological agents living in the environment and their relations with humans, in the very wide concepts of ecological relationships, parasitism, immunolgical defenses and infectious disease mechanisms. All these concepts must be studied and considered in the event of criminal use of biological agents (bioterrorism) aimed at harming human populations in time and in geographical space."
7512,Infektiöse Pneumonien,"Definition, Ätiologie und Epidemiologie. Pneumonien sind akut- und chronisch-entzündliche Krankheiten des Lungenparenchyms. Man kann sie nach Ursache, Alter des Patienten sowie anatomischer Lokalisation bzw. dem Röntgenbefund einteilen. Sie werden vorwiegend von Infektionserregern verursacht. Seltenere Auslöser von Pneumonien sind allergische, chemische und physikalische Noxen sowie Autoimmunkrankheiten, die an anderer Stelle abgehandelt werden. Die Pneumonien des Neugeborenen werden in ▸ Kap. 60 besprochen. Unter den ambulant erworbenen Pneumonien dominieren in den ersten Lebensjahren virale Erreger, die vorwiegend eine Entzündung des Lungeninterstitiums hervorrufen. Am häufigsten werden Respiratory-syncytial-Viren (RSV), Parain-fluenza-, Influenza-, Adeno- und humane Metapneumoviren gefunden. Gelegentlich sind sie Wegbereiter für nachfolgende bakterielle Sekundärinfektionen (unbekapselte Haemophilus influenzae, Staphylococcus aureus, Pneumokokken u. a.). Im späteren Kleinkind- und Schulalter überwiegen Bakterien, insbesondere Pneumokokken und Haemophilus influenzae, als Pneumonieerreger. Zunehmend treten in diesem Alter auch Mykoplasmen in Erscheinung (Abb. 139.1)."
7513,General Pulmonary Question and Answer Items,"An overview of the general pediatric pulmonary topics necessary for ward knowledge, clinical acumen, and board examination preparation is presented in an easy-to-study question-and-answer format."
7514,Role of Proteases in Inflammatory Lung Diseases,"Proteases are enzymes that have the capacity to hydrolyze peptide bonds and degrade other proteins. Proteases can promote inflammation by regulating expression and activity of different pro-inflammatory cytokines, chemokines and other immune components in the lung compartment. They are categorized in three major subcategories: serine proteases, metalloproteases and cysteine proteases especially in case of lung diseases. Neutrophil-derived serine proteases (NSPs), metalloproteases and some mast cell-derived proteases are mainly focused here. Their modes of actions are different in different diseases for e.g. NE induces the release of IL-8 from lung epithelial cells through a MyD88/IRAK/TRAF-6-dependent pathway and also through EGFR MAPK pathway. NSPs contribute to immune regulation during inflammation through the cleavage and activation of specific cellular receptors. MMPs can also influence the progression of various inflammatory processes and there are many non-matrix substrates for MMPs, such as chemokines, growth factors and receptors. During lung inflammation interplay between NE and MMP is an important significant phenomenon. They have been evaluated as therapeutic targets in several inflammatory lung diseases. Here we review the role of proteases in various lung inflammatory diseases with emphasis on their mode of action and contribution to immune regulation during inflammation."
7515,Current and Future Issues in Global Health Diplomacy,"This chapter provides an overview of the issues that are addressed by global health diplomacy and are discussed in more detailed case studies in the remaining chapters of this book. These are health issues that transcend national boundaries to affect the health of people in rich and poor countries and require concerted international effort to address them. Many such issues arise from the impact of globalization on health, which serves to accelerate not only the transmission of communicable disease but also the spread of unhealthy products and lifestyles. Health in fragile states poses complex challenges for global health diplomacy, requiring even greater engagement with all parties. This need for wider engagement to create a global movement for health and to establish pathways through which multiple actors can work together is the common theme that emerges at many different levels. It heralds a new era of global health governance recognizing the voice and contribution of all parties."
7516,Novel Therapeutics Against West Nile Virus,"No effective therapy is currently available for clinical treatment of flavivirus infections. Recent advances in the structural and molecular biology of flaviviruses have provided new opportunities for the development of antiviral therapies. This chapter summarizes the current status of West Nile virus (WNV) therapeutics. First, strategies for identifying and characterizing small molecular inhibitors are reviewed. These strategies include structure-based rational design, biochemical enzyme-based screening, and reverse genetic system-based screening. Second, known WNV inhibitors are summarized. Both small and macromolecular inhibitors have been identified to inhibit WNV. The macromolecular inhibitors include WNV antibodies, interferon, and nucleic acid-based agents (i.e., antisense oligomer and siRNA). Since the antibody-based therapy is reviewed elsewhere in this book, this chapter emphasizes the nonantibody macromolecular and small molecular inhibitors. Finally, new potential antiviral targets and issues related to WNV therapeutics are discussed."
7517,Microfluidic Applications in Biodefense,
7518,Spleen and Liver,"In liver cirrhosis, the spleen is a source of nitric oxide which affects a hyperdynamic state typical of portal hypertension. It is generally accepted that pancytopenia results predominantly from the increased phagocytosis and destruction of hemocytes in splenic macrophages. In addition, liver fibrosis is amplified by migrated Th2 lymphocytes and transforming growth factor beta from the spleen. There is a possibility that increase of the spleen stiffness is the primary factor of idiopathic portal hypertension. Spleen stiffness is caused by bleeding, fibrosis, and calcareous deposits after increase in red pulp pressure due to venous congestion. In nonalcoholic steatohepatitis, macrophage activity in the spleen is upregulated. In addition, high levels of inflammatory cytokines are produced and T cell shows increased proliferation in the spleen. In autoimmune hepatitis model, CD4(+) T cells are differentiated into follicular helper T cells (T(FH)) in the spleen. T(FH) cells promoted hypergammaglobulinemia and antinuclear antibodies production. T(FH) cells migrate from the spleen to the liver, triggering induction of autoimmune hepatitis in this model. IgM-positive B cells localize in the CD21-positive lymph follicle in the spleen of primary biliary cholangitis. These findings prove that the spleen influences on the pathogenesis and severity of several kinds of liver disease."
7519,Infection Control and the Need for Family-/Child-Centered Care,"Patient- and family-centered care (FCC) has become central to the delivery of medical care over the last 20 years and has been shown to improve patient outcomes. Infection control practices have the potential to greatly influence family centeredness and care providers, and hospital personnel must consider the potential impacts of isolation and the use of personal protective equipment (PPE). Approaching infection control with the perspective of FCC requires balancing patient safety and overall patient well-being. In this chapter, authors consider infection control and the benefits of FCC, family and sibling visitation, the use of playrooms, animals in healthcare settings including animal-assisted interventions, the potential adverse effects of infection control practices, and strategies to mitigate these impacts."
7520,Diseases,
7521,"Microbes, Transmission and Protection","This chapter is a short survey—in table form—concerning clinical types of infections, the most important microbes in medicine, recommended methods to isolate patients with infections and recommended use of personal protective equipment."
7522,Antibody-Capture Enzyme-Linked Immunosorbent Assay for Detection of Antibody to Turkey Coronavirus Using Infectious Bronchitis Virus or Recombinant Nucleocapsid Protein as Coating Antigen,"Turkey coronavirus (TCoV) infection continues to threaten turkey industry. Because specific treatment and effective vaccination program are not available, rapid and cost-effective detection of antibodies to TCoV infection is an important control measure to monitor the disease status in the fields. Two antibody-capture enzyme-linked immunosorbent assay (ELISA) procedures for detection of antibodies to TCoV are outlined in this chapter. One ELISA method uses chicken infectious bronchitis coronavirus (IBV) as the coating antigen based on antigenic cross-reactivity between TCoV and IBV. The other method relies on a recombinant TCoV nucleocapsid protein. Both methods are useful for serological diagnosis of TCoV infection in the turkey flocks."
7523,The Role of Managerial Epidemiology in Infection Prevention and Control,1. Understand the roles and responsibilities of health care managers in infection prevention and control in health care organizations. 2. Apply epidemiologic principles to manage an outbreak of a transmissible disease in a health care setting. 3. Develop a strategy for infection prevention in a health care setting.
7524,Dominant Risks and Risk Management Practices in Supply Chains,"Supply chains are inherently susceptible to risky events. Earlier articles in supply chain management by Kraljic (1983) and Treleven, and Schweickhart (1988) stressed the importance to consider the risks arising from interconnected flows of material, information and funds in inter-organizational networks. However, during the last several years, the interest in this topic has significantly gained momentum. A large body of recent literature reports on events that disrupted supply chains and on their negative impact on businesses. These reports are paralleled by numerous articles from researchers and practitioners proposing best practices, guidelines, and concepts for risk management strategies that aim to ultimately create resilient supply chains. But what actually fuelled this recent attention to supply chain risks and their management? There are arguably at least two significant factors."
7525,The Human Coronaviruses,"The human coronaviruses have been shown to be a major player in clinical microbiology and frequently occur as pathogens responsible for mild to severe respiratory infections. Moreover, two of the most dangerous viral respiratory infections are caused by novel coronaviruses, namely, the SARS and the MERS coronavirus. This chapter briefly summarizes the most important facts and knowledge required for the appropriate laboratory diagnostics of infections caused by the human coronaviruses."
7526,"A Web-Based System for Infectious Disease Data Integration and Sharing: Evaluating Outcome, Task Performance Efficiency, User Information Satisfaction, and Usability","To better support the surveillance of infectious disease and epidemic outbreaks by public health professionals, we design and implement BioPortal, an advanced Web-based system for cross-jurisdictional information sharing and integration. In this paper, we report two empirical studies that evaluate the outcomes, task performance efficiency, user information satisfaction, and usability associated with BioPortal. Overall, our results suggest that the use of BioPortal can improve users’ surveillance performance as measured by analysis accuracy and efficiency (i.e., the amount of time required to complete an analysis task). Our subjects were highly satisfied with the information support of BioPortal and considered it reasonably usable. Our evaluation findings show the effectiveness and value of BioPortal and, at the same time, shed light on several areas where its design can further improve."
7527,Viral Infections of the Respiratory Tract,"Viral infections of the respiratory tract are common events in all age groups and are the leading cause of mortality in children under 5 years of age in developing countries [1]. These infections cause significant economic burden, with estimated direct and indirect medical costs in the US exceeding $70 billion annually [2, 3]. Children under the age of 5 have an average incidence rate of four to six viral respiratory infections/year and the rate gradually decreases to one to two/year in most adults [4]."
7528,Forced Migration and Refugee Policy,"This chapter focuses on international, regional and national legal norms, policies, organizational roles and relations and good practices that are applicable to a broad range of humanitarian crises that have migration consequences. These crises and the resulting displacement differ by their causes, intensity, geography, phases and affected populations. The chapter examines movements stemming directly and indirectly from: persecution, armed conflict, extreme natural hazards that cause extensive destruction of lives and infrastructure; slower onset environmental degradation, such as drought and desertification, which undermine livelihoods; manmade environmental disasters, such as nuclear accidents, which destroy habitat and livelihoods; communal violence, civil strife and political instability; and global pandemics that cause high levels of mortality and morbidity. Demographic trends are themselves drivers of displacement in conjunction with other factors. This can play out in two ways—demography as a macro-level factor and demographic composition as a micro-level driver of movement. The chapter compares the paucity of legal, policy and institutional frameworks for addressing crisis-related movements with the more abundant frameworks for addressing the consequences of refugee movements. The chapter discusses the policy implications of the findings, positing that State-led initiatives such as the Nansen and Migrants in Countries in Crisis initiatives are useful mechanisms to fill protection gaps in the absence of political will to adopt and implement more binding legal frameworks. It also argues that, in the context of slow onset climate change, in particular, there is a need for better understanding of how population density, distribution and growth as well as household composition affect vulnerability and resilience to the drivers of displacement."
7529,Intestinal/Multivisceral Transplantation,"Intestinal/multivisceral transplantation has evolved from an experimental procedure to the treatment of choice for patients with irreversible intestinal failure and serious complications related to long-term parenteral nutrition. Children who are likely to suffer permanent intestinal failure and benefit from intestinal transplantation include those with a remaining small bowel length of less than 30–40 cm, absence of the ileocecal valve, colonic resection and malabsorptive syndromes. Indications for transplant include frequent severe bouts of catheter associated sepsis, threatened loss of vascular access and the development of liver cirrhosis from cholestasis. Children who are more likely to experience cholestasis from total parenteral nutrition include those who experience persistent hyperbilirubinemia (greater than 6 mg/dl despite enteral nutrition), those with recurrent sepsis and/or bacterial overgrowth and those with minimal tolerance of any enteral feeds in the first few months post resection. The 1 year survival rate after intestinal transplantation has markedly improved over the last several years but long term survival rates have remained unchanged. The improved short term survival rates have led to an increased prevalence of this patient population in intensive care units. Management of intestinal and multivisceral transplant recipients is uniquely challenging because of complications arising from the high incidence of transplant rejection and its treatment. In the ICU, the complexity of medical care for the transplant recipient requires a multidisciplinary approach with coordination by an intensivist in collaboration with the transplant surgeon, gastroenterologist, and other specialists."
7530,Genetics and Severe Sepsis,
7531,"RMSF and Serious Tick-Borne Illnesses (Lyme, Ehrlichiosis, Babesiosis and Tick Paralysis)","Rocky Mountain spotted fever (RMSF) and other tick-borne illnesses, a burden predominantly in the summer season, produce symptoms ranging from fever to paralysis. Although often benign, sequela can range from chronic arthritis to neurologic or cardiac illness. Especially in the areas of the North America where tick-borne illnesses are more prevalent, tick-borne illnesses require vigilance on the provider’s part to inquire about recent outdoor activity. Prevention is paramount including the use of protective clothing and tick repellent."
7532,Pegylated Interferons: Clinical Applications in the Management of Hepatitis C Infection,
7533,Nucleic Acid Extraction Techniques,"Since thermostable Taq DNA polymerase was discovered in 1987, nucleic acid amplification techniques have made great strides and contributed greatly to progress in the life sciences. These techniques were introduced into the clinical laboratory and have produced great changes in diagnostic tools and tests. In particular, there have been many innovative molecular testing developments in the field of diagnostic microbiology."
7534,Infectious Diseases,"Infectious disease agents include viruses, bacteria, fungi, protozoa, parasites, and proteins called prions. Some patients are asymptomatic from their infection, whereas in other patients, clinical or subclinical illness affects the patient during the perioperative period. Transmission of the agents can occur through airborne inhalation, through contact with contaminated body fluids, via food, through physical contact, or through vector organisms. Additionally, patient-patient and patient-healthcare worker (HCW) transmission of infectious diseases remain a high concern. The perioperative period represents a unique challenge in the prevention of transmission. While diligent hand washing remains a staple in the standard of care, other measures must be implemented with certain infectious agents. Several of the major infectious diseases will be reviewed in this section, and universal precautions will be examined. Careful perioperative planning and situational awareness should be practiced by the healthcare worker taking care of patients with transmissible diseases."
7535,Application and evaluation of entomopathogens for control of livestock and poultry pests,"The control of livestock and poultry pests presents unique challenges. The hosts are warmblooded vertebrate animals, capable of a wide range of behaviors and movement. Range cattle and sheep in arid environments, for example, may occupy sparse grassland regions of thousands of hectares and move freely over many kilometers in search of forage. In these situations, pest management strategies must be effective and sustainable with minimal human input or supervision."
7536,The Role of Infections and Autoimmune Diseases for Schizophrenia and Depression: Findings from Large-Scale Epidemiological Studies,"An immunologic component to schizophrenia and depression has been increasingly recognized, which has led to extensive research into the associations with infections and autoimmune diseases. Large-scale nationwide epidemiological studies have displayed an increased prevalence of both autoimmune diseases and infections among persons with schizophrenia and depression. Autoimmune diseases, and especially the number of infections requiring hospitalization, increase the risk of schizophrenia and depression in a dose–response relationship. Infections are a common exposure and a broad spectrum of infections are associated with schizophrenia and depression. Particularly the autoimmune diseases with a potential presence of brain-reactive antibodies were associated with psychiatric disorders. However, the associations seem to be bidirectional, since the risk of autoimmune diseases and infections is also increased after diagnosis with schizophrenia and depression. The risk of autoimmune diseases was particularly increased in individuals with prior hospital contacts for infections. It has been suggested that inflammation and autoimmunity could be involved in the etiology and pathogenesis of some patients with symptoms of schizophrenia and depression. The psychiatric symptoms can be directly triggered by immune components, such as brain-reactive antibodies and cytokines, or infections reaching the central nervous system (CNS), or be secondary to systemic inflammation indirectly affecting the brain. However, the associations could also be caused by shared genetic factors, other environmental factors, or common etiological components. Nonetheless, autoimmune diseases and infections should be considered by clinicians in the treatment of individuals with psychiatric symptoms, since treatment would probably improve the psychiatric symptoms, quality of life, and the survival of the individuals."
7537,Modeling Brain Tumors Using Avian Retroviral Gene Transfer,RCAS/tv-a is a system for postnatal cell-type-specific gene transfer. It is used for the modeling of gliomas and medulloblastomas. This system provides a combination of lineage tracing from the cell origin with oncogenesis induced by mis-expression of specific genes. The genes that are most potent at inducing tumors are those that encode components of signal transduction and undifferentiated cells are most capable of serving as the cell of origin. The system effectively generates tumors with the histologic characteristics of human disease. Mice bearing RCAS/tv-a-induced brain tumors are currently being used for preclinical trials to understand the biology of therapeutic response in the various cell types that make up gliomas and medulloblastomas.
7538,Intestinal Transplantation from Living Donors,"Intestinal transplantation (ITx) represents the physiologic alternative to total parenteral nutrition (TPN) for patients suffering from life-threatening complications of irreversible intestinal failure. The number of transplants performed worldwide has been increasing for several years until recently. ITx has recently become a valid therapeutic option with a graft survival rate between 80 % and 90 % at 1 year, in experienced centers. These results have been achieved due to a combination of several factors: better understanding of the pathophysiology of intestinal graft, improved immunosuppression techniques, more efficient strategies for the monitoring of the bowel graft, as well as control of infectious complications and posttransplant lymphoproliferative disease (PTLD). In fact, this procedure is associated with a relatively high rate of complications, such as infections, acute rejection, graft versus host disease (GVHD), and PTLD, if compared to the transplantation of other organs. These complications may be, at least in part, the consequence of the peculiarity of this graft, which contains gut-associated lymphoid tissue and potentially pathogenic enteric flora. Furthermore, in these patients, the existing disease and the relative malnutrition could predispose them to infectious complications. Additionally, other factors associated with the procedure, such as laparotomy, preservation injury, abnormal motility, and lymphatic disruption, could all be implicated in the development of complications."
7539,"Shellfish-Associated Enteric Virus Illness: Virus Localization, Disease Outbreaks and Prevention","Numerous outbreaks of shellfish-borne enteric virus illness have been reported worldwide. Most notable among the outbreaks are those caused by NoV and HAV. Lessons learned from outbreak investigations indicate that most outbreaks are preventable. Anthropogenic sources of contamination will continue to invade shellfish growing waters. Shellfish, by their very nature, will continue to bioconcentrate these contaminants, including enteric viruses. There is no quick fix for enteric virus contamination of shellfish; however, vigilance on behalf of the industry, regulatory agencies, and the consumer could substantially reduce the incidence of illness. Enhanced monitoring in all areas of shellfish production, harvesting, distribution, and processing would help to reduce viral illnesses. Pollution abatement and improved hygienic practices on behalf of the industry and consumers are needed. Improved analytical techniques for the detection of enteric viruses in shellfish will lead to enhanced shellfish safety and better protection for the consumer and the industry. Better reporting and epidemiological follow-up of outbreaks are keys to reducing the transmission of foodborne viral infections. It is anticipated that recent advances in analytical techniques, particularly for NoV, will lead to better monitoring capabilities for food and water and a reduction in the incidence of enteric virus illness among shellfish consumers."
7540,Viral Proteins that Enhance Membrane Permeability,
7541,Article 11 Applicability of Air Regulations,"Subject to the provisions of this Convention, the laws and regulations of a contracting State relating to the admission to or departure from its territory of aircraft engaged in international air navigation, or to the operation and navigation of such aircraft while within its territory, shall be applied to the aircraft of all contracting States without distinction as to nationality, and shall be complied with by such aircraft upon entering or departing from or while within the territory of that State."
7542,Disease Outbreaks Caused by Emerging Paramyxoviruses of Bat Origin,"Newly emerging and re-emerging infections are recognized as a global problem and 75% of these are potentially zoonotic (Woolhouse & Gowtage-Sequeria, 2005). Emergence of a new “killer” disease in any part of the world is likely to be a threat world wide in today’s society with very rapid means of transportation of both human and animal/animal products. Recent examples include the global outbreaks of severe acute respiratory syndrome (SARS), H5N1 avian influenza, and the outbreaks of West Nile virus in United States. The rapid economic development in the Asian region during the last few decades was accompanied by massive urbanization and environmental changes, which are believed to be one of the triggers leading to the emergence of new zoonotic diseases. Wildlife animals play an ever-increasing role in the emergence of zoonotic diseases, and bats have been identified as natural reservoir host of several lethal zoonotic viruses that emerged in recent times. This review will focus on the disease outbreaks caused by emerging bat viruses in the family Paramyxoviridae."
7543,Viral Hemorrhagic Fever Preparedness,"The 2014–2016 outbreak of Ebola virus disease (EVD) in West Africa marked the 25th such occurrence but was noteworthy in its massive scope, causing more human morbidity and mortality than the previous 24 recorded outbreaks combined. As of April 2016, there were 28,652 cases resulting in at least 11,325 deaths, nearly all in the three nations of Guinea, Liberia, and Sierra Leone (Centers for Disease Control and Prevention. http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/index.html. Accessed 2 June 2016). Moreover, the 2014–2016 outbreak was the first in which patients, albeit few in number, were afforded sophisticated intensive care in the United States and in Europe. This “high-level containment care” (HLCC) was provided in specially designed purpose-built biocontainment units (BCUs). In this chapter, we explore the history and evolution of biocontainment, discuss its unique engineering and infection control modalities, and offer recommendations for the clinical and operational management of Ebola and other viral hemorrhagic fevers (VHFs)."
7544,Becoming a Successful Corporate Communication Practitioner in International Business Consultancy,"Corporate communication practitioners have a very wide range of professional responsibilities ranging from the almost ubiquitous, for example, media relations, public relations, communication strategy, crisis communications and public policy, to those that are less common, such as investor relations, government relations, technical communications and ethics (Goodman MB, Hirsch PB, Corporate communication: strategic adaptation for global practice. Peter Lang, New York, 2010). This chapter examines how the most frequently encountered of these responsibilities are discharged and highlights the skills and technical practices that are necessary for their successful execution. It further examines the leadership roles of corporate communication professionals in the corporation, among the more commonly encountered of which include counsel to the CEO and the corporation, manager of the company’s reputation, driver of the company’s publicity and manager of the company’s image (Goodman MB, Hirsch PB, Corporate communication: strategic adaptation for global practice. Peter Lang, New York, 2010). It is these leadership roles of corporate communicators that highlight their importance both internally and externally in protecting, maintaining and enhancing the company’s reputation. It also conditions the relationship of corporate communicators with those executives who have primary responsibility for critical programmes, such as investor and government relations, where corporate communicators have a secondary role. It is the task of corporate communicators working as a team with directors and senior managers to formulate and agree a coherent narrative that best represents the company’s activities, aspirations and strategy. In undertaking this work, corporate communicators may call on the support of communication consultancies (and they may themselves choose to spend part of their careers in consultancy), and the chapter discusses their differing roles and how optimum results can be achieved from their combined efforts."
7545,Conidiobolus,"Conidiobolus coronatus, C. incongruus, C. lamprauges"
7546,Transfusionshepatitis,
7547,Utilising Media and Text-Based Sources,"An often-underestimated, valuable source of naturally occurring data is that of media sources, such as television programmes, documentaries, newspapers, and magazines. Often in traditional textbooks these are positioned as secondary sources. We argue that they can be considered primary data, as well as naturally occurring data. This type of naturally occurring data is of interest for qualitative research, and in this chapter, we focus on the use of policy documents, medical notes, health guidelines, as well as other data sources such as police transcripts, court transcripts, and social care reports whereby health is invoked, to illustrate the value of analysing texts that occur naturally in the field of health."
7548,Bat-Related Zoonoses,"The many emerging infectious diseases associated with Chiropteran species can have major impacts on both ecosystem and public health. As such, the scope of this chapter is to provide an overview of those potential bat-related zoonoses and their clinical relevance to people. With increased disease surveillance and a trend toward more human contact with bat populations, it is likely that additional zoonotic diseases will continue to be identified. Bat infection dynamics are driven by a complex interplay of ecological, immunological, behavioral, and anthropogenic factors. Interdisciplinary work will be needed in the future to better understand the drivers of disease emergence in bat populations and ultimately mitigate the threats that face both people and bats themselves."
7549,Dangerous Microbes,"The most dangerous microbes for humans are those that are easily transmitted, virulent and invasive to central organs like the blood and lung, robust survivors in the environment, have a low infection dose and are without any specific treatment or vaccine. Most of them are zoonoses transmitted from animals and often with insects as vectors. The most dangerous microbes cause a very high mortality, are identified as high-risk agents or “biohazard-level 4” agents and are treated at the highest level of infection protection with strict isolation measures. Dangerous microbes occur as a problem mostly in countries with low hygiene standards/high population density and in tropical-subtropical areas. Infection control must always be based on hygienic measures and strict infection protection. This chapter is a short information about the most virulent and pathogenic agents, geographic area and severity of disease."
7550,Neuropeptidases,"Neuropeptides are neurotransmitters and modulators distributed in the central nervous system (CNS) and peripheral nervous system. Their abnormalities cause neurological and mental diseases. Neuropeptidases are enzymes crucial for the biosynthesis and biodegradation of neuropeptides. We here focus on the peptidases involved in the metabolism of the well-studied opioid peptides. Bioactive enkephalins are formed from propeptides by processing enzymes—prohormone thiol protease, prohormone convertase 1 and 2 (PC 1 and 2), carboxypeptidase H/E, and Arg/Lys aminopeptidase. After they exert their biological effects, enkephalins are likely to be inactivated by degrading enzymes—angiotensin-converting enzyme (ACE), aminopeptidase N (APN), puromycin-sensitive aminopeptidase (PSA), and endopeptidase 24.11. Recently, a neuron-specific aminopeptidase (NAP), which was a putative enkephalin-inactivating enzyme at the synapses, was found. Neuropeptidases are useful drug targets and their inhibitors can be therapeutic. Synthetic anti-enkephalinases and anti-aminopeptidases are being developed. They are potent analgesics but have fewer side effects than the opiates."
7551,Infecties van de onderste luchtwegen en tuberculose,"Tot de onderste luchtwegen behoren alle onderdelen van de luchtwegen en de longen onder de stembanden (trachea, bronchi en bronchioli). Onder normale omstandigheden zijn de onderste luchtwegen vrij van micro-organismen. Deze situatie wordt gehandhaafd door de continue activiteit van de trilharen, die zorgen voor eliminatie van de partikels. De deeltjes die toch in de alveoli terechtkomen, worden door de macrofagen gefagocyteerd en verwijderd. Ontstaat er toch een ontsteking, dan vindt vanuit de bloedbaan toestroom plaats van granulocyten en lymfocyten om pathogenen te verwijderen. Daarnaast bevatten de luchtwegen nog een aantal beschermende eiwitten die de gastheer beschermen tegen kolonisatie. Bij patiënten met chronische obstructieve longaandoeningen (COPD) treedt vernauwing en deformatie van de luchtwegen op, wat kan leiden tot een lokale afvloedbelemmering en kolonisatie met micro-organismen. Ook zijn er zeldzame aandoeningen zoals mucoviscidose (taaislijmziekte/cystische fibrose), het immotieleciliasyndroom en hypo- of agammaglobulinemie die predisponeren tot luchtweginfecties. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1117-0_3) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers."
7552,"Thorax, Mediastinum","Für die Analyse der normalen Topographie müssen in der Thoraxaufnahme p.a. die Organsysteme der Trachea, des Mediastinums, des Zwerchfells, der Fissuren, der Lunge, der Hiluskonfigurationen, der Weichteilstrukturen und der ossären Strukturen evaluiert werden (◘ Abb. 19.1). Wichtige Kriterien sollen für jedes dieser Organsysteme dezidiert vorgestellt werden."
7553,Transgenic Vegetables and Fruits for Control of Insects and Insect-Vectored Pathogens,"Fruits and vegetables are major components of a healthy diet, but are subject to severe pest pressure. Approximately 30% of all insecticides applied worldwide are used to control insects affecting vegetables and fruits. Transgenic, or more commonly referred to as genetically modified (GM), vegetables and fruits offer unique opportunities for controlling insects and the pathogens they transmit. Aphid transmitted viruses have been particularly difficult to manage by tactics aimed at reducing aphid populations and in many cases there has not been virus resistant plant germplasm. Farmers in the USA have benefited from having GM virus resistant squash and papaya available to them as tools in their overall IPM programs. In the USA, Bt sweet corn has proven effective for control of Lepidoptera and continues to be accepted in the fresh market. However, the best opportunities for GM vegetables and fruits are in developing countries where 83% of the world’s population lives, the majority of vegetables and fruits are produced and pest problems are most acute."
7554,"Distribution Theory, Stochastic Processes and Infectious Disease Modelling","The occurrence of a major outbreak, the shape of the epidemic curves, as well as the final sizes of outbreaks, are realizations of some stochastic events with some probability distributions. These distributions are manifested through some stochastic mechanisms. This chapter divides a typical outbreak in a closed population into two phases, the initial phase and beyond the initial phase. For the initial phase, this chapter addresses several aspects: the invasion (i.e. the risk of a large outbreak); quantities associated with a small outbreak; and characteristics of a large outbreak. In a large outbreak beyond the initial phase, the focus is on its final size. After a review of distribution theories and stochastic processes, this chapter separately addresses each of these issues by asking questions such as: Are the latent period and/or the infectious period distributions playing any role? What is the role of the contact process for this issue? Is the basic reproduction number R (0) sufficient to address this issue? How many stochastic mechanisms may manifest observations that may resemble a power-law distribution, and how much detail is really needed to address this specific issue? etc. This chapter uses distribution theory and stochastic processes to capture the agent–host–environment interface during an outbreak of an infectious disease. With different phases of an outbreak and special issues in mind, modellers need to choose which detailed aspects of the distributions and the stochastic mechanisms need to be included, and which detailed aspects need to be ignored. With these discussions, this chapter provides some syntheses for the concepts and models discussed in some proceeding chapters, as well as some food for thought for following chapters on case studies."
7555,Respiratory Diseases of Pregnancy,"Pregnant patients can suffer from the same respiratory diseases as the general population in addition to unique syndromes of pregnancy (such as pre-eclampsia and tocolytic induced pulmonary edema, and pregnancy induced cardiomyopathy). Pregnancy by itself may add certain challenges such as difficult intubation. The critically ill pregnant patient requires a multidisciplinary approach and early inclusion of obstetrical expertise is paramount in managing these patients especially in the third trimester."
7556,Regional Therapy of Cancer,"Surgical resection is the primary treatment and typically the only curative therapy for most solid malignancies. Throughout this surgical textbook, virtually all chapters dealing with individual organs have some portion of that chapter devoted to the surgical treatment of primary cancer at that site. For example, Chapter 96 on breast disease primarily discusses the treatment of cancer because this is by far the predominant surgical disease in that organ. On the other hand, Chapter 49 on the small intestine has a much smaller proportion dealing with cancer as primary malignancies comprise a smaller fraction of the surgical diseases involving the small intestine. A specialized type or category of surgical treatment for cancer can be categorized as regional therapy. As opposed to straightforward surgical resection, in this type of therapy a specific region or area of the body is treated. Regional therapy is primarily applicable to metastatic disease limited to one site or area of the body. There are two broad categories of regional therapy of cancer: (1) vascular-based treatments and (2) intracavitary treatments. The most successfully treated areas of the body by vascular means are the extremities and the liver."
7557,Infectious Diseases: Need for Targeted Drug Delivery,"Infectious diseases are a leading cause of death worldwide, with the constant fear of global epidemics. It is indeed an irony that the reticuloendothelial system (RES), the body’s major defence system, is the primary site for intracellular infections which are more difficult to treat. Pro-inflammatory M1 macrophages play an important role in defence. However, ingenious pathogen survival mechanisms including phagolysosome destruction enable their persistence. Microbial biofilms present additional challenges. Low intracellular drug concentrations, drug efflux by efflux pumps and/or enzymatic degradation, emergence of multi-drug resistance (MDR), are serious limitations of conventional therapy. Targeted delivery using nanocarriers, and passive and active targeting strategies could provide quantum increase in intracellular drug concentration. Receptor mediated endocytosis using appropriate ligands is a viable approach. Liposomes and polymeric/lipidic nanoparticles, dendrimers micelles and micro/nanoemulsions could all be relied upon. Specialised targeting approaches are demonstrated for important diseases like tuberculosis, HIV and Malaria. Application of targeted delivery in the treatment of veterinary infections is exemplified and future possibilities indicated. The chapter thus provides an overview on important aspects of infectious diseases and the challenges therein, while stressing on the promise of targeted drug delivery in augmenting therapy of infectious diseases."
7558,Selecting Genotyping Oligo Probes Via Logical Analysis of Data,"Based on the general framework of logical analysis of data, we develop a probe design method for selecting short oligo probes for genotyping applications in this paper. When extensively tested on genomic sequences downloaded from the Lost Alamos National Laboratory and the National Center of Biotechnology Information websites in various monospecific and polyspecific in silico experimental settings, the proposed probe design method selected a small number of oligo probes of length 7 or 8 nucleotides that perfectly classified all unseen testing sequences. These results well illustrate the utility of the proposed method in genotyping applications."
7559,"Role of ACE, ACE2 and Neprilysin in the Kidney",
7560,Environmental Influences in Experimental Autoimmune Encephalomyelitis,"Environmental factors, in particular infectious agents, are thought to have a major influence on the development and course of MS. Some of these influences are also reflected in the animal model, EAE. In this chapter, the role of infectious agents in the development and course of autoimmunity in EAE is discussed. Other environmental agents including trauma, solar radiation exposure, temperature, stress, toxins, are discussed in terms of their relevance to MS and EAE."
7561,Characterization of Proprotein Convertases and Their Involvement in Virus Propagation,"Proprotein convertases (PCs), also known as eukaryotic subtilases, are a group of serine proteases comprising furin (PACE), PC1 (PC3), PC2, PC4, PACE4, PC5 (PC6), and PC7 (LPC, PC8) that generate bioactive proteins and peptides, such as hormones, receptors, and growth factors by cleaving precursor proteins at multibasic motifs. Two other family members, SKI-1/S1P and PCSK9, cleave regulator proteins involved in cholesterol and fatty acid homeostasis at nonbasic peptide bonds. Furin is ubiquitous in eukaryotic tissues and cells. PACE4, PC5, and PC7 are also widespread, whereas the expression of the other PCs is more restricted. PCs are synthesized as multi-segmented zymogens which are autocatalytically activated. The prodomains have regulatory and inhibitory functions. The catalytic domains are the most conserved domains among the PCs. The architecture of the catalytic active furin domain is known in different binding states. The C-terminal parts of the PCs differ in length and structure and contain encoded peptide signatures guiding the PCs to the subcellular destinations on the secretory pathways: SKI-1/S1P to the cis-Golgi, furin, PC5B, and PC7 to the TGN region but also to the plasma membrane. PACE4, PC5A, and PCSK9 are attached at the cell surface. Truncated, soluble furin and SKI-1/S1P, as well as PC1 and PC2, are released into the extracellular matrix. Many enveloped viruses are activated by furin and furin-like PCs and arenaviruses and a few bunyaviruses by SKI-1/S1P. The PCs cleave the viral fusion glycoprotein to trigger fusion of viral envelopes with cellular membranes to deliver the viral genome into host cells. Cleavage by PCs, occasionally in concert with other endoproteases, enables conformational changes in the viral membrane proteins needed for correct oligomerization of glycoprotein spikes and their effective incorporation into virions. Mutational alterations of PC cleavage sites can reduce the fusion potential of viral surface proteins and thus facilitate the development of secure live attenuated vaccines. Alternatively, agents preventing cleavage of viral surface (glyco)proteins block fusion capacity and multicyclic virus replications. PC inhibitors are suggested as promising antiviral drugs for quite a number of viruses causing severe infections."
7562,Conclusion: Ethnographic Data as Medical Evidence,"The Conclusion returns to the larger question of the role of ethnography in the development of plague science during the third pandemic. Discussing the challenges of rendering ethnographic data into epidemiological evidence within the context of epistemological entropy, it is argued that epidemiological reasoning developed on the basis of plague ethnographies entailed a two-way process: on the one hand, the ethnographic configuration of plague, as an infectious disease whose decipherment relied on the medical objectification of ethnographic data; and on the other hand, the representation of native societies in terms of being either cultural vectors of or culturally immune to the disease. It is hence argued that, in the case of the north-east Chinese-Russian frontier, this interpretive strategy condemned Mongol and Buryat societies to a static condition of functional unreason. Discussing how this form of ontological and epistemological enclosure continues to inform our postcolonial world, the Conclusion underscores the need for a critical and relational understanding of infectious disease."
7563,Bioterrorism—a clear and present danger,"Until a few years ago, the thought of anyone highjacking a crowded airliner and deliberately crashing it into skyscraper buildings in one of the world's major cities would have been dismissed as fantasy. The event would have been unthinkable. But then, on September 11, 2001 fantasy was turned into chilling fact."
7564,A SIS Epidemiological Model Based on Cellular Automata on Graphs,The main goal of this work is to introduce a new SIS epidemic model based on a particular type of finite state machines called cellular automata on graphs. The state of each cell stands for the fraction of the susceptible and infected individuals of the cell at a particular time step and the evolution of these classes is given in terms of a local transition function.
7565,Modeling the Spread of Preventable Diseases: Social Culture and Epidemiology,"This paper uses multiagent simulation to examine the effect of various awareness interventions on the spread of preventable diseases in a society. The work deals with the interplay between knowledge diffusion and the spreading of these preventable infections in the population. The knowledge diffusion model combines information acquisition through education, personal experiences, and the spreading of information through a scale-free social network. A conditional probability model is used to model the interdependence between the risk of infection and the level of health awareness acquired. The model is applied to study the spread of HIV/Aids, malaria, and tuberculosis in the South African province Limpopo. The simulation results show that the effect of various awareness interventions can be very different and that a concerted effort to spread health awareness through various channels is more likely to control the spread of these preventable infections in a reasonable time."
7566,Curtailing Agriculture Projects’ Practices That Can Harm Urban Food Security and Public Health,"Many old and “modern” cities have been built on terrain that was previously vegetated and part of biologically diverse ecosystems. This was often on productive farmland that was not protected from encroachment as municipalities expanded and opened pristine areas to development. The encroachment continues as rural citizens and their families are attracted to urban centers for the way of life they seemed to offer. This starts with employment possibilities, education for workers children, and family health services as manufacturing/industrial operations and large and small businesses that serviced them spurs economic development. Agricultural projects are located mainly away from population centers, be they major metropolises or smaller cities. They provide food security for urban citizens through “brought into markets” in-ground crops, bush crops, and tree crops they cultivate, and through animal husbandry (e.g., beef and dairy cattle, poultry, hogs, sheep). The last chapter described how manufacturing/industrial endeavors can present potential harm to the health of urban and rural citizens and to natural resource rich ecosystems that help sustain them, and how to find solutions to the problems. This chapter will discuss the problems that food production methods present, the threats they pose to urban populations that are generally distant from them, and possible solutions to such problems."
7567,Risks,"Risk is our daily work and often our obsession – as risk researchers we are working on research projects which are intended to increase our knowledge about all aspects of risks. Being a “risk researcher” means looking at things through a specific ­perspective – the perspective of what negative consequences a natural or man-made event, a technology, a decision could probably have on the world we live in. Our perspective is a socio-scientific one. This means, we are analyzing what consequences do risks have on the society and what can we do to decrease or prevent them. This includes the possible actions of a single consumer as well as strategies of whole governments to manage risks. How are risks perceived by people? What kinds of knowledge are needed to deal with different kinds of risks? Who should be involved, and when? What to do if conflicts evolve about how to handle risks? How to communicate risks? It is our job to answer questions like these. We are dealing with these questions in many different thematic areas: food safety, climate change, chemicals, nanotechnology, electromagnetic fields, etc. These risks pose very different problems and it seems difficult to find general strategies to deal with them."
7568,Zukunftsszenarien für die Logistikdienstleistung im Jahr 2025,"Die Logistik hat die Zukunftsforschung und ihre Möglichkeiten für sich noch nicht entdeckt. Die Logistikdienstleistungsbranche liegt im Bereich der Zukunftsforschung deutlich hinter der Pharma-, Automobil- und Telekommunikationsbranche, die die langfristige Zukunft ihrer Branchen schon seit vielen Jahren sehr systematisch analysieren, um Veränderungen zu antizipieren und Wettbewerbsvorteile zu erzielen (Darkow, von der Gracht, 2006). Warum sollte dies nicht auch in der Logistikdienstleistung möglich sein? Das Supply Management Institute (SMI) und die FutureManagementGroup AG haben aus diesem Anlass eine Studie zur Zukunft der Logistikdienstleistungsbranche in Deutschland 2025 durchgeführt, die im Februar 2008 gemeinsam mit der Bundesvereinigung Logistik (BVL) veröffentlicht wurde (Von der Gracht et al., 2008). Mit diesem Projekt sollen die Bedeutung und Möglichkeiten der Zukunftsforschung in der Logistik herausgestellt und ein weiter Blick in die Zukunft geworfen werden.(1)"
7569,Nanomaterials – the Next Great Challenge for Qsar Modelers,"In this final chapter a new perspective for the application of QSAR in the nanosciences is discussed. The role of nanomaterials is rapidly increasing in many aspects of everyday life. This is promoting a wide range of research needs related to both the design of new materials with required properties and performing a comprehensive risk assessment of the manufactured nanoparticles. The development of nanoscience also opens new areas for QSAR modelers. We have begun this contribution with a detailed discussion on the remarkable physical–chemical properties of nanomaterials and their specific toxicities. Both these factors should be considered as potential endpoints for further nano-QSAR studies. Then, we have highlighted the status and research needs in the area of molecular descriptors applicable to nanomaterials. Finally, we have put together currently available nano-QSAR models related to the physico-chemical endpoints of nanoparticles and their activity. Although we have observed many problems (i.e., a lack of experimental data, insufficient and inadequate descriptors), we do believe that application of QSAR methodology will significantly support nanoscience in the near future. Development of reliable nano-QSARs can be considered as the next challenging task for the QSAR community."
7570,Molecular Mechanism of Drug Resistance,"The treatment of microbial infections has suffered greatly in this present century of pathogen dominance. Inspite of extensive research efforts and scientific advancements, the worldwide emergence of microbial tolerance continues to plague survivability. The innate property of microbe to resist any antibiotic due to evolution is the virtue of intrinsic resistance. However, the classical genetic mutations and extrachromosomal segments causing gene exchange attribute to acquired tolerance development. Rampant use of antimicrobials causes certain selection pressure which increases the resistance frequency. Genomic duplication, enzymatic site modification, target alteration, modulation in membrane permeability, and the efflux pump mechanism are the major contributors of multidrug resistance (MDR), specifically antibiotic tolerance development. MDRs will lead to clinical failures for treatment and pose health crisis. The molecular mechanisms of antimicrobial resistance are diverse as well as complex and still are exploited for new discoveries in order to prevent the surfacing of “superbugs.” Antimicrobial chemotherapy has diminished the threat of infectious diseases to some extent. To avoid the indiscriminate use of antibiotics, the new ones licensed for use have decreased with time. Additionally, in vitro assays and genomics for anti-infectives are novel approaches used in resolving the issues of microbial resistance. Proper use of drugs can keep it under check and minimize the risk of MDR spread."
7571,Application of Ionic Liquids in Multicomponent Reactions,"This chapter reports the applicability of ionic liquids in the formation of different types of multicomponent reactions. Easy work-up, relatively short reaction times, good to high yields of the desired products, mild reaction conditions, low cost, availability, and reusability of the employed ionic liquids are the striking ­features of the reported methodologies."
7572,Managing risk,"recognize the omnipresence of risk of various kinds; identify the main strategic responses to the existence of risk; understand when avoidance is the best form of risk management; distinguish between the management and mitigation of risk; understand how diversification is one way of managing risk; consider how, using scenario building and planning, risk management can be made part of the overall strategic orientation of those making strategy."
7573,Dealing with Global Infectious Disease Emergencies,"The microbes that cause human infectious diseases are complex, dynamic, and constantly evolving. They reproduce rapidly, mutate frequently, adapt with relative ease to new environments and hosts, and frequently breach the species barrier between animals and humans. Social, economic, and environmental factors linked to a host of human populations and activities can accelerate and amplify these natural phenomena. The ability of infectious diseases to spread internationally—carried by humans, insect vectors, food and food products, and livestock—has been greatly augmented by the pressures of a crowded, closely interconnected, and highly mobile world. When they spread internationally, infectious diseases often lead to global emergencies."
7574,Infektionen,"Trotz Weiterentwicklung moderner Antibiotika in den letzten Jahren sind die Letalitätszahlen der bakteriellen (eitrigen) Meningitis weiterhin hoch; Überlebende haben häufig neurologische Residuen. Die ungünstigen klinischen Verläufe der bakteriellen Meningitis sind meist Folge intrakranieller Komplikationen, wie z. B. eines generalisierten Hirnödems, einer zerebrovaskulären arteriellen oder venösen Beteiligung oder eines Hydrozephalus. Als Folge dieser Komplikationen kommt es häufig zu einem Anstieg des intrakraniellen Drucks. Bei schweren, komplizierten klinischen Verläufen der bakteriellen Meningitis kommen oft adjuvante Therapiemaßnahmen (z. B. intravenöse Gabe von hyperosmolaren Substanzen, externe Ventrikeldrainage) zum Einsatz. Bei Nachweis einer meningitisassoziierten septischen Sinus-/Venenthrombose erfolgt die dosisadaptierte intravenöse Heparintherapie."
7575,Alcohol and Cancer Epidemiology,"In a comprehensive worldwide assessment of cancer risk related to food and nutrition, the American Institute for Cancer Research (AICR 2007) identified alcohol consumption as a “convincing” or “probable” risk factor for esophageal, mouth, and laryngeal cancers, for liver cancer, for breast cancer in women, and for colorectal cancer especially in men. The World Health Organization’s Global Burden of Disease Project concluded that “A total of 390,000 cases of cancer are attributable to alcohol drinking worldwide, representing 3.6% of all cancers (5.2% in men, 1.7% in women)” each year, with a corresponding annual mortality rate of 233,000, representing 3.5% of all cancer deaths (Boffetta et al. 2006). For the USA, the Alcohol-Related Disease Impact (ARDI) report indicates an annual rate of 2,464 deaths in six different alcohol-related cancer categories for the period 2001–2006 (CDC 2010)."
7576,Parasites and Their World Records in Their Fight for Survival,"Parasites are animals that enter plants, animals and humans – but are not welcome. Therefore they had to develop strategies for invasion and survival – outside and inside of hosts. For this purpose they developed amazing, often unbelievable skills during evolution. Thirteen of them are presented in this chapter showing that they are fit for the future thus threatening mankind, if there are no precautions in the future."
7577,Acute Liver Failure in Children,"“Acute liver failure” (ALF) and “fulminant liver failure” are terms used interchangeably to describe severe and sudden onset of liver cell dysfunction leading on to synthetic and detoxification failure across all age groups. Considerable variations exist between ALF in children and adults, in terms of aetiology and prognosis. Encephalopathy is not essential to make a diagnosis of ALF in children but when present has a bad prognosis. Early recognition of ALF and initiation of supportive management improve the outcome. Liver transplantation remains the only definitive treatment when supportive medical management fails."
7578,A Stakeholder Approach to Risk Management,"In crisis management, risk management has been conceived mainly as a proactive pre-crisis management effort where it is deployed for crisis prevention and preparedness efforts. This chapter argues that risk management extends into the entire crisis management continuum, as crises ignite new types of risks with their associated stakeholders. Organizations should continually identify, manage and communicate risks to key stakeholders during the different phases of crisis management. A stakeholder orientation demands that organizations seek and involve risk stakeholders in the risk management process. The level of involvement will depend on both the identified risks and how stakeholders are expected to be affected by the proposed solutions and decision-making processes."
7579,Acute Liver Failure,"Acute liver failure is a highly unpredictable disease that can evolve to a life-threatening situation within few hours. In a simplified manner, acute liver failure is the acute liver dysfunction with multiorgan damaging associated with numerous complications, and very poor prognosis, being caused by varied etiologies. Despite the numerous advances on pathophysiology, intensive care treatment, and transplantation techniques from the last decades, is still characterized by increased mortality. At present, the patients with acute liver failure should be managed in Intensive Care Unit where the therapy should be applied based on the specific etiology of the acute liver failure and it should be started as early as possible."
7580,Drug-Induced Delayed Multi-organ Hypersensitivity Syndrome,"Drug-induced delayed multi-organ hypersensitivity syndrome (DIDMOHS), also known as drug reaction (or rash) with eosinophilia and systemic symptoms (DRESS), drug-induced hypersensitivity syndrome (DIHS), or drug hypersensitivity syndrome (DHS) is a rare, potentially fatal, drug-induced hypersensitivity reaction characterized by cutaneous eruption, fever, lymphadenopathy, hematologic abnormalities, and visceral manifestations. Anticonvulsants such as carbamazepine, phenytoin, lamotrigine, and phenobarbital as well as allopurinol and sulfonamides, are the most common causes of DIDMOHS. Impaired drug detoxification and herpes virus reactivation play a key role in DIDMOHS pathogenesis. Human leukocyte antigen (HLA) haplotypes also contribute. Early cutaneous findings generally include a morbilliform eruption characterized by diffuse, erythematous, pruritic macules across the face, upper trunk, and upper extremities with later extension to the lower extremities. Rapid confluence and progression are characteristic. DIDMOHS frequently involves the lymphatic, hematologic, and hepatic systems. Renal, pulmonary, and cardiac dysfunction may also ensue. Early recognition and diagnosis with prompt withdrawal of the culprit drug is paramount. Corticosteroid therapy is widely accepted as the cornerstone of DIDMOHS management. Moving forward, haplotyping and assays such as the lymphocyte transformation test (LTT) will aid in the primary prevention and diagnosis of DIDMOHS. Novel steroid-sparing immunomodulatory agents also have significant therapeutic potential."
7581,Virus Glycoproteins Tagged with the Human Fc Domain as Second Generation Vaccine Candidates,"Traditional vaccines such as inactivated or live attenuated vaccines, are gradually giving way to more biochemically defined vaccines that are most often based on a recombinant antigen known to possess neutralizing epitopes. Such vaccines can offer improvements in speed, safety and manufacturing process but an inevitable consequence of their high degree of purification is that immunogenicity is reduced through the lack of the innate triggering molecules present in more complex preparations. Targeting recombinant vaccines to antigen presenting cells (APCs) such as dendritic cells however can improve immunogenicity by ensuring that antigen processing is as efficient as possible. Immune complexes, one of a number of routes of APC targeting, are mimicked by a recombinant approach, crystallizable fragment (Fc) fusion proteins, in which the target immunogen is linked directly to an antibody effector domain capable of interaction with receptors, FcR, on the APC cell surface. A number of virus Fc fusion proteins have been expressed in insect cells using the baculovirus expression system and shown to be efficiently produced and purified. Their use for immunization next to non-Fc tagged equivalents shows that they are powerfully immunogenic in the absence of added adjuvant and that immune stimulation is the result of the Fc-FcR interaction."
7582,TLR Signaling and Tumour-Associated Macrophages,"The role that Toll-like receptor (TLR) signaling may have in stimulating macrophages to become tumor promoting is not yet clearly defined. However, given the role macrophages play in restoring tissue homeostasis such as in the tissue repair response, it is likely that tumor-induced TLR signaling provides macrophages with signals of persistent injury. In this chapter, we review the molecular determinants of TLR signaling, the role TLR signaling plays in infection, wound healing, and tumorigenesis and discuss how TLR signaling in tumor-associated macrophages may result in tumor progression."
7583,Methods for Testing Immunological Factors,"Hypersensitivity reactions can be elicited by various factors: either immunologically induced, i.e., allergic reactions to natural or synthetic compounds mediated by IgE, or non-immunologically induced, i.e., activation of mediator release from cells through direct contact, without the induction of, or the mediation through immune responses. Mediators responsible for hypersensitivity reactions are released from mast cells. An important preformed mediator of allergic reactions found in these cells is histamine. Specific allergens or the calcium ionophore 48/80 induce release of histamine from mast cells. The histamine concentration can be determined with the o-phthalaldehyde reaction."
7584,Blastomycosis in Mammals,"Blastomycosis is a serious fungal disease of dogs, humans, and occasionally other mammals caused by geographically restricted, thermally dimorphic Blastomyces species. Blastomycosis is primarily a canine disease, with approximately ten dogs diagnosed for every human case. Dogs also develop disease more rapidly, thus becoming sentinels for possible human disease. Human and canine blastomycosis may differ according to epidemiology/epizoology, clinical features, performance and use of diagnostics, and management."
7585,Power Shifts in Global Health Diplomacy and New Models of Development: South–South Cooperation,"South–South cooperation represents an alternative ideal to the model of rich northern countries providing aid to the poor countries of the southern hemisphere. It offers the prospect of mutual advantages for developing and emerging countries as well as a stronger voice in global diplomacy on social and economic issues. This chapter sets out to provide a balanced view of opportunities and challenges of South–South cooperation, outlining pertinent questions that emerge from this new dynamic of global governance. In the following sections, we briefly outline the history of South–South cooperation and describe its main mechanism and its application to health. We then discuss the paradigm shift from the former bipolar system during the Cold War to today’s global multipolar system. We demonstrate how the consolidation of multipolarity is particularly reflected in the (re)formation of regional blocks, notably in terms of their spheres of coordination and their engagement in different South–South cooperation mechanisms. The African Union (AU), the Association of Southeast Asian Nations (ASEAN), and the Union of South American Nations (UNASUR in its official Spanish acronym) serve as key examples to illustrate both the current state of South–South cooperation and emerging challenges that need to be addressed if South–South cooperation is to be effective and viable in the long term."
7586,New Concepts and Emerging Issues in Sepsis,"Severe sepsis and septic shock are manifestations of the host's immune uncontrolled response to infection. The term sepsis is a poorly defined, but commonly used term in the medical literature, and it is derived from the Greek word “Sépsis” meaning decay. Sepsis is best defined as a life-threatening condition or complex caused by overwhelming inflammatory response to infection associated with dysregulation of the body's immune mechanism. Sepsis is the leading cause of death in critically ill patients in most intensive care units (ICUs). It has been estimated that in the United States sepsis develops in 750,000 people annually, and more then 210,000 of those die(1,2)! Infants and children in >42,000 cases of severe sepsis occur annually in the United States and millions worldwide.(2) The incidence of septicemia and sepsis have been increasing in the past 3 decades in many countries because of several factors, including longer lifespan with a greater population of the elderly; treatment with immunosuppressives with a greater number of subjects with organ transplantations and cancers; use of invasive and novel treatment with prosthesis, long-term or permanent catheters; and the expanding acquired immunodeficiency syndrome (AIDS) epidemic. In national hospital discharge surveys in the United States, the incidence of septicemia had increased from 73.6 per 100,000 patients in 1979 to 175.9 per 100,000 patients in 1987.(3) Surveys in the United States and Europe have estimated that severe sepsis accounts for 2–11& of all admission to hospital or ICUs.(1) Observational studies indicate that 30–50& of the cases are admitted through the emergency department, rather than developing in hospitals.(4,5) The incidence of sepsis appears to continue to increase by 8.7& annually (with an adjusted rate of increase of nearly 300& from 1979 to 2000),(6) but may be greater in the United States (US) with an incidence of 240–300 per 100,000 populations, compared to some European countries (Austria, Germany) with rates of 54–116 per 100,000 population.(7) Despite progress in our understanding of the pathophysiology of sepsis, the mortality rate is still high (in those with severe sepsis and septic shock). Although the mortality rate overall has fallen in the United States from 27.8& to 17.9& in septic patients over 2 decades, the mortality rate was 30& in those with any organ failure and 70& in those with multiple organ failure.(6) Patients with infections and severe sepsis require prolonged stay in ICU and hospital, resulting in increase health care costs. Estimates of direct costs per sepsis patient in the United States are about $50,000 whereas European costs are lower, $26,450–33,350.(7) Thus a crude estimate of the direct annual cost of severe sepsis in the United States is about $17.0 billion.(1)"
7587,Coronavirus Receptors,"The major receptor for murine coronavirus, mouse hepatitis virus (MHV), is identified as a protein, cell-adhesion molecule 1 in the carcinoembryonic antigen family (CEACAM1), which is classified in the immunoglobulin superfamily. There are four CEACAM1 isoforms, with either four or two ectodomains, resulting from an alternative splicing mechanism. CEACAM1 is expressed on the epithelium and in endothelial cells of a variety of tissues and hemopoietic cells, and functions as a homophilic and heterophilic adhesion molecule. It is used as a receptor for some bacteria as well. The N terminal domain participates in mediating homophilic adhesion. This domain is also responsible for binding to the MHV spike (S) protein; the CC’ face protruding in this domain interacts with an N terminal region of the S protein composed of 330 amino acids (called S1N330). The binding of CEACAM1 with MHV S protein induces S protein conformational changes and converts fusion-negative S protein to a fusion-positive form. The allelic forms of CEACAM1 found among mouse strains are thought to be an important determinant for mouse susceptibility to MHV."
7588,Travel in a small world,
7589,Food Security in an Insecure Future,"Food security in the Middle East is directly affected by a challenging combination of ongoing destructive conflicts, a global economic downturn, widespread poverty, high population growth, corruption, intolerance, and the potentially damaging consequences of climate change. Many Arab countries demonstrate nearly all the features of those countries classified as poor, less developed, or failing to achieve the eight Millennium Goals. Even the economies of the richer oil-exporting countries in the Region have been seriously damaged by the downturn in oil and gas prices as new sources come on stream elsewhere and demand falls as a result of renewable sources of energy becoming available."
7590,"Structure, Immunopathogenesis and Vaccines Against SARS Coronavirus","A new disease, severe atypical respiratory syndrome (SARS), emerged in China in late 2002 and developed into the first epidemic of the 21st century. The disease was caused by an unknown animal coronavirus (CoV) that had crossed the species barrier through close contact of humans with infected animals, and was identified as the etiological agent for SARS. This new CoV not only became readily transmissible between humans but also was also more pathogenic. The disease spread across the world rapidly due to the air travel, and infected 8096 people and caused 774 deaths in 26 countries on 5 continents. The disease is characterized by flu-like symptoms, including high fever, malaise, cough, diarrhea, and infiltrates visible on chest radiography. The overall mortality was about 10%, but varied profoundly with age; the course of disease seemed to be milder in the pediatric age group and resulted rarely in a fatal outcome, but the mortality in the elderly was as high as 50%. Aggressive quarantine measures taken by the health authorities have successfully contained and terminated the disease transmission. As a result there are no SARS cases recorded recently. Nevertheless there is a possibility that the disease may emerge in the population with high vigor. Significant progress has been made in understanding the disease biology, pathogenesis, development of animal models, and design and evaluation of different vaccines, and these are the focus of this chapter."
7591,Traveler to Uganda,"A 25-year-old, otherwise healthy woman traveled to Uganda. Two weeks after her return, she complained of dyspnea on exertion and cough. Several people who traveled with her displayed similar symptoms, and she suspected that she had an infection."
7592,Pneumonia,"Hospital-acquired pneumonia (HAP) is usually caused by bacterial, viral, or fungal pathogens that occur ≥48 h after hospital admission.(1,2) Overall, more than 80% of HAP episodes are related to invasive airway management (in patients with endotracheal intubation or tracheostomy) with mechanical ventilation, which is known as ventilator-associated pneumonia (VAP).(3) VAP is defined as pneumonia developing more than 48 h after intubation and mechanical ventilation. Healthcare-associated pneumonia (HCAP) is part of the continuum of pneumonia, which includes patients who were hospitalized in an acute-care hospital for ≥2 days within 90 days of the infection; resided in a long-term care facility; received recent intravenous antibiotic therapy, chemotherapy, or wound care within the past 30 days of the current infection; or attended a hospital or hemodialysis clinic.(1,2) Although this document focuses more on HAP and VAP, many of the principles are also relevant to the management of HCAP. HAP, VAP, and HCAP are the second most common nosocomial infections after urinary tract infection, but are the leading causes of mortality due to hospital-acquired infections.(4,5)"
7593,Epidemiology and Etiology of Mental Retardation,"Mental retardation (MR) is a manifestation of a heterogeneous set of impairments and conditions that result in cognitive limitation. It is a condition of medical, educational, and social importance. Physicians identify profound, severe, and moderate MR but rarely diagnose mild MR unless it is associated with a genetic or medical syndrome. From a medical perspective, the quest for etiology and the possibility of medical or surgical intervention to minimize deterioration are paramount. Educators, on the other hand are less concerned with causation than with academic achievement and school success. The majority of cases of mild MR is identified in school settings. Finally, the public uses the label to describe poor adaptive skills. Adults with MR who hold jobs, live independently, and participate in society are not always described as having MR. Thus some individuals characterized in childhood or adolescence as having mild MR become indistinguishable from the general population in adulthood."
7594,Toxicity Evaluation and Human Health Risk Assessment of Surface and Ground Water Contaminated by Recycled Hazardous Waste Materials,"Prior to the 1970s, principles involving the fate and transport of hazardous chemicals from either hazardous waste spills or landfills into ground water and/or surface water were not fully understood. In addition, national guidance on proper waste disposal techniques was not well developed. As a result, there were many instances where hazardous waste was not disposed of properly, such as the Love Canal environmental pollution incident. This incident led to the passage of the Resource Conservation and Recovery Act (RCRA) of 1976. This act gave the United States Environmental Protection Agency regulatory control of all stages of the hazardous waste management cycle. Presently, numerous federal agencies provide guidance on methods and approaches used to evaluate potential health effects and assess risks from contaminated source media, i.e., soil, air, and water. These agencies also establish standards of exposure or health benchmark values in the different media, which are not expected to produce environmental or human health impacts. The risk assessment methodology is used by various regulatory agencies using the following steps: i) hazard identification; ii) dose-response (quantitative) assessment; iii) exposure assessment; iv) risk characterization. The overall objectives of risk assessment are to balance risks and benefits; to set target levels; to set priorities for program activities at regulatory agencies, industrial or commercial facilities, or environmental and consumer organizations; and to estimate residual risks and extent of risk reduction. The chapter will provide information on the concepts used in estimating risk and hazard due to exposure to ground and surface waters contaminated from the recycling of hazardous waste and/or hazardous waste materials for each of the steps in the risk assessment process. Moreover, this chapter will provide examples of contaminated water exposure pathway calculations as well as provide information on current guidelines, databases, and resources such as current drinking water standards, health advisories, and ambient water quality criteria. Finally, specific examples of contaminants released from recycled hazardous waste materials and case studies evaluating the human health effects due to contamination of ground and surface waters from recycled hazardous waste materials will be provided and discussed."
7595,Case Study – Greece,"Biological terrorism and the need for biological defence is a relatively new concept for Greece. Although defence against weaponized pathogens was part of CBRN training in the military, it was the 9/11 massacre followed by the anthrax letters horror that triggered a more active involvement of the Greek public health sector. In that historical moment a third bullet was added to the already existing disease outbreak classification – naturally, accidental and now deliberate. These incidents and the subsequent 2004 Olympic Games in Athens drove the Greek government to focus on biodefence and revise existing civil emergency planning by inclusion of new emerging threats."
7596,Cryptosporidiosis in Farmed Animals,"Cryptosporidiosis was first identified as a disease of veterinary, rather than human medical, importance, and infection of farmed animals with different species of Cryptosporidium continues to be of veterinary clinical concern. This chapter provides insights into Cryptosporidium infection in a range of farmed animals – cattle, sheep, goats, pigs, cervids, camelids, rabbits, water buffalo and poultry – presenting not only an updated overview of the infection in these animals, but also information on clinical disease, infection dynamics and zoonotic potential. Although extensive data have been accrued on, for example, Cryptosporidium parvum infection in calves, and calf cryptosporidiosis continues to be a major veterinary concern especially in temperate regions, there remains a paucity of data for other farmed animals, despite Cryptosporidium infection causing significant clinical disease and also, for some species, with the potential for transmission of infection to people, either directly or indirectly."
7597,Acute Exacerbation of Idiopathic Pulmonary Fibrosis,"Acute exacerbation (AEx) of idiopathic pulmonary fibrosis (IPF) is a clinically important complication of IPF that carries a high morbidity and mortality. In the last decade we have learned much about this event, but there are many remaining questions: What is it? Why does it happen? How can we prevent it? How can we treat it? This chapter attempts to summarize and update our current understanding of the epidemiology, etiology, and management of acute exacerbation of IPF and point out areas where additional data are needed."
7598,The Role of Angiotensin–(1-7) in Cancer,"The rationale to investigate the role of angiotensin-(1-7) [Ang-(1-7)] in cancer relies on the fact that the heptapeptide inhibits the growth of several cell lines. The first studies showed that Ang-(1-7) accelerated hematopoietic recovery in the peripheral blood and bone marrow after chemotherapy and inhibits lung cancer cell growth through the activation of Mas receptor. In this chapter, we summarize studies on the role of Ang-(1-7) in different types of cancer, especially lung, breast, prostate, hepatocellular cancers and in gliobalstoma multiforme (GBM). The antitumor effect of Ang-(1-7) was due to reduction of angiogenesis, cancer-associated fibrosis, osteoclastogenesis, tumor-induced inflammation, and metastasis as well as inhibition of cancer cell growth and proliferation. In clinical trials, Ang-(1-7) was well tolerated with limited toxic or quality-of-life side effects and showed clinical benefit in cancer patients with solid tumors. Further clinical trials are needed to confirm safety, to determine doses and clinical indications."
7599,"Die Ökologie des Menschen: Bevölkerungswachstum, Krankheiten und Versorgung mit Nahrung","In diesem Kapitel werden wir erörtern, wie wir mithilfe der Ökologie besser verstehen können, welche Probleme das menschliche Bevölkerungswachstums, Krankheiten, die Landwirtschaft und der Ressourcenverbrauch mit sich bringen. Selbstverständlich hat alleine schon das Wachstum der menschlichen Bevölkerung Auswirkungen auf die Umwelt und die natürlichen Ökosystemfunktionen, genauso wesentlich sind aber der beträchtliche Anstieg des Pro-Kopf-Verbrauchs und der diesem zugrunde liegende stetige Ausbau neuer Technologien (Abb. 14.1). In der ersten Hälfte des 20. Jahrhunderts ist die Weltbevölkerung um 40 % angewachsen – von 1,8 auf 2,5 Mrd. Menschen. Seither hat sich Bevölkerung beinahe verdreifacht auf über 7 Mrd. Menschen. Das globale Bruttoinlandsprodukt (engl. gross domestic production) ist in der ersten Hälfte des 20. Jahrhunderts um 75 % angestiegen – von 3 auf 5,3 Bio. US-Dollar – und seitdem sogar um mehr als das Zehnfache auf 55 Bio. US-Dollar. Welche Konsequenzen hat dieser Wohlstand? Der Verbrauch von Nahrung, Energie und materiellen Gütern hat erheblich zugenommen – mit entsprechend gravierenden Folgen auf lokaler und globaler Ebene. Die Ökologie kann als Wissenschaft dazu beitragen, diese Folgen besser zu verstehen und Möglichkeiten für einen nachhaltigeren Fortschritt zu finden."
7600,Severe Infections in the Returning Traveler,"The ease of air travel has made spread of infectious agents a global problem. There are a multitude of tropical diseases ranging from benign viral illnesses to highly contagious and life-threatening diseases and it is important to take a detailed clinical and travel history from the ill returning traveller, especially in the fi rst 4 weeks of return."
7601,Adverse Transfusion Reactions in Critically Ill Patients,"Although transfusion therapy in the past 30 years has achieved high levels of safety, severe adverse reactions can still complicate a red blood cell, plasma, or platelet transfusion. Adverse events can be either of infectious nature (Infectious Adverse Reactions to Transfusion–IARTs) or noninfectious (NIARTs). The former are due to viruses, bacteria, or protozoa present in the transfused component. Medical doctors faced with an infectious disease in a hospitalized patient should always collect an accurate clinical history that must include transfusion of blood components and take into consideration that the viral/bacterial/protozoan infection could be related to a transfusion event. If a transfusion-transmitted infection is suspected, the clinician must contact the transfusion center that will provide a look-back of the blood products and a follow-up of the involved donors. NIARTs may be of immunological and nonimmunological nature. This chapter provides an overview of pathogenesis, presentation, therapy, and prevention of the main NIARTs. Finally, organizational measures for the management of NIARTs are presented, in order to ensure the highest possible level of safety for the patients."
7602,Autoimmune Encephalitis in the Intensive Care Unit,"Autoimmune encephalitis is a rapid, progressive encephalopathy due to an autoimmune response directed against the brain parenchyma. It is associated with significant morbidity, often necessitating evaluation and treatment in the intensive care unit (ICU). Patient management centers on rapid diagnosis of the autoimmune encephalitis syndrome with careful assessment for other etiologies of acute encephalopathy, the initiation of immunosuppressive therapy, and the management of associated sequelae including status epilepticus, respiratory failure, elevated intracranial pressure, and dysautonomia."
7603,Epitope-Based Immunome-Derived Vaccines: A Strategy for Improved Design and Safety,"Vaccine science has extended beyond genomics to proteomics and has come to also encompass ‘immunomics,’ the study of the universe of pathogen-derived or neoplasm-derived peptides that interface with B and T cells of the host immune system. It has been theorized that effective vaccines can be developed using the minimum essential subset of T cell and B cell epitopes that comprise the ‘immunome.’ Researchers are therefore using bioinformatics sequence analysis tools, epitope-mapping tools, microarrays, and high-throughput immunology assays to discover the minimal essential components of the immunome. When these minimal components, or epitopes, are packaged with adjuvants in an appropriate delivery vehicle, the complete package comprises an epitope-based immunome-derived vaccine. Such vaccines may have a significant advantage over conventional vaccines, as the careful selection of the components may diminish undesired side effects such as have been observed with whole pathogen and protein subunit vaccines. This chapter will review the pre-clinical and anticipated clinical development of computer-driven vaccine design and the validation of epitope-based immunome-derived vaccines in animal models; it will also include an overview of heterologous immunity and other emerging issues that will need to be addressed by vaccines of all types in the future."
7604,1 Zorgvuldig en verantwoord handelen in de basiszorg,"In dit hoofdstuk besteden we aandacht aan zorgvuldig en verantwoord handelen, veiligheid, vrijheidsbeperkende maatregelen, hygiëne en infectiepreventie en ergonomisch werken. Deze belangrijke onderwerpen zijn van toepassing op zorgsituaties van de gezondheidspatronen van Gordon die in de diverse hoofdstukken aan de orde komen. Kennis hiervan is van belang voor de basisverpleegkunde."
7605,Norovirus and Other Viral Gastroenteritis,"New and old entero-pathogenic viruses are increasing in the society and in the healthcare, like the Calicivirus family (Norovirus, Sapovirus, Astrovirus), Reovirus family (Rotavirus) (especially infant, toddler and elderly) and rarely other viral types such as adenovirus (especially serotype 40, 41), bocavirus, parechovirus, enterovirus and a variety of other types. In all types of gastroenteritis, infection prevention measures are performed as with norovirus, described below. The following chapter is focused on practical measures to detect and prevent transmission of entero-pathogenic viruses in healthcare institutions."
7606,Supply Chain Risk Management: A Neural Network Approach,"Effective supply chain risk management (Hallikas et al. 2002; Harland et al. 2003; Henke et al. 2006) requires the identification, assessment and monetization of risks and disruptions, as well as the determination of the probability of their occurrence and the development of alternative action plans in case of disruptions (cf. Zsidisin 2003; Zsidisin et al. 2004; Zsidisin et al. 2000; Vidal a. Goetschalckx, 2000). Companies traditionally use multiple sources for material procurement and/or hold safety stocks to avoid vulnerability. However, these strategies can negatively impact the supply chain performance, leading to higher purchase and logistics costs. The aim of this chapter is to illustrate how the implementation of the supply chain risk management concept can be improved by using a neural network approach."
7607,Automated Knowledge Extraction from Internet for a Crisis Communication Portal,"This paper describes the development of an Automated Knowledge Extraction Agent (AKEA) which was designed to acquire online news and document from the internet for the establishment of a knowledge based crisis communication portal. It was recognized that in times of crisis, an effective communication mechanism is essential to maintain peace and calmness in the community by providing timely and appropriate information. It is proposed that the incorporation of software agents into the crisis communication portal will be capable to send alert news to subscribed users via internet and mobile services. The proposed system consists of crawler, wrapper, name-entity tagger, AIML (Artificial Intelligence Markup language) and an animated character is used in the front-end for human computer communication."
7608,Infectious Disease Epidemiology,"The following chapter intends to give the reader an overview of the current field of applied infectious disease epidemiology. Prevention of disease by breaking the chain of transmission has traditionally been the main purpose of infectious disease epidemiology. While this goal remains the same, the picture of infectious diseases is changing. New pathogens are identified and already known disease agents are changing their behavior. The world population is aging; more people develop underlying disease conditions and are therefore more susceptible to certain infectious diseases or have long term sequelae after being infected."
7609,Chirurgische Infektionen,"Der menschliche Organismus ist von einer unzähligen Menge von Mikroorganismen umgeben. Dringen diese Krankheitserreger in uns ein, dann laufen Wechselbeziehungen zwischen dem Eindringling und dem Wirtsorganismus ab. Krankheit resultiert, wenn die Mikroorganismen aufgrund ihrer verschiedenen Determinanten der Pathogenität und Virulenz den Wettlauf mit der Infektabwehr des Makroorganismus gewonnen haben. Mit diesem Problem hatten sich Chirurgen zu allen Zeiten auseinanderzusetzen—und es hat bis heute nicht an Aktualität verloren."
7610,The Antiviral Potential of Host Protease Inhibitors,"The replication of numerous pathogenic viruses depends on host proteases, which therefore emerged as potential antiviral drug targets. In some cases, e.g., for influenza viruses, their function during the viral propagation cycle is relatively well understood, where they cleave and activate viral surface glycoproteins. For other viruses, e.g., Ebola virus, the function of host proteases during replication is still not clear. Host proteases may also contribute to the pathogenicity of virus infection by activating proinflammatory cytokines. For some coronaviruses, human proteases can also serve in a nonproteolytical fashion simply as receptors for virus entry. However, blocking of such protein-protein contacts is challenging, because receptor surfaces are often flat and difficult to address with small molecules. In contrast, many proteases possess well-defined binding pockets. Therefore, they can be considered as well-druggable targets, especially, if they are extracellularly active. The number of their experimental crystal structures is steadily increasing, which is an important prerequisite for a rational structure-based inhibitor design using computational chemistry tools in combination with classical medicinal chemistry approaches. Moreover, host proteases can be considered as stable targets, and their inhibition should prevent rapid resistance developments, which is often observed when addressing viral proteins. Otherwise, the inhibition of host proteases can also affect normal physiological processes leading to a higher probability of side effects and a narrow therapeutic window. Therefore, they should be preferably used in combination therapies with additional antiviral drugs. This strategy should provide a stronger antiviral efficacy, allow to use lower drug doses, and minimize side effects. Despite numerous experimental findings on their antiviral activity, no small-molecule inhibitors of host proteases have been approved for the treatment of virus infections, so far."
7611,"Preventie, gezondheidsbescherming en -bevordering","Preventieve voorzieningen kunnen, voor zover ze bij menselijk gedrag aanknopen, op het individu of op collectiviteiten zijn gericht.(1) Individuele preventie vindt onder andere plaats in het kader van de relatie tussen de patiënt en de behandelend arts, bijvoorbeeld als er een dieet wordt voorgeschreven, een leefadvies of erfelijkheidsadvisering wordt gegeven. Maar ook curatieve activiteiten kunnen een individueel preventief aspect hebben, voor zover ze verergering van ziekte of de gevolgen van een ziekte beogen te voorkomen. Deze individuele preventieve activiteiten blijven in dit hoofdstuk buiten beschouwing."
7612,Microorganisms and Biotic Interactions,"Most ecosystems are populated by a large number of diversified microorganisms, which interact with one another and form complex interaction networks. In addition, some of these microorganisms may colonize the surface or internal parts of plants and animals, thereby providing an additional level of interaction complexity. These microbial relations range from intraspecific to interspecific interactions, and from simple short-term interactions to intricate long-term ones. They have played a key role in the formation of plant and animal kingdoms, often resulting in coevolution; they control the size, activity level, and diversity patterns of microbial communities. Therefore, they modulate trophic networks and biogeochemical cycles, regulate ecosystem productivity, and determine the ecology and health of plant and animal partners. A better understanding of these interactions is needed to develop microbe-based ecological engineering strategies for environmental sustainability and conservation, to improve environment-friendly approaches for feed and food production, and to address health challenges posed by infectious diseases. The main types of biotic interactions are presented: interactions between microorganisms, interactions between microorganisms and plants, and interactions between microorganisms and animals."
7613,Pathogenesis of Fever,"The generation of fever involves the following steps: numerous substances from outside the body, exogenous pyrogens, initiate the fever cycle. Endotoxin of Gram-negative bacteria, with their pyrogenic component lipopolysaccaride, is the most potent exogenous pyrogen. Fever is also a common finding in children without obvious evidence of infection, for example hypersensitivity reaction, autoimmune diseases and malignancy. Exogenous pyrogens initiate fever by inducing host cells (primarily macrophages) to produce and release endogenous pyrogens such as interleukin-1, which has multiple biological functions essential for the immune response. Endogenous pyrogens are transmitted to the hypothalamic thermoregulatory centre, specifically organum vasculosum of the lamina terminalis (OVLT), where they induce synthesis of prostaglandins, of which PGE2 is the most important. These raise the thermostatic set point to initiate the febrile response. The hypothalamic thermoregulatory centre accomplishes heat production by inducing shivering and heat conservation through vasoconstriction. At an established degree, fever is regulated (even at a temperature of over 41.0 °C) and heat production approximates loss, as in health, though at a higher level of the set point. Therefore fever does not climb up relentlessly. In addition to the function as an endogenous pyrogen, IL-1 activates T-lymphocytes to produce various factors, such as INF and IL-2, which are vital for immune response. The production of fever simultaneously with lymphocyte activation constitutes the clearest and strongest evidence in favour of the protective role of fever. The induction of fever results in inhibition of bacterial growth, increased bactericidal effects of neutrophils, production of acute-phase protein synthesis and other physiological changes such as anorexia and somnolence. These changes suggest that fever has an adaptive role in the host’s survival during infection."
7614,The CD95/CD95L Signaling Pathway: A Role in Carcinogenesis,"Apoptosis is a fundamental process contributing to tissue homeostasis, immune response, and development. CD95, also called Fas, is a member of the tumor necrosis factor receptor (TNFR) superfamily. Its ligand, CD95L, was initially detected at the plasma membrane of activated T-lymphocytes and natural killer (NK) cells where it contributes to the elimination of transformed and infected cells. Given its implication in immune homeostasis and immune surveillance combined with the fact that various lineages of malignant cells exhibit loss-of-function mutations, CD95 was initially classified as a tumor suppressor gene. Nonetheless, in different pathophysiological contexts, this receptor is able to transmit non-apoptotic signals and promote inflammation and carcinogenesis. Although the different non-apoptotic signaling pathways (NF-κB, MAPK, and PI3K) triggered by CD95 are known, the initial molecular events leading to these signals, the mechanisms by which the receptor switches from an apoptotic function to an inflammatory role, and, more importantly, the biological functions of these signals remain elusive."
7615,Ultrastructural Telepathology: Remote EM Diagnostic via Internet,"The digital revolution has given rise to new tools in different disciplines of science; much of this new knowledge has been assimilated into different telemedicine applications and also extends the boundaries of pathology, a diagnostic medical discipline. The tissue-based pathologic diagnosis is the gold standard for all subsequent medical procedures - especially surgery and tumour treatment - and electron microscopy, owing to its high-resolution, can provide significant data not discernible by light microscopy to render the correct diagnosis. In case of diagnostic difficulty remote experts can instantly examine pathologic samples directly using an ultrastructural telepathology system: the consulting “second opinion” expert is no longer constrained by problems inherent in preselected images. Growing Internet bandwidth and developing Grid technology foster such interactive telemicroscopy solutions enabling savings of time and resources in healthcare, research and distance teaching."
7616,Terror Medicine: Education and Training,"If a mass casualty incident (MCI) occurs on American territory, the main difficulty with disaster response is not from a lack of resources or volunteers but from a lack of a properly managed disaster plan. In fact, first responders and local healthcare practitioners, and even non-clinical locals rush to the scene and to local healthcare facilities to offer their services or make donations. The presence of so many volunteers and donations can be of great help during a disaster if properly managed. Even before 9/11, hospitals were required to have a disaster plan and ensure that their employees were familiar with it. Very few hospitals, however, actually worked on coordinating their disaster response plans with other hospital facilities, Emergency Medical Services (EMS), or local governmental facilities to offer a united response in case of a disaster.(1) Healthcare institutions therefore had difficulties not only working with other institutions preparing for a disaster but also were often unprepared for managing unexpected resources from the community."
7617,"Fungal, Viral, and Other Oddball Infections and the Immunosuppressed Patient","Infections with fungal and viral pathogens in the surgical intensive care unit (ICU) are not uncommon. Often, however, diagnosis tends to be either delayed or superimposed on bacterial infections. In some scenarios, definitive diagnosis can be challenging and a high index of suspicion is warranted to promptly manage critically ill patients. This approach is critical especially in immunosuppressed patients given their relative vulnerability to a multitude of infectious processes. Although rare, oddball infections with rare viruses and fungi can significantly affect the clinical course and recovery of patients if timely diagnosis is delayed. This chapter highlights important fungal, viral, and rare infections in the context of critically ill and high-risk patients, including the immunosuppressed patients, in the surgical ICU."
7618,Pharmacology of Chloroquine and Hydroxychloroquine,"The 4-aminoquinolines are weak bases that are completely absorbed from the gastrointestinal tract, sequestered in peripheral tissues, metabolized in the liver to pharmacologically active by-products, and excreted via the kidneys and the feces. The parent drugs and metabolites are excreted with a half-life of elimination of approximately 40 days. However, slow release from sequestered stores of the drugs means that after discontinuation, they continue to be released into the plasma for years. Correct dosing is based on the ideal body weight of the patient, which depends on height. The 4AQs diminish autoimmunity without compromising immunity to infections."
7619,Viral Processes by Random Walks on Random Regular Graphs,"We study the SIR epidemic model with infections carried by k particles making independent random walks on a random regular graph. We give a edge-weighted graph reduction of the dynamics of the process that allows us to apply standard results of Erdős–Renyi random graphs on the particle set. In particular, we show how the parameters of the model produce two phase transitions: In the subcritical regime, O(ln k) particles are infected. In the supercritical regime, for a constant C determined by the parameters of the model, Ck get infected with probability C, and O(ln k) get infected with probability (1 − C). Finally, there is a regime in which all k particles are infected. Furthermore, the edge weights give information about when a particle becomes infected. We demonstrate how this can be exploited to determine the completion time of the process by applying a result of Janson on randomly edge weighted graphs."
7620,Trench-Fieber,
7621,Potential Impact of Climate Change on Pandemic Influenza Risk,Health problems related to the environment continue to be a major source of concern all over the world. Society needs to develop measures that will eliminate or considerably reduce hazardous factors from the environment that can result in health risk to humans.
7622,The Age of Transformation,"The world is going through a transformation. We face a number of tremendous societal challenges for which traditional approaches no longer work. Mankind has gone through big changes before: moving from the agricultural economy to the industrial economy, and more recently, into the ‘experience’ economy and the knowledge economy. This chapter explores the paradigm shifts of the past and the present, to set the scene for the rest of the book. Most of all, facing the current societal challenges will require collaboration between profit and non-profit organizations as well as connected individuals, to create meaningful innovations that will guide people and society through the transformation."
7623,Andrographolide,"Andrographolide is a diterpene lactone compound extracted from Andrographis paniculata (Burm. F) Nees, which is commonly used as traditional Chinese medicine. Andrographolide has effects of anti-inflammatory, antibacterial, antivirus, antitumor, and immune regulation and is used in treatment of cardiovascular-cerebrovascular diseases and protection of the liver and gallbladder. Andrographolide water solubility is poor and its bioavailability is low; its pharmacological effects are extensive but weak, so the preparation requirements are strict."
7624,Now and Future Practice,"In the past 11 chapters, we have visited some heroes, diseases, and treatments that are part of the heritage of the healing professions, we have discussed some of the language of medicine and some thoughts of our most erudite predecessors, and we have examined some instances of clinical practice, including a few times when what happened was not what we today would have wished. I hope that the 231 pages that we have traveled together so far have convinced you of the rich and (usually) honorable traditions of medicine. The tales are sometimes epic, at times tragic, sporadically triumphant, and occasionally lamentable. This last chapter suggests some ways that you, as a health professional or informed consumer, will now—I hope—learn more about medicine’s history and lore."
7625,Helminth,"Strongyloides stercoralis, an intestinal nematode commonly known as the human threadworm, affects millions of people worldwide.(1) It is endemic in Southeast Asia, Latin America, sub-Saharan Africa, and parts of the southeastern USA.(2) In the USA, the highest prevalence rates are found in eastern Kentucky and rural Tennessee. A unique feature of Strongyloides stercoralis infection is the occurrence of an autoinfection cycle which permits persistence of the parasite years after the normal host has left an endemic area. In this cycle, the rhabditiform larvae in the duodenojujenal portion of the small intestine transform directly into filariform (infective) larvae. The filariform larvae without leaving the body can reinfect the patient by penetrating the intestinal mucosa. This distinctive characteristic of Strongyloides, to persist and replicate within the host for decades, produces minimal or no symptoms. Immunocompromised patients may develop a fulminant illness due to a unique process in the life cycle of Strongyloides in which there are dramatic increases in the number of filariform larvae. In the hyperinfection syndrome, massive numbers of larvae migrate through the intestinal mucosa and into the lungs (the usual migration pattern) and disseminate to involve other organ systems not ordinarily a part of the life cycle of the parasite. Larvae may be found in the central nervous system, kidneys, liver, and almost any other organ."
7626,Noninvasive Positive-Pressure Ventilation in Patients with Acute Hypoxemic Respiratory Failure and HIV/AIDS,"Pulmonary complications, especially acute respiratory failure (ARF), contribute to morbidity and mortality in immunocompromised patients. The etiology, pathophysiology, and reversibility of lung injury and the severity of ARF are key to the therapeutic response and prognosis for these patients."
7627,Arguing from Ignorance,"It might seem that it can never be rational to argue from a state of ignorance. But this is not the case. Ignorance arguments abound in our everyday thinking such as when we conclude that a train does not stop in York because York is not listed in the timetable. These arguments also tend to be the first line of defence when the safety of food or prescribed medications is called into question. The statement ‘There is no evidence that beef is unsafe’, which is a premise in an ignorance argument, was used so extensively by health officials and government ministers during the BSE epidemic in the UK that it came to be called the mantra of the BSE affair by the public inquiry into the epidemic. A similar ignorance premise is often used to frame the conclusion of systematic reviews into the effectiveness of a particular medical or health intervention. This chapter examines the various purposes for which ignorance arguments are advanced in medicine and health and considers the epistemic conditions under which these arguments are more or less rationally warranted."
7628,"Risico’s, melden en controles","Waar mensen werken worden fouten gemaakt. Ze raken door routine soms hun alertheid kwijt of hebben door tijdgebrek de nodige hygiënische maatregelen overgeslagen. Ook krijgen veel zorgverleners een slecht voorbeeld van collega’s: handen worden slecht gewassen en slecht gedroogd, zo blijkt uit diverse onderzoeken."
7629,Maintenance of Preparedness,"The medical management of patients with highly hazardous communicable diseases (HHCD) will suddenly become important during public health emergencies of international concern but will receive little attention in between those events. It is very important to use those times to maintain and improve the level of preparedness and adjust it to advances in the field. The infrastructure provided needs to be regularly adjusted but also requires intensive maintenance. Every high-level isolation unit (HLIU) needs to plan individually and very precisely what kind of equipment, materials and medications need to be stockpiled and in what amount, in order to be able to provide adequate care. Providing HLIU treatment is a highly qualified and differentiated task, and training efforts should provide a multidisciplinary HLIU team with an intricate training schedule. The medical and psychological aspects of occupational health and safety need to be addressed as well in order to maintain preparedness."
7630,Common Cold and Flu,"Most of the causative agents of the common cold are viruses. The respiratory system consists of an air conduction portion and a respiratory portion. The direct initiating factor of the common cold is low temperature, especially relative coldness. When people feel cold or chilly, vascular constriction around the inlet area of air occurs, resulting in a reduction of mucus secretion containing various antiviral soluble mediators and followed by an explosive increase in the nasal viral flora. A relatively low temperature and dryness are good conditions for viral proliferation and invasion to the body. The first symptom of the common cold is usually a runny nose, followed by a sore throat and/or systemic fever. Acute symptoms of the common cold are usually terminated within 3 days, at the longest 5~7 days. The mortality rate of severe acute respiratory syndrome (SARS) has reached around 10%. A novel swine-origin influenza A (H1N1) virus caused the occurrence of more than 130,000 patients and dead cases of more than 800 people. H5N1 avian influenza showed an extremely high mortality rate, even though its infectivity is low. A new serotype of AI (H7N9) has appeared in some areas of China. Vitamin C can prevent the onset of a cold. Vitamin C can even prevent influenza virus from spreading down from the upper respiratory tract to the lower one. In addition, levels of interferon (IFN) in the bronchoalveolar lavage (BAL) fluid are markedly low in vitamin C-insufficient mice. Inflammatory cells are markedly increased in BAL fluid, providing the immunological evidences that daily supplementation of high-dose vitamin C can prevent influenza infection and that, in extreme case, it can save the life."
7631,Biomaterial and Therapeutic Applications,"Sepsis, a condition in which the bloodstream is fighting a systemic infection, is a major health concern in both developed and developing countries."
7632,Toward Control of Infectious Disease: Ethical Challenges for a Global Effort,"Despite the devastating pandemic of HIV/AIDS that erupted in the early 1980s, despite the failure to eradicate polio and the emergence of resistant forms of tuberculosis that came into focus in the 1990s, and despite newly emerging diseases like Severe Acute Respiratory Syndrome (SARS) in 2003 and the fearsome prospect of human-to-human avian flu, it is nevertheless a time of some excitement over prospects for effective control of much of infectious disease. Funded by national and international governmental and nongovernmental organizations (NGOs), private foundations, and even popular entertainers, large-scale new efforts are under way to address global killers like AIDS, tuberculosis, and malaria, among others. This “marvelous momentum” can be seen as part of a continuing effort from the time of Jenner onward. Extrapolating from this, we explore the notion of a “comprehensive global effort for the eradication, elimination or control of infectious disease,” with particular attention to the ethical issues that arise. This is to “think big” about disease-control efforts that are now often done in piecemeal ways. This chapter identifies five tracks along which such efforts need to be pursued: (1) national and international organizations and the development of collective will; (2) epidemiological and health care infrastructure; (3) scientific development; (4) religious, social, and cultural considerations; (5) legal and social protections for individuals and groups. Each of these poses significant ethical issues which, we argue, should be viewed in a comprehensive way, to ensure that practice, research, and policy in each of these areas understands the person with communicable infectious disease as both victim and (potential) vector."
7633,The Application of Nucleic Acid Amplification Strategies in Theranostics,"Targeting nanoparticles equipped with diagnosis “tools” to malignant cells or tissues for optimal therapy is a popular concept of theranostics. As one of the most reliable and sensitive diagnosis “tools,” nucleic acid detection is of growing practical interest with respect to molecular diagnostics of cancer and other genetic diseases. Particularly, PCR-based and other nucleic acid amplification strategies are most widely used in theranostics. This chapter aims at systematization and critical summarization of the applications of DNA- or RNA-targeted nucleic acid amplification strategies in theranostics."
7634,Bead-Based Flow Cytometric Assays: A Multiplex Assay Platform with Applications in Diagnostic Microbiology,"Researchers have focused on developing specific assays for conclusively identifying and measuring the levels of bacteria, fungi, protozoa, viruses (microbes), and their associated products (biomarkers) that cause disease in humans and animals (Murray et al., 2003). Traditional methods using microscopy and chemical or immunological stains, test cultures with selective media or target cells, or serological assays have been used effectively to identify infectious agents in biological specimens or environmental samples. However, due to increasing veterinary, medical, and public health concerns, faster and more accurate diagnostic tools have been sought. Multiplex array-based assays allow for a range of biomarkers to be rapidly and simultaneously measured within specimens (Robertson and Nicholson, 2005). Recently, multiplex bead-based flow cytometric immunoassays have been developed and applied that show great promise for improving the study, diagnosis, and therapeutic management of infectious diseases (Alvarez-Barrientos et al., 2000; Jani et al., 2002)."
7635,The Role of Receptor for Advanced Glycation Endproducts (RAGE) in Infection,"During evolution, multicellular organisms have developed an impressive arsenal of defense and repair mechanisms to counteract threats such as infection and trauma. Such an inflammatory response begins with the detection of the potential life-threatening event by recognizing so-called danger signals. These signal molecules have been classically divided into: i) Exogenous, pathogen-associated molecular patterns (PAMPs) [1], which are conserved motifs on pathogens that are not found in higher eukaryocytes; and ii) endogenous innate danger molecules, also named damage-associated molecular patterns (DAMPs) or alarmins, which are structurally diverse proteins rapidly released by the host itself during infection or (sterile) tissue damage [2]."
7636,Respiratory Tract and Mediastinum,"Normal cytology, abnormal and atypical cells, non-cellular components, and infectious cell changes are largely described together with benign, malignant, and neuroendocrine lesions regarding exfoliative and aspiration cytology of the lung. A separate section broadly addresses diagnostic findings and differential diagnoses in bronchoalveolar washings. The section ‘Fine needle aspiration biopsy of mediastinal disorders’ covers in particular biopsy techniques, accuracy of liquid-based cytology, and the complex lesions of the thymus gland. Cytodiagnostic algorithms of the major benign and malignant pulmonary and mediastinal lesions and their respective differential diagnoses are additionally presented in synoptic setups."
7637,STICHWORTVERZEICHNIS,
7638,Rapid Detection of Viruses Using Loop-Mediated Isothermal Amplification (LAMP): A Review,"Most of the diseases caused by viral infection are found to be fatal, and the diagnosis is difficult due to confusion with other causative agents. So, a highly efficient molecular-based advance detection technique, i.e., loop-mediated isothermal amplification (LAMP) method, is developed for diagnosis of viral infections by various workers. It is based on amplification of DNA at very low level under isothermal conditions, using a set of four specifically designed primers and a DNA polymerase with strand displacement activity. This technique is found to be superior than most of the molecular techniques like PCR, RT-PCR, and real-time PCR due to its high specificity, sensitivity, and rapidity. Major advantage of LAMP method is its cost-effectiveness as it can be done simply by using water bath or dry bath. Here, in this review information regarding almost all the effective LAMP techniques which is developed so far for diagnosis of numerous viral pathogens is presented."
7639,Infecties van de bovenste luchtwegen,"Luchtweginfecties in het algemeen en infecties van de bovenste luchtwegen in het bijzonder komen wereldwijd zeer veel voor en zijn de voornaamste reden om een arts te consulteren. In de niet-geïndustrialiseerde landen zijn luchtweginfecties bovendien nog steeds de belangrijkste doodsoorzaak op de kinderleeftijd. Infecties van de bovenste luchtwegen worden meestal veroorzaakt door virussen, en ook zijn er bacteriële verwekkers. Deze behoren meestal tot de eigen flora; S. pneumoniae is de belangrijkste. Op klinische gronden kan geen onderscheid worden gemaakt tussen de verschillende verwekkers van bovenste luchtweginfecties. Antibiotische behandeling van bovenste luchtweginfecties is slechts zelden nodig. Etiologische laboratoriumdiagnostiek voor influenza-achtige ziektebeelden is vooral van belang bij risicogroepen en in gezondheidsinstellingen vanwege de beschikbaarheid van antivirale behandeling en eventuele maatregelen ter voorkoming van nosocomiale verspreiding van influenzavirussen. Jaarlijkse griepvaccinatie is geïndiceerd bij risicogroepen ter voorkoming van een ernstig ziektebeloop en bij gezondheidswerkers ter voorkoming van nosocomiale verspreiding. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1117-0_2) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers."
7640,Impfungen,"Bedeutung. Impfungen sind die wichtigsten und kosteneffektivsten Präventivmaßnahmen der modernen Medizin. Mit der breiten Nutzung von Vakzinen hat die Inzidenz der impfpräventablen Infektionskrankheiten in den vergangenen Jahrzehnten weltweit dramatisch abgenommen. Trotz der nachgewiesenen Erfolge sind die Bedenken der Öffentlichkeit gegenüber potenziellen Risiken von Impfstoffen gewachsen und bestimmen heute in hohem Maße Akzeptanz und Nutzung von Impfungen. Öffentliche Impfempfehlungen stellen ein dynamisches Gleichgewicht zwischen Risiken und Vorteilen von Impfungen dar. Unverändert sind Impfungen der sicherste und beste Weg, Gesundheitsvorsorge zu betreiben und Infektionskrankheiten zu kontrollieren."
7641,NIAID International Research Programs: Global Impact,"NIAID conducts and supports a global program of research aimed at improving diagnosis, treatment, and prevention of immunologic, allergic, and emerging infectious diseases. This research has led to new therapies, vaccines, diagnostic tests, and other technologies that have improved the health of millions of people in the United States and around the world (http://www3.niaid.nih.gov/topics/GlobalResearch/default.htm)"
7642,Rule Generation Using NN and GA for SARS-CoV Cleavage Site Prediction,"Cleavage site prediction is an important issue in molecular biology. We present a new method that generates prediction rules for SARS-CoV protease cleavage sites. Our method includes rule extraction from a trained neural network and then enhancing the extracted rules by genetic evolution to improve its quality. Experimental results show that the method could generate new rules for cleavage site prediction, which are more general and accurate than consensus patterns."
7643,White-Collar Crimes and the Fear of Crime: A Review,
7644,Biomarker Development in Chronic Inflammatory Diseases,"Chronic inflammatory diseases, such as inflammatory bowel disease—namely, Crohn’s disease and ulcerative colitis—psoriasis, multiple sclerosis, rheumatoid arthritis, and many others affect millions of people worldwide, causing a high burden of disease, socioeconomic impact, and healthcare cost. These diseases have common features including autoimmune pathogenesis and frequent co morbidity. The treatment of these chronic inflammatory diseases usually requires long-term immunosuppressive therapies with undesirable side effects. The future of chronic inflammatory disease prevention, detection, and treatment will be greatly influenced by the use of more effective biomarkers with enhanced performance. Given the practical issues of collecting tissue samples in inflammatory diseases, biomarkers derived from body fluids have great potential for optimized patient management through the circumvention of the abovementioned limitations. In this chapter, peripheral blood, urine, and cerebrospinal fluid biomarkers used in chronic inflammatory conditions are reviewed. In detail, this chapter reviews biomarkers to fore used or emerging to be used in patients with chronic inflammatory conditions. Those include inflammatory bowel diseases, chronic inflammatory conditions of the liver, biliary tract, pancreas, psoriasis, atopic disease, inflammatory skin diseases, rheumatic diseases, demyelination, and also the chronic inflammatory component of various other diseases in general medicine—including diabetes, cardiovascular disease, renal disease, and chronic obstructive pulmonary disease. Development of personalized medicine is closely linked to biomarkers, which may serve as the basis for diagnosis, drug discovery, and monitoring of diseases."
7645,Sepsis,"The management of the child with sepsis represents the sine qua non of pediatric critical care medicine. Overwhelming sepsis and septic shock often manifest with concurrent derangements of cardiovascular function, intravascular volume status, respiratory function, immune regulation, renal function, coagulation, hepatic function, and metabolic function – sepsis literally affects every organ system to some degree. The degree to which any of these derangements are manifest in a given child is highly variable and influenced by multiple host and pathogen factors, including the child’s developmental stage, the presence or absence of co-morbidities, the host’s immune/inflammatory state, the host’s genetic background, and the specific pathogens involved. These factors combine, in turn, to profoundly influence the ultimate outcome. Successful management of critically ill children depends upon early recognition, early treatment with antibiotics, and early reversal of shock."
7646,Le infezioni da Papillomavirus,"Evidenze epidemiologiche molecolari indicano che il DNA di almeno uno dei 15 tipi oncogeni di Papillomavirus umano (HPV) viene rilevato virtualmente in tutte le lesioni carcinomatose e che l’infezione persistente da HPV ad alto-rischio è la causa necessaria ma non sufficiente per il processo carcinogenico. Sebbene il rilevamento di DNA di HPV in tutte le lesioni cancerose non sia prova definitiva del suo ruolo causale nella carcinogenesi, è stato valutato che il rischio relativo di cancro associato con i genotipi oncogeni di HPV è addirittura più alto del rischio di carcinoma polmonare associato con il fumo. In natura sono stati identificati più di 120 genotipi di HPV, di cui circa 40 possono infettare il tratto genitale; di questi, 15 sono fortemente associati al cancro della cervice. Il meccanismo biologico di trasformazione maligna è stato ben caratterizzato. In sintesi, il potenziale oncogenico di questi virus è legato ai geni virali E6 e E7. La oncoproteina virale E6 inizia la degradazione della proteina anti-oncogenica (p53), mentre la oncoproteina virale E7 porta all’inattivazione di un’altra proteina di soppressione tumorale (RB). Questi effetti sinergici sono passaggi importanti della carcinogenesi in quanto danno luogo alla perdita del controllo del ciclo cellulare. Sulla base della loro presenza in lesioni benigne o maligne della cervice, questi virus sono stati definiti come HPVs a basso, medio od alto rischio oncogeno. Gli HPV vengono tipicamente trasmessi nelle donne entro pochi anni dall’inizio della loro attività sessuale e, prevalentemente, sono causa di infezioni transitorie e clinicamente irrilevanti che nella maggior parte dei casi si risolvono spontaneamente senza alcuna conseguenza patologica e con cambiamenti citologici temporanei. Fortunatamente, a seguito dell’infezione primaria, soltanto una minoranza di donne mantiene una infezione persistente (circa il 10% dopo 5 anni) ed è questo gruppo più piccolo che ha un sostanziale rischio (più del 50%) di sviluppare lesioni precancerose ad alta malignità (HSIL) o, in assenza di uno screening efficace, il carcinoma della cervice (CC) uterina."
7647,Chronic Lung Pathologies That Require Repair and Regeneration,"Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, are a major cause of mortality worldwide. With the increasing incidence with ageing, the full impact of these diseases is yet to be realised. For most chronic lung diseases there are limited treatments options, with the existing approaches mainly addressing symptom relief. Little progress has been made, in recent years, in the development of new therapeutic strategies for managing these burdensome pathologies. There is an urgent need to increase our understanding of the mechanisms underlying these diseases. Endogenous progenitor cells (stem cells) have been recognised in many organs, including the lungs where they are suggested to maintain a population of cells that are able to facilitate the endogenous repair processes. Emerging knowledge of how these repair processes are disrupted in chronic lung diseases and the potential to capitalise upon the regenerative capacity of stem cell populations raise the hopes of the field worldwide for innovative treatment approaches for these devastating diseases in the future. This chapter outlines the series of diseases that may benefit from these emerging new therapeutic outlooks."
7648,Approach to the Febrile Patient in the Intensive Care Unit,"Fever occurs in approximately one-third of all medical patients during their hospital stay and in more than 90% of critically ill patients with severe sepsis [1]. According to the Society of Critical Care Medicine (SCCM) and the Infectious Diseases Society of America (IDSA), a temperature above 38.3°C (101°F) should be considered as fever necessitating a clinical assessment. The mean body temperature in healthy individuals is 36.8°C (98.2 °F), with a range of 35.6°C (96°F) to 38.2°C (100.8 °F) and a slight diurnal/circadian variation of between 0.5 and 1.0°C [2, 3]. Patients with elevated temperature in the ICU are in a closed monitoring system undergoing accurate and reproducible measurements using a variety of methods (instruments and techniques) at different body sites (Table 1.1) [4]."
7649,"The Way Forward: Prevention, Treatment and Human Rights","There now is a considerable body of evidence to support the view that an effective HIV/AIDS strategy integrates prevention, treatment and human rights. In this chapter, we emphasize the importance of each of these aspects and draw upon the conclusions reached in previous chapters to map out the future of HIV/AIDS. While medicine and science have a crucial role to play in addressing pandemics, whether slow-moving (like HIV/AIDS) or fast-moving (like influenza), the social, legal, political, financial and economic ramifications of pandemics can not be ignored. Well-considered social, legal, political and financial strategies are essential in order to address any pandemic effectively."
7650,Introduction: Human Security Development and the Future of East Asia,"For more than a decade, a group of North Koreans have languished in a legal gray zone: Despite being prima facie refugees, they have not been accorded refugee status in accordance with international law. These North Koreans, most famously personified by their daring escapades into foreign consulates in China, are not unknown to the authorities. But the United Nations High Commission for Refugees (UNHCR) and the governments of China, Russia, and the two Koreas have instead chosen to pursue a less politically messy agenda of sweeping it under the proverbial carpet. Despite the adoption of the human security agenda by the international community, these refugees who have fled North Korea to escape the widespread starvation and poverty brought about by large-scale famines since the 1990s seem to have fallen through the gaps. This chapter examines the efficacy, or the lack thereof, of the human security paradigm in the nexus between politics and refugees. Any attempt to resolve the matter can only begin with a re-conceptualization of the entire security paradigm, including the adoption of “sustainable security,” and to perceive human security as an ethos to pave way for a more constructive political culture of reconciliation instead of recrimination."
7651,Infektionsimmunologie,"Im Laufe der Entwicklung der Lebewesen traten die Organismen gegeneinander in Konkurrenz und entdeckten andere Spezies als eigene Lebensgrundlage oder Nahrung. Bei höheren Lebewesen sehen wir dies als selbstverständlich an und teilen Sie in Fleisch- und Pflanzenfresser ein. Bei niederen Lebewesen bezeichnen wir dies jedoch als pathogene Eigenschaft oder als parasitäre Lebensweise, wenn wir ihnen als Nahrungsgrundlage dienen (Abb. 8.1). Zur Abwehr der Krankheitserreger entwickelten alle höheren Lebewesen ein Immunsystem, um das Fortbestehen der Spezies zu garantieren. Je weiter sich die Lebewesen entwickelt haben, desto höher hat sich auch das Immunsystem in einer Coevolution in Konkurrenz zu den Erregern entwickelt. Da das Immunsystem in der Evolution zur Infektionsabwehr entstanden ist, leiten sich seine übrigen physiologischen und pathophysiologischen Mechanismen von denen der Infektionsabwehr ab."
7652,Text Mining the Biomedical Literature for Identification of Potential Virus/Bacterium as Bio-Terrorism Weapons,"There are some viruses and bacteria that have been identified as bioterrorism weapons. However, there are a lot other viruses and bacteria that can be potential bioterrorism weapons. A system that can automatically suggest potential bioterrorism weapons will help laypeople to discover these suspicious viruses and bacteria. In this paper we apply instance-based learning & text mining approach to identify candidate viruses and bacteria as potential bio-terrorism weapons from biomedical literature. We first take text mining approach to identify topical terms of existed viruses (bacteria) from PubMed separately. Then, we apply a text mining method bridge these terms as instances with the remaining viruses (bacteria) and thus to discover how much these terms describe the remaining viruses (bacteria). In the end, we build an algorithm to rank all remaining viruses (bacteria). We suspect that the higher the ranking of the virus (bacterium) is, the more suspicious they will be potential bio-terrorism weapon. Our findings are intended as a guide to the virus and bacterium literature to support further studies that might then lead to appropriate defense and public health measures."
7653,Discovery of the Proprotein Convertases and their Inhibitors,"The members of the convertase family play a central role in the processing of various protein precursors ranging from hormones and growth factors to viral envelope proteins and bacterial toxins. The proteolysis of these precursors that occurs at basic residues is mediated by the proprotein convertases (PCs), namely: PC1, PC2, Furin, PACE4, PC4, PC5 and PC7. The proteolysis at non-basic residues is performed by subtilisin/kexin-like isozyme-1 (S1P/SKI-1) and the newly identified neural apoptosis-regulated convertase-1 (NARC-1/PCSK9). These proteases have key roles in many physiological processes and various pathologies including cancer, obesity, diabetes, neurodegenerative diseases and autosomal dominant hypercholesterolermia. Here we summarize the discovery of the proprotein convertases and their inhibitors, discuss their properties, roles, resemblance and differences"
7654,Cyanine Dye–Nucleic Acid Interactions,"Cyanine dyes are widely used in biotechnology due to their ability to form fluorescent complexes with nucleic acids. This chapter describes how the structure of the dye determines the mode in which it binds to nucleic acids as well as the fluorescence properties of the resulting complexes. Related dyes, such as hemicyanines and styryl dyes, are briefly described as well. In addition, covalent conjugates of cyanines with nucleic acids or with nucleic acid-binding ligands allow fluorescent labeling and probing of DNA/RNA structure and function. Several examples of different types of conjugates and their applications are described."
7655,T Cells in Viral Infections: The Myriad Flavours of Antiviral Immunity,"Viral diseases are a major cause of morbidity and mortality and result in a significant public health burden. T lymphocytes first identified in the chordate lineage and constitute a highly sophisticated branch of adaptive immune system. Apart from B cells, it is the only cell type that exhibits antigenic specificities; achieved by gene rearrangement. T cells are unique with respect to diversity of their subsets, which have distinct effector specificities, proliferative abilities, memory generation, and life span. T cells are impactful in viral infections by virtue of their capability to combat intracellular pathogens. The effector functions of T cells are mediated through cytokines/chemokines and by direct cytotoxicity of infected cells. T cell response can be beneficial or detrimental to host; prognosis depending on qualitative and quantitative differences in the response. Persistent viral infections are associated with functionally suboptimal, exhausted T cell responses, which are unable to clear virus. Specific subsets such as regulatory T cells (Tregs) dampen antiviral responses; thereby favouring viral persistence. However, Tregs protect the host from immunopathology by limiting perpetual inflammation. Certain other subsets such as Th17 cells may contribute to autoimmune component of viral infections. The importance of T cells is highlighted by the fact that modern vaccination and therapeutic approaches focus on modulating T cell frequencies and effector functions. This chapter emphasises the understanding how T cells influence outcomes of viral infections, modern vaccination and therapeutic strategies with thrust on T cell biology."
7656,Environment Problems in the Coastal Zone,Understanding coastal dynamics and natural history is important in developing a better understanding of natural systems and human impacts in coastal zones. This chapter outlines the characteristics of sedimentary environments in coastal zones which must be understood in order to manage and preserve coastal environments.
7657,Dietary Phytochemicals Target Cancer Stem Cells for Cancer Chemoprevention,"Cancer is a multistep process involving genetic and epigenetic changes in the somatic genome. Genetic mutations as well as environmental factors lead to the initiation, promotion, and progression of cancer. Cancer progression ends in tumor metastasis to distant sites, and metastasis is the major reason for cancer patient deaths. Recent experimental evidence suggests the pivotal role of cancer stem cells. A tumor is heterogeneous and composed of different cell types. The cancer stem cells in the tumor have the capacity both to self-renew and differentiate to sustain the tumor. Features of cancer stem cells are described in this review, with an emphasis on the role that dietary phytochemicals may play in cancer chemoprevention. Ingredients in the diet can inhibit cancer cells and cancer stem cells. These compounds include curcumin from curry, epigallocatechin gallate from green tea, resveratrol from red wine, genistein from soy, sulforaphane from broccoli, and many others. Current research findings advocate the beneficial effects towards cancer chemoprevention via uptake of a combination of different dietary phytochemicals."
7658,Febrile Neutropenia in Transplant Recipients,"Febrile neutropenic patients are at increased risk of developing infections. During the initial stages of neutropenia, most of these infections are bacterial. The spectrum of bacterial infections depends to some extent on whether or not patients receive antimicrobial prophylaxis when neutropenic. Since most transplant recipients do, Gram-positive organisms predominate, due to the fact prophylaxis is directed primarily against Gram-negative organisms. Staphylococcus species (often methicillin-resistant), Streptococcus species (viridans group streptococci, beta-hemolytic streptococci), and Enterococcus species (including vancomycin-resistant strains) are isolated most often. Therefore, potent empiric Gram-positive coverage is recommended by many in this setting. Escherichia coli, Pseudomonas aeruginosa, and Klebsiella species are the most common Gram-negative pathogens isolated. Non-fermentative Gram-negative bacilli (Stenotrophomonas maltophilia, Acinetobacter species) are emerging as important pathogens. Many of these organisms acquire multiple mechanisms of resistance that render them multidrug resistant. The administration of prompt, broad-spectrum, empiric, antimicrobial therapy is essential and is generally based on local epidemiology and susceptibility/resistance patterns. Response rate to the initial regimen is generally in the range of 75–85%. Fungal infections develop in patients with prolonged neutropenia (greater than 7–10 days). Candida species and Aspergillus species are the predominant fungal pathogens, although many other fungi are opportunistic pathogens in this setting. Fungal infections are seldom documented microbiologically or on histopathology, and the administration of empiric antifungal therapy, when such infections are suspected, is the norm. Therapy is often prolonged, and outcomes are still suboptimal. The importance of infection control and antimicrobial stewardship cannot be overemphasized."
7659,Acquired Nonneoplastic Neonatal and Pediatric Diseases,"The lung biopsy is an established procedure to procure a pathologic diagnosis in a child with a suspected pneumonic process of undetermined etiology. Improvements in pediatric anesthesia and surgery have reduced the operative complications to a minimum. A biopsy can usually be taken through a small intercostal incision when localization is not especially important in a patient with diffuse changes (see Chapter 1). The alternative method for tissue sampling is the endoscopic transbronchial biopsy. There is less risk to the patient, but the specimen is smaller and crush artifacts from the instrument are more common."
7660,Human Rights and State Responsibilities,"This chapter lays out an argument that citizens’ human rights are the responsibility of the corresponding State, meaning that citizens of a territorial State claim particular rights that State is obliged to deliver. In return, in an aspect which is often neglected in analyses of human security, citizens also owe allegiance to the State. Citizens’ rights have been expanded to encompass not only physical protection within a territory but also a host of economic and welfare provisions. Despite the increasingly international discourse on human security rights, their legal home remains with the national State vis-à-vis its citizens. The chapter argues that the rules of the State-based order are shifting, with no clear loci of responsibility and accountability for human security."
7661,Pandemics and Dual-Use Research,"Biological risks and threats come in many forms which can contribute to the globalisation of insecurity. The end of the twentieth century saw increased momentum to reframe infectious diseases from purely health issues to those of security concern. HIV/AIDS, SARS, bird flu, and swine flu pandemics in the twenty-first century have challenged nation-states and international institutions. Added to this challenge are the developments and breakthroughs in scientific experiments. While such progress has the potential to eradicate disease and improve human well-being, it also has the potential to present new risks and possible threats to society if the knowledge is used inappropriately. Biological dual-use research can inherently have both beneficial and dangerous consequences. Several incidents have highlighted the potential dangers associated with scientific experiments such as the accidental creation of the highly virulent mousepox, the reconstruction of the 1918 influenza virus, and the manipulation of the H5N1 bird flu virus. Almost all items necessary to produce lethal biological agents are dual-use and can be readily found in pharmaceutical laboratories. The ability to obtain a pathogen, weaponise the agent, and employ or disperse it, needs to be considered in terms of capability and intent and the increasing franchisation of terrorist groups such as Al Qaeda. The availability of open-source information and material, developments in biotechnology sciences, and inexpensive equipment make the production of bioweapons an attractive option for non-state actors. For example, in recent times individuals and non-state actors have developed or obtained ricin and anthrax with the intention of using it for either personal or political harm. Biological agents are not constrained by sovereign borders and can have a devastating effect either in the form of an infectious disease pandemic or as a result of scientific experimentation. This chapter analyses key issues and problems associated with biological security issues and dual-use research including governance arrangements to address those concerns."
7662,Border Inspection and Trade Diversion: Risk Reduction vs. Risk Substitution,"International trade increasingly brings previously separated geographical regions into contact with one another and increases the frequency of those contacts. These trends bring many benefits to the trading partners involved, but increasing international trade also facilitates the spread of pathogens and increases disease risks. The rapid growth of trade, transport, and travel across national borders has increased the frequency of introduction, establishment, and spread of invasive infectious pathogens (Jones et al. 2008). The development of new trade pathways and the growth in the number and volume of commodities traded increase the likelihood that novel infectious pathogens are introduced to importing or stop-over countries. The growth in trade volumes has increased the risk that introduced pathogens establish and spread, because it has increased the frequency with which infectious pathogens are introduced (Cassey et al. 2004; Dalmazzone 2000; Semmens et al. 2004). Other factors such as the bioclimatic similarities between trading partners, the vulnerability of ecosystems in the importing countries, and risk management policies adopted by both importing and exporting countries also influence the risks of invasive infectious pathogens (Wiens and Graham 2005)."
7663,Porcine Epidemic Diarrhea,"Porcine epidemic diarrhea (PED) first appeared in England and Belgium in the 1970s. The etiological agent of the disease is porcine epidemic diarrhea virus (PEDV), which belongs to Coronaviridae. The disease has spread globally and became an endemic disease in many Asian and European countries causing transient diarrhea in postweaning pigs with low mortalities for several decades. Since late 2010, field outbreaks of PED, which reemerged in China, spread to Asian and some European countries and emerged in North America; all led to enormous economic losses in porcine industry. New variants of PEDV exhibit not only significant genetic variations as compared to historic PEDV strains but also more virulent causing severe vomiting and watery yellowish diarrhea in suckling piglets under 1 week of age. Factors underlying the potential pathogenesis of the recent PEDV outbreaks include the mutation of the virus, the lacking of maternal antibodies for the protection of piglets, and the slower turnover rate of enterocytes (5–7 days) of the neonatal piglets as compared to postweaning pigs (2–3 days). The emerging and reemerging of the new variants of PEDV highlight the importance of reviewing the etiology, pathogenesis, diagnosis, and epidemiology of the disease."
7664,The Process and Practice of Negotiation,"Global health diplomacy has been defined as the art and practice of negotiation in relation to global health issues. This chapter draws on generic concepts of negotiation as a process of diagnosis, formula development, exchange and implementation, reflecting the shared and sometimes contested values, power relationships and interests of the many different actors involved. It sets out a framework for understanding the main phases of global health negotiation process as they arise in many different contexts. The negotiation of global health issues is shown to be a driver of the regimes of global health governance institutions that are shaped by the new trends in global governance described in the previous chapter. The leadership and development of diplomatic negotiations at every level with an increasing range of actors is therefore key to global governance for health."
7665,"Microbes, Transmission Routes and Survival Outside the Body","Microbes like bacteria, virus, parasites and fungi may naturally colonize skin and mucous membranes without any sign of illness, for a longer or shorter period, in all humans, animals, fish, parasites, plants and all other living beings. Some types may be more invasive in human tissue than others. Many microbes are free-living in the environment—in water, soil and air and on equipment—as a part of the normal microbial flora on the Earth. Most of them are not dangerous and live in peaceful symbiosis with other living beings and may also be transferred between living species, from man to animal or man to plants and environment—and vice versa. New and old human pathogenic microbes are increasing all over the world. Some agents, like drug-resistant bacteria and highly pathogenic viruses, are more dangerous than others, and some microbes may cause chronic devastating diseases. Transmission routes depend on the robustness of the microbe in the environment, virulence, infectious dose, anatomical site in the body, etc. Pathogenic microbes are spread by contact, air, water, food, beverages, contaminated equipment and environment and are more seldom vector-borne, by insects or animals. The following chapter is focused on the most frequent pathogenic microbes, their preselected localization in the body, transmission routes and survival in the environment."
7666,"Services Innovation: Decision Attributes, Innovation Enablers, and Innovation Drivers","Innovation in the services area — especially in the electronic services (e-services) domain — can be characterized by six decision-oriented attributes: decision-driven, information-based, real-time, continuously-adaptive, customer-centric and computationally-intensive. These attributes constitute the decision informatics paradigm. In turn, decision informatics is supported by information and decision technologies and based on the disciplines of data fusion/analysis, decision modeling and systems engineering. Out of the nine major innovation enablers in the services area (i.e., decision informatics, software algorithms, automation, telecommunication, collaboration, standardization, customization, organization, and globalization), decision informatics is shown to be a necessary enabler. Furthermore, four innovation drivers (i.e., collaboration, customization, integration and adaptation) are identified; all four are directed at empowering the individual — that is, at recognizing that the individual can, respectively, contribute in a collaborative situation, receive customized or personalized attention, access an integrated system or process, and obtain adaptive real-time or just-in-time input. In addition to expanding on current innovations in services and experiences, white spaces are identified for possible future innovations; they include those that can mitigate the unforeseen consequences or abuses of earlier innovations, safeguard our rights to privacy, protect us from the always-on, interconnected world, provide us with an authoritative search engine, and generate a GDP metric that can adequately measure the growing knowledge economy, one driven by intangible ideas and services innovation."
7667,Nanomaterial Effects on Viral Infection,"The potential for environmental and occupational exposures of populations to nanomaterials (NMs) has fostered concerns of associated adverse health effects, with a particular emphasis on pulmonary injury and disease. Many studies have revealed that several types of NMs can evoke a variety of biological responses, such as pulmonary inflammation and oxidative stress, which contribute to allergy, fibrosis, and granuloma formation. Less attention has been paid to health effects that may result from exposure to NMs and additional stressors such as pathogens, with a particular focus on susceptibility to viral infection. This chapter will summarize the current body of literature related to NMs and viral exposures with a primary focus on immune modulation. A summary of the studies performed and major findings to date will be discussed, highlighting proposed molecular mechanisms behind NM-driven host susceptibility, challenges, limitations, and future research needs. Specific mechanisms discussed include direct interaction between NMs and biological molecules, activation of pattern recognition receptors (PRRs) and related signaling pathways, production of oxidative stress and mitochondrial dysfunction, inflammasome activation, and modulation of lipid signaling networks."
7668,"Severe Influenza Infection: Pathogenesis, Diagnosis, Management and Future Therapy",
7669,Climate Change and Geoecology of South and Southeast Asia: An Introduction,"Climate change is projected to impact human health in many ways including changes in water availability and quality, air quality and sanitation, availability and access to food and nutrition and transmission of vector-borne diseases. Environmental consequences of climate change, such as extreme heat waves, rising sea levels, changes in precipitation resulting in flooding and droughts, intense hurricanes (cyclones, typhoons) and degraded air quality, can affect directly and indirectly the physical, social and psychological health of humans. Climate change and human health have emerged as an important focus of research in the World Health Organization since 2008. However, the First International Conference on Health and Climate organised by the WHO in August 2014 in Geneva recognises the relevance of the impact of climate change on human health from a global-change and health perspective. This chapter also highlights policies of the United States, China and India towards GHG emission reduction and the successful climate agreement in Paris in December 2015."
7670,2 Aangeboren immuniteit en acute ontsteking,"Een van de belangrijkste functies van het immuunsysteem is het beschermen van ons lichaam tegen infecties. Om deze bescherming te kunnen realiseren, moet aan een aantal voorwaarden worden voldaan: 1) het immuunsysteem moet het pathogeen ter plaatse en liefst specifiek kunnen herkennen; 2) het immuunsysteem moet het pathogeen zo snel mogelijk onschadelijk maken en opruimen; en 3) het immuunsysteem moet een geheugen opbouwen, zodat hetzelfde pathogeen een volgende maal sneller en efficiënter geëlimineerd kan worden. Hoewel het derde aspect een speciale eigenschap is van de adaptieve immuniteit, is voor de eerste twee punten een nauwe samenwerking tussen de innate (aangeboren) en de adaptieve (verworven) immuniteit noodzakelijk. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1613-7_2) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers."
7671,Viral Lower Respiratory Tract Infections,"Lower respiratory tract infections in children are often viral in origin. Unfortunately in this time of significant antimicrobial resistance of infectious organisms, especially bacteria, there is still a tendency for clinicians to manage a child who coughs with antibiotics. In addition, the World Health Organization (WHO) has defined “pneumonia” as a condition that only occurs in children who have “fast breathing or chest wall indrawing”. That would delineate upper respiratory tract infections from those in the lower airway. However, in addition to pneumonia another important entity exists in the lower respiratory tract that is almost always viral in origin. This condition is acute viral bronchiolitis. The concept of “acute lower respiratory tract infection” (ALRTI) has emerged and it is becoming increasing evident from a number of studies that the infectious base of both acute pneumonia (AP) and acute bronchiolitis in children has a mixed etiology of microorganisms. Therefore, whilst certain clinical phenotypes do not require antibiotics the actual microbial etiology is much less distinct."
7672,Modelling the Dynamics of Host-Parasite Interactions: Basic Principles,"Mathematical modelling is a valuable tool for the analysis of the infectious diseases spread. Dynamical models may help to represent and summarize available knowledge on transmission and disease evolution, to test assumptions and analyse scenarios, and to predict outcomes of the host-pathogen interactions. This chapter aims at introducing basic concepts and methods of epidemiological modelling, in order to provide a starting point for further developments. After positioning modelling in the process of disease investigation, we first present the main principles of model building and analysis, using simple biological and also mathematical systems. We then provide an overview of the methods that can be employed to describe more complex systems. Last, we illustrate how the modelling approach may help for different practical purposes, including evaluation of control strategies. A brief conclusion discusses the challenge of including genetic and molecular variability in epidemiological modelling."
7673,The ER in Replication of Positive-Strand RNA Viruses,"All eukaryotic positive-sense single-strand RNA viruses, (+)ssRNA, replicate their genome in associationwith membranes of host cells. The presence of a replicating virus frequently induces proliferationand rearrangement of the host membranes into various cytopathic structures, including invaginations, vesicles,spherules or membranous webs. Such structures are considered to be virus-induced organelles specializedin replication functions. Virtually all membranes are able to be rearranged to support replication. Thus,membranes from peroxisomes, endosomes, lysosomes, vacuoles, mitochondria, and chloroplasts are used for(+)ssRNA virus replication, but the endoplasmic reticulum (ER) is by far the preferred organelle. The specifictype of membrane system utilized in assembling the viral replication complex is strictly dependent on individualviruses and is likely to be genetically determined. The various molecular interactions that govern ER targetingof plant viruses highlight how viruses can exploit the diversity of interactions that occurs between proteinsand membrane or lipid structures."
7674,Influenza,"Influenza, briefly known as flu, is an acute respiratory infectious disease caused by influenza virus. It spreads via droplets, with strong infectivity. Its incident rate ranks first in legal infectious diseases, with occurrences of outbreaks or pandemics. Its clinical symptoms are characterized by acute onset of high fever, fatigue, systemic muscular soreness and pain, as well as mild respiratory tract symptoms. Influenza more commonly occurs in autumns and winters. Although it has a short disease course and is self-limited, it may be complicated by pneumonia and other serious complications in populations including the elderly, infants and young children, patients with cardiac or pulmonary diseases, patients with other chronic diseases, and patients with compromised immunity. In some serious cases, death may even occur."
7675,Microspheres for Drug Delivery,"With advances in biotechnology, genomics, and combinatorial chemistry, a wide variety of new, more potent and specific therapeutics are being created. Because of common problems such as low solubility, high potency, and/or poor stability of many of these new drugs, the means of drug delivery can impact efficacy and potential for commercialization as much as the nature of the drug itself. Thus, there is a corresponding need for safer and more effective methods and devices for drug delivery. Indeed, drug delivery systems—designed to provide a therapeutic agent in the needed amount, at the right time, to the proper location in the body, in a manner that optimizes efficacy, increases compliance and minimizes side effects—were responsible for $47 billion in sales in 2002, and the drug delivery market is expected to grow to $67 billion by 2006."
7676,Pharmacogenomics and Personalized Medicine for Infectious Diseases,"Humans have been plagued by the scourge of invasion by pathogens leading to infectious diseases from the time in memoriam and are still the cause of morbidity and mortality among millions of individuals. Trying to understand the disease mechanisms and finding the remedial measures have been the quest of humankind. The susceptibility to disease of an individual in a given population is determined by ones genetic buildup. Response to treatment and the disease prognosis also depends upon individual’s genetic predisposition. The environmental stress induces mutations and is leading to the emergence of ever-increasing more dreaded infectious pathogens, and now we are in the era of increasing antibiotic resistance that has thrown up a challenge to find new treatment regimes. Discoveries in the science of high-throughput sequencing and array technologies have shown new hope and are bringing a revolution in human health. The information gained from sequencing of both human and pathogen genomes is a way forward in deciphering host-pathogen interactions. Deciphering the pathogen virulence factors, host susceptibility genes, and the molecular programs involved in the pathogenesis of disease has paved the way for discovery of new molecular targets for drugs, diagnostic markers, and vaccines. The genomic diversity in the human population leads to differences in host responses to drugs and vaccines and is the cause of poor response to treatment as well as adverse reactions. The study of pharmacogenomics of infectious diseases is still at an early stage of development, and many intricacies of the host-pathogen interaction are yet to be understood in full measure. However, progress has been made over the decades of research in some of the important infectious diseases revealing how the host genetic polymorphisms of drug-metabolizing enzymes and transporters affect the bioavailability of the drugs which further determine the efficacy and toxicology of the drugs used for treatment. Further, the field of structural biology and chemistry has intertwined to give rise to medical structural genomics leading the way to the discovery of new drug targets against infectious diseases. This chapter explores how the advent of “omics” technologies is making a beginning in bringing about a change in the prevention, diagnosis, and treatments of the infectious diseases and hence paving way for personalized medicine."
7677,Smallpox as a Weapon for Bioterrorism,
7678,Genetic Basis of Myocarditis: Myth or Reality?,"The genetic basis of myocarditis remains an intriguing concept, at least as long as the definition of myocarditis constitutes the definitive presence of myocardial inflammation sufficient to cause the observed ventricular dysfunction in the setting of cardiotropic infections. Autoimmune or immune-mediated myocardial inflammation constitutes a complex area of clinical interest, wherein numerous and not yet fully understood role of hereditary auto-inflammatory diseases can result in inflammation of the pericardium and myocardium. Finally, myocardial involvement in hereditary immunodeficiency diseases, cellular and humoral, is a possible trigger for infections which may complicate the diseases themselves. Whether the role of constitutional genetics can make the patient susceptible to myocardial inflammation remains yet to be explored."
7679,Lungengefäßerkrankungen,"Das Lungenödem ist charakterisiert durch eine vermehrte interstitielle und/oder alveoläre Flüssigkeitseinlagerung. Zugrunde liegt entweder eine Erhöhung des kapillären Filtrationsdrucks, die zumeist kardial verursacht ist, oder eine erhöhte Durchlässigkeit der pulmonalen Gefäßschranke (⊡ Tab. 9.1)."
7680,Protecting Information with Cybersecurity,"Virtually every system today confronts the cybersecurity threat, and the system architect must have the ability to integrate security features and functions as integral elements of a system. In this chapter, we survey this large, complex, and rapidly evolving subject with the goal of giving the reader a level of understanding that will enable incorporation of cybersecurity within an MBSE process and effective interaction with security experts. We begin by introducing the subject and describing the primary aspects of the current cybersecurity environment. We define fundamental terminology and concepts used in the cybersecurity community, and we describe the basic steps to include cybersecurity risk in an overall risk management process, which is a central SE responsibility. We then list some of the primary sources of information, guidance, and standards upon which a systems engineer can and should draw. Next, we summarize the major aspects of incorporating security controls in a system architecture and design to achieve an acceptable level of security risk for a system. We extend this to the increasingly important world of service-oriented, network-based, and distributed systems. We conclude with a brief presentation of the application of MBSAP to the specific issues of cybersecurity and summarize the characteristics of a Secure Software Development Life Cycle aimed at creating software with minimum flaws and vulnerabilities. We illustrate the application of cybersecurity principles and practices using the Smart Microgrid example. Chapter Objective: the reader will be able to apply the MBSAP methodology to systems and enterprises that require protection of sensitive data and processes against the growing cybersecurity threat and to work effectively with cybersecurity specialists to achieve effective secure system solutions."
7681,Infectious Diseases: The Role of the Healthcare Professional,"For the healthcare professional dealing with infections presents two main problems. First, managing detainees or police personnel who have contracted a disease and may be infectious or unwell, and second, handling complainants of assault, including police officers, who have potentially been exposed to an infectious disease. This chapter addresses some general principles of infection control and safety in the working environment and then goes on to discuss some infections that may be encountered in police custody and how they can best be managed."
7682,Part 3: Practical Implementation of Data Protection Environment,"A wide range of cloud related professionals (both legal and technical) in California have been interviewed regarding their experience with data protection and in particular the effects of the EU law on their business operations and the industry in general. Hereinafter, the results of these interviews will be analyzed and key issues addressed with a special focus on the new EU General Data Protection Regulation (GDPR)."
7683,An Introduction to Networks in Epidemic Modeling,"We use a stochastic branching process to describe the beginning of a disease outbreak. Unlike compartmental models, if the basic reproduction number is greater than one there may be a minor outbreak or a major epidemic with a probability depending on the nature of the contact network. We use a network approach to determine the distribution of outbreak and epidemic sizes."
7684,Reticular Diseases,
7685,Cases 27–65,A 73-year-old Caucasian woman presented with hematemesis. She had been diagnosed with cryptogenic cirrhosis several years previously but her disease was well compensated. She was seen at a local hospital and underwent esophagogastroduodenoscopy (EGD) that demonstrated no signs of esophageal varices but a large mass in the fundus and some nodular changes in the stomach. The concern was for a gastric malignancy. She is transfused and sent to you for further investigation.
7686,Mosquitoes as Arbovirus Vectors: From Species Identification to Vector Competence,"Mosquitoes and other arthropods transmit a large number of medically important pathogens, in particular viruses. These arthropod-borne viruses (arboviruses) include a wide variety of RNA viruses belonging to the Flaviviridae family (West Nile virus (WNV), Usutu virus (USUV), Dengue virus (DENV), Japanese encephalitis virus (JEV), Zika virus (ZIKV)), the Togaviridae family (Chikungunya virus (CHIKV)), and Bunyavirales order (Rift Valley fever virus 1. Who could contribute to such an outbreak? Information about mosquito species resident or imported, potential hosts and viruses able to infect vectors and hosts in Germany is needed. 2. Where would competent mosquito species meet favorable conditions for transmission? Information on the minimum requirements for efficient replication of the virus in a given vector species and subsequent transmission is needed. 3. How do viruses and vectors interact to facilitate transmission? Information on the vector immunity, vector physiology, vector genetics, and vector microbiomes is needed."
7687,Trends and Perspectives,"Throughout the book chapters, researchers have highlighted the recent advancement in microfluidic areas, particularly those involving microdroplets."
7688,Diagnosis of Tuberculosis: Nanodiagnostics Approaches,"Tuberculosis (TB) remains one of the most devastating infectious diseases worldwide. The burden of TB is alarmingly high in developing countries, where diagnosis latent TB infection (LTBI), Extra-pulmonary tuberculosis (EPTB), drug-resistant tuberculosis (DR-TB), HIV-associated TB, and paediatric TB is still a challenge. This is mainly due to delayed or misdiagnosis of TB, which continues to fuel its worldwide epidemic. The ideal diagnostic test is still unavailable, and conventional methods remain a necessity for TB diagnosis, though with poor diagnostic ability. The nanoparticles have shown potential for the improvement of drug delivery, reducing treatment frequency and diagnosis of various diseases. The engineering of antigens/antibody nanocarriers represents an exciting front in the field of diagnostics, potentially flagging the way toward development of better diagnostics for TB. This chapter discusses the presently available tests for TB diagnostics and also highlights the recent advancement in the nanotechnology-based detection tests for M. tuberculosis."
7689,SARS,"Severe acute respiratory syndrome (SARS) is an acute respiratory tract infectious disease induced by SARS-CoV and mainly transmitted through the short-distance air droplets and close contact. Its main clinical characteristics is abrupt onset of the disease and the initial symptom is fever accompanied with systematic symptoms of headache, soreness and fatigue, and respiratory tract symptoms such as cough, chest dullness, and dyspnea. A few cases may progress to acute respiratory distress syndrome (ARDS). Due to its self-limiting feature, the prognosis is predominantly good but may be poor in severe cases, with mortality about 9.3 %. Some patients may develop such complications such as lung fibrosis and necrosis of the head of femur. On April 8, 2003, SARS was defined as a legal infectious disease by the Ministry of Heath of China."
7690,Histopathology in Coronavirus-Induced Demyelination,"The experimental model system of coronavirus mouse hepatitis virus (MHV) induced demyelination in 4–6 week old C57Bl/6 or Balb/c mice exhibits a biphasic disease and two distinct forms of virus-induced demyelination. During the acute phase of the disease MHV infection causes acute encephalitis, and some strains of virus cause also hepatitis. Infection with the JHM strain of MHV causes severe panencephalitis, whereas MHV-A59 causes mild to moderate encephalitis involving specific limbic and limbic related areas of the brain and brain stem. The target cells are neurons and glia including oligodendrocytes. Demyelination during the acute stage is due to cytolytic infection of oligodendrocytes. After two weeks, the disease process enters a chronic stage of immune-mediated demyelination, in the presence of high levels of anti-viral antibodies and persistent low levels viral RNA in glial cells, without detectable levels of infectious virus or viral antigens."
7691,SOARS: Spot Oriented Agent Role Simulator — Design and Implementation,"In this paper we present the design of an agent-based simulation language called SOARS (Spot Oriented Agent Role Simulator). SOARS is designed to describe agent activities according to roles within social and organizational structures. Role taking processes can be described in our language. SOARS is also designed according to the theory of agent-based dynamic systems. Decomposition of multi-agent interaction is one of the most important characteristics of our framework. The notion of spot and stage gives spacial and temporal decomposition of interaction among agents. We apply our multi-agent framework to policy analysis of emerging virus protection in the case of SARS. In the latter part of the paper, we explain the implementation of the SOARS simulation platform. The simulation engine and related built-in functional objects are implemented in Java language. An application user can describe the agent-based simulation model only by writing script in SOARS script language without knowledge of Java classes. If needed, the user can customize the function of SOARS by implementing additional Java classes. The easiest way to customize is to develop special functional objects, and the SOARS platform will be the interface between such customized objects."
7692,Disaster Perceptions,"Generally speaking, perception includes individuals’ subjectivity in terms of how they see or assess the characteristics of a phenomenon. Risk perception is vital to understanding what risks people consider to be acceptable, and what risk reduction programs have a better chance of being accepted. Risk perception is influenced by a variety of factors including the kind of information available and how that information is processed; the personality and emotional state of the perceiver; their personal experiences and prejudices; and socio-economic factors, to name but a few. Risk perception, risk tolerance, and high or low risk-taking behaviors are all interconnected. The nature and consequences of a potential threat, as well as its proximity, also contribute to how it is perceived by society. In this era of social media, the media is vital to ensuring that disaster news is covered more objectively. This chapter includes survey-based studies conducted in Canada as powerful testimonies to the importance of risk perception among various groups, including average citizens and emergency managers."
7693,Infestationen und Infektionen bei Migranten – Die wichtigsten Erkrankungen,"Skabies (Krätze) ist bei Migranten sehr häufig. Über den Gängen der Krätzmilbe ist die Haut entzündlich verändert. An Händen und Füssen sind die Veränderungen vor allem in den interdigitalen Räumen erkennbar. Kopfläuse nehmen als Problem zu. Sie sind nur am menschlichen Kopf überlebensfähig. Flohstiche entstehen auch an bedeckten Körperstellen. An der Stichstelle entwickelt sich eine stark juckende Quaddel mit einer zentralen Blutung. Die Bettwanze sticht in der Nacht und saugt Blut. Stiche sind typischerweise longitudinal angeordnet. Unter den Parasiten haben Würmer eine große Bedeutung. Bei Kindern in Deutschland kommen Madenwürmer (Oxyuren) am häufigsten vor. Wurmeier werden anal, perianal und auch vaginal abgelegt und führen zu einem starken nächtlichen analen Pruritus. Unter den Infektionen hat die Tuberkulose bei Migranten eine höhere Prävalenz als in Deutschland gewohnt. Unter den Migranten aus dem subsaharischen Afrika ist auf das Vorliegen von HIV-Infektionen zu achten."
7694,Fibrous Layer Filter,"Granular layer, fibrous layer, microporous membrane, membrane covered fibrous layer, screen mesh and perforated plate can be used to remove particles, which are classified as barrier-type filter."
7695,Public Health Law and Biological Terrorism,
7696,Case Study: The continuous realization of growth synergies,"Following the single cause study approach for investigating our empirical research question, this chapter presents an in-depth case report of the continuous realization of growth synergies at our research site ElectroCorp. It provides the context and basis for our interference of constructs and propositions in the next chapter."
7697,Pediatric Interstitial (Diffuse) Lung Disease,"Interstitial (diffuse) lung diseases in infants and children comprise a rare heterogeneous group of parenchymal lung disorders, with clinical syndromes characterized by dyspnea, tachypnea, crackles, and hypoxemia. They arise from a wide spectrum of developmental, genetic, inflammatory, infectious, and reactive disorders. In the past, there has been a paucity of information and limited understanding regarding their pathogenesis, natural history, imaging findings, and histopathologic features, which often resulted in enormous diagnostic challenges and confusion. In recent years, there has been a substantial improvement in the understanding of interstitial lung disease in pediatric patients due to the development of a structured classification system based on the etiology of the lung disease, established pathologic criteria for consistent diagnosis, and the improvement of thoracoscopic techniques for lung biopsy. Imaging plays an important role in evaluating interstitial lung diseases in infants and children by confirming and characterizing the disorder, generating differential diagnoses, and providing localization for lung biopsy for pathological diagnosis. In this chapter, the authors present the epidemiology, challenges, and uncertainties of diagnosis and amplify a recently developed classification system for interstitial lung disease in infants and children with clinical, imaging, and pathological correlation."
7698,Measles,"Measles is an acute respiratory infectious disease caused by measles virus. Clinically, it is characterized by fever, rhinorrhea, conjunctival congestion, respiratory catarrh symptoms, oral mucosa spots, and red skin maculopapules. The patients with acute measles are the only source of its infection, who are infectious from the final 1–2 days of the incubation period to the day 5 after skin rash. Measles is commonly transmitted via respiratory droplets, with occurrence all year round but more commonly in winters and springs. Measles is the most common infectious disease in children, with strong infectivity. In recent years, the cases of measles in adults are increasing. Elimination of measles has been listed as the next objective of WHO after elimination of poliomyelitis."
7699,Virus-like Particle Vaccines for Norovirus Gastroenteritis,"Gastroenteritis (GE) and its associated diarrheal diseases remain as one of the top causes of death in the world. Noroviruses (NoVs) are a group of genetically diverse RNA viruses that cause the great majority of nonbacterial gastroenteritis in humans. However, there is still no vaccine licensed for human use to prevent NoV GE. The lack of a tissue culture system and a small animal model further hinders the development of NoV vaccines. Virus-like particles (VLPs) that mimic the antigenic architecture of authentic virions, however, can be produced in insect, mammalian, and plant cells by the expression of the capsid protein. The particulate nature and high-density presentation of viral structure proteins on their surface render VLPs as a premier vaccine platform with superior safety, immunogenicity, and manufacturability. Therefore, this chapter focuses on the development of effective NoV vaccines based on VLPs of capsid proteins. The expression and structure of NoV VLPs, especially VLPs of Norwalk virus, the prototype NoV, are extensively discussed. The ability of NoV VLPs in stimulating a potent systemic and mucosal anti-NoV immunity through oral and intranasal delivery in mice is presented. The advantages of plant expression systems as a novel production platform for VLP-based NoV vaccines are discussed in light of their cost-effectiveness, production speed, and scalability. Recent achievements from the first successful demonstration of NoV VLP production in plant expression system under the current Good Manufacture Practice (cGMP) regulation by the US Food and Drug Administration (FDA) are detailed. Moreover, results of human clinical trials demonstrating the safety and efficacy of insect and plant-derived NoV VLPs are also presented. Due to the diversity of capsid protein among different NoV strains and its rapid antigenic drift, we speculate that vaccine development should focus on multivalent VLP vaccines derived from capsid proteins of the most prevalent strains. With the very recent approval of the first plant-made biologics by the FDA, we also speculate that plant-based production systems will play an important role in manufacturing such multivalent VLP-based NoV vaccines."
7700,The G8/G20 and Global Health Governance: Extended Fragmentation or a New Hub of Coordination,"This chapter provides an overview of the current position and the possible future of Global Health Governance (GHG)—in terms of the connections and disconnections with the overall architecture of international organizations engaged in global governance. The main focus of this discussion is on the relationship between GHG and leadership summits, including both the “G8” and “G20.” The discussion first notes that while GHG has become a central focus for international diplomacy it has become ever more fragmented as new actors and venues negotiate aspects of global health without apparent reference to a central agency or process. It then briefly reviews the growing role of foundations before focusing on the role of G8 summitry in GHG. The final section and conclusion consider how the G20 could provide a further venue for GHG."
7701,Priming Time: How Cellular Proteases Arm Coronavirus Spike Proteins,"Coronaviruses are enveloped RNA viruses that infect mammals and birds. Infection of humans with globally circulating human coronaviruses is associated with the common cold. In contrast, transmission of animal coronaviruses to humans can result in severe disease: The severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) are responsible for hundreds of deaths in Asia and the Middle East, respectively, and are both caused by members of the genus Betacoronavirus, SARS-CoV, and MERS-CoV that were zoonotically transmitted from an animal host to humans. At present, neither vaccines nor specific treatment is available to combat coronavirus infection in humans, and novel antiviral strategies are urgently sought. The viral spike protein (S) mediates the first essential step in coronavirus infection, viral entry into target cells. For this, the S protein critically depends on priming by host cell proteases, and the responsible enzymes are potential targets for antiviral intervention. Recent studies revealed that the endosomal cysteine protease cathepsin L and the serine proteases furin and TMPRSS2 prime the S proteins of SARS-CoV and MERS-CoV and provided evidence that successive S protein cleavage at two sites is required for S protein priming. Moreover, mechanisms that control protease choice were unraveled, and insights were obtained into which enzyme promotes viral spread in the host. Here, we will provide basic information on S protein function and proteolytic priming, and we will then discuss recent progress in our understanding of the priming of the S proteins of SARS-CoV and MERS-CoV."
7702,Compartmental Models in Epidemiology,"We describe and analyze compartmental models for disease transmission. We begin with models for epidemics, showing how to calculate the basic reproduction number and the final size of the epidemic. We also study models with multiple compartments, including treatment or isolation of infectives. We then consider models including births and deaths in which there may be an endemic equilibrium and study the asymptotic stability of equilibria. We conclude by studying age of infection models which give a unifying framework for more complicated compartmental models."
7703,E. Individuelle Gesundheitsleistungen von A – Z,"Die nachfolgend aufgelisteten Leistungen sind die Grundlage für ggf. weitere zusätzliche apparative Untersuchungen (EKG, BelastungsEKG, Sono, Lungenfunktion, Röntgen, CT, NMW, Doppler, EEG, ENG, EMG) oder für die Behandlung."
7704,Evaluating the Use of Alternative Distance Metrics in Spatial Regression Analysis of Health Data: A Spatio-temporal Comparison,"A method is discussed to enhance the reliability of multivariate spatial regression analysis: alternative values of the Minkowski distance metric are used in the spatial weight matrix. The method is tested on an analysis of the association between heart disease incidence and a pool of socio-economic variables in Calgary over two consecutive census surveys. The method provides a reliable model, which can guide locational decisions to mitigate present and future disease incidence. The model is underpinned by a quantitative definition of neighbourhood connectivity throughout the city. Such connectivity, usually described by Euclidean distance, can be more effectively described by a specifically calibrated distance metric. The analytical results are meaningful, robust to neighbourhood size, and relatively constant over time. Owing to its effectiveness and simplicity, the procedure is generalizable to other health and socio-economic analysis. An automatic implementation is suggested, to assist in the definition of reliable spatial regression models."
7705,Foodborne Disease in the Middle East,"Food safety is a concern worldwide and according to the World Health Organization, developing countries are probably more at risk of foodborne illness because many of these, including those in the Middle East, have limited disease surveillance and prevention and control strategies. Specifically, the Middle East and North Africa (MENA) region has the third highest estimated burden of foodborne diseases per population, after the African and South-East Asia regions. However, it is difficult to determine what the burden is since little is published in peer-reviewed journals or government reports for public access. This chapter reviews 16 autonomous nations, namely, Afghanistan, Bahrain, Egypt, Iran, Iraq, Israel, Palestine, Kuwait, Lebanon, Oman, Pakistan, Qatar, Saudi Arabia (KSA), Syrian Arab Republic (Syria), United Arab Emirates (UAE) and Yemen. Countries range in size from Bahrain with 1.8 million inhabitants to Pakistan with a population of 184 million. Agriculture and local food production is much influenced by water availability for irrigation. Water shortages are most severe in the Gulf countries which rely on aquifers, desalination, and recycled waste water for most of their water supplies. This means that most food is imported which is expensive if not subsidized through petrodollars. This impacts food security which is a particular concern in countries under conflict, particularly, Syria, Yemen and Iraq. Gastrointestinal infections are frequent in this region from Salmonella Typhi and other Salmonella spp., Shigella spp., Campylobacter jejuni and C. coli, rotavirus, hepatitis A virus, parasites, and more rarely from Aeromonas, Yersinia enterocolitica, Brucella spp., and Middle East Respiratory Syndrome coronavirus (MERS-CoV). Reports indicate that children are the most susceptible and that many isolates are multidrug resistant. Chemical contamination of water supplies and crops are probably more of a concern than published reports indicate, because of widespread indiscriminate use of fertilizers, antibiotics, and pesticides, coupled with increased industrial pollution affecting the water supplies. Like many other parts of the developing world, foodborne disease surveillance is limited and outbreaks are most often reported through the Press but with insufficient detail to determine the etiological agents and the factors contributing to the outbreaks, leading to speculation to the cause by those interested or responsible for food prevention and control. However, there are some well investigated outbreaks in the region that have those details, and reveal where the shortcomings of both the establishments and the inspection systems have been. Where the causative agents are known, the kinds of pathogens are generally similar to those found in the West, e.g., Salmonella, but many outbreaks seem to have short incubation periods that point to a toxin of some kind of chemical or biological origin, but these are almost never identified. Because of sectarian warfare, residents and refugees have been given food that has made them sick and solders? have been deliberately poisoned. Research has been focused on microbial contamination of locally-sold foodstuffs and manager and employee knowledge of food safety and hygienic conditions in food preparation establishments. An innovative pilot project in Qatar is to use seawater and sunlight for raising crops through the Sahara Forest Project. All countries have some kind of food establishment inspection system, but they tend to be punitive if faults are found in management or employees on the premises rather than being used for their education for improving food safety. Restaurants may be closed down and owners and employees fined for often unspecified infringements. However, some food control agents are moving towards employee training through seminars and courses before problems occur, which is a good disease prevention strategy. Unfortunately, many of the food handlers are from Asian countries with languages other than Arabic and English, which makes effective food safety communication and training difficult. Tourists visiting popular resorts in Turkey and Egypt have suffered from foodborne illnesses, usually of unknown origin but poor hygienic conditions are blamed with law suits following, and the adverse publicity affects the long-term viability of some of these resorts. Food exports, important for local economies, have occasionally been contaminated resulting in recalls and sometimes illnesses and deaths, notably fenugreek seeds from Egypt (E. coli O104:H4), pomegranate arils from Turkey (hepatitis A virus), and tahini from Lebanon (Salmonella). Overall, in recent decades, the Middle East has made strides towards improving food safety for both residents and foreign visitors or ex-pat workers. However, within the countries there are large discrepancies in the extent of effective public health oversight including food safety and food security. Currently, almost all of the countries are involved to a greater or lesser extent in the civil wars in Syria and Yemen, or are affected through political tensions and strife in Egypt, Iraq, Iran, Israel, Palestine, Lebanon and Turkey. In addition, the current overproduction of oil on a world-wide scale has led to a rapid decrease in revenues to most Gulf states. All this points to a severe setback, and an uncertain foreseeable future for improvements in obtaining both sufficient and safe food for residents in this region."
7706,Ribosomal Frameshifting in Decoding Plant Viral RNAs,"Frameshifting provides an elegant mechanism by which viral RNA both encodes overlapping genes and controls expression levels of those genes. As in animal viruses, the −1 ribosomal frameshift site in the viral mRNA consists of a canonical shifty heptanucleotide followed by a highly structured frameshift stimulatory element, and the gene translated as a result of frameshifting usually encodes the RNA-dependent RNA polymerase. In plant viruses, the −1 frameshift stimulatory element consists of either (i) a small pseudoknot stabilized by many triple-stranded regions and a triple base pair containing a protonated cytidine at the helical junction, (ii) an unusual apical loop–internal loop interaction in which a stem-loop in the 3(′) untranslated region 4 kb downstream base pairs to a bulged stem-loop at the frameshift site, or (iii) a potential simple stem-loop. Other less well-characterized changes in reading frame occur on plant viral RNAs, including a possible +1 frameshift, and net −1 reading frame changes that do not utilize canonical frameshift signals. All these studies reveal the remarkable ways in which plant viral RNAs interact with ribosomes to precisely control protein expression at the ratios needed to sustain virus replication."
7707,Uncertainty and Immunity in Public Communications on Pandemics,"This chapter examines uncertainty in the expert advice on pandemics given to members of the general public. The chapter draws on research conducted in Australia and Scotland on public engagements with the 2009 influenza (swine flu) pandemic and discusses implications for communications on more recent infectious disease outbreaks, including Ebola and Zika. It shows how public health messages aim to achieve a workable balance of warning and reassurance and deflect problems of trust in experts and science. The chapter considers how uncertainties which prevail in pandemics reinforce the personalization of responses to pandemic risk, in ways that undermine the cooperation and collective action which are also needed to respond effectively to pandemics."
7708,Introduzione,"Sebbene a livello planetario non figurino tra le prime cause di morte per malattie infettive, le zoonosi sono sempre più al centro dell’attenzione delle autorità sanitarie nazionali e internazionali. I motivi di preoccupazione sono sostanzialmente due: da un lato, diverse zoonosi, catalogate tra le patologie emergenti o riemergenti, sono considerate tra le maggiori minacce di nuove pericolose pandemie; dall’altro, la prevenzione, il controllo e il trattamento di numerose zoonosi, anche classiche e ben conosciute, comportano costi economici e sociali rilevanti e crescenti."
7709,Genomics and Foodborne Viral Infections,"Foodborne viral illness, resulting from the consumption of contaminated food or water containing pathogenic viruses, remains a major public health problem globally with substantial economic impact. Major challenges regarding recognizing, detecting, characterizing, and effectively responding to foodborne viral threats to health exist. Adequate health crisis management is largely dependent on early detection of potential public health threats, which is hampered by changing trends in disease outbreaks, from localized clusters of disease in confined populations to dispersed outbreaks with excellent opportunity for further transmission. In addition, no precise and consistent global baseline syndrome and diagnostic surveillance information exists. An integrated multidisciplinary approach with a combination of sustained pathogen syndrome and diagnostic surveillance, genomics-based, and standardized global analytical networks gathering clinical, epidemiological and genetic data alike would be required to understand the dynamics of foodborne viral infection and to mitigate potential effects of future threats. A huge global effort in virus syndrome and diagnostic surveillance may be justified in the light of global health impact in general, and timely with the development of new metagenomics tools that hold the promise of not only identifying viral pathogens, but possibly the complete microbiome in a single assay."
7710,10 Kindergeneeskunde,"Ieder kind maakt tijdens zijn of haar groei en ontwikkeling ziekten door. Veelal betreft het onschuldige aandoeningen, vaak van infectieuze aard. Meestal zijn deze aandoeningen ‘self-limiting’ en horen ze bij een normale ontwikkeling."
7711,Infections in the Intensive Care Unit,"After studying this chapter, you should be able to: Understand the pathophysiology of specific infections in the ICU. Identify infectious complications in critically ill patients. Conduct appropriate diagnostic work-up for infections encountered in the ICU. Develop a systematic approach for managing ICU-related infections. Execute effective measures to prevent infectious complications in the ICU. Understand how to effectively work up and treat patients with sepsis. Choose the appropriate antimicrobial regimen for either empiric or culture-focused treatment of ICU infections."
7712,Antimicrobial Resistance Among Streptococcus pneumoniae,"Antibiotic resistance in Streptococcus pneumoniae (pneumococcus), the main pathogen responsible for community-acquired pneumonia (CAP), meningitis, bacteremia, and otitis media, is a major concern for clinicians. This pathogen is associated with high rates of morbidity and mortality, especially among children under 2 years old, immunocompromised persons, and the elderly population. The major anti-pneumococcus agents are β-lactams and macrolides, with fluoroquinolones ranking third. The emergence of antibiotic-resistant pneumococcus due to overuse of antibiotics is a global concern. While the discovery of novel classes of antibiotics for the pneumococcus is at a standstill, significant progress in reducing the problem of resistance is associated with antibacterial vaccines. Nevertheless, the World Health Organization recently considered drug-resistant S. pneumoniae as ranking among the 12 bacteria, for which there is an urgent need for new treatments. A challenge is to slow the evolution of new strains that are resistant to the vaccines."
7713,Bronchiolitis Obliterans Syndrome and Chronic Lung Allograft Dysfunction: Evolving Concepts and Nomenclature,"Bronchiolitis obliterans syndrome (BOS) eventually occurs in the majority of lung transplant recipients who survive beyond 1 year, can greatly impair quality of life, and is, directly or indirectly, the major cause of delayed allograft dysfunction and recipient death. A number of associated events or conditions are strongly associated with the risk for developing BOS; these include acute rejection, gastroesophageal reflux, infections, and autoimmune reactions that can occur in the setting of alloimmune responses to the lung allograft as recipients are given intense immunosuppression to prevent allograft rejection. The term chronic lung allograft dysfunction (CLAD) is being increasingly used to refer to recipients with late allograft dysfunction that meets the spirometric criteria for the diagnosis of BOS, but clinicians should recognize that such dysfunction can occur for a variety of reasons other than BOS. The recently identified entity of restrictive allograft syndrome, which is now recognized as a relatively distinct phenotype of CLAD, has features that differentiate it from classic obstructive BOS. A number of other entities that can also significantly affect allograft function must also be considered when significant allograft dysfunction is encountered following lung transplantation."
7714,Fault Tolerance Patterns Mining in Dynamic Databases,"Mining of frequent patterns in database has been studied for several years. However, real-world data tends to be dirty and frequent pattern mining which extracts patterns that are absolutely matched is not enough. An approach, called frequent fault-tolerant pattern (FT-pattern) mining, is more suitable for extracting interesting information from real-world data that may be polluted by noise. Previous research on frequent fault-tolerant pattern mining has been widely studied. However, all of the researches focus on static database. In this paper, we propose an efficient framework to analyze the frequent FT-patterns mining in dynamic database. To avoid re-scanning the whole database, beside of keeping the fault-tolerance pattern, we will also keep the potential fault-tolerance pattern that has higher possibility of becoming a fault-tolerance pattern. The experimental results show that by re-using the existing pattern that had been generated, the proposed algorithms are highly efficient in terms of execution time and maximum memory usage for mining fault-tolerance frequent pattern in dynamic database compare to FFM algorithm."
7715,South and East Asian Insurance Market Growth and Development,"Recent economic research, notably by King and Levine (1993a, 1993b), Levine and Zervos (1998), Levine (1999), Levine, et al. (2000), and Beck, et al. (2000), indicates that financial services and its various components, including insurance and banking, have substantial potential for spreading positive externalities throughout the commercial sector of an economy. Such benefits can stem from improved access to capital by firms, better allocation of capital to investment projects, greater risk management, and enhanced portfolio diversification and liquidity for individual investors. While existing economic research shows the development of financial services is generally important for economic growth, a number of previous studies by Outreville (1990) and Ward and Zurbruegg (2000) provide empirical evidence that insurance market development in its own right can promote economic development. The importance of the insurance industry to the wider economy is seen to stem from the relative size of the insurance industry to GDP in many developed economies, the transfer of risks, and the scale of insurance companies’ financial intermediary functions."
7716,Legal and Moral Reflections on Modern Biotechnology in Use & Misuse,"It is an established truth that science serves humanity by developing new and useful technologies, discovering new phenomena, forwarding knowledge and understanding. ‘Science seeks certainty … and tells us what we can do… but it is for the law to tell [science] whether and how to do’, even if it is in a climate of uncertainties. As a natural phenomenon, scientists tend to concentrate on the beneficial uses of scientific research, but each of them should also concentrate on the potential destructive misuses, in as far as is known, assumed or reasonably predicted. Considering the fast accumulation of sophisticated scientific and biotechnological information, it is upon the scientist and his community to inform and warn the public about the potential destructive misuses of biotechnological research and findings. It is instrumental for the public to be aware of the risks posed by certain dangerous biological agents that are used, manipulated or developed in the course of biotechnological research. The public must be aware of and be reminded that certain biological agents can be used as biological lethal weapons for mass-destruction, or misused for deliberately inflicting infectious diseases. This can be done either by directly spreading common pathogens or by indirectly contaminating food-products, water resources, crops, animal food and feed, etc. It is known that certain lethal biological agents can be transformed into more lethal forms or may even be specifically engineered as such. It is upon the public at large, in applying its collective moral conscience, guided by relevant knowledge and information, to choose what scientific research and advanced technologies should be furthered, banned, or temporarily withheld. It is to be emphasized that the international community has already long ago expressed its determination ‘to exclude completely the possibility of bacteriological (biological) agents and toxins being used as weapons…[it being] repugnant to the conscience of mankind’."
7717,8 Infectieziekten,"In dit hoofdstuk wordt beoogd de belangrijkste nieuwe ontwikkelingen waarvan de huisarts moet kennisnemen, te bespreken. Voor specifieke therapie wordt verwezen naar hoofdstuk 25 Antimicrobiële therapie waaraan wij ook hebben bijgedragen."
7718,Tissue Culture Models,"The use of tissue cultures as a research tool to investigate the pathophysiological bases of diseases has become essential in the current ag of molecular biomedical research. Although it will always be necessary to translate and validate the observations seen in vitro to the patient or animal, the ability to investigate the role(s) of individual variables free from confounders is paramount toward increasing our understanding of the physiology and their role in disease. Additionally, it is not feasible to conduct certain research in humans because of ethical constraints, yet investigators may still be interested in the physiological response in human tissues; in vitro characterization of human tissue is an acceptable choice. Tissue culture techniques have been utilized extensively to investigate questions pertaining to physiology and disease. The isolation and propagation of human epithelial cells has allowed investigators to begin to characterize the interactions and reactions that occur in response to various stimuli. Moreover, the culture of other human tissue has allowed researchers to investigate pathological cascades as well as other physiological responses. Combining cultured endothelial cells and leukocytes together in vitro under laminar flow conditions has helped elucidate the critical interactions that occur in rolling and emigration of leukocytes during the inflammatory response. Cultured embryonic stem cells that had been subjected to various growth conditions have advanced our understanding of cellular differentiation and growth."
7719,Influence of Gender on Outcome of Severe Sepsis,"Whether gender influences the outcome of severe sepsis remains a matter of debate. Because many confounding variables may affect observed associations between gender and mortality, high-quality statistical analyses are essential to carefully adjust the two groups of patients. About 55% to 65% of patients with sepsis have chronic co-morbidities associated with immune dysfunction (e.g., chronic renal failure, diabetes mellitus, human immunodeficiency virus [HIV] infection, and alcohol abuse), which increase the susceptibility to sepsis [1]. Genetic polymorphisms that affect the susceptibility to infection and/or the severity of the systemic response to infection [2] may lead to variability among individuals and between males and females [3]. Access to healthcare, another determinant of the incidence and outcome of sepsis, varies according to age, ethnic group, and gender, although a recent study conducted in the USA found only relatively small quality-of-care differences between males and females or across income groups compared to the gap for each subgroup between observed and desirable quality of health care [4]. Here, we review the data on the existence of, and reasons for, associations between gender and outcome of severe sepsis (Fig. 1)."
7720,Human Security: A South American Perspective,"For over a decade, human security has been in the global and hemispheric agenda. During this time it became a central concept within the United Nations system."
7721,Wie schützt das Immunsystem bei Infektionen?,"Der Vielfalt der Erreger und ihres Verhaltens muss die Immunantwort angepasst sein, um ein Optimum in der Balance zwischen wirksamer Abwehr und unvermeidlichem Begleitschaden für den Organismus zu erzielen. Es sind folglich verschiedene Qualitäten der Immunantwort notwendig, wobei das Habitat der Infektionserregerdie optimale Abwehrstrategie bestimmt."
7722,Influenza,"Influenza is a highly contagious, acute respiratory illness afflicting humans. Although influenza epidemics occur frequently, their severity varies (1). Not until 1933, when the first human influenza virus was isolated, was it possible to define with certainty which pandemics were caused by influenza viruses. In general, influenza A viruses are more pathogenic than are influenza B viruses. Influenza A virus is a zoonotic infection, and more than 100 types of influenza A viruses infect most species of birds, pigs, horses, dogs, and seals. It is believed that the 1918–1919 pandemic originated from a virulent strain of H1N1 from pigs and birds."
7723,"The Role of Other Bacteria, Fungi, and Viruses in Bronchiectasis","Bronchiectasis, a heterogeneous disease, is characterized by a vicious cycle of airway infection and inflammation that results in structural damage to the airways and the surrounding lung parenchyma [1]. Many microorganisms have been associated with bronchiectasis, both as a complication of the anatomic abnormalities and possibly as a cause of the structural disease as well [2, 3]. Diverse polymicrobial communities are present in the airways of patients with bronchiectasis [4]. Studies using standard microbiologic culture techniques have demonstrated the presence of bacterial, fungal, and viral pathogens in the lungs of bronchiectasis patients both when the patient is clinically stable and when there is an exacerbation of disease [2, 5]. Newer molecular techniques have broadened our understanding of the microbiome in bronchiectasis patients [4, 6]. Pseudomonas aeruginosa has been repeatedly shown to be a problematic pathogen in patients with bronchiectasis and is associated with a worse prognosis [7, 8]. Multiple epidemiologic reports have shown that approximately 20–35% of patients worldwide with bronchiectasis are chronically infected with P. aeruginosa [2, 9, 10]. Several antibiotic trials have been published where the main target of therapy is Pseudomonas aeruginosa [11–17]. (See Chap. 10.1007/978-3-319-61452-6_11 for a full review of P. aeruginosa infections associated with bronchiectasis.) Another problematic group of pathogens, nontuberculous mycobacteria (NTM), is a common infecting organism in bronchiectasis, particularly in the United States and in parts of Asia [2, 18]. NTM infection is fully discussed in Chap. 10.1007/978-3-319-61452-6_13. In this chapter, we will review the role of bacterial pathogens other than P. aeruginosa and the impact of fungal and viral infections in bronchiectasis patients. (See Table 13.1.)"
7724,Import- en reizigersziekten,"Import- en reizigersziekten zijn ziekten die zich specifiek voordoen bij reizigers en die in Nederland niet (meer) endemisch zijn. Infecties vormen een belangrijk onderdeel van de import- en reizigersgeneeskunde en zijn meestal gerelateerd aan de (sub)tropen, waar (parasitologische) infecties prominent vertegenwoordigd zijn. Morbiditeit bij reizigers wordt vooral veroorzaakt door infecties, terwijl de belangrijkste doodsoorzaak in deze groep het gevolg is van ongelukken en trauma’s. Groeiend reizigersverkeer en migratie van bevolkingsgroepen door oorlogen of andere oorzaken dragen bij tot de verspreiding van infecties in soms epidemische vorm; zo kunnen nieuwe infecties of resistente vormen van reeds aanwezige infecties in een bepaald gebied worden geïntroduceerd. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1117-0_19) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers."
7725,Coronaviridae: Infectious Bronchitis Virus,"The abstract is published online only. If you did not include a short abstract for the online version when you submitted the manuscript, the first paragraph or the first 10 lines of the chapter will be displayed here. If possible, please provide us with an informative abstract. Avian infectious bronchitis virus is the prototype of the gammacoronavirus, which is responsible for highly contagious disease in chicken. It continues to be one of the most common diseases in chicken and probably endemic in all countries that raise chicken. The virus infection causes considerable economic losses in both commercial meat- and egg-type birds. The virus tropism includes respiratory tract, proventriculus, cecal tonsils, oviduct and kidney. Infections mainly cause respiratory distress in young chickens. In broiler chicken,the virus causes respiratory distress but some strains produce interstitial nephritis while others cause proventriculitis. In laying hens, the virus causes considerable decrease in egg production and quality. Antigen detection and the reverse transcription polymerase chain reaction (RT-PCR) are commonly used methods for rapid virus diagnosis. RT-PCR and direct gene sequence of the S1 gene or restriction fragment length polymorphism (RFLP) are used for virus genotyping. The control strategy against infectious bronchitis virus (IBV) is conducted by live attenuated vaccine. To date, more than 65 genotypes and variants are characterized worldwide with poor cross protection. In addition, recombination could increase the variety of strains since live attenuated IBV vaccine viruses may recombine with virulent wild-type strains, and the resultant viruses have caused outbreaks of respiratory disease and production problems in chicken flocks."
7726,Theories of Carcinogenesis,"The oldest description of human cancer, referring to eight cases of tumors of the breast, was found in the Egyptian Edwin Smith Papyrus, written around 3000–1500 BC. The oldest specimens of human cancers were detected in the remains of a female skull dating back to the Bronze Age (1900–1600 BC), and in fossilized bones of ancient Egypt. The mummified skeletal remains of Peruvian Incas, dating about 2,400 years ago, contained lesions suggestive of malignant melanoma. The term “cancer” goes back to Hippocrates (460–370 BC), who named a group of diseases καρκινοσ and καρκινομα, the ancient Greek word for crab. It is a metaphor for the hard center and spiny projections of the tumors he studied. Cancer is the Latin word for crab and its use has been traced back to Galen (AD 129–199). A snapshot of theories of carcinogenesis, devised in the course of the last two centuries, reflects the progress of insight from the cellular level via biochemistry to an understanding of damaging influences and oncogenes, and to a more wholistic approach in the regulatory theory. It shows the relative success of reductionism as well as the current need to put the insights of various research endeavors into broader paradigmatic contexts."
7727,"Dogs and Transmission of Infection to Man, “Respected Member of the Family?”","Numerous reviews on dog zonoses address long-lasting lists of zoonotic infections, observed worldwide or very specifically in certain regions only. Here we describe the average family dog in the Western hemisphere owned by an average family without sufficient knowledge about potential hazards their pet might transmit to family members. This chapter is based on semi quantitative risk analysis in order to rank potential health risk transmitted from family dogs to human. Surprisingly every day risk is different from the generally expected potential risk according to traditional ranking of hazards (zoonoses) in dogs in general. Attention is given to human behavior regarding the family dog and responsible dog ownership. Modern trends include pet travel or pet import from endemic to non-endemic areas, without sufficient knowledge amongst pet owners or public health institutes. Of great value is information provided by ESCCAP (www.esccap.org) with information for European countries (veterinarians and pet-owners) on prevalences and prevention of parasitic infections in dogs and cats in the major languages of Europe. Eventually attention is paid to new trends in dog feed such as feeding bones and raw meat. This may have serious consequences for the spread of ordinary zoonoses like Salmonella and parasitic infections not only between dogs, but also to family members. A last point of attention is the prevention of attracting wild life zoonoses via dogs to family members (eg. Echinococcus multilocularis and Baylisascaris spp.). Authorities responsible for public health should be encouraged to pay more attention, not only in providing more regulations, but primary in enforcement of existing rules and stimulating responsible pet-ownership. Companion animal veterinarians and (local) public health authorities, including physicians, should contribute equally in zoonoses prevention programs (‘One health’ approach)."
7728,Directly Identify Unexpected Instances in the Test Set by Entropy Maximization,"In real applications, a few unexpected examples unavoidably exist in the process of classification, not belonging to any known class. How to classify these unexpected ones is attracting more and more attention. However, traditional classification techniques can’t classify correctly unexpected instances, because the trained classifier has no knowledge about these. In this paper, we propose a novel entropy-based method to the problem. Finally, the experiments show that the proposed method outperforms previous work in the literature."
7729,Sarcophaga spp.,
7730,Natural Products from Sponges,"The sponge is one of the oldest multicellular invertebrates in the world. Marine sponges represent one of the extant metazoans of 700–800 million years. They are classified in four major classes: Calcarea, Demospongiae, Hexactinellida, and Homoscleromorpha. Among them, three genera, namely, Haliclona, Petrosia, and Discodemia have been identified to be the richest source of biologically active compounds. So far, 15,000 species have been described, and among them, more than 6000 species are found in marine and freshwater systems throughout tropical, temperate, and polar regions. More than 5000 different compounds have been isolated and structurally characterized to date, contributing to about 30% of all marine natural products. The chemical diversity of sponge products is high with compounds classified as alkaloids, terpenoids, peptides, polyketides, steroids, and macrolides, which integrate a wide range of biological activities, including antibacterial, anticancer, antifungal, anti-HIV, anti-inflammatory, and antimalarial. There is an open debate whether all natural products isolated from sponges are produced by sponges or are in fact derived from microorganisms that are inhaled though filter-feeding or that live within the sponges. Apart from their origin and chemoecological functions, sponge-derived metabolites are also of considerable interest in drug development. Therefore, development of recombinant microorganisms engineered for efficient production of sponge-derived products is a promising strategy that deserves further attention in future investigations in order to address the limitations regarding sustainable supply of marine drugs."
7731,Molecular Epidemiology and Evolutionary Genetics of Infectious Diseases,"This chapter does not attempt to provide a comprehensive catalogue of the various methods of analysis and technologies used to characterize pathogens (molecular epidemiology). Rather it argues why molecular epidemiology should not be conceived without an extensive use of the concepts of population genetics and evolutionary biology. Moreover, it stresses that characterizing pathogens should open up to evaluating the impact of pathogens’ genetic diversity on their relevant medical properties (downstream studies). Lastly, it presents the foreseeable future developments in this field, which has been upset by the exponential development of megatechnologies (massive sequencing, postgenomic studies, and bioinformatics)."
7732,Emergence of New Tickborne Infections,"Several tickborne infectious diseases such as Lyme borreliosis, ehrlichiosis, anaplasmosis, babesiosis, and others have been expanding to new endemic regions in the world for over a decade. Moreover, new pathogens transmitted by ticks have recently been recognized in animals and humans from diverse regions of the globe, widely separated in distance. These include new phleboviruses of the Bunyaviridae family, exemplified by severe fever with thrombocytopenia syndrome virus [SFTSV] recognized in China in 2010, and the Heartland virus, a closely related but distinct virus, presenting with similar clinical features and discovered in Missouri in 2012. Other newly recognized tickborne infections include a novel spirochete of the relapsing fever group, Borrelia miyamotoi, first reported to cause human infection in Russia in 2011 and subsequently discovered to cause clinical disease in the Netherlands, Japan, and the United States, with transmission by the black-legged deer tick Ixodes scapularis. In Europe a new tickborne disease, neoehrlichiosis caused by Candidatus neoehrlichia mikurensis belonging to the Anaplasmataceae family, has been described recently. Furthermore, new tickborne rickettsial infections continue to be recognized in Europe such as tickborne lymphadenopathy identified in 1997 and caused by Rickettsia slovaca. Novel tickborne infectious diseases will continue to emerge worldwide for the foreseeable future and be a challenge to the health of human populations. Innovative methods of prevention for a broad variety of tick-transmitted diseases are needed, and one approach is to develop a universal tick vaccine that can be given to animal hosts or humans."
7733,6 Lagere luchtwegen,"Bronchiën zijn vertakkingen van de luchtpijp die samen een soort ‘boom’ in de longen vormen. Bronchiën horen bij de lagere luchtwegen. De allerkleinste bronchiën gaan over in het longweefsel zelf, de longblaasjes."
7734,Biomedical Waste,"Biomedical waste comprises of all liquid and solid wastes generated from medical establishments and activities involving biological materials. Besides health care, the relevant activities include clinical research, research involving animals, animal farms, dead animals, and others. The generation of biomedical waste is not restricted to specific activity or organisations. It can originate from homes during dialysis and using insulin injections, animal health activities in rural areas, butchering of sick animals in butcher houses, medical shops, use of sanitary napkins and ear buds, use of diapers, and air ports when passengers through away restricted medicines without prescription."
7735,Global Warming and Trans-Boundary Movement of Waterborne Microbial Pathogens,"Potential ramifications of climate change, as they relate to waterborne pathogens (primarily viruses, bacterial and parasitic protozoa), are the focus of this chapter. It seems clear that climate change will impact on waterborne pathogens in various ways (Rose et al. 2001), pertinent to transboundary issues are: (1) increases in intense storm events (increasing sewage/animal waste flows into waterways/aquifers) (Charron et al. 2004; Schijven and de Roda Husman 2005; Yang and Goodrich 2009; De Toffol et al. 2009; Richardson et al. 2009); (2) warmer surface water temperatures or salinity changes (for increased autochthonous pathogen growth) (Niemi et al. 2004; Koelle et al. 2005; Lebarbenchon et al. 2008); and (3) changes in food production, as most obvious in animal diseases (Lightner et al. 1997; Rapoport and Shimshony 1997), but also of concern with zoonoses and from changes in social behavior (Schwab et al. 1998; Nancarrow et al. 2008; CDC 2009a). When considering trans-boundary effects on waterborne pathogens, it is therefore the flow of pathogens in surface water (fresh and marine) and in groundwater, as well as in the varying ways water is used/reused in association with human activities (e.g., food production) that are the trans-boundary issues discussed in this chapter (examples in Table 5.1). Changes in infectious and vector-borne diseases associated with rising sea levels, losses of habitat, international travel etc. are not addressed in this chapter."
7736,Disease And Welfare,
7737,Comfort Energetics: Thermal Comfort Under Energy Constraints,"This chapter represents an energy-conscious approach to understanding thermal comfort. With the environmental variable of T, MRT, RH and wind v as its structure, it begins with a psychrometric analysis where the roles of temperature and humidity are denominated in PMV votes and the power needed to improve those votes. The role of humidity is critically reviewed with a case made for challenging the accepted norms an optimum RH range. Finally the efficacy of moving air is analysed in the different ways it can be employed."
7738,The Discovery and Development of Daclatasvir: An Inhibitor of the Hepatitis C Virus NS5A Replication Complex,"The discovery of the hepatitis C virus (HCV) NS5A replication inhibitor daclatasvir (1) had its origins in a phenotypic screening lead. However, during the optimization campaign, it was observed that some members of the chemotype underwent a radical dimerization under the assay conditions. This redirected the effort to focus on palindromic molecules, a species subsequently shown to complement the dimeric nature of the NS5A protein. The most challenging aspect of the discovery program was extending antiviral activity to encompass GT-1a virus which was accomplished only after the development of extensive structure-activity relationships. In clinical trials, oral administration of daclatasvir (1) produced a profound effect on viral load with onset that was more rapid than had been seen previously with either NS3 protease or NS5B polymerase inhibitors. A groundbreaking clinical trial that combined daclatasvir (1) with the protease inhibitor asunaprevir (52) established that a chronic HCV infection could be cured with small molecule therapy in the absence of immune stimulation, setting the stage for approval of this regimen for the treatment of GT-1b-infected subjects by the Japanese health authorities on July 4, 2014."
7739,"Genomics, Other “Omic” Technologies, Personalized Medicine, and Additional Biotechnology-Related Techniques","The products resulting for biotechnologies continue to grow at an exponential rate, and the expectations are that an even greater percentage of drug development will be in the area of the biologics. In 2011, worldwide there were over 800 new biotech drugs and treatments in development including 23 antisense, 64 cell therapy, 50 gene therapy, 300 monoclonal antibodies, 78 recombinant proteins, and 298 vaccines (PhRMA 2012). Pharmaceutical biotechnology techniques are at the core of most methodologies used today for drug discovery and development of both biologics and small molecules. While recombinant DNA technology and hybridoma techniques were the major methods utilized in pharmaceutical biotechnology through most of its historical timeline, our ever-widening understanding of human cellular function and disease processes and a wealth of additional and innovative biotechnologies have been, and will continue to be, developed in order to harvest the information found in the human genome. These technological advances will provide a better understanding of the relationship between genetics and biological function, unravel the underlying causes of disease, explore the association of genomic variation and drug response, enhance pharmaceutical research, and fuel the discovery and development of new and novel biopharmaceuticals. These revolutionary technologies and additional biotechnology-related techniques are improving the very competitive and costly process of drug development of new medicinal agents, diagnostics, and medical devices. Some of the technologies and techniques described in this chapter are both well established and commonly used applications of biotechnology producing potential therapeutic products now in development including clinical trials. New techniques are emerging at a rapid and unprecedented pace and their full impact on the future of molecular medicine has yet to be imagined."
7740,Radiological Terrorism,"Radiological terrorism is the use of radioactive material to cause human casualties, environmental destruction and maximum disruption, panic and fear (1) in the general population for political purposes. Since the atomic bombing of Hiroshima in 1945, with 150,000 casualties and 75,000 fatalities (2), people have feared nuclear explosives more than any other weapons of mass destruction, because of the ability of these weapons to cause immediate devastation and trauma, and because radiation, undetected by human senses, can cause ongoing morbidity and mortality, including cancer, years after exposure (3)."
7741,Advanced Pathology Techniques for Detecting Emerging Infectious Disease Pathogens,"Detection and surveillance for emerging and reemerging pathogens need a multidisciplinary approach. The intertwining complexity of these pathogens with their diverse tissue tropisms, direct effects on host cells, multiphasic immunological responses, and additional influence of superimposed secondary agents is beyond the expertise of a single discipline in modern medicine. A combined evaluation of patient’s history, clinical manifestations, and physical examination may suggest a list of differential diagnosis, but it is often insufficient to determine the specific infectious etiology. Laboratory methods are essential to identify an etiologic agent from testing clinical samples, such as blood, serum, nasopharyngeal swab, etc. These methods, including traditional microbiological techniques, conventional immunological assays, and modern molecular methods, remain the mainstay in today’s practice of clinical microbiology and infectious disease medicine. Nevertheless, there are technical and logistic issues associated with these methods, and the test results often lack a clinicopathologic correlation that can confound the interpretation of their clinical significance. For example, microbiological culture may fail to grow a causative organism, while the organism isolated by the laboratory in vitro may arise from contamination and does not represent the actual infective agent in vivo."
7742,YEAH: One Story of Inspiration and Success,"Nineteen years ago, I could not have imagined that I would end up founding Australia’s first youth-focused HIV/AIDS prevention organization. Nineteen years ago, when I was 8 years old, my connection with HIV/AIDS began; my Mom, divorced and raising me as a single parent, was diagnosed HIV-positive (herein HIV+). It was the mid-1980s and the Australian social climate surrounding AIDS was one laden with fear. During that time, Australia’s profound early response to what would become the worldwide HIV/AIDS pandemic was taking form."
7743,Pneumonien,"Die heute gebräuchlichen Definitionen der unterschiedlichen Formen der Pneumonie haben nicht nur eine begrifflich ordnende Funktion, sondern bezeichnen jeweils spezifische ätiopathogenetische, diagnostische und therapeutische Konzepte. Es kommt ihnen somit ein klinisch handlungsanweisender Wert zu."
7744,Acute Otitis Media and Acute Coalescent Mastoiditis,"Acute otitis media is a frequent manifestation of otitis media, mainly during the early childhood. The multifactorial pathogenesis and risk factors are exposed along with its most microbiological agents. The clinical manifestations and their differential diagnoses are presented. General concepts and different actual guidelines of the treatment are described, also the efficient preventive measures are proposed. The second main issue of this chapter is to deal with the complications of acute otitis media, especially the acute coalescent mastoiditis, that is the most common suppurative complication of AOM. The pathogenesis of coalescent acute mastoiditis, its epidemiology, risk factors and the microbiological agents are presented. The clinical features and differential diagnosis are described, as the specific imaging findings. Complications of acute coalescent mastoiditis are typically the subperiosteal abscess, due to the cortical bony necrosis of the mastoid and its septa, or the intracranial spread of the infection (meningitis, intracranial abscesses and venous sinus thrombosis). The general concept of management is exposed, with emphasis on the antimicrobial treatment and the different surgical options."
7745,Imaging of ICU Patients,"Imaging in intensive care unit (ICU) is integral to patient management. The portable chest radiograph is the most commonly requested imaging examination in ICU, and, despite its limitations, it significantly contributes to the decision-making process. Multidetector CT (MDCT) is reserved for relatively complex and challenging clinical scenarios. Bedside ultrasound is emerging as a promising imaging modality as it does not subject the patients to risks and resources involved in the transportation of these patients to the CT facility. Ultrasound is an effective modality to triage patients and is being increasingly incorporated into the emergency and intensive care management algorithms."
7746,Thrombocytopenia in the Intensive Care Unit,"The evaluation and management of thrombocytopenia is a daily challenge for clinicians in the intensive care unit (ICU). Thrombocytopenia is incredibly common, present in upwards of 60% of ICU patients. Additionally, thrombocytopenia in the critically ill is rarely caused by a single etiology. Several causes of thrombocytopenia in the ICU including heparin-induced thrombocytopenia (HIT) and thrombotic thrombocytopenic purpura demand urgent recognition and intervention. This chapter provides a general overview of thrombocytopenia in the ICU and highlights important diagnostic and management considerations for some of the most common etiologies."
7747,Reconstructing k-Reticulated Phylogenetic Network from a Set of Gene Trees,"The time complexity of existing algorithms for reconstructing a level-x phylogenetic network increases exponentially in x. In this paper, we propose a new classification of phylogenetic networks called k-reticulated network. A k-reticulated network can model all level-k networks and some level-x networks with x > k. We design algorithms for reconstructing k-reticulated network (k = 1 or 2) with minimum number of hybrid nodes from a set of m binary trees, each with n leaves in O(mn (2)) time. The implication is that some level-x networks with x > k can now be reconstructed in a faster way. We implemented our algorithm (ARTNET) and compared it with CMPT. We show that ARTNET outperforms CMPT in terms of running time and accuracy. We also consider the case when there does not exist a 2-reticulated network for the input trees. We present an algorithm computing a maximum subset of the species set so that a new set of subtrees can be combined into a 2-reticulated network."
7748,"Isotope-Aided Methods for Biological NMR Spectroscopy: Past, Present, and Future","This chapter starts by providing a historical background of our research endeavors over the past half-century to develop various isotope-aided methods in biological NMR spectroscopy, since innovations bloom only on the rich ground cultivated by previous investigators. We then focused on the stereo-array isotope-labeling (SAIL) method, one of our recent accomplishments, which culminates the isotope-aided NMR technologies for structural studies of proteins from various aspects: accurate structural determinations of large proteins, elaboration for automated structural determination, highly efficient and versatile residue-selective methyl labeling with newly developed auxotrophic E. coli strains, large-amplitude slow-breathing motion (LASBM) as revealed by the aromatic ring flipping of the residues in ligand-binding interfaces, and applications of the deuterium-induced (13)C-NMR isotope shift to investigate the hydrogen exchange phenomena of side-chain polar groups. Meanwhile, the expected role of NMR spectroscopy has been rapidly shifting from structure determinations to dynamics studies of biologically interesting targets, such as membrane proteins and larger protein complexes. The dynamic aspects of protein–protein and protein–ligand interactions are closely related to their biological functions and can be efficiently studied by using proteins residue selectively labeled with amino acids bearing optimized labeling patterns, prepared by cellular expression. We are absolutely confident that biological NMR spectroscopy will continually develop with further innovations of isotope-labeling technologies in the coming era, featuring ultrahigh field spectrometers beyond 1 GHz."
7749,Recombinant Turkey Coronavirus Nucleocapsid Protein Expressed in Escherichia coli,Expression and purification of turkey coronavirus (TCoV) nucleocapsid (N) protein from a prokaryotic expression system as histidine-tagged fusion protein are presented in this chapter. Expression of histidine-tagged fusion N protein with a molecular mass of 57 kDa is induced with isopropyl β-d-1-thiogalactopyranoside (IPTG). The expressed N protein inclusion body is extracted and purified by chromatography on nickel-agarose column to near homogeneity. The protein recovery can be 10 mg from 100 ml of bacterial culture. The purified N protein is a superior source of TCoV antigen for antibody-capture ELISA for detection of antibodies to TCoV.
7750,Tubulointerstitielle Erkrankungen,
7751,Indoor Air Pollution and Its Control in China,"ABSTRACT: The status of indoor air pollution and its control in China are reviewed by introducing the pollution characteristics of major indoor air pollutants, the strategies and measures adopted to control indoor air pollution, as well as the major problems existing in the current indoor air pollution control. Although indoor pollution of formaldehyde and benzene has been effectively alleviated in recent years in China, indoor pollution of toluene and xylenes is still serious. Besides, studies show that indoor pollution of particulate matter (PM), biological pollutants, and semi-volatile organic compounds (SVOCs) might also be serious in China. The establishment and implementation of indoor air quality (IAQ)-related regulations and standards, the research on indoor air pollution and its control, and the development of indoor environmental monitoring and cleaning industry have played significant roles in preventing and controlling indoor air pollution in China. However, problems such as lack of mandatory standards for IAQ, lack of regulation and labeling of pollutant emissions from indoor decorating and refurbishing materials, lack of an effective performance evaluation system for air cleaning products, and lack of proper maintenance of air cleaners remain to be solved for further improvement of IAQ. GRAPHICAL ABSTRACT: [Image: see text]"
7752,Nationale Sicherheit und der sich wandelnde Gegenstand der öffentlichen Gesundheit,"Im November 2005 gab die Busch-Regierung eine 7,1 Milliarde teure Pandemie- Vorsorge-Strategie bekannt, die der US-Gesundheitsminister als den solidesten Vorschlag bezeichnete, der je zur Unterstützung der öffentlichen Gesundheit gemacht wurde (Leavitt 2005). Der Maßnahmenkatalog umfasste die Finanzierung von Programmen, die die Entwicklung von Krankheiten überwachen sollten, die Vorratshaltung von antiviralen Wirkstoffen sowie die Erforschung neuer Methoden der Impfstoffgewinnung. Die Einzelheiten dieser Planung wurden innerhalb der Public Health-Community scharf kritisiert. Moniert wurde die ihrer Ansicht nach zu starke Betonung pharmazeutischer Interventionen bei gleichzeitig zu geringer Beachtung der Bedarfe der Gesundheitsbehörden auf nationaler wie auf der Ebene der einzelnen Bundesstaaten. In einigen Punkten bestand jedoch Einigkeit: Erstens war man sich einig, dass die Strategien im Umgang mit Pandemien eine dringende Angelegenheit sei, zweitens, dass die USA bislang nicht annähernd genügend auf ein derartiges Ereignis vorbereitet seien, und drittens, dass – egal, ob es eine Pandemie geben würde oder nicht – die vorbereitenden Maßnahmen sie zugleich für diverse andere Bedrohungslagen wappnen würde oder wie es ein Mitglied des US-Senats beschrieb: „Selbst wenn wir von einer Grippe-Pandemie verschont bleiben, wird die Arbeit, die wir heute leisten, in einem nationalen Notfall, der eines Tages eintreffen könnte, hilfreich sein“ (US Senate 2006a)."
7753,Connections to Support Learning About Science,"This chapter discusses the need for greater levels of scientific literacy in contemporary society. It identifies three major curriculum thrusts that collectively inform scientific literacy – learning science, learning about science, and doing science – with a principal focus on learning about science, often referred to as nature of science (NoS). Particular emphasis is given to the importance of the language of science, the values, norms and traditions of scientists, and the reality of contemporary practice. The remainder of the chapter discusses direct and indirect connections with scientists and the impact of these on developing understanding about science. The chapter concludes with a discussion of the possibilities and pitfalls of such connections."
7754,"A Heuristic Approach to Future Disasters and Crises: New, Old, and In-Between Types","Disasters and crises have been part of the human experience since people started living in groups. Through the centuries, however, new hazards and risks have emerged that have added to the possibilities of new disasters and crises arising from them. Only a very small fraction of risks and hazards actually lead to a disaster or crisis, but they are usually a necessary condition for such surfacing. New types have emerged while older ones have not disappeared. The development of synthetic chemicals in the 19th century and nuclear power in the 20th century created the risk of toxic chemical disasters and crises from radioactive fallouts. Ancient disasters such as floods and earthquakes remain with us today. This chapter raises the question of whether we are at another important historical juncture with the emergence of a new distinctive class of disasters and crises not seen before."
7755,European Trends in Science Communication,"This chapter reports on current trends in science communication in Europe in the light of several recent studies by the European Commission. The author investigates why the European public’s scientific knowledge, as measured by the surveys, has increased substantially over the past few years. He then reviews coverage of science in the European media and analyses the relationships between European scientists and journalists and recent trends in reportage. Noting that it has become harder to gain public acceptance of scientific and technological innovations in Europe, the author argues that the science–society dialogue is insufficiently developed because a genuine communication culture is lacking in the science and technology sector. This lack may hamper the advancement of the sector."
7756,Litigations for HIV Related Complications,"In 1992, a 27-year-old male with same sex exposure requested human immuno-deficiency virus (HIV) testing anonymously at a walk-in clinic. He was advised that the test (HIV serology) was positive and he requested a repeat test (anonymously) 1 month later, which was also reported as being positive. About 2 years later, he was assessed by a general practitioner for symptoms of depression and continued medical care. At that time, investigations revealed a CD4 T-cell count of about 700 cells/uL. Sometime in 1996 a repeat blood test revealed a CD4 cell count just <500 cells/uL. No consultation to an infectious diseases specialist or HIV clinic was made. The GP(general practitioner) then initiated a regimen consisting of didanosine, lamivudine, and saquinavir for HIV infection. At that time, testing for HIV viral load was not generally available to the medical community, but became procurable in 1997. Initially, the patient tolerated the regimen well and over the next 3 years his CD4 cell count was maintained above 600–700 cells/uL and the HIV viral load remained undetectable (<50 copies). However, the patient started to show morphologic changes of moderate facial and peripheral lipoatrophy, developed mild sensory peripheral neuropathy, and increased liver enzymes attributable to fatty liver, and elevations of the fasting serum glucose. In the summer of 2000, although the CD4 cell count remained stable, the HIV viral load was reported as being over 7,000 copies/uL. At this time, the patient was referred to a university hospital HIV clinic."
7757,RFID in Healthcare – Current Trends and the Future,"Radio Frequency Identification (RFID) enables automatic identification of objects using radio waves. The identified objects can be in and out of the line of sight and there is no need for physical contact with them. RFID technology is deployed in a wide range of industries such as supply chain management, inventory control, farming (to track animals), e-Passports, the tracking of humans (in prisons and hospitals) and in healthcare [1]. The three key elements of an RFID system are the tags, readers and the backend server. Tags are devices physically attached to objects and readers (wired or mobile) recognize the presence of objects in its range."
7758,The Infections Causing Acute Respiratory Failure in Elderly Patients,"The immune system of older individuals declines with advancing age (“immunosenescence”) increasing susceptibility to infection, as well as to an increased risk of a worse outcome. Severe community-acquired pneumonia and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are causes of acute respiratory failure (ARF) in elderly patients. Non-invasive mechanical ventilation (NIV) is effective in the treatment of patients with ARF, above all in case of AECOPD."
7759,Mammalia: Chiroptera: Immunology of Bats,"Bats are a large and diverse group comprising approximately 20% of all living mammalian species. They are the only mammals capable of powered flight and have many unique characteristics, including long lifespans, echolocation, and hibernation, and play key roles in insect control, pollination, and seed dispersal. The role of bats as natural reservoirs of a variety of high-profile viruses that are highly pathogenic in other susceptible species yet cause no clinical disease in bats has led to a resurgence of interest in their immune systems. Equally compelling is the urgency to understand the immune mechanisms responsible for the susceptibility of bats to the fungus responsible for white syndrome, which threatens to wipe out a number of species of North American bats. In this chapter we review the current knowledge in the field of bat immunology, focusing on recent highlights and the need for further investigations in this area."
7760,Guidelines for Health Organizations: European Perspectives and Experience in Pandemics,"In Europe, the rate of noninvasive ventilation (NIV) use in intensive care units (ICUs) is about 35 % for ventilated patients and higher (roughly 60 %) in respiratory ICUs or emergency departments. In North America, this form of ventilation is begun most often in emergency departments (EDs), most patients being transferred to the ICU or step-down units in hospitals with such facilities. This low rate of use in some hospitals is related to scarce knowledge on or experience with this technique, insufficient technical equipment, and inadequate funding. Despite these limitations, NIV is increasingly being used outside traditional and respiratory ICUs, including EDs, postsurgical recovery rooms, cardiology, neurology, and oncology wards, and palliative care units."
7761,"Negative Pressure Noninvasive Ventilation (NPNIV): History, Rationale, and Application","Man has recognized the vital role of breathing since antiquity, beginning with archeological findings depicting inhalation therapy using herbs, oils, and other substances since 6000 BC. Man has taken the automaticity of breathing for granted, expecting its adequacy for all activities whether awake or asleep. Dickinson W. Richards, MD, Nobel Laureate, said in 1962: “Breathing is that essential physiologic function that is straddled between the conscious & the unconscious and subject to both.” The understanding of the components of this critical physiologic function that starts at birth, and must be continuous and widely adaptable to support all levels of physical, metabolic, and functional needs, has evolved slowly over the millennia by many brilliant scientists from a combination of keen observation, imagination, daring experimentation, trial and error, and necessity, while overcoming dogma, religious inhibitions, and politics. It is this gradual chronologic process, still evolving, which guides what we do for patients today."
7762,Schnupfen,
7763,Lipidmediatoren und ihre Rolle bei Entzündungen und Allergien,"Lipidmediatoren sind als lokal agierende Lipide nach dem Eindringen eines Krankheitserregers oder nach Gewebsverletzung im Zusammenspiel mit Interleukinen und Chemokinen zunächst für die sinnvollen proinflammatorischen Prozesse wie Calor, Rubor, Dolor, Tumor verantwortlich. Nach erfolgreich abgewehrter Infektion sind es wieder Lipidmediatoren, die mithelfen, die unschädlich gemachten Viren und Bakterien sowie nekrotisches Material aus dem Gewebe zu eliminieren, die Entzündungsreaktion zu stoppen und geschädigtes oder zerstörtes Gewebe zu regenerieren. Mit den Lipidmediatoren hat die Evolution wunderbare molekulare Netzwerke für kontrollierte Immunantworten auf Infektionen und Verletzungen geschaffen, die perfekt koordiniert zu einer Restitutio ad integrum führen und die die Homöostase im Gewebe wiederherstellen. Lange Zeit konzentrierte man sich auf die wissenschaftliche Beobachtung der entzündungsauslösenden Wirkung der Prostaglandine und Leukotriene. In letzter Zeit fokussiert die Forschung jedoch immer mehr auch die antiinflammatorischen und entzündungsauflösenden, schützenden und die Regeneration mediierenden Effekte der Lipidmediatoren, weil diese vor der Pathogenese von chronischen Erkrankungen, wie zum Beispiel Allergien, schützen können."
7764,Disease Protection in Sea Coast (and Inland) Cities: Problems in Dense Populations with Shantytowns/Slums,"As discussed earlier in this book, there are sea coast cities worldwide that are at risk from floods, storm surges, and extreme weather conditions such as wind-driven high category hurricanes (typhoons, monsoons), or drought and heat waves, plus along Pacific Ocean coasts, earthquakes and tsunamis. A municipality and its public health services have to be prepared to adapt to their preparations to deal with what contemporary experiences and history reveal are the most likely physical hazards and diseases to impact it. The two main preparatives are first to be able to care for the injured during a hazard event at well-staffed and supplied hospitals and medical clinics or field hospitals. The second is to fill the basic needs of affected populations with clean water, food, shelter, toilets, waste collection, and if necessary power restoration. These primary responses will help to reduce the chance of an onset and spread of disease. It is important to activate search and rescue teams help citizens isolated or trapped by the event that did not or could not evacuate such as in the case of extreme weather and flooding. In addition, where there have been deaths, bodies should be recovered and interred as soon as possible in order to prevent sickness that might originate from them. For instances of collapsed structures with people trapped inside, equipment that can move debris and rescue people or recover the deceased is necessary as would be the case for less common strong earthquakes as well as some extreme storm events. What was just described may be a good template to follow, but in reality, many sea coast cities in developing and less developed countries do not have the resources to cope with severe hazards that might impact them. Here, the World Health Organization and developed nations, large and small, have sent in personnel, supplies, and equipment to help an impacted sea coast city (or inland city) in the past and will surely continue to do so in the future."
7765,Chemical Sensors and Measurement,"Chemical sensors have been widely used in the biomedical field. With the rapid development of microelectronics and microprocessing technology, chemical sensors have grown to be more and more miniaturized and integrated. Combined with new information processing technology, intelligent chemical sensor arrays such as e-Nose and e-Tongue have been developed. Meanwhile, microfluidic chips enable continuous monitoring of chemical substances in living organisms."
7766,Neutral Evolution,"Neutral evolution is the default process of the genome changes. This is because our world is finite and the randomness is important when we consider history of a finite world. The random nature of DNA propagation is discussed using branching process, coalescent process, Markov process, and diffusion process. Expected evolutionary patterns under neutrality are then discussed on fixation probability, rate of evolution, and amount of DNA variation kept in population. We then discuss various features of neutral evolution starting from evolutionary rates, synonymous and nonsynonymous substitutions, junk DNA, and pseudogenes."
7767,Approaches on H5N1 Avian Influenza Spreading in Relation with Human Health Risk,"Recent experiences with highly pathogenic H5N1 avian influenza have given the world its first advance warning that another influenza pandemic may be imminent. Given the serious consequences of past pandemics, this advance warning has stimulated a search for ways to prevent such an event from occurring through preparedness, rapid response and containment. The rapid response and containment strategy aims to stop, or at least slow the spread of pandemic influenza at the source of its emergence in order to minimize global morbidity and mortality."
7768,Role of Proteases in Lung Disease: A Brief Overview,"Proteases play an important role in health and disease of the lung. In the normal lungs, proteases maintain their homeostatic functions that regulate processes like its regeneration and repair. Dysregulation of proteases–antiproteases balance is crucial in the manifestation of different types of lung diseases. Chronic inflammatory lung pathologies are associated with a marked increase in protease activities. Thus, in addition to protease activities, inhibition of anti-proteolytic control mechanisms are also important for effective microbial infection and inflammation in the lung. Herein, we briefly summarize the role of different proteases and to some extent antiproteases in regulating a variety of lung diseases."
7769,Membrane-Anchored Serine Proteases: Host Cell Factors in Proteolytic Activation of Viral Glycoproteins,"Over one third of all known proteolytic enzymes are serine proteases. Among these, the trypsin-like serine proteases comprise one of the best characterized subfamilies due to their essential roles in blood coagulation, food digestion, fibrinolysis, or immunity. Trypsin-like serine proteases possess primary substrate specificity for basic amino acids. Most of the well-characterized trypsin-like proteases such as trypsin, plasmin, or urokinase are soluble proteases that are secreted into the extracellular environment. At the turn of the millennium, a number of novel trypsin-like serine proteases have been identified that are anchored in the cell membrane, either by a transmembrane domain at the N- or C-terminus or via a glycosylphosphatidylinositol (GPI) linkage. Meanwhile more than 20 membrane-anchored serine proteases (MASPs) have been identified in human and mouse, and some of them have emerged as key regulators of mammalian development and homeostasis. Thus, the MASP corin and TMPRSS6/matriptase-2 have been demonstrated to be the activators of the atrial natriuretic peptide (ANP) and key regulator of hepcidin expression, respectively. Furthermore, MASPs have been recognized as host cell factors activating respiratory viruses including influenza virus as well as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses. In particular, transmembrane protease serine S1 member 2 (TMPRSS2) has been shown to be essential for proteolytic activation and consequently spread and pathogenesis of a number of influenza A viruses in mice and as a factor associated with severe influenza virus infection in humans. This review gives an overview on the physiological functions of the fascinating and rapidly evolving group of MASPs and a summary of the current knowledge on their role in proteolytic activation of viral fusion proteins."
7770,Coronaviruses,"Coronaviruses of humans were first identified more than 60 years ago from individuals with respiratory infections, mainly mild. Two different viruses, 229E and OC43 were initially recognized. Because of difficulty in isolating them using standard techniques, many of the early studies of their occurrence were seroepidemiologic. They were confirmed to be worldwide in distribution, and, in the North Temperate Zone, mainly occurring in the winter season. With the development of the reverse transcriptase polymerase chain reaction (PCR) technique, two additional distinct viruses have been identified, HKU1 and NL63. The four viruses have now been recognized as important in the etiology of common respiratory infections, second only to the rhinoviruses. In 2002, a previously unrecognized betacoronavirus emerged from a zoonotic reservoir in Southern China and spread during the following year to several major cities of the world. The resulting illness was termed Severe Acute Respiratory Syndrome (SARS) because of its potential lethality. More than 8,000 probable cases were reported during 2003, mainly from Hong Kong and mainland China, producing social and economic disruption in those areas affected. A constant feature of the outbreak was the importance of nosocomial spread. In spite of an estimated basic reproductive number higher than influenza, the outbreak was ended, in large part because of control of in-hospital transmission. In 2012, another betacoronavirus has emerged in the Arabian peninsula which is producing a somewhat similar illness, termed Middle East Respiratory Syndrome (MERS), also marked by extensive nosocomial transmission. The outcome of this emergence is currently unknown."
7771,Schwarze Piedra,
7772,Immune Measures in Behavioral Medicine Research: Procedures and Implications,"Immune system activity is heavily influenced by the central nervous system. These interactions provide us the means to study mind–body interactions and how they affect health. In general, measures of immune system activity can be divided into two categories: those that are evident in the circulation and those that need to be elicited. For example, leukocytes can be collected from the circulation, counted, and their function accessed in cell culture. To test the ability of the immune system to respond to an experimental challenge more directly, studies involving wound healing, or involving the response to an infectious agent, can be performed. The purpose of this chapter is briefly to describe immune assays that are commonly employed in behavioral medicine research, including a rationale for their use as well as a brief description of the methodology. This chapter also describes previous studies in which circulatory and elicited immune measures have been studied in human subjects experiencing different psychological stressors, with an emphasis on studies involving medical students experiencing academic stress and caregivers of a spouse with Alzheimer’s disease. Finally, the chapter discusses the important role that the employment of animal models can play in studies of stress and health and in defining how nervous system activity can influence the immune response."
7773,Acute Bacterial Rhinosinusitis,"Acute bacterial rhinosinusitis (ABRS) is a highly prevalent disease associated with significant direct and indirect costs. It is paramount that a practitioner can distinguish between acute viral rhinosinusitis and ABRS to avoid unnecessary antibiotic usage. It is also important to understand that establishing a diagnosis of ABRS does not necessitate the prescribing of antibiotics, unless the ABRS patient presents with severe or worsening symptoms or an ABRS complication. Complications include extension of infection to the orbit and central nervous system. Injudicious use of antibiotics imparts societal costs in terms of financial expense as well as contributing to higher levels of bacterial resistance. This chapter reviews the epidemiology, clinical features, diagnosis, and treatment of ABRS."
7774,Viral-Bacterial Interactions in Childhood Respiratory Tract Infections,"Acute respiratory infection (ARI) is an important cause of childhood morbidity and mortality worldwide. ARIs are caused primarily by viruses and bacteria that are often co-detected in respiratory specimens. Although viral-bacterial co-infections are frequently reported in children with ARI, their clinical significance and the mechanisms leading to ARI are not well understood. The respiratory tract is a reservoir of a diverse community of microorganisms, including both commensals and potential pathogens and there is growing evidence that the interactions between viruses and bacteria play a key role in the development of ARI. A better understanding of the interactions between viruses and bacteria in the respiratory tract may enhance insight into the pathogenesis of ARI, and potentially reveal new prevention and treatment strategies. This chapter summarizes the current knowledge on viruses, bacteria and viral-bacterial interactions in childhood ARI and the possible mechanisms by which these interactions may lead to disease."
7775,6 Uitvoering en organisatie van de publieke gezondheidszorg,"Onder publieke gezondheidszorg verstaan wij het bevorderen van de volksgezondheid en van gelijke kansen op gezondheid, door collectieve interventies gericht op gezondheidsbescherming, gezondheidsbevordering en ziektepreventie. Onder deze Nederlandse variant op de Engelse definitie van public health (zie paragraaf 1.1.2) vallen in ons land verschillende activiteiten en organisaties, waaronder ook grote delen van de jeugdgezondheidszorg en de bedrijfsgezondheidszorg, die respectievelijk in hoofdstuk 7 en 8 worden besproken. In dit hoofdstuk zullen we het begrip publieke gezondheidszorg echter in engere zin opvatten, als benaming voor een aantal gemeentelijke en landelijke organisaties die zich (voornamelijk) met preventie bezighouden."
7776,Coronavirus Genome Replication,"Viruses belonging to the family Coronaviridae are unique among RNA viruses because of the unusually large size of their genome, which is of messenger- or positive- or plus-sense. It is ∼30,000 bases or 2–3 times larger than the genomes of most other RNA viruses. Coronaviruses belong to the order Nidovirales, the other three families being the Arteriviridae, Toroviridae and Roniviridae. (For a review of classification and evolutionary relatedness of Nidovirales see Gorbalenya et al. 2006.) This grouping is based on the arrangement and relatedness of open reading frames within their genomes and on the presence in infected cells of multiple subgenomic mRNAs that form a 3'-co-terminal, nested set with the genome. Among the Nidovirales, coronaviruses (and toroviruses) are unique in their possession of a helical nucleocapsid, which is unusual for plus-stranded but not minus-stranded RNA viruses; plus-stranded RNA-containing plant viruses in the Closteroviridae and in the Tobamovirus genus also possess helical capsids. Coronaviruses are very successful and have infected many species of animals, including bats, birds (poultry) and mammals, such as humans and livestock. Coronavirus species are classified into three groups, which were based originally on cross-reacting antibodies and more recently on nucleotide sequence relatedness (Gonzalez et al. 2003). There have been several reviews of coronaviruses published recently and the reader is referred to them for more extensive references (Enjuanes et al. 2006; Masters 2006; Pasternak et al. 2006; Sawicki and Sawicki 2005; Sawicki et al. 2007; Ziebuhr 2005)."
7777,Blut und Blutprodukte,"Die Blutgruppe richtet sich nach der Antigeneigenschaft der Erythrozyten. Die Blutgruppenantigene A und B des AB0-Systems befinden sich an der Erythrozytenoberfläche. Das Antigen 0 gibt es nicht, man spricht allenfalls vom Merkmal H."
7778,IPR Issues and High Quality Genetic Testing,"– Patents for genes and genetic tests – Patent thickets and refusal to license – Facilitating access to patents – Research exemption, licensing, patent pools, clearing houses – Compulsory licenses – BRCA saga"
7779,Ethics,"The following chapter will focus on ethics. Pertinent questions, answers, and rationale will be reviewed. Answers for this chapter can be found beginning on page 162."
7780,Pulmonary Delivery of Plasmid DNA for Disease Prevention and Therapy,"For gene delivery to the lung, the challenges are high, but successful treatment of cystic fibrosis or achieving immunity against the global infectious diseases provide an allure that cannot be ignored. This chapter summarizes and reviews nonviral DNA delivery for both gene therapy and DNA vaccination in the lung. Aerosolization of DNA is evaluated, and the stability during this process is discussed. Carriers for DNA are then discussed including lipoplexes and polyplexes, with a particular focus on systems that achieve good transfection and minimize potential toxicity. Then principles of DNA vaccination are introduced, and the advantages of pulmonary vaccination are discussed. Finally, the transport of plasmid DNA vaccines into the lungs is reviewed."
7781,"Experimental Design for Gene Expression Analysis: Answers Are Easy, Is Asking the Right Question Difficult?","More and more, array platforms are being used to assess gene expression in a wide range of biological and clinical models. Technologies using arrays have proven to be reliable and affordable for most of the scientific community worldwide. By typing microarrays or proteomics into a search engine such as PubMed, thousands of references can be viewed. Nevertheless, almost everyone in life science research has a story to tell about array experiments that were expensive, did not generate reproducible data, or generated meaningless data. Because considerable resources are required for any experiment using arrays, it is desirable to evaluate the best method and the best design to ask a certain question. Multiple levels of technical problems, such as sample preparation, array spotting, signal acquisition, dye intensity bias, normalization, or sample-contamination, can generate inconsistent results or misleading conclusions. Technical recommendations that offer alternatives and solutions for the most common problems have been discussed extensively in previous work. Less often discussed is the experimental design. A poor design can make array data analysis difficult, even if there are no technical problems. This chapter focuses on experimental design choices in terms of controls such as replicates and comparisons for microarray and proteomics. It also covers data validation and provides examples of studies using diverse experimental designs. The overall emphasis is on design efficiency. Though perhaps obvious, we also emphasize that design choices should be made so that biological questions are answered by clear data analysis."
7782,Future Directions,"There are many areas ripe for research in the area of kidney development. With the current advances in technology available to image and examine the developing kidney along with transgenic animal technology, many new strategies can be employed to answer old questions as well as devising new ones. In the following sections, we consider a few very recent areas of interest in the field of renal development."
7783,Molecular tools in drug research — translational medicine,"The advent of high-throughput and increasingly sensitive research techniques in molecular biology in the last 20 years has altered fundamentally our understanding of molecular biology. The unraveling of the human genome has provided unprecedented insights into the molecular pathophysiology of diseases. DNA sequencing techniques allowed collecting huge amounts of genetic information, revealing genetic variation and variable expression of genes pinpointing to the molecular level of diseases. In parallel, analytical methods for evaluating large sets of proteins become available facilitating studies on the functional relevance of transient or stable expression of these molecules for a disease phenotype. These novel molecular techniques are nowadays at the heart of modern drug research as they allow identifying and validating novel molecular targets of disease, drug screening as well as the discovery of biomarkers for predicting and monitoring response to drug therapy."
7784,The Role of Nuclear Matrix Attachment Regions in Plants,"Regions of DNA that bind to the nuclear matrix, or nucleoskeleton, are known as Matrix Attachment Regions (MARs). MARs are thought to play an important role in higher-order structure and chromatin organization within the nucleus. MARs are also thought to act as boundaries of chromosomal domains that act to separate regions of gene-rich, decondensed euchromatin from highly repetitive, condensed heterochromatin. Herein I will present evidence that MARs do indeed act as domain boundaries and can prevent the spread of silencing into active genes. Many fundamental questions remain unanswered about how MARs function in the nucleus. New findings in epigenetics indicate that MARs may also play an important role in the organization of genes and the eventual transport of their mRNAs through the nuclear pore."
7785,Proteolytic Processing of Filovirus Glycoproteins,"Filoviruses (Marburg virus and Ebola virus) have a single envelope glycoprotein (GP) that initiates infection. GP is a class I fusion protein that forms trimeric spikes composed of heterodimers of the subunits GP1 and GP2. GP1 and GP2 are derived from the precursor pre-GP by furin cleavage during exocytosis. GP1 contains a receptor-binding core topped by a glycan cap and a heavily glycosylated mucin-like domain, while GP2 contains a fusion loop and a membrane anchor. After entering cells by macropinocytosis, the glycan cap and the mucin-like domain are removed from GP1 by endosomal cathepsins B and L exposing the binding site for the Niemann-Pick C1 receptor. It appears that there is no strict requirement for specific proteases involved in GP processing. Thus, furin is not indispensible for GP1-2 cleavage, and GP1 may be trimmed not only by cathepsins B and L but also by other endosomal proteases. Two soluble glycoproteins of Ebola virus are also processed by host proteases. A significant amount of GP1,2 is cleaved by the metalloprotease TACE and shed from the surface of infected cells (GP1,2 delta). The secreted protein sGP is derived from the precursor pre-sGP by furin cleavage."
7786,Systemic Transitional Fluidity,"This chapter traces the trajectory along which the international system became unipolar and how the post-Cold War ‘sole superpower’ sought to rationalise and perpetuate its hegemonic status. It introduces the theoretical frameworks applied in the study and reviews the literature on the erosion of primacy, the processes of power-shift and power-diffusion, and a progressive deepening of Sino-US mutual distrust as the two powers changed from tacit allies to ‘near-peer-rivals’. Chinese perspectives on changing measures of ‘comprehensive national power’ defining competitive positions of major actors within the system, and Beijing’s emphasis on historical experience as a fountainhead of wisdom for managing China’s modern challenges offer insights into evolving Chinese thinking. Dramatic economic turbulence and its strategic consequences for US primacy and Sino-US relations provide the backdrop against which Barack Obama assumed office."
7787,Bioactive Products from Fungi,"Fungi are amazing producers of natural products. They are crucial to the health and the well-being of people throughout the world. They are excellent producers of hydrolytic enzymes, biofuels, organic acids, polysaccharides, and secondary metabolites such as antibiotics, anticancer drugs, hypocholesterolemic agents, immunosuppressants, and others. This chapter centers on these fungal products, especially valuable secondary metabolites, the discovery of which goes back eighty-seven years when penicillin was discovered by Alexander Fleming."
7788,Acute and Chronic Health Challenges in Sub-Saharan Africa: An Unfinished Agenda,"The concept of a “Double Burden of Disease” conceived in the second half of the last century has by now turned into a success story in sub-Saharan Africa. It has been instrumental in creating the regional and global political momentum to address the “unfinished agenda of infectious diseases” and to fight against HIV/AIDS, Tuberculosis and Malaria in a concerted and sustainably financed action. An estimated three million children under the age of five have been saved from malaria, and the incidence of new HIV cases in sub-Saharan Africa has fallen by more than half between 2001 and 2012. The concept also created an awareness of the rising epidemic of non-communicable diseases (NCDs) in this part of the world. It is too early to predict whether or not this success in the area of infectious disease will repeat itself in the domain of non-communicable diseases. There are some obstacles to overcome. The countries of SSA have to integrate the two separately conceived policies and their different funding into one and to avoid competition in resource allocation between the two areas. They need to develop integrated strategies that begin in the primary health care sector and finally they need to define strategies on how to engage constructively with the private sector."
7789,General Information,"Many bacteria, viruses, parasites, fungi and prions may cause serious infections and lead to the isolation of those who are infected from those who are susceptible. Isolation may be done in single rooms or in special isolation units. A modern isolate for patients with infections comprises (1) a sluice with a good space for dressing and undressing of personal protective equipment (PPE) and for hand hygiene, (2) a large patient room and (3) a bathroom/disinfection room with own decontaminator or autoclave and with separate entrance from the patient’s room. Isolates for airborne and droplet-transmitted infections have in addition a defined negative air pressure and hepafiltered exhaust. In all isolates, doors must be closed in such a way that contaminants do not escape the isolate. A modern isolate for patients with impaired immune defence is similar to the infection isolates, with following exceptions: usually no need for decontaminator, hepafiltered clean air into the room and with a defined positive air pressure. A positive pressure isolate should never be used for patients with infections, and a negative pressure isolate should never be used for patients with impaired immune defence, except if the patient also has an infection that needs isolation."
7790,The Role of T Cell Epitopes in Coronavirus Infection,"Multiple MHV-specific CD4 and CD8 T cell epitopes have been identified in C57Bl/6 and BALB/c mice. In particular, at least two CD8 T cell epitopes are recognized in C57Bl/6 mice. In one model of MHV persistence, mutations are detected in the immunodominant CD8 T cell epitope recognized in this strain. These mutations contribute to virus persistence and to the development of more severe clinical disease."
7791,Cell-Autonomous (Cell-Intrinsic) Stress Responses,"In this chapter, the role of cell-intrinsic stress responses is examined which include autophagic processes, the oxidative stress response, the heat shock response, the unfolded proteins response, and the DNA damage response. Autophagy (macroautophagy, microautophagy, and chaperone-mediated autophagy) is a self-digestive process in response to environmental stress to eukaryotic cells, by which cytoplasmic components are delivered to the lysosome for recycling and degradation. The oxidative stress response is directed against any oxidative stress and is mediated by antioxidative defense systems including antioxidant enzymes such as superoxide dismutase, detoxifying enzymes such as glutathione peroxidase, and energy-dependent efflux pumps. The heat shock response is induced upon exposure of cells to any stress condition and characterized by emission of heat shock proteins which operate as DAMPs to maintain and restore homeostasis. The unfolded protein response is induced by any stress of the endoplasmic reticulum that is perceived by three sensor molecules. Under remediable endoplasmic reticulum stress conditions, the sensors trigger signalling pathways to resolve this stress. However, in severe irremediable endoplasmic reticulum stress, the unfolded protein response may lead to pro-inflammatory and pro-apoptotic responses resulting in regulated cell death. Finally, the DNA damage response is induced by any DNA damage that occurs in a variety of exogenous and endogenous conditions. When successful, this stress response leads to DNA repair and is associated with the emission of various DAMPs which contribute to restoration of homeostasis. When unsuccessful, the DNA damage response, like the unsuccessful unfolded protein response, can result in regulated cell death, either in form of apoptosis or necrosis. Together, the ultimate goal of all the stress responses is to maintain cellular homeostasis and ensure cell integrity. When they fail, the incidence of regulated cell death is frequently observed."
7792,DSM in China: In Touch with Evolving Needs in the Specialty Chemicals Market,
7793,Biological conservation and parasitism,
7794,The Human Virome,"In this chapter we discuss changing approaches to viral discovery and human health, summarize the current understanding of the human-associated viral community, and review contemporary methods in viral metagenomics. The virome is the community of viruses that populate an organism or ecosystem at any given time. This includes the “core” set of commensal viruses that do not give rise to clinical symptoms or viremia, combined with any acute or persistent infections that may be present. Recent technological advances enable us to sequence viral genomes without culturing or cloning. These methods permit not only the discovery of a wider range of viral pathogens, but also a broader assessment of the human virome in the absence of clinically recognized disease. A new focus in contemporary virology is the natural viral community of the human body. This will provide a background for recognition of emerging and previously unrecognized viruses. It should be possible to detect viral infection before the emergence of symptoms, which will have significant implications for health-care delivery."
7795,3 Pathofysiologie van de longen,De ademhaling omvat alle processen die betrokken zijn bij de opname van zuurstof en de afgifte van koolzuur. Deze gaswisseling is van doorslaggevende betekenis voor alle metabole gebeurtenissen in het lichaam.
7796,Stevens Johnson Syndrome – “Steven Who? And Why I Should Care About His Johnson?”,"Diagnosing rashes in the emergency department can be challenging. If the rash is extensive and targetoid, include Stevens-Johnson Syndrome (SJS) on your differential and be sure to obtain a thorough history to identify possible offending agents. Additionally, prioritize supportive care and obtaining a dermatology/burn consult to coordinate appropriate care."
7797,Alemtuzumab,"Alemtuzumab (Campath(®), MabCampath(®), Genzyme) is an IgG1k anti-CD52 humanized monoclonal antibody (mAb) that was first licensed in March 2001 by FDA. EMEA granted its approval in July 2001 and Health Canada in November 2005. The initial indication was limited to B-CLL previously treated and resistant to alkylating agents. Starting from 2007, alemtuzumab was approved also as first-line therapy of B-CLL. So far, it has been experienced in over 60 countries. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/978-88-470-5313-7_7) contains supplementary material, which is available to authorized users."
7798,Vaccinia Virus-Based Reverse Genetics for Feline Coronaviruses,"For decades, the genetic modification of coronavirus genomes and the generation of recombinant coronaviruses have been hampered mostly due to the extraordinary large size of the coronaviral genome. The very first reverse genetic system for feline coronaviruses (FCoVs) was established in the early 2000s; the respective approach exclusively enabled the manipulation of the 3′-third of the viral genome. Later on, vaccinia virus- and bacterial artificial chromosome (BAC)-based systems have been developed. Both systems have the advantage that the entire FCoV genome is amenable for mutagenesis. The main focus of this chapter is the vaccinia virus-based reverse genetic system for FCoVs. Here we present protocols for (1) the generation of a full-length cDNA clone, (2) the manipulation of the FCoV genome, and (3) the rescue of recombinant FCoVs."
7799,Paving the Road for Mesenchymal Stem Cell-Derived Exosome Therapy in Bronchopulmonary Dysplasia and Pulmonary Hypertension,"Bronchopulmonary dysplasia (BPD) is a chronic neonatal lung disease characterized by inflammation and arrest of alveolarization. Its common sequela, pulmonary hypertension (PH), presents with elevated pulmonary vascular resistance associated with remodeling of the pulmonary arterioles. Despite notable advancements in neonatal medicine, there is a severe lack of curative treatments to help manage the progressive nature of these diseases. Numerous studies in preclinical models of BPD and PH have demonstrated that therapies based on mesenchymal stem/stromal cells (MSCs) can resolve pulmonary inflammation and ameliorate the severity of disease. Recent evidence suggests that novel, cell-free approaches based on MSC-derived exosomes (MEx) might represent a compelling therapeutic alternative offering major advantages over treatments based on MSC transplantation. Here, we will discuss the development of MSC-based therapies, stressing the centrality of paracrine action as the actual vector of MSC therapeutic functionality, focusing on MEx. We will briefly present our current understanding of the biogenesis and secretion of MEx, and discuss potential mechanisms by which they afford such beneficial effects, including immunomodulation and restoration of homeostasis in diseased states. We will also review ongoing clinical trials using MSCs as treatment for BPD that pave the way for bringing cell-free, MEx-based therapeutics from the bench to the NICU setting."
7800,Setting the Ventilator in the NICU,"Success in providing respiratory support to the neonate requires a clear understanding of the context in which it is being applied. Perhaps more than for any other age group, the array of different situations in which ventilation is applied to the newborn infant is extremely broad, with in each case different pathophysiological disturbances and often the need to use a specific approach to apply ventilation optimally. Table 42.1 provides a list of the more common situations in which conventional ventilation is used in the neonate and includes some considerations regarding ventilator settings for each situation. For each situation, a suggested mode of ventilation is indicated, along with target ranges for positive end-expiratory pressure (PEEP) and tidal volume (V (T)). Further discussion of the physiological rationale and available evidence for ventilator settings is set out below."
7801,Inflammatory and Infectious Disorders,
7802,Trachom,
7803,Influenza A (H1N1),"In March 2009, an outbreak of human-infected swine influenza occurred in Mexico, with reports of deaths. Soon afterward, such cases were reported worldwide, namely, a pandemic outbreak. The prevailing disease is then defined as an acute respiratory infectious disease caused by swine-origin influenza A (H1N1) virus, a new variant of influenza virus. Its viral strains contain gene segments of three types of influenza viruses, namely swine influenza virus, avian influenza virus and human influenza virus. And the virus is mainly transmitted among humans via direct and indirect contact or respiratory tract."
7804,Medikamentenprofile – alphabetisch nach Substanzname,"In diesem Kapitel werden 184 onkologische Medikamente in alphabetischer Reihenfolge beschrieben. Zu jedem Medikament finden sich strukturierte, für die Pflege wichtige Angaben, bspw. zu Auflösung und Verdünnung, zu Verabreichung, zu Lagerung, zu Maßnahmen bei Extravasation, zu unerwünschten Wirkungen sowie für die Patienten nützliche Informationen."
7805,Network Analysis of Comorbidities: Case Study of HIV/AIDS in Taiwan,"Comorbidities are the presence of one or more additional disorders or diseases co-occurring with a primary disease or disorder. The purpose of this study is to identify diseases that co-occur with HIV/AIDS and analyze the gender differences. Data was collected from 536 HIV/AIDS admission medical records out of 1,377,469 admission medical records from 1997 to 2010 in Taiwan. In this study, the comorbidity relationships are presented in the phenotypic disease network (PDN), and φ-correlation is used to measure the distance between two diseases on the network. The results show that there is a high correlation in the following pairs/triad of diseases: human immunodeficiency virus infection with specified conditions (042) and pneumocystosis pneumonia (1363), human immunodeficiency virus infection with specified malignant neoplasms (0422) and kaposi’s sarcoma of other specified sites (1768), human immunodeficiency virus acquired immunodeficiency syndrome, and unspecified (0429) and progressive multifocal leukoencephalopathy (0463), and lastly, human immunodeficiency virus infection with specified infections (0420), meningoencephalitis due to toxoplasmosis (1300), and human immunodeficiency virus infection specified infections causing other specified infections (0421)."
7806,The Impact of Community Structure of Social Contact Network on Epidemic Outbreak and Effectiveness of Non-pharmaceutical Interventions,"The topology structure of social contacts network has a big impact on dynamic patterns of epidemic spreading and effectiveness of non-pharmaceutical interventions. Corresponding to individuals’ behavioral or functional units, people are commonly organized in small communities, meaning that most of social contacts networks tend to display community structure property. Through empirical investigation and Monte-Carlo simulation on a big H1N1 outbreak in a Chinese university campus, this paper explores the impact of community structure property of social contacts network on epidemic spreading and effectiveness of interventions. A stochastic model based on social contacts networks among students is constructed to simulate this outbreak, revealing that epidemic outbreaks commonly occur in local community. Moreover, effectiveness of three quarantine-based interventions is quantitatively studied by our proposed model, finding that community structure of social networks determines the effects these measures."
7807,The Burden of Communicable and Non-Communicable Diseases in Developing Countries,"Worldwide, developed and developing countries are facing the double burden of communicable and 10.1007/978-0-387-78665-0_6205. However, developing countries are more exposed and more vulnerable due to a multitude of factors, including geographic, demographic and socio-economic factors. Noncommunicable diseases like cardio-vascular diseases, cancer, diabetes, chronic obstructive pulmonary disease and mental disorders are affecting developing countries with an increasing trend. In parallel, 10.1007/978-0-387-78665-0_5343 such as HIV/AIDS, malaria, tuberculosis, acute respiratory infections and diarrheal disease are causing high mortality rates especially in low and middle income countries. Other diseases like the so-called neglected diseases are exclusively afflicting developing countries. Low-income countries are particularly affected by lymphatic filariasis, leishmaniasis, schistosomiasis, Buruli ulcer, cholera, cysticercosis, dracunculiasis, foodborne trematode infections, hydatidosis, soil-transmitted helminthiasis (ascariasis, trichuriasis, hookworm diseases), trachoma, sleeping sickness, onchocerciasis, Chagas disease, dengue and others. Beyond the high mortality and morbidity rates caused by communicable and/or noncommunicable diseases in developing countries, the global burden includes economic losses due to care for diseases and disabilities but also as a lack of productivity. More generally, communicable and noncommunicable diseases are impeding human development in developing countries by their negative impact on education, income and life expectancy and other health indicators. In sub-Saharan African countries, devastating consequences are already strikingly apparent in terms of life expectancy and 10.1007/978-0-387-78665-0_5839 (HDI) in general. A large part of the burden caused by noncommunicable diseases like cardio vascular diseases, cancer, diabetes, obesity and others can be avoided by preventive measures, early diagnosis and detection and mainly by controlling risk factors such as smoking, alcohol, diet, and physical inactivity. Similarly, the impact of communicable diseases can be alleviated by efficient strategies, including affordability of treatments, development of new vaccines and medicines, improvement of environmental conditions and general incentives and sensitization."
7808,Toxoplasma gondii,Toxoplasma gondii
7809,Computational Tools: RNA Interference in Fungal Therapeutics,"There is steady rise in the number of immunocompromised population due to increased use of potent immunosuppression therapies. This is associated with increased risk of acquiring fungal opportunistic infections in immunocompromised patients which account for high morbidity and mortality rates, if left untreated. The conventional antifungal drugs to treat fungal diseases (mycoses) are increasingly becoming inadequate due to observed varied susceptibility of fungi and their recurrent resistance. RNA interference (RNAi), sequence-specific gene silencing, is emerging as a promising new therapeutic approach. This chapter discusses various aspects of RNAi, viz., the fundamental RNAi machinery present in fungi, in silico siRNA features, designing guidelines and tools, siRNA delivery, and validation of gene knockdown for therapeutics against mycoses. Target gene identification is a crucial step in designing of gene-specific siRNA in addition to efficient delivery strategies to bring about effective inhibition of fungi. Subsequently, designed siRNA can be delivered effectively in vitro either by soaking fungi with siRNA or by transforming inverted repeat transgene containing plasmid into fungi, which ultimately generates siRNA(s). Finally, fungal inhibition can be verified at the RNA and protein levels by blotting techniques, fluorescence imaging, and biochemical assays. Despite challenges, several such in vitro studies have spawned optimism around RNAi as a revolutionary new class of therapeutics against mycoses. But, pharmacokinetic parameters need to be evaluated from in vivo studies and clinical trials to recognize RNAi as a novel treatment approach for mycoses."
7810,The Role of Context for Crisis Management Cycle,"This chapter establishes the major role of the sense making and ­situation-understanding process in crisis management, and outlines the importance of the contextualisation of information in this process. As a result of a wider analysis of past crisis-management feedback, we define the term crisis and propose a crisis-management cycle, along with a set of decision support activities. From a system point of view, crisis management functionalities are structured along three crucial steps: information gathering, situation understanding, and decision making. For each step, the processes involved are described and for each one some relevant techniques are proposed to implement the processes. For the information-gathering step, the use of ontology allows the building and structuring of a coherent ­situation model. The initial overall picture of the situation, obtained by some on-line ­information extraction and fusion, is then consolidated in the situation understanding step to provide meaningful real-time situation awareness. This provides the essential base to derive the final decision-making step. In the decision phase, the context has a dual impact on the decision-making process; the context first constrains the resolution of the resource allocation problem, but it also contributes to discriminate between several resource allocation solutions. It is thus shown that each step of the crisis management process relies on the availability and quality of the crisis context, and that this in-time contextualisation is required to enhance the overall process of crisis management. To summarise, this chapter highlights the key role of situation understanding for crisis management and reveals the crucial necessity of in-time contextualisation at each step of the crisis management process."
7811,Development of Nano-Antimicrobial Biomaterials for Biomedical Applications,"Around the globe, there is a great concern about controlling growth of pathogenic microorganisms for the prevention of infectious diseases. Moreover, the greater incidences of cross contamination and overuse of drugs has contributed towards the development of drug resistant microbial strains making conditions even worse. Hospital acquired infections pose one of the leading complications associated with implantation of any biomaterial after surgery and critical care. In this regard, developing non-conventional antimicrobial agents which would prevent the aforementioned causes is under the quest. The rapid development in nanoscience and nanotechnology has shown promising potential for developing novel biocidal agents that would integrate with a biomaterial to prevent bacterial colonization and biofilm formation. Metals with inherent antimicrobial properties such as silver, copper, zinc at nano scale constitute a special class of antimicrobials which have broad spectrum antimicrobial nature and pose minimum toxicity to humans. Hence, novel biomaterials that inhibit microbial growth would be of great significance to eliminate medical device/instruments associated infections. This chapter comprises the state-of-art advancements in the development of nano-antimicrobial biomaterials for biomedical applications. Several strategies have been targeted to satisfy few important concern such as enhanced long term antimicrobial activity and stability, minimize leaching of antimicrobial material and promote reuse. The proposed strategies to develop new hybrid antimicrobial biomaterials would offer a potent antibacterial solution in healthcare sector such as wound healing applications, tissue scaffolds, medical implants, surgical devices and instruments."
7812,Electroporation-Mediated DNA Vaccination,"There are many positive attributes to DNA vaccination that make it a conceptually desirable platform. In clinical studies, however, standard DNA injection alone generally induces low levels of transgene-specific immunity when compared to other vaccine approaches. In order to boost the immunogenicity of this platform, next-generation DNA vaccines require additional techniques such as the administration of electroporation. This new method involves the generation of a brief electric field in tissue around a local injection site that results in the transient poration, or permeabilization, of the cellular membranes. As a result, antigen-specific immune responses are greatly enhanced and are likely due to increased DNA uptake and antigen expression. Thus, electroporation-mediated DNA vaccination represents a promising new strategy for the elicitation of strong immune responses directed against the expressed antigen(s) and not the vector, and ongoing studies are currently underway to optimize the working parameters of this technique. Here, we review the uses of this technology in conjunction with vaccination and suggest future directions for its further exploration."
7813,Exam 4 Questions,"1. A 73-year-old male with a history of hypertension and hyperlipidemia is currently in the stroke unit after suffering a right middle cerebral artery infarct. His symptoms started 2 h prior to arrival at the hospital, and tPA was administered. The patient is plegic on the left side and with mild dysarthria, but is otherwise neurologically intact. His labwork is within normal limits. Which of the following describes the optimal deep venous thrombosis (DVT) prophylaxis regimen for this patient? A. Wait 6 h post tPA, then administer unfractionated heparin (UFH) along with intermittent pneumatic compression (IPC). B. Wait 24 h post tPA, then administer UFH along with IPC. C. Wait 6 h post tPA, then administer low molecular weight heparin (LMWH) along with IPC. D. Wait 24 h post tPA, then administer LMWH along with IPC. E. IPC only for the first 72 h, then LMWH or UFH after obtaining follow-up imaging. 2. All of the following causes of acute encephalitis have the matching characteristic radiological features except: A. Autoimmune limbic encephalitis: T2/FLAIR hyperintensity in the mesial temporal lobes. B. Cytomegalovirus: T2/FLAIR hyperintensity in the subependymal white matter. C. JC virus: T2/FLAIR hyperintensity in the parieto-occipital lobes and corpus callosum. D. Herpes simplex virus type 1: restricted diffusion in frontal/temporal lobes and insular cortex. E. Varicella zoster: T2/FLAIR hyperintensity in the brainstem. 3. Which of the following categorizations is most accurate regarding acute respiratory distress syndrome (ARDS) in the setting of subarachnoid hemorrhage (SAH)? A. Non-neurogenic, non-cardiogenic. B. Neurogenic, non-cardiogenic. C. Neurogenic, cardiogenic. D. Non-neurogenic, cardiogenic. E. None of the above accurately reflect ARDS in SAH. 4. A 52-year-old female is admitted to the ICU with a Hunt-Hess 1, modified Fisher 2 subarachnoid hemorrhage. Her past medical history is significant for hypertension, diabetes mellitus, and chronic renal insufficiency. She undergoes craniotomy for surgical clipping of an anterior cerebral artery aneurysm, and does not experience any additional complications. Two weeks later, she begins complaining of left calf pain, and a lower extremity sonogram demonstrated a proximal deep venous thrombosis (DVT). The patient weighs 60 kg. Her laboratory values are as follows: sodium 142 mEq/L, potassium 3.4 mEq/L, carbon dioxide 18 mEq/L, blood urea nitrogen (BUN) 70 mg/dL, and serum creatinine 2.5 mg/dL. What would be the optimal treatment for this patient’s proximal DVT? A. Unfractionated heparin infusion for at least 5 days concomitantly with warfarin therapy. B. Low molecular weight heparin 60 mg twice a day for at least 5 days concomitantly with warfarin therapy. C. Fondaparinux 7.5 mg daily for 5 days followed by warfarin therapy. D. Apixaban 10 mg twice daily for 7 days followed by 5 mg twice daily. E. Rivaroxaban 15 mg twice daily for 21 days followed by 20 mg once daily. 5. All of the following are currently implicated in uremic encephalopathy except: A. Derangements in cerebral metabolism. B. Alterations in the blood-brain barrier. C. Accumulation of circulating toxins. D. Imbalance of endogenous neurotransmitters. E. Recurrent lobar hemorrhages. 6. A 70-year-old female is hospitalized with a recent ischemic infarct. As part of stroke core measures, you obtain a hemoglobin A1c of 10.0. What is an approximate estimation of this patient’s average blood glucose level over the last several months? A. 70 mg/dL. B. 100 mg/dL. C. 130 mg/dL. D. 190 mg/dL. E. 240 mg/dL. 7. A 28-year-old female with no known past medical history is in the ICU in status epilepticus, with anti-N-methyl D-aspartate (NMDA) receptor antibodies isolated in the cerebrospinal fluid. Which of the following is most likely to identify the root cause of her illness? A. Transvaginal ultrasound. B. Contrast-enhanced CT of the chest. C. Contrast-enhanced CT of the brain. D. Virtual colonography. E. Thorough examination of the skin, particularly in sun-exposed areas. 8. A 17-year-old male with no significant past medical history collapses during a high school football game, and goes into cardiac arrest. He did not have any complaints earlier in the day. The patient is brought to a nearby hospital, where is he resuscitated, intubated, and transferred to the ICU for further management. The patient is currently undergoing therapeutic hypothermia, and a work-up is underway to determine the cause of his sudden collapse. Which of the following is the most likely diagnosis? A. Rupture of a previously undiagnosed cerebral aneurysm. B. Hypertrophic cardiomyopathy. C. Commotio cordis. D. Severe hyponatremia and cerebral edema. E. Brugada syndrome. 9. A 31-year-old female at 38 weeks gestation is currently hospitalized for the treatment of preeclampsia. Due to her medical condition, her obstetrician is currently considering induced labor. At which point will this patient no longer be at risk for developing frank seizure activity as a result of her condition? A. 48 h postpartum. B. 1 week after delivery. C. 2 weeks after delivery. D. 4 weeks after delivery. E. 6 weeks after delivery. 10. A 38-year-old male with no prior medical history presents to the emergency department with fever and severe headaches for several days. A CT scan of the brain is unremarkable, and the results of a lumbar puncture are pending. What is the most appropriate empiric antimicrobial regimen at this time? A. Cefazolin and vancomycin. B. Ceftriaxone and vancomycin. C. Ceftriaxone, vancomycin and ampicillin. D. Piperacillin/tazobactam and vancomycin. E. Meropenem and vancomycin. 11. The majority of intramedullary spinal cord neoplasms are: A. Astrocytomas. B. Meningiomas. C. Metastatic lesions. D. Ependymomas. E. Hemangioblastomas. 12. Which of the following derived parameter formulas is correct? A. Cardiac index = cardiac output x body surface area. B. Stroke volume = cardiac output/heart rate. C. Systemic vascular resistance = 80 × (mean arterial pressure/cardiac output). D. Pulmonary vascular resistance = 80 × (mean pulmonary artery pressure/cardiac output). E. All of the above are correct. 13. A 23-year-old female marathon runner is currently in the ICU after suffering from heat stroke following an outdoor run on a particularly hot summer day. She was initially delirious in the emergency department, but progressed to coma and respiratory failure requiring mechanical ventilation. Her oral temperature is 42.1 °C. Which of the following would be most effective in reducing this patient’s severe hyperthermia? A. Regularly scheduled alternating acetaminophen and ibuprofen. B. Spraying room temperature water on the patient, followed by fanning. C. Ice water immersion. D. Dantrolene sodium, 2.5 mg/kg. E. Application of ice packs to the groin and axilla. 14. Hyperinsulinemia-euglycemia (HIE) therapy may be useful for toxicity related to which of the following? A. Tricyclic antidepressants. B. Calcium channel blockers. C. Aspirin. D. Digoxin. E. Lithium. 15. A 71-year-old female with a history of alcohol abuse is currently intubated in the ICU following a catastrophic spontaneous left basal ganglia hemorrhage with resultant herniation. You have just declared her brain dead. The patient’s family agrees to make her an organ donor, and the organ donation coordinator requests you initiate levothyroxine therapy. Which of the following benefits would be expected with this treatment? A. Increase the number of solid organs available for transplant. B. Eliminate the need for hepatic biopsy prior to liver transplant. C. Eliminate the need for cardiac catheterization prior to heart transplant. D. Eliminate the need for bronchoscopy prior to lung transplant. E. Reduce the need for supplementation of sodium, potassium, calcium, and magnesium. 16. Which of the following is not an element of the Full Outline of Unresponsiveness (FOUR) score? A. Eye opening. B. Respiratory function. C. Brainstem reflexes. D. Motor response. E. Verbal response. 17. A 23-year-old female is currently in the ICU with status asthmaticus. She was initially on noninvasive positive pressure ventilation, with an arterial blood gas (ABG) as follows: pH 7.13, pCO(2) 60 mmHg, PaO(2) is 61 mmHg, HCO(3) 24 mmol/L, and oxygen saturation of 90%. She is given continuous inhaled albuterol, intravenous steroids, and magnesium sulfate. She subsequently becomes more lethargic and is intubated, with settings as follows: volume assist-control, rate of 12 breaths/min, tidal volume of 500 cc, PEEP of 5 cm H(2)O, and FiO(2) of 50%. Peak airway pressure is 50 cm H(2)O and plateau pressure is 15 cm H(2)O. A stat portable chest x-ray shows hyperinflation with no pneumothorax. A repeat ABG after 30 min of invasive ventilation shows the following: pH of 7.24, pCO(2) 49 mmHg, PaO(2) 71 mmHg, HCO(3) A. Increase rate to 16. B. Increase tidal volume to 600 cc. C. Initiate bicarbonate infusion. D. Switch to pressure assist-control. E. Maintain current settings. 18. Which of the following mechanisms is implicated in super-refractory status epilepticus? A. Influx of proinflammatory molecules. B. Upregulation of NMDA receptors. C. Upregulation of molecular transport molecules. D. Downregulation of GABA receptors. E. All of the above. 19. A 85-year-old male with a history nephrolithiasis, mild dementia, and alcohol abuse presented to the emergency department after a fall from standing, and was found to a right holohemispheric subdural hematoma. His clot was evacuated successfully, in spite of his oozing diathesis in the operating room (INR on arrival was 1.4 with a platelet count of 88 × 10(3)/μL). His serum transaminases are twice the normal value, and he has had refractory chronic hyponatremia. He has had three convulsions during this week of hospitalization, in spite of levetiracetam therapy at 1.5 g twice a day. Over the past 24 h, he has had a marked increase in agitation. He has also just had a 5-s run of non-sustained ventricular tachycardia, and his systolic blood pressure is now 85 mmHg. You are considering discontinuing his levetiracetam and starting a new agent. Which of the following would be the best choice in this scenario? A. Carbamazepine. B. Phenytoin. C. Valproate. D. Lacosamide. E. Topiramate. 20. A 65-year-old male with a history of COPD on rescue albuterol and ipratropium is diagnosed with myasthenia gravis, and started on an acetylcholinesterase inhibitor. He returns several days later complaining of increased salivation and worsening bronchial secretions in the absence of fevers, purulent sputum, or increasing dyspnea. These symptoms are not relieved by use of his albuterol. On exam, he has slightly decreased air movement throughout both lung fields without any clear wheezing, no focal rales, and a normal inspiratory to expiratory ratio. Which treatment option is most likely to be beneficial? A. Increase frequency of short-acting ß(2) agonist use. B. Add a standing long-acting inhaled ß(2) agonist. C. Add glycopyrrolate as needed. D. Add inhaled corticosteroids. E. Add oral systemic corticosteroids. 21. Regarding states of impaired consciousness, which of the following statements regarding arousal and awareness is correct? A. Coma: intact arousal, but impaired awareness. B. Minimally conscious state: impaired arousal and impaired awareness. C. Persistent vegetative state: intact arousal, but impaired awareness. D. Locked-in state: intact arousal, but impaired awareness. E. All of the above are correct. 22. A 62-year-old female is currently in the ICU following craniotomy for clipping of a cerebral aneurysm. Postoperatively, she is noted to have an oxygen saturation of 92% on 50% non-rebreather face mask, and her respiratory rate is 32 breaths/min. She denies chest pain. Her blood pressure is 96/72 mmHg and heart rate is 120 beats/min. Nimodipine has been held according to blood pressure parameters. A portable chest x-ray shows hazy opacities bilaterally, and bedside echocardiogram shows decreased left ventricular systolic function with apical, septal, lateral, anterior, anteroseptal and inferolateral wall akinesis, along with apical ballooning. Which of the following should be performed next? A. Intubate the patient and begin mechanical ventilation. B. Call urgent cardiology consult for cardiac catheterization. C. Start noninvasive positive airway pressure ventilation. D. Administer broad spectrum antibiotics. E. Administer albuterol and systemic corticosteroids. 23. Which of the following is the most common etiology of acute spinal cord ischemia and infarction? A. Atherosclerotic disease. B. Rupture of an abdominal aortic aneurysm. C. Degenerative spine disease. D. Cardioembolic events. E. Systemic hypotension in the setting of other disease processes. 24. A 62-year-old female with a history of coronary artery disease has just been admitted to the ICU with a left-sided spontaneous basal ganglia hemorrhage. The patient takes 325 mg of aspirin daily at home, and you are considering platelet transfusion. Which of the following has been demonstrated regarding platelet transfusion in this setting? A. Improved chances of survival to hospital discharge. B. Decreased hospital length-of-stay. C. Improved chances of survival at 3 months. D. Improved modified Rankin scale at 3 months. E. None of the above. 25. Which of the following therapies has been shown to decrease the incidence of delayed cerebral ischemia (DCI) in the setting of subarachnoid hemorrhage (SAH)? A. Atorvastatin. B. Magnesium. C. Methylprednisolone. D. Nicardipine. E. None of the above. 26. A 70-year-old male with a history of diabetes, hypertension, and cigarette smoking (one pack per day for the last 40 years) is currently in the ICU with a COPD exacerbation. This is his third exacerbation this year, and was discharged from the hospital only 3 weeks prior. On your examination, he is alert, his breathing is labored, and he has rales at the right lung base. His vital signs are as follows: blood pressure 90/60 mmHg, heart rate 120 beats per minute, respirations 28 per minute, and temperature 38.3 °C. His oxygen saturation on 50% face mask is 93%, and his most recent PCO(2) is 55 mmHg. Labs are notable for the following: white blood cell count 14.4 × 10(9)/L with 90% neutrophils, blood urea nitrogen (BUN) 30 mg/dL, serum creatinine 1.2 mg/dL, and glucose 240 mg/dL. Ketones are negative. He is currently on noninvasive positive pressure ventilation at 10/5 cm H(2)O and 50% FiO(2), and broad spectrum antibiotics have been administered. An hour later, the nurse pages you because his heart rate is now 140 beats per minute and irregular, blood pressure is 85 systolic, oxygen saturation is 85%, and he is minimally responsive. You now hear bilateral rales, most prominently in the right lung base, and scattered wheezes. Which of the following should be performed next? A. Increase inspiratory pressure to 15 and FiO(2) to 100%. B. Start a continuous diltiazem infusion and give intravenous furosemide. C. Start a continuous phenylephrine infusion targeting a mean arterial pressure (MAP) > 65. D. Give 125 mg of solumedrol and administer albuterol via nebulizer. E. Intubate the patient and initiate mechanical ventilation. 27. A 57-year-old male with a history of epilepsy is currently in the stroke unit following a large right middle cerebral artery infarction. A nasogastric tube has been inserted, and 24 h continuous enteral feeds have been initiated. The patient is currently on 100 mg of phenytoin every 8 h for seizure prophylaxis. Which of the following measures should be taken to prevent the patient from developing subtherapeutic phenytoin levels? A. Change to 18 h tube feeds, and only administer phenytoin at night. B. Change to 18 h tube feeds, and only administer phenytoin twice daily. C. Switch from standard to hydrolyzed tube feeds. D. Switch from standard to glycemic control tube feeds. E. Hold tube feeds for 2 h before and after phenytoin administration. 28. A 37-year-old female presents to the emergency department with approximately 2 weeks of progressively worsening clumsiness and drastic mood swings. Her past medical history is significant only for Crohn’s disease, for which she takes both natalizumab and infliximab. A contrast-enhanced CT scan of her head is performed, revealing hypodense, non-enhancing lesions in the cortical white matter of the frontal and parietal lobes. Despite treatment, the patient expires 1 month later. Which of the following is true regarding the most likely diagnosis? A. The diagnosis may be confirmed via CSF analysis. B. The pathologic process spares oligodendrocytes. C. It is a prion-based disease. D. The condition is universally fatal despite treatment. E. All of the above. 29. A 58-year-old female presents to the emergency department with dry cough, fever and rapidly progressive dyspnea over 1 week. She has a history of rheumatoid arthritis (RA) and is maintained on weekly methotrexate and daily prednisone (which was increased to 30 mg starting 1 month ago for an acute flare). She takes no other medications. Her vital signs are as follows: blood pressure 100/70 mmHg, heart rate 110 beats/min, respiratory rate 20 breaths/min, and temperature 38.0 °C. In the ED she develops progressive hypoxemia with oxygen saturation 92% on 100% nonrebreather, and is increasingly diaphoretic. She is emergently intubated, and a chest x-ray post intubation shows extensive bilateral lung opacities. Which of the following should be administered at this time? A. Ceftriaxone and azithromycin. B. Vancomycin and piperacillin-tazobactam. C. Vancomycin, cefepime, and fluconzole. D. Ceftriaxone, levofloxacin, and trimethoprim-sulfamethoxazole. E. Tigecycline only 30. A 45-year-old woman undergoes uncomplicated transsphenoidal resection of a pituitary macroadenoma. She appears well hydrated and is not complaining of excessive thirst. Post-operatively, she is noted to have increased urine output. Serum sodium is 137 mEq/L, and serum osmolarity is 275 mOsm/kg. What is the most likely cause of her polyuria? A. Syndrome of inappropriate antidiuretic hormone. B. Diabetes insipidus. C. Cerebral salt wasting. D. Fluid mobilization. E. All of the above are equally likely. 31. A 36-year-old female with a recent lumbar puncture to rule out subarachnoid hemorrhage is now complaining of a severe headache unlike anything she has experienced previously. She reports her headache is worse when standing, and better upon lying flat. She is otherwise neurologically intact. All of the following medications may be beneficial in this scenario except: A. Acetaminophen. B. Ibuprofen. C. Caffeine. D. Aminophylline. E. Methylprednisolone. 32. Which of the following is the most common overall cause of acute myocardial infarction? A. Coronary dissection. B. Plaque rupture. C. Imbalance between oxygen demand and supply across a fixed obstruction. D. Coronary vasospasm. E. Ischemia related to hypotension and decreased perfusion. 33. A 78-year-old male is in the ICU recovering from sepsis and pneumonia. He was just recently extubated after 2 days of mechanical ventilation and sedation with a fentanyl infusion. Over the ensuing days, he develops worsening abdominal distention, poor bowel sounds, and no stool output. CT scan reveals significant colonic distention, but no mass or obstruction. Records demonstrate a normal routine colonoscopy performed 6 weeks ago. You have appropriately hydrated the patient, corrected any electrolyte abnormalities, placed a rectal tube, withheld all opiates, and given intravenous erythromycin, but to no avail. Abdominal x-rays continue to demonstrate marked cecal dilatation greater than 12 cm in diameter. What is the next best appropriate therapy for this patient? A. Neostigmine. B. Naloxone. C. Metoclopromide. D. Surgical consultation for hemicolectomy. E. Endoscopic percutaneous cecostomy tube placement. 34. Which of the following is the most common cerebral vascular malformation in the general population? A. AV malformation. B. Dural AV fistula. C. Developmental venous anomaly. D. Cavernous malformation. E. Vein of Galen malformation. 35. A 49-year-old female with a history of acute lymphoblastic leukemia and recent subcutaneous cerebrospinal fluid (CSF) reservoir placement presents to the emergency department with fever, chills, and increased confusion for the past 3 days. Her CSF reservoir was last accessed 1 week ago. A thorough work-up reveals no other obvious infectious source, and there is concern for CSF reservoir-associated meningitis. Which of the following is the most likely causative organism? A. Coagulase-negative staphylococci. B. Propionobacterium acnes. C. Methicillin-resistant Staphylococcus aureus. D. Klebsiella pneumoniae. E. Neisseria meningitidis. 36. A 47-year-old woman presents to the emergency department with headache, nausea, and vomiting. Non-contrast head CT is performed, revealing subarachnoid blood in the right Sylvian fissure, and conventional angiography reveals the presents of a large right-sided MCA aneurysm. The patient undergoes successful surgical clipping of her aneurysm, and is being observed in the ICU. On admission, the patient’s serum sodium was 142 mEq/L and the hematocrit was 37%; by the seventh post-operative day, the serum sodium is 127 mEq/L and the hematocrit is 44%. Bedside ultrasonography demonstrates an IVC diameter of approximately 0.9 cm. Which of the following interventions would be least reasonable at this time? A. Fludrocortisone, 0.2 mg twice a day. B. 2% hypertonic saline, infused peripherally. C. 3% hypertonic saline, infused centrally. D. Sodium chloride oral tablets. E. 1500 mL daily fluid restriction. 37. Which of the following is true regarding central (non-infectious) fever? A. Less common in subarachnoid hemorrhage. B. More common versus infectious fever. C. Earlier onset versus infectious fever. D. Easier to confirm versus infectious fever. E. All of the above. 38. Flaccid paralysis is most commonly associated with which of the following forms of encephalitis? A. West Nile. B. Varicella zoster. C. Rabies. D. Herpes simplex. E. Epstein-Barr. 39. Which of the following would not be considered appropriate therapy for heparin-induced thrombocytopenia (HIT)? A. Discontinuation of heparin products alone. B. Danaparoid. C. Fondaparinux. D. Argatroban. E. All of the above are acceptable treatment options. 40. A 45-year-old male with severe blunt traumatic brain injury (TBI) from a motor vehicle collision suffered a ventricular fibrillation cardiac arrest at the time of injury with return of spontaneous circulation (ROSC) in the field after endotracheal intubation and one dose of epinephrine. On arrival to the emergency department, no regional wall motion abnormalities were noted on surface echocardiography and no ST segment changes were seen on the presenting EKG. Head CT revealed cerebral contusions but no extra-axial mass lesions. The patient is now in the ICU and found to be comatose without sedation. Mild therapeutic hypothermia to 33° is being considered in the management of this post-arrest patient. Which of the following statements is true? A. Mild therapeutic hypothermia is contraindicated due to the risk of induced epilepsy. B. Mild therapeutic hypothermia is contraindicated with any intracranial pathology on CT imaging. C. Mild therapeutic hypothermia does not induce a clinically significant coagulopathy. D. Patients who have sustained ROSC after an arrest associated with TBI do not benefit from therapeutic hypothermia. E. Endovascular cooling is superior to surface cooling in young patients with ROSC. 41. A 35-year-old male is in the intensive care unit following resection of a large right-sided meningioma. He is currently intubated and sedated on a continuous fentanyl infusion. The nurse calls you to the bedside due to concerns over “unusual ventilator waveforms”. Upon arrival, you note the following (see Image 1). What is the best way to describe this phenomenon? A. Reverse triggering. B. Double triggering. C. Breath stacking. D. Missed triggering. E. None of the above; normal ventilator waveforms are present;"
7814,Platelets and Inflammation,"Platelets play a major physiological role in control of vascular integrity at the site of vascular lesions. However, the pathophysiological role of platelets is much broader than regulation of hemostasis and thrombosis. Platelets are critical elements in linking and modulating thrombosis, inflammation, and tissue repair. Platelets are stimulated by a variety of agonists including thrombin or ADP and also by inflammatory agents such as antibodies, complement, bacteria, and others. Platelets contribute to inflammation by interacting with inflammatory cells via adhesion and secretion of prestored proinflammatory mediators. Thus, platelets are critical elements in the pathophysiology of inflammation and modulate significantly a variety of inflammatory diseases. A profound understanding of the molecular mechanisms underlying the role of platelet in inflammation may result in new therapeutic strategies in acute and chronic inflammatory diseases."
7815,"Immunomic Discovery of Adjuvants, Delivery Systems, and Candidate Subunit Vaccines: A Brief Introduction","Mass vaccination, when coupled to profound improvements in general sanitation, has given rise to the most remarkable transformation in public health in human history. Yet the development of vaccines remains largely trapped in the past, a hostage to the methodology of Pasteur. Infectious disease continues to threaten humanity, with new and renascent diseases emerging continually. The last two decades have seen a breath-taking revival in the commercial market for vaccines and the simultaneous emergence of a whole tranche of new technologies that promise to free vaccine development from the muddle of empirical thinking. In this short introduction, we set the scene for this renaissance, and explore how the combination of computational and experimental techniques promise so much for the future development of vaccines and the science of vaccinology."
7816,Characterization of Viral Exposures in United States Occupational Environments,"Viruses are considered to be the most abundant biological particles and have the capability to infect all forms of life leading to a variety of diseases. American workers in specific occupational environments are threatened by viral exposures, highlighting the importance to recognize the type and risk of exposure, as well as the preventive measures that can be taken to reduce the risk of exposure. For example, healthcare workers can potentially be exposed to air and blood-borne pathogens, such as hepatitis and the human immunodeficiency virus. These types of exposures have led to the development of preventive equipment and regulations intended to reduce viral exposures in occupational settings. This chapter will discuss the characteristics of viruses and the occupationally relevant viruses of which people in varying occupations can potentially encounter. Regulatory guidelines and protective strategies will also be reviewed."
7817,Globalizzazione e salute: nuove prospettive e nuovi rischi nell’era della genomica,"Il binomio globalizzazione/salute salta usualmente alla ribalta di fronte alle emergenze sanitarie come la SARS(1), o più recentemente l’influenza aviaria, che godono fin troppo spesso dell’onore delle cronache. Considerata la velocità con cui si possono diffondere nuovi germi patogeni, giustamente è cresciuta la preoccupazione per il rischio di pandemie. Tuttavia, possiamo sentirci rassicurati, almeno in parte, dal fatto che la globalizzazione si porta dietro anche un’elevata capacità di rispondere alle emergenze su scala planetaria, com’è successo per il controllo della diffusione della SARS e si spera che succeda nel caso dell’influenza aviaria."
7818,Nanobiotechnology and Ethics: Converging Civil Society Discourses,"Nanobiotechnology as a “converged” technological platform (CT = Converging Technologies) is discussed in relation to discourse within civil society. The conflicts and ethical debates surrounding nanobiotechnology can be intuited from these larger discursive frames of reference. Complimenting Glimell and Fogelberg's (2003) research documenting an emergent epistemic culture amongst scientists researching and working on nanotechnologies, and more recent research on the multiple meanings of nanotechnology in the political economy (Wullweber, 2007), this paper traces an emergent ethnography of engaged actors within civil society as they develop discursive and mobilization repertoires. Whilst on occasion ambivalent about the combination of specific promises and risks in relation to nanobiotechnology, in general a broad critique of the politics of technology is emerging as a counter epistemology or “Master Frame” (Snow & Benford, 1992) amongst certain predisposed UK civil society groups. Converging Technologies provide the issue around which this broad critique is solidifying. Thus whilst many of the specific risks raised by nanobiotechnology (and other CT) are definitively new, many of the p?tential risks and grievances, have been raised before in relation to other issues of scientific and environmental controversy, often by the same actor groups. Thus convergence is a useful metaphor for appreciating that broader frame of reference from within which the emerging conflicts and ethical debates about nanobiotechnology are being situated. If you go ten, fifteen years in the future, you're not going to be able to distinguish between what's nano technology, what's bio technology, what's information technology or what's genetic engineering. They're all going to be the same kind of technologies … just employed in different ways and different places. (“Mike”, technology watchdog campaigner, in interview January 2004)"
7819,Food Safety and Bioterrorism from Public Health Perspective,"The chapter discusses the issues of food safety and bioterrorism from the position of public health. The author gives the overview of the problem focusing on agricultural sector as a particularly vulnerable element in the farm-to-table food continuum, describes the possible scenarios of bioterroristic attacks and the necessary preventive activities to provide food safety. The article also contains the results of the original study conducted in two Russian regions on the perception of risk related to food safety by consumers."
7820,Silver Nanoparticles: Synthesis and Applications,"Nanotechnology involves the production, manipulation, and use of materials ranging in size from less than a micron to that of individual atoms, is an emerging field of modern science, and utilizes nanoscaled systems. Nanoparticles (NPs) are being viewed as fundamental building blocks of nanotechnology. Although nanomaterials may be synthesized using chemical approaches, it is now possible to include the use of biological systems such as bacteria, fungi, and plants. Currently, silver nanoparticles have shown great importance due to its large surface ratio and unique properties with myriad activities applicable in a number of applied sectors including microbial resistant applications (antibacterial/antifungal/anticancer/antiviral), water treatment, protective dressings, catalysis, and optical devices. This chapter encompasses the fabrication methods and dispersed applications of silver nanoparticles."
7821,13 Infectieziekten,welke verschillende ziekteverwekkers infectieziekten kunnen veroorzaken; welke geneesmiddelen worden gebruikt bij de behandeling van infectieziekten; welk gevolg onoordeelkundig gebruik van deze geneesmiddelen kan hebben; welke gebruiksadviezen je moet geven bij de verschillende middelen tegen infectieziekten.
7822,Influenza A (H1N1),"Influenza A (H1N1) is an acute respiratory infectious disease caused by mutant influenza A virus subtype H1N1. The pathogen is a new virus emerging after virus gene recombination of swine influenza, avian influenza, and human influenza. Influenza A (H1N1) is transmitted commonly via respiratory droplets and direct or indirect contact. Clinically, influenza A (H1N1) is characterized by influenza-like symptoms such as fever, cough, and rhinorrhea. But in rare serious cases, the condition may progress rapidly, with occurrence of viral pneumonia, respiratory failure, and multiple organ failure. Even death occurs in serious cases, with a mortality rate of 23–25 %. On April 30, 2009, influenza A (H1N1) was officially listed into Class B infectious diseases in China. Since then, it has been managed according to the Infectious Disease Prevention and Control Act in China. Meanwhile, it has been introduced into the category of quarantinable infectious disease for management based on the Frontier Health and Quarantine Law of China."
7823,Epidemiology of Highly Pathogenic Avian Influenza Virus Strain Type H5N1,"Highly pathogenic avian influenza (HPAI) is a severe disease of poultry. It is highly transmissible with a flock mortality rate approaching 100% in vulnerable species (Capua et al. 2007a). Due to the potentially disastrous impact the disease can have on affected poultry sectors, HPAI has received huge attention and is classified as a notifiable disease by the World Organisation for Animal Health (OIE)."
7824,Acute Respiratory Distress Syndrome,"Acute Respiratory Distress Syndrome (ARDS) is a well-described disease process that can have numerous underlying causes, is commonly seen in the critical care setting, and is often under-recognized. ARDS is characterized by pulmonary edema with refractory hypoxemia, and was traditionally associated with a high mortality rate. The past few decades have generated many studies examining therapeutic interventions for ARDS; however, there are few Level 1 evidence-based interventions to this day that have been shown to improve mortality and outcomes. Lung protective ventilation remains the most studied and evidence-based intervention for the treatment of ARDS."
7825,"Pain, Fatigue, and Trauma",Neurological function figures prominently in essentially all of the 11 symptoms related to cancerrelated fatigue in the proposed diagnostic criteria. Some studies have suggested that quality-of-life measures may be as important as predictors of survival in cancer as is response to chemotherapy.
7826,Openbare gezondheid en preventie,In dit hoofdstuk staat de wetgeving op het gebied van de openbare gezondheidszorg en gezondheidspreventie centraal. Het zal duidelijk worden dat openbare gezondheidszorg een heel scala van activiteiten omvat. Dit varieert van bevolkingsonderzoeken tot aan de bestrijding van infectieziekten.
7827,Genomics of Acute Lung Injury and Vascular Barrier Dysfunction,"Acute lung injury (ALI) is a devastating ­syndrome of diffuse alveolar damage that develops via a variety of local and systemic insults such as sepsis, trauma, ­pneumonia, and aspiration. It is interestingly to note that only a subset of individuals exposed to potential ALI-inciting insults develop the disorder and the severity of the disease varies from complete resolution to death. In addition, ALI susceptibility and severity are also affected by ethnicity as evidenced by the higher mortality rates observed in African-American ALI patients compared with other ethnic groups in the USA. Moreover, marked differences in strain-specific ALI responses to inflammatory and injurious agents are observed in preclinical animal models. Together, these observations strongly indicate genetic components to be involved in the pathogenesis of ALI. The identification of genes contributing to ALI would potentially provide a better understanding of ALI pathobiology, yield novel biomarkers, identify individuals or populations at risk, and prove useful for the development of novel and individualized therapies. Genome-wide searches in animal models have identified a number of quantitative trait loci that associate with ALI susceptibility. In this chapter, we utilize a systems biology approach combining cellular signaling pathway analysis with population- based association studies to review established and suspected candidate genes that contribute to dysfunction of endothelial cell barrier integrity and ALI susceptibility."
7828,Heat Shock Proteins in Inflammation,"HSPs are important mediators of a number of key intracellular reactions. Of importance to the care of the critically ill are their involvement in protein repair and tertiary structure. HSP70 is known to modulate inflammation and apoptosis. In models of acute lung injury and ARDS, over-expression of HSP70 improves outcome, ameliorates lung injury and attenuates inflammation. The involvement of HSP70 in other aspects of lung injury and in other components of MODS is under investigation."
7829,Complication from Desensitization,"Sensitization to human leukocyte antigens (HLAs) has been one of the major clinical challenges for successful kidney transplantation. In end-stage renal disease, kidney transplantation provides benefits compared with dialysis in terms of improved patient survival better quality of life, and lower ongoing costs after the first year. Living donor kidney transplantation has an advantage with improved allograft survival, and performed earlier and electively compared with deceased donor transplantation. However sensitized patients are increasing in number on transplant waiting lists, and their prospect of getting a transplant is less than nonsensitized patients due to immunological incompatibility with the donor. Strategy for sensitized patients are listing for a compatible deceased donor transplant or, if they have a living donor, either selecting a kidney exchange program or undergoing a desensitization procedure. Desensitization procedures may be undertaken to increase access to either living or deceased donor transplants, and in some situations may also be employed to facilitate participation in a kidney exchange, in less immunological barrier to be overcome. The question of whether individuals are better off with a desensitization treatment followed by HLA-incompatible living donor transplantation or waiting on the deceased donor kidney transplant list for a compatible transplant has recently been addressed by two large multicenter studies, with conflicting results. A multicenter study from the United States published in the New England Journal of Medicine [365;318 326.2011] concluded that there was a strong survival benefit for sensitized patients undergoing desensitization followed by HLA-incompatible living donor kidney transplant compared with those remaining on the waiting list. Of interest, a second study, published in the Lancet, [389;727 734.2017] found no significant survival advantage for desensitized patients compared with similar patients remaining on the waiting list in the United Kingdom. Controversies still remain regarding how desensitization can be achieved and which techniques are effective and safe. In this chapter various complications from the desensitization will be dealt with in current use of medications or armamentum."
7830,Pathology of Lung Rejection: Cellular and Humoral Mediated,"Acute rejection is an important risk factor for bronchiolitis obliterans syndrome, the clinical manifestation of chronic airway rejection in lung allograft recipients. Patients with acute rejection might be asymptomatic or present with symptoms that are not specific and can be also seen in other conditions. Clinical tests such as pulmonary function tests and imaging studies among others usually are abnormal; however, their results are also not specific for acute rejection. Histopathologic features of acute rejection in adequate samples of transbronchial lung biopsy of the lung allograft are currently the gold standard to assess for acute rejection in lung transplant recipients. Acute alloreactive injury can affect both the vasculature and the airways. Currently, the guidelines of the 2007 International Society of Heart and Lung Transplantation consensus conference are recommended for the histopathologic assessment of rejection. There are no specific morphologic features recognized to diagnose antibody-mediated rejection (AMR) in lung allografts. Therefore, the diagnosis of AMR currently requires a “triple test” including clinical features, serologic evidence of donor-specific antibodies, and pathologic findings supportive of AMR. Complement 4d deposition is used to support a diagnosis of AMR in many solid organ transplants; however, its significance for the diagnosis of AMR in lung allografts is not entirely clear. This chapter discusses the currently recommended guidelines for the assessment of cellular rejection of lung allografts and summarizes our knowledge about morphologic features and immunophenotypic tests that might help in the diagnosis of AMR."
7831,The Darkened Horizon: Two Modes of Organizing Pandemics,"This chapter deals with the recent darkening of the future horizon in the global fight against pandemics. Since roughly the year 2000, the World Health Organization has collaborated with a large number of local actors and made a concentrated effort to protect the world’s population against emerging infectious diseases, such as severe acute respiratory syndrome (SARS), swine flu, Ebola and Zika. Although efforts have been made so that the spread of future infectious diseases will be contained through early intervention, the actors in charge anticipate that the extant measures will fail to some degree. They believe it is simply impossible to prevent all pandemics from happening. But steps can and should be taken to lessen the impact of an unavoidable pandemic through emergency preparation. This chapter deals with organizations and organizational networks as key actors in these processes of emergency planning. Without the capacity of organizations to produce binding decisions for their members, which makes planning for an uncertain future possible, pandemic preparedness would not be feasible—especially not on a global scale."
7832,Civil and Criminal Legislation Regarding Money Laundering and the Protection of Cultural Heritage,"The aim of this chapter is to understand how States combat money laundering and its possible links to organized crime and other financial crimes. The illegal flow of capital poses a great threat to States. Through international joint actions, States can fight crime and curtail the enjoyment of property illegally acquired through criminal activity, particularly with respect to the acquisition of works of art on the black market."
7833,Risk Assessment in Smallpox Bioterrorist Aggression,
7834,Immunological Detection and Characterization,"Immunological methods have been used for viral diagnosis for more than 100 years. Although molecular methods are replacing many older methods of viral diagnosis, there is still a significant role for immunological methods to guide patient care and in the performance of epidemiologic studies. Identification of viral antigens in clinical samples can be accomplished rapidly through the use of point-of-care lateral immunoassays or through the use of more traditional immunofluorescence and enzyme immunoassays in the virology laboratory. Serological assays are also a valuable tool for the clinician and epidemiologist. Many of the available diagnostic assays have enzyme immunoassay formats, but functional assays such as hemagglutination-inhibition and neutralizing antibody tests are also available. In some instances, virus infection can be diagnosed with a single serum sample (e.g., HIV and hepatitis C virus infections) while in other instances paired sera are needed (e.g., those caused by common respiratory viruses). Point-of-care antibody assays are also available for testing blood and saliva samples for some viruses. An understanding of the principles of immunological detection methods is important in the application and interpretation of test results."
7835,Afwijkingen van het respiratoire systeem,"Respiratoire afwijkingen komen zeer frequent voor als primaire aandoening of secundair aan een maligniteit, infectie of systeemziekte. Zoals voor veel inwendige aandoeningen geldt, is een goede anamnese en lichamelijk onderzoek onontbeerlijk bij de analyse van pulmonale aandoeningen. De eerste paragrafen van dit hoofdstuk zullen hier dieper op ingaan. Helaas zijn de klachten vaak weinig specifiek en noodzaken dikwijls tot verder beeldvormend onderzoek. De X-thorax is vaak het beginpunt van een dergelijk diagnostisch traject. In de latere paragrafen zullen specifieke bevindingen op de X-thorax verder worden uitgediept. In veel gevallen is naast laboratoriumonderzoek ook functieonderzoek en computertomografie van de thorax noodzakelijk om de differentiële diagnose verder te versmallen. Het verkrijgen van weefsel is bij interstitiële longaandoeningen, tuberculose en maligniteit vaak het sluitstuk van de diagnostiek. Nieuwe endoscopische echogeleide technieken komen steeds meer in de plaats van invasief onderzoek zoals mediastinoscopie of thoracotomie. Ook kan met behulp van PCR-technieken sneller en meer specifiek een juiste diagnose worden verkregen."
7836,Respiratory Disorders,"Like it or not, patients with respiratory complaints are a part of our practice. The common cold is often referred to as the most frequent illness occurring in humans: over 40% of Americans suffer from a “cold” each year, accounting for more lost productivity than any other illness. Pharyngitis affects almost 30 million patients annually, with over 10% of all school-aged children seeking medical care each year. Seventeen million patients a year are diagnosed with asthma, with more females than males among adult-onset patients. Whether it is the reason for our patient’s visit or an incidental complaint, we are involved with the diagnosis and management of these problems."
7837,Prevention of Postoperative Wound Infections,"Surgery creates most hospital infections, injuries, accidents, invalidity and death in the global healthcare system. The number of surgically treated patients per year is high and increasing. Surgical site infection (SSI) is dependent on type of operation and may occur in 5–20% after surgery, triggers 7–11 extra postoperative days in hospitals and results in 2–11 times higher risk of death than comparable, noninfected patients. Up to 60% of SSI can be prevented. Prevention of postoperative wound infection is done by good general hygiene, operative sterility and effective barriers against transmission of infections, before, during and after surgery. A basic support by hospital leaders, knowledge and skill of the surgical teams, enough resources, excellent treatment of the complete patient admission and monitoring patients after discharge may lead to significant reduction of SSIs, lower death rates and a less expensive health system."
7838,Defending Against Catastrophic Terrorism,
7839,Longziekten,"Longziekten komen zeer frequent voor. De meeste longaandoeningen ontstaan in de luchtwegen. Aandoeningen die zich vooral in het longparenchym afspelen, zijn veel zeldzamer. Aandoeningen van de longvaten komen als geïsoleerde ziekte weinig voor. Ziekteprocessen in de luchtwegen of in het longweefsel, of afwijkingen in de longcirculatie, hebben een groot effect op het functioneren van het lichaam. Een stoornis in de longfunctie leidt al snel tot een vermindering van de inspanningscapaciteit evenals tot het ontstaan van kortademigheidsklachten. Ondanks de goede afweer van de longen kunnen door de expositie aan de buitenwereld veel ziekten ontstaan die worden bepaald door een verminderde of een afwijkende afweer tegen partikels en micro-organismen in de ingeademde lucht. Bij systeemziekten zijn verschillende organen aangedaan, en staan soms de symptomen, verschijnselen en functiestoornissen van de longen op de voorgrond. Deze symptomen kleuren het klinische beeld en daarom worden deze systeemziekten vaak ook als longziekten besproken. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1841-4_16) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers."
7840,Biogenesis of Dense-Core Secretory Granules,"Dense core granules (DCGs) are vesicular organelles derived from outbound traffic through the eukaryotic secretory pathway. As DCGs are formed, the secretory pathway can also give rise to other types of vesicles, such as those bound for endosomes, lysosomes, and the cell surface. DCGs differ from these other vesicular carriers in both content and function, storing highly concentrated cores’ of condensed cargo in vesicles that are stably maintained within the cell until a specific extracellular stimulus causes their fusion with the plasma membrane. These unique features are imparted by the activities of membrane and lumenal proteins that are specifically delivered to the vesicles during synthesis. This chapter will describe the DCG biogenesis pathway, beginning with the sorting of DCG proteins from proteins that are destined for other types of vesicle carriers. In the trans-Golgi network (TGN), sorting occurs as DCG proteins aggregate, causing physical separation from non-DCG proteins. Recent work addresses the nature of interactions that produce these aggregates, as well as potentially important interactions with membranes and membrane proteins. DCG proteins are released from the TGN in vesicles called immature secretory granules (ISGs). The mechanism of ISG formation is largely unclear but is not believed to rely on the assembly of vesicle coats like those observed in other secretory pathways. The required cytosolic factors are now beginning to be identified using in vitro systems with purified cellular components. ISG transformation into a mature fusion-competent, stimulus-dependent DCG occurs as endoproteolytic processing of many DCG proteins causes continued condensation of the lumenal contents. At the same time, proteins that fail to be incorporated into the condensing core are removed by a coat-mediated budding mechanism, which also serves to remove excess membrane and membrane proteins from the maturing vesicle. This chapter will summarize the work leading to our current view of granule synthesis, and will discuss questions that need to be addressed in order to gain a more complete understanding of the pathway."
7841,Trichomonas,"The most widely known trichomonad in veterinary medicine is Tritrichomonas foetus. It is the etiologic agent of bovine tritrichomonosis, a sexually transmitted disease in extensively managed herds throughout many geographic regions worldwide. The same trichomonad species is also regarded as the causative agent of chronic diarrhea in the domestic cat, although more recent studies observed molecular differences between bovine- and feline-derived T. foetus. Trichomonosis in cats has a worldwide distribution and is mainly present among cats from high-density housing environments. Other trichomonads are found as inhabitants of the gastrointestinal tract in birds, such as Trichomonas gallinae. Particularly, Columbiformes, Falconiformes, Strigiformes, and wild Passeriformes can be severely affected by avian trichomonads. Diagnosis of trichomonosis is often complicated by the fragility of the parasite. To ensure valid test results, it is essential to collect and handle specimens in the right way prior to analysis. Cultivation tests, the specific amplification of parasites, or a combination of both test methods is the most efficient and most commonly used way to diagnose trichomonosis in animals. Bovine tritrichomonosis is mainly controlled by the identification and withdrawal of infected animals from bovine herds. The control of feline and avian trichomonosis relies mainly on preventive measures."
7842,Infection Control in the Intensive Care Unit,"Many patients admitted to critical care units carry healthcare-associated multiresistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), or may have a communicable infectious disease, such as pulmonary tuberculosis (TB). Special measures are, therefore, frequently required to prevent the spread of these pathogens to other patients on the unit. In general, these are referred to as infection control procedures."
7843,The Epidemic Process in Zoonoses and Sapronoses,"This chapter could also be called eco-epidemiological basics or background information for zoonoses and sapronoses. Epidemiology is the study of the process of the origin and spread of transmissible (communicable) infectious diseases of man, and their control. The modern conception of epidemiology is broader in that it also includes non-infectious diseases (such as diabetes, heart attack, cardiovascular diseases and carcinomas) and variables that influence their distribution in the human population. In both the classical and modern conception of epidemiology, these factors include variables concerning the host (age, sex, nutrition, occupation), the agent (virulence, antigenic variability), and the environment (chemical factors, contamination, emissions, temperature, precipitation and humidity, illumination, ionising radiation, noise etc.). Epidemiological data are then analysed, and the results of these studies can then be used for the prevention and control of these human diseases."
7844,Falciparum Malaria,"Malaria is one of the most common infectious diseases in the world today, being the most important parasitic infection, and Plasmodium falciparum is the organism responsible for most of the mortality [1]. It has been estimated that approximately 300–500 million people contract malaria every year, with approximately 1–2 million deaths, most of these occurring in children [1–5]. Plasmodium falciparum, Mycobacterium tuberculosis and measles currently compete for the title of the single most important pathogen causing human morbidity and mortality [2, 3]. Infection with Plasmodium falciparum has a wide variety of potential clinical consequences [4, 6, 7]."
7845,Sequences Promoting Recoding Are Singular Genomic Elements,"The distribution of sequences which induce non-standard decoding, especially of shift-prone sequences, is very unusual. On one hand, since they can disrupt standard genetic readout, they are avoided within the coding regions of most genes. On the other hand, they play important regulatory roles for the expression of those genes where they do occur. As a result, they are preserved among homologs and exhibit deep phylogenetic conservation. The combination of these two constraints results in a characteristic distribution of recoding sequences across genomes: they are highly conserved at specific locations while they are very rare in other locations. We term such sequences singular genomic elements to signify their rare occurrence and biological importance."
7846,Schwimmerulkus,
7847,Intellectual Property Rights in Animal Biotechnology,Highlights: Animal biotechnology is oriented toward developing products at commercial scale. IPRs are essential components of animal biotechnology research and development.
7848,Introduction to Bioterrorism Risk Assessment,
7849,Main Factors Influencing College Student Health and Countermeasures Proposal in Network Environment—From Physical Health Education Perspective,"This dissertation adopts document-data method, comparative analysis method and Inductive deductive method to analyze main factors influencing college students’ physical and mental health from physical health education perspective. It elaborates the significance of physical health education and put up “health first” guideline for promoting health knowledge and cultivate sports skills, creating favorable conditions for physical health education implementation and switching college physical education focus to reform colleges and universities physical education assessment system."
7850,Surveillance and Control of Communicable Disease in Conflicts and Disasters,To describe the principles of health surveillance in conflict and disaster situations. To assist in organising a health surveillance system in conflict and disaster situations. To describe the principles of control of communicable diseases in conflict and disaster situations. To assist in organising a response to outbreaks and epidemics. To introduce the challenges associated with health surveillance and communicable diseases in conflict and disaster situations.
7851,Introduction to Socioecological Dimensions of Infectious Diseases and Health in Southeast Asia,"Global changes affect host-pathogen interactions, through the modification of the epidemiological environment (climate, land use, biodiversity), leading to new and sometimes unexpected risks. Epidemics, emergence and re-emergence of infectious diseases are outcomes of these changes, and they constitute serious global threats for health. Although some local emergences have a potential for global threat (i.e. SARS, avian influenza, etc.), most of infectious diseases affect rural and poor populations particularly in developing countries, which are particularly vulnerable to the consequences of global change. Southeast Asia is both a hotspot of infectious emerging diseases of potential global pandemics and of biodiversity, particularly at threat due to dramatic changes in land use (Morand et al. 2014). These may explain why international organizations, developmental agencies and non-governmental conservationist organizations have specially focused on Southeast Asia. Infectious diseases are still a major concern in most Southeast-Asian countries (Coker et al. 2011)."
7852,Picornaviruses,"The picornavirus family contains several major human and animal pathogens. Vaccines against some of these pathogens are available. However, the availability of potent antiviral compounds would be an appreciable advantage in fighting these pathogens. Inside their non-enveloped capsid, picornaviruses possess a positive sense RNA genome with a single open reading frame. Upon release into the cytoplasm, the genome is translated into a single polyprotein that is processed by virally encoded proteinases. These proteinases represent excellent targets for the development of anti-virals for two reasons. First, efficient polyprotein processing is essential for successful viral replication. Second, the picornaviral proteinases show notable differences to cellular proteinases. To aid in the development of anti-virals, detailed knowledge of the mechanisms, substrate specificities and structures of these proteinases is needed. This chapter reviews recent progress, discusses selected substances with antiviral activity against picornavirus proteinases and outlines several new avenues for the design of novel anti-virals."
7853,"Epidemiology and Control: Principles, Practice and Programs","Infectious disease epidemiology is concerned with the occurrence of both infection and disease in populations and the factors that determine their frequency, spread, expression and distribution. Viruses show characteristic infectivity, virulence and pathogenicity. The most well established host factors are age, sex and race, but other host biological and behavioral factors affect acquisition of viral infection and/or its course and manifestations. The physical, chemical and biological environment operates on the virus itself and may also alter the host biological or behavioral response. Viral infections have incubation periods lasting days or weeks, while their pathologic sequelae may not manifest for years or decades. Likewise the degree or intensity of host response and clinical expression may range from largely inapparent to highly lethal. The degree of cell, tissue and organ specificity is high. Common syndromes involve the respiratory, gastrointestinal, and central nervous systems, the liver, and mucocutaneous surfaces. Vertical transmission may produce a variety of congenital and perinatal conditions. Viruses spread by multiple modes, using nearly every bodily surface or fluid as a route of exit or entry, either by direct contact or indirectly through an animal vector or other inanimate vehicle. Different viral Infections occur nearly ubiquitously or sporadically; they may be present continuously throughout a population (endemic) or occur in seasonal rhythm or in unexpectedly explosive form (epidemic). Many viruses are refractory to all known therapeutic agents, while for a few, the increasing number of highly effective agents holds great promise. Vaccines have produced many historical successes including the ultimate goal of eradication, but many viral infections continue to elude effective vaccine development. Major government and private sector programs for treatment and prevention have raised expectations of successful control for certain widespread and serious viral diseases; however, in every case a unique set of scientific, socioeconomic, political and behavioral barriers remains to be overcome."
7854,Management of Fluid Overload in the Pediatric ICU,"The implications and management of fluid overload in pediatric critical care remain areas of ongoing controversy. Consensus definitions and methods of quantitating fluid overload continue to evolve, paralleling our growing understanding of fluid dynamics in critically ill patients. Fluid overload has been associated with adverse outcomes in some patient populations; guidelines for fluid management therapies are sparse and have little supporting data. Conflicting data for efficacy of therapies such as diuretic medications and renal replacement therapy are likely reflective of an incomplete understanding of the dynamic relationship between critical illness and fluid overload. Although some guidance regarding diuresis, continuous renal replacement therapy, and fluid balance goals is elucidated in the following chapters, it is important to recognize that further research into these management strategies is required before standardized approaches to management can be established."
7855,Nanotechnology — In Relation to Bioinformatics,"The first use of word “Nanotechnology” has been attributed to Norio Taniguchi in a paper published in 1974. Eric Drexler, in 1986, published book “Engines of Creation” in which he described his ideas of molecular nanotechnology used to build miniature machines and devices from the bottom up using self-assembly. Many scientists from mainstream disciplines—biology, chemistry or physics—will argue of course that they are and have been ‘doing’ nanotechnology for years and that it is nothing new. Indeed chemists play with atoms and molecules which are sub-nano and molecular biology deals with the understanding and application of biological nano-scale components. Nature has used nanotechnology and, in fact, it has taken millions of years to develop this by a process of evolution and natural selection. Nanotechnology is an emerging research field which promises to have a wide range of interesting applications. Nanotechnology, encompasses all technology that aims to create nanometre-scaled structures or is able to address or manipulate matter at the nanometre level."
7856,Fundamental Principles for Luminescence Sensing Measuring Devices Used for the Detection of Biological Warfare Agents,This chapter surveys the current detection technologies used in commercially available luminescence biosensor detection equipments currently employed for identifying warfare biological agents (BAs). Brief technical descriptions of these technologies are presented with emphasis placed on the principles of detection. Much of the content presented was obtained from the open-source literature and is an introduction to biosensor fundamentals
7857,Infection Prevention in Pediatric Oncology and Hematopoietic Stem Cell Transplant Recipients,"Pediatric patients with malignancies and transplant recipients are at high risk of infection-related morbidity and mortality. Children at the highest risk for infections are those with acute myeloid leukemia (AML), relapsed acute lymphoblastic leukemia (ALL), and hematopoietic stem cell transplant recipients (HSCT). These patients are at high risk for life-threatening bacterial, viral, and fungal infections which are associated with prolonged hospital stay, poor quality of life, and increased healthcare cost and death. Recognition of risk factors which predisposes them to infections, early identification of signs and symptoms of infections, prompt diagnosis, and empiric/definitive treatment are the mainstay in reducing infection-related morbidity and mortality. Infection control and prevention programs also play a crucial role in preventing hospital-acquired infections in these immunosuppressed hosts."
7858,Life Threatening Tropical Infections,"Infectious diseases are among the most common pediatric illnesses and are frequently encountered in the pediatric intensive care unit. Tropical infections, on the other hand, are relatively uncommon in children in developed countries, except those with pertinent travel histories or recent immigration. Clinicians who participate in mission work and disaster relief work also encounter these diseases as they are endemic in many developing nations. For the most part these infections do not result in critical illness however some do and this chapter will focus on a few of the more common infections with potential to be acutely life threatening. The epidemiology, pathophysiology, clinical manifestations, and current clinical management are presented for severe malaria, dengue fever, typhoid, and leptospirosis."
7859,Cryptococcosis,"Cryptococcosis is an infectious disease caused by the encapsulated fungi Cryptococcus neoformans and Cryptococcus gattii. Once a relatively uncommon cause of human disease, cryptococcal infection can develop in apparently immunocompetent hosts and has emerged as an important opportunistic infection in humans over the past several decades as immunocompromised populations expand in the setting of HIV/AIDS, organ transplantation, malignancies, and treatment for other conditions. Clinical manifestations are myriad but pulmonary and central nervous system (CNS) infections are the most common. Improvements in diagnostic testing and standardized approaches to antifungal therapy, when available, have made considerable impact in the management of this infection. While the widespread use of highly active antiretroviral therapy (HAART) has improved the outcome of cryptococcosis in many HIV-infected patients, cryptococcosis remains an entity of considerable morbidity and mortality in many parts of the world, and restoration of host immunity can present management challenges that require individualized management. As immunocompromised populations continue to expand, it is likely that cryptococcosis will remain an important opportunistic fungal infection of humans requiring ongoing investigation."
7860,Grid Computing for Disaster Mitigation,"The infamous 2004 Andaman tsunami has highlighted the need to be prepared and to be resilient to such disasters. Further, recent episodes of infectious disease epidemics worldwide underline the urgency to control and manage infectious diseases. Universiti Sains Malaysia (USM) has recently formed the Disaster Research Nexus (DRN) within the School of Civil Engineering to spearhead research and development in natural disaster mitigation programs to mitigate the adverse effects of natural disasters. This paper presents a brief exposition on the aspirations of DRN towards achieving resilience in communities affected by these natural disasters. A brief review of the simulations of the 2004 Andaman tsunami, with grid application is presented. Finally, the application of grid technology in large scale simulations of disease transmission dynamics is discussed."
7861,Structural and Functional Properties of Viral Membrane Proteins,"Viruses have developed a large variety of transmembrane proteins to carry out their infectious cycles. Some of these proteins are simply anchored to membrane via transmembrane helices. Others, however, adopt more interesting structures to perform tasks such as mediating membrane fusion and forming ion-permeating channels. Due to the dynamic or plastic nature shown by many of the viral membrane proteins, structural and mechanistic understanding of these proteins has lagged behind their counterparts in prokaryotes and eukaryotes. This chapter provides an overview of the use of NMR spectroscopy to unveil the transmembrane and membrane-proximal regions of viral membrane proteins, as well as their interactions with potential therapeutics."
7862,Whistleblowing and Research Integrity: Making a Difference Through Scientific Freedom,"Whistle-blowers, who speak out in the public interest, are important players in challenging abuses of power. In science, where trust in processes and outcomes is vital, whistle-blowing is especially important. Case studies of US research whistle-blowers show the challenges they face, the reprisals they suffer, and the significant difference they make through their efforts. Legal protections for whistle-blowers are valuable but not enough on their own. Key potential allies for whistle-blowers are scientific peers, government agencies, legislators, media, and NGOs. These allies can provide corroboration, advocacy, and solidarity."
7863,Introduction to Bioterrorism Risk Communication,
7864,A Web Search Method Based on the Temporal Relation of Query Keywords,"As use of the Web has become more popular, searching for particular content has been refined by allowing users to enter multiple keywords as queries. However, simple combinations of multiple query keywords may not generate satisfactory search results. We therefore propose a search method which automatically combines query keywords to generate queries by extracting the relations among query keywords. This method consists of two Web search processes: one to determine the temporal relations between query keywords, and one to generate queries based on the obtained temporal relations. We discuss these two processes along with experimental results and implementation issues regarding a prototype system."
7865,Current Status and Future Outlook for Nonwovens in Japan,"More than half a century has already passed since the production of nonwovens began in Japan. In January 1996, the Ministry of International Trade and Industry (presently the Ministry of Economy, Trade and Industry) modified the contents of production dynamics, and statistical surveys of nonwovens have come to be independently reported. Up to 2000, the nonwoven industry in Japan had been developing steadily. After the industry experienced a slowdown, it began to grow again and marked historical records consecutively in 2007 and 2008. However, the industry stopped growing and decreased in 2009 due to simultaneous declines of the world’s economies. At present, there are certain signs of a recovery, but people engaged in the industry are uncertain whether the business will continue to grow in the future."
7866,DCD for Islet Transplantation,"Pancreatic islet transplantation has the potential to become the most physiologically advantageous and minimally invasive procedure for the treatment of type 1 diabetes mellitus. Since the first clinical islet transplantation was performed at the University of Minnesota in 1974 [1], the results have been far from ideal for more than two decades in spite of an improvement of islet isolation technique by Ricordi et al. [2–4]. The introduction of the Edmonton protocol, with a highly improved rate of insulin independency, encouraged us to promote clinical islet transplantation [5, 6]. In Japan, we organized the Working Group (The Japanese Islet Transplant Registry) in 1997 under the Japanese Society for Pancreas and Islet Transplantation for the purpose of starting clinical islet transplantation. The first issue of the Working Group was to construct a system of clinical islet transplantation in Japan including the registration of the recipients, procurement of the pancreas for islet isolation and transplantation of the isolated islets. In Japan, afterwards, various problems facing to a start of clinical islet transplantation have been discussed and we completed the guideline for clinical islet transplantation in Japan. The Japanese Organ Transplant Law was enforced in 1997 and organ transplantations using brain dead (DBD) donors were finally started. Since the islet transplantation was not included in the Japanese Organ Transplant Law because it was categorized as tissue transplantation, we were able to use the pancreas only from DCD donors for islet transplantation. The first islet isolation from the human pancreas was performed in 2003.9 and the first islet transplantation was performed in 2004.4 [7–9]. Sixty-five islet isolations and 34 islet transplantations were performed in our country from 2003.9.12 to 2007.3.11 [10]. In this chapter, we describe the current status of clinical islet transplantation using DCD donors in Japan."
7867,Update on Avian Influenza for Critical Care Physicians,"Human influenza pandemics over the last 100 years have been caused by H1, H2, and H3 subtypes of influenza A viruses. More recently, avian influenza viruses have been found to directly infect humans from their avian hosts. The recent emergence, host expansion, and spread of a highly pathogenic avian influenza (HPAI) H5N1 subtype in Asia has heightened concerns globally, both in regards to mortality of HPAI H5N1 in humans and the potential of a new pandemic. In response, many agencies and organizations have been working collaboratively to develop early detection systems, preparedness plans, and objectives for further research. As a result, there has been a large influx of published information regarding potential risk, surveillance, prevention and control of highly pathogenic avian influenza, particularly in regards to animal to human and subsequent human to human transmission. This chapter will review the current human infections with avian influenza and its public health and medical implications."
7868,A Multiplex Polymerase Chain Reaction for Differential Detection of Turkey Coronavirus from Chicken Infectious Bronchitis Virus and Bovine Coronavirus,"A multiplex polymerase chain reaction (PCR) method for differential detection of turkey coronavirus (TCoV), infectious bronchitis virus (IBV), and bovine coronavirus (BCoV) is presented in this chapter. Primers are designed from the conserved or variable regions of nucleocapsid (N) or spike (S) protein genes of TCoV, IBV, and BCoV and used in the same PCR reaction. Reverse transcription followed by PCR reaction is used to amplify a portion of N or S gene of the corresponding coronaviruses. Two PCR products, a 356-bp band corresponding to N gene and a 727-bp band corresponding to S gene, are obtained for TCoV. In contrast, one PCR product of 356 bp corresponding to a fragment of N gene is obtained for IBV strains and one PCR product of 568 bp corresponding to a fragment of S gene is obtained for BCoV."
7869,Myroides odoratus/odoratimimus,
7870,"Phenotypes of Liver Diseases in Infants, Children, and Adolescents","Liver disease in childhood is rare and is frequently the cause of dismay as the medical care provider attempts to recall the myriad of diagnoses that they read about during their training but may never have encountered. The aim of this chapter is to describe hepatic disease phenotypes based on age and primary manifestation of liver disease such as cholestasis, hepatomegaly, or acute liver failure and to provide a reasonably comprehensive list of hepatic diseases that may present with the clinical phenotypes. The hope is to help primary medical providers determine the differential diagnosis and thus guide early studies and appropriate referral and pediatric gastroenterologists and trainees to determine a comprehensive differential diagnosis for their patients on which to base a rational work-up and management plan. Our patients range from day-old premature infants to 18-year-old postpubescent teens and from seemingly healthy children in the outpatient clinic to profoundly sick infants in ICU on life support. The best way to determine a diagnosis safely and efficiently is to develop a deep understanding of the pathophysiology of liver disease, but even for the most experienced, a checklist of diagnostic possibilities may be helpful to ensure no oversights."
7871,The Acute Respiratory Distress Syndrome: Diagnosis and Management,"Acute respiratory distress syndrome (ARDS) is characterized by a new acute onset of hypoxemia secondary to a pulmonary edema of non-cardiogenic origin, bilateral lung opacities and reduction in respiratory system compliance after an insult direct or indirect to lungs. Its first description was in 1970s, and then several shared definitions tried to describe this clinical entity; the last one, known as Berlin definition, brought an improvement in predictive ability for mortality. In the present chapter, the diagnostic workup of the syndrome will be presented with particular attention to microbiological investigations which represent a milestone in the diagnostic process and to imaging techniques such as CT scan and lung ultrasound. Despite the treatment is mainly based on supportive strategies, attention should be applied to assure adequate respiratory gas exchange while minimizing the risk of ventilator-induced lung injury (VILI) onset. Therefore will be described several therapeutic approaches to ARDS, including noninvasive mechanical ventilation (NIMV), high-flow nasal cannulas (HFNC) and invasive ventilation with particular emphasis to risks and benefits of mechanical ventilation, PEEP optimization and lung protective ventilation strategies. Rescue techniques, such as permissive hypercapnia, prone positioning, neuromuscular blockade, inhaled vasodilators, corticosteroids, recruitment maneuvers and extracorporeal life support, will also be reviewed. Finally, the chapter will deal with the mechanical ventilation weaning process with particular emphasis on extrapulmonary factors such as neurologic, diaphragmatic or cardiovascular alterations which can lead to weaning failure."
7872,Lungenparenchymerkrankungen,"Das Lungenemphysem ist pathologisch-anatomisch definiert. Man versteht darunter eine irreversible abnorme Erweiterung der lufthaltigen Räume distal der Bronchioli terminales, die mit einer Destruktion der Alveolarsepten einhergeht. Neben der chronischen Bronchitis und der Bronchiolitis ist das Lungenemphysem eine der morphologischen Komponenten der chronisch-obstruktiven Lungenkrankheit (COPD). Bei fortgeschrittenen Formen der COPD besteht mit Regelmäßiigkeit ein erhebliches Lungenemphysem."
7873,Study of Inhibitors Against SARS Coronavirus by Computational Approaches,"Called by many as the biology's version of Swiss army knives, proteases cut long sequences of amino acids into fragments and regulate most physiological processes. They are vitally important in life cycle and have become a main target for drug design. This Chapter is focused on a special protease that plays a key role in replicating SARS (Severe Acute Respiratory Syndrome) coronavirus, the culprit of SARS disease. The progresses reported here are mainly from various computational approaches, such as structural bioinformatics, pharmacophore modelling, molecular docking, and peptide-cleavage site prediction, among others. It is highlighted that the compounds C(28)H(34)O(4)N(7)Cl, C(21)H(36)O(5)N(6) and C(21)H(36)O(5)N(6), as well as KZ7088, a derivative of AG7088, might be the promising candidates for further investigation, and that the octapeptides ATLQAIAS and ATLQAENV, as well as AVLQSGFR, might be converted to effective inhibitors against the SARS protease. Meanwhile, how to modify these octapeptides based on the “distorted key” theory to make them become potent inhibitors is explicitly elucidated. Also, a brief introduction is given for how to use computer-generated graphs to rapidly diagnose SARS coronavirus. Finally, a step-by-step protocol guide is given on how to use ProtIdent, a web-server developed recently, to identify the proteases and their types based on their sequence information alone. ProtIdent is a very user-friendly bioin-formatics tool that can provide desired information for both basic research and drug discovery in a timely manner. With the avalanche of protein sequences generated in the post-genomic age, it is particularly useful. ProtIdent is freely accessible to the public via the web-site at http://www.csbio.sjtu.edu.cn/bioinf/Protease/."
7874,Glycyrrhiza glabra,Liquorice foliage
7875,Abkürzungen,
7876,Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): Immunologic Reactions,"Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immunologic reactions to several stimuli, mostly medications, which present as a spectrum of primarily widespread mucocutaneous lesions, but also with other organ involvement. Pathology is characterized by full thickness necrosis of the epithelial layer of the involved organ due to immune-mediated apoptosis of the resident keratinocytes. High suspicion for early detection and quick withdrawal of the culprit medication are the most important steps in stopping this reaction. Aggressive supportive care is often necessary as the patient recovers. Steroids, other immunosuppressants, and plasmapheresis have all been studied as treatments, but high-quality evidence supporting their contributions, either together or separately, in decreasing length of hospital stay or prolonging survival have not been consistently demonstrated. Further studies of the mechanism of action and novel treatment modalities are still needed to improve outcomes in patients with this rare but often fatal condition."
7877,"Communicable Diseases and Emerging Pathogens: The Past, Present, and Future of High-Level Containment Care","High-level containment care involves the management of patients with highly hazardous communicable diseases in specialized biocontainment units possessing a unique collection of engineering, administrative, and personnel controls. These controls are more stringent than those found in conventional airborne infection isolation rooms and provide additional safeguards against nosocomial disease transmission. Borne amidst a convergence of events in 1969, the employment of HLCC units was validated during the 2014–2016 Ebola virus disease outbreak, and the United States (as well as many other nations) is in the process of expanding its HLCC capacity. Beyond Ebola, however, the specific diseases that might warrant care in a HLCC unit remain unclear. We review here the fascinating history of HLCC and of biocontainment units and make recommendations regarding those highly hazardous communicable diseases that might optimally be managed in these units."
7878,Spezifische Infektionen,"Die Tuberkulose ist die weltweit häufigste infektionsbedingte Todesursache und führt nur selten zur Aufnahme auf der Intensivstation. Hauptgründe für eine Intensivtherapie sind eine respiratorische Insuffizienz, Thoraxeingriffe, fortgeschrittene Tbc-Meningitis, tuberkulöse Perikarditis, Nebenwirkungen von Tuberkulostatika und eine tuberkuloseassoziierte Addison-Krise [11]."
7879,Infectious Atypical Pneumonia,"Infectious atypical pneumonia, also known as severe acute respiratory syndrome (SARS), is an acute respiratory infectious disease caused by SARS coronavirus (SARS-CoV). Clinically, it is characterized by fever, headache, muscular soreness, fatigue, dry cough rarely with phlegm, and diarrhea. Most patients experience accompanying pneumonia. In severe cases, the conditions may develop into acute lung injury, acute respiratory distress syndrome (ARDS), or even multiple organ failure that causes death. In China, SARS has been legally listed as one of the class B infectious diseases but is managed as class A infectious diseases, like anthrax and human infection of avian influenza."
7880,Surgical Complications of Childhood Tumors,"Most childhood tumors will first present to a physician; some tumors will present in an atypical manner and may mimic a surgical condition. The diagnosis may be missed if the surgeon is not aware of the possibility of cancer. A very great number of rare presentations of childhood cancer have been described in the literature. It is important that the surgeon who is not experienced in the management of childhood cancer is aware that an apparently benign condition could be a manifestation of an underlying malignancy [71, 83] (Table 22.1)."
7881,Methods to Induce Cardiac Hypertrophy and Insufficiency,"Animal models of cardiac hypertrophy and insufficiency have been reviewed by Hasenfuss (1988), Muders and Elsner (2000), Vanoli et al. (2004), Patten and Hall-Porter (2009), Dubi and Arbel (2010), Gomes et al. (2013), and Szymanski et al. (2012)."
7882,Chemokines in Coronavirus-Induced Demyelination,"Inflammation within the central nervous system (CNS) is critical in the development of the neuropathology associated with the human demyelinating disease multiple sclerosis (MS). Recent studies have identified a family of soluble proinflammatory molecules called chemokines that are able to direct leukocyte infiltration into the CNS in response to infection or injury. Identification of chemokines within and around demyelinating lesions in MS patients indicate a potential role for these molecules in contributing to the pathogenesis of MS. To address this issue, we have used mouse hepatitis virus (MHV) infection of the CNS to understand the dynamic interaction of chemokine expression as it relates to inflammation and neuropathology. Our results indicate that chemokine expression within the CNS results in persistent recruitment of both T lymphocytes and macrophages and results in subsequent myelin destruction. Herein, we demonstrate the complexity of the chemokine response to MHV infection of the CNS and the delicate balance that exists between host defense and development of disease."
7883,"Brain and the Liver: Cerebral Edema, Hepatic Encephalopathy and Beyond",Occurrence of brain dysfunction is common in both chronic liver disease as well as acute liver failure. While brain dysfunction most commonly manifests as hepatic encephalopathy is chronic liver disease; devastating complications of cerebral edema and brain herniation syndromes may occur with acute liver failure. Ammonia seems to play a central role in the pathogenesis of brain dysfunction in both chronic liver disease and acute liver failure. In this chapter we outline the pathophysiology and clinical management of brain dysfunction in the critically ill patients with liver disease.
7884,Heat Shock Proteins and the Resolution of Inflammation by Lymphocytes,"Depletion of phagocytes that infiltrate host organs like the lungs reduces inflammatory damage to tissues. Understanding the mechanisms by which this process occurs could lead to new therapeutic approaches to limit the detrimental effects of inflammation. The lungs, gastrointestinal tract, and skin are particularly prone to infection. Specialized immune cells protect these organs from tissue damage by eliminating phagocytes from inflamed tissues by recognizing signals produced by the phagocytes. One such signal is heat shock proteins (HSP) expressed on the cell surface of phagocytes. These HSP closely resemble their microbial equivalents, and therefore phagocytes that are labeled by HSP are recognized as target cells. T lymphocytes bearing γδT cell receptor (TCR) elicit fast responses to invading pathogens. Since the γδTCR has limited germline-encoded diversity, HSP are an ideal target for recognition by these cells. γδT cells exert cytotoxic actions towards macrophages and neutrophils that express Hsp60 or Hsp70, respectively, on their cell surface. Through the recognition of HSP on the cell surface of inflamed cells, γδT cells eliminate phagocytes from inflammatory sites, thereby preventing host tissue damage"
7885,Bioinformatics,"After reading this chapter, you should know the answers to these questions:"
7886,Cardiovascular Activity,
7887,Reisemedizin,"Tauchgebiete befinden sich oft in exotischen, subtropischen oder tropischen Gebieten. Der Taucherarzt sollte neben Ratschlägen zum Tauchen auch Information über Krankheiten und deren Prophylaxe vermitteln."
7888,The Ecology of Eating Systems,
7889,Waterborne Viral Gastroenteritis: An Introduction to Common Agents,"Acute gastroenteritis is among the most common illnesses of human beings, and its associated morbidity and mortality are greatest among those at the extremes of age; children and elderly. During the 1970s, several viruses were associated with this syndrome, which are now known to be caused mainly by viruses belonging to four distinct families—rotaviruses, caliciviruses, astroviruses, and adenoviruses. Other viruses, such as the toroviruses, picobirnaviruses, coronavirus, and enterovirus 22, may play a role as well. Transmission by food or water has been documented for astroviruses, caliciviruses, rotaviruses, and norovirus. In developing countries, gastroenteritis is a common cause of death in children <5 years, while deaths from diarrhea are less common, much illness leads to hospitalization or doctor visits. Laboratory confirmation of waterborne illness is based on demonstration of virus particles or antigen in stool, detection of viral nucleic acid in stool, or demonstration of a rise in specific antibody to the virus. Newer methods for syndrome surveillance of acute viral gastroenteritis are being developed like multiplex real-time reverse transcriptase PCRs. Application of these more sensitive methods to detect and characterize individual agents is just beginning, but has already opened up new avenues to reassess their disease burden, examine their molecular epidemiology, and consider new directions for their prevention and control through vaccination, improvements in water quality, and sanitary practices."
7890,Role of Zinc and Selenium in Oxidative Stress and Immunosenescence: Implications for Healthy Ageing and Longevity,"Ageing is an inevitable biological process with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. Some nutritional factors (zinc and selenium) may remodel these changes leading to a possible escaping of diseases with subsequent healthy ageing, because they are especially involved in improving immune functions as well as antioxidant defense. Experiments performed “in vitro” (human lymphocytes exposed to endotoxins) and “in vivo” (old mice or young mice fed with low zinc dietary intake) show that zinc is important for immune response both innate and adoptive. Selenium provokes zinc release by Metallothioneins (MT), via reduction of glutathione peroxidase. This fact is crucial in ageing because high MT may be unable to release zinc with subsequent low intracellular free zinc ion availability for immune response. Taking into account the existence of zinc transporters (ZnT and ZIP family) for cellular zinc efflux and influx, respectively, the association between ZnT and MT is important in maintaining satisfactory intracellular zinc homeostasis in ageing. Improved immune performance occur in elderly after physiological zinc supplementation, which also induces prolonged survival in old, nude and neonatal thymectomized mice. The association “zinc plus selenium” improves humoral immunity in old subjects after influenza vaccination. Therefore, zinc and selenium are relevant for immunosenescence in order to achieve healthy ageing and longevity."
7891,The Role of Metalloproteinases in Corona Virus Infection,"Infection with neurotropic strains of mouse hepatitis virus (MHV) results in rapid leukocyte infiltration into the central nervous system (CNS). The inflammatory response controls virus replication but fails to mediate sterile clearance. The persistence of viral RNA and inflammatory cells within the CNS is associated with the development of ongoing demyelination. Matrix metalloproteinases (MMPs) are a family of proteases involved in degradation of the extracellular matrix (ECM). During inflammatory responses MMPs are thought to play a significant role in breaking down the basement membrane surrounding blood vessels as well as parenchymal ECM thereby facilitating leukocyte infiltration. MMPs have also been associated with activation of chemokines and perhaps more significantly the degradation of myelin proteins and generation of autoantigens. Recent examination of MMP expression during MHV infection suggests that MMP-3, -9 and -12 are involved in the inflammatory response. The proinflammatory effects of these MMPs are likely tempered by induction of tissue inhibiter of metalloproteinase-1 expression."
7892,A Practical Way to Improve Access to Essential Medicines Against Major Infectious Diseases,"With the frequent outbreak of major infectious diseases such as HIV/AIDS, SARS, and H1N1, it is increasingly important for countries to have the capability to safeguard the health of their citizens and manage public health crises. The key to success lies in the availability and accessibility of essential medicines. Pushed by developing countries and international nongovernmental organizations, the conflicts regarding public access to essential medicines and protection of patented drugs have gained global attention. This chapter briefly introduces the history of the global response to the above challenges, beginning with the Trade-Related Aspects of Intellectual Property Rights (TRIPS) agreement through the adoption of the Doha declaration and the protocol amending the World Trade Organization’s (WTO) agreement on TRIPS. Then, it discusses the practice of compulsory licenses in both developing and developed countries and describes the huge market demand for generic drugs against infectious disease in developing countries. Finally, the chapter describes the capacity of generic drug production in major developing countries, such as India and China, as well as the roles of these countries in providing generic drugs to patients at home and to other developing countries. History has repeated itself many times due to a continued lack of essential medicines; the initial epidemic of infectious disease in developing countries has become pandemic, spreading throughout the globe. Therefore, any efforts taken by developing countries to increase access to essential medicines against infectious disease are beneficial to people in both developing and developed countries. The developing countries with the capacity and experience to develop generic drugs for public use should learn from each other and collaborate in the research, production, and distribution of generic drugs under the rights granted by the WTO agreement. Developed countries and big pharmaceutical companies should be allies rather than opponents for the ultimate goal of health promotion for all of mankind."
7893,Fever Management in Intensive Care Patients with Infections,"Fever is one of the cardinal signs of infection and, nearly 120 years after William Osler’s statement in his address to the 47(th) annual meeting of the American Medical Association [1], infectious diseases remain a major cause of morbidity and mortality. Despite this, it is unclear whether fever itself is truly the enemy or whether, in fact, the febrile response represents an important means to help the body fight infection. Furthermore, it is unclear whether the administration of antipyretic medications or physical cooling measures to patients with fever and infection is beneficial or harmful [2, 3]. Here, we review the biology of fever, the significance of the febrile response in animals and humans, and the current evidence-base regarding the utility of treating fever in intensive care patients with infectious diseases."
7894,eMicrob: A Grid-Based Spatial Epidemiology Application,"The use of Grid technologies allows us to make progress in the prediction accuracy of epidemiological patterns, epidemiological modeling, risk predictions of infectious diseases etc by combining the geo-information and molecular simulation analysis methods. In this paper, we mainly design the eMicrob, in particular, build up the e-Microbe miniGrid deployed in IRSA, CAS and IME, the Chinese PLA. The architecture is as follows: Firstly we review related grid applications that are motivating widespread interest in Grid concepts within the scientific and engineering communities. Secondly we talk about the key methodologies and strategies involved in the construction of eMicrob. In the third section, the system design of the eMicrob, in particular about the architecture of the eMicrob miniGrid is discussed. Finally, we draw some conclusion in the process of the building of eMicrob and make some discussion about the challenges. It has been proven that the methods based on the Grid technologies are revolutionary and high efficient through the experience of the establishment and deployment of the e-Microbe miniGrid."
7895,Antiviral Resistance in Influenza Viruses: Clinical and Epidemiological Aspects,"There are three classes of antiviral drugs approved for the treatment of influenza: the M2 ion channel inhibitors (amantadine, rimantadine), neuraminidase (NA) inhibitors (laninamivir, oseltamivir, peramivir, zanamivir), and the protease inhibitor (favipiravir); some of the agents are only available in selected countries [1, 2]. These agents are effective at treating the signs and symptoms of influenza in patients infected with susceptible viruses. Clinical failure has been demonstrated in patients infected with viruses with primary resistance, i.e., antivirals can be present in the virus initially infecting the patient, or resistance may emerge during the course of therapy [3–5]. NA inhibitors are active against all nine NA subtypes recognized in nature [6], including highly pathogenic avian influenza A/H5N1 and recent low-pathogenic avian influenza A/H7N9 viruses [7]. Since seasonal influenza is usually an acute, self-limited illness in which viral clearance usually occurs rapidly due to innate and adaptive host immune responses, the emergence of drug-resistant variants would be anticipated to have limited effect on clinical recovery in otherwise healthy patients, as has been demonstrated clinically [3, 8, 9]. Unfortunately, immunocompromised or immunologically naïve hosts, such as young children and infants or those exposed to novel strains, are more likely to have mutations that confer resistance emergence during therapy; such resistant variants may also result in clinically significant adverse outcomes [10–13]."
7896,Killing More than Pain: Etiology and Remedy for an Opioid Crisis,"The search for effective pain relief has been ever present across human history. The discovery of opium’s ability to relieve pain stimulated the refinement of opium and generation of synthetic analogues to create more effective, potent, and faster-acting analgesics. The social and economic value of opioids has remained high not only due to their demonstrated efficiency in mitigating pain but also their noteworthy ability to reliably produce rewarding psychological effects. Consequently, at various times during the past several hundred years, opioids have sparked wars, fueled black markets and cartel crime, and triggered numerous opioid addiction and overdose death epidemics around the world. The increased therapeutic desire to address pain together with pharmaceutical discoveries in medication design, rapid manufacture, and highly effective opioid marketing and distribution has led more recently to increased availability and accessibility to potent prescription opioids, which has sparked the deadliest overdose crisis in human history. This chapter describes the etiology and epidemiology of the opioid crisis using public health and Health Belief Model frameworks and reviews approaches that have been applied to address supply (e.g., overprescribing) and demand (e.g., medication treatments) sides of the equation. Causes of the growth and spread of the overdose epidemic are analyzed as a way to inform a successful end to the current crisis as well as to prevent future epidemics."
7897,"Airway Anatomy, Physiology, and Inflammation","Approximately 10,000 l of air and 8,000 l of blood transit the respiratory system each day driven by small pressure gradients developed in response to rhythmic contraction and relaxation of striated muscle under both voluntary and involuntary control of the central nervous system. Matching of air- and blood flow results from central and local reflexes responding to both internal and external stimuli and subsequently controlling the pumps, as well as the smooth muscle in walls of the airways and blood vessels. A wide range of neural and immune mechanisms protect the lungs against environmental insults, and many are adaptive in nature, resulting in memory that increases sensitivity and responsiveness upon repeated exposure to stimuli. In over 10 % of the population, the responses to environmental stimuli become pathological, resulting in excessive sensitivity and aberrant responses to both specific and nonspecific stimuli, and culminate in physical remodeling of the airways and lungs. Prevention, definitive diagnosis, and effective treatment of the disorders require a better understanding of the mechanisms underlying excessive responses to environmental stimuli."
7898,Medical Management of Acute Rhinosinusitis in Children and Adults,"Acute rhinosinusitis is a commonly seen disease that is frequently diagnosed based on clinical symptomatology without any objective evidence. The most common form of treatment is antibiotics, even though many cases may not have a bacterial etiology. The most common bacterial organisms in childhood sinusitis belong to the group that cause many childhood upper respiratory and lower respiratory infections and include Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Besides antibiotics, other treatments are aimed at assisting with drainage, and this can be accomplished by reducing the inflammation and edema that prevents venting of the sinus structures. These medications can include antihistamines, decongestants, intranasal steroids, nasal saline irrigation, and, in some countries, mucolytics. Complementary and alternative medicine (CAM) techniques including Chinese herbal medications are often used, but there is little scientific evidence to support their use. The use of immunotherapy has not been found to be effective in the management of acute rhinosinusitis in children or adults."
7899,Haut und Tiere,"Tiere spielen in der Pathogenese zahlreicher Hautkrankheiten eine bedeutende Rolle. Für den Hautarzt sind klinische Angaben zu vorausgegangenem Tierkontakt von großer klinischer und differenzialdiagnostischer Bedeutung. Tiere können als Vektoren gefährlicher pathogener Krankheitserreger wie Viren, Bakterien, Protozoen, Pilze und Würmer fungieren, Ektoparasiten auf die Haut übertragen, selbst auf beziehungsweise in der Haut parasitieren, aber auch durch Tierallergene und Toxine lokale kutane Intoleranzreaktionen, systemische toxische sowie anaphylaktische Reaktionen mit tödlichem Ausgang herbeiführen [9, 43, 111, 114]"
7900,Cancer of Reproductive System: Receptors and Targeting Strategies,"Carcinogenesis in the different organs of the reproductive system, particularly, prostate, ovarian, and cervical tissues, involves aberrant expression of various physiological receptors belonging to different superfamilies. This chapter provides insights into the physiological receptors that are associated with the genesis, progression, metastasis, management, as well as the prognosis of the cancers of the male and female reproductive systems. It also highlights the structural and binding characteristics of the highly predominant receptors, namely, androgen, estrogen, progesterone, and gonadotropin-releasing hormone (GnRH) receptors, which are overexpressed in these cancers and discusses various strategies to target them."
7901,Mechanisms of Acute Liver Failure,"Acute liver failure (ALF) is characterized by the sudden onset of liver failure in a patient without evidence of chronic liver disease. This definition is important, as it differentiates patients with ALF from patients who suffer from liver failure owing to end-stage chronic liver disease [1]."
7902,Anesthesia for Open Abdominal Aortic Aneurysm Repair,"Abdominal aortic aneurysms (AAAs) are the 13th leading cause of death in the United States 1 and approximately 40,000 patients undergo elective AAA repair each year.2 With the population aging, this number is expected to increase. Although the use of endovascular AAA repair is becoming more common, open repair, first reported by Dubost et al. in 1951 remains the gold standard.2 This chapter will review the etiology, risk factors, diagnosis, pathophysiology, operative technique, perioperative management, and postoperative complications of patients undergoing open AAA repair."
7903,Hepatitis Delta Virus: HDV-HBV Interactions,"The hepatitis delta virus (HDV) is a subviral agent that utilizes the envelope proteins of the hepatitis B virus (HBV) for cell to cell propagation. In infected human hepatocytes, the HDV RNA genome can replicate and associate with multiple copies of the delta protein to assemble a ribonucleoprotein (RNP). However the RNP cannot exit the cell because of the lack of an export system. This is provided by the HBV envelope proteins, which are capable of budding at an internal cellular membrane to assemble mature HDV virions when RNPs are present. This review covers advances in the molecular aspects of the HDV-HBV interactions, with an emphasis on the HBV properties that are instrumental in HDV maturation, in particular the central role of the small HBV envelope protein."
7904,“Disease Knows No Borders”: Pandemics and the Politics of Global Health Security,"Since the 1990s, the threat of pandemics has gained increased prominence on policy-makers’ agendas due to the emergence and resurgence of infectious diseases and an increasingly interconnected world. Encapsulated by the phrase “disease knows no borders,” this new risk environment has led to the rise of a new global health security regime, codified in the 2005 International Health Regulations. It is based on a paradigm of rapid detection and response to outbreak events, and on a norm of collective action. Drawing on examples from the 2014–2015 Ebola epidemic, we argue that pandemic preparedness is not just a technical matter, but also a political and normative one. We show that the global health security regime carries tensions that reflect asymmetries in actors’ capacities to put forward their priorities."
7905,Shaping Ethical Guidelines for an Influenza Pandemic,"This chapter describes the process of shaping ethical guidelines for an influenza pandemic by the North Carolina Institute of Medicine (NC IOM)/North Carolina Department of Public Health (NCDPH) Task Force. The author discusses the threat of a pandemic in the twenty-first century, comparing a potential pandemic with past flu pandemics as well as the Severe Acute Respiratory Syndrome (SARS) outbreak in Canada and parts of Asia. Also discussed are the ways in which influenza would spread, be treated, and hopefully contained. Addressed are the ways in which one becomes ethically prepared for an influenza pandemic, as well as the challenges to incorporating ethical guidelines in preparations. Tong also addresses the role of a duty/obligation/responsibility to work by health care personnel, the role of volunteers, and when health care personnel may refuse to treat someone. Also taken into consideration are such issues as the distribution of food and vaccines, quarantines, work stoppage, both physical and social infrastructure, the role of military and police forces, and the effect of a pandemic, isolation, and quarantine on various industries. Tong shows the complicated nature of working on a task force and the complexity of incorporating ethics into logistical planning."
7906,Genomic and Postgenomic Research,The word genomics was first coined by T. Roderick from the Jackson Laboratories in 1986 as the name for the new field of science focused on the analysis and comparison of complete genome sequences of organisms and related high-throughput technologies.
7907,Bakterielle Infektionen,"Definition. Durch Staphylokokken verursachte Krankheiten können lokal begrenzt bleiben, generalisiert auftreten oder sich als Intoxikation äußern. Die frühere Einteilung der Staphylokokken nach der Produktion eines gelben Pigmentes in S. aureus und S. albus ist weitgehend verlassen worden. Wegen der Korrelation mit klinischen Krankheitsbildern hat sich dagegen die Einteilung der Staphylokokken in koagulasepositive (KPS) und koagulasenegative Staphylokokken (KNS) bewährt."
7908,An Agent-Based Infectious Disease Model of Rubella Outbreaks,"This study proposes a simulation model of rubella. SIR (Susceptible, Infected, Recovered) model has been widely used to analyse infectious diseases such as influenza, smallpox, bioterrorism, to name a few. On the other hand, agent-based model begins to spread in recent years. The model enables to represent the behaviour of each person on the computer. It also reveals the spread of infection by simulation of the contact process among people in the model. The study designs a model based on smallpox and Ebola fever model in which several health policies are decided such as vaccination, the gender-specific workplace and so on. The infectious simulation of rubella, which has not yet vaccinated completely for men in Japan, is implemented in the model. As results of experiments using the model, it has been found that preventive vaccine to all the men is crucial factors to prevent the spread in women."
7909,Legionnaires’ Disease,"The incidence of legionnaires’ disease (LD) seems to increase with age, particularly in males [36]. It was considered an infrequent cause of pneumonia in the past, but it currently ranks second to pneumococcus in the list of etiologic agents of severe community-acquired pneumonia (CAP) of bacterial origin [2, 24, 60, 89]. Considering less severe cases, in a series of 145 pneumonias in which BCYE culture, serology and the Legionella urinary antigen (LUA) test were systematically applied, Vergis et al. [91] reported a prevalence of LD of 13.7%. In another series of 392 adult patients with CAP treated in a university hospital, Sopena et al. found a prevalence of 12.5%, and LD was the second cause of pneumonia [83]."
7910,Compulsory Licences: Law and Practice in Thailand,"When the WTO/TRIPS Agreement entered into force in 1995, around 100 countries had adopted compulsory licensing under national intellectual property law. The compulsory licensing measure can be effective in dealing with situations inhibiting access to medicines, for example when a patent holder fails to use the patent in the granting country or when he or she maintains artificially high prices for patented articles. Despite the significant international development, it remains to be seen how the flexibility margins provided by the TRIPS provisions can be used as safeguards to protect public health interests of the poor countries. Effective mechanisms are also required to support countries that are unable to make effective use of compulsory licensing due to the inefficiency of manufacturing capacity. This chapter examines the problem of using the legal mechanism of compulsory licensing by developing countries. It looks at Thailand’s experiences with the use of compulsory licensing to increase access to medicines. Since the majority of compulsory licences issued around the world are related to pharmaceutical patents, the chapter highlights the use of compulsory licensing in the context of a range of public health responses. It first discusses the use by Thailand of the compulsory government use licensing to increase access to medicines. It also examines international rules on compulsory licensing, including the provisions of the Paris Convention, the TRIPS Agreement, and the Doha Declaration on the TRIPS Agreement and Public Health. Finally, the chapter discusses various legal issues under the Thai Patent Act regarding the compulsory licensing provisions. It also highlights the possible impact, in a broad sense, of the use of legal mechanisms such as compulsory licensing, which aims to effectively maintain fair market competition and dilute the monopoly power of the patent holder."
7911,Social Resilience and Critical Infrastructure Systems,"Resilience analysis and thinking serve as emerging conceptual frameworks relevant for applications assessing risk. Connections between the domains of resilience and risk assessment include vulnerability. Infrastructure, social, economic, and ecological systems (and combined social-ecological systems) are vulnerable to exogenous global change, and other disturbances, both natural and anthropologically derived. Resilience analysis fundamentally seeks to provide the groundwork for a ‘soft landing’, or an efficient and robust restoration following disturbance as well as the ability to reduce harms while helping the targeted system rebound to full functionality as quickly and efficiently where possible. Such applications are consistent with The National Academy of Sciences (NAS) definition of resilience, which more broadly denotes the field as “the ability to plan and prepare for, absorb, recover from, and adapt to adverse events” (Larkin S, Fox-Lent C, Eisenberg DA, Trump BD, Wallace S, Chadderton C, Linkov I (2015) Benchmarking agency and organizational practices in resilience decision making. Environ Sys Decisions 35(2):185–195). Given this definition, we seek to describe how resilience analysis and resilience thinking might be applied to social considerations for critical infrastructure systems. Specifically, we indicate how resilience might better coordinate societal elements of such infrastructure to identify, mitigate, and efficiently recover from systemic shocks and stresses that threaten system performance and service capacity."
7912,Acute Hepatic Failure,"Acute liver failure (ALF) is an unpredictable and rapidly progressive, life-threatening multisystem condition that ensues when an insult causes diffuse necrosis of liver parenchyma disrupting hepatocyte function in patients who have no preexisting liver injury. The subsequent development of encephalopathy and coagulopathy within days or weeks represents the key features of ALF, but critically often culminates with multi-organ failure (MOF), which impacts significantly on mortality. Timely referral to specialist centres with expertise in the management of ALF and liver transplantation is crucial."
7913,Equine Coronavirus Infection,"Equine coronavirus (ECoV) is an emerging virus associated clinically and epidemiologically with fever, depression, anorexia, and less frequently colic or diarrhea in adult horses. Sporadic cases and outbreaks have been reported with increased frequency since 2010 from Japan, the USA, and more recently from Europe. A feco-oral transmission route is suspected, and clinical or asymptomatic infected horses appear to be responsible for direct and indirect transmission of ECoV. A presumptive clinical diagnosis of ECoV infection may be suggested by clinical presentation and hematological abnormalities such as leukopenia due to lymphopenia and/or neutropenia. Confirmation of ECoV infection is provided by specific ECoV nucleic acid detection in feces by quantitative PCR or demonstration of coronavirus antigen by immunohistochemistry or electron microscopy in intestinal biopsy material obtained ante- or postmortem. The disease is generally self-limiting and horses typically recover with symptomatic supportive care. Complications associated with disruption of the gastrointestinal barrier have been reported in some infected horses and include endotoxemia, septicemia, and hyperammonemia-associated encephalopathy. This chapter reviews current knowledge concerning the etiology, epidemiology, clinical signs, diagnosis, pathology, treatment, and prevention of ECoV infection in adult horses."
7914,Conservation Medicine: A Solution-Based Approach for Saving Nonhuman Primates,"Challenges that threaten the long-term survival of nonhuman primates (NHP) include habitat fragmentation, hunting, and increasingly, infectious diseases. In addition to direct mortality from noninfectious diseases (e.g., hunting) and infectious diseases (e.g., Ebola), human-driven alterations of environments that support NHP often contribute to a decline in population viability. This decline is frequently the result of physiological stress, poor reproduction, decreased immunity, and exposure to novel pathogens. To better understand the diseases that threaten NHP populations, a conservation medicine approach—the application of medicine to augment the conservation of wildlife and ecosystems—is imperative so that we may provide management solutions to help ensure the long-term survival of NHP. Additionally, it is crucial that we gain a better understanding of pathogens at the interface of nonhuman and human primates since the zoonotic potential may create conservation challenges, or alternatively may provide the impetus for conservation actions to be practiced (e.g., minimize bushmeat trade)."
7915,Miscellaneous Pulmonary Disease,"In this chapter, a series of cases is presented that have provoked significant thought on the part of the consulting and consulted pathologists. Most of these cases don’t fall neatly into the context of other chapters in this volume. A number of these cases illustrate patterns of pulmonary disease that are not diagnostic and challenge the pathologist to offer an intelligent differential diagnosis. A brief discussion of some of these relevant diagnoses follows."
7916,Incorporating Geographical Contacts into Social Network Analysis for Contact Tracing in Epidemiology: A Study on Taiwan SARS Data,"In epidemiology, contact tracing is a process to control the spread of an infectious disease and identify individuals who were previously exposed to patients with the disease. After the emergence of AIDS, Social Network Analysis (SNA) was demonstrated to be a good supplementary tool for contact tracing. Traditionally, social networks for disease investigations are constructed only with personal contacts. However, for diseases which transmit not only through personal contacts, incorporating geographical contacts into SNA has been demonstrated to reveal potential contacts among patients. In this research, we use Taiwan SARS data to investigate the differences in connectivity between personal and geographical contacts in the construction of social networks for these diseases. According to our results, geographical contacts, which increase the average degree of nodes from 0 to 108.62 and decrease the number of components from 961 to 82, provide much higher connectivity than personal contacts. Therefore, including geographical contacts is important to understand the underlying context of the transmission of these diseases. We further explore the differences in network topology between one-mode networks with only patients and multi-mode networks with patients and geographical locations for disease investigation. We find that including geographical locations as nodes in a social network provides a good way to see the role that those locations play in the disease transmission and reveal potential bridges among those geographical locations and households."
7917,Emerging and Re-emerging Infectious Diseases,Emerging diseases include outbreaks of previously unknown diseases or known diseases whose incidence in humans has significantly increased in the past two decades. Re-emerging diseases are known diseases that have reappeared after a significant decline in incidence (http://www3.niaid.nih.gov/research/topics/emerging).
7918,Overview of Retrovirology,"In the 100 years since their discovery, retroviruses have played a special role in virology and in molecular biology. These agents have been at the center of cancer research and shaped our understanding of cell growth, differentiation and survival in ways that stretch far beyond investigations using these viruses. The discovery of retroviral oncogenes established the central paradigm that altered cellular genes can provide a dominant signal initiating cancer development. Their unique replication mechanism and their integration into cellular DNA allow these viruses to alter the properties of their hosts beyond the life span of the infected individual and contribute to the evolution of species. This same property has made retroviral vectors an important tool for gene therapy. Indeed, the impact of retrovirus research has been far-reaching and despite the amazing progress that has been made, retroviruses continue to reveal new insights into the host – pathogen interaction."
7919,Rechtliche Grundlagen und hygienerelevante untergesetzliche Regelwerke,"Maßnahmen zur Infektionsvermeidung sind immer nur so wirksam, wie sie konsequenterweise angewendet werden. Nicht Gesetze, Verordnungen, Empfehlungen oder Handlungsanweisungen sind dafür das Entscheidende, sondern das ständige Bewusstsein der eigenen Verantwortung als permanenter Begleiter bei jedem Handgriff am Patienten und für den Patienten. Zunehmende Meldungen über Infektionen mit multiresistenten Infektionserregern und über angebliche Hygienemängel in deutschen Kliniken haben die Politik zu Verschärfungen des Infektionsschutzgesetzes bewogen, damit in Medizinischen Einrichtungen eigentlich selbstverständliche (und seit Langem bekannte) Handlungsempfehlungen endlich beachtet und umgesetzt werden. In diesem Kapitel werden die für den Hygienebeauftragten Arzt besonders hygienerelevanten Gesetze und Verordnungen so wie untergesetzliche Regelwerke wie Richt- u. Leitlinien, Empfehlungen zusammengefasst und kommentiert. Hierzu gehören in erster Linie das Infektionsschutzgesetz, die Hygieneverordnungen der Länder, die Empfehlungen von KRINKO und ART sowie die Biostoffverordnung, die TRBA und das Sozialgesetzbuch V."
7920,Adjuncts to Resuscitation,"Damage control resuscitation has been increasingly adopted and practiced over the last decade. The concepts used are not new to this era of medicine but are novel in combination. This chapter will focus on adjuncts to damage control resuscitation (DCR) including massive transfusion protocols, the “other” tenets of damage control resuscitation, hypertonic saline, tranexamic acid, pharmacologic resuscitation, Factor VIIa, and prothrombin complex, and viscoelastic testing."
7921,Kann das Immunsystem unterwandert werden?,"Infektionserreger haben sich in ihrer Evolution darauf spezialisiert, in einem immunkompetenten Wirt zu leben und ein breites Repertoire origineller Tricks entwickelt, das Immunsystem zu unterwandern. Die Tabelle 20.1 zeigt Beispiele."
7922,Molecular Techniques for Blood and Blood Product Screening,"The Food and Drug Administration (FDA) is responsible for ensuring the safety of the more than 15 million units of blood and blood components donated each year in the United States. “Blood banking has become a manufacturing industry, an industry that must conform to high standards and quality control requirements comparable to those of pharmaceutical companies or other regulated industries,” said David A. Kessler, MD, former FDA commissioner [1]. Screening donated blood for infectious diseases that can be transmitted through blood transfusion is a very important step in ensuring safety. The United States has the safest blood supply in the world [1] and the FDA is striving to keep it safe by decreasing the risk of infectious disease transmission. The regulatory agency is continuously updating its requirements and standards for collecting and processing blood. As mentioned earlier, an important step in ensuring safety is the screening of donated blood for infectious diseases. In the United States, tests for infectious diseases are routinely conducted on each unit of donated blood, and these tests are designed to comply with regulatory requirements (Table 28.1). The field of clinical microbiology and virology are now focusing on molecular technology. Currently, nucleic acid testing techniques have been developed to screen blood and plasma products for evidence of very recent viral infections that could be missed by conventional serologic tests. It is time for all blood safety procedures to include molecular detection techniques. This approach can significantly aid in blood safety to reduce the risk of transmission of serious disease by transfusion. This chapter reviews the current antigen/antibody-based technology, molecular biological technology, and published regulatory policy data for blood safety."
7923,Blut und Blutprodukte,"die Blutgruppe richtet sich nach der Antigeneigenschaft der Erythrozyten; die Blutgruppenantigene A und B des AB0-Systems befinden sich an der Ery throzytenoberfläche. Das Antigen 0 gibt es nicht, man spricht allenfalls vom Merkmal H; die Blutgruppe A lässt sich in A(1) und A(2) unterteilen. Der Hauptunterschied zwischen den Untergruppen besteht darin, dass die Agglutination von A(1)-Erythrozyten bei Kontakt mit Anti-A-Serum wesentlich stärker und rascher verläuft. Für die Transfusion ist diese Unterteilung nicht von Bedeutung, da Antigen-Antikörper-Reaktionen zwischen A(1) und A(2) sehr selten auftreten und nur sehr schwach sind (Verteilung: A(1) ≈ 20%, A(2) ≈ 80%);"
7924,Preventieve gezondheidszorg,"Het doel van preventie is enerzijds de gezondheid te bevorderen, anderzijds de gezondheid te beschermen. Dit kan bereikt worden door ziekten en aandoeningen te voorkomen of in een vroeg stadium op te sporen en door complicaties te voorkomen. De Wet publieke gezondheid (Wpg) regelt de taken en de bevoegdheden van de overheid op het terrein van infectieziektenbestrijding en collectieve preventie. In het kader van de publieke gezondheidszorg is ook de Wet op het bevolkingsonderzoek (WBO) van belang."
7925,Microecology of Infections Associated with Surgery and Trauma,"Trauma is one of the leading worldwide causes of death at present and fatal trauma cases are the fourth highest cause of death in youths. As a consequence of improved emergency medical treatment, early death rates (48 h post injury) have been significantly reduced. However, death rates resulting from trauma-related complications have not diminished. The most common and dangerous complication that can develop post surgery/trauma is infection caused by opportunistic pathogens, which pose a significant challenge to the healing process ([1]). In addition to interference with the healing process and direct damage to infected tissues caused by the infecting organism, systemic complications, including acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), systemic inflammatory response syndrome (SIRS) and acute renal failure (ARF) can develop. These complications significantly exacerbate a patient’s already deteriorating health and increase recovery times that correlate directly with increased mortality. Therefore, these infections are a major threat to trauma patients, early detection and control of respective infectious agents is essential in decreasing the rates of post trauma-associated morbidity and mortality."
7926,Crisis Management in the Twenty-First Century: “Unthinkable” Events in “Inconceivable” Contexts,"“Unbelievable,” “unthinkable,” “inconceivable”: the twenty-first century opens a new era in the field of risk and crisis management. Many of the major recent crises, including the unconventional 9/11 terrorist attacks; the swift worldwide contamination by the bovine spongiform encephalopathy (BSE, “mad cow disease”), SARS virus, or avian flu; continental blackouts occurring within a few seconds, continent-wide effects of a tsunami in unstable geopolitical zones; and Hurricane Katrina seem to differ fundamentally from the seminal cases that gave birth to disaster research in the 1950s and the 1960s (specific floods, hurricanes, earthquakes) and the crisis management studies in the 1980s (e.g., the Tylenol tampering). The trend seems to be accelerating, so that crises today are increasingly global, intertwined, and “non-textbook” events."
7927,Fever in Common Infectious Diseases,"Infection of the upper airways is very common and is the most common acute illness evaluated in the outpatient setting. The infection is usually caused by viruses including rhinoviruses, influenza viruses, parainfluenza and respiratory syncytial viruses. Influenza is the only viral infection preventable by vaccination and occurs predominately during annual winter epidemics. Bacterial infection such as acute rhinopharyngitis is uncommon and usually presents with either persistent symptoms of an URTI lasting over a week or worsening course after initial improvement or acute onset with high fever and inflammatory changes confined to the pharynx. Fever is common in both bacterial and viral gastroenteritis. High fever is commonly present in many bacterial causes (e.g. Shigella, Salmonella, Shiga toxin-producing E. coli). Fever is often absent or low-grade in other diseases (e.g. enteropathogenic E. coli, cholera). Other febrile conditions cause diarrhoea and need to be differentiated. Fever in CNS infection is the most common presenting symptom in children beyond the neonatal age owing to the presence of inflammatory mediators, particularly IL-1 and TNF in the blood or within the CNS. In MCD, fever was the first symptom in children younger than 5 years and 94% developed fever at some point. Viral exanthems are common causes of febrile illness in children. More than 50 viral agents are known to cause a rash. Historically, exanthems were numbered in the order in which they were differentiated from other exanthems. Thus the first was measles; second, scarlet fever; third, rubella; forth, so-called Filatov-Dukes disease (no longer recognized as an entity); fifth, erythema infectiosum; and sixth, exanthema subitum. As more exanthems were described, numerical assignment became impractical."
7928,Animal Models for the Study of Neuroimmunological Disease,"The development and use of numerous animal models of human autoimmune diseases have provided important advances in our understanding of pathogenic mechanisms of disease and provided robust and reliable models to test novel therapeutic strategies. However, few preclinical studies of therapeutic treatments have demonstrated efficacy in the clinic, possibly because of the biological differences between humans and other animals. Although animal models of human disease are imperfect, it is important to understand the differences between the human disease and its animal models and to design experimental studies using animal models appropriately for the questions being asked. This review provides an overview of the currently used animal models of three human neuroimmunological diseases, multiple sclerosis, Guillain-Barré syndrome, and myasthenia gravis, as well as the advantages and disadvantages of each model and how they correlate or differ from their human counterpart."
7929,The Ophthalmic Examination as It Pertains to General Ocular Toxicology: Basic and Advanced Techniques and Species-Associated Findings,"Ocular toxicology pertains to toxicologic effects of drugs administered topically, intraocularly, or systemically. It should also include evaluation of adverse effects of ophthalmic devices such as contact lenses, intraocular lenses, and glaucoma implants. The ophthalmic examination is able to provide detailed in-life information and is used in combination with clinical observations, clinical pathology, and histopathology to assess potential toxicologic effects. The ophthalmologist must be familiar with the wide range of species used in the field of toxicology, be familiar with the anatomic variations associated with these species, be able to determine what is an inherited or a breed-related finding from a study-related effect, be competent with the required ophthalmic equipment, and be capable of examining this wide range of animals."
7930,Control of Foodborne Viruses at Retail,"Although the number of viruses associated with foodborne outbreaks is relatively small in comparison to their bacterial counterparts, they represent a significant threat to global public health. Moreover, the emergence of novel viruses in food with a greater potential to cause morbidity and mortality suggests that control at the retail level is important. Due to the ability of viruses to persist in the environment and resist many disinfection methods, only a few options are currently viable, yet recent advancements suggest other options may be available in the future. This chapter will provide an overview of the viruses known and postulated to be potential sources of foodborne infection at the retail level, their routes of spread, current regulatory mechanisms in place to prevent infection, as well as explore both proven and new methods for control."
7931,Life-threatening Respiratory Failure from H1N1 Influenza: Lessons from the Southern Cone Outbreak,"A sharp increase in the hospitalization rate for pneumonia, particularly among adults between 20 and 40 years old, and an unusual series of deaths, coincident with an increase in laboratory-confirmed influenza cases, were reported in the spring of 2009 in Mexico. This outbreak appeared after the end of influenza season, and was associated with mortality in a younger age-group than the pattern observed in temperate areas in the northern hemisphere [1]. The concurrent finding of a novel, swine-origin influenza A virus (so called pandemic influenza [H1Nl] 2009) from infected children in the United States [2] completed the picture."
7932,Apoptotic Cell Death in Experimental Autoimmune Encephalomyelitis: Apoptosis of effector cells as a safe mechanism in the termination of an autoimmune inflammatory attack,"Particularly in the vulnerable CNS with a low capacity for regeneration specialized mechanisms must be active for the fast and gentle elimination of dysregulated autoaggressive immune cells. In EAE, local apoptosis of autoimmune T-cells has been identified as a safe means for the removal of these unwanted cells. T-cell apoptosis in situ followed by phagocytic clearance of apoptotic remnants by glia assures a minimum of detrimental bystander damage to the local parenchyma and down-regulates the local inflammatory reaction. The pharmacological augmentation of local apoptosis of inflammatory effector cells might gain therapeutic importance also in human neuroimmunological diseases such as multiple sclerosis."
7933,"Diagnosis, Discovery and Dissection of Viral Diseases","Only a few years ago, viral diagnosis was largely an exercise for academic researchers and public health practitioners with focus on epidemiologic analyses and outbreak prevention, detection, and control. Opportunities for therapeutic intervention were limited to only a few applications such as herpesvirus infections, influenza, and HIV/AIDS; hence, once a bacterial or fungal infection was excluded, clinicians were limited to providing supportive care for what was presumed to be a viral syndrome. Public health organizations tracked the incidence of viral infections and the development of resistance to the few antiviral drugs in use and provided input to governments and the pharmaceutical industry regarding selection of vaccine targets. More recently, interest in viral diagnostics has burgeoned with the advent of new tools for detection and discovery, global recognition of pandemic risk, high-throughput drug screening, rational drug design, and immunotherapeutics. An additional impetus has been the implication of viruses in chronic illnesses not previously attributed to infection. The objective of this chapter is to review the factors responsible for the rise in awareness of viral infections, methods for diagnosis and monitoring viral infections, and future prospects for improvements in discovery, detection, and response to the challenges of clinical virology."
7934,Tracing and Preventing Infections,"A total of 10–20% of somatic patients experience hospital infections during/after hospitalization. Pneumonia, sepsis, surgical site infections and urinary tract infections are most often associated with patient-related use of medical devices for approximately 65% of cases, while nontechnical equipment may be linked to 35% of cases. It is resource-intensive to detect the cause of infection outbreaks and even more expensive not to take action. Unexplained causes of outbreaks may lead to uncertainty and reduced activity at the hospital. To trace and prevent hospital outbreaks, joint efforts from hospital management, microbiology and infection control are needed. This chapter is focused on practical measures to trace and prevent hospital outbreaks."
7935,Epidemiology of SFTS in China,"Severe fever with thrombocytopenia syndrome (SFTS) is a novel emerging virus infection that was first found and reported in Peoples’ Republic of China in 2009 and 2011, respectively. SFTS was later reported in Japan and South Korea, suggesting that SFTS is endemic to East Asian countries. Among these countries, the most SFTS cases have been reported in China. Geographically, SFTS cases have been mainly reported in rural and mountainous areas of the Eastern, Central, and North-Eastern China. So far, the number of SFTS cases has increased and the geographical distribution has expanded in China. From epidemiological studies, it was suggested that various factors including occupation, habit, tick bites, animal contact, environment, meteorological factor, demographic data, clinical symptoms, or laboratory data were associated with SFTS infection or fatal outcome. In this article, epidemiology of SFTS in China is described in detail to assess distributions over time, place, and person."
7936,Immunology,"The concept of forbidden foods that should not be eaten goes back to the Garden of Eden and apart from its religious meanings it may also have foreshadowed the concept of foods that can provoke adverse reactions. Thus we could say that allergic diseases have plagued mankind since the beginning of life on earth. The prophet Job was affected by a condition that following the rare symptoms described by the Holy Bible might be identified as a severe form of atopic dermatitis (AD). The earliest record of an apparently allergic reaction is 2621 B.C., when death from stinging insects was first described by hieroglyphics carved into the walls of the tomb of Pharaoh Menes depicting his death following the sting of a wasp. In 79 A.D., the death of the Roman admiral Pliny the Elder was ascribed to the SO(2)-rich gases emanating from the eruption of Mount Vesuvius. Hippocrates (460–377 B.C.) was probably the first to describe how cow’s milk (CM) could cause gastric upset and hives, proposing dietetic measures including both treatment and prevention for CM allergy."
7937,Evaluating Research: Research Designs in Evidence-Based Medicine/Evidence-Based Practice,"Once you have located some research reports that can help answer your practice question, Step 3 in the evidence-based medicine (EBM) and evidence-based practice (EBP) decision-making model is to appraise the quality and relevance of this research. An initial inspection of materials should help differentiate those that are relevant for your purposes from those that are not. Relevance may often be determined by examining the research question that each study addresses. Studies should have clear and relevant research questions, fitting your practice needs. That is, the topics should fit your clinical question, and the sample should be similar in age and other background criteria. Once these ‘apparently relevant’ studies are identified, the appraisal shifts to issues of research methodology. Even studies that appear be quite relevant initially may later on prove to have important limitations as the details of their methods are explored."
7938,Fattori maschili dei disturbi della fertilità,"In passato sono state tenute conferenze e workshop per stilare delle linee guida sui diversi aspetti dell’andrologia. Questi hanno affrontato, tra l’altro, le seguenti tematiche: l’utilità delle tecniche diagnostiche avanzate di analisi del liquido seminale (ESHRE 1996; Comhaire 1997; Fraser et al. 1997), la gestione dei tumori a cellule germinali testicolari (Krege et al. 2001), la contraccezione delle coppie (Neal e Groat 1976), il ruolo di consulto attento alle coppie infertili (Monach 2003), l’inversione della vasectomia (Chawla et al. 2004) e un’assistenza adeguata (Hull 1996). Allo scopo di limitare la confusione sulla terminologia utilizzata nel campo dell’infertilità (Easton 1998), la WHO ha introdotto alcune definizioni (Rowe et al. 1993)."
7939,TADs in the Dromedary,"The transboundary diseases in camel are mainly linked to the regional camel meat market from Sahelian countries (from Mauritania to Somalia) to the Arabian peninsula and North Africa. Indeed, the camel flow in relationship with this market is based on live animals’ export. Because the camel trade can be formal and informal with interconnections between both sectors and despite veterinary controls in the main exporting ports, some diseases such as Rift Valley fever (RVF), PPR-like disease, and MERS-coronavirus can spread from exporting countries to importing ones. However, the epidemiological status of these different diseases is quite variable and the transmission to humans in case of zoonosis (RVF and MERS-Cov) is not necessarily due to transboundary camel trade despite the impact of outbreak on the regional camel market. Globally, dromedary camel is less affected than other ruminants by infectious diseases under transboundary surveillance. But, because camel breeding is concentrated in countries where the disease surveillance systems often lack means, where the frontiers in desert areas are often “porous,” and where the herd mobility is difficult to assess, the risk of transboundary diseases’ transmission through borders is not negligible. Nowadays, the challenge of TADs control is limited to Rift Valley fever, but special attention must be paid to emerging diseases, including the recent discovery of prion disease in Algeria."
7940,Innovative Technologies for Advancement of WHO Risk Group 4 Pathogens Research,"Risk Group 4 pathogens are a group of often lethal human viruses for which there are no widely available vaccines or therapeutics. These viruses are endemic to specific geographic locations and typically cause relatively infrequent, self-limiting, but often devastating human disease outbreaks (e.g. Ebola virus, Kyasanur Forest disease virus, Lassa virus). The overall rarity of disease outbreaks with the associated lack of clinical data and the requirement for research on Risk Group 4 pathogens to be performed in maximum (biosafety level 4) containment necessarily impede progress in medical countermeasure development. Next-generation technologies may aid to bridge the current gaps of knowledge by increasing the amount of useful data that can be gleaned from individual diagnostic samples, possibly even at point-of-care; enable personalized medicine approaches through genomic virus characterization in the clinic; refine our comprehension of pathogenesis by using ex vivo technologies such as organs-on-chips or organoids; identify novel correlates of protection or disease survival that could inform novel medical countermeasure development; or support patient and treatment response monitoring through non-invasive techniques such as medical imaging. This chapter provides an overview of a subset of such technologies and how they may positively impact the field of Risk Group 4 pathogen research in the near future."
7941,Sindrome acuta da stress respiratorio (ARDS),"L’esatta incidenza dell’ARDS non è nota, poiché nella maggior parte delle diagnosi non viene impiegata una definizione univoca. Si può, comunque, affermare che sussiste una frequenza di circa 2–8 casi di malattia per 100.000 abitanti."
7942,Systems Approaches to Map In Vivo RNA–Protein Interactions in Arabidopsis thaliana,"Proteins that specifically interact with mRNAs orchestrate mRNA processing steps all the way from transcription to decay. Thus, these RNA-binding proteins represent an important control mechanism to double check which proportion of nascent pre-mRNAs is ultimately available for translation into distinct proteins. Here, we discuss recent progress to obtain a systems-level understanding of in vivo RNA–protein interactions in the reference plant Arabidopsis thaliana using protein-centric and RNA-centric methods as well as combined protein binding site and structure probing."
7943,Human monoclonal antibodies for prophylaxis and therapy of viral infections,
7944,Spatial Structure: Patch Models,"Discrete spatial heterogenity is introduced into disease transmission models, resulting in large systems of ordinary differential equations. Such metapopulation models describe disease spread on a number of spatial patches. In the first model considered, there is no explicit movement of individuals; rather infectives can pass the disease to susceptibles in other patches. The second type of model explicitly includes rates of travel between patches and also takes account of the resident patch as well as the current patch of individuals. A formula for and useful bounds on the basic reproduction number of the system are determined. Brief descriptions of application of this type of metapopulation model are given to investigate the spread of bovine tuberculosis and the effect of quarantine on the spread of influenza."
7945,Shellfish-Associated Viral Disease Outbreaks,"Numerous outbreaks of shellfish-borne enteric virus illness have been reported worldwide. Most notable among the outbreaks are those involving norovirus illness and hepatitis A. Lessons learned from outbreak investigations indicate that most outbreaks are preventable. Anthropogenic sources of contamination will continue to invade shellfish growing waters, and shellfish, by their very nature, will continue to bioconcentrate these contaminants, including enteric viruses. There is no quick fix for enteric virus contamination of shellfish; however, vigilance on behalf of the industry, regulatory agencies, and the consumer could substantially reduce the incidence of illness. Enhanced monitoring in all areas of shellfish production, harvesting, distribution, and processing would help to reduce viral illnesses. Pollution abatement and improved hygienic practices on behalf of the industry and consumers are needed. New processing and analytical technologies, such as high hydrostatic pressure processing and molecular biological assays, will enhance shellfish safety and continue to provide new avenues to protect the consumer and the industry. Better reporting and epidemiological follow-up of outbreaks are keys to the development of interventions against the foodborne transmission of viral infections."
7946,Necrotizing Enterocolitis,"Necrotizing enterocolitis (NEC) is the most common life threatening surgical and medical emergency affecting the gastrointestinal tract encountered in the neonatal intensive care unit. NEC occurs in 2–5% of all preterm infants although the majority of cases develop in infants less than 36 weeks of gestational age. It has been noted that infants born at earlier gestational age, develop NEC at a later chronological age. The average age of onset of disease is 20.2 days for infants born less than 30 weeks of gestation whereas disease onset is reduced to 13.8 days for infants born at 31–33 weeks and 5.4 days for infants born after 34 weeks of gestation. Epidemiological studies have identifi ed multiple risk factors for NEC, although a history of hypoxia, asphyxia and the introduction of enteral feeding are characteristically associated with premature infants that develop NEC. Despite its predilection for premature infants, NEC has also been described in term infants particularly those with cyanotic heart disease. There is no clear evidence to suggest that geographical origin, ethnicity or gender alter the incidence of NEC."
7947,Interstitial Pneumonias,"The idiopathic interstitial pneumonias are part of the wide spectrum of diffuse parenchymal lung diseases (Fig. 19.1).1 While recognition of diffuse interstitial pulmonary fibrosis can be traced back to studies by Hamman and Rich2 in the 1930s and 1940s, they were first classified as a set of histopathologic patterns in the 1960s by Liebow and Carrington3 into usual interstitial pneumonia (UIP), desquamative interstitial pneumonia (DIP), bronchiolitis obliterans with interstitial pneumonia (BIP), giant cell interstitial pneumonia (GIP) and lymphoid interstitial pneumonia (LIP). At about the same time, Scadding4 in the United Kingdom proposed the term fibrosing alveolitis, suggesting (incorrectly) that DIP and UIP were early and late phases of a single disorder.5 There has subsequently been much discussion and controversy over what patterns should be included in such a classification system, in terms of both histology and what these patterns represent regarding clinical disease. As a result, some patterns have now been categorized according to their recognized causes; for example, GIP has been reclassified as a pneumoconiosis, the cause being exposure to cobalt during the production of hard metals or during diamond polishing (see Chapter 26).6,7"
7948,Halamine Chemistry and its Applications in Biocidal Textiles and Polymers,
7949,Healthcare-Associated Infections in Pediatric Hematology-Oncology,"Pediatric hematology-oncology and hematopoietic stem cell transplant (HSCT) patients are at high risk of infections, including healthcare-associated infections (HAIs), resulting in a need to prevent these occurrences when possible. Central line-associated bloodstream infections (CLABSI), Clostridium difficile infection (CDI), ventilator-associated pneumonia (VAP), catheter-associated urinary tract infections (CAUTI), and respiratory viral infections are of particular concern, and the incidence, definition, and other features are reviewed. Currently, standard prevention guidelines exist for selected HAIs, and so the prevention approach for each infection must be considered separately. Prevention strategies have emerged through collaborative efforts, as well as measurement of both process and outcome data. Measurement includes surveillance of infection occurrence; identification and reporting of prevention methods, such as bundles; and the outcomes associated with these approaches. These prevention and measurement approaches are only successful when approached collaboratively with engagement across the entire healthcare team. Through continued measurement and process improvement based on the data collected, more sustainable approaches to infection prevention can be developed. With systematic effort, the occurrence of HAI should be reduced, and patient harm will be prevented."
7950,Pandemic Influenza Management and Control Policies: Hospital Coordination During an Influenza Pandemic,"Since its initial outbreak in April 2009, the pandemic H1N1 virus has posed a challenge to health systems around the world, compelling them to make available the benefits of scientific and medical progress to the entire population. Some of the most significant demands were access to early diagnostics, vaccines, and antiviral treatments as well as the responsiveness of hospital care, particularly in seriously ill patients who required attention in intensive care units (ICUs). The increased demand of medical care during an influenza pandemic is a heavy burden for any health system as it is added to the regular demand for heath care, which should not become paralyzed [1]."
7951,Longziekten,"Deze aandoeningen, die soms met ‘verkoudheid’ of ‘griep’ betiteld worden, doen zich regelmatig – en vaak epidemisch – voor; bij kinderen (drie- tot viermaal per jaar) vaker dan bij volwassenen (een- tot tweemaal per jaar). Bij verkoudheid of griep is er vrijwel uitsluitend sprake van een virusinfectie. Slechts een deel van de verwekkers is bekend: influenzavirussen, para-influenzavirussen, adenovirussen en rinovirussen. Zo veroorzaken rinovirusinfecties vooral ontstekingsverschijnselen van het neusslijmvlies. Zij geven meestal weinig algemene ziekteverschijnselen. Adenovirusinfecties beginnen met keelpijn en neusirritatie en worden vaak vergezeld van bronchitis, terwijl koorts en algemene malaise als regel vanaf het begin aanwezig zijn. Infecties door influenzavirus uiten zich meestal door ernstige algemene symptomen (koorts, spierpijn, ‘doodziek’), terwijl lokale ziekteverschijnselen (keelpijn, hoest) op de achtergrond staan of zelfs achterwege kunnen blijven. Virale luchtweginfecties doen zich vooral voor in het najaar (vanaf september) en in het voorjaar (tot april). Zowel meteorologische (temperatuurwisselingen) als sociale (schoolgaan) omstandigheden lijken een rol te spelen."
7952,Social Network Representation and Dissemination of Pre-Exposure Prophylaxis (PrEP): A Semantic Network Analysis of HIV Prevention Drug on Twitter,"Daily oral pre-exposure prophylaxis (PrEP) is a new approach to HIV prevention. The study aims to examine how PrEP has been represented and disseminated on one of the most popular social networking sites - Twitter. We collected 1435 public tweets containing the word “Truvada.” After computer-mediated and manual de-duplication, we analyzed 447 unique tweets and calculated weights between two words to measure their co-occurrence in 7-word windows. Semantic networks of PrEP-related tweets were constructed. We found that Twitter was used to generate public discussions and collectively interpret new medical information, especially in frequently propagated tweets and from users with more followers. In the meantime, the results revealed the presence of illicit online pharmacies that marketed and sold PrEP without the need for a prescription. We discussed implications for public health and made urgent call for better regulation of online pharmacies."
7953,The Molecular Virology of Enteric Viruses,"Foodborne and waterborne viruses cause a range of illnesses, from acute gastroenteritis (caliciviruses –noroviruses and sapoviruses-, rotaviruses, astroviruses, and enteric adenoviruses), to hepatitis (hepatitis A virus and hepatitis E virus), and other diseases. Recently, next-generation sequencing technologies have allowed the discovery of new enteric viruses (novel astroviruses, kobuviruses, saliviruses, etc.). Noroviruses are the leading cause of acute gastroenteritis outbreaks and sporadic cases in children and adults worldwide and they still remain refractory to routine cell culture propagation. Recent studies have shown that histo-blood group antigens (HBGAs) are cellular carbohydrates that serve as receptors and host susceptibility factors for human noroviruses. They evolve based on antigenic changes and differential glycan binding specificities. In the last years there have been significant advances in the knowledge of their replication mechanisms, pathogenicity and genetic evolution. The strain diversity and the evolution of rotaviruses are also a matter of concern, despite the introduction of rotavirus vaccines. Similarly, molecular analyses of orally transmitted viruses causing hepatitis are clarifying the phylogenetic relationships between these viruses and other viral genera, as well as their pathophysiological mechanisms."
7954,Anthrax-Euronet and Beyond – Challenges of Scientific Research on High Risk Agents,
7955,Goal-directed Coagulation Management in Major Trauma,"Severe tissue trauma is frequently associated with hemorrhagic shock and subsequent pronounced coagulopathy [1]. Uncontrolled bleeding is the second most common cause of death, and hemorrhage is directly responsible for 40 % of all trauma-related deaths [2]. Coagulopathy can be detected with standard coagulation tests immediately after arrival in the emergency room (ER) in approximately 25–35 % of all trauma patients [1], [2]. Moreover, early trauma-induced coagulopathy is associated with a 4-fold increase in mortality [1]. Blood coagulation monitoring is essential in order to assess the underlying coagulation disorder and to tailor hemostatic treatment. Thromboelastometry (TEM) and thrombelastography (TEG) are promising point-of-care technologies providing rapid information on the initiation process of clot formation, clot quality, and stability of the clot [3]."
7956,Depressive Störungen,"Das Spektrum depressiver Erkrankungen macht den Hauptteil affektiver Störungen aus und gehört mit einer Inzidenz von ca. 8–20% zu den häufigsten psychischen Erkrankungen. Depressionen werden nach wie vor zu selten einer adäquaten Therapie (Antidepressiva, störungsspezifische Psychotherapie wie z. B. kognitive Verhaltenstherapie) zugeführt."
7957,Acute Exacerbation of Idiopathic Pulmonary Fibrosis,"Acute exacerbation of idiopathic pulmonary fibrosis (IPF) is a clinically important complication of IPF that carries a high morbidity and mortality. In the last decade, we have learned much about this event, but there are many remaining questions: What is it? Why does it happen? How can we prevent it? How can we treat it? This chapter attempts to summarize our current understanding of the epidemiology, etiology, and management of acute exacerbation of IPF and point out areas where additional data are sorely needed."
7958,PCR Amplification and Sequencing Analysis of Full-Length Turkey Coronavirus Spike Gene,"Turkey coronaviral enteritis caused by turkey coronavirus (TCoV) continues to infect turkey flocks, resulting in significant economic loss. Determining and understanding genetic relationships among different TCoV isolates or strains is important for controlling the disease. Using two-step RT-PCR assays that amplify the full length of TCoV spike (S) gene, TCoV isolates can be sequenced, analyzed, and genotyped. Described in this chapter is the protocol on PCR amplification and sequencing analysis of full-length TCoV S gene. Such protocol is useful in molecular epidemiology for establishing an effective strategy to control the transmission of TCoV among turkey flocks."
7959,Health and Diseases in Africa,"Compared with other regions of the world; Africa faces more serious health concerns, a heavy burden of diseases and more severely constrained resources for tackling these problems. This state of affairs has been exacerbated by recurring natural disasters, poor economic performance and military conflicts. Under these circumstances, it is not surprising that Africa’s health indicators are worse than those of other parts of the world with serious implications for African development. The chapter argues that despite the recognition of these important health challenges, an understanding of what must be done to improve the health and wellbeing of Africans remains a largely unfinished agenda in today’s development process. This chapter therefore examines the health and disease trajectories with a view to demonstrating and documenting their development implications. It also analyses the various initiatives (regional and global) adopted over time for improved health in Africa, as well as investigating the constraints for achieving health and development in Africa. Actions needed for improved performance are also highlighted."
7960,Kawasaki Disease,"Kawasaki disease, or mucocutaneous lymph node syndrome, was first described in Japan in the late 1960s as an illness characterized by persistent fever, conjunctivitis, mucous membrane changes, acral erythema with desquamation, and cervical adenopathy, associated with coronary arteritis (1,2). While earlier descriptions of the disease were limited to Asia and Hawaii, the disease is now known to occur worldwide. The disease is primarily one of young children, with 85% of cases occurring in children under five years. It is uncommon in children less than 6 months. There have been some epidemiologic investigations linking Kawasaki disease to freshly cleaned carpets, humidifier use, and living near a body of water, but these associations have not been observed consistently (3)."
7961,Structural Genomics: A Special Emphasis on Membrane Proteins,"Drug discovery based on structural knowledge has proven useful as several structure-based medicines are already on the market. Structural genomics aims at studying a large number of gene products including whole genomes, topologically similar proteins, protein families and protein subtypes in parallel. Particularly, therapeutically relevant targets have been selected for structural genomics initiatives. In this context, integral membrane proteins, which represent 60–70% of the current drug targets, have been of major interest. Paradoxically, membrane proteins present the last frontier to conquer in structural biology as some 100 high resolution structures among the 30,000 entries in public structural databases are available. The modest success rate on membrane proteins relates to the difficulties in their expression, purification and crystallography. To facilitate technology development large networks providing expertise in molecular biology, protein biochemistry and structural biology have been established. The privately funded MePNet program has studied 100 G protein-coupled receptors, which resulted in high level expression of a large number of receptors at structural biology compatible levels. Currently, selected GPCRs have been purified and subjected to crystallization attempts"
7962,"Inflammation and Inflammatory Diseases, Markers, and Mediators: Role of CRP in Some Inflammatory Diseases","The knowledge of inflammation records dates back in first century AD. Initially discovered with features of rubor, tumor, calor, and dolor, scientific investigations have revealed chemical components, cells, and pathways involved in the process of inflammation. The body’s initial defense in response to infection, trauma, or inflammation is through the acute-phase response (APR). APR is a multifaceted set of systemic reactions seen shortly after the experience of a triggering event. One of the many aspects of an APR is the increased hepatic synthesis of positive acute-phase proteins (APPs) leading to increased serum concentration of these proteins. The serum level of these APPs returns to base concentration when the stimulating factor is not anymore present. Today a plethora of inflammatory diseases are causing concern to global health. All the key players and mediators of inflammation change its role with the change in setup of disease and patients. The biomarkers of inflammation and inflammatory mediators are also used as therapeutic targets in under-trial animal models. Even in clinical diagnosis of an inflammatory patient, some broad-spectrum markers were analyzed without individual dissection of each mediator or biomarker. This chapter also provides a review of the acute-phase protein C-reactive protein and its possible use as inflammatory biomarker in diseases. We have highlighted case studies of some patients from Kolkata, India, revealing inflammation from disease together with their clinical history. The question which we probe in here is that whether there is a correlation with the clinical history, C-reactive protein, and inflammation and whether CRP can act as a unique diagnostic and prognostic biomarker in some diseases. The future course of this chapter lies in identifying clinical markers for inflammation, the sequential flow of inflammatory responses for a wide spectrum of diseases and its diagnostic, and therapeutic application to screen out pro-inflammatory diseases vs. anti-inflammatory conditions."
7963,Profiling and Searching for RNA Pseudoknot Structures in Genomes,A new method is developed that can profile and efficiently search for pseudoknot structures in noncoding RNA genes. It profiles interleaving stems in pseudoknot structures with independent Covariance Model (CM) components. The statistical alignment score for searching is obtained by combining the alignment scores from all CM components. Our experiments show that the model can achieve excellent accuracy on both random and biological data. The efficiency achieved by the method makes it possible to search for the pseudoknot structures in genomes of a variety of organisms.
7964,Pulmonary Infection in a Patient After Stem Cell Transplantation,"A 69-year-old man with a history of hypertension, diabetes mellitus, and acute myelogenous leukemia presented with recurrent fever and cough. He had undergone allogeneic hematopoietic stem cell transplantation from a matched unrelated donor 17 months previously. His posttransplant course was complicated by graft versus host disease and multiple central venous catheter infections with coagulase-negative Staphylococcus spp., vancomycin-resistant Enterococcus, Lactobacillus, and alpha-hemolytic Streptococcus. During his initial course, he also developed a nodular pneumonia, and the subsequent workup included a bronchoscopy that was nondiagnostic."
7965,Severe Community-Acquired Pneumonia,"A 58-years-old male, smoker (8 pack-years) and having Diabetes mellitus and Hypertension for 8 years, presented to the ED with fever and acute dyspnoea for the last 48 h. On examination, respiratory rate was 34 breaths/min, blood pressure-150/96 mm Hg, heart rate-112/min, regular, and Oxygen saturation of 86% on 4L of oxygen by mask. He was conscious and oriented. His chest X-ray showed left lower zone consolidation."
7966,Mikrobiologie: Erreger der nosokomialen Pneumonie,"Das Erregerspektrum der nosokomialen Pneumonie ist breit und unterscheidet sich deutlich von dem der ambulant erworbenen Pneumonie. Im Rahmen der „early onset“ Pneumonie sind S. aureus (MSSA), Haemophilus influenzae und S. pneumoniae führend, während bei der „late onset“ Pneumonie außer den beiden erstgenannten Erregern zusätzlich vor allem eine Reihe von Enterobakterien (am häufigsten E.coli und Klebsiella spp.) sowie Nonfermenter (P. aeruginosa, A. baumannii) gefunden werden. Ein seltener, aber relevanter Erreger ist Aspergillus spp., während Candida spp. keine Erreger sind. Anaerobier spielen eine sehr untergeordnete Rolle; die Bedeutung der Viren ist noch nicht hinreichend geklärt. Legionella spp. können im Rahmen von nosokomialen Ausbrüchen vorkommen. Mikrobiologie, Übertragung, Risikofaktoren, Pathogenese und klinisches Bild werden für die wichtigsten Erreger beschrieben."
7967,Microbiology,
7968,Lexikalischer Hauptteil,"a-, an-, gr. Präfixe in Wortzusammensetzungen: 1. als privativum ( α priv.) eine Verneinung od. ein Fehlen, Nichtvorhandensein bezeichnend wie lat. in- od. deutsch un.; vor Konsonanten stets a-, vor Vokalen an-, vor r dagegen als ar- angeglichen; wiedergegeben mit un-, -los od. ohne; 2. als α intensivum eine Verstärkung ausdrückend (kommt seltener vor); 3. als α protheticum mit euphonetischer, rein lautlicher od. wohlklingender Funktion ohne Bedeutungseinfluss, z. B. in astér Stern; 4. a: Analader im Insektenflügel (a(1), a(2) usw.)."
7969,Spatial Components in Disease Modelling,"Modelling of infectious diseases could help gain further understanding of their diffusion processes that provide knowledge on the detection of epidemics and decision making for future infection control measures. Conventional disease transmission models are inadequate in considering the diverse nature of a society and its location-specific factors. A new approach incorporating stochastic and spatial factors is necessary to better reflect the situation. However, research on risk factors in disease diffusion is limited in numbers. This paper mapped the different phases of spatial diffusion of SARS in Hong Kong to explore the underlying spatial factors that may have interfered and contributed to the transmission patterns of SARS. Results of the current study provide important bases to inform relevant environmental attributes that could potentially improve the spatial modelling of an infectious disease."
7970,Hygiene und Arbeitsschutz,"Im Rettungsdienst werden unter dem Begriff „Hygiene“ alle vorsorglichen Vorkehrungen und Maßnahmen zusammengefasst, die alle im Krankentransport und Rettungsdienst Tätigen, sowie die zu betreuenden Patienten, vor schädlichen und krankmachenden Einflüssen durch Mikroorganismen schützen sollen."
7971,The Welfare Of Feral Cats,
7972,Acute and Chronic Right Ventricular Failure,"Right ventricular failure is the subject of renewed attention as the importance of RV function in a variety of disease states has been recognized. The RV is highly compliant, and is able to accommodate a wide range of preload conditions. Yet, it is afterload-sensitive, and normal physiology is dependent on its association with the low resistance of the pulmonary vasculature. Changes in the pulmonary vascular resistance, either acutely or over time, provoke a series of adaptations that are designed to maintain a normal cardiac output, but ultimately lead to decompensation and RV failure. Through ventricular interdependence, RV failure may impair left ventricular diastolic and systolic function, further reducing cardiac performance. Both echocardiography and magnetic resonance imaging can provide detailed information about RV structure, with MRI providing better assessment of ventricular volumes and RV function. Right heart catheterization is often necessary for definitive diagnosis of the etiology of RV failure and for determining the best therapeutic options. The treatment of RV failure is highly dependent on the underlying etiology, which should be corrected if possible. Targeted medical therapy is particularly useful in cases of pulmonary arterial hypertension, and is under investigation for broader use in other causes of pulmonary hypertension."
7973,Gene Regulation by HMGA and HMGB Chromosomal Proteins and Related Architectural DNA-Binding Proteins,The eukaryotic abundant high mobility group HMGA and HMGB proteins can act as architectural transcription factors by promoting the assembly of higher-order protein-DNA complexes which can either activate or repress gene expression. The structural organisation of both classes of protein is similar with either a single or repeated DNA binding domain preceding a short negatively charged C-terminal tail. In the HMGB class of proteins the HMG DNA-binding domain binds non-specifically and introduces a sharp bend into DNA whereas the AT-hook in the HMGA protein binds preferentially to A/T rich regions of DNA and stabilises a B-DNA structure. The acidic tails are hypothesised to facilitate the interaction of the proteins with nudeosomes by binding to the positively charged histone tails. Both classes of protein also interact with a large number of transcription factors that bind to specific DNA sequences.
7974,Pediatric Lung Transplantation,"Children undergoing lung transplantation present a unique constellation of issues that require compulsive management based upon their underlying diagnosis, state of debilitation, post-transplant needs, and immunosuppression. The ventilator management is also somewhat different from a typically ill child. This chapter will focus on those unique aspects of this group of children with an emphasis on complications seen and the management recommended."
7975,Medical Course and Complications After Lung Transplantation,"Lung transplant prolongs life and improves quality of life in patients with end-stage lung disease. However, survival of lung transplant recipients is shorter compared to patients with other solid organ transplants, due to many unique features of the lung allograft. Patients can develop a multitude of noninfectious (e.g., primary graft dysfunction, pulmonary embolism, rejection, acute and chronic, renal insufficiency, malignancies) and infectious (i.e., bacterial, fungal, and viral) complications and require complex multidisciplinary care. This chapter discusses medical course and complications that patients might experience after lung transplantation."
7976,Operation Department: Infection Control,"Infection control in the operation department is the result of many single factors and routines, based on experience, documentation and expert panels through more than a hundred years. Many factors and routines in surgery are evidence-based, but most of them are still lacking evidence and can probably never be investigated because of ethical problems. Consequently, consensus and guidance are used to a great extent. Surgery opens into sterile tissues for hours, where there is massive tissue damage by knife, diathermy, clogging of vessels, pressure against and drying of tissues, decreased blood supply, impaired phagocytosis and impaired infection defence. Microbes deposited in this devitalized tissues may find a good basis for growth and proliferation if there is lack of infection control and sterility. For patients with ongoing infections and who need surgery, special routines are made to prevent the spread of infections in the operation department. This chapter is a practical description of many important preventive procedures that may protect the surgical patient against surgical site infection (SSI)."
7977,Global Spread (October 2014),"As the Ebola outbreak continued to rage in West Africa, Western countries began to be directly affected by the disease. On the last day of September 2014, the first active Ebola case was diagnosed in the United States. Officials in Dallas, Texas, scrambled to contain the virus. A few weeks later, tension rose dramatically when two of the nurses who treated the initial US patient developed Ebola. One of the nurses traveled to Ohio and back before becoming sick. She flew by plane and had contact with other travelers. Officials were very worried that Ebola flare-ups would start to occur across the country. On October 6, 2014, a nursing assistant in Spain was diagnosed with Ebola. Like the US nurses, she had helped treat a repatriated Ebola victim. On October 23, 2014, a new US case was identified. A doctor was diagnosed with Ebola in New York City after returning from Guinea. On the same day, an Ebola case was discovered in the West African country of Mali. The Ebola outbreak seemed out of control and poised to start a major international epidemic. In West Africa, however, a corner had been turned. Healthcare efforts had shifted from treating all Ebola patients in medical facilities to providing families with supplies to take care of sick patients at home. Toward the end of October 2014, reports started to surface about there being fewer cases in West Africa, especially in Liberia. These reports were initially treated with caution. As time progressed, however, it became clear that the drop in cases was real."
7978,Hormone Replacement Therapy: A Critical Review,"The aim of this chapter is to review the most recent aspects of hormone replacement therapy (HRT), and to clarify its impact on associated health conditions amidst growing uncertainties. Special emphasis has been placed on its effect on cardiovascular conditions and breast cancer, the two most important outcomes affected by HRT, and on identifying ideal candidates for HRT as well as defining the optimum new HRT regimens."
7979,Lower Respiratory Tract Infections,"Lower respiratory tract infections are common and are important in the critical care setting either because they precipitate admission to the critical care unit, e.g. severe viral pneumonia or because they complicate the course of a patient with significant underlying disease or following major surgery, e.g. after multiple trauma. Furthermore, respiratory failure requiring artifical ventialtion is a well recognised reason for critical care support but it can be difficult to determine if this is due to an underlying non-infectious condition such as chronic obstructive pulmonary disease (COPD), infection or a combination of both. The early diagnosis and management of respiratory infection combined with appropriate ventilatory support aids prognosis and the efficient use of critical care facilities given the number of patients affected."
7980,Block based semi-global alignment scheme for the analysis of Given DNA sequences,"Pair wise sequence alignment scheme has been emerged as an efficient computational tool to find region of similarity among sequences of proteins and nucleic acids. As new disease causing viruses are emerging rapidly, new alignment schemes with the advent of fast computers have gained its importance recently. In this paper, we have proposed a block based semi-global alignment scheme to evaluate the optimal alignment between any given two DNA sequences. DNA sequences are divided into blocks of equal length and alignment between the block is determined using dynamic programming. The performances are evaluated in terms of overall matrix score and percentage of similarity. It is inferred from the results, that higher the percentage of similarity between any two blocks, it may code for the same protein/amino acids. The computational complexity of the proposed algorithm is much less compared to that of the general global alignment scheme with O (M, N)."
7981,Rationale for the Existence of Zoos,"This chapter looks at the stated goals of zoo mission statements and provides examples of how zoos are addressing their missions. Moreover, with the pressure of zoos to become biological conservation mentors, zoos assume five roles as the executor of the relationship between society and nature. First, zoos take on the role of the “model citizen” by conveying a conservation message. They advocate for a sensible, sustainable use of natural resources and promote less wasteful, green-building alternatives. Many zoological institutions are developing organizational plans that include the use of solar, wind, and thermal power in their daily operations. Additionally, they are growing food for the animals, composting, and using recycled materials in their exhibit design. Second, zoos are maintaining a viable and genetically diverse collection. Zoos are managed under the premise that wildlife conservation is of foremost importance. As zoological institutions have become more active in field studies, their research findings are being applied to larger conservation efforts. Moreover, the conservation research that takes place in situ and ex situ is important in saving small fragmented wild populations. Third, zoos directly influence the attitudes and behaviors of the community in relation to the conservation of plants, animals, and habitats. Due to their urban locations within heavily populated cities, zoos have a unique geographic placement within the community. The urban location of zoos provides them with a unique opportunity to influence government policy. Fourth, the zoo is a conservation mentor. Through mentoring efforts, future generations of scientists and citizens will be more aware of the benefits of long-term conservation. As conservation mentors, zoos must lead the public to become citizen conservationist. Fifth, zoos are a place for people to learn basic facts about organisms and their behavior."
7982,Research and application of physical protection technology and equipment against biological contamination in mainland of China,"Biological contamination is considered to be great hazardous and related to national security, it is very important to strengthen physical protection against biological contamination accordingly. Key technologies of physical protection against biological contamination were described in terms of isolation, positive/negative pressure, air filtration, antibacterial material and disinfection. Present situation of research and development about Chinese physical protection equipment against biological contamination were presented involving individual protection, collective protection, disinfections, quality control and ergonomics. Finally, Chinese and overseas status about physical protection equipment against biological contamination were analyzed and compared in the areas of administration, research and market. It was concluded that Chinese physical protection equipment against biological contamination fell behind in administration, research and industrialization. As a result, some suggestions with Chinese characteristics were presented to promote development of Chinese physical protection equipment against biological contamination."
7983,ACE Inhibition in Heart Failure and Ischaemic Heart Disease,
7984,Antibiotic Resistance of Non-Pneumococcal Streptococci and Its Clinical Impact,"Viridans streptococci (VGS) form a phylogenetically heterogeneous group of species belonging to the genus Streptococcus (1). However, they have some common phenotypic properties. They are alfa- or non-haemolytic. They can be differentiated from S. pneumoniae by resistance to optochin and the lack of bile solubility (2). They can be differentiated from the Enterococcus species by their inability to grow in a medium containing 6.5% sodium chloride (2). Earlier, so-called nutritionally variant streptococci were included in the VGS but based on the molecular data they have now been removed to a new genus Abiotrophia (3) and are not included in the discussion below. VGS belong to the normal microbiota of the oral cavities and upper respiratory tracts of humans and animals. They can also be isolated from the female genital tract and all regions of the gastrointestinal tract (2, 3). Several species are included in VGS and are listed elsewhere (2, 3). Clinically the most important species belonging to the VGS are S. mitis, S. sanguis and S. oralis."
7985,Pathology of Small Airways,The small conducting airways consist of the membranous bronchioles and the respiratory bronchioles. Bronchiolitis is a generic term for inflammatory and fibrotic injuries of these small airways. The histology of normal bronchioles is discussed in detail in Chapter 2. A brief review is warranted here before discussing the histopathologic patterns associated with small airway injury.
7986,Krupp (Pseudokrupp),
7987,Acute Lower Respiratory Infections,
7988,Central Nervous System Infections,"Central nervous system (CNS) infections—i.e., infections involving the brain (cerebrum and cerebellum), spinal cord, optic nerves, and their covering membranes—are medical emergencies that are associated with substantial morbidity, mortality, or long-term sequelae that may have catastrophic implications for the quality of life of affected individuals. Acute CNS infections that warrant neurointensive care (ICU) admission fall broadly into three categories—meningitis, encephalitis, and abscesses—and generally result from blood-borne spread of the respective microorganisms. Other causes of CNS infections include head trauma resulting in fractures at the base of the skull or the cribriform plate that can lead to an opening between the CNS and the sinuses, mastoid, the middle ear, or the nasopharynx. Extrinsic contamination of the CNS can occur intraoperatively during neurosurgical procedures. Also, implanted medical devices or adjunct hardware (e.g., shunts, ventriculostomies, or external drainage tubes) and congenital malformations (e.g., spina bifida or sinus tracts) can become colonized and serve as sources or foci of infection. Viruses, such as rabies, herpes simplex virus, or polioviruses, can spread to the CNS via intraneural pathways resulting in encephalitis. If infection occurs at sites (e.g., middle ear or mastoid) contiguous with the CNS, infection may spread directly into the CNS causing brain abscesses; alternatively, the organism may reach the CNS indirectly via venous drainage or the sheaths of cranial and spinal nerves. Abscesses also may become localized in the subdural or epidural spaces. Meningitis results if bacteria spread directly from an abscess to the subarachnoid space. CNS abscesses may be a result of pyogenic meningitis or from septic emboli associated with endocarditis, lung abscess, or other serious purulent infections. Breaches of the blood–brain barrier (BBB) can result in CNS infections. Causes of such breaches include damage (e.g., microhemorrhage or necrosis of surrounding tissue) to the BBB; mechanical obstruction of microvessels by parasitized red blood cells, leukocytes, or platelets; overproduction of cytokines that degrade tight junction proteins; or microbe-specific interactions with the BBB that facilitate transcellular passage of the microorganism. The microorganisms that cause CNS infections include a wide range of bacteria, mycobacteria, yeasts, fungi, viruses, spirochaetes (e.g., neurosyphilis), and parasites (e.g., cerebral malaria and strongyloidiasis). The clinical picture of the various infections can be nonspecific or characterized by distinct, recognizable clinical syndromes. At some juncture, individuals with severe acute CNS infections require critical care management that warrants neuro-ICU admission. The implications for CNS infections are serious and complex and include the increased human and material resources necessary to manage very sick patients, the difficulties in triaging patients with vague or mild symptoms, and ascertaining the precise cause and degree of CNS involvement at the time of admission to the neuro-ICU. This chapter addresses a wide range of severe CNS infections that are better managed in the neuro-ICU. Topics covered include the medical epidemiology of the respective CNS infection; discussions of the relevant neuroanatomy and blood supply (essential for understanding the pathogenesis of CNS infections) and pathophysiology; symptoms and signs; diagnostic procedures, including essential neuroimaging studies; therapeutic options, including empirical therapy where indicated; and the perennial issue of the utility and effectiveness of steroid therapy for certain CNS infections. Finally, therapeutic options and alternatives are discussed, including the choices of antimicrobial agents best able to cross the BBB, supportive therapy, and prognosis."
7989,Aerodrome Security,"The airport is the frontier between the outside world and the State in which the airline passenger lands. It is also the final point at which a person can be checked before embarking on a flight. Moreover, the aerodrome is where cargo is loaded into an aircraft before takeoff. Therefore, security at the airport carries multiple dimensions, from border control to body scanning; from cargo security to security of the aircraft and its passengers."
7990,Shiny Framework Based Visualization and Analytics Tool for Middle East Respiratory Syndrome,"People in the Middle East have been affected by the Middle East Respiratory Syndrome CoronaVirus (MERS Co-V) since 2012. New cases are continuously reported especially in the Kingdom of Saudi Arabia, and the risk of exposure remains an issue. Data visualization plays a vital role in effective analysis of the data. In this paper, we introduce an interactive visualization application for MERS data collected from the Control and Command Centre, Ministry of Health website of Saudi Arabia. The data corresponding to the period from January 1, 2019 to February 28, 2019 was used in the present work. The attributes considered include gender, age, date of reporting, city, region, camel contact, description and status of the patient. The visualization tool has been developed using Shiny framework of R programming language. The application presents information in the form of interactive plots, maps and tables. The salient feature of the tool is that users can view and download data corresponding to the period of their choice. This tool can help decision makers in the detailed analysis of data and hence devise measures to prevent the spread of the disease."
7991,The Threat from Viruses,"Infectious disease represent the most significant threat to human health. Significant geologic cataclysmic events have caused the extinction of countless species, but these “Wrath of God” events predate the emergence of Homo sapiens. Pandemic infections have accompanied the rise of human civilization frequently re-occurring leaving a lasting imprint on human history punctuated by profound loss of life. Emerging infections become endemic and are here to stay marking their presence with an annual death toll. Each decade brings a new onslaught of emerging infectious agents. We are surprised again and again but are never prepared. The long-term consequences often remain unrecognized and are always inconvenient including cancer, cardiovascular disease and immune associated diseases that threaten our health. Reliance on clusters of clinical symptoms in the face of diverse and non-descriptive viral infection symptoms is a foolhardy form of crisis management. Viral success is based on rapid replication resulting in large numbers. Single-stranded RNA viruses with their high replication error rate represent a paradigm for resilience."
7992,History and Promise of Plant-Made Vaccines for Animals,"Plant-made vaccines are now a well-established and well-tested concept in veterinary medicine—yet the only product so far licenced was never produced commercially. This is puzzling, given the breadth of exploration of plant-made animal vaccines, and their immunogenicity and efficacy, over more than twenty years of research. The range of candidate vaccines that have been tested in laboratory animal models includes vaccines for E. coli, Salmonella, Yersinia pestis, foot and mouth disease virus, rabbit haemorrhagic disease virus, rabbit and canine and bovine papillomaviruses, mink enteritis and porcine circovirus, and lately also bluetongue virus, among many others. There are many proofs of efficacy of such vaccines, and regulatory pathways appear to have been explored for their licencing. This review will briefly explore the history of plant-made vaccines for use in animals, and will discuss the unique advantages of plant-made vaccines for use in a veterinary medicine setting in detail, with a proposal of their relevance within the “One Health” paradigm."
7993,Studying Vulnerable Populations in the Context of Enhanced Vulnerability,"The many needs that arise during and immediately following a disaster normally stretch local and national governments and humanitarian organisations to the limit. Both human and financial resources are often inadequate to meet the requirements of medical care, clean water, sufficient food and shelter for victims of the disaster. How, then, can one justify conducting research during or shortly after disaster strikes? People caught in the wake of a disaster are rendered vulnerable by a variety of factors, including injuries, fear, grief, inadequate food and water, loss of housing, and disease outbreaks that sometimes accompany disasters. In addition, an entire population or segments of the population may have been vulnerable to some extent before the disaster struck: they may have food insecurity, lack of potable water, inadequate health care, or be at risk from endemic diseases. Therefore, many people are rendered doubly or even triply vulnerable in the wake of a disaster. The ethical question that arises is whether the vulnerability of victims of a disaster militates against conducting research during or soon after the event."
7994,Viral Hepatitis B,"Hepatitis B virus (HBV) was first discovered on aboriginal Australians in 1963. Epidemiological studies soon recognized that HBV is a global chronic liver disease, with the highest prevalence rates in Asia and Africa. HBV is highly infectious, and in most cases transmitted from family members. Infections acquired during the perinatal period have a 90% chance of progressing to persistent HBV infection. This rate decreases to 2.3% when infection occurs at college student age. The persistent HBV infection starts with the immune tolerance phase when our immune system may recognize HBV antigens, but does not produce significant inflammation. An immune clearance reaction may develop to terminate HBV replication two to four decades later. When this immune clearance reaction successfully suppresses HBV replication, HBsAg carriers may progress to the residual phase. About 50% of HBsAg carriers ultimately clear HBsAg at age 80. Those patients unable to clear HBV replication smoothly have increased risk of chronic hepatitis, liver cirrhosis, and hepatocarcinogenesis. Current therapies decrease hepatic decompensation and increase survival rate. However, the sustained virologic response rate is lower than 40%. About 50% of patients experience a clinical flare within one year after therapy ends. Further studies will be needed to improve sustained virologic response rate."
7995,Bioterrorism Alert for Health Care Workers,
7996,Pandemic Influenza: Potential Contribution to Disease Burden,"Records of disease outbreaks resembling influenza date to the writings of Hippocrates (fifth century BPE). Since then, influenza has afflicted humans around the globe. The most severe (“Spanish Flu” 10.1007/978-0-387-78665-0_6287) of three major outbreaks of the twentieth century killed approximately 20–50 million people worldwide. More recently, the global spread of highly pathogenic bird-adapted strain H5N1 is considered a significant pandemic threat. Since 2003, a total of 379 cases and 239 deaths have been reported. This chapter provides an overview of the genetic characteristics of the virus that elucidate its ability to continuously evade a host’s immune system; it describes some of the approaches used to quantify the burden of influenza and discusses their implications for the prevention and containment of future pandemics. The preliminary findings of the studies discussed here suggest that influenza-related burden is highly underestimated in tropical and subtropical regions of the world. This implicates that proper assessment of influenza-related morbidity and mortality worldwide is essential in planning and allocating resources to protect against what could be one of mankind’s most devastating challenges. A summary of learned lessons from past influenza pandemics are described and new intervention strategies aim at curtailing a future pandemic are discussed. More importantly, however, is the discussion of today’s challenges such as antiviral resistance, limited resources in a world that is globally connected and the imminent gap between the capacity (resources available) of developed and developing parts of the world to respond to a pandemic."
7997,China's Pharmaceutical Market: Business Environment and Market Dynamics,
7998,The Good of Patients and the Good of Society: Striking a Moral Balance,The relationship between the good of individual patients and the special good is examined when they are in conflict. The proposition is advanced that the ethical resolution of such conflicts requires an ethic of social medicine comparable to the existing ethic of clinical medicine. Comparing and contrasting the obligations clinicians incur under both aspects of the ethics of medicine is propadeutic to any ordering of priorities between them. The suggested partition of obligations between patient good and the common good is applicable beyond medicine to the other health professions.
7999,High-Altitude Pulmonary Edema,"High-altitude pulmonary edema (HAPE) is an uncommon form of pulmonary edema that occurs in healthy individuals within a few days of arrival at altitudes above 2,500–3,000 m. The crucial pathophysiology is an excessive hypoxia-mediated rise in pulmonary vascular resistance (PVR) or hypoxic pulmonary vasoconstriction (HPV) leading to increased microvascular hydrostatic pressures despite normal left atrial pressure. The resultant hydrostatic stress can cause both dynamic changes in the permeability of the alveolar capillary barrier and mechanical damage leading to leakage of large proteins and erythrocytes into the alveolar space in the absence of inflammation. Bronchoalveolar lavage (BAL) and pulmonary artery (PA) and microvascular pressure measurements in humans confirm that high capillary pressure induces a high-permeability non-inflammatory-type lung edema; a concept termed “capillary stress failure.” Measurements of endothelin and nitric oxide (NO) in exhaled air, NO metabolites in BAL fluid, and NO-dependent endothelial function in the systemic circulation all point to reduced NO availability and increased endothelin in hypoxia as a major cause of the excessive hypoxic PA pressure rise in HAPE-susceptible individuals. Other hypoxia-dependent differences in ventilatory control, sympathetic nervous system activation, endothelial function, and alveolar epithelial sodium and water reabsorption likely contribute additionally to the phenotype of HAPE susceptibility. Recent studies using magnetic resonance imaging in humans strongly suggest nonuniform regional hypoxic arteriolar vasoconstriction as an explanation for how HPV occurring predominantly at the arteriolar level can cause leakage. This compelling but not yet fully proven mechanism predicts that in areas of high blood flow due to lesser vasoconstriction edema will develop owing to pressures that exceed the structural and dynamic capacity of the alveolar capillary barrier to maintain normal alveolar fluid balance. Numerous strategies aimed at lowering HPV and possibly enhancing active alveolar fluid reabsorption are effective in preventing and treating HAPE. Much has been learned about HAPE in the past four decades such that what was once a mysterious alpine malady is now a well-characterized and preventable lung disease. This chapter will relate the history, pathophysiology, and treatment of HAPE, using it not only to illuminate the condition, but also for the broader lessons it offers in understanding pulmonary vascular regulation and lung fluid balance."
8000,Policy Innovations for Health,"We are at a turning point in health policy. It has become increasingly clear that changes in the existing health care system will not be sufficient to maintain and improve our health at this historical juncture. Both our extensive knowledge on what creates health as well as the exponentially rising rates of chronic disease obesity, and mental health problems indicate that we need to shift course and apply a radically new mind-set to health and health policy. This is what we mean by policy innovations for health. The boundaries of what we call the “health system” are becoming increasingly fluid and health has become integral to how we live our everyday life. Health itself has become a major economic and social driving force in society. This shifts the pressure for policy innovation from a focus on the existing health system to a reorganization of how we approach health in 21st century societies. The dynamics of the health society challenge the way we conceptualize and locate health in the policy arena and the mechanisms through which we conduct health policy. They also redefine who should be involved in the policy process. This concern is beginning to be addressed within government through Health in All Policy approaches and beyond government through new partnerships for health. Most importantly, the role of citizen and patient is being redefined – a development that will probably lead to the most significant of the policy innovations for health in the 21st century."
8001,Diagnostic Radiology in Hematological Patients with Febrile Neutropenia,"Radiologists have a special role in the management of neutropenic patients. The appropriate investigational technique, specific differential diagnoses, and particular risks of these patients need to be understood by referring physicians as well as by radiologists. Thus, communication and cooperation, also including other clinical disciplines such as pulmonology, are required. Early detection of an infectious focus is the major goal in febrile neutropenic patients. As pneumonia is the most common focus, chest imaging is a special radiological task. The sensitivity of chest x-ray, especially in supine position, is low. Therefore, the very sensitive thin-section multislice CT became a gold standard in neutropenic hosts and might be cost effective in comparison to antibiotic treatment. CT-based localization can be used to guide invasive procedures in order to obtain samples for microbiological workup. Furthermore, the radiological characterization of infiltrates gives a first and rapid hint to discriminate between infectious (viral, typical bacterial, atypical bacterial, fungal) and noninfectious etiologies. Radiological follow-up has to take into account aspects according to disease, immune recovery, and treatment modalities. Due to a high incidence of fungal-related lung infiltrates, interpretation of follow-up findings must include further parameters besides lesion size. Apart from the lungs, also other organ systems such as the brain, liver, and paranasal sinuses need attention and are to be imaged with the appropriate technique."
8002,Community-Acquired Pneumonia,"Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality in the world, with an annual incidence ranking from 1.6 to 10.6 per 1.000 people in Europe. The incidence is age related, peaking over 65 years. Up to 75 % of CAP patients with pulmonary diseases need hospitalization, and up to a 10 % of these are admitted to an intensive care unit (ICU) due to complications like sepsis, septic shock, and acute respiratory distress syndrome (ARDS) [1–3]. Up to 8 % of CAP patients die within 90 days of disease onset; 21 % die within a year [4] making CAP the most frequent cause of death from infection in Europe and the third most common cause of death in general [5]. Mortality is highest in ICU patients."
8003,"The Peritoneal Cavity, Retroperitoneum, and Abdominal Wall",Early detection of peritoneal changes is essential for the management of several neoplastic and non-neoplastic conditions in veterinary patients. The peritoneal and retroperitoneal spaces are normally included in abdominal MDCT examination. Contrast-enhanced MDCT scans with near-isotropic or isotropic resolution are necessary for fine evaluation of the abdominal cavity in dogs and cats. Isotropic imaging and post-processing with dorsal and sagittal reformation can fully delineate the peritoneal and retroperitoneal spaces and extent of diseases.
8004,Optimal Time Delay in the Control of Epidemic,"A mathematical model to address the efficiency of the isolation and quarantine strategies in the containment of epidemics is constructed based on the SIR model with time delay. The model is investigated with numerical simulation that demonstrates the importance of quick measure in identifying the infected and the subsequent quarantine of his/her neighbors. The model also provides a theoretical framework for the estimation of the cost involved in the containment of the epidemics. Based on a general estimate of the cost, we demonstrate the procedure for the calculation of the optimal set of parameters in our isolation and quarantine strategy through numerical simulation on a model social network. We find an important parameter π which is a combination of several general parameters for the SIR model so that when π> 0, the isolation and quarantine strategy will fail to contain the outbreak. The procedure outlined provides some general guidance in the selection of strategies in the containment of real epidemics, where the balance between social cost and risk must be carefully handled."
8005,Erreger,"Das Erregerspektrum von Pneumonien unter Immunsuppression ist breit und umfasst definierte bakterielle Erreger (Rhodococcus spp. und Nokardien), Mykobakterien (M. tuberculosis und nichttuberkulöse Mykobakterien), Pilze, Pneumocystis jirovecii, Viren (respiratorische Viren und Herpesviren) und Parasiten. Mikrobiologie, Übertragungsmechanismen, Risikofaktoren, Pathogenese, klinische Präsentation, Diagnostik, antimikrobielle Therapie und Prävention dieser Erreger werden im Einzelnen vorgestellt. Die Kenntnis dieser Zusammenhänge eröffent eine frühe und rationelle Diagnostik sowie eine gezielte Therapie auf dem Boden valider Erregernachweise."
8006,Reducing Costs – Increasing the Efficiency and Effectiveness through IT,"There is a natural limit to how IT can generate economic benefits and increase corporate value: It’s IT cost. Many value-oriented IT projects are discontinued, not because the resulting benefits cannot be quantified but because the company’s focus has shifted. And this shift does not necessarily have to include changes in the long-term corporate strategy, as would be caused by external developments in market and competition: To produce less-than-positive effects, all a company needs to do is shift its focus from IT growth drivers to IT-driven cost reductions, as often happens in times of economic downturns or internal restructuring."
8007,Decision-Making,"Chapter 7 focuses on decision-making. It introduces and discusses the relevant actors and agents responsible for identifying health risks, and developing and ordering responses at the local, national, and international levels. Then it delves into the functions of trust and history in disordering (and potentially re-ordering) health: such as the role of reactance and the ostensible reclaiming of rights by refusing vaccination(s). The latter has been the case in the former East Germany for example, which experienced a large measles outbreak in 2015, as well as in California. The chapter explores ways and means for overcoming such political and policy gaps to promote health rights and responsibilities. Finally, the chapter explores ways in which decision-makers and decision-making respond to health threats that can(not) be contained."
8008,Cell and Tissue Reactions,"Similar types of tissue reaction result as a final common pathway from a wide array of different internal brain pathophysiological states and external insults. Since these cellular and tissue reactions are largely independent of the specific type of insults, they are, therefore, non-specific. The tissue reactions are to be differentiated according to their specific pathogenetic mechanisms, though these mechanisms as well as the phenomena are overlapping as demonstrated in Fig. 4.1; brain ischemia as a type of metabolic disturbance, edema, intracranial pressure, necrosis, herniation and inflammation are influencing themselves and are dependent on each other. Some will be mentioned again in later chapters as viewed from different forensic aspects; therefore, a certain redundancy is unavoidable. Immediately following, we offer a survey of the individual types of reaction and their fundamental pathophysiological principles and morphology."
8009,"Populations, Patients, Germs and Genes: Ethics Of Genomics and Informatics in Communicable Disease Control","This chapter will explore the ways in which genomics (and the informatics tools needed to analyze and interpret them) could, potentially, transform our understanding of infectious disease epidemiology, improve disease management and prevention and save lives. The integration of microbiological, clinical and environmental data into personalized clinical decision support and risk assessment tools will improve both the care of patients with infectious diseases and public health protection. Integrated electronic health information systems will be faster, safer and more cost-effective than the current inefficient miscellany of individual medical records and disease surveillance systems. Technical, commercial and economic barriers to system implementation are unlikely to be insurmountable, but the largely uncharted ethical hazards are potentially more challenging. Prospective evaluation of clinical and public health impact and cost-effectiveness of new diagnostic and surveillance methods and information systems, designed to protect privacy and security of health data without placing unnecessary restrictions on access to essential public health data, will be needed. The interests, priorities and concerns of all stakeholders, including patients and potential patients, health professionals and administrators, public health officials and politicians, must be openly debated and addressed. Otherwise, unnecessary delays or a failure to implement better systems will allow unnecessary suffering and preventable mortality to continue."
8010,Forensic Histopathology,"Forensic histopathology is the application of histological techniques and examination to forensic pathology practice. It is a unique and specialised aspect of pathology practice. This chapter highlights several differences in forensic histopathology practice compared to clinical and surgical histopathology practice. The various roles of microscopic tissue examination in forensic pathology practice are categorised and discussed. These are in relation to definitive pathological diagnosis, confirmation of equivocal and occult pathology, serving as a form of permanent record, and providing invaluable material for education and research. Case examples are included to illustrate the impact of routine histological examinations, special stain techniques, as well as immunohistochemistry where appropriate, towards relevant pathological diagnoses, which may or may not be directly relevant to the establishment of the cause of death. Lastly, the chapter also aims to highlight some recent advances as well as the challenges ahead in this field."
8011,Using Viral-Mediated Gene Transfer to Study Depressive-Like Behavior,"The use of viral-mediated gene transfer in animal behavioral experiments has become very popular over the last decade. Altering gene regulation and assessing subsequent behavior can be a useful tool in unraveling a specific gene’s contributions to complex behavioral processes such as depressive-like behavior. However, these types of experiments require detailed planning and designs to avoid pitfalls associated with issues such as surgical procedure or the peak of viral expression. This chapter is intended to be a primer on the design of such experiments and aims to discuss factors that must be considered in the early phases of experimental planning."
8012,Our World as a Learning System: A Communities-of-Practice Approach,"We live in a small world, where a rural Chinese butcher who contracts a new type of deadly flu virus can infect a visiting international traveller, who later infects attendees at a conference in a Hong Kong hotel, who within weeks spread the disease to Vietnam, Singapore, Canada, and Ireland. Fortunately, the virulence of the Severe Acute Respiratory Syndrome (SARS) was matched by the passion and skill of a worldwide community of scientists, health care workers, and institutional leaders who stewarded a highly successful campaign to quarantine and treat those who were infected while identifying the causes of the disease and ways to prevent its spread. In such a world, we depend on expert practitioners to connect and collaborate on a global scale to solve problems like this one – and to prevent future ones."
8013,Microbial Agents in the Indoor Environment: Associations with Health,"There is international consensus that damp buildings and indoor mould can increase the risk of asthma, rhinitis, bronchitis and respiratory tract infections but we do not know which types of microbial agents that are causing the observed adverse health effects. Microbial indoor exposure is a broader concept than microbial growth in buildings. Other sources of indoor microbial exposure include the outdoor environment, humans (crowdedness) and furry pet keeping. Microbial exposure can have different health effects depending on the dose, different exposure route, genetic disposition and the timing of exposure. Microbial stimulation linked to large microbial diversity in early life can protect against disease development, especially for allergic asthma and atopy. Protective effects are more often reported for bacterial exposure and adverse health effects are more often linked to mould exposure. There are many studies on health associations for indoor exposure to endotoxin, mainly from homes. The risk of getting atopic asthma may be less if you are exposed to endotoxin in childhood but the risk of non-atopic asthma may increase if exposed to endotoxin especially in adulthood. Moreover, genetic disposition modifies health effects of endotoxin. Epidemiological studies on muramic acid (from gram-positive bacteria) or ergosterol (from mould) are few. Studies on health effects of indoor exposure to beta-1-3-glucan (from mould) have conflicting results (positive as well as negative associations). Epidemiological studies on health effects of indoor exposure to mycotoxins are very few. Some studies have reported health associations for MVOC, but it is unclear to what extent MVOC has microbial sources in indoor environments. Many studies have reported health associations for fungal DNA, especially as a risk factor for childhood asthma at home. Since most studies on health effects of indoor exposure to mould, bacteria and microbial agents are cross-sectional, it is difficult to draw conclusions on causality. More prospective studies on indoor microbial exposure are needed and studies should include other indoor environments than homes, such as day care centers, schools, hospitals and offices."
8014,Aspects of Microparticle Utilization for Potentiation of Novel Vaccines: Promises and Risks,"Many recombinant vaccines against novel (HIV, HCV) or ever-changing (influenza) infectious agents require the presence of adjuvants/delivery vehicles to induce strong immune responses. The necessity of their improvement led to the major effort towards development of vaccine delivery systems that are generally particulate (e.g., nano- and microparticles) and have comparable dimensions to the pathogens (viruses or bacteria). The mode of action of these adjuvants is not fully understood but implies the stimulation of the innate or antigen-specific immune responses, and/or the increase of antigen uptake or processing by antigen-presenting cells (APC). Moreover, enhancement of adjuvant activity through the use of micro- and nanoparticulate delivery systems often resulted from the synergistic effects producing immune responses stronger than those elicited by the adjuvant or delivery system alone. Among particulate adjuvants, biodegradable micro- and nanoparticles of poly(D,L-lactide-co-glycoside) (PLGA) or poly(D,L-lactide) (PLA) have been reported to enhance both humoral and cellular immune responses against an encapsulated protein antigen. Cationic and anionic polylactide co-glycolide (PLG) microparticles have been successfully used to adsorb a variety of agents, which include plasmid DNA, recombinant proteins and adjuvant active oligonucleotides and are also currently tested in several vaccine applications. Another approach envisions specific targeting of APC, especially peripheral DC and exploitation of particulate systems that are small enough for lymphatic uptake (polystyrene nanobeads). Micro- and nanoparticles offer the possibility of enhancement of their uptake by appropriate cells through manipulation of their surface properties. Still, questions regarding toxicity and molecular interaction between micro- and nano-particles and immune cells, tissues and whole organisms remain to be addressed. These risks and other possible side effects should be assessed in detail especially if mass-production and massive administration of such preparations is to be considered."
8015,Complex Situations in Patients with Adult-Onset Still’s Disease,"Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology, characterized by quotidian or double quotidian fever, a peri-febrile cutaneous eruption, polyarthritis, and multiorgan involvement. AOSD is a challenging disease with protean disease manifestations and rare, albeit potentially life-threatening, complications. In such cases, prompt diagnosis and treatment may prove life-saving. The purpose of this chapter is to review the diagnosis and management of challenging clinical situations in AOSD patients that are associated with significant morbidity and mortality and to provide the readers with information that could aid their decision-making process."
8016,Chemokine Actions in the CNS: Insights from Transgenic Mice,"Historically the central nervous system (CNS) has been viewed as a relatively immune sheltered tissue. Under physiological conditions the CNS is devoid of leukocytes, including professional antigen presenting cells (APC), is deficient in key immune accessory molecules such as major histocompatibility molecules (MHC) and is protected by an effective blood brain barrier. Significantly, however, in numerous pathological states including infectious diseases and autoimmune disorders (e.g. multiple sclerosis) immune cells are effectively recruited to and infiltrate in the CNS. This immune response can be a two-edged sword required on the one hand to control infection and facilitate tissue repair and regeneration but on the other causing tissue injury that can result in life threatening complications. Therefore, understanding the mechanisms that control the trafficking of leukocytes to the CNS and the subsequent interactions between these cells that contribute to tissue injury has significant implications."
8017,Hepadnaviruses have a narrow host range — do they?,"Host range describes the range of species that a virus can infect to productively propagate itself. Productive infection requires compatibility between virus and host molecules. Thus host range may be restricted by lack of appropriate permissivity factors;alternatively, hosts may actively counteract infection using restriction factors. Incompatibility between virus and host can manifest on the level of individual cells,of tissues or organs,and of the entire organism. All hepatitis B viruses are hepatotropic,but individual viruses infect the livers of only selected mammalian (orthohepadnaviruses) and avian (avihepadnaviruses) hosts. Hence a narrow host range is thought to be a salient feature of hepadnaviruses. Here we briefly review general mechanisms of host range restriction,and summarise older as well as recent data pertaining to hepadnaviral host range. Clearly,the term species-specific is inadequate for many hepadnaviruses because they can infect different species from one genus,and even species from different genera. For a few others,only a single species,or genus,has been identified that supports efficient infection;however,this could as well relate to the restricted number of experimentally addressable test species. Together with the uncertainty about quantitative phylogenetic relationships between species,still largely based on morphological rather than molecular criteria,this leaves the term narrow open to interpretation. Finally,few if any of the host molecules enabling productive infection by a hepadnavirus have unambiguously been identified,the role of restriction factors has not yet been assessed,and even on the virus side the so-called host determining regions in the PreS domains of the large envelope proteins appear to be relevant only under specialised experimental conditions. Hence this important aspect of hepadnavirus biology is still far from being understood."
8018,Metal-Based Drugs for Treatment of Malaria,"Despite the incessant efforts to decrease exorbitant number of daily deaths, malaria remains a major threat to the public health in many countries. Transmitted by Anopheles mosquitoes, it is caused by infection with Plasmodium parasites that have become resistant to many antimalarial drugs. In this context, series of metal-based compounds have been screened for optimal activity against different Plasmodium species and strains. This chapter briefly reviews current and potential uses of metal complexes (such as iron, cobalt, nickel, gallium, copper, gold, and silver), metal chelators, and organometallic compounds, as interesting medicinal agents that greatly benefits the fight against malaria."
8019,Identifying Multiple Propagation Sources,"The global diffusion of epidemics, computer viruses and rumors causes great damage to our society. One critical issue to identify the multiple diffusion sources so as to timely quarantine them. However, most methods proposed so far are unsuitable for diffusion with multiple sources because of the high computational cost and the complex spatiotemporal diffusion processes. In this chapter, we introduce an effective method to identify multiple diffusion sources, which can address three main issues in this area: (1) How many sources are there? (2) Where did the diffusion emerge? (3) When did the diffusion break out? For simplicity, we use rumor source identification to present the approach."
8020,"Fabrication of Nanostructures with Bottom-up Approach and Their Utility in Diagnostics, Therapeutics, and Others","Nanofabrication has been a critical area of research in the last two decades and has found wide-ranging application in improvising material properties, sensitive clinical diagnostics, and detection, improving the efficiency of electron transport processes within materials, generating high energy densities leading to pulse power, novel therapeutic mechanisms, environmental remediation and control. The continued improvements in the various fabrication technologies have led to realization of highly sensitive nanostructure-based devices. The fabrication of nanostructures is in principle carried out primarily using top-down or bottom-up approaches. This chapter summarizes the important bottom-up nanofabrication processes for realizing nanostructures and also highlights the recent research conducted in the domain of therapeutics and diagnostics."
8021,"The Phytochemical Composition, Biological Effects and Biotechnological Approaches to the Production of High-Value Essential Oil from Geranium","Geraniaceae family plants are highly reputed aromatic and medicinal perennial branched herbs. The high economic value of these plants is due to their secondary metabolites, especially essential oil of foliage, which is a complex mixture of volatile phytochemicals, such as terpenes, esters, aldehydes, alcohols, ketones and phenols. The main phytoconstituents of the essential oil belong to the terpenoid group of metabolites, such as monoterpenes, sesquiterpenes, diterpenes and their esters. Of these, geraniol, linalool, citronellol and their esters (50–70%) generally constitute a major portion of essential oil, responsible for its fragrance. Essential oil is biosynthesized in specialized tissues known as glandular trichomes present in leaves, green branches and fresh flowers. Geraniaceae family plants have been highly useful in the perfumery, cosmetics, aromatherapy, pharmaceuticals and food industries. Several pharmacological properties such as antifungal, anti-inflammatory, anti-cancerous, anti-depressant, antibacterial, antioxidant, antiseptic, anti-dysentery, and antidiabetic properties are attributed to the presence of geranium oil. Further, it improves blood circulation, treats congestion, cleans the lymphatic system, strengthens the immune system, and is effective in combating nervousness, constipation, insomnia, anxiety and high blood pressure. The chapter discusses the phytochemical composition, pharmacological properties, genomics of essential oil biosynthetic pathway, enhancement of essential oil yield, and several biotechnological approaches to enhance the quantity as well as quality of essential oil in geranium."
8022,Akutes und chronisches Leberversagen,
8023,Severe acute respiratory syndrome: clinical features,
8024,Fluorescence In Situ Hybridization (FISH) and Its Applications,"Fluorescence in situ hybridization (FISH) is the most convincing technique for locating the specific DNA sequences, diagnosis of genetic diseases, gene mapping, and identification of novel oncogenes or genetic aberrations contributing to various types of cancers. FISH involves annealing of DNA or RNA probes attached to a fluorescent reporter molecule with specific target sequence of sample DNA, which can be followed under fluorescence microscopy. The technique has lately been expanded to enable screening of the whole genome simultaneously through multicolor whole chromosome probe techniques such as multiplex FISH or spectral karyotyping or through an array-based method using comparative genomic hybridization. FISH has completely revolutionized the field of cytogenetics and has now been recognized as a reliable diagnostic and discovery tool in the fight against genetic diseases."
8025,Kutane Lymphome,"Kutane Lymphome (cutaneous lymphomas: CL) umfassen die Gruppe der kutanen T-Zell-Lymphome (cutaneous T-cell lymphomas: CTCL), kutanen B-Zell-Lymphome (cutaneous B-cell lymphomas: CBCL) und die sog. hämatodermischen Neoplasien (HN). CL gehören zur Gruppe der Non-Hodgkin-Lymphome (NHL) und stellen in der Subgruppe der extranodalen NHL die zweithäufigste Gruppe hinter den gastrointestinalen Lymphomen dar (Jaffe et al. 2009). Man unterscheidet zwischen primären und sekundären CL. Primäre CL haben ihren Ursprung in der Haut und bleiben in der Regel darauf auch längere Zeit beschränkt, während sekundäre Lymphomekutane CL kutane Manifestationen von primär nodalen oder extranodalen Lymphomen darstellen (Willemze 2005). Die primären CL unterscheiden sich hinsichtlich klinischem Verlauf, Therapieoptionen und Prognose erheblich von nodalen und extrakutanen Lymphomen. So zeigen z. B. die primär kutanen CD30(+) Lymphome einen gutartigen Verlauf, wogegen die nodalen Varianten als aggressiv eingestuft werden. Da die CL zumeist weniger aggressiv sind, werden sie weniger aggressiv behandelt."
8026,Infectious Disease,
8027,Spread-of-Disease Modeling in a Microbiology Course,"Microbiology is the study of microorganisms. Most college courses in microbiology emphasize the biology of bacteria and viruses, including those that are human pathogens. One challenging aspect of the course is to introduce students to epidemiology, which considers the causes, dispersal, and control of disease. Although disease transmission models have helped develop successful strategies for managing epidemics, most science students are unaware of their advantages and complexities. To address this challenge, the microbiology course at Wofford College has incorporated a sequence of three or four laboratories on modeling the spread of disease. Emphasis in Computational Science students who have studied modeling and simulation in depth serve as laboratory assistants and mentors. Evidence from test scores and self-assessment support the hypothesis that the sequence of laboratories has improved student understanding of human disease dynamics and demonstrated the utility of computational models."
8028,Non-poisson Processes of Email Virus Propagation,"Email viruses are one of the main security problems in the Internet. In order to stop a computer virus outbreak, we need to understand email interactions between individuals. Most of the spreading models assume that users interact uniformly in time following a Poisson process, but recent measurements have shown that the intercontact time follows heavy-tailed distribution. The non-Poisson nature of contact dynamics results in prevalence decay times significantly larger than predicted by standard Poisson process based models. Email viruses spread over a logical network defined by email address books. The topology of this network plays important role in the spreading dynamics. Recent observations suggest that node degrees in email networks are heavy-tailed distributed and can be modeled as power law network. We propose an email virus propagation model that considers both heavy-tailed intercontact time distribution, and heavy-tailed topology of email networks."
8029,Characteristics of B Cells and B Cell Responses in Aged Individuals,"Ageing individuals are immunologically characterized by loss of immunological protection and responsiveness, and autoimmunity occurs with increased incidence. Here we review studies on specific age-related changes in B cell generation, activation, and maintenance as well as characteristics of B cell responses and antibody levels during ageing in relation to other cells and factors that are interwoven with B cell biological processes. In the elderly, fewer new B cells are generated, B cell responsiveness to antigens is impaired, and smaller and fewer germinal centers are formed within an immune response with participation of less potent T cells and follicular dendritic cells, leading to the production of reduced, often insufficient plasma cell numbers. Recall responses in the elderly appear to be limited by the cells’ proliferative capacity. Hence, vaccine responsiveness is often insufficient and autoantibody production emerges in the elderly. In total, B cells appear to be less affected by age as compared with T cells. Recently, new concepts have been developed to counteract immunosenescence beyond active vaccination, comprising the generation of specific monoclonal antibodies for passive vaccination, immune rejuvenation by immunoablation followed by autologous stem cell transplantation, and modulation of lifestyle."
8030,Growth Factors,"Any cell needs extracellular signals for its growth, proliferation, and survival, among other events. Chemical, mechanical, electrical, and other physical interactions of cells with the extracellular matrix yield functional and structural signals for normal cellular activity as well as formation and maintenance of three-dimensional tissues. Environmental chemical signals are transmitted by hormones (Sect. 1.4) and growth factors (Table 3.1), in addition to nervous cues (Sect. 1.1)."
8031,SARS Epidemic: SARS Outbreaks in Inner-land of China,"Severe Acute Respiratory Syndrome (SARS), also known in China as Infectious Atypical Pneumonia (IAP), is the 21st century’s first infectious disease to severely threaten the public health of the human population (WHO, 2003a). A respiratory transmitted disease caused by a virus, SARS is highly infectious and is rapidly transmitted, inflicting severe complications and a high case fatality rate. The first round of the SARS pandemic led to global panic and billions of dollars economic losses, for due to lack of effective SARS drugs, governments throughout the world had to take rigid steps toward prevention and treatment of the disease. The SARS epidemic began with the first reported case in Guangzhou, China (Wang et al., 2004), on 16 November 2002. Eight months later, the disease had spread to 26 countries in Asia, America, and Europe, resulting in a reported 8,096 cases and 774 deaths (WHO, 2004). In this global epidemic, China, with 7,429 cases and 685 deaths, accounted for 91.8% of the world’s reported cases and 88.5% of the deaths (5,327 SARS cases and 349 deaths were reported in 24 provinces in the inner-land of China – mostly in Beijing and Guangzhou, which, with a combined 4,033 cases, accounted for 75.7% of the total number in the inner-land of China; Hong Kong had 1,755 cases, 299 deaths; Taiwan: 346 cases, 37 deaths; Macao: 1 case, 0 deaths) (He et al., 2003; Peng et al., 2003; Yang et al., 2003; Leadership Group of SARS Prevention and Control in Beijing, 2003; Chinese Center for Disease Control and Prevention, 2003)."
8032,Historical Overview,"“Poisons” were originally considered as the causative agents of illnesses that we know as viral diseases today. At that time, there were no standard methods to detect pathogenic (disease-causing) organisms such as bacteria and protozoa in the supposed “poisonous materials”. Only animal experiments performed by Louis Pasteur at the end of the nineteenth century, in which no dilution of the poisonous properties was achieved even after several passages, suggested that the disease-causing agent was able to multiply in the organism. Therefore, there was talk of a reproducible “virus” (Latin for “poison” or “slime”) in living organisms, and later also in cells. In St. Petersburg in 1892, Dimitri I. Ivanovski demonstrated that tobacco mosaic disease is caused by an “ultrafilterable” agent, whose size is significantly smaller than that of bacteria: tobacco mosaic virus (bacteria filters have a pore size of approximately 0.2 μm, however, most viruses are smaller than 0.1 μm). Soon afterwards, Martinus Willem Beijerinck came to the same conclusion: he developed, for the first time, the notion of a self-replicating, “liquid” agent (contagium vivum fluidum). The discovery of foot-and-mouth disease virus by Friedrich Loeffler and Paul Frosch in Greifswald in 1898 was the first evidence of an animal pathogenic virus."
8033,"Hypoxemic Respiratory Failure: Evidence, Indications, and Exclusions","ECMO is increasingly being used to manage severe ARDS with refractory hypoxemia and hypercapnia, and to facilitate lung-protective ventilation and minimize ventilator-associated lung injury. However, there is limited high-level evidence to support its use. Early randomized trials did not show a benefit, though these studies were hampered by high mortality rates, limited experience with ECMO, and antiquated technology. Since the advent of more advanced circuit components and increased experience with the use of this technology, survival rates with ECMO for ARDS have improved. There is only one randomized trial to date which used a more modern ECMO circuit. This trial, which has significant limitations, demonstrated a survival benefit from referral to a specialized center for consideration for ECMO. However, a prospective randomized trial comparing ECMO, using modern equipment, to standard-of-care mechanical ventilation has yet to be performed. There are no universally accepted guidelines for initiation of ECMO for ARDS, however suggested criteria include PaO(2) to FIO(2) ratio less than 80, uncompensated respiratory acidosis, and excessively high plateau airway pressures despite optimal ventilator management. Relative contraindications include prolonged ventilation at high airway pressures or high FIO(2), contraindications to anticoagulation, and concurrent severe, irreversible comorbidities."
8034,One Health: From Concept to Practice,"One Health (OH) is an approach, focusing on emergent infectious diseases, which looks at health in the context of human, animal and environment relationships. Governments worldwide through the International Ministerial Conferences on Avian and Pandemic Influenza (IMCAPI) meetings have made a commitment to OH. There is unanimous agreement from the international organizations to the community level that this is a necessary approach in an increasingly populous world. It is a world, however, in which professions have moved to specialization and expertise within their own realm rather than in collaboration and cross discipline. This chapter reports on the operationalization of OH to date and consideration of the forward path in examination of the key areas of: leadership, relationships, infrastructure, skills and capacity, communication and technology, and resources."
8035,Antiviral Probiotics: A New Concept in Medical Sciences,"In recent decades, probiotics have shown beneficial effects on animal and human health. Probiotics can protect the host against several health threats, including infectious diseases. Before 1995, researchers believed that the effect of probiotics was only on gut microbiota which can restore the gut flora and thus prevent pathogenic bacteria from triggering gastroenteritis. Recent studies have shown that the immunomodulatory activity is the most important mechanism of action of probiotics. From this information, researchers started to evaluate the effect of some immunobiotics, not only on pathogenic bacteria but also on viruses, including enteric and respiratory viruses. Several studies have confirmed the potential antiviral activity of some probiotics due to the immunomodulatory effect. These studies were conducted on humans (clinical trials) and in animal models. In this chapter, probiotics with antiviral effect against respiratory and enteric viruses will be presented and discussed, as well as their mechanisms of action."
8036,Global Governance,
8037,Caspase-6,
8038,How to Choose the Right Journal,"Authors of a scientific manuscript wish their paper to be published in a journal and then read, used and cited by their peers. However, there can be many stumbling blocks in this process. One such impediment is submitting the manuscript to an inappropriate journal. At one extreme, it may result in a journal editor summarily rejecting the manuscript without even commissioning an external peer review; this results in the need to resubmit the manuscript to another journal and a consequent delay in publication. At the other extreme, the paper may be published in a journal that is rarely accessed or read by those interested in the work. Either way, the authors’ efforts to disseminate their knowledge have been frustrated."
8039,Respiratory Emergencies,"Causes of cough: Acute cough (<3 weeks): Respiratory tract infections: viral upper respiratory tract infection, viral rhinosinusitis, common cold, acute bacterial sinusitis, acute bronchitis, pneumonia, acute exacerbation of COPD; pertussis. Inhalation of direct irritants: dust, smoke, ozone, air pollutants. Inhalation of specific allergen in the asthmatic: pollen, or low concentration of non-specific irritants: cigarette smoke, perfume; house dust mites. Allergic rhinitis. Chemical exposure: chloramines in swimming pools. Medication: ACE inhibitors. Subacute cough (3–8 weeks): Post-infectious cough: prior viral upper respiratory tract infection. Bordetella pertussis infection. Subacute bacterial sinusitis. Asthma. Neoplasm. Chronic cough (>8 weeks): Persistent airway inflammation: COPD, asthma, bronchiectasis. Smoking. Neoplasm. Interstitial lung disease: pulmonary fibrosis. Persistent infection: tuberculosis; bronchiectasis. Raised left atrial pressure: mitral stenosis, left ventricular failure. Inhaled foreign body. Iatrogenic: ACE inhibitors, radiation pneumonitis, steroid aerosols. Aspiration syndrome: gastro-oesophageal reflux disease; bulbar dysfunction; oesophageal dysmotility. Psychogenic. Post-nasal drip syndrome (posterior nasal discharge and night cough): sinusitis; rhinitis (allergic; non-allergic; vasomotor). Primary ciliary dyskinesia."
8040,Refugee Crisis As a Potential Threat to Public Health,"The refugee crisis in Europe continues to persist despite recent data, showing a drop in the number of refugees seeking asylum. The EU has called this as “an unprecedented displacement crisis” and has aimed at devising a comprehensive approach to tackle it, which has been widely criticized. Concerns about public healthcare aspects of the crisis have permanently entered the media and policy discourse even though no systematic association between migration and the importation of infectious diseases has been recorded. In this context, the literature has not filled the existing gap between discourse and evidence, and almost no publications with reliable empirical data exist, both thematic (epidemiology) and geographical (Eastern Europe and Bulgaria). Among the existing publications, the focus has been on TB and HIV (Odone et al., Euro J Public Health 25(3):506–512, 2015). In light of this, the aim of this research is to contribute to the debate by providing an overview of the refugee situation in Bulgaria, as a primary entry-point for refugees entering the EU. In order to achieve this, the article analyses the case of the refugee camp in city of Harmanly, close to the Bulgarian-Turkish border, and assesses the public health risks related to this specific situation. Based on a study of 128 patients with different symptoms we aim to draw wider implications about the linkages between public health and migration. The in-depth review of this specific case shows that both the probability and impact of migration on public health increases when the hosting country is relatively poor, the domestic public healthcare system is not efficient, and there is lack of trust in the government and public services. The study contributes to understanding better these risks in order to identify potential mitigation strategies in the region and the EU as a whole."
8041,Community Acquired Pneumonia,"Early identification of patients with severe community-acquired pneumonia (CAP) who require ICU care is important as delayed transfer is associated with increased mortality. In such patients, aggressive diagnostic testing is warranted given the increased probability of detecting a pathogen resistant to usual empirical therapy. In the absence of risk factors for healthcare-associated pneumonia or drug resistant pathogens, adequate coverage of Streptococcus pneumoniae and Legionella pneumophila is crucial. When Pseudomonas is suspected, dual anti-pseudomonal therapy is required. When methicillin-resistant Staphylococcus aureus is suspected, linezolid is superior to vancomycin. Several aspects of managing severe CAP remain without consensus and include the risks associated with multidrug resistant pathogens, antibiotic use to suppress toxin formation in the setting of pneumonia caused by S. aureus, and adjuvant assessment tools such as procalcitonin."
8042,Probing Biology with Small Molecule Microarrays (SMM),"In the continuous drive to increase screening throughput and reduce sample requirement, microarray-based technologies have risen to the occasion. In the past 7 years, a number of new methodologies have been developed for preparing small molecule microarrays from combinatorial and natural product libraries with the goal of identifying new interactions or enzymatic activities. Recent advances and applications of small molecule microarrays are reviewed."
8043,Pulmonology,"Respiratory conditions are very common among children. This chapter aims to provide a quick review of common respiratory conditions with which the general pediatrician preparing for the certifying board exam should be familiar. The chapter begins with a review of common diagnostic testing methods used in the evaluation of respiratory diseases. Subsequently, the reader will find a description as well as recommended evaluation, differential diagnosis, and management of general signs and symptoms frequently encountered in respiratory medicine. Summaries of specific conditions follow, which provide brief high-yield facts on background, clinical presentation, evaluation, and management. Specific conditions are grouped similarly to the content outline for the ABP into conditions of the upper airway, lower airway, pulmonary parenchyma, chest wall disease, and disorders in breathing. More extensive summaries regarding asthma and cystic fibrosis are also included."
8044,Human Insecurity in the People’s Republic of China: The Vulnerability of Chinese Women to HIV/AIDS,"HIV/AIDS has become one of the world’s leading causes of human insecurity for both men and women. In addition to physiological factors, women’s vulnerability to HIV transmission is primarily fuelled by gender inequality and gender-based discrimination and violence. Therefore, women’s vulnerability to HIV transmission is closely linked to issues of empowerment and gender-based power relations. Even with this realization however, women are still sometimes overlooked in many HIV/AIDS prevention and treatment campaigns, such as those in the People’s Republic of China (PRC), and responses to HIV/AIDS do not always actively seek to empower women. Therefore, a deficiency in women’s human security increases their HIV/AIDS vulnerability. This chapter examines the intersection of gender inequality and HIV vulnerability as it applies to women in the PRC. The unequal status of many women in China, and the privileged position accorded to Chinese men, strongly indicates that Chinese women face a heightened vulnerability to HIV transmission. While many of these vulnerabilities are similar to women elsewhere in the world and certainly are not unique to China, by overlooking the many social, cultural, economic and political factors that contribute to HIV/AIDS vulnerability and transmission of the virus, particularly those faced by women, China has a long way to go before Chinese women are protected from HIV transmission. Given that HIV/AIDS heightens human insecurity, the stage is set for Chinese women (and men) to face an insecure future if the Chinese government does not fully implement international best practice, meaning a gendered response, into its overall HIV/AIDS response."
8045,Antiviral Resistance in Influenza Viruses: Clinical and Epidemiological Aspects,"Two classes of anti-viral agents, the M2 ion channel inhibitors (amantadine, rimantadine) and neuraminidase (NA) inhibitors (oseltamivir, zanamivir) are available for treatment and prevention of infl uenza in most countries of the world. The principle concerns about emergence of antiviral resistance in infl uenza viruses are loss of drug effi cacy, transmission of resistant variants, and possible increased virulence or transmissibility of resistant variants (1). Because seasonal infl uenza is usually an acute, self-limited illness in which viral clearance occurs rapidly due to innate and adaptive host immune responses, the emergence of drug-resistant variants would be anticipated to have modest effects on clinical recovery, except perhaps in immunocompromised or immunologically naïve hosts, such as young infants or during the appearance of a novel strain. In contrast to the limited impact of resistance emergence in the treated immunocompetent individual, the epidemiologic impact of resistance emergence and transmission could be considerable, including loss of both prophylactic and therapeutic activity for a particular drug, at the household, community, or perhaps global level. Infl uenza epidemiology in temperate climates is expected to provide some protection against widespread circulation of resistant variants, as viruses do not persist between epidemics but rather are re-introduced each season and new variants appear often (2, 3)."
8046,Cell and Tissue Gene Targeting with Lentiviral Vectors,"One of the main advantages of using lentivectors is their capacity to transduce a wide range of cell types, independently from the cell cycle stage. However, transgene expression in certain cell types is sometimes not desirable, either because of toxicity, cell transformation, or induction of transgene-specific immune responses. In other cases, specific targeting of only cancerous cells within a tumor is sought after for the delivery of suicide genes. Consequently, great effort has been invested in developing strategies to control transgene delivery/expression in a cell/tissue-specific manner. These strategies can broadly be divided in three; particle pseudotyping (surface targeting), which entails modification of the envelope glycoprotein (ENV); transcriptional targeting, which utilizes cell-specific promoters and/or inducible promoters; and posttranscriptional targeting, recently applied in lentivectors by introducing sequence targets for cell-specific microRNAs. In this chapter we describe each of these strategies providing some illustrative examples."
8047,Gastroenterologie,"Dieses Kapitel behandelt die wichtigsten diagnostischen Möglichkeiten, die man im Bereich der Gastroenterologie mittels Auskultation, Palpation und Perkussion hat, und gibt klinisch-praktische Beispiele sowie Hilfen für die Umsetzung. Ferner wird durch die Vertiefung der Pathologien (Welche Begleitsymptome können auftreten? An welche Differenzialdiagnosen sollte gedacht werden?) der ganzheitlich-medizinische Blick geschult."
8048,Krankheiten des Herz-Kreislauf-Systems,"Definition. Basale Regulationsmechanismen des Kreislaufs, die von der übergeordneten nervalen und humoralen Steuerung unabhängig sind."
8049,Gryphon: A Hybrid Agent-Based Modeling and Simulation Platform for Infectious Diseases,"In this paper we present Gryphon, a hybrid agent-based stochastic modeling and simulation platform developed for characterizing the geographic spread of infectious diseases and the effects of interventions. We study both local and non-local transmission dynamics of stochastic simulations based on the published parameters and data for SARS. The results suggest that the expected numbers of infections and the timeline of control strategies predicted by our stochastic model are in reasonably good agreement with previous studies. These preliminary results indicate that Gryphon is able to characterize other future infectious diseases and identify endangered regions in advance."
8050,Molecular Biology,"Genetic information is passed with high accuracy from the parental organism to the offspring and its expression governs the biochemical and physiological tasks of the cell. Although different types of cells exist and are shaped by development to fill different physiological niches, all cells have fundamental similarities and share common principles of organization and biochemical activities. This chapter gives an overview of general principles of the storage and flow of genetic information. It aims to summarize and describe in a broadly approachable way, from the point of view of molecular biology, some general terms, mechanisms and processes used as a base for the molecular computing in the subsequent chapters."
8051,The Airway and Lungs,"Extremely useful and relevant information can be obtained when analysing the position assumed by patients with dyspnoea. Relief of breathlessness in a sitting or standing position compared to the recumbent position is referred to as orthopnoea. While increased venous return in the supine patient is well tolerated in individuals with a preserved heart function, this leads to pulmonary venous congestion, an increase in interstitial lung water and a subsequent reduction of lung capacities with resultant shortness of breath in patients with impaired heart function. Accordingly, patients with heart failure prefer to sit upright (e.g. supporting their back with pillows to achieve a maximum upright position) (Fig. 5.1). Conversely, placing the patient into a supine position may be used as a stress test to exclude respiratory distress due to heart failure or (pulmonary) fluid overload. A history of paroxysmal nocturnal dyspnoea characterized by repeated awakening due to breathlessness while sleeping in the recumbent position is a typical symptom of heart failure."
8052,Coronavirus infections in veterinary medicine,
8053,"Evaluation of current strategies to inhibit HIV entry, integration and maturation",
8054,Hematologic Disorders,"This chapter reviews hematologic disorders which are conditions that affect millions of people each year in the United States. From malignancies to acquired coagulopathies, this chapter covers common and uncommon disorders found in this area in patients admitted to the ICU. Special consideration is given to conditions that are related to therapeutic interventions such as heparin-induced thrombocytopenia."
8055,Unequal Vulnerability to Social Risks: Analysis of Hong Kong’s Social Strata (1993–2013),"This chapter demonstrates the vulnerability to social risks of varying social strata in Hong Kong. We consolidate and compare the income, occupational statistics and employment conditions vis-à-vis key economic indicators from 1993 to 2013. The study period covers several global economic crises with which Hong Kong significantly afflicted since its handover to China—notably the Asian financial storm (1998), the epidemic crisis of Severe Acute Respiratory Syndrome (SARS) (2003), and the global financial tsunami (2008–09). Despite the recovery of Hong Kong’s economy since the aftermath of the financial tsunami, data show divergent employment conditions between the ‘haves’ and ‘have-nots’ throughout the study period. The findings are indicative of unequal vulnerability to social risks of different social strata. This study thus echoes to the scholarly dialogue surrounding risk society theory, in particular the unequal distribution of social risk to those with varying socio-economic conditions."
8056,Levels and Stability of Expression of Transgenes,"It is well known that in a given cell, at a particular time, only a fraction of the entire genome is expressed. Expression of a gene, nuclear, or organellar starts with the onset of transcription and ends in the synthesis of the functional protein. The regulation of gene expression is a complex process that requires the coordinated activity of different proteins and nucleic acids that ultimately determine whether a gene is transcribed, and if transcribed, whether it results in the production of a protein that develops a phenotype. The same also holds true for transgenic crops, which lie at the very core of insert design. There are multiple checkpoints at which the expression of a gene can be regulated and controlled. Much of the emphasis of studies related to gene expression has been on regulation of gene transcription, and a number of methods are used to effect the control of gene expression. Controlling transgene expression for a commercially valuable trait is necessary to capture its value. Many gene functions are either lethal or produce severe deformity (resulting in loss of value) if over-expressed. Thus, expression of a transgene at a particular site or in response to a particular elicitor is always desirable."
8057,Herpesvirus,Name: Herpesvirus
8058,Global Health Security and Weapons of Mass Destruction Chapter,"The global proliferation of weapons of mass destruction (WMD) presents a clear and present danger to global health security. Unlike conventional weapons that confine themselves to a defined and targeted area, WMD’s cross international boundaries and borders. Moreover, the release of WMDs can be achieved using a low technology approach resulting in a transformation and redefinition of the mission of global health providers. This chapter will focus on the ease of access to WMDs, the impact biological weapons and bioterrorism plays on global health security, United States global policies on public health, and the role actors and non-state actors play in the global health landscape. In addition, this chapter will focus on global WMD proliferation prevention to include international efforts, treaties, and conventions. The chapter will conclude with a discussion of ongoing research initiatives, identification of emerging threats, and additional recommended readings."
8059,Ecological and Environmental Monitoring After Reservoir Impoundment,"The Three Gorges reservoir began to store water in June 2003. By November 5, the water level had risen to El.139 meters."
8060,Ischemia-reperfusion Injury of the Lung: Role of Surfactant,
8061,Human Metapneumovirus,Name of Virus: Human metapneumovirus
8062,The Notion of a Health Good in China and Elsewhere,"Is the intervention of the state in the healthcare market legitimate and efficient? To answer this question, a clear definition of a health good and its implications is needed. Can we just apply the general definition of a public good for all health goods? Should we consider different types of health goods? If yes, how do we delimit the frontier between a public good and a private good? With a rapid glance at the diversity of organizations in the healthcare system that exist in the world, it appears there is little consensus on what can and should be defined as a public good. Generally speaking, all countries have a mixed health system, combining pro-market elements with welfare state safeguards, and China is no exception: all reforms of the healthcare system implemented since the 1980s have swung between both. To understand the Chinese health system and its recent evolution, we need to start by defining the global framework in which the “health good” is set."
8063,Influenza Virus: The Biology of a Changing Virus,"Influenza viruses are members of the family Orthomyxoviridae and include influenza virus types A, B, and C. This introduction provides an overview of influenza virus classification, structure, and life cycle. We also include a brief review of the clinical manifestations of influenza and the molecular determinants for virulence. The genetic diversity of influenza A viruses and their capability to successfully infect an array of hosts, including avian and mammalian species, are highlighted in a discussion about host range and evolution. The importance of viral receptor-binding hemagglutinins and host sialic acid distribution in species-restricted binding of viruses is underscored. Finally, recent advances in our understanding of the seasonality and transmission of influenza viruses are described, and their importance for the control of the spread of these viruses is discussed."
8064,Size Effect in Physical and Other Properties of Nanostructured Coatings,"This chapter starts the discussion about size effect in physical and other (except electrochemical and mechanical) properties of nanocoatings and its real usage through different examples. It starts from the usage of nanostructured materials in microelectronics and goes through different reported papers in this field. Size effect in nanometric scale has been compared with larger scales by some examples. Detailed discussions about some methods with enough examples were presented in this chapter. Different parts of this chapter include discussions about microelectronics, silicides specifications, size effect in sensing characterization, size effect in optical properties of nanostructured films, self-cleaning glasses, using nanocomposite coating for food packaging and using polarizer nano-layers to produce LCD monitors."
8065,Structure–Activity Relationship Study of PD 404182 Derivatives for the Highly Potent Anti-HIV Agents,"Using facile synthetic approaches to pyrimido[1,2-c][1,3]benzothiazin-6-imines and related tricyclic derivatives, the parallel structural optimizations were investigated for the central 1,3-thiazin-2-imine core, the benzene part, and the cyclic amidine part of PD 404182. Replacement of the 6-6-6 pyrimido[1,2-c][1,3]benzothiazin-6-imine framework with 5-6-6 or 6-6-5 derivatives led to a significant loss of anti-HIV activity, and introduction of a hydrophobic group at the 9- or 10-positions improved the potency. The most potent PD 404182 derivative exerts anti-HIV effects at an early stage of viral infection including binding and fusion."
8066,Leitsymptomorientierte Sonographie,"Symptomenkomplex bestehend aus akutem Beginn und akuter Funktionsstörung intra-, aber auch extraabdomineller Organe mit möglicherweise lebensbedrohlichen Folgen."
8067,Building Porosity for Better Urban Ventilation in High-Density Cities,"Given that building typology is one of the key elements in architectural design and that the drag force of surface roughness on airflow directly depends on building typologies, it is important to expand our understandings on wind environment from urban and neighborhood scale to the building scale. In this chapter, CFD simulation was conducted to provide the detailed understandings on pedestrian-level wind environment and building typologies. First, [Formula: see text] SST turbulence model was validated by comparing modeling results with data from the wind tunnel experiment. Second, the impact of various building typologies on pedestrian-level airflow were investigated in a parametric study, in which various parametric cases with different wind porosities were designed, and wind speed was classified based on PET to evaluate outdoor thermal comfort. Subsequently, critical design issues were identified, and the corresponding mitigation strategies were developed. From both the accuracy and practical point of view, this chapter introduces a study that allows architects to improve building porosity efficiently for better pedestrian-level urban ventilation."
8068,Laboratory Processing of Specimens,"Although not always the first topic discussed when preparing for a bioemergency, the availability of a competent clinical laboratory is vital for the optimal care of a patient with a risk group 4 (RG-4) high-consequence pathogen. The recent development of highly specialized facilities in the United States to assess and treat patients with highly hazardous communicable diseases has led to the design of dedicated laboratories or the redesign of laboratory space to safely process and test specimens that might contain one of these pathogens. For frontline and other acute care facilities to be prepared, safety practices need to be assessed and reviewed as necessary as pertaining to all laboratory activities, to include the pre-analytical (specimen collection and processing), analytical (specimen testing), and post-analytical (specimen disposal/waste management and reporting) processes. Laboratorians and administrative personnel need to consider the risks in handling specimens containing these pathogens and subsequently develop or revise processes to mitigate risks. In addition, issues such as scalability to handle large volume testing, the availability of trained staff, and long-term sustainability to meet the requirements of regulatory agencies need to be adopted within a fiscally responsible budget setting. This chapter provides generalized information on how clinical laboratories, from those supporting small frontline medical facilities to highly specialized laboratories supporting acute care treatment centers, can safely manage specimens from a patient known or potentially infected with a high-consequence pathogen."
8069,Major Issues of Air Pollution,"Environmental issues change from place to place and time to time. The issues include local as well as global issues. The understanding of issues is necessary to find solution. Air pollution issues have changed over a period of time. Issues like atmospheric brown cloud, climate change, hazardous air pollutants, black/muddy snow which are hardly discussed few decades back have now gaining importance. This chapter elaborates major issues due to air pollution."
8070,Respiratory Infections,"Respiratory infections are the most frequent cause of athletes’ visits in medical practices. Simultaneously, contradictory beliefs are generally held regarding influence of repeated exercise on immunity reflected in susceptibility to infections. Many tend to claim that exercise weakens the immunity and renders regular exercisers more prone to develop airway infections. On the other hand, voices are heard in favor of the possible beneficial influence of regular exercise on immune system efficiency. This chapter focuses on the associations of various kinds of exercise with respiratory infection susceptibility. Influence of exercise, in particular associated with competitive performance, on selected innate and acquired immune response mechanisms is also addressed."
8071,The HCV Replicase Complex and Viral RNA Synthesis,"Replication of hepatitis C virus (HCV) is tightly linked to membrane alterations designated the membranous web, harboring the viral replicase complex. In this chapter we describe the morphology and 3D architecture of the HCV-induced replication organelles, mainly consisting of double membrane vesicles, which are generated by a concerted action of the nonstructural proteins NS3 to NS5B. Recent studies have furthermore identified a number of host cell proteins and lipids contributing to the biogenesis of the membranous web, which are discussed in this chapter. Viral RNA synthesis is tightly associated with these membrane alterations and mainly driven by the viral RNA dependent RNA polymerase NS5B. We summarize our current knowledge of the structure and function of NS5B, the role of cis-acting replication elements at the termini of the genome in regulating RNA synthesis and the contribution of additional viral and host factors to viral RNA synthesis, which is still ill defined."
8072,Fettsenker gegen Grippe,In China sind an der Vogelgrippe mit dem H7N9-Erreger nach offiziellen Angaben bisher zehn Menschen gestorben. Die Zahl der neuen Fälle geht zurück. Zum einen hat China aus der SARS-Pandemie 2002 gelernt und zum anderen scheint das Grippevirus keine Sommerhitze zu vertragen.
8073,History and Philosophy of Science and the Teaching of Macroevolution,"Although macroevolution has been the subject of sustained attention in the history and philosophy of science (HPS) community, only in recent years have science educators begun to more fully engage with the topic. This chapter first explores how science educators have conceptualized macroevolution and how their perspectives align with the views from HPS. Second, it illustrates how science educators’ limited engagement with HPS scholarship on macroevolution has influenced construct delineation, measurement instrument development, and educational arguments about which aspects of macroevolution are most important for students to learn. Third, it discusses how scientific debates about the causal factors responsible for macroevolutionary patterns have been exploited by creationists and have impacted the teaching of evolution. Finally, it emphasizes that the rich perspectives that HPS has to offer on the important topic of macroevolution have yet to be integrated into science education scholarship."
8074,Demyelination,"Acute disseminated encephalomyelitis (ADEM) is a demyelinating disease that affects all ages, except children less than 2 years. It occurs during the course of various infections, particularly the acute exanthematous diseases of childhood (measles, rubella, chickenpox, and smallpox immunization), other common viral infections (i.e., Epstein-Barr virus, adenovirus, cytomegalovirus, influenza, rhinoviruses, coronaviruses), and following vaccination against smallpox, measles, and rabies. The clinical features are the same regardless of the inciting event. The symptoms develop days to weeks after the onset of the predisposing cause. The symptoms and signs of acute disseminated encephalomyelitis are related to the portion of the central nervous system (CNS) that is most severely damaged. Death occurs in 20%–30%. There are neurological deficits in survivors."
8075,Disease Outbreaks: Critical Biological Factors and Control Strategies,"Disease outbreaks remain a major threat to human health and welfare especially in urban areas in both developed and developing countries. A large body of theoretical work has been devoted to modeling disease emergence, and critical factors that predict outbreak occurrence and severity have been proposed. In this chapter, we focus on biological factors that underlie both theoretical models and urban planning. We describe the SARS 2002–2003 pandemic as a case study of epidemic control of a human infectious disease. We then describe theoretical analyses of disease dynamics and control strategies. An important conclusion is that epidemic control will be strongly dependent on particular aspects of pathogen biology including host breadth, virulence, incubation time, and/or mutation rate. The probability, and potential cost, of future outbreaks, may be high and lessons from both past cases and theoretical work should inform urban design and policy. Interdisciplinary collaboration in planning, swiftness of information dissemination and response, and willingness to forgo personal liberties during a crisis may be key factors in resilience to infectious disease outbreaks."
8076,Besmettingsbronnen,"Infectieziekten kunnen zich op twee manieren voordoen (Van Furth e.a., 1992): endemisch en epidemisch. Een endemische infectie komt over een langere tijd in constante frequentie in een bevolkingsgroep voor. Van een epidemie wordt gesproken indien er in relatief korte tijd een sterke toename is van het aantal ziektegevallen. Wat nog endemisch heet en wat een epidemie is, hangt af van de aard van de ziekte en de omstandigheden."
8077,Prediction of Ribosomal -1 Frameshifts in the Escherichia coli K12 Genome,"Ribosomal frameshifting at a particular site can yield two protein products from one coding sequence or one protein product from two overlapping open reading frames. Many organisms are known to utilize ribosomal frameshifting to express a minority of genes. However, finding ribosomal frameshift sites by a computational method is difficult because frameshift signals are diverse and dependent on the organisms and environments. There are few computer programs available for public use to identify frameshift sites from genomic sequences. We have developed a web-based application program called FSFinder2 for predicting frameshift sites of general type. We tested FSFinder2 on the Escherichia coli K12 genome to detect potential -1 frameshifting genes. From the genome sequence, we identified 18,401 frameshift sites following the X XXY YYZ motif. 11,530 frameshift sites out of the 18,401 sites include secondary structures. Comparison with the GenBank annotation produced 11 potential frameshift sites, including 3 known frameshift sites. The program is useful for analyzing frameshifts of various types and for discovering new genes expressed by frameshifts."
8078,Danger in Paradise,"A 31-year-old man presented to the Student Health Center for evaluation 3 days after departing Hong Kong. On the last day of his 3-week-long trip to Southeast Asia, he developed sudden onset of fever, arthralgia, and headache. He initially attributed his symptoms to exhaustion, but the symptoms persisted. He also had several loose, non-bloody stools, a problem that resolved without intervention."
8079,Preoperative Evaluation and Arrangements for Multiorgan Donation: General Principles and Contraindications,"In this chapter we discuss these points:1) Donor coordinator’s duties. Promote and facilitate the entire donation process. Provide support to families regarding organ and tissue donation. Ensure that donation proceeds in line with national legislation, policies, and procedures. Obtain all information to allow transplant centers to assess the suitability of potential donors. Assist in the optimization of organs for transplant through appropriate donor management. Maximize the placement of organs for transplant. Train donation services’ team members.Collect data for organ donation-related audits. Facilitate and support the education of healthcare professionals and the general public.2) Exclusion criteria for infection transmission of organ donors.3) Donor exclusion criteria for hearth, lung, liver, kidney, pancreas and intestine."
8080,Mental Health Care for Survivors and Healthcare Workers in the Aftermath of an Outbreak,"When pandemics sweep across communities, they leave behind tremendous suffering in their wake. It is not only the illness that becomes a pandemic, but the same can be inferred about fear, mourning, and despair. The reverberations of loss are felt in a multitude of ways by those left behind. Often times, the mental health issues of affected persons and entire communities do not receive the attention they deserve in the light of other competing, immediate needs imparted by the devastation of the pandemic. This chapter aims to develop strategies for providing psychiatric care to survivors and their families, in the aftermath of a pandemic outbreak. Lastly, special considerations in the application of psychopharmacological interventions are reviewed."
8081,Defense Against Biological Weapons (Biodefense),"Biological warfare (germ warfare) is defined as the use of any disease-causing organism or toxin(s) found in nature as weapons of war with the intent to destroy an adversary. Though rare, the use of biological weapons has occurred throughout the centuries."
8082,Emerging and Rare Viral Infections in Transplantation,"Immunocompromised patients such as those undergoing solid organ or hematopoietic stem cell transplantation are at substantial risk for infection with numerous pathogens. Infections with cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein–Barr virus (EBV), and human herpesvirus-6 (HHV-6) are well-described complications of transplantation. As viruses previously believed to be quiescent through widespread vaccination (e.g., measles and mumps) reemerge and molecular diagnostic techniques are refined, rare and emerging viral infections are increasingly diagnosed in transplant recipients. This chapter will review the clinical manifestations, diagnosis, and potential antiviral therapies for these viruses in the transplant population."
8083,Immunology,"The immune defence mechanisms by which an organism combats viral infections can be divided into two systems. On the one hand, there are the unspecific, non-adaptive immune reactions, which recognize and eliminate invading foreign pathogens. This so-called natural or innate immune system becomes primarily active after a virus has overcome the external physical protection barriers of the body (skin, mucous membranes). It consists of dendritic cells, granulocytes, monocytes, macrophages and natural killer cells (NK cells). They have proteins that serve as receptors, e.g. Toll-like receptors (TLRs) and complement receptors, for specific structures of pathogens and for the soluble products of the innate immune system (acute-phase proteins, factors of the complement system, cytokines, chemokines and interferons). The effects and functions of cytokines, chemokines and interferons will be discussed separately in Chap. 8. The specific, adaptive immune response is the second line of defence, and is developed only during or after the establishment of an infection. It includes antibody-producing B cells – the humoral immune system – as well as T-helper (T(H)) cells and cytotoxic T lymphocytes, which collectively constitute the cellular defence system. The adaptive immune reactions can selectively recognize certain pathogen types or subtypes, and in the case of a reinfection, they are able to recognize the pathogens again and eliminate them. They are long-lasting and a subset of stimulated lymphocytes transform into memory cells during their development, which confers on the organism an efficient protective immunity against infections with the same pathogen. The systems of the specific and non-specific immune responses are in close contact with each other, particularly via cytokines, chemokines and interferons. An immune response is generally triggered by antigens. These may be the infectious pathogens, individual protein components or sugar structures. The immune system recognizes these as foreign, and thus can distinguish between endogenous and exogenous components. However, the antigens must be of a certain size to trigger different immune responses. Molecules with a molecular mass of less than 3–4 kDa are usually incapable of doing that."
8084,Inner Ear,"Herpes zoster oticus, herpes zoster cephalicus, Ramsay Hunt syndrome."
8085,Emergency Care,Children less than 6 years have the greatest risk for accidental ingestion and poisoning.
8086,The Safety Profile of Filgrastim and Pegfilgrastim,"The discovery of endogenous proteins that regulate hematopoiesis led to the identification of human granulocyte colony-stimulating factor (G-CSF). With the advent of recombinant DNA technology, it became possible to manufacture bioactive recombinant proteins for medicinal use. Since the approval of recombinant human G-CSF (rHuG-CSF), such as filgrastim in 1991 and pegfilgrastim in 2002, millions of patients at risk for severe myelosuppression have received these products. Overall, filgrastim and pegfilgrastim have a high margin of safety for short-term use; however, rare severe adverse events have emerged and questions remain regarding the long-term safety and consequences of use of these products. This chapter primarily focuses on the safety and adverse event profile of the most widely used commercially available rHuG-CSF, Neupogen (filgrastim) and Neulasta [a modified (pegylated) filgrastim, pegfilgrastim]. As safety information can change rapidly, we suggest readers consult the latest package inserts for any changes that have occurred from the time of this writing. Other chapters in this volume discuss key studies in specific disease settings in greater detail than is the purview of this chapter, and we encourage the interested reader to reference them for further information."
8087,Virus-Induced Demyelination: The Case for Virus(es) in Multiple Sclerosis,"Multiple Sclerosis (MS) is the most common demyelinating disease of man with over 400,000 cases in the United States and over 2.5 million cases worldwide. There are over 64,000 citations in Pubmed dating back as far as 1887. Much has been learned over the past 129 years with a recent burst in therapeutic options (mostly anti-inflammatory) with newer medications in development that are neuroprotective and/or neuroreparative. However, with all these advancements the cause of MS remains elusive. There is a clear interplay of genetic, immunologic, and environmental factors that influences both the development and progression of this disorder. This chapter will give a brief overview of the history and pathogenesis of MS with attention to how host immune responses in genetically susceptible individuals contribute to the MS disease process. In addition, we will explore the role of infectious agents in MS as potential “triggers” of disease. Models of virus-induced demyelination will be discussed, with an emphasis on the recent interest in human herpesviruses and the role they may play in MS disease pathogenesis. Although we remain circumspect as to the role of any microbial pathogen in MS, we suggest that only through well-controlled serological, cellular immune, molecular, and animal studies we will be able to identify candidate agents. Ultimately, clinical interventional trials that either target a specific pathogen or class of pathogens will be required to make definitive links between the suspected agent and MS."
8088,Hepatobiliäre Funktionsstörungen und Leberversagen,Als »sepsisinduzierte Cholestase« bezeichnet man das Auftreten einer konjugierten Hyperbilirubinämie als Folge einer extrahepatischen bakteriellen Infektion ohne direkte Invasion der Leber durch Erreger.
8089,Harnessing T-Cell Immunity to Target Brain Tumors,"T-cell mediated immunotherapy is a conceptually attractive treatment option to envisage for glioma, since T lymphocytes can actively seek out neoplastic cells in the brain, and they have the potential to safely and specifically eliminate tumor. Some antigenic targets on glioma cells are already defined, and we can be optimistic that more will be discovered from progress in T-cell epitope identification and gene expression profiling of brain tumors. In parallel, advances in immunology (regional immunology, neuroimmunology, tumor immunology) now equip us to build upon the results from current immunotherapy trials in which the safety and feasibility of brain tumor immunotherapy have already been confirmed. We can now look to the next phase of immunotherapy, in which we must harness the most promising basic science advances and existing clinical expertise, and apply these to randomized clinical trials to determine the real clinical impact and applicability of these approaches for treating patients with currently incurable malignant brain tumors."
8090,Surveillance and Control of Communicable Disease in Conflicts and Disasters,
8091,Viral Infections,"Despite major advances in basic and applied research and the availability of several vaccines, viral diseases still account for a large proportion of the human infectious disease burden. Many viruses cause self-limiting and relatively mild infections, but several, including human immunodeficiency virus and influenza virus, are responsible for millions of deaths every year throughout the world. Several factors contribute to the enormous impact that viruses have on human health. For example, there are very few therapeutic options available for the treatment of viral infections, and many of those that are available possess a limited spectrum of activity or are designed for the treatment of diseases caused by specific viruses (e.g., oseltamivir is intended for the treatment of influenza only). In addition, the rapid evolution of viruses has led to the emergence of drug-resistant strains against which no currently available therapeutics are effective. Coupled with these and other issues are the appearance of never before seen viruses and the emergence of known but previously underappreciated viruses. Since the beginning of the twenty-first century, numerous “new” viruses, including the coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the 2009 pandemic influenza A virus, and Lujo hemorrhagic fever virus, have made their debut and have proved to be formidable threats to human health. Recently, the appearance of Ebola virus (Zaire ebolavirus) in West Africa, a region that has not previously seen an outbreak of this virus, was marked by an epidemic that afflicted nearly 30,000 individuals and killed more than 11,000 of those who were infected. Most recently, the far-reaching and rapid spread of Zika virus, a mosquito-borne virus that was discovered in the 1940s in Uganda, in the Western Hemisphere has invoked considerable public and scientific attention and has given rise to perhaps the largest concerted effort by scientists to rapidly develop a vaccine to halt the transmission of a virus. Each of these points underscores the importance of further research into improved surveillance, diagnosis, treatment, and prevention of viral diseases."
8092,Protein Microarrays for the Detection of Biothreats,"Although protein microarrays have proven to be an important tool in proteomics research, the technology is emerging as useful for public health and defense applications. Recent progress in the measurement and characterization of biothreat agents is reviewed in this chapter. Details concerning validation of various protein microarray formats, from contact-printed sandwich assays to supported lipid bilayers, are presented. The reviewed technologies have important implications for in vitro characterization of toxin–ligand interactions, serotyping of bacteria, screening of potential biothreat inhibitors, and as core components of biosensors, among others, research and engineering applications."
8093,DC-SIGN Family of Receptors,"In the immune system, C-type lectins and CTLDs have been shown to act both as adhesion and as pathogen recognition receptors. The Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) and its homologs in human and mouse represent an important C-type lectin family. DC-SIGN contains a lectin domain that recognizes in a Ca(2+)-dependent manner carbohydrates such as mannose-containing structures present on glycoproteins such as ICAM-2 and ICAM-3. DC-SIGN is a prototype C-type lectin organized in microdomains, which have their role as pathogen recognition receptors in sensing microbes. Although the integrin LFA-1 is a counter-receptor for both ICAM-2 and ICAM-3 on DC, DC-SIGN is the high affinity adhesion receptor for ICAM-2/-3. While cell–cell contact is a primary function of selectins, collectins are specialized in recognition of pathogens. Interestingly, DC-SIGN is a cell adhesion receptor as well as a pathogen recognition receptor. As adhesion receptor, DC-SIGN mediates the contact between dendritic cells (DCs) and T lymphocytes, by binding to ICAM-3, and mediates rolling of DCs on endothelium, by interacting with ICAM-2. As pathogen receptor, DC-SIGN recognizes a variety of microorganisms, including viruses, bacteria, fungi and several parasites (Cambi et al. 2005). The natural ligands of DC-SIGN consist of mannose oligosaccharides or fucose-containing Lewis-type determinants. In this chapter, we shall focus on the structure and functions of DC-SIGN and related CTLDs in the recognition of pathogens, the molecular and structural determinants that regulate the interaction with pathogen-associated molecular patterns. The heterogeneity of carbohydrate residues exposed on cellular proteins and pathogens regulates specific binding of DC-expressed C-type lectins that contribute to the diversity of immune responses created by DCs (van Kooyk et al. 2003a; Cambi et al. 2005)."
8094,Risks and Safety Aspects of MR-PET,"The introduction of MR-PET systems into medical practice not only may lead to a gain in clinical diagnosis as compared to PET-CT imaging due to the superior soft tissue contrast of the MR technology but can also substantially reduce exposure of patients to ionizing radiation. On the other hand, there are also risks and health effects associated with the use of diagnostic MR devices that have to be considered carefully. In this chapter, the biophysical and biological aspects relevant for the assessment of health effects related to the use of ionizing radiation in PET and (electro)magnetic fields in MR are summarized. On this basis, the current safety standards will be presented – which, however, do not address the possibility of synergistic effects of ionizing radiation and (electro)magnetic fields. In the light of the developing MR-PET technology, it is of utmost importance to investigate this aspect in more detail for exposure levels that will occur at MR-PET systems. Finally, some considerations concerning the justification and optimization of MR-PET examination will be made."
8095,The Aliens in Us and the Aliens Out There: Science Fiction in the Movies,"The notion and images of aliens are for the most part an outcome of collective societal occurrences that often consists of personalized accounts of encounters with other beings, and in many ways are like our own dreams which are based on our life experiences. Cinematic portrayals of aliens can tell us much about what is going on in human minds. And it works the other way around as well: just as movies can reflect social distress, they also have the capacity to add to, or exacerbate social distress. Movies are similar to dreams and nightmares in that they employ the language of dreams to powerful effect. Aliens appear in human folklore because they are equipped by us with traits and characteristics we secretly desire such immortality. There are as many types of aliens as there are social dreams. During the Cold War era some of the prevailing social dreams were haunted by the specter of nuclear annihilation, and the idea of alien threat continues to make up the majority of film science fiction productions. Yet aliens are not always treated as malevolent beings that have come to usurp our societies, seize control of the planet, and pilfer our resources: the human/alien crews in Star Trek represent a social dream that society perceives as desirable."
8096,"Health Policy, Programmes and Initiatives","Environment as an input for good health and wellbeing should be protected and preserved. Reflecting on the growing urban spaces associated with increasing number of city inhabitants, it becomes imperative to plan for particularly urban health. Keeping in mind the future needs and demands, the government plans to build 100 new smart cities in India. This is in cognizance with the Sustainable Cities and Human Settlements and Sustainable Development Goals to build planned resilient sustainable cities that are prepared for disasters and promote health and wellbeing. The present chapter encapsulates landmark policies, acts and programmes undertaken by the government of India to promote good health and wellbeing and pave way for bringing sustainable urban development."
8097,Grundlagen der Zellbiologie,"Die Vorstellung, dass Lebewesen aus einer oder mehreren Zellen bestehen, die alle mehr oder weniger nach dem gleichen Prinzip funktionieren, existiert bereits seit langer Zeit und konnte sich infolge der Entdeckung der Mikroskopie nach und nach durchsetzen. Der Engländer R. Hooke (1635–1703) führte Untersuchungen von Pflanzengewebe mithilfe eines relativ einfachen Gerätes durch. Das Korkgewebe erschien ihm als eine Aneinanderreihung von Kästen, die er als „Zellen“ bezeichnete (Abb. 1.1). Der Holländer A. van Leeuwenhoeck (1632–1723) entwickelte etwas später das erste Mikroskop. Es handelte sich um eine einfache Anordnung von schmalen Lupen, die zusammen mit dem Objekt vor dem Auge platziert wurden. Leeuwenhoeck konnte auf diese Weise eine Vergrößerung auf das 200-Fache erreichen. Er führte zahlreiche Beobachtungen und Beschreibungen einzelliger Organismen wie Protozoen und Bakterien durch. Erst viel später kam mit den Zoologen und Botanikern T. Schwann (1810–1882) und M. Schleiden (1804–1881) die Theorie von der Zelle auf. Sie bestätigten, dass alle Lebewesen, auch die hoch Entwickelten, aus Zellen und deren Zellprodukten aufgebaut sind. R. Virchow (1821–1902) ergänzte diese Theorie 1855 durch eine zweite Behauptung: Omnis cellula e cellula – „Jede Zelle entsteht aus einer anderen Zelle“."
8098,Mers-CoV and Zika Virus,"Chapter 6 analyses the recent emergence of Mers-CoV and the spread of Zika virus around the globe. With a glace into the future, especially with regard to emerging infectious diseases (EID), it explores the most important indicators of such emergence and spread, asking which local, national, and international characteristics come to the fore to heighten or mitigate such threats. It further initially evaluates how these might interact with accelerators such as climate change and migration, exploring in particular the allocation of health rights and responsibilities across borders. Between the timelines of response and the anticipation of new outbreaks, the chapter offers some pointers on what decision-makers need to take into account to prepare for EIDs."
8099,"Work, Health, Safety and Well-Being: Current State of the Art","This introductory chapter will present a review of the current state of the art in relation to employee health, safety and well-being (HSW). The work environment and the nature of work itself are both important influences on HSW. A substantial part of the general morbidity of the population is related to work. It is estimated that workers suffer 270 million occupational accidents and 160 million occupational diseases each year. The chapter will first define HSW. It will then review the current state of the art by outlining key HSW issues in the contemporary world of work, identifying key needs. It will then discuss the evolution of key theoretical perspectives in this area by linking theory to practice and highlighting the need for aligning perspectives and integrating approaches to managing HSW in the workplace."
8100,Psoriasis: Overview and Diagnosis,"Psoriasis is a chronic, common, inflammatory skin disease. The classic skin lesions can be described as sharply demarcated, scaly, erythematous plaques often found on the extensor surfaces. Several variants of psoriasis have also been described, including palmoplantar, pustular, erythrodermic, and guttate forms. Although psoriasis is usually diagnosed clinically, characteristic histologic findings include hyperkeratosis, parakeratosis, and acanthosis of the epidermis with dilated blood vessels and a lymphocytic infiltrate. Psoriasis is an immune-mediated disease, and although the etiology is not fully understood, genetic and environmental factors have been implicated. Importantly, psoriasis is associated with a number of systemic complications and comorbidities that have a high impact on affected patients."
8101,Biosensors in Tissue and Organ Fabrication,"We begin this chapter by looking at the role of sensors during tissue and organ fabrication. We provide a working model for sensor technology to support different parts of the tissue fabrication pathway. We next look at biological sensors in nature, with IGF-1 signaling as an example and study the intracellular signaling events which take place in response to IGF-1 signaling. Next, we look at the design requirements for sensors to support the culture and fabrication of 3D artificial tissue. The next three sections are dedicated to three specific sensing mechanisms, which include acoustic sensors, magnetic sensors and optical sensors. For each of the three sensor mechanism, we provide an overview of the theory, along with some applications to illustrate the principles of operation. We then look at flexible sensors and how they have been used for various applications and the potential role of flexible sensors in tissue engineering. We conclude this chapter by providing a case study from the Artificial Heart Laboratory; the case study is focused on the development of novel sensors to record the EKG properties of 3D artificial heart muscle."
8102,Obstetric Medicine,"—to maintain adequate uterine perfusion, fetal oxygenation, and nutrient delivery. May potentially mask serious illness"
8103,Thermal investigation on whole plants and plant tissues,"In recent years, plant calorimetry has finished its sleeping beauty dormancy that lasted more or less continuously since the beginning of last century and realizes quite a number of scientifically attractive princes around it. They appeared with new armours and weapons and are eager to dedicate their life to her beauty. New sophisticated calorimeter allow investigations that were excluded before, combination with other highly specific instruments renders more information than gathered earlier by calorimetry alone, rigid and flexible light guides illuminate the otherwise dark vessels and open the field to photosynthesis experiments, infrared thermography provides a means to determine temperature distributions without injuring or even only touching the object. Imagination and technical skill are asked for further developments in plant calorimetry that will for sure come. A special issue of Thermochimica Acta in 2004 will be dedicated to the outcomes of the XIII(th) Conference of the International Society for Biological Calorimetry Energetics of Adaptation and Development — From Molecular Mechanisms to Clinical Practice that took place in Würzburg / Germany 2003. Many contributions deal with photocalorimetry and its application to plant systems as well as with conventional heat flow and combustion calorimetry for plant cells. Among other, topics like A new calorespirometric instrument, Calorespirometric ratios and metabolic efficiency, Energy processes in model plant cells, Heat production and respiration of wheat roots, Calorimetric studies of vegetable tissue wounding, Life zones for key plant species can be predicted with calorespirometry and temperature measurements; Photo-Bio-Calorimetry of Chlorella vulgaris growth, Energetic evaluation of forest formations by bomb calorimetry will be approached. This issue is recommended for further information."
8104,Lymphocyte trafficking and chemokine receptors during pulmonary disease,
8105,Disease Surveillance in Georgia: Benefits of International Cooperation,
8106,An Evaluation of China’s Influenza A (H1N1) Emergency Response Measures,"In order to stay up to date on epidemic trends and monitor possible mutations of the virus in the wake of an outbreak, China invested nearly 400 million RMB on testing large amounts of specimens and expanding the influenza monitoring network to include 411 influenza monitoring network laboratories and 556 sentinel hospitals - a network which covered all prefectural-level cities and some priority districts and counties. All of these laboratories and hospitals were in operation by September, 2009 (see Fig. 5.1)."
8107,Bioinformatics,"Why is sequence, structure, and biological pathway information relevant to medicine? Where on the Internet should you look for a DNA sequence, a protein sequence, or a protein structure? What are two problems encountered in analyzing biological sequence, structure, and function? How has the age of genomics changed the landscape of bioinformatics? What two changes should we anticipate in the medical record as a result of these new information sources? What are two computational challenges in bioinformatics for the future?"
8108,Pneumonia,"This chapter describes the imaging patterns of pneumonia (lobar, lobular, interstitial, round) and its complications (abscess, empyema, pneumatocele); bacterial, fungal, and viral infections; and the many manifestations of pulmonary tuberculosis. ELECTRONIC SUPPLEMENTARY MATERIAL : The online version of this chapter (10.1007/978-3-030-16826-1_6) contains supplementary material, which is available to authorized users."
8109,"Endogenous DAMPs, Category I: Constitutively Expressed, Native Molecules (Cat. I DAMPs)","This chapter provides the reader with a collection of endogenous DAMPs in terms of constitutively expressed native molecules. The first class of this category refers to DAMPs, which are passively released from necrotic cells, and includes the most prominent subclasses of high mobility group box I and heat shock proteins. Further subclasses of DAMPs that are passively released from necrotic cells include S100 proteins, nucleic acids, histones, pro-forms of interleukin-1-family members, mitochondria-derived N-formylated peptides, F-actin, and heme. A particular subclass of these passively released DAMPs are molecules, which indirectly activate the inflammasome, including adenosine-5′-triphosphate, monosodium urate crystals, cholesterol crystals, some lipolytic species, and beta-amyloid. All these passively released DAMPs are characterized by their capability to promote necroinflammatory responses. The second class of this Category I refers to molecules, which are exposed on the surface of stressed cells. They include the subclass of phagocytosis-facilitating molecules such as calreticulin, as well as the subclass of MHC-I-related molecules such as MHC-I-related molecule A and B. These DAMPs are capable of inducing the activation of innate lymphoid cells and unconventional T cells. One of these DAMPs, the major histocompatibility complex I-related molecule A, is shown to act as a bona fide transplantation antigen. In sum, the endogenous constitutively expressed native molecules represent an impressive category of DAMPs with extraordinary properties, which play a critical role in the pathogenesis of many human diseases."
8110,"Birds, Pigs, and People: The Rise of Pandemic Flus","In early April 2009, a ten-year-old boy in San Diego County, California, showed up at an outpatient clinic with fever, severe cough, and vomiting. Suspecting flu, the health worker took a routine throat swab and sent it to the county laboratory."
8111,Global Stability Analysis of HIV+ Model,"We developed and studied a mathematical model of HIV+. Two equilibriums points were found, disease free and endemic equilibrium, and basic reproduction ratio [Formula: see text] was also calculated by the use of next generation matrix. Global stability analysis of the equilibria was carried out by the use of Lyapunov function, and it was shown that the stability of the equilibria depends on the magnitude of the basic reproduction ratio. When [Formula: see text] , the disease free equilibrium is globally asymptotically stable, and disease dies out. On the other hand if [Formula: see text] , the endemic equilibrium is globally asymptotically stable and epidemics occurs. Reported cases of 13646 HIV-1 positive were obtained in the year 2016 from Ministry of Health, Turkey (MOH). This data is used to present the numerical simulations, which supports the analytic result. [Formula: see text] was found to be 1.98998, which is bigger than 1, this shows the threat posed by HIV in Turkey."
8112,Human and Animal Viruses in Food (Including Taxonomy of Enteric Viruses),"In recent years, there has been an increase in the incidence of foodborne diseases worldwide, with viruses now being recognized as a major cause of these illnesses. The most common viruses implicated in foodborne disease are enteric viruses, which are found in the human gastrointestinal tract, excreted in human feces and transmitted by the fecal-oral route. Many different viruses are found in the gastrointestinal tract but not all are recognized as foodborne pathogens. The diseases caused by enteric viruses fall into three main types: gastroenteritis, enterically transmitted hepatitis, and illnesses that can affect other parts of the body such as the eye, the respiratory system and the central nervous system leading to conjunctivitis, poliomyelitis, meningitis and encephalitis. Viral pathogens excreted in human feces include noroviruses, sapoviruses, enteroviruses, adenoviruses, hepatitis A virus (HAV), hepatitis E virus (HEV), rotaviruses, and astroviruses. Most of these viruses have been associated with foodborne disease outbreaks. Noroviruses and HAV are commonly identified as foodborne causes of gastroenteritis and acute hepatitis, respectively."
8113,Infektionsverlauf und Pathogenität,"Die Ausbreitung eines Virus im Organismus ist je nach Virus verschieden. Es gibt akute, persistierende und latente Virusinfektionen. Die pathogenen Eigenschaften eines Virus können durch das Virus direkt ausgelöste Schäden in den infizierten Zellen sowie indirekt durch die Auswirkungen der Immunantwort auf die Virusinfektion bedingt sein. Bei erstmaligem Kontakt mit einem Virus lösen Mechanismen der angeborenen Immunität (Basisabwehr) eine Entzündung aus, welche die adaptive Immunität anregt; gemeinsam blockieren sie die weitere Replikation und Ausbreitung. Bei einer Zweitinfektion reagiert die adaptive Immunität blitzschnell (»Gedächtnis«) fast ohne Entzündungen. Polymorphismen des Wirtes oder des Virus beeinflussen den Ablauf der Infektion."
8114,Case Study – France,"Emerging health risks, weapons of mass destruction, and terrorism – including biological weapons and bioterrorism – are identified in the 2008 White Paper on defence and national security as threats for France and its citizens. Since the beginning of the century, the 2001 anthrax attacks in the USA and subsequent hoaxes as well as the global SARS outbreak and influenza pandemic threats have all contributed to raise public awareness about health emergencies, leading authorities to adapt and improve planning for such events. This chapter focuses on natural and intentional public health threats and on biopreparedness from a French perspective, describing legal and organizational frameworks, plans and guidelines."
8115,Infektionen des ZNS,"Die Involvierung des Zentralnervensystems (ZNS) ist grundsätzlich eher eine seltene Manifestation einer viralen Infektion, wesentlich häufiger als das Hirngewebe werden die Meningen betroffen. Obwohl eine spezifische Therapie nur bei wenigen Viren, die eine Enzephalitis verursachen, verfügbar ist, ist eine frühestmögliche Diagnose und die daraus sich eventuell ableitende antivirale Therapie sowie eine maximale supportive/symptomatische Therapie essenziell, um die bestmögliche Prognose zu erreichen."
8116,Thrombotic Microangiopathy Syndrome in the ICU,"Major studies designed to improve our understanding of the pathophysiology of TMA have been conducted over recent years. This improved knowledge opens up new perspectives for more targeted treatment. However, until these innovative treatments become available, early diagnosis of these diseases is essential in order to rapidly initiate specific treatment, as the interval between diagnosis and initiation of plasma exchange is a decisive element in the prognosis of TTP. Treatment must not be stopped too early or too rapidly and must take into account the various associated factors, especially the presence of infection."
8117,Study of Sentiment Analysis Using Hadoop,"In the current world of Internet people express themselves, present their views and feelings about specific topics or entities using various social media application. These posts from users present a huge opportunity for the organizations to increase their market value by analyzing the posts and using information in decision making. These posts can be studied using various machine learning and lexicon-based approaches for extracting its sentiments. With more and more people moving to internet, huge data is being produced every second and challenge is to store this large data and process it efficiently in real time to infer knowledge from this data. This paper presents different approaches for real-time and scalable ways of performing sentiment analysis using Hadoop in a time efficient manner. Hadoop and its component tools like MapReduce, Mahout, and Hive are being surveyed in different scholar articles for this paper."
8118,High-Frequency Oscillatory Ventilation,
8119,Transgenic Farm Animals: Current Status and Perspectives for Agriculture and Biomedicine,"The first transgenic livestock were produced in 1985 by microinjection of foreign DNA into zygotic pronuclei. This was the method of choice for more than 20 years, but more efficient protocols are now available, based on somatic cell nuclear transfer (SCNT) which permits targeted genetic modifications. Although the efficiency of transgenic animal production by microinjection technology is low, many animals with agriculturally important transgenic traits were produced. Typical applications included improved carcass composition, lactational performance, and wool production as well as enhanced disease resistance and reduced environmental impact. Transgenic animal production for biomedical applications has found broad acceptance. In 2006 the European Medicines Agency (EMEA) approved the commercialization of the first recombinant protein drug produced by transgenic animals. Recombinant antithrombin III, produced in the mammary gland of transgenic goats, was launched as ATryn® for prophylactic treatment of patients with congenital antithrombin deficiency. Pigs expressing human immunomodulatory genes have contributed to significant progress in xenotransplantation research with survival periods of non-human primates receiving transgenic porcine hearts or kidneys approaching six months. Lentiviral vectors and small interfering ribonucleic acid (siRNA) technology are also emerging as important tools for transgenesis. As the genome sequencing projects for various farm animal species progress, it has become increasingly practical to target the removal or modification of individual genes. We anticipate that this approach to animal breeding will be instrumental in meeting global challenges in agricultural production in the future and will open new horizons in biomedicine."
8120,Next-Generation Sequencing and Its Application: Empowering in Public Health Beyond Reality,"Next-generation sequencing has the ability to revolutionize almost all fields of biological science. It has drastically reduced the cost of sequencing. This allows us to study the whole genome or part of the genome to understand how the cellular functions are governed by the genetic code. The data obtained in huge quantity from sequencing upon analysis gives an insight to understand the mechanism of pathogen biology, virulence, and phenomenon of bacterial resistance, which helps in investigating the outbreak. This ultimately helps in the development of therapies for public health welfare against human pathogen and diagnostic reagents for the screening. This chapter includes the basic of Sanger’s method of DNA sequencing and next-generation sequencing, different available platforms for sequencing with their advantages, and limitations and their chemistry with an overview of downstream data analysis. Furthermore, the breadth of applications of high-throughput NGS technology for human health has been discussed."
8121,Etiquette with Chinese Characteristics,"As China modernizes, it imports more and more Western culture and etiquette. The pace at which this is happening is at least as fast as the economy is growing. Over time, Western etiquette has been skillfully assimilated into the Chinese mainstream. It now looks and feels Chinese."
8122,Insect Biotechnology,"For the purpose of this work, insect biotechnology, which is also known as yellow biotechnology, is the use of insects as well as insect-derived cells or molecules in medical (red biotechnology), agricultural (green biotechnology), and industrial (white) biotechnology. It is based on the application of biotechnological techniques on insects or their cells to develop products or services for human use. Such products are then applied in agriculture, medicine, and industrial biotechnology. Insect biotechnology has proven to be a useful resource in diverse industries, especially for the production of industrial enzymes including chitinases and cellulases, pharmaceuticals, microbial insecticides, insect genes, and many other substances. Insect cells (ICs), and particularly lepidopteran cells, constitute a competitive strategy to mammalian cells for the manufacturing of biotechnology products. Among the wide range of methods and expression hosts available for the production of biotech products, ICs are ideal for the production of complex proteins requiring extensive posttranslational modification. The progress so far made in insect biotechnology essentially derives from scientific breakthroughs in molecular biology, especially with the advances in techniques that allow genetic manipulation of organisms and cells. Insect biotechnology has grown tremendously in the last 30 years."
8123,Norovirus Infection,"Norovirus (NoV) was first reported as causative agent of gastroenteritis in 1972, when students and staff of an elementary school located in Norwalk, Ohio, USA, presented vomitus and diarrhoea. After this, a number of studies definitively associated the NoV infection with outbreaks of acute gastroenteritis. Nowadays, NoV is considered the leading cause of nonbacterial gastroenteritis outbreaks and severe childhood diarrhoea worldwide, including water- and food-borne outbreaks. In animals, NoV infections have been reported in swine, bovine, ovine, canine, feline, and murine. The pathogenic role of NoV infection and its impact in animal health are not completely clear. Most of the epidemiological studies detected NoV in asymptomatic animal hosts worldwide. However, there are studies that associated the NoV infection with disease, especially enteritis, in swine, bovine, canine, and feline. This chapter presents the NoV properties and describes the pathogenesis, epidemiology, and available techniques for diagnosis of the virus infection. Additionally, the NoV infection management and prophylaxis measures for livestock animal species are approached."
8124,Why This Book? An Introduction,"For the sake of simplicity, let us start by naming an infectious agent a “germ.” There are countless germs that can infect human, animal, and plant hosts. Germs can be transmitted directly between hosts via respiratory air droplets or bodily fluids (e.g., saliva, blood, or secretions from sexual organs). Germs can also be transmitted indirectly through an intermediary source, for instance via mosquitoes, ticks, rodents, environmental particles (e.g., contaminated water and food) or contaminated blood products. Germs evolve and transform while new germs emerge regularly, implying their supply can be considered infinite. A broad distinction is often made between microscopically small germs with relatively short life spans, which replicate within their hosts (often called microparasites such as viruses, bacteria, and fungi), and much larger germs with relatively longer life spans (often called macroparasites such as parasitic worms). Many germs live inside or on the surface of their hosts’ bodies without causing illness or even discomfort."
8125,Introduction: Infectious Animals and Epidemic Blame,"The Introduction to the edited volume summarises the chapters of the volume and discusses their contribution in the context of current historical and anthropological studies of zoonotic and vector-borne disease, with a particular focus on how epidemic blame is articulated in different historical, social and political contexts."
8126,Photo-Generation of Carbohydrate Microarrays,"The unparalleled structural diversity of carbohydrates among biological molecules has been recognized for decades. Recent studies have highlighted carbohydrate signaling roles in many important biological processes, such as fertilization, embryonic development, cell differentiation and cellȁ4cell communication, blood coagulation, inflammation, chemotaxis, as well as host recognition and immune responses to microbial pathogens. In this chapter, we summarize recent progress in the establishment of carbohydrate-based microarrays and the application of these technologies in exploring the biological information content in carbohydrates. A newly established photochemical platform of carbohydrate microarrays serves as a model for a focused discussion."
8127,"Towards Real Time Epidemiology: Data Assimilation, Modeling and Anomaly Detection of Health Surveillance Data Streams","An integrated quantitative approach to data assimilation, prediction and anomaly detection over real-time public health surveillance data streams is introduced. The importance of creating dynamical probabilistic models of disease dynamics capable of predicting future new cases from past and present disease incidence data is emphasized. Methods for real-time data assimilation, which rely on probabilistic formulations and on Bayes’ theorem to translate between probability densities for new cases and for model parameters are developed. This formulation creates future outlook with quantified uncertainty, and leads to natural anomaly detection schemes that quantify and detect disease evolution or population structure changes. Finally, the implementation of these methods and accompanying intervention tools in real time public health situations is realized through their embedding in state of the art information technology and interactive visualization environments."
8128,Infektionskrankheiten,
8129,A Writer’s Attic,"This chapter presents a miscellany of facts about writing: America’s first and oldest medical journal; the most remarkable feat of medical writing in more or less modern times; and the change in focus in medical journals. The chapter describes “authorisms,” neosyndromes, and classic gaffes in the medical literature. There is advice about what to think about when invited to edit a clinical reference book. There are also tales of retracted scientific articles and fake medical journals, and advice for aspiring medical writers, including books and websites to consult."
8130,Metabolische Störungen,"Bei fortgeschrittenem Organversagen von Niere, Herz, Leber oder Lunge stellt eine Organtransplantation meist das einzige kurative Therapieverfahren dar. Daneben ist die allogene bzw. in Sonderfällen auch die autologe Knochenmarktransplantation eine Therpieoption bei Leukämien, Lymphomen, myelodysplastischen Syndromen, angeborenen Stoff wechsel- und Immundefekten sowie auch in seltenen Fällen bei schweren Autoimmunerkrankungen."
8131,Community-Acquired Pneumonia and Health Care-Associated Pneumonia Clinical Guidelines,"The Infectious Disease Society of America (IDSA) produced clinical guidelines on the care of community-acquired pneumonia (CAP) in immunocompetent adults in 2000 and 2003 (1,2). Throughout the guidelines, a grading system is used to categorize the strength of evidence behind various recommendations (3), as listed in Table 1."
8132,Towards Identifying and Predicting Spatial Epidemics on Complex Meta-population Networks,"In the past decade, the network science community has witnessed huge advances in the threshold theory, prediction and control of epidemic dynamics on complex networks. While along with the understanding of spatial epidemics on meta-population networks achieved so far, more challenges have opened the door to identify, retrospect, and predict the epidemic invasion process. This chapter reviews the recent progress towards identifying susceptible-infected compartment parameters and spatial invasion pathways on a meta-population network as well as the minimal case of two-subpopulation version, which may also extend to the prediction of spatial epidemics as well. The artificial and empirical meta-population networks verify the effectiveness of our proposed solutions to the concerned problems. Finally, the whole chapter concludes with the outlook of future research."
8133,Plasmofluidics for Biosensing and Medical Diagnostics,"Plasmofluidics, an extension of optofluidics into the nanoscale regime, merges plasmonics and micro-/nanofluidics for highly integrated and multifunctional lab on a chip. In this chapter, we focus on the applications of plasmofluidics in the versatile manipulation and sensing of biological cell, organelles, molecules, and nanoparticles, which underpin advanced biomedical diagnostics."
8134,Alveolar Lung Diseases,"Alveolar lung diseases (ALD) are group of disorders characterized by pathological insult involving mainly the alveoli. The alveoli can be imagined as an empty cup, and alveolar diseases are classified according to the content of this cup. Alveolar diseases are characterized by filling of the alveoli with materials that impede its normal physiological function (ventilation). Alveolar diseases can be localized (focal) or diffuse. Names of the conditions depend upon the content of the material filling the alveoli."
8135,Hygiene auf der IMC-Station,Laut Aussage des Bundesgesundheitsministeriums im Juli 2011 erkranken in Deutschland jährlich 400.000–600.000 Menschen an einer Krankenhausinfektion. Schätzungsweise zwischen 7.500 und 15.000 Menschen sterben jährlich an einer Krankenhausinfektion. 20–30% der Infektionen könnten durch die Einhaltung von Hygienemaßnahmen vermieden werden (BMG 2012).
8136,"Optische und Elektronenmikroskopische Detektion – Erregerschnelldiagnostik, hochauflösende Lichtmikroskopie und Live-Cell-Imaging","Die Kombination aus Zellbiologie und Mikrobiologie hat mit der Zellulären Mikrobiologie eine neue Disziplin geschaffen, deren primäres Ziel die Erforschung des Zusammenspiels von Wirt und Erregern auf der Ebene des Gewebes, der Zelle und letztlich von einzelnen Molekülen ist. Die Entschlüsselung dieser dynamischen Interaktionen erlaubt ein tiefgreifendes Verständnis von Infektionsmechanismen sowie zellulärer Logistik und bereitet damit den Weg für die Entwicklung wirkungsvoller Therapeutika."
8137,Characterization of Synonymous Codon Usage in the Newly Identified Duck Plague Virus UL16 Gene,"A comparative analysis of the codon usage bias in the newly identified UL16 gene(GenBank accession no.EU195095) of DPV and the UL16 gene of 22 reference herpesviruses was performed. In this study, the synonymous codon usage bias of UL16 gene in the 23 herpesviruses have been analyzed and the results showed obvious differences by the CAI, RSCU, ENC and GC(3s). The results revealed that the synonymous codons with A and T at the third codon positon have widely usage in the codon of UL16 gene of DPV. The ENC-GC(3s) plot revealed that the genetic heterogeneity in UL16 gene of herpesviruses was constrained by G+C content at the third codon position. The phylogenetic analysis suggested that DPV was evolutionarily closer to herpesviruses which further clustered into Alphaherpesvirinae. Furthermore the ORF of DPV UL16 gene has sequential rare codons. There were 21 codons showing distinct usage differences between DPV with Escherichia coli, 19 codons showing distinct usage differences between DPV with yeast, and 20 between DPV and Human. Therefore the Escherichia coli, Yeast and Human expression system were suitable for the expression of DPV UL16 gene if some codons could be optimized."
8138,What Is a Virus?,"Viruses are built from short sequences of nucleic acid, either DNA or RNA wrapped in a protein shell. Until the invention of the electron microscope, it was impossible to visualize a virus. The first viruses to be visualized were bacteriophage, which appeared to have a head and tail-like structure. Only the nucleic acid entered the bacterial cell through the tail. Animal viruses were described as spherical or rod-shaped; they were bound to receptors and were taken up by the cell. After the crystallization of the tobacco mosaic virus, there was much discussion as to whether viruses were “living” organisms; the controversy continues to this day. Although viruses were defined in part on the basis of size and filterability, viruses much larger than the traditional viruses have recently been isolated. Studies of viral replication indicate that most viruses self-assemble as a result of interactions between the viral proteins to form a viral capsid that interacts with the nucleic acid to form the whole. The viral replication cycle and synthesis is presented in this chapter. Viral classification into a Linnaean scheme has been proposed, but newer methods using nucleic acid homologies are changing classification. Viruses are spread in the human population by various means, including airborne particles, fecal-oral contact, clothing, insects, and contact with other animals (zoonosis)."
8139,Vaccines,"Vaccines are predominantly used for prevention; that means they should establish a protection in immunized people or animals which will protect them from a possible infection and the subsequent illness when they come into contact with the respective pathogens. Fundamentally, there are two kinds of immunization: active and passive. The latter is based on the administration of immunoglobulin preparations that can neutralize a specific virus. Therefore, passive vaccination is applied only in special cases, such as when the person to be protected recently had verifiable contact with a specific virus (postexposure prophylaxis), or if the risk of exposure to pathogens cannot be ruled out in the following weeks and an active vaccination is not possible, as in short-term planned trips to Third World countries (exposure prophylaxis). An example is the administration of antibodies specific for hepatitis B virus in cases of contamination with blood from people who have an acute or chronically persistent infection with this virus, and thus have high concentrations of infectious particles in the blood. Such accidents occur primarily in medical personnel by needlestick injury (10.1007/978-3-642-20718-1_19). In certain cases, the administration is performed in combination with an active vaccination (active–passive immunization). Specific immunoglobulin preparations are also administered when people have been bitten by animals that may be infected with the rabies virus (10.1007/978-3-642-20718-1_15). In the case of early application (together with an active vaccination), the antibodies can neutralize the virus, and impede its spread in the body. Since the time between contact with the virus and its spread in the organism is often very short, passive immunization is limited to a period shortly before or after exposure to the infective agent (usually within 4 days). Therefore, it is reserved for cases in which the contact with the potential pathogen is well documented and the type of infection is known, and when an appropriate immunoglobulin preparation is available. The protection afforded by antibody preparations lasts just a few weeks, as immunoglobulins are rapidly degraded in the organism. Therefore, postexposure administration of active vaccines is increasingly preferred, e.g. in the context of outbreak-control vaccination. In veterinary medicine, passive immunization is employed occasionally in young animals which were born in a flock with high infection pressure. This approach is applied, for example, in kennels when infections occur with canine parvovirus (10.1007/978-3-642-20718-1_20). However, its value is controversial, as the immunoglobulins administered hinder the more advantageous active immunization."
8140,Survival and Transport of Enteric Viruses in the Environment,
8141,Gastroenterologie,"Die Gastroenterologie umfasst neben den klassischen Erkrankungen des Magen-Darm-Trakts (wie z .B. Ösophagitis, Hiatushernien, Gastritis, gastroduodenale Ulkuskrankheit, Malassimilationssyndrome, M. Crohn, Colitis ulcerosa, kolorektales Karzinom etc.) auch die pathologischen Veränderungen an Pankreas (Bauchspeicheldrüsenentzündung und Pankreaskarzinom), Leber (Hepatitis, Zirrhose, Leberversagen etc.) und Gallenblase bzw. -wege (PSC, PBC, Cholelithiasis, maligne Entartungen). Darüber hinaus werden in diesem Kapitel auch die neuroendokrinen Tumoren (NET) behandelt."
8142,"MMPs, inflammation and pulmonary arterial hypertension","Pulmonary arterial hypertension (PAH) is characterised by remodelling of small pulmonary arteries leading to a progressive increase in pulmonary vascular resistance and right ventricular failure [1]. PAH can be idiopathic, familial, or associated with a number of conditions or diseases, such as connective tissue disease. Its prognosis is poor, less than 3 yr from diagnosis. The aetiology of severe unexplained pulmonary hypertension remained largely unknown until a few years ago. The gene underlying familial PAH was identified in 2000, the BMPR-2 gene. However its mutations are not always present, and it probably does not explained the full scope of the disease. PAH is associated with structural alterations in pulmonary arteries including intimal fibrosis, medial hypertrophy and adventitial changes, pointing towards extracellular matrix remodelling which have raised the question of involvement of the matrix degrading enzymes. Among them, serine proteases, such as plasmina and endogenous vascular elastase (EVE), and matrix metalloproteases have been studied. In experimental models, the three of them are increased. Accordingly, their inhibition has preventing and in some cases therapeutic effects. However it should be stressed that opposite consequence of protease inhibition on PAH can be observed depending on the experimental model, either chronic hypoxia-induced PAH (deleterious) or toxic moncrotalin-induced PAH (positive). In humans, only sparse reports exist, that found increase in the MMP inhibitor, TIMP-1, and MMP-2 expression and decreased collagenase (MMP-1). Inflammation is part of the PAH, and accordingly, protease production is a well known part of the inflammatory response. Answering the question whether protease inhibition might represent a therapeutic option in human PAH is however certainly too early."
8143,A Case of Fever and Rash After a Tick Bite,"A 55-year-old man who lived in rural Indiana with a history of diabetes mellitus type 2 presented to the Emergency Department in May with 5 days of headache, fever to 104 °F, diffuse myalgias, and generalized weakness. He frequently performed yardwork. He had noticed a tick on his arm 10 days before that he removed with tweezers. He reported that it was not engorged. Three weeks prior to presentation, he went camping in the forest and slept in a cabin. He had frequent contact with his 3-year-old granddaughter who had a recent febrile upper respiratory illness."
8144,The Human Clone Market,"Imagine the following scenario. A few years from now, those who can afford it will contract cloning labs to grow clones to supply duplicate organs or replace body parts. Clones will be genetically matched to clients so they can be used in transplants without being attacked by the client’s immune system. To side-step the ethical argument of what is considered human, the client’s clones will be grown as headless embryos, without a brain or a central nervous system. Destined never to leave the lab, these cloned embryos will develop all the necessary body parts, including a heart, a circulatory system, lungs, and a digestive system. For those without deep pockets, the cloning labs will offer economy clones featuring one or more specific organs. Using embryo cloning techniques developed in Britain in the late 1990s, the cloning labs will grow these headless clones to match each stage of a child’s or adult’s development, so that organs will be available throughout the client’s life."
8145,Platelets and Airway Diseases,"The role of platelets as inflammatory cells is now well established. Given the peculiar characteristics of the lung circulation, with a broad capillary bed, platelets are especially involved with the physiology of the lungs and play a key role in a number of inflammatory lung disorders. The platelet precursors, megakaryocytes, are detected in the lung microcirculation; moreover platelets with their endothelium-protective and vascular reparative activities contribute to the lung capillary blood barrier integrity. Given the function of the lungs as first wall against pathogen invasion, platelets participate in immune defence of the normal lung. On the other hand, platelets may turn into effectors of the inflammatory reaction of the lungs to allergens, to infectious agents, to chemical agents and may contribute strongly to the perpetuation of chronic inflammatory reactions, largely by their ability to interact with other inflammatory cells and the endothelium. In this chapter we provide an overview of the role of platelets in several inflammatory lung disorders discussing the pathophysiologic bases of platelet involvement in these conditions and the experimental and clinical evidence for a role of platelets in lung diseases."
8146,Spread of Epidemics and Rumours with Mobile Agents,We propose a simple model of infection that enables to study the coincidence time of two random walkers on an arbitrary graph. By studying the coincidence time of a susceptible and an infected individual both moving in the graph we obtain estimates of the infection probability. The main result of this paper is to pinpoint the impact of the network topology on the infection probability.
8147,Gastroenterologie,
8148,Noninvasive Oxygen Therapies in Oncologic Patients,"Acute hypoxemic respiratory failure (ARF) is the most common cause of critical illness in oncologic patients. Despite significant advancements in survival of oncologic patients who develop critical illness, mortality rates in those requiring invasive mechanical ventilation have improved but remain high. Avoiding intubation is paramount to the management of oncologic patients with ARF. There are important differences between the oncologic patient with ARF compared to the general ICU population that likely underlie the increased mortality once intubated. Noninvasive oxygen modalities have been recognized as an important therapeutic approach to prevent intubation. Continuous low-flow oxygen therapy, noninvasive ventilation, and high-flow nasal cannula are the most commonly used noninvasive oxygen therapies in recent years. They have unique physiologic properties. The data surrounding their efficacy in the general ICU population and oncologic population has evolved over time reflecting the changes in the oncologic population. This chapter reviews the three different noninvasive oxygen modalities, their physiologic impact, and evidence surrounding their effectiveness."
8149,Essentials of the Production of Safe and Efficacious State-of-the-Art Polyclonal IgG Concentrates,"Severe noninfectious adverse events (AEs) and transmission of pathogens by plasma-derived protein concentrates from the very beginning of their clinical use were threats for recipients (see Chap. 10.1007/978-3-319-68038-5_11 for additional information). “Standard IgG” preparations were the first available for clinical use. They were produced by the cold-ethanol fractionation methods and did not make an exception. Noninfectious severe AEs occurred while infectious AEs were rarely reported. Indeed, prior to the introduction of mass screening for infection markers of plasma donations, inadvertent transmission of HIV to recipients of factor VIII and factor IX concentrates did occur, while IgG concentrates obtained from the same plasma pool did rarely transmit HIV (Morgenthaler 2001). Rare transmissions were restricted to products not exposed to low pH. The very few incidences of HIV and some incidences of HCV transmission by IgG concentrates in the early 1990s together with many cases of coagulation factor concentrates transmitted viral disease clearly demonstrated the need to establish standardized measures to render plasma products pathogen safe. In the second half of the 1990s, authorities shifted regulatory emphasis from a scientific review of the processes to a focus on compliance to current good manufacturing practice (cGMP). The focus on cGMP compliance was applied to all aspects of plasma fractionation and the clinical use of plasma products. Court injunctions and warning letters were the consequences of this paradigm shift by authorities. This in turn resulted in a paradigm shift how the modern plasma industry operates (Steinhardt 1998)."
8150,Molecular Inhibitors of Growth Signals,"Signal transduction associated with growth factor receptors typically mediates the activation of cell cycle promoting gene products or the inactivation of cell cycle checkpoints. These signals are frequently transduced through G-Protein pathways, kinase receptor pathways, or nuclear receptor pathways (Fig. 4.1), are dependent on proto-oncogenic transcription factors, and lead to the expression of Cyclins and Cyclin-Dependent Kinases (CDKs), which are drivers of the cell cycle (Fig. 4.2). Physiologically, growth signals are transient and entirely depend on the engagement of a growth factor receptor by its cognate ligand. Upon termination of this interaction, the growth signal ceases. Gain-of-function mutations in cancer keep the growth signal active, regardless of the presence of the transient growth factor-receptor interaction. Such deregulated signaling cascades are appropriate drug targets in the treatment of cancer."
8151,What Went Wrong? The World Health Organization from Swine Flu to Ebola,"Since 2001, the World Health Organization (WHO) has been actively promoting its ability to manage global health security. Recent events such as the 2009 H1N1 influenza pandemic and the 2014 Ebola outbreak have, however, led to questions being raised about the WHO’s abilities and extensive calls for the organisation’s reform. This chapter examines a series of mistakes and the structural, cultural, political and epidemiological factors that contributed to the WHO’s mishandling of the first pandemic of the twenty-first century and the world’s largest ever outbreak of Ebola. The chapter then concludes by examining the reforms currently being implemented to strengthen the WHO’s global health security capabilities and what these signify for the future."
8152,Care of the Critically Ill Pediatric Sickle Cell Patient,"Sickle cell disease is the most common inherited disease in the United States. Through the effects of hemolysis and vaso-occlusion, it has the potential to incite critical illness involving multiple organ systems. Children with sickle cell disease are at risk of multiple types of shock resulting in a need for ICU care. Our youngest patients with sickle cell disease are at highest risk of infection due to lack of splenic function, and this can present with septic shock. Hypovolemic shock can occur secondary to severe acute anemia as seen with splenic sequestration or a delayed transfusion reaction. As one ages, the risk of cardiac dysfunction – diastolic and systolic dysfunction as well as pulmonary hypertension – can result in cardiogenic shock. In addition to shock, patients with sickle cell disease are at risk for respiratory failure from acute chest syndrome as well as acute neurologic deterioration from stroke. For these reasons, critical care physicians must be familiar with the unique management of sickle cell complications in order to provide the best possible care for this vulnerable population."
8153,The ‘Next People’: And the Zombies Shall Inherit the Earth,"On Halloween night 2014 I stood with thousands of others along the side of a large boulevard in Amsterdam. There was an excited buzz rippling through the crowd and young children zipped in and out, threading their way around their parents and friends, vying for the best viewing locations. Their cries and laughter filled the air alongside the adult conversation and the sound of phones ringing as people attempted to find each other in the crowd. We were all waiting with mounting excitement for the annual Halloween Parade. It was running late. Heads turned down the street, cameras and phones at the ready, watching for any sign that the parade was arriving. Expectation hung in the air. Finally … music. And then a truck disguised as a giant metal dragon belching smoke and music lurched into view, followed by a slow moving phalanx of participants, all in Halloween costumes. Some of the walkers were waving at the crowd, others were ignoring us, while still others lunged at unsuspecting individuals with threatening roars and grimaces. An armada of decorated vehicles, flanked by phalanxes of monsters and ghouls moved slowly along the street."
8154,"Risk, Media and Japanese Young People","Theories of risk in society have defined and extrapolated on risk in multiple ways depending on the object of study and types of claims made by the author. Zinn (2008b) lists six main traditions, including risk society, cultural turn, and governmentality. One of the central problems that more recent work on risk has focused on is how risk varies according to the fabric of particular everyday lives in particular societies and under various types of social arrangements (Tulloch and Lupton, 2003; Tulloch, 2004). In this chapter I explore this problem of risk theory by looking at the views Japanese young people have about risk in Japanese society."
8155,Hochsicherheitslabor,"Das Planen, Bauen und Betreiben eines Hochsicherheitslabors muss sehr gut vorbereitet werden. Nutzer, spätere Anlagenbetreiber (Technik und Bau) und die Genehmigungsbehörde sollten rechtzeitig in das Verfahren eingebunden werden. Umfangreiche technische Kenntnisse, insbesondere das Zusammenspiel gewerksübergreifender Funktionen, sind notwendig. Dabei steht die Sicherheit an oberster Stelle. Dieses Kapitel gibt einen fundierten Überblick über die rechtlichen Grundlagen und Sicherheitsaspekte, die bei der Planung, der Errichtung und dem Betrieb von Hochsicherheitslaboren beachtet werden müssen."
8156,Care of the Surgical ICU Patient with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension,"Chronic obstructive pulmonary disease (COPD) is a progressive chronic disease characterized by airflow limitation that is frequently progressive and associated with respiratory impairment. As the fourth leading cause of death in the United States and Europe, COPD results in a substantial and ever increasing economic and social burden [1]. Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are frequently encountered in the intensive care unit (ICU). Although there is no standardized definition, AECOPD are characterized by a significant change in patient symptoms from baseline accompanied by overall increased airway resistance [2]. These exacerbations carry a significant risk to patients, with 10 % in-hospital mortality and 1-year and 2-year all-cause mortality rates of 43 % and 49 %, respectively, in patients with hypercapnic exacerbations [3]. Other studies note in-hospital mortality rates as high as 30 % with worse outcomes associated with older age, severity of respiratory and non-respiratory organ dysfunction, and hospital length of stay [4]. Given that patients transferred to the ICU with AECOPD are at high risk for complications and adverse outcomes, early diagnosis and management are critical to improve patient outcomes and survival in this population."
8157,Zoonotic Viruses and Conservation of Bats,"Many of the recently emerging highly virulent zoonotic diseases have a likely bat origin, for example Hendra, Nipah, Ebola and diseases caused by coronaviruses. Presumably because of their long history of coevolution, most of these viruses remain subclinical in bats, but have the potential to cause severe illnesses in domestic and wildlife animals and also humans. Spillovers from bats to humans either happen directly (via contact with infected bats) or indirectly (via intermediate hosts such as domestic or wildlife animals, by consuming food items contaminated by saliva, faeces or urine of bats, or via other environmental sources). Increasing numbers of breakouts of zoonotic viral diseases among humans and livestock have mainly been accounted to human encroachment into natural habitat, as well as agricultural intensification, deforestation and bushmeat consumption. Persecution of bats, including the destruction of their roosts and culling of whole colonies, has led not only to declines of protected bat species, but also to an increase in virus prevalence in some of these populations. Educational efforts are needed in order to prevent future spillovers of bat-borne viruses to humans and livestock, and to further protect bats from unnecessary and counterproductive culling."
8158,Mechanisms of symptoms of common cold and flu,"It is the familiar symptoms of sore throat, runny nose, sneezing, and nasal congestion, muscle aches, chilliness and fever, etc., that define the common cold and flu syndromes as self-diagnosed illnesses. Although there is much information about the molecular biology of the viruses that cause the common cold and flu syndromes, there is relatively little research on the immunological, physiological and pathophysiological mechanisms involved in generating the symptoms. This chapter studies the mechanisms that cause local symptoms associated with local inflammation of the airway (sore throat, sneezing, rhinorrhoea and purulent nasal discharge, nasal congestion, sinus pain, watery eyes and cough), and the mechanisms that cause systemic symptoms associated with release of cytokines from leukocytes (headache, chilliness and fever, psychological effects, malaise and mood changes, loss of appetite, and muscle aches and pains)."
8159,Immunorecognition of Biological Agents: An Introduction to Immunology,"The main mechanims and concepts regulating the functioning of the human immune system are illustrated, with the general aims of improving disease prevention and ecosystem dynamics knowledge. These concepts must be known for the best management of infectious diseases and in the paramount view of ecology and parasitism, which are at the basis of stage-sharing of the environment by different species of life, each defending its own uniqueness and biological existence. Man is only one of the many living species sharing the stage of the planet. These considerations are fundamental in the fields of infectious diseases and of bioterrorism which have to be efficiently contrasted."
8160,Porcine Coronaviruses,"Transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhoea virus (PEDV), and porcine deltacoronavirus (PDCoV) are enteropathogenic coronaviruses (CoVs) of swine. TGEV appearance in 1946 preceded identification of PEDV (1971) and PDCoV (2009) that are considered as emerging CoVs. A spike deletion mutant of TGEV associated with respiratory tract infection in piglets appeared in 1984 in pigs in Belgium and was designated porcine respiratory coronavirus (PRCV). PRCV is considered non-pathogenic because the infection is very mild or subclinical. Since PRCV emergence and rapid spread, most pigs have become immune to both PRCV and TGEV, which has significantly reduced the clinical and economic importance of TGEV. In contrast, PDCoV and PEDV are currently expanding their geographic distribution, and there are reports on the circulation of TGEV-PEDV recombinants that cause a disease clinically indistinguishable from that associated with the parent viruses. TGEV, PEDV and PDCoV cause acute gastroenteritis in pigs (most severe in neonatal piglets) and matches in their clinical signs and pathogenesis. Necrosis of the infected intestinal epithelial cells causes villous atrophy and malabsorptive diarrhoea. Profuse diarrhoea frequently combined with vomiting results in dehydration, which can lead to the death of piglets. Strong immune responses following natural infection protect against subsequent homologous challenge; however, these viruses display no cross-protection. Adoption of advance biosecurity measures and effective vaccines control and prevent the occurrence of diseases due to these porcine-associated CoVs. Recombination and reversion to virulence are the risks associated with generally highly effective attenuated vaccines necessitating further research on alternative vaccines to ensure their safe application in the field."
8161,Deubiquitinating Enzymes as Novel Targets for Cancer Therapies,"Most ubiquitinated proteins can be recognized and degraded by the 26S proteasome. In the meantime, protein deubiquitination by various deubiquitinating enzymes (DUBs) regulates protein stability within cells, and it can counterbalance intracellular homeostasis mediated by ubiquitination. Numerous reports have demonstrated that an aberrant process of the ubiquitin-proteasome pathway (UPP) regulated by the ubiquitination and deubiquitination systems results in failure of balancing between protein stability and degradation, and this failure can lead to tumorigenesis in various organs and tissues of mammals. The identification of molecular properties for various DUBs is very critical to understand cancer development and tumorigenesis. Therefore, knowledge of DUBs and their association with cancer and diseases is indispensible for developing effective inhibitors for DUBs. This chapter describes various features and functions of cancer-related DUBs. In addition, we summarize several inhibitors that specifically target certain DUBs in cancer and suggest that DUBs may be one of the most ideal and attractive therapeutic targets."
8162,Viral Proliferation and Replication,"As obligate cellular parasites, viruses do not have their own metabolism; therefore, they must infect cells for reproduction. The virus particles must be able to recognize specific receptor molecules on the cytoplasmic membrane of the host cell and to bind to them. This process is known as attachment. In enveloped viruses, this interaction is mediated by proteins that are embedded within the viral envelope. This is the case in influenza viruses as well as retroviruses and herpesviruses. Binding of viral envelope proteins to cellular surface structures is to some extent very specific: this is the case for the interaction between the surface protein gp120 of human immunodeficiency virus (HIV) and the CD4 receptor, a polypeptide that occurs almost exclusively in the cytoplasmic membrane of T-helper cells and macrophages (Sect. 10.1007/978-3-642-20718-1_18). In other cases, viral proteins bind to cellular structures that are found on many cell types. One example is the binding of haemagglutinin of influenza viruses (Sect. 10.1007/978-3-642-20718-1_16) to terminal N-acetylneuraminic acid residues of complex oligosaccharides, which are found as protein and lipid modifications on the membrane surface of various cells."
8163,Isolierungsmaßnahmen,"Die Kenntnis des infektionsspezifischen Übertragungsweges einer Erkrankung ist die entscheidende Voraussetzung zur Festlegung sinnvoller, d. h. effektiver Präventionsmaßnahmen, zu denen auch heute noch die räumliche Isolierung von Patienten gehört. Die in der Vergangenheit empfohlenen pauschalen Maßnahmen, die weder den Übertragungsweg noch die Virulenz eines Infektionserregers angemessen berücksichtigten, führten oftmals zu erkennbarer Überisolierung, mit der Folge, dass in der täglichen Praxis notwendige Isolierungsmaßnahmen eher nachlässig gehandhabt wurden. Die Konsequenzen waren vermeidbare Kontaktinfektionen in Kliniken. Andererseits birgt die Unterbringung in einem Isolierzimmer die Gefahr einer schlechteren medizinischen wie pflegerischen Versorgung und damit einer Gefährdung des Patienten. Erreger- und maßnahmenbezogene Isolierkriterien mit disziplinierter Befolgung erforderlicher Verhaltensregeln seitens aller Beschäftigten, der isolierten Patienten und ihrer Besucher sind die Voraussetzung einer erfolgreichen Vermeidung von Infektionsübertragungen. Die Vermeidung unnötiger Isolierungsmaßnahmen spart erhebliche Kosten, reduziert die Belastung von Ärzten wie Pflegekräften und damit die Gefahr der Noncompliance bei essenziellen Präventionsmaßnahmen wie Händedesinfektion und andere Maßnahmen der Basishygiene."
8164,Respiratorische Erkrankungen,
8165,Big Data and Biodefense: Prospects and Pitfalls,"This chapter will provide an overview of how “big data” and “big data” analytics can be brought to bear on the pressing biodefense challenges of: (1) threat awareness; and (2) surveillance and detection. The chapter will also discuss potential problems that can arise by relying exclusively on “big data” approaches, which have properties and limitations inherent in their composition that may not be initially recognized but which may lead to erroneous results. The chapter will conclude by discussing how multi-disciplinary teams of researchers using hybrid systems, involving “big data” and “small data,” could more effectively and accurately contribute to understanding biodefense problems."
8166,Basic Knowledge and Developing Tendencies in Epidemic Dynamics,"Infectious diseases have been a ferocious enemy since time immemorial. To prevent and control the spread of infectious diseases, epidemic dynamics has played an important role on investigating the transmission of infectious diseases, predicting the developing tendencies, estimating the key parameters from data published by health departments, understanding the transmission characteristics, and implementing the measures for prevention and control. In this chapter, some basic ideas of modelling the spread of infectious diseases, the main concepts of epidemic dynamics, and some developing tendencies in the study of epidemic dynamics are introduced, and some results with respect to the spread of SARS in China are given."
8167,The technology of pharming,
8168,Genome organization and structural aspects of the SARS-related virus,
8169,Lung,
8170,Allgemeine Notfälle,"Sie werden als Notarzt zu einem 54 Jahre alten Mann gerufen, der über Schmerzen in der Brust klagt, die seit etwa 45 min bestehen. Eine koronare Herzkrankheit ist anamnestisch bekannt. Der Blutdruck ist 150/90 mmHg, die Herzfrequenz 110/min. Der Patient ist kaltschweißig und klagt über Übelkeit. Das 12-Kanal-EKG zeigt einen Linkslagetyp mit normalem Sinusrhythmus, Zeichen einer akuten Ischämie (ST-Hebungen) sind nicht zu sehen."
8171,Adenoviren,"Adenoviren verursachen akute Erkältungskrankheiten, Pharyngitis, Konjunktivitis, Keratokonjunktivitis, Gastroenteritis, hämorrhagische Zystitis, Pneumonien, Meningitis und Enzephalitis. Sie interferieren mit dem Angriff des Immunsystems auf infizierte Zellen und persistieren mehrere Jahre in den Tonsillen (»Adenoiden«). Bei Immunsuppression können sie reaktiviert werden und dann lebensbedrohlich disseminieren. Das Virus wurde erstmals 1953 in Explantaten von Tonsillengewebe anhand seines zytopathischen Effekts in vitro nachgewiesen. 1956 erhielten die Isolate die Bezeichnung »Adenoviren«. Typ 12 war das erste humanpathogene Virus, bei dem man Onkogenität im Versuchstier beobachtete. Eine ursächliche Beteiligung von Adenoviren bei menschlichen Neoplasien ist aber nicht gesichert."
8172,Gold Nanoparticles for DNA/RNA-Based Diagnostics,"The remarkable physicochemical properties of gold nanoparticles (AuNPs) have prompted development in exploring biomolecular interactions with AuNPs-containing systems, pursuing biomedical applications in diagnostics. Among these applications, AuNPs have been remarkably useful for the development of DNA/RNA detection and characterization systems for diagnostics, including systems suitable for point of need. Here, emphasis will be on available molecular detection schemes of relevant pathogens and their molecular characterization, genomic sequences associated with medical conditions (including cancer), mutation and polymorphism identification, and the quantification of gene expression."
8173,The Role of Animal Models In Influenza Vaccine Research,"A major challenge for research on influenza vaccines is the selection of an appropriate animal model that accurately reflects the disease and the protective immune response to influenza infection in humans. Vaccines for seasonal influenza have been available for decades and there is a wealth of data available on the immune response to these vaccines in humans, with well-established correlates of protection for inactivated influenza virus vaccines. Many of the seminal studies on vaccines for epidemic influenza have been conducted in human subjects. Studies in humans are performed less frequently now than they were in the past. Therefore, as the quest for improved influenza vaccines continues, it is important to consider the use of animal models for the evaluation of influenza vaccines, and a major challenge is the selection of an appropriate animal model that accurately reflects the disease and the protective immune response to influenza infection in humans. The emergence of highly pathogenic H5N1 avian influenza (AI) viruses and the threat of a pandemic caused by AI viruses of this or another subtype has resulted in a resurgence of interest in influenza vaccine research. The development of vaccines for pandemic influenza presents a unique set of obstacles, not the least of which is that the demonstration of efficacy in humans is not possible. As the correlates of protection from pandemic influenza are not known, we rely on extrapolation of the lessons from seasonal influenza vaccines and on data from the evaluation of pandemic influenza vaccines in animal models to guide our decisions on vaccines for use in humans. The features and contributions of commonly used animal models for influenza vaccine research are discussed. The recent emergence of the pandemic 2009 H1N1 influenza virus underscores the unpredictable nature of influenza viruses and the importance of pandemic preparedness."
8174,Bispecific Antibodies for Diagnostic Applications,"Bispecific monoclonal antibodies (BsMAb) are unique engineered macromolecules that have two different pre-determined binding specificities. Their ability to simultaneously bind to a specific antigen and a given detection moiety enables them to function as excellent bifunctional immunoprobes in diagnostic assays. BsMAb are being exploited for the development of simple, rapid, and highly sensitive immunoassays for diagnosis of bacterial and viral infectious diseases. This chapter describes the use of BsMAb for the detection of Mycobacterium tuberculosis, Escherichia coli O157:H7, Bordetella pertussis, Severe Acute Respiratory Syndrome coronavirus, and Dengue virus. Further, BsMAb have been utilized for diagnosis of various types of cancers. The use of BsMAb in detection of prostate cancer and in cancer diagnostic imaging is also discussed."
8175,Intensivtherapie der HIV-Infektion,Bei HIV-infizierten Patienten hat sich durch die Einführung der antiretroviralen Kombinationstherapie die Langzeitprognose erheblich verbessert und das Spektrum der zum Intensivaufenthalt führenden Erkrankungen verschoben.
8176,Super-Gau: Ausrottung der Menschheit durch Krieg und Naturkatastrophen,"Die Vernichtung der Menschheit durch Krieg oder Naturkatastrophen weist in ihren Konsequenzen große Überschneidungen auf, weshalb ich sie auch zu einem übergeordneten Typus „Super-Gau – Ausrottung der Menschheit“ zusammengefasst habe. Im Prinzip lehren uns die dystopischen Filme generell, dass die Menschheit stets selbst an ihrem Unheil schuld ist. Dies unterscheidet auch die von Giddens als high-consequence risks bezeichneten modernen Risiken von früheren Katastrophen wie Sintfluten, Dürren oder Epidemien, die der Mensch nicht beeinfl ussen konnte. Wenn man jedoch genauer hinsieht, dann ist die Zuschreibung der Verantwortlichkeit des Menschen für das, was in der Umwelt passiert, keine moderne Erfindung."
8177,Cell Polarity: A Key Defence Mechanism Against Infection and Cancer Cell Invasion?,"It is now emerging that a number of cellular targets of pathogens are involved in the establishment and/or maintenance of epithelial cell polarity. Increasing evidence also suggests that cancer-causing pathogens such as Helicobacter pylori (H. pylori) and human papilloma virus (HPV) may induce oncogenesis by disrupting cell polarity. This is mainly achieved through their ability to deregulate the function of cell polarity components and/or regulators. Hence cell polarity represents the first line of defence against infection. Interestingly, EGFR/RAS oncogenic signals also induce cancer cell invasion by inducing epithelial to mesenchymal transition (EMT). Since the loss of cell polarity is a prerequisition of EMT, cell polarity also represents the last line of defence against cancer cell invasion. As such we argue that cell polarity may be a key defence mechanism against infection and cancer cell invasion. The potential role of cell polarity as a gatekeeper against cancer through its ability to regulate asymmetric cell division and tumour suppression has been discussed in a number of recent reviews. In this review we will focus on the role of cell polarity as a potential target of infection and cancer cell invasion."
8178,Vitamin D and respiratory infections in infants and toddlers: a nutri-shine perspective,"There is compelling evidence of a global problem of poor vitamin D status in expecting mothers and postnatal life; and even more critical, is the evidence showing the association of vitamin D deficiency with increased morbidity and mortality risks from respiratory infections. Viral and bacterial pneumonia kills more children than any other illness, accounting for 19 % of all deaths in children less than five years of age worldwide; and under-nutrition, which includes vitamin D insufficiency/deficiency, has been implicated in 53 % of all these deaths. Poor vitamin D status is a result of insufficient sunlight exposure and/or poor dietary intake. Greater understanding of the role of vitamin D deficiency in precipitating lung infections grew from the use of rodent models and observational and intervention studies in infants and toddlers. Vitamin D adequacy is important to maintaining the key protective mechanism of developing lungs since it mediates the synthesis of antimicrobial peptides, the lungs strongest defense against viral and bacterial pathogens. If vitamin D intervention currently under study in several clinical trials is proven successful, then implementation of new fortification practices, revised guidelines for healthy sun exposure and public health programs for vitamin D supplementation of pregnant/lactating women and their infants may be effective strategies to aide in preventing neonates and children under five from developing pneumonia. Globally, there is potential to save more than a million young lives with preventive treatment, a compelling reason why the efficacy of optimizing vitamin D mediated defense against respiratory pathogens in infants and children merits further study."
8179,Influenza vaccines have a short but illustrious history,"Isolation of the causative virus of influenza in 1933, followed by the discovery of embryonated hen eggs as a substrate, quickly led to the formulation of vaccines. Virus-containing allantoic fluid was inactivated with formalin. The phenomenon of antigenic drift of the virus HA was soon recognized and, as WHO began to coordinate the world influenza surveillance, it became easier for manufacturers to select an up-to-date virus. Influenza vaccines remain unique in that the virus strain composition is reviewed yearly but modern attempts are being made to free manufacturers from this yolk by investigating internal virus proteins including M2e and NP as “universal” vaccines covering all virus sub types. Recent technical innovations have been the use of Vero and MDCK cells as the virus cell substrate, the testing of two new adjuvants and the exploration of new presentations to the nose or epidermal layers as DNA or antigen mixtures. The international investment into public health measures for a global human outbreak of avian H5N1 influenza is leading to enhanced production of conventional vaccine and to a new research searchlight on T cell epitope vaccines, viral live attenuated carriers of influenza proteins and even more innovative substrates to cultivate virus, including plant cells."
8180,Super Refractory Status Epilepticus,"Earlier definitions of status epilepticus (SE) were based on the duration of seizures, but newer definitions rely more on a pragmatic staging based on treatment failures (Table 23.1). Refractory status epilepticus (RSE) is defined as SE that continues despite administration of both benzodiazepines and an appropriately dosed second-line antiseizure drug. Depending on the semiology of the seizures and comorbidities of the patient, this stage may be treated with further antiseizure drugs or anesthesia. When seizures recur upon weaning the anesthetic agent, typically after 24 h of seizure suppression, or in the rare cases where seizure control cannot be achieved with anesthesia, status epilepticus is considered to be super refractory (SRSE). The incidence of status epilepticus has been increasing, from 3.5 to 12.5/100,000 population between 1979 and 2010. During this time hospital mortality has not changed [1]."
8181,Befunde der Untersuchung,"Die Fallstudien und die Befragung dieser Studie bieten viele Antworten auf die Fragen nach den Eigenschaften von Patentpools und den Einflussfaktoren, die auf die Teilnahmebereitschaft der Akteure wirken. Im Folgenden wird anhand der Fallstudien in der IKT und den Life Sciences aufgezeigt, wie Patentpools gestaltet sind und welche Eigenschaften von Patentpools besonders wichtig sind, um zu verstehen, warum diese Form der Patentübereinkunft von Patentinhabern genutzt wird. Anhand der Fallstudien werden auch die Anreize und Motive der Akteure beleuchtet, Patentpools zu gründen oder sich anderweitig an ihnen zu beteiligen. Die Schlüsselfaktoren der einzelnen Fälle werden in der Fallstudiensynthese für einen Vergleich zusammengeführt."
8182,The Accuracy of Mean-Field Approximation for Susceptible-Infected-Susceptible Epidemic Spreading with Heterogeneous Infection Rates,"The epidemic spreading over a network has been studied for years by applying the mean-field approach in both homogeneous case, where each node may get infected by an infected neighbor with the same rate, and heterogeneous case, where the infection rates between different pairs of nodes are also different. Researchers have discussed whether the mean-field approaches could accurately describe the epidemic spreading for the homogeneous cases but not for the heterogeneous cases. In this paper, we explore if and under what conditions the mean-field approach could perform well when the infection rates are heterogeneous. In particular, we employ the Susceptible-Infected-Susceptible (SIS) model and compare the average fraction of infected nodes in the metastable state, where the fraction of infected nodes remains stable for a long time, obtained by the continuous-time simulation and the mean-field approximation. We concentrate on an individual-based mean-field approximation called the N-intertwined Mean Field Approximation (NIMFA), which is an advanced approach considered the underlying network topology. Moreover, for the heterogeneity of the infection rates, we consider not only the independent and identically distributed (i.i.d.) infection rate but also the infection rate correlated with the degree of the two end nodes. We conclude that NIMFA is generally more accurate when the prevalence of the epidemic is higher. Given the same effective infection rate, NIMFA is less accurate when the variance of the i.i.d. infection rate or the correlation between the infection rate and the nodal degree leads to a lower prevalence. Moreover, given the same actual prevalence, NIMFA performs better in the cases: 1) when the variance of the i.i.d. infection rates is smaller (while the average is unchanged); 2) when the correlation between the infection rate and the nodal degree is positive. Our work suggests the conditions when the mean-field approach, in particular NIMFA, is more accurate in the approximation of the SIS epidemic with heterogeneous infection rates."
8183,What Has Been Learned from Postmortem Studies?,"Infectious and noninfectious pulmonary diseases are commonly found on postmortem autopsy studies in patients with hematological malignancy. Despite the technological advances in diagnostic testing and imaging modalities, obtaining an accurate clinical diagnosis remains difficult and often not possible until autopsy. Major diagnostic discrepancies between clinical premortem diagnoses and postmortem autopsy findings have been reported in these patients. The most common missed diagnoses are due to opportunistic infections and cardiopulmonary complications. These findings underscore the importance of enhanced surveillance, monitoring and treatment of infections and cardiopulmonary disorders in these patients. Autopsies remain important in determining an accurate cause of death and for improved understanding of diagnostic deficiencies, as well as for medical education and quality assurance."
8184,Carcinogenic Effect of Wireless Communication Radiation in Rodents,"The potential health effects of radio frequency (RF) radiation associated with cellular mobile telephones and related wireless devices remain a focus of concern. Although our knowledge regarding the health effects of RF radiation has increased considerably, the scientific evidence on biological effects of RF radiation associated with these wireless devices is still tentative. The uncertainties persist, in part, because of the limited number and scope of studies that have been conducted. Aside from the lack of a scientific consensus on experimental studies that provide clear evidence either refuting or supporting the cancer induction or promotion potential of RF radiation from cell phones, there is a concern that an established effect from wireless radiation, however small, could have a considerable impact in terms of public health. This chapter provides an updated review on recent research results on cancer induction and promotion in normal and transgenic mice and rats subjected to prolonged or life-long exposure to modulation schemes such as GSM, TDMA, CDMA, UMTS, and others. A majority of the laboratory mouse and rat studies did not exhibit a significant difference in carcinogenic incidences between exposed and sham-exposed animals. Although this observation may be comforting from the perspective of safety evaluation, most of the studies are one-of-a-kind investigations – only three mouse and perhaps four rat studies were designed as replication or confirmation studies. It is noteworthy that the findings of these studies have not been consistent, making it difficult to arrive at a definitive conclusion. It could be a major flaw that in a majority of the investigations, cage-control animals were not part of the investigation or were not included in the data analyses. Moreover, restraining the experimental animals during exposure could have introduced a stress factor, which further complicates interpretation of the results since stress has often been associated with cancer induction in these animals."
8185,Evidence-Based Medicine in the Intensive Care Unit,
8186,Acute Pneumonia and Importance of Atypical Bacteria,"The diagnosis of pulmonary infection caused by Mycoplasma and Chlamydia pneumoniae, Coxiella burnetii, and different species of Legionella, is often long and challenging although they are the major etiologic agents of pneumonia. For this reason, the treatment of these infections remains probabilistic. Advances in new diagnostic techniques, such as PCR sequencing, show the relative predominance of atypical organisms and serves to identify emerging pathogenic agents. Moreover, these techniques should clarify the correlation between common and atypical pathogens."
8187,China’s Institutional Mechanisms for Influenza A (H1N1) Prevention and Control,"Innovation in institutional mechanisms is a fundamental issue in effectively dealing with public health emergencies. In the wake of the 2003 SARS Epidemic, China initially established a public health emergency management system and an emergency organization and management network, placing emphasis on “government leading, unified command, local management, responsibility on all levels, management by classifications, and inter-departmental coordination,” which strengthened the existing health emergency preparation system."
8188,Sapelovirus,"Sapelovirus (SPV), an emerging virus in the family Picornaviridae, is detected in several animal and bird species irrespective of their age. Amid all SPVs, porcine sapeloviruses (PSVs) are more ubiquitously present all over the world in porcine population. These viruses are highly stable in different environmental conditions and spread easily within the susceptible animals mainly through faeco-oral route. Usually, PSVs cause asymptomatic infections but are also clinically associated with encephalomyelitis, respiratory distress, fertility disorders and skin lesions. PSV-associated outbreaks have been reported where death occurs due to polioencephalitis and respiratory paralysis. Till date, PSVs have been detected from several European and Asian countries with moderate-to-high prevalence and clinical course. Viral capsid proteins are immunogenic and mutations in these proteins are responsible for the diverse nature of the viruses. Further, genomic analysis shows the varied evolutionary patterns and the presence of recombination within PSV strains. These viruses also exist as concurrent infections with several enteric bacterial, viral and parasitic pathogens. Classical to modern biotechnological assays are in use to detect PSV involving virus isolation in cell culture, immunohistochemistry, conventional nucleic acid amplification techniques, quantitative real-time amplification assays and isothermal amplification molecular techniques. Till date, there is no vaccine available against PSVs."
8189,"Challenges, Opportunities and Theoretical Epidemiology","Lessons learned from the HIV pandemic, SARS in 2003, the 2009 H1N1 influenza pandemic, the 2014 Ebola outbreak in West Africa, and the ongoing Zika outbreaks in the Americas can be framed under a public health policy model that responds after the fact. Responses often come through reallocation of resources from one disease control effort to a new pressing need. The operating models of preparedness and response are ill-equipped to prevent or ameliorate disease emergence or reemergence at global scales. Epidemiological challenges that are a threat to the economic stability of many regions of the world, particularly those depending on travel and trade, remain at the forefront of the Global Commons. Consequently, efforts to quantify the impact of mobility and trade on disease dynamics have dominated the interests of theoreticians for some time. Our experience includes an H1N1 influenza pandemic crisscrossing the world during 2009 and 2010, the 2014 Ebola outbreaks, limited to regions of West Africa lacking appropriate medical facilities, health infrastructure, and sufficient levels of preparedness and education, and the expanding Zika outbreaks, moving expeditiously across habitats suitable for Aedes aegypti. These provide opportunities to quantify the impact of disease emergence or reemergence on the decisions that individuals take in response to real or perceived disease risks. The case of SARS 2003 in 2003, the efforts to reduce the burden of H1N1 influenza cases in 2009, and the challenges faced in reducing the number of Ebola cases in 2014 are the three recent scenarios that required a timely global response. Studies addressing the impact of centralized sources of information, the impact of information along social connections, or the role of past disease outbreak experiences on the risk-aversion decisions that individuals undertake may help identify and quantify the role of human responses to disease dynamics while recognizing the importance of assessing the timing of disease emergence and reemergence. The co-evolving human responses to disease dynamics are prototypical of the feedbacks that define complex adaptive systems. In short, we live in a socioepisphere being reshaped by ecoepidemiology in the “Era of Information.”"
8190,Alveolar Disease,"Diffuse alveolar damage (DAD) is the histopathological substrate for most patients diagnosed clinically with the acute respiratory distress syndrome. The two terms are not synonymous, however, as some patients presenting with acute unexplained respiratory failure will be found to have a more specific disease. The benchmark for DAD is the hyaline membrane. Some authors have used the term acute interstitial pneumonitis for cases where the etiology of the DAD is unknown, and restricted the term DAD to cases where the etiology is known. The disease, when usually sampled, is subacute (weeks), principally alveolar rather than interstitial (alveoli filled by myxoid fibrosis), and not a pneumonitis (principally fibrosis rather than inflammation)."
8191,Infectious Diseases,Infect Dis Clin North Am 2007;21:4
8192,An Overview of What Global Health Is,"There have been significant improvements in the state of health in the world over the decades: the average global life expectancy since 1960 has increased from just over 50 to over 71; smallpox has been wiped out and the number of deaths from measles, 871,000 in 1999, rapidly fell to an estimated figure of 12,000 in 2012 (thanks to vaccination). However, though there are more than 7 billion people in the world, only 1 billion can expect to lead a long and healthy life. Unlike in the past, health problems are no longer confined within the individual countries. The SARS epidemic, which started in China in 2002, rapidly spread to 29 different countries in 8 months. The emissions of CO(2) in the United States and China may be causing an increase in floods in Bangladesh, as we show in the book. Global health has been defined by the United States Institute of Medicine as all those “health problems, issues, and concerns that transcend national boundaries, may be influenced by circumstances or experiences in other countries, and are best addressed by co-operative actions and solutions.” The concept of global health is connected with another important phenomenon, that of the epidemiological transition, or the continuous process according to which some diseases decline (many infectious diseases and those caused by malnutrition) and others spread (chronic “ non-communicable” diseases). According to many indicators, including health, there is a general convergence of the countries in the world but also great internal inequalities in each country. In this chapter addresses the new health issues raised by globalisation, including the impact of economic and technological changes. In doing so, it tells three exemplary stories of globalisation and health: Nauru (a very early example of the impact of globalisation), Greece (the consequences of the economic crisis) and Bangladesh (one of the countries currently most exposed to the effects of climate change)."
8193,A Pairwise Alignment Algorithm for Long Sequences of High Similarity,"Alignment algorithms are important in bioinformatics for comparing the similarity among sequences. The algorithm of Needleman–Wunsch is well known for globally aligning two sequences. However, this algorithm is unsuitable for sequences of long length. Many heuristic algorithms are proposed, such as BLAST and FASTA. However, they are still unsuitable for long sequences. In this paper, we study the alignment problem on highly similar sequences. By taking SARS viruses as an example, our result shows that our algorithm runs faster than Clustalx for aligning two SARS viruses. It implies that our algorithm is suitable for viruses of high similarity."
8194,Viral Infections,"Although influenza remains indisputably the most significant viral pathogen in adults, other viruses such as respiratory syncytial virus, parainfluenza viruses, and human metapneumovirus are now recognized as significant pathogens in older populations. Oseltamivir and zanamivir are antiviral agents that are effective for the treatment and prophylaxis of influenza A and B. For treatment and for optimal effect, therapy should be initiated within 48 h of symptom onset. Infection with hepatitis viruses may be more severe in older adults with more fulminate disease as observed with acute hepatitis A and a more rapid progression to cirrhosis with hepatitis C. Outbreaks of viral gastroenteritis are common in long-term care facilities, and infection may lead to death due to dehydration and oliguria. The incidence of herpes zoster increases with advancing age and carries with it a significant risk of post herpetic neuralgia. The use of antiviral medications and corticosteroids may reduce the incidence and severity of chronic pain."
8195,Platelet-Derived Inhibitors of Platelet Activation,"Negative regulators of platelet activation are a relatively unexplored aspect of platelet physiology yet have an important role in tempering thrombus development by contributing much needed negative regulation to a process that is amplified by several positive feedback mechanisms. Some negative regulators, such as RASA3 and JAM-A, act as gatekeepers that modulate key mediators of activation and provide barriers that must be deactivated to permit full activation and stable thrombus formation. Other negative regulators, such as PECAM-1 and other proteins that signal through ITIMs, come into play once platelets are activated and provide restraining, negative feedback for activatory pathways. Many platelet-derived inhibitors have been identified but not fully characterised and so questions remain regarding the mechanisms that underlie the effects on platelet activity following their activation, inhibition or genetic disruption. However, dysregulation of inhibitory signals is believed to contribute to enhanced risk of thrombosis in diseases such as diabetes and other pathological conditions. In this chapter we have described platelet-derived inhibitors of platelet function that are secreted by or expressed within platelets themselves to provide inhibition or negative regulation to the processes that underpin activation."
8196,Tag 2: Infektionskrankheiten,"Das Kapitel gibt einen Überblick über die außergewöhnliche Bedeutung von Infektionskrankheiten aufgrund der schnelle Übertragbarkeit und der Entwicklung von Antibiotikaresistenzen. Nach der Darstellung von Übertragungswegen und den Prinzipien der Diagnostik und Therapie werden die wichtigsten Krankheitsbilder systematisch behandelt. Dazu gehören Sepsis, Meningitis, Pneumonie, Osteomyelitis, Harnwegsinfektionen und Gastroenteritis. Die erregerbezogene Systematik mit typischen klinischen Manifestationen wird unterteilt in besonders relevante Bakterien (Streptokokken und Staphylokokken), Viren (Masern-, Mumps-, Röteln- und Herpesviren), Pilze, Würmer und Arthropoden. Ein weiterer Fokus ist die Infektionsprophylaxe durch aktive und passive Impfungen."
8197,Acronyms and Abbreviations in Surgery and Medicine,The patient went from the ER to the OR and then to the ICU.” It is an irrefutable fact that doctors' speech is full of abbreviations. Healthcare professionals in general and surgeons in particular use at least ten abbreviations per minute (this is just a guesstimate; please don't quote us). This high prevalence has led us to consider medical abbreviations an important challenge.
8198,Exam 1 Questions,"1. Which of the following is the most common form of incomplete spinal cord injury? A. Central cord syndrome. B. Cauda equina syndrome. C. Anterior spinal cord syndrome. D. Posterior spinal cord syndrome. E. Brown-Sequard lesion. 2. A 64-year-old male with a history of chronic alcohol abuse and congestive heart failure is currently recovering from excision of a large right shoulder lesion suspicious for melanoma. Postoperatively, he is experiencing bleeding and oozing from his surgical site that has persisted despite suture repair and direct pressure for an extended period of time. His labs are drawn, and are as follows: platelets 141 × 10(3)/mL, INR 1.2, fibrinogen 90 mg/dL. Which of the following blood products should be administered next? A. Fresh frozen plasma. B. Cryoprecipitate. C. Prothrombin complex concentrate. D. Recombinant activated factor VII. E. Aminocaproic acid. 3. A 75-year-old, 90 kg male with a history of peripheral vascular disease, coronary artery disease, and epilepsy following a recent cerebral infarction presents to the emergency department after having three witnessed seizures at home. He was intubated at the scene by the paramedics, and received 8 mg of intravenous lorazepam and 1 g of phenytoin. While you are evaluating him, he has another generalized tonic-clonic seizure, and the nurse asks if you would like to initiate a continuous propofol infusion. His blood pressure is 94/42 mmHg, and he is having numerous premature ventricular contractions (PVCs) on the electrocardiographic monitor. He has no history of platelet or liver dysfunction. Which of the following should be performed next? A. Complete the phenytoin load to attain 20 mg/kg, then start propofol infusion. B. Complete the phenytoin load to attain 20 mg/kg only C. Administer valproate, 30 mg/kg over 10 min, as well as midazolam 0.2 mg/kg. D. Start immediate midazolam infusion at 2 mg/kg/h. E. Give a 1 L normal saline bolus, and start a norepinephrine infusion to normalize blood pressure. 4. A 38-year-old male is brought to the emergency department after a motor vehicle accident. He is found to have significant ecchymoses on his chest and face, with multiple apparent rib fractures. He is in mild respiratory distress, with an oxygen saturation of 89% on room air, and hypotensive, with a systolic blood pressure of 88 mmHg. He has absent breath sounds on the right side. There is currently a delay in obtain a bedside portable chest x-ray. Which of the following should be performed next? A. 28-French chest tube placement. B. 16-French chest tube placement. C. Obtain computed tomography (CT) of the chest. D. Administer 30 cc/kg crystalloid. E. Obtain urgent cardiothoracic surgery consult. 5. Stress ulcer prophylaxis is often undertaken to prevent clinically important upper gastrointestinal (GI) bleeding. Which of the following factors puts patients at highest risk for such bleeding episodes? A. Respiratory failure. B. History of alcohol abuse. C. NPO status. D. Diverticulitis. E. All of the above. 6. In an intact heart, the Frank-Starling mechanism describes contractility increases in responses to: A. Decreased preload. B. Increased afterload. C. Decreased left ventricular end-diastolic pressure. D. Increased left ventricular end-diastolic volume. E. Increased pulmonary vascular resistance. 7. A 68-year-old female with a history of hyperlipidemia, hypothyroidism, and gastric cancer on total parenteral nutrition is currently in the ICU following a small traumatic subdural hemorrhage. On hospital day 5, the patient begins to spike fevers that persist despite broad spectrum antibiotic coverage with vancomycin and piperacillin-tazobactam. She is otherwise hemodynamically stable. The lab calls you to notify you that multiple sets of blood cultures display budding yeast forms and pseudohyphae. Which of the following should be administered next? A. Fluconazole. B. Posaconazole. C. Anidulafungin. D. Caspofungin. E. Amphotericin B. 8. A 56-year-old male with a past medical history of hypertension, hyperlipidemia, and morbid obesity is currently intubated in the ICU following a left middle cerebral artery infarct. The respiratory therapist alerts you the fact that the patient has become markedly dysynchronous with the ventilator, including breath holding episodes, breath stacking, and resisting ventilator-delivered breaths. A variety of pressure- and volume-regulated ventilator modes have been attempted without improvement, as well as boluses of both fentanyl and midazolam. The most recent arterial blood gas is as follows: pH 7.19, PaCO(2) 78 mmHg, PaO(2) A. Prone the patient. B. Administer nitric oxide at 10 parts per million. C. Administer 10 mg of cisatracurium. D. Administer a mixture of 60% helium/40% oxygen. E. Administer a continuous infusion of phenobarbital. 9. Compared to lactulose for the treatment of hepatic encephalopathy, polyethylene glycol (PEG) has been shown to: A. Decrease in-hospital mortality. B. More rapidly improve symptoms. C. Increase the rate of gastrointestinal complications. D. Increase the incidence of major electrolyte abnormalities. E. None of the above. 10. Which of the following neurologic insults is the least likely to cause central (non-infectious) fever in the ICU? A. Intracranial neoplasm. B. Intraventricular hemorrhage. C. Normal pressure hydrocephalus. D. Subarachnoid hemorrhage. E. Traumatic brain injury. 11. A 57-year-old male with a history of epilepsy and medication noncompliance is admitted to a small community hospital after a brief tonic-clonic seizure. A non-contrast head CT on admission is normal. On the second hospital day, the patient begins to complain of severe substernal chest pressure, and an urgent bedside EKG shows evidence of an acute inferior myocardial infarction (MI). The nearest percutaneous coronary intervention (PCI) capable center is approximately 150 min away by the fastest transport method available. Which of the following is the most appropriate next step in this patient’s care? A. Arrange for transport to the closest PCI center with anticipated balloon time within 30 min of arrival. B. Prepare to administer fibrinolytic therapy. C. Consult cardiothoracic surgery for possible coronary artery bypass grafting (CABG). D. Place the patient on a continuous nitroglycerine infusion and administer aspirin, clopidogrel, and heparin. E. Await serum cardiac biomarkers and repeat EKG in 1 h. 12. A 62-year-old male with unknown past medical history who recently immigrated from El Salvador is currently in the stroke unit after suffering from an acute left middle cerebral artery infarction. The patient is aphasic; his wife states that he been in his usual state of health lately, and denies any recent weakness, dizziness, chest pain, cough, shortness of breath, or fevers. On reviewing this patient’s belongings, the nurse discovers a bottle of isoniazid, as well as paperwork demonstrating a positive quantiferon gold test performed at a local clinic approximately 3 weeks ago. He does not appear to be on any other medications. A bedside portable chest x-ray is performed, which preliminarily appears normal. Which of the following should be performed next? A. Move the patient to a negative pressure isolation room, continue isoniazid. B. Isolate the patient, continue isoniazid, add rifampin. C. Isolate the patient, continue isoniazid, add rifampin and pyrazinamide. D. Isolate the patient, continue isoniazid, add rifampin, pyrazinamide and ethambutol. E. None of the above. 13. A 56-year-old, 70 kg female patient in oliguric renal failure would be expected to have a daily urine output of: A. No more than 50 mL. B. No more than 400 mL. C. No more than 800 mL. D. Less than 70 mL/h. E. Less than 35 mL/h. 14. A 37-year-old female with a history of epilepsy is admitted to the ICU with status epilepticus. She required several doses of lorazepam in the emergency department in addition to fosphenytoin, intubation, and a continuous propofol infusion. There was concern for aspiration in the prehospital setting. Approximately 3 days after being admitted to the hospital, her respiratory status has worsened; she is increasingly hypoxic, and her chest x-ray demonstrates diffuse bilateral interstitial infiltrates. The patient is afebrile with minimal secretions. Her most recent arterial blood gas is as follows: pH 7.21, PaO(2) 107 mmHg, PCO(2) 55 mmHg, 100% FiO(2), and a positive end-expiratory pressure (PEEP) of 8 cm H(2)O. According to the Berlin criteria, how would you categorize this patient’s acute respiratory distress syndrome (ARDS)? A. Acute lung injury (ALI). B. Mild ARDS. C. Moderate ARDS. D. Severe ARDS. E. None of the above. 15. An 80-year-old male presents to the emergency department with multiple episodes of bright red blood per rectum. He is on aspirin and clopidogrel for a history of coronary artery disease and a previous transient ischemic attack. He underwent aortic graft surgery for repair of an abdominal aortic aneurysm 2 years ago. A complete blood count and coagulation profile are all within normal limits. His vital signs are as follows: blood pressure 102/58 mmHg, heart rate 98 beats/min, respiratory rate 18 breaths/min, oxygen saturation 98% on room air, and temperature 98.3 °F. Which of the following is the next best step in the care of this patient? A. Transfuse platelets, fresh frozen plasma, and recombinant factor VIIa. B. Consult gastroenterology for emergent upper endoscopy. C. Consult gastroenterology for emergent colonoscopy. D. CT angiogram of the abdomen and pelvis. E. Expectant management with fluids and blood transfusions. 16. A thrombus in which of the following veins would not be considered a deep vein thrombosis (DVT)? A. Popliteal vein. B. Soleal vein. C. Femoral vein. D. Gastrocnemius vein. E. Greater saphenous vein. 17. After partial resection of the pituitary stalk, secretion of which of the following hormones will be most affected? A. Oxytocin. B. Adrenocorticotrophic hormone. C. Melanocyte-stimulating hormone. D. Thyroid-stimulating hormone. E. All will be equally affected. 18. A 58-year-old female with a history of hypertension, rheumatoid arthritis, metastatic ovarian cancer, and bilateral deep venous thrombosis status post recent inferior vena cava filter placement presents to the emergency department with right flank pain. She states the pain began approximately 1 h ago when bending down to pick something off the floor, and that it is constant and severe in nature. She denies dysuria or hematuria. Her vital signs are as follows: blood pressure 108/62 mmHg, heart rate 121 beats/min, respiratory rate 20 breaths/min, oxygen saturation 99% on room air, and temperature 99.6 °F. A CT scan of the abdomen is obtained (see Image 1). Which of the following is the next best step in this patient’s management? A. Administer vancomycin and cefepime, and draw two sets of blood cultures. B. Urgent vascular surgery consult. C. Immediately place the patient on her left side. D. Rapid sequence intubation with mechanical ventilation. E. Perform bedside diagnostic peritoneal lavage;"
8199,The liver in critical illness,"The liver is in some ways the forgotten organ in intensive care practice. Very many more laboratory and clinical studies have investigated the role, function, and support of the lung, heart, brain, and kidney in critical illness than have studied the liver. Nevertheless, in the time of the Greek scholars, there was already acknowledgement of the role of the liver in non-hepatic diseases such as systemic sepsis, and an understanding that such involvement confers a poorer prognosis – hence the inclusion of the wisdom of Hippocrates in this compilation of classic papers. In the review article by Matuschak and Rinaldo, the reasons why liver dysfunction is associated with a poorer outcome in critical illness are explored, and the concept of the liver being a ‘driving force’ in multiple organ dysfunction is developed. In addition, jaundice without significant liver dysfunction is associated with left ventricular dysfunction, at least in the dog model developed by Professor Otto Better and his colleagues in Israel. This observation is relevant to the progressive resistance to inotropic and vasopressor agents in jaundiced critically ill patients."
8200,A Model for Coupled Outbreaks Contained by Behavior Change,"Large epidemics such as the recent Ebola crisis in West Africa occur when local efforts to contain outbreaks fail to overcome the probabilistic onward transmission to new locations. As a result, there may be large differences in total epidemic size from similar initial conditions. This work seeks to determine the extent to which the effects of behavior changes and metapopulation coupling on epidemic size can be characterized. While mathematical models have been developed to study local containment by social distancing, intervention and other behavior changes, their connection to larger-scale transmission is relatively underdeveloped. We make use of the assumption that behavior changes limit local transmission before susceptible depletion to develop a time-varying birth-death process capturing the dynamic decrease of the transmission rate associated with behavior changes. We derive an expression for the mean outbreak size of this model and show that the distribution of outbreak sizes is approximately geometric. This allows a probabilistic extension whereby infected individuals may initiate new outbreaks. From this model we characterize the overall epidemic size as a function of the behavior change rate and the probability that an infected individual starts a new outbreak. We find good agreement between the analytical results and stochastic simulations leading to novel findings including critical learning rates that demarcate large and small epidemic sizes."
8201,Virtual Screening for RNA-Interacting Small Molecules,"Computational virtual screening is useful and powerful strategy for rapid discovery of small biologically active molecules in the early stage of drug discovery. The discovery of a broad range of important biological processes involved by RNA has increased the importance of RNA as a new drug target. To apply structure-based virtual screening methods to the discovery of RNA-binding ligands, many RNA 3D structure prediction programs and optimized docking algorithms have been developed. In this chapter, a number of successful cases of virtual screening targeting RNA will be introduced."
8202,Immunosuppression,
8203,Conclusions,"The aim of this thesis was to explain different regime outcomes and the variance in the degree of democracy in post-Soviet space by studying the influence of the two main external actors, the EU and Russia. This thesis contributes to the increasing body of literature that studies the causes of democratic recession and authoritarian backlash in post-Soviet states and the role of external actors in these processes. The main focus of the study was on two most important regional actors – the EU and Russia – and on their interaction in the post-Soviet area."
8204,L-Type Lectins in ER-Golgi Intermediate Compartment,"L-type lectins possess a luminal carbohydrate recognition domain (CRD) that binds to high-mannose-type oligosaccharides in aCa(2+)-dependent manner. The L-type CRD is named after the lectins found in abundance in the seeds of leguminous plants, such as concanavalin A from jack beans. The history of L-type lectins is as old as discovery of plant lectins from seeds of leguminous plants in nineteenth century. The structural motifs of L-type lectins are now known to be present in a variety of glycan-binding proteins from other eukaryotic organisms. The domain is present in plant, fungal, and animal proteins, but plant and animal L-type lectins have divergent sequences and different molecular properties. While plant lectins are secreted-soluble proteins and found at high level in specialised tissues, animal L-type lectins are (often membrane-bound) luminal proteins that are found at low levels in many different cell types. This observation suggests that animal L-type lectins have different functions. The crystal structures of some of the legume seed lectins show structural similarities among these lectins and to some other lectins, including the galectins and a variety of other lectins. Therefore, the term “L-lectins” has been designated as a classification for all lectins with this legume seed lectin-like structure. The L-type lectin-like domain has an overall globular shape composed of a β-sandwich of two major twisted antiparallel β-sheets. The β-sandwich comprises a major concave β-sheet and a minor convex β-sheet, in a variation of the jelly roll fold (Velloso et al. 2002, 2003; Satoh et al. 2006, 2007)."
8205,Cancer Treatment-Related Lung Injury,"Lung injury associated with cancer therapeutics is often the limiting factor that trumps otherwise successful cancer therapy. Thoracic radiation as well as cancer pharmacotherapeutics, including conventional chemotherapy, molecular targeted agents, and cancer immunotherapies, have been associated with a unique spectrum of histopathologic injury patterns that may involve the lung parenchyma, pleura, airways, and/or pulmonary vasculature. Injury patterns may be idiosyncratic, unpredictable, and highly variable from one agent class to the next. Variability in lung injury patterns within a specific therapeutic class of drugs also occurs, adding to the conundrum. Drug-induced toxicities to the thoracic cavity are infrequent, and early recognition of clinical clues portends a good outcome in most cases. Failure to recognize early clinical signs, however, may result in irreversible and potentially lethal consequences. This chapter provides an overview of our current knowledge of thoracic complications associated with cancer pharmacotherapies. The review is not intended to be a treatise of all cancer agents that adversely affect the lungs, but rather a discussion of established risk factors and histopathologic patterns of lung injury associated with broad classes of cancer agents. Optimal management strategies, based on existing clinical experience, will also be discussed. Complications associated with thoracic radiation are also reviewed. It is hoped that these discussions will facilitate early recognition and management of treatment-related thoracic complications and, ultimately, better patient outcomes."
8206,Management of Severe Malaria,"Imported malaria is the principal, preventable, life-threatening infection among US travelers. Using a base case scenario, we will discuss the most recent information on the management and treatment for Severe Malaria."
8207,ADAM 17 endopeptidase,
8208,Methods to Determine the End of an Infectious Disease Epidemic: A Short Review,"Deciding the end of an epidemic is frequently associated with forthcoming changes in infectious disease control activities, including downgrading alert level in surveillance and restoring healthcare workers’ working shift back to normal. Despite the practical importance, there have been little epidemiological and laboratory methods that were proposed to determine the end of an epidemic. This short review was aimed to systematically discuss methodological principles of a small number of existing techniques and understand their advantages and disadvantages. Existing epidemiological methods have been mostly limited to a single-and-brief exposure setting, while the application to human-to-human transmissible disease epidemic with stochastic dependence structure in the observed case data has remained to be a statistical challenge. In veterinary applications, a large-scale sampling for laboratory testing has been commonly adapted to substantiate a freedom from disease, but such study has only accounted for binomial sampling process in estimating the error probability of elimination. Surveillance and mathematical modeling are two complementary instruments in the toolbox of epidemiologists. Combining their strengths would be highly beneficial to better define the end of an epidemic."
8209,Cardiovascular Risk Factors and Markers,"Cardiovascular risk is assessed for the prediction and appropriate management of patients using collections of identified risk markers obtained from clinical questionnaire information, concentrations of certain blood molecules (e.g., N-terminal proB-type natriuretic peptide fragment and soluble receptors of tumor-necrosis factor-α and interleukin-2), imaging data using various modalities, and electrocardiographic variables, in addition to traditional risk factors."
8210,Universal Participation Without Taiwan? A Study of Taiwan’s Participation in the Global Health Governance Sponsored by the World Health Organization,"This chapter focuses on the health risk of Taiwan’s absence in intergovernmental health governance networks. It provides a review of Taiwan’s bidding strategies for the World Health Organization between 1997 and 2009. The country’s participation in the World Health Assembly (WHA) and the International Health Regulations (IHR) network since 2009 was a significant improvement, but this experience failed to extend to other governing bodies. The chapter goes on to discuss the global public health risk of excluding Taiwan from cross-national health cooperation, and why such a conundrum remains difficult to resolve. Taiwan’s compliance regarding health governance relies heavily on self-regulation and the help of its allies. The United States has played a key role in enforcing global health regulations on Taiwan. Unlike other sources of threat in health governance, Taiwan currently does not represent a high health risk to other countries. As a result, Taiwan finds it difficult to persuade WHO members to manifest “universal participation” by including Taiwan in various intergovernmental health networks. This pattern of governance, however, lacks transparency. Other countries will find it difficult to monitor or intervene in the event Taiwan’s health authority is unable to deal with a transnational health emergency."
8211,"Catastrophic Anachronisms: The Past, Present and Future of Disaster Medicine","There is a worldwide spiraling risk for more frequent catastrophic events involving multiple casualties, not only in terms of acute injury and illness, but also subsequent psychological and public health concerns. Today, such events will likely be multinational in nature, even when localized to a particular venue and this require international cooperation in terms of prevention, mitigation and relief. The best approach to preparing for disasters is to expand, modify and enhance current local ∖Jobname: S34055 Batch number: 00060 infrastructures and capabilities for managing the multiple types of disaster scenarios and create a number of inter-facility cooperative agreements in advance. Aside from safer internal locations for ICUs and surgical theaters, certain structural changes will need to be installed such as modified ventilation systems, protected water supplies, decontamination mechanisms and security renovations. A key strategy will be to proliferate interoperable, multi-disciplinary, all-hazards training initiatives such as the AMA National Disaster Life Support courses. Purchases of cadres of antidotes, antibiotics and hemoglobin-based oxygen carriers should be coordinated regionally, stored in secure locations and made readily-available for the applicable disaster scenario."
8212,The Context of Tropical Rainforest Deforestation and Degradation,"The author begins Chap. 10.1007/978-3-319-63236-0_2 with the general locations of rainforests (Afrotropical, Neotropical, and Indo-Pacific region) and outlines the specific countries that host rainforests. The author then provides a historical and current context of tropical rainforest deforestation and degradation. Maps are provided showing the forest cover loss from 2000 to 2014 in these select regions. The author then presents a more detailed discussion about the role of cattle, soybeans, and palm oil, along with the role of timber, pulp and paper, forest fires, population and consumption, and infrastructure. The author then concludes with an explanation of why tropical rainforests are important, such as due to their provisioning services, regulating services, habitat or supporting services, and cultural services."
8213,Travel Medicine,"Before travelling to other countries, thorough travel advice should be provided. Not only information about diseases of specific countries but also general advice for travelling should be given on this consultation."
8214,"Fate of the Mongooses and the Genet (Carnivora) in Mediterranean Europe: None Native, All Invasive?","The Mediterranean Basin (MB), connected by cultural exchanges since prehistoric times, provides an outstanding framework to study species introductions, notably in mammals. Carnivores are among the most successful mammalian invaders. As such, a number of middle-sized representatives (“mesocarnivores”) such as the domestic cat and mongooses have been pinpointed for their deleterious impact on the native fauna. In the MB, three species of mongooses (Herpestidae) and one genet (Viverridae) are or have recently been recorded and none of them has been considered native: the Indian grey mongoose Herpestes edwardsii, the small Indian mongoose H. auropunctatus, the Egyptian mongoose H. ichneumon, and the common genet Genetta genetta. In order to clarify the history of introduction and status of the mongooses and genet in Europe, I review various bodies of evidence including (1) their natural history and relationships with humans in their native ranges, (2) their history of introduction in Europe, (3) the enlightenments—and sometimes contradictions—brought by recent genetic analyses on their dispersal histories, and (4) their range dynamics and ecological interactions with the European fauna. The species of herpestids and viverrids present in Europe fall into three categories: (1) introduced and spreading (G. genetta, H. auropunctatus), (2) introduced and extinct (H. edwardsii), and (3) natural disperser and spreading (H. ichneumon). In view of the reviewed evidence, there is weak support for a deleterious impact of the mongooses and genet on the European fauna (except possibly on the herpetofauna of small Adriatic islands in the case of H. auropunctatus), notably in comparison with genuine invasive species such as the black rat and the domestic cat. Rather than inefficient control programs such as those targeting H. ichneumon in Portugal and H. auropunctatus in Croatia, we suggest that a greater attention is focused on the restoration of large Carnivores (the natural regulators of mesocarnivore populations), mesocarnivore communities and natural habitats, to contribute to a more sustainable way of “managing” the mongooses and genet in Europe."
8215,History of Discovery of Parasitic Crustacea,"Parasitic Crustacea have been present in scientific literature since Linnaeus introduced the first classification system (binomial nomenclature). Crustaceans are considered to be the most morphologically diverse arthropods, with currently 19 parasitic orders known to science. This chapter reviews the history of discovery for each of the major parasitic Crustacea groups, highlighting some of the key developments that have influenced our current understanding of these parasites. Each taxonomic group is briefly introduced, followed by a synopsis on some of the outstanding contributions within that group. Knowledge development is followed, from the first parasites discovered to other historical highlights that influenced the groups up to this point. Other important discoveries (both taxonomic and ecological) are also noted, serving as a preview to the host-parasite interactions covered in the subsequent chapters. Additionally, several researchers who have added significant contributions to our knowledge of the parasitic Crustacea (specifically in taxonomy and discovery) are introduced, along with photographs of a select few. This historical review of the crustacean parasites provides a background to these diverse and abundant organisms and will contribute to a better understanding of their unique niche in the aquatic environment."
8216,Mikrobiologische Diagnostik und Infektiologie,"Die Gewinnung mikrobiologischer Proben ist ein wichtiger Schritt in der Diagnostik und Therapie von Infektionskrankheiten. Fehler, die bei der Probengewinnung gemacht werden, kann auch das beste Labor nicht ausgleichen. Dieses Kapitel beschreibt Indikationen für, Abnahme und richtigen Umgang mit, und die Bewertung von mikrobiologischen Proben."
8217,Fibrosing Alveolitis in Hematologic Malignancy Patients Undergoing Hematopoietic Cell Transplantation,"Although advances in antineoplastic therapy have considerably improved the survival of patients with hematological malignancies, current treatment modalities increase the risk of late complications. Several forms of chronic pulmonary dysfunction due to infectious or noninfectious causes commonly occur in the months to years after chemo-radiotherapy and can be fatal or result in long-term morbidity. The judicious use of prophylactic antimicrobial agents has tipped the balance toward noninfectious etiologies. Hence, while opportunistic infections still contribute to chronic lung disease, late sequelae resulting from antineoplastic therapy have been identified and reported. Patients who proceed to receive hematopoietic cell transplantation (HSCT) are particularly prone to developing lung complications. Pulmonary dysfunction occurring after HSCT may manifest with obstructive or restrictive pulmonary mechanics and may range in severity from subtle, subclinical functional changes to frank respiratory failure. Insights generated using animal models suggest that the immunologic mechanisms contributing to lung inflammation after HSCT may be similar to those responsible for graft-versus host disease. In sum, chronic fibrotic pulmonary dysfunction is a frequent and significant complication facing survivors of hematologic malignancies and their practitioners. The high incidence and suboptimal response to current support care and immunosuppressive therapy underscore the need for heightened awareness and continued research in this area."
8218,"Präeklampsie, Eklampsie und HELLP-Syndrom","Schwangerschaftshypertonie: Erstmanifestation einer Hypertonie nach der 20. Schwangerschaftswoche (SSW) mit systolischen und/oder diastolischen Blutdruckwerten >140 bzw. >90 mm Hg, die 2-mal im Abstand von mindestens 6 h bei Fehlen einer Proteinurie gemessen werden. Schwangerschaftskomplikationen sind selten. Meist steigt der Blutdruck im Verlauf der Schwangerschaft nicht weiter an, bisweilen wird ein progredienter Anstieg ohne weitere Präeklampsiesymptome (außer einer möglichen fetalen Wachstumsrestriktion) beobachtet, selten die Progression in eine Präeklampsie. Postpartal normalisiert sich der Blutdruck wieder. Chronische Hypertonie: Hypertonie, die bereits vor der Schwangerschaft oder später als 12 Wochen nach der Entbindung besteht. Bei einer Pfropfpräeklampsie mit einer Inzidenz von etwa 25% sind die Risiken der Frühgeburtlichkeit, der fetalen Wachstumsrestriktion, der vorzeitigen Plazentalösung und des akuten Nierenversagens höher als bei der neu aufgetretenen Präeklampsie. Präeklampsie/Eklampsie: Schwangerschaftshypertonie mit Proteinurie, die durch >300 mg Protein im 24-h-Sammelurin bzw. durch zwei qualitative Bestimmungen (Uristix) mindestens einfach positiv im Abstand von mehr als 4 h definiert ist. Die Eklampsie als Komplikation einer schweren Präeklampsie äußert sich in tonisch-klonischen Krämpfen."
8219,Die Medizinische Mikrobiologie im 21. Jahrhundert,"Die Medizinische Mikrobiologie befasst sich mit der ursächlichen Rolle von pathogenen (d. h. krankheitserzeugenden) Mikroorganismen bei der Entstehung von Störungen im Funktionsablauf des menschlichen Organismus. Störungen dieser Art entstehen durch Ansiedlung und Vermehrung von Mikroorganismen im Sinne des Parasitismus; sie treten als Infektionskrankheit in Erscheinung. Demgemäß betrachtet man die parasitierenden Mikroorganismen als Krankheitserreger; das befallene Individuum wird als “Wirt„ oder als “Makroorganismus„ bezeichnet. Da bei der Betrachtung von Infektionen sowohl der Wirt mit seinen Reaktionen als auch die krankheitserzeugenden Eigenschaften eines Mikroorganismus (d. h. seine Pathogenität) im Vordergrund stehen, lässt sich die Medizinische Mikrobiologie am ehesten als Infektionslehre begreifen — als Lehre von der Auseinandersetzung des Wirts mit den krankheitserzeugenden Eigenschaften des Erregers."
8220,"Immune Response in Human Pathology: Infections Caused by Bacteria, Viruses, Fungi, and Parasites","In the middle of the nineteenth century, it became clear that micro-organisms could cause disease. Effective treatment, however, was not possible at that time; prevention and spread of infectious diseases depended solely on proper hygienic means. At the beginning of the twentieth century, passive and active vaccination procedures were developed against a number of these PATHOGENIC MICRO-ORGANISMS to prevent the diseases in question (rabies, diphtheria, tetanus, etc.). Thanks to the discovery of antimicrobial chemicals (by Paul Ehrlich) and antibiotics (by Sir Alexander Fleming), the threat of infectious diseases seemed to be minimised. Large-scale vaccination programmes against childhood diseases (diphtheria, whooping cough, and polio), started in the early 1950s, raised hopes of finally being able to eradicate these diseases from the planet. This approach was successful for smallpox (1980). However, new infectious diseases have emerged [e.g., Legionella, HUMAN IMMUNODEFICIENCY VIRUS (HIV), Helicobacter, SARS, etc.], and new vaccines and antibiotics are needed. Furthermore, due to intensive medical treatment with antibiotics and immunosuppressive drugs, hospital infections are a growing problem. Bacteria hitherto deemed harmless are causing OPPORTUNISTIC INFECTIONS in immunocompromised patients. The pathogens have developed resistance to many antibiotics, and sometimes no effective antibiotics are available to treat these patients."
8221,Pharmacology of Glutamate Transport in the CNS: Substrates and Inhibitors of Excitatory Amino Acid Transporters (EAATs) and the Glutamate/Cystine Exchanger System x(c)(−),"As the primary excitatory neurotransmitter in the mammalian CNS, l-glutamateparticipates not only in standard fast synaptic communication, but also contributes to higher order signalprocessing, as well as neuropathology. Given this variety of functional roles, interest has been growingas to how the extracellular concentrations of l-glutamate surroundingneurons are regulated by cellular transporter proteins. This review focuses on two prominent systems, eachof which appears capable of influencing both the signaling and pathological actions of l-glutamatewithin the CNS: the sodium-dependent excitatory amino acid transporters (EAATs) and the glutamate/cystineexchanger, system x (c) (−)(Sx (c) (−)). Whilethe family of EAAT subtypes limit access to glutamate receptors by rapidly and efficiently sequesteringl-glutamate in neurons and glia, Sx(c) (−)provides a route for the export of glutamate from cells into the extracellular environment. The primaryintent of this work is to provide an overview of the inhibitors and substrates that have been developedto delineate the pharmacological specificity of these transport systems, as well as be exploited as probeswith which to selectively investigate function. Particular attention is paid to the development of smallmolecule templates that mimic the structural properties of the endogenous substrates, l-glutamate,l-aspartate and l-cystine andhow strategic control of functional group position and/or the introduction of lipophilic R-groups can impactmultiple aspects of the transport process, including: subtype selectivity, inhibitory potency, and substrateactivity."
8222,Toward a Realistic Modeling of Epidemic Spreading with Activity Driven Networks,"Models of epidemic spreading are widely used to predict the evolution of an outbreak, test specific intervention scenarios, and steer interventions in the field. Compartmental models are the most common class of models. They are very effective for qualitative analysis, but they rely on simplifying assumptions, such as homogeneous mixing and time scale separation. On the other end of the spectrum, detailed agent-based models, based on realistic mobility pattern models, provide extremely accurate predictions. However, these models require significant computing power and are not suitable for analytical treatment. Our research aims at bridging the gap between these two approaches, toward time-varying network models that are sufficiently accurate to make predictions for real-world applications, while being computationally affordable and amenable to analytical treatment. We leverage the novel paradigm of activity driven networks (ADNs), a particular type of time-varying network that accounts for inherent inhomogeinities within a population. Starting from the basic incarnation of ADNs, we expand on the framework to include behavioral factors triggered by health status and spreading awareness. The enriched paradigm is then utilized to model the 2014–2015 Ebola Virus Disease (EVD) spreading in Liberia, and perform a what-if analysis on the timely application of sanitary interventions in the field. Finally, we propose a new formulation, which is amenable to analytical treatment, beyond the mere computation of the epidemic threshold."
8223,Macrophage Activation Syndrome,"Hemophagocytic lymphohistiocytosis (HLH), or termed macrophage activation syndrome (MAS) when associated with rheumatic disorders, is a frequently fatal complication of infections, rheumatic disorders, and hematopoietic malignancies. Clinically, HLH/MAS is a life-threatening condition that is usually diagnosed among febrile hospitalized patients (children and adults) who commonly present with unremitting fever and a shock-like multiorgan dysfunction scenario. Laboratory studies reveal pancytopenia, elevated liver enzymes, elevated markers of inflammation (ESR, CRP), hyperferritinemia, and features of coagulopathy. In about 60% of cases, excess hemophagocytosis (macrophages/histiocytes engulfing other hematopoietic cell types) is noted on biopsy specimens from the bone marrow, liver, lymph nodes, and other organs. HLH/MAS has been hypothesized to occur when a threshold level of inflammation has been achieved, and genetic and environmental risk factors are believed to contribute to the hyperinflammatory state. A broad variety of infections, from viruses to fungi to bacteria, have been identified as triggers of HLH/MAS, either in isolation or in addition to an underlying inflammatory disease state. Certain infections, particularly by members of the herpesvirus family, are the most notorious triggers of HLH/MAS. Treatment for infection-triggered MAS requires therapy for both the underlying infection and dampening of the hyperactive immune response."
8224,Adventure Tourism in the Canadian Arctic,"The Canadian Arctic is defined and described and the numbers of tourists for the various regions estimated. The impact of adventure tourism on wildlife is documented, such as polar bear hunting and polar bear viewing, and the management approaches to conserve this iconic species are outlined; the possible spread of Giardia by tourists is discussed; and the impact of tourism on marine mammals and their management is described for beluga, narwhal and seals. There are impacts on birds too and on terrestrial vegetation in the tundra. Examples of aboriginal tourism are documented, including the development of the world-class Carcross mountain bike trails. Pleasure craft and cruise tourism have impacts, and the management approaches to minimise these are discussed. Finally the maintenance of the rich and diverse archaeological and historical sites in the face of tourist impacts is discussed."
8225,Evaluating Protective Effects of Vaccination,"Evaluating the direct protective effects of vaccines in the individuals who were vaccinated has been the focus of vaccine studies over the past century. Generally, interest has been in the ability of vaccination to prevent or to ameliorate disease rather than to prevent infection (Clements-Mann 1998). Ascertainment of cases is often done by finding suspected cases in the population under study in people who exhibit a set of symptoms. The suspected cases are then tested for biological confirmation of the infectious agent of interest. Alternatively, surveillance can ascertain cases reported in central registries. However they are ascertained, with most vaccines, clinical disease is the primary outcome of interest. When ascertainment is on clinical cases, most asymptomatic infections may go undetected. A different situation arises when infection is the primary outcome. To ascertain infections in asymptomatic people, an active follow-up method of testing asymptomatic people is needed. In this chapter we consider estimation and inference for direct protective effects of vaccination, VE(S) and VE(SP), in studies that do not condition on exposure to infection.We consider aspects of the design of such studies. Several examples of randomized, double-blind (double-masked) controlled vaccine trials illustrate the standard approach to design and analysis of such studies. Our choice of studies to present was motivated largely because of their use as illustrations in other sections of the book. Most randomized and pivotal studies of vaccines have been based on VE(SP) or VE(S). Much has been written on studies to meet the approval of the regulatory agencies, and the design of clinical trials generally. Our goal here is to consider how VE(S) and VE(SP) relate to other measures of vaccine effects within the dependent happening context, and consider a few design considerations. Because VE(S) and VE(SP) do not condition on exposure to infection, assumptions about the relative exposure opportunity in the vaccine and control groups are important."
8226,Epidemiologie und Prävention von nosokomialen Infektionen,"Eine nosokomiale Infektion (griechisch: nosokomeíon = Krankenhaus) ist laut Infektionsschutzgesetz definiert als eine „Infektion mit lokalen oder systemischen Infektionszeichen als Reaktion auf das Vorhandensein von Erregern oder ihrer Toxine, die im zeitlichen Zusammenhang mit einer stationären oder einer ambulanten medizinischen Maßnahme steht, soweit die Infektion nicht bereits vorher bestand“. Bei länger hospitalisierten Kindern bestehen häufig Grundkrankheiten, die invasive diagnostische und therapeutische Maßnahmen erfordern. Dies und die Exposition gegenüber einer Vielzahl potenziell pathogener Mikroorganismen bei evtl. noch unreifem Immunsystem bestimmen das Risiko, eine nosokomiale Infektion zu erwerben. Mit unterschiedlichen Altersgruppen sind unterschiedliche Übertragungswege bzw. klinische Manifestationen von Infektionskrankheiten verbunden. Die Inzidenz von Atemwegsinfektionen, Gastroenteritiden sowie Meningitiden ist im Säuglingsalter höher als bei älteren Kindern."
8227,Multiple Sklerose,"Die multiple Sklerose (MS) ist eine der häufigsten neurologischen Erkrankungen, für deren Ursache es bislang keine einheitliche Erklärung gibt. Grundpfeiler der Diagnostik ist die Klinik, ergänzt durch die Magnetresonanztomographie (MRT). Eine Liquoruntersuchung zum Nachweis der entzündlichen Genese nachgewiesener multifokaler Störungen ist bei allen unklaren Fällen und bei älteren Patienten erforderlich. Zur Bestätigung und Verlaufskontrolle sind elektrophysiologische Verfahren hilfreich."
8228,Case Study – United States of America,"The United States (US) considers the intentional use of a biological agent a serious national security threat. Over the last decade, federal, state, and local governments in the US have made concerted efforts to enhance preparedness within the public health, medical, and emergency response systems to address this threat. These activities span a wide range of areas from the enactment of new legal authorities and legislative changes to significant financial investments to enhance multiple detection and response system capabilities and the adoption of a national command and control structure for response. Many of these investments, although prompted by the concern for bioterrorism, have served to strengthen public health, medical, and emergency response systems overall and have proven invaluable in responses to other large-scale emergencies, such as the 2009 H1N1 influenza pandemic."
8229,Vaccines and Prevention,"I was in my first week as a newly graduated doctor when I encountered a vaccine-skeptic – a patient who was convinced vaccines were dangerous and could weaken the human race. I remember thinking – as a doctor, I am supposed to take a detailed history, but I hope you forgive me if I switch off just for a little bit, because right now isn’t the time for this debate. You learn something at medical school and immediately try to tell people about it, but you can’t convince them – not easily, anyway. Especially if you have been indoctrinated with factual information along the lines of this: an estimated 1.5 million children die each year—one every 20 s—from vaccine-preventable diseases such as diarrhea and pneumonia."
8230,Adenoiditis,"Synonyms: Nasopharyngitis, coryza. Definition: Acute manifestation of an initially afebrile catarrhal (predominantly viral) infection of the mucosa of the nasopharynx, adenoids and mostly also of the nose."
8231,Cough,"Pharmacists play an important role in the assessment and management of patients with cough. By obtaining a focused clinical history from the patient, they can identify patients who need to be referred to their physician or to the emergency room, as well as which patients can be managed at home. Red flags that prompt referral include severe systemic illness, respiratory distress, hemoptysis, and altered level of consciousness. Patients with underlying chronic illnesses such as chronic obstructive pulmonary disease, asthma, and heart failure who present with cough should be assessed for possible exacerbation of their illness and should be referred if this is suspected. Determining the duration of cough is an important step, as this helps identify possible etiologies. Cough <3-week duration is categorized as acute, 3- to 8-week duration is subacute, and > 8-week duration is a chronic cough. Patients with cough lasting >3 weeks should generally be referred for further evaluation and management. Acute cough is often infectious but can also be due to exacerbation of underlying illness or could be medication-related. Upper airway cough syndrome (UACS) is one of the most common causes of subacute and chronic cough. Several different etiologies lead to UACS, which is thought to be caused by postnasal drip ± sensitization of cough receptors in the respiratory tract. First-generation antihistamines or decongestants are therapeutic options when UACS is suspected. It is important to note that antitussive medications such as dextromethorphan can actually prolong illness in patients with a productive cough and are thus not recommended. Monitoring parameters and frequency of follow-up depend on underlying cause, severity of illnesses, past medical history, as well as medication changes."
8232,Genus: Calanthe to Cyrtosia,"This large chapter describe the herbal usage and pharmacology of 73 species in 12 genera (Calanthe, Callostylis, Cephalanthera, Cleisostoma, Coelogyne, Conchidium, Corymborkhis, Cremastra, Crepidium, Cymbidium, Cypripedium and Cyrtosia). A good percentage of the orchids are commonly cultivated as ornamental plants and many hybrids have been produced with Calanthe and Cymbidium. TCM makes use of 14 species of Calanthe and Rumphius who authored Hut Amboinesche Kruidboek [the Amboinese Herbal, Volumes 1–6 (1741–1750), published posthumously] described Calanthe triplicata. Calanthe species contain compounds with antitumour and hair-restoring properties. Fourteen species of Coelogyne are medicinal and several have been studied phytochemically by Majumder’s group in Calcutta. Another large group, Cymbidium, with 17 medicinal species, is also much studied. Lectins present in some species suppress replication of coronaviruses, toroviruses and viruses. An interesting compound that suppresses angiogenesis has been discovered in Cremastra appendiculata and it may find a role in preventing blindness and spread of cancers. Cyrtosia is a homomycotrophic genus and should be an interesting subject for phytochemical studies."
8233,Impact of Non-cardiac Comorbidities in Adults with Congenital Heart Disease: Management of Multisystem Complications,"The prevalence and impact of non-cardiac comorbidities in adult patients with congenital heart disease increase over time, and these complications are often specifically a consequence of the long-term altered cardiovascular physiology or sequelae of previous therapies. For the ACHD patient admitted to the intensive care unit (ICU) for either surgical or medical treatment, an assessment of the burden of multisystem disease, as well as an understanding of the underlying cardiovascular pathophysiology, is essential for optimal management of these complex patients. This chapter takes an organ-system-based approach to reviewing common comorbidities in the ACHD patient, focusing on conditions that are directly related to ACHD status and may significantly impact ICU care."
8234,Bioaerosols Over the Indo-Gangetic Plain: Influence of Biomass Burning Emission and Ambient Meteorology,"Bioaerosols (particles of biological origin) can be produced from living or dead plants and animals. They can potentially serve as the cloud condensation and ice nuclei (CCN and IN). Their role in global carbon cycle further highlights importance of studying their variability to link up with climate relevance parameters. Focusing on tropical region reveals that it holds wealthy number of human population and has massive vegetation cover-area. From Indian region, production estimates of bioaerosols from human population (current: ~1.25 billion; of which over 45% resides in Indo-Gangetic Plain: IGP) and Wildlife Sanctuaries and National Parks (100 in numbers, situated from north to south and east to west) is not known. Most of the forest fires in India occur during March–June (hot and drier season). The detailed information on chemical composition, fingerprinting and radiative forcing from regional forest fires is also lacking. Unlike natural sources (forest cover and fires), the seasonal variability of pollutants emission characteristic and chemical, optical and radiative forcing are relatively well studied from anthropogenic biomass (post-harvest paddy- and wheat-residue and biofuels) burning emission in India. However, the abundance of bioaerosols and their variability over a large stretch of IGP (north-west to north-east) was not well documented. Towards this, we have undertaken a year-long campaign to study and document (first-attempt) bioaerosols variability over a complete annual cycle from central IGP. We observed a parallel enhancement in concentrations of fine-particulate matter (PM(2.5) in October–November: 158 ± 89 µg m(−3) as compared to June–September months: 40 ± 18 µg m(−3); two-tailed t = 8.2, p < 0.05) and bioaerosols (particularly Gram-negative bacteria: GNB, a source of endotoxin in ambient air; 186 ± 87 CFU/m(3) during October-November as compared to 114 ± 58 CFU/m(3); t = 4.0, p < 0.05) with the biomass burning emissions intensification period. The abundance of bioaerosols exhibits influence of ambient meteorology, for example GNB exhibited negative correlations with T, wind speed and heavy (>4 mm daily) precipitation, whereas it showed positive correlations with RH and low precipitation amount (<4 mm). Studying bioaerosols and establishing its linkage to health and climate appear to be of utmost importance."
8235,"Influenzapandemieplanung: Eine Herausforderung für die Arbeitsmedizin, den öffentlichen Gesundheitsdienst und Unternehmen","The term pandemic refers to an international or worldwide outbreak of an infectious disease which is limited in time. Due to their high infectiousness and easy person-to-person transmission, flu viruses repeatedly lead to pandemics (approx. 3 pandemics per century.). In contrast to an epidemic, a pandemic is not restricted to one area. The mortality of an influenza pandemic is greater than the seasonal flu wave, and is not restricted to the classical risk groups: high rates of infection can occur in all age groups, with peaks frequently occurring amongst young adults. The specific virological characteristics of the influenza virus represent a great challenge for the health system. In principle, any influenza virus which has never before — or at least not for a long time — circulated within the population can develop into a pandemic virus. One possible candidate amongst others appears to be the influenza virus A-H5N1. Influenza pandemics usually occur at intervals of 11 to 39 years, and 30 years have now passed since the last pandemic. At the moment, the national and international pandemic plans have in most cases not yet been completely worked out. The co-operation between the individual countries should be intensified, and in Germany in particular, efforts should be made — in view of the different concepts of the individual federal states — to arrive at a uniform action plan. The consequences of a pandemic affect both the economic and the social sphere. Hospitals, practicing doctors and public health services must jointly develop action plans in order to be able to care for large numbers of patients within a very short time. Occupational medical specialists should form a link between health services, companies and doctors and hospitals, and already be developing plans and their communication for the companies under their care."
8236,Critical Illness Stress-induced Immune Suppression,"Despite the use of Centers for Disease Control and Prevention (CDC) recommended practices to minimize infection risk, nosocomial sepsis and multiple organ failure (MOF) remain a leading cause of morbidity and mortality in critically ill patients. It is well documented that the use of immunosuppressant therapies dramatically increases this risk in patients with cancer, transplantation, and immunologic disease. Although immune monitoring has yet to be universally embraced, withdrawal of immunosuppressant therapies and use of immune restoration therapies is the standard of care when these patients develop sepsis. Critical illness stress can also induce a level of immunosuppression which is as life-threatening as is seen in the purposefully immunosuppressed patient. This chapter reviews the role of critical illness stress-induced immunosuppression in the development of nosocomial sepsis and MOF, and outlines clinical strategies which can be employed to maintain and restore immune function, and reduce morbidity and mortality in critically ill patients."
8237,Pediatric infectious diseases — Quo vadis 2015?,"In modern medicine the discipline pediatric infectious diseases is an essential medical specialty. The challenging and complex tasks in the next years include meticulous consolidation and careful extension of existing activities aiming at conducting high level research, offering high standard teaching, and providing high quality patient management. This can only be accomplished by exquisitely dedicated individuals with extraordinary communication and integrative skills following painstaking continued training and formation. Potential careers in the discipline can be envisioned not only in academics, but also in government, public health, and industry, whilst less likely in private practice."
8238,Key Global Organizations,
8239,Community-acquired pneumonia: paving the way towards new vaccination concepts,"Despite the availability of antimicrobial agents and vaccines, community-acquired pneumonia remains a serious problem. Severe forms tend to occur in very young children and among the elderly, since their immune competence is eroded by immaturity and immune senescence, respectively. The main etiologic agents differ according to patient age and geographic area. Streptococcus pneumoniae, Haemophilus influenzae, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV-3) are the most important pathogens in children, whereas influenza viruses are the leading cause of fatal pneumonia in the elderly. Effective vaccines are available against some of these organisms. However, there are still many agents against which vaccines are not available or the existent ones are suboptimal. To tackle this problem, empiric approaches are now being systematically replaced by rational vaccine design. This is facilitated by the growing knowledge in the fields of immunology, microbial pathogenesis and host response to infection, as well as by the availability of sophisticated strategies for antigen selection, potent immune modulators and efficient antigen delivery systems. Thus, a new generation of vaccines with improved safety and efficacy profiles compared to old and new agents is emerging. In this chapter, an overview is provided about currently available and new vaccination concepts."
8240,"Knowledge Dissemination and Best Practice Transfer on Biosafety, Biosecurity and Biorisk Management Through a Sustainable and Effective Education and Awareness System","Education is the first step to create a society that respects the others and the environment and that works to design and build a peaceful future. An effective and sustainable education system could rely on a tailored methodology that synergizes self-evaluation, gap-analysis, and train-the-trainers methods. This combination allows gathering information about real needs and expectations of training targets, elaborating a made-to-measure educational program and training future educators on topics of interest, making education and awareness system sustainable. Using these methodologies, we set up a knowledge development and transfer of best practice system on biosafety/biosecurity/biorisk management, in order to spread awareness and know-how on these topics. Twenty-two countries, in four different regions (South East Europe, South East Asia, North and West Africa) were involved in the project titled “Knowledge development and transfer of best practice on biosafety, biosecurity and biorisk management”. National Experts (NEs) from each country have been trained by intensive and e-learning courses to improve learning efficacy, to raise awareness and to foster networking as well as best practice sharing within each region. Consequently, the trained NEs disseminated the knowledge in their own countries, tailoring the courses on their local needs and expectations, amplifying the educational impact of the project. Here, we review the methodologies applied to develop a sustainable education and awareness system and the training contents related to biosafety/biosecurity/biorisk management."
8241,Mikrobiologische Labordiagnostik – Verlässlichkeit und Grenzen,"Fieber ist ein wichtiges Leitsymptom für viele Infektionskrankheiten, das einen ersten Hinweis auf eine bestehende Infektion geben kann. Hierbei spielen sowohl die Höhe der Temperatur als auch der Verlauf der Fieberkurve eine Rolle, wie z. B. bei der Malaria mit zyklisch auftretenden Fieberanfällen. Bei Infektionen mit Exanthem, wie z. B. Varizellen, ist das klinische Bild des Sternenhimmelphänomens mit Erythem, Papeln und Pusteln richtungweisend und bedarf nur in Ausnahmefällen einer weiteren labordiagnostischen Abklärung. Eine Schwellung der peripheren Lymphknoten und der Milz kann jedoch bei vielen Infektionskrankheiten auftreten und sollte labordiagnostisch näher untersucht werden."
8242,"Biologische Waffen — eine Herausforderung an Diagnostik, Therapie, Klinik und Prävention","Die im Oktober 2001 erfolgten Milzbrandattacken in den USA haben biologische Waffen zu Bewusstsein gebracht, Mediziner und Wissenschaftler müssen die Gefahren, die von solchen Waffen ausgehen, kennen und über mögliche vorsätzlich freigesetzte Mikroorganismen informiert sein, um Bevölkerung und Patienten behandeln und ggf. beruhigen zu können."
8243,Cordycepin: A Biotherapeutic Molecule from Medicinal Mushroom,"Cordyceps is one of the most well-known mushroom with numerous bioactive compounds possess wide range of biotherapeutic activities. This mushroom has been used for many years as medicinal food particularly in China and in different regions of south East Asia. Cordycepin is a nucleoside compound extracted from different species of Cordyceps and considered as one of the most important bioactive metabolites of this fungus. This low molecular weight compound exhibit several medicinal functions as anticancer, antitumor, antioxidant, anti-inflammatory, hypoglycemic, immunomodulatory agent. In this chapter we reviewed recent published research on the cordycepin chemistry, production, extraction, isolation, purification, biotherapeutic activities and applications."
8244,"Donor-Derived Infections: Incidence, Prevention, and Management","Organ donors reflect the diverse US population, and there are an increasing number of donors born in, who have resided in, or who have traveled to underdeveloped areas of the world or areas with geographically restricted infections. As such, these donors are exposed to pathogens that can potentially be transmitted to recipients of the donor’s organs. Additionally, there are newer techniques to identify many pathogens that may be transmitted from the donor to the transplant recipients. Finally, high-profile reports of several donor-derived infections have heightened awareness of donor-derived infections and have likely contributed to increased recognition. In this chapter, the incidence, methods of identification and prevention, and management of unexpected donor-derived infections will be reviewed."
8245,Microbiology,"Microbial contamination of pharmaceutical preparations may cause health hazard to the patient (e.g. infection, pyrogenic or allergic reaction), altered therapeutic activity of the product, or other decrease in quality (turbidity, loss of consistency, altered pH). This chapter provides a general introduction on pharmaceutical microbiology by focusing on the essential properties of micro-organisms. First of all the basic characteristics of life and the types of biological contaminants and potentially infectious agents of pharmaceutical products will be discussed: viz. prions, viruses, mollicutes, bacteria, fungi, and endotoxins. In the next section factors affecting survival and growth of micro-organisms are discussed. In addition to well-known factors such as time, temperature, and chemical and physical characteristics of the environment, attention will be paid to biofilm formation. Primary microbiological contamination is prevented by implementing an adequate microbiological quality control and quality assurance program and by following cGMPs during production. Microbiological quality control of pharmaceutical preparations and monitoring of production areas depend on the detection and quantification of micro-organisms. The classical, growth based, methods and some of the commercially available alternative methods are discussed. Understanding essential microbiological concepts is necessary in designing both microbiologically stable pharmaceutical products and ensuring an effective quality control and monitoring program within the manufacturing or preparation facility."
8246,Common Respiratory Viruses and Pulmonary Mucosal Immunology,
8247,Emerging Infectious Diseases: A Historical and Scientific Review,"The chapter defines Emerging Infectious Diseases (EIDs) and provides an historical and scientific overview, to illustrate how emerging diseases have evolved over the last few decades. For various reasons, including to control and curb the spread of these diseases, global funders, researchers and epidemiologists have established in Africa, and together with African governments set up research centers both during the pre- and post-colonial era to better understand the causative agents, epidemiology and control of infectious diseases. The chapter provides historical and current perspectives of some of these research centers, including their role in the detection and control of human and animal diseases in Africa. Given the immense health and economic burdens of EIDs on both the human and animal populations in Africa, there is an urgent need for African countries to own the means and processes of disease prevention and control, and invest in preparedness measures against the outbreak of diseases."
8248,President R. Gerald Ford,"President Ford, when faced with the emergence of a virus that appeared to be related to the one that caused the horrendous pandemic of 1918, moved vigorously to prepare for the possibility of another such onslaught. There was widespread agreement that the possibility of another such pandemic existed, and that prudence demanded quick action. Securing quick approval from a Democratic Congress, the Republican president launched the National Influenza Immunization Program to vaccinate virtually the entire population."
8249,Globalized Perspectives on Infectious Disease Management and Trade in Africa: A Conceptual Framework for Assessing Risk in Developing Country Settings,"In the era of globalization, internationalized representations of infectious disease threats have profound implications for understandings of infectious disease problems and their management in developing countries, particularly in Sub-Saharan Africa. By examining the policy implications of the key narratives around public health, animal health and trade, it becomes possible to clarify the relationship between global understandings of infectious disease risk and their impact on the development of local responses to disease problems. We highlight the tensions that resource-constrained countries face in the nexus of animal health-public health and trade, including the perception that resource-constrained countries are both source and victims of potential infectious disease threats. Given this scenario, it is important to think about how developing countries, particularly those in Sub-Saharan Africa, can approach infectious disease risk management as it relates to pandemic scale threats such as avian and pandemic influenza. We outline some of the key considerations in defining and assessing disease risk using avian and pandemic influenza in Zambia as an example. We conclude that the key to the feasibility of the analysis of the risk of multi-sectoral affecting emerging infectious diseases such as zoonotic avian influenza is flexibility in how risk is framed across the public health, animal health and trade systems."
8250,Proteomics Defines Protein Interaction Network of Signaling Pathways,"Protein interactions play fundamental roles in signaling transduction. Analysis of protein–protein interaction (PPI) has contributed numerous insights to the understanding of the regulation of signal pathways. Different approaches have been used to discover PPI and characterize protein complexes. In addition to conventional PPI methods, such as yeast two-hybrid (YTH), affinity purification coupled with mass spectrometry (AP-MS) is emerging as an important and popular tool to unravel protein complex and elucidate protein function through the interaction partners. With the AP-MS method, protein complexes are prepared first by affinity purification directly from cell lysates, followed by characterization of their components by mass spectrometry. In contrast to most PPI methods, AP-MS reflects PPI under near physiological conditions in the relevant organism and cell type. AP-MS is also able to probe dynamic PPI dependent on protein posttranslational modifications, which is common for signal transduction. AP-MS mapping protein interaction network of various signal pathways has dramatically increased in recent years. Here, I’ll present the strategies toward obtaining an interactome map of signal pathway and the methodology, detailed protocols, and perspectives of AP-MS."
8251,The Kidney and the Tropics,"In this age of rapid globalization and travel, diseases that were previously prevalent in warmer countries within the tropics are increasingly found in other countries with more temperate climates. A sound knowledge of such “tropical” renal diseases is essential for the practicing general pediatrician or nephrologist. This chapter describes tropical renal diseases as broadly divided into “infectious” conditions such as malaria, rickettsial infections, and viral hemorrhagic fevers, among others, and “toxic” conditions including snakebite and use of indigenous medicines which result in renal injury. In general, severe and progressive renal damage is preventable with early diagnosis and treatment of the underlying condition and provision of supportive care."
8252,Living Together,"The social life of bats is a complex and multifaceted one of constant interaction between males and females, between females and their pups, and between rivals, relatives, and other bats. Bats can form lasting friendships, they groom each other, they alert each other to danger, they form a united front against inquisitive owls, they steal and share food, and they look after each other’s young. The strategies of co-existence are almost as many as there are bat species. While some form stable, monogamous couples, others live in colonies of millions of individuals. Some live in small family groups or harems that stick together throughout the year (sometimes year after year), others change their groupings according to season."
8253,AIDS Policy: China’s Tipping Point,"China’s pioneering AIDS researchers were not content simply to build up evidence about HIV and the programmes that might prevent its spread. From early on, they worked actively to get the nation’s leaders to pay attention to the threat that a widespread HIV epidemic would pose to the country. As early as 1996, an inter-ministerial body called the State Council Coordination Mechanism Committee for AIDS/STD Control and Prevention was created under the chairmanship of Vice Premier Li Lanqing. The State Council is the highest administrative body in China, and the coordinating mechanism was able to bring together 21 ministries, providing each with guidance on its roles and responsibilities, to work on HIV prevention."
8254,Bats and Buildings: The Conservation of Synanthropic Bats,"Humans have shared buildings with bats for thousands of years, probably as early as first humans built primitive huts. Indeed, many bat species can be defined as synanthropic, i.e., they have a strong ecological association with humans. Bats have been observed using buildings as roosting and foraging sites, temporary shelters, for reproduction and hibernation. A synanthropic lifestyle may result in direct fitness benefits owing to energetic advantages in warmer roosts, which may ultimately lead to more rapid gestation and faster development of juveniles, or by being less exposed to natural predators in urban environments. All these benefits may allow bats to use buildings as stepping stones to exploit habitats otherwise devoid of roosting structures and may even lead to the expansion of geographic ranges. Yet, the coexistence with humans also comes with some risks. Bats may be exposed to chemical pollutants, particularly preservation chemicals used on lumber or during pest control measures. Bats may also be at risk of direct persecution or they may die accidently if trapped within buildings. In general, eviction of bats from buildings should follow the general rule of avoidance–mitigation–compensation. When considering conservation measures for synanthropic bats, it is most important to assess the role of the building for different life stages of bats. Construction work at buildings should be conducted in a manner that minimizes disturbance of bats. Artificial roosts can replace lost roosts, yet bats will often not accept alternative roosts. Demographic changes in human populations may lead to the abandonment of buildings, for example, in rural areas and to increased conflicts in urban areas when old buildings are replaced by new buildings or when previously unoccupied space in buildings is renovated. We advocate maintenance and enhancement of roosts for synanthropic bats, in addition to outreach and education campaigns, to improve the tolerance of humans for synanthropic bats."
8255,Neonatologie,"Noch vor 20 Jahren war die häufigste Todesursache Frühgeborener das akute Lungenversagen. Die sensationellen Ergebnisse von Mary Ellen Avery ebneten dann den Weg für eine kausale Therapie des Atemnotsyndroms. M.E. Avery beobachtete, dass die Lungen eines verstorbenen Frühgeborenen luftleer und »schwer« waren und kein »schäumendes Material« (»foam«) enthielten. Wie sie durch Experimente belegen konnte, fehlte diesen Lungen in der Tat eine Substanz, die die Oberflächenspannung in den Alveolen vermindert: das pulmonale Surfactant. Die 1959 publizierten Ergebnisse ihrer Untersuchungen fanden zunächst nicht die ihnen gebührende Aufmerksamkeit. Um die weitere Resonanz auf ihre Entdeckung zu beschreiben, verweist M.E. Avery gerne darauf hin, dass sich neues Wissen in 3 Phasen verbreitet: Die 1. Phase, in der neue Ergebnisse bekannt gegeben werden, wird meist ignoriert. In der 2. Phase rufen die inzwischen von anderen nicht mehr zu leugnenden Ergebnisse Feindseligkeiten hervor, in der 3. und letzten Phase besteht eine generelle Übereinstimmung darüber, dass man schon immer von dieser Tatsache ausgegangen sei."
8256,Epidemiology and etiology of Kawasaki disease,"Kawasaki disease was first reported in Japan in 1967 by Dr. Tomisaku Kawasaki. It has since been recognized worldwide, and in at the United States and Japan is the most important cause of acquired heart disease in children, surpassing other more recognized conditions such as rheumatic fever, endocarditis and myocarditis. It is primarily a disease of children less than 5 years of age but has been reported in older children and adults. Risk factors for the illness include Asian ancestry, male gender and certain familial predispositions. Observations such as similarity to certain exanthematous infectious diseases, temporal-geographic clustering of cases and seasonality in incidence favors an infectious etiology. Pathology and pathogenesis of the disease indicate that it is a medium-sized artery vasculitis that results from a dramatic immune activation that in most cases reversed by immune modulating agents such as intravenous immunoglobulin. Unfortunately, the etiology of the illness remains obscure, although recent studies favor a possible viral etiology."
8257,Introduction: Origins of Human Security,"Human security denotes a human-denominated, as opposed to State, focus for security. It highlights the duality of individual, universal—universalizable—human rights. This duality is central to the notion of human rights tied to human security. The idea of human security beyond borders is fundamentally an exercise in reimagining the traditionally State-based loci of responsibility for those individual but also universal human rights. This chapter introduces the challenges of geopolitical shifts compounded by unprecedented impacts of climate change, migration, and pandemic (potential). It makes a case for rethinking human security of citizens and non-citizens alike—beyond borders."
8258,"SIRS, Sepsis und Multiorganversagen",
8259,Lessons Learned and Reordering Policy Prescriptions,"The final Chapter 8 offers practical policy suggestions towards (re)ordering health. It takes into account that not all health rights and threats are of the same caliber, that prioritization is a necessity. It also acknowledges that not all risks and threats can be anticipated or annulled. Bearing these limitations in mind, the chapter re-frames health risks in terms of a re-ordering of health security at the level of local, national, and global policy. It also offers theoretical as well as concrete suggestions on how it might be possible to conceptualize, communicate, and confront health risks and threats with states, non-state actors and other agents to facilitate health rights responsibility within and across borders."
8260,Genetic Polymorphisms in Critical Care and Illness,
8261,Computational Fluid and Particle Dynamics (CFPD): An Introduction,"Computational Fluid Particle Dynamics (CFPD) is an emerging research field that involves interdisciplinary research areas with a broad range of applications. Fluid-particle flows can be found all around us, from the airborne particles we breathe to industrial applications such as fuel spray in internal combustion engines, fluidised bed combustors, and mineral processing to name a few. In the health, pharmaceutical, and biomedical fields, interest is increasing in the use of computational modelling for inhalation toxicology analysis, effectiveness of drug delivery systems, respiratory and physiological flows. Computational modelling is being used in many industries as a valuable tool for cost and cycle time reductions during product development, and it can provide proof of concept for model designs. This technique has been encouraged by the rapid developments in computational models to reflect the physics, which is in line with the increase in computing power."
8262,Cardiovascular Disease: An Introduction,"Cardiovascular disease (CVD) is a collective term designating all types of affliction affecting the blood circulatory system, including the heart and vasculature, which, respectively, displaces and conveys the blood."
8263,Leadership and Health in Africa,"A second generation of leaders has now assumed power in Africa, replacing those who inherited the colonial state following independence during the 1960s and 1970s and, in a few cases thereafter. Since independence, two or three governing trends have become clear on the continent. Foremost, it seems that, to the committed first group of leaders who inherited the colonial state, the most important goal was to eliminate ethnic divisions and create new nations, where the state was sacrosanct."
8264,Gastroenterologie,
8265,Komplementsystem und Komplementdefekte,"Unter den Mechanismen, die zum Selbstschutz des Körpers beitragen, ist das Komplementsystem von herausragender Bedeutung. Als Teil der angeborenen Abwehr ist es jederzeit verfügbar und somit bereits in der Präimmunphase von unschätzbarem Wert, bevor es zur Bereitstellung spezifischer Antikörper und T-Lymphozyten kommt. Zu seinen Effektorfunktionen zählen neben der lytischen Zerstörung pathogener Mikroorganismen die Beseitigung von Immunkomplexen, die Opsonisierung nicht nur von Krankheitserregern, sondern auch von autoantigenem Material für eine effiziente Phagozytose sowie die Rekrutierung und Aktivierung von Entzündungszellen. Darüber hinaus moduliert das Komplementsystem aber auch die Antwort des erworbenen Immunsystems. Außerdem wird in zunehmendem Maße die Rolle des Komplementsystems in so unterschiedlichen biologischen Prozessen wie der Hämatopoese, Fortpflanzung und der Organregeneration deutlich, so dass die Vorstellung von Komplement als reinem Abwehrsystem erweitert werden muss zu einem mit vielen biologischen Funktionen vernetzten und steuernden System zur Aufrechterhaltung der Homöostase. Etwa 5 % aller Plasmaproteine sind Komplementfaktoren, die zum überwiegenden Teil in der Leber und durch Makrophagen synthetisiert werden. Aber auch Fibroblasten, Epithelzellen der Lunge und des Magen-Darmtraktes und weitere Gewebszellen, wie Astrozyten, Haut-und Muskelzellen, sind prinzipiell zur Synthese zumindest bestimmter Komplementproteine fähig."
8266,Risk of Globalization of the Disease in Europe,"Risk of dissemination of ZIKV disease is based on multiple factors, including environmental (climate, socioeconomically, deforestation or industrialization) and travel/traveller factors. Both the disease (viremic travellers) and vector movement to mosquito-free area contributes to the introduction and establishment of autochthonous ZIKV transmission. Mass gathering events can contribute to magnify transmission due to close crowd life in a confined area. Also, multitudinary events can promote the introduction of an infectious disease to a previously naïve area when returning home. Although mathematical models estimate a low risk for introduction of ZIKV in Europe, specific European regions (mainly Portuguese Island of Madeira) account with suitable and efficient vector and opportune climate conditions to harbour the disease. Clinicians should be aware to enable early detection of autochthonous ZIKV cases. International and local guidelines can help clinicians on how to handle suspicious cases, how to confirm the infection and how to report suspected and confirmed cases. In case of autochthonous ZIKV detection, public authorities should perform surveillance and provide adequate resources to sustain enhanced mosquito control."
8267,Historical Aspects of Polyclonal IgG Preparations,"Today we can choose between several polyclonal IgG products for both replacement and immunomodulation. However, it was a long way to go to reach this stage. In this chapter, we try to illustrate the major stages of IgG product development which began more than 70 years ago."
8268,Switching Control Strategies,"This chapter is motivated by the application of control strategies to eradicate epidemics. In part, the previous switched epidemic models are reintroduced with continuous (e.g., vaccination of newborns continuously in time) or switching control (i.e., piecewise continuous application of vaccination or treatment schemes) for evaluation and optimization. As discussed earlier, infectious disease models are a crucial component in designing and implementing detection, prevention, and control programs (e.g., the World Health Organization’s program against smallpox, leading to its global eradication by 1977). The switched SIR model is first returned to for consideration and analysis of vaccination of the susceptible group (e.g., newborns or the entire cohort). Subsequently, the developed theoretical methods are applied to the switched SIR model with a treatment program in effect. Common Lyapunov functions are used to provide controlled eradication of diseases modeled by the so-called SEIR (Susceptible-Exposed-Infected-Recovered) model with seasonal variations captured by switching. A screening process, where traveling individuals are examined for infection, is proposed and studied for the switched multi-city model of the previous chapter. Switching control of diseases such as Dengue and Chikungunya which are spread via mosquito–human interactions, is investigated."
8269,Viszeralchirurgie,
8270,Bioterrorism,
8271,Animal Health Policy,"The EU remains under threat of communicable diseases of livestock that may have a severe economic impact or that are of public health significance or both. Such diseases may be introduced and spread by the trading of animals and their products. Measures in line with international agreements are required to prevent the introduction of disease, to control its spread and to protect animal and human health, and to provide safe, wholesome food for European consumers. The EU’s Animal Health Strategy 2013–2017, the Common Financial Framework and the Animal Health Law contributed to the recent update of the EU’s animal health policy. Although the EU’s animal health policy is evaluated to be clearly effective, its cost-effectiveness (efficiency) is difficult to determine."
8272,Safety and Efficacy of Hemoglobin-Vesicles and Albumin-Hemes,"Keio University and Waseda University have worked together on artificial O(2) carrier research for 20 years in close cooperation. Two candidate materials have been selected from the viewpoints of safety, efficacy, and cost performance. One is Hemoglobin-vesicles (HbV) and the other is albumin-heme (rHSA-heme). This chapter summarizes our video presentation that introduced the recent results of our research into HbV and rHSA-heme."
8273,China’s Prevention and Control and Policy Changes to the Influenza A (H1N1) Pandemic,"The first case of Influenza A (H1N1) in China was found in Hong Kong, on May 1st, 2009, where the patient had flown from Mexico to Hong Kong via Shanghai. On May 11th, Sichuan Province reported the first imported Influenza A (H1N1) case in mainland China, and the first domestic case was reported on May 29th."
8274,The Synthetic Nature of Biology,"For centuries, biology was centred on the analysis of the microscopic and macroscopic worlds, but since the end of the 19th century it progressively adopted synthesis as a means to understand biological systems, strengthened recently by the dawn of synthetic biology. Contemporary synthetic biology is essentially composed of various “research tribes” with different methods, languages, metaphors and agendas willing to understand biological systems and—in particular—to engineer them for solving health, food, energy and environmental problems. Synthetic biology is not only an extension of traditional genetic engineering where Genetically Modified Organisms (GMOs) are produced, but it is also endowed of various elements that allow the emergence of new artificial life forms. In this chapter, a brief history of synthetic biology is presented, followed by a description of its most prominent “tribes” and a proposition for categorising the various engineering approaches currently practiced in the field. An overview of existing and nascent GMOs is also given, including some of their applications as well as biosafety and biosecurity risks. Finally, some challenges, dilemmas and paradoxes in synthetic biology beyond the bench are very briefly examined, particularly with regard to global social justice, democratization of molecular biology, environmental concerns, policy regulation, the GMO debate, media hype, public acceptance, and the issue of resurrecting extinct life."
8275,Transplantation,"The intensive care unit (ICU) is integral in any successful transplant program, as the care of these transplant recipients requires exhaustive multidisciplinary care. After transplantation, these patients have a host of hemodynamic changes that affect both the allograft and global end-organ function. All organ systems remain intricate in the ICU and must be monitored closely as the acuity remains high even after the immediate postoperative period. Managing these patients requires an in-depth understanding of immunosuppressive medications as well as their side effect profiles and drug interactions to safely navigate the care of these patients. Not surprisingly, given these patients have an innate immunosuppressive state in addition to these medications, they remain susceptible to aggressive post-transplant infections. Communication between the ICU and the transplant team remains key to the success of each individual transplanted graft and patient."
8276,Respiratory Syncytial Virus and Human Metapneumovirus Infection in Transplant Recipients,"Respiratory viral infections due to respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause infections in immunocompromised transplant patients ranging from mild upper respiratory infections to severe lower respiratory tract disease with respiratory failure. These viruses are more readily diagnosed due to improvements in sensitive molecular diagnostic methods. The epidemiology of RSV and hMPV is similarly becoming more readily appreciated in hematopoietic stem cell transplant (HSCT) patients of all ages as well as solid organ transplant (SOT) patients, with lung transplant recipients having evidence of more frequent and severe complications related to these viruses. RSV and hMPV infection typically but not always present with upper respiratory signs and symptoms that progress to lower respiratory tract disease. Treatment options for RSV are limited, with aerosolized, intravenous, and oral ribavirin all studied in HSCT and lung transplant patients. No antiviral therapy for the treatment of hMPV is available, although ribavirin has shown some effectiveness in vitro. New antiviral agents including RSV fusion inhibitors and nucleoside analogs are being developed, with some under clinical evaluation."
8277,Aeromedical Evacuation of Patients with Contagious Infections,"Most patients with infectious diseases, including biologic warfare casualties, can be safely transported by aeromedical evacuation (AE) using standard precautions. However, certain contagious diseases (e.g., tuberculosis, pneumonic plague, viral hemorrhagic fever) require transmission-based precautions to protect the other patients, medical personnel, and aircrew. AE planning for these patients must take into account international public health regulations. Given adequate resources, foresight, and expertise, the AE of infected patients and biologic warfare casualties can be safely accomplished. This chapter provides a review of the aeromedical evacuation of patients with communicable diseases. Topics include a review of the ecology of aircraft cabins and engineering features of aircraft ventilation systems that minimize the risk of disease transmission; examples of point source outbreaks related to air travel; in-flight preventive measures including the use of patient isolators; and US military and international policy and legal aspects of transporting patients with communicable diseases. Examples include in-flight transmission of tuberculosis, severe acute respiratory syndrome (SARS), smallpox, and measles.The chapter will also discuss experience in transporting patients with contagious diseases including viral hemorrhagic fevers and new patient isolation technologies that were used for the long-distance transport of patients with Ebola virus disease during the 2014–2016 West African epidemic."
8278,Acute Right Heart Failure,"Heart failure is defined as a life-threatening complex clinical syndrome with exacerbation of symptoms signifying decompensation and requires emergent treatment. In its acute state it presents within 24 hours with symptoms such as shortness of breath, volume overload including pulmonary edema, sometimes forward failure and even cardiogenic shock. Two forms of acute heart failure exist: newly diagnosed “de novo” or acutely decompensated chronic heart failure. This chapter summarizes the clinical and prognostic classification of acute right heart failure, epidemiology, diagnostic work-up and the principles behind treatment and management options that focus on preload optimization, afterload reduction and improvement of contractility."
8279,Low-cost Paper Analytical Devices for Environmental and Biomedical Sensing Applications,"Over the last decade, the fabrication of analytical devices utilizing microfluidic structures and lab-on-a-chip platforms has shown breakthrough advancements, both for environmental and biological applications. The ASSURED criteria (affordable, sensitive, specific, user-friendly, robust, equipment-free, delivered), developed by the WHO for diagnostics devices, point towards the need of paper-based analytical devices (PAD) for diagnostics. On the other hand, cost-effective PADs owing the great advantage of affordable applicability in both resource-rich and -limited settings are recently employed for on-site environmental monitoring. In this book chapter, we will discuss about the brief history of paper analytical devices, fabrications, need, and its environmental and biomedical applications."
8280,"Other Potentially Life-Threatening Conditions with Mucocutaneous Findings (Leptospirosis, Typhoid Fever, Dengue, Diphtheria, Murine Typhus)","There are several conditions with mucocutaneous findings that are potentially life-threatening, particularly in certain vulnerable populations. In this chapter, leptospirosis, typhoid fever, dengue, diphtheria, and murine typhus are reviewed. The disease time course of classic and atypical presentations is detailed to assist making the diagnosis in subtle cases. Associated symptoms are discussed as well as a comparison with disease mimics and differential diagnoses. Key diagnostic features are emphasized, and evidence-based management of each condition is detailed in this chapter."
8281,"Risk, Health and Medicine in The New York Times","The study provides evidence for the increasing usage of risk words in reporting on health and illness. Chronic and civilisation illnesses are well represented and contribute to this trend. Infectious diseases often inform short risk hypes. AIDS’ long-term presence has become a less prominent topic, as treatment improves and panic subsides. An epidemiological worldview and strong references to scientific studies carry the instantiation of risk. There is less conscious and/or agentive risk-taking in the reporting on health and illness than in other social domains. While women and children (for example) are frequently represented in relation to risk, they are less likely to be presented as taking risks, and more likely to experience them."
8282,"ER Stress, UPR and Virus Infections in Plants","The endoplasmic reticulum (ER) endomembrane is a central site for protein synthesis. Perturbation of ER homeostasis can result in an accumulation of unfolded proteins within the ER lumen, causing ER stress and the unfolded protein response (UPR). In humans, ER stress and UPR are closely associated with a vast number of diseases, including viral diseases. In plants, two arms that govern the UPR signaling network have been described: one that contains two ER membrane–associated transcription factors (bZIP17 and bZIP28) and the other that encompasses a dual protein kinase (RNA-splicing factor IRE1) and its target RNA (bZIP60). Although early studies mainly focus on the essential roles of the UPR in abiotic stresses, the significance of UPR in plant diseases caused by virus infections has recently drawn much attention. This chapter summarizes the latest scenario of ER stress and UPR in virus-infected plant cells, highlights the emerging roles of the IRE1 pathway in virus infections, and outlines exciting future directions to spark more research interest in the UPR field in plants."
8283,Hämotherapie und Patient Blood Management,"Blutprodukte können Leben retten, z. B. bei schwerverletzten Patienten oder großen Operationen, aber ihre Anwendung kann auch mit teilweise erheblichen Risiken verbunden sein, z. B. Infektionsrisiko, akute Lungenschädigung oder ggf. sogar ein erhöhtes Tumorrisiko. Daher müssen die Indikationen zur Fremdblutgabe genau bekannt sein, aber auch das richtige Vorgehen bei der Bluttransfusion sowie alle Maßnahmen, um eine Transfusion bestmöglich zu verhindern. Das vorliegende Buchkapitel befasst sich mit den Grundlagen und allen praktischen Aspekten der Bluttransfusion, der maschinellen Autotransfusion und stellt auch das Konzept »Patient Blood Management« dar."
8284,"Physiology, Benefits and Risks of Red Blood Cell Transfusion",
8285,Performance evaluation of a Bayer Healthcare Diagnostics research-based SARS coronavirus assay,
8286,Chapter 1,"“I have Japanese Encephalitis,” a woman on the phone told her. “Really? Have you been to a doctor?” Eliza scratched the letters JE on her purple notepad and began to take the report. “No, I just think, I mean, I am pretty sure that’s what I have.” “Ok. Why do you think that? Have you traveled outside of the country recently?” “No, I think I must be the first person to get it in the United States. I looked up my symptoms on the internet and that sounds exactly like what I have.”"
8287,Exploitation of Bats for Bushmeat and Medicine,"Bat hunting for consumption as bushmeat and medicine is widespread and affects at least 167 species of bats (or c. 13 % of the world’s bat species), in Africa, Asia, across the islands of Oceania, and to a lesser extent in Central and South America. Hunting is particularly prevalent among the large-bodied fruit bats of the Old World tropics, where half (50 %, 92/183) the extant species in the family Pteropodidae are hunted. Pteropodids that are hunted are six times more likely to be Red Listed as threatened: 66 % of species in IUCN threatened categories (CR, EN, VU, NT), compared to 11 % of species in the ‘Least Concern’ (LC) category. However, there still appears to be an information gap at the international level. One third of the hunted species on the Red List are not considered threatened by that hunting, and nearly a quarter of the bat species included in this review are not listed as hunted in IUCN Red List species accounts. This review has resulted in a comprehensive list of hunted bats that doubles the number of species known from either the IUCN Red List species accounts or a questionnaire circulated in 2004. More research is needed on the impacts of unregulated hunting, as well as on the sustainability of regulated hunting programs. In the absence of population size and growth data, legislators and managers should be precautionary in their attitude towards hunting. Roost site protection should be a priority as it is both logistically simpler than patrolling bat foraging grounds and reduces the comparatively larger scale mortality and stress that hunting at the roost can cause. Education and awareness campaigns within local communities should demonstrate how bats are a limited resource and emphasize characteristics (nocturnal, slow reproducing and colonial) that make them particularly vulnerable to hunting pressure."
8288,Hämatologie,
8289,Minimally Invasive Diagnostic Strategy in Immunocompromised Patients with Pulmonary Infiltrates,"Acute respiratory failure (ARF) is the main reason for ICU admission in patients with haematological malignancies. High mortality rates of up to 50% are reported in this situation, and mortality is highest when mechanical ventilation is needed. Rapid and accurate diagnostic methods are needed in these vulnerable patients to ensure the prompt initiation of effective treatment. However, the broad array of possible cause of ARF raises diagnostic challenges. In this review, we discuss the DIRECT strategy, which identifies the most plausible diagnosis in each patient based on the type of immune deficiency and clinical presentation. We will focus on non-invasive laboratory tests developed in recent years, discussing their sensitivity and specificity. We also discuss the usefulness in cancer patients with specific organ dysfunctions of biomarkers introduced over the past few years."
8290,Building the Infrastructure and Regulations Needed for Public Health and Fitness,"1. To recognize the importance to the maintenance of good health of adequate public health regulations and an infrastructure that provides clean water and appropriate waste management. 2. To see the lack of such amenities over many centuries, but the progressive development of public health bureaucracies dedicated to provision of an appropriate infrastructure for healthy cities, beginning during the Victorian Era. 3. To observe how responsibility for the provision of adequate housing for poorer city dwellers has been shared between government, benevolent entrepreneurs and charities. 4. To note the new challenges to public health presented by such current issues as the abuse of tobacco and mood-altering drugs, continuing toxic auto-emissions, the epidemic of HIV/AIDS, a decreased acceptance of MMR vaccinations, and the ready spread of infectious diseases by air travel."
8291,Centralising Information: Predicting and Managing the Risk of Pandemics at the WHO,"In order to analyse the centralisation of information, the research team went to the SHOC Room of the World Health Organization (WHO) in Geneva, a critical hub through which passes all information destined to managing worldwide epidemic risks. The description of the WHO’s surveillance device for epidemic diseases has brought to our attention the fact that an information becomes ‘alive’ only if seized, translated and transmitted to the next level, which in turn, undertakes the same process, and so on, thus creating a succession of ‘captures’. Furthermore, the socio-technical intermediaries, which are constantly being perfected by technological advancements, have allowed to broaden, in response to the SARS crisis, the notion of risk and to display the emergence of a novel spatiality on the scene of world affairs. This broadening also tampers with temporality. The WHO must now not only come to terms with the ‘during’, but must also invest in the analysis of all potentially sensitise information, such as rumours."
8292,Postoperative Liver Failure,"Technical innovations in surgical techniques, anaesthesia, critical care and a spatial understanding of the intra-hepatic anatomy of the liver, have led to an increasing number of liver resections being performed all over the world. However, the number of complications directly attributed to the procedure and leading to inadequate or poor hepatic functional status in the postoperative period remains a matter of concern. There has always been a problem of arriving at a consensus in the definition of the term: postoperative liver failure (PLF). The burgeoning rate of living donor liver transplants, with lives of perfectly healthy donors involved, has mandated a consensual definition, uniform diagnosis and protocol for management of PLF. The absence of a uniform definition has led to poor comparison among various trials. PLF remains a dreaded complication in resection of the liver, with a reported incidence of up to 8 % [1], and mortality rates of up to 30–70 % have been quoted [2]. Several studies have quoted a lower incidence of PLF in eastern countries, but when it occurs the mortality is as high as in the West [3]."
8293,Respiratory Viruses,"The respiratory viruses as a group are the most common cause of an acute infectious illness in developed societies. The immunocompromised state of many cancer patients constitutes the basis for the frequent failure of the host to promote a normal and rapid recovery from an acute respiratory viral infection and results in a more severe and prolonged infection that causes significant morbidity and mortality in these patients. Those respiratory viruses that are most prevalent and most prone to produce lower respiratory illnesses and pneumonia in healthy hosts, RSV, influenza viruses, and parainfluenza viruses, are those most likely to cause severe illness and pneumonia leading to hospitalization in immunocompromised persons. However, viruses less prone to produce a lower respiratory illness but that are highly prevalent, such as rhinoviruses, may frequently be associated with severe illness. The limited availability of antivirals and vaccines for the acute respiratory viruses means that these infections will continue to be important for many years and dictate a need for utilizing infection control procedures as much as possible, particularly in hospitals and institutions, so as to minimize spread. Efforts to develop specific vaccines are important as their use could prevent as well as reduce exposure of cancer patients to these viruses. Development of specific antivirals is important for use in immunocompromised patients as normal recovery mechanisms may be seriously impaired."
8294,A Security Culture,"Since the events of 11 September 2001, there have been several attempts against the security of aircraft in flight. These threats have ranged from shoe bombs to dirty bombs to explosives that can be assembled in flight with liquids, aerosols and gels. In every instance the global community has reacted with pre emptive and preventive measures which prohibit any material on board which might seemingly endanger the safety of flight. Some jurisdictions have even gone to extremes in prohibiting human breast milk and prescriptive medications on board."
8295,Croup,"Case 1 A 20-month-old boy is brought to his family practitioner by his mother. The boy has a 12-hour history of a loud cough, slight fever to 101°F, and a hoarse voice. The mother reports that the child had a difficult time sleeping the previous night because of the harsh cough. On examination, the boy is playful and smiling with a temperature of 99°F. It is noticed that he has a seal-like barking cough and subtle evidence of audible stridor.His chest is clear on auscultation with a normal respiratory rate.No chest wall recession is noted. The rest of the exam is unremarkable. The patient is sent home with a suspected upper respiratory infection. Later that evening, the family practitioner receives a phone call from the emergency department informing him that the patient has had worsening respiratory difficulty with visible signs of inspiratory stridor and is being admitted to the hospital for further observation."
8296,Virale Gastroenteritiserreger,"Gastroenteritiden gehören zu den häufigsten Erkrankungen des Menschen und sind verbunden mit einer hohen Krankheitslast und Mortalität. Besonders betroffen sind Säuglinge und Kleinkinder in den Tropen, wo jährlich schätzungsweise 1–2 Mio. Kinder an einer Gastroenteritis versterben. Viren gehören zu den häufigsten Auslösern dieser Erkrankungen. Seit der elektronenmikroskopischen Entdeckung des Norwalkvirus 1972 wächst die Zahl der bekannten Erreger (◘ Tab. 65.1)."
8297,Design and Simulation of Isolation Room for a Hospital,"Heating, ventilation and air conditioning (HVAC) of hospitals is a highly specialized field and critical care units like isolation rooms and operation theatres deserve special attention, as infected patients must be isolated from ambient environment in order to prevent the infection from spreading and to save the life of the patient. This manuscript aims to optimize the ventilation strategy towards contaminant suppression in the isolation room. 3D Navier-Stokes and energy equation using finite volume method (FVM) with a domain of isolation room is solved for appropriate boundary conditions. The patient’s body is approximated as a semi-cylindrical shape resting on a bed and is treated as a constant heat source. Velocity and temperature profile inside the isolation room for various configurations are simulated. Our results suggest that immune-suppressed patients should be kept near the air supply and infectious patients near the exhaust."
8298,Similarity and Diversity in Chemical Design,"Following a simple introduction to drug discovery research, this chapter presents some mathematical formulations and approaches to problems involved in chemical database analysis that might interest mathematical/physical scientists. With continued advances in structure determination, genomics, and high-throughput screening and related (more focused) techniques, in silico drug design is playing an important role as never before. Thus, traditional structure-directed library design methods in combination with newer approaches like fragment-based drug design [496, 1447], virtual screening [453, 1179], and system-scale approaches to drug design [236, 278, 649] will form important areas of research."
8299,Acute Viral Rhinitis,"Rhinitis refers to any kind of inflammatory condition of the nasal mucosal linings. Generally, acute rhinitis is associated with environmental allergies or respiratory viral infections. Viral microbes with numerous types and subtypes can infect the respiratory epithelium of the nasal cavity in a repetitive fashion throughout the year, or during a specific period of time such as winter or fall. Among all forms of inflammatory diseases of the nasal mucosa, acute viral rhinitis (AVR) has unique epidemiological, clinical, and therapeutic characteristics. As the most prevalent type of rhinitis, AVR is also the most common form of any infectious disease of the human body. Although it is almost always self-limiting, in rare circumstances disease might progress and the clinical scenario could become complicated. Common complaints and physical findings related to AVR are similar to those seen with other types of rhinitis such as allergic, hormonal, senile, or drug induced. The clinician must interpret these symptoms and findings in the context of other parameters such as “duration, environmental factors, and patient characteristics” to establish an accurate diagnose and appropriate therapeutic management. In this chapter, we aim to discuss the epidemiology, pathogenesis, clinical findings, differential diagnosis, and therapeutic management of AVR in light of the recent literature knowledge. It is our hope that this chapter may aid medical professionals who encounter AVR in daily practice."
8300,Specific Virology: Viruses as Diseases,1796: Jenner transfers cowpox material from a milkmaid to a boy and shows evidence of immunity generated by re-vaccination with virulent pox material.
8301,Infektionen bei Immundefizienz,
8302,"Hazards, Disasters, and Risks","In this chapter, we will elaborate on three basic terms in the field of disaster risk science: hazards, disasters, and risks. We will also discuss the classification, indexes, temporal and spatial patterns, and some other fundamental scientific problems that are related to these three terms."
8303,Evaluations from Different Parties on Influenza A (H1N1) Prevention and Control,"Assessments of policy formulation and implementation by domestic and international stakeholders, especially domestic stakeholders, comprise a crucial component of policy evaluation. The end goals of the state’s prevention and control efforts were: to ensure the public health and safety, protect social order, and maintain the status quo in work and life. Thus, assessments on the state’s responses by patients, close contacts, medical personnel, the public, and international community could reflect in many ways the degree of completion for expected objectives and the social effects of adopted prevention and control efforts."
8304,Integrating the Veterinarian Scientist to the One Health Concept,"One health is the integrative effort of multiple disciplines working together to attain optimal health for people, animals, and the environment. One health is thus at the intersection of human, animal, and environment health, and in the one health paradigm, these three different domains merge into one superposed and universal goal. The number of outbreaks around the world is increasing, in terms of total number and diversity of outbreaks and the richness of pathological agents. Identifying the origin of these outbreaks is important to ensure appropriate capacity to respond to potentially pandemic threats. Many (re-)emerging pathogens come from animals, and there is a compelling need to understand the epidemiology of these diseases, including the role of animals as disease reservoirs. In parallel, the progressive phasing out of antibiotics in animal foods around the world has been achieved through active collaboration of physicians and veterinarians, and it is to be hoped that this continued interaction will help align human and veterinary medicine with the objectives of the one health paradigm. Indeed, a multi-sector cooperative approach between human and veterinarian health will contribute to improved preparedness and capacity for response to current and future health threats using the one health concept."
8305,Viral Infections by Nonhepatotropic Viruses,
8306,Desire and the Law: Creative Resistance in the Reluctant Passenger and the Heart of Redness,"This chapter offers a critique of animal rights approaches for their weakness in relying on the passage of laws, and in depending upon their proper administration by legal authorities to attempt the protection of animals. Where some thinkers espouse an animal rights perspective, this chapter argues that postcolonial desire is vital to protecting communities in ways that rights discourse and the law cannot in the context of the biopolitical workings of the state and globalized capitalism. Drawing from Deleuze and Guattari’s work on desire and the law in Kafka (1986), the chapter considers the potential of desire to offer creative alternatives, outside of legal discourse, toward the protection of animals and the larger community. Additionally, it recognizes how indigenous environmental knowledge and notions of desire offer ways of relating to animals that can challenge capitalist instrumentalization."
8307,Apoptosis in Critical Illness: A Primer for the Intensivist,"The complexities of the cell cycle have occupied a prominent place in the history of cellular biology. Recognition of the process of mitosis dates back over a century, when Fol, Butschli, and Strasburger identified a network of intracellular points and lines, then called the karyokinetic figure, and today known as the mitotic apparatus. This discovery, dating to 1873, laid the foundation for the discovery of chromosomes and, later, the fundamental biologic processes of mitosis and meiosis [1]. But, while cellular growth and proliferation were understood to be essential to the emergence of multicellular organisms, the corollary — that controlled cell death must be part of this calculus of cellular homeostasis — was not appreciated until quite recently. Although cell death was first described in 1859 by Virchow, it took more than a century to appreciate the importance of programmed cell death as a physiological process that eliminated unwanted cells [2]. The term ‘apoptosis’ was coined in 1972 by Kerr, Wyllie, and Currie to describe a distinct type of cell death characterized by the degradation of cellular constituents into membrane-bound apoptotic bodies [3]. Since then, recognition of the importance of apoptosis in health and disease, and an understanding of its cellular mechanisms, has increased exponentially."
8308,Adrenal Insufficiency,"The stress system receives and integrates a diversity of cognitive, emotional, neurosensory and peripheral somatic signals that are directed to the central nervous system through distinct pathways. The stress response is normally adaptive and time limited and improves the chances of the individual for survival. The stress response is mediated largely by activation of the hypothalamic-pituitary-adrenal (HPA) axis with the release of cortisol. In general, there is a graded cortisol response to the degree of stress, such as the type of surgery. Cortisol levels also correlate with the severity of injury, the Glasgow Coma Scale and the APACHE score. Cortisol effects the transcription of thousands of genes in every cell of the body. In addition, the cortisol-glucocorticoid receptor complex effects cellular function by non-transcriptional mechanisms. Cortisol has several important physiologic actions on metabolism, cardiovascular function and the immune system. Cortisol increase the synthesis of catecholamines and catecholamine receptors which is partially responsible for its positive inotropic effects. In addition, cortisol has potent anti-inflammatory actions including the reduction in number and function of various immune cells, such as T and B lymphocytes, monocytes, neutrophils and eosinophils at sites of inflammation. Cortisol is the most important inhibitor of the transcription of pro-inflammatory mediators (inhibits NF-kB and AP-1 by multiple mechanisms) [1]."
8309,Utilization Management in a Large Community Hospital,"The utilization management of laboratory tests in a large community hospital is similar to academic and smaller community hospitals. There are numerous factors that influence laboratory utilization. Outside influences like hospitals buying physician practices, increasing numbers of hospitalists, and hospital consolidation will influence the number and complexity of the test menu that will need to be monitored for over and/or under utilization in the central laboratory and reference laboratory. CLIA’88 outlines the four test categories including point-of-care testing (waived) and provider-performed microscopy that need laboratory test utilization management. Incremental cost analysis is the most efficient method for evaluating utilization reduction cost savings. Economies of scale define reduced unit cost per test as test volume increases. Outreach programs in large community hospitals provide additional laboratory tests from non-patients in physician offices, nursing homes, and other hospitals. Disruptive innovations are changing the present paradigms in clinical diagnostics, like wearable sensors, MALDI-TOF, multiplex infectious disease panels, cell-free DNA, and others. Obsolete tests need to be universally defined and accepted by manufacturers, physicians, laboratories, and hospitals, to eliminate access to their reagents and testing platforms."
8310,Public Health Informatics and the Health Information Infrastructure,"What are the three core functions of public health, and how do they help shape the different foci of public health and medicine? What are the current and potential effects of a) the genomics revolution; and b) 9/11 on public health informatics? What were the political, organizational, epidemiological, and technical issues that influenced the development of immunization registries? How do registries promote public health, and how can this model be expanded to other domains (be specific about those domains) ? How might it fail in others?Why? What is the vision and purpose of the National Health Information Infrastructure? What kinds of impacts will it have, and in what time periods? Why don’t we have one already? What are the political and technical barriers to its implementation? What are the characteristics of any evaluation process that would be used to judge demonstration projects?"
8311,Discovery of Beclabuvir: A Potent Allosteric Inhibitor of the Hepatitis C Virus Polymerase,"The discovery of beclabuvir occurred through an iterative series of structure-activity relationship studies directed at the optimization of a novel class of indolobenzazepines. Within this research, a strategic decision to abandon a highly potent but physiochemically problematic series in favor of one of lower molecular weight and potency was key in the realization of the program’s objectives. Subsequent cycles of analog design incorporating progressive conformational constraints successfully addressed off-target liabilities and identified compounds with improved physiochemical profiles. Ultimately, a class of alkyl-bridged piperazine carboxamides was found to be of particular interest, and from this series, beclabuvir was identified as having superior antiviral, safety, and pharmacokinetic properties. The clinical evaluation of beclabuvir in combination with both the NS5A replication complex inhibitor daclatasvir and the NS3 protease inhibitor asunaprevir in a single, fixed-dose formulation (Ximency) resulted in the approval by the Japanese Pharmaceutical and Food Safety Bureau for its use in the treatment of patients infected with genotype 1 HCV."
8312,Transgenerational Consequences of Human Visitation,"Human interactions with wild animals may result in changes in behavior across generations with consequences for population trends and hence threat status. Exposure to humans and tameness of animals when exposed to humans may also imply significant costs such as the rapid spread of viruses and other microorganisms that constitute reservoirs or vectors of serious diseases. Ecotourism and nature-based tourism are factors that may affect the behavior of animals living in natural habitats, including their stress and fear responses. Here I review a scarce and scattered literature dealing with changes in animal behavior across generations and critically assess the relative importance of the mechanisms that potentially underlie these changes. Animals may show short-term changes in behavior across generations as a consequence of microevolution (a genetic change in behavior), nongenetic so-called epigenetic changes, reductions in the response to behavioral stimuli with repeated exposure to a stimulus (habituation), and the nonrandom distribution of animals that differ in behavior among sites (so-called phenotypic sorting). I conclude with a plea for future research to allow assessment of the underlying causes of long-term changes in behavior of animals exposed to human disturbance, particularly those changes caused by ecotourists’ activities."
8313,Late Noninfectious Pulmonary Complications in Hematopoietic Stem Cell Transplantation,"Hematopoietic stem cell transplantation (HSCT) is an established therapeutic modality for a number of malignant and nonmalignant conditions. Pulmonary complications following HSCT are associated with increased mortality and morbidity. These complications may be classified into infectious versus noninfectious, and early versus late based on the time of occurrence post-transplant. Thus, exclusion of infectious etiologies is the first step in the diagnoses of pulmonary complications. Late onset noninfectious pulmonary complications typically occur 3 months post-transplant. Bronchiolitis obliterans is the major contributor to late-onset pulmonary complications, and its clinical presentation, pathogenesis, and current therapeutic approaches are discussed. Idiopathic pneumonia syndrome is another important complication which usually occurs early, although its onset may be delayed. Organizing pneumonia is important to recognize due to its responsiveness to corticosteroids. Other late onset noninfectious pulmonary complications discussed here include pulmonary venoocclusive disease, pulmonary cytolytic thrombi, pleuroparenchymal fibroelastosis, thoracic air leak syndrome, and posttransplant lymphoproliferative disorders."
8314,Biochip Platforms for DNA Diagnostics,"This chapter looks at the use of microlithographically fabricated biochip platforms for DNA diagnostics and prognostics, although protein and RNA biochips are also briefly considered. Biodetection methods such as ion-selective electrodes (ISEs), microelectromechanical systems (MEMS) devices such as microcantilevers, optical, piezoelectric-based acoustic wave, and mass spectrometry are briefly discussed. Emphasis is given to label-free electrochemical (impedimetric, voltammet-ric, and amperometric) detection. The production of DNA biochips is highlighted as are the operation and design of the experiments to reveal gene expression and SNP data. Applications discussed include the monitoring of microbes, cancer classification studies, and patient stratification in drug development. Finally, challenges and issues facing the development of diagnostic and prognostic biochips are discussed in detail."
8315,Introduction to Computer Network Vulnerabilities,"System vulnerabilities are weaknesses in the software or hardware on a server or a client that can be exploited by a determined intruder to gain access to or shut down a network. Donald Pipkin defines system vulnerability as a condition, a weakness of or an absence of security procedure, or technical, physical, or other controls that could be exploited by a threat (Pipkin D, Information security: protecting the global enterprise. Prentice Hall PTR, Upper Saddle River, 2000)."
8316,Leber und Gallenwege,"Patienten mit einer akuten Gallenblasenkolik müssen im Verlauf mit erneuten Beschwerden oder Komplikationen rechnen (siehe Übersicht). Sie sollten daher so bald wie möglich einer Cholezystektomie zugeführt werden, weil sich dadurch die Morbidität während der Wartezeit für eine elektive Cholezystektomie und wiederholte notfallmäßige Vorstellungen in der Notaufnahme vermeiden lassen. Die frühe laparoskopische Cholezystektomie scheint dabei mit einer niedrigeren Konversionsrate, einer kürzeren Operationszeit und einem kürzeren Krankenhausaufenthalt einherzugehen (Duncan u. Riall 2013)."
8317,Reiseimpfungen und allgemein empfohlene Impfungen,"Nach Schätzungen der World Tourism Organisation (WTO) verreisen jedes Jahr ca. 7,2 Millionen Deutsche nach Übersee. Hiervon entfällt ein Großteil auf Reisen in nicht tropische Gebiete: die USA, gefolgt von der Türkei und Tunesien, sind die häufigsten Ziele von Interkontinentalreisenden (www.world-tourism.org). Im Gegensatz hierzu sind Ost- und vor allem Westafrika, die von erkrankten Tropenrückkehrern am häufigsten als Infektionsgebiete genannt werden, bei den Reisezielen nur zu einem sehr geringen Ausmaß vertreten. Die internationale Reisetätigkeit boomt weltweit und gerade in Deutschland genießen Auslandsreisen einen besonderen Stellenwert. Die Forschungsgruppe Urlaub und Reisen gibt die Gesamtzahl der grenzüberschreitenden Reisen, die von Deutschen getätigt wurden, mit 56–63 Millionen pro Jahr an. Von den geschätzten 7,2 bis 7,8 Millionen interkontinentalen Reisen führten ca.4 Millionen in die Tropen."
8318,Hygiene in der Repatriierungsmedizin,Nicht zu vernachlässigen sind die hygienischen Bedürfnisse des Patienten unmittelbar vor und während des Transportes.
8319,Biophysik,"In den vorhergehenden Kapiteln sind wir einmal durch unser gesamtes Weltall gewandert. Als viel aufregender und gestaltenreicher empfinden wir hingegen die biologischen Wunder, die sich täglich um uns herum auf unserem Heimatplaneten zutragen, die wir Menschen nunmehr seit etwa einer Million Jahren bewusst erleben und noch immer nicht (voll) durchschauen, obwohl auch sie den Gesetzen der Physik in Strenge zu gehorchen scheinen. Hier spielen sich alle Prozesse, wo gewünscht, direkt vor unseren Augen, Ohren, Nasen und Gefühlen ab, wir haben gelernt – nach einer Million Jahren – wo in unseren Körpern unsere Baupläne (DNS) liegen und mit welchen physikalisch-chemischen Werkzeugen (Proteinen) ihre Anweisungen ausgeführt werden, oft von Hunderten oder sogar Tausenden unterschiedlicher Makro-Moleküle zugleich, in korrelierten Aktionen. Aber bei jedem konkreten Problem enden unsere Forschungen leicht mit mehr Fragen als Antworten, mit mehr Staunen als Einsichten."
8320,Health Security and Disease Detection in the European Union,"In a globalised world, national and international institutions in charge of health security can no longer only rely on traditional disease reporting mechanisms, not designed to recognise emergence of new hazards. New approaches are developing to improve the capacity of surveillance systems in detecting previously unknown threats. More recently, surveillance institutions have been actively searching for information about health threats using internet scanning tools, email distribution lists or networks that complement the early warning function of routine surveillance systems. Since its foundation, ECDC has developed an epidemic intelligence framework that encompasses all activities related to early identification of potential health hazards, their verification, assessment and investigation, in order to recommend public health control measures. Since June 2005, about 900 threats have been monitored by ECDC. Several threats made it necessary to develop formal risk assessments or to dispatch ECDC experts to outbreak areas. Examples of recent events, identified through the epidemic intelligence activity, are presented to illustrate the course of action from threat detection through risk management in Europe."
8321,Design of Real-time Systems for QoS,"It was discovered early, that in order to achieve the desired QoS properties a design methodology for real-time systems has to include appropriate measures to ensure that the QoS criteria are considered during the entire life-cycle. These have been joined in the framework of the ISO/IEC 13236 [31] and ISO/IEC TR 13243 [32] standards for QoS in information technology, and the standard IEC 61508 [28], which includes the necessary activities for safety-related systems from a project’s start until the end of its life-cycle. Like safety, security is also an issue that is gaining importance for embedded (real-time) applications [76], and which must be dealt with during the design phase, too."
8322,Epidemiology of Acute Respiratory Failure and Mechanical Ventilation,"Acute respiratory failure, and the need for mechanical ventilation, remains one of the most common reasons for admission to the intensive care unit (ICU). The burden of acute respiratory failure is high in terms of mortality and morbidity as well as the cost of its principal treatment, mechanical ventilation. Very few epidemiologic studies have evaluated the prevalence and outcome of acute respiratory failure and mechanical ventilation in general. Most of the published literature has focused on specific forms of acute respiratory failure, particularly acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In this chapter, we provide a brief review of the pathophysiology of acute respiratory failure, its definition and classification, and then present the incidence and outcomes of specific forms of acute respiratory failure from epidemiologic studies."
8323,"Global Emerging Pathogens, Poverty and Vulnerability: An Ethical Analysis","In the last few decades, the world has witnessed the emergence and re-emergence of new and old infectious diseases. Emerging infectious diseases (EIDs) have the capacity to spread rapidly from one region of the world to another, within a very short time, due to world travel and increased global interdependence. The impact of this varies from one region to another. Resource poor countries suffer the most due to an already high disease burden, poor infrastructures, lack of clean, potable water and sanitation, as well as an acute shortage of qualified health personnel to manage, control and contain the crisis/spread. Poor and marginalized communities are the most vulnerable because infectious diseases cause not only suffering and death, but also severe economic hardship. The outbreak of HIV/AIDS, tuberculosis and Ebola Virus Disease (EVD) in the developing world has shown the extent to which economic and social conditions can affect vulnerable populations. These socio-economic, cultural and environmental conditions accelerate the spread of, and exacerbate the negative impact of emerging pathogens. This chapter will undertake an analysis of the trend in global emerging pathogens, their economic impact, the global vulnerability status and ethical implications."
8324,Biocontainment Principles for Pediatric Patients,"The need for medical communities to prepare for highly hazardous communicable disease outbreaks was perhaps best exemplified in the 2014–2016 Ebola virus outbreak. To date, most efforts of preparedness have focused on adult medical providers, though it is critical that pediatric institutions achieve the same level of preparedness for children who may present with these illnesses. Care of pediatric patients exposed and/or infected with these unique pathogens requires advanced planning and training in order to offer the highest level of care while at the same time being able to ensure the safety of both the hospital staff and the community. In this chapter, we will discuss the basic principles of biocontainment and care in a unique pediatric setting and offer guidelines on how to navigate the identification, isolation, family-centered care, and clinical care of children with highly hazardous communicable diseases."
8325,Parvovirus,Name of Virus: Parvovirus
8326,Legal problems of pharming,
8327,Laboratory Methods for Detecting Viral Infections,"The first methods for detection of bacterial infections were available around 1880. After staining, bacterial pathogens were recognized in the light microscope because of their size and could be cultivated in culture media. Viruses evaded this approach, as they are significantly smaller, and as obligate parasites are not able to multiply in cell culture media. Although some viral infections could be associated with specific cellular changes and certain depositions in the infected tissue around the turn of the century, e.g. Negri inclusion bodies in nerve cells during rabies, a specific diagnosis was only possible through the development of cell culture methods and modern molecular biology. Today, viral infections can be detected directly by determining the agents, individual viral proteins, or their genetic information, or other materials in the blood of infected people or animals by using appropriate methods. Direct detection of viruses is possible, with the exception of latent or persistent infection forms, only during the acute phase of the disease. In some cases, the pathogens are present in the infected organism only before the symptomatic phase, so the direct detection of the virus is frequently not successful. Therefore, infections or contact with pathogens is usually demonstrated in virus diagnostics indirectly by characterization of the developing specific immune response."
8328,Human Security in East Asia: Assembling a Puzzle,"This chapter describes the motivation of the research project, provides the theoretical framework of the entire book, and gives a summary of the findings of the case study chapters. In the process of diffusion of human security norms in East Asia, several features have emerged. First, East Asians have accepted a comprehensive definition of human security regarding the perception of threats. Second, East Asians tend to think that human security and state security are complementary. Third, the constituent elements of the human security norms such as freedom from fear and from want, freedom to live in dignity, protection, and empowerment are already accepted by East Asian nations. We need an extra effort to elevate human security to a full-fledged norm in the region."
8329,Pediatric Natural Deaths,"Autopsies are important in the investigation of childhood deaths. Most natural deaths are unlikely to come to the attention of the forensic pathologist, particularly in cases where death occurs in hospital. During the neonatal period (up to 28 days of age), deaths most commonly occur as a result of prematurity and related conditions, chromosomal abnormalities, or congenital malformations. Beyond the neonatal period, trauma-related deaths and sudden infant death syndrome are more common. In terms of natural acquired diseases of childhood, certain conditions are prevalent based on age and may be encountered at autopsy. Common acquired diseases that cause death in infants and children up to 5 years of age include pneumonia and other respiratory diseases, other infectious diseases, and malignancies. In older children, mortality due to natural disease declines substantially with trauma being the major cause of death, and malignancies the major cause of acquired disease. Sudden and/or unexpected deaths in which a natural disease state was previously unknown are most likely to come under the jurisdiction of the medical examiner or coroner and may be related to an underlying natural disease. Depending on the underlying disease process, the approach can differ, and therefore familiarity with common causes of death during childhood is important in order to focus the autopsy so that special techniques can be used along with obtaining proper ancillary testing to arrive at an accurate diagnosis and cause of death."
8330,Herpetofauna Used in Traditional Folk Medicine: Conservation Implications,"This chapter provides an overview of the global use of herpetofauna in traditional folk medicine and the implications for conservation. The results indicate that 331 species (284 reptiles and 47 amphibians) are used in traditional folk medicine around the world. Among the species recorded, 182 reptiles and 42 amphibians are listed in the IUCN Red List. Additionally, 93 reptiles are in some of the appendices of CITES. These numbers demonstrate the importance of understanding such medicinal uses in the context of reptile conservation as well as the need for considering sociocultural factors when establishing management plans directed toward the sustainable use of these reptiles."
8331,Differential Diagnosis of Asthma,"Asthma is one of the most common chronic syndromes worldwide (Moorman et al., Vital Health Stat 3(35), 2012). It is not a diagnosis but a clinical syndrome based on a constellation of signs and symptoms (Li et al., Ann Allergy Asthma Immunol 81:415–420(IIa), 1998). The classic symptoms of asthma include chest tightness, wheeze, cough, and dyspnea (Moorman et al., Vital Health Stat 3(35), 2012). The term asthma encompasses a spectrum of pulmonary diseases sharing the hallmark of reversible airway obstruction and can be classified as allergic or non-allergic (Löwhagen, J Asthma. 52(6):538–44, 2015). Asthma designated allergic is due to an immunoglobulin E (IgE)-mediated process, but as noted not all asthma is allergic in etiology (Romanet-Manent et al., Allergy 57:607–13, 2002). The differential diagnosis for asthma is broad and requires a detailed history with supportive pulmonary function tests to be properly diagnosed."
8332,Pathogenesis of Sepsis,"Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. Both hyperinflammation and immune suppression ensue, to an extent that is harmful to the host. The inflammatory balance is disturbed, and this is associated with a failure to return to homeostasis. All pathogens with sufficient load and virulence can cause sepsis, after they succeed to adhere and pass the mucosal barrier of the host. The host defense system can recognize molecular components of invading pathogens, called pathogen-associated molecular patterns (PAMPs), with specialized receptors known as pattern recognition receptors (PRRs). Through several signaling pathways, overstimulation of PRRs has proinflammatory and immune suppressive consequences. Hyperinflammation is characterized by activation of target genes coding for proinflammatory cytokines (leukocyte activation), inefficient use of the complement system, activation of the coagulation system, and concurrent downregulation of anticoagulant mechanisms and necrotic cell death. The release of endogenous molecules by injured cells, called danger-associated molecular patterns (DAMPs) or alarmins, leads to deterioration in a vicious cycle by further stimulation of PRRs. Features of immune suppression are massive apoptosis and thereby depletion of immune cells, reprogramming of monocytes and macrophages to a state of a decreased capacity to release proinflammatory cytokines and a disturbed balance in cellular metabolic processes."
8333,Plant Endogenous Retroviruses? A Case of Mysterious ORFs,"Endogenous retroviruses have traditionally been defined as descendants of extinct retroviruses that infected and integrated into the chromosomes of host germ-line cells and were thereafter transmitted vertically as part of host genomes. Most retain at least the vestiges of genes once required for infectious horizontal transfer, namely envelope genes. In contrast, the long evolutionary histories of retrotransposons are presumed not to have included infectious ancestors. With the characterization of the Gypsy retrotransposon in Drosophila melanogaster as an infectious, endogenous retrovirus, these distinctions have blurred. A number of plant LTR retroelements possess coding regions whose conceptual translations produce hypothetical proteins with predicted structural elements found in viral envelope proteins, and the term endogenous retrovirus began to be applied to these elements. The question of whether any of the many plant retroelement genes now annotated as “env-like” generate proteins that have or had envelope functions remains unanswered. This review reevaluates the available data."
8334,Employing Live Microbes for Vaccine Delivery,"The employment of live attenuated vaccines has a long-standing record in human and veterinary medicine. Most of the vaccines in current use were empirically developed during the last century. Today, due to the great advances in fields such as immunology and bioengineering, the rational development of live attenuated vaccines becomes increasingly feasible. Moreover, live vaccines can be used as carrier systems for heterologous antigens or therapeutic factors. In each case, the development of a recombinant live attenuated vaccine is a complex task where properties such as targeting specificity, antigen synthesis, antigen release, and safety aspects have to be integrated. A range of such recombinant vaccine candidates have successfully been tested in the clinics, but very few have been approved so far. In many cases, further optimization of such vaccines is necessary with regard to their efficacy and safety profiles. In the present chapter, we focus on current strategies which are employed for the development of new and the optimization of first generation recombinant live vaccines based on bacteria and viruses."
8335,East Asian Regionalism: The Macroregional Dimensions of Relations,"This chapter presents macroregional dimension of East Asian regionalism. In this context, two structures that are the base of relations in the region are described: APT and EAS."
8336,Foundations for the Study of Structure and Function of Proteins,"Proteins are the most abundant biological macromolecules, occurring in all cells and all parts of cells. Moreover, proteins exhibit enormous diversity of biological function and are the most final products of the information pathways. Protein is a major component of protoplasm, which is the basis of life. It is translated from RNA and composed of amino acid connected by peptide bonds. It participates in a series of complicated chemical reactions and finally leads to the phenomena of life. So we can say it is the workhorse molecule and a major player of life activity. Biologists focus on the diction of structure and function of proteins by the study of the primary, secondary, tertiary, and quaternary dimensional structures of proteins, posttranscriptional modifications, protein-protein interactions, the DNA-proteins interactions, and so on."
8337,Consultative and Comanagement,This chapter covers the role of the hospitalist as a consultant and their interaction with surgical specialties. Included are discussions of perioperative care in the hospital and clinic. Oral and parenteral nutrition for the hospitalized patient are examined. A special emphasis is placed on palliative care for the hospitalized patient. Comanagement of surgical patients with an emphasis on orthopedics is reviewed.
8338,The Emerging Threat of Ebola,"Ebola is one of the deadliest infectious disease of the modern era. Over 50% of those infected die. Prior to 1976, the disease was unknown. No one knows exactly where it came from, but it is postulated that a mutation in an animal virus allowed it to jump species and infect humans. In 1976 simultaneous outbreaks of Ebola occurred in what is now South Sudan and the Democratic Republic of the Congo (DRC). For 20 years, only sporadic cases were seen, but in 1995 a new outbreak occurred killing hundreds in the DRC. Since that time the frequency of these outbreaks has been increasing. It is uncertain why this is occurring, but many associate it with increasing human encroachment into forested areas bringing people and animals into more intimate contact and increased mobility of previously remote population. This chapter will navigate Ebola in the context of global health and security. There are multiple objectives of this chapter. First is to provide a basic understanding of Ebola disease processes and outbreak patterns. Second, is to explore the interplay between social determinants of health and Ebola. The role of technology in spreading Ebola outbreaks will be explained as will Ebola’s potential as a bioweapon. Readers will gain understanding of the link between environmental degradation and Ebola outbreaks. This chapter will be divided into five main sections. These are (1) a case study; (2) Ebola Disease process; (3) Social determinants of health and Ebola; (4) Ebola in the modern era, and (5) the link between Ebola and environmental degradation."
8339,Grundlagen der systemischen Therapie,"Die Einführung sog. »zielgerichteter Medikamente« hat einen Paradigmenwechsel in der Systemtherapic maligner Erkrankungen ausgelöst. Voraussetzung hierfür waren die in den letzten 25 Jahren gesammelten Erkenntnisse der molekularbiologischen, molekulargenetischen und immunologischen Grundlagenforschung, die ein besseres Verständnis der pathogenetischen Prozesse im Rahmen der malignen Transformation und Tumorprogression sowie die Identifikation strategischer Zielstrukturen (»Targets«) ermöglichen. Auf diese Weise wurde ein neuer Ansatz der Entwicklung antineoplastischer Therapeutika angestoßen, der auf die Wirkung an spezifischen Molekülaktivitäten und nicht primär auf zelluläre Endpunkte (Wachstumshemmung, Zelltod) ausgerichtet ist."
8340,Epidemiology,"The term “epidemiology” was originally used for the science of major, humanity-threatening diseases. Today, it refers to the science of all transmissible and non-transmissible diseases in a population, irrespective of whether they occur frequently in time or space. In the field of microbiology, epidemiology deals with diseases which are caused by transmissible agents such as bacteria, viruses or prions, and in particular with the spread and consequences of infections. Therefore, epidemiological studies are very important for the health of the world population, and are the basis for general and veterinary measures such as quarantine or vaccinations to prevent and control pandemics and epidemics. Furthermore, they allow the development of guidelines and regulations for vaccinations and other measures that prevent infections."
8341,Antivirals for the common cold,"Despite a 60-year history of discovery, trial and evaluation of scores of different compounds, there are no currently licensed effective antivirals for the common cold. The history of the development and abandonment of all potential compounds so far teaches us some important lessons for the continuation of our fight against colds. First, the common cold is a benign self-limiting condition, making the consumption of ‘harmless’ antivirals a requisite of prime importance for regulators. Second, the common cold is a syndrome caused by a myriad of known and unknown agents, which reduces the effectiveness of compounds that interfere with single specific agents or types of agents. The multifactorial nature of the genesis of colds makes it difficult for compounds showing in vitro efficacy to ‘make the jump’ to field effectiveness. Last, despite the heavy burden that the cold imposes on society, the vagueness and shortness of symptoms make it difficult for sufferers to present in time for physicians to prescribe antivirals, which are only effective if taken within a short time frame. Attention should be paid to the development of compounds with a non-virus-specific action."
8342,Infektiologie,"Die Infektiologie ist ein Gebiet, das zahlreiche Schwerpunkte der Inneren Medizin, wie z. B. die Pulmologie oder Gastroenterologie, streift. Entsprechend behandelt das Kapitel alle wichtigen und häufigen Infektionen, mit denen ein Internist in der Praxis konfrontiert sein kann: von den unterschiedlichen Pneumonieformen, der Tuberkulose und Influenza über Noro-Virus-Erkrankungen, Cholera und EHEC-Infektionen bis hin zu sexuell übertragbaren Erkrankungen (HIV, Lues, Gonorrhö), die unterschiedlichen Herpes-Virus-Infektionen (Varizella-Zoster-, Herpes-simplex-, Eppstein-Barr- und Zytomegalie-Virus-Infektionen), Mykosen (Candidiasis, Aspergillose etc.) und andere häufig vorkommende Infektionskrankheiten."
8343,Regulatory Aspects in Using Surrogate Markers in Clinical Trials,
8344,Continuities and Change in IPE at the Start of the Twenty-first Century,"This chapter reviews changes and continuities for the development of International Political Economy (IPE) in the twenty-first century. We highlight four themes, which authors in this handbook subsequently explore. These include necessary adaptations of IPE theory in response to changing global conditions; how global reordering affects global economic governance, production, and power relations; the diverse global crises to which actors must respond, often under intense time pressure; and a variety of emerging IPE issues on which we need new and/or more attention from IPE scholars and students. We conclude by identifying five trends which we argue would help enhance IPE understandings, ensure the policy relevance of our discipline, and prepare our students in the coming decade."
8345,DNA helicase 3.6.4.12,"EC number 3.6.4.12 Systematic name ATP phosphohydrolase (DNA helix unwinding) Recommended name DNA helicase Synonyms 3’ to 5’ DNA helicase <28> [35] 3’-5’ DNA helicase <11> [55] 3’-5’ PfDH <11> [55] 5’ to 3’ DNA helicase <26,27> [19,42] AvDH1 <47> [37] BACH1 helicase <19> [34] BLM <3> [28] BLM protein <3> [28] BRCA1-associated C-terminal helicase <19> [34] BcMCM <8> [52] CeWRN-1 <43> [9] DDX25 <3,48> [36] DNA helicase 120 <7> [15] DNA helicase A <4> [8] DNA helicase E <5> [44] DNA helicase II <9> [7] DNA helicase III <4> [27] DNA helicase RECQL5β <44> [17] DNA helicase VI <3> [45] Dbp9p <46> (<46> a member of the DEAD box protein family [24]) [24] DmRECQ5 <1> [50] DnaB helicase <29> [23] E1 helicase <17> [58] GRTH/DDX25 <3,48> [36] HCoV SF1 helicase <23> [3] HCoV helicase <23> [3] HDH IV <3> [45] Hel E <5> [44] Hmi1p <40> [60] MCM helicase <6,5,38> [43,54] MCM protein <6,35> [43] MER3 helicase <22> [30] MER3 protein <22> [30] MPH1 <28> [35] NS3 <12,50> (<12,50> ambiguous [38,65,66]) [38,65,66] NS3 NTPase/helicase <14> (<14> ambiguous [67]) [67] NS3 protein <12> (<12> ambiguous [63]) [63] NTPase/helicase <12,16> (<12> ambiguous [61]) [61,64] PDH120 <7> [15] PIF1 <33> [51] PIF1 helicase <33> [51,53] PcrA <37> [20] PcrA helicase <37,41,49> [20,21,39] PcrASpn <41> [21] PfDH A <11> [55] Pfh1p <27> [42] RECQ5 <1> [49,50] RECQ5 helicase <1> (<1> small isoform [49]) [49] RECQL5b <44> [17] REcQ <31> [13] RSF1010 RepA <30> [5] RecG <45> [6] RecQ helicase <32> [56] RecQsim <32> [56] Rep52 <24> [40] Rrm3p <26> [19] Sgs1 <36> [29] Sgs1 DNA helicase <36> [29] TWINKLE <21> [33] Tth UvrD <20> [16] UvrD <20,42> [16,22] UvrD helicase <39> [18] WRN <18> [31] WRN RecQ helicase <18> [12] WRN helicase <18> [12] WRN protein <18> [12] WRN-1 RecQ helicase <43> [9] Werner Syndrome helicase <18> [31] Werner syndrome RecQ helicase <18> [12] dheI I <1> [46] dnaB <29> [23] hPif1 <33> [53] helicase DnaB <2> [10] helicase II <25> [25] helicase PcrA <49> [39] helicase UvrD <20> [16] helicase domain of bacteriophage T7 gene 4 protein <10> [47] non structural protein 3 <12> (<12> ambiguous [61,62]) [61,62] nonstructural protein 3 <12,14,50,51> (<12,14,50> ambiguous [38,63,65,66,67]; <51> ambigous [4]) [4,38,63,65,66,67] protein NS3 <12> (<12> ambiguous [62]) [62] scHelI <4> [26] urvD <25> [25]"
8346,The History of Fluid Resuscitation for Bleeding,"Damage control resuscitation (DCR) is a bundle of care first described by Holcomb et al. that is aimed at reducing death from hemorrhage for patients with severe traumatic bleeding. DCR principles include compressible hemorrhage control; hypotensive resuscitation; rapid surgical control of bleeding; avoidance of the overuse of crystalloids and colloids, prevention or correction of acidosis, hypothermia, and hypocalcaemia; and hemostatic resuscitation (blood-based resuscitation). Remote damage control resuscitation (RDCR) is defined as the prehospital application of DCR concepts. The term RDCR was first published by Gerhardt and has been disseminated by the (Trauma Hemostasis and Oxygenation Research), or THOR Network. The history of DCR and RDCR starts well before the inception of the terms. The concepts behind the principles of DCR and RDCR stretch far back into the past. This chapter provides an outline of this history, but it is limited to the fluid resuscitation aspect of DCR/RDCR."
8347,Avida: Evolution Experiments with Self-Replicating Computer Programs,
8348,Infectious Diseases and Microbiological Threats,"“The time to close the book on infectious disease” is far from near. Infections seem to be here to stay and have increased in importance in spite of enormous success in the field of prophylactic efforts, hygiene, vaccinology, and treatment. A large number of new agents and infections have appeared during the last decades. Conditions earlier thought to have other etiologies are today known to be distinct and have been proven to be of infectious origin. Infections alone can constitute major incidents, or they can be part of or a consequence of an incident. Even in the relatively new incident category of terrorism, infections must be seriously considered. Climate change and other changes in nature today constitute major threats of increasing infectious incidents. The increasing problem with antimicrobial resistance is, at present, considered to be one of the strongest disease threats. Infectious incidents are unique in the sense that they usually have an insidious onset, have a time span before they are detected as present or even as serious. Once the infection has started to spread, the development and increase can be extremely quick, even logarithmic. The extent of infectious incidents can be larger than that of most other disasters, and is best exemplified through different pandemics. The most important weapon to control infectious outbreaks or epidemics is active surveillance, leading to different kind of actions."
8349,Networks and Models with Heterogeneous Population Structure in Epidemiology,"Heterogeneous population structure can have a profound effect on infectious disease dynamics, and is particularly important when investigating “tactical” disease control questions. At times, the nature of the network involved in the transmission of the pathogen (bacteria, virus, macro-parasite, etc.) appears to be clear; however, the nature of the network involved is dependent on the scale (e.g. within-host, between-host, or between-population), the nature of the contact, which ranges from the highly specific (e.g. sexual acts or needle sharing at the person-to-person level) to almost completely non-specific (e.g. aerosol transmission, often over long distances as can occur with the highly infectious livestock pathogen foot-and-mouth disease virus—FMDv—at the farm-to-farm level, e.g. Schley et al. in J. R. Soc. Interface 6:455–462, 2008), and the timescale of interest (e.g. at the scale of the individual, the typical infectious period of the host). Theoretical approaches to examining the implications of particular network structures on disease transmission have provided critical insight; however, a greater challenge is the integration of network approaches with data on real population structures. In this chapter, some concepts in disease modelling will be introduced, the relevance of selected network phenomena discussed, and then results from real data and their relationship to network analyses summarised. These include examinations of the patterns of air traffic and its relation to the spread of SARS in 2003 (Colizza et al. in BMC Med., 2007; Hufnagel et al. in Proc. Natl. Acad. Sci. USA 101:15124–15129, 2004), the use of the extensively documented Great Britain livestock movements network (Green et al. in J. Theor. Biol. 239:289–297, 2008; Robinson et al. in J. R. Soc. Interface 4:669–674, 2007; Vernon and Keeling in Proc. R. Soc. Lond. B, Biol. Sci. 276:469–476, 2009) and the growing interest in combining contact structure data with phylogenetics to identify real contact patterns as they directly relate to diseases of interest (Cottam et al. in PLoS Pathogens 4:1000050, 2007; Hughes et al. in PLoS Pathogens 5:1000590, 2009)."
8350,"Finding Those at Risk, China’s Way","One of the people who heard Vice Premier Wu Yi’s plea for greater openness in the aftermath of the SARS epidemic was Li Keqiang, now China’s Premier but at the time the Party Secretary of Henan province. As we saw in Chap. 10.1007/978-981-10-3746-7_2, national specialists such as Xiwen Zheng estimated the number of HIV-infected plasma sellers in Henan at around 80,000, and activists were claiming ten times as many. However, provincial officials stuck stubbornly to an estimate of 10,000 infections. Backed by the central government’s renewed determination to find out the true extent of the epidemic, Li Keqiang encouraged his staff to do whatever was necessary to get to the truth."
8351,Host Immune Responses to SARS Coronavirus in Humans,"The severe acute respiratory syndrome (SARS) is a newly identified infectious disease caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. The risk of SARS reemergence in humans remains high due to the large animal reservoirs of SARS-CoV-like coronavirus and the genome instability of RNA coronaviruses. An epidemic in 2003 affected more than 8,000 patients in 29 countries, with 10% mortality. SARS infection is transmitted by air droplets. Clinical and laboratory manifestations include fever, chills, rigor, myalgia, malaise, diarrhea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase, alanine aminotransferase, and creatine kinase activities. Health care workers are a high-risk group, and advanced age is strongly associated with disease severity. Treatment has been empirical, and there is no licensed SARS vaccine for humans so far. However, presence of long-lived neutralizing antibodies and memory T- and B-lymphocytes in convalescent SARS patients raises hope for active immunization. Furthermore, results from preclinical SARS vaccines expressing spike protein to elicit neutralizing antibodies and cellular responses that are protective in mouse and nonhuman primate models are encouraging. Very little is known of the early events in viral clearance and the onset of innate and inflammatory responses during the SARS infection. Regulation of the innate immune response is associated with the development of adaptive immunity and disease severity in SARS infection. Notably, SARS-CoV has evolved evasive strategies to suppress antiviral type I interferon responses in infected cells. In addition, inflammatory responses are characterized by upregulation of proinflammatory cytokines/chemokines such as IL-6, IP-10, and MCP-1 in tissues and serum, and massive infiltrations of inflammatory cells such as macrophages in infected tissues. Due to the lack of animal models that mimic the clinical manifestations of human SARS infection for mechanistic study and vaccine evaluation, development of a safe prophylactic SARS vaccine for human use remains a huge challenge. This chapter is written to summarize and highlight the latest clinical, serological, and immunological parameters relevant to the pathogenesis and protective immunity of SARS infection in humans."
8352,Apocalypse how?,"The probability of humankind’s long-term survival is encouragingly high, roughly 70%. This implies survival long enough to colonize the solar system and perhaps the galaxy either with Homo sapiens or some sort of conscious artificial creatures that we regard as our intellectual descendants (cyborgs, androids, whatever)."
8353,Hematology,"—stress (Gaisböck’s syndrome), decreased intravascular volume"
8354,The Impact of Ebola Virus Disease on Government Expenditure in Sierra Leone,"Ebola Virus Diseases (EVD) epidemic had a pronounced socio-economic impact in Guinea, Liberia and Sierra Leone, which led to a considerable negative effect on the total governments' budgets. One of the Ebola-welfare transmission mechanism is the decreasing government revenue resulting from the closure of mining and food companies of the affected countries, which impact negatively on the growth of the economy and government expenditures of the affected country. This study investigates the effect of Ebola outbreak on the capital expenditure of the Sierra Leonean government. The study employs Endogenous Growth Model of Public Expenditure, which assumes that Gross National Income (GNI) growth is determined by forces governing the production process rather than by forces outside it. The data for the study were obtained from the World Bank Data repository and the International Monetary Fund, and covered the period 2006–2014. The results show that EVD impacted negatively on government capital expenditure in Sierra Leone. Hence, it is suggested that focus should be given more to the prevention of the epidemic of communicable disease."
8355,Entzündliche Erkrankungen,"Unter einer Meningitis versteht man eine Entzündung von Pia mater und Arachnoidea. Das Erregerspektrum ist weit und reicht von Bakterien, die hämatogen-metastatisch, fortgeleitet oder durch offene Hirnverletzung zur eitrigen Meningitis führen, über Viren zu Pilzen und Parasiten. Insbesondere bei den unbehandelt häufig letal verlaufenden eitrigen Meningitiden ist eine rasche Diagnose mit Erregernachweis notwendig. Unverzüglich ist daraufhin eine spezifische, der regionalen Resistenzentwicklung angepasste Therapie einzuleiten. Die meningeale Affektion im Rahmen einer Listeriose oder Tuberkulose verdient aufgrund des klinischen Bildes, des Verlaufs und der spezifischen Therapie besondere Beachtung. Die fungalen Infektionen werden, da klinisch häufig als Meningoenzephalitis imponierend, in Abschn. 33.3 abgehandelt."
8356,Case Study 3: The World Health Organization (WHO),"The WHO is the UN specialized agency for health and was formally established on April 7, 1948 (Lee 2009: 1-45; Burci and Vignes 2004: 15-19). Its ultimate goal is the “attainment by all peoples of the highest possible level of health” as stipulated in Article 1 of the WHO constitution. The broad definition of health as one of the fundamental human rights of all peoples and the principle of universality are key elements in the constitution of the WHO, which makes frequent reference to “all peoples”, stipulates that membership is open to “all states” and, in contrast to other UN organizations, allows membership based on a simple majority of votes in the WHA, instead of on a two-thirds majority. As of April 2012, the WHO had 193 member states and two associate members."
8357,Pneumologie,"Alter, Geschlecht, BMI (Body Mass Index). Vorerkrankungen: Hypertonie, KHK, Myokardinsuffizienz, Myokardinfarkt. Voroperationen. Fieber, Belastbarkeit, Unwohlsein. Nikotinabusus. Medikamente, Drogenkonsum. Berufliche Exposition: Gase, Dämpfe, Staub. Genetische Exposition: Familienanamnese, α1-Proteinase-Inhibitor-Mangel;"
8358,Public Health Laboratories,"This chapter will review the multiple functions of Public Health Laboratories (PHLs), including their differences to commercial clinical laboratories. For example, the types of samples submitted to PHLs differ from those submitted to commercial clinical laboratories. PHLs are critically important to population based healthcare; playing an essential role in the detection of disease outbreaks. This chapter will describe the hierarchical organization of the PHL system in the Unites States, as well as the networks that have been created to support diverse PHL functions such as food safety testing and emergency response to terrorisms or natural disaster. It will briefly describe the standards used by PHLs and how the implementation of standards should further improve patient safety as a whole. In this chapter the reader will be introduced to PHL informatics in the context of the laboratories operational workflow – from test ordering, interfacing with diagnostic instruments, quality control and result reporting and analysis. The reader will also understand the impact of PHL informatics collaboration efforts and its effect on ongoing policy development."
8359,Akute Gastroenteritis und postenteritisches Syndrom,"Die akute Gastroenteritis ist im Säuglings- und Kleinkindesalter häufig. Die überwiegende Anzahl der Kinder, die an einem Brechdurchfall erkranken, ist jünger als 1 Jahr. Durch den schweren Wasser- und Elektrolytverlust kommt es zur Dehydratation. Bei 70 % der Patienten tritt eine isotone, bei 10 % eine hyponatriämische und bei 20 % eine hypertone (hypernatriämische) Dehydratation auf. Der Typ der Dehydratation ist unabhängig vom Erreger. Der Flüssigkeitsverlust kann das 2- bis 3-Fache des zirkulierenden Blutvolumens betragen, nämlich 150–250 ml/kg KG/Tag. Um das Blutvolumen konstant zu halten, entzieht der Körper dem Intrazellularraum Flüssigkeit. Dies führt zur Exsikkose. Das Ausmaß des Flüssigkeitsverlusts wird klinisch beurteilt und nach der WHO in drei Schweregrade eingeteilt (Tab. 119.1 ). Die Schleimhaut des Dünndarms setzt sich aus zwei verschiedenen Zelltypen zusammen: den reifen Enterozyten, die die Hydrolyse und Absorption von Nahrungsstoffen übernehmen – sie befinden sich in der Mitte und Spitze der Zotten – und; den unreifen Kryptenzellen, die durch Zellteilung aus Stammzellen die lebenslange Reserve für die an der Zottenspitze abgestoßenen Enterozyten darstellen. Sie sind sekretorische Zellen, die über den in den Kryptzellen lokalisierten CFTR („cystic fibrosis transmembrane conductance regulator“) Cl(–) in das Kryptenlumen sezernieren."
8360,Return to Play After Infectious Disease,"Acute illnesses are of significant concern for the health and performance of athletes. Sports medicine physicians face the challenge of promoting sufficient recovery and responding to the demands of the coaches and athletes. This chapter presents the evidence behind the risk factors for acute illness in athletes, the negative consequences of sports participation during illness and the recommendations for safe sports participation. Risk factors for infection and illness may be intrinsic (e.g. postexercise suppression of the immune system, recent acute illness, female gender) and extrinsic (e.g. training load, nutrition, resting periods). Fever during illness contributes to systemic symptoms such as headache and myalgia but also to dehydration, muscle breakdown and reduction in cardiometabolic function. The consequences of exercise during illnesses may be aggravation of illness, loss of muscle strength and endurance, cardiac complications, transmission of infection to others, neurological dysfunctions including coordination problems, rhabdomyolysis and in the worst case sudden death. Recommendations for safe return to sport include clearance of infection allowing full recovery and thereafter gradual progress of exercise volume combined with monitoring of remaining symptoms of illness. Different actions can be taken to prevent acquiring, aggravating and spreading of infections by the athlete (e.g. hygiene, physical contact, covering of the body, sharing of equipment, nutrition), the coaches (e.g. individualised plan of training, competition, nutrition, recovery and recovery measures) and the physicians (monitor and implement illness prevention, identify and arrange for high-risk athletes, educate athletes and staff)."
8361,"Aging, Immunity, and Neuroinflammation: The Modulatory Potential of Nutrition","Aging influences an organism’s entire physiology, affecting functions at the molecular, cellular, and systemic levels and increasing susceptibility to many major chronic diseases. The changes in the immune system that accompany human aging are very complex and are generally referred to as immunosenescence. The factors and mechanisms of immunosenescence are multiple and include, among others, defects in the bone marrow, thymic involution, and intrinsic defects in the formation, maturation, homeostasis, and migration of peripheral lymphocytes. Aging affects both the innate and adaptive arms of the immune system. The process of aging is commonly accompanied by low-grade inflammation thought to contribute to neuroinflammation and to many age-related diseases. Numerous attempts to define the role of chronic inflammation in aging have implicated chronic oxidative stress, mitochondrial damage, immunosenescence, epigenetic modifications, and other phenomena. Several lifestyle strategies, such as intervening to provide an adequate diet and physical and mental activity, have been shown to result in improved immune and neuroprotective functions, a decrease in oxidative stress and inflammation, and a potential increase in individual longevity. The studies published thus far describe a critical role for nutrition in maintaining the immune response of the aged, but they also indicate the need for a more in-depth, holistic approach to determining the optimal nutritional and behavioral strategies that would maintain immune and other physiological systems in elderly people. In this chapter, we focus first on the age-related changes of the immune system. Further, we discuss possible deleterious influences of immunosenescence and low-grade inflammation (inflammaging) on neurodegenerative processes in the normally aging brain. Finally, we consider our current understanding of the modulatory potential of nutrition that may mediate anti-inflammatory effects and thus positively affect immunity and the aging brain."
8362,"Computational Biosensors: Molecules, Algorithms, and Detection Platforms","Advanced nucleic acid-based sensor-applications require computationally intelligent biosensors that are able to concurrently perform complex detection and classification of samples within an in vitro platform. Realization of these cutting-edge computational biosensor systems necessitates innovation and integration of three key technologies: molecular probes with computational capabilities, algorithmic methods to enable in vitro computational post processing and classification, and immobilization and detection approaches that enable the realization of deployable computational biosensor platforms. We provide an overview of current technologies, including our contributions towards the development of computational biosensor systems."
8363,Risks and Epidemiology of Infections After Intestinal Transplantation,"Intestinal transplantation has become a well-accepted and successful procedure to save the lives of patients suffering from intestinal failure and who have developed life-threatening complications of parenteral nutrition. Advances in all aspects of care, from the role of multidisciplinary intestinal rehabilitation services prior to transplant to the development strategies for early recognition of infectious sequelae and even the increasing availability of preventive strategies, have led to improved outcomes and a dramatic decline in infection-associated morbidity and mortality in children undergoing intestinal transplantation. Improvements in surgical techniques and immunosuppressive regimens have been essential components in these improvements, reducing risk of infection through reduction of technical complications and more optimal immunosuppression regimens. In addition, the development of molecular tools for early recognition of viral pathogens and an understanding of the timing and risks for infection have allowed for earlier and more successful treatments. Despite these improvements, infectious sequelae remain an important problem in this population, and additional efforts are needed to further minimize the risk of infectious sequelae in those children requiring this procedure."
8364,"Infektionskrankheiten weltweit: Epidemiologie, Erfassung, Surveillance","Nach aktueller WHO-Statistik (2005) liegen Infektionskrankheiten mit 41 % der Todesfälle weltweit als häufigste Todesursache deutlich vor den Herz-Kreislauf- Erkrankungen (20 %), den Krebserkrankungen (18 %) und den zerebrovaskulären Erkrankungen (13 %). Bezogen auf die regionale Verteilung ergeben sich allerdings hierbei erhebliche Unterschiede, so dass für die Drittländer die Letalität durch Infektionskrankheiten deutlich höher als 60 % rangieren kann (► Abb. 1). Bezüglich der Häufigkeitsverteilung der Infektionskrankheiten stehen Pneumonien an erster Stelle vor Tuberkulose, Gastroenteritiden, Malaria, AIDS und Hepatitis B."
8365,Current status of therapy of SARS,
8366,Respiratory Viruses in the Neonatal Intensive Care Unit,"Respiratory viral infections (RVIs) pose a unique challenge for clinicians in the neonatal intensive care unit (NICU) due to preterm infants’ increased susceptibility to infections (Maitre NL and Williams JV, Res Rep Neonatol. 6:41–49, 2016). RVIs often present with nonspecific symptoms and currently lack effective treatments (Baraldi et al., Ital J Pediatr. 40:65, 2014). Death due to viral bronchiolitis is a major cause of morbidity and mortality in developing nations and industrialized nations alike, and patients with bronchiolitis frequently require intensive care and use of mechanical ventilation (Thompson et al., JAMA 289:179–186, 2003). Infants who acquire RVI during their birth hospitalizations have significantly longer length of stay and are more likely to develop chronic respiratory disease, particularly bronchopulmonary dysplasia (Bennett et al., J Pediatr 161:814–818, 2012). Furthermore, infants with RVIs are often placed on empiric antibiotic therapy, which can frustrate antimicrobial stewardship efforts (Bennett et al., J Pediatr 161:814–818, 2012; Cantey et al., Lancet Infect Dis 2016;16:1178–1184). RVIs are also associated with increased costs to both health systems and families due to increased care and lost productivity. In 2016, Zinna et al. (Pediatrics 138:e20161675, 2016) showed that infants with hospital-acquired RVI in the United Kingdom had hospital charges more than double those of uninfected infants. Similarly, the Sentinel-1 Study (Anderson et al., Am J Perinatol 34:51–61, 2017) in the United States demonstrated that each hospitalization for respiratory syncytial virus (RSV), the most common etiological agent of viral bronchiolitis in children age <1 year, costs more than $55,000, even excluding the additional outpatient visits before and after hospitalization. The goal of this chapter is to address the epidemiology, pathogenesis, diagnosis, treatment, and prevention of respiratory viruses in the highly vulnerable patient population in the NICU."
8367,"Bioterrorismus, infektiologische Aspekte","Infektionskrankheiten sind ständige Begleiter und gefürchtete Geißeln der Menschheit. Pest und Pocken versetzen als todbringende Seuchen die Menschen nicht erst seit dem Altertum in Schrecken (lat.: terror). Archaische Ängste und vor allem eine hohe Medienaufmerksamkeit sorgen immer wieder für Panik und irrationale Reaktionen: Im indischen Surat setzte im Herbst 1994 während eines ungewöhnlichen Pestausbruchs eine Massenflucht ein, nachdem die Presse den Verdacht auf Lungenpest und terroristische Anschläge verbreitet hatte. Über 800.000 Menschen, darunter auch zahlreiche Ärzte und Pflegekräfte, verließen daraufhin ihre Arbeitsplätze und Wohnorte. Allein die drastischen Flug- und Handelsbeschränkungen brachten Indien einen ökonomischen Schaden von etwa 3 Milliarden US $."
8368,Chirurgische Infektionen bei Kindern und Jugendlichen,"Der menschliche Organismus ist von einer unzähligen Menge von Mikroorganismen umgeben. Dringen diese Krankheitserreger in uns ein, dann laufen Wechselbeziehungen zwischen dem Eindringling und dem Wirtsorganismus ab. Krankheit resultiert, wenn die Mikroorganismen aufgrund ihrer verschiedenen Determinanten der Pathogenität und Virulenz den Wettlauf mit der Infektabwehr des Makroorganismus gewonnen haben. Mit diesem Problem hatten sich Chirurgen zu allen Zeiten auseinanderzusetzen und es hat bis heute nicht an Aktualität verloren."
8369,Mobile Phone Media and Its Public Opinion Management,"This chapter mainly discusses the concept, characteristics and cases of the mobile media and mobile media public opinion as well as their management, and lays stress on studying the development and characteristics of WeChat, the major social media and mobile payment platform in China."
8370,Blood Products,"Perioperative hemorrhage, anemia, thrombocytopenia, and coagulopathy are common in the surgical intensive care unit. As a result, blood product transfusion occurs frequently. While red blood cell, plasma, and platelet transfusions have a lifesaving role in the resuscitation of patients with trauma and hemorrhagic shock, their application in other settings is under scrutiny. Current data would suggest a conservative approach be taken, thus avoiding unnecessary transfusion and associated potential adverse events. New and developmental products such as prothrombin complex concentrates offer appealing alternatives to traditional transfusion practice—potentially with fewer risks—however, further investigation into their safety and efficacy is required before practice change can take place."
8371,"Indoor Microbial Aerosol and Its Health Effects: Microbial Exposure in Public Buildings – Viruses, Bacteria, and Fungi","Mechanisms of aerosolization of microorganisms, composition and dynamics of microbioaerosol are characterized. As well as methods of its detection, incl. modern equipment set-ups and sampling procedures recommended are outlined. Medical impact of (indoor) air disperged viral, bacterial and fungal propagules (allergies, intoxications, infections), together with the related European legislation is summarized. An overview of real mycoaerosol conditions in our dwellings and their outdoors with different microclimate, settlement and building types, household characteristics and health state of occupants is given, too. Finally, examples of several possible health damages due to exposition to (aerosolized) fungal toxicants in vitro and in vivo are demonstrated."
8372,Neonatal Care and Data,"Neonatology encompasses the care of all infants: from term newborns to extremely premature infants, from healthy infants to those suffering from severe infections or genetic disorders. While the management of infants can vary greatly, there are essential core data and knowledge that is needed to care for them."
8373,Respiratory Disorders,"This chapter provides the reader with a concise outline of the topics required for general pediatric board examination, respiratory component. Basic diagnostic testing is reviewed. Common upper airway problems, lower airway issues, and parenchymal diseases are covered. Congenital malformations and common diseases of the lung are reviewed. The physiology of extrapulmonary problems is reviewed. Sleep disordered breathing and the evaluation of apneas and ALTE/SIDS are also discussed. Hints regarding physiology, clinical features, diagnostic testing, and management are present with references to national guidelines and resources."
8374,In the Midst of Stories: Is Seeing Believing?,"In this chapter, the author explores issues and challenges in the narrative inquiry into Chinese families’ lived experience on landscapes of schools in transition from China to Canada. Entering the research field, the issue of narrative truth became a methodological challenge as the researcher was bounced between the boundaries of educational research. By understanding story as the phenomenon, and narrative as the inquiry (Clandinin & Connelly, Narrative inquiry: Experience and story in qualitative research, Jossey-Bass Publishers, San Francisco; 2000), the researcher asked two questions when she was located in a place of stories: “Who tells whose stories and why?” and “Which is true, ‘To see is to believe’, or ‘To believe is to see’?” In this methodologically focussed chapter ethical issues and considerations are also discussed."
8375,Hierarchical Self-Assembled Peptide Nano-ensembles,"A variety of peptides can be self-assembled, i.e. self-organized spontaneously, into large and complex hierarchical structures, reproducibly by regulating a range of parameters that can be environment driven, process driven, or peptide driven. These supramolecular peptide aggregates yield different shapes and structures like nanofibers, nanotubes, nanobelts, nanowires, nanotapes, and micelles. These peptide nanostructures represent a category of materials that bridge biotechnology and nanotechnology and are found suitable not only for biomedical applications such as tissue engineering and drug delivery but also in nanoelectronics."
8376,A Virus from the Nile,"It probably happened in August. Beyond that, no one can say when the tiny brown wisp settled upon Enrico Gabrielli’s body. The sixty-year-old cherished summer evenings among the red geraniums and purple cosmos in his garden, in the Italian neighborhood of Whitestone in Queens, New York— and never more so than in the summer of 1999. In July the temperature broke ninety-five degrees for eleven straight days—the hottest month ever recorded in the city."
8377,Models for Endemic Diseases,"We have been studying SIR models, in which the transitions are from susceptible to infective to removed, with the removal coming through recovery with full immunity (as in measles) or through death from the disease (as in plague, rabies, and many other animal diseases). Another type of model is an SIS model in which infectives return to the susceptible class on recovery because the disease confers no immunity against reinfection. Such models are appropriate for most diseases transmitted by bacterial or helminth agents, and most sexually transmitted diseases (including gonorrhea, but not such diseases as AIDS, from which there is no recovery). One important way in which SIS models differ from SIR models is that in the former there is a continuing flow of new susceptibles, namely recovered infectives. Later in this chapter we will study models that include demographic effects, namely births and deaths, another way in which a continuing flow of new susceptibles may arise."
8378,"Colostrum Antibodies, Egg Antibodies and Monoclonal Antibodies Providing Passive Immunity for Animals","Passive immunity can be provided to animals by several sources of antibodies including from colostrum, avian eggs, and monoclonal sources. These antibodies have been shown protect production and companion animals from a number of pathogens. This chapter reviews the immune system for the principles of immune response to antigens and the synthesis of immunoglobulins of the five classes of antibodies in the body. Colostrum antibodies are described for passive immunity protection in animals such as calves. Chicken egg antibodies are another source of antibodies for passive immunity. Therapeutic monoclonal antibodies are also used to provide passive immunity in the veterinary field."
8379,Hydrocephalus in Animals,"Naturally occurring internal hydrocephalus is diagnosed in all kinds of mammals including exotic species as well as in birds. The underlying pathomechanisms are extremely variable and species-specific. In ruminants, teratogenic viruses are the main underlying cause for congenital hydrocephalus. Intrauterine infections do not play a role in equids, and the site of obstruction of CSF flow typically remains undetermined. In birds and large felids, hydrocephalus is usually acquired and often associated with vitamin A deficiency. In dogs and cats, it can be congenital but also associated with impaired skull and vertebral growth. Reduced cranial capacity impairing cerebral compliance and malformations of the craniovertebral junction (atlantoaxial instability, occipito-atlantoaxial overlap syndrome, and “Chiari-like malformation”) are the most common causes for an impaired CSF flow and communicating hydrocephalus in a high number of brachycephalic breeds. With increasing knowledge and the increasing disposition of patient owners, veterinary specialists and researchers enduringly invest in the patient management; ventriculoperitoneal shunting techniques have become a reasonable treatment strategy in dogs."
8380,Effekte technologischer Angebotsschocks,"Das Wachstum der Gesundheitswirtschaft in Deutschland ist von einer überdurchschnittlich starken Dynamik geprägt. Beleg hierfür sind die Entwicklungen makroökonomischer Kennzahlen wie die Anzahl der Erwerbstätigen und der Bruttowertschöpfung im Zeitablauf. In den Jahren 2007–2012 entspricht die durchschnittliche Wachstumsrate der gesamtwirtschaftlichen Bruttowertschöpfung einem Wert von 2,3 Prozent; im selben Zeitraum ist die Gesundheitswirtschaft jahresdurchschnittlich mit 3,7 Prozent deutlich schneller gewachsen (vgl. BMWi 2013, S. 4)."
8381,Illustrationsbeispiel „Grenzwerte für Schadstoffe im Wasser“,"Zu Beginn möchte ich versuchen, auf die konkrete Problematik eines im Januar 2012 veröffentlichten Entwurfs einer EU-Verordnung mit Veränderungen der Grenzwerte für Schadstoffe im Wasser einzugehen."
8382,Pneumonia and Empyema,
8383,"Bombs, Mines, Blast, Fragmentation, and Thermobaric Mechanisms of Injury",
8384,Pneumonie,Die maximale Inzidenz von ventilatorassoziierter Pneumonie (VAP) liegt nach Ibrahim et al. (2001) zwischen dem 6. und dem 10. Tag (◘ Abb. 13.1).
8385,Global Mass Society,"Economic globalization has resulted in corporations, unaccountable to states, making key decisions within an otherwise anarchic world order, rendering normal democratic functioning almost impossible. Global gridlock has resulted from the same issues that plague democracies today. Although transnational civil society has tried to achieve a degree of democratic global governance, the result mostly has been to reinforce the global power structure."
8386,Evolution of Intensive Care Unit Nursing,"The specialties of critical care medicine and critical care nursing arose to provide special treatment and care to the most severely ill hospital patients. However, critical care medicine does not seem to have made any major therapeutic progress in the past 30 years. The reduction of mortality in intensive care units (ICUs) is due essentially to improvements in both supportive care and the relevant technologies. In future, increases in the number of ICU beds relative to bed numbers in other hospital wards will probably be contemplated, even in a scenario of decreasing costs; clinical protocols will be computerized and/or nurse-driven; more multicenter and international trials will be performed; and organizational strategies will concentrate ICU personnel in a few large units, to promote the flexible management of these healthcare workers. Moreover, extracorporeal organ support technologies will be improved; technology informatics will cover all the bureaucratic aspects of healthcare work, aiding the staff in workload assessment; and critical care multidisciplinary rounds and follow-up services for post-ICU patients will be implemented. Lastly, a better continuum of care between the pre-hospital phase, the emergency care phase, the ICU phase, and the post-ICU phase should be achieved. Also, policies should be drafted to manage sudden large demands for critical care beds in mega-emergencies. The main lines of discussion in critical care nursing research should include nursing research priorities in critical care patients, holistic approaches to the patient, the humanization of care, special populations of ICU patients, and challenges related to critical care nursing during emerging outbreaks of infectious diseases."
8387,Aviation and Intervention,"In October 2013, CNN reported that 400 civilians had been killed in Pakistan by unmanned aircraft (UA) since President Obama took office in 2009. Transnational legal theory suggests that such attacks are illegal and, in 2009, the United Nations special rapporteur on extra judicial killings suggested that the use of drones by the Obama administration in Afghanistan and Pakistan was untenable and contrary to international law."
8388,Anesthesia Management of Liver Transplantation,"Anesthesia for liver transplantation pertains to a continuum of critical care of patients with end-stage liver disease. Hence, anesthesiologists, armed with a comprehensive understanding of pathophysiology and physiologic effects of liver transplantation on recipients, are expected to maintain homeostasis of all organ function. Specifically, patients with fulminant hepatic failure develop significant changes in cerebral function, and cerebral perfusion is maintained by monitoring cerebral blood flow and cerebral metabolic rate of oxygen, and intracranial pressure. Hyperdynamic circulation is challenged by the postreperfusion syndrome, which may lead to cardiovascular collapse. The goal of circulatory support is to maintain tissue perfusion via optimal preload, contractility, and heart rate using the guidance of right-heart catheterization and transesophageal echocardiography. Portopulmonary hypertension and hepatopulmonary syndrome have high morbidity and mortality, and they should be properly evaluated preoperatively. Major bleeding is a common occurrence, and euvolemia is maintained using a rapid infusion device. Pre-existing coagulopathy is compounded by dilution, fibrinolysis, heparin effect, and excessive activation. It is treated using selective component or pharmacologic therapy based on the viscoelastic properties of whole blood. Hypocalcemia and hyperkalemia from massive transfusion, lack of hepatic function, and the postreperfusion syndrome should be aggressively treated. Close communication between all parties involved in liver transplantation is also equally valuable in achieving a successful outcome."
8389,Reintroduction,"The introduction presents the concepts of health in relation to order, disorder, and re-ordering. It defines health and the right to health along with the concomitant responsibilities for its realization ascribed to nation-state and non-state actors. It discusses the remit of health security as the provision and protection of health rights through responsibilities at the local, national, and global levels of community and governance. Finally, it argues that health risks and threats cannot be completely eliminated, but rather must be identified and responded to in a coordinated manner involving individuals, communities, national states, international organizations, and the global (conceptual) community."
8390,SARS and H5N1,"Chapter 5 looks at bird flu (H5N1) pandemics and Severe Acute Respiratory Syndrome (SARS). This chapter shifts the focus from the relationship between individual health rights and state requirements, notably immunization, and responsibilities, particularly in providing security against health threats, to international requirements and responsibilities for health. Through the lens of the SARS and the H5N1, it traces the newest evolution of the International Health Regulations (IHRs). It analyses the positions and compromises of states, notably with regard to their sovereignty, in reaching the final compromise: to share responsibility in safeguarding global health. It takes to task the regulations’ lack of ‘teeth’: the fact that despite international treaty status, the IHRs operate on a voluntary basis without an enforcement mechanism."
8391,Human metapneumovirus infection,"Initially, human metapneumovirus (hMPV) was isolated from children with clinical symptoms of respiratory syncytial virus (RSV) infection in whom RSV could not be detected. Since then, numerous reports have described the detection of hMPV in clinical specimens from children, adults and the elderly (both immunocompetent and immunocompromised patients), diagnosed with an acute respiratory illness all over the world. hMPV is associated with a substantial number of respiratory tract infections in otherwise healthy children, with clinical illnesses similar to those associated with other common respiratory viruses. Serological surveys have shown that hMPV is a ubiquitous virus that infects all children by the age of 5–10 years and has been circulating in humans for at least 50 years. hMPV is a member of the Metapneumovirus genus of the Paramyxoviridae family, a group of negative-stranded RNA viruses. Genetic studies on hMPV have demonstrated the presence of two distinct hMPV serotypes each divided in two subgroups. Diagnosis is made by RT-PCR assays on respiratory secretions. Rapid antigen detection tests are not yet available and its growth in cell cultures is fastidious. No vaccines, antibodies (monoclonal or polyclonal), or chemotherapeutic agents are currently licensed for use to prevent or treat hMPV infections. The contribution of hMPV to pediatric respiratory tract infections suggests that it will be important to develop a vaccine against this virus in combination with those being developed for RSV and parainfluenza viruses. Reverse genetics technology is currently used to develop multivalent vaccines against hMPV and a variety of other important respiratory viruses such as RSV. Additional research to define the pathogenesis of this viral infection and the host’ specific immune response will enhance our knowledge to guide the search for preventive and therapeutical strategies."
8392,Stem Cell Therapy in the Treatment of Rheumatic Diseases and Application in the Treatment of Systemic Lupus Erythematosus,"Current systemic therapies help to improve the symptoms and quality of life for patients with severe life-threatening rheumatic diseases but provide no curative treatment. For the past two decades, preclinical and clinical studies of stem cell transplantation (SCT) have demonstrated tremendous therapeutic potential for patients with autoimmune rheumatic diseases. Herein, the current advances on stem cell therapies, both in animal models and clinical studies, are discussed, with particular attention on systemic lupus erythematosus (SLE). Despite extensive research and promising data, our knowledge on mechanisms of action for SCT, its administration route and timing, the optimal dose of cells, the cells’ fate and distribution in vivo, and the safety and efficacy of the treatments remains limited. Further research on stem cell biology is required to ensure that therapeutic safety and efficacy, as observed in animal models, can be successfully translated in clinical trials. Current understanding, limitations, and future directions for SCT with respect to rheumatic diseases are also discussed."
8393,Critical Care Pandemic Preparedness Primer,"The first half decade of the 21(st) century has brought with it infectious outbreaks such as severe acute respiratory syndrome (SARS) [1], bioterrorism attacks with anthrax [2], and the spread of H5N1 influenza A in birds across Asia and Europe [3, 4] sparking concerns reminiscent of the days of the Black Plague. These events, in the context of an instantaneous global-media world, have placed an unprecedented emphasis on preparing for a human influenza pandemic [5, 6]. Although some argue that the media have exaggerated the threat, the warnings of an impending pandemic are not without foundation given the history of past influenza pandemics [7], incidence of H5N1 infections among humans [8], and the potential impact of a pandemic. Reports of the 1918 pandemic vary, but most suggested that approximately one third of the world’s population was infected with 50 to 100 million deaths [9]. Computer modeling of a moderate pandemic, less severe then in 1918, in the province of Ontario, Canada predicts 73,252 admissions of influenza patients to hospitals over a 6-week period utilizing 72% of the hospital capacity, 171% of intensive care unit (ICU) capacity, and 118% of current ventilator capacity. Pandemic modeling by the Australian and New Zealand Intensive Care Society also showed that critical care resources would be overwhelmed by even a moderate pandemic [10]. This chapter will provide intensivists with a review of the basic scientific and clinical aspects of influenza as well as an introduction to pandemic preparedness."
8394,Introduction: A Prelude to Mathematical Epidemiology,"Recorded history continuously documents the invasion of populations by infectious agents, some causing many deaths before disappearing, others reappearing in invasions some years later in populations that have acquired some degree of immunity, due to prior exposure to related infectious pathogens. The “Spanish” flu epidemic of 1918–1919 exemplifies the devastating impact of relatively rare pandemics; this one was responsible for about 50,000,000 deaths worldwide, while on the mild side of the spectrum we experience annual influenza seasonal epidemics that cause roughly 35,000 deaths in the USA each year."
8395,"Rhinovirus, Coronavirus, Enterovirus, and Bocavirus After Hematopoietic Cell Transplantation or Solid Organ Transplantation","Respiratory viral infections represent a significant cause of morbidity and mortality in immunocompromised hosts. Newer molecular detection assays have allowed for the characterization of several respiratory viruses not previously recognized as having significant clinical impact in the immunocompromised population. Human rhinoviruses are the most common respiratory viruses detected in the upper respiratory tract of hematopoietic cell transplant and lung transplant recipients, and evidence on the impact on clinical outcomes is mounting. Other respiratory viruses including enteroviruses (EVs), coronaviruses (CoVs), and bocavirus may also contribute to pulmonary disease; however, data is limited in the immunocompromised population. Further studies are needed to define the epidemiology, risk factors, and clinical outcomes of these infections; this data will help inform decisions regarding development of antiviral therapy and infection prevention strategies."
8396,Applied Bioinformatics Tools,A hands-on course mainly for the applications of bioinformatics to biological problems was organized at Peking University. The course materials are from http://abc.cbi.pku.edu.cn. They are divided into individual pages (separated by lines in the text):
8397,New and Re-Emerging Infectious Diseases in Sub-Saharan Africa,"Over the past 30 years, Africa has achieved significant health gains. Life expectancy has risen while infant, child, and maternal mortality have declined. Despite these improvements, the continent still faces serious challenges from infectious diseases. The chapter covers HIV and AIDS and other epidemics in sub-Saharan Africa. It addresses the origins, evolution, mortality, morbidity, and socio-economic impacts of the epidemics, as well as the policies and programs put in place to combat them. The chapter concludes with a review of the funding and the sustainability of such financial efforts."
8398,A Young Adult with Cough and Wheezing Since Infancy,"A 20-year-old man presented for outpatient evaluation of treatment options for recurrent respiratory papillomas. He was born with vocal cord paralysis. At 4 weeks of life, he underwent tracheostomy. In childhood his tracheostomy was closed, and he was found to have occasional, small papillomas in the trachea. During puberty, he experienced a dramatic increase in the number and size of the papillomas."
8399,Colonization of Parasites and Vectors,"Colonization comprises the physical arrival of a species in a new area, but also its successful establishment within the local community. Oceanic islands, like the Hawaiian and the Galapagos archipelagos, represent excellent systems to study the mechanisms of colonization because of their historical isolation. In this chapter, we first review some of the major mechanisms by which parasites and vectors could arrive to an oceanic island, both naturally or due to human activities, and the factors that may influence their successful establishment in the insular host community. We then explore examples of natural and anthropogenic colonization of the Galapagos Islands by parasites and vectors, focusing on one or more case studies that best represent the diversity of colonization mechanisms that has shaped parasite distribution in the archipelago. Finally, we discuss future directions for research on parasite and vector colonization in Galapagos Islands."
8400,Antibody Phage Display,
8401,Pneumologie,
8402,Secondary Metabolite Production in Transgenic Hairy Root Cultures of Cucurbits,"Cucurbits are important group of vegetables due to their nutritional significance and are also used for valuable traditional medicine. The infection of plants by Agrobacterium rhizogenes results in a hairy root (HR) phenotype characterized by rapid growth in hormone-free medium, an unusual ageotropism and extensive lateral branching. These genetically transformed root cultures (hairy roots) can produce levels of secondary metabolites comparable to that of intact plants. Hairy root cultures offer promise for high production and productivity of valuable secondary metabolites in many plants. High stability and productivity features allow the exploitation of HRs as valuable biotechnological tool for the production of plant secondary metabolites. While these chemical compounds are employed by plants for interactions with their environment, humans have long since explored and exploited plant secondary metabolites for medicinal and practical uses. The main constraint for commercial exploitation of hairy root cultivations is the development and scaling up of appropriate reactor vessels (bioreactors) that permit the growth of interconnected tissues normally unevenly distributed throughout the vessel. Emphasis has focused on designing appropriate bioreactors suitable to culture the delicate and sensitive plant hairy roots. To this end, hairy root culture presents an excellent platform for producing valuable secondary metabolites. For these reasons, this chapter describes the establishment of hairy roots and production of secondary metabolites from hairy roots of cucurbits and also phytochemicals uses for biological activity."
8403,Biological and Chemical Weapons,"The five anthrax letters put in the US mail in 2001 greatly raised concerns about BW and CW. In general, chemical weapons are considered about as lethal per unit mass as conventional explosives and much less lethal than either nuclear or biological weapons (dirty bombs are much less lethal, Chap. 10.1007/978-3-319-25367-1_13). Biological weapons can be as lethal as nuclear weapons if dispersed effectively, but that is not easy to do. For BW to be effective, the bio-materials must be chemically robust, remaining stable, not decaying in sunlight, moisture and rain. This can be accomplished with spores and aerosols. BW material must be dispersed widely, not clumping in few locations. BW can be delivered by cluster bomblets from small missiles. BW can be delivered by helicopter or low-flying crop-duster, or BW can be released in many locations in many small spray cans."
8404,Myocarditis,"Viruses are the most common cause of myocarditis in economically advanced countries. Enteroviruses and adenoviruses are the most common etiologic agents. Viral myocarditis is a triphasic process. Phase 1 is the period of active viral replication in the myocardium during which the symptoms of myocardial damage range from none to cardiogenic shock. If the disease process continues, it enters phase 2, which is characterized by autoimmunity triggered by viral and myocardial proteins. Heart failure often appears for the first time in phase 2. Phase 3, dilated cardiomyopathy, is the end result in some patients. Diagnostic procedures and treatment should be tailored to the phase of disease. Viral myocarditis is a significant cause of dilated cardiomyopathy, as proved by the frequent presence of viral genomic material in the myocardium, and by improvement in ventricular function by immunomodulatory therapy. Myocarditis of any etiology usually presents with heart failure, but the second most common presentation is ventricular arrhythmia. As a result, myocarditis is one of the most common causes of sudden death in young people and others without preexisting structural heart disease. Myocarditis can be definitively diagnosed by endomyocardial biopsy. However, it is clear that existing criteria for the histologic diagnosis need to be refined, and that a variety of molecular markers in the myocardium and the circulation can be used to establish the diagnosis. Treatment of myocarditis has been generally disappointing. Accurate staging of the disease will undoubtedly improve treatment in the future. It is clear that immunosuppression and immunomodulation are effective in some patients, especially during phase 2, but may not be as useful in phases 1 and 3. Since myocarditis is often selflimited, bridging and recovery therapy with circulatory assistance may be effective. Prevention by immunization or receptor blocking strategies is under development. Giant cell myocarditis is an unusually fulminant form of the disease that progresses rapidly to heart failure or sudden death. Rapid onset of disease in young people, especially those with other autoimmune manifestations, accompanied by heart failure or ventricular arrhythmias, suggests giant cell myocarditis. Peripartum cardiomyopathy in economically developed countries is usually the result of myocarditis."
8405,Misguided Responses to Public Health Emergencies,"This chapter considers some misguided responses to public health emergencies, or perceived emergencies. At one extreme was the arrest and lifetime confinement in Hawaii and elsewhere of sufferers from leprosy, or Hansen’s disease. This, of course, was not an example of presidential policy, but is included as an example of horrible overreach. An opposite approach was the refusal of the Eisenhower administration to mount a vaccination program to deal with the Asian flu pandemic of 1957. President Eisenhower was devoted to private solutions to such emergencies, and these were manifestly inadequate. There was yet another extreme example of a misguided approach, and that was President Woodrow Wilson’s militant passivity to the 1918 influenza pandemic. Disregarding advice from medical consultants, he refused to discontinue the shipment of troops abroad to fight in the Great War, which resulted in an even greater spread of the contagion because of the great numbers of men confined to small quarters aboard ships. Incompetence can always be a danger in public health emergencies. Although this was not a pandemic, the George W. Bush administration handled the health crisis caused by Hurricane Katrina so poorly that it became a national scandal. On the other hand, President Bush did move to plan wisely for a possible influenza pandemic when he ordered the creation of national stockpiles of antiviral medication."
8406,Laboratory Diagnosis of Viral Disease,
8407,Infectious Diseases Prevention and Control,"China is a big country with huge regional differences in social economic development. The large population, high population density and mobility, as well as significant regional differences in life style make infectious diseases a major threat to China. With strong outburst and fast spread, infectious diseases are also more difficult to control in China. So China has to stick to a strategy which emphasizes both prevention and therapy in infectious disease control."
8408,DLI Induced by Herbal Medicine: What Are the Characteristics of DLI due to Herbal Medicines?,"In many countries, herbal medicine has been developed and is currently practiced. Herbal medicine involves the use of the stalks, roots, leaves, flowers, and berries of several different plant species for medical treatment. Many practitioners believe that herbal medication has no side effects because of its natural origin. Thus, herbal medication has been used for a long time with little awareness of its side effects. However, there is an increasing incidence of interstitial pneumonia due to a drug-induced lung injury (DLI), which could be induced by common drugs. Moreover, increasing cases of bronchiolitis obliterans and pulmonary hypertension are being reported; further, these are drug-induced conditions. Clinicians should be more aware of DLI symptoms caused by herbal medication and interrogate patients regarding their use of herbal medication and supplements as well as prescription drugs."
8409,"Collectivism–Individualism, Family Ties, and Philopatry","As predicted by the parasite-stress theory of values, variation in parasite stress correlated with collectivism–individualism across nations, USA states, and indigenous societies. In regions with high adversity of infectious diseases, human cultures are characterized by high collectivism, whereas in regions of low parasite stress cultures are highly individualistic. The prediction from the parasite-stress theory of values that infectious disease transmissible among humans (nonzoonotics) will be more important in predicting collectivism–individualism than those that humans can contract only from nonhuman animals (zoonotics) was supported. Evidence in human movement patterns for nations, states of the USA, and indigenous societies supports the hypothesis that the absence of dispersal (high philopatry) is a defense against contact with novel parasites in out-groups and their habitats. We show that human cultures with high degrees of collectivism have high degrees of cooperative breeding, and propose that the parasite-stress theory of sociality offers a general theory of family structure across humans as well as nonhuman animal taxa. We propose that a major context for the evolution of human reciprocity was in gaining benefits from out-group interactions during periods of relatively low disease threat. The parasite-stress theory of values offers a novel perspective to explain the evolution of reciprocity and human unique cognitive abilities. The parasite-stress theory suggests useful new research directions for the study of the demographic transition, patriotism, xenophobia, ethnocentrism, and moral foundations theory. We include discussion of ecological correlations and the ecological fallacy. The fact that all scientific findings are correlational is explained."
8410,Selective and Dual Targeting of CCR2 and CCR5 Receptors: A Current Overview,"The chemokine receptor 2 (CCR2) and chemokine receptor 5 (CCR5) are important mediators of leukocyte trafficking in inflammatory processes. The emerging evidence for a role of CCR2 and CCR5 receptors in human inflammatory diseases led to a growing interest in CCR2- and CCR5-selective antagonists. In this review, we focus on the recent development of selective CCR2/CCR5 receptor ligands and dual antagonists. Several compounds targeting CCR2, e.g., INCB8761 and MK0812, were developed as promising candidates for clinical trials, but failed to show clinical efficacy as presumed from preclinical models. The role of CCR5 receptors as the second co-receptor for the HIV-host cell fusion led to the development of various CCR5-selective ligands. Maraviroc is the first CCR5-targeting drug for the treatment of HIV-1 infections on the market. The role of CCR5 receptors in the progression of inflammatory processes fueled the use of CCR5 antagonists for the treatment of rheumatoid arthritis. Unfortunately, the use of maraviroc for the treatment of rheumatoid arthritis failed due to its inefficacy. Some of the ligands, e.g., TAK-779 and TAK-652, were also found to be dual antagonists of CCR2 and CCR5 receptors. The fact that CCR2 and CCR5 receptor antagonists contribute to the treatment of inflammatory diseases renders the development of dual antagonists as promising novel therapeutic strategy."
8411,Taxonomy,This chapter addresses the classification and taxonomy of viruses with special attention to viruses that show pneumotropic properties. Information provided in this chapter supplements that provided in other chapters in Parts II–V of this volume that discuss individual viral pathogens.
8412,Searching for Superspreaders: Identifying Epidemic Patterns Associated with Superspreading Events in Stochastic Models,"The importance of host transmissibility in disease emergence has been demonstrated in historical and recent pandemics that involve infectious individuals, known as superspreaders, who are capable of transmitting the infection to a large number of susceptible individuals. To investigate the impact of superspreaders on epidemic dynamics, we formulate deterministic and stochastic models that incorporate differences in superspreaders versus nonsuperspreaders. In particular, continuous-time Markov chain models are used to investigate epidemic features associated with the presence of superspreaders in a population. We parameterize the models for two case studies, Middle East respiratory syndrome (MERS) and Ebola. Through mathematical analysis and numerical simulations, we find that the probability of outbreaks increases and time to outbreaks decreases as the prevalence of superspreaders increases in the population. In particular, as disease outbreaks occur more rapidly and more frequently when initiated by superspreaders, our results emphasize the need for expeditious public health interventions."
8413,Pathogenesis of COPD (Persistence of Airway Inflammation): Why Does Airway Inflammation Persist After Cessation of Smoking?,"The structural features of airways in patients with COPD are airway wall inflammation, fibrosis, muscle hypertrophy, and goblet cell metaplasia. These structural cellular changes contribute to mucus hypersecretion and destruction of the alveolar walls and a decline in forced expiratory volume in one second (FEV(1)). At the cellular level, macrophages, T lymphocytes, and neutrophils, driven by cytokines including interleukin-8 (IL-8), gather on the airways. The main cause of COPD inflammation is cigarette smoke. Smoke causes an increase in the secretion of matrix metalloproteinase (MMPs) and neutrophilic elastase from epithelial cells and neutrophils, which are responsible for mucin production and destruction of the lung. Initially, cigarette smoke influences the expression of pattern recognition receptors (PRRs) including Toll-like receptors (TLRs), the intracellularly located nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), and receptors for advanced glycation end products (RAGE) on lung epithelial cells, endothelial cells, and leukocytes in the lung. These actions bring about the production of cytokines and activation of inflammatory cells, leading to production of MMPs and neutrophilic elastase. The inflammatory changes persist for several months and years after smoking cessation and are sometimes irreversible. Damage-associated molecular patterns (DAMPs) released from dying cells after cigarette smoking increase the number of apoptotic cells, suppress efferocytosis, induce hypoxia and oxidative stress, and prolong the inflammatory changes, even after smoking cessation. Viral and bacterial infections of the respiratory tract then fortify these inflammatory responses. Exacerbations of COPD then worsen the deterioration of COPD."
8414,When a Diagnosis Is Reportable,
8415,Emerging Viruses,"Emerging viruses are viruses that appear suddenly in the human population. These are viruses to which man has no history of exposure and thus no or limited immunity; they are not new evolutionary creations, but are viruses than man meets due to environmental changes, such as deforestation, entering into new habitats, or viruses that are transmitted from one species of animal to humans. Most of these viruses are terrifying, and cause hemorrhagic fever, a complete destruction of the circulation system; they include Lassa fever, Nipah virus, Ebola, HIV, Severe acute respiratory syndrome (SARS), and, recently, Middle East respiratory syndrome (MERS), which is the latest in a series of “new” respiratory viruses infecting man. It is possible that unknown emerging viruses are the cause of death, often listed as “death due to an unknown cause,” as in the retrospective cases of HIV. Emerging viruses might also include poliovirus and influenza, since their introduction into the human population is (was) often sudden and due to changes in the environment or due to contact with other animal species. For examples, polio was a result of changes in sanitation in the countries of North America and Western Europe, and influenza is constantly jumping from aquatic birds to man and other animal species where genomic reassortment occurs."
8416,Die medizinische Mikrobiologie im 21. Jahrhundert,"Die medizinische Mikrobiologie befasst sich mit der ursächlichen Rolle pathogener (d. h. krankheitserzeugender) Mikroorganismen bei der Entstehung von Störungen im Funktionsablauf des menschlichen Organismus. Störungen dieser Art entstehen durch Ansiedlung und Vermehrung von Mikroorganismen im Sinne des Parasitismus; sie treten als Infektionskrankheit in Erscheinung. Demgemäß betrachtet man die parasitierenden Mikroorganismen als Krankheitserreger; das befallene Individuum wird als »Wirt« oder »Makroorganismus« bezeichnet. Da bei der Betrachtung von Infektionen sowohl der Wirt mit seinen Reaktionen als auch die krankheitserzeugenden Eigenschaften eines Mikroorganismus (d. h. seine Pathogenität) im Vordergrund stehen, lässt sich die medizinische Mikrobiologie am ehesten als Infektionslehre begreifen – als Lehre von der Auseinandersetzung des Wirtes mit den krankheitserzeugenden Eigenschaften des Erregers."
8417,Severe Sepsis in the Elderly,
8418,The Role of Bats as Reservoir Hosts of Emerging Neuroviruses,"Recent studies have clearly shown that bats are the reservoir hosts of a wide diversity of novel viruses with representatives from most of the known animal virus families. In many respects bats make ideal reservoir hosts for viruses: they are the only mammals that fly, thus assisting in virus dispersal; they roost in large numbers, thus aiding transmission cycles; some bats hibernate over winter, thus providing a mechanism for viruses to persist between seasons; and genetic factors may play a role in the ability of bats to host viruses without resulting in clinical disease. Within the broad diversity of viruses found in bats are some important neurological pathogens, including rabies and other lyssaviruses, and Hendra and Nipah viruses, two recently described viruses that have been placed in a new genus, Henipaviruses in the family Paramyxoviridae. In addition, bats can also act as alternative hosts for the flaviviruses Japanese encephalitis and St Louis encephalitis viruses, two important mosquito-borne encephalitogenic viruses, and bats can assist in the dispersal and over-wintering of these viruses. Bats are also the reservoir hosts of progenitors of SARS and MERS coronaviruses, although other animals act as spillover hosts. This chapter presents the physiological and ecological factors affecting the ability of bats to act as reservoirs of neurotropic viruses, and describes the major transmission cycles leading to human infection."
8419,Pulmonary Complications Associated with HSCT,"While outcomes for patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) have improved over the past 10–20 years, pulmonary complications after allogeneic HSCT remain a leading cause of morbidity and mortality. Overall, 25–50% of pediatric HSCT patients will develop pulmonary complications. Thus, prevention, early detection, and intervention are key to minimizing the sequelae from HSCT-associated pulmonary complications. HSCT-associated pulmonary complications can be classified as infectious or noninfectious, and they often follow a predictable timeline, occurring during discrete phases of HSCT (pre-engraftment, early post-engraftment, late post-engraftment). However, certain post-HSCT pulmonary complications span the entire post-HSCT course. The most common causes of noninfectious pulmonary complications are related to the conditioning regimen used which can result in varying degrees of acute or delayed lung injury, the degree of recipient–donor HLA histoincompatibility, the hematopoietic stem cell (HSC) source, the degree of graft manipulation, and the development of graft-versus-host disease (GvHD), both acute and chronic. Infectious etiologies can be caused by any class of pathogen including bacterial, viral, fungal, and protozoan. They usually occur during periods of profound and/or prolonged neutropenia and/or impaired or delayed cellular and humoral immune recovery. Immunosuppression used to prevent or treat GvHD also places a HSCT recipient at high risk for developing pulmonary infections that can be life-threatening. This chapter discusses the most common pulmonary complications associated with HSCT by time period post-HSCT."
8420,Public Health in Africa: Theoretical Framework,These are examined as parts of the health or medical systems from an historical perspective that enables the reader to link the present to the past and vice-versa.
8421,Antiphospholipid (Hughes) Syndrome: An Overview,"In conclusion, the following observations can be made. aPL are present in approximately 2% to 4% of the normal population and the prevalence increases with age. There is a high prevalence among patients with autoimmune connective tissue disorders, especially SLE. There is an association with both venous and arterial thrombosis as well as with pregnancy morbidity, but the strength of association varies amongst studies. This probably reflects different populations, study designs, and different assays and definitions used. In several studies the risk of thrombosis appears to be higher with LA and the data suggests a true association rather than epiphenomenon. In a given patient, both aCL and LA should be measured. A significant impact on long-term survival has been noted and aPL also contribute significantly to accumulated damage in diseases such as SLE. The clinical spectrum of APS features is enormous and continues to expand. It behoves us all as clinicians and health care professionals to consider an early diagnosis of Hughes syndrome, with its distinct clinical and serological features, to reduce the risk of morbidity and mortality in our patients."
8422,Kardiologie,
8423,How Disease Affected the End of the Bronze Age,"Dr. Norrie provides a summary of the fifteen currently accepted causes for the end of the Bronze Age in the Near East and then goes on to discuss the sixteenth reason—infectious disease epidemics. These are the real reason that the end of the Bronze Age in the Near East was called either the “catastrophe” or the “collapse” due to its short time frame of 50 years, the mass migration of the general population and the “Sea Peoples” plus the abandonment of cities such as Hattusa, the capital of the Hittite Empire c.1200 bce. The diseases most likely to cause this collapse are smallpox, bubonic plague and tularemia."
8424,Contagio cine qua non oder wie Al Gore die Zukunft in Brand steckte: Zukunftswissen im Filmszenario,"Die Antwort eines Handbuchs der Szenariotechnik auf die Frage, was ein Szenario ist, lautet wie folgt."
8425,Evolution of the BCL-2-Regulated Apoptotic Pathway,"The mitochondrion descends from a bacterium that, about two billion years ago, became endosymbiotic. This organelle represents a Pandora’s box whose opening triggers cytochrome-c release and apoptosis of cells from multicellular animals, which evolved much later, about six hundred million years ago. BCL-2 proteins, which are critical apoptosis regulators, were recruited at a certain time point in evolution to either lock or unlock this mitochondrial Pandora’s box. Hence, particularly intriguing is the issue of when and how the “BCL-2 proteins–mitochondria–apoptosis” triptych emerged. This chapter explains what it takes from an evolutionary perspective to evolve a BCL-2-regulated apoptotic pathway, by focusing on the events occurring upstream of mitochondria."
8426,Pathophysiologic Role of Autophagy in Human Airways,"Lung diseases are among the most common and widespread disorders worldwide. They refer to many different pathological conditions affecting the pulmonary system in acute or chronic forms, such as asthma, chronic obstructive pulmonary disease, infections, cystic fibrosis, lung cancer and many other breath complications. Environmental, epigenetic and genetic co-factors are responsible for these pathologies that can lead to respiratory failure, and, even, ultimately death. Increasing evidences have highlighted the implication of the autophagic pathways in the pathogenesis of lung diseases and, in some cases, the deregulated molecular mechanisms underlying autophagy may be considered as potential new therapeutic targets. This chapter summarizes recent advances in understanding the pathophysiological functions of autophagy and its possible roles in the causation and/or prevention of human lung diseases."
8427,Exam 3 Questions,"1. Which of thefollowing is true regarding the Barrow classification system for carotid cavernous fistulae? A. Type A shunts are indirect shunts between branches of the internal carotid artery (ICA) and cavernous sinus. B. Type B shunts are direct shunts between the ICA and cavernous sinus. C. Type C shunts are indirect shunts between branches of the external carotid artery (ECA) and cavernous sinus. D. Type D shunts are high-flow shunts. E. All of the above. 2. A 80-year-old male with an intracranial neoplasm presents to the emergency department with weight loss, drowsiness, and tachypnea for 1 month. On examination, his respiratory rate is 28 breaths/minute with a normal oxygen saturation. His lungs are clear to auscultation. An arterial blood gas reveals the following: pH 7.60, PCO(2) 14 mmHg, PaO(2) A. Central neurogenic hyperventilation. B. Cheyne-Stokes respirations. C. Apneustic breathing. D. Ataxic breathing. E. Cluster breathing. 3. A 48-year-old female is admitted to the ICU with a Hunt-Hess 2 modified Fisher 2 subarachnoid hemorrhage (SAH). She remains intact neuro-cognitively, but has transcranial doppler (TCD) mean flow velocities up to 150 cm/s, and a serum platelet count twice her baseline. You are worried about vasospasm and impending delayed cerebral ischemia. Which of the following should be performed next? A. An additional 100 mL/h of normal saline should be given on top of maintenance fluids. B. CT perfusion scan to assess for any ongoing hypoperfusion. C. Evaluate volume status with hemodynamic monitoring and give fluid boluses accordingly. D. Induce hypertension to a systolic pressure of 160 mmHg. E. Conventional angiography. 4. A 25-year-old male is currently in the ICU with an anoxic brain injury after diving into shallow waters and suffering a high cervical cord transection. Two weeks after his injury, he remains comatose, has diffuse loss of gray-white differentiation on noncontrast head CT, and exhibits myoclonic status epilepticus. The family is devastated by his poor prognosis, and distraught by his uncontrollable shaking. What is your rationale behind your decision about starting an antiepileptic regimen? A. Phenytoin and propofol will be used, and escalated until eradication of his myoclonus to assess his underlying brain damage. B. Levetiracetam and lacosamide will be used, and escalated until eradication of his myoclonus to assess his underlying brain damage. C. If EEG reveals dyssynchronous spikes on a severely slow background, myoclonus invariably portends death or a vegetative state, and midazolam should only be used for palliative purposes. D. Regardless of EEG or clinical exam, half of patients in myoclonic status epilepticus will have a good neurologic recovery by 90 days. E. Regardless of EEG or clinical exam, myoclonic status epilepticus is always ominous, not amenable to treatment. and should lead to immediate withdrawal of life-support. 5. An 18-year-old female presents to the emergency department with several months of progressive left-sided hearing loss and tinnitus. An MRI of the brain is performed, demonstrating bilateral enhancing dumbbell shaped lesions extending from the auditory canal to the cerebellopontine angle. Which of the following genetic disorders is associated with this finding? A. Von Hippel-Lindau syndrome. B. Neurofibromatosis type II. C. Tuberous sclerosis. D. Schwannomatosis. E. Alport syndrome. 6. A 23-year-old female is brought to the emergency department by her boyfriend with difficulty breathing. She cannot provide her history, but her boyfriend states that she has asthma, although he is unsure of her medications. On physical exam the woman is noted to have nasal flaring, is diaphoretic, cannot lie flat, and is breathing at a rate of 40 breaths/minute. She is given short acting ß(2) agonist treatments with no obvious relief of her symptoms. Serial arterial blood gases are done and show a pCO(2) A. Continue short-acting ß(2) agonist treatment, as her pCO(2) is normalizing, and continue observation in the emergency department. B. Intubate the patient and admit to the ICU. C. Administer intravenous corticosteroids and admit to the general medical ward. D. Place the patient on non-invasive positive pressure ventilation and admit to the general medical ward. E. Administer a long-acting ß(2) agonist agent and admit to the general medical ward. 7. Cerebellar hypoplasia without displacement through the foramen magnum is best described as a: A. Chiari I malformation. B. Chiari II malformation. C. Chiari III malformation. D. Chiari IV malformation. E. Chiari V malformation. 8. A 77-year-old female with a history of hypertension, atrial fibrillation, and diabetes mellitus has recently been taken off of warfarin due to frequent falls and gait instability. She has not had any prior significant bleeding or ischemic events. A recent echocardiogram demonstrates moderate aortic regurgitation with grossly preserved systolic and diastolic function. Which of the following elements is not a stroke risk factor in this patient? A. Age. B. Female gender. C. Hypertension. D. Diabetes mellitus. E. Aortic regurgitation. 9. Which of the following is the most effective measure to prevent aspiration in an intubated patient? A. Elevation of the head of the bed. B. Subglottic drainage. C. Gastric volume monitoring. D. Nasogastric tube placement. E. Percutaneous endoscopic gastrotomy. 10. Which of the following is a unique feature of Comprehensive Stroke Centers? A. Dedicated stroke unit availability. B. 24/7 ability to administer tPA. C. 24/7 interventional neuroradiology availability. D. 24/7 CT angiography availability. E. Ambulance receiving capability. 11. Which of the following segments of the internal carotid artery is farthest from it’s origin? A. Ophthalmic segment. B. Petrous segment. C. Cavernous segment. D. Clinoid segment. E. Lacerum segment. 12. A 44-year-old male is intubated secondary to a high-grade subarachnoid hemorrhage, and is admitted to the ICU. On the sixth postoperative day, he develops worsening hypoxemia and bilateral interstitial infiltrates on his chest x-ray, consistent with acute respiratory distress syndrome (ARDS). Which of the following interventions has not been demonstrated to improve outcomes in ARDS in a prospective randomized trial? A. Prone positioning. B. Lung-protective ventilation. C. Extracorporeal membrane oxygenation (ECMO). D. Neuromuscular blocking agents. E. High-frequency oscillatory ventilation (HFOV). 13. A 56-year-old female is currently intubated in the ICU following a left basal ganglia hemorrhage. The nurse reports the patient is having copious thick secretions, and you are considering initiating inhaled N-acetylcysteine therapy. What element of the patient’s past medical history may serve as a relative contraindication to this treatment? A. Amiodarine-induced pulmonary fibrosis. B. Newly diagnosed metastatic adenocarcinoma of the lung. C. Recent course of outpatient antibiotics for community-acquired pneumonia. D. Poorly controlled asthma. E. All of the above. 14. An 18-year-old female is currently being evaluated for amenorrhea. In addition, she endorses fatigue, cold intolerance, polyuria and dizziness upon standing. On examination, she is thin but appears well hydrated. Blood pressure and heart rate when supine are 90/60 mmHg and 80 beats/minute, respectively. When standing, they are 60/40 mmHg and 120 beats/minute, respectively. Pubic and axillary hair growth is sparse. Eye examination reveals an asymmetric bitemporal hemianopsia. Imaging reveals a cystic, calcified suprasellar mass. Which of the following statements is true regarding the most likely diagnosis? A. Medical management is the mainstay of treatment. B. Recovery of pituitary function is common. C. This patient likely has the papillary subtype of this neoplasm. D. This neoplasm has a bimodal age distribution. E. This neoplasm arises from modified glial cells that reside in the infundibular neurohypophysis. 15. A 55-year-old female presents to the emergency department after collapsing at home. The patient was arguing with her husband before she suddenly became unresponsive. The patient is intubated, and a non-contrast head CT is performed (see Image 1). The patient then undergoes conventional angiography, revealing occlusion of the proximal bilateral middle cerebral and anterior cerebral arteries with extensive collateral vessels noted. All of the following are true regarding the most likely diagnosis except: A. The disease can be either congenital or acquired. B. Patients may suffer recurrent infarcts, or remain completely asymptomatic. C. There are no effective surgical interventions available. D. It is more commonly seen in women than in men. E. Patients may initially present with persistent headaches;"
8428,Adult-Onset Still’s Disease,"Adult-onset Still’s disease (AoSD) is a rare but clinically well-known, polygenic, systemic autoinflammatory disease. It is typically characterized by four main (cardinal) symptoms: spiking fever ≥39 °C, arthralgia or arthritis, skin rash, and hyperleukocytosis (≥10,000 cells/mm(3)). However, many other clinical features are possible, and it can appear in all age groups with potentially severe inflammatory onset accompanied by a broad spectrum of disease manifestation and complications. Hence, it remains a diagnostic challenge, and the clinician should first rule out infectious, tumoral, or inflammatory differential diagnoses. Determination of the total and glycosylated ferritin levels, although not pathognomonic, can help in diagnosis. New biomarkers have recently been described, but they need to be validated. The disease evolution of AoSD can be monocyclic, polycyclic, or chronic. In chronic disease, a joint involvement is often predominant, and erosions are noted in one-third of patients. Many progresses have been made in the understanding of the pathogenesis over the last decades. This chapter provides a comprehensive insight into the complex and heterogeneous nature of AoSD describing the identified cytokine signaling pathways and biomarkers. It also discusses the current evidence for the usage of biologics in AoSD to provide guidance for treatment decisions, taking into account both the efficacy and the safety of the different therapeutic options."
8429,The Chemical and Biological Properties of Propolis,"The term propolis comes from two Greek words, pro (which means for or in defence of) and polis (which means the city); thus, propolis means in defence of the city or beehive. Propolis is a sticky resinous substance, which is gathered from buds and the bark of trees. It is also known as “bee glue” as bees use it to cover surfaces, seal holes and close gaps in their hives, thus providing a sterile environment that protects them from microbes and spore-producing organisms, including fungi and molds. It can be considered to be a potent chemical weapon against bacteria, viruses, and other pathogenic microorganisms that may invade the bee colony. Also, bees use propolis as an embalming substance, to mummify invaders such as other insects, that have been killed and are too heavy to remove from the colony. Thus, propolis is important for bee health but it also has activity against many human diseases. It is a powerful anti-oxidant and can modulate the activity of reactive oxygen species within the human body. The most studied aspect of propolis is its anti-bacterial activity, which is almost always present at a moderate to high level depending on the exact type of propolis. It is in general more active against Gram positive than Gram negative bacteria, but activity against Gram negative bacteria has been observed. Propolis has been found to be active against a range of viruses and also is almost always active against protozoa such as Tryanosoma brucei and Leishmania donovani. Propolis also shows activity against cardiovascular diseases and diabetes and has immunomodulatory effects. Anti-cancer activity has also been observed. In summary, propolis is remarkable for its range of biological activities and for the variety of its chemical composition. It may be of great importance both to bees and humans."
8430,Case Study – Romania,"Countering bioterrorism, as other health threats caused by infectious agents, requires good preparedness, and early warning and response, which can be achieved by an efficient epidemiological surveillance system. In 1990, Romania inherited a functional and quite efficient epidemiological surveillance system from the former communist regime, based on pyramidal and autocratic principles where the state control was absolute. In 2001, the assessment conducted by WHO/Europe showed many unsatisfactory elements of the remaining epidemiological surveillance system for communicable diseases, with a lack of procedures, poor microbiology laboratory capacities, and overlapping responsibilities. The lack of a coordinating body was evident, especially during bioterrorist threats following 9/11 attacks in New York. In 2003 and 2004, the PHARE Project offered an important opportunity for Romania to improve the Romanian System of Epidemiological Surveillance and Control of Communicable Diseases. At the end of this project many of the technical capacities had been improved, specialized trainings of epidemiologists and microbiologists were carried out, and a coordinating body of the epidemiological surveillance network was established [1]. Furthermore, a National Plan of Action was approved by the Minister of Health with the declared objective to improve the system in order to comply with EU standards. At present, the National Institute of Public Health hosts the National Center for Communicable Diseases Surveillance and Control which coordinates the epidemiological network and serves as the Romanian focal point for international institutions such as WHO and ECDC. Each year, comprehensive reports regarding surveillance in Romania of many communicable diseases are published, including diseases potentially related to bioterrorism. Until now, no evidence of a bioterrorism event has been registered in Romania."
8431,Time and Travel,
8432,Nanomolecular Diagnostics,
8433,Phylogenetics Algorithms and Applications,"Phylogenetics is a powerful approach in finding evolution of current day species. By studying phylogenetic trees, scientists gain a better understanding of how species have evolved while explaining the similarities and differences among species. The phylogenetic study can help in analysing the evolution and the similarities among diseases and viruses, and further help in prescribing their vaccines against them. This paper explores computational solutions for building phylogeny of species along with highlighting benefits of alignment-free methods of phylogenetics. The paper has also discussed the application of phylogenetic study in disease diagnosis and evolution."
8434,SARS coronavirus main proteinase 3.4.22.69,"EC number 3.4.22.69 Recommended name SARS coronavirus main proteinase Synonyms 3C-like protease <2,3> [9,16,38,49,51] 3CL protease <2> [14,48] 3cLpro <1,2,3> [7,11,13,16,19,28,38,49,51] C30.004 (Merops-ID) Mpro SARS 3C-like protease <2> [17] SARS 3C-like proteinase <2> [15,18,27] SARS 3CL protease <2> [31] SARS 3CLpro <2> [49] SARS CoV main proteinase <2> [1,2,4,5] SARS CoVMpro <2> [33] SARS Mpro <2> [25] SARS coronavirus 3C-like protease <2> [48] SARS coronavirus 3C-like proteinase <2> [50] SARS coronavirus 3CL protease <2> [20] SARS coronavirus main peptidase <2> [23] SARS coronavirus main protease <2> [25] SARS coronavirus main proteinase <2> [5,33] SARS main protease <2> [12,25] SARS-3CL protease <2> [48] SARS-3CLpro <2> [29,50] SARS-CoV 3C-like peptidaseSARS-CoV 3C-like peptidase<2> [24] SARS-CoV 3C-like protease<1> [19] SARS-CoV 3CL protease <2> [22,30,44,46] SARS-CoV 3CLpro <2> [32,36,38,44,45] SARS-CoV 3CLpro enzyme <2> [11] SARS-CoV Mpro <2> [21,40] SARS-CoV main protease <2> [21,26,43] SARS-coronavirus 3CL protease <2> [8] SARS-coronavirus main protease <2> [47] TGEV Mpro coronavirus 3C-like protease <1> [19] porcine transmissible gastroenteritis virus Mpro severe acute respiratory syndrome coronavirus 3C-like protease <2> [41,42] severe acute respiratory syndrome coronavirus main protease <2> [21] severe acute respiratory syndrome coronavirus main proteinase <2> [33] CAS registry number 218925-73-6 37353-41-6"
8435,Inflammation,Inflammation was described as early as 3000 BC in an Egyptian papyrus [1] and is still a common problem despite continuous advancements in prevention and treatment methods. The delineation of the site and extent of inflammation are crucial to the clinical management of infection and for monitoring the response to therapy [2].
8436,Intensivmedizin bei neurologischen Erkrankungen,"Eine 73-jährige Frau wird verwahrlost und wesensverändert im Treppenhaus ihres Wohnhauses vorgefunden. Die Notärztin stellt eine Temperatur von 39,5°C, eine deutliche Exsikkose und basale Rasselgeräusche beidseits fest. Die Patientin lehnt eine stationäre Krankenhausbehandlung vehement ab und muss daher mittels Psychisch-Kranken-Gesetz (PsychKG) eingewiesen werden. Bei Verdacht auf eine Pneumonie ruft die Pflegekraft in der Notaufnahme den diensthabenden Internisten hinzu."
8437,"Synthetic Biology, Dual Use Research, and Possibilities for Control","The anthrax attack on the human population in the United States in 2001/2002 may be considered the naissance of modern bioterrorism. This attack, e.g. the planned killing by means of deadly microorganisms (Bacillus anthracis) caused enormous public concern, because, numerous other deadly agents, now known as “select agents”, occur in nature and are available for misuse. The anthrax attack coincided with the first report in 2002 of the de novo synthesis in the test tube of a pathogenic human virus, poliovirus, that was equally shocking because it indicated that dangerous infectious agents could be produced in laboratories outside of government control. These events were synchronous with the advent of a new discipline, Synthetic Biology, which was an emerging area of research that can broadly be described “as the design and construction of novel artificial biological pathways, organisms or devices, or the redesign of existing natural biological systems.” The synthesis of viruses, or more broadly expressed: each experiment in Synthetic Biology, fits the definition of “Dual Use Research” – the dual use dilemma in which the same technologies can be used for the good of humans and misused for bioterrorism. In view of these threats the US Government has formulated rules that can lower the chances of misuse of biological research. That includes all research with select agents or the modification of agents to acquire dangerous traits (“Gain of Function”). It also calls for the continuous education of all generations entering research: to be aware that results of research can be dangerous, if not immediately then possibly at later times."
8438,"The Microbe: The Basics of Structure, Morphology, and Physiology as They Relate to Microbial Characterization and Attribution","This chapter is meant to (1) review classical methods used to characterize and classify microbes and (2) introduce new molecular methods used in microbial characterization. The fundamental composition of microbes is discussed as well as their importance in classification of microbes into genus and species. Classical microbiological methods in general seek to define the common features of specific bacterial groups as a means of classification and identification of microbes. Thus, the focus was to describe the common features which discriminated closely related groups of organisms. In contrast, the newer molecular methods often seek to expand the classification of microbes not only as a means to organize microbial phylogeny but also to differentiate signatures between microbes identified within a species in greater detail. Molecular biology tools are used both as an adjunct to established methods and as replacement for classical methods for detection, discrimination, or identification of bacterial and viral species."
8439,Intensivmedizin bei neurologischen Erkrankungen,"Eine 73-jährige Frau wird verwahrlost und wesensverändert im Treppenhaus ihres Wohnhauses vorgefunden. Die Notärztin stellt eine Temperatur von 39,5°C, eine deutliche Exsikkose und basale Rasselgeräusche beidseits fest. Die Patientin lehnt eine stationäre Krankenhausbehandlung vehement ab und muss daher mittels Psychisch-Kranken-Gesetz (PsychKG) eingewiesen werden. Bei Verdacht auf eine Pneumonie ruft die Pflegekraft in der Notaufnahme den diensthabenden Internisten hinzu."
8440,In-Vehicle Exposures at Transportation and the Health Concerns,"In-vehicle environment is a special indoor environment, which is mobile, either open or closed. This chapter reviewed in-vehicle air quality and passenger exposures for roadway commuters, commercial airplanes, and marine transportation. The sources of pollutants in-vehicle can be categorized as the same as other indoor environments, including outdoor air, human activity, emission from building material and interior furnisher, and biological metabolic process from animals and microbes. However, the exposure in vehicles varies from now and then, influenced by window open/closed, speed, air flow, ventilation on/off, air conditioner on/off, pollutants from ambient outdoor air, interior material, and number of passengers. There are few studies on health condition of passengers, except infectious disease during airway transportation. Some health studies of related occupations are reviewed."
8441,Pneumologie,
8442,Environmental survival and microbicide inactivation of coronaviruses,
8443,Carbohydrate Microarrays,"Carbohydrates, like nucleic acids and proteins, are essential biological molecules. Owing to their intrinsic physicochemical properties, carbohydrates are capable of generating structural diversity in a multitude of ways and are prominently displayed on the surfaces of cell membranes or on the exposed regions of macromolecules. Recent studies highlight that carbohydrate moieties are critical for molecular recognition, cell-cell interactions, and cell signaling in many physiological and pathological processes, and for biocommunication between microbes and host species. Modern carbohydrate microarrays emerged in 2002 and brought in new high-throughput tools for “glyco code” exploration. In this section, some basic concepts of sugar chain diversity, glyco-epitope recognition, and the evolving area of glyco-epitomics and biomarker discovery are discussed. Two complementary technologies, carbohydrate antigen arrays and photogenerated glyco-chips, serve as models to illustrate how to apply carbohydrate microarrays to address biomedical questions."
8444,Allgemeine Chirurgie,"Die chirurgische Diagnostik, bestehend aus Anamnese, klinischer Untersuchung und der meist nachfolgenden technischen Diagnostik, unterscheidet sich in ihren Grundprinzipien grundsätzlich nicht von denen anderer klinischer Fachgebiete. Bei akuten Erkrankungen muss sie schnell und zielführend erfolgen, um die Indikationsstellung zu einer Operation oder dem interventionellen oder konservativem Behandlungsverfahren nicht zu verzögern."
8445,Nephrologie,"Zentrale Themen in der Nephrologie und auch in diesem Kapitel sind akute und chronische Niereninsuffizienz. Ebenfalls behandelt werden Krankheiten aus der Gruppe der Glomerulonephritiden (wie z. B. IgA-Nephropathie oder rasch progrediente Glomerulonephritis), der tubulointerstitiellen Nierenerkrankungen (z. B. infolge von Hanta-Virus-Infektionen oder die Analgetika-Nephropathie) und der Nierentumoren/-zysten. Darüber hinaus ist ein Abschnitt den Harnwegsinfektionen sowie den Nierensteinen gewidmet."
8446,Multiple Sequence Alignment,"The multiple sequence alignment (MA) plays an important role in sequence analysis. However, it has been proven to be an NP-hard problem. This means the computation complexity of MSA increases exponentially with the number of sequences. The presented algorithms are mostly heuristic and many of them are based on pairwise sequence alignment. Hence we begin with pairwise alignment of multiple sequences and discuss the topological space induced by pairwise alignment of multiple sequences, since different optimization criteria may lead to different results. We discuss several optimization indices here: the sum of pairs (SP); Shannon entropy; similarity rate and the rate of virtual symbols. Based on this discussion, we present a new multiple sequence alignment based on SPA called super multiple sequence alignment (SMA). We give a detailed description of the algorithm and compare it to some popular MA algorithms and find that it works well enough, especially with respect to speed. An example of SARS multiple sequence alignment is given at the end of this chapter."
8447,Emerging Viral Infections,"Emerging viral pathogens are a major cause of severe infections that constitute serious complications in patients with hematological disorders. During the last decade, a large number of viruses were discovered using optimized molecular techniques and systematic screening approaches. Most of the newly detected viruses affect the respiratory tract, causing common colds and also, especially in high-risk patients, life-threatening events. On the other hand, a substantial proportion of patients are reinfected by old viruses that were previously described only rarely or not at all in cancer patients. This chapter focuses on both emerging viruses and reemerging viral infections that affect patients with hematological malignancies."
8448,"Update in Pediatric Emergency Medicine: Pediatric Resuscitation, Pediatric Sepsis, Interfacility Transport of the Pediatric Patient, Pain and sedation in the Emergency Department, Pediatric Trauma","This chapter summarizes the state-of-the-art approach to several critical aspects of pediatric emergency care. While the field of pediatric emergency medicine is much broader, we have chosen some key topics which are essential for every physician providing care to children. The resuscitation section highlights the challenges and the particularities of pediatric airway management as well as the correct technique for effective cardiopulmonary resuscitation, defibrillation and vascular access. The sepsis section stresses that the key to a successful outcome is early recognition; it outlines the clinical spectrum of sepsis, the systemic inflammatory response and the pathophysiology of septic shock, with emphasis on early clinical signs, airway management, volume resuscitation, vasoactive support and antibiotic therapy. In the last decade, attention to pediatric pain management has resulted in increasing awareness of assessment tools and pharmacologic as well as non-pharmacologic strategies for pain control and anxiolysis. The pain section updates these important aspects of pediatric care and includes management of procedural sedation. Although the general principles of trauma care in children are similar to those of adults, the trauma section highlights the key differences, with respect to anatomy and physiology, and how these impact on early recognition of hemorrhagic shock, susceptibility to specific injuries, indications for imaging (no pan-CTs!) and the more prevalent non-surgical management. Healthcare providers must also know how to safely transport a child who requires additional resources or an escalation in level of care. The regionalization of pediatric intensive care units and trauma services has made it imperative for pediatricians to understand the general principles of transport medicine outlined in this chapter. The overview of pediatric inter-facility transport discusses choice of transport team and modality, emphasizes patient stabilization prior to transport and outlines required medications and supplies."
8449,Prevention Strategies and Promoting Psychological Resilience to Bioterrorism Through Communication,
8450,A Compact Imaging Ellipsometer for Label-free Biosensor,"A compact model of imaging ellipsometer is used for the data acquisition and analysis of label free protein microarray. Its principle, methodology, and experimental setup as well as sampling conditions and a demonstration result are presented here. Furthermore, results of protein adsorption and protein interaction in the microarray may be deduced. This shows that the compact model is effectively performed as a reader for the protein microarray sampling and provides a potential for applications of label free protein microarrays on site of care."
8451,Pathogenesis,"Pathogenesis describes the spread of a virus in the organism and the mutual relationship between the pathogen and its host during infection. These processes can be analysed in several ways by using different histological, virological and immunological methods. Viral infections can be with or without symptoms (also called apparent or inapparent infection courses). In both cases, the host organism responds with immunological defence responses, which usually lead to overcoming the primary disease symptoms and to the elimination of the virus. The immune response may also contribute in the context of immunopathogenesis to specific disease symptoms and either temporary or permanent damage to the host."
8452,A Historical Perspective on Paper Microfluidic Based Point-of-Care Diagnostics,"Paper-based microfluidic systems have emerged as one of the most favorable technologies used in many potential applications such as point-of-care diagnostics, flexible electronics, energy storage, etc. From the past several decades, paper-based technology has readily accepted in the academic research lab and industries as well. The paper-based devices have changed the life of humankind. The distinguishing characteristics of paper substrate like low cost, biodegradability, biocompatibility, and ease of fabrication helped their adaptability in biosensing applications. This chapter gives a concise overview of the historical perspective of paper-based devices, classification of paper types, and their recent applications."
8453,Applications of Microbial Biopolymers in Display Technology,"Microorganisms produce a variety of different polymers such as polyamides, polysaccharides, and polyesters. The polyesters, the polyhydroxyalkanoates (PHAs), are the most extensively studied polymers in regard to their use in display technology. The material properties of bacterial PHAs in combination with their biocompatibility and biodegradability make them attractive substrates for use in display technology applications. By translationally fusing bioactive molecules to a gene encoding a PHA-binding domain, the appropriate functionalization for a given application can be achieved such that the need for chemical immobilization is circumvented. By separately extracting and processing the biopolymer, using it to coat a surface, and then treating this surface with the fusion proteins, surface functionalization for immunodiagnostic microarray or tissue engineering applications can be accomplished. Conversely, by expressing the fusion protein directly in the PHA-producing organisms, one-step production of functionalized beads can be achieved. Such beads have been demonstrated in diverse applications, including fluorescence-activated cell sorting, enzyme-linked immunosorbent assays, microarrays, diagnostic skin test for tuberculosis, vaccines, protein purification, and affinity bioseparation."
8454,Lungenfunktionsdiagnostik,"Lungenfunktionsdiagnostik beinhaltet eine Vielzahl von Messmethoden, mit denen jeweils bestimmte Qualitten der Lungen in verschiedenen Altersgruppen überwiegend nichtinvasiv untersucht werden können."
8455,A Tour of the Basic Reproductive Number and the Next Generation of Researchers,"The Mathematical and Theoretical Biology Institute (MTBI) is a national award winning Research Experience for Undergraduates (REU) that has been running every summer since 1996. Since 1997, students have developed and proposed their own research questions and derived their research projects from them as the keystone of the program. Because MTBI’s mentors have no control over what students are interested in, we need to introduce a suite of flexible techniques that can be applied to a broad variety of interests. In this paper, we walk through examples of some of the most popular techniques at MTBI: epidemiological or contagion modeling and reproductive number analysis. We include an overview of the next generation matrix method of finding the basic reproductive number, sensitivity analysis as a technique for investigating the effect of parameters on the reproductive number, and recommendations for interpreting the results. Lastly, we provide some advice to mentors who are looking to advise student-led research projects. All examples are taken from actual student projects that are generally available through the MTBI website."
8456,Volume 6 Indexes,This index lists all 3367 normalized pharmacological activity terms appeared in the encyclopedia in alphabetical order and a number code sequence of the related compounds follows the bold term immediately.
8457,Medical Technology Management in Hospital Certification in Mexico,"Mexican health policy is promoting the quality of health services by hospital certification meeting the NMX-CC standards family, which is the Mexican equivalent of the ISO 9000 standards family. These standards can help both product- and service-oriented organizations achieve standards of quality that are recognized and respected throughout the world in developing a quality management system (QMS)."
8458,Blut und Blutprodukte,
8459,"Bildgebende Verfahren: Röntgen, Ultraschall, CT, Nuklearmedizin","In der Intensivmedizin findet die radiologische Diagnostik überwiegend am Krankenbett statt (»bedside radiology«). Etwa 90 % der radiologischen Untersuchungen in der Intensiv- und Notfallmedizin stellen projektionsradiographische Röntgenaufnahmen des Thorax, des Abdomens und des Skelettsystems dar. In zunehmendem Maße werden neben den klassischen Aufnahmen auch die Schnittbildverfahren eingesetzt. Hier kommt der Ultraschalldiagnostik eine führende Rolle zu, gefolgt von der Computertomographie (CT)."
8460,Sports-Related Injuries and Deaths,"Physical activity in children and adolescents should be strongly encouraged. While there is a very low risk of death associated with participation in athletics within this age group, the epidemic of childhood obesity and sedentary lifestyle must be combated to ensure the long-term health and quality of life of today’s youth. Sports-related deaths due to trauma are usually readily identified; others require careful examination, adjunctive testing, and/or the expertise of consultants. A thorough investigation of circumstances surrounding the death, review of the medical records, and autopsy is mandated in these cases."
8461,Hyperlipidemias and Obesity,"The organs require oxygen and other types of nutrients (amino acids, sugars, and lipids) to function, the heart consuming large amounts of fatty acids for oxidation and adenosine triphosphate (ATP) generation."
8462,Survival of Microorganisms on Inanimate Surfaces,"In healthcare settings microbial contaminated surfaces play an important role in indirect transmission of infection. Especially surfaces close to the patients’ environment may be touched at high frequencies, allowing transmission from animated sources to others via contaminated inanimate surfaces. Therefore, the knowledge on the survival of bacteria, fungi, viruses and protozoa on surfaces, and hence, in a broader sense, in the human environment, is important for implementing tactics for prevention of Healthcare-acquired Infections (HAI). This chapter will elaborate the role of surfaces in the transmission of pathogens. Particular emphasis is laid on the current knowledge of the survival time and conditions favouring survival of the pathogens. Finally, mechanisms of transmission from inanimate surfaces to patients are highlighted. Within the multi-barrier strategy of the prevention of HAI, environmental disinfection policies should be based on risk assessments for surfaces with different risks for cross contamination such as high- and low-touched surfaces with appropriate standards for adequate disinfection measures under consideration of the persistence and infectious dose of the pathogens. As a result, surface disinfection is indicated in the following situations: Frequently touched surfaces adjacent to patients. Surfaces with assumed or visible contamination. Terminal disinfection in rooms or areas where infected or colonized patients with easily transferable nosocomial pathogens are cared for, and in outbreak situations. Furthermore, the knowledge of the persistence of pathogens will also support ensuring the biosafety in microbiological and biomedical laboratories, food-handling settings, and for hygienic behaviour in the everyday life to prevent transmission of infectious diseases."
8463,The Nucleolus: Structure and Function,"The nucleolus is the largest nuclear organelle and is the primary site of ribosome subunit biogenesis in eukaryotic cells. It is assembled around arrays of ribosomal DNA genes, forming specific chromosomal features known as nucleolar organizing regions (NORs) which are the sites of ribosomal DNA transcription. While the nucleolus main activity involve different steps of ribosome biogenesis, the presence of proteins with no obvious relationship with ribosome subunit production suggests additional functions for the nucleolus, such as regulation of mitosis, cell cycle progression, stress response and biogenesis of multiple ribonucleoprotein complexes. The many novel factors and separate classes of proteins identified within the nucleolus support this view that the nucleolus may perform additional functions beyond its known role in ribosome subunit biogenesis. Here we review our knowledge of the nucleolar functions and will provide a detailed picture of how the nucleolus is involved in many cellular pathways."
8464,SARS coronavirus infection: pathology and pathogenesis of an emerging virus disease,
8465,Cardiology,"myocardial—myocardial infarction, angina, myocarditis"
8466,Dried Plasma,"Dried plasma provides an alternative for early plasma transfusion in the resuscitation of hemorrhagic shock in environments where fresh frozen plasma is not immediately available. It is produced by freeze-drying or spray-drying liquid or thawed plasma. It is shelf-stable for prolonged periods, can be stored at room temperature, and is easy to transport, reconstitute, and administer. It was widely used in WWII but fell out of favor due to the risk of infectious disease transmission. The German and French experiences with lyophilized plasma are the most extensive and show a good track record of efficacy and safety. Recent studies show many beneficial effects of dried plasma in the treatment of shock in large animal models. Currently, no FDA-licensed product is available in the USA, but several are under development."
8467,Importance of Natural Proteins in Infectious Diseases,"Proteins are important biomolecules, extensively involved in almost all biological processes. A number of proteins are also implicated in infectious diseases. Bacterial proteins used in adhesion to host epithelium, bacterial toxins, and viral membrane glycoproteins are some of the proteins involved in infectious diseases. Even components of the host innate immune system like Toll-like receptors and Nod-like receptors and adaptive immune components like immunoglobulins aiding in defense against pathogens are important biological proteins. Chaperones like acid and heat shock proteins provide protection from high temperatures, metabolic poisons, and other stressful conditions. Several natural and artificial proteins are components of vaccines, a key strategy to control fatal diseases, lacking empirical treatment. It is necessary to investigate these proteins, to develop new biomedical tools and technologies, aiding in eradication of various diseases. Thus, further research should be carried out in this field, for saving and improving quality of human lives."
8468,Current Concepts of Severe Pneumococcal Community-acquired Pneumonia,"Community-acquired pneumonia (CAP) is a major health problem, even in developed countries, being the leading cause of death due to infectious diseases in the USA [1]. CAP has a wide clinical spectrum of severity: up to 80% of patients are successfully managed in primary care, but 1% of patients with CAP are classified as having severe disease, needing intensive care unit (ICU) admission, with 20–50% dying despite all available support and treatment options being utilized. Streptococcus pneumoniae is the most common cause of CAP, enclosing the subset group of patients having severe disease [2]. Moreover, bacteremia is not uncommon in pneumococcal CAP (20%) and has been associated with increased severity and mortality compared with non-bacteremic pneumonia [3]."
8469,Argument from Analogy,"Similarities between objects, people and places pervade our thinking and influence our interaction with the environment. Many of these similarities serve no logical purpose but have a descriptive or explanatory function in our cognitive affairs. However, for the substantial number of analogies which are used in argument, their logical and other attributes have long been a source of fascination for investigators in a range of disciplines. It is argued in this chapter that cognitive agents use the argument from analogy as a facilitative heuristic to guide their judgements about public health problems when evidence or knowledge is not available in a particular context. To this extent, the argument is one type of adaptation of our rational procedures to the problem of uncertainty in the cognitive domain. Several examples of the use of this argument in a public health context are examined. The dialectical and epistemic features of this argument are addressed within a discussion of the use of analogical argument in systematic and heuristic reasoning. The results of a study of public health reasoning reveal that members of the public are adept at identifying the conditions under which the use of analogical argument is more or less rationally warranted."
8470,Vaccinia and Pox-Virus,"Vaccinia virus has been studied extensively since its discovery as a smallpox vaccine in 1798. Its use as a smallpox vaccine documented its safety profile. It was later found that its large size and ability to accept large fragments of DNA combined with its natural tumor affinity make it an attractive agent for cancer therapy. This chapter discusses the history of the vaccinia, the various strains available, the biology of the virus as well as the steps in creating recombinants. The various clinical and safety considerations will be addressed. We will also discuss the various methods used to treat cancer using the vaccinia virus and will review the recent clinical trials using vaccinia in the treatment of cancer."
8471,Economic aspects of vaccines and vaccination: a global perspective,
8472,Infectious Diseases,"Commercial airline travel creates conditions conducive to the spread of infectious diseases: the proximity of passengers in a confined space and the origin of flights from anywhere on the globe. This chapter describes symptoms of infectious diseases that might emerge in an airline passenger and the steps that a responding medical professional can take to stabilize the person and minimize the exposure risk for other passengers and the crew. It also reviews guidelines issued by the Centers for Disease Control regarding infectious diseases that might be encountered during flights, procedures for working with pilots to alert ground crews about passengers’ medical needs, and requirements for reporting incidents to authorities after landing."
8473,The Basic Concept of Microbiology,"Aseptic technique is a method that involves target-specific practices and procedures under suitably controlled conditions to reduce the contamination from microbes. It is a compulsory laboratory skill to conduct research related in the field of microbiology. Mycologist/microbiologists must follow aseptic techniques for multiplicity procedures such as screening of isolates/strains, pure cultures, slant cultures, single spore cultures, microbes transferring cultures, inoculating media, and conducting several microbiological experiments. Proper aseptic technique has prevented the cultures contamination from inborn and outborn microbes in the environment. As example, airborne microbes (e.g., fungi) handpicked from the surveyor’s health, the lab benchtop, unsterilized glassware and equipment, dust, and other areas, thus interfering to get proper experiment results. Using the proper aseptic technique can significantly reduce/minimize the risk of contamination."
8474,Respiratory Viruses and Other Relevant Viral Infections in the Lung Transplant Recipient,"As advances occur in surgical technique, postoperative care, and immunosuppressive therapy, the rate of mortality in the early postoperative period following lung transplantation continues to decline. With the improvements in immediate and early posttransplant mortality, infections and their sequel as well as rejection and chronic allograft dysfunction are increasingly a major cause of posttransplant mortality. This chapter will focus on infections by respiratory viruses and other viral infections relevant to lung transplantation, including data regarding the link between viral infections and allograft dysfunction."
8475,Computer Network Vulnerabilities,
8476,Attainment – achieving compliance with ESARIS standards,"The ESARIS Attainment Model (or: ESARIS Compliance Attainment Model) relates to activities ensuring that the ESARIS security standards are actually implemented and comprise methods for verifying this (Sect. 7.1). In the first place, the ESARIS security standards have to be developed by starting with requirements engineering as the basis (Sect. 7.2). The “Attainment” is organized into five ESARIS Attainment Levels which relate to the achievement of milestones in delivering ICT services according to the methods, procedures, and standards of ESARIS. The first three levels are related to more technical activities (IT engineering, implementation), the set-up for delivery (operations) and include methods for measuring the compliance (Sect. 7.3). The other two levels relate to the integration into portfolio and service catalogs. The portfolio development and the consideration of security in service catalogs (Sect. 7.4) are important for user organizations or even the next party in the internal supply chain of the ICT Service Provider."
8477,Noncoding RNA Expression During Viral Infection: The Long and the Short of It,"New technologies have expanded our view of viral–host interactions with the growing identification of non-coding RNAs (ncRNAs) that act as key regulators of viral infection. In this chapter, we explore novel genomics-based approaches used to characterize ncRNAs involved in viral infection, focusing mainly on microRNAs and long noncoding RNAs. We present recent evidence implicating virally encoded and host-derived ncRNAs in viral replication and pathogenesis regulation, focusing on four different viral diseases (IAV, KHSV, HIV, and HBV). Finally, we discuss the current knowledge of ncRNAs modulation of innate and adaptive immune responses to viral infection. These findings highlight the complexity of host–pathogen networks determining the outcome of viral disease. Understanding the role of ncRNAs in these networks may offer novel antiviral therapy and diagnostic tools."
8478,Public Health Lessons: Practicing and Teaching Public Health,"The following four cases represent events that actually occurred at the local, statewide, national, and international levels. A general, succinct overview is provided of each case with references listed should the reader want to access additional resource materials. The concise format of these cases is intended to generate questions. Following the general overview of each case, I examine the lessons learned from the practitioner and educator perspective and I list the skills necessary to address the issues in the case. The reader will note that there are skills that are essential for the public health practitioner to master, whether one is in an internship, entry-level position, or the director of a public health organization and so these skills are consistently listed. I encourage the reader to regularly keep abreast of the news locally and abroad and to set aside time before a staff meeting or supervisory group meeting, or use the first few minutes of a class to discuss these issues. Ask your workforce or students, “Are we ready to handle such an event if it were to occur here?”; “What resources would we need to have accessible?”; “Have we partnered with the correct agencies in the community?”; “Do we have an established, trusted presence in the community?”; “Who else do we need on our team?”; “Do we need training in a specialty area, e.g., emergency preparedness?”; “What skills have we mastered and what skills do we need to obtain?” The discussion-based questions are endless but one runs the risk of not being prepared, either individually, or in their agency, should they not discuss how public health events are occurring around us daily. I encourage you to adapt these selected cases to use in your organization and/or classroom. Discussing these issues and reviewing the lessons learned will only help us to be better prepared public health practitioners and educators of public health students."
8479,Herbonanoceuticals: A Novel Beginning in Drug Discovery and Therapeutics,"The Indian pharmaceutical industry is the world’s second largest industry (by volume) that develops products and market drugs licensed for use as medications. Medicines manufactured in the modern era are associated with major controversies such as non–target specificity, resistance, repeated administration, immune rejection, and other adverse effects on the body. Thus, there is a great need to find drugs that do not raise the aforementioned issues. Nature is an excellent hub providing a diverse range of phytoconstituents that open the way to phototherapeutics, which need a scientific path to deliver the active elements in a supported way to increase patient compliance and reduce the need for repeated administration. To discover a novel phytochemical as a lead compound for a therapeutic purpose is a real challenge. In former times, drug discovery was a complex process, as it took several years to find a lead compound for use against a particular disease. Nowadays, however, virtual screening methods have been developed, which are target specific, time consuming, and cost effective. To avoid increased and repeated administration of a drug, nanosized drug delivery systems for herbal drugs have been developed to enhance the activity and overcome problems associated with synthetic medicines. This review summarizes three main fields: drug discovery, docking for drug design, and last—but not least—drug delivery systems. Nowadays, nanobased drug delivery systems are in demand for delivery of herbal medicines used for therapeutic purposes. Herbonanoceuticals—herbal drugs of a nanosize—have better remedial value and fewer detrimental effects than modern medicines. Therefore, herbonanoceuticals can be a boon in the field of therapeutics."
8480,MedCERTAIN/MedCIRCLE: Using Semantic Web Technologies for Quality Management of Health Information on the Web,
8481,Histopathology,"During the last 30 years, advances in intensive and critical care units, organ transplantation, concomitant use of immunosuppressive drugs, and increasing prevalence of chronic diseases, malnutrition, and other debilitating conditions, as well as the human immunodeficiency virus pandemic, have increased the incidence of systemic mycotic diseases, the most serious form of fungal diseases are the ones that comprise the central nervous system, representing the most dangerous clinical situations. In those cases, starting an adequate therapy through a rapid and assertive diagnosis is absolutely necessary. Considering the fastidious microbiological nature of some fungi (longtime requirement, specific culture conditions, and biohazard issues), as well as the lack of alternative testing availability, a rapid diagnosis is always challenging. When a tissue or liquid specimen is available, its pathological analysis constitutes a rapid and cost-effective way to provide a presumptive or definitive diagnosis of an invasive fungal infection; however, microbiologists, pathologists, and clinicians need to be aware of the limitations of microscopical diagnosis. In this chapter, we review the usual histological presentation of the most frequent central nervous system fungal infections."
8482,"A Farewell to the “Sick Man of East Asia”: The Irony, Deconstruction, and Reshaping of the Metaphor","Susan Sontag revealed how a disease could be turned into a metaphor in social evolution, from merely a disease of the body to moral judgment or even political oppression. In her article “AIDS and its Metaphors” written in 1989, she offers a plan to do away with the metaphor: “With this illness, one that elicits so much guilt and shame, the effort to detach it from these meanings, these metaphors, seems particularly liberating, even consoling. But the metaphors cannot be distanced just by abstaining from them. They have to be exposed, criticized, belabored, used up” (Songtag 2003). In Sontag’s terms, “metaphor” mainly refers to the symbolic social oppression of the diseases. For example, cancer is a metaphor for the defect of the sick person in personality. While diseases were a biological phenomenon, the “metaphor” was a social one. What I would like to demonstrate here was none other than the related “political metaphor” started by the “anti-germ warfare.”"
8483,"Ear, Nose, and Throat","This chapter reviews otolaryngology conditions most commonly seen by pediatricians. Included are issues involving the ears, nose, and nasopharynx; the sinuses, throat, mouth, and oropharynx; and the neck. The most common surgical otolaryngologic procedures will also be discussed. Many of these conditions can be effectively identified, diagnosed, and treated by primary care physicians. However, for certain conditions, prompt identification and timely referral to an otolaryngologist is required."
8484,Organoselenium in Nature,"Selenium, among the naturally occurring elements, is nowadays considered the most relevant for the redox homeostasis of living systems. In this chapter, its role in plants, bacteria, and humans is scholarly discussed. Some plants have the possibility to accumulate this element, thus becoming a natural source for animals and humans, in which selenium is embedded in selenoproteins, as the 21(st) amino acid, selenocysteine (l-Sec). The main classes of selenoenzymes (glutathione peroxidase, thioredoxin reductase, and iodothyronine deiodinases) are reported here and the molecular mechanism that characterizes their physiological action is discussed."
8485,"Allergie, Mikrobiom und weitere epigenetische Faktoren","Die chinesische Medizin hat schon vor 2000 Jahren einen Zusammenhang zwischen Lunge und Dickdarm erkannt. Nach den Prinzipien der 5 Wandlungsphasen impliziert jegliche Behandlung des Yin-Organs Lunge (bzw. des Respirationstraktes) eine Regulation und Mitbehandlung des gekoppelten Yang-Organs, des Dickdarms. Nicht nur diese beiden Organe sind dem Element Metall zugeordnet, sondern auch die Haut als zugehörige Körperschichte und die Nase als Öffner (◘ Abb. 4.1)."
8486,Allgemeine Chirurgie,Die sechs klassischen Leitsymptome des Patienten erfordern eine sequenzielle Diagnostik.
8487,Nanomicrobiology,
8488,Kardiologie,"—. meist bakterielle (selten mykotische) Entzündung der Herzinnenhaut unter Beteiligung der Herzklappen; —. oft Vorbestehen einer prädisponierenden strukturellen Herzerkrankung, z. B. Klappenvitium oder kongenitaler Herzfehler; —. Befall der Mitralklappe und Aortenklappe am häufigsten, bei i.v. Drogenabusus Befall der Herzklappen des rechten Herzens durch Staphylokokken; —. Streptokokken (60–80% aller Fälle, davon >50% S. viridans), Staphylokokken (20–35%), Enterokokken, gramnegative Bakterien und andere seltene Erreger, z. B. Pilze (10%); —. —. Destruktionen und Vegetationen an gesunden Herzklappen (Endocarditis ulcerosa et polyposa) durch hochvirulente Erreger; —. Erregerspektrum: β-hämolysierende Streptokokken, Staphylococcus aureus, Pneumokokken, Gonokokken, gramnegative Bakterien; —. —. meist an vorgeschädigten Herzklappen, z. B. nach rheumatischer Endokarditis; —. Erregerspektrum: Streptococcus viridans, Enterokokken, gramnegative Bakterien der Darmflora, Staphylokokken, Pilze;"
8489,Engineering Ceramic Fiber Nanostructures Through Polymer-Mediated Electrospinning,"Electrospinning is increasingly used as a simple and straightforward technique to fabricate one-dimensional fibers from both organic and inorganic materials. These one-dimensional fibers with controlled sizes possess some unique features such as large surface area to volume ratio, high porosity, and low density. Compared to other conventional materials, these features make them attractive for applications such as energy harvesting, energy storage, super-hydrophobic membranes, and sensors. This chapter provides an overview on the synthesis of inorganic fibers through polymer-mediated electrospinning. Some of the common techniques employed by many researchers, such as solgel combined with electrospinning, emulsion electrospinning, and electrospinning combined with solid–gas reaction, to fabricate metal oxide fibers are discussed. In addition, techniques to fabricate ceramic and metal oxide fibers having different morphologies and hierarchical structures are described. Recent applications of electrospun metal oxide fibers are finally highlighted with a focus on filtration, sensors, photocatalysis, and energy."
8490,Neurochirurgie,"Das Gebiet der Neurochirurgie umfasst die Erkennung, operative, perioperative und konservative Behandlung, Nachsorge und Rehabilitation von Erkrankungen, Verletzungen, Verletzungsfolgen und Fehlbildungen des zentralen Nervensystems, seiner Gefäße und seiner Hüllen, des peripheren und vegetativen Nervensystems (Bundesärztekammer 06/2010)."
8491,Health System in China,"The health of China’s population improved dramatically during the first 30 years of the People’s Republic, established in 1949. By the mid-1970s, China was already undergoing the epidemiologic transition, years ahead of other nations of similar economic status, and by 1980, life expectancy (67 years) exceeded that of most similarly low-income nations by 7 years. Almost 30 years later, China’s 2009 health reforms were a response to deep inequity in access to affordable, quality healthcare resulting from three decades of marketization, including de facto privatization of the health sector, along with decentralized accountability and, to a large degree, financing of public health services. The reforms are built on earlier, equity-enhancing initiatives, particularly the reintroduction of social health insurance since 2003, and are planned to continue until 2020, with gradual achievement of overarching objectives on universal and equitable access to health services. The second phase of reform commenced in early 2012. China’s health reforms remain encouragingly specific but not prescriptive on strategy; set in the decentralized governance structure, they avoid the issue of reliance on local government support for the national equity objective, leaving the detailed design of health service financing, human resource distribution and accountability, essential drug lists and application of clinical care pathways, etc. to local health authorities answerable to local government, not the Ministry of Health. Community engagement in government processes, including in provision of healthcare, remains limited. This chapter uses the documentation and literature on health reform in China to provide a comprehensive overview of the current situation of the health sector and its reform in the People’s Republic."
8492,The “City Operator” and the Tianyi Square Redevelopment Project,"After describing today’s Tianyi Square, this chapter looks at the dilapidated conditions of this area before the redevelopment. Then it depicts the nation-wide fever of building Central Business Districts in Chinese cities since the late 1990s as the background. Afterward it analyzes the mechanism of the “city operator” (chengshi yunyingshang) in the Tianyi Square redevelopment project, which describes the role played by an entrepreneurial state and its subordinate urban development corporation in downtown redevelopment in Ningbo, as well as the origin of this mechanism back in the city of Dalian in the 1990s. It also analyzes the methods of compensating relocated residents, financing with land mortgage loans, historic conservation, promotion, and governance structure in the Tianyi Square project."
8493,Mikrobiologie und Antiinfektiva,"Bei einem 38-jährigen Patienten wurde eine Analfistel operiert. Am 3. postoperativen Tag kommt es zur akuten Verschlechterung des Gesundheitszustands mit hämodynamischer Instabilität und Fieber. Daraufhin wird der Patient in eine Klinik der Maximalversorgung verlegt. Beim Eintreffen im Schockraum ist der Patient somnolent und kaltschweißig. Der Blutdruck beträgt 70/40 mmHg, die Herzfrequenz 120/min und die Körpertemperatur 39,6°C. Das Hautkolorit ist blass-grau. Im Verlegungsbericht wird bei stark ödematös geschwollenem Skrotum der Verdacht auf eine Fournier-Gangrän nach Analfistel-OP gestellt. Der diensthabende Intensivmediziner muss nun parallel die hämodynamische Situation stabilisieren, mikrobiologisches Material gewinnen, eine kalkulierte antimikrobielle Therapie beginnen und weitere Maßnahmen zur Diagnosesicherung einleiten."
8494,Makroamputationsverletzungen im Bereich der oberen Extremität,Alle Amputationsverletzungen im Bereich der oberen Extremität distal des Radiokarpalgelenks werden als Mikroamputationsverletzungen bezeichnet.
8495,Advances in Gastrointestinal Surgery,"Carcinoma of the stomach is a global disease with the highest incidence in Asia, South America and Eastern Europe. The disease is least common in USA and Western Europe [1]. The disease is common among smokers. Other risk factors are H. pylori infection, atrophic gastritis, Menetrier’s disease and previous gastrectomy. The disease can be genetic as in familial adenomatous polyposis, hereditary non-polyposis colorectal cancer, Peutz-Jegher’s syndrome, etc. [2]. Screening for gastric carcinoma is done in high incidence areas such as Japan, Korea and China."
8496,Gastroenteritis and Intractable Diarrhea in Newborns,"Gastroenteritis (GE) still represents a major cause of morbidity and mortality in children worldwide. Although the implementation of effective measures resulted in a significant decrease of global mortality, much remains to be done. The burden of GE in the neonatal age is generally reduced in relation to some protective factors (breastfeeding, minimal exposure to water and contaminated food, passive maternal immunity). In newborns, the contribution of the various causative agents could differ from that of the other pediatric age groups, nevertheless Rotavirus and pathogenic strains of E. coli remain the main etiologies. The acquisition of the pathogen generally occurs through the contaminated birth canal or by the use of contaminated tools, objects, or hands of the caregivers. The clinical presentation may vary widely from an acute, self-limiting disease to life-threatening complicated infections. The assessment of the dehydration and its rapid correction represent the cornerstones of the management of any GE. Antibiotic therapy should be reserved to cases with systemic symptoms, severe dehydration, or in the presence of bloody diarrhea. While the occurrence of diarrhea in the neonatal age is mainly caused by acute gastrointestinal infections, differential diagnosis with several other diseases including forms of severe congenital disorders should be considered."
8497,Management of Peritoneal Malignancies,"Peritoneal malignancies may result in a widespread disease process, peritoneal carcinomatosis (PC), which has significant morbidity and mortality for patients afflicted by this disease. Dissemination into the peritoneum and throughout the abdomen can be due to a primary peritoneal cancer or other primary malignancies that have metastasized, including (but not limited to) colorectal cancer, gastric cancer, pancreatic cancer, appendiceal cancer, ovarian cancer, and mesothelioma. Patients with gastrointestinal (GI) or gynecologic malignancies with peritoneal carcinomatosis may have dismal survival due to a high disease burden within the abdominal cavity. Some studies suggest the average survival for patients with peritoneal carcinomatosis of colorectal origin is 18–48 months, for high-grade appendiceal adenocarcinoma 12–36 months, and for low-grade appendiceal neoplasms >60 months. As the understanding of peritoneal malignancies and peritoneal carcinomatosis evolved, it may now be acceptable to treat this as locoregional disease."
8498,Lung Biopsy in Acute Respiratory Distress Syndrome,
8499,Disaster Resilient Future in Korea,"The Republic of Korea has not only monumentally progressed socially, economically, and politically since 1948, but has taken the arduous undertaking of reforming the way it reduces disaster risk, mitigates the impact, and prepares for and responds to disasters for a resilient future. The administrative and organizational reforms have not been without its setbacks or obstacles; however, they were not so insurmountable that they could not be overcome by one of Korea’s greatest assets: persisting endeavors to build back better and to enhance resilience. Starting with an independent national agency in 2004 to manage natural and human-caused disasters and preparedness, the government quickly realized, through focusing events, it was insufficient to handle the increasing complexity and intensifying of disasters striking the nation. Therefore, through political will and hindsight, it continuously coalesced pertinent disaster management responsibilities into newer and newer agencies until 2016, when it enacted a progressively more ubiquitous and self-propelling agency. However, although the agency is apt for current disasters, it will not be for future disaster, which needs the integration of resilience into Disaster Risk Management (DRM). Therefore, we suggest five tenets on how to make Korea’s resilient future as well as for other nations that are and will follow in Korea’s footsteps, especially for those nations in Asia and Africa. A future that is resilient against all types of disaster risks, especially being prepared well for “low probability and high impact” focusing events that are located in the long-tail of the Power-law Distribution."
8500,Non-viral Vector for Muscle-Mediated Gene Therapy,"Non-viral gene delivery to skeletal muscle was one of the first applications of gene therapy that went into the clinic, mainly because skeletal muscle is an easily accessible tissue for local gene transfer and non-viral vectors have a relatively safe and low immunogenic track record. However, plasmid DNA, naked or complexed to the various chemistries, turn out to be moderately efficient in humans when injected locally and very inefficient (and very toxic in some cases) when injected systemically. A number of clinical applications have been initiated however, based on transgenes that were adapted to good local impact and/or to a wide physiological outcome (i.e., strong humoral and cellular immune responses following the introduction of DNA vaccines). Neuromuscular diseases seem more challenging for non-viral vectors. Nevertheless, the local production of therapeutic proteins that may act distantly from the injected site and/or the hydrodynamic perfusion of safe plasmids remains a viable basis for the non-viral gene therapy of muscle disorders, cachexia, as well as peripheral neuropathies."
8501,Childhood’s End,"When things stop working in an organizational system—a firm, a nonprofit, or a political entity—people have two choices in addressing the failure: to leave or to protest. Both can be powerful. As the author of this thesis, economist Albert Hirschman, pointed out in his 1970 book Exit, Voice, and Loyalty, it is possible for even an entire country (e.g., the United States or Liberia) to be created by people who leave behind unhappy circumstances and start something new elsewhere. Likewise, examples of the success of protest (“voice” and related action) in achieving major changes are plentiful. Consider the French Revolution and the multitude of regime changes and coups d’état that dot human history—not to mention the many times that a regime has been replaced by popular demand of voters."
8502,Stumpfe Wunderwaffe(3),"Bevor wir den Test für Krankheitserreger erklären, möchten wir noch eine andere Geschichte erzählen."
8503,Sendungen: Nachrichten,Nachrichten sind knapp gefasste Informationen; sie enthalten nichts Überflüssiges. Nachrichten sind besonders glaubwürdig; sie unterscheiden sich grundsätzlich von meinungsbetonten journalistischen Beiträgen.
8504,Communicable and Non-Communicable Diseases and Health Communication in Mainland China and Hong Kong,"This chapter discusses how rapid development in China has caused a number of environmental hazards, food insecurity, and communicable health diseases. How the Chinese government has tackled pollution and major epidemics such as severe acute respiratory syndrome (SARS) and airborne diseases in major cities, and how Hong Kong has handled its major epidemics, are analyzed in depth. Also, non-communicable disease emerging from the change of lifestyle in China will be discussed. Health Communication Policies and Planning in China will be assessed with recommendations and lessons learned from China and Hong Kong. Political-economic policies will be considered together with health communication policies regarding communicable and non-communicable diseases."
8505,Fakten auf einen Blick,
8506,The respiratory system,
8507,Severe Epigastric Pain with Nausea and Vomiting,"A 41-year-old woman presents to the emergency department complaining of severe and continuous epigastric pain for the past 24 hours. The pain radiates straight through to her back. She has had progressive nausea with vomiting. The vomit is bile-stained and without blood. She has had similar but less severe episodes of abdominal pain in the past, usually after eating heavy meals, but they always resolved within a few hours. She is gravida two and para two, with last menses 2 weeks ago, and does not consume any alcohol. On exam, she is afebrile, heart rate is 115 beats/min, blood pressure of 128/86 mmHg, and respiratory rate is 18/min. Her abdomen is not distended. She has no surgical scars on her abdomen and no obvious masses visible. She has no bruising around her umbilicus or along her flank. Bowel sounds are hypoactive. She has marked tenderness to palpation in her epigastrium, without guarding or rebound. The remainder of her abdomen is soft and non-tender to palpation. No masses or organomegaly are appreciated. Laboratory examination reveals a white blood cell count of 17.2 × 10(3)cells/μL (normal 4.1–10.9 × 10(3) cells/uL), amylase of 1545 u/L (30–110 u/L), lipase of 1134 u/L (7–60 u/L), ALT of 245 u/L (7–56 u/L), AST of 263 u/L (5–35 u/L), serum glucose of 156 mg/dl (65–110 mg/dL), and LDH 180 u/L (0–250 u/L). An abdominal series demonstrates gas throughout the small and large bowel and a focal dilated loop of proximal small bowel without air fluid levels. There is no free air under the diaphragm."
8508,Network Structures of Multiple Sequences Induced by Mutation,"As fast multiple alignment (MA) algorithms become a reality, analyses and applications of their results become the central problem of genome research. In this chapter, we introduce the general methods of constructing the phylogenetic tree from multiple alignments, such as UPGMA, neighbor-joining, the maximum parsimony method, maximum-likelihood method and Bayesian methods. We then discuss the network structure theory of the multi-sequences induced by mutations. Using the distance matrix and the mutation information, we find the network structure of multi-sequences. Furthermore, we introduce the orthogonalization theorem for a mutation network. We may easily obtain the mutation relations for data structures among a multiple sequence from the network structure and the orthogonalization procedure of a mutation network. Finally, we give some examples of the network structure and explain the basic steps needed to analyze these multi-sequences."
8509,Definition and Overview of Emerging Threats,The risks posed by bioterrorism and the proliferation of biological weapons capabilities have increased concern about how the rapid advances in genetic engineering and biotechnology could enable the production of biological weapons with unique and unpredictable characteristics. The nature of the biotechnology problem—indeed the nature of the biological research enterprise—is vastly different from that of theoretical and applied nuclear physics in the late 1930s. Evolving biotechnology presents an inextricably linked combination of opportunity and danger and that distinction turns on projected consequences and attributed intentions at the level of fundamental research. Matthew Meselson gave a stark warning of the potential dangers posed by the destructive applications of biotechnology at the annual meeting of the National Academy of Sciences in May 2000.
8510,The Human Nature of Infectious Disease,"Infectious disease raises questions about humans’ abilities to eliminate harm through the control of nature. People work to understand microbial life in order to manage the ways microbes mutate, adapt, and evolve, even while recognizing organisms’ essential nature. Public health practices from the past and present exemplify this ongoing quest to “solve” disease. Eradicating pathogens persists as a public health objective, even as new microbes emerge in the human environment. “Superbugs” and antibiotic resistance exemplify the problem-solution-problem cycle of disease. Moving from solutions-based thinking enables new imaginings of the microbial world in which humans reside."
8511,Obstruktive Atemwegserkrankungen,"In den folgenden Abschnitten werden die verschiedenen Formen der obstruktiven Atemwegserkrankungen erläutert, die je nach Alter, prädisponierenden Risikofaktoren und auch je nach Art der Auslöser verschiedenartige Ausprägungen und Verlaufsformen (Phänotypen) annehmen können."
8512,"Perception, Amplification and Communication: A Case Study of Food Safety Risks","In recent years, China has seen a rapid increase in public health incidents, among which food safety incidents have drawn the most attention. Every major food safety incident is a challenge to the safety warning line and leads to various social consequences in addition to economic losses. Food is the first necessity of the people, and food safety is of paramount importance. Any incident concerning food safety will spark public concern, and if not properly handled, may cause social panic."
8513,Alveolar Diseases,"Adenocarcinoma has surpassed squamous cell carcinoma as the leading histologic type, accounting for 30 % of all cases of lung cancer. The new 2015 WHO classification provided the basis for a multidisciplinary approach emphasizing the close correlation among radiologic and histopathologic pattern of lung adenocarcinoma. The term “bronchioloalveolar carcinoma” has been eliminated, introducing the concepts of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and the use of descriptive predominant patterns in invasive adenocarcinomas (lepidic, acinar, papillary, solid, and micropapillary patterns). Invasive mucinous adenocarcinoma is the new definition for mucinous bronchioloalveolar carcinoma."
8514,"Behavioral Health Support for Patients, Families, and Healthcare Workers","During the 2014–2016 Ebola outbreak in West Africa, over 850 healthcare workers contracted Ebola, and over 500 died. These tragic numbers underscore the need for strict adherence to infection control precautions when caring for patients with Ebola and other diseases that are both highly infectious and potentially fatal. In addition to the use of personal protection equipment (PPE), such measures include source isolation of infected patients. In the process of confining infectious pathogens, however, it is essential that health systems do not overlook the psychological needs of patients nor that of the medical staff who care for them. This chapter is divided into two sections. The first explores the experiences of patients cared for in source isolation, highlighting the possible iatrogenic psychological consequences of treatment in a biocontainment unit. Strategies for mitigating the potentially harmful psychological effects of isolation are reviewed, including considerations for children. The second section considers the experiences of healthcare workers. The discussion outlines the psychological impact of treating patients with infectious diseases, risk factors for emotional distress, and strategies to promote psychological well-being and resilience."
8515,Hightech in der Infektiologie: Diagnose und Therapie,"Jeden Tag sterben weltweit etwa 13 Millionen Menschen an den Folgen viraler, bakterieller oder parasitärer Erkrankungen."
8516,Respiratory Infections,"The majority of respiratory tract infections (RTIs) are community acquired and are the single most common cause of physician office visits and among the most common causes of hospitalizations. The morbidity and mortality associated with RTIs are significant and the financial and social burden high due to lost time at work and school. The scope of clinical symptoms can significantly overlap among the respiratory pathogens, and the severity of disease can vary depending on patient age, underlying disease, and immune status, thereby leading to inaccurate presumptions about disease etiology. The rapid and accurate diagnosis of the causative agent of RTIs improves patient care, reduces morbidity and mortality, promotes effective hospital bed utilization and antibiotic stewardship, and reduces length of stay. This chapter focuses on the clinical utility, advantages, and disadvantages of viral and bacterial tests cleared by the Food and Drug Administration (FDA), and new promising technologies for the detection of bacterial agents of pneumonia currently in development or in US FDA clinical trials are briefly reviewed."
8517,Recombinant poxvirus vaccines in biomedical research,"In biomedical research recombinant poxviruses are investigated as important candidate medicines to derive advanced options for prevention and/or treatment of infectious diseases or cancer. Genetically engineered viruses can readily synthesize biologically active heterologous proteins, serve to determine relevant targets of cell-mediated and humoral immunity, and identify types of immune responses needed for protection against a multitude of different specific diseases. Substantial progress in vaccine development is based on the availability of exceptionally safe but efficient carrier viruses, on increasingly versatile vector technologies and on the feasibility of large scale manufacturing. Moreover, advances in deciphering the molecular pathways regulating poxvirus-host interactions will provide additional means to potently activate innate immune stimulation upon vaccination and to derive vectors with specifically targeted replicative capacity for experimental tumor therapy."
8518,An Unexpected Diagnosis of Pulmonary Tuberculosis,"Pulmonary tuberculosis is rare in critically ill cancer patients. We report the case of a man treated for Hodgkin’s lymphoma and admitted to the ICU for acute respiratory failure. All investigations were negative, and he died with a presumptive diagnosis of bleomycin-related pulmonary toxicity and Escherichia coli endocarditis. Several weeks after his death, cultures of sputum and BAL fluid samples were found positive for Mycobacterium tuberculosis. Postmortem pulmonary biopsies confirmed the diagnosis of pulmonary tuberculosis."
8519,Infections in the PICU,
8520,Computer Network Vulnerabilities,"System vulnerabilities are weaknesses in the software or hardware on a server or a client that can be exploited by a determined intruder to gain access to or shut down a network. Donald Pipkin defines system vulnerability as a condition, a weakness of or an absence of security procedure or technical, physical, or other controls that could be exploited by a threat [1]."
8521,Cytokines,"Cytokines, currently known to be more than 130 in number, are small MW (<30 kDa) key signaling proteins that modulate cellular activities in immunity, infection, inflammation, and malignancy. Key to understanding their function is recognition of their pleiotropism and often overlapping and functional redundancies. Classified here into 9 main families, most of the 23 approved cytokine preparations (19 different cytokines and 4 pegylated), all in recombinant human (rh) form, are grouped in the hematopoietic growth factor, interferon (IFN), platelet-derived growth factor (PDGF), and transforming growth factor β (TGFβ) families. In the hematopoietin family, approved cytokines are aldesleukin (rhIL-2), oprelvekin (rhIL-11), filgrastim and tbo-filgrastim (rhG-CSF), sargramostim (rhGM-CSF), metreleptin (rh-leptin), ancestim (rh-SCF), and the rh-erythropoietins, epoetin and darbepoetin alfa. Anakinra, a recombinant receptor antagonist for IL-1, is in the IL-1 family; recombinant interferons alfa-1, alfa-2, beta-1, and gamma-1 make up the interferon family; palifermin (rhKGF) and becaplermin (rhPDGF) are in the PDGF family; and rhBMP-2 and rhBMP-7 represent the TGFβ family. The main physicochemical features, FDA-approved indications, modes of action and side effects of these approved cytokines are presented. Underlying each adverse events profile is their pleiotropism, potency and capacity to release other cytokines producing cytokine “cocktails.” Side effects, some serious, occur despite cytokines being endogenous proteins, and this therefore demands caution in attempts to introduce individual members into the clinic. This caution is reflected in the relatively small number of cytokines currently approved by regulatory agencies and by the fact that 15 of the FDA-approved preparations carry warnings, with 10 being black box warnings."
8522,Role of Biomarkers in Health Care,Study of biomarkers of various diseases will help to improve the management in three ways: 1. By providing a better understanding of the disease pathomechanism 2. By improving the diagnosis and determining the prognosis 3. By providing a basis for development of therapeutics and monitoring the effect of therapeutics on the disease
8523,Transmission of colds,"Rhinorrhea, nasal congestion, and sore throat herald the beginning of the cold season for both children and adults. Although the common cold is a self-limited infection, there are no effective treatments presently available and complications, missed time from work and school, and overall discomfort are not insignificant. Understanding how infections are transmitted may lead to interventions to reduce rates of infection. In order to establish a route of transmission, certain conditions must be met. The virus must be produced and shed at the site of infection. The virus must be deposited in the environment and be able to survive there. The virus must then be able to reach the portal of entry. Finally, interruption of the proposed route of transmission must reduce the incidence of infection under natural conditions. Applying this framework, there is clear evidence in both experimental and home settings that colds can be transmitted via self-inoculation. A small amount of evidence is available relating to large and small particle aerosol transmission. Because rhinovirus is responsible for half of all colds, it has been used as the model to understand how virus is transmitted from one person to another in experimental settings. Rhinovirus has been shown to infect via self-inoculation following hand-to-hand contact with contaminated hands or hand-to-surface contact with contaminated objects in the environment. Similarly, there is convincing evidence that the self-inoculation method of cold virus transmission occurs in the home environment, where colds arre most often transmitted. Aerosol transmission has been studied in the experimental setting and may provide another, albeit less common method for transmission of rhinovirus infection. As more is understood about the transmission of cold viruses, effective methods to interrupt transmission may be devised."
8524,Overview and Historical Review,"This book investigates and scrutinizes the lessons learned in the Republic of Korea during a five-decade swath of disasters – from 1948 to 2015 – and results in the disaster response policy change model in the wake of major disasters for resilience building. This book is structured of power-law relation between disaster loss and frequency in Korea from 1948 to 2015, focusing events in the power-law distribution, Disaster-Triggered Policy Change Model, and suggestions for resilient future. To start with the historical review, how to understand disaster throughout the ages was investigated: from an Act of God to Mother Nature’s will to societies’ inherent risk. As we journey through disaster’s history, we start to see the categorization of disasters by cause, principle, and risk – drawing to an understanding of risk through hazard and vulnerability."
8525,Rhinitis and Sinusitis,"Rhinitis is defined as inflammation of the nose, which can extend into and affect the sinuses. The term rhinosinusitis is used to describe inflammation of both the nose and the sinuses. An example of rhinitis is allergic rhinitis, caused by sensitization and exposure to aeroallergens, which, along with other allergic diseases, such as asthma, affect up to one-third of women in the childbearing age. The most common type of rhinosinusitis is infectious, either acute or chronic, which commonly occurs secondarily to a viral respiratory tract infection. Both rhinitis and rhinosinusitis significantly affect the quality of life. The purpose of this chapter is to introduce and describe the differential diagnosis and treatment of these two common clinical entities during pregnancy."
8526,The Effects of Network Relationships on Global Supply Chain Vulnerability,"In this chapter, we analyze the effects of levels of social relationship on the global supply chain networks vulnerability. Relationship levels in our framework are assumed to influence transaction costs as well as risk for the decision-makers. We propose a network performance measure for the evaluation of the global supply chain networks efficiency and vulnerability. The measure captures risk, transaction cost, price, transaction flow, revenue, and demand information in the context of the decision-makers behavior the network. The network consists of manufacturers, retailers, and consumers. Manufacturers and retailers are multicriteria decisionmakers who decide about their production and transaction quantities as well as the level of social relationship they want to pursue in order to maximize net return and minimize risk. The model allows us to investigate the interplay of the heterogeneous decision-makers in the supply chain and to compute the resultant equilibrium pattern of product outputs, transactions, product prices, and levels of social relationship. The results show that high levels of relationship can lead to lower overall cost and therefore lower price and higher product transaction. Moreover, we use the performance measure to assess which nodes in the supply networks are themost vulnerable in the sense that their removal will impact the performance of the network in the most significant way."
8527,Allografts in Anterior Cruciate Ligament Reconstruction,"Usual allograft sources for anterior cruciate ligament (ACL) reconstruction are patellar ligament, Achilles tendon, tibialis anterior, and posterior. The advantages of the use of allograft include reduced donor-site morbidity, shorter operative time, smaller incisions, and no size restrictions. The disadvantages include increased cost, slower graft embodiment, and the risk of viral or bacterial infection, which may occur either by transmission from an infected donor or by contamination by the healthcare provider. Careful donor selection, aseptic graft procurement and processing, and tissue sterilization, by irradiation or proprietary chemical processing, are the three major steps of the graft preparation procedure. Successful allograft implantation depends on sterility, reduction of antigenicity, and preservation of the biomechanical properties of the graft. To date, reports on the clinical and functional outcomes of allograft compared to autograft ACL reconstruction are controversial. Overall, graft choice depends on surgeon and patient preference, since no graft can perfectly match the properties of the native ACL."
8528,Pulmonary Manifestations of Predominantly Antibody Deficiencies,"Predominantly antibody deficiencies (PADs) are the most frequent forms of primary immunodeficiency diseases (PIDs). Commonly accompanied with complications involving several body systems, immunoglobulin substitution therapy along with prophylactic antibiotics remained the cornerstone of treatment for PADs and related complications. Patients with respiratory complications should be prescribed an appropriate therapy as soon as possible and have to be adhering to more and longer medical therapies. Recent studies identified a gap for screening protocols to monitor respiratory manifestations in patients with PADs. In the present chapter, the pulmonary manifestations of different PADs for each have been discussed. The chapter is mainly focused on X-linked agammaglobulinemia, common variable immunodeficiency, activated PI3K-δ syndrome, LRBA deficiency, CD19 complex deficiencies, CD20 deficiency, other monogenic defects associated with hypogammaglobulinemia, immunoglobulin class switch recombination deficiencies affecting B-cells, transient hypogammaglobulinemia of infancy, and selective IgA deficiency."
8529,Host–Symbiont Relationships: Understanding the Change from Guest to Pest,"The several meanings for the term “symbiosis” create confusion, which can be avoided when the author provides details of the interrelationships between the symbiotic organism and the “host” so that a reader can clearly understand what definition is implied in each case. For example, we, as opposed to many other mentioned readers, consider a symbiont as an organism living in an association with another regardless of whether it causes a pathologic response or not, but from our title, the reader may incorrectly infer that we consider a parasite to be different from a symbiont. A symbiont is an organism that uses another organism as a habitat. This chapter discusses the primary associations and associated conflicts involving the terminology. It also provides both differentiation between and conflicting views regarding the interpretation of the terms “infect” and “infest,” “infection” and “disease,” and other terms. Many seemingly harmless symbionts of a wide array of taxonomic groups are triggered to become pathogenic or virulent, and we provide several examples of the provoking (stimulating) triggers, with the understanding that in most cases, the conditions for the triggered activities are much more complex and complicated than presented. Examples of triggers follow: environmental ones like temperature, toxic chemicals (dose), chemotherapeutics, dietary changes, and geographic habits; internal ones like host site, host resistance or susceptibility, and host modifications; and combinations of these and other conditions. We provide examples involving multiple triggers for organisms associated with termites, for an endemic virus being affected by multiple factors and having multiple effects on its commercial penaeid shrimp hosts, and for contrasting variables associated with two exotic viruses in wild and cultured commercial penaeid shrimps with an emphasis on hypothesizing how the pathogenicity developed in these two viruses. The chapter ends by trying to answer the question of why would a symbiont become pathogenic in some hosts and not in others from an evolutionary perspective. It uses two hypotheses to explain the increased virulence."
8530,How Behaviour and the Environment Influence Transmission in Mobile Groups,"The movement of individuals living in groups leads to the formation of physical interaction networks over which signals such as information or disease can be transmitted. Direct contacts represent the most obvious opportunities for a signal to be transmitted. However, because signals that persist after being deposited into the environment may later be acquired by other group members, indirect environmentally-mediated transmission is also possible. To date, studies of signal transmission within groups have focused on direct physical interactions and ignored the role of indirect pathways. Here, we use an agent-based model to study how the movement of individuals and characteristics of the signal being transmitted modulate transmission. By analysing the dynamic interaction networks generated from these simulations, we show that the addition of indirect pathways speeds up signal transmission, while the addition of physically-realistic collisions between individuals in densely packed environments hampers it. Furthermore, the inclusion of spatial biases that induce the formation of individual territories, reveals the existence of a trade-off such that optimal signal transmission at the group level is only achieved when territories are of intermediate sizes. Our findings provide insight into the selective pressures guiding the evolution of behavioural traits in natural groups, and offer a means by which multi-agent systems can be engineered to achieve desired transmission capabilities."
8531,Upper Respiratory Infections and Acute Bronchitis,"Upper respiratory infections include the following: uncomplicated upper respiratory infections also known as the “common cold,” acute otitis media, pharyngitis/tonsillitis, and acute sinusitis. These conditions, along with acute bronchitis, are very common illnesses that are commonly seen in outpatient settings and are widely treated with antibiotics. In fact, these conditions are the primary indications for outpatient antibiotic prescriptions. These conditions tend to have overlapping clinical characteristics yet evidence regarding the utility of antimicrobial treatments varies across conditions."
8532,Knowledge-Based Tweet Classification for Disease Sentiment Monitoring,"Disease monitoring and tracking is of tremendous value, not only for containing the spread of contagious diseases but also for avoiding unnecessary public concerns and even panic. In this chapter, we present a near real-time sentiment analysis service of public health-related tweets. Traditionally, it is impossible for humans to effectively measure the degree of public health concerns due to limited resources and significant time delays. To solve this problem, we have developed a computational intelligence approach for Epidemic Sentiment Monitoring System (ESMOS) to automatically analyze the disease sentiments and gauge the Measure of Concern (MOC) expressed by Twitter users. More specifically, we present a knowledge-based approach that employs a disease ontology to detect the outbreak of diseases and to analyze the linguistic expressions that convey subjective expressions and sentiment polarity of emotions, feelings, opinions, personal attitudes, etc. with a sentiment classifier. The two-step sentiment classification method utilizes the subjective vocabulary corpus (MPQA), sentiment strength corpus (AFINN), as well as emoticons and profanity words that are often used in social media postings. It first automatically classifies the tweets into personal and non-personal classes, eliminating many tweets such as non-personal “retweets” of news articles from further consideration. In the second stage, the personal tweets are classified into Negative and non-Negative sentiments. In addition, we present a model to quantify the public’s Measure of Concern (MOC) about a disease, based on sentiment classification results. The trends of the public MOC are visualized on a timeline. Correlation analyses between MOC timeline and disease-related sentiment category timelines show that the peaks of the MOC are weakly correlated with the peaks of the News timeline without any appreciable time delay or lead. Our sentiment analysis method and the MOC trend analyses can be generalized to other topical domains, such as mental health monitoring and crisis management. We present the ESMOS prototype for public health-related disease monitoring, for public concern trending and for mapping analyses."
8533,Infectious Diseases in Cancer Patients: An Overview,"The predisposition of cancer patients to infectious diseases which contribute to the gravity of their prognosis is well documented. The current success in therapy of both malignancies and infections is unprecedented. However, the overall co-morbidity of these conditions is still a major problem in management of these patients. Paradoxically, to some degree the problem of containing infectious complications is directly associated with the vigor of the anti-cancer therapeutic regimens. The objective of this chapter is to provide an up to date overview of our understanding of the infectious complications in cancer patients based on the type of infection and immune responses."
8534,"Microbiology, Antimicrobial Susceptibility, and Antibiotic Treatment","Acute otitis media (AOM) is among the largest drivers of antibiotic use in children. As such, it is critical to understand the microbiology of this condition in detail to best delineate which antibiotics are most appropriate to use for patients with AOM and under what circumstances. Importantly, bacteria and/or viruses can be detected in the middle ear fluid in up to 96 % of AOM cases. The bacteriology of the condition has dramatically changed since the advent of universal pneumococcal vaccination. This chapter examines in detail the changing microbiology of otitis media (OM), along with guidelines for most appropriate antibiotic usage."
8535,Teschovirus,"Teschoviruses are emerging pathogens, belonging to the family Picornaviridae, and infects porcine population only. Among all, porcine teschoviruses (PTVs) are of high prominence leading to clinical illness and consequent economic loss to the livestock sector. These are associated with extremely lethal non-suppurative polioencephalomyelitis (Teschen disease) and are distributed world over. Its milder form, Talfan disease, inflicts low morbidity and mortality and general clinical disease. The first epizootics of Teschen disease occurred in 1929 in the Czech Republic. Mature virions are small (23–30 nm) and stable in environmental conditions (pH range 2–9, heat, lipid solvents). Genetic variations in the major surface protein, VP1, lead to the evolution of several new types. As of now, 13 genotypes in PTV are approved, namely PTV-1–13. Among all, PTV-1 is highly virulent and causes severe mortality and morbidity in the porcine population, domestic as well as wild. Ingestion is the main spreading route of infection, though intra-nasal infection and virus secretion in the urine are also noted. Along with encephalitis, PTVs are also responsible for reproductive disorders, diarrhoea, pneumonia, pericarditis and myocarditis. PTVs are also found as co-infection with several bacterial, viral and parasitic pathogens. Several conventional and modern diagnostics tools are available for their detection. Alternative of serological typing, VP1 and VP2 gene-based molecular typing is now preferred to know the epidemiological pattern. Although initially vaccines were used for its eradication in Europe, due to the sporadic reports of mild PTV infection in several countries, the approach was discontinued. Moreover, due to the presence of multiple serotypes, developing a multivalent PTV vaccine to protect against all strains is a major challenge."
8536,Flavonoids and Their Biological Secrets,"Flavonoids are tricyclic polyphenolic compounds naturally occurring in plants. Being nature’s antioxidants flavonoids have been shown to reduce the damages induced by oxidative stress in cells. Besides being an antioxidant, flavonols are demonstrated to have anti-infective properties, i.e., antiviral, antifungal, anti-angiogenic, anti-tumorigenic, and immunomodulatory bioproperties. Plants use them as one of their defense mechanisms against radiation-induced DNA damage and also for fungal infections. The use of flavonols for fabrication of new drugs has been underway with objectives to develop safer and effective therapeutic agents. This review covers 15 flavonols for their structure, biological properties, role in plant metabolisms, and current research focused on computational drug design using flavonols for searching drug leads."
8537,Selecting Accurate Classifier Models for a MERS-CoV Dataset,"The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a viral respiratory disease that is spreading worldwide necessitating to have an accurate diagnosis system that accurately predicts infections. As data mining classifiers can greatly assist in enhancing the prediction accuracy of diseases in general. In this paper, classifier model performance for two classification types: (1) binary and (2) multi-class were tested on a MERS-CoV dataset that consists of all reported cases in Saudi Arabia between 2013 and 2017. A cross-validation model was applied to measure the accuracy of the Support Vector Machine (SVM), Decision Tree, and k-Nearest Neighbor (k-NN) classifiers. Experimental results demonstrate that SVM and Decision Tree classifiers achieved the highest accuracy of 86.44% for binary classification based on healthcare personnel class. On the other hand, for multiclass classification based on city class, the decision tree classifier had the highest accuracy among the remaining classifiers; although it did not reach a satisfactory accuracy level (42.80%). This work is intended to be a part of a MERS-CoV prediction system to enhance the diagnosis of MERS-CoV disease."
8538,RNA helicase 3.6.4.13,"EC number 3.6.4.13 Systematic name ATP phosphohydrolase (RNA helix unwinding) Recommended name RNA helicase Synonyms 1a NTPase/helicase <16> [5] ATP/dATP-dependent RNA helicase <1,42> [32] ATPase <10,12> [1,36] ATPase/RNA helicase <1,42> [32] ATPase/helicase <10> [36,41] BMV 1a protein <16> [5] BmL3-helicase <1,42> [32] Brr2p <6> [50] DBP2 <24> [30] DDX17 <33> [12] DDX19 <43> [56] DDX25 <23,34,35> [12,21] DDX3 <25> [8] DDX3X <25> (<25> the gene is localized to the X chromosome [12]) [12] DDX3Y <29> (<29> the gene is localized to the Y chromosome [12]) [12] DDX4 <30> [12] DDX5 <32> [12] DEAD box RNA helicase <1,2,3> [32,45,52] DEAD box helicase <2> [45] DEAD-box RNA helicase <4,5,7,38,47,48> [9,14,16,25,53,55] DEAD-box protein DED1 <38> [11] DEAD-box rRNA helicase <5> [26] DEAH-box RNA helicase <24> [30] DEAH-box protein 2 <24> [30] DED1 <38> [11,14] DENV NS3H <10> [41] DEXD/H-box RNA helicase <43> [56] DEx(H/D)RNA helicase <12> [23] DHX9 <44> [58] DbpA <5> [10,25,26] Dhx9/RNA helicase A <13> [61] EhDEAD1 <7> [16] EhDEAD1 RNA helicase <7> [16] FRH <9> [54] FRQ-interacting RNA helicase <9> [54] GRTH <3> [57] GRTH/DDX25 <3,35> [21,51] HCV NS3 helicase <12> [48] KOKV helicase <27> [7] Mtr4p <31> [22] NPH-II <8> [18,28] NS3 <10,12,17,20,39,41> (<12,39> ambiguous [27,42,44]) [1,2,4,27,35,36,39, 42,44,46] NS3 ATPase/helicase <10> [41] NS3 NTPase/helicase <17> (<17> ambiguous [46]) [46] NS3 helicase <10,12,17> [15,44,46] NS3 protein <10,12,17,18> (<12> ambiguous [39]) [15,39,40,41,62] NTPase/helicase <12> (<12> ambiguous [37]) [37,39] RHA <6> [31,49] RNA helicase <2> [45] RNA helicase A <6,44> [31,49,58] RNA helicase CrhR <14> [59] RNA helicase DDX3 <25> [8] RNA helicase Ddx39 <47> [53] RNA helicase Hera <4> [9] RNA-dependent ATPase <37> [34] RNA-dependent NTPase/helicase <12> [1] RTPase <10> [36] RhlB <5> [43] SpolvlgA <48> [55] Supv3L1 <46> [64] TGBp1 NTPase/helicase domain <22,28> [24] Tk-DeaD <15> [47] VRH1 <26> [33] YxiN <2> [45] eIF4A <36> [20] eIF4A helicase <36> [20] eIF4AIII <37> [34] eukaryotic initiation factor eIF 4A <36> [20] gonadotropin-regulated testicular RNA helicase <3> [51,57] helicase <10> [41] helicase B <5> [43] helicase/nucleoside triphosphatase <10> [4] non structural protein 3 <12> (<12> ambiguous [37,38]) [37,38] non-structural 3 <10> [36] non-structural protein 3 <17> [46] non-structural protein 3 protein <18> [40] nonstructural protein 3 <12,17,20,39,40,41> (<12,17,39,40> ambiguous [6,27, 39,42,44,46]) [1,2,6,27,35,39,42,44,46] nucleoside 5’-triphosphatase <10> [4] nucleoside triphosphatase/RNA helicase and 5’-RNA triphosphatase <20> [2] nucleoside triphosphatase/helicase <16> [5] p54 RNA helicase <45> [60] p68 RNA helicase <3,6> [52,63] protein NS3 <12> (<12> ambiguous [38]) [38]"
8539,Prioritization of Risks in Supply Chains,"Modern supply chains are very complex, with physical, financial, and information flows occurring simultaneously in order to ensure that products are delivered in the right quantities, to the right place in a cost-effective manner. Maintaining uninterrupted supply chain flows is a prerequisite for the success of a supply chain in the marketplace. But there are always associated risks in each of these flows which require suitable strategies to mitigate them. The issue of risks in supply chains has assumed importance in wake of the understanding that supply chain failures are fatal to the existence of all the partners’ in a supply chain. The severity of supply chain failures are more felt by small and medium enterprises (SMEs) who form the majority at tier II and tier III levels of a supply chain. This is because of the limited resources and lack of adequate planning to counter supply chain risks. Management of risk in supply chains is a multi-criteria decision making problem. The research presented in this chapter proposes a Fuzzy-AHP based framework to prioritize various risks in supply chains. An exhaustive literature review complimented with the experts’ opinion was undertaken from the perspective of SMEs to formulate a hierarchical structure of risks in supply chains. A fuzzy analytic hierarchical process (F-AHP) is then utilized to ascertain the relative weightings which are subsequently used to prioritize these risks. Understanding the priorities would help the firms to accord importance and develop suitable strategies to manage supply chain risks according to their relative importance. This provides effective management of scarce resources available to SMEs to manage risks resident in their supply chains."
8540,The Political Economy of US Antibiotic Use in Animal Feed,"This chapter examines the evidence for antibiotic resistance in the United States and globally, the public health implications, and the impact of—and related industry and political responses to—antibiotic use in animal feed. In 1969, the Swann Report in the United Kingdom noted a dramatic increase in antibiotic-resistant bacteria in food animals receiving low levels of antibiotics in their feed. While the Food and Drug Administration of the United States sought to control antibiotics in animal feed as far back as 1977, only in 2016 were such regulations fully implemented. The farm-level costs of such controls are estimated by the US Department of Agriculture’s Economic Research Service to be minimal, while the Centers for Disease Control and Prevention’s estimates of the public health costs of antibiotic resistance without implementing controls are $7 billion annually. The complex interactions which exist between economic interests, regulatory policy, and human and animal health are explored in this chapter."
8541,China’s Belt and Road: An Evolving Network,"This chapter consolidates the accretive imagery presented by the proponents and managers of Beijing’s dynamic BRI vision, to enable an appreciation of the enterprise’s variegated, eclectic, even diffuse, nature. For an understanding of the physical manifestations of BRI’s ‘final’ impression as espoused by Xi Jinping, the CPC Politburo Standing Committee (PBSC), the State Council and the National Development and Reform Commission (NDRC), the chapter focuses on the Silk Road Economic Belt (SREB) undertaking, reviewing the narrative’s variations and modifications refined by successive Chinese leaders since 1994. It finally examines longitudinal SREB/MSR connectors in an empirical preview of BRI’s purposes and prospects."
8542,Acute Cough,"A 62-year-old man, Mr. M., comes to your office with a chief complaint of a cough. He states that it started about 1 week ago with a “runny nose and scratchy throat.” The cough is dry, nonproductive, and is interfering with the patient (and his wife) being able to get a full, restful night’s sleep. Mr. M. denies any other symptoms, such as headache, sinus pressure, chest pain, and shortness of breath, but thinks that he may have had a fever “off and on the last few days.” He has taken Tylenol® and has been drinking fluids, but his cough won’t go away. The patient is requesting an antibiotic to “get this thing kicked out of my system.” Mr. M. states that he is “tired of people at work looking at me like I have the plague.”"
8543,Portale Hypertension,"Während die Pathologie, die zur portalen Hypertension führt, im prähepatischen, hepatischen und posthepatischen venösen Gefäßbett liegen kann, machen die intrahepatischen Erkrankungen mit Abstand den Großteil aus. In unseren Breitengraden ist es die durch Alkoholabusus bedingte ethyltoxische Leberzirrhose, weltweit die durch Infektionen (HCV, HBV) bedingten Zirrhosen. Die chronische Hepatitis C mit ihren Komplikationen (Leberzellversagen, portale Hypertension und hepatozelluläres Karzinom) wird in den kommenden Jahren trotz moderner Therapieverfahren noch an Bedeutung gewinnen."
8544,"Scrub Typhus and Its Causative Agent, Orientia tsutsugamushi","The obligate intracellular bacterium Orientia tsutsugamushi is responsible for more than one million cases of scrub typhus annually throughout the Asia-Pacific region. Human infection occurs via the bite of the larval form (chigger) of several species of trombiculid mites. While in some patients the result of infection is a mild, febrile illness, others experience severe complications, which may even be fatal. This review discusses the genome and biology of the causative agent, the changing epidemiology of scrub typhus, the challenges of its diagnosis, and current treatment recommendations."
8545,Medical Ethics Education in China,"Medical ethics education has a long history in China. At the same time, it is also a new field of study, along with the introduction of western medicine to China in the past two centuries. Due to the different cultural traditions, different Chinese medical ethics scholars hold various viewpoints on medical ethics and bioethics research and practice. This paper is organized as follows: In the first section, a brief historical review of the overall development of Chinese medical ethics is presented. The next section presents three different schools of scholars in Chinese medical ethics and research. Then, section three discusses the current popular research topics, which represent state of the art Chinese medical ethics research. The last section analyzes and evaluates the viewpoints from different schools and concluding remarks are offered."
8546,Arf Proteins and Their Regulators: At the Interface Between Membrane Lipids and the Protein Trafficking Machinery,"The Arf small GTP-binding (G) proteins regulate membrane traffic and organelle structure in eukaryotic cells through a regulated cycle of GTP binding and hydrolysis. The first function identified for Arf proteins was recruitment of cytosolic coat complexes to membranes to mediate vesicle formation. However, subsequent studies have uncovered additional functions, including roles in plasma membrane signalling pathways, cytoskeleton regulation, lipid droplet function, and non-vesicular lipid transport. In contrast to other families of G proteins, there are only a few Arf proteins in each organism, yet they function specifically at many different cellular locations. Part of this specificity is achieved by formation of complexes with their guanine nucleotide-exchange factors (GEFs) and GTPase activating proteins (GAPs) that catalyse GTP binding and hydrolysis, respectively. Because these regulators outnumber their Arf substrates by at least 3-to-1, an important aspect of understanding Arf function is elucidating the mechanisms by which a single Arf protein is incorporated into different GEF, GAP, and effector complexes. New insights into these mechanisms have come from recent studies showing GEF–effector interactions, Arf activation cascades, and positive feedback loops. A unifying theme in the function of Arf proteins, carried out in conjunction with their regulators and effectors, is sensing and modulating the properties of the lipids that make up cellular membranes."
8547,Hygiene und Arbeitsschutz,"Im Rettungsdienst werden unter dem Begriff »Hygiene« alle vorsorglichen Vorkehrungen und Maβnahmen zusammengefasst, die alle im Krankentransport und Rettungsdienst Tätigen, sowie die zu betreuenden Patienten, vor schädlichen und krankmachenden Einflüssen durch Mikroorganismen schützen sollen."
8548,Pleural Disorders,"This chapter provides an overview of both benign and malignant pleural disorders, starting with the relevant anatomy and physiology. The focus is on the management of pneumothoraces and pleural effusions—conditions that are commonly encountered on a general thoracic surgery service. The pleural cavity is lined by parietal and visceral pleura, which are smooth membranes that are continuous with one another at the hilum and pulmonary ligaments. Parietal Pleura: innermost chest wall layer, divided into cervical, costal, mediastinal and diaphragmatic pleura."
8549,The Use of a Bookclub to Enhance Science Literacy and Understanding of Infectious Disease Epidemiology,"This chapter describes the activities of the Bad Bugs Bookclub, which brings scientists and non-scientists together to read novels where infectious disease formed part of the plot, and considers how these novels could be used to promote a better understanding of disease, epidemiology and the work of the professional scientist. A particular focus of the bookclub was to suggest how teachers in Higher Education might use these novels in their practice, although this specialised format can be used to benefit a wide range of professional (and non-professional) audiences. The Bad Bugs Bookclub has also been targeted towards students reading for a degree in Biomedical Science, accredited by the Institute of Biomedical Sciences: graduates are professionally qualified to be employed as biomedical scientists."
8550,Mikrobiologische Untersuchungstechniken,Ausgehend von den einzelnen Erregern werden im Folgenden Nachweismethoden vorgestellt und bewertet.
8551,China Takes Charge of a Changing Epidemic,"When the AIDS warriors in China’s academies and health institutions started experimenting with responses to the epidemic, their efforts were largely funded with foreign money. UN agencies; the international development wing of the governments of Australia, the United Kingdom, the United States and other nations; multilateral organisations such as the Global Fund to Fight AIDS, Tuberculosis and Malaria; and private charities such as the Ford Foundation and the Bill and Melinda Gates Foundation – all of these provided support for HIV prevention and/or treatment activities in China. The Chinese government’s contribution to the response rose dramatically following the “tipping point” described in Chap. 10.1007/978-981-10-3746-7_4. But even then, most of the original funding for provision of treatment to people in areas with epidemics driven by plasma sales was provided by the Global Fund."
8552,Host Cell Proteases: Cathepsins,"Cathepsins are proteolytic enzymes with a broad spectrum of substrates. They are known to reside within endo-lysosomes where they acquire optimal conditions for proteolytic activity and substrate cleavage. However, cathepsins have been detected in locations other than the canonical compartments of the endocytotic pathway. They are often secreted from cells in either proteolytically inactive proform or as mature and active enzyme; this may happen in both physiological and pathological conditions. Moreover, cytosolic and nuclear forms of cathepsins have been described and are currently an emerging field of research aiming at understanding their functions in such unexpected cellular locations. This chapter summarizes the canonical pathways of biosynthesis and transport of cathepsins in healthy cells. We further describe how cathepsins can reach unexpected locations such as the extracellular space or the cytosol and the nuclear matrix. No matter where viruses and cathepsins encounter, several outcomes can be perceived. Thus, scenarios are discussed on how cathepsins may support virus entry into host cells, involve in viral fusion factor and polyprotein processing in different host cell compartments, or help in packaging of viral particles during maturation. It is of note to mention that this review is not meant to comprehensively cover the present literature on viruses encountering cathepsins but rather illustrates, on some representative examples, the possible roles of cathepsins in replication of viruses and in the course of disease."
8553,The role of animal models in influenza vaccine research,"A major challenge for research on influenza vaccines is the selection of an appropriate animal model that accurately reflects the disease and the protective immune response to influenza infection in humans. Vaccines for seasonal influenza have been available for decades and there is a wealth of data available on the immune response to these vaccines in humans, with well-established correlates of protection for inactivated influenza virus vaccines. Many of the seminal studies on vaccines for epidemic influenza were conducted in human subjects. Studies in humans are performed less frequently now than they were in the past. Therefore, as the quest for improved influenza vaccines continues, it is important to consider the use of animal models for the evaluation of influenza vaccines, and a major challenge for research on influenza vaccines is the selection of an appropriate animal model that accurately reflects the disease and the protective immune response to influenza infection in humans. The emergence of highly pathogenic H5N1 avian influenza (AI) viruses and the threat of a pandemic caused by AI viruses of this or another subtype has resulted in a resurgence of interest in influenza vaccine research. The development of vaccines for pandemic influenza presents a unique set of obstacles, not the least of which is that the demonstration of efficacy in humans is not possible. Since the correlates of protection from pandemic influenza are not known, we rely on extrapolation of lessons from seasonal influenza vaccines and on data from the evaluation of pandemic influenza vaccines in animal models to guide our decisions on vaccines for use in humans. The features and contributions of commonly used animal models for influenza vaccine research are discussed."
8554,Thoracoabdominal Injuries,"Trauma to the thorax and abdomen can occur during participation in sports. This chapter reviews some of the more common presentations of such injuries and how such injuries should be best managed. Thoracic injuries reviewed include internal injuries such as pneumothorax, pulmonary contusion, hemothorax, commotio cordis, and cardiac contusion. Chest wall injuries are also reviewed such as rib fractures, costochondritis, and slipping rib syndrome plus sternal and scapular fractures. Abdominal injuries reviewed are focused on internal organ trauma to the spleen and liver, kidney, pancreas, and bowel. There is attention to the effect of Epstein-Barr virus and infectious mononucleosis, seen very frequently in high school and collegiate athletes. Finally, groin pain and athletic pubalgia are described. In addition to anatomy and clinical presentation, imaging modalities that characterize such trauma are reviewed for each diagnosis. Prevention of thoracoabdominal injuries and return-to-play decisions are described at the chapter conclusion."
8555,Cost-Benefit Analysis for China’s Influenza A (H1N1) Prevention and Control,"The impact of a public health emergency on a society and economy depends upon two factors: one is the harmful nature of the event along with its duration, and the other is the effect of the social response and measures. Both of these factors are wrought with uncertainty. Firstly, the nature of the event itself is uncertain, for example there may be a lack of understanding regarding the virulence of the epidemic. Secondly, different intervention measures bring about varying uncertainties, such as the potentially infected cases reduced using the health campaigning measures to change people’s actions in an epidemic."
8556,Acute Respiratory Failure in Patients with Hematologic and Solid Malignancies: Global Approach,Acute respiratory failure (ARF) is the principal cause for ICU admission and mortality in cancer patients. Early diagnosis and management of these patients entail unique challenges to the intensivist. This chapter reviews the common causes of ARF in cancer patients along with a global diagnostic and management approach. Oncologists and intensivists as a team must establish clear treatment goals for every cancer patient requiring mechanical ventilation.
8557,Internationale Gesundheitsrisiken,"Machtverhältnisse drücken sich in der Zuschreibung von Risiken aus. Spezifisches Wissen um Risiken dient dabei als Katalysator, Machtressourcen aufzubringen und steuernd in gesellschaftliche Prozesse einzugreifen. Dabei zeigt sich, dass die Steuerung trotz operativer Kooperation in internationalen Institutionen wie Europol oder geheimdienstlicher Zusammenarbeit noch weitgehend national organisiert ist, was die rechtlichen Rahmenbedingungen ebenso wie die diskursive Einbettung terroristischer Risiken betrifft. Weniger kontrovers sind ‚weiche‘ Themen wie Gesundheitsvorsorge und Management von Pandemien. Hier setzen internationale Institutionen Standards durch, die als Risikomanagement deutliche Eingriffe in staatliche Steuerungsautonomie bedeuten."
8558,Epidemiologische Grundlagen nosokomialer Infektionen,"Viele Faktoren tragen zu erhöhten nosokomialen Infektionsraten bei. Der Anteil alter Patienten mit chronischen Krankheiten und Immunsupprimierter steigt. Fortschritte in Diagnostik und Therapie resultieren immer häufiger in invasiven Eingriffen. Antibiotikaresistenzen und Folgen nosokomialer Infektionen erfordern daher eine verlässliche Epidemiologie. Konsequenzen nosokomialer Infektionen betreffen einerseits Patienten (Morbidität und Letalität), aber auch das Gesundheitswesen, dem zusätzliche, teilweise vermeidbare finanzielle Belastungen entstehen."
8559,Other Pediatric Accidental Deaths,"Injury, both intentional and accidental, is the most common cause of death in children throughout the world. Many injury patterns that are seen in children are similar to those in adult populations; however, others differ, reflecting the age, stature, and development of children. This chapter focuses on differences in injury patterns of children across the spectrum of childhood development and growth, including injuries and fatalities that primarily occur in infancy and early childhood. Risk factors for injury and death are identified within the context of childhood development. Topics covered include deaths associated with motorized and nonmotorized vehicles including pedestrian, occupant, and operator fatalities; farming and ranching deaths; drowning, boating, and diving deaths; fires and burns, including electrical deaths; animal-related deaths; falls; and airway-associated deaths. There are significant disparities in childhood injury and death among racial, ethnic, geographic, and socioeconomic groups. A brief consideration of these differences is provided to assist in forensic case examination."
8560,Pneumologie,
8561,Regulated Cell Death,"In this chapter, the various subroutines of regulated cell death are neatly described by highlighting apoptosis and subforms of regulated necrosis such as necroptosis, ferroptosis, pyroptosis, and NETosis. Typically, all forms of regulated necrosis are defined by finite rupture of the plasma cell membrane. Apoptosis is characterized by an enzymatic machinery that consists of caspases which cause the morphologic features of this type of cell death. Mechanistically, apoptosis can be instigated by two major cellular signalling pathways: an intrinsic pathway that is initiated inside cells by mitochondrial release of pro-apoptotic factors or an extrinsic pathway that is initiated at the cell surface by various death receptors. In necroptosis, the biochemical processes are distinct from those found in apoptosis; in particular, there is no caspase activation. As such, necroptosis is a kinase-mediated cell death that relies on “receptor-interacting protein kinase 3” which mediates phosphorylation of the pseudokinase “mixed lineage kinase domain-like protein.” While ferroptosis is an iron-dependent, oxidative form of regulated necrosis that is biochemically characterized by accumulation of ROS from iron metabolism, oxidase activity, and lipid peroxidation products, pyroptosis is defined as a form of cell death (predominantly of phagocytes) that develops during inflammasome activation and is executed by caspase-mediated cleavage of the pore-forming protein gasdermin D. Finally, NETosis refers to a regulated death of neutrophils that is characterized by the release of chromatin-derived weblike structures released into the extracellular space. The chapter ends up with a discussion on the characteristic feature of regulated necrosis: the passive release of large amounts of constitutive DAMPs as a consequence of final plasma membrane rupture as well as the active secretion of inducible DAMPs earlier during the dying process. Notably, per cell death subroutine, the active secretion of inducible DAMPs varies, thereby determining different immunogenicity of dying cells."
8562,Clinical Ethics and Professionalism,"The act of confronting problems that are too large for the patients, helping them navigate their way through health, wellness, sickness, and dying, and trying to find a balance among conflicting values, beliefs, ethics, and morals can complicate the doctor–patient relationship. The doctor–patient relationship is complex and is built upon trust. That trust can be affected by many different factors, as discussed in Chap. 8. What happens when the ethical principles that create and strengthen the doctor–patient relationship conflict? In this chapter, we address many of the ethical principles that create a foundation for this relationship. Some of the principles that we explore include beneficence, acting in a patient’s best interests, and doing no harm. Balancing these principles with a patient’s right to make autonomous decisions to guide their own medical care, especially when a patient refuses a recommended treatment, can be difficult."
8563,Analysis of Codon Usage Bias in Interferon Alpha Gene of the Giant Panda (Ailuropoda Melanoleuca),"The analysis on codon usage bias of IFN-a gene of giant panda (Ailuropoda melanoleuca) may provide a basis for understanding the evolution relationship of giant panda and for selecting appropriate host expression systems to improve the expression of target genes. In this paper, the codon usage bias in the mature IFN-a sequence of giant panda and 15 reference species have been analyzed. The results showed that the synonymous codons with G and C at the third codon position were widely used and the ENC-GC3S plot revealed that the genetic heterogeneity in IFN-a gene was main constrained by mutational bias. Contrastive analysis revealed that there were 40 codons showing distinct usage differences between GpIFN-a and Escherichia coli, 38 codons between GpIFN-a and yeast. and only 30 between GpIFN-a and Homo sapiens. Therefore the Homo expression system may be more suitable for the expression of GpIFN-a genes."
8564,Narratives in Healthcare,"In this chapter, the narrative is defined and the elements of the narrative are elucidated. Three lenses through which one can view the role of narratives in healthcare are discussed. First, organizational narratives help to foster social capital in the organization and, therefore, contribute to the people aspect of the knowledge management initiative in the organization. Second, the recuperative and relationship building roles of illness narratives are described. Third, narratives from the practice of narrative medicine are explored. The chapter concludes by proposing four requirements for narratives to be effective, namely, effective listening skills, the availability of time and place for storytelling, and the codification of narratives."
8565,ARF-Like (ARL) Proteins,"The ARF-like (ARL) proteins, within the ARF family, are a collection of functionally diverse GTPases that share extensive (>40 %) identity with the ARFs and each other and are assumed to share basic mechanisms of regulation and a very incompletely documented degree of overlapping regulators. At least four ARLs were already present in the last eukaryotic common ancestor, along with one ARF, and these have been expanded to >20 members in mammals. We know little about the majority of these proteins so our review will focus on those about which the most is known, including ARL1, ARL2, ARL3, ARL4s, ARL6, ARL13s, and ARFRP1. From this fragmentary information we extract some generalizations and conclusions regarding the sources and extent of specificity and functions of the ARLs."
8566,Wastewater-Based Epidemiology for Early Detection of Viral Outbreaks,"The immense global burden of infectious disease outbreaks and the need to establish prediction and prevention systems have been recognized by the World Health Organization (WHO), the National Institutes of Health (NIH), the United States Agency of International Development (USAID), the Bill and Melinda Gates Foundation, and the international scientific community. Despite multiple efforts, this infectious burden is still increasing. For example, it has been reported that between 1.5 and 12 million people die each year from waterborne diseases and diarrheal diseases are listed within the top 15 leading causes of death worldwide. Rapid population growth, climate change, natural disasters, immigration, globalization, and the corresponding sanitation and waste management challenges are expected to intensify the problem in the years to come."
8567,Remaking Eco-civilization by Sustainable Decision-Making,"Is there something in humanity’s nature that makes us seek out unsafety and risk? Already in the hunter-gatherer society of prehistory, a pattern of communal living for the sake of survival and cooperation to obtain food, clothing, and shelter was universal. Well before recorded history, as humankind progressed from the New Stone Age to the Bronze Age and then the Iron Age, groups of people specialized in making farming tools, weapons, horse tackle, and other forms of metalworking and needed a system of cooperation at the level of the village, community, and state. Meanwhile, from the time of the first agricultural revolution, ruling the waters, for instance, by predicting the timing of river floods to assist with seed sowing, tilling, and harvesting, was the basis for the existence of the state."
8568,Convergence Toward the Pan-Canadian Electronic Health Record,
8569,Adverse Medication Reactions,"Cutaneous adverse drug reactions (ADRs) are among the most frequent adverse reactions in patients receiving drug therapy. They have a broad spectrum of clinical manifestations, are caused by various drugs, and result from different pathophysiological mechanisms. Hence, their diagnosis and management is challenging. Severe cutaneous ADRs comprise a group of diseases with major morbidity and mortality, reaching 30 % mortality rate in cases of Toxic Epidermal Necrolysis. This chapter covers the terminology, epidemiology, pathogenesis and classification of cutaneous ADR, describes the severe cutaneous ADRs and the clinical and laboratory approach to the patient with cutaneous ADR and presents the translation of laboratory-based discoveries on the genetic predisposition and pathogenesis of cutaneous ADRs to clinical management guidelines."
8570,The Respiratory System,"One of the most critical events of birth is the conversion of the fluid-filled lung, unimportant to fetal intrauterine existence, into a hollow organ distended with air and capable of gaseous exchange sufficient to support life. Indeed, it has been argued that the major determinant of perinatal survival is respiratory function (Wigglesworth and Desai 1982). The failure to make this conversion adequately may lead, directly or indirectly, to infant death, and the pathologist often needs to assess the contribution made by respiratory inadequacy to the sequence of events leading to death. In the preterm infant, problems are mainly related to pulmonary immaturity and associated therapy. In the mature infant, birth asphyxia primarily results in cerebral damage but can engender significant respiratory complications when associated with aspiration of meconium. Even in stillbirths, where primary pulmonary pathology is rarely a cause of death, lung pathology may provide clues to antecedent events. Poor lung growth and maturation may point to the presence of pathology elsewhere. Consequently, adequate pathological investigation of the fetal or infant respiratory system is critical in any perinatal autopsy."
8571,Pneumologie,"Die Pneumologie als Teilgebiet der Inneren Medizin widmet sich den Erkrankungen des Lungenparenchyms, des Lungenkreislaufes, der Atmung und der Pleura. Entsprechend werden in diesem Kapitel die wesentlichen medizinischen Fakten zu folgenden Themen dargestellt: obstruktive Lungenerkrankungen (u. a. Asthma bronchiale, chronische Bronchitis, Mukoviszidose), Lungenparenchymerkrankungen (hierzu zählt das Lungenemphysem ebenso wie die Lungenfibrose, aber auch das ARDS und die Silikose etc.) und Störungen im kleinen Kreislauf (Embolie, Blutung, Ödem, Hypertonie). Darüber hinaus wird auf das Schlafapnoe-Syndrom, das Hyperventilationssyndrom, den Pneumothorax und die Pleuritis/den Pleuraerguss näher eingegangen."
8572,Spezifische Infektionen,
8573,Avian influenza viruses: a severe threat of a pandemic in children?,"Influenza virus is a leading cause of human respiratory illnesses, causing significant annual morbidity and mortality. The greatest severity of illness due to seasonal influenza occurs in infants less than 6 months of age and the elderly. In recent years, avian influenza virus infections with high mortality have occurred in humans. Many of these avian influenza virus infections have occurred in children, and unlike seasonal influenza, the most severe disease and highest death rates have occurred in children and young adults. Treatment and prevention options for avian influenza viruses are limited at present, although much research effort is directed toward these areas. Avian-derived influenza viruses are potential causes of pandemic influenza that could have a dramatic impact on children worldwide."
8574,Hygiene und Arbeitsschutz,"In diesem Kapitel wird ein Überblick über Impfungen, meldepflichtige Erkrankungen sowie allgemeine Hinweise zur Hygiene im notfallmedizinischen Umfeld gegeben."
8575,Pulmonary Arterial Hypertension,"The first description of the circulation of blood through the lungs has been attributed to Ibn Nafis (1210–1288).1 The concept was rediscovered by Michael Servetus, a Spanish physician during the Renaissance (1511–1553) and recorded, oddly enough, in two pages of his religious treatise, Christianismi Restitutio (1553).2 The definitive exposition of the pulmonary circulation was made by William Harvey in DeMotu Cordis (1628).3 The first observation of the pulmonary capillaries was first reported by Marcellus Malpighi (1661).4 Heart catheterization in humans, driven by a desire to obtain the perfect mixed venous specimen and measure cardiac output, was first performed in 1929 by the German urologist Forssmann,5 using a ureteral catheter to access his own right atrium. Over a decade later, Cournand and Richards at Columbia University in New York subsequently used right heart catheterization to record pulmonary artery pressure (PAP) in patients with shock and secondary forms of pulmonary hypertension (PHT). For these accomplishments, which were inspired by an interest in the pulmonary circulation and PHT related to mitral stenosis, Forssmann, Cournand, and Richards received the Nobel Prize in 1956."
8576,Coronaviridae: a review of coronaviruses and toroviruses,
8577,Conclusion,This book has discussed the history of disease in ancient times. The purpose of this book was to show that disease was a significant contributing causal factor in history; especially in ancient times and reflects the fact that history is not just made up of dates of battles and the list of monarchs and when they reigned. Second it looked at the possible diseases may of the era and third it questioned the status quo such as whether the 1322 bce Hittite epidemic ended the Hittite Empire.
8578,Assessment Considerations in Pediatric Patients,"Pharmacy assessment of pediatric patients is similar in many ways to that of adults; however there are many specific nuances that need to be considered in addition to the typical aspects included in an adult assessment. There is a lack of pediatric-specific medication research and a much higher rate of “off label” medication use, so children are at higher risk of medication errors and related harm. Pharmacokinetic differences and other age-related differences result in highly variable responses to medications throughout childhood. Pharmacists need to be aware of this variability and use every patient encounter as an opportunity for assessment of many aspects of medication including dose, formulation, administration, and indication. Infants and children also have physiological differences that need to be considered especially when assessing efficacy, toxicity, and the patient’s overall response to medications through physical exam or use of laboratory values. Lastly, a lack of appropriate medication formulations for children creates a requirement for pharmacists to specifically assess the formulations, measurement, and administration of pediatric medications. This chapter provides an approach to pediatric assessment, highlights common sources of error, and provides strategies for managing pediatric medications."
8579,Prioritätensetzung im Katastrophenschutz,"Die Frage der „Prioritätensetzung bei Rettungsmaßnahmen“ lässt sich in unterschiedlichen Reichweiten betrachten. Sehr eng fokussiert kann man sie auf die Auswahl reduzieren, wer von mehreren Verletzten zuerst behandelt wird, wenn (zunächst) zu wenige Rettungskräfte vorhanden sind, um alle zugleich zu behandeln. Im Zusammenhang mit komplexen Schadenslagen stellt sich die Frage der Prioritätensetzung jedoch sehr viel umfassender dar. Sie betrifft bereits die Katastrophenvermeidung und -vorsorge. In der konkreten Lagebewältigung spielen verschiedene Rechtsgüter und die Wechselwirkungen zwischen ihnen eine erhebliche Rolle. Dabei existieren kaum rechtliche Regelungen, die die Prioritätensetzung steuern."
8580,Introduction to Survival Analysis,
8581,Epidemiology of Acute Respiratory Failure in Patients with HM (ICU Only),"Pulmonary complications are common in hematological patients, particularly those receiving a hematological stem cell transplant (HSCT), and a significant percentage of them will require intensive care unit (ICU) admission. Acute respiratory failure in these patients is a threatening event, with a very poor outcome, particularly when mechanical ventilation (MV) is required. For many years, oncologists and intensivists had a pessimistic vision of the dismal outcome of those hematological patients requiring admission to the ICU. The bleak experience in this population led some authors to suggest early withdrawal of support, or even withholding the option of mechanical ventilation altogether. However, over the last years this vision seems to be changing. Great progress has been made in stem cell transplantation that can be ascribed to a better understanding of the human leukocyte antigen (HLA) system for donor selection, more effective and less toxic immunosupression for prevention and treatment of graft-versus host disease (GVHD), and significant advances in infectious disease therapy. Also improvements in ventilatory and supportive care, such as the early implantation of noninvasive ventilation (NIV), may avoid intubation in a significant percentage of patients suffering from acute respiratory failure. As a result of all this, the proportion of both hematological patients requiring management in the ICU and those requiring MV is decreasing. Also the survival rate of HSCT recipients admitted to the ICU has been steadily improving. In this chapter we will report on the epidemiology of acute respiratory failure in patients with hematological malignancies."
8582,Consolidation,"Consolidation refers to an area of homogeneous increase in lung parenchymal attenuation that obscures the margins of vessels and airway walls [1]. Air bronchograms may be present with consolidative area. Pathologically, consolidation represents an exudate or other product of disease that replaces alveolar air, rendering the lung solid [2, 3]."
8583,"Fluorescence Observables and Enzyme Kinetics in the Investigation of PPI Modulation by Small Molecules: Detection, Mechanistic Insight, and Functional Consequences","The potential of fluorescence-based methods and kinetic analysis in the screening and molecular-scale mechanistic investigation of PPI modulation by small molecules is discussed through several representative examples collected and commented. These experimental approaches take advantage of a variety of observables. Changes in the protein aggregation pattern have been monitored through fluorescence properties such as spectra, intensities (related to quantum yields), time-decays, and anisotropies of intrinsic protein fluorophores, of extrinsic fluorescent tags and, even, of the same small molecules added to modulate PPIs, as well as through bimolecular excited-state processes such as static and collisional quenching, including electron and excitation-energy transfer, or exciton interaction, whose efficiencies are crucially structure dependent. Besides allowing for qualitative and quantitative information on the small-molecule induced PPI modulation, these approaches can take advantage from the sensitivity of fluorescence observables on fine structural details to shed light on the molecular-scale mechanisms of action and their functional consequences. Direct investigation of the latter by kinetic inhibition analysis represents a useful change in perspective whenever PPI are relevant for enzyme activity. Dissociative inhibition, that is, the ability of some small molecules to inhibit enzymes by disrupting their active oligomeric assembly is shortly reviewed."
8584,Infection Prevention and Control Issues After Solid Organ Transplantation,"Infections are an important cause of morbidity and mortality in solid organ transplant recipients. Consequently, infection prevention is an essential component of any organ transplant program. Given their frequent and often prolonged contact with the healthcare system, solid organ transplant recipients are at high risk for healthcare-associated infections, including those caused by antibiotic-resistant organisms. In this chapter we review several different healthcare-associated infections of importance to transplant recipients, including those caused by bacterial, viral, and fungal organisms. We also describe infection prevention and control strategies applicable to this patient population. These practices focus on clinical interventions and environmental controls designed to prevent the spread of potentially pathogenic organisms in the healthcare setting. We also describe post-exposure interventions applicable to solid organ transplant recipients exposed to potential pathogens in order to reduce their risk of subsequent infection."
8585,Krankheiten der Atmungsorgane,"gereinigt (Filterwirkung der Nasenhaare, Partikelniederschlag auf dem Nasenschleim, rachenwärts gerichtete Zilienbewegung des Epithels); erwärmt (fast bis auf Körpertemperatur); befeuchtet (nahezu vollst.ndige Sättigung mit Wasserdampf)."
8586,Specialized Agencies of the UN,
8587,The Last Natural Brain,"The work of the brain would be easy if we knew what we needed to remember or understand in the future. Life is full of surprises – new people whom we need to know, names we have to remember, problems we try to solve."
8588,"Vaccines, Sera and “New” Viruses: Ebola, Zika and Other Infectious Challenges for Human Health","Following the basic description of the immunological science, we may now go in more detail into the practical applications involving immunological prevention against infectious diseases (vaccine use, requiring availability of suitable antigenic preparations, safe and effective immunization schedules and time to allow for immunity to develop) and immunotherapy of dangerous infective conditions (serotherapy, involving availability of immune sera and their use for injection in subjects needing protection against infectious agents). All this is discussed with special regard of the many new micro-organisms described in human pathology and also in situations in which the deliberate use of them for biological warfare or related menace (bioterrorism) is realized."
8589,Information Diffusion in Social Networks,"In this chapter, we will discuss concepts of information diffusion in social networks. We are interested in knowing how a piece of information (knowledge) is spread through a network. These may be computer viruses spreading on the Internet or a network of computers, diseases through a social network, or rumors and ideas through a social network. Information diffusion methods are commonly used in viral marketing, in collaborative filtering systems, in emergency management, in community detection, and in the study of citation networks."
8590,Effects of the West African Ebola Epidemic on Health Care of Pregnant Women: Stigmatization With and Without Infection,"Following the end of the Ebola virus outbreak in West Africa in March 2016, the lingering effects of stigma on Ebola survivors, as well as children orphaned by the disease, have become evident. However, there was little scholarly attention paid to stigma while the outbreak was still active. This chapter explores the effects of stigmatization on the health care services that pregnant women, both with and without Ebola, were able to access and receive during the outbreak. We propose three primary ways in which stigma operated to reduce pregnant women’s access to health care services during the outbreak: (1) Women and their relatives were afraid to go to health facilities for fear of being infected with Ebola while there, i.e., stigmatization of health care facilities; (2) Health care workers frequently died due to their occupational exposure to EVD while caring for others, i.e., they were stigmatized as carriers or transmitters of Ebola; and (3) Pregnant women themselves were refused services at health facilities due to fears that they were infected with Ebola, i.e., the physiological processes of birth, which involve high levels of potential for exposure to bodily fluids, led to health care workers’ stigmatization of these women when they sought services during pregnancy or, particularly, at the time of giving birth. In several of the countries that experienced the worst of the outbreak, women already faced some of the world’s highest rates of pregnancy-related death even prior to the advent of the epidemic. We argue that the high fatality rate for pregnant women with Ebola, the drastic effects of the epidemic on countries’ health care workforce, and the inherent messiness of birth, all coalesced to create heightened discrimination and stigma around seeking care during pregnancy and birth."
8591,Split Blood Products,"The last 20 years have seen many advances in transfusion therapy and safety. Blood products are biological products engendering complex interactions with the immune system. Prestorage leukoreduction results in a reduced risk of febrile reactions, CMV transmission, and immune modulation, proving to be safer for patients than non-leuko reduced products. Simple patient identification issues and clerical error continue to be the primary causes of ABO-incompatible transfusions. Rigorous donor screening as well as serologic and nucleic acid testing for transfusion transmitted infection have brought the blood supply to a very safe level, although transmission of these agents continues to be a problem in underdeveloped countries. Emerging infectious diseases, beyond current laboratory detection capabilities, combined with global travel, pose unknown imminent risks everywhere. We also briefly discuss the current risks of transfusion-transmitted infections. We review currently available hemostatic blood products, their compositions, and their clinical indications; we mention product modifications currently in development; and we touch upon the hemostatic properties and drawbacks of whole blood, which is currently gaining popularity as an alternative to split blood products. We conclude with an in-depth overview of the risks associated with transfusion, including incompatibility, hemolytic transfusion reactions, transfusion-associated circulatory overload (TACO), and transfusion-related acute lung injury (TRALI)."
8592,Allgemeine Hygiene- und Präventionsmaßnahmen,"a. Robert Koch gilt als Begründer der modernen Händehygiene in der Medizin. b. Der Einsatz von Wasser und Seife ist genauso effektiv wie die alkoholische Händedesinfektion. c. Die Händedesinfektion wird vor und nach jedem Patientenkontakt empfohlen. d. Die »Aktion Saubere Hände« richtet sich gegen Korruption in Ländern der Dritten Welt. e. Die Compliance mit der erforderlichen Händehygiene beträgt auf Intensivstationen je nach Beobachtungsstudie ca. 50 %, wobei der ärztliche Dienst tendenziell schlechter abschneidet als das Pflegepersonal."
8593,A Survey of Social Web Mining Applications for Disease Outbreak Detection,"Social Web Media is one of the most important sources of big data to extract and acquire new knowledge. Social Networks have become an important environment where users provide information of their preferences and relationships. This information can be used to measure the influence of ideas and the society opinions in real time, being very useful on several fields and research areas such as marketing campaigns, financial prediction or public healthcare among others. Recently, the research on artificial intelligence techniques applied to develop technologies allowing monitoring web data sources for detecting public health events has emerged as a new relevant discipline called Epidemic Intelligence. Epidemic Intelligence Systems are nowadays widely used by public health organizations like monitoring mechanisms for early detection of disease outbreaks to reduce the impact of epidemics. This paper presents a survey on current data mining applications and web systems based on web data for public healthcare over the last years. It tries to take special attention to machine learning and data mining techniques and how they have been applied to these web data to extract collective knowledge from Twitter."
8594,Hepatic Failure,"The progression of liver disease can cause several physiologic derangements that may precipitate hepatic failure and require admission to an intensive care unit. The underlying pathology may be acute, acute-on chronic, or chronic in nature. Liver failure may manifest with a variety of clinical signs and symptoms that need prompt attention. The compromised synthetic and metabolic activity of the failing liver affects all organ systems, from neurologic to integumentary. Supportive care and specific therapies should be instituted in order to improve outcome and minimize time of recovery. In this chapter we will discuss the definition, clinical manifestations, workup, and management of acute and chronic liver failure and the general principles of treatment of these patients. Management of liver failure secondary to certain common etiologies will also be presented. Finally, liver transplantation and alternative therapies will also be discussed."
8595,The Current Bioweapons Threat,"According to unclassified U.S. government sources, states of biological weapons (BW) proliferation concern include China, Iran, North Korea, Russia, and Syria. Assessing the BW threat is challenging, however, because illicit development and production can be concealed at dual-use industrial sites such as vaccine plants, and only tens of kilograms of an agent like dried anthrax spores can be militarily significant. The lack of unambiguous technical signatures of BW-related activity means that most estimates of foreign capabilities draw heavily on human intelligence sources, yet spies and defectors are notoriously unreliable. A key factor driving BW proliferation is the perceived military utility of biological weapons, which may include strategic deterrence, asymmetric warfare, or covert operations. Globalization of the biotechnology industry has expanded trade in dual-use materials and production equipment, increasing the risks of diversion and misuse for BW purposes. With the advent of flexible biological manufacturing systems, it has also become possible for countries to acquire a “latent” capacity for BW production during a crisis or war. Since the 2001 anthrax letter attacks, sub-state actors have become a prominent part of the threat matrix, but terrorist acquisition and use of BW requires both the motivation to use disease as a weapon and the technical capability to do so, a combination that is quite rare. At present the threat of mass-casualty BW attacks emanates primarily from nation-states, while terrorist use of biological weapons will likely remain limited in scale and impact. Nevertheless, the emergence of new biotechnologies with a potential for misuse could result in more damaging incidents of bioterrorism in the future."
8596,Nephrologie,
8597,The Physical Burden of Immunoperception,"The previous chapter introduced the ImmunoEmotional Regulatory System (IMMERS). Also, there was a brief discussion about psychological states/psychiatric disorders that so far have been linked to the IMMERS. The present chapter considers another aspect of the IMMERS in which physiological states/physical diseases can be fit to the IMMERS."
8598,Making Universities Grow: The New Zealand Experience,"The New Zealand tertiary education system consists of eight Universities, numerous polytechnical institutes and other smaller tertiary providers. Despite the preferential treatment for international doctoral students, the New Zealand sector suffered a serious drop in international student enrolments beginning in 2004, after the damaging closure of two English-language institutes which received significant negative media coverage in one of New Zealand’s most important markets for international students—the People’s Republic of China. New Zealand Universities have aspired to create stronger linkages with institutions overseas to access external research income that may be funnelled through principal investigators at overseas Universities. In November 2015, the New Zealand government asked the “Productivity Commission” to write a report with recommendations on how to create “new models” for tertiary education. The Commission was tasked to investigate “how trends in technology, internationalisation, population, tuition costs and demand for skills may drive changes in models of tertiary education”. For future growth, the Universities need to partner more effectively with industry and create a culture that truly believes that a country like New Zealand deserves a great University system, and that the Universities are a true asset, essential for the country to thrive. This kind of strategy will ensure that the Universities continue to grow despite the vicissitudes of chance events or geopolitical developments beyond the control of the New Zealand government or University administrators."
8599,Mikrobiologie und Antiinfektiva,"Bei einem 38-jährigen Patienten wurde eine Analfistel operiert. Am 3. postoperativen Tag kommt es zur akuten Verschlechterung des Gesundheitszustands mit hämodynamischer Instabilität und Fieber. Daraufhin wird der Patient in eine Klinik der Maximalversorgung verlegt. Beim Eintreffen im Schockraum ist der Patient somnolent und kaltschweißig. Der Blutdruck beträgt 70/40 mmHg, die Herzfrequenz 120/min und die Körpertemperatur 39,6°C. Das Hautkolorit ist blass-grau. Im Verlegungsbericht wird bei stark ödematös geschwollenem Skrotum der Verdacht auf eine Fournier-Gangrän nach Analfistel- OP gestellt. Der diensthabende Intensivmediziner muss nun parallel die hämodynamische Situation stabilisieren, mikrobiologisches Material gewinnen, eine kalkulierte antimikrobielle Therapie beginnen und weitere Maßnahmen zur Diagnosesicherung einleiten."
8600,Pneumologie,"—. : —. allergisches Asthma („extrinsic asthma“): IgE-vermittelte Sofortreaktion vom Typ I auf Inhalationsallergene; —. : • Analgetikaasthma: pseudoallergische Reaktion bei erhöhter Aktivität der LTC(4)-Synthetase in Mastzellen und eosinophilen Granu- lozyten, ausgelöst durch ASS oder andere NSAR, meist auch Intoleranz gegenüber Sulfit (Wein), Tyramin (Käse), Glutamat; • Infektasthma; • durch Exposition gegenüber chemisch-toxischen Stoffen; • infolge gastroösophagealen Refluxes; —. unspezifische Stimuli: kalte Luft, körperliche Belastung, Aerosole, Rauche, Gase und Stäube; —. Prävalenz 5-10%; <30. Lebensjahr meist allergisches Asthma, >40. Lebensjahr überwiegend nicht-allergisches Asthma; —. bei allergischem Asthma polygene Anlage auch für andere atopische Erkrankungen, z. B. allergische Rhinitis, Neurodermitis; —. bei 25% der Patienten „Etagenwechsel“ nach allergischer Rhinitis; —. Allergenexposition/Infektion → Degranulation bzw. Aktivierung von Mastzellen, eosinophilen Granulozyten, T-Lymphozyten → Entzündung der Bronchialschleimhaut → Freisetzung von Mediatoren (Histamin, Leu- kotriene, Bradykinin) → bronchiale Hyperreaktivität → Bronchokonstriktion (Sofortreaktion) → Schleimhautödem (Spätreaktion) → Hyperkrinie/ Dyskrinie (chronische Entzündungsreaktion);"
8601,Coronavirus main proteinase: target for antiviral drug therapy,
8602,Neusverstopping,"Acute neusverstopping is een frequente aandoening. Meestal is het geen geïsoleerd symptoom, maar treedt zij gecombineerd op met andere klachten van de neus. In overgrote meerderheid is de oorzaak een virale infectie die vanzelf overgaat, en heeft verdere diagnostiek geen consequenties voor de therapie. Bij chronische klachten is verdere diagnostiek wel zinvol; een allergie of hyperreactiviteit is het meest waarschijnlijk. Bij chronische neusverstopping is aandacht voor chronisch gebruik van decongestieve neusdruppels van belang. Persisterende eenzijdige neusverstopping, zeker wanneer dit gepaard gaat met bloederige afscheiding, is een alarmsymptoom. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1274-0_15) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers."
8603,Seltene Infektionen und Hygiene auf der Intensivstation,"Ein Patient wird seit 2 Wochen auf der Intensivstation aufgrund einer infektexazerbierten chronisch obstruktiven Lungenerkrankung beatmet. Der Verlauf wurde durch eine nosokomiale Pneumonie kompliziert. Bei der Morgenvisite wird berichtet, dass der Patient innerhalb der letzten 2 h 4-mal massiv wässrig abgeführt hat. Die Temperatur beträgt 38,7°C, die Leukozyten 16.000/μl. Der Intensivarzt und seine Oberärztin besprechen die möglichen Ursachen und überlegen, ob spezielle Hygienemaßnahmen erforderlich sind."
8604,Komplexe Gerinnungsstörungen,"Die thrombotisch-thrombozytopenische Purpura (TTP) und das hämolytischurämische Syndrom (HUS) sind thrombotische Mikroangiopathien, gekennzeichnet durch eine Endothelzellschädigung mit nachfolgender Bildung von Thromben in der Mikrozirkulation mit intravasaler Hämolyse und Thrombozytopenie. Ischämische Organdysfunktionen im Gehirn, den Nieren und anderen Organen Prägen das klinische Bild. Während bei Erwachsenen das Auftreten einer neurologischen Symptomatik zur Diagnose TTP führt, wird bei Kindern mit dem Leitsymptom Nierenversagen die Diagnose HUS gestellt."
8605,SARS Coronavirus Pathogenesis and Therapeutic Treatment Design,"Emerging pathogens are either new or newly recognized or those that are increasing in incidence and spread. Since the identity of emerging pathogens from animal reservoirs is difficult to predict, the development for pathogen-specific therapeutics and vaccines is problematic. The highly pathogenic SARS coronavirus (SARS-CoV) emerged from zoonotic pools in 2002 to cause a global epidemic of severe acute respiratory syndrome (SARS). Many patients with SARS-CoV experienced an exacerbated form of disease called acute respiratory distress syndrome (ARDS) requiring mechanical ventilation and supplemental oxygen and half of these patients died. Similar to other viral pathogens like influenza and West Nile Virus, the severity of SARS-CoV disease increased with age. Unfortunately, successful vaccination in the most vulnerable populations is a difficult task because of immunological deficiencies associated with aging (immune senescence). Due to the rapidity of virus emergence, technologies like synthetic biology can be harnessed to facilitate rapid recombinant virus construction for studying the novel virus biology, pathogenesis and the evaluation of therapeutic interventions. Since predicting the antigenic identity of future emergence is difficult, candidate vaccines and therapeutics should have a maximal breadth of cross-protection, and panels of antigenically divergent synthetically reconstructed viruses can be used as tools for this evaluation. We discuss how synthetic reconstruction of many animal and human SARS-CoV has provided a model to study the molecular mechanisms governing emergence and pathogenesis of viral diseases. In addition, we review the evolution, epidemiology, and pathogenesis of epidemic and zoonotic SARS-CoV with focus on the development of broadly reactive therapeutics and vaccines that protect aged populations from the zoonotic pool."
8606,Artificial Intelligence Applications in Tracking Health Behaviors During Disease Epidemics,"The threat of emerging and re-emerging infectious diseases to global population health remains significantly enormous, and the pandemic preparedness capabilities necessary to confront such threats must be of greater potency. Artificial Intelligence (AI) offers new hope in not only effectively pre-empting, preventing and combating the threats of infectious disease epidemics, but also facilitating the understanding of health-seeking behaviors and public emotions during epidemics. From a systems-thinking perspective, and in today’s world of seamless boundaries and global interconnectivity, AI offers enormous potential for public health practitioners and policy makers to revolutionize healthcare and population health through focussed, context-specific interventions that promote cost-savings on therapeutic care, expand access to health information and services, and enhance individual responsibility for their health and well-being. This chapter systematically appraises the dawn of AI technology towards empowering population health to combat the rise of infectious disease epidemics."
8607,Recombinant Live Vaccines to Protect Against the Severe Acute Respiratory Syndrome Coronavirus,"The severe acute respiratory syndrome (SARS) coronavirus (CoV) was identified as the etiological agent of an acute respiratory disease causing atypical pneumonia and diarrhea with high mortality. Different types of SARS-CoV vaccines, including nonreplicative and vectored vaccines, have been developed. Administration of these vaccines to animal model systems has shown promise for the generation of efficacious and safe vaccines. Nevertheless, the identification of side effects, preferentially in the elderly animal models, indicates the need to develop novel vaccines that should be tested in improved animal model systems. Live attenuated viruses have generally proven to be the most effective vaccines against viral infections. A limited number of SARS-CoV attenuating modifications have been described, including mutations, and partial or complete gene deletions affecting the replicase, like the nonstructural proteins (nsp1 or nsp2), or the structural genes, and drastic changes in the sequences that regulate the expression of viral subgenomic mRNAs. A promising vaccine candidate developed in our laboratory was based on deletion of the envelope E gene alone, or in combination with the removal of six additional genes nonessential for virus replication. Viruses lacking E protein were attenuated, grew in the lung, and provided homologous and heterologous protection. Improvements of this vaccine candidate have been directed toward increasing virus titers using the power of viruses with mutator phenotypes, while maintaining the attenuated phenotype. The safety of the live SARS-CoV vaccines is being increased by the insertion of complementary modifications in genes nsp1, nsp2, and 3a, by gene scrambling to prevent the rescue of a virulent phenotype by recombination or remodeling of vaccine genomes based on codon deoptimization using synthetic biology. The newly generated vaccine candidates are very promising, but need to be evaluated in animal model systems that include young and aged animals."
8608,Carbon Nanostructures for Enhanced Photocatalysis for Biocidal Applications,"In the last few decades, the demand for safer environmental conditions has increased dramatically. The burden of infectious diseases worldwide, related to contamination via contact with contaminated surfaces (fomites), is a growing issue. Globally, these infections are linked to an estimated 1.7 million deaths a year from diarrheal disease and 1.5 million deaths from respiratory infections [1]. Apart from hospitals, the problem has become a growing liability at places where food is prepared and handled [2], where there is a growing risk associated with the cross-contamination of edible goods and where large amounts are handled by a single facility [3]. Already many E. coli and Salmonella outbreaks have been recorded and linked to single a facility [2, 4, 5]. The problem of cross-contamination via surfaces can also be traced, in smaller scale, to households where common areas can accumulate pathogens that can potentially become a threat, especially to more sensitive population groups [6]. There are also biological threats in forms of dangerous epidemic outbreaks (Ebola and SARS) and biological warfare weapons (anthrax and smallpox). The need for effective and efficient disinfection is driving the industry in the development of a wide range of products. These products can currently be divided into three major categories:"
8609,Pulmonary and Hepatic Complications of Hematopoietic Cell Transplantation,"Significant advances have been made in allogeneic transplantation for both adults and pediatric transplant recipients over the past 20 years, corresponding with dramatic declines in treatment-related mortality (TRM). The cumulative incidence of TRM at 1 year following unrelated donor transplants has decreased from 40 to 15 % between 1987 and 2006 for children with acute leukemia, the primary indication for transplant in the pediatric population (MacMillan et al., Biol Blood Marrow Transpl 14(9 Suppl):16–22, 2008). Improvements in conditioning regimen, supportive care, and human leukocyte antigen (HLA) testing have all been associated with incremental improvements in survival during this period. In particular, the management of both infectious and noninfectious organ complications has changed dramatically, with improved sensitivity for diagnostic testing for pathogens and tremendous improvements in our understanding of organ complications. Two organ complications in particular, pulmonary and hepatic, have been a major focus of investigation over the past several decades. The introduction of tumor necrosis factor (TNF) inhibitors for the management of acute, noninfectious lung injury and the introduction of an endothelial stabilizing agent (defibrotide) for the management of hepatic veno-occlusive disease have been major advances in the past decade."
8610,Probabilistic Reasoning for Closed-Room People Monitoring,"In this chapter, we present a probabilistic reasoning approach to recognizing people entering and leaving a closed room by exploiting low-level visual features and high-level domain-specific knowledge. Specifically, people in the view of a monitoring camera are first detected and tracked so that their color and facial features can be extracted and analyzed. Then, recognition of people is carried out using a mapped feature similarity measure and exploiting the temporal correlation and constraints among each sequence of observations. The optimality of recognition is achieved in the sense of maximizing the joint posterior probability of the multiple observations. Experimental results of real and synthetic data are reported to show the effectiveness of the proposed approach."
8611,Antimicrobial Agents in Ophthalmology,"Many types of antimicrobial agents have been introduced for the treatment of ocular infectious diseases. Some ocular infections have been eradicated such as smallpox, while others have been controlled by public health measures such as trachoma. The resilience of viruses and the tenacity of bacteria have led to the evolution of old diseases and the emergence of new infections. Continuous search for new antimicrobial agents for the treatment of infectious diseases is, therefore, highly desirable. New infectious agents are discovering the human race, and the ecological changes are exposing mankind to new viruses and bacteria. In addition, air travel and disruption of geographic barriers are leading to new forms of infectious diseases. In the twentieth century, there was a widespread false optimism that infectious diseases are eradicated by antimicrobial agents. It was soon discovered that many infections require new strategies for the treatment of ocular infections. The new antimicrobial agents that have been introduced over the past century can be classified into four major categories including (1) antibiotics that inhibit cell wall synthesis and integrity, (2) antibiotics that inhibit and suppress cell membrane functions, (3) antibiotics that interfere the protein synthesis, and (4) antibiotics that modulate nucleic acid synthesis. The selection of antimicrobial agents for the treatment of ocular infectious diseases is based on the most frequently encountered organisms, the pharmacokinetics of the antibiotics, the dosage required, the ocular penetration, and the cost of therapy. The stumbling blocks to safe and effective antimicrobial therapy in ocular infections include the resistance of the microorganisms, toxicity of the drug, and poor ocular penetration of antimicrobial agents."
8612,Kawasaki Disease,"Kawasaki disease (KD) is the commonest cause of acquired heart disease in children in the developed world and is increasingly being reported from developing countries. KD has a predilection for the coronary arteries. Etiology of this disorder is remains an enigma. Diagnosis of KD is essentially clinical with the help of set of clinical criteria. Incomplete KD is said to occur when these criteria are not fulfilled. However, incomplete KD should not be considered as a milder form of the disease. 2D-echocardiography remains the imaging modality of choice for evaluation and monitoring of cardiac complications but often needs to be supplemented by CT coronary angiography. Intravenous immunoglobulin along with aspirin is the gold standard therapy of treatment for KD. However, there is no consensus on treatment of resistant forms of KD. Patients with KD should be on long-term follow-up especially if they have developed coronary artery abnormalities during the acute stage."
8613,Bushmeat and Emerging Infectious Diseases: Lessons from Africa,"Zoonotic diseases are the main contributor to emerging infectious diseases (EIDs) and present a major threat to global public health. Bushmeat is an important source of protein and income for many African people, but bushmeat-related activities have been linked to numerous EID outbreaks, such as Ebola, HIV, and SARS. Importantly, increasing demand and commercialization of bushmeat is exposing more people to pathogens and facilitating the geographic spread of diseases. To date, these linkages have not been systematically assessed. Here we review the literature on bushmeat and EIDs for sub-Saharan Africa, summarizing pathogens (viruses, fungi, bacteria, helminths, protozoan, and prions) by bushmeat taxonomic group to provide for the first time a comprehensive overview of the current state of knowledge concerning zoonotic disease transmission from bushmeat into humans. We conclude by drawing lessons that we believe are applicable to other developing and developed regions and highlight areas requiring further research to mitigate disease risk."
8614,Antibiotic Resistance of Non-pneumococcal Streptococci and Its Clinical Impact,"The taxonomy of streptococci has undergone major changes during the last two decades. The present classification is based on both phenotypic and genotypic data. Phylogenetic classification of streptococci is based on 16S rRNA sequences [1], and it forms the backbone of the overall classification system of streptococci. Phenotypic properties are also important, especially for clinical microbiologists. The type of hemolysis on blood agar, reaction with Lancefield grouping antisera, resistance to optochin, and bile solubility remain important for grouping of clinical Streptococcus isolates and therefore treatment options [2]. In the following chapter, two phenotypic classification groups, viridans group streptococci (VGS) and beta-hemolytic streptococci, will be discussed."
8615,THE INTERCONNECTION BETWEEN THE BUILT ENVIRONMENT ECOLOGY AND HEALTH,"The built environment (BE) affects ecosystems, ecosystem services and human health and well being. While, formally, the BE ranges from the smallest hut to the largest city, this chapter focuses upon the health effects of urban areas, which increasingly are the preferred human habitat. Urban areas have many attractive and beneficial influences to human well‐being. But at the same time, many effects of urban areas are harmful to well‐being, and many are not even recognized as such. Most publications about these topics have described the effects of the BE separately, on either ecosystems or on human health. The interconnectivity between these two effects relative to BE is rarely studied. This paper focuses on the mutual influence and interactions between three related aspects of the BE which can impact ecosystems and human health: transportation, land use, and life style. It also explores some of the links between the BE, human health, and human security."
8616,Of Ducks and Men: Ecology and Evolution of a Zoonotic Pathogen in a Wild Reservoir Host,"A hallmark of disease is that most pathogens are able to infect more than one host species. However, for most pathogens, we still have a limited understanding of how this affects epidemiology, persistence and virulence of infections—including several zoonotic pathogens that reside in wild animal reservoirs and spillover into humans. In this chapter, we review the current knowledge of mallard (Anas platyrhynchos) as host for pathogens. This species is widely distributed, often occupying habitats close to humans and livestock, and is an important game bird species and the ancestor to domestic ducks—thereby being an excellent model species to highlight aspects of the wildlife, domestic animal interface and the relevance for human health. We discuss mallard as host for a range of pathogens but focus more in depth of it as a reservoir host for influenza A virus (IAV). Over the last decades, IAV research has surged, prompted in part to the genesis and spread of highly pathogenic virus variants that have been devastating to domestic poultry and caused a number of human spillover infections. The aim of this chapter is to synthesise and review the intricate interactions of virus, host and environmental factors governing IAV epidemiology and evolution."
8617,Flashes,"Because punctuated reality is episodic—waves come and go—the social structure of modern life is also episodic. Social groups form spontaneously and often without obvious reasons. Flashmobs ravage innocent bystanders, online raves spring up and just as quickly die out, protesters flair-up on Wall Street and then disappear. Why? These bursts occur because of the increasingly connected super hive we call the Internet. More importantly, they rise and fall because of how society is wired together. Ever-tightening self-organization and the resulting hub-like structure of society magnifies the impact and spreads these events like a wildfire. If you want to control the Internet animali, seek out and control the center."
8618,A Global Ethical Framework for Public Health Disasters,"Public health disasters reflect a class of global problems that generate moral quandaries and challenges. As such, they demand a global bioethical response involving an approach that is sufficiently nuanced at the local, trans-national, and global domains. Using the overlapping ethical issues engendered by Ebola and pandemic influenza outbreaks, atypical drug-resistant tuberculosis, and earthquakes, this chapter develops a global ethical framework for engaging PHDs. This framework exhibits sufficient responsiveness to local, global, microbial, and metaphysical realities as well as scientific concerns."
8619,Immunität und Ansteckung: Roberto Espositos Kritik des Sicherheitsdenkens,"Todd Haynes’ Film [SAFE] (USA 1995) erzählt die Geschichte von Carol White, die in einer US-amerikanischen Vorstadt ein sehr tristes und einsames Leben als Hausfrau führt, bis sie plötzlich an immer stärker werdenden körperlichen (Über-) Reaktionen auf chemische Stoffe und Abgase zu leiden beginnt. Sie bricht beim Baby shower einer Freundin und im Waschsalon zusammen oder bekommt im Straßenverkehr keine Luft mehr. Ihre immer schlimmer werdenden Attacken bringen sie dazu, dass sie sich bei verschiedenen Stellen Hilfe sucht, wodurch sie erfährt, dass sie in ihrem Leiden nicht allein ist: „Multiple Chemical Sensitivity“ sei eine „environmental illness“ oder auch „die Krankheit des 20. Jahrhunderts“, die mittlerweile pandemische Ausmaße angenommen habe.Todd Haynes’ Film [SAFE] (USA 1995) erzählt die Geschichte von Carol White, die in einer US-amerikanischen Vorstadt ein sehr tristes und einsames Leben als Hausfrau führt, bis sie plötzlich an immer stärker werdenden körperlichen (Über-) Reaktionen auf chemische Stoffe und Abgase zu leiden beginnt. Sie bricht beim Baby shower einer Freundin und im Waschsalon zusammen oder bekommt im Straßenverkehr keine Luft mehr. Ihre immer schlimmer werdenden Attacken bringen sie dazu, dass sie sich bei verschiedenen Stellen Hilfe sucht, wodurch sie erfährt, dass sie in ihrem Leiden nicht allein ist: „Multiple Chemical Sensitivity“ sei eine „environmental illness“ oder auch „die Krankheit des 20. Jahrhunderts“, die mittlerweile pandemische Ausmaße angenommen habe. Ihr wird geraten, sich von Umwelteinflüssen möglichst fern zu halten und ihren Körper weitestgehend zu „reinigen“, so dass sich Carol letztlich entschließt, in eine Art spirituelles Sanatorium zu ziehen, das in der Wüste liegt und von der Außenwelt abgeschieden ist. Doch auch hier hören ihre Anfälle nicht auf, am Ende bewegt sich Carol nur noch mit einer Sauerstoffflasche umher und bewohnt schließlich ein Porzellan-Iglu, das sie in größtmöglichem Maße vor allen schädlichen Umwelteinflüssen schützen soll. Die letzten Szenen von [SAFE] wirken, als zeigten sie eine surreale Mondlandschaft. Während also der Film die Existenz der Gefahr, der Carol ausgesetzt ist, nicht leugnet, macht er auf eine grundlegende Ironie aufmerksam: Das exzessive Streben nach Sicherheit für das Leben führt letztlich in eine Isolation, die selbst absolut unlebbar ist."
8620,Brief History of Pandemics (Pandemics Throughout History),"Intermittent outbreaks of infectious diseases have had profound and lasting effects on societies throughout history. Those events have powerfully shaped the economic, political, and social aspects of human civilization, with their effects often lasting for centuries. Epidemic outbreaks have defined some of the basic tenets of modern medicine, pushing the scientific community to develop principles of epidemiology, prevention, immunization, and antimicrobial treatments. This chapter outlines some of the most notable outbreaks that took place in human history and are relevant for a better understanding of the rest of the material. Starting with religious texts, which heavily reference plagues, this chapter establishes the fundamentals for our understanding of the scope, social, medical, and psychological impact that some pandemics effected on civilization, including the Black Death (a plague outbreak from the fourteenth century), the Spanish Flu of 1918, and the more recent outbreaks in the twenty-first century, including SARS, Ebola, and Zika."
8621,Plant Nanobionics: Application of Nanobiosensors in Plant Biology,"Nanobiosensors (NBSs) are a class of chemical sensors which are sensitive to a physical or chemical stimulus (heat, acidity, metabolism transformations) that conveys information about vital processes. NBSs detect physiological signals and convert them into standardized signals, often electrical, to be quantified from analog to digital. NBSs are classified according to the transducer element (electrochemical, piezoelectric, optical, and thermal) in accordance with biorecognition principle (enzyme recognition, affinity immunoassay, whole sensors, DNA). NBSs have varied forms, depending on the degree of interpretation of natural processes in plants. Plant nanobionics uses mathematical models based on qualitative and less quantitative records. NBSs can give information about endogenous concentrations or endogenous fluxes of signaling molecules (phytohormones). The properties of NBSs are temporal and spatial resolution, the ability of being used without significantly interfering with the system. NBSs with the best properties are the optically genetically coded NBSs, but each NBS needs specific development efforts. NBS technologies using antibodies as a recognition domain are generic and tend to be more invasive, and there are examples of their use in plant nanobionics. Through opportunities that develop along with technologies, we hope that more and more NBSs will become available for plant nanobionics. The main advantages of NBSs are short analysis time, low-cost tests and portability, real-time measurements, and remote control."
8622,Translational Recoding and RNA Modifications,"During protein synthesis, codons in mRNA are translated sequentially in frame on the ribosome following strict decoding rules. This process is usually very accurate. However, in some cases, recoding events occur at selected codons, leading to a high frequency of frameshifting or stop codon readthrough. The factors influencing these noncanonical decoding events are very diverse; among them are the codon usage and context, the presence of a stable mRNA secondary structure downstream of the decoding sites and the type and relative abundance of normally modified tRNA. Here, we discuss the role of certain modified nucleotides of tRNAs in a few cases of frameshifting and readthrough that occur in Bacteria and Eukarya. While in some cases the effect of a given modified nucleotide in a tRNA is to increase accuracy of the recoding process, in a few other cases the reverse has been observed. This review illustrates the power of using well characterized recoding systems, coupled with specific defects of RNA modification enzymes to assay for translational fidelity under in vivo conditions."
8623,The Changing Landscape for New Drug Development: Medical Countermeasures (MCMs) as a Case Study,"This chapter is comprised of materials adapted from previous publications authored by the Center for the Study of Drug Development at Tufts University School of Medicine (Tufts CSDD) over a ten-year period from 2010 through 2019. In addition, there are occasional infusions of updated commentary to “connect the dots” of how we got to where we are today. These publications may be requested from Tufts CSDD (if originally published in-house) or through the usual channels for requesting articles published in the public domain (permission to reprint the articles having been granted, where required). The text of the chapter is structured basically in a chronological fashion beginning with Tufts CSDD analysis of the early era of MCM evolution as a sub-sector from various extant therapeutic areas. It then chronicles the changes to the R&D paradigm in response to the challenges that emerged for both MCMs and biopharma in general. Finally, it ends with an exploration of the devolution of the MCM sub-sector back into its roots in the infectious disease area as an increase in actual outbreaks as well as other signals of global vulnerability to pandemic threats have minimized the MCM emphasis on biodefense against a wide range of CBRN agents in favor of public health tactics to address humankind’s maladaptation to a world in which it is constantly assailed by its microbial competitors and symbionts, or to novel public health crises of its own making."
8624,Pathologie,Im Rahmen der Pathologie („Lehre der Leiden“) werden Krankheiten aller Fachgebiete und deren grundlegende Prinzipien diagnostiziert und erforscht. Die vitale Diagnostik (am Lebenden) steht dabei immer mehr im Vordergrund.
8625,Neuroimaging,"Imaging of infection in the CNS has been handled using cross-sectional imaging for more than two decades now resulting in a large array of descriptive diagnostic criteria, capable, in most circumstances of narrowing the differential diagnosis, detecting life-threatening complications and establishing baseline for assessment of treatment response. Limitations however exist, and in many circumstances, both cross-sectional imaging and nonspecific molecular imaging, such as (18)F-FDG, fail to establish a diagnosis. The availability of pathogen-specific imaging agents/ligands would have a great effect on the management of patients with CNS infection. Besides early diagnosis, avoidance of diagnostic brain biopsies can have significant effect on the mortality and morbidity of patients."
8626,Pandemic,Pandemics such as the Black Death have altered the course of history. The ravages of the Spanish Flu pandemic were so terrible that at least one culture decided the most humane way of dealing with the aftermath was simply to ignore it—to pretend the disease had not happened. Could a new pandemic possibly be worse than the Black Death or the Spanish Flu? Could it be as bad as the Scarlet Plague of Jack London’s story?
8627,Acute Respiratory Distress Syndrome in Cancer Patients,"Acute respiratory distress syndrome (ARDS) is a heterogeneous form of acute, diffuse lung injury that is characterized by dysregulated inflammation, increased alveolar-capillary interface permeability, and non-cardiogenic pulmonary edema. In the general population, the incidence and mortality associated with ARDS over the last two decades have steadily declined in parallel with optimized approaches to pneumonia and other underlying causes of ARDS as well as increased utilization of multimodal treatment strategies that include lung-protective ventilation. In the cancer settings, significant declines in the incidence and mortality of ARDS over the past two decades have also been reported, although these rates remain significantly higher than those in the general population. Epidemiologic studies identify infection, including disseminated fungal pneumonias, as a major underlying cause of ARDS in the cancer setting. More than half of cancer patients who develop ARDS will not survive to hospital discharge. Those who do survive often face a protracted and often incomplete recovery, resulting in significant long-term physical, psychological, and cognitive sequelae. The residual organ dysfunction and poor functional status after ARDS may delay or preclude subsequent cancer treatments. As such, close collaboration between the critical care physicians and oncology team is essential in identifying and reversing the underlying causes and optimizing treatments for cancer patients with ARDS. This chapter reviews the diagnosis and common causes of ARDS in cancer and gives an update on the general management principles for cancer patients with ARDS in the ICU."
8628,Arena-Viren,"Die Gruppe der Arena-Viren (arenosus = körnig) umfasst das LCM-Virus (Meningitis des Menschen), das Virus des Lassa-Fiebers, eines nur in den Tropen vorkommenden schweren hämorrhagischen Fiebers sowie das Virus einer Reihe von südamerikanischen hämorrhagischen Fieber (z. B. Bolivianisches (Machupo-Virus) und Argentinisches (Jun-in-Virus) Hämorrhagisches Fieber)."
8629,Blut und Blutprodukte,"die Blutgruppe richtet sich nach der Antigeneigenschaft der Erythrozyten; die Blutgruppenantigene A und B des AB0-Systems befinden sich an der Erythrozytenoberfläche. Das Antigen 0 gibt es nicht, man spricht allenfalls vom Merkmal H; die Blutgruppe A lässt sich in A(1) und A(2) unterteilen. Der Hauptunterschied zwischen den Untergruppen besteht darin, dass die Agglutination von A(1)-Erythrozyten bei Kontakt mit Anti-A-Serum wesentlich stärker und rascher verläuft. Für die Transfusion ist diese Unterteilung nicht von Bedeutung, da Antigen-Antikörper-Reaktionen zwischen A(1) und A(2) sehr selten auftreten und nur sehr schwach sind (Verteilung: A(1) ≈ 20%, A(2) ≈ 80%);"
8630,Application of Service Robots for Disinfection in Medical Institutions,"Service robots are increasingly present in all fields of medicine. This paper presents a review of the service robots in medicine with an emphasis on service robots for disinfection in medical institutions. It is shown and described how more and more disinfectant service robots are contributing to a very simple, fast and effective disinfection in medical institutions. Work of the service robot with all necessary components for its function as well as its good and bad sides are in details elaborated and clarified. The aim is to demonstrate the application and use these service robots in medical institutions. Use of these service robots reduces the risk of infection, cost of traditional cleaning and disinfection, and most importantly acquires confidence and security in medical facilities."
8631,Seltene Infektionen und Hygiene auf der Intensivstation,"Ein Patient wird seit 2 Wochen auf der Intensivstation aufgrund einer infektexazerbierten chronisch obstruktiven Lungenerkrankung beatmet. Der Verlauf wurde durch eine nosokomiale Pneumonie kompliziert. Bei der Morgenvisite wird berichtet, dass der Patient innerhalb der letzten 2 h 4-mal massiv wässrig abgeführt hat. Die Temperatur beträgt 38,7°C, die Leukozyten 16.000/μl. Der Intensivarzt und seine Oberärztin besprechen die möglichen Ursachen und überlegen, ob spezielle Hygienemaßnahmen erforderlich sind."
8632,Perspectives on Global Public Health Informatics,"Public health professionals’ functions are rapidly expanding beyond their countries’ borders. Many academic centers are recognizing the importance of global health and are creating programs to train students to meet this growing demand. Global health centers and institutes also are being created to focus on the research and programmatic efforts needed to understand the burden of disease worldwide, as well as the financial, political, medical, policy, workforce, and infrastructure issues surrounding any solutions. Due to this emerging interest by the public health community, we need to understand where the intersection between global health and informatics occurs. For many years, the promise of what technology can do to alleviate suffering and support disease surveillance and other public health activities took precedence over understanding the environment in which the technology has to function. People and their participation in the implementation of the technological solution are critical for success. In resource-poor environments, the deployment of technological solutions faces other challenges for success. Lack of stable electrical power, availability of Internet connections, and a workforce that can support the information technology remain barriers to successful implementation. Yet, through experiences in the implementation of information technology as supported by international donors and the US President’s Emergency Plan for AIDS Relief, lessons are being learned to move forward towards the benefits that global health informatics can bring."
8633,Posttransplant Complications and Comorbidities,"Infectious complications cause significant acute morbidity and mortality after pediatric lung transplantation. With the lung graft in direct communication with the environment, it is susceptible to a variety of bacterial, fungal, and viral pathogens. Appreciation for pretransplant risk factors in addition to perioperative and posttransplant exposures is necessary to anticipate, diagnose, and treat infections in this population. Further, epidemiologic associations between infection and chronic allograft dysfunction have been reported and suggest consequences of infectious events may have substantial impact."
8634,Expected and Unexpected Effects of Vaccination,Vaccination is widely considered to be one of the greatest medical achievements of civilization and one of the top major breakthroughs of humanity.
8635,Pulmonology,"The pleura are composed of two layers, parietal and visceral layers, separated by a pleural space. The parietal pleuron is supplied by systemic vessels and drains into the right atrium via the azygos, hemiazygos, and internal mammary veins. The visceral pleuron is supplied by bronchial and pulmonary vessels and drains into the pulmonary veins."
8636,Zoonoses in Cancer Patients,"Prevention of zoonoses in cancer patients is the theme of this chapter and it is hoped that it will encourage and help doctors caring for such patients to educate them to avoid the infections. Avoidance need not include separation from a pet or occupation or recreation, but the use of caution conditioned by knowledge of the sources of infection and the ways we contact them should lead to effective prevention."
8637,Gastroenterology,"organic—infections, tumors, multiple sclerosis, vestibular nerve or brain stem lesions"
8638,Beauveria bassiana: Biocontrol Beyond Lepidopteran Pests,"Beauveria bassiana has been extensively employed since the last century for biocontrol of lepidopteran pests. B. bassiana has also been explored for diverse functions including bioremediation of toxic industrial effluents and heavy-metal polluted soils. Investigations on multifarious applications of chemically diverse secondary metabolites of this entomopathogenic fungus offer promising implications in pharmaceutical and agricultural sectors. In addition, the development of eco-friendly bioremediation strategies using abiotic stress-tolerant strains of B. bassiana will contribute to maintain the sustainability of agroecosystem."
8639,Pharmaceutical Intellectual Property Rights in China,"Recalling the history of China’s pharmaceutical intellectual property right (IPR) protection in the past 20 years, China adopted many international standards for pharmaceutical IPR protection. At the same time, China also issued a series of national regulatory policies to encourage domestic drug innovations (Ding, J Technol Manage Innov 6(2):1–13, 2011) . Therefore, both those policies for incentive innovations and the IPR laws have played important roles in drug development in China. As declared by the 17th National Congress in 2006, China’s national development core strategy has prioritized the adherence to regulatory policies in order to construct a technologically innovative country and the country also wishes to become a global leading country for the implementation of the intellectual properties by 2020 as declared in the “National Intellectual Property Strategy Compendium” by Chinese State Council in 2008. In this chapter, we’ll briefly introduce the basic knowledge of the Chinese IPR system, the key regulatory policies, and the differences between China and western countries. We hope this section for Pharmaceutical Patent Protection may help overseas and multinational pharmaceutical companies gain basic knowledge of IPR, design an optimized IPR protection strategy to best fit their products, and achieve a successful product protection for their intellectual property in China."
8640,Abdominalchirurgische Intensivmedizin,"Die Intensivmedizin in der Allgemeinchirurgie umfasst v. a. die Behandlung akuter Abdominalerkrankungen, wie z. B. der akuten Pankreatitis, gastrointestinaler Blutungen, Ileus und Peritonitis sowie postoperativer Komplikationen bei bauchchirurgischen Eingriffen, wie z. B. Peritonitis, Ileus oder Nachblutungen. Hinzu kommen die postoperative Intensivüberwachung und -behandlung größerer Operationen, bei denen in der Frühphase bestimmte Komplikationen zu erwarten sind. Nicht selten treten zu den spezifischen Risiken allgemeinchirurgischer Eingriffe postoperative Störungen einzelner oder mehrerer Organe hinzu und komplizieren den postoperativen Verlauf."
8641,Sessile Innate Immune Cells,"In this chapter, sessile cells of the innate immune system are briefly introduced. Defined as cells equipped with diverse pattern recognition molecules capable of detecting MAMPs and DAMPs, they encompass cells such as epithelial cells, fibroblasts, vascular cells, chondrocytes, osteoblasts, and adipocytes. Located at the body surfaces, epithelial cells represent the first line of innate immune defense against invading microbial pathogens. They are significant contributors to innate mucosal immunity and generate various antimicrobial defense mechanisms. Also, epithelial cells critically contribute to tissue repair via the phenomenon of re-epithelialization. Fibroblasts operate as classical sentinel cells of the innate immune system dedicated to responding to MAMPs and DAMPs emitted upon any tissue injury. Typically, fibroblasts synthesize most of the extracellular matrix of connective tissues, thereby playing a crucial role in tissue repair processes. Vascular cells of the innate immune system represent an evolutionarily developed first-line defense against any inciting insult hitting the vessel walls from the luminal side including bacteria, viruses, microbial toxins, and chemical noxa such as nicotine. Upon such insults and following recognition of MAMPs and DAMPs, vascular cells react with an innate immune response to create an acute inflammatory milieu in the vessel wall aimed at curing the vascular injury concerned. Chondrocytes, osteoblasts, and osteoclasts represent other vital cells of the skeletal system acting as cells of the innate immune system in its wider sense. These cells mediate injury-promoted DAMP-induced inflammatory and regenerative processes specific for the skeletal systems. Finally, adipocytes are regarded as highly active cells of the innate immune system. As white, brown, and beige adipocytes, they operate as a dynamic metabolic organ that can secrete certain bioactive molecules which have endocrine, paracrine, and autocrine actions."
8642,Blut und Blutprodukte,
8643,Infantile Viral Illnesses,"Viruses are the predominant cause of lower respiratory tract illness in infants and a major cause of hospitalization in this vulnerable population. This chapter will review the common respiratory viral agents in infants and young children, including epidemiology and clinical and radiographic features. The role of the laboratory in diagnosis is emphasized with respect to rapid diagnostic techniques and histopathologic features in tissue sections. A brief summary of each of the major infantile respiratory viruses is provided, including respiratory syncytial virus, parainfluenza virus, adenovirus, and influenza virus, as well as the more recently detected and increasingly significant lower respiratory tract viruses, such as human metapneumovirus, coronavirus, rhinovirus, and bocavirus. Congenital and neonatal forms of viral pneumonia, such as cytomegalovirus, herpes simplex virus, and measles virus, are also discussed. Postinfectious complications of viral bronchiolitis are included in this chapter due to the significant persistent morbidity during infancy in many patients."
8644,Zoonoses Animal and Human Diseases Endo and Ectoparasites Mainly Mammal I,"The definition of a zoonosis is that it must affect man but the term is used often outside of medical terminology of animal diseases where man is not involved. Zoonoses are diseases naturally transmitted between animals and man and comprise in total about 80% of all described human infections. Attempts have been made to define different classes of zoonoses according to the man-animal relationship but generally this does not seem to have been accepted. Elton in 1927 stressed the field of wild animal pathology was still virtually untouched, and in 1968 McDiarmid reiterated the view that it remained one of the most neglected aspects of animal ecology. There is now an extensive literature but it is rarely incorporated into ecological texts although disease is often the driving force in population dynamics. The primary driver of infectious disease dynamics is transmission between individuals, yet in most important respects remarkably little is known about the subject (Craft et al. 2008, Haydon 2008). Occasionally, under high population densities, an organism may infect a host outside of its normal range with highly pathogenic effect in its adventitious host."
8645,Corticosteroids,"CORTISOL secretion by the cortex of e adrenal glands (Fig. 32.1) increases in response to any stress in the body, whether physical (such as illness, trauma, surgery or temperature extremes) or psychological. However, this hormone is more than a simple marker of stress levels—it is necessary for the correct functioning of almost every part of the body. Excesses or deficiencies of this crucial hormone also lead to various physical symptoms and disease states [1]. Although cortisol is not essential for life per se, it helps an organism to cope more efficiently with its environment with particular metabolic actions on glucose production and protein and fat catabolism. Nevertheless, loss or profound diminishment of cortisol secretion leads to a state of abnormal metabolism and an inability to deal with stressors, which, if untreated, may be fatal [1, 2]."
8646,Cell Defence and Survival,"Central to immune defence mechanisms is the role of transcription factor nuclear factor kappa B (NF-kB). This is a complex biochemical topic with ever more controls revealed. NF-kB determines the production of proinflammatory cytokines and chemokines. Pharmacologists step in with possible means of control. Other systems involved in defence include the cyclooxygenase 2 (Cox-2) enzyme and perioxisome proliferator-activated receptors. Insulin receptor activation needs to be seen in context. The mTOR system directs uptake of nutrients by cells. mTOR is suppressed by rapamycin, whose usage is now quite considerable in the control of transplant rejection."
8647,An Innovative Big Data Predictive Analytics Framework over Hybrid Big Data Sources with an Application for Disease Analytics,"Nowadays, big data are everywhere. Examples of big data include weather data, web-search data, disease reports, as well as epidemic data and statistics. These big data can be easily generated and collected from a wide variety of data sources. A data science framework—such as predictive analytics framework—helps mining data from various big data sources to find useful information and discover knowledge, which can then be transformed into wisdom for appropriate actions. In this paper, we present an innovative big data predictive analytics framework over hybrid big data sources. To demonstrate the effectiveness and practicality of our framework, we conduct several case studies, including one on applying the framework to disease analytics. More specifically, we integrate, incorporate and analyze weather data and web-search data to predict and forecast dengue cases based on a hybrid of three kernels in support vector machine (SVM) ensemble. Results show how our predictive analytics framework benefits health agencies in disease control and prevention."
8648,"Atomic Force Microscopy: Interaction Forces Measured in Phospholipid Monolayers, Bilayers and Cell Membranes","Atomic force microscopy (AFM) is a powerful technique which is commonly used to image surfaces at the nanoscale and single-molecule level, as well as to investigate physical properties of the sample surface using a technique known as force spectroscopy. In this chapter, we review our recent research where we used AFM to investigate physical properties of phospholipid monolayers, bilayers, and cell membranes. We describe the experimental procedures for AFM imaging, force measurements, and theoretical models to analyze force spectroscopy data. The data obtained allowed correlations between AFM topography and local adhesion and mechanoelastic properties of supported lipid bilayers in water, supported pulmonary surfactant films in air, and the plasma membrane of epithelial type II cells. Finally, AFM was applied to help elucidate the effect of anesthetics and cholesterol present in the lipid films."
8649,Therapeutic Strategies for DLI: How Should DLI Be Treated?,"The lungs are vulnerable to toxins because of their large surface area and act as a metabolic site for some substances. Drugs may induce specific respiratory reactions, or the lungs may be affected as part of a generalized response. Drug-induced lung injury (DLI) can involve the airways, lung parenchyma, mediastinum, pleura, pulmonary vasculature, and/or the neuromuscular system. The most common form of DLI is drug-induced interstitial lung disease. There are no disease types specific to DLI, and DLIs are diagnosed on the basis of clinical findings, chest CT images, and histopathologic findings. The first principle of management of DLI is early detection and cessation of treatment with the suspected drug. Response to corticosteroid therapy depends on the histopathologic pattern of drug-induced interstitial lung disease. Prognosis depends on the specific drug and underlying clinical, physiologic, and pathologic severity of lung disease. To minimize DLI morbidity and mortality, all health-care providers should be familiar with the possible adverse effects of medications they prescribe. Individual variability in drug response is an important concern in clinical practice and drug development. Such variability is multifactorial and includes extrinsic factors such as environmental features and genetic and intrinsic factors that affect the pharmacokinetics and pharmacodynamics of drugs."
8650,Vaccines Against Viral Infections,"Vaccines are one of the miracles of modern medicine. Without vaccines, the population—particularly children—would be troubled with multitudinous infectious diseases such as diphtheria, scarlet fever, whooping cough, and measles, just to name a few. Vaccines are available against both viral and bacterial infections; they have saved millions of lives and continue to do so. The World Health Organization hopes to have vaccinated all children under a year old against most infectious diseases by 2020. The history of the public’s acceptance of vaccines has been a stormy one. Anti-vaccination movements have been active since the creation or development of the smallpox vaccine in the eighteenth century and in government-mandated vaccination until the present. An example of this is the fabricated information spread about the relationship between measles vaccine and autism. A successful polio vaccine was developed in the 1950s thanks to the research of three groups, led by Koprowski, Salk and Sabin, although each of these vaccines has its advantages and disadvantages. An oral vaccine has the advantage of ease of administration and a herd effect. Polio vaccine workers have become targets of extremists in Nigeria and Pakistan. Recently, recombinant DNA technology, was used to develop new vaccines in order to avoid the side effects, since live virus is not involved. The future may see the production of vaccines in edible plants, allowing for cheap production and ease in worldwide distribution."
8651,Sequential stages of clinical trials and overview of issues to be considered,
8652,Emerging and Enabling Technologies in Biodefense,"The emergence of new biotechnologies provides great promise for biodefense, especially for key objectives of biosurveillance and early warning, microbial forensics, risk and threat assessment, horizon scanning in biotechnology, and medical countermeasure (MCM) development, scale-up, and delivery. Understanding and leveraging the newly developed capabilities afforded by emerging biotechnologies require knowledge about cutting-edge research and its real or proposed application(s), the process through which biotechnologies advance, and the educational and research infrastructure that promotes multi-disciplinary science. Innovation in research and technology development are driven by sector-specific needs and the convergence of the physical, chemical, material, computer, engineering, and/or life sciences. Biotechnologies developed for other sectors could be applied to biodefense, especially if the individuals involved are able to innovate in concept design and development. Of all biodefense objectives, biosurveillance seems to have reaped the most benefit from emerging biotechnologies, specifically the integration and analysis of diverse clinical, biological, demographic, and other relevant data. More recently, scientists have begun applying synthetic biology, genomics, and microfluidics to the development of new products and platforms for MCMs. Unlike these objectives, investments in microbial forensics have been few, limiting its ability to harness biotechnology advances for collecting and analyzing data. Looking to the future, emerging biotechnologies can provide new opportunities for enhancing biodefense by addressing capability gaps."
8653,Biodiversity and the Ecology of Emerging Infectious Diseases,"The question of how biodiversity influences the emergence of infectious diseases is the subject of ongoing research. A set of nonlinear differential equations is been used to explore the interactions between ecology and epidemiology. The model allows for frequency-dependent transmission of infection within host species, and density-dependent transmission between species, via the environment or a vector. Three examples are discussed. It is shown that removing a pathogen may increase a consumer population, decreasing its resource. It is then shown that the presence of a pathogen could enable a predator and a prey species to coexist. Finally the dilution effect, by which increasing biodiversity reduces the transmission of an infectious disease, is investigated."
8654,Cervical: Lymphadenopathy,"The neck region contains around 300 lymph nodes (LNs) out of 800 LNs in the whole body. The detailed study of LNs by Rouviere in 1932 [1] and the later illustration of metastatic predilection of head and neck malignancies to certain LN regions by Lindberg et al. [2] paved the road to a clinically sound classification. The American Academy of Otolaryngology and Head and Neck Surgery (AAO-HNS) and the American Joint Committee on Cancer (AJCC) developed the currently widely accepted levels classification of the cervical LNs (Table 8.1, Figs. 8.1 and 8.2)."
8655,Update on Avian Influenza for Critical Care Physicians,"Human influenza pandemics over the last 100 years have been caused by H1, H2, and H3 subtypes of influenza A viruses. More recently, avian influenza viruses have been found to directly infect humans from their avian hosts. The recent emergence, host expansion, and spread of a highly pathogenic avian influenza (HPAI) H5N1 subtype in Asia has heightened concerns globally, both in regards to mortality of HPAI H5N1 in humans and the potential of a new pandemic. In response, many agencies and organizations have been working collaboratively to develop early detection systems, preparedness plans, and objectives for further research. As a result, there has been a large influx of published information regarding potential risk, surveillance, prevention and control of highly pathogenic avian influenza, particularly in regards to animal to human and subsequent human to human transmission. This chapter will review the current human infections with avian influenza and its public health and medical implications."
8656,Quantitative Reverse Transcriptase Polymerase Chain Reaction,"Since the first documentation of real-time polymerase chain reaction (PCR),(1) it has been used for an increasing and diverse number of applications, including mRNA expression studies, DNA copy number measurements in genomic or viral DNAs,(2–7) allelic discrimination assays,(8,9) expression analysis of specific splice variants of genes(10–13) and gene expression in paraffin-embedded tissues,(14,15) and laser captured microdissected cells.(13,16–19) Therefore, quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR) is now essential in molecular diagnostics to quantitatively assess the level of RNA or DNA in a given specimen. QRT-PCR enables the detection and quantification of very small amounts of DNA, cDNA, or RNA, even down to a single copy. It is based on the detection of fluorescence produced by reporter probes, which varies with reaction cycle number. Only during the exponential phase of the conventional PCR reaction is it possible to extrapolate back in order to determine the quantity of initial template sequence. The “real-time” nature of this technology pertains to the constant monitoring of fluorescence from specially designed reporter probes during each cycle. Due to inhibitors of the polymerase reaction found with the template, reagent limitation or accumulation of pyrophosphate molecules, the PCR reaction eventually ceases to generate template at an exponential rate (i.e., the plateau phase), making the end point quantitation of PCR products unreliable in all but the exponential phase."
8657,Food Security: Microbiological and Chemical Risks,"Food Security within a health security context relates to systems dealing with the prevention and control of not only acute but also sporadic and chronic foodborne diseases. The description of food security and safety systems in this chapter will hence include oversight of both microbiological and chemical hazards, which both can cause acute as well as chronic disease events. The Chapter includes a description of existing national and international surveillance systems for foodborne diseases and regulatory systems enabling risk mitigation action for both chemical and microbiological hazards, with specific inclusion of the concerning increase in antimicrobial resistance (AMR) of foodborne microorganisms also related to the animal production systems. The Chapter also includes descriptions of methodology for the quantitative assessment of sustainability of food production systems."
8658,Coronaviren,"Man unterscheidet 5 humanpathogene Coronaviren, die entweder zum Genus Alpha-Coronavirus oder zum Genus Beta-Coronavirus gehören (Subfamilie Coronavirinae, Familie Coronaviridae). Humane Coronaviren (◘ Tab. 58.1) verursachen akute Erkrankungen des oberen Respirationstraktes, die meist problemlos verlaufen, jedoch gelegentlich zu schweren Pneumonien führen. Eine ursächliche Beteiligung an Gastroenteritiden ist möglich, spielt jedoch klinisch und zahlenmäßig keine große Rolle. Zahlreiche animale Coronaviren sind vor allem an respiratorischen und gastrointestinalen Erkrankungen von Säugetieren und Vögeln beteiligt (◘ Tab. 58.1)."
8659,Cell Regeneration in Lung Injury,"The acute respiratory distress syndrome (ARDS) is a lethal inflammatory disorder of the lung. Its incidence is estimated at 75 cases per 100,000 population and appears to be increasing [1]. Even with optimal treatment, mortality is about 30% [1–3]. As such, ARDS represents a major public health problem. The effects of two recent crises created by unusual viral infections of the respiratory tract — the severe acute respiratory syndrome (SARS) epidemic caused by the novel SARS coronavirus [4], [5] and the bird flu [6] highlight the importance of research into ARDS. Both viruses cause an ARDS-like picture. Because lung repair and regeneration contribute substantially to the pathophysiology of ARDS, understanding these processes is essential [7]. This chapter focuses on specific cell populations and markers involved in cell division and regeneration. In addition, a brief review of two pathways intimately associated with cell division is provided because of their potential for pharmacologic manipulation."
8660,Kawasaki Disease,"Kawasaki disease is an acute systemic vasculitis syndrome in infants and young children of unknown etiology, which mainly affects small and medium-sized arteries, particularly the coronary artery. Clinical features include an acute febrile illness associated with mucocutaneous involvements and lymphadenopathy. The coronary aneurysms develop in about 10% to 20% of patients, some of which may cause myocardial infarction or lead to ischemic heart disease. Combinations of high-dose gamma globulin and aspirin are the essential treatments for acute Kawasaki disease patients. Bypass surgery and the catheter intervention are the optional treatments for the coronary artery sequelae of Kawasaki disease. Some patients with coronary artery sequelae may develop into adult coronary artery disease."
8661,Changing Resource-Based Manufacturing Industry: The Case of the Rubber Industry in Malaysia and Thailand,"This chapter explores the development potential of the rubber industry in Malaysia and Thailand, which have been leaders in the production of natural rubber (NR) since the 20th century. The analysis of NR producing (upstream segment), processing (midstream segment) and rubber-based manufacturing (downstream segment) in Malaysia and Thailand will find the different timing and sectoral composition in the development of the rubber sector of two countries. It will become clear that in spite of such differences, the two countries share a development pattern in one important respect: The public sector played a crucial role in the development of the upstream segment, while the successful development of the downstream segment largely depends on innovative activities of private entrepreneurs to explore niche international markets for specialized rubber products."
8662,"The Role of Informal Digital Surveillance Systems Before, During and After Infectious Disease Outbreaks: A Critical Analysis","Background One of the main limitations of traditional surveillance systems for disease detection is their inability to detect epidemics in real-time. In addition to syndromic surveillance, a number of informal digital resources have been developed. These systems are based on data collected through media sources such as news reports on the Internet, mailing lists, and RSS (Really Simple Syndication) feeds. The role of such systems at all stages of the epidemic remains unclear. Methods A literature review was carried out on informal digital resources for infectious disease surveillance. We examined the source of information, the manner in which they process and disseminate the information, their role in each phase of disease outbreaks, and whether and to what extent these systems are capable of early detection and management of infectious disease epidemics. Results Informal digital resources use similar sources of data for surveillance. However, they use different algorithms to create their output, and cover different geographic areas. In this regard, they complement each other with respect to information completeness. There is evidence in the literature on the systems’ usefulness in communicating information to public health professionals, as well as to the general public during and after previous epidemics. Retrospective studies of some systems have shown a theoretical decrease in the time of epidemic detection compared to conventional surveillance. However, there is no evidence of the ability for real-time detection. Conclusions Currently, there is little prospective evidence that existing informal systems are capable of real-time early detection of disease outbreaks. Most systems accumulate large amounts of information on a wide variety of diseases, making it difficult to extract critical information. Presenting critical information clearly and precisely remains a challenge."
8663,Extracorporeal Membrane Oxygenation in the Treatment of Novel Influenza Virus Infection: A Multicentric Hospital-Based Health Technology Assessment in Lombardy Region,"ECMO or Extracorporeal Membrane Oxygenation is a specialized heart-lung bypass machine used to take over the body’s heart and lung function while the body heals from injury or illness. One of the disturbing hallmarks of the novel A/H1N1 flu virus is that it produces severe lung damage resulting in ARDS (Acute Respiratory Distress Syndrome). Normally, patients with ARDS are placed on mechanical ventilation in Intensive Care Units (ICUs) and treated with a variety of pharmacological agents to reduce infection and lung inflammation. With A/H1N1 viral pneumonia, mechanical ventilation often does not result in adequate oxygenation so with ECMO the burden of pumping and oxygenating the blood is taken from the heart and lungs, and they are given time to heal. San Matteo Polyclinic Hospital was nominated by the Lombardy Region and the Ministry of Health as national reference for the installation of ECMO to deal severe heart failure and pulmonary caused by novel A/H1N1 flu virus. Clinical Engineering Department of the hospital had a fundamental coordination role in biomedical technology-related issues. It supported high-level management decisions (strategy, management, planning, procurement and maintenance) to answer to Lombardy’s guidelines about the organization of ECMO machines in the region. Moreover it had an important role in the assessment, by the use of HTA procedures, of ECMO alternative technologies."
8664,Rituximab-Related Pulmonary Toxicity,"We report the case of an 80-year-old man treated for follicular grade 3B non-Hodgkin’s lymphoma (NHL). Immunochemotherapy consisted of rituximab (375 mg/m(2)) and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) every 21 days. Since the patient complained of mild dyspnea on effort with bilateral basilar crackles audible on auscultation, PET-CT was performed and showed disappearance of the initial 18F-FDG uptake, but new abnormal sites of 18F-FDG uptake were evident in the sub-pleural areas of the lung, mostly on the right side. After starting the fifth cycle of rituximab-CHOP, the dyspnea worsened. Chest-X ray and HRCT were consistent with an interstitial infiltration, including sub-pleural air-space consolidation, and “ground-glass” opacities, small pulmonary cysts and thickening of the interlobular septa were also seen. Trans-bronchial biopsy was performed and revealed interstitial inflammation of the lung parenchyma, as well as swelling and hyperplasia of atypical type II alveolar cells. Alternative diagnoses than drug-related pulmonary toxicity are discussed, and a literature review is provided."
8665,Krankheitsbilder,"Das Spektrum der pneumologischen Krankheitsbilder ist groß und oft fächerübergreifend. Neben den häufigsten Erkrankungen wie COPD, Asthma bronchiale oder Tumoren des Thorax werden hier weitere häufige und seltene Erkrankungen dargestellt, die im Alltag das Bild einer pneumologischen Station prägen. Die führende Symptomatik, der diagnostische Weg und auch therapeutische Vorgehensweisen werden verständlich erörtert, um so den Umgang mit pneumologischen Erkrankungsbildern zu erleichtern."
8666,Pulmonary Hypertension in an Oncologic Intensive Care Unit,"Pulmonary hypertension (PH) is the condition of elevated pressures in the pulmonary circulation. PH can develop acutely in patients with critical illness such as acute respiratory distress syndrome, sepsis, massive pulmonary embolism, left ventricular dysfunction, or after surgery. In a cancer patient, unique etiologies such as myeloproliferative disorders, tyrosine kinase inhibitors, or tumor emboli may result in PH. Early recognition and treatment of the causative condition may reverse acute PH or return chronic PH to its baseline status. Progression of the disease or its decompensation due to infection, a thromboembolic event, or other triggers can lead to admission to an intensive care unit. Regardless of etiology, the development or worsening of PH may precipitate hypoxemia, hemodynamic instability, or right ventricular failure, which can be challenging to manage or even fatal. In select cases, rapid institution of advanced treatment modalities may be warranted. This chapter reviews the etiology, epidemiology, pathophysiology, clinical features, diagnosis, and prognosis of PH and presents a comprehensive analysis of PH and right heart failure management strategies in the critical care setting. In particular, a unique perspective on oncologically relevant PH is provided."
8667,Bakterielle Infektionen,"Vor der Einführung von Antibiotika führten schwere bakterielle Infektionen wie Sepsis, Diphtherie und Meningitis fast zwangsläufig zum Tod. Heute meist folgenlose Erkrankungen wie Typhus, Scharlach oder bakterielle Gelenksinfektionen führten früher zu Tod oder schweren Behinderungen. Gefahren gehen heute v. a. durch Resistenzentwicklungen gegen Antibiotika (z. B. bei der Tuberkulose) und durch mangelnde Impffreudigkeit (z. B. bei Diphtherie) aus. So sind bakterielle Infektionen weiterhin nicht zu verharmlosen."
8668,DNA Damaging Drugs,"The classical anti-cancer agents comprise cytotoxic compounds. Mostly, these drugs act by exerting DNA damage. In essence, there are two major response phenotypes available to a cell upon DNA damage, such as a chemotherapeutic drug action, to arrest the cell cycle and repair the damage, to initiate a pathway to apoptosis (programmed cell death)."
8669,Adeno-Viren,"Adeno-Viren erzeugen akute Erkältungskrankheiten, Konjunktivitis, Keratitis, Meningitis, Zystitis und Gastroenteritis. Sie wirken immunmodulatorisch und persistieren lange Jahre in den Tonsillen und können bei Immundefekten reaktiviert werden. Das Virus wurde erstmals 1953 in Explantaten von Tonslllengewebe anhand seines zytopathischen Effekts in vitro nachgewiesen. 1956 erhielten die Isolate die Bezeichnung “Adeno-Viren„ (Tonsillen = adenoides Gewebe). Der Typ 12 war das erste Human-Virus, bei dem man Tumorigenität im Tier beobachtete, beim Menschen gibt es keine entsprechenden Hinweise."
8670,Advances in Molecular Diagnostic Approaches for Biothreat Agents,"The advancement in Molecular techniques has been implicated in the development of sophisticated, high-end diagnostic platform and point-of-care (POC) devices for the detection of biothreat agents. Different molecular and immunological approaches such as Immunochromatographic and lateral flow assays, Enzyme-linked Immunosorbent assays (ELISA), Biosensors, Isothermal amplification assays, Nucleic acid amplification tests (NAATs), Next Generation Sequencers (NGS), Microarrays and Microfluidics have been used for a long time as detection strategies of the biothreat agents. In addition, several point of care (POC) devices have been approved by FDA and commercialized in markets. The high-end molecular platforms like NGS and Microarray are time-consuming, costly, and produce huge amount of data. Therefore, the future prospects of molecular based technique should focus on developing quick, user-friendly, cost-effective and portable devices against biological attacks and surveillance programs."
8671,Antimicrobial Use in Surgical Intensive Care,"Judicious antimicrobial use is essential in modern surgical intensive care. This requires careful clinical assessment and aggressive diagnostics to identify sources of infection as well as their noninfectious mimics. Because antimicrobial agents affect the ecology of resistant organisms in neighboring patients and the wider environment, as well as cause other common adverse effects, restrained initiation of antibiotics may be as valuable among hemodynamically stable patients with possible infection as is urgent empiric coverage in those threatening septic shock. Early collaboration with infectious disease and pharmacy consultants yields more appropriate treatment and improved morbidity, duration of hospital care, costs, and survival."
8672,Infection Prevention and Control: A Biodefense Measure,"Infection prevention and control (IPC) is the foundation for preventing the spread of infectious diseases, regardless of source, during medical treatment. Biological attacks will inevitably involve the medical management of sick individuals, which will not only tax the healthcare system, but also highlight the vital importance of infection control. Reducing the capacity for disease transmission will be pivotal in not only the early stages of an outbreak or biological attack, but also during times of crisis. Infection control programs also conduct disease surveillance and reporting to public health departments, which is crucial during an attack or outbreak. Infection control failures, like those in the 2013–2016 Ebola virus disease outbreak and continued Middle East respiratory syndrome (MERS) outbreaks, act as amplifiers for pathogen transmission. In the event of a biological attack, the strength and stamina of a hospital’s infection control program will be critical to early recognition, isolation, treatment, and reducing the spread of infection."
8673,China Declares Global State of Emergency: An Urgent Telegram from Taihu,"May 18th, 2013, China’s 4th most powerful politician, Yu Zhengsheng, Chairman of the National Committee of the CPPCC (Chinese People’s Political Consultative Conference) opened the Second Conference of the (carbon-neutralized) Taihu World Cultural Forum in Hangzhou, a city 1 h by speed train southwest of Shanghai. “What kind of a planet will we leave to our descendants? This is an urgent subject which deserves the collective attention of the whole world,” he said with a sincere air of emergency."
8674,"Disaster Response Policy Change in the Wake of Major Disasters, Labeled Focusing Events","Responding to the will of the people or the will of the government after a focusing event is complex and fraught with perils; this is none more so than after a major disaster that has brought on the sudden death of many people or the initial incalculable destruction of property or the environment. Korea has experienced several of these types of focusing events that have had major social and policy implications between the years 1948 and 2015. We analyzed them to glean their impact on disaster response policy, organizational and law reform, and first response and national countermeasures – and presented them in a clear and logical array so that the information could lead to a new type of disaster management model. Additionally, we look at how these focusing events altered the political, policy alternative and problem streams, as well as media coverage and policy change in the wake of the focusing event. And finally, we analyze disaster-triggered policy change in Korea to find out if the relation between the focusing event and institutional reforms for disaster response is path-dependent."
8675,Bio-Gefahren und Seuchen,"Zukunftsvorstellungen basieren gemeinhin auf Utopien, auf nur in der Vorstellung möglichen Szenarien. In diesen kommen haufenweise super-intelligente, metallisch glänzende neuartige Gegenstände, Roboter, fliegende Autos, Raumanzüge und Speisen in Pillenform vor. Es gibt aber auch Schreckensvisionen wie die von der Wiederkehr der Pest, die einst ein Drittel der europäischen Bevölkerung dahinraffte, oder von einer Influenza- Pandemie, wie sie 1918-19 wütete, und die 20 bis 40 Millionen Menschen das Leben kostete."
8676,Targeted Delivery of Surface-Modified Nanoparticles: Modulation of Inflammation for Acute Lung Injury,"Nanocarriers have been widely employed in the diagnosis and treatment of various diseases. The drug release kinetics and pharmacodynamics could be adjusted by changing the materials, designs, and physicochemical properties of the carriers. Furthermore, the carrier surface could be modified to minimize the particle clearance, increase the circulation duration, escape the biological protective mechanisms, penetrate through physical barriers, and prolong the residence of the drug at the target site. Among lung diseases, acute lung injury has been considered life-threatening with approximately 190,000 cases and 74,500 deaths per year in the USA. Numerous researches have reported the efficacy of drug-encapsulated nanoparticles in the treatment of acute lung injury. The use of nanoparticles could help minimize the effect of airway defenses in the lung, thus provides a prolonged retention, sustained drug release, and targeted delivery to the lung tissues. Meanwhile, the toxicity of nanoparticles in the lungs needs to be investigated thoroughly to alleviate the safety concerns. In this chapter, we discuss the targeted pulmonary delivery of surface-modified nanocarriers to efficiently treat acute lung injury."
8677,Gastrointestinal Infections,"Establishing a specific etiology for gastrointestinal infections can be challenging because of the common clinical features and wide variety of causative microorganisms. In many cases, the etiologic agent cannot be determined using traditional diagnostic methods and may result in unnecessary antibiotic use or prolonged periods of illness. Molecular tests provide many advantages over traditional laboratory methods but, with the exception of a few analytes, are still largely in the developmental phase for gastrointestinal pathogens and are not widely used. The main advantages of molecular tests include increased sensitivity and the ability to detect agents which will not grow in culture. To test for all possible gastrointestinal pathogens at one time would require a large panel that would include a variety of bacterial, viral and parasitic agents. Challenges inherent in developing diagnostic molecular panels include ensuring that all variants of a particular microorganism can be detected as well as the rapid evolution of pathogens. In this chapter, the diagnostic merit of molecular tests as well as available tests will be presented for the major groups of gastrointestinal pathogens."
8678,The Indonesian Construction Industry,"This chapter describes an overview of the Indonesian construction industry. It starts with introducing a general profile of the country, its location, demography, form of state and legal system, and its economic performance. This section is then followed by an overview of the Indonesian construction industry. It describes the industry’s activities, contribution to the national’s economic growth, its stakeholders and support infrastructure, regulations and management systems, latest developments and lessons learned. The third section is a description about Indonesian construction firms, which focuses on the contractors and their business activities. The last section of this chapter links the Indonesian contractors with the background of this study, which is a review of the crises faced by the Indonesian contractors."
8679,Antiviral Host Defence Peptides,"The ongoing global mortality and morbidity associated with viral pathogens highlights the need for the continued development of effective, novel antiviral molecules. The antiviral activity of cationic host defence peptides is of significant interest as novel therapeutics for treating viral infection and predominantly due to their broad spectrum antiviral activity. These peptides also display powerful immunomodulatory activity and are key mediators of inflammation. Therefore, they offer a significant opportunity to inform the development of novel therapeutics for treating viral infections by either directly targeting the pathogen or by enhancing the innate immune response. In this chapter, we review the antiviral activity of cathelicidins and defensins, and examine the potential for these peptides to be used as novel antiviral agents."
8680,Emerging and Transboundary Animal Viral Diseases: Perspectives and Preparedness,"The epidemics and pandemics of a few infectious diseases during the past couple of decades have accentuated the significance of emerging infectious diseases (EIDs) due to their influence on public health. Although Asia region has been identified as the epicentre of many EIDs and upcoming infections, several new pathogens have also emerged in the past in other parts of the world. Furthermore, the emergence of new viral diseases/infections, such as Rift Valley fever, West Nile fever, SARS coronavirus, Hendra virus, avian influenza A (H5N1), Nipah virus, Zika virus and swine influenza A (H1N1) virus, from time to time is a glaring example threatening adversely both animal and public health globally. Infectious diseases are dynamic and concerning due to their epidemiology and aetiological agents, which is manifested within a host, pathogen and environment continuum involving domestic animals, wildlife and human populations. The complex relationship among host populations and other environmental factors creates conditions for the emergence of diseases. The factors driving the emergence of different emerging infectious disease (EID) interfaces include global travel, urbanisation and biomedical manipulations for human EIDs; agricultural intensification for domestic animal EIDs; translocation for wildlife EIDs; human encroachment, ex situ contact and ecological manipulation for wildlife–human EIDs; encroachment, new introductions and ‘spill-over’ and ‘spill-back’; and technology and industry for domestic animal–human EIDs. The concepts of sanitary and phytosanitary (SPS) measures and biosecurity have gained recognition globally in almost all the realms of human activities, including livestock health and production management. This chapter provides the experience gained in the control and management of a few important TADs and EIDs along with the successes, constraints, limitations and future research needs for developing better control approaches."
8681,Natural Virucidal Compounds in Foods,"Many plant essential oils, extracts, and individual chemical components have been demonstrated to possess antiviral efficacy against enveloped and/or non-enveloped viruses. In general, plant antimicrobials exhibit greater antiviral efficacy against enveloped viruses than non-enveloped viruses (though not in all cases). There appear to be multiple mechanisms of antiviral action for plant antimicrobials; nevertheless, the majority of antimicrobials appear to act either directly on the virus itself (e.g., on the envelope or capsid) or during the early stages of virus replication following internalization of the virus into its host cell."
8682,Fuzzy Decision Making in Public Health Strategies,"Making decision is one of the most fundamental activities of human beings (Klir & Yuan, 1995; Yager & Filev, 1994; Zadeh, 1973). This is particularly true in Public Health where decisions usually have relevance for millions of people. In the field of vaccination strategies design, decision making concerning the target population for the immunization program, the proportion of susceptibles to be vaccinated, the optimal age to immunize children and the nature of the strategy, e.g. selective or indiscriminate, are examples of the variables to be optimized, subject to a set of constraints. As an example, we present in this chapter a fuzzy model to decision making applied to the design of the vaccination campaign against measles in São Paulo, Brazil (Massad et al., 1999)"
8683,Disasters as Extreme Events and the Importance of Network Interactions for Disaster Response Management,"We discuss why disasters occur more frequently and are more serious than expected according to a normal distribution. Moreover, we investigate the interaction networks responsible for the cascade-like spreading of disasters. Such causality networks allow one to estimate the development of disasters with time, to give hints about when to take certain actions, to assess the suitability of alternative measures of emergency management, and to anticipate their side effects. Finally, we identify other fields where network theory could help to improve disaster response management."
8684,Influenzavirus A/H1N1/2009 – ein Überblick vom Ausbruch bis zur Vakzination,"Influenzaepidemien und Influenzapandemien treten immer wieder auf, unterscheiden sich aber deutlich im Schwergrad der klinischen Symptome. Ein Beispiel hierfür ist der Ausbruch von Influenza A/H1N1/2009, der im April 2009 in Mexiko und Kalifornien beschrieben wurde und vermutlich schon einige Wochen zuvor aufgetreten war. Dieses Virus ist genetisch nicht näher mit der zirkulierenden saisonalen Influenza aber mit zirkulierenden Schweineviren verwandt. Der neue Virusstamm ist eine Reassortante zwischen zwei verschiedenen Virusstämmen, die bei Schweinen vorkommen, und kann nun auch von Mensch zu Mensch übertragen werden. Entsprechend den Leitlinien der WHO handelt es sich um ein pandemisches Virus, bis Juli 2010 wurden weltweit insgesamt ca. 18.000 Todesfälle gemeldet."
8685,Infektionskrankheiten,"Erreger. Morbilli-Virus, ein RNA-Virus aus der Familie der Paramyxoviren."
8686,Isolation Precautions for Visitors to Healthcare Settings,"Visitors may be involved in infection transmission within healthcare settings; however, there is currently limited published data on this subject. This chapter describes situations in which visitor-associated infection transmission occurred and highlights the potential role of visitors in the transmission of pathogenic organisms that can lead to outbreaks in healthcare settings. Infection prevention measures, including isolation precautions and visitor restriction, may be utilized and potentially adapted in order to protect patients and their visitors as well as healthcare personnel. The practical and ethical challenges regarding the use of isolation precautions among visitors to healthcare facilities are discussed."
8687,Adult Still’s Disease,1. The clinical features of adult Still’s disease resemble the systemic form of JRA a. Seronegative chronic polyarthritis associated with a systemic inflammatory illness b. Initially described in 1897 by George F. Still (pathologist) c. Subsequently detailed in adults in 1971 by Eric Bywaters 2. Epidemiology a. Rare b. Affects both genders equally c. Exists worldwide d. Majority present at age 16–35 years i. 75% before age 35
8688,Adverse Drug Reactions,"Adverse events and adverse drug reactions are common in clinical practice. Side effects range from the common to the rare and may be confused with other mucocutaneous manifestations resulting from several medications to treat infections, other medical conditions, and in the clinical setting of oncologic treatment. The objective of this chapter to review current data on adverse drug reactions, here classified as (i) severe adverse drug reactions, (ii) uncomplicated cutaneous adverse drug reactions, and (iii) adverse drug reactions caused by chemotherapy drugs, particularly those cases whereby the dermatologist is requested to issue a report and asked to comment on the safety and viability of readministration of a specific drug. We describe aspects associated with these events, presenting a detailed analysis of each of them."
8689,Special Engineering Aspects,"The specific characteristics of mammalian cells discussed in Chap. 2 require adapted solutions for bioreactor design and operation. Especially, cell damage by shear stress and aeration has to be considered. Therefore this chapter starts with a detailed discussion of shear stress effects on mammalian cells (anchorage-dependent and suspendable cells) in model systems and bioreactors, respectively, and consequences for reactor design. Appropriate oxygen supply is another critical issue, as adapted oxygen supply systems are required. Techniques for immobilization of cells, either grown on microcarriers in suspension culture or within macroporous carriers in fixed bed or fluidized bed reactors, are discussed as well. With respect to the operation of bioreactors, the characteristics of different culture modes (batch, fed-batch, chemostat, perfusion) are introduced and practical examples are given. Finally, concepts for monitoring of bioreactors, including offline and online methods as well as control loops (e.g. O(2), pH), are considered."
8690,Clinical Management of Patients Infected with Highly Pathogenic Microorganisms,"The clinical management of high consequence infectious diseases (HCID) poses an immense challenge, seen largely varying standards in terms of infection prevention control (IPC) as well as in quality of clinical care. This chapter gives an overview of possible treatment as well as IPC options. Lessons learned within the German Permanent Working Group of Competence and Treatment Centres for highly infectious, life-threatening diseases (STAKOB) are taken into account."
8691,Spezielle Erreger und Infektionen,"MRE, MRSA, VRE und andere Erreger bis hin zu den viralen hämorrhagischen Fiebererregern erfordern spezielle Risikoanalysen und risikoadaptierte Maßnahmen. Dieses Kapitel fasst die Empfehlungen zusammen und gibt tabellarische Übersichten, was wann zu tun ist."
8692,Major Advances in the Development of Synthetic Oligosaccharide-Based Vaccines,"Because of their involvement in a variety of different biological processes and their occurrence onto pathogens and malignant cell surface, carbohydrates have been identified as ideal candidates for vaccine formulation. However, as free oligosaccharides are poorly immunogenic and do not induce immunological memory in the most at risk population (infants and young children, elderly and immunocompromised patients), glycoconjugate vaccines containing the same carbohydrate antigen covalently linked to an immunogenic carrier protein have gained a prominent role. Accordingly, a number of glycoconjugate vaccines mostly directed against infections caused by bacterial pathogens have been licensed and are currently available on the market. However, also glycoconjugate vaccines suffer from significant drawbacks. The challenging procedures required for the isolation and purification of the carbohydrate antigen from its natural source often lead to poor homogeneity and presence of biological contaminants, resulting in batch-to-batch variability. Moreover, in some cases, the overwhelming immunogenicity of the carrier protein may induce the carbohydrate epitope suppression, causing hyporesponsiveness. The development of synthetic oligosaccharide-based vaccine candidates, characterized by the presence of pure and well-defined synthetic oligosaccharide structures, is expected to meet the requirement of homogeneous and highly reproducible preparations. In the present chapter, we report on the major advances in the development of synthetic carbohydrate-based vaccines. First of all, we describe different strategies developed during the last years to circumvent the inherent difficulties of classical oligosaccharide synthesis, such as the one-pot glycosylation and the solid-phase synthesis, and their application to the preparation of carbohydrate antigens apt to conjugation with protein carriers. Next, we discuss the most representative methodologies employed for the chemical ligation of oligosaccharide structures to proteins. Finally, in the last section, we report significant examples of fully synthetic vaccines exploiting the multivalency effect. These constructs are based on the concept that the conjugation of multiple copies of synthetic oligosaccharide antigens to multivalent scaffolds, such as dendrimers, (cyclo)peptides, gold nanoparticles, and calixarenes, raises cooperative interactions between carbohydrates and immune receptors, leading to strong enhancement of the saccharide antigen immunogenicity."
8693,Study on the Law of Diffusion of Sudden Pollutants in Subway Ventilation Shaft,"The underground subway stations have become the targets of terrorism due to the features of staff-intensive and poor ventilation. In the present study, the dynamic mesh model was used to predict the dynamic change of the flow field in the tunnel induced by the train motion. The DPM model was employed to simulate the interaction between the continuous phase of the air and the discrete phase of pollution particles. Accordingly, the dispersion of sudden pollutants released in the ventilation shaft was investigated. The results show that the submicron particles have a good following performance with the air. The dispersion characteristics of the particles highly depend on the unsteady flow field in the tunnel, which is significantly affected by the piston effect induced by the train motion. It can be concluded that particle diffusion experiences three stages: vertical forward and reverse diffusion in the wind shaft, vertical positive diffusion in the wind shaft, and longitudinal stable diffusion in the interval tunnel. It hopes that the study can provide guides for future biochemical protection in the subway system."
8694,Migration of NK cells,"NK cells were initially thought to be endowed with a particular migratory pattern and to mainly circulate in the blood. The recent findings reviewed here highlight that NK cells can exhibit different predilictions for tissue compartments, i.e., lymph nodes, inflamed tissues, etc., where they can play an important role as active participants in directing DC maturation and T cell response polarization and/or as cytotoxic effector cells. The mechanisms regulating tissue-selective NK cell homing and functional specialization are just starting to be unraveled, but the importance of tissue microenvironment is becoming increasingly clear. An example is given by decidual NK cells whose differentiation, accumulation and functional program are under hormonal influence."
8695,Infektionen,"Trotz Weiterentwicklung moderner Antibiotika in den letzten Jahren sind die Letalitätszahlen der bakteriellen (eitrigen) Meningitis weiterhin hoch; Überlebende haben häufig neurologische Residuen. Die ungünstigen klinischen Verläufe der bakteriellen Meningitis sind meist Folge intrakranieller Komplikationen, wie z. B. eines generalisierten Hirnödems, einer zerebrovaskulären arteriellen oder venösen Beteiligung oder eines Hydrozephalus."
8696,Koorts bij volwassenen,"Koorts wordt bij niet-immuungecompromitteerde volwassenen in de eerste lijn zonder recent verblijf in het buitenland meestal veroorzaakt door een luchtweginfectie. Bij ouderen vormen urineweginfecties een relatief frequente oorzaak van koorts. Bij ontbreken van richtinggevende voorgeschiedenis, klachten of verschijnselen volstaat men in eerste instantie met lichamelijk onderzoek van KNO-gebied en longen. Bij negatieve bevindingen volgt urineonderzoek. Wanneer geen afwijkingen gevonden worden, gaat men uit van een onschuldige virale oorzaak. Bij een ernstig zieke indruk of verminderd bewustzijn is het lichamelijk onderzoek allereerst gericht op eventuele stoornissen in de vitale functies, omdat deze onmiddellijke therapeutische implicaties hebben. Als de koorts een week aanhoudt of eerder bij verandering van het beeld, dient een uitgebreide anamnese en algemeen lichamelijk onderzoek plaats te vinden om diagnostische aanknopingspunten op te sporen. Ook kan de arts dan aanvullend onderzoek laten verrichten: in eerste instantie bloed-, urine- en fecesonderzoek en een X-thorax, eventueel gevolgd door X-sinussen en een mantoux-reactie. Medicatie wordt zo veel mogelijk gestaakt om een allergie aan te tonen of uit te sluiten. Na enkele dagen herhaalt men anamnese en lichamelijk onderzoek. Twee weken onbegrepen koorts is reden voor verdere (poli)klinische evaluatie. Concrete aanwijzingen op grond van steeds herhaalde anamnese en lichamelijk onderzoek zijn richtinggevend voor de inzet van complex aanvullend onderzoek. Dit bestaat onder meer uit bloedkweken, uitgebreider bloedonderzoek, leverbiopsie, beenmergpunctie en CT-scan buik en thorax. Bij patiënten ouder dan 55 jaar met koorts en een verhoogde bezinking is een biopsie van de arteria temporalis zinvol. ELEKTRONISCH AANVULLEND MATERIAAL: De online versie van dit hoofdstuk (doi:10.1007/978-90-368-1274-0_5) bevat aanvullend materiaal, dat beschikbaar is voor geautoriseerde gebruikers."
8697,Introduction to Computer Network Vulnerabilities,"System vulnerabilities are weaknesses in the software or hardware on a server or a client that can be exploited by a determined intruder to gain access to or shut down a network. Donald Pipkin defines system vulnerability as a condition, a weakness of or an absence of security procedure, or technical, physical, or other controls that could be exploited by a threat [1]."
8698,Plant Virus Diversity and Evolution,"Historically, the majority of plant virology focused on agricultural systems. Recent efforts have expanded our knowledge of the true diversity of plant viruses by studying those viruses that infect wild, undomesticated plants. Those efforts have provided answers to basic ecological questions regarding viruses in the wild, and insights into evolutionary questions, regarding the origins of viruses. While much work has been done, we have merely scratched the surface of the diversity that is estimated to exist. In this chapter we discuss the state of our knowledge of virus diversity, both in agricultural systems as well as in native wild systems, the border between these two systems and how viruses adapt and move across this border into an artificial, domesticated environment. We look at how this diversity has affected our outlook on viruses as a whole, shifting our past view of viruses as purely antagonistic entities of destruction to one where viruses are in a mutually beneficial relationship with their hosts. Additionally, we discuss the current work that plant virology has put forth regarding the evolutionary mechanisms, the life histories, and the deep evolution of viruses."
8699,"Phyllospheric Microbiomes: Diversity, Ecological Significance, and Biotechnological Applications","The phyllosphere referred to the total aerial plant surfaces (above-ground portions), as habitat for microorganisms. Microorganisms establish compositionally complex communities on the leaf surface. The microbiome of phyllosphere is rich in diversity of bacteria, fungi, actinomycetes, cyanobacteria, and viruses. The diversity, dispersal, and community development on the leaf surface are based on the physiochemistry, environment, and also the immunity of the host plant. A colonization process is an important event where both the microbe and the host plant have been benefited. Microbes commonly established either epiphytic or endophytic mode of life cycle on phyllosphere environment, which helps the host plant and functional communication with the surrounding environment. To the scientific advancement, several molecular techniques like metagenomics and metaproteomics have been used to study and understand the physiology and functional relationship of microbes to the host and its environment. Based on the available information, this chapter describes the basic understanding of microbiome in leaf structure and physiology, microbial interactions, especially bacteria, fungi, and actinomycetes, and their adaptation in the phyllosphere environment. Further, the detailed information related to the importance of the microbiome in phyllosphere to the host plant and their environment has been analyzed. Besides, biopotentials of the phyllosphere microbiome have been reviewed."
8700,Polymers in the Delivery of siRNA for the Treatment of Virus Infections,"Viral diseases remain a major cause of death worldwide. Despite advances in vaccine and antiviral drug technology, each year over three million people die from a range of viral infections. Predominant viruses include human immunodeficiency virus, hepatitis viruses, and gastrointestinal and respiratory viruses. Now more than ever, robust, easily mobilised and cost-effective antiviral strategies are needed to combat both known and emerging disease threats. RNA interference and small interfering (si)RNAs were initially hailed as a ‘‘magic bullet’’, due to their ability to inhibit the synthesis of any protein via the degradation of its complementary messenger RNA sequence. Of particular interest was the potential for attenuating viral mRNAs contributing to the pathogenesis of disease that were not able to be targeted by vaccines or antiviral drugs. However, it was soon discovered that delivery of active siRNA molecules to the infection site in vivo was considerably more difficult than anticipated, due to a number of physiological barriers in the body. This spurred a new wave of investigation into nucleic acid delivery vehicles which could facilitate safe, targeted and effective administration of the siRNA as therapy. Amongst these, cationic polymer delivery vehicles have emerged as a promising candidate as they are low-cost and easy to produce at an industrial scale, and bind to the siRNA by nonspecific electrostatic interactions. These nanoparticles (NPs) can be functionally designed to target the infection site, improve uptake in infected cells, release the siRNA inside the endosome and facilitate delivery into the cell cytoplasm. They may also have the added benefit of acting as adjuvants. This chapter provides a background around problems associated with the translation of siRNA as antiviral treatments, reviews the progress made in nucleic acid therapeutics and discusses current methods and progress in overcoming these challenges. It also addresses the importance of combining physicochemical characterisation of the NPs with in vitro and in vivo data."
8701,Host defenses,"Repeated episodes of viral upper respiratory tract infections occur anywhere from four to eight times per year in healthy individuals Local and systemic defense mechanisms exist to battle respiratory tract pathogens. Clinical manifestations are mainly due to host inflammatory response. Unfortunately, the host defense mechanisms are very often not sufficient to prevent subsequent/repeated episodes of infections(s). Further insight into the interaction of infectious agent and host immune response, genetic factors, and environmental factors is needed for a better understanding of why humans repeatedly and frequently suffer from infections with respiratory agents and develop a disease syndrome known as common cold."
8702,Helix-helix interaction patterns in membrane proteins,"Membrane-spanning α-helices represent major sites of protein-protein interaction in membrane protein oligomerization and folding. As such, these interactions may be of exquisite specificity. Specificity often rests on a complex interplay of different types of residues forming the helix-helix interfaces via dense packing and different non-covalent forces, including van der Waal’s forces, hydrogen bonding, charge-charge interactions, and aromatic interactions. These interfaces often contain complex residue motifs where the contribution of constituent amino acids depends on the context of the surrounding sequence. Moreover, transmembrane helix-helix interactions are increasingly recognized as being dynamic and dependent on the functional state of a given protein."
8703,Acute Respiratory Failure and Management,"Acute respiratory failure is a common reason for admission to the pediatric intensive care unit in oncology patients. Acute respiratory complications are also common after pediatric hematopoietic stem cell transplant (HSCT), accounting for a high proportion of HSCT-related morbidity and mortality. Evaluation of these patients requires a thorough workup that includes identification and treatment of infectious etiologies, and treatment for noninfectious causes once infectious causes are ruled out. These patients should be closely monitored for development of pediatric acute respiratory distress syndrome (PARDS) with early escalation of respiratory support. Patients undergoing a trial of noninvasive ventilation (NIV) should be continuously monitored to ensure they are responding. Prolonged delay of endotracheal intubation in patients who do not improve or worsen on NIV could worsen their outcome. Optimal treatment of immunocompromised patients with acute lung failure requires early and aggressive lung protective ventilation, prevention of fluid overload, and rapid diagnosis of underlying causes to facilitate prompt disease-directed therapy."
8704,Conclusion,"This chapter provides a summary of the global response to the AIDS pandemic and offers seven valuable lessons that can be learned from its history, which will hopefully be of value to the global community when confronted with future pandemics. These lessons relate to the behavior of donors, the importance of accountability, the need to understand the reality of the UN system, the advantage of a balanced and comprehensive approach to global challenges, and the importance of engaging civil society. The future of the World Health Organization, and its ability to provide leadership in addressing global pandemics and restore its credibility and legitimacy as the world’s leader in global health, is unclear. Hopefully, reforms now underway and the election of a new Director General, Tedros Ghebreyesus will enable this transformation."
8705,The Discovery and Early Clinical Evaluation of the HCV NS3/4A Protease Inhibitor Asunaprevir (BMS-650032),"The discovery of asunaprevir (1) began with the concept of engaging the small and well-defined S(1)’ pocket of the hepatitis C virus (HCV) NS3/4A protease that was explored in the context of tripeptide carboxylic acid-based inhibitors. A cyclopropyl-acyl sulfonamide moiety was found to be the optimal element at the P(1)-P(1)’ interface enhancing the potency of carboxylic acid-based prototypes by 10- to >100-fold, dependent upon the specific background. Optimization for oral bioavailability identified a 1-substituted isoquinoline-based P(2)* element that conferred a significant exposure advantage in rats compared to the matched 4-substituted quinoline isomer. BMS-605339 (30) was the first cyclopropyl-acyl sulfonamide derivative advanced into clinical trials that demonstrated dose-related reductions in plasma viral RNA in HCV-infected patients. However, 30 was associated with cardiac events observed in a normal healthy volunteer (NHV) and an HCV-infected patient that led to the suspension of the development program. Using a Langendorff rabbit heart model, a limited structure-cardiac liability relationship was quickly established that led to the discovery of 1. This compound, which differs from 30 only by changes in the substitution pattern of the P(2)* isoquinoline heterocycle and the addition of a single chlorine atom to the molecular formula, gave a dose-dependent reduction in plasma viral RNA following oral administration to HCV-infected patients without the burden of the cardiac events that had been observed with 30. A small clinical trial of the combination of 1 with the HCV NS5A inhibitor daclatasvir (2) established for the first time that a chronic genotype 1 (GT-1) HCV infection could be cured by therapy with two direct-acting antiviral agents in the absence of exogenous immune-stimulating agents. Development of the combination of 1 and 2 was initially focused on Japan where the patient population is predominantly infected with GT-1b virus, culminating in marketing approval which was granted on July 4, 2014. In order to broaden therapy to include GT-1a infections, a fixed dose triple combination of 1, 2, and the allosteric NS5B inhibitor beclabuvir (3) was developed, approved by the Japanese health authorities for the treatment of HCV GT-1 infection on December 20, 2016 and marketed as Ximency(®)."
8706,Rethinking Sepsis: New Insights from Gene Expression Profiling Studies,"Critically ill patients encompass an enormously heterogeneous population and, as such, therapeutic interventions, including drug therapy, can produce multiple outcomes in different patient subgroups. For example, researchers not only look for an ‘average effect’ of a drug on a typical patient, but also seek to understand individual variability. The presence of variability impacts significantly on the success of clinical trials and failure to identify this variability can result in the clinical trial being under-powdered to detect a treatment effect. For clinicians, failure to recognize variability can result in unintended toxicity or excessive harm in certain patients. Hence, understanding variability is critically important in both research and clinical practice."
8707,Fortsetzung des Wandels unter Präsident Mbeki (1999–2009),"Sowohl seitens des ANC als auch der SACP, und zwar vor wie nach den Wahlen 1999, wurde die fortdauernde Bedeutung des RDP hervorgehoben und es kam zu einer auch vom COSATU unwidersprochenen und geradezu zelebrierten Neubestätigung bzw. Wiederbestätigung des RDP („reaffirmation of the RDP“) durch die Tripartite Alliance."
8708,Nanoparticles as Precious Stones in the Crown of Modern Molecular Biology,"The interdisciplinary field of research on biosystems at the nanoscale involving physical sciences, molecular engineering, biology, biotechnology, and medicine supplements the knowledge of synthesizing new drugs, targeted delivery, regenerative medicine, and neuromorphic engineering forms the booming research in the present society. The present chapter deals with the role of nanoparticles in modern molecular biology. This is an interesting area of research that creates great impact on the healthcare of the society. The prime focus is to give the reader a historic background of nanomaterial application in biology and medicine. We have also provided the overview of most recent developments in this field leading to discussion of hard road to commercialization."
8709,Multi-agents Simulation on Unconventional Emergencies Evolution Mechanism in Public Health,"Based on the cellular automaton principle and multi-agents theory of complex systems, this essay studied the public health unconventional emergencies generation and evolution mechanism, established evolution model and carried out simulation of the public health unconventional emergencies evolution mechanism, and finally took SARS emergency for an example. Research results showed that the evolution of the public health emergency often promots other linkage emergencies, the damage of linkage system is larger than that of promotion system, and the damage is uncontrolled except for controlling the promotion system effectively, just like isolation measures or inject vaccine for individual of the promotion system so as to prevent promotion system from producing linkage hazards."
8710,Regional Innovation Systems Analysis and Evaluation: The Case of the Czech Republic,"Regional innovation systems (RIS) have become a very important regional policy instrument. This instrument is based on linkages among the region’s institutions from the public and private sector. These linkages are very important because they provide an environment for the innovation process, which is the primary goal of the RIS. In this paper, we have defined and described the main characteristics common to every RIS. Knowledge of these characteristics allows us to create a new method to make it possible to analyze individual RISes. The goal of this chapter is to present a new method for evaluating RISes. The method must by easily applied in order for it to be used practically to map the development of the individual innovative systems in a region. The method is based on evaluating both qualitative and quantitative indicators and on applying WSA methods. The paper presents the application of this method on individual regions in the Czech Republic (NUTS3)."
8711,"Live-Attenuated Bacterial Vectors for Delivery of Mucosal Vaccines, DNA Vaccines, and Cancer Immunotherapy","Vaccines save millions of lives each year from various life-threatening infectious diseases, and there are more than 20 vaccines currently licensed for human use worldwide. Moreover, in recent decades immunotherapy has become the mainstream therapy, which highlights the tremendous potential of immune response mediators, including vaccines for prevention and treatment of various forms of cancer. However, despite the tremendous advances in microbiology and immunology, there are several vaccine preventable diseases which still lack effective vaccines. Classically, weakened forms (attenuated) of pathogenic microbes were used as vaccines. Although the attenuated microbes induce effective immune response, a significant risk of reversion to pathogenic forms remains. While in the twenty-first century, with the advent of genetic engineering, microbes can be tailored with desired properties. In this review, I have focused on the use of genetically modified bacteria for the delivery of vaccine antigens. More specifically, the live-attenuated bacteria, derived from pathogenic bacteria, possess many features that make them highly suitable vectors for the delivery of vaccine antigens. Bacteria can theoretically express any heterologous gene or can deliver mammalian expression vectors harboring vaccine antigens (DNA vaccines). These properties of live-attenuated microbes are being harnessed to make vaccines against several infectious and noninfectious diseases. In this regard, I have described the desired features of live-attenuated bacterial vectors and the mechanisms of immune responses manifested by live-attenuated bacterial vectors. Interestingly anaerobic bacteria are naturally attracted to tumors, which make them suitable vehicles to deliver tumor-associated antigens thus I have discussed important studies investigating the role of bacterial vectors in immunotherapy. Finally, I have provided important discussion on novel approaches for improvement and tailoring of live-attenuated bacterial vectors for the generation of desired immune responses."
8712,Communication III (Immunological Control),"One of controlling systems in the body which the body also uses for communication (externally and internally) is the Immune system, based upon existence of MHC molecules fundamental for recognition, and other molecules responsible for antigen-presentation and immediate or postponed reaction to it. The fundamental unique feature of immune system cells is the capability of distinguishing “self” from “non-self” cells and proteins. Communication between different cell types of the immune system is critical in the recognition of self, surveillance, defense, and clearance of foreign invaders. These signaling mechanisms involve direct cell–cell signaling as well as autocrine and paracrine signaling. The essential feature of particular cells of immunological system is memory and although still known at the level of phenomenology, presents the basis for vaccines."
8713,Genus Parapoxvirus,"Highly contagious pustular skin infections of sheep, goats and cattle that were unwittingly transmitted to humans from close contact with infected animals, have been the scourge of shepherds, herdsmen and dairy farmers for centuries. In more recent times we recognise that these proliferative pustular lesions are likely to be caused by a group of zoonotic viruses that are classified as parapoxviruses. In addition to infecting the above ungulates, parapoxviruses have more recently been isolated from seals, camels, red deer and reindeer and most have been shown to infect man. The parapoxviruses have one of the smallest genomes of the poxvirus family (140 kb) yet share over 70% of their genes with the most virulent members. Like other poxviruses, the central core of the genomes encode factors for virus transcription and replication, and structural proteins, whereas the terminal regions encode accessory factors that give the parapoxvirus group many of its unique features. Several genes of parapoxviruses are unique to this genus and encode factors that target inflammation, the innate immune responses and the development of acquired immunity. These factors include a homologue of mammalian interleukin (IL)-10, a chemokine binding protein and a granulocyte-macrophage colony stimulating factor /IL-2 binding protein. The ability of this group to reinfect their hosts, even though a cell-mediated memory response is induced during primary infection, may be related to their epitheliotropic niche and the immunomodulators they produce. In this highly localised environment, the secreted immunomodulators only interfere with the local immune response and thus do not compromise the host’s immune system. The discovery of a vascular endothelial growth factor-like gene may explain the highly vascular nature of parapoxvirus lesions. There are many genes of parapoxviruses which do not encode polypeptides with significant matches with protein sequences in public databases, separating this genus from most other mammalian poxviruses. These genes appear to be involved in inhibiting apoptosis, manipulating cell cycle progression and degradation of cellular proteins that may be involved in the stress response, thus allowing the virus to subvert intracellular antiviral mechanisms and enhance the availability of cellular molecules required for replication. Parapoxviruses in common with Molluscum contagiosum virus lack a number of genes that are highly conserved in other poxviruses, including factors for nucleotide metabolism, serine protease inhibitors and kelch-like proteins. It is apparent that parapoxviruses have evolved a unique repertoire of genes that have allowed adaptation to the highly specialised environment of the epidermis."
8714,B-Cell Targeted Therapies in Autoimmune Cytopenias and Thrombosis,"Ever since the advent of Rituximab and subsequently the emergence of other compounds targeting B cells, a cornucopia of medical applications have been found for this family of compounds. After their establishment as standard of care in many conditions such as rituximab in lymphoma and rheumatoid arthritis, they have been progressively found to aid in the treatment of many other conditions. This area constituted a fertile area of research in the past 12 years. Physicians have investigated the B-cell depleting agents use in cases of autoimmune hematologic cytopenias such as immune thrombocytopenia, Evans syndrome, cold and warm autoimmune hemolytic anemia, and other thrombophilic disorders such as the antiphospholipid syndrome and thrombocytopenic purpura. This chapter presents a historical perspective reviewing the various studies that have been published in this field. In addition, it offers a current assessment of the evidence regarding the use of B-cell depleting agents in the aforementioned conditions."
8715,The Use of Antimicrobial Nanoparticles to Control Oral Infections,"The potential of antimicrobial nanoparticles to control oral infections is reviewed. Such particles can be classified as having a size no greater than 100 nm and are produced using traditional or more novel techniques. Exploitation of the toxic properties of nanoparticles to bacteria, fungi and viruses, in particular metals and metal oxides, and their incorporation into polymeric materials have increased markedly over the past decade. The potential of nanoparticles to control the formation of biofilms within the oral cavity, as a function of their biocidal, anti-adhesive and delivery capabilities, is now receiving close attention. The latest insights into the application of nanoparticles within this field, including their use in photodynamic therapy, will be discussed. Possible approaches to alter biocompatibility and desired function will also be covered."
8716,The Biological Fight Against Pathogenic Bacteria and Protozoa,"The animal gastrointestinal tract is a tube with two open ends; hence, from the microbial point of view it constitutes an open system, as opposed to the circulatory system that must be a tightly closed microbial-free environment. In particular, the human intestine spans ca. 200 m(2) and represents a massive absorptive surface composed of a layer of epithelial cells as well as a paracellular barrier. The permeability of this paracellular barrier is regulated by transmembrane proteins known as claudins that play a critical role in tight junctions."
8717,Tuberkulose und andere durch Luft übertragbare Infektionserkrankungen: Krankenhaushygiene zur Vermeidung und Eindämmung,"Die Tuberkulose (TB) gehört weltweit zu den am häufigsten auftretenden Infektionskrankheiten und wird fast ausschließlich über die Luft (aerogen) übertragen. Nachdem in Deutschland die Lungentuberkulosefallzahlen über Jahre hinweg stagnierten, ist seit 2013 wieder ein Anstieg der Inzidenzen zu verzeichnen (RKI 2016). Als Ursache hierfür werden die aktuellen demographischen Entwicklungen (Migration und Mobilität) gesehen. Die Kenntnis der epidemiologischen Situation ist von zentraler Bedeutung, um bei Vorliegen der Verdachtsdiagnose Tuberkulose sowie der Einbeziehung einer möglichen Resistenzproblematik frühzeitig adäquate krankenhaushygienische Maßnahmen einzuleiten. Als aerogen übertragbar werden auch die Aspergillose sowie Masern, Windpocken und Herpes zoster eingestuft (CDC 2007). Die Aspergillose ist eine relativ seltene, aber häufig letal verlaufende Pilzinfektion, die überwiegend bei immunsupprimierten Patienten auftritt. Krankenhaushygienische Schutzmaßnahmen können die Risiken einer Exposition und somit das Erkrankungsrisiko minimieren. Die zentralen Maßnahmen zur Kontrolle und Prävention von aerogen übertragbaren Infektionen sind Gegenstand dieses Kapitels."
8718,Nierentransplantation,"Die Nierentransplantation ist die effektivste Behandlungsmethode der chronischen terminalen Niereninsuffizienz. Seit den 1960er Jahren entwickelte sie sich zu einer Standardtherapie. Wichtige Voraussetzungen waren die Entdeckung des HLASystems, die Entwicklung der Immunsuppressiva sowie die technische Perfektionierung des Organerhaltes außerhalb eines lebenden Körpers. Die 5- Jahres-Überlebensrate für Allotransplantate beträgt etwa 65%, diejenige von Lebendspenden 79%. Die Einrichtung von zentralen Erfassungsstellen, wie z. B. Eurotransplant (Deutschland, Benelux- Staaten, Österreich, Slowenien), ist für die Organisation des zeitgebundenen Ablaufes von großer Bedeutung. Bei diesen Institutionen sind alle potentiellen Nierenempfänger registriert. Dort werden auch alle potentiellen Spenderorgane gemeldet und dem passenden Empfänger zugeordnet."
8719,Nanomolecular Diagnostics,"Clinical application of molecular technologies to elucidate, diagnose, and monitor human diseases is referred to as molecular diagnosis. It is a broader term than DNA (deoxyribonucleic acid) diagnostics and refers to the use of technologies that use DNA, RNA (ribonucleic acid), genes, or proteins as bases for diagnostic tests. The scope of the subject is much wider and includes in vivo imaging and diagnosis at the single-molecule level. A more detailed description of molecular diagnostics is presented elsewhere (Jain 2012a)."
8720,Modeling and Predicting Human Infectious Diseases,"The spreading of infectious diseases has dramatically shaped our history and society. The quest to understand and prevent their spreading dates more than two centuries. Over the years, advances in Medicine, Biology, Mathematics, Physics, Network Science, Computer Science, and Technology in general contributed to the development of modern epidemiology. In this chapter, we present a summary of different mathematical and computational approaches aimed at describing, modeling, and forecasting the diffusion of viruses. We start from the basic concepts and models in an unstructured population and gradually increase the realism by adding the effects of realistic contact structures within a population as well as the effects of human mobility coupling different subpopulations. Building on these concepts we present two realistic data-driven epidemiological models able to forecast the spreading of infectious diseases at different geographical granularities. We conclude by introducing some recent developments in diseases modeling rooted in the big-data revolution."
8721,Diagnostic Approach to Life-Threatening Pulmonary Infiltrates,"Diagnosis of pulmonary disease is typically based upon consideration of presenting symptoms, physical examination, and pulmonary function testing in combination with classification of radiographic features, to guide diagnostic tests and initiate empiric treatment. When diagnostic efforts and/or empiric treatment fails, thoracic surgeons have traditionally been called upon to perform surgical biopsy of the lung to aid in the diagnosis of indeterminate, life-threatening pulmonary disease. Such biopsy has been requested specifically in the case of diffuse lung disease among patients receiving treatment for solid-organ or hematologic cancers, particularly when symptoms of respiratory failure progress and when noninvasive diagnostic tests and empiric treatments fail to halt progression. In such circumstances, radiologists, pulmonologists, and thoracic surgeons may be consulted and asked to provide tissue specimens that will allow rapid, accurate diagnosis leading to specific treatment. It is imperative that biopsy take place before respiratory failure supervenes [1], and that the specimens provided to clinical laboratories, pathologists, and microbiologists are comprehensive and properly preserved."
8722,"Pederin, Psymberin and the Structurally Related Mycalamides: Synthetic Aspects and Biological Activities","Pederin, psymberin, and mycalamides are related members of a relatively new family of potent natural antiviral and antitumor compounds originally isolated from marine sponges in 1988. This natural family of chemicals is of great interest to medicinal chemists and biologists, stemming from its extremely low abundance in source organisms and strikingly potent biological activity. They have clearly emerged as promising new synthetic targets, and are the focus of quite an interdisciplinary approach to molecular characterization. In this chapter we review diverse synthetic approaches to this family of natural products that has been demonstrating remarkable biological activity. We discuss relevant history, biological origins with the latest information on source organisms and their hosts, in-depth synthetic approaches, and biological data supporting their potential as therapeutic compounds."
8723,Transformation and Carcinogenesis,"It was acknowledged long ago that viruses may cause cancer in animals. In 1911, Peyton Rous described viruses as causing sarcomas in poultry. The tumour-inducing virus responsible was later named after him, Rous sarcoma virus. In the following decades, a large number of viruses were discovered that can cause various cancers in poultry and rodents, such as lymphomas, sarcomas and carcinomas. Many of them belong to the family Retroviridae, and were classified into the genera Alpharetrovirus, Betaretrovirus and Gammaretrovirus. Most of these pathogens were isolated from inbred strains of the respective species or from cell cultures; under natural conditions, these strains are likely irrelevant as a cause of cancer in the corresponding species. An exception is feline leukaemia virus (10.1007/978-3-642-20718-1_18). The tumorigenic potential of oncogenic retroviruses is based on transformationally active proteins. They are similar to cellular products which are ordinarily involved in the regulation of cell division. In contrast to the cellular products, viral oncogene proteins are altered by mutations in such a way that they are not subject to regulatory control, and are thus constitutively active. In fact, the discovery of viral oncogenes was pioneering and has paved the way for deciphering cellular oncogenes, and thus for understanding the molecular basis of carcinogenesis. Evidence for the existence of retroviruses that cause cancer in humans was found only in 1982 when Robert Gallo discovered human T-lymphotropic virus (HTLV; 10.1007/978-3-642-20718-1_18)."
8724,Disaster Risk Management in China,"Disasters have been endemic throughout history. In Judeo history, the flood survived by Noah was about as complete a disaster to contemporary humankind as can be imagined. Egypt was plagued with droughts and floods of the Nile. In Greek/Roman culture, events such as eruptions of Mount Vesuvius caused tremendous suffering and damage. Similar disasters disrupted human activity throughout the world, to include unrecorded events at Easter Island. The International Federation of Red Cross and Red Crescent Societies stated that over a recent 10 year period, almost two billion people have been affected by disasters. People in Asia accounted for almost 89% of the population affected by natural disasters between 1975 and 2003."
8725,The Impact of Movement on Disease Dynamics in a Multi-city Compartmental Model Including Residency Patch,"The impact of population dispersal between two cities on the spread of a disease is investigated analytically. A general SIRS model is presented that tracks the place of residence of individuals, allowing for different movement rates of local residents and visitors in a city. Provided the basic reproduction number is greater than one, we demonstrate in our model that increasing the travel volumes of some infected groups may result in the extinction of a disease, even though the disease cannot be eliminated in each city when the cities are isolated."
8726,Pandemic Influenza Planning for the Mental Health Security of Survivors of Mass Deaths,"Influenza A pandemics have been documented to occur at 10- to 50-year intervals—an average of three events per century, dating back from the 16th century. Each recorded pandemic has resulted in an increase in annual mortality rates in the infected population, with mass deaths in one pandemic wave equalling fatalities sustained over six months of an epidemic season. This chapter aims to rectify the oversight in pandemic preparedness plans by presenting a compendium of guidelines and recommendations by international health organisations, pandemic fatality experts, and experienced mass death management professionals. Its objective is to have available a mass fatality framework to complement the WHO Pandemic Influenza Preparedness and Response (2009) guideline, from which individual national pandemic preparedness plans are based. It is written in a format that incorporates WHO’s emphasis on finding the ethical balance between human rights and successful plan implementation; the assimilation of national pandemic plans with existing national emergency measures; and the ‘whole group’ system of engaging individuals, families, localities, and business establishments in the process. This chapter is also written such that it can be made applicable to analogous infectious disease outbreaks such as SARS and Ebola, as well as comparable mass fatality events."
8727,The Biologics Revolution and Endotoxin Test Concerns,"The advent of “at will” production of biologics in lieu of harvesting animal proteins (i.e. insulin) or human cadaver proteins (i.e. growth hormone) has revolutionized the treatment of disease. While the fruits of the biotechnology revolution are widely acknowledged, the realization of the differences in the means of production and changes in the manner of control of potential impurities and contaminants in regard to the new versus the old are less widely appreciated. This chapter is an overview of the biologics revolution in terms of the rigors of manufacturing required to produce them, their mechanism of action, and caveats of endotoxin control. It is a continulation of the previous chapter that established a basic background knowledge of adaptive immune principles necessary to understand the mode of action of both disease causation and biologics therapeutic treatment via immune modulation."
8728,"Intraoperativer Volumenersatz, Transfusion und Behandlung von Gerinnungsstörungen",Sowohl der operative Eingriff als auch die Narkose führen zu Veränderungen des intravasalen Volumenstatus des Patienten.
8729,Modelling of Experimental Infections,"This chapter aims to give a clear idea of how mathematical analysis for experimental systems could help in the process of data assimilation, parameter estimation and hypothesis testing."
8730,Metaphernreflexion und -analyse in sozialwissenschaftlichen Disziplinen,"Im vierten Kapitel erfolgt eine umfassende Rekonstruktion von Metaphernanalysen in den Disziplinen Soziologie, Erziehungswissenschaften, Soziale Arbeit, Politologie, Gesundheitswissenschaften und Psychologie sowie in einem Exkurs zur Geschlechterforschung. Metaphernanalysen haben sich in den verschiedenen Bereichen seit der Herausbildung des für sozialwissenschaftliche Forschungen anschlussfähigen Metaphernbegriffs in unterschiedlichem Tempo und mit heterogener Methodik entwickelt. Hier interessieren die bereits explorierten Fragestellungen, ihre Ergebnisse und die im Feld entwickelten methodische Besonderheiten."
8731,Genotyping Arrays,"Although the most common use of DNA microarrays is gene expression profiling, microarrays are also used for many other applications, including genotyping, resequencing, SNP analysis, and DNA methylation assays. Here we describe genotyping arrays for Influenza A subtype identification and for upper respiratory pathogen diagnostics using standard hybridization techniques and we also describe resequencing, SNP, and methylation assays using an enzyme-based strategy [25, 26]."
8732,Differential Diagnosis of Vasovagal Syncope: Postural Orthostatic Tachycardia,"Postural tachycardia syndrome (POTS) is a syndrome defined as an increase in heart rate (HR) of ≥30 bpm within 10 min of assuming an upright posture in the absence of orthostatic hypotension (decrease in blood pressure (BP) >20/10 mmHg). The prevalence of POTS has been estimated as 500,000–3,000,000 patients in the USA. Because it affects mainly women between 13 and 50 years of age, the impact on productivity at work and lifestyle can be devastating. Considerable clinical overlap exists between POTS and vasovagal syncope (VVS) with patients experiencing similar orthostatic symptoms related to insufficient adaptation to blood volume shifts during upright posture. Nevertheless, differences emerge during head up tilt table testing. In patients with POTS, during upright tilt, sympathetic tone increases, there is an early and sustained tachycardia, and patients complain of presyncope without frank syncope. In contrast, patients with VVS experience delayed symptoms and abrupt drops in BP and HR and are more likely to lose consciousness. Treatment of POTS includes exercise and medications directed at decreasing sympathetic tone or increasing blood volume."
8733,History Repeating? A Comparison of the Launch and Uses of Fixed and Mobile Phones,
8734,Health Effects of Changing Environment,"Environment plays a crucial role in our economic, social and cultural behaviour as well as on health. However, since the beginning of industrialization era, focus on economic development has caused detrimental effects on the environment. Last two centuries have witnessed changes in global environmental factors such as rise in temperature leading to global warming, depletion of stratospheric ozone layer, loss of biodiversity and marked degradation in air and water quality due to atmospheric pollution, thereby causing upsurge in infectious and non-infectious diseases. Environmental health has emerged as an important part of medicine. The World Health Organization (WHO) estimates that 24% of global disease burden and 23% of all deaths can be attributed to environmental factors. Deaths from heart disease, cancer, respiratory disorders and many vector-borne diseases such as malaria, dengue, chikungunya and cholera have increased due to changes in climate, especially in developing countries. Besides limited attention to sanitation, hygiene, as well as quality of food and drinking water, factors such as deforestation, increasing vehicular traffic, migration from rural to urban areas, decreasing water resources and inadequate drainage systems contribute to increase incidence of diseases. The need of the hour is to sensitize ourselves about the way our ecology is being degraded and the health effects it is causing. A holistic view is needed to address the problem of environmental health where agriculture, animal husbandry, public health, water safety and air pollution need to be looked at in a combined manner for education, planning and resource allocation. Therefore, a close association between scientists, public health professionals and administrators is needed for integrated design and development of framework to attain harmony between man and nature."
8735,Technical Annexes,This chapter provides guidance on technical issues in the health sector. The annexes contain selective compilations of frequently used reference information.
8736,Challenges for the Application of GIS Interoperability in Emergency Management,"This paper highlights application challenges for GIS interoperability for emergency management with emphasis on critical infrastructure sectors. In the first part, this paper provides a comparative analysis of emergency management operations in the City of Vancouver; the City of Toronto, the Kitchener Waterloo Region, and the Dufferin County. A variety of qualitative research methods were employed for gathering information from key decision-makers involved with emergency management. The second part of this paper presents a scenario-based case study, which aims to provide a demonstration of the utility of GIS interoperability, for disaster management. This paper also discusses the strengths and weaknesses of leveraging GIS interoperability for disaster management."
8737,Rapid and Low-Cost Tools Derived from Plants to Face Emerging/Re-emerging Infectious Diseases and Bioterrorism Agents,"Whether naturally occurring or man-made, biological threats pose a severe risk in an increasingly globalized world. The dual-use nature of biological research, with its most recent advances in biotechnology (‘synthetic biology’, gene editing, nanotechnologies etc.) and the rapid diffusion of knowledge, raise proliferation concerns of biological weapons by non-state actors. Thus, there is an urgent need to develop measures intended to enhance diagnostic, prophylactic and therapeutic capabilities and capacities to improve the ability of society to combat infectious diseases outbreaks, as well as to alleviate the effects of bioterrorism attacks. We present here two examples of biotechnology usage for biodefence purposes: (i) plants as biofactories for the rapid production of improved biopharmaceuticals (‘Plant Molecular Farming’), and (ii) plant sequences as immune-modulating agents to enhance the efficacy of genetic vaccines. These platforms represent two promising (and complementary) approaches for the rapid and low-cost production of countermeasures (diagnostics and vaccine candidates) against emerging, re-emerging and bioterrorism-related infections."
8738,The molecular basis of paediatric malarial disease,"Severe falciparum malaria is an acute systemic disease that can affect multiple organs, including those in which few parasites are found. The acute disease bears many similarities both clinically and, potentially, mechanistically, to the systemic diseases caused by bacteria, rickettsia, and viruses. Traditionally the morbidity and mortality associated with severe malarial disease has been explained in terms of mechanical obstruction to vascular flow by adherence to endothelium (termed sequestration) of erythrocytes containing mature-stage parasites. However, over the past few decades an alternative ‘cytokine theory of disease’ has also evolved, where malarial pathology is explained in terms of a balance between the pro- and anti-inflammatory cytokines. The final common pathway for this pro-inflammatory imbalance is believed to be a limitation in the supply and mitochondrial utilisation of energy to cells. Different patterns of ensuing energy depletion (both temporal and spatial) throughout the cells in the body present as different clinical syndromes. This chapter draws attention to the over-arching position that inflammatory cytokines are beginning to occupy in the pathogenesis of acute malaria and other acute infections. The influence of inflammatory cytokines on cellular function offers a molecular framework to explain the multiple clinical syndromes that are observed during acute malarial illness, and provides a fresh avenue of investigation for adjunct therapies to ameliorate the malarial disease process."
8739,Use of Filgrastim (r-metHuG-CSF) in Human Immunodeficiency Virus Infection,"In 2008, an estimated 33.4 million individuals worldwide were infected with the human immunodeficiency virus (HIV) [1]. Only a few years ago, infection with HIV almost invariably culminated in the development of the acquired immunodeficiency syndrome (AIDS), characterized by severe depletion of CD4(+) lymphocytes leading to derangements predominantly affecting cell-mediated immunity, but affecting humoral immunity as well [2]. In the later stages of AIDS, neutropenia and neutrophil functional deficits were common sequelae of HIV infection, other opportunistic infections, or HIV- or opportunistic infection-related treatment [3]. The care of the HIV-infected patient was palliative in nature, and the possibility that use of filgrastim (rHuG-CSF) might extend survival in late-stage AIDS patients with severe neutropenia or severe opportunistic infections, or might be a treatment for HIV infection itself, was explored [4]. Subsequently, however, the development of protease inhibitors and the widespread adoption of their use in multidrug regimens of highly active antiretroviral therapy (HAART) revolutionized the care of HIV-infected patients, and the number of patients dying from HIV decreased dramatically [5]."
8740,Evaluation Findings and Policy Suggestions,"The foregoing Chaps. 10.1007/978-981-13-0644-0_3–10.1007/978-981-13-0644-0_7 have dealt with the five aspects of China’s Influenza A (H1N1) prevention and control efforts respectively, namely, strategies, systems and mechanisms, emergency response measures, costs and benefits, and social comments. This chapter will summarize the evaluation team’s findings in three respects of Influenza A (H1N1) prevention and control—main effects, basic experience, and inadequacies, and go on to raise issues worth further discussion and provide relevant policy suggestions."
8741,Emerging Viral Zoonoses from Wildlife Associated with Animal-Based Food Systems: Risks and Opportunities,"Zoonotic viruses of wildlife origin have caused the majority of recent emerging infectious diseases (EIDs) that have had significant impacts on human health or economies. Animal consumption-based food systems, ranging from the harvest of free-ranging wild species (hereafter, wild harvest systems) to the in situ stocking of domestic or farmed wild animals (hereafter, animal production systems), have been implicated in the emergence of many of these viruses, including HIV, Ebola, SARS, and highly pathogenic avian influenza (HPAI)."
8742,Infectious Diseases,"This chapter introduces infectious diseases faced by many populations in the world. The role of the environment and how and why these diseases are transmitted as well as prevention strategies are also discussed. The story takes place at a disco funeral in Kenya, where HIV prevalence is high and risky sexual behavior takes place."
8743,Local and Recurrent Regional Metastases of Melanoma,"Up to 10% of patients with cutaneous melanoma will develop recurrent locoregional disease. While surgical resection remains the mainstay of treatment for isolated recurrences, locoregional melanoma can often present as bulky, unresectable disease and can pose a significant therapeutic challenge. This chapter focuses on the natural history of local and regionally recurrent metastases and the multiple treatment modalities which exist for advanced locoregional melanoma, including regional perfusion procedures such as hyperthermic isolated limb perfusion and isolated limb infusion, intralesional therapies, and neo-adjuvant systemic therapy strategies for borderline resectable regional disease. Hyperthermic limb perfusion (HILP) and isolated limb infusion (ILI) are generally well-tolerated and have shown overall response rates between 44% and 90%. Intralesional therapies also appear to be well-tolerated as adverse events are usually limited to the site of injection and minor transient flu-like symptoms. Systemic targeted therapies have shown to have response rates up to 85% when used as neoadjuvant therapy in patients with borderline resectable disease. While combination immunotherapy in the neoadjuvant setting has also shown promising results, this data has not yet matured."
8744,Donor Evaluation for Hematopoietic Stem and Progenitor Cell Collection,"With the increasing incidence of hematopoietic allogeneic cell transplantation (allo-HCT), the importance of securing a cellular product, safely from a donor, and ensuring that the product is without additional risk to the recipient, continues to be of paramount importance. The evaluation of the donor’s medical eligibility and suitability is designed to identify and limit the risk of transmitting infectious, genetic, or neoplastic diseases to the recipient through the product. It also aims to ensure a maximum level of safety for the donor and informs them of the risks of donation. Several regulatory agencies, national and international registries, and accreditation bodies have facilitated the availability and safe provision of human cells, tissues, and cellular- and tissue-based products not only at local institutions but also through international exchange."
8745,Bluttransfusion,"Bei einem 58-jährigen Patienten mit einem Hb-Wert von 6,5 g/dl, der nach operativer Ausschaltung eines Bauchaortenaneurysmas auf der Intensivstation unerwartet nachblutet, soll eine Bluttransfusion durchgeführt werden. Wenige Minuten nach der Anforderung aus der Blutbank treffen die bestellten Erythrozytenkonzentrate ein – es sind Erythrozytenkonzentrate der Blutgruppe A. Sie sind eindeutig auf den Namen des Patienten ausgezeichnet, die Identität des Patienten wird erneut überprüft. Der durchgeführte Bedside-Test zeigt aber die Blutgruppe B! Was muss der Intensivarzt nun tun?"
8746,Modern Patient Blood Management in Arthroplasty,"One of the oldest and still commonest procedures in clinical practice, allogeneic blood transfusion (ABT), is not fully supported by available evidence. In the last few decades, increasing concerns about unfavorable outcomes associated with ABT, anticipation of future insufficient blood supply, and awareness of the cost (direct and indirect) of transfusion have led to the promotion of patient blood management (PBM) as a cost-effective strategy, beneficial for patients as well as for society (Shander et al. 2010). PBM programs utilize a series of measures with a proven ability to reduce ABT and to be cost-effective. Despite that the impact of PBM on patient clinical outcomes needs to be fully defined and future studies are needed, PBM should be adopted as a new standard of care."
8747,Prediction of TGEV Spike Protein Secondary Structure and B Cell Epitopes,"The spike gene of TGEV TH98 strain was translated into amino sequence by Editseq. The secondary structure and B cell epitope of spike protein of TGEV TH98 strain were predicted by Protean. Combining the results according to these methods, the spike protein of TGEV TH98 strain has complicated secondary structure. There are several epitopes of the B-cells in spike protein, including 43-56aa, 97-104aa, 117-128aa, 132-173aa, 238-257aa, 391-398aa, 535-706aa, 779-799aa, 918-987aa, 1165-1200aa, 1257-1266aa and 1430-1446aa."
8748,Kidney-Organ Interaction,"The practice of critical care nephrology demands an intimate understanding of the interactions and “crosstalk” that occurs between the kidney and multiple organ systems, in particular the heart, lung, gut, and brain. Accumulating evidence suggests that acute injury and dysfunction to the kidney can incite and propagate cardiac, pulmonary, gastrointestinal, and neurologic injury and dysfunction through a host of mechanisms."
8749,Die medizinische Mikrobiologie im 21. Jahrhundert,"Die medizinische Mikrobiologie befasst sich mit der ursächlichen Rolle pathogener (d. h. krankheitserzeugender) Mikroorganismen bei der Entstehung von Störungen im Funktionsablauf des menschlichen Organismus. Störungen dieser Art entstehen durch Ansiedlung und Vermehrung von Mikroorganismen im Sinne des Parasitismus; sie treten als Infektionskrankheit in Erscheinung. Demgemäß betrachtet man die parasitierenden Mikroorganismen als Krankheitserreger; das befallene Individuum wird als »Wirt« oder »Makroorganismus« bezeichnet. Da bei der Betrachtung von Infektionen sowohl der Wirt mit seinen Reaktionen als auch die krankheitserzeugenden Eigenschaften eines Mikroorganismus (d. h. seine Pathogenität) im Vordergrundstehen, lässt sich die medizinische Mikrobiologie am ehesten als Infektionslehre begreifen – als Lehre von der Auseinandersetzung des Wirtes mit den krankheitserzeugenden Eigenschaften des Erregers."
8750,Lagos the Mega-City: A Report on How the Metropolis Handled an Outbreak of the Ebola Epidemic,"Lagos State, Nigeria, is a mega-city with an estimated population of 16–21 million people. In the last ten years, the mega-city has made tremendous progress in terms of: sustained rapid economic growth, improved infrastructure and services, and a significant reduction in crime rates. This has provided an enabling environment for millions of Lagos state inhabitants to find their way out of poverty. The Lagos State Government has also made great strides in its quest to: increase value for money in public spending; improve the business climate in Lagos; maintain fiscal sustainability; and properly monitor and manage financial and health risks."
8751,Modeling State Interventions,"In the context of the modern nation state, the ecology of infectious diseases cannot be described by interacting populations alone, as much of the modeling literature implicitly presumes (Wallace and Wallace 2016). Modern states incorporate elaborate public health bureaucracies tasked with either containing or eliminating pathogen outbreaks. States are thus highly cognitive entities at the institutional level. It is then appropriate, indeed arguably necessary, to reconsider vector-borne infection from a control theory perspective."
8752,Risks and Epidemiology of Infections After Lung or Heart–Lung Transplantation,"Nowadays, lung transplantation is an established treatment option of end-stage pulmonary parenchymal and vascular disease. Post-transplant infections are a significant contributor to overall morbidity and mortality in the lung transplant recipient that, in turn, are higher than in other solid organ transplant recipients. This is likely due to several specific factors such as the constant exposure to the outside environment and the colonized native airway, and the disruption of usual mechanisms of defense including the cough reflex, bronchial circulation, and lymphatic drainage. This chapter will review the common infections that develop in the lung or heart–lung transplant recipient, including the general risk factors for infection in this population, and specific features of prophylaxis and treatment for the most frequent bacterial, viral, and fungal infections. The effects of infection on lung transplant rejection will also be discussed."
8753,Future Directions in Food Safety,"The recent success that the USDA Food Safety Inspection Service has had in 2003 and 2004 of reversing the steadily increasing trend in Class 1 recalls is welcomed. In agreement with those statistics are the FSIS microbiological results for Escherichia coli O157:H7 in raw ground beef, which also showed a decrease in 2003. But there is much work to be done in food safety and much more to achieve. It is imperative that while addressing food-safety issues, we should understand the role that the environmental microbiology, public health epidemiology, aerobiology, molecular microbial ecology, occupational health, industrial processes, municipal water quality, and animal health have on food safety. Although it is a difficult task, a concerted effort by industry, academic, and governmental researchers can accomplish the goal. Here we discuss the future directions and applications in the distribution and spread of foodborne hazards, methods for microbial detection and differentiation, intervention strategies for farm pathogen reduction, targeting waste at animal production sites, considerations on antimicrobial resistance, food-safety storage and preparation strategies, food irradiation, new and emerging food-safety hazards, and quantitative microbial food-safety risk assessment. Although this does not comprise an exhaustive list of food-safety issues, these are the areas that, we think, require considerable attention by researchers. Not only we need to strive to improve food safety through new strategies, processes, and applications, but we also need to be flexible and observant to readily handle the new and emerging food-safety problems, whether they are within our borders or global. At present, the United States has one of the safest food-safety systems in place. However, although this is not a time for complacency, our research endeavors should be designed to keep pace with the food-safety needs of the future."
8754,Evaluation of the Person Under Investigation,"A person under investigation (PUI) is defined as a patient who presents with both clinical and epidemiological risk factors for a specific infectious disease. In the case of infectious diseases that present risks of transmission to healthcare workers (HCWs) and patients, the use of the identify-isolate-inform framework is essential to protect staff and patients and the delivery of safe and effective care. This includes early identification of PUIs, institution of appropriate transmission-based precautions including use of specific personal protective equipment (PPE) and isolation, and prompt notification of relevant personnel, including relevant experts and authorities. Depending on the specific infection suspected, once appropriate infection control measures have been implemented, clinical evaluation of PUIs can vary in complexity. In the case of Ebola virus disease (EVD), the need for specialized PPE and training, well-developed procedures, and dedicated space can be extremely resource-intensive and costly for facilities. In addition, depending upon the need to reduce risks to other patients and HCWs, regular laboratory and imaging equipment may not be available (or available at the standard frequency or turnaround time) to support medical care. Lastly, diagnostic tests needed to confirm the diagnosis may not be available at the healthcare facility and may instead be accessible through public health authorities. This testing may take several days to confirm the diagnosis or rule out the presence of the suspected infection. Thus, the potential period of evaluation for a PUI can extend well beyond a typical clinic or emergency department (ED) visit. Thoughtful and coordinated planning efforts are required across the community and across the hospital to be able to adequately care for the PUI."
8755,SARS and West Nile Virus,"Clinical presentation of SARS is nonspecific; the important clinical findings in West Nile virus infection are those associated with neurological complications. Rapid and accurate diagnosis of SARS and West Nile virus infection remains an important clinical challenge. Older adults are at higher risk of complications, including death from SARS and West Nile virus. At present, there is no effective therapy for these infections. Although efforts are under way, there are presently no effective vaccines for SARS or West Nile virus."
8756,Population Genomics of Human Viruses,"Viruses, and a few RNA viruses in particular, represent one of the greatest threats for human health. High mutation rates, large population sizes, and short generation times contribute to their typically fast evolutionary rates. However, many additional processes operate on their genomes, often in opposite directions, driving their evolution and allowing them to adapt to diverse host populations and antiviral drugs. Until recently, the high levels of genetic variation of most viruses have been explored only at a few genes or genome regions. The recent advent and increasing affordability of next-generation sequencing techniques have allowed obtaining complete genome sequences of large numbers of viruses, mainly HIV, HCV, influenza A, and others associated with emerging infections, such as Zika, chikungunya, or dengue virus. This opens the possibility to explore the effects of the different processes affecting viral diversity and evolution at the genome level. Consequently, population genomics provides the conceptual and empirical tools necessary to interpret genetic variation in viruses and its dynamics and drivers and to transform these results into information that may complement the epidemiological surveillance of the virus and its disease. This chapter provides an overview of human viruses from a population genomics perspective, with a special emphasis on RNA viruses, and the potential benefits of “genomic surveillance” to establish public health policies that improve the control and monitoring of the diseases caused by these viruses."
8757,Hämatologie,"Die Hämatologie umfasst alle Erkrankungen, die das Blut, Blutbestandteile und die Blutfunktionen betreffen. In diesem Kapitel werden die Ätiologie, Pathologie, Klinik, Diagnostik und Therapie der wichtigsten Anämien (u. a. Eisenmangel-, Kugelzell-, Sichelzellänamie) und der akuten Leukämien (AML bzw. ALL) behandelt. Des Weiteren stehen maligne Lymphome und das multiple Myelom im Fokus. Darüber hinaus ist ein eigener Abschnitt den Gerinnungsstörungen gewidmet, darunter die Thrombozytopenien, Hämophilien und Koagulopathien. Abschließend wird auf Immundefizienzen und die Amyloidose eingegangen."
8758,Public Health Disasters,"Public health disasters reflect the uncharted conceptual, ethical, and pragmatic intersections between public health ethics and the emerging discourse on disaster bioethics. This novel concept reflects public health issues with calamitous social consequences such as infectious disease outbreaks, the attendant public health impacts of natural or man-made disasters, and currently latent or low prevalence public health issues with the potential to rapidly acquire pandemic capacities. The attendant moral dilemmas that PHDs generate have local and global dimensions. For this reason, they demand a multifaceted ethically grounded and pragmatically oriented approach. This chapter presents the conceptual foreground to the ethical and pragmatic dimensions of these issues."
8759,Infection in Kidney Transplantation,"Infection is an important cause of morbidity and mortality after kidney transplantation. It has been estimated that 70% of kidney transplant recipients will experience an infection episode within the first 3 years after transplantation (Dharnidharka et al. 2007). After cardiovascular disease, infection is the second leading cause of death in recipients with allograft function (Snyder et al. 2009). The immunosuppressive therapy required to prevent organ rejection places the kidney transplant recipient at increased risk for donor-derived, nosocomial, and community-acquired infections as well as reactivation of latent pathogens. Pretransplant screening, immunizations, and optimal antibacterial and antiviral prophylaxis can help to reduce the impact of infection. Awareness of the approach to infection in the transplant recipient including diagnostic and management strategies is essential to optimizing outcomes."
8760,Control Strategies,This chapter studies control strategies. Control strategies are listed and explained. It focuses on modeling vaccination in single-strain and multistrain diseases. Different modes of introducing vaccination in models are shown. Imperfect vaccination as a mechanism leading to backward bifurcation and strain replacement is explained. Strain replacement with perfect vaccination is demonstrated. Quarantine and isolation are discussed and included in a model. Introduction to optimal control theory is incorporated and the theory is illustrated on a specific example with optimal control treatment. Matlab code for computing the optimal control is included.
8761,Ecological Context of Epidemiology,"This chapter is focused on ecoepidemiology. It introduces and studies a number of models related to infectious diseases in animal populations. Animals are typically subject to ecological interactions. The chapter first introduces SI and SIR models of species subject to a generalist predator and studies the impact of selective and indiscriminate predation. The classical Lotka–Volterra predator–prey and competition models are reviewed together with their basic mathematical properties. Furthermore, the chapter includes and discusses a Lotka–Volterra predator–prey model with disease in prey and a Lotka–Volterra competition model with disease in one of the species. Hopf bifurcation and chaos are found in some of the ecoepidemiological models."
8762,Common respiratory infections diagnosed in general practice,"Acute respiratory infections are one of the most common causes for presentation to a general practitioner. The range of symptoms associated with each infection can be wide ranging in both presentation and severity, depending on age of the patient, underlying co-morbidities and other confounding factors. In this chapter we describe the most common respiratory infections ranging from relatively mild infections such as the common cold, through to more serious presentations including pneumonia. Data are presented from a general practitioner morbidity surveillance system based in England and Wales. Each acute respiratory syndrome is described in respect of seasonality, secular trends and microbiological aetiology providing an insight into the complex nature of these acute respiratory episodes. The more serious endpoints of acute respiratory infections are hospitalisation and death. Many acute respiratory infections are mild in nature and generally self-limiting and therefore do not commonly require further medical interventions. However, despite major advances in the prevention and treatment of acute respiratory infections in recent years, hospitalisation and deaths continue to exert pressures on national health resources and provide an economic burden in countries across the world on an annual basis."
8763,Quantitative Man-Made Risks’ Modelling,"Catastrophe modelling began with earthquakes, then expanded to cover windstorms, floods, tsunamis, volcanic eruptions and other natural hazards, and has evolved in the twenty-first century to cover significant man-made risks like terrorism, and cyber crime. The modelling of man-made risks is reviewed, with particular attention given to the principles of terrorism risk modelling. Pandemic risk is also covered because of its historical linkage with political risk. The application of man-made risk modelling to financial risk transfer is discussed."
8764,Gastroenterologie,"—. : —. gastrointestinale Passagestörung, z. B. Magenausgangsstenose, Duodenalstenose, mechanischer Ileus; —. andere gastrointestinale Störungen, z. B. Gallenkolik, Gastroenteritis, Pankreatitis, Ulcus ventriculi/duodeni, Ileus, „Afferent-loop“-Syndrom nach Billroth-II-Magen, Achalasie, Zenker-Divertikel, obere GI-Blutung; —. zentralnervös, z. B. Meningitis, Enzephalitis, Hirntumor, Hirndrucksteigerung; —. vestibulär, z. B. M. Menière, Kinetosen; —. Stoffwechselentgleisungen, z. B. diabetische Ketoazidose, Urämie; —. schmerzbedingt, z. B. Nierenkolik, Myokardinfarkt; —. medikamentös-toxisch, z. B. Alkohol, Zytostatika; —. Schwangerschaft (β-HCG-assoziiert); —. Essstörungen, z. B. Anorexia nervosa, Bulimie;"
8765,Recent Developments in 3D QSAR and Molecular Docking Studies of Organic and Nanostructures,"The development of quantitative structure–activity relationship (QSAR) methods is going very fast for the last decades. OSAR approach already plays an important role in lead structure optimization, and nowadays, with development of big data approaches and computer power, it can even handle a huge amount of data associated with combinatorial chemistry. One of the recent developments is a three-dimensional QSAR, i.e., 3D QSAR. For the last two decades, 3D-OSAR has already been successfully applied to many datasets, especially of enzyme and receptor ligands. Moreover, quite often 3D QSAR investigations are going together with protein–ligand docking studies and this combination works synergistically. In this review, we outline recent advances in development and applications of 3D QSAR and protein–ligand docking approaches, as well as combined approaches for conventional organic compounds and for nanostructured materials, such as fullerenes and carbon nanotubes."
8766,Early disease management strategies in case of a smallpox outbreak,"As a consequence of the threat of smallpox being potentially used as a means of bioterrorism, many countries have developed preparedness plans for smallpox in the past few years. This chapter summarizes some of the most important issues for the management of smallpox. Usually, the strategy for the management of clinical cases of poxviruses includes the early detection of cases, rapid laboratory diagnosis, an assessment of the risk of further spread and containment measures. For the early detection, different systems are being tested to identify suspected cases before a diagnosis is confirmed (e.g., syndromic surveillance). Also it is necessary to provide special training on the disease pattern, including differential diagnosis, to clinicians and practitioners. If a suspected case has been identified, rapid diagnostic tests are required. In addition to the national and international notifications based on given case definitions, certain measures are necessary to allow an initial risk assessment of the epidemic development. For a rapid risk assessment, the investigations should follow the algorithms of epidemiological outbreak investigation such as the tracing and identification of exposed contacts and the sources of infection. Further decisions have to be taken on the basis of a continuous risk assessment. Countermeasures can be divided into medical and non-medical ones. The choice of an adequate vaccination strategy as a medical countermeasure for the case of a re-emergence of smallpox very much depends on the epidemic scenario, and the general availability and quality of a vaccine. Logistic aspects of the vaccination strategies have to be considered in preparedness planning (e.g., resources necessary for the implementation of mass vaccinations), and also the prioritization of groups to be vaccinated. In addition non-medical measures to prevent the spread of infection, such as the isolation of cases and quarantining of exposed persons (e.g., contact persons of confirmed cases) have to be foreseen. The effectiveness of other measures like prohibition of mass gatherings or closure of institutions is often assessed in the light of historical events. However, they have to be considered within today’s ethical and societal context, taking into account, in particular, the increased number of people who are immunocompromised. Since our knowledge of how the virus would behave today is limited to extrapolations from historical data and is therefore imperfect, these measures are still under discussion. All relevant groups should be involved in exercises to assure the effective operation of the plan mainly regarding communication and cooperation."
8767,Pulmonary System,"Pulmonary disease is a highly prevalent cause of premature morbidity and mortality in long-term childhood cancer survivors. Pulmonary toxicity is frequently reported in survivors of Hodgkin lymphoma, germ cell tumors, acute lymphoblastic lymphoma and metastatic Wilms tumor survivors, as the chemotherapy, radiation and surgeries used to treat these pediatric cancer (among others) can result in permanent lung damage. This damage can manifest as acute pneumonitis, late onset fibrosis, and structurally induced dysfunction from developmental abnormalities due to impaired growth of the thorax attributable to surgery or radiation. The cumulative incidence of pulmonary problems after childhood cancer increases with time since diagnosis, as with other late-effects, suggesting that survivors are at an elevated risk of developing later-onset pulmonary morbidities as they age."
8768,Promoting Universal Coverage of Basic Public Services Among Urban Residents,"In 2012, China’s urbanization rate reached 52.57 % but, if we counted only people with urban hukous, this was only 35.29 %; there were 263 million migrant workers in China, where they have already been playing a leading role in urbanization. Nonetheless, governments are still managing applications for new permanent urban residents’ registration, demanded by rural migrant workers, by using the long-established hukou-based public service policies. This has constituted a big obstacle to the citizenization of rural migrant workers in China, caused a great deal of problems with urban management, and is contrary to social justice. In 2013, it was made clear in the Report on the Work of the Government that relevant authorities should accelerate reform of the household registration system and related institutions; that they should register eligible rural workers as permanent urban residents in an orderly manner, “progressively expand the coverage of basic public services in urban areas to include all their permanent residents and create an equitable institutional environment for freedom of movement and for people to live and work in contentment.” Accordingly, in order to protect the rights of migrants and improve the quality of the process of social urbanization in China, the most significant tasks involve investigating the current status of basic public services in Chinese towns and cities, especially the public services provided for potential new permanent migrant worker residents, and exploring methods to expand the coverage of these basic public services in urban areas to all their permanent residents."
8769,"Great Plains Societal Considerations: Impacts and Consequences, Vulnerability and Risk, Adaptive Capacity, Response Options","A variety of factors related to climate variability and change will impact the Great Plains across human and ecological communities. The changes and associated stress are triggering response strategies and other mitigation and adaptation measures from land managers, government officials and staff, and various industries. The impacts and responses address water, energy, and other essential resources for both human and environmental well-being."
8770,Examples of Applications of Electrophysiology,"All the techniques that we have discussed, flux measurements, steady-state and transient current measurements, as well as single-channel recordings and the corresponding analysis can be applied to the analysis of structure-function relationships. Such structure-function information can be obtained if we characterize and compare the function of wild-type and chemically or genetically modified transporters by using these techniques. The latter also includes naturally occurring mutations that are the source of various diseases; this is an important feature for the understanding and curing of such diseases. For many of the transporters the amino acid sequence and the possible orientation of the protein in the membrane, or even the three-dimensional structures have been determined. In this chapter on Examples of Applications of Electrophysiology, we will illustrate the strategy of an electrophysiologist in investigating structure, function and regulation of membrane transport using as an example the Na(+),K(+)-ATPase, the neurotransmitter transporter GAT (Na(+)-dependent GABA transporter), and the nucleotide receptors that form channels in the presence of extracellular ATP. For an understanding of drug action as well as the development of new drugs for the treatment of diseases, electrophysiology is a powerful method to elucidate drug receptor interaction. As an example, this will be illustrated for viral ion channels that are essential for virus reproduction."
8771,Gastrointestinal Disorders,"This chapter reviews extensively gastrointestinal bleeding that require intensive care unit admission. Its management, including with assessment of the airway, breathing, and circulation (ABCs), is emphasized as well as the use of proton pump inhibitors and H(2)-receptor blockers to prevent further hemorrhage. Acute mesenteric ischemia (AMI), an acute reduction in blood flow to the intestine leading to inadequate perfusion, is reviewed. Acute pancreatitis, an inflammatory process of the pancreas, having alcoholism, gallstones, hyperlipidemia, trauma, and infections as the most common etiologies, is also reviewed."
8772,RNAi for Resistance Against Biotic Stresses in Crop Plants,"RNA interference (RNAi)-based gene silencing has become one of the most successful strategies in not only identifying gene function but also in improving agronomical traits of crops by silencing genes of different pathogens/pests and also plant genes for improvement of desired trait. The conserved nature of RNAi pathway across different organisms increases its applicability in various basic and applied fields. Here we attempt to summarize the knowledge generated on the fundamental mechanisms of RNAi over the years, with emphasis on insects and plant-parasitic nematodes (PPNs). This chapter also reviews the rich history of RNAi research, gene regulation by small RNAs across different organisms, and application potential of RNAi for generating transgenic plants resistant to major pests(.) But, there are some limitations too which restrict wider applications of this technology to its full potential. Further refinement of this technology in terms of resolving these shortcomings constitutes one of the thrust areas in present RNAi research. Nevertheless, its application especially in breeding agricultural crops resistant against biotic stresses will certainly offer the possible solutions for some of the breeding objectives which are otherwise unattainable."
8773,The Network Source Location Problem in the Context of Foodborne Disease Outbreaks,"In today’s globally interconnected food system, outbreaks of foodborne disease can spread widely and cause considerable impact on public health. Food distribution is a complex system that can be seen as a network of trade flows connecting supply chain actors. Identifying the source of an outbreak of foodborne disease distributed across this network can be solved by considering this network structure and the dimensions of information it contains. The literature on the network source identification problem has grown widely in recent years covering problems in many different contexts, from contagious disease infecting a human population, to computer viruses spreading through the Internet, to rumors or trends diffusing through a social network. Much of this work has focused on studying this problem in analytically tractable frameworks, designing approaches to work on trees and extending to general network structures in an ad hoc manner. These simplified frameworks lack many features of real-world networks and problem contexts that can dramatically impact transmission dynamics, and therefore, backwards inference of the transmission process. Moreover, the features that distinguish foodborne disease in the context of source identification have not previously been studied or identified. In this article we identify these features, then provide a review of existing work on the network source identification problem, categorizing approaches according to these features. We conclude that much of the existing work cannot be implemented in the foodborne disease problem because it makes assumptions about the transmission process that are unrealistic in the context of food supply networks—that is, identifying the source of an epidemic contagion whereas foodborne contamination spreads through a transport network-mediated diffusion process, or because it requires data that is not available—complete observations of the contamination status of all nodes in the network."
8774,Business Continuity Management (BCM),"This chapter elaborates on a review of BCM. As the background, it describes the historical development of BCM and its relationships with other concepts. It will be followed by reviews on BCM as a management system, BCM’s main principles, and Business Continuity Planning overview. The next section will describe the implementation of BCM, related with regulations or standards that support the concept and the development of BCM level of preparedness. Several reviews on BC plans from various sectors are elaborated in the final part of the chapter, followed by reviewing the need for BCM in organizations based on its benefits and challenges."
8775,Care of the Patient with Liver Failure Requiring Transplantation,"Patients undergo liver transplantation to address chronic liver failure, acute fulminant liver failure, or primary liver cancer. Depending on acuity, patients with decompensated chronic or acute fulminant liver failure generally require preoperative intensive care unit admission to manage organ dysfunction. Those with chronic liver failure are allocated an organ based on waiting list position determined by their local organ procurement organization (OPO). This position is dependent upon blood type and Model for End- Stage Liver Disease (MELD) score. These patients thus are critically ill and require preoperative ICU monitoring and care. Patients with hepatocellular carcinoma (HCC) who require liver transplantation are given a MELD exception and rarely require preoperative ICU care. The patient’s ability to undergo liver transplant in the setting of HCC is determined by the Milan criteria or the University of California, San Francisco (UCSF) criteria."
8776,Secondary Metabolites of Plants,"Orchid phytochemicals that have been studied include alkaloids, bibenzyls, phenanthrenes, stilbenoids, phenols, flavonoids, anthocyanins and polysaccharides. Many of these compounds exhibit antioxidant, anti-inflammatory, antimicrobial, antihelminthic, anticoagulant, antidiabetic and lipid-lowering properties. Some compounds are cytotoxic, prevent angiogenesis and tumour spread and promote programmed cell death of cancer cells. Some compounds protect nerve cells against chemicals and oxygen deprivation (stroke), promote nerve cell regeneration, protect the skin from ultraviolet damage, protect the liver against poisons such as carbon tetrachloride, prevent calcium loss from bone and enhance foetal lung maturation. This chapter provides a short account of the characteristics of the various groups of compounds, including their properties."
8777,Fulfilling a Promise: Universal Care,"Even before the extent of the epidemic became more reliably known, China’s leaders had signalled their renewed determination to tackle HIV in all of its dimensions, social and economic as well as medical. Because dedicated health officials and researchers had been running pilot programmes and building up evidence for well over a decade, there was a lot of information available about which approaches might work best. But most of these approaches went against the grain for many of the local politicians and senior bureaucrats who would have to implement them across the nation."
8778,Genetic Variability in RNA Viruses: Consequences in Epidemiology and in the Development of New Stratgies for the Extinction of Infectivity,
8779,Influenza,"Influenza is a highly contagious virus that causes an acute respiratory tract infection. Disease occurs in yearly outbreaks in humans, lasting 2–6 weeks in length. Influenza A and B predominate in these outbreaks, with more severe disease occurring with Influenza A. Additional infections with avian subtypes of influenza have also occurred in humans in the past decade, with notably increased morbidity and mortality. Vaccination is the mainstay for preventing disease. Antiviral drugs may be effective in decreasing duration and severity of disease, but evolving resistance has narrowed treatment options. This chapter provides a broad overview of influenza, from basic virology to epidemiology, disease, treatment, and prevention."
8780,"A Comprehensive Analytical Framework for Risks, Disasters and Crises","Early warning and emergency management is a comprehensive and integrated system that deals with all sorts of emergencies, risks and crises, and involves various sectors of society and government departments. A consistent and holistic approach, however, has previously been lacking in both research and practice."
8781,Economic Implications of Influenza and Influenza Vaccine,"The objective of this chapter is to review and summarize the current economic estimates of influenza and the cost-effectiveness of its vaccines. We reviewed the published assessments of the economic costs of human seasonal and pandemic influenza internationally. Seasonal influenza costs Germany, France, and the USA between $4 and $87 billion annually. Depending upon the intensity of transmission and severity of disease, pandemic influenza may cause as many as 350 million deaths and result in economic losses topping $1 trillion – an impact great enough to create a worldwide recession. We then reviewed 100 papers primarily from more than a dozen countries which studied the cost-effectiveness of influenza vaccine in children, adults, and the elderly. These studies demonstrate that influenza vaccination is quite cost-effective among children 6 months to 18 years old, in health care workers and pregnant women, and in high-risk individuals. Remarkably, compared with the other recently introduced vaccines for children, such as rotavirus and pneumococcal polysaccharide, vaccinating children and school attendees results in societal cost savings because it obviates lost productivity and wages among infected individuals and their caretakers. Vaccination for children is recommended in the USA and in Canada, but public health policy makers in Europe have undervalued this vaccine and not recommended it so widely."
8782,Dengue,"Dengue is one of the most important mosquito-borne viral infections caused by single-stranded RNA virus that are transmitted by the Aedes aegypti and Aedes albopictus mosquito species. Dengue is endemic in over 140 countries in Asia, the USA, the Eastern Mediterranean, and Africa. The World Health Organization (WHO) estimated that there are more than 2.5 billion people—mainly occurs in children living in tropical and subtropical countries—at risk of dengue infection with one or more dengue viruses. There are estimated nearly 100 million symptomatic dengue infections occurring worldwide annually, nearly 75% in Asia and the Western Pacific region [1]. During the past decades, the outbreaks of dengue infection have been reported throughout the world with increased severity. Ecologic and demographic changes are considered to be the contributing factors to the emergence of dengue infection in the past decades. Dengue has expanded into new countries and into urban settings associated with increased distribution of A. aegypti, population growth, urbanization, development of slums, migration of population, movement of dengue virus by infected travelers, trade development, and improved diagnostic capabilities in medical practice [2, 3]. Increased transmission of dengue virus in tropical urban areas has been created by substandard housing and crowding as well as deterioration in water, sewer, and waste management systems, all of which are intimately associated with unplanned urbanization [4–7]. So it is likely that dengue will expand its geographic reach and become an increasing burden on health resources in affected areas during the next decade. An effective vector-control management is the only means to reduce dengue infection in endemic areas. Because vector control has achieved only limited success so far in reducing the transmission of dengue, the usage of effective dengue vaccine in target population along with the preventive measures already used such as raising public awareness may be the means to effectively control of this disease in endemic area [8]."
8783,Hemostatic Resuscitation,"Component therapy is useful for the majority of patients when blood requirements are minimal and there is no associated coagulopathy. Of concern are requirements for massive transfusion and resuscitation that absorb resources and create a short-fall for patients whose injuries are less severe. Additionally, the conventional massive transfusion model of packed RBCs, plasma and platelets actually further dilutes the patient compared to the blood he or she has lost and thus is not the ideal fluid for patients who require this massive transfusion of products. Fresh whole blood has three vital properties: oxygen carrying capacity, volume, and hemostatic effect. In the austere environment of combat the practice of fresh whole blood transfusion has proven beneficial to patients who are coagulopathic and require massive transfusion. Appropriate use following established guidelines can be beneficial and may even be superior to packed RBCs. A fluid containing the vital properties of fresh whole blood would serve as a bridge to allow a patient to be resuscitated without initiating the ‘bloody cycle of death’ that is seen all too often in our current paradigm of massive resuscitation."
8784,Introduction: A Short History of Virology,"Viral infections have been recorded unknowingly from the beginning of recorded history. The ancient Greeks and Romans described plagues of unknown origin. In general, infections were blamed on sins and punishment, balances of “vital humors” or on “miasma,” (rotten smells). In the sixteenth century, Girolamo Fracastoro suggested that infectious agents might spread disease, as did Agostino Bassi, studying diseases of silkworms. The development of the microscope by Hook and Van Leeuwenhoek in the seventeenth century led to the discovery of a new living world inhabited by very small creatures. Edward Jenner in England demonstrated that smallpox, a dreaded disease, could be prevented by inoculation with an organism that caused pockmarks on cows and dairymaids; this was the beginning of the concept of vaccination. Louis Pasteur proved that fermentation only occurred in the presence of air and was due to microorganisms. Pasteur and Pierre Roux, a colleague, as well as Jacob Henle and Robert Koch, proved that germs caused bacterial diseases such as anthrax and tuberculosis; Pasteur and Roux developed a vaccine against rabies by passaging the infectious material through rabbits. By the end of the nineteenth century it had been established that most infectious diseases were the result of germs. In parallel with this research, plant scientists had isolated material that passed through a low pore filter that was infectious to tobacco plants. This was called a “virus,” from the Latin for poison. Viruses were also found to be associated with leukemia and other cancers of chickens. The twentieth century saw the discovery of bacteriophage, viruses that attack bacteria, and the use of such bacteriophage to launch studies of molecular biology, and DNA and RNA structure."
8785,Influenza Vaccines Have a Short but Illustrious History of Dedicated Science Enabling the Rapid Global Production of A/Swine (H1N1) Vaccine in the Current Pandemic,"Vaccines for the swine flu pandemic of 2009 have been produced in an exquisitely short time frame. This speed of production comes because of 50 years of hard work by virologists worldwide in pharma groups, research laboratories, and government licensing units. The present chapter presents the background framework of influenza vaccine production and its evolution over 50 years. Isolation of the causative virus of influenza in 1933, followed by the discovery of embryonated hen eggs as a substrate, quickly led to the formulation of vaccines. Virus-containing allantoic fluid was inactivated with formalin. The phenomenon of antigenic drift of the virus HA was soon recognized and as WHO began to coordinate the world influenza surveillance, it became easier for manufacturers to select an up-to-date virus. Influenza vaccines remain unique in that the virus strain composition is reviewed yearly, but modern attempts are being made to free manufacturers from this yolk by investigating internal virus proteins including M2e and NP as “universal” vaccines covering all virus subtypes. Recent technical innovations have been the use of Vero and MDCK cells as the virus cell substrate, the testing of two new adjuvants, and the exploration of new presentations to the nose or epidermal layers as DNA or antigen mixtures. The international investment into public health measures for a global human outbreak of avian H5N1 influenza together with a focus of swine influenza H1N1 is leading to enhanced production of conventional vaccine and to a new research searchlight on T-cell epitope vaccines, viral live-attenuated carriers of influenza proteins, and even more innovative substrates to cultivate virus, including plant cells."
8786,"Impacts of Climate Change on the Environment, Economy, and Society of China","This chapter evaluates the characteristics and extent of impacts of modern climate change on the hydrology, ecology, agriculture, health, economy, and society of China. The impacts of climate change on water resources, hydrological processes, the cryosphere, and ocean hydrological processes are analyzed, as well as the impacts on land ecosystems, desertification, and soil erosion. The impact of global sea-level change on marine ecology and the coastal environment is comprehensively assessed. The chapter also summarized the impact of climate change on farming, animal husbandry, forestry, aquaculture, and fisheries."
8787,A Mathematical Model of Cytokine Dynamics During a Cytokine Storm,"Cytokine storms are a potentially fatal exaggerated immune response consisting of an uncontrolled positive feedback loop between immune cells and cytokines. The dynamics of cytokines are highly complex and little is known about specific interactions. Researchers at the Ontario Veterinary College have encountered cytokine storms during virotherapy. Multiple mouse trials were conducted where a virus was injected into mice whose leukocytes lacked expression of the type I interferon receptor. In each case a rapid, fatal cytokine storm occurred. A nonlinear differential equation model of the recorded cytokine amounts was produced to obtain some information on their mutual interactions. Results provide insight into the complex mechanism that drives the storm and possible ways to prevent such immune responses."
8788,Environmental Risks,"Production and consumption pose a number of burdens on our ecological systems. The risk of causing damage to human health by environmental contamination is called, in general, environmental risk. Climate changes and infection to new pandemic influenza are believed also to be caused by the global human activities affecting global environment and ecological systems; thus, they often make part of environmental risks in the broad sense. This chapter explains each of these risks and unveils our unique methods in counter them."
8789,Infectious Complications,"Infections remain a cause of significant morbidity and mortality following hematopoietic stem cell transplantation (HSCT). The conditioning regimen (chemotherapy, radiation therapy), mucosal damage, type of transplant, immune suppressive therapy, and graft-versus-host disease (GVHD) all predispose the HSCT recipient to infection. Abnormal B- and T-lymphocyte function results in impaired humoral and cellular immunity, respectively. Neutrophil function is impaired by the use of corticosteroids and other medications. Hypogammaglobulinemia and functional asplenia are common. The occurrence of infections in an individual patient varies according to the phase of the transplant process and reflects the type(s) of immune defect(s), underlying disease, endogenous host flora, exposure history, and pre-treatment infections."
8790,Viral Pulmonary Disorders in Animals: Neoplastic and Nonneoplastic,"Respiratory infections in animal species are as ubiquitous as they are in humans. Species that may be affected include mammals, birds, and reptiles. In these animal species some viruses primarily infect the respiratory tract, while other viruses infect non-respiratory organs. Viruses are generally classified according to the type of their nucleic acid, their protein structure, and whether or not they have a lipid-containing envelope surrounding the viral particle. In general, most viruses gain entry into the lungs via the conducting airways. In nonprimate mammalians these infections are most prominent in the cranioventral lung lobes because of their horizontal position. Table 24.1 lists some of the major viruses that cause pneumonia and other lung diseases in animals."
8791,Akuttherapie,"In Kürze: Die Anforderungen zum Monitoring und zur Basisdiagnostik nach stattgehabtem Schlaganfall wurden bereits ausführlich in 7 Abschn. 5.1 dargestellt. Ziel der Basistherapie auf der Stroke Unit ist vornehmlich eine allgemeine Stabilisierung der Vitalparameter, der Homöostase sowie die Verhinderung von Komplikationen. Sie schafft damit die Voraussetzung für spezifische Therapien und die frühe Erholung der Patienten. Die im Folgenden aufgeführten generellen Überlegungen orientieren sich an den Empfehlungen der Europäischen Schlaganfall Organisation (ESO) (Ringleb 2008, Schellinger 2008)."
8792,Avian Influenza,
8793,Application of Molecular Beacons in Real-Time PCR,"Real-time PCR or quantitative PCR (QPCR) is a powerful technique that allows measurement of PCR product while the amplification reaction proceeds. It incorporates the fluorescent element into conventional PCR as the calculation standard to provide a quantitative result. In this sense, fluorescent chemistry is the key component in QPCR. Till now, two types of fluorescent chemistries have been adopted in the QPCR systems: one is nonspecific probe and the other is specific. As a brilliant invention by Kramer et al. in 1996, molecular beacon is naturally suited as the reporting element in real-time PCR and has been adapted for many molecular biology applications. In this chapter, we briefly introduce the working principle of QPCR and overview different fluorescent chemistries, and then we focus on the applications of molecular beacons-like gene expression study, single-nucleotide polymorphisms and mutation detection, and pathogenic detection."
8794,The Pharmacological Activities of Glycyrrhizinic Acid (“Glycyrrhizin”) and Glycyrrhetinic Acid,"Glycyrrhizin or, more correctly, Glycyrrhizinic acid is a triterpenoid saponin obtained from the root and rhizome extracts of Licorice (Glycyrrhiza glabra), being commonly used as a sweetener, being reported as – at least – 30 times sweeter than sucrose. This natural product, along with its aglycone glycyrrhetinic acid, is known in the literature for its several pharmacological and biological activities. This chapter summarizes the activities reported in the literature for the saponin and its aglycone since 2010."
8795,"Sociality, Parasites, and Pathogens in Bats","Little is known about the ecology of many of the parasites and pathogens affecting bats, but host social behavior almost certainly plays an important role in bat-parasite dynamics. Understanding parasite dynamics for bats is important from a human public health perspective because of their role as natural reservoirs for recent high-profile emerging zoonotic pathogens (e.g. Ebola, Hendra) and from a bat conservation perspective because of the recent emergence of white-nose syndrome (WNS) in North America highlighting the potential population impacts of parasites and pathogens. Although some bat species are among the most gregarious of mammals, species vary widely in terms of their social behavior and this variation could influence pathogen transmission and impacts. Here, we review the literature on links between bat social behavior and parasite dynamics. Using standardized search terms in Web of Science, we identified articles that explicitly tested or discussed links between some aspect of bat sociality and parasite transmission or host population impacts. We identified social network analysis, epidemiological modeling, and interspecific comparative analyses as the most commonly used methods to quantify relationships between social behavior and parasite-risk in bats while WNS, Hendra virus, and arthropod ectoparasites were the most commonly studied host-parasite systems. We summarize known host-parasite relationships in these three systems and propose testable hypotheses that could improve our understanding of links between host sociality and parasite-dynamics in bats."
8796,"Hydroids (Cnidaria, Hydrozoa): A Neglected Component of Animal Forests","Hydroids, one of the dominant components of the zoobenthic communities, share comparable growth patterns with higher plants because of their modular body organization, high potential of asexual reproduction, and phenotypic plasticity. These features, together with the ability to enter dormancy to overcome unfavorable conditions, make hydroids successful organisms adaptable to a wide range of environmental scenarios. Depending on their wide range of shapes and sizes, hydroids form three-dimensional forests at different dimensional scales, establishing both trophic and non-trophic relationships with several other organisms, from virus to vertebrates. Despite numerous researches conducted to study the hydroid ecology, the putative importance of hydroids in structuring zoobenthic communities is underestimated. Here, information available about hydroid ecology is summarized, in order to emphasize the role of hydroids as forest formers, as well as their function in the bentho-pelagic coupling."
8797,Fremddarstellung – Selbstdarstellung: Über Grenzen der Medialisierung menschlichen Leidens,"Der zwölfte Beitrag behandelt die Frage nach den Grenzen der Medialisierung menschlichen Leidens am Beispiel der Medialisierung von Aids. Während aber Aids als gesellschaftliche Metapher das endlose und globale Zirkulieren von Menschen, Bildern, Waren, Müll, Informationen und Kapital anzeigt, deutet inzwischen eine andere Krankheit, nämlich Alzheimer, sozusagen auf das Herz oder genauer gesagt auf das Gehirn der Informationsgesellschaft hin."
8798,Pleuropulmonary Changes Induced by Drugs in Patients with Hematologic Diseases,"Patients with hematologic diseases who are being treated with therapy drugs, or receive radiation therapy or blood transfusions may develop a host of potentially fatal infectious and noninfectious pulmonary complications [1]. The increased complexity of multimodality and high-dose treatment regimens with the intended benefit of augmented antineoplastic efficacy and prolonged disease-free survival, the use of a panel of novel drugs to treat malignant and nonmalignant hematologic conditions (e.g., azacytidine, bortezomib, cladribine, dasatinib, fludarabine, imatinib, lenalidomide, rituximab, and thalidomide), total body irradiation (TBI) and hematopietic stem cell transplantation (HSCT) have increased the incidence of severe sometimes life-threatening pulmonary complications."
8799,Ziekten en afwijkingen die de zwangerschap compliceren,"In dit hoofdstuk komen aan de orde: frequent voorkomende ziekten en afwijkingen die de zwangerschap kunnen compliceren, zoals"
8800,Sphingolipid Metabolism in Systemic Inflammation,"The inflammatory response — induced and regulated by a variety of mediators such as cytokines, prostaglandins, and reactive oxygen species (ROS) — is the localized host’s response of the tissue to injury, irritation, or infection. In a very similar and stereotyped sequence, the mediators are thought to induce an acute phase response orchestrated by an array of substances produced locally or near the source or origin of the inflammatory response. Despite its basically protective function, the response can become inappropriate in intensity or duration damaging host tissues or interfering with normal metabolism. Thus, inflammation is the cause and/or consequence of a diversity of diseases and plays a major role in the development of remote organ failure. Better knowledge of the underlying mechanisms of these processes is, therefore, a fundamental pre-requisite fostering the molecular understanding of novel therapeutic targets or diagnostic variables."
8801,Pathogenesis of Kingella kingae Disease,"The pathogenesis of Kingella kingae disease begins with colonization of the oropharynx, a process facilitated by type IV pili and a non-pilus trimeric autotransporter adhesin called Knh, factors that mediate adherence to respiratory epithelial cells. A potent RTX cytotoxin with broad cellular specificity may play a role in disrupting the epithelial barrier and facilitating invasion of the bloodstream, possibly in concert with a viral coinfection. Once in the bloodstream, the organism can disseminate to sites of invasive disease, primarily the joints, bones, and endocardium. Survival in the bloodstream and dissemination are likely aided by expression of a capsular polysaccharide and an exopolysaccharide galactan. The evidence for antigenic diversity of K. kingae surface exposed protein epitopes and the observation that type IV pili are selected against during invasive disease suggest that immune system pressure plays an important role in K. kingae pathogenicity."
8802,"Biosensors for Security and Bioterrorism: Definitions, History, Types of Agents, New Trends and Applications","Biosensors are making a large impact in environmental, food, biomedical, and in many other applications. They provide many advantages. in comparison to standard analytical detection methods (i.e., chromatographic techniques) such as minimal sample preparation and handling, faster time analysis, simpler steps of analysis, rapid detection of the analytes of concern, use of non-skilled personnel, and portability for uses in the field applications. The aim of this chapter is to focus on novel research related to the rapid detection of agents and weapons of bioterrorism and provide a comprehensive review of the research topics most pertinent to advancing devices applicable to the rapid real-time detection of toxicants and bioterrorism weapons such as microbes, pathogens, toxins, virus, or nerve gases. The ongoing war on terrorism and the rising security concerns are driving the need for newer faster biosensing devices against bio-warfare agents for both military and civil defense applications. Readers of these review article will learn new schemes of biological weapons that can lead to the construction of devices that will minimize the risk of bio-terrorism."
8803,The genetic transformation of plastids,"Biolistic delivery of DNA initiated plastid transformation research and still is the most widelyused approach to generate transplastomic lines in both algae and higher plants. The principal designof transformation vectors is similar in both phylogenetic groups. Although important additions tothe list of species transformed in their plastomes have been made in algae and in higher plants, thekey organisms in the area are still the two species, in which stable plastid transformation was initiallysuccessful, i.e., Chlamydomonas reinhardtii and tobacco. Basicresearch into organelle biology has substantially benefited from the homologous recombination-basedcapability to precisely insert at predetermined loci, delete, disrupt, or exchange plastid genomesequences. Successful expression of recombinant proteins, including pharmaceutical proteins, hasbeen demonstrated in Chlamydomonas as well as in higher plants,where some interesting agronomic traits were also engineered through plastid transformation."
8804,Holistic Integrative Medicine,"Many people engaging in medical science asked me, “You’ve been working on the exploration of Holistic Integrative Medicine (HIM) for quite a while. What is the progress you have made in your research? Have you got your article published? May I be your first reader?” Each time I was confronted with such a situation, I felt embarrassed and speechless. Just as an old saying goes, it is easy to put the boat along with the current but it is difficult to sail against the current [1]."
8805,Open Source Chemoinformatics Software including KNIME Analytics,"In this chapter, we present a brief description of compound datasets and programs developed to serve chemoinformatics as well as, more specifically, nanoinformatics purposes. Emphasis has been placed on publicly available tools and particularly on KNIME (Konstanz Information Miner), the most widely used freely available platform for data processing and analysis. Among a multitude of studies that have demonstrated the usefulness of chemoinformatics tools to chemical and medicinal applications, herein we present indicative cases of five successful KNIME-based approaches. The first two studies include the risk assessment of nanoparticles (NPs) through the Enalos InSilicoNano platform, namely, (1) the prediction of the toxicity of iron oxide NPs and (2) the cellular uptake prediction of computationally designed NPs with the aid of reliable quantitative nanostructure–activity relationships (QNAR) models. The third case study deals with the recognition of organic substances as corrosion inhibitors though the construction of predictive quantitative structure–property relationships (QSPR) models with Enalos KNIME nodes. Finally, two more cases are briefly described and involve the accurate prediction of yellow fever inhibitors from the ChEMBL database and the de novo design of compounds with the reaction vectors methodology. The aim of this work is to familiarize the interested reader with the freely available in silico tools in KNIME analytics platform and to demonstrate their value and effectiveness toward specific computational applications."
8806,Dynamical Behavior of an SVIR Epidemiological Model with Two Stage Characteristics of Vaccine Effectiveness and Numerical Simulation,"An SVIR epidemiological model with two stage characteristics of vaccine effectiveness is formulated. By constructing the appropriate Lyapunov functionals, it is proved that the disease free equilibrium of the system is globally stable when the basic reproduction number is less than or equal to one, and that the unique endemic equilibrium of the system is globally stable when the basic reproduction number is greater than one."
8807,Context and Ethical Challenges During the Ebola Outbreak in West Africa,"The philosophical discipline of ethics examines good, bad, right, wrong and how people live as individuals within a community. Bioethics investigates research in healthcare and medicine, examining public policy as it relates to healthcare and how resources are allocated. This includes: difficult, private, individual decisions, which occur in clinical settings; dilemmas during clinical trials; and controversies surrounding novel research. It is important to understand that ethical considerations related to health care ethics and those that pertain to public health are often seen from different perspectives. In public health, decisions are made within a context and a framework through principles which guide action that affect communities and populations. These decisions and actions are made with and involve, stakeholders to include: traditional, community and religious leaders; government officials; and private and commercial stake holders. The underlying principles of both public health ethics and bioethics are the same, namely equality, justice, beneficence, non-maleficence, veracity and fidelity. Health care ethics supports the rights of individuals. Under the same umbrella of health care ethics are medical ethics, clinical ethics and research ethics. These disciplines offer views that support the rights of individuals. Ethics in public health is very complex with a myriad of issues to include diverse groups of people in different situations, which have to be taken into account from the view of what is best for the population. Evaluating the components of a public health system, how resources are developed and the economic support available to communities is crucial. Access to care and the equitable and just allocation of resources are important factors; and questions about equal access for the poor, the socially disadvantaged and immigrants should be examined."
8808,The Perioperative Use of Albumin,"Human serum albumin (HSA) is the predominant product of hepatic protein synthesis and one of the more abundant plasma proteins. HSA is a monomeric multidomain macromolecule, representing the main determinant of plasma oncotic pressure and the main modulator of fluid distribution between body compartments. HSA displays an essential role in maintaining the integrity of the vascular barrier. HSA is the most important antioxidant capacity of human plasma, in addition to its ability to protect the body from the harmful effects of heavy metals such as iron and copper and reduce their ability to produce reactive oxygen radicals. HSA is the main depot for nitric oxide (NO) transport in the blood. HSA represents the main carrier for fatty acids, affects pharmacokinetics of many drugs, and provides the metabolic modification of some drugs and displays pseudo-enzymatic properties. HSA has been widely used successfully for more than 50 years in many settings of perioperative medicine including hypovolemia, shock, burns, surgical blood loss, sepsis, and acute respiratory distress syndrome (ARDS). Recently, the use of HSA has shown a promising neuroprotective effect in patients with subarachnoid hemorrhage. The most recent evidence-based functions and uses of HSA in the perioperative period are reviewed in this chapter."
8809,Acute and Chronic Respiratory Failure in Cancer Patients,"In 2016, there was an estimated 1.8 million new cases of cancer diagnosed in the United States. Remarkable advances have been made in cancer therapy and the 5-year survival has increased for most patients affected by malignancy. There are growing numbers of patients admitted to intensive care units (ICU) and up to 20% of all patients admitted to an ICU carry a diagnosis of malignancy. Respiratory failure remains the most common reason for ICU admission and remains the leading causes of death in oncology patients. There are many causes of respiratory failure in this population. Pneumonia is the most common cause of respiratory failure, yet there are many causes of respiratory insufficiency unique to the cancer patient. These causes are often a result of immunosuppression, chemotherapy, radiation treatment, or hematopoietic stem cell transplant (HCT). Treatment is focused on supportive care and specific therapy for the underlying cause of respiratory failure. Noninvasive modalities of respiratory support are available; however, careful patient selection is paramount as indiscriminate use of noninvasive positive pressure ventilation is associated with a higher mortality if mechanical ventilation is later required. Historically, respiratory failure in the cancer patient had a grim prognosis. Outcomes have improved over the past 20 years. Survivors are often left with significant disability."
8810,Infectious Diseases in Pregnancy,"Many infectious diseases have the potential to complicate pregnancy. Some illnesses may only impact maternal health, but others can infect the fetus with possible devastating or long-term sequelae. In this chapter we aim to review common infectious diseases such as urinary tract infections and influenza as well as those that can cause major neonatal morbidity and mortality including TORCH infections. We will also discuss the challenges that pregnancy creates for the management of these infectious diseases as some antibiotics that would typically be used may not be safe for the developing fetus depending on the stage of pregnancy."
8811,Rethinking the financial network,"On 16 November 2002, the first official case of Severe Acute Respiratory Syndrome (SARS) was recorded in Guangdong Province, China. Panic ensued. Uncertainty about its causes and contagious consequences brought many neighbouring economies across Asia to a standstill. Hotel occupancy rates in Hong Kong fell from over 80 % to less than 15 %, while among Beijing’s 5-star hotels occupancy rates fell below 2 %."
8812,Neue Infektionserreger mit pandemischem Potential: Ursache – Verbreitung – Management,"Die im vergangenen Jahrhundert errungenen Erfolge bei der Reduzierung der Mortalität durch Infektionskrankheiten können nicht verdecken, dass beständig neue Infektionskrankheiten mit weltweiter Verbreitung auftreten. Diese gehen entweder auf „neue“ Erreger zurück („emerging diseases“), oder sind durch bekannte Erreger bedingt, die neue Verbreitungsgebiete erobert haben. Bei der Expansion der endemischen Zirkulation von Infektionserregern spielen anthropogene Faktoren eine entscheidende Rolle, und eine große Zahl völlig unterschiedlicher Erreger kommt für solche Geschehen in Betracht (Kaufmann 2010)."
8813,Disaster Theory,"To find a conclusive definition for contemporary purposes and uses, we look at many of the various definitions of disasters through cataclysmic events, historical records, public policies, laws, and organizational usage. Our natural progression leads us to modern theories of disaster and Disaster Risk Management (DRM) that have had to tackle new types of disasters that are being brought about by the interconnectivity of societies, people, diseases, technology, etc., increasing in magnitude and complexity like what was seen in Fukushima, Japan, in 2011 and on-setting disasters like climate change. After looking at all the historical evidence, we come to a definition for the term disaster for modern usage and what it means for policy implications."
8814,Role of Immunoglobulin Therapy to Prevent and Treat Infections,"Immunoglobulins have been used widely in medicine for a variety of diseases including infectious diseases. While the main clinical applications of immunoglobulin therapy concern their use as replacement for patients with primary immunodeficiencies, or as treatment for autoimmune and inflammatory disorders, their role in infectious disease is limited largely to viral and toxin neutralization and replacement therapy in patients with immunoglobulin deficiencies. Many aspects of the therapeutic regimen of immunoglobulins even in the established indications remain open. Recently, due to the worldwide surge of immunosuppression caused by AIDS, organ transplantation, cancer, and autoimmune therapies, as well as the emergence of multidrug-resistant bacteria, there has been renewed interest in the use of antibody preparation to prevent infections in high-risk groups. Knowing the limitations of the current anti-infective armamentarium, approaches that target the host through manipulations to augment the host immune response provide a helpful aid to conventional treatment options. A substantial body of evidence has demonstrated that strategies aiming to support or stimulate immune response could be feasible approaches that would benefit immunocompromised patients. In the present chapter, we present contemporary indications of immunoglobulin administration for therapy and prophylaxis of infections in the immunocompromised population."
8815,Cryptococcosis,Infection with encapsulated yeast Cryptococcus neoformans or gattii. C. neoformans is found in bird and bat droppings and contaminated soil/dust; C. gattii colonizes trees/wood debris.
8816,Vaccines,"Since the introduction of smallpox vaccination more than two centuries ago, vaccines have been—and still are—instrumental in the prevention of infectious diseases. Nowadays vaccines form a heterogeneous group of pharmaceutical products that differ in several aspects from other biopharmaceuticals. In this chapter, after a brief introduction we first cover immunological principles that are important for vaccine design. Next, we give an overview of the different vaccine categories and current approaches to vaccine development, illustrated with representative examples. We also describe current trends in the field of vaccines against non-infectious diseases, such as therapeutic vaccines against cancer and other diseases. Moreover, routes of administration relevant to vaccination and pharmaceutical aspects of vaccines are briefly discussed."
8817,Healthcare-Associated Infections in Pediatrics,
8818,Volume 3 Isolated Compounds (H-M),"Hemanthamine [466-75-1] C17H19NO4 (301.35). mp 203~203.5ºC, [a]D 25 = +19.7º (c = 3.8, methanol), [a]D 25 = +33 (c = 1.25, CHCl3). Pharm: Antihypertensive (mild); antiretroviral and cytotoxic (ID50 = 0.8µg/mL, TC50 = 1.0µg/mL, TI50 (TC50/ID50) = 1.3)[5026]."
8819,"Gewinnung, Herstellung und Lagerung von Blut und Blutkomponenten","Blutspender leisten einen wertvollen Dienst für die Gemeinschaft: Die ständige Verfügbarkeit von Blutkomponenten ist zur unverzichtbaren Voraussetzung für viele Bereiche der Medizin geworden. Nicht nur die Gewinnung und Aufarbeitung von Blut und Blutbestandteilen zur Sicherstellung einer qualitativ wie quantitativ guten Versorgung, sondern auch die kompetente Betreuung der Spender ist eine der großen Aufgaben der Transfusionsmedizin."
8820,Tonsillitis and Peritonsillar Abscess,"Tonsillitis is one of the most common childhood infections. Occasionally, it can lead to one of the most common deep space head and neck infections, peritonsillar abscess. The epidemiology, microbiology and treatment of tonsillitis and peritonsillar abscess are similar and crucial for the primary care physician, infectious disease specialist, otolaryngologist, and emergency medicine physician to understand. The routine use of tonsillectomy as a treatment option for recurrent tonsillitis and peritonsillar abscess has decreased over the last decade and clearer indications for surgery have emerged. This chapter provides an overview of the most recent literature regarding the epidemiology, microbiology, diagnosis, complications and management of tonsillitis and peritonsillar abscess. It also discusses the indications for tonsillectomy along with its complications."
8821,Applications of Infrared Thermography for Noncontact and Noninvasive Mass Screening of Febrile International Travelers at Airport Quarantine Stations,"Infrared thermography (IRT), one of the most valuable tools, is used for noncontact, noninvasive, and rapid monitoring of body temperature; this has been used for mass screening of febrile travelers at places such as airport quarantine stations for over 10 years after the 2003 severe acute respiratory syndrome (SARS) outbreak. The usefulness of thermography for mass screening has been evaluated in many recent studies; its sensitivity varies from 40 to 89.4% under various circumstances. In this chapter, we perform IRT evaluations for detecting febrile international travelers entering Japan at Nagoya Airport, immediately after the SARS epidemic, from June 2003 to February 2004, and at Naha International Airport from April 2005 to March 2009. The correlation of body surface temperature measured via thermography with the axillary temperature was significant. Through IRT, febrile individuals were detected with good accuracy and the detection accuracy was improved by corroborating surveillance with self-reporting questionnaires. However, there are several limitations associated with the use of IRT for fever screening. For instance, taking antifebrile medications results in rapid modification of the body temperature and directly affects the efficiency of IRT. To solve this unreliability and obtain higher accuracy in mass screening, we have developed a novel infection screening system using multisensor data, i.e., heart and respiration rates are determined by microwave radar in noncontact manner and facial skin temperature is monitored through IRT. The detection accuracy of the system improved, which is notably higher compared to the conventional screening method using only IRT."
8822,Mikrobiologische Schnelltests und molekularbiologische Analytik,"Die meisten der derzeit am Markt verfügbaren mikrobiologischen Schnelltests basieren auf immunologischen Nachweisverfahren. Charakteristisch für alle immunologischen Verfahren ist, dass sie auf einer hochspezifischen Antigen-Antikörper-Reaktion beruhen. Mittels dieses immunologischen Prinzips ist sowohl der qualitative Nachweis eines Analyten als auch die quantitative Bestimmung seiner Konzentration möglich. Der Testaufbau eines immunchemischen Tests kann besonders hinsichtlich der Entstehung und Auswertung der Testsignale erheblich variieren. Bewährte und für mikrobiologische Schnelltests häufig benutzte Formate sind die Partikelagglutination und die Immunchromatographie sowie die daraus hervorgegangenen Weiterentwicklungen, beispielsweise der optische Immunoassay. Auf Basis von Nukleinsäure-Amplifikationstechniken (vor allem der Polymerase- Kettenreaktion, PCR) sind bislang nur wenige POC-Tests verfügbar; ihre Praktikabilität und Bewährung in der Praxis wird sich erst in den nächsten Jahren zeigen."
8823,Interferons,"Interferon was discovered by Alick Isaacs and Jean Lindenmann in 1957. It was originally thought that interferon could be used as a general anti-viral agent and in anti-cancer therapy. There are many different types of interferons, now known as interferons “alpha,” “beta,” “gamma” and “lambda,” with different cellular receptors and modes of action, and there are possibly 24 different types of alpha interferon. Independently and simultaneously, a group of Japanese scientists found an “interfering factor,” which upon subsequent analysis turned out to be interferon, probably of the alpha type. The interferon alpha gene was the first mammalian gene to be cloned in a bacterial system and became the prototype for gene cloning technology. Until the cloning of the interferons in Escherichia coli, and expression of the interferon genes in mammalian cells in culture, it was impossible to obtain enough material for clinical use. Interferon today is predominantly used in the treatment of hepatitis B and C, leukemia and Kaposi’s sarcoma. As an anti-viral agent, interferon has not lived up to its initial promise, since in vitro most viruses block the activity of interferon and clinical trials have given inconclusive results with severe side effects. Interferon induces hundreds of genes in vivo and in vitro, each interferon producing overlapping and distinct gene profiles. The mechanism of both interferon induction and anti-viral response is complicated and involves the interaction of many regulatory molecules. Interferon is now known to be a component of the large family of cytokines or interleukins."
8824,Short- and Long-Term Reaction of European Airlines to Exogenous Demand Shifts,
8825,Carriage of Dangerous Goods by Air,"The subject of carriage of dangerous goods by air is addressed in Annex 18 to the Chicago Convention. The material in this Annex was developed by the Air Navigation Commission in response to a need expressed by Contracting States for an internationally agreed set of provisions governing the safe transport of dangerous goods by air. In order to assist in achieving compatibility with the regulations covering the transport of dangerous goods by other modes of transport, the provisions of this Annex are based on the Recommendations of the United Nations Committee of Experts on the Transport of Dangerous Goods and the Regulations for the Safe Transport of Radioactive Materials of the International Atomic Energy Agency. More than half of the cargo carried by all modes of transport in the world is dangerous cargo—explosive, corrosive, flammable, toxic and even radioactive. These dangerous goods are essential for a wide variety of global industrial, commercial, medical and research requirements and processes. Because of the advantages of air transport, a great deal of this dangerous cargo is carried by aircraft."
8826,National E-Commerce Strategy,"Before discussing national e-commerce strategies in detail, we would like to explain why we determined to write this chapter in such a rich and colorful manner and the motivation for our further research at the national level. It is this point which makes this book different from others of the same kind."
8827,Nanoparticles: Antimicrobial Applications and Its Prospects,"Nowadays, nanomaterials [NPs; size, 1–100 nm] have emerged as unique antimicrobial agents. Specially, several classes of antimicrobial NPs and nanosized carriers for antibiotic delivery have proven their efficacy for handling infectious diseases, including antibiotic-resistant ones, in vitro as well as in animal models, which can offer better therapy than classical drugs due to their high surface area-to-volume ratio, resulting in appearance of new mechanical, chemical, electrical, optical, magnetic, electro-optical, and magneto-optical properties, unlike from their bulk properties. Thus, scientifically NPs have been validated to be fascinating in fighting bacteria. In this chapter, we will discuss precise properties of microorganisms and their modifications among each strain specifically. The toxicity mechanisms vary from one stain to another. Even the NP’s efficacy to treat against bacteria and drug-resistant bacteria and their defense mechanisms change according to strains in particular composition of cell walls, the enzymic composition, and so on. Thus, we provide an outlook on NPs in the microbial world and mechanism to overcome the drug resistance by tagging antibiotics in NPs and its future prospects for the scientific world."
8828,Regulation of Neutrophil Serine Proteases by Intracellular Serpins,"Neutrophil granules contain serine proteases that are central components of the antimicrobial weapons of the innate immune system. Neutrophil proteases also contribute to the amplification and resolution of inflammatory responses through defined proteolytic cleavage of mediators, cell surface receptors, and extracellular matrix proteins. In the blood and at mucosal surfaces, neutrophil serine proteases are regulated by serpins found in plasma and by non-serpin secreted inhibitors. Distinct mechanisms leading to neutrophil cell death have been described for the granule serine proteases, neutrophil elastase, cathepsin G, and proteinase-3. Granule leakage in neutrophils triggers death pathways mediated by cathepsin G and proteinase-3, and both proteases are tightly regulated by their inhibitor SERPINB1 in a cell intrinsic manner. Although stored in the same types of granules, neutrophil elastase does not significantly contribute to cell death following intracellular release from granules into the cytoplasm. However, heterozygous mutations in ELANE, the gene encoding elastase, are the cause of severe congenital neutropenia, a life-threatening condition characterized by the death of neutrophils at an early precursor stage in the bone marrow. This chapter focuses on recent work exploring the biology of clade B intracellular serpins that inhibit neutrophil serine proteases and their functions in neutrophil homeostasis and serine protease control at sites of inflammation."
8829,Der Mann ohne Worte,"Ein Patient sucht verwirrt die Notaufnahme auf. Er kann nicht mehr sprechen, hat Kopfschmerzen. Dann kommen epileptische Anfälle dazu. Das Ärzte-Team steht vor einem Rätsel. Nichts scheint die Symptome zu erklären, keine Therapie schlägt an. Endlich gibt es eine Spur. Doch wer ist der Kranke eigentlich? Als der Zustand des Patienten sich dramatisch verschlechtert, beginnt ein Wettlauf mit der Zeit."
8830,Practice of Humidification During Noninvasive Mechanical Ventilation (NIV): Determinants of Humidification Strategies,1. Who will benefit from humidification? 2. When to apply humidification? 3. How to incorporate humidification into NIV?
8831,Bacterial Infections,"Molecular techniques have revolutionized the detection and identification of microorganisms. Real-time PCR has allowed for the rapid and accurate detection of MRSA, VRE, and group B Streptococcus. The identification of difficult and slow-growing organisms has been expedited by sequence-based methods such as 16S rRNA gene sequencing. Rapid identification of organisms and detection of resistance markers directly from positive blood culture bottles has become a reality. Finally, a transformation is taking place with the introduction of MALDI-TOF into clinical laboratories that promises to improve the accuracy and speed of bacterial and fungal identifications by days. The advantages of these methodologies and their associated clinical applications, along with their inherent pitfalls and problems, are elucidated in this chapter."
8832,Management of Ventilator-associated Pneumonia,"Pneumonia is the most important respiratory infection in mechanically ventilated patients. It is defined as the presence of microorganisms in the pulmonary parenchyma leading to the development of an inflammatory response by the host, which may be localized in the lung or may extend systemically. Nosocomial pneumonia is an infectious process which develops within 48 hours after admission to the hospital and that was not incubating at the time of hospitalization. Ventilator-associated pneumonia (VAP) is considered as a subgroup of nosocomial pneumonia and is an infectious pulmonary process which develops 48 hours after the presence of an artificial airway and mechanical ventilation. Since a large proportion of the patients who develop nosocomial pneumonia are intubated and receive mechanical ventilation, most epidemiological and clinical studies on nosocomial pneumonia have been focused on critically ill patients and those receiving mechanical ventilation. From a clinical point of view, nosocomial pneumonia is of great importance not only because of the consequences of the important morbidity and mortality but also due to the high costs associated with development of this disease."
8833,The Lung Endothelial Barrier in Acute Inflammation,"In the lungs, alveolar endo- and epithelial cells and their merged basal laminae form a delicate membrane, which allows rapid and effective gas exchange between alveolar and vascular lumen and, at the same time, provides a barrier to protect against inhaled particles and pathogens. Following infectious or sterile inflammatory conditions, strictly controlled endothelial leakiness is required for leukocyte transmigration. However, increased permeability caused by host-dependent inflammatory mechanisms or pathogen-induced endothelial injury may lead to uncontrolled protein-rich fluid extravasation, lung edema and finally acute respiratory distress syndrome (ARDS), which still carries an unacceptably high mortality rate. This chapter gives an overview of major mechanisms underlying pulmonary endothelial barrier regulation and disruption, focusing on the role of specific cell populations, complement and coagulation systems and mediators including angiopoietins, sphingolipids, adrenomedullin, as well as reactive oxygen and nitrogen species in the regulation of pulmonary vascular permeability. Further, current therapeutic strategies targeting the pulmonary endothelial barrier to improve barrier function are discussed."
8834,Monitoring the ECMO,"The ECMO device is complex and requires a precise, thorough, and constant management. The aim of this chapter is to describe and explain the different aspects of managing ECMO patients at bedside after implantation. We will be discussing here only about centrifugal pumps. The monitoring of an ECMO patient starts first like the surveillance of any ICU patient starting with a head-to-toe assessment of the patient. In addition to these regular ICU rounds will be added the following: The monitoring of the ECMO device itself. The surveillance of all the potential risks linked to the ECMO. Some clues to troubleshoot the main adverse events."
8835,"Diagnosis, Treatment, and Management of Hemophagocytic Lymphohistiocytosis in the Critical Care Unit","Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening condition characterized by uncontrolled inflammation. The management of HLH is challenging, in part, due to the multiple etiologies of the disease, the variations in presentations, and the rapidity of the progression of the disease. Due to the severity of their disease, these patients often require significant critical care support. HLH can be due to familial (genetic) causes or can be secondary to triggers such as infections, autoimmune disorders, and malignancy. Underlying conditions such as sepsis or malignancy could pose as major confounders while applying universal diagnostic criteria and therefore could lead to delay in diagnosis. This chapter focuses on the characteristics of the disease, pathophysiology, diagnostic criteria, treatment, and intensive care management of pediatric patients with HLH."
8836,Anti-infective Compounds from Marine Organisms,"The marine environment is a prolific source of bioactive compounds. During the last decades, research on marine-derived plants, animals, and microbes has provided an impressive number of structurally diverse anti-infective agents with antibacterial, antifungal, antiprotozoal, or antiviral activities. Moreover, several of these compounds possess novel mechanisms of action, which underlines their potential as leads in drug discovery. The present chapter provides an overview on marine-derived anti-infective agents, covering the literature between 2010 and 2016, with special focus on their structural features and mechanisms of action."
8837,"Biologische Waffen – eine Herausforderung an Diagnostik, Therapie, Klinik und Prävention","Es existiert keine international akzeptierte Legaldefinition für den Begriff »biologische Waffe« (B-Waffe). Manchmal werden bestimmte Erreger und Toxine als Biowaffen bezeichnet. Experten sprechen normalerweise erst dann von solchen, wenn biologische Agenzien (Organismen, Toxine, sich replizierende Einheiten) durch Konzentrationsprozesse, Stabilisatoren und andere Zusätze in Kampfstoffe verwandelt wurden oder/und wenn sich diese in Vorrichtungen zur Dispersion und Dissemination befinden."
8838,Attachment of human immunodeficiency virus to cells and its inhibition,"The entry of enveloped viruses involves virus adsorption followed by close apposition of the viral and plasma membranes. This multistep process is initiated by specific binding interactions between glycoproteins in the viral envelope and appropriate receptors on the cell surface. In the case of HIV-1, attachment of virions to the cell surface is attributed to a high affinity interaction between envelope spike glycoproteins (Env, composed of the surface protein gp120 and the transmembrane protein gp41) and a complex made of the primary CD4 receptor and a seven-transmembrane co-receptor (e.g., CXCR4 or CCR5) (reviewed in [1]). Then a chain of dynamic events take place that enable the viral nucleocapsid to penetrate within the target cell following the destabilization of membrane microenvironment and the formation of a fusion pore."
8839,Express Transmissible Gastroenteritis Virus Spike Gene B and C Antigen Sites in Multiple Expression Systems,"In order to illuminate the antigenicity of porcine transmissible gastroenteritis virus (TGEV) spike protein B and C antigen sites, the truncated spike gene including B and C antigen sites of Chinese isolate TH-98 was expressed respectively in E.coli, baculovirus and pichia pastoris expression systems. Dot enzyme-linked immunosorbent assays (Dot-ELISA) based on these three recombinant proteins were developed preliminarily. Ten sera obtained correspondingly from ten piglets two months old which showed up clinical symptom were used for examination. The study indicates that the assays are rapid, reliable and sensitive and it has the potential for use as serological methods for TGEV diagnosis."
8840,Neurologie,
8841,Monitoring Immune Dysfunction in Septic Patients: Toward Tailored Immunotherapy,"Septic syndromes represent a major although largely under-recognized healthcare problem worldwide accounting for thousands of deaths every year [1–3]. Mortality remains high ranging from 20 % for sepsis to over 50 % for septic shock despite almost 20 years of anti-inflammatory clinical trials [1–3]. The inability of these therapies to mitigate the devastating effects of this condition indicates that the initial hypotheses for sepsis pathophysiology may have been misconstrued or inadequately addressed. Two major explanations have been proposed: 1) Septic patients have mainly been treated as a group despite the extreme heterogeneity characterizing this population [1]; 2) The postulate that death after sepsis is solely due to an overwhelming pro-inflammatory immune response may actually be inaccurate [1, 3]. Indeed, several lines of evidence have now established that death from septic shock is probably due to the effect of distinct mechanisms over time [1–3]. Early in the course of the disease, a massive release of inflammatory mediators (normally designed to trigger an immune response against pathogens) is occurring that may be responsible for organ dysfunction and hypoperfusion [1, 3]. Concomitantly, the body develops compensatory mechanisms to prevent overwhelming inflammation and dampen an over-zealous anti-infectious response [1–3]. These negative feedback mechanisms, although having protective effects during the first initial hours, may paradoxically become deleterious as they persist over time leading to immune paralysis (Fig. 1) [1, 3]. Indeed, considerable clinical and experimental evidence indicates that patients rapidly present with numerous compromised immune functions [1, 3]. As our capacity to treat patients during the very first hours of shock has improved (early and aggressive initial supportive therapy) [1], many patients now survive this critical step but eventually die later in a state of immunosuppression that is illustrated by difficulty fighting the primary bacterial infection and decreased resistance to secondary nosocomial infections [1, 3]. Consequently, immunostimulatory therapies are now considered as an innovative strategy for the treatment of sepsis [1, 3]. However, the first critical step is to be able to identify patients who would actually benefit from these therapies [2, 3]. Indeed, in the absence of specific clinical signs of immune status, it is critical to determine the best biological tools to stratify patients according to their immune status (a missing step in most previous clinical trials) [1–3]. This would define the right action (i.e., stimulating innate immunity and/or adaptive immunity, blocking apoptosis, restoring other altered functions) at the right time (early or delayed treatment) in the right patient (individualized/tailored therapy)."
8842,Disasters from 1948 to 2015 in Korea and Power-Law Distribution,"The Korean peninsula is no stranger to disaster, experiencing natural disasters such as severe downpours, floods, and typhoons and human-caused disasters such as industrial accidents, building collapses, and infernos. Fortunately, for the purposes of learning from each event, it has well documented many aspects of each disaster, policy and law changes, institutional reforms, and future risk management alternatives. However, to take the almost 2000-year documented history of Korea in a more manageable period, we focus on the major disaster events, those that are quantifiable and that took place between 1948 and 2015 to see if the disaster trend in Korea is producing power-law distributed disasters. We specifically analyzed the statistical characteristics of these major disaster events and their functional relationship between frequency and magnitude to see if a change in one produces a proportional relative change in the other."
8843,Allgemeine Chirurgie,"Definition. Retrograder Transport von Magen- bzw. Dünndarminhalt durch Speiseröhre und Mund nach außen, begleitet durch Würgen und Übelkeit (Nausea) Symptomatik. Der Zeitpunkt des Erbrechens in Relation zur Nahrungsaufnahme und das Aussehen bzw. der Geruch des Erbrochenen können Hinweise auf die Lokalisation des Passagehindernisses geben."
8844,Disease management strategies in SARS,
8845,Infectious Disease in Wild Animal Populations: Examining Transmission and Control with Mathematical Models,"The mathematical modeling of ecological interactions is an essential tool in predicting the behavior of complex systems across landscapes. The scientific literature is growing with examples of models used to explore predator-prey interactions, resource selection, population growth, and dynamics of disease transmission. These models provide managers with an efficient alternative means of testing new management and control strategies without resorting to empirical testing that is often costly, time-consuming, and impractical. This chapter presents a review of four types of mathematical models used to understand and predict the spread of infectious diseases in wild animals: compartmental, metapopulation, spatial, and contact network models. Descriptions of each model’s uses and limitations are used to provide a look at the complexities involved in modeling the spread of diseases and the trade-offs that accompany selecting one modeling approach over another. Potential avenues for the improvement and use of these models in future studies are also discussed, as are specific examples of how each type of model has improved our understanding of infectious diseases in populations of wild animals."
8846,Kardiologie,"Die Kardiologie ist ein wichtiges und sehr umfangreiches Themengebiet der Inneren Medizin. In diesem Kapitel werden die wichtigsten Pathologien, die sich am Herzen manifestieren können, ihre Diagnostik und Therapie dargestellt. Hierzu zählen vor allem Erkrankungen des Endokards, Herzklappenfehler (erworben wie angeboren), Herzrhythmusstörungen, aber auch Erkrankungen des Myo- und Perikards. Ebenso werden die Herzinsuffizienz und die koronare Herzkrankheit (KHK) in einem eigenen Abschnitt behandelt. Am Ende des Kapitels wird kurz auf die seltenen Tumoren am Herzen und funktionelle Herzbeschwerden eingegangen."
8847,Primate Infectious Disease Ecology: Insights and Future Directions at the Human-Macaque Interface,"Global population expansion has increased interactions and conflicts between humans and nonhuman primates over shared ecological space and resources. Such ecological overlap, along with our shared evolutionary histories, makes human-nonhuman primate interfaces hot spots for the acquisition and transmission of parasites. In this chapter, we bring to light the importance of human-macaque interfaces in particular as hot spots for infectious disease ecological and epidemiological assessments. We first outline the significance and broader objectives behind research related to the subfield of primate infectious disease ecology and epidemiology. We then reveal how members of the genus Macaca, being among the most socioecologically flexible and invasive of all primate taxa, live under varying degrees of overlap with humans in anthropogenic landscapes. Thus, human-macaque interfaces may favor the bidirectional exchange of parasites. We then review studies that have isolated various types of parasites at human-macaque interfaces, using information from the Global Mammal Parasite Database (GMPD: http://www.mammalparasites.org/). Finally, we elaborate on avenues through which the implementation of both novel conceptual frameworks (e.g., Coupled Systems, One Health) and quantitative network-based approaches (e.g., social and bipartite networks, agent-based modeling) may potentially address some of the critical gaps in our current knowledge of infectious disease ecology at human-primate interfaces."
8848,Interventions to prevent transmission of the common cold,"Theoretically, there are several ways of preventing the common cold: quarantine, immunisation (or vaccination); early treatment of effected individuals; or physical barriers to reduce transmission. All these methods can be dismissed after considering the epidemiology of the common cold, apart from the last. Evidence for effectiveness for physical barriers (which include masks to reduce aerosol transmission; handwashing; and gloves and gowns) come from a variety of empirical studies. The chance of bias for these studies is variable, but we can conclude that all of these barrier methods have important potential for preventing transmission of the common cold, although some methods will not be acceptable to the community currently."
8849,Hemotransfusion in Combat Trauma,"The collaboration of blood transfusion service in the management of severely combat-injured individuals has proved to be an essential factor for the successful treatment of these patients. While the operating and anesthesiology teams are engaged in maintaining the vital signs and controlling blood loss of the injured, the transfusion service representatives follow the information on the amount of blood products given and the latest laboratory tests, as well as provide consultations regarding further blood component requirements on the basis of data obtained. A major effort of the treating team should be aimed at diagnosis and correction of coagulopathy, acidosis, and hypothermia. For the massively bleeding combat trauma injured, which can amount to as high as 8% of all trauma patients, a generous use of plasma at a one-to-one ratio with packed cells, along with the early addition of platelets and cryoprecipitates, should be considered. Early point-of-care thromboelastography is helpful for identification of coagulopathies. The use of a preset massive transfusion protocol is beneficial; however, it should be tailored according to the patient’s actual needs, depending on the type of injury and the individual’s general condition."
8850,Food Policies’ Roles on Nutrition Goals and Outcomes: Connecting of Food and Public Health Systems,"Nutrition exists when food security is combined with a sanitary environment, adequate health services, and proper care and feeding practices to ensure a healthy life for all household members. Despite increased attention to undernutrition, it remains a devastating multi-faceted problem for infants, young children, and women around the world, resulting in increased morbidity, mortality, and long-term disability. Undernutrition can also lead to poor health into adulthood, which affects social and economic development of nations. On the other end of the malnutrition spectrum, overweight and obesity are growing problems, linked to changing diets and activity patterns, which also lead to serious health problems and impact the economies of nations. This chapter attempts to unpack the importance of food and agriculture policies on nutrition outcomes and why engagement of food and public health systems remain critically important. External pressures, such as climate variability and population growth, that tax these systems are discussed, as well as the globalization of our food system and why that has shifted dietary patterns and nutrition and health status trends. The multi-sectoral integration of food and health systems and its importance to improve nutrition is demonstrated through three models. Three very brief case studies are presented that help exemplify some of the food and health system trends that influence policy and ultimately, nutrition outcomes."
8851,Infektiologische Erkrankungen,"Sytemische Reaktion des Körpers auf generalisierte Infektionen (Bakteriämie, Fungämie, Virämie, Parasitämie oder schwere Organinfektion). Klinisch nicht zu unterscheiden von SER = SIRS (systemische entzündliche Reaktion), z.B. durch Trauma, Verbrennung u.a."
8852,Phytochemical Constituents and Pharmacological Effects of Licorice: A Review,"Licorice (or “liquorice”) is one of most widely used in foods, herbal medicine, and extensively researched medicinal plants of the world. In traditional medicine licorice roots have been used against treating many ailments including lung diseases, arthritis, kidney diseases, eczema, heart diseases, gastric ulcer, low blood pressure, allergies, liver toxicity, and certain microbial infections. Licorice extract contains sugars, starch, bitters, resins, essential oils, tannins, inorganic salts, and low levels of nitrogenous constituents such as proteins, individual amino acids, and nucleic acids. A large number of biological active compounds have been isolated from Glycyrrhiza species, where triterpene saponins and flavonoids are the main constitutes which show broad biological activity. This review examines recent studies on the phytochemical and pharmacological data and describes some side effects and toxicity of licorice and its bioactive components."
8853,Notification and Disease Control: Obligations of the Medical Practitioner Under Public Health Legislation,"Effective disease control requires a strong partnership between clinicians and public health personnel. The vital role medical practitioners play is reflected globally in the obligation under health legislation for medical practitioners to notify the public health authority of specific details of named patients suspected of having these diseases. While the principle is universal that the notification include the identity of the patient, to allow prompt and direct public health action, if needed, jurisdictions have varying approaches to many other aspects of notification: the actual list of notifiable conditions; who must notify and based on what degree of diagnostic certainty; in what timeframe and with what specific details; what information is to be provided to the case; and who bears responsibility for contact tracing. In addition, in some jurisdictions, medical practitioners have associated statutory obligations and powers, related to the examination of a patient directed for assessment by the public health authority, the furnishing of reports of such examinations, the role of the practitioner in ordering a patient into isolation, and responsibilities of medical practitioners in public health emergencies. Following a concise historical survey, finishing with the impact of the International Health Regulations 2005, this chapter systematically discusses the statutory obligations of medical practitioners for disease notification and related provisions, taking examples from English-language public health legislation used in Oceania, Europe, North America, Asia, and Africa."
8854,Caspase-7,
8855,Work-Associated Trauma,"Traumatic events are experienced by most people at some point in their life. Following a traumatic event many individuals return to previous functioning and some feel an increased sense of efficacy. However, a sizable minority experience adverse psychological and behavioral effects. These effects include distress reactions, health risk behaviors, and psychiatric disorders. Workplace traumatic events and responses most studied in physicians include exposure to injured and dying patients, medical errors and complications, bullying, disasters, and workplace violence. Developmental issues confer specific risks for medical students and residents, as well as early and late career physicians. Prevention measures which reduce exposure to workplace trauma are optimal. Physicians exposed to traumatic events will benefit from the use of prompt, evidence-based interventions. Many will seek and benefit from self-help interventions and peer support, but some may need formal assessment and treatment through employee assistance programs and traditional psychiatric care. Effective prevention and treatment can enhance physician well-being and career retention as well as patient outcomes."
8856,A Tool for Comparing Outbreak Detection Algorithms,"Despite of the main objective of recent biosurveillance researches is bioterrorist attack threats, detection of natural outbreaks are also being tried to solve by governments all over the world. Such that, international foundations as WHO, OECD and EU publish public declaration about necessity of an international central surveillance system. Each data source and contagious disease carries its own patterns. Therefore, standardizing the process of outbreak detection cannot be applicable. Various methods have been analyzed and published on test results in biosurveillance researches. In general, these methods are the algorithms in literature of SPC and Machine Learning, although specific algorithms have been proposed like Early Aberration Reporting System (EARS) methods. Differences between published results show that, the characteristic of time series are tested with algorithm and the chosen parameters of this algorithm are also determine results. Our tool provides preprocessing of data; testing, analyzing and reporting on anomaly detection algorithms specialized at biosurveillance. These functionalities make it possible to use outputs for comparing algorithms and decision making."
8857,Lessons from History,"Resilience has a lengthy history of practice and implementation for events of extreme consequence and high uncertainty. One of the clearest cases of embryonic resilience thinking includes Medieval Venice, which was forced to grapple with the recurring threat of plague that threatened to destroy the fabric of European society and cripple the juggernaut of Venetian maritime trade (Linkov et al. 2014a, b, c, d, e; Lane 1973). This early resilience thinking did not fully inoculate Venetian society from the ravages of disease—on the contrary, limitations of medical knowledge and border control allowed for outbreaks throughout the early modern era—yet it did allow Venetian policymakers to begin to address the question of how to combat deadly disease. The cumulative successes in reducing disease incidence and spread throughout the city and its dependent settlements eventually brought policymakers to embrace resilience thinking for other unrelated projects ranging from climate change to land reclamation efforts—all centered on the idea of strengthening Venetian social, economic, and cultural capabilities in the midst of an uncertain future (Vergano and Nunes 2007; Linkov et al. 2014a, b, c, d, e). This all goes to show that while resilience thinking and resilience analysis are growing buzzwords in the early twenty-first century, their roots go back centuries before even the printing press or functional medicine."
8858,Prevention and Treatment of Respiratory Virus Infection,"There is increasing recognition of infections caused by respiratory viruses (RVs) as a major cause of morbidity and mortality in solid organ transplant (SOT) recipients, especially within the thoracic and pediatric population. In addition to their direct, cytopathic, and tissue-invasive effects, RVs can create an inflammatory environment, autoimmune responses, resulting in acute and chronic rejection, although this relationship remains controversial. A laboratory diagnosis in SOT with respiratory syndrome should be performed with nucleic acid amplification tests on respiratory specimens, mainly nasopharyngeal swabs (NPS) and bronchoalveolar lavage (BAL). Treatment options remain limited and consist of supportive care, reduction of immunosuppression, and, if available, antiviral therapy. The use of immunomodulatory agents remains a clinical dilemma. Since treatment options for RVs are limited, maximizing prevention measures against viral infections in SOT is mandatory. The main preventive strategy against influenza remains the administration of yearly inactivated influenza vaccine in all SOT. The aim of this review is to summarize the evidence-based recommendations on the diagnostic, preventive, and therapeutic strategies to decrease the burden of RV infections in SOT recipients."
8859,Intensivtherapie bei HIV-Infektion,In den ersten Jahren der AIDS-Epidemie war die Behandlung von HIV-assoziierten Komplikationen mit einer ICU-Mortalität von 80–90% verknüpft [6]. Mit der rascheren Diagnose und besseren Therapie zuerst der opportunistischen Erkrankungen und der HIVInfektion verbesserte sich die Prognose deutlich [9]. Heute ist die Langzeitprognose HIV-infizierter Patienten mit einer wirksamen antiretroviralen Therapie am ehesten vergleichbar mit der anderer chronischer Erkrankungen [1].
8860,Erkrankungen des Kehlkopfs,"Der Kehlkopf bildet als Teil des Atemtrakts den Übergang vom Rachen zur Luftröhre im vorderen Halsbereich. Embryonal entsteht er sich aus dem 4.–6. Kiemenbogen. Der Kehlkopf besteht aus drei großen Knorpel, dem Schildknorpel (Cartilago thyroideus), dem Ringknorpel (Cartilago cricoides) und dem Kehldeckel (Epiglottis) sowie den zwei kleineren Stellknorpeln (Cartilago arytaenoidea). Der Schildknorpel bildet die vordere Wand des Kehlkopfs und ist v. a. an seiner Oberkante von außen zu sehen und zu tasten. Der Kehlkopf hat im Wesentlichen zwei Funktionen: er schützt die Luftröhre vor Speisestücken, in dem der Kehlkopf beim Schlucken nach vorne oben gezogen und damit mit dem Kehldeckel verschlossen wird und zum anderen regulieren die Stimmlippen den Strom der Atemluft und erzeugen durch ihre Schwingungen Töne bzw. die menschliche Stimme."
8861,SARS,
8862,Novel vaccination strategies,
8863,The State of Health System(s) in Africa: Challenges and Opportunities,"As study after study has pointed out, the health care systems in Africa pay little attention to the critical interface between education and good health, especially when it comes to the education of women and mothers, who are the primary line of defense against child diseases, and perform simultaneously most domestic chores and critical agricultural activities. While many medical educational institutions on the continent tend to perpetuate, at times, skewed and irrelevant Eurocentric health training, the national pyramidal health structure, weakened at the village level, and disproportionately favoring the provincial and national hospitals, gives the illusion that rural areas are well-served, when in actuality they are not. This chapter endorses the restrengthening of an uncompromised health care system to make it effective and efficient for both rural and urban areas; one that finds ways of trimming financial and human resource waste; revamps the institutions that train health care and service providers to make the system responsive to the real health needs of the people and not just the wealthy; one that compensates physicians just as civil servants; and aligns the educational system with targeted and expected measurable health outcomes."
8864,Prospective Study About the Influence of Human Mobility in Dengue Transmission in the State of Rio de Janeiro,"Dengue is a human arboviral disease transmitted by Aedes mosquitoes and it is currently a major public health problem in which around 2–5 billion people are at risk of infection each year. Climate changes and human mobility contribute to increase the number of cases and to spread the disease all around the world. In this work, the influence of human mobility is evaluated by analyzing a sequence of correlations of dengue incidence between cities in southeastern Brazil. The methodology initially identifies the cities were the epidemy begins, considered as focus for that epidemic year. The strength of the linear association between all pairs of cities were calculated identifying the cities which have high correlations with the focus-cities. The correlations are also calculated between all pairs considering a time lag of 1, 2 or 3 weeks ahead for all cities except the focus ones. Centred differences of the notification number are used to detect the outbreaks. The tests were made with DATASUS-SINAN data of the state of Rio de Janeiro, from January 2008 to December 2013. Preliminary results indicate that the spread of dengue from one city to another can be characterized by the development of the sequence of shifted correlations. The proposal may be useful to consider control strategies against disease transmission."
8865,Das Virus aus dem Labor (1),"Kann uns das drohen? Eine Grippe-Pandemie, ausgelöst durch einen Laborunfall mit einer »aufgerüsteten« Version des Vogelgrippe-Virus H5N1? Die US-Regierung sieht das offenbar so. In einem bisher beispiellosen Schritt hat sie Wissenschaftler aufgefordert, eine Arbeit zum Vogelgrippevirus nicht vollständig zu veröffentlichen."
8866,Towards a Practical Cosmopolitanism,"Claiming the airport as an exemplar of contemporary global space and the incessant logics of movement seen to be at the heart of globalisation, the introductory chapter asks what is it to move in the airport space? What is the choreography of the airport? Reviewing debates on critical cosmopolitanism, and the corporeal and spatial turns, this chapter argues for the need to further embodied analysis of global movement through a kind of kinaesthetic ethnography, which puts the wealth of thinking about moving bodies in space from dance studies into dialogue with mobility studies. Such an approach, the chapter argues, can lead us to important knowledge about the ongoing tensions between sameness and difference, national and transnational, self and other, as experienced in the transit spaces of global mobility—a practice of cosmopolitanism."
8867,"‘Black Swans’, ‘Dragon Kings’ and Beyond: Towards Predictability and Suppression of Extreme All-Hazards Events Through Modeling and Simulation","Shocks to regional, national and global systems stemming from natural or man-made hazards can have dramatic implications. Disasters such as Katrina (2005), Hurricane Sandy (2012), Alberta (Canada) Floods (2013), and Super Typhoon Haiyan (2013) are examples that highlight the vulnerability of communities to natural hazards and the crippling effect they have on the social and economic well-being. Through foresight and scenario planning, such events can be expected but can they be predicted to support resilience and enable suppression of the impacts? With consideration of emerging and systemic risks and inherent uncertainty associated with surprising events, planning for and managing risk, crisis and disasters requires understanding of the outliers that challenge our resilience. ‘Black Swans’ represent the unpredictable. They represent “… our misunderstanding of the likelihood of surprises” (Taleb in The black swan: the impact of the highly improbable, 2007). A ‘Black Swan’ is described by Taleb (2007) as that which is an outlier, that which is outside the realm of regular expectations which carries with it an extreme impact such as natural disasters, market crashes, catastrophic failure of complex socio-technical systems and terrorist events such as 9/11. Sornette (Int J Terraspace Sci Eng 2(1):1–18, 2009) identifies a different class of extreme events (outliers) that he calls ‘Dragon Kings’. Sornette (2009) argues that Dragon Kings may have properties that make them not only identifiable in real time but also predictable. The evolving science on complexity (and, more specifically, on complex networks) and on resilience suggest that modeling and simulation of such extreme events can assist in the predictability and the suppression of low probability extremely high consequence events such as natural hazards (flood, earthquake, wildfire, tsunami, extreme weather), cyber-attacks, and financial events. Furthermore, the science of complex networks is developing rapidly and has fundamentally reshaped our understanding of complexity, potentially leading to innovative methods for the prediction of emergent behavior on natural and technological networks, as well as specific strategies for designing networks that are more resistant (resilient) to both failure and attack. Governments and owners of critical physical and digital infrastructure may benefit from analyses, advice and exercises that involve predictable and suppressible “Dragon-King” type of low probability extremely high consequence extreme events, as well as from the utilization of recent advances in complex network theory, to ultimately enhance resiliency. This chapter contributes to the discourse on Dragon Kings arguing for continued and concerted efforts to explore this domain."
8868,Proinflammatory and Antiinflammatory Mediators in Critical Illness,
8869,angiotensin-converting enzyme 2 3.4.17.23,"EC number 3.4.17.23 Recommended name angiotensin-converting enzyme 2 Synonyms ACE <4> [12] ACE 2 <10,12,13> [74] ACE-2 <2,3,4,9> [38,68] ACE-related carboxypeptidase <9> [3] ACE2 <1,2,3,4,5,6,9,10,11,12,13> [1,2,3,5,6,9,14,15,16,17,19,20,22,25,26,30,37,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,65,66,67,68,69,70,71,72,73,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97] ACE2 homologue <2> [41] ACEH <9> [7] Ang converting enzyme 2 <10,12,13> [74] angiotensin II converting enzyme 2 <3> [81] angiotensin converting enzyme 2 <2,3,4,6,9,10,11,12,13> (<3> functions as a carboxypeptidase [41]) [14,41,43,46,47,51,55,57,58,60,63,74,78,84] angiotensin converting enzyme II <9> [95] angiotensin converting enzyme-2 <2,3,4> [38] angiotensin-converting enzyme <4,9> [22] angiotensin-converting enzyme 2 <4,8,9,10,12,13> [10,19,67,68,70,76] angiotensin-converting enzyme homolog <9> [7] angiotensin-converting enzyme homologue <9> [6] angiotensin-converting enzyme type 2 <13> [79] angiotensin-converting enzyme-2 <3,4> [37,53,97] angiotensin-converting enzyme-like protein <9> [7] angiotensin-converting enzyme-related carboxypeptidase <9> [1,6] angiotensinase <9> [4] hACE2 <3,10,13> [36,67,74] CAS registry number 328404-18-8"
8870,"Biologische Waffen – eine Herausforderung an Diagnostik, Therapie, Klinik und Prävention","Mediziner und Wissenschaftler müssen die Gefahren, die von biologischen Waffen ausgehen, kennen und über mögliche vorsätzlich freigesetzte Mikroorganismen informiert sein, um Bevölkerung und Patienten behandeln und ggf. beruhigen zu können."
8871,Nanowire Field-Effect Transistor Sensors,"Sensitive and quantitative analysis of proteins and other biochemical species are central to disease diagnosis, drug screening and proteomic studies. Research advances exploiting SiNWs configured as FETs for biomolecule analysis have emerged as one of the most promising and powerful platforms for label-free, real-time, and sensitive electrical detection of proteins as well as many other biological species. In this chapter, we first briefly introduce the fundamental principle for semiconductor NW-FET sensors. Representative examples of semiconductor NW sensors are then summarized for sensitive chemical and biomolecule detection, including proteins, nucleic acids, viruses and small molecules. In addition, this chapter discusses several electrical and surface functionalization methods for enhancing the sensitivity of semiconductor NW sensors."
8872,Targeting Immunomodulatory Agents to the Gut-Associated Lymphoid Tissue,"In addition to fluid haemostasis and lipid absorption, the lymphatic system and lymphoid tissues serve as the major host of immune cells where immune responses are evoked. Impaired function of the immune system might lead to serious diseases which are often treated by immunomodulators. This chapter briefly explores the physiology of an important part of the lymphatic system, the gut-associated lymphoid tissues (GALT). Currently used strategies for targeting GALT by immunomodulators for enhanced activity and/or decreased side effects are discussed. Strategies range from simple oral co-administration of immunomodulators with lipids to more advanced lipid-based formulations, polymer-based nanoparticle formulations and prodrugs. These targeting approaches successfully increase the concentration of immunomodulators achieved in the GALT and, more importantly, enhance immunomodulatory effects. Therefore, targeting immunomodulators to GALT represent a promising approach in the treatment of diseases where the immune system is actively involved."
8873,Epidemic Models,"Communicable diseases such as measles, influenza, and tuberculosis are a fact of life. We will be concerned with both epidemics, which are sudden outbreaks of a disease, and endemic situations, in which a disease is always present. The AIDS epidemic, the recent SARS epidemic, recurring influenza pandemics, and outbursts of diseases such as the Ebola virus are events of concern and interest to many people. The prevalence and effects of many diseases in less-developed countries are probably not as well known but may be of even more importance. Every year millions, of people die of measles, respiratory infections, diarrhea, and other diseases that are easily treated and not considered dangerous in the Western world. Diseases such as malaria, typhus, cholera, schistosomiasis, and sleeping sickness are endemic in many parts of the world. The effects of high disease mortality on mean life span and of disease debilitation and mortality on the economy in afflicted countries are considerable."
8874,Krisenmanagement,"Erfolgreiche Unternehmen und Organisationen entwickeln ein umfassendes Bewusstsein für mögliche Krisen, sie betreiben professionelle Krisenprävention. Das Rezept für eine dauerhafte und erfolgreiche Krisenprävention lautet: Jeden Tag nach vorne schauen, Risiken wahrnehmen, richtig abschätzen und möglichst neutralisieren. Systematische Verfahren zur Früherkennung von Warnsignalen spielen dabei eine wichtige Rolle. Krisenpotenziale erkennen und antizipieren, Infrastrukturen schaffen, Abläufe einüben und Mitarbeiter schulen sind gute Voraussetzungen, um in krisenhaften Situationen souverän zu agieren, statt in einen Schockzustand zu verfallen. Leider sind noch zu viele Unternehmen und Organisationen von diesem Ideal weit entfernt. Krisen gefährden außerdem immer das Image und die Reputation eines Unternehmens. In diesem Zusammenhang darf das mediale Interesse nicht unterschätzt werden. Die Mediengesellschaft, in der wir leben, liebt und produziert deswegen unentwegt große und kleine Krisen, indem sie schlicht jede Gelegenheit zur Berichterstattung nutzt. Schließlich ist die Krise – mehr noch als die bloß schlechte Nachricht – ein hervorragend verkäufliches Gut (Mörle 2004). Leider verfügen noch zu wenig Unternehmen über professionelle Konzepte, die auch den Aspekt der Krisenkommunikation hinreichend berücksichtigen. Auch ist einzelnen Studien zu entnehmen, dass das Bewusstsein in Deutschland für das Thema Krisenprävention und ‑bewältigung in einigen Branchen noch nicht hinreichend ausgeprägt ist."
8875,Lost Trust: Socio-biological Hazard—From AIDS Pandemic to Viral Outbreaks,"Iatrogenic HIV infection refers here to cases of infection with the human immunodeficiency virus (HIV) caused by private and public administration of blood products [1]. Following the discovery of acquired immunodeficiency syndrome (AIDS) in 1981, numerous warnings were issued by specialists regarding the use of blood products. In spite of this, no effective measures such as a switch to cryoprecipitate were taken, and the authorization of safe heated products was also delayed, as a result of which 40 % of Japanese hemophiliacs, or some 2000 people, fell victim as a result of ‘human error’ [2]. Additionally, since insufficient risk data was provided, the infection spread to partners, families, and other associates of hemophiliacs through secondary and tertiary infection. In connection, questions were asked as to the degree of responsibility of those institutions involved in the outbreak and spread of the infection."
8876,Commercial Buildings,"Applications for UVGI systems in commercial buildings vary with the type of building, but virtually every type of building can benefit from the use of in-duct air disinfection and many buildings can benefit from the use of other types of UV systems. The health hazards and microbiological problems associated with various types of commercial buildings are often unique to the type of facility. The problem of air quality is paramount in commercial office buildings while the problem of biocontamination is of the highest concern in the food industry. Other types of buildings have their own microbial concerns and even their own standards. The pharmaceutical industry has the highest aerobiological air quality standards (and lowest airborne microbial levels) while the other extreme, the agricultural industry, has the highest airborne microbial levels and unique aerobiological concerns. The individual problems of these facilities are addressed in the following sections, and industry experience relating to UV applications are discussed, along with recommendations for how UV systems can be applied. The specific types of UVGI systems are described in previous chapters and these should be referred to for detailed information on such applications."
8877,Molekulare Struktur eukaryotischer Chromosomen,"Die Chromosomen sind die lichtmikroskopisch sichtbaren, materiellen Träger der Gene. Bedeutet das aber, dass sie lediglich eine Ansammlung kettenartig aneinandergefügter Gene sind? Aus cytologischen Beobachtungen wissen wir, dass die Chromosomen, und damit die Gene, in Mitose und Meiose gleichmäßig auf die Tochterzellen verteilt werden. In den Centromerbereichen der Chromosomen dienen die Kinetochore als Ansatzpunkte für die Mikrotubuli des Spindelapparates. So werden die Chromosomen bzw. deren Untereinheiten, die Chromatiden, bei der Zellteilung auf die Tochterzellen aufgeteilt. Besondere terminale Domänen, die Telomere, gewährleisten, dass die freien Enden der DNA im Chromosom nicht von Exonukleasen abgebaut werden oder durch Reparaturenzyme mit den freien Enden der DNA eines anderen Chromosoms verschmelzen."
8878,"Viruses: Definition, Structure, Classification","Viruses are infectious units with diameters of about 16 nm (circoviruses) to over 300 nm (poxviruses; Table 2.1). Their small size makes them ultrafilterable, i.e. they are not retained by bacteria-proof filters. Viruses have evolved over millions of years, and have adapted to specific organisms or their cells. The infectious virus particles, or virions, are composed of proteins and are surrounded in some species of viruses by a lipid membrane, which is referred to as an envelope; the particles contain only one kind of nucleic acid, either DNA or RNA. Viruses do not reproduce by division, such as bacteria, yeasts or other cells, but they replicate in the living cells that they infect. In them, they develop their genomic activity and produce the components from which they are made. They encode neither their own protein synthesis machinery (ribosomes) nor energy-generating metabolic pathways. Therefore, viruses are intracellular parasites. They are able to re-route and modify the course of cellular processes for the optimal execution of their own reproduction. Besides the genetic information encoding their structural components, they additionally possess genes that code for several regulatory active proteins (such as transactivators) and enzymes (e.g. proteases and polymerases)."
8879,Acute Myeloid Leukemia: Epidemiology and Etiology,"Although acute leukemias are infrequent diseases, they are highly malignant neoplasms responsible for a large number of cancer-related deaths. Acute myeloid leukemia (AML) is the most common type of leukemia in adults, yet continues to have the lowest survival rate of all leukemias. While results of treatment have improved steadily in younger adults over the past 20 years, there have been limited changes in survival among individuals of age >60 years [1, 2]."
8880,Pulmonary Complications,"After hematopoietic stem cell transplant (HSCT), up to 60 % of patients develop pulmonary complications. In spite of antibacterial, antiviral, and antifungal prophylaxis, reduced host defenses render the HSCT patient vulnerable to pulmonary and other infections in the early weeks and even months post-transplantation. This chapter suggests an integrative approach followed by a description of the most common pulmonary syndromes seen in HSCT patients, including diffuse alveolar hemorrhage (DAH), idiopathic pneumonia syndrome (IPS), bronchiolitis obliterans syndrome (BOS), and cryptogenic organizing pneumonia (COP). The high risk of developing pulmonary complications after HSCT necessitates a pre-transplant pulmonary workup. Pulmonary function tests (PFTs) are done prior to HSCT and include spirometry and diffusion capacity of carbon monoxide (DLCO). Low DLCO and alveolar–arterial oxygen gradient on PFTs carry increased mortality post-HSCT. Decreased DLCO and forced expiratory volume in one second (FEV1) < 80 % are indicators of developing respiratory failure post-HSCT. Investigating new pulmonary complaints is challenging. All patients should undergo an extensive workup of new pulmonary findings, including dyspnea, cough, fever, and hypoxia. In the first 4–6 weeks post-HSCT, immunocompromised patients can develop bacterial pneumonia. Pathogens include gram-negative rods (Pseudomonas or Klebsiella), Staphylococcus aureus, and Nocardia. While chest X-rays could show typical lobar or multilobar opacities, computed tomography (CT) scan of the chest (noncontrast CT scans are adequate for workup of infectious processes) may yield additional characteristic findings (nodules, ground glass opacities, etc.). Fungal pneumonias, primarily aspergillus, can also develop in this early period. There is a very strong association between invasive Aspergillus pneumonia and neutropenia lasting more than 10 days. Viral pneumonia may develop as well in this patient population; however, it tends to occur later. Cytomegalovirus (CMV) is the most common viral pathogen, but with monitoring and preemptive therapy, the incidence has declined. Other viruses have emerged as pathogens, including respiratory syncytial virus (RSV), influenza, parainfluenza, and human metapneumovirus (see Chap. 17)."
8881,Infections in the Immunocompromised Host,
8882,Modeling Disease Spread at Global Mass Gatherings: Data Requirements and Challenges,"Spread of infectious diseases at global mass gatherings can pose health threats to both the hosting country and the countries where participants originate. The travel patterns at the end of these international events may result in epidemics that can grow to pandemic levels within a short period of time. Computational models are essential tools to estimate, study, and control disease outbreaks at mass gatherings. These models can be integrated in the planning and preparation process of mass gatherings. In this paper, we present a review of the key data requirements and the challenges encountered when modeling infectious diseases epidemics initiated by global mass gatherings. This review can assist epidemic modeling at global mass gatherings providing researchers with insights of the main aspects and possible big data opportunities in this emerging research area."
8883,Viral Evolution,"Viruses are ideal objects for studying evolutionary processes because of their short generation time, high numbers of offspring that they produce during infection and not least because of their simple structure. Viruses must continuously adapt to the conditions of their host or their host populations, so selection mechanisms are accessible to experimental approaches. In this context, different criteria play an important role, such as the antigenic diversity, the extent of virus excretion, and the degree of virulence. The complete adaptation of a virus to its host, which leads to a minimization of virulence of the infectious agent, is for both parties the desirable consequence: i.e. a problem-free coexistence and survival. For example, hepatitis G virus (GB virus C) which was initially isolated from patients with liver inflammation, seems to persist in many people without causing illnesses. A similar situation is observed with torque teno viruses (10.1007/978-3-642-20718-1_14 and 10.1007/978-3-642-20718-1_20). Spumaviruses are also found in many animal species and humans without causing symptomatic infections (10.1007/978-3-642-20718-1_18). For many viruses, the maximum exploitation of genetic variability is not always useful. Viruses reach a limit at which a greater variance is no longer advantageous: the proportion of non-infectious virus variants among the progeny becomes too high, whereby the potentially possible error limit is reached."
8884,Blut und Blutprodukte,"Um Blut oder Blutprodukte bei Bedarf substituieren zu können, sind grundlegende Kenntnisse zu den Blutgruppen, Serumantikörpern und den Blutprodukten selbst nötig. Das Kapitel enthält hierzu die wesentlichen Fakten und zeigt Indikationen spezieller Blutprodukte (z. B. FFP oder TK) auf."
8885,Integrating Landscape Hierarchies in the Discovery and Modeling of Ecological Drivers of Zoonotically Transmitted Disease from Wildlife,"Changes in landscape and land use can drive the emergence of zoonoses, and hence, there has been great interest in understanding how land cover change and the cascade of ecological effect associated with it are associated with emerging infectious diseases. In this chapter, we review how a spatially hierarchical approach can be used to guide research into the links between landscape properties and zoonotic diseases. Methodological advances have played a role in the revival of landscape epidemiology and we introduce the role of methodologies such as geospatial analysis and mathematical modeling. Importantly, we discuss cross-scale analysis and how this would provide a richer perspective of the ecology of zoonotic diseases. Finally, we will provide an overview of how hierarchical research strategies and modeling might be generally used in analyses of infectious zoonoses originating in wildlife."
8886,Measles Virus,Name of Virus: Measles virus
8887,Innovationen im Dialogmarketing,"Das Dialogmarketing steht durch technische Innovationen vor massiven Veränderungen. Vor allem die digitale Kommunikation in sozialen Netzwerken rückt zunehmend in den Fokus des Dialogmarketing und stellt neue Herausforderungen an das Management. Diese bestehen insbesondere in der Analyse der sozialen Struktur der Kommunikation und den Beziehungen der Akteure zueinander. Die Kernaufgaben in der Initiierung eines Dialoges im Rahmen von sozialen Netzwerken liegen darin, (1) diejenigen Personen im Netzwerk zu identifizieren, die als „Superspreader“ fungieren und (2) diese dann so zu motivieren, dass sie sich als Multiplikatoren im Netzwerk einsetzen."
8888,(13)C Chemical Shifts in Proteins: A Rich Source of Encoded Structural Information,"Despite the formidable progress in Nuclear Magnetic Resonance (NMR) spectroscopy, quality assessment of NMR-derived structures remains as an important problem. Thus, validation of protein structures is essential for the spectroscopists, since it could enable them to detect structural flaws and potentially guide their efforts in further refinement. Moreover, availability of accurate and efficient validation tools would help molecular biologists and computational chemists to evaluate quality of available experimental structures and to select a protein model which is the most suitable for a given scientific problem. The (13)C(α) nuclei are ubiquitous in proteins, moreover, their shieldings are easily obtainable from NMR experiments and represent a rich source of encoded structural information that makes (13)C(α) chemical shifts an attractive candidate for use in computational methods aimed at determination and validation of protein structures. In this chapter, the basis of a novel methodology of computing, at the quantum chemical level of theory, the (13)C(α) shielding for the amino acid residues in proteins is described. We also identify and examine the main factors affecting the (13)C(α)-shielding computation. Finally, we illustrate how the information encoded in the (13)C chemical shifts can be used for a number of applications, viz., from protein structure prediction of both α-helical and β-sheet conformations, to determination of the fraction of the tautomeric forms of the imidazole ring of histidine in proteins as a function of pH or to accurate detection of structural flaws, at a residue-level, in NMR-determined protein models."
8889,Infectious Diseases,"Infectious disease is one of the most common causes of acute care visits to outpatient pediatric clinics, urgent care facilities, and hospital emergency departments."
8890,Philosophy and Public Health,"In order to develop a new theory of reasoning, public health must embrace certain logical and epistemological concepts which have almost exclusively been examined within philosophy. These concepts include presumption and a group of arguments known as the informal fallacies. It is argued that presumption is a highly versatile concept which has not received the attention it deserves in epistemology. Features of this concept such as its defeasibility make it well suited to reasoning in contexts of uncertainty. However, in order to achieve any purchase in reasoning, presumption must find a logical home. It is argued that that home is as part of a group of arguments known as the informal fallacies. Throughout the long history of logic, informal fallacies have been characterized as weak or bad forms of reasoning. However, with the emergence of informal logic, traditionally negative characterizations of these arguments have lost some of their dominance. The journey taken by these arguments, from their treatment in the logical treatises of historical thinkers to present-day analyses, is examined in this chapter."
8891,Informatics in Disease Prevention and Epidemiology,"This chapter provides a description of the components of disease prevention and control programs, and then focuses on information systems designed to support public health surveillance, epidemiologic investigation of cases and outbreaks, and case management. For each such system, we describe sources used to acquire necessary data for use by public health agencies, and the technology used to clean, manage, organize, and display the information. We discuss challenges and successes in sharing information among these various systems, and opportunities presented by emerging technologies. Systems to support public health surveillance may support traditional passive case-reporting, as enhanced by electronic laboratory reporting and (emerging) direct reporting from electronic health records, and also a wide variety of different surveillance systems. We address syndromic surveillance and other novel approaches including registries for reporting and follow-up of cases of cancer, birth defects, lead poisoning, hepatitis B, etc., and population-based surveys (such as BRFSS or PRAMS). Systems to support epidemiologic investigation of outbreaks and clusters include generic tools such as Excel, SAS, SPSS, and R, and specialized tool-kits for epidemiologic analysis such as Epi-Info. In addition to supporting outbreak investigation, agencies also need systems to collect and manage summary information about outbreaks, investigations, and responses. Systems to support case management, contact tracing, and case-based disease control interventions are often integrated to some degree with surveillance systems. We focus on opportunities and choices in the design and implementation of these systems."
8892,Epidemic Models with Switching,"In this chapter, the methods developed thus far are applied to a variety of infectious disease models with different physiological and epidemiological assumptions. Many of the previous results are immediately applicable, thanks to the flexibility of the simple techniques used here. However, some complicating modeling assumptions lead to a need for different switched systems techniques not present in the previous chapter. First, the so-called SIS model is considered, followed by incorporation of media coverage, network epidemic models with interconnected cities (or patches), and diseases spread by vector agents (e.g., mosquitoes) which are modeled using time delays. Straightforward extensions of eradication results are given for models with vertical transmission, disease-induced mortality, waning immunity, passive immunity, and a model with general compartments."
8893,Household-Based Studies,"In Chapter 2 we introduced vaccine efficacy parameters that require conditioning on exposure to infection. Household studies were used as the basis for defining exposure to infection in vaccine studies as early as the 1930s in evaluating the efficacy of pertussis vaccines (Kendrick and Eldering 1939). In addition to evaluating vaccine efficacy, household studies have been used to learn about transmission and natural history of many infections. Aspects of the natural history studied in households include the transmissibility, the incubation and latent periods, the duration of infectiousness, and the serial interval between cases (Hope-Simpson 1952; Bailey 1957). Household studies have also been used to evaluate other interventions, such as post-exposure prophylaxis with influenza antiviral agents (Welliver et al 2001; Hayden et al 2004). Exposure to an infectious case within a household can be used as a natural challenge study, for example, when studying immunological correlates of protection (Storsaeter et al 1998). Longitudinal studies of pneumococcal carriage in households and schools have been used to estimate the acquisition and clearance rates for asymptomatic pneumococcal carriage. The general idea of a transmission unit is that individuals make contact sufficient for transmission within it. Households are the most common form of transmission unit used in studies. It allows easy identification of contacts between a case and susceptibles, and families are convenient units of study. Many other settings are also used as transmission units in studies and analyses that condition on exposure to infection. These include sexual partnerships, classrooms, schools, school buses, airplanes, day care centers, and workplaces, among others. Here we talk mostly about household studies, but many of the study designs and analyses are applicable with possibly slight modification to other transmission units as well. The term household is much easier for exposition than is “transmission unit”."
8894,Intensivtherapie nach Transplantation solider Organe,"Der Intensivmedizin kommt eine zentrale Bedeutung in Rahmen der Transplantationsmedizin zu. Aufgrund ihrer marginalen Organfunktion benötigen die Patienten nicht selten bereits im Vorfeld der Transplantation eine intensivmedizinische Versorgung, zu der dann auch die Evaluation und Listung sowie die Koordination des zeitkritischen Transplantationsablaufs gehören können. Die direkte postoperative Betreuung nach komplexen Organtransplantationen bedarf fast ausschließlich der Versorgung im Rahmen von Überwachungsstationen, in denen sowohl direkt transplantationsassoziierte Komplikationen als auch Nebenerkrankungen eine intensivmedizinische Behandlungen notwendig machen. Sie zielt auf die Stabilisierung der Organfunktion, Behandlung begleitender Organdysfunktionen, adäquate Induktion der Immunsuppression und die möglichst frühe Wiedererlangung der Eigenständigkeit des Transplantierten ab."
8895,Is Peking Man Still Our Ancestor?—Race and National Lineage,"Since China participated in the Human Genome Project in the 1990s, implications of the debate surrounding the Homo erectus Peking Man’s ancestorship for nationalism wrapped in scientific jargon have been well comprehended by various segments of the society with ultranationalists and a liberal public opinion as the two extremes contesting each other. This divergence also cuts through the Chinese party-state. The discourse on a pure ancestry, an ancestral home, a natural bond between this ancestor and the environment, and most of all, a narrative that attributes remarkable lineal continuity to physical, mental, intellectual and even moral traits unique to this ancestor and its posterity, support fanatical racial nationalisms."
8896,"Price Matters – Relevance of Strategic Pricing for Swiss Tourism in the Past, Present and Future","In his paper from 2003, Peter Keller postulates that a strategic pricing policy can pose an opportunity for Swiss tourism, strengthening the competitiveness and growth of the industry. This contribution from Peter Keller’s celebratory publication on the occasion of his 20th presidency of the International Association of Scientific Experts in Tourism (AIEST) picks up on this assumption and discusses the touristic development and enhancement of strategic pricing over the past ten years of Swiss tourism. In the first section of this paper, empirical evidence of the development of Swiss tourism over time and a discussion of its challenges are presented. The second section addresses the postulated value-based pricing concept, including practical examples from Swiss tourism over the past ten years. The third section offers a conclusion, which discusses the relevance of strategic pricing as a means to strengthen competitiveness with respect to future terms. Peter Keller has been involved in scientific tourism research as the president of the AIEST for 20 years. Believing strongly in the fact that sustainable tourism research should be dedicated to a holistic, systemic as well as pragmatic approach, he constantly warned of disciplinary and autarchic traits of tourism research (Keller 2007, S. 96ff.). As an advocate of tourism science, which should be concerned with a human, social and cultural scientific reflection without excluding the viewpoint of economics or business administration, he also crucially influenced national tourism politics as a head of the Tourism Department at the State Secretariat for Economic Affairs (SECO). In his article ""Strategic pricing policy as a chance for Swiss tourism"" (Keller, 2003, S. 193ff.), he emphasises a ""back-to-growth strategy"" for Swiss tourism by focusing on a strategic marketing approach, which is oriented towards the ""value-based pricing principle"" and focuses more on price as a constitutive element. The following paper discusses the past development of the Swiss tourism industry since Peter Keller’s article was published in 2003 and notes the valuebased pricing approach. For this purpose, we examine the development of Swiss tourism, outline the postulated ""value-based pricing principle"" and discuss some practical applications from daily touristic business. Finally, we draw a conclusion about the applicability of strategic pricing in the future."
8897,Public Health Surveillance,"Public health surveillance enables public health practitioners to assess and monitor changes in the population’s health and make recommendations for action. The systematic, ongoing collection, analysis and dissemination of data ensures that the right information is available at the right time to inform public health action. This chapter will introduce you to the key concepts and objectives of public health surveillance, and will help you to understand how effective surveillance systems are based on four basic steps: data collection, analysis, interpretation and response. This chapter will also help you to understand the advantages and disadvantages of the different surveillance systems which are used to collect information on public health. The chapter concludes with a look at how advances in technology, social media and the internet are shaping the future of public health surveillance. After reading this chapter you will be able to: Describe the purpose and key features of public health surveillance. Describe the basic steps which underpin public health surveillance systems. Define different surveillance systems and critically compare their advantages and disadvantages."
8898,Bispecific Antibodies and Gene Therapy,"Gene therapy is the transfer of therapeutic genes, via gene transfer vectors, into patients for therapeutic purposes. Different gene therapy strategies are being pursued, including long-term gene correction of monogenetic diseases, eradication of tumor cells in cancer patients, or genetic vaccination for infectious diseases. Bispecific antibodies and gene therapy are connected in two ways. First, bispecific antibodies are tools of interest for the development of targeted gene transfer vectors. Different gene therapy strategies require different vectors, frequently replication-ablated viruses. Similar to the role of antibody engineering in antibody therapy, the engineering of gene transfer vectors has become key to the implementation of genetic therapies. Cytoablative cancer gene therapy and efficient genetic vaccination, for example, depend on vectors that are targeted to cancer cells and antigen-presenting cells, respectively, in order to avoid side effects and vector sequestration. To this end, bispecific antibodies have been engineered as adapters that link the vector to a specific molecule on the targeted cell and at the same time block the interaction with the native virus receptor. Different formats of bispecific antibodies and related molecules have been developed and succeeded in re-directing vectors to target cells in vitro and in vivo. These adapters also improved gene therapies in animal models. Second, gene transfer is a promising tool for delivery of bispecific antibodies to patients. Therefore, vectors can be injected directly into patients for antibody gene transfer, or cells isolated from patients can be genetically modified in vitro and then re-injected for in vivo antibody production. Genetic antibody delivery, compared with standard antibody injection, can be advantageous with respect to achieving persistent antibody titers or effective antibody biodistribution in patients. Initial studies have shown antibody production and therapeutic activity in animal models, setting the stage for more widespread investigations. Moreover, gene therapy can enable novel therapeutic applications for bispecific antibodies by facilitating the delivery of membrane associated or intracellular antibody formats."
8899,Spezifische Infektionen,"In diesem Kapitel wird auf die Infektionen eingegangen, die nicht im Rahmen der einzelnen Erkrankungsentitäten in den übrigen Kapiteln behandelt werden. Der Schwerpunkt liegt dabei auf den Infektionen bzw. Erregern, die auch dem Intensivmediziner häufiger begegnen können. Fragestellungen außerhalb dieser Gruppe sollten mit Hilfe spezieller Literatur beantwortet werden, Hilfestellungen geben auch die Verweise auf Webseiten am Ende des Kapitels."
8900,"Infektiologie, Immunologie","Die Infektiologie besch ä ftigt sich mit der Entstehung, Klinik, Diagnostik, Therapie und Pr ä vention von Infektionskrankheiten. Hierzu bedient sie sich der Methoden der Mikrobiologie, Inneren Medizin, Epidemiologie und Hygiene. Sie ist eng mit anderen medizinischen Fachgebieten wie Innere Medizin, Chirurgie, Dermatologie/Venerologie, P ä diatrie oder Pharmakologie verzahnt."
8901,Radiological and Nuclear Terrorism: The Oncologic Emergency Response,"Public concern about the possibility of terrorism involving radiological materials has grown rapidly since the September 11, 2001 terrorist attacks on New York City, the Pentagon, and Pennsylvania. Such concern is driven by the widespread availability of radiological materials and the intentions of malfeasants and organizations around the world to do harm to others. In contrast to nuclear materials, radiological materials are ubiquitous and are found in most cities throughout the country at academic institutions, hospitals, and many businesses and industrial settings. In contrast, nuclear materials are difficult to access because of their rarity and the security of the settings in which they are found. A radiological or nuclear incident of any kind will require prompt assessment of the location and nature of the incident, activation of mass casualty response systems, followed by immediate consultation of hematology, health and medical physics, and nuclear medicine personnel. Radiation-induced injuries and illnesses are typically delayed. Successful assessment and management of individuals with acute radiation syndrome (ARS), including the hematopoietic subsyndrome (HS), is required to support management of injuries resulting from a high radiation dose, including injuries to the gastrointestinal and neurovascular systems. Administration of cytokines within 24 h of exposure shortens the period of granulocytopenia and is strongly recommended by subject matter experts in the management of the HS. Hematopoietic stem cell transplantation after failure of a 2–3 week trial of cytokines has been clearly documented and is weakly recommended in selected individuals with the HS. Administration of prophylactic and therapeutic broad-spectrum antimicrobials (including antibacterial, antiviral, and antifungal agents) is recommended and should be guided by recommendations of the Infectious Diseases Society of America for management of febrile neutropenia. This article provides an overview for clinicians who are called upon in a radiological and/or nuclear incident to manage individuals with ARS and other radiation-related illnesses."
8902,"Biotechnology, In Vitro Production of Natural Bioactive Compounds, Herbal Preparation, and Disease Management (Treatment and Prevention)","Biotechnology uses living systems to develop products and plant biotechnology generates useful products or services, e.g., different bioactive secondary metabolites including alkaloids, flavonoids and other phenolics, saponins, terpenoids, steroids, glycosides, tannins, volatile oils, etc., from plant cells, tissues or organs culture independent of geographical and climatic factors under aseptic conditions. These bioactive compounds are economically important as drugs (pharmaceuticals), flavors, perfumes (fragrances), pigments (dyes), agrochemicals as well as cosmetics, food additives, etc. Different strategies, e.g., genetic transformation of plants with Agrobacterium rhizogenes, hairy roots and others can be applied for the improvement of production of bioactive compounds of secondary metabolic origin. Recombinant DNA techniques can be used to manipulate metabolic pathways and produce protein pharmaceuticals such as antibodies, and protein hormones. Bioinformatics and genomics can find application in drug discovery from plant-based products and biotechnological procedures can enhance and advance the studies of medicinal plants. Molecular biotechnology uses laboratory techniques to study and modify nucleic acids and proteins for applications in areas such as human and animal health, agriculture, and the environment. Herbal extracts are now widely used in the management of chronic diseases like diabetes, hypertension, cancer, etc., as a part of CAM therapy. Plant-derived immune stimulators diverse small or large molecules (saponins, tomatine, inulin, polysaccharides), fungal β-glucans, complex molecules from marine sponge (α-galactosylceramide), shrimp chitin (chitosan), etc., have established adjuvant activity. Immunotherapy may be activation immunotherapy or suppression immunotherapy. Vaccines provide immune protection against diseases and plant-based edible vaccine production mainly involves the integration of transgene into the plant cells to produce the antigen protein for specific disease."
8903,Critical Care Management: Sepsis and Disseminated and Local Infections,"Local and systemic infections are a significant cause of morbidity and mortality among immunocompromised children, including but not limited to patients with hematologic and solid malignancies, congenital or acquired immunodeficiencies, or hematopoietic cell or solid organ transplantation patients. Progression to septic shock can be rapid and profound and thus requires specific diagnostic and treatment approaches. This chapter will discuss the diagnosis and the initial hemodynamic management strategies of septic shock in immunocompromised children, including strategies to improve oxygen delivery, reduce metabolic demand, and monitor hemodynamic response to resuscitation. This chapter also discusses strategies to reverse septic shock pathobiology, including the use of both empiric and targeted anti-infective strategies and pharmacologic and cell therapy-based immunomodulation. Specific consideration is also paid to the management of high-risk subpopulations and the care of septic shock patients with resolving injury."
8904,Cycloadditions for Studying Nucleic Acids,"Cycloaddition reactions for site-specific or global modification of nucleic acids have enabled the preparation of a plethora of previously inaccessible DNA and RNA constructs for structural and functional studies on naturally occurring nucleic acids, the assembly of nucleic acid nanostructures, therapeutic applications, and recently, the development of novel aptamers. In this chapter, recent progress in nucleic acid functionalization via a range of different cycloaddition (click) chemistries is presented. At first, cycloaddition/click chemistries already used for modifying nucleic acids are summarized, ranging from the wellestablished copper(I)-catalyzed alkyne–azide cycloaddition reaction to copper free methods, such as the strain-promoted azide–alkyne cycloaddition, tetrazole-based photoclick chemistry and the inverse electron demand Diels–Alder cycloaddition reaction between strained alkenes and tetrazine derivatives. The subsequent sections contain selected applications of nucleic acid functionalization via click chemistry; in particular, site-specific enzymatic labeling in vitro, either via DNA and RNA recognizing enzymes or by introducing unnatural base pairs modified for click reactions. Further sections report recent progress in metabolic labeling and fluorescent detection of DNA and RNA synthesis in vivo, click nucleic acid ligation, click chemistry in nanostructure assembly and click-SELEX as a novel method for the selection of aptamers."
8905,Gesundheitsberichterstattung,"Die Gesundheitsberichterstattung (GBE) des Bundes stellt kontinuierlich aktuelle Daten und Informationen zum Gesundheitszustand und zur Gesundheitsversorgung der Bevölkerung in Deutschland bereit. Das Themenspektrum ist vielfältig und reicht von Krankheiten, Beschwerden und Risikofaktoren über die subjektive Gesundheit und gesundheitsbezogene Lebensqualität bis hin zur Inanspruchnahme von Präventions- und Versorgungsangeboten sowie den Strukturen und Kosten des Gesundheitswesens. Die Themen werden auf breiter Datengrundlage und unter Berücksichtigung ihrer gesellschaftlichen Relevanz sowie der sozialen, ökonomischen und politischen Rahmenbedingungen behandelt. Die Ergebnisse werden fortlaufend veröffentlicht, wobei unterschiedliche, auf den Informationsbedarf der jeweiligen Adressaten abgestimmte Publikationsformen genutzt werden."
8906,Glucocorticoids (as an Etiologic Factor),"Adrenocortical hormones were first prepared from the adrenal gland as a new compound by Kendall in 1935 [1]. Thirteen years later, Hench et al. [2] observed a miraculous effect of cortisone in a patient with severe rheumatoid arthritis, which opened new doors to innovative treatments for a variety of inflammatory diseases. Against this background, Kendall, Hench, and Reichstein were awarded the 1950 Nobel Prize for Physiology or Medicine. Since then, glucocorticoids have been used as a first-line therapy for immune-mediated conditions or as an adjunctive therapy in many inflammatory, infectious, or malignant diseases."
8907,Emergency Preparedness in Ambulatory Surgery Centers and Office-Based Anesthesia Practices,"Natural or manmade disasters, mass causality events, and other emergencies can disrupt healthcare delivery and change the demand for healthcare services. In order to protect patients, staff, and facilities it is essential that healthcare facilities be prepared for such emergency events. Ambulatory surgery centers (ASC) and Office Based Anesthesia (OBA) practices are unique healthcare settings that necessitate specific emergency planning since they typically do not have rapid response or code teams on site. In addition, they typically operate with fewer personnel and have staff members who often perform multiple functions. Previously there has been variability in the emergency preparedness amongst ASCs and OBA practices. The Centers for Medicare & Medicaid Services (CMS) has recently identified three requirements for maintaining healthcare services during an emergency. These are 1) safeguarding human resources, 2) maintaining business operations, and 3) protecting physical resources. In 2016 CMS issued new rules establishing national emergency preparedness requirements for Medicare and Medicaid participating providers in the United States. In addition there are requirements specifically for ASCs and OBAs. The first step in emergency preparedness is performing a risk assessment for a practice using an “all-hazards” approach. In this approach, the practice attempts to identify all hazards that could potentially affect the practice as well as evaluating the likelihood of such hazards. This risk assessment is then incorporated into an emergency plan for the facility. In addition to reviewing specific components of an emergency plan for ASCs and OBAs, the need to test the plan and create a subsequent corrective action plan is reviewed. It is important that healthcare providers at all ambulatory surgery centers and office based anesthesia practices are aware of regulations for emergency preparedness and work to ensure that patients, staff and physical resources are protected during natural disasters and other emergencies."
8908,Pneumonia After Thoracic Surgery,"The most frequent and severe complication after thoracic surgery is pneumonia. Hypoventilation due to pain and insufficient cough is the reason for postoperative pneumonia after thoracic surgery. There is a risk index developed from preoperative patients and operation-specific risk factors. The risk index may be useful for high-risk patients; therefore giving these patient groups more attention in the perioperative period and taking preventive measures may reduce the incidence of pneumonia. Postoperative period composed of pulmonary rehabilitation and analgesia includes breathing exercise, cough training, self-management education, and psychosocial support, and they have been shown to decrease complications. According to some new studies, paravertebral block has similar analgesic effects with thoracic epidural analgesia (TEA). Although paravertebral block has fewer adverse effects, TEA is still the gold standard for pain relief after thoracotomies. The incidence of pneumonia varies in the literature because there is no gold standard for the diagnosis of postoperative pneumonia. Many centers use only clinical criteria, whereas others use invasive diagnostic techniques. Empirical antibiotic treatment should be started based on patient factors, local infection, and susceptibility patterns."
8909,Intelligenzminderung,Schwachsinn Der Gebrauch des Terminus »Schwachsinn« ist wegen seines globalen und wenig präzisen Charakters und durch seine historisch und umgangssprachlich bedingte sozial diskriminierende Tönung inzwischen in der wissenschaftlichen Literatur zu Recht weitgehend aufgegeben worden. In der Rechtsprechung speziell in der Forensik ist Schwachsinn als eine schuldausschließende bzw. schuldminderende juristische Kategorie ein nach wie vor gebräuchlicher Begriff.
8910,Processing of Mass Spectrometry Data in Clinical Applications,"Mass spectrometry-based proteomics has become the leading approach for analyzing complex biological samples at a large-scale level. Its importance for clinical applications is more and more increasing, thanks to the development of high-performing instruments which allow the discovery of disease-specific biomarkers and an automated and rapid protein profiling of the analyzed samples. In this scenario, the large-scale production of proteomic data has driven the development of specific bioinformatic tools to assist researchers during the discovery processes. Here, we discuss the main methods, algorithms, and procedures to identify and use biomarkers for clinical and research purposes. In particular, we have been focused on quantitative approaches, the identification of proteotypic peptides, and the classification of samples, using proteomic data. Finally, this chapter is concluded by reporting the integration of experimental data with network datasets, as valuable instrument for identifying alterations that underline the emergence of specific phenotypes. Based on our experience, we show some examples taking into consideration experimental data obtained by multidimensional protein identification technology (MudPIT) approach."
8911,Disaster Medicine,"Millions of people every day face disasters, for example, typhoons, terrorist attacks, earthquakes, famine, civil wars, explosions, and tornadoes. Disaster is defined as every event that causes serious disruption which exceeds the ability of the affected community or society to cope using its own resources. Disasters are usually categorized as natural or man-made and are described using a series of steps called the disaster cycle, defined in four phases: mitigation and prevention, preparedness and planning, response, and recovery. Disaster medicine is an emerging specialty that integrates the medical response to disaster with the systems of disaster management."
8912,Stable-Isotope-Aided NMR Spectroscopy,"Boundless progress in isotope-aided NMR methods still continues to provide the driving force for developing novel NMR strategies for structural biology research of proteins. In the first edition of this book, we described an overview of the isotope labeling methods available at that time. In this second edition, we will mainly focus on newer isotope-aided NMR methods, such as the methyl-specific labeling and stereo-array isotope labeling (SAIL) methods, which have rapidly developed during the past decade. The methyl-specific labeling is currently used as the most practical technique applicable to large protein complexes and membrane proteins. The standard methyl labeling protocols employ isotope-labeled α-keto acid precursors, which enable selective observations of the methyl groups of Ile, Leu, and Val residues. More recently, the stereo-specific isotope labeling methods of prochiral methyl groups have become available, using either regio-selectively isotope-labeled precursors or stereo-specifically (13)CH(3)-labeled amino acids. We also focus on the stereo-array isotope labeling (SAIL) method, which is a breakthrough isotope labeling technology using stereo- and regio-selectively [(2)H, (13)C, (15)N]-labeled amino acids with isotope labeling patterns optimized for NMR studies. Various applications of SAIL and related methods to structural studies, including protein dynamics such as aromatic ring-flipping motions, hydrogen-deuterium exchange rates, conformational analysis, and dynamics about disulfide bonds, will be discussed."
8913,Seltene Lungenerkrankungen,"Die interstitiellen Lungenerkrankungen (ILE) des Kindesalters sind eine heterogene Gruppe seltener, chronischer Lungenerkrankungen, die charakterisiert sind durch entzündliche und fibrotische Veränderungen im Bereich der Alveolen und der angrenzenden distalen Atemwege."
8914,Microbiology of Rhinosinusitis and Antimicrobial Resistance,"Acute rhinosinusitis (ARS) is the inflammation of the nasal mucous membrane and can be separated into acute viral and acute bacterial rhinosinusitis. It is frequently observed after viral rhinitis or common cold. Viral, post-viral, and acute bacterial ARS (ABRS) display significantly similar clinical presentation and inflammatory mechanism. Viral infection of the sinus cavity can cause numerous changes such as post-viral inflammation and epithelial damage, which enhance the susceptibility to bacterial infection. The most common virus families that cause ARS are coronavirus and rhinovirus. Approximately 50% of common colds are caused by the human rhinovirus. Other viral offenders include parainfluenza, influenza, respiratory syncytial virus (RSV), adenovirus, and enterovirus. The most widely recognized bacteria in ABRS are S. pneumonia, H. influenza, and M. catarrhalis and S. aureus, while other species and anaerobic bacteria may also contribute to the infection (Payne and Benninger, Clin Infect Dis 45(10):e121–7, 2007; Anonymous, Otolaryngol Head Neck Surg 130(1 SUPPL):1–45, 2004; Brook, Arch Otolaryngol Head Neck Surg 128(5):583–5, 2002). Interestingly, Payne and colleagues performed a meta-analytic study on reports about the microbiology of ABRS, which evaluated the most common bacterial occurrence within the sinus. S. aureus is commonly associated with the pathogenesis of sphenoid sinusitis. The 7-valent pneumococcal vaccine was presented in the United States in 2000 and aided in the reduction of the recovery rate for S. pneumoniae and the increase in the rate of H. influenza. Chronic rhinosinusitis (CRS) vary in comparison to ARS. Bacteria that have been recorded in many samples acquired by endoscopy or sinus puncture in CRS patients are Staphylococcus aureus (both MSSA and MRSA), Staphylococci (coagulase-negative) (SCN), H. influenza, M. catarrhalis, S. pneumonia, S. intermedius, P. aeruginosa, N. species, and other anaerobic bacteria. In this chapter, microbiology of rhinosinusitis and antimicrobial resistance are discussed."
8915,Ultraviolet Radiation for Disinfection,"Natural water, such as surface water and groundwater, exists as an open system. Natural and/or synthesized organic substances, oxygen, nutrients are thus able to enter various waters. Owing to the presence of these key elements, microbial growth eventually becomes possible. Different microorganisms can therefore exist and grow in the waters. Similarly, domestic and industrial wastewater and treated wastewater contain significantly high amounts of microorganisms."
8916,Toxicant-Induced Hepatic Injury,"The sudden failure of a previously healthy and functioning liver is a dramatic and devastating event. Acute liver failure is the common final pathway of a multitude of conditions and insults, all of which result in massive hepatic necrosis or loss of normal hepatic function. The ensuing multiorgan system failure frequently has a fatal outcome, with mortality rates in most series ranging from approximately 55% to 95% [1]. Acute liver failure (ALF, previously often referred to as fulminant hepatic failure (FHF)) knows no age boundaries, with many cases occurring in those younger than 30 years. Short of excellent intensive care unit (ICU) support and liver transplantation in selected cases, few viable treatment options are available. Over the past few decades, however, survival has been improved by anticipation, recognition, and early treatment of associated complications, as well as the application of prognostic criteria for early identification of patients requiring liver transplantation (along with improvement in the techniques and science of transplantation itself). The etiology of ALF varies from country to country and the incidence change over time. Paracetamol (acetaminophen) has now replaced viral hepatitis as the leading cause of ALF [2]. In a study from London including 310 patients with ALF in the period 1994–2004, 42% of the cases were caused by paracetamol [3], whereas this was only the cause in 2% of 267 patients in Spain from 1992 to 2000 [4]. However, less than 10% of all liver transplants are performed in patients with ALF [5, 6]."
8917,Transplantationsmedizin in der Intensivmedizin,Die postoperative intensivmedizinische Behandlung von Patienten nach Herztransplantation basiert häufig auf Erfahrung und deren Weitergabe zwischen den Transplantationszentren (hohe Variabilität).
8918,Nucleic Acid Extraction and Enrichment,"Nucleic acid extraction is the first step of any amplification experiment no matter what kind of amplification is used to detect a specific pathogen. Efficient nucleic acid extraction is essential to obtain good results using any molecular test. The optimal extraction method should fulfill the following conditions: speed, short working time, cost-effectiveness, high sensitivity and specificity, good reproducibility, and safety. The methods can be divided into solution or column based according to differences of their principles. The automated extraction instruments have many advantages, and these have proven to be very useful. Moreover, in recent years, fully automated instruments combining NA extraction and amplification have been commercially available. However, the method itself does not provide assurance, and the DNA recovery can be different among various kits or instruments that use the similar principles. Therefore, it is important to carefully evaluate the performance of any extraction method used in the clinical microbiology laboratory even though manufacturers may have reported good validation results with specific organisms."
8919,"Hospital-Based HTA and Know4Go at MEDICI in London, Ontario, Canada",The majority of healthcare in Canada is universally provided and publicly funded through the provincial government.
8920,Strategies and Challenges for the Development of Industrial Enzymes Using Fungal Cell Factories,"Industrial enzymes have been produced from microorganisms for more than a century. Today, a large share of enzyme products is manufactured using recombinant microorganisms. This chapter focuses on major industrial fungal species belonging to the ascomycetes like Aspergillus niger, A. oryzae, and Trichoderma reesei. Many of the commercially available recombinant enzymes are manufactured using fungi. Examples of fungal enzymes used in food products are described. The enzyme industry is to a large extent cost-driven, so the enzyme product needs to meet strict COGS (cost of goods sold) targets. Therefore, the cell factory must be very efficient to produce the enzyme in high titers and efficiently utilize raw materials. Secondly, it must be designed for a robust and generic fermentation process. When developing fungal hosts for enzyme production, several properties of the system need to be considered relating to efficiency of the cell factory, purity of the product, and safety of both the cell factory and the product. Purity is secured by engineering of the cell factory, and properties related to safety must also be engineered into the fungal host. The methods used for strain improvement are continuously being developed to increase yields and are described herein. More automation using precision tools for modification of the genome (i.e., CRISPR) and low-cost sequencing have vastly expanded the possibilities and enabled fast strain development. Using systems biology approaches, better understanding of cellular processes is now possible enabling advanced engineering of fungal cell factories. Surprisingly, a survey of innovation in the field revealed a decrease in the number of patent applications in recent years. Finally, the requirements for enzyme approval, especially in food and feed, have increased significantly worldwide in the last few years. A description of the regulatory landscape and its challenges in food and feed is included."
8921,Challenges in Economics,"In the same way as the Hilbert Program was a response to the foundational crisis of mathematics [1], this article tries to formulate a research program for the socio-economic sciences. The aim of this contribution is to stimulate research in order to close serious knowledge gaps in mainstream economics that the recent financial and economic crisis has revealed. By identifying weak points of conventional approaches in economics, we identify the scientific problems which need to be addressed. We expect that solving these questions will bring scientists in a position to give better decision support and policy advice. We also indicate, what kinds of insights can be contributed by scientists from other research fields such as physics, biology, computer and social science. In order to make a quick progress and gain a systemic understanding of the whole interconnected socio-economic-environmental system, using the data, information and computer systems available today and in the near future, we suggest a multi-disciplinary collaboration as most promising research approach."
8922,Epidemiology,"The common cold is the result of an upper respiratory tract infection causing an acute syndrome characterised by a combination of non-specific symptoms, including sore throat, cough, fever, rhinorrhoea, malaise, headache, and myalgia. Respiratory viruses, alone or in combination, are the most common cause. The course f illness can be complicated by bacterial agents, causing pharyngitis or sinusitis, but the are a rare cause of cold and flu-like illnesses (CFLIs). Our understanding of CFLI epidemiology has been enhanced by molecular detection methods, particularly polymerase chain reaction (PCR) testing. PCR has not only improved detection of previously known viruses, but within the last decade has resulted in the detection of many divergent novel respiratory virus species. Human rhinovirus (HRV) infections cause nearly all CFLIs and they can be responsible for asthma and chronic obstructive pulmonary disease exacerbations. HRVs are co-detected with other respiratory viruses in statistically significant patterns, with HRVs occurring in the lowest proportion of co-detections, compared to most other respiratory viruses. Some recently identified rhinoviruses may populate an entirely new putative HRV species; HRV C. Further work is required to confirm a causal role for these newly identified viruses in CFLIs. The burden of illness associated with CFLIs is poorly documented, but where data are available, the impact of CFLIs is considerable. Individual infections, although they do not commonly result in more severe respiratory tract illness, are associated with substantial direct and indirect resource use. The product of frequency and burden for CFLIs is likely to be greater in magnitude than for any other respiratory syndrome, but further work is required to document this. Our understanding of the viral causes of CLFIs, although incomplete, has improved in recent years. Documenting burden is also an important step in progress towards improved control and management of these illnesses."
8923,Neurologie,"Bewusstsein. Orientierung (zu Zeit, Ort, Situation und Person). Aufmerksamkeit und Gedächtnis (amnestische Funktion). Affektivität. Antrieb;"
8924,Bacterial Sepsis and Shock,
8925,The Ecology of Pathogen Spillover and Disease Emergence at the Human-Wildlife-Environment Interface,"Novel diseases are increasingly emerging into human populations through the complex—and often, unseen—stepwise process of spillover from a combination of wildlife, livestock, vectors, and the abiotic environment. Characterizing and modeling the spillover interface are a key part of how eco-epidemiologists respond to the growing global burden of emerging infectious diseases; but the diversity of pathogen life cycles and transmission modes poses a complex challenge for ecologists and clinicians alike. We review our current understanding of the spillover process and present a framework that relates spillover rates and human-to-human transmissibility to the basic reproduction number (R (0)). Using pathogens that exemplify important transmission pathways (anthrax, Ebola, influenza, and Zika), we illustrate key aspects of the spillover interface and discuss implications to public health and management of emerging infectious disease."
8926,Infektionen,Die Meldung und Erfassung von Infektionskrankheiten ist in Deutschland durch das Infektionsschutzgesetz (IfSG) geregelt. In §6 sind meldepflichtige Krankheiten nach gewissen Vorgaben geregelt.
8927,Establishment and Development of the Disease Surveillance System,"Disease surveillance is the long-term, continuous, systematic collection of information about diseases and their relevant influencing factors, followed by analysis of the data in a timely manner to guide intervention measures and evaluate their effectiveness. This definition reflects the three basic characteristics of disease surveillance: (1) distributions and trends of diseases can be evaluated only through long-term, continuous, systematic collection of data; (2) original data can be translated to valuable information only through analysis and interpretation of the data; and (3) results can be fully utilized in the real world only after information is provided back to the relevant departments and personnel – hence the importance of timely feedback."
8928,Simulation and Modeling Applications in Global Health Security,"Global health security (GHS) is dependent upon having an adequate and prepared health security workforce. There are currently numerous challenges in establishing and maintaining a health security workforce. The frequency and magnitude of disasters have increased significantly over the past 30 years. Current and future GHS threats, both manmade and natural, require a prepared and flexible healthcare provider workforce ready to respond to current or emerging GHS threats. Developing and maintaining GHS -specific skills in the healthcare workforce is a tremendous logistical challenge. Innovative education technologies, including simulation and digital learning, can be leveraged to achieve preparedness for GHS threats. This chapter focuses on the application of modeling and simulation to support Global Health Security planning, preparedness and operations."
8929,Genus Avipoxvirus,"Poxviruses identified in skin lesions of domestic, pet or wild birds are assigned largely by default to the Avipoxvirus genus within the subfamily Chordopoxvirinae of the family Poxviridae. Avipoxviruses have been identified as the causative agent of disease in at least 232 species in 23 orders of birds. Vaccines based upon attenuated avipoxvirus strains provide good disease control in production poultry, although with the large and intensive production systems there are suggestions and real risks of emergence of strains against which current vaccines might be ineffective. Sequence analysis of the whole genome has revealed overall genome structure and function resemblance to the Chordopoxvirinae; however, avipoxvirus genomes exhibit large-scale genomic rearrangements with more extensive gene families and novel host range gene in comparison with the other Chordopoxvirinae. Phylogenetic analysis places the avipoxviruses externally to the Chorodopoxvirinae to such an extent that in the future it might be appropriate to consider the Avipoxviruses as a separate subfamily within the Poxviridae. A unique relationship exists between Fowlpox virus (FWPV) and reticuloendothelosis viruses. All FWPV strains carry a remnant long terminal repeat, while field strains carry a near full-length provirus integrated at the same location in the FWPV genome. With the development of techniques to construct poxviruses expressing foreign vaccine antigens, the avipoxviruses have gone from neglected obscurity to important vaccine vectors in the past 20 years. The seminal observation of their utility for delivery of vaccine antigens to non-avian species has driven much of the interest in this group of viruses. In the veterinary area, several recombinant avipoxviruses are commercially licensed vaccines. The most successful have been those expressing glycoprotein antigens of enveloped viruses, e.g. avian influenza, Newcastle diseases and West Nile viruses. Several recombinants have undergone extensive human clinical trials as experimental vaccines against HIV/AIDS and malaria or as treatment regimens in cancer patients. The safety profile of avipoxvirus recombinants for use as veterinary and human vaccines or therapeutics is now well established."
8930,Pneumonie,
8931,Etiopathogenesis and Pathophysiology of Malaria,"Malaria is a parasitic disease caused by Plasmodium protozoan parasites and transmitted by Anopheles mosquitoes. The disease is diffused in tropical areas, where it is associated with high morbidity and mortality. P. falciparum is the most dangerous species, mainly affecting young children. The parasite cycle occurs both in humans (asexual stages) and in mosquitoes (sexual stages). In humans, Plasmodium grows and multiplies within red blood cells using hemoglobin as essential source of nutrients and energy. However, this process generates toxic heme that the parasite aggregates into an insoluble inert biocrystal called hemozoin. This molecule sequesters in various organs (liver, spleen, and brain), potentially contributing to the development of malaria immunopathogenesis. Uncomplicated falciparum malaria clinical frame ranges from asymptomatic infection to classic symptoms such as fever, chills, sweating, headache, and muscle aches. However, malaria can also evolve into severe life-threatening complications, including cerebral malaria, severe anemia, respiratory distress, and acute renal failure."
8932,Entzündliche Erkrankungen,"Meningitiden zeigen die Trias Kopfschmerz, Meningismus und Fieber mit positiven Dehnungszeichen. Bei Kindern sind gramnegative Enterokeime und Hämophilus, bei Erwachsenen Meningo- und Pneumokokken wichtigste Erreger der bakteriellen Meningitis. Entscheidend für die Diagnose ist die Liquordiagnostik mit Gramfärbung. Empirisch werden ein Cephalosporin der dritten Generation und Ampicillin eingesetzt."
8933,Virus-Gastroenteritis,"Zu den Viren, die eine Gastroenteritis verursachen, zählt man Rota- und Adeno-Viren, ferner Calici-Viren (Genus Noro- und Sapo-Virus u.a.) sowie Astro- und Corona-Viren u.a. (➤ Kap.59). Die viral bedingte Gastroenteritis ist die Hauptursache der hohen Säuglings- und Kleinkindersterblichkeit in den Tropen. Man schätzt, dass dort pro Jahr etwa 1–2 Mio. Kinder an einer Virus-Gastroenteritis sterben."
8934,Pathology of Sepsis,
8935,The TIE Receptor Family,"The endothelial TIE1 and TIE2 receptor tyrosine kinases form a distinct subfamily characterized by their unique extracellular domains. Together with the angiopoietin growth factors (ANGPT1, ANGPT2, ANGPT4, also abbreviated as ANG), the TIE receptors form an endothelial specific signaling pathway with important functions in the regulation of lymphatic and cardiovascular development and vascular homeostasis. Angiopoietins exist in multimeric forms that activate the TIE receptors via unique mechanism. In endothelial cell–cell contacts, angiopoietins induce the formation of homomeric in trans TIE receptor complexes extending across the cell junctions, whereas matrix-bound angiopoietin-1 (ANG1) activates the TIE receptors in a cis configuration. In comparison to the vascular endothelial growth factor receptors, the TIE receptors undergo little ubiquitin-mediated degradation after activation, whereas TIE2 signaling is negatively regulated by the vascular endothelial protein tyrosine phosphatase, VE-PTP. ANG1 activation of TIE2 supports vascular stabilization, whereas angiopoietin-2 (ANG2), a context-dependent weak TIE2 agonist/antagonist, promotes pathological tumor angiogenesis, vascular permeability, and inflammation. Recently, ANG2 has been found to mediate some of its vascular destabilizing and angiogenic functions via integrin signalling. The circulating levels of ANG2 are increased in cancer, and in several human diseases associated with inflammation and vascular leak, for example, in sepsis. Blocking of ANG2 has emerged as a potential novel therapeutic strategy for these diseases. In addition, preclinical results demonstrate that genetic TIE1 deletion in mice inhibits the vascularization and growth of tumor isografts and protects from atherosclerosis, with little effect on normal vascular homeostasis in adult mice. The ability of the ANG-TIE pathway to control vessel stability and angiogenesis makes it an interesting vascular target for the treatment of the various diseases."
8936,"Antigenicity, Immunogenicity, Allergenicity","The term “immune” pertains to the body keeping itself free from diseases, not to trigger any diseases. In this regard, it makes sense for us to divide antigenicity into immunogenicity and allergenicity. This distinction allows for the characterization of all types of modern antigens, i.e., to evaluate and modify a priori the allergenicity of an antigen before it is applied to humans. In this chapter, we also formulated the hypothesis that “Balanced Stimulation by Whole Antigens” is essential for immune development. This hypothesis revives the practicality of the “Hygiene Hypothesis” and can provide a fundamental solution to curb the increasing prevalence of allergic disease, namely, early exposure, at 0–1 year old or earlier, in utero, of representative allergens/protein antigens with immunogenicity retained or improved and allergenicity attenuated or eliminated."
8937,Protein Structure Prediction by Protein Threading,"The seminal work of Bowie, Lüthy, and Eisenberg (Bowie et al., 1991) on “the inverse protein folding problem” laid the foundation of protein structure prediction by protein threading. By using simple measures for fitness of different amino acid types to local structural environments defined in terms of solvent accessibility and protein secondary structure, the authors derived a simple and yet profoundly novel approach to assessing if a protein sequence fits well with a given protein structural fold. Their follow-up work (Elofsson et al., 1996; Fischer and Eisenberg, 1996; Fischer et al., 1996a,b) and the work by Jones, Taylor, and Thornton (Jones et al., 1992) on protein fold recognition led to the development of a new brand of powerful tools for protein structure prediction, which we now term “protein threading.” These computational tools have played a key role in extending the utility of all the experimentally solved structures by X-ray crystallography and nuclear magnetic resonance (NMR), providing structural models and functional predictions for many of the proteins encoded in the hundreds of genomes that have been sequenced up to now."
8938,From “Health for All” to “Health as Investment:” The Role of Economic Rationalities in the Transition from International to Global Health 1978–2013,"This chapter examines the role of economic rationalities in the transition from international health to global health since the late 1970s. It focuses, in particular, on the recent rise to prominence of non-communicable diseases on the global health agenda. Once considered to be diseases of affluence, non-communicable diseases (NCDs) such as cancer, diabetes, cardiovascular disease have recently come to be seen as a threat to both the global population and the global economy. Strategies to combat the proliferation of NCDs have simultaneous been shown to be particularly cost-effective, making NCD interventions a solid global health investment. This chapter contrasts the current era of global health, in which health is imagined in as a form of human capital and a site of investment with a post-war era of international health during which health was advocated as a human right and public good. Drawing on empirical material including historical documents, published reports and the scientific literature, it argues that the transition from international to global health can be best understood as resulting from the rise of economic rationalities in the field of world health over the last 25 years."
8939,SARS Accessory Proteins ORF3a and 9b and Their Functional Analysis,"The SARS coronavirus (CoV) positive-stranded RNA viral genome encodes 14 open reading frames (ORFs), eight of which encode proteins termed as “accessory proteins.” These proteins help the virus infect the host and promote virulence. In this chapter we describe some of our latest investigations into the structure and function of two such accessory proteins: ORF3a and 9b. The ORF3a accessory protein is the largest accessory protein in SARS-CoV and is a unique membrane protein consisting of three transmembrane domains. It colocalizes on the cell membrane and host Golgi networks and may be involved in ion channel formation during infection. Similarly the ORF9b accessory protein is 98 amino acids, associates with the spike and nucleocapsid proteins and has unusual membrane binding properties. In this chapter we have suggested possible new roles for these two accessory proteins which may in the long run contain answers to many unanswered questions and also give us new ideas for drugs and vaccine design."
8940,Erkrankungen der Atemwege und der Lunge,"Der italienische Arzt Girolamo Cardano (1501–1576), der zu seiner Zeit als einer der größten Gelehrten und Ärzte in ganz Europa galt, wurde im Jahre 1552 von John Hamilton, dem Erzbischof von St. Andrews in Edinburgh, zur Konsultation eingeladen. Hamilton, der Bruder des Regenten von Schottland, litt seit mehreren Jahren an Husten, Dyspnoe und Expektoration, die nach Ansicht der königlichen Leibärzte von einem kalten und feuchten Hirn herrührten, in dem sich durch Destillation Phlegma anhäufte, das anschließend durch die Luftröhre in die Lunge absank. Cardano beobachtete seinen Patienten 40 Tage lang und kam zu dem Schluss, dass asthmatische Beschwerden durch eine Unverträglichkeit von Bettfedern mitverursacht werden. Heute ist bekannt, dass Allergien – wie in diesem Fall die Hausstaubmilbenallergie – oft an der Auslösung des kindlichen Asthma bronchiale beteiligt sind. In Mitteleuropa ist das Asthma mittlerweile die häufigste chronische Erkrankung im Kindes- und Jugendalter. Maßnahmen der Allergenkarenz sind auch heute noch von essenzieller Bedeutung."
8941,The ‘delayed infection’ (aka ‘hygiene’) hypothesis for childhood leukaemia,"The common variant of childhood acute lymphoblastic leukaemia (cALL) is the most frequent paediatric cancer subtype. Its incidence rate appears to have increased substantially in Western societies during the mid-20th century and continues to increase at ∼1%/year. Worldwide cALL appears to track with affluence of societies. The ‘delayed infection’ hypothesis, first formulated in 1988, parallels the hygiene hypothesis and has an evolutionary foundation in the concept of a mismatch between prior genetic selection and programming (of the immune system) and contemporary social circumstances. In essence, the hypothesis predicts that ALL is triggered by an abnormal immune response to one or more common microbial infections and that the abnormality arises for two reasons: (i) infectious exposures being delayed beyond the immunologically anticipated period of infancy; (ii) some degree of inherited genetic susceptibility via, for example, allelic variation in genes involved in the MHC and/or immune response network. The hypothesis also has a framework in the underlying cell and molecular biology of ALL and its natural history. Epidemiological studies of social contacts in infancy (as a proxy for common infections) and risk of ALL provide indirect but strong support for the hypothesis. The idea still requires mechanistic and genetic endorsement and the appropriate studies are in progress."
8942,Engineering Spirulina for Enhanced Medicinal Application,"Cyanobacteria are prokaryotes which can perform photosynthesis like higher plants. Their genomic organisation is very simple and thus is suitable for the study of detailed photosynthesis mechanism at a molecular level also for many other genomic manipulations relevant to benefit of living organisms. This unicellular alga, Spirulina has a thin thread like elongated structure and classified under Cyanobacteriaceae which is blue green in colour. Under microscope it looks like bunch of bright helical threads (Fig. 11.1)."
8943,Types of Recombinant Vaccines,"The original scientific strategy behind vaccinology has historically been to “isolate, inactivate, and inject,” first invoked by Louis Pasteur."
8944,Infectious Diseases,"As infectious diseases are very commonly seen in the ICU, this chapter covers both typical and atypical infections found in this setting. If the patient has been transferred to the ICU after a prolonged stay in the hospital, the treatment should be focused on a nosocomial infection. This chapter emphasizes that the first thing to do is to identify the organisms causing the patients’ infection, keeping in mind frequently found organisms. Pneumonia, severe adult respiratory syndrome (SARS), sepsis, toxic shock syndrome, and infections in patients with AIDS are among the most common infectious diseases treated in the ICU. An appropriate initial empiric therapy and correct treatment once cultures and susceptibility become available are crucial for a successful treatment."
8945,Health in Africa and the Role of International Organizations,"For Africa, international health financial organizations, such as the United Nations (UN) through the World Health Organization, and bi-lateral assistance programs represent a curse and a blessing simultaneously. While they provide needed assistance and help meet the health needs of Africans, they make the continent dependent on hand-outs, unwittingly encouraging unscrupulous leaders not to generate or make national resources available to the people. Worse even, foreign assistance leaves a vacuum when it is depleted or, for various reasons, withdrawn. Foreign funds are also easily prone to misuse by leaders and unscrupulous high and middle level civil servants. Furthermore, as is the case with the IMF, assistance has always come with strings attached, forcing Africa to rely on international generosity to meet the health needs the West deems a priority for the continent. These conditions often imply at times that the donors know best what is good for Africans. While not denying the usefulness and the need for international assistance, the author argues that the use of financial assistance must be completely transparent to prevent misuse and abuse, not condescending, and always respectful of Africa’s sovereignty. In this context, world leaders must also note that the globalizing trend is often one-sided, unidirectional—from North to South—always exploitative in nature and accompanied by a cultural baggage that corrupts the youth, unwittingly promotes violence, sex, decadent practices, and unhealthy behaviors, such as the consumption of fast foods and tobacco, bad diets and alcohol abuse, thus contributing to non-communicable diseases, such as liver and stomach cancers, now dubbed by the UN as Africa’s second disease burden."
8946,Fibrinogen α-Chain as a Serum Marker of Liver Disease,"Liver fibrosis is the hepatic response to an insult characterized by an accumulation of extracellular matrix proteins. If the underlying cause is not treated or eliminated, the disease can progress and may lead to several clinical complications including hepatocellular carcinoma or even death. Thus, detection, staging, and follow-up of liver fibrosis are the main issues in the prognosis and treatment of patients with chronic liver disease. In recent years, new advances in mass spectrometry-based proteomics technology and protein fractionation techniques have improved protein identification as well as protein quantification in many different samples and diseases including liver fibrosis. In particular, the fibrinogen α chain and more specifically the serum levels of the 5.9 kDa fragment of fibrinogen α C-chain have shown to be altered in several hepatic etiologies. In fact, these results have been reproduced by different laboratories, and recently a marked downregulation of this protein fragment has also been described in the initial stages of liver fibrosis. In this chapter, we have described the potential role of fibrinogen α chain and particularly the 5.9 kDa fragment of fibrinogen α C-chain as a circulating marker of liver fibrosis."
8947,Virological laboratory diagnosis of SARS,
8948,Biomolecular Structure and Modeling: Historical Perspective,"physics, chemistry, and biology have been connected by a web of causal explanation organized by induction-based theories that telescope into one another. … Thus, quantum theory underlies atomic physics, which is the foundation of reagent chemistry and its specialized offshoot biochemistry, which interlock with molecular biology — essentially, the chemistry of organic macromolecules — and hence, through successively higher levels of organization, cellular, organismic, and evolutionary biology. … Such is the unifying and highly productive understanding of the world that has evolved in the natural sciences."
8949,WhyZombie? Zombie Pop Culture to Improve Infection Prevention and Control Practices,"Wikipedia currently lists 383 feature length ‘A-list’ zombie films, released between 1932 and 2014. These films indicate a number of causes of ‘zombification.’ A significant number of these films had an infectious cause of some kind (viral, bacterial, parasite, extra-terrestrial, zoonotic or other biological cause). The chapter explores this phenomenon and indicates that global health issues result in an increase in the release of infectious biohorror films in the years following outbreaks such as SARS and pandemic influenza, influencing pop culture. There are clear indications that contemporary infection prevention control (IPC) technologies are evident in these films, successful or not. Using contemporary cultural influences allows healthcare workers and the public to contextualise IPC theory and practice in an accessible and memorable way."
8950,Mathematical Studies of Dynamics and Evolution of Infectious Diseases,
8951,"Epidemiology, etiology, and risk factors of bacterial pneumonia","Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection after urinary tract infections. The incidence of HAP ranges from 5 to 15 cases per 1000 hospital admissions, and is a frequent problem in general wards (incidence ranging from 1.6 to 3.67 cases per 1000 admissions)."
8952,Besondere Patientengruppen im Intensivtransport,"Neben den im vorrangegangenen Kapitel besprochenen Krankheitsbildern gibt es im Rahmen der Durchführung eines Intensivtransportes Patienten, die nicht »krank« im eigentlichen Sinne sind, jedoch aufgrund spezieller Entwicklungs-, Krankheits- oder Therapieverläufe einer besonderen Aufmerksamkeit bedürfen. Hierzu zählen Früh - und Neugeborene ebenso wie Patienten, bei denen eine Infektion mit therapieresistenten Erregern besteht."
8953,A Novel Disease Outbreak Prediction Model for Compact Spatial-Temporal Environments,"One of the popular research areas in clinical decision supporting system (CDSS) is Spatial and temporal (ST) data mining. The basic concept of ST concerns about two combined dimensions of analyzing: time and space. For prediction of disease outbreak, we attempt to locate any potential uninfected by the predicted virus prevalence. A popular ST-clustering software called “SaTScan” works by predicting the next likely infested areas by considering the history records of infested zones and the radius of the zone. However, it is argued that using radius as a spatial measure suits large and perhaps evenly populated area. In urban city, the population density is relatively high and uneven. In this paper, we present a novel algorithm, by following the concept of SaTScan, but in consideration of spatial information in relation to local populations and full demographic information in proximity (e.g. that of a street or a cluster of buildings). This higher resolution of ST data mining has an advantage of precision and applicability in some very compact urban cities. For proving the concept a computer simulation model is presented that is based on empirical but anonymized and processed data."
8954,Gastroenterologie,
8955,"Pulmonary Hemorrhage, Transient Tachypnea, and Neonatal Pneumonia","The intent of this chapter is to address three other common pulmonary causes of respiratory distress in the high-risk infant. These other forms of parenchymal lung disease range in severity from mild, as seen in transient tachypnea, to severe as is often the case in pulmonary hemorrhage. It is worth noting that on occasion, one or more of these conditions may coexist in the same patient. The treatment for all conditions is largely supportive or involves the use of targeted antimicrobial therapy."
8956,Impacts on Human Health Caused by Zoonoses,"Zoonosis is an infectious disease and a potential bioterrorism agent. Bioterrorism aimed at a society, government, and/or its citizens is meant to cause destabilization, fear, anxiety, illness, and death in people, animals, or plants using biological agents. A bioterrorism attack is the intentional release of biological agents such as viruses, bacteria, fungi, rickettsial or chlamydial organisms, toxins, or other harmful agents. This chapter focuses on the induction, monitoring, and prevention of some zoonotic diseases that have potential as bioterrorism agents. The etiology, clinical manifestations, transmission routes, and treatment of these zoonotic agents are briefly discussed."
8957,Disaster Risk Management,"This chapter illustrates disaster and risk management. The disaster management includes hazard management and disaster issue management. Disaster risk management relies on the institution, policy, and scientific and technological progress for disaster reduction. Improving disaster risk management capacity is the key point to improving the utilization efficiency and effectiveness of disaster reduction resources, which is also an important guarantee for disaster risk reduction."
8958,Nephrologie,"—. primäre/idiopathische Glomerulonephritis: primäre Erkrankung der Glomeruli; —. sekundäre Glomerulonephritis: Systemerkrankung mit renaler Beteiligung; —. : —. Immunkomplexnephritis (z. B. akute postinfektiöse Glomerulonephritis); —. Anti-Basalmembran-Glomerulonephritis (z. B. rasch progrediente Glomerulonephritis); —. IgA-Nephropathie; —. : —. initial asymptomatisch/oligosymptomatisch: (Mikro-)Hämaturie, in der Regel ohne Proteinurie, normale Nierenfunktion, evtl. Hypertonie; —. akut: Mikrohämaturie, leichte Proteinurie, evtl. nephrotisches Syndrom, akutes oligoanurisches Nierenversagen; —. chronisch-progredient: Erythrozyturie, Proteinurie, meist Hypertonie, langsames Fortschreiten der Niereninsuffizienz; —. verantwortlich für 10% aller chronischen Niereninsuffizienzen;"
8959,Proportionality Review in EU Gambling Law,"This chapter starts with a thorough introduction to gambling addiction according to the current state of research. It explains the nature and mechanisms of this mental disorder. These findings lay the ground to analyse the proportionality review: judicial views are contrasted with empirical findings. It is shown that the Court of Justice's – legally relevant(!) – assumptions on gambling addiction are (only) partly supported by empirical evidence. The chapter also establishes that different standards of review have applied to different aspects of gambling regulation, with the most lenient review being applied to national choices of licensing models and the strictest to penalties and procedural requirements in licensing tenders. In a next step, the Court’s review practice is compared to judgments in other areas that involved similar consumer protection concerns (alcohol addiction and youth drinking; internet threats). Again, a diverging standard of review is noted. The chapter inquires the causes for the Court’s peculiar approach to gambling issues. It analyses in particular the political context of the early case law and it identifies passages in the jurisprudence that illustrate a subjective-moral rather than objective-scientific perspective on gambling-related risks. Finally, the chapter addresses the consequences of the Court’s diverging approach. Dealing with gambling as a ‘peculiar issue’ and a topos of public morality led to a lack of a science-informed assessment of gambling-related risks. The chapter notes a ‘judicial vacuum’ in the review practice; the numerous cases referred to the Court of Justice are an expression of this problem as predicted by the late Advocate General Colomer."
8960,Hämostyptika,"Desmopressin (DDAVP) wurde 1966 als Abkömmling des antidiuretischen Hypophysenhormons Arginin-Vasopressin synthetisch hergestellt. Zu den antidiuretischen Indikationen zählen Diabetes insipidus und Enuresis nocturna, zudem wird es in Tests zur Bestimmung der Nierenkonzentrationsfähigkeit verwendet"
8961,Nanomicrobiology,"Microbiology plays an important role in practice of medicine. Nanodiagnostics have refined the detection of infectious diseases and many new nanotechnology-based therapies, particularly of viral diseases, are in development."
8962,"Transcriptomics of the Fungal Pathogens, Focusing on Candida albicans","The past century brought the availability of vaccines and antibiotics, leading to a dramatic fall in mortalities caused by infectious diseases. This led to the assumption that infectious disease has been defeated by medicine. In 1969 the United States Surgeon General actually claimed that “we can close the book on infectious diseases”. However, today we know that this assumption was naïve, not taking into account that evolution is a constant motor in adapting the existing organisms to changing environmental conditions, including the adaptation of pathogens to changes in the host. Today nearly 25% of the annual deaths world-wide are directly related to pathogens (Morens et al. 2004). This can be attributed to the appearance of new diseases, like HIV, SARS or West Nile Virus, but also to an increase of resistance to antibiotics in pathogens thought to be defeated, like Mycobacterium tuberculosis or Staphylococcus and Enterococcus strains. In addition the progress in medical care results in a large proportion of immune-deficient patients and consequently in an increase in opportunistic infections. Especially fungi have gained an infamous reputation during recent decades as being highly detrimental to patients with haematologiconcologic diseases, neutropenia or after organ transplantation. A review of the current literature identified 1415 species as known to be pathogenic to humans, including 538 bacteria and 307 fungi (Cleaveland et al. 2001). The fungi are a large group of diverse eukaryotic organisms. Only about 74 000 to 120 000 of the estimated 1.5×10(6) existing species of fungi have been described. Of the approximately 300 fungal species that are known to cause human infections, the most commonly observed live threatening systemic infections are caused by opportunistic infections of Candida species or Aspergilli. Therefore the major scientific interest with regard to fungal pathomechanisms has focused on these organisms in the past decade. The early availability of the genome sequence of Candida albicans (the first assembly of the genome sequence was publicly available in 2000, at http://www-sequence.stanford.edu/group/candida),the availability of molecular tools and the use of Saccharomyces cerevisiae as a model for many characteristics of C. albicans relevant for pathogenesis (including morphogenesis and signalling pathways involved in stress response) resulted in a major body of work concerning this opportunistic fungal pathogen (Berman and Sudbery 2002; Braun et al. 2005; Jones et al. 2004). Until 2004 C. albicans was actually the only fungal pathogen on which genome-wide transcriptomics using arrays had been published. The sequences of other pathogenic fungi or the tools required for genome-wide transcriptomics had not been available to the public until then. However, a major body of molecular work has been performed on other opportunistic fungal pathogens, including C. glabrata, C. parapsylosis, C. tropicalis, Cryptococcus neoformans and Aspergillus species, where Aspergillus fumigatus is leading the clinically relevant species, as well as on the genera of primary fungal pathogens, including Blastomyces, Coccidioides, Histoplasma and Paracoccidioides. Due to the advancement of Candida albicans transcriptomics this chapter mainly focuses on this organism and only briefly touches the current work on other fungal pathogens."
8963,Immunization and Vaccination,"Vaccines have been recognized as one of the most successful public health measures. In this chapter, we provide a historical overview of immunization measures and discuss the basics of immunization and vaccination in the context of a pandemic outbreak. We will also discuss vaccine hesitancy, the factors that lead to vaccine acceptance and refusal, the determinants of individual decision-making about vaccination, and strategies of how to approach it on an individual, community, and global level."
8964,Global control of infectious diseases by vaccination programs,"In both industrialized and developing countries, childhood immunization has become one of the most important and cost-effective public health interventions. National immunization programs have prevented millions of deaths since WHO initiated the ‘Expanded Program on Immunization’ in 1974. Smallpox was eradicated in 1979, poliomyelitis is on the verge of eradication, and two thirds of developing countries have eliminated neonatal tetanus. Global immunization coverage was at 78% in 2005. Through their impact on childhood morbidity and mortality, immunization programs are contributing to reaching the ‘Millennium Development Goal 4’ — a two-thirds reduction of under-five mortality by 2015. However, the failure to reach more than 20% of the world’s children with existing vaccines was responsible for at least 2.5 million of an estimated 10.5 million deaths of children under 5 years, mainly in developing countries. Of these deaths, 1.4 million could have been prevented by vaccines currently recommended by WHO. Rapid progress in our understanding of the pathogenesis of infectious diseases, immunology, and biotechnology has increased the number of candidate vaccine antigens available. Pressures are growing on public health decision makers to establish evidence-based ways to decide which new vaccines should be introduced on a large scale into national immunization programs. The gap in access to new vaccines between the developing and industrialized worlds is still wide, and wealthy countries are still the first to introduce and use new vaccines. Interest from countries and partner agencies in vaccination, as one of the most cost-effective public health interventions, continues to be strong, also due to rapid progress in biotechnology and vaccine development and the emergence of global infectious disease threats, including HIV/AIDS, SARS, and influenza. The establishment of the Global Alliance for Vaccines and Immunization has focused global activities to support vaccination programs through raising considerable funds, and to assist especially poorer countries in improving and expanding their vaccination programs. Global efforts concentrate on further reducing the gap in the access to all existing vaccines between industrialized and developing countries."
8965,Sepsis,"1. Hyperthermie (>38,5 °C) oder Hypothermie (<36,0 °C). 2. Tachykardie (Herzfrequenz >2SD über der altersentsprechenden Norm) oder Bradykardie (Herzfrequenz <10. Perzentile) im Alter <1 Jahr. 3. Tachypnoe (Atemfrequenz >2SD über der altersentsprechenden Norm). 4. Leukozytose oder Leukozytopenie oder Linksverschiebung (>10 % unreife Neutrophile), 5. Nachweis oder Verdacht auf eine Infektion;"
8966,Staphylococcal Infections,
8967,"Geschichte, Theorie und Ethik der Medizin","Von Medizin kann erst dann die Rede sein, wenn zur heilkundlichen Praxis eine Theorie hinzukommt, die sich an der jeweils aktuellen Naturwissenschaft ausrichtet."
8968,Modeling the Case of Early Detection of Ebola Virus Disease,"The most recent Ebola outbreak in West Africa highlighted critical weaknesses in the medical infrastructure of the affected countries, including effective diagnostics tools, sufficient isolation wards, and enough medical personnel. Here, we develop and analyze a mathematical model to assess the impact of early diagnosis of pre-symptomatic individuals on the transmission dynamics of Ebola virus disease in West Africa. Our findings highlight the importance of implementing integrated control measures of early diagnosis and isolation. The mathematical analysis shows a threshold where early diagnosis of pre-symptomatic individuals, combined with a sufficient level of effective isolation, can lead to an epidemic control of Ebola virus disease."
8969,Corona-Viren,"Im Genus Corona-Virus finden sich 5 humanpathogene Viren, welche Erkrankungen der oberen Luftwege, Gastroenteritis sowie schwere Pneumonien hervorrufen können. Der Name leitet sich von dem wie eine Krone (“Corona„) aussehenden Besatz der äußeren Hülle des Virus mit knöpfchentragenden Spikes (= Glykoproteine) her. Bei Vögeln und Säugetieren kennt man Corona-Viren als Erreger von schwerer Bronchitis und Gastroenteritis."
8970,Herpes Simplex Virus Pneumonia in Patients with Hematologic Malignancies,"Herpes simplex virus (HSV) pneumonia is rare and is usually seen in immunocompromised patients. Patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) are at risk. Most of the cases of HSV pneumonia are caused by HSV-1; however, cases caused by HSV-2 have also been reported. Mucocutaneous disease often precedes the development of pneumonia, with nonspecific symptoms that include fever, cough, and dyspnea. Worsening oxygenation and failure to wean off mechanical ventilation despite broad-spectrum antimicrobial coverage is also a common presentation. Diagnosis requires a high degree of suspicion and is based on isolation of the virus from respiratory secretions and demonstration of cytopathic effects on histopathology. Acyclovir is the most widely used drug for treatment and prophylaxis. With increasing evidence of resistance to acyclovir and its analogs, newer agents such as foscarnet and cidofovir are being recommended as treatment options. Prophylaxis in patients with seropositive HSV undergoing chemotherapy or in the immediate post-HSCT period has been shown to reduce HSV disease rates and mortality rates. This chapter will focus on incidence and transmission, pathogenesis, risk factors, clinical features, diagnosis, and management of HSV pneumonia in patients with hematologic malignancies and HSCT, as well as outcome and prognosis."
8971,Building Applied Mathematics Knowledge Base in East Africa,"There is vast demand in Africa for technological development including modernization of higher education. Reforms in industrial processes through engineering skills are pivotal for the environmental concern and goals of sustainable development. Lappeenranta University of Technology has actively contributed to the spread of Industrial Mathematics in East African region over the past decade through development projects financed by the Finnish Ministry of Foreign Affairs. In this article, we summarize these projects and present their achievements. The story of European Consortium for Mathematics in Industry (ECMI) and the accumulated experience over 25 years have been the encouragement and inspiration for our initiatives. They were focused on Applied Mathematics curriculum development in Partner countries, and on organization of ECMI-style practical workshops like modeling weeks. There is obvious demand to broaden the cooperation between Africa and the European applied mathematics community."
8972,Respiratory Syncytial Virus,Name of Virus: Respiratory Syncytial Virus
8973,Applications of Loop-Mediated Isothermal Amplificaton Methods (LAMP) for Identification and Diagnosis of Mycotic Diseases: Paracoccidioidomycosis and Ochroconis gallopava infection,"Loop-mediated isothermal amplification (LAMP) methods are now useful for the detection of a specific gene in infectious diseases, genetic diseases, and/or genetic disorders in the large number of medical fields, and it was recently introduced to fungal investigation. It is characterized by the use of four different primers specifically designed to recognize six distinct regions of the target gene, and the reaction process proceeds at a constant temperature using strand displacement reaction. Quickness and simplicity is the advantage of the method. Amplification and detection of gene can be completed in a single step, by incubating the mixture of samples, primers, DNA polymerase with strand displacement activity and substrates at a constant temperature. The method was applied to two fungal infections; paracoccidioidomycosis (PCM), a deep mycosis caused by Paracoccidioides brasiliensis and Ochroconis gallopava infection. For PCM a combination of F3, B3, FIP, and BIP primers designed from the partial sequence of P. brasiliensis gp43 gene was used. The PCR products amplified by the primer set; F3 and B3 showed species specificity for P. brasiliensis and the detection limit of the PCR was 100 fg of fungal genomic DNA. The specific DNA banding pattern of P. brasiliensis was detected in the clinical and nine-banded armadillo derived isolates, paraffin-embedded tissue sample or sputum from PCM patient. LAMP method was used also for the identification of O. gallopava by using species-specific primer sets based on the D1/D2 domain of the LSU rDNA sequence. The method successfully detected the gene from both fungal DNA derived from brains and spleens of experimentally-infected mice with O. gallopava and environmental isolates. In conclusion, LAMP method for PCM and O. gallopava seemed to be useful for identification, diagnosis or retrospective study with advantage in the quickness and simplicity procedure, but require strictly-controlled environments."
8974,PCR in Integrated Microfluidic Systems,"Miniaturized integrated DNA analysis systems offer the potential to provide unprecedented advances in cost and speed relative to current benchtop-scale instrumentation by allowing rapid bioanalysis assays to be performed in a portable self contained device format that can be inexpensively mass-produced. The polymerase chain reaction (PCR) has been a natural focus of many of these miniaturization efforts, owing to its capability to efficiently replicate target regions of interest from small quantities template DNA. Scale-down of PCR has proven to be particularly challenging, however, due to an unfavorable combination of relatively severe temperature extremes (resulting in the need to repeatedly heat minute aqueous sample volumes to temperatures in the vicinity of 95°C with minimal evaporation) and high surface area to volume conditions imposed by nanoliter reactor geometries (often leading to inhibition of the reaction by nonspecific adsorption of reagents at the reactor walls). Despite these daunting challenges, considerable progress has been made in the development of microfluidic devices capable of performing increasingly sophisticated PCR-based bioassays. This chapter reviews the progress that has been made to date and assesses the outlook for future advances."
8975,Diseases of the Pulmonary Vascular System,
8976,Urgent Epidemic Control Mechanism for Aviation Networks,"In the current century, the highly developed transportation system can not only boost the economy, but also greatly accelerate the spreading of epidemics. While some epidemic diseases may infect quite a number of people ahead of our awareness, the health care resources such as vaccines and the medical staff are usually locally or even globally insufficient. In this research, with the network of major aviation routes as an example, we present a method to determine the optimal locations to allocate the medical service in order to minimize the impact of the infectious disease with limited resources. Specifically, we demonstrate that when the medical resources are insufficient, we should concentrate our efforts on the travelers with the objective of effectively controlling the spreading rate of the epidemic diseases."
8977,Pulmonary Surfactant: Biology and Therapy,
8978,Biosurveillance and Dentistry,"Events of public health concern continue to present a challenge for the general population. A key element to address appropriate health responses is the establishment of modern public health surveillance mechanisms. In this chapter we explore possible scenarios/use cases where dentists can use electronic dental record technology to increase the accuracy, coverage, and timeliness of existing public health surveillance efforts. We identify organizational, technical, and regulatory elements that influence the adoption of such approaches and possible benefits when integrated to the public health system at large."
8979,The Economy and the Construction Industry,"Generally, there are three levels to define construction within the literature (Dang and Low in Infrastructure Investments in Developing Economies. Springer, 2015). At one extreme, construction is referred to as an economic activity that involves the entire construction process from producing raw and manufactured building materials and components, and providing professional services such as design and project management, to executing the physical work on site."
8980,Hämatologie,"—. Anämie = Hämoglobinkonzentration (Hb) ↓ unterhalb des alters-/geschlechtsspezifischen Normwertes; —. Hb korreliert mit dem Hämatokrit (Hkt), aber nicht direkt mit der Erythrozytenzahl; —. jede Anämie bedarf der Ursachenabklärung ➲ Memo keine Therapie ohne Diagnose!); —. Einteilung der Anämien nach mittlerem korpuskulärem Volumen (MCV) und mittlerem korpuskulärem Hb-Gehalt (MCH) (▸ Tabelle) [Image: see text] —. —. Kopfschmerzen, Konzentrationsschwäche; —. Ohrgeräusche; —. verminderte Leistungsfähigkeit, leichte Ermüdbarkeit; —. Belastungsdyspnoe; —. Schwindel- und Schwächegefühl Tachykardie, evtl. systolisches Herzgeräusch (Strömungsgeräusch infolge von Turbulenzen bei verminderter Viskosität; DD Endokarditis lenta mit Infektanämie); —. Blässe der Haut und Schleimhäute; —. Einteilung der Anämien nach ihrer Åtiologie (▸ Tabelle); —. mit 80% häufigste Anämieform; 80% aller Fälle sind Frauen; —. Eisenverluste durch chronische Blutungen (80% der Fälle): meist genitale Blutungen bei der Frau (z. B. Uterus myomatosus) oder Blutungen aus dem Verdauungstrakt; —. mangelnde Eisenzufuhr: v. a. bei Säuglingen, Kleinkindern und Vegetariern; —. ungenügende Eisenresorption: Anazidität nach Magenresektion, Malassimilationssyndrom, CED; —. gesteigerter Eisenbedarf: Gravidität, Stillperiode, Wachstum;"
8981,Triterpene einschließlich Steroide,"Die Triterpene gehören zur Naturstoffgruppe der Isoprenoide (vgl. Kap. 23). Sie stellen eine außerordentlich umfangreiche Klasse von Terpenen dar. Sie werden in diesem Kapitel zusammen mit den sich davon ableitenden Steroiden zusammengefasst. Die Muttersubstanz aller Triterpene ist der azyklische C(30)-Kohlenwasserstoff Squalen. Seine Zyklisierung wird durch Epoxidierung einer endständigen Doppelbindung eingeleitet. Da die Squalen-2,3-Epoxidstufe vor der Zyklisierung obligat durchlaufen werden muss, enthalten nahezu alle Triterpene und Steroide in Position C-3 eine Sauerstofffunktion. Vom Squalen ausgehend lassen sich zwei Hauptwege erkennen: Der eine führt zu den tetra- und pentazyklischen Triterpenen, der andere über Cycloartenol zu den Cucurbitacinen und via das wichtigste Stoffwechselintermediärprodukt, das Cholesterol, zu den Phytosterolen, Cardenoliden und Bufadienoliden sowie zu den Steroidsapogeninen."
8982,Southeast Asia: Beyond Crises and Traps,"There is persistent concern that Southeast Asian economies may eventually fall into the ‘middle-income trap’ due to the slow upgrading of their technological capabilities. However, the five Southeast Asian countries (Malaysia, Thailand, Indonesia, Philippines, and Vietnam) covered by this volume have performed much better economically than many non-Asian middle-income countries although not as well as the four East Asian ‘tiger economies’ and China. Those Southeast Asian economies have derived an important part of their vitality by pursuing economic growth and competitiveness along lesser known or recommended pathways such as niche-oriented activities, natural resource processing, and cheap labour-based production, or a combination of these. In the final analysis the technological upgrading of industries and services, including resource-based and niche-oriented ones, will remain the most plausible way to continue catching up with the advanced economies and to stay competitive vis-à-vis emerging rivals. However, just as past development trajectories had been shaped by domestic socio-political configurations and the international/regional environment, so future prospects for these countries depend on how well they adapt to the fluid conditions of global competition and the uncertain state of global markets. They would also have to overcome a sort of ‘socio-political trap’ of oligarchic aggrandizement and populist pressures that result in fragmented interests without a national consensus for upgrading industries and services."
8983,Risks and Epidemiology of Infections After Hematopoietic Stem Cell Transplantation,"Infections following HCT are frequently related to risk factors caused by the procedure itself. Neutropenia and mucositis predispose to bacterial infections. Prolonged neutropenia increases the likelihood of invasive fungal infection. GVHD and its treatment create the most important easily identifiable risk period for a variety of infectious complications, particularly mold infections. Profound, prolonged T cell immunodeficiency, present after T cell-depleted or cord blood transplants, is the main risk factor for viral problems like disseminated adenovirus disease or EBV-related posttransplant lymphoproliferative disorder."
8984,Life-threatening Respiratory Failure from H1N1 Influenza: Lessons from the Southern Cone Outbreak,"A sharp increase in the hospitalization rate for pneumonia, particularly among adults between 20 and 40 years old, and an unusual series of deaths, coincident with an increase in laboratory-confirmed influenza cases, were reported in the spring of 2009 in Mexico. This outbreak appeared after the end of influenza season, and was associated with mortality in a younger age-group than the pattern observed in temperate areas in the northern hemisphere [1]. The concurrent finding of a novel, swine-origin influenza A virus (so called pandemic influenza [H1N1] 2009) from infected children in the United States [2] completed the picture."
8985,Ventilator-Associated Pneumonia,"The area of the alveolar epithelium of the lung is approximately 70 m(2). This area is constantly in contact with the ambient air and is therefore vulnerable to contamination with airborne microbes and particles of respirable size. Due to the configuration of the respiratory tract, airborne particles having diameters in the range of 0.5-2.0 μ can reach and deposit in the terminal part of the tracheobronchial tree - most bacteria are of this size. In reality, very few bacteria cause infections by spreading via the airborne route (e.g., mycobacteria, viruses, and legionella). Most bacteria cause pneumonia by first colonizing the upper respiratory tract and later descending into the tracheobronchial tree."
8986,Intensivbehandlung nach Transplantation solider Organe,
8987,Macrophage Inflammatory Protein-1 Alpha (MIP-1 alpha)/CCL3: As a Biomarker,"Macrophage inflammatory protein-1 alpha (MIP-1α/CCL3) is a chemotactic chemokine secreted by macrophages. It performs various biological functions, such as recruiting inflammatory cells, wound healing, inhibition of stem cells, and maintaining effector immune response. It activates bone resorption cells and directly induces bone destruction. Cells that secrete MIP-1α/CCL3 are increased at sites of inflammation and bone resorption. MIP-1α/CCL3 plays an important role in the pathogenesis of various inflammatory diseases and conditions that exhibit bone resorption, such as periodontitis, multiple myeloma, Sjögren syndrome, and rheumatoid arthritis. Biological fluids from patients with these diseases exhibit elevated levels of MIP-1α/CCL3. This finding indicates that MIP-1[Formula: see text] /CCL3 protein may have diagnostic potential for the detection of several inflammatory diseases and conditions. This chapter discusses the biological functions of MIP-1α/CCL3; describes several diseases associated with MIP-1α/CCL3, particularly periodontitis; and delineates the potential application of MIP-1α/CCL3 as a biomarker."
8988,Identification of Essential Genes as a Strategy to Select a Sars Candidate Vaccine Using a SARS-CoV Infectious cDNA,
8989,Roadmap of Agricultural Production and Food Safety Science and Technology Development,"As Food is related to human survival and health, the country’s reputation and image, and the economic benefit and position in the international trade, it has become one of the hottest issues in the world now. As the continuous growth of world population, the constant changes of human life style and the continued deterioration of natural environment, higher requests for food safety are put forward by human society. Therefore, we should not only ensure the safety of quantity, but also to ensure the safety of quality in the food safety field by 2050. New concepts and technological means should be adopted to ensure the constant production and supply of the “green” and safe agricultural production to meet the people’s great need for food safety, nutrition and health."
8990,Infektiologie,
8991,Pulmonary Effects of Antineoplastic Therapy,"Pulmonary toxicity is common after cancer therapy and can result from all therapeutic modalities. The consequential decrease in lung function ranges in severity from subclinical to life-threatening or even fatal and can manifest in the acute setting or many years after completion of therapy. Radiation effects are due to direct insult to the pulmonary parenchyma and, for younger children, impaired thoracic musculoskeletal development. Radiation pneumonitis can occur in the acute/subacute setting, as well as fibrosis with comprised gas exchange as a late effect of direct lung irradiation; thoracic wall malformation can cause restriction of function as a chronic sequela. The pulmonary effects of cytotoxic drugs usually present as acute effects, but there is the potential for significant late morbidity and mortality. Of course, surgical interventions can also cause both acute and/or late pulmonary effects as well, depending on the specific procedure. Although treatment approaches for the management of pediatric cancers are continually adapted to provide optimal therapy while minimizing toxicities, to a varying degree all therapies have the potential for both acute and late pulmonary toxicity. Of note, the cumulative incidence of pulmonary complications rises with increasing time since diagnosis, which suggests that adult survivors of childhood cancer require lifelong monitoring and management of potential new-onset pulmonary morbidity as they age. Knowledge of cytotoxic therapies and an understanding of lung physiology and how it may be altered by therapy facilitate appropriate clinical care and monitoring of long-term survivors."
8992,Ergebnisdarstellung: Fallrekonstruktionen und Typisierungen,"In diesem Kapitel werden die empirischen Befunde der Arbeit vorgestellt. Die nachfolgend präsentierten Interpretationsergebnisse stellen das Resultat einer abstrahierenden Typisierung dar, zu deren Zustandekommen folgendermaßen vorgegangen wurde: Zunächst wurde jeder Fall aus jeder Samplegruppe einzeln betrachtet und anhand des im letzten Kapitels vorgestellten Vorgehens analysiert; infolgedessen zeigte sich, dass sich dabei fallübergreifende Gemeinsamkeiten herausstellten. Indem nach Abschluss der Fallrekonstruktion festgestellt werden konnte, dass sich die Fälle einer Subgruppe unter eine gemeinsame übergreifende Orientierung fassen ließen, wurde eine samplegruppenbezogene Abstrahierung vorgenommen. Dass im Folgenden zwölf generalisierte Orientierungsrahmen präsentiert werden, ist sowohl auf die Sample- als auch auf die dreigeteilte Themenstruktur zurückzuführen."
8993,Valuable Secondary Metabolites from Fungi,"Fungi are amazing producers of natural products, including secondary metabolites. These compounds are crucial to the health and well-being of people throughout the world. They also provide agriculture and livestock with many essential products. Production of secondary metabolites is improved by mutagenesis and recombinant DNA technologies allowing commercial production of these valuable compounds. This chapter centers on these fungal beneficial products, the discovery of which goes back 85 years to the time that penicillin was discovered by Alexander Fleming."
8994,Stem Cells and Organ Transplantation: Resetting Our Biological Clocks,"The human body has only a limited ability to repair itself. Illness, injury, and aging can overwhelm its built-in capability to replace dysfunctional, damaged, or destroyed tissues. We can at best only partly regenerate our organs and cannot grow back a whole limb."
8995,Anaesthetic and Perioperative Management for Liver Transplantation,"This chapter concerns about perioperative anaesthesiologic management of liver transplantation. Liver cirrhosis and its complications often involve different organs whose derangements could severely worsen postoperative outcome; hence, their preoperative diagnosis and treatment are fundamental; the first part of this chapter describes the most frequent complications of cirrhosis and their implications in preoperative care. Liver transplantation is a challenging task for the anaesthesiologist because of the risk of bleeding, cardiovascular derangements, coagulation impairment and metabolic disturbances; the second part of this chapter describes the main anaesthetic and monitoring techniques used for liver transplantations and the most important intraoperative problems which need to be faced by the anaesthesiologist in each phase of the intervention. Early postoperative management of liver transplant recipients is crucial because of their comorbidities and the potential surgical and medical complications of the intervention; the third part of this chapter describes the ICU management after liver transplantation and the main medical complications for every organ system that needs a critical care approach."
8996,"Hygiene, Mikrobiologie, Virologie","Die Mikrobiologie und Infektionsepidemiologie umfasst die Laboratoriumsdiagnostik mikrobiell bedingter Erkrankungen und die Aufklärung ihrer epidemiologischen Zusammenhänge und Ursachen. Weiterhin gehört in dieses Gebiet die Unterstützung der in der Vorsorge, in der Krankenbehandlung und im Öffentlichen Gesundheitsdienst tätigen Ärzte bei der Diagnose von Infektionskrankheiten, ihrer Prophylaxe und Bekämpfung sowie bei der mikrobiologischen Bewertung antimikrobieller Substanzen."
8997,Lebererkrankungen,"Die Leber als größtes inneres Organ des menschlichen Körpers ist ein zentrales Organ in Kohlehydrat- und Fettstoffwechsel, in der Herstellung zahlreicher Eiweiße, Enzyme und Gerinnungsfaktoren und in der Entgiftung und Ausscheidung verschiedenster Substanzen. Dieses Kapitel gibt einen Überblick über angeborene und erworbene Lebererkrankungen, deren Epidemiologie, Pathophysiologie, klinische Symptome, Komplikationen und Verlauf, typische Befunde zur Diagnosestellung und Differentialdiagnosen sowie therapeutische Möglichkeiten und Prognose. Das breite Spektrum der Lebererkrankungen umfasst angeborene Defekte des Eisen- und Kupferstoffwechsels, virale und bakterielle Infektionen, Parasitenbefall, vaskuläre und autoimmune Erkrankungen, Schädigung durch Alkohol oder Verfettung, sowie benigne und maligne primäre und sekundäre Lebertumore."
8998,Infektionen des ZNS,"Durch Bakterien hervorgerufene Meningitis mit der klassischen Trias Kopfschmerzen, Fieber und Meningismus"
8999,Pathogenität — Infektionsverlauf,Die Pathogenität von Viren ist die Voraussetzung für die Entstehung von Krankheiten. Sie kommt durch vielfältige Eigenschaften des Wirts und des Virus zustande. Im Brennpunkt stehen der virusbedingte primäre Zellschaden und die Entzündung mit sekundären immunpathologischen Zellschädigungen.
9000,Viral Hepatitis: Other Viral Hepatides,"Non-hepatotropic viruses cause acute hepatitis and/or acute liver failure, without causing any chronic damage to the liver. These viruses do not primarily target the liver. These viruses include the herpes viruses (Epstein-Barr virus, cytomegalovirus, and herpes simplex virus), parvovirus, adenovirus, influenza, and severe acute respiratory syndrome (SARS)-associated coronavirus. The risk of acquiring infection from any of the non-hepatotropic viruses is specific to each virus. Infection with the herpesviruses is ubiquitous, with clinically significant hepatitis being less common. Considerations for determining the risk of hepatitis from non-hepatotropic viruses include prior exposure (risk of reactivation), host immune status (increase severity in immunosuppressed), and duration of infection in the contact. Diagnosis is made with a combination of serology, polymerase chain reaction, or liver biopsy. Treatment is supportive in the majority. In certain clinical scenarios, such as cytomegalovirus infection in transplant patients, and acute liver failure from herpes simplex virus, specific antiviral therapy is warranted."
9001,Role of the Microbial Burden in the Acquisition and Control of Healthcare Associated Infections: The Utility of Solid Copper Surfaces,"For more than a century, healthcare has been challenged to keep environmental surfaces clean to control microbes and improve patient outcomes. However despite an annual cost exceeding ten billion dollars cleaning with disinfection has done little to reduce the incidence of healthcare-associated infections (HAI). This chapter will review the scientific evidence delineating the role that the environment and healthcare workers play in the acquisition and movement of the microbes implicated in HAI and how through controlling the microbial burden of the built clinical environment it is possible to mitigate the rate of HAI acquisition. Specifically evidence demonstrating the effectiveness of solid copper surfaces for its ability to continuously limit the concentration of bacteria found on surfaces and objects within the built environment will be reviewed in concert with a discussion of how through the mitigation of the environmental burden copper surfaces are able to concomitantly reduce the incidence of HAI. Insights provided by this chapter are intended to facilitate an understanding and importance of the need to use a comprehensive or systems based approach to fight healthcare associated infections."
9002,Applications of Multi-Type Branching Processes,Two applications of multi-type branching processes to epidemic models are presented. The first application is to an SEIR epidemic model and the second application is to the same epidemic model but with dispersal. The SEIR epidemic is modeled as a two-type branching process. Occurrence of an outbreak depends on the number of exposed and infectious individuals. It is shown that the offspring pgfs for the exposed and infectious populations lead to an explicit formula for the probability of an outbreak.
9003,Hygiene auf der IMC-Station,"Im Kapitel Hygiene auf der IMC-Station wird dargelegt, dass die Einhaltung von Hygienemaßnahmen nach den neuesten wissenschaftlichen Erkenntnissen zu den Basismaßnahmen einer jeden IMC-Station gehört. Neben den Standard-Hygienemaßnahmen einer IMC-Station werden die besonderen Aspekte der hygienischen Körperpflege beschrieben. Die erforderlichen Interventionen zur Vermeidung von Katheterinfektionen werden begründet. Die Vorbereitung, Anlage und Pflege der Katheter werden detailliert dargestellt, sodass jeder Lernende dies als Handlungsanweisung verwenden kann und dem Erfahrenen eine Detailprüfung ermöglicht wird. Wichtige Aspekte der Wund-, Drainagen- und Stomapflege werden besprochen und eine Kurzübersicht zur Pflege von Patienten mit MRE gegeben."
9004,Recombinant Human Deoxyribonuclease I,"Human deoxyribonuclease I (DNase I) is an endonuclease that catalyzes the hydrolysis of extracellular DNA and is just one of the numerous types of nucleases found in nature. The enzymatic mechanism for a single turnover is reasonably well understood based on biochemical and structural studies that are consistent with divalent metal ion dependent nonspecific nicking of a phosphodiester bond in one of the strands of double stranded DNA. Recombinant human DNase I (rhDNase I, rhDNase, Pulmozyme(®), dornase alfa) has been expressed in mammalian cell culture in Chinese hamster ovary cells and developed clinically where it is aerosolized into the airways for treatment of pulmonary disease in patients with cystic fibrosis (CF). rhDNase I hydrolyzes the DNA in purulent sputum of CF patients and reduces sputum viscoelasticity. Reduction of high molecular weight DNA into smaller fragments by treatment with aerosolized rhDNase I has been proposed as the mechanism to reduce the mucus viscosity and improve mucus clearability from obstructed airways in patients. The improved clearance of the purulent mucus enhances pulmonary function and reduces recurrent exacerbations of respiratory symptoms. rhDNase I was approved for clinical use in 1993 and has been widely used as a safe and effective therapy for CF patients. The use of rhDNase I has also been investigated in other diseases where exogenous DNA has been implicated in the disease pathology."
9005,Social Dilemma Analysis of the Spread of Infectious Disease,"Understanding and controlling the spread of infectious disease is a pressing issue for our society. Contemporary globally connected civilization is more at risk from various modern infectious diseases than classical ones such as pests, cholera, and tuberculosis. Over the last few years, pandemic outbreaks of highly virulent influenza, possibly related to avian flu, severe acute respiratory syndrome (SARS), and middle-eastern respiratory syndrome coronavirus (MARSE) have been a threat. Beyond this, the intentional spread of infectious disease, e.g., “bioterrorism”, has come to be recognized as being just as dangerous as nuclear weapons. An infectious disease spreads on human social networks. Each individual can protect himself through several measures. Pre-emptive vaccination is thought to be most effective, although it incurs a partial cost to each individual. This brings about a social dilemma, because an individual may be able to rely on so-called “herd immunity” to avoid his own infection without himself being vaccinated. Also, besides vaccination, there may be several practical ways to protect against contagion, such as wearing a mask, keeping away from crowds, and self-isolation by leaving the home less often, which may be less costly and less effective than vaccination. In any case, there is a human-decision-making process regarding what steps should be taken, while the dynamics of infectious-disease spread can themselves be evaluated as a diffusion problem that has been well-studied in physics for many years. Thus, based on the concept of human–environment–social interaction, a basic-physics model for this diffusion problem that considers evolutionary game theory (EGT) may lead us to obtain some meaningful solutions that can be proposed to our society. Following the previous chapter explaining how EGT can be applied to traffic-flow analysis, this chapter describes this practical problem."
9006,China,
9007,"Humans, Other Animals and ‘One Health’ in the Early Twenty-First Century","This chapter explores the history of recent movements for One Health, which argue that because many of today’s pressing health problems lie at the interface of human, animal and environmental health, they can only be managed effectively by breaking down traditional disciplinary silos. It explores how Schwabe’s work influenced, and was reconfigured by, this movement, and locates its early development in several different research and policy networks, which produced not one but several different forms of One Health. The chapter also examines how human–animal health relationships have inspired and shaped One Health, and how they are represented—in sometimes contradictory ways—in the texts and images produced by One Health researchers and advocates. It argues that in foregrounding the roles of animals as transmitters of diseases to humans, and as experimental models of human disease, One Health rebrands existing longstanding research agendas that are more concerned with the health of humans than that of animals."
9008,Short- and Long-Term Reaction to Exogenous Demand Shifts,"In less than 10 years, the liberalization of the European airline industry has placed flag carriers in a highly competitive and dynamic environment. One of the reasons for the demand dynamic clearly results from the peculiarity of the industry: airline carriers have to produce one of the most perishable goods (passenger transport). This fact has forced carriers to implement and refine practices and strategies in order to react promptly to the ups and downs of the demand. In Chap. 2 we described the common practices employed to face short-term demand fluctuations that usually rely on advanced pricing policies, called ‘yield management’. Long-lasting demand shifts require a reaction in terms of capacity supply described in Sect. 2.4.2 as ‘network planning’."
9009,We Do Not Live in an Age of Cosmopolitanism but in an Age of Cosmopolitization: The ‘Global Other’ is in Our Midst,"The collapse of a world order is often a moment for reflection on the dominant social theory and research of the time, but surprisingly this is not the case today. Mainstream social theory still floats loftily above the lowlands of epochal transformations (climate change, financial crisis, nation-states) in a condition of universalistic superiority and instinctive certainty. This universalistic social theory, whether structuralist, interactionist, Marxist, critical or systems-theory, is now both out of date and provincial."
9010,Influence of Gender on Outcome of Severe Sepsis,"Whether gender influences the outcome of severe sepsis remains a matter of debate. Because many confounding variables may affect observed associations between gender and mortality, high-quality statistical analyses are essential to carefully adjust the two groups of patients. About 55% to 65% of patients with sepsis have chronic co-morbidities associated with immune dysfunction (e.g., chronic renal failure, diabetes mellitus, human immunodeficiency virus [HIV] infection, and alcohol abuse), which increase the susceptibility to sepsis [1]. Genetic polymorphisms that affect the susceptibility to infection and/or the severity of the systemic response to infection [2] may lead to variability among individuals and between males and females [3]. Access to healthcare, another determinant of the incidence and outcome of sepsis, varies according to age, ethnic group, and gender, although a recent study conducted in the USA found only relatively small quality-of-care differences between males and females or across income groups compared to the gap for each subgroup between observed and desirable quality of health care [4]. Here, we review the data on the existence of, and reasons for, associations between gender and outcome of severe sepsis (Fig. 1)."
9011,Cardiopulmonary Resuscitation Injuries in Children,"Cardiopulmonary resuscitation (CPR) is an emergency intervention to maintain circulation and breathing in an unresponsive individual suffering from cardiopulmonary arrest. However, CPR is not without its own risks. Injuries secondary to compression and ventilation are well documented in the medical and scientific literature. Most of these injuries are minor, but some can result in significant morbidity and even death. It is important to identify those injuries that could be secondary to CPR versus inflicted traumatic injuries of child maltreatment."
9012,General Medicine and Surgery for Dental Practitioners: Infections and Infection Control,Infection control and knowledge of common infectious agents are cornerstones of safe dental practice. This paper summarises the measures that need to be taken to control cross infection and discusses some of the infectious agents of concern to dental practitioners.
9013,The Pancreas,
9014,Human Security in Practice: The Chinese Experience,"This chapter elaborates on how the idea of human security is defined and understood by the government and various actors in China. As one of the permanent members of the United Nations (UN) Security Council, China, has been supportive of international norms advocated by the UN, and even though the term human security has not been frequently used, in effect it has been vigorously practiced. For both the government and the academic community in China, human security and national security are not necessarily in confrontation but rather can complement and strengthen one another. The purpose is to improve the quality of people’s everyday life and the government is expected to contribute to this end. Chinese people expect the government to extend a parental roof over the people."
9015,Case Studies,"Ms A was a 28 year old woman in her second pregnancy (she had one previous termination of pregnancy) who booked-in at 19 weeks’ gestation. She was known to have sickle cell disease (specifically sickle cell anaemia [HbSS]), and her last crisis had occurred 3 years before this pregnancy."
9016,"Bildgebende Verfahren: Röntgen, Ultraschall, CT, Nuklearmedizin",
9017,Chronic Kidney Disease in the Intensive Care Unit,"The incidence and prevalence of chronic kidney disease (CKD) and end-stage renal disease are increasing, and these patients have a higher risk of developing critical illness and being admitted to the intensive care unit (ICU) compared to the general population. The higher prevalence of comorbid disease puts this population at higher risk for worse short- and long-term outcomes following ICU admission compared to the general population, although short-term mortality seems to be determined largely by the acute illness severity rather than CKD status per se. The pathophysiologic changes accompanying CKD present unique challenges to the management of acute critical illness most notably volume and metabolic homeostasis and drug dosing adjustment. CKD is an important risk factor for the development of acute kidney injury (AKI) complicating critical illness and can predispose to further accelerated decline in kidney function among ICU survivors. Renal replacement therapy (RRT) support is frequently used in ICU settings, and continuous renal replacement therapy modality remains the most commonly used among critically ill patients."
9018,Role of CD14 in Lung Inflammation and Infection,"Toll-like receptors (TLR) on the surface of cells of the respiratory tract play an essential role in sensing the presence of microorganisms in the airways and lungs. These receptors trigger inflammatory responses, activate innate immune responses, and prime adaptive immune responses to eradicate invading microbes [1]. TLR are members of a family of pattern-recognition receptors, which recognize molecular structures of bacteria, viruses, fungi and protozoa (pathogen-associated molecular patterns or PAMPs), as well as endogenous structures and proteins released during inflammation (damage/danger-associated molecular patterns or DAMPs). To date, ten different TLR have been identified in humans and twelve in mice. TLR are expressed on all cells of the immune system, but also on parenchymal cells of many organs and tissues. The binding of a PAMP to a TLR results in cellular activation and initiates a variety of effector functions, including cytokine secretion, proliferation, co-stimulation or phagocyte maturation. To facilitate microbial recognition and to amplify cellular responses, certain TLR require additional proteins, such as lipopolysaccharide (LPS) binding protein (LBP), CD14, CD36 and high mobility group box-1 protein (HMGB-1). In this chapter, the role of CD14 as an accessory receptor for TLR in lung inflammation and infection is discussed. The central role of CD14 in the recognition of various PAMPs and amplification of immune and inflammatory responses in the lung is depicted in Figure 1."
9019,Ocimum Genome Sequencing—A Futuristic Therapeutic Mine,"Next-generation sequencing (NGS) platforms from the past decade are in the continuous efforts of changing the impact of sequencing on our current knowledge about plant genes, genomes, and their regulation. Holy basil (Ocimum tenuiflorum L. or sanctum L.) genome sequencing has also paved the path for deeper exploration of the medicinal properties of this beneficial herb making it a true ‘elixir of life.’ The draft genome sequence of the holy basil has not only opened the avenues for the drug discovery but has also widened the prospects of the molecular breeding for development of new improved plant varieties."
9020,Laryngeal Infections,"The following chapter is a review of the most common viral and bacterial etiologies of pediatric laryngeal infections. The chapter reviews the diagnostic approach to laryngeal infections, focusing on key points of the history and physical exam, including concerning signs and symptoms suggestive of airway distress. Viral and bacterial laryngitis, croup, epiglottis, recurrent respiratory papillomatosis, as well as some less common causes of bacterial infections are discussed in detail with each etiology’s epidemiology, clinical features, associated diagnostic evaluation, and management reviewed."
9021,G-Protein-Coupled Receptors,"Receptors coupled to heterotrimeric guanine nucleotide-binding proteins, the socalled G-protein-coupled receptors (GPCR), represent the largest set of plasmalemmal receptors"
9022,Coronavirus,Name of Virus: Coronavirus
9023,Hematopoietic Stem Cell Transplantation,"Hematopoietic stem cell transplantation offers patients the only prospect of long-term survival for a substantial variety of otherwise incurable malignant neoplasms as well as selected non-neoplastic conditions. This therapeutic modality, however, carries significant risks and is associated with a wide range of complications affecting not only the bone marrow but many organ systems, in particular by graft-versus-host disease. Patients before, during, and following stem cell transplantation thus require close monitoring and the pathologist is frequently implicated in this process. The aim of this chapter is to provide the pathologist with the tools required to interpret biopsies from these patients at all stages of the transplantation process. Following an overview of hematopoietic stem cell transplantation and graft-versus-host disease, the chapter will focus on the histopathologic findings of graft-versus-host disease and other complications in several organs and tissue including bone marrow, skin, lung, kidney, gastrointestinal tract and liver, with emphasis on the diagnostic criteria and approaches to graft-versus-host disease."
9024,Bioinformatics and Nanotechnologies: Nanomedicine,"In this chapter we focus on the bioinformatics strategies for translating genome-wide expression analyses into clinically useful cancer markers with a specific focus on breast cancer with a perspective on new diagnostic device tools coming from the field of nanobiotechnology and the challenges related to high-throughput data integration, analysis, and assessment from multiple sources. Great progress in the development of molecular biology techniques has been seen since the discovery of the structure of deoxyribonucleic acid (DNA) and the implementation of a polymerase chain reaction (PCR) method. This started a new era of research on the structure of nucleic acids molecules, the development of new analytical tools, and DNA-based analyses that allowed the sequencing of the human genome, the completion of which has led to intensified efforts toward comprehensive analysis of mammalian cell struc ture and metabolism in order to better understand the mechanisms that regulate normal cell behavior and identify the gene alterations responsible for a broad spectrum of human diseases, such as cancer, diabetes, cardiovascular diseases, neurodegenerative disorders, and others."
9025,The role of viruses in the etiology and pathogenesis of common cold,"Numerous viruses are able to cause respiratory tract infections. With the availability of new molecular techniques, the number of pathogens detected in specimens from the human respiratory tract has increased. Some of these viral infections have the potential to lead to severe systemic disease. Other viruses are limited to playing a role in the pathogenesis of the common cold syndrome. This chapter focuses on the viral pathogens that are linked to common cold. It is not the intention to comprehensively review all the viruses that are able to cause respiratory tract infections—this would go beyond the scope of this book. The list of viruses that are briefly reviewed here includes rhinoviruses, respiratory syncytial virus, parainfluenza virus, adenovirus, metapneumovirus and coronavirus. Bocavirus is discussed as one example of a newly identified pathogen with a less established role in the etiology and pathogenesis of common cold. Influenza virus does not cause what is defined as common cold. However, influenza viruses are associated with respiratory disease and the clinical picture of mild influenza and common cold frequently overlaps. Therefore, influenza virus has been included in this chapter. It is important to note that a number of viruses are frequently co-detected with other viruses in humans with respiratory diseases. Therefore, the viral etiology and the role of viruses in the pathogenesis of common cold is complex, and numberous questions remain to be answered."
9026,Chirurgische Infektionen,"Der menschliche Organismus ist von einer unzähligen Menge von Mikroorganismen umgeben. Dringen diese Krankheitserreger in uns ein, dann laufen Wechselbeziehungen zwischen dem Eindringling und dem Wirtsorganismus ab. Krankheit resultiert, wenn die Mikroorganismen aufgrund ihrer verschiedenen Determinanten der Pathogenität und Virulenz den Wettlauf mit der Infektabwehr des Makroorganismus gewonnen haben. Mit diesem Problem hatten sich Chirurgen zu allen Zeiten auseinanderzusetzen und es hat bis heute nicht an Aktualität verloren."
9027,Anti-angiogenic Targets: Angiopoietin and Angiopoietin Receptors,"Tumor blood vessel formation (angiogenesis) is essential for tumor growth and metastasis. Two main endothelial ligand–receptor pathways regulating angiogenesis are vascular endothelial growth factor (VEGF) receptor and angiopoietin-TIE receptor pathways. The angiopoietin-TIE pathway is required for the remodeling and maturation of the blood and lymphatic vessels during embryonic development after VEGF and VEGF-C mediated development of the primary vascular plexus. Angiopoietin-1 (ANGPT1) stabilizes the vasculature after angiogenic processes, via tyrosine kinase with immunoglobulin-like and EGF-like domains 2 (TIE2) activation. In contrast, ANGPT2 is upregulated at sites of vascular remodeling. ANGPT2 is secreted by activated endothelial cells in inflammation, promoting vascular destabilization. ANGPT2 has been found to be expressed in many human cancers. Intriguingly, in preclinical models inhibition of ANGPT2 has provided promising results in preventing tumor angiogenesis, tumor growth, and metastasis, making it an attractive candidate to target in tumors. However, until now the first ANGPT2 targeting therapies have been less effective in clinical trials than in experimental models. Additionally, in preclinical models combined therapy against ANGPT2 and VEGF or immune checkpoint inhibitors has been superior to monotherapies, and these pathways are also targeted in early clinical trials. In order to improve current anti-angiogenic therapies and successfully exploit ANGPT2 as a target for cancer treatment, the biology of the angiopoietin-TIE pathway needs to be profoundly clarified."
9028,Nanomaterial-Based Antibacterial Paper,"Antibacterial materials are widely used in everyday life and plays important roles in the public health system. There are a wide range of materials that have been known to prevent attachment and proliferation of microbes on material surfaces. These include antibiotics, metal ions and quaternary ammonium compounds. Given the availability of these various antibacterial materials, concerns about antibiotics-resistance, environmental pollution, relatively complex processing and high cost have been of much recent interest. Antimicrobial properties of nanomaterials have been explored to meet these challenges. Various nanomaterials including silver nanoparticles (AgNPs), titanium oxide nanoparticles and carbon nanotubes (CNTs) have been found to be highly effective bacterial-killing materials. The most well-known examples are silver and silver-based compounds, which were well known to be antiseptic to a spectrum of bacterium even in ancient times. AgNPs have proven to possess high antibacterial activity with minimal perturbation to human cells. Consequently, widespread applications of AgNPs have been found in medical and environmental areas [1]. More recently, carbon nanomaterials have emerged as a type of novel antibacterial nanomaterials, including CNTs and graphene. In this chapter, we aim to provide a review on the fabrication of nanomaterials-based paper-like films and their antibacterial applications."
9029,Disease Spreading in Time-Evolving Networked Communities,"Human communities are organized in complex webs of contacts that may be represented by a graph or network. In this graph, vertices identify individuals and edges establish the existence of some type of relations between them. In real communities, the possible edges may be active or not for variable periods of time. These so-called temporal networks typically result from an endogenous social dynamics, usually coupled to the process under study taking place in the community. For instance, disease spreading may be affected by local information that makes individuals aware of the health status of their social contacts, allowing them to reconsider maintaining or not their social contacts. Here we investigate the impact of such a dynamical network structure on disease dynamics, where infection occurs along the edges of the network. To this end, we define an endogenous network dynamics coupled with disease spreading. We show that the effective infectiousness of a disease taking place along the edges of this temporal network depends on the population size, the number of infected individuals in the population and the capacity of healthy individuals to sever contacts with the infected, ultimately dictated by availability of information regarding each individual’s health status. Importantly, we also show how dynamical networks strongly decrease the average time required to eradicate a disease."
9030,Applications,"The ability of materials to dramatically change their properties at nanoscale has opened up the possibility of making new devices, instruments and consumer goods to function in a much better way than was possible earlier. We have seen in Chaps. 10.1007/978-3-319-09171-6_10 and 10.1007/978-3-319-09171-6_11 that nanomaterials have enabled us to design new products which were not possible using bulk materials. Rapid progress in the synthesis and understanding of nanomaterials in just a few years has led them to enter the world market in a big way. Figure 12.1 shows an overview of various fields in which nanomaterials have entered or are about to enter. In this chapter we shall briefly discuss some of these applications."
9031,Pandemic Influenza: A Comparative Ethical Approach,"Community-networks such as families and schools may foster and propagate some types of public health disasters. For such disasters, a communitarian-oriented ethical lens offers useful perspectives into the underlying relational nexus that favors the spread of infection. This chapter compares two traditional bioethical lenses—the communitarian and care ethics framework—vis-à-vis their capacities to engage the moral quandaries elicited by pandemic influenza. It argues that these quandaries preclude the analytical lens of ethical prisms that are individual-oriented but warrant a people-oriented approach. Adopting this dual approach offers both a contrastive and a complementary way of rethinking the underlying socioethical tensions elicited by pandemic influenza in particular and other public health disasters generally."
9032,Software Support for Common Criteria Security Development Process on the Example of a Data Diode,"The data diodes are very often used to protect users’ networks and sensitive data and that is why additional assurance of those devices is demanded. This assurance can be obtained by applying the Common Criteria security development process. The process is very difficult and time-consuming specially for those not familiar with the standard. Although there are many guidelines and templates telling how to define the security problem still there is a lack of computer aiding tools. This paper describes the plug-in application which supports identification of protected assets, threats, security objectives and security functions – the main elements of security specification. The tool facilitates and speeds up the security development process of IT products."
9033,Extracorporeal Membrane Oxygenation (ECMO)/Extracorporeal Carbon Dioxide Removal (ECCO(2)R),"Extracorporeal membrane oxygenation (ECMO) is a means of supporting severe pulmonary and cardiac dysfunction. It stabilizes critical derangements of oxygenation and ventilation, allowing time to diagnose, treat, and recover from the underlying cause of organ failure. The extracorporeal circuit has three main components: large-bore cannulae and circuit tubing to provide access to the native circulation, an artificial membrane lung to provide gas exchange, and an active pump to facilitate perfusion. Multiple clinical studies have evaluated this technology, the strongest evidence to date supporting its use being the Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial, which showed survival advantage when patients were treated with a protocol that included ECMO. Extracorporeal carbon dioxide removal (ECCO(2)R) is similar in concept to ECMO, but has a lower flow rate and does not significantly oxygenate the patient. It is a primary treatment for hypercarbic respiratory failure or is an adjunct to reduce potentially injurious levels of mechanical ventilator support in hypoxemic respiratory failure. Complications are common occurrences on both types of therapy. Strong institutional commitment and a team approach are critical to successful implementation. Additional randomized trials are needed to clarify the appropriate indications and best practices for these lifesaving therapies."
9034,"Respiratory Filters and Ventilator-Associated Pneumonia: Composition, Efficacy Tests and Advantages and Disadvantages","Respiratory filters are devices with a high capacity to prevent the passage of microorganisms. The use of respiratory filters interposed in respiratory circuits to avoid ventilator-associated pneumonia (VAP) was proposed after reports between 1952 and 1972 of several outbreaks of respiratory infections attributed to contamination of anesthesia machines; however, none of the reports presented a bacteriological demonstration of a cause-and-effect relationship. The use of respiratory filters has not decreased the incidence of VAP in patients on anesthesia machines and in critically ill patients. Besides, respiratory filters could have some undesirable effects such as the increase of resistance to inspiratory airflow, increase of resistance to expiratory airflow and increase of dead space in the breathing circuit. Thus, the use of respiratory filters is not routinely necessary; however, they should be used in patients with suspected or confirmed highly communicable respiratory infections (such as bacillary pulmonary tuberculosis) and who require mechanical ventilation)."
9035,Transfusion of Blood and Blood Products,"In transfusion medicine, several blood products can be prepared and used as replacement therapy; however, four of these products are more commonly used in general practice: RBCs, fresh frozen plasma (FFP), platelets and cryoprecipitate. RBC transfusions are mainly administered to improve tissue oxygenation in cases of anaemia or acute blood loss due to trauma or surgery. FFP, platelets and cryoprecipitate are used for the prevention and treatment of bleeding."
9036,“Can’t Stop Coughing (But I Need to Get Back to the Shelter by 6)”,"In this chapter, we will explore a case involving an outbreak of tuberculosis that occurred among men living in a homeless shelter. The case delves into both the public health challenges involved in investigating a disease outbreak in a vulnerable population and the delicate balance of protecting individuals’ autonomy and confidentiality while protecting the public’s health. By the conclusion of the case, learners will be able to apply the socioecological model to tuberculosis, analyze an outbreak of disease using epidemiologic tools, and identify conflicts in balancing autonomy and justice while managing potential public health threats."
9037,Diagnosis of Pulmonary Parasitic Diseases,"The protozoal and helminthic parasites that traverse the respiratory tract during their life cycles can cause lung diseases, though the most common habitats of these parasites are the gastrointestinal tract and the blood or lymphatic circulations. These diseases are commonly encountered in the tropical regions of the world. However, parasitic lung diseases are increasingly being reported from other parts of the world due to an increase in the occurrence of immunosuppression (acquired immunodeficiency syndrome, organ transplantations, the use of immunosuppressive drugs) and transcontinental travel. The lung diseases that may result from these infections range from asymptomatic phase to life-threatening acute respiratory distress syndrome. These diseases can also mimic common respiratory diseases such as bacterial pneumonias, pulmonary tuberculosis, lung cancer, bronchial asthma, interstitial lung disease, and pulmonary hypertension. The diagnosis of parasitic lung diseases is a challenge to physicians, if they are not aware of the entity or these diseases are not investigated properly. The diagnosis of these diseases is based on the identification of the causative organism in the stool, sputum, other body fluids, or tissue specimens. Radiological imaging studies of the thorax including chest radiographs, high-resolution computerized tomograms, and ultrasonograms may aid in the diagnosis. In certain situations, invasive investigations such as fiberoptic bronchoscopic evaluation (transbronchial lung biopsies and bronchoalveolar lavage studies) and thoracic surgical procedures (thoracoscopy and open lung biopsy) may be required for a diagnosis and also to exclude other lung diseases. Serologic and molecular diagnostic methods are being developed for accurate diagnosis of the parasitic diseases."
9038,"Extraglandular Manifestations of Sjögren’s Syndrome (SS): Dermatologic, Arthritic, Endocrine, Pulmonary, Cardiovascular, Gastroenterology, Renal, Urology, and Gynecologic Manifestations","Primary Sjögren’s syndrome (1° SS) is an autoimmune disorder characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth due to lymphocytic infiltrates of lacrimal and salivary glands. However, SS also affects many extraglandular systems. In SS patients, the pattern of extraglandular manifestations may have a close similarity with the vasculitic features seen in SLE patients that are mediated by immune complexes and complement. However, SS patients also have an increased frequency of lymphocytic infiltration into extraglandular tissues, as might be expected by their increased frequency of lymphoma in comparison to SLE patients. For example, SS patients need to be evaluated for interstitial nephritis (in contrast to the glomerulonephritis of SLE) or interstitial pneumonitis (in comparison to pleurisy of SLE). This chapter will focus on the clinical extraglandular manifestations of primary SS that are not specifically covered in other chapters. These extraglandular manifestations have led to a recently introduced “disease activity” and “organ damage index.” The recognition of these extraglandular manifestations is important since they have prognostic and therapeutic implications. The differential diagnosis of these extraglandular manifestations includes overlapping features with other autoimmune diseases (particularly systemic lupus erythematosus (SLE), scleroderma, dermatomyositis, celiac sprue, and small- and medium-sized vessel vasculitis), infectious diseases that mimic autoimmune disease (particularly hepatitis C, HIV, syphilis, tuberculosis), and predisposition to drug toxicities that may involve extraglandular organs (particularly skin rashes, nephritis, pneumonitis, myositis, and hematopoietic abnormalities)."
9039,Sicherheitspolitische Bedrohungen und Risiken und das „geltende“ Recht in der 2. Hälfte des 2. Jahrzehnts des 21. Jahrhunderts unter besonderer Berücksichtigung der Sicherstellungs- und Vorsorgegesetze. Sicherheitspolitik in Zeiten der Uneindeutigkeit,"Das Grundgesetz (GG) kennt klare Regelungen zum Spannungs- und Verteidigungsfall, vgl. nur Art. 80a, 115a Abs. 1 GG. Diese Bestimmungen wurden unter den Bedrohungslagen des Kalten Krieges und seiner gefährlichsten Tage in der Kuba- Krise in einer Notstandsverfassung zusammengefasst, bei einer großen Wintex-Übung im Ausweichsitz der Verfassungsorgane in Mariental erprobt und von der ersten großen Koalition „verabschiedet“ (1966–1969, Kabinett Kiesinger/Brandt). Veränderungen folgten."
9040,Akute Störungen der Atmung: spezielle Krankheitsbilder,"Postoperative respiratorische Insuffizienz, Rippenserienfrakturen, Lungenkontusion, akutes Lungenversagen, pulmonale Aspiration von Magensaft, Pneumonie und akut dekompensierte COPD gehören zu den häufigsten Erkrankungen, die eine intensivmedizinische Behandlung mit apparativer Unterstützung der Atmung erfordern. Bei schwersten Formen – v. a. bei ARDS – ist ein erheblicher apparativer und personeller Aufwand erforderlich, nicht selten trotz aller Maßnahmen mit tödlichem Ausgang."
9041,Volume 4 Isolated Compounds (N-S),
9042,Life Cycle and Life History Strategies of Parasitic Crustacea,"Different parasitic life strategies are described including four new life cycles: complex rebrooding, micro-male, mesoparasite and prey-predator transfer. Four new life cycle behaviours are named: nursery hiding, mid-moult stage, positive precursor (intraspecific antagonism) and negative precursor (ambush strategy). Further strategies discussed are opossum attack, double parasitism (doubling of the normal reproductive set), duplex arrangement (separated male-female pairs), simple rebrooding, and describing how displaced parasites and superinfections may partly elucidate life cycles. Proportional stunting masks life history effects of parasitism; cuckoo copepods are true parasites and not just associates; burrowing barnacles (acrothoracicans) are not parasites. Further findings based on life cycle information: branchiurans and pentastomes are possibly not related; firefly seed shrimp are not parasites; copepod pre-adult life cycle stages are common in the western pacific but rare in Caribbean; harpacticoids on vertebrates are not parasites; cuckoo copepods are true parasites; explained the importance of pennellid intermediate hosts. Crustacean parasite life cycles are largely unknown (1% of species). Most crustacean life cycles represent minor modifications from the ancestral free-living mode. Crustacean parasites have less complex and less modified life cycles than other major parasite groups. This limits their exploitation of, and effectiveness, in parasitism. However, these life cycles will be an advantage in Global Change. Most metazoan parasites will be eliminated while crustaceans (and nematodes) will inherit the new world of parasites."
9043,The Way Forward: The Power of Diversity,"This chapter wraps up the discussion of all chapters by incorporating perspectives of JICA practitioners. We can advance the human security practice in the three dimensions: national, regional, and global. In the national dimension, capacity development and empowerment will play a key role. In the regional dimension, the diversity of “ASEAN Plus Three” can be the source of dynamic community formation in East Asia. In the global dimension, human security can effectively supplement the Sustainable Development Goals (SDGs) by means of its emphasis on risks and vulnerability. Finally, the entanglement of human security and responsibility to protest (R2P) is discussed. Making much of national ownership and dignity, human security is expected to reinforce its influence in East Asia and worldwide."
9044,Emerging Diseases from Animals,"December 2013, an outbreak of the deadly Ebola virus began in a small village in southern Guinea, the first outbreak of the Zaire Ebola strain in West Africa. Within a year’s time, the outbreak, which was not officially noticed by health authorities until March 2014, had led to approximately 18,000 known human cases and 6,300 deaths, posing an unprecedented challenge to global public health. Air travel helped the disease leap from West Africa to other continents, including North America and Europe."
9045,Inpatient Medicine,"This chapter covers all aspects of inpatient care including emergency room evaluation, ongoing care in a standard medical unit, and care of the patient in the intensive care unit. The format consists of clinical vignettes with questions pertaining to diagnosis and treatments. There is an emphasis on actual complex cases and practical solutions supported by current evidence. Psychiatry, Neurology, General Internal Medicine, and its subspecialties are reviewed in this section."
9046,Platforms for Plant-Based Protein Production,"Plant molecular farming depends on a diversity of plant systems for production of useful recombinant proteins. These proteins include protein biopolymers, industrial proteins and enzymes, and therapeutic proteins. Plant production systems include microalgae, cells, hairy roots, moss, and whole plants with both stable and transient expression. Production processes involve a narrowing diversity of bioreactors for cell, hairy root, microalgae, and moss cultivation. For whole plants, both field and automated greenhouse cultivation methods are used with products expressed and produced either in leaves or seeds. Many successful expression systems now exist for a variety of different products with a list of increasingly successful commercialized products. This chapter provides an overview and examples of the current state of plant-based production systems for different types of recombinant proteins."
9047,Biomolecular Structure and Modeling: Problem and Application Perspective,"The experimental progress described in the previous chapter has been accompanied by an increasing desire to relate the complex three-dimensional (3D) shapes of biomolecules to their biological functions and interactions with other molecular systems. Structural biology, computational biology, genomics, proteomics, bioinformatics, chemoinformatics, and others are natural partner disciplines in such endeavors."
9048,Introduction to In Vitro Diagnostic Devices,"Healthcare investment keeps on increasing substantially in recent years. Such investment has also focused on fighting major diseases, enabled by the novel invention of cost-effective and valid drug development for treatment and side effect reduction, along with improved vector control. In addition, the demand for diagnostics that is essential in determining prognosis, identifying disease stages, monitoring treatment, and assessing the spreading as health services has expanded. Molecular-based diagnostics is critical for prevention, identification, and treatment of disease. Current laboratory analyses support correct diagnosis in over 70 % of all diseases and can be used to aid the continuous monitoring of drug therapy. However, classic diagnostic technologies are not completely well suited to meeting the expanded testing requirement because they rely on complicated sample purification and sophisticated instruments which are labor-intensive, timely, and expensive and require well-trained operators. One of the main challenges for industry is to develop fast, relatively accurate, easy-to-use, and inexpensive devices. In addition to the improved efficiency in laboratory diagnostics, there has been a trend toward a more decentralized diagnostics which occurs directly at patients’ bedside, in outpatient clinics, or at the sites of accidents, so-called point-of-care (POC) systems. The concept of POC testing is mainly for the patient, so short turnaround time, minimum sample preparation, reagent storage and transferring, user-friendly analytical instruments, and digital or visible quantitative or semiquantitative single readout are required. POC test is a great option of potential in vitro diagnostics (IVD) for resource-limited settings. It is clear that on-site or minimum sample preparation and on-chip storage limit the delays that caused by transport and preparation of clinical samples. Shorter turnaround time leads to rapid clinical decision-making and may save fatal consequences. No previous knowledge in sample analysis should be required, so elders can perform the tests at home with minimum training to improve health outcome. Lateral-flow immunoassay (LFIA) devices, for example, which were originally proposed in the 1980s, remain popular largely because of their design simplicity. The purpose of this article is to introduce readers with basic information regarding the LFIA approach that we think the most representative product of IVD test for solving global health issues."
9049,Alveolar Pattern,"An alveolar pattern is defined by the existence of more or less broad portions of the lung more opaque than normal due to partial or complete alveolar filling. With a few exceptions, the pulmonary architecture is overall preserved, and, if signs of interstitial involvement are present, they are not prevalent. On HRCT the different opacity of the alveolar pattern reminds the variable density of the clouds."
9050,Expression and Functions of SARS Coronavirus Replicative Proteins,"The discovery of a previously unknown coronavirus as the causative agent of the SARS epidemic in 2002/2003 stimulated a large number of studies into the molecular biology of SARS coronavirus (SARS-CoV) and related viruses. This research has provided significant new insight into the functions and activities of the coronavirus replicase–transcriptase complex, a multiprotein complex that directs coordinated processes of both continuous and discontinuous RNA synthesis to replicate and transcribe the large coronavirus genome, a single-stranded, positive-sense RNA of ~30 kb. In this chapter, we review our current understanding of the expression and functions of key replicative enzymes, such as RNA polymerases, helicase, ribonucleases, ribose-2′-O-methyltransferase and other replicase gene-encoded proteins involved in genome expression, virus–host interactions and other processes. Collectively, these recent studies reveal fascinating details of an enzymatic machinery that, in the RNA virus world, is unparalleled in terms of the number and nature of virally encoded activities involved in virus replication and host interactions."
9051,Etiology of the common cold: Modulating factors,"The development of a “cold-like illness” (CLI) usually requires infection with an upper respiratory virus such as rhinovirus, influenza virus, respiratory syncytial virus, parainfuluenza virus, coronavirus or adenovirus, among others, and the development of sufficient signs, symptoms and pathophysiologies to qualify as being ill based on personal and cultural definitions. A viral upper respiratory tract infection (vURTI) in the absence of overt illness (subclinical vURTI) will not be made manifest to the individual or to observers and, therefore, will not be diagnosed as a CLI. The degree of illness occurring during a vURTI is directly related to the extent of provoked inflammation, which in turn depends on the engagement of antiviral defense systems. Thus, risk factors for CLI can modulate either the vURTI risk by affecting virus exposure and/or susceptibility to infection, or the CLI risk given a vURTI by affecting immunocompetence, the provoked inflammation and/or the interpretation of ilness as a CLI. In this chapter, we review published studies for evidence of CLI risk-modulating factors and report that climate, crowding and perhaps female gender can affect the probability of exposure to vURTI viruses, that extant immunological factors and age can affect the probability of virus infection given exposure, that stress levels (moderated by social environment), health practices (exercise, tobacco and alcohol consumption, sleep efficiency) and genetics contribute to CLI risk most probably by modulating the immune-inflammatory response to infection, and that other factors such as pollution, home environment and certain personality traits affect CLI risk by biasing illness interpretation for a given set of symptoms and signs."
9052,Nephrologie,
9053,Synthesis and Antimicrobial Activity of Copper Nanomaterials,"Bioactive copper nanomaterials are an emerging class of nano-antimicrobials providing complimentary effects and characteristics, as compared to other nano-sized metals, such as silver or zinc oxide nanoparticles. In this chapter, copper nano-antimicrobials are reviewed and classified firstly as a function of the preparation methods, and secondly as a function of the target microorganism used for testing their antimicrobial activity. The antimicrobial activity of copper-based nanostructures depends on the microbial species and on the experimental set-up. As a consequence, in this chapter details are provided on methods, as well as on experimental details such as contact time, microorganism strain, concentration of the interacting species, etc. Finally, real-life applications of copper-based nanoantimicrobials are briefly discussed."
9054,Entzündliche Erkrankungen,"Meningitiden zeigen die Trias Kopfschmerz, Meningismus und Fieber mit positiven Dehnungszeichen. Bei Kindern sind gramnegative Enterokeime und Hämophilus, bei Erwachsenen Meningo- und Pneumokokken wichtigste Erreger der bakteriellen Meningitis. Entscheidend für die Diagnose ist die Liquordiagnostik mit Gramfärbung. Empirisch werden ein Cephalosporin der dritten Generation und Ampicillin eingesetzt. Der Hirnabszess entsteht hämatogen oder fortgeleitet und zeigt sich in der CT oder MRT mit ringförmigem Enhancement. Wichtige Erreger sind Streptokokken, Bacteroides und andere Anaerobier, Enterobakterien und Staphylokokken. Enzephalitiden führen zu Bewusstseinsstörung, fokalen Symptomen und epileptischen Anfällen, wichtigster Erreger ist Herpes simplex. Diagnose mittels Liquor (PCR), EEG, CT und MRT (ab dem 2. Tag), Therapie mit Aciclovir parenteral bereits bei begründetem Verdacht."
9055,Hospital Systems Management,"All concepts of hospitals systems including professional standards, ethics, quality improvement, and resource utilization are covered in this chapter. The structure of successful hospitalist programs is used as a template. Then tools utilized for quality improvement, which have been adopted from other industries, are discussed as well. The transition to post-acute care and the complications encountered are examined in this chapter."
9056,Variation in Active Site Amino Residues of H1N1 Swine Flu Neuraminidase,"In this paper, we report the variations of amino acid residues between H5N1 and H1N1 swine flu neuraminidase sequences at protein level. Random search in NCBI Flu database resulted in Canadian viral gene and analysis using blast technique revealed sites that are variant among sequences for which 3-dimensional structures were known. PDB summary database and multiple alignments were employed for validation of the results. Based on the mutations observed within active site region, homology derived model was constructed using swiss-pdb viewer. The residue variation observed was with respect to Tyr347 in H5N1 versus Asn344 in H1N1 neuraminidase sequence, which resulted in geometrical modification of ligand binding domain."
9057,Reverse Pharmacology and Drug Discovery: Artemisia annua and Its Anti-HIV Activity,"There are various ways in which new drugs can be developed. One approach is in silico drug design based on our existing knowledge of the biology of a specific disease and the specific target site binding chemistry. Based on this knowledge, a range of molecules will be designed and synthesised after which they will be tested in in vitro bioassays for activity and toxicity. The best candidates, called lead compounds, will then be “fine-tuned” by chemical derivatisation in order to improve their activity and/or to reduce their toxicity. Lead compounds are then tested in various animal models before entering clinical trials in people. Another approach is to screen a large number of biological samples (plants, bacteria and fungi) for activity against a specific disease. Any active extract, consisting of many compounds, will be fractionated by chromatographic techniques, and each fraction will be tested for in vitro activity. Active fractions will again be fractionated until the active compound is identified. This process, also called bioguided fractionation, can go through a number of fractionation cycles before the active compound is identified. The active compound will be chemically derivatised in order to improve its properties before in vivo animal studies will be conducted. Based on these test results, the most promising lead compounds will then be tested in clinical trials in people. There are however a number of shortcomings with both approaches. It is expensive, time consuming, makes use of in vitro bioassays and it suffers from a very low success rate. Due to these shortcomings, it is currently estimated that the development of one new drug costs around $1–1.5 billion, simply because so many lead compounds fail during clinical trials. Keeping these high costs in mind, one would think that all registered drugs are effective and importantly non-toxic. Unfortunately, this is not the case, as there are a number of drugs currently on the market that are causing severe side effects and whose efficacy should be questioned. This holds true particularly for cancer chemotherapeutics. It was estimated that cancer chemotherapy improves the average 5-year survival rate of patients (for all cancer types) by only 2 % (Morgan et al. 2004). Another relatively unknown fact is that each year, 200,000 people die in the EU due to adverse drug reactions (all types of drugs), highlighting the severe shortcomings of the drug development and drug licensing pipelines (Archibald and Coleman 2012). To put this into perspective, there are a large number of drugs that work perfectly well and are safe to use, but we have to concede that our approach to drug discovery and our overall approach to health care suffers from some major problems."
9058,"Responses of Tropical Bats to Habitat Fragmentation, Logging, and Deforestation","Land-use change is a key driver of the global biodiversity crisis and a particularly serious threat to tropical biodiversity. Throughout the tropics, the staggering pace of deforestation, logging, and conversion of forested habitat to other land uses has created highly fragmented landscapes that are increasingly dominated by human-modified habitats and degraded forests. In this chapter, we review the responses of tropical bats to a range of land-use change scenarios, focusing on the effects of habitat fragmentation, logging, and conversion of tropical forest to various forms of agricultural production. Recent landscape-scale studies have considerably advanced our understanding of how tropical bats respond to habitat fragmentation and disturbance at the population, ensemble, and assemblage level. This research emphasizes that responses of bats are often species and ensemble specific, sensitive to spatial scale, and strongly molded by the characteristics of the prevailing landscape matrix. Nonetheless, substantial knowledge gaps exist concerning other types of response by bats. Few studies have assessed responses at the genetic, behavioral, or physiological level, with regard to disease prevalence, or the extent to which human disturbance erodes the capacity of tropical bats to provide key ecosystem services. A strong geographic bias, with Asia and, most notably, Africa, being strongly understudied, precludes a comprehensive understanding of the effects of fragmentation and disturbance on tropical bats. We strongly encourage increased research in the Paleotropics and emphasize the need for long-term studies, approaches designed to integrate multiple scales, and answering questions that are key to conserving tropical bats in an era of environmental change and dominance of modified habitats (i.e., the Anthropocene)."
9059,Konstruktion von Zukunftsängsten über dystopische Filme – Vier Rahmungen (Settings),"Die Entscheidung, die filmischen Imaginationen von zukünftigen gesellschaftlichen Bedrohungen in ihrer vollen Breite in den Blick zu nehmen, um dann spezielle Filme tiefergehend zu betrachten, hatte zur Konsequenz, dass aufgrund des umfangreichen Datenmaterials ein vorstrukturierender Analyseschritt zwingend notwendig war. Aus der qualitativen Inhaltsanalyse und den Grobsichtungen der Filme ergaben sich vier übergeordnete Rahmungen – vier fi lmische Settingtypen –, von denen sich wiederum drei in Untertypen gliedern, die zunächst im Gesamten vorgestellt werden und denen anschließend eigene ausführliche Kapitel gewidmet sind."
9060,Glycyrrhiza glabra: Chemistry and Pharmacological Activity,"Nature is an attractive source of new therapeutic candidate compounds as a tremendous chemical diversity is found in millions of species of plants, animals, marine organisms, and microorganisms as potential medicinal agents. This chapter of research is an effort to highlight the phytochemical/chemical constituents of an ancient medicinal plant G. glabra and their pharmacological importance. G. glabra is an old age medicinal plant that belongs to Leguminosae/Fabaceae/Papilionaceae family and commonly known as mulaithi in north India. The chemical composition of G. glabra is glycyrrhizin, glycyrrhetic acid, isoliquiritin, isoflavones, etc., and their derivatives have been reported for several pharmacological activities like, expectorant, antidemulcent, antiulcer, anticancer, anti-inflammatory, antidiabetic, etc. These phytochemicals hold strong promise for designing new herbal drugs, and derivatives of these compounds are being generated to evaluate their pharmacological purposes for future drug use. Natural products have been a prime source for the treatment of many forms of ailments, many of which are consumed daily with the diet. They provide significant protection against various diseases and disorders."
9061,"Uncharakteristisches Fieber (UF), afebrile Allgemeinreaktion (AFAR), Luftwegekatarrhe, Tonsillitis","In diesem Kapitel werden jene Fälle behandelt, die diagnostisch und therapeutisch eng zusammengehören und die sich durch ihre überragende Häufigkeit auszeichnen."
9062,Infektiologie,"—. akute oder chronische Entzündung des Alveolarraumes und/oder des Interstitiums der Lunge; —. häufigste infektionsbedingte Todesursache; —. Einteilung der Pneumonien nach Pathologie (lobär, interstitiell), Åtiologie (bakteriell, viral, mykotisch, parasitär, physikalisch- oder chemischtoxisch, allergisch) und Klinik (typisch, atypisch) möglich; —. : —. : • bei Neugeborenen/Säuglingen Pneumokokken, Haemophilus influenzae, Staphylococcus aureus, Chlamydia pneumoniae, Mycoplasma pneumoniae, Respiratory-syncytial-Viren; • im Erwachsenenalter zusätzlich Legionellen, Influenza-Virus, Parainfluenza-Virus, Adeno-Virus, Corona-Viren, z. B. SARS („severe acute respiratory syndrome“); bei älteren Patienten vermehrt gramnegative Erreger (Klebsiellen, Enterobacter, Escherichia coli); —. : • bis zum 5. Tag der Hospitalisierung Keimspektrum der ambulant erworbenen Pneumonien; • nach dem 5. Tag der Hospitalisierung gehäuft Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiellen, Enterobacter, Escherichia coli; • nach Aspiration Anaerobierinfektionen; • Problemkeime, z. B. methicillinresistenter Staphylococcus aureus (MRSA), penicillinresistente Pneumokokken, vancomycinresistente Enterokokken, ESBL („extended spectrum beta-lactamase“)-Bildner; —. bei Immunsuppression Pneumocystis jirovecii, Zytomegalie-, Herpessimplex-, Varizella-Zoster-Virus, Mycobacterium tuberculosis, atypische Mykobakterien (M. avium, M. intracellulare, M. xenopi u. a.), Pilze; —. : —. Anschoppung am 1. Tag (Hyperämie und alveoläres Ödem); —. rote Hepatisation am 2./3. Tag (Konsolidierung durch alveoläre Infiltration mit Erythrozyten und durch fibrinreiches Exsudat); —. gelbe Hepatisation am 4.–8. Tag (Leukozyten-/Makrophageninfiltration); —. Lyse nach dem 8. Tag (enzymatische Auflösung und Resorption des Exsudats); —. bei fehlender Lyse chronisch karnifizierende Pneumonie durch Granulationsgewebe; —. bei Lobulärpneumonie „buntes Bild“ (alle Stadien der Lobärpneumonie) mit initial einzelnen, verstreuten alveolär-pneumonischen Herden, die im Verlauf konfluieren; —. bei interstitieller Pneumonie interlobuläre, peribronchioläre und selten alveoläre Formen;"
9063,Infections,"Lower respiratory tract infection is a very common illness in children and is a significant cause of morbidity and mortality. Clinical signs and symptoms are nonspecific especially in infants and younger children and some even present with nonrespiratory complaints. Infectious agents causing pneumonia is not limited to viruses and bacteria, but it could also be due to Mycoplasma, Mycobacteria, fungi, protozoa, and parasites. Coinfection with two or more microbial agents can also occur. The etiologic agent of lower respiratory infection in a child is often difficult to obtain, but the patient’s age can help narrow the possible cause. Microbiological tests are important but could be difficult to obtain especially in younger children. Various medical imaging modalities not only play an important role as an aid in diagnosis but can also help during and after therapy. Imaging can also help evaluate complications to pneumonia and exclude other causes of respiratory distress including underlying developmental anomalies, foreign body, gastroesophageal reflux disease, and aspiration. In this chapter, the imaging modalities utilized in the detection of pulmonary infections will be discussed. The spectrum of typical imaging findings for various etiologic agents in both immunocompetent and immunocompromised children will be presented."
9064,Laboratory Surveillance of Hospital-acquired Infection Rates of Respiratory Viruses in a Tertiary Care Hospital from 2012 to 2014,
9065,CYBER NEWS,
9066,What's coming in Annals January 2004,
9067,Safe zone in isolation rooms,
9068,Frederick Chapman Robbins,
9069,The Twenty-Second International Conference on Antiviral Research,
9070,The Twenty-First International Conference on Antiviral Research,
9071,New CHEs – Nouveaux titulaires CHE,
9072,Reversible splenial lesion syndrome: A differential diagnosis of corpus callosum lesions,
9073,Beyond our pages(),
9074,VIRUS-INDUCED WHEEZING IN CHILDREN: Respiratory Syncytial Virus (RSV) and Rhinovirus,"The strong association between infantile wheezing and respiratory tract infections caused by the respiratory syncytial virus (RSV) has been well established. In studies of older children, rhinovirus becomes the major virus associated with asthma. These relationships are outlined in the box on page 36. In the past, this relationship was more difficult to appreciate, because rhinovirus does not always grow well in culture. In addition, the linkage between asthma and atopy during childhood has raised the question whether viral infections alone can precipitate exacerbations of asthma. Use of the polymerase chain reaction (PCR) to measure viral nucleic acid material has provided the opportunity to study virus-induced wheezing among children in greater detail, and investigations of experimental rhinovirus infections in adults have demonstrated how this virus can augment both the early and late phase manifestations of airway hyperreactivity. This article reviews recent advances that have enhanced our understanding of virus-induced wheezing, along with new information indicating that interactions between viral infections and allergic inflammation may be critical to the pathogenesis of acute symptoms."
9075,NOVEL THERAPEUTIC APPROACHES FOR ALLERGIC RHINITIS,"The last 2 decades have witnessed enormous changes in our understanding of allergic rhinitis. As we have begun to unravel the complex underlying immunologic and inflammatory pathophysiology of the disease, new therapeutic strategies as well as specific molecular and cellular constituents have emerged as potential targets for clinical intervention. These efforts also have shed light on the mechanisms by which current antiallergy medications act—or sometimes fail to be effective.7, 31, 51, 89 The similar pathophysiologic basis for allergic rhinitis and the often comorbid condition, asthma, was underscored in the recently published American Thoracic Society Workshop Summary on the Immunobiology of Asthma and Rhinitis: Pathogenic Factors and Therapeutic Options.(18) In his conclusion, workshop chair, Thomas Casale,(18) counsels readers to consider that “…allergic asthma and rhinitis represent a systemic disease affecting two organs, the lung and the nose. Asthma and allergic rhinitis share many of the same pathogenic factors, but they operate in different parts of the airway. Inflammatory cells and mediators are often the same, and there may be common alterations that occur in the immune system.” Thus, therapeutic strategies and potential therapeutic agents found to be beneficial in the treatment of one airway target may show similar effects in the other. For this reason, and because many of the therapies now being developed are at early stages in their evolution, physicians interested in rhinitis therapy also must examine what is known about these agents in asthma. One avenue of active research has been the role of leukotrienes and other mediators in the pathophysiology of asthma and rhinitis. Three leukotriene modifiers now have been approved for the treatment of asthma in the United States; their potential use in the treatment of rhinitis has been a focus of considerable speculation and investigation. An early “day in the park” study showed that with antileukotriene therapy, patients with rhinitis had demonstrable improvements in their rhinitic symptoms.(29) Roquet et al(83) reported that in the treatment of asthma, there was a synergistic effect when an antileukotriene agent and an antihistamine were used, compared with either drug alone. A product combining an antileukotriene with an antihistamine is currently under development. The most exciting developments, however, may be in the immunology arena. As described by Baraniuk elsewhere in this issue, the pathophysiology of allergic rhinitis is highly complex. Multiple interacting, interdependent, and redundant pathways and molecular and cellular constituents are involved in the pathogenesis of allergic rhinitis. Briefly, exposure of the nasal mucosa to allergen in a sensitized individual leads to the release and further production of inflammatory mediators and the release of cytokines.(5) These released cytokines activate endothelial cells, thereby inducing expression of adhesion receptors on the cell surface and initiating a cascade of events that facilitates transendothelial migration of inflammatory cells. T lymphocytes also are activated by these cytokines. Within a given tissue, specific patterns of cytokines are released, dependent on the dominant subset of local T lymphocytes. These, in turn, lead to the preferential activation and recruitment of specific inflammatory cells and the characteristic cellular inflammation observed in allergic rhinitis."
9076,Impacts and responsibilities for sustainable tourism: a tour operator’s perspective,"Tourism is currently responsible for the largest, annual human migration in history. This great movement of people has significant positive and negative consequences on nature, societies, cultures and economies. Desired worldwide for its economic benefits, tourism is anticipated to double during the next 20 years, and the multiple consequences of such rapid growth, call for a preventative approach at all strategic and professional levels, in order to avoid negative impacts. Considering mass tourism as a reality of our contemporary life that cannot be neglected by current efforts to endorse sustainable tourism, this paper draws attention to one of its key players—the tour operators—advancing the proposition that they play significant roles in affecting changes in behaviors and attitudes towards more responsible forms of tourism. Aiming to facilitate a constructive debate on the matter, the article presents a few of the most important arguments that underscore the potential that tour operators’ have in promoting sustainable tourism."
9077,Developing animal model systems for embryo technologies in rare and endangered wildlife(),
9078,An empirical study on the impact of quality antecedents on tax payers' acceptance of Internet tax-filing systems,"This study used the Technology Acceptance Model (TAM) to examine taxpayers' acceptance of the Internet tax-filing system. Based on data collected from 141 experienced taxpayers in Taiwan, the acceptance and the impact of quality antecedents on taxpayers' perceived usefulness (PU) and perceived ease of use (PEOU) of the system were assessed and evaluated. The results indicated that the model of Internet tax-filing system was accepted with a reasonable goodness-of-fit. Three important findings include the following items. First, TAM proves to be a valid model to explain the taxpayers' acceptance of the Internet tax-filers' system. Meanwhile, PU has created more impact than PEOU on taxpayers' intention to use the system. Second, PU is positively influenced by such factors as information system quality (ISQ), information quality (IQ), as well as perceived credibility (PC). Third, IQ has a positive impact on PEOU. Based on the research findings, implications and limitations are then discussed for future possible research."
9079,Infectious Diseases in Pregnancy,
9080,Culture and decision making,"The study of culture and decision making addresses variations in how and why people from different cultures sometimes tend to decide differently. This review is organized around what is intended to be a comprehensive analysis of the distinct fundamental questions that people must answer in the process of making virtually all real-life decisions. Our emphasis was on recent developments as well as identifying important yet neglected topics (e.g., how decision episodes get started—or not, and why some decisions are never implemented). Early as well as current efforts have focused mainly on East Asian and North American Caucasian cultures, with little treatment of other populations. In such studies, individualism and collectivism have been the dominant explanatory factors although related but distinct concepts such as “tightness” and “looseness” have been welcome additions to recent discussions. Throughout, the review emphasizes practical concerns, such as the challenges of intercultural learning and collaboration."
9081,Pneumonia in the Hospital Setting,
9082,What's news,
9083,Balaji Sadasivan – 1955–2010,
9084,"Science foresight using life-cycle analysis, text mining and clustering: A case study on natural ventilation","Science foresight comprises a range of methods to analyze past, present and expected research trends, and uses this information to predict the future status of different fields of science and technology. With the ability to identify high-potential development directions, science foresight can be a useful tool to support the management and planning of future research activities. Science foresight analysts can choose from a rather large variety of approaches. There is, however, relatively little information about how the various approaches can be applied in an effective way. This paper describes a three-step methodological framework for science foresight on the basis of published research papers, consisting of (i) life-cycle analysis, (ii) text mining and (iii) knowledge gap identification by means of automated clustering. The three steps are connected using the research methodology of the research papers, as identified by text mining. The potential of combining these three steps in one framework is illustrated by analyzing scientific literature on wind catchers; a natural ventilation concept which has received considerable attention from academia, but with quite low application in practice. The knowledge gaps that are identified show that the automated foresight analysis is indeed able to find uncharted research areas. Results from a sensitivity analysis further show the importance of using full-texts for text mining instead of only title, keywords and abstract. The paper concludes with a reflection on the methodological framework, and gives directions for its intended use in future studies."
9085,Flaviviruses,
9086,The Twenty-Third International Conference on Antiviral Research,
9087,"Integral membrane protein structure: transmembrane α-helices as autonomous folding domains: Current opinion in structural biology 1993, 3: 532–540","The transmembrane region of many integral membrane proteins is made up of a bundle of hydrophobic α-helices. Such a structure could result from a two-stage folding process, during which preformed transmembrane helices with independent stability pack without topological rearrangement. This view was originally prompted by experiments in which fragments of transmembrane regions were separately refolded into lipid bilayers and subsequently brought together to yield a functional protein. Other lines of evidence, including the existence of ‘one-helix’ miniproteins, gene-fusion experiments, helix-driven oligomerization of bitopic proteins, and sequence rearrangements in the course of evolution support this view. Although it forms a useful basis for structural predictions, the limitations of the two-stage folding hypothesis are not clearly defined, and the proportion of integral membrane proteins to which it applies remains uncertain. The papers discussed in the present review illustrate recent progress along these lines."
9088,Epidemic dynamics on information-driven adaptive networks,"Research on the interplay between the dynamics on the network and the dynamics of the network has attracted much attention in recent years. In this work, we propose an information-driven adaptive model, where disease and disease information can evolve simultaneously. For the information-driven adaptive process, susceptible (infected) individuals who have abilities to recognize the disease would break the links of their infected (susceptible) neighbors to prevent the epidemic from further spreading. Simulation results and numerical analyses based on the pairwise approach indicate that the information-driven adaptive process can not only slow down the speed of epidemic spreading, but can also diminish the epidemic prevalence at the final state significantly. In addition, the disease spreading and information diffusion pattern on the lattice as well as on a real-world network give visual representations about how the disease is trapped into an isolated field with the information-driven adaptive process. Furthermore, we perform the local bifurcation analysis on four types of dynamical regions, including healthy, a continuous dynamic behavior, bistable and endemic, to understand the evolution of the observed dynamical behaviors. This work may shed some lights on understanding how information affects human activities on responding to epidemic spreading."
9089,Helicases as molecular motors: An insight,"Helicases are one of the smallest motors of biological system, which harness the chemical free energy of ATP hydrolysis to catalyze the opening of energetically stable duplex nucleic acids and thereby are involved in almost all aspect of nucleic acid metabolism including replication, repair, recombination, transcription, translation, and ribosome biogenesis. Basically, they break the hydrogen bonding between the duplex helix and translocate unidirectionally along the bound strand. Mostly all the helicases contain some conserved signature motifs, which act as an engine to power the unwinding. After the discovery of the first prokaryotic DNA helicase from Escherichia coli bacteria in 1976 and the first eukaryotic one from the lily plant in 1978, many more (>100) have been isolated. All the helicases share some common properties, including nucleic acid binding, NTP hydrolysis and unwinding of the duplex. Many helicases have been crystallized and their structures have revealed an underlying common structural fold for their function. The defects in helicases gene have also been reported to be responsible for variety of human genetic disorders, which can lead to cancer, premature aging or mental retardation. Recently, a new role of a helicase in abiotic stress signaling in plant has been discovered. Overall, helicases act as essential molecular tools for cellular machinery and help in maintaining the integrity of genome. Here an overview of helicases has been covered which includes history, biochemical assay, properties, classification, role in human disease and mechanism of unwinding and translocation."
9090,Infectious Disease and Bioterrorism,
9091,The Twentieth International Conference on Antiviral Research,
9092,"Marian Horzinek, Obituary",
9093,Feature-based recommendations for one-to-one marketing,"Most recommendation systems face challenges from products that change with time, such as popular or seasonal products, since traditional market basket analysis or collaborative filtering analysis are unable to recommend new products to customers due to the fact that the products are not yet purchased by customers. Although the recommendation systems can find customer groups that have similar interests as target customers, brand new products often lack ratings and comments. Similarly, products that are less often purchased, such as furniture and home appliances, have fewer records of ratings; therefore, the chances of being recommended are often lower. This research attempts to analyze customers' purchasing behaviors based on product features from transaction records and product feature databases. Customers' preferences toward particular features of products are analyzed and then rules of customer interest profiles are thus drawn in order to recommend customers products that have potential attraction with customers. The advantage of this research is its ability of recommending to customers brand new products or rarely purchased products as long as they fit customer interest profiles; a deduction which traditional market basket analysis and collaborative filtering methods are unable to do. This research uses a two-stage clustering technique to find customers that have similar interests as target customers and recommend products to fit customers' potential requirements. Customers' interest profiles can explain recommendation results and the interests on particular features of products can be referenced for product development, while a one-to-one marketing strategy can improve profitability for companies."
9094,The scientific basis of multiple sclerosis,
9095,Synthesis of both enantiomers of halitunal,"Both enantiomers of halitunal (1), a novel diterpene aldehyde having an iridoid carbon framework with a heteroaromatic 10π-system, have been synthesized from (+)-genipin (2)."
9096,Volume TOC,
9097,"Greek measles epidemic strain, 2005–2006",
9098,PIV-20 Detection of WU/KI polyomaviruses in respiratory samples from Leeds Teaching Hospitals NHS Trust,
9099,O.7.5 Human bocavirus infections have seasonal transmission dynamics,
9100,ProMED update,
9101,Infectious disease surveillance update,
9102,Subject index volume 7 international journal of infectious diseases,
9103,Other: Impact and consequences of attending the Canadian Pain Society annual conference in Toronto during the SARS crisis: Survey of delegates,
9104,OP3-4 Alternative method for airborne virus detection in only few hours/innovative microbial air sampler,
9105,Evaluation of the new NucliSens easyMAG(®) nucleic acid extraction system,
9106,Self Collection of Nasal Swabs for Diagnosis of Respiratory Viruses in Immunocompetent Volunteers and Hematopoietic Stem Cell Transplant (HCT) Recipients,
9107,Prevalence of two recently described HBV mutations and their effect on adefovir therapy,
9108,PP-181 A novel 2-tailed CUSUM control-chart for evaluating new therapies: hypertonic-saline in bronchiolitis compared to nebulized adrenaline,
9109,486. Plasmid DNA Constructs Expressing SARS-CoV Antigens Are Immunogenic in Mice and Rabbits,
9110,Technology and public health,
9111,Asia takes action on drug-resistant tuberculosis,
9112,O.7.6 Enhanced etiological diagnosis of respiratory virus infections and outbreaks using nucleic acid amplification testing against an expanded range of targets,
9113,"Neuroinfection & neuroimmunology: New opportunities, new challenges",
9114,37: Incidence of Upper and Lower Airway Viral Infections in a Cohort of Lung Transplant Recipients (LTRs),
9115,HealthMap: the future of infectious diseases surveillance?,
9116,320. Selection of Lentiviral Vectors for Gene Transfer to Porcine Airways,
9117,CS15-01 Can We Prevent Hepatocellular Carcinoma in Chronic Hepatitis B?,
9118,Papers to Appear in Forthcoming Issues,
9119,M-III Laboratory diagnosis of viral gastroenteritis,
9120,Infectious disease surveillance update,
9121,Diagnosis of human metapneumovirus by immunofluorescence-the newcastle experience,
9122,Non-traditional outbreak surveillance - the 15 year experience,
9123,"PP-178 Surveillance of antimicrobial resistance in patients with community acquired pneumonia in tertiary care hospital, Manipal",
9124,PI-6 West Nile virus (WNV) seroprevalence in blood donors from Central Anatolia,
9125,Infectious diseases: A never-ending threat,
9126,Free Communications (Poster Sessions),
9127,The innovative qiasymphony system from Qiagen takes ease of use to a new level,
9128,Corrections,
9129,13th International Congress on Infectious Diseases Abstracts (Oral Presentations),
9130,RNA Virus Vectors,
9131,O.7.7 Impact of duration of illness on viral load and detection rate of viral pathogens by multiplex PCR in respiratory tract infections,
9132,"Exotic Viral Diseases: A Global Guide: S.A. Berger, C.H. Calisher and J.S. Keystone; BC Decker – Inc, Hamilton and London, 2003, 252 pages, Paperback, ISBN 1-55009-205-7 ($29.95)",
9133,OP3-1 Evaluation of Clart® Pneumovir DNA arrays for the detection of respiratory viruses among children hospitalised in intensive care unit,
9134,Methylation profile of bovine Oct4 gene coding region in relation to three germ layers,"Previous studies have shown that octamer-binding transcription factor 4 (Oct4) plays a significant role in early embryonic development of mammalian animals, and different Oct4 expression levels induce multi-lineage differentiation which are regulated by DNA methylation. To explore the relationship between the methylation pattern of Oct4 gene exon 1 and embryonic development, in this work, five different tissues (heart, liver, lung, cerebrum and cerebellum) from three germ layers were chosen from low age (50–60 d) and advanced age (60–70 d) of fetal cattle and the differences between tissues or ages were analyzed, respectively. The result showed that the DNA methylation level of Oct4 gene exon 1 was significant different (P<0.01) between any two of three germ layers in low age (<60 d), but kept steady of advanced age (P>0.05) (>60 d), suggesting that 60-d post coital was an important boundary for embryonic development. In addition, in ectoderm (cerebrum and cerebellum), there was no significant methylation difference of Oct4 gene exon 1 between low age and advanced age (P>0.05), but the result of endoderm (liver and lung) and mesoderm (heart) were on the contrary (P<0.01), which indicated the development of ectoderm was earlier than endoderm and mesoderm. The methylation differences from the 3rd, 5th and 9th CpG-dinucleotide loci of Oct4 gene exon 1 were significantly different between each two of three germ layers (P<0.05), indicating that these three loci may have important influence on bovine embryonic development. This study showed that bovine germ layers differentiation was significantly related to the DNA methylation status of Oct4 gene exon 1. This work firstly identified the DNA methylation profile of bovine Oct4 gene exon 1 and its association with germ layers development in fetus and adult of cattle. Moreover, the work also provided epigenetic information for further studying bovine embryonic development and cellular reprogramming."
9135,JOGC Guidelines index English,
9136,152* Microevolution of the major common Pseudomonas aeruginosa clones C and PA14 in cystic fibrosis lungs,
9137,Human herpesvirus-6 viraemia in children with primary immunodeficiency undergoing stem-cell-transplantation,
9138,Summaries,
9139,Poster Presentations,
9140,À propos du COVD-19 : note de l’éditeur et des rédacteurs en chef de la revue GOFS,
9141,Evaluation of Infection Risk Factors in Adult Hematologic Malignancy Patients,"INTRODUCTION: Hematologic malignancies (HM) are often highly aggressive processes requiring multi-chemotherapy regimens and potentially hematopoietic stem cell transplant (HSCT) for treatment. Totally implantable venous access ports (TIVAP) are the standard access for administration of these regimens. The regimens usually involve periods of neutropenia for which infection can increase morbidity and require removal of the port. Although deemed safe for use in cancer populations, many studies have only looked at patients with TIVAP in solid tumor malignancies. Herein, we report our single institution experience identifying modulators for infection related to TIVAP in this high-risk population. OBJECTIVES: To identify risk factors for port infection in HM patients. METHODS: We performed an IRB-approved single institution retrospective review of HM patients who had a TIVAP removed for port infection versus completion of therapy. Medical records were evaluated for patient demographics and tumor type, details of previous therapy regimens such as chemotherapy and HSCT status, laboratory values including albumin, white blood cell, neutrophil and platelet counts, as well as characteristics of the TIVAP. Univariate and multivariate regression analyses were performed between the two cohorts to identify clinical predictors of port infection necessitating TIVAP removal. RESULTS: Between March 2015 and July 2018, 104 TIVAPs were removed from HM patients, 34 (33%) for infection and 70 (67%) for completion of treatment. Median patient age was 60 years (range 22-86) and there was an even number of men and women (n=52). Most TIVAPs were double lumen (n=98, 94%) and placed in the right IJV (n=100, 96%). The median number of port days was 49 in the infection group and 414 in the completion group, with removal of 12 (35%) of the infected ports within 30 days. Multiple factors were significant predictors of port infection on univariate analysis, including diagnosis of AML or ALL (p=0.0019), no prior HSCT (p=0.0148), neutropenia within 30 days of removal (p<0.0001), ANC <1500 (p <0.0001), leukopenia the day prior to removal (p<0.0001), thrombocytopenia (p <0.0001), and hypoalbuminemia (p<0.0001). Steroid use, leukopenia or leukocytosis the day of placement, and leukocytosis the day prior to removal were not significantly different between the two groups. On multivariate analysis, no prior HSCT (OR=48.08, 95% CI 2.64-875.63, p=0.009), neutropenia within 30 days of removal (OR=67.60, 95% CI 1.68-2726.66, p=0.026), and hypoalbuminemia (OR=405.52, 95% CI 15.64-10517.89, p<0.0001) remained significant. CONCLUSION: In patients with HM, significant predictors of port infection requiring TIVAP removal included neutropenia within 30 days of removal and hypoalbuminemia. Interestingly, patients who underwent HSCT were less likely to a develop a port infection requiring TIVAP removal."
9142,Abstracts accepted for publication only,
9143,M-I Submitting an article to Journal of Clinical Virology,
9144,Update to the Latin American Thoracic Society (ALAT) Recommendations on Community-Acquired Pneumonia,
9145,Multiplex real time PCRs for respiratory viral infections,
9146,P441 – P678,
9147,"Membrane protein expression made easy: Gong, F-C., Giddings, T.H., Meehl, J.B., Staehelin, L.A. and Galbraith, D.W. (1996) Z-membranes: artificial organelles for overexpressing recombinant integral membrane proteins, Proc. Natl Acad. Sci. USA 93, 2219–2223",
9148,P175 Extended incubation of cystic fibrosis cultures: is it worth it?,
9149,Forum,
9150,Infectious disease surveillance update,
9151,"PI-4 Rat-to-human cowpoxvirus outbreaks, France 2009",
9152,Summaries,
9153,P.060 Influenza A viruses host ultrastructural nuclear modifications: specific different patterns between avian and human strains?,
9154,Contents page.,
9155,Microbead array based technology for detection and quantitation of viral respiratory pathogens associated with pneumonia among children,
9156,Health activists in China unlawfully discriminated against,
9157,"Innate Immunity to Pulmonary Infection, Novartis Foundation series No. 279",
9158,"DNA ladders connecting animals and plants: Ryerson, D.E. and Heath, M.C. (1996) Cleavage of nuclear DNA into oligonucleosomal fragments during cell death induced by fungal infection or by abiotic treatments, Plant Cell 8, 393–402 Wang, H., Li, J., Bostock, R.M. and Gilchrist, D.G. (1996) Apoptosis: a functional paradigm for programmed plant cell death induced by a host-selective phytotoxin and invoked during development, Plant Cell 8, 375–391",
9159,Infectious disease surveillance update,
9160,Author/Title Index,
9161,L’usage des corticoïdes en réanimation,
9162,"Subject Index: 2004: Volume 26, Numbers 1–12",
9163,PIV-2 The Ibis T5000 for high-throughput identification and discrimination of the pandemic H1N1 influenza virus in Chicago,
9164,Polyhydroxybutyrate microarray for immunodiagnostics and pathogen detections by immobilizing fusion proteins,
9165,PI-8 Vaccine induced and naturally acquired antibodies against mumps virus,
9166,Author index of Volume 7,
9167,CS15.1 CMV in transplant recipients,
9168,I-48 The clinical characteristics and therapy for SARS,
9169,The role of diabetes in the severity of 2009 influenza A (H1N1) and the Middle East respiratory syndrome coronavirus (MERS-CoV): A systematic review and meta-analysis,
9170,Chapter 2 Biogenesis and Sorting of Plasma Membrane Proteins,"The cell surface membrane is the boundary between a cell and its environment. In case of polarized epithelial cells, the apical plasma membrane is frequently the boundary between an organism and its environment. The plasmalemma possesses the elements that endow a cell with the capacity to converse with its environment. Plasmalemmal receptor and transducer proteins allow the cell to recognize and respond to various external influences. Membrane-associated proteins anchor cells to their substrata and mediate their integration into tissues. Many properties of a given cell type may be attributed to the protein composition of its plasma membrane. Most cells go to large lengths to control the nature and distribution of polypeptides that populate their plasmalemmas. Cells regulate the expression of genes encoding plasma membrane proteins. Proteins destined for the insertion into the plasma membrane pass through a complex system of processing organelles prior to arriving at their site of ultimate functional residence. Each of these organelles makes a unique contribution to the maturation of these proteins as they transit through them. This chapter discusses the postsynthetic steps involved in the biogenesis of plasma membrane proteins. The chapter discusses some of the events common to all plasmalemmal polypeptides, with special emphasis on those that contribute directly to the character of the cell surface. The chapter then discusses the specializations, associated with cell types, possessing differentiated cell surface sub-domains. The chapter highlights some of the important and fascinating questions confronting investigators interested in the cell biology of the plasma membrane."
9171,Infectious disease surveillance update,
9172,Control of Virus-\associated Hemophagocytic Syndrome by Peroxisome Proliferator Activated Receptor Agonists in a Rabbit Model,
9173,P174 High aerosol production of potentially infectious cough aerosols in people with cystic fibrosis during coughing,
9174,OP3-5 Possible independent replication of HBV in the CNS of HIV-1 infected patients,
9175,Recently in The Lancet,
9176,PIV-25 Phylogenetic analysis of Italian human metapneumovirus (HMPV) and human bocavirus (HBOV) strains,
9177,"Particles, aerosols, and their transport in the built environment",
9178,SARS sequencing paves the way for better diagnostics,
9179,"PIV-27 Viral pathogens of respiratory tract infections in Ankara, Turkey",
9180,Pandemic: tracking contagions,
9181,B5/133 – Longer-term follow up of aerobic capacity in children affected by Severe Acute Respiratory Syndrome (SARS),
9182,Development and validation of different indirect ELISAs for MERS-CoV serological testing,
9183,Infectious disease surveillance update,
9184,PIV-35 Evaluation of two newly developed QIAsymphony sp protocols for efficient isolation of influenza virus RNA from different respiratory samples,
9185,I-59 The interaction between M1 protein of influenza virus and host cell factors,
9186,Subject index of Volume 5,
9187,No end in sight to SARS,
9188,Naturally-occurring hepatitis C virus protease variants: implications for resistance to new antivirals,
9189,European lab network prepares for high-risk pathogen threat,
9190,PP-179 Preparation of overlapping peptides of human being' SARS virus M protein and its application as diagnose SARS,
9191,Bodysnatchers,
9192,From Anthrax to Zika: memoirs of a disease detective,
9193,"Multiple introductions of MERS-CoV in a 2014 hospital outbreak in Riyadh, Saudi Arabia",
9194,Erratum,
9195,Global early warning signs for health threats at the human animal ecosystem interface,
9196,Infectious disease surveillance update,
9197,CDC updates quarantine rules,
9198,RNAi Delivered across the Blood-Brain Barrier,
9199,"Keyword index, Volume 31 (2007)",
9200,Infectious disease surveillance update,
9201,Table of Contents Page 2,
9202,Universal Virus Detection,
9203,Molecular evolution of SARS coronavirus tracked,
9204,"OP4-4 Prevalence, quantification and cut-off level of parvovirus B19 DNA in endomyocardial biopsies of cardiac patients and non-cardiac control subjects",
9205,PIV-33 Detection of oseltamivir-resistant influenza A(H1N1) viruses with H274Y mutation during 2007–2008 influenza season from central and eastern part of Turkey,
9206,Pediatric Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection – UAE,
9207,Incidence and Impact of Community Respiratory Viral Infection (CRV) in Haploidentical and Matched Sibling Donors Receiving Post-Transplant Cyclophosphamide (PTCy): A CIBMTR Analysis,"There are reports of high rates of viral infections after haploidentical transplant, particularly in the setting of PTCy (HaploCy) but detailed data on incidence are lacking. We describe here the comparative incidence of community respiratory virus (CRV) infections occurring by day 180 post-transplant by donor source and their impact on outcomes including survival, relapse, chronic GVHD, and transplant related mortality (TRM) using CIBMTR registry data. The analysis included 2765 patients, all > 2 years of age, who underwent first allogeneic HCT for AML, ALL or MDS from 100 centers between 2012 and 2017 receiving either HaploCy (n=757), Matched related donor (MRD) transplant with PTCy (SibCy n= 403), and MRD transplant with calcineurin inhibitor and either MTX or MMF (SibCNI n= 1605). The cumulative incidences of CRV in the HaploCy, SibCy and SibCNI were: 3% (99% CI, 1.6-4.8), 3% (1.3-5.5) and 2.4 %(1.5-3.5) respectively at day 30 (P =0.649, NS), but notably higher at 15.5% (12.3-19), 16.2% (11.7-21.2) and 9.4 %(7.6-11.4) at 6 months (P<.001) post-transplant [Figure 1]. Identified CRV included primarily Rhinovirus, Parainfluenza, and RSV accounting for approximately 70% of all CRV reported [Table 1]. Figure 2 shows the multivariable models through 2 years post-transplant for survival, relapse, TRM, and chronic GVHD with a reference group of SibCNI without CRV infection for the main effect variable of donor type and infection. Patients in the HaploCy cohort who developed a CRV by day 180 had a higher risk of TRM [p=0.002] and inferior survival [p = 0.001] compared to the reference group. Older age, more advanced disease, and higher HCT-CI were all associated with increased mortality. The incidence of CRVs is higher for patients receiving PTCy, regardless of donor. This finding justifies further studies to understand long-term antiviral immune recovery in different donor sources and GVHD prophylaxis regimens. The higher overall mortality for HaploCy patients developing CRV infection warrants consideration for patient education and heightened awareness for clinicians, as well as long term follow up studies of such patients."
9208,P.037 PCR on Dried Salivary Swab (DSS-test): a useful method for diagnosis of congenital cytomegalovirus infection?,
9209,SARS case was influenza H5N1,
9210,International trends in integrative medicine—The Chinese perspective,
9211,Detection of human metapneumovirus in clinical specimens using a novel immunoassay,
9212,Contents page 1,
9213,Subject index of Volume 7,
9214,"Africa, Asia, and Europe",
9215,PIV-34 A fast procedure for the detection of the new influenza virus A/H1N1 variant,
9216,P.038 Virological-molecular study of aetiological agents associated to Influenza-Like Illness (ILI),
9217,Infectious disease surveillance update,
9218,PIV-22 Specimen quality control for respiratory pathogen detection using molecular tests: are specimens collected by community-based healthcare staff reliable?,
9219,20.130 ISARIC – enhancing the clinical research response to epidemics,
9220,Atlas of Travel Medicine and Health,
9221,"Volume contents, author and keyword indices",
9222,Infectious disease surveillance update,
9223,PIV-24 Multiple agents commonly involved in respiratory tract infections in children,
9224,PIII-2 Diagnosing human papillomavirus and human papillomavirus type 16 by real-time PCR in patient undergone to colposcopy and significance of the diagnosis,
9225,Diagnosis of Marek's disease virus in broiler chickens by histopathology and nested-PCR in Iran,
9226,News & Views,
9227,Infectious disease surveillance update,
9228,News & Views,
9229,What is ahead for health policy and technology in the 2020s?,
9230,What can we learn from MERS outbreak in South Korea?,
9231,"Index to Volume 10, 2008",
9232,Attenuation of pulmonary hypertension secondary to left ventricular dysfunction in the rat by HMG-CoA reductase inhibitor,
9233,"Influenza A detection, typing and assessment of antiviral resistance",
9234,Interferon response in murine plasmacytoid dendritic cells after SARS coronavirus infection,
9235,Evaluation of the bioMérieux easyMAG automated extraction system,
9236,Animal Disease Control: Challenges and Perspectives,
9237,Papers to Appear in Forthcoming Issues,
9238,HIV and HCV adaptation to polymorphic host responses,
9239,"PI-5 The seropositivity of HBV, HCV, HIV among blood donors in Istanbul, Turkey",
9240,Poster Presentation Abstracts,
9241,237. Lentiviral Vector Gene Transfer to Porcine Sinus and Pulmonary Airways,
9242,Respiratory Virus (RV) from Broncho Alveolar Lavage (BAL) Prior to Hematopoietic Cell Transplantation (HCT): A Strong Predictor for Allo-Immune Mediated Lung Syndromes (allo-LS),
9243,M-IV Anti-viral resistance testing in hepatitis B virus infection,
9244,Foodborne pathogens: microbiology and molecular biology,
9245,Strategies for new problems on healthcare-associated infections in Taiwan,
9246,Carbapenem resistance in Hong Kong,
9247,Performance evaluation of real-time PCR based assays for the detection and quantitation of hepatitis B virus DNA,
9248,The epidemiology and pathogenesis of necrotizing enterocolitis,"Necrotizing enterocolitis (NEC), a syndrome characterized by crepitant necrosis of the bowel, has emerged as the most common neonatal gastrointestinal emergency in many countries of the world. In the United States, NEC strikes 1 to 8% of patients admitted to neonatal intensive care units, almost all of whom are premature infants. The incidence is low in certain countries wity a low premature birth rate, e.g., Japan. Two theories of pathogenesis are: the Santulli theory, which implicates three factors: ischaemia, bacteria and substrate; and the Lawrence theory, which stresses the injurious role of bacterial toxins on the immature gut of the preterm infant. Clinical and experimental evidence support each of the theories, but neither theory can explain certain clinical phenomena, particularly the resistance to NEC manifested by more than 90% of preterm infants, who never develop the syndrome. A unifying hypothesis of pathogenesis and a mathematical model of NEC are outlined. Because clustering of cases may occur, the design of clinical trials of preventive measures for NEC must include simultaneous control infants."
9249,Sessions orales,
9250,CS15-04 The Role of Polo-like Kinase 1 as a Therapeutic Target in Hepatocellular Carcinoma,
9251,EPS4.7 Cytokine dynamics in upper airway epithelial lining fluid of CF patients in relation to the status of colonization with Pseudomonas aeruginosa,
9252,Manson's tropical diseases,
9253,Infectious disease in the aging,
9254,"Ocular mucins: Purification, metabolism and functions","Mucins are present at the ocular surface in both secreted and membrane-bound forms. Mucins are produced in partby the conjunctial goblet cells, and are complemented by non-globet secretions. This review focuses on secreted ocular mucins. They are present in the tear film, probably both in gel and soluble form, and play a role in lubrication and ocular defense. It is apparent that mucins are highly adapted to their functions. State of the art techniques for mucin purification and analysis are presented. Density gradient centrifugation, gel filtration, ion-exchange chromatography and agarose gel electrophoresis are discussed, together with methods of oliogosaccharide analysis. Reagents for the detection of mucin are considered in conjunction with these methods, which we have employed in the analysis of human and canine ocular mucins. The general structure of mucins is reviewed. The biosyntheas and glycosylation of ocular mucins are not yet fully understood, and are discussed in relation to currently established concepts. The impaact of disease on the nature and secretion of mucins is considered, as well as the physiological and pathological significance of mucus degradation."
9255,Cross species influenza: emerging zoonosis,"Emerging infection is usually an important public health concern. Within the past decade, there are many new emerging infectious diseases. An important concern is on the pandemic of those new emerging infections. The cross species infection from animal to human, zoonosis, is usually problematic and hard to manage. The well-known situations are on new emerging atypical influenza infections. In this brief article, the author discuss on three important cross species emerging influenza, H5N1 bird flu, H1N1 swine flu and H7N9 bird flu. The basic details of those new influenzas genetic aberration and the concept for surveillance and prediction of new mutation that result in the new cross species emerging zoonosis are also mentioned in this article."
9256,I-60 Structural study of RNA polymerase PA subunit from an avian influenza virus,
9257,Nucleic acid amplification assays for investigation of respiratory viruses,
9258,Emerging Infections: What Have We Learned After 15 Years?,
9259,Contents page 1,
9260,Inferno,
9261,News and insights,
9262,Economics of sustainable forest management,
9263,A duplex RT-PCR assay for detection of H9 subtype avian influenza viruses and infectious bronchitis viruses,"H9 subtype avian influenza virus (AIV) and infectious bronchitis virus (IBV) are major pathogens circulating in poultry and have resulted in great economic losses due to respiratory disease and reduced egg production. As similar symptoms are elicited by the two pathogens, it is difficult for their differential diagnosis. So far, no reverse transcription-polymerase chain reaction (RT-PCR) assay has been found to differentiate between H9 AIV and IBV in one reaction. Therefore, developing a sensitive and specific method is of importance to simultaneously detect and differentiate H9 AIV and IBV. In this study, a duplex RT-PCR (dRT-PCR) was established. Two primer sets target the hemagglutinin (HA) gene of H9 AIV and the nucleocapsid (N) gene of IBV, respectively. Specific PCR products were obtained from all tested H9 AIVs and IBVs belonging to the major clades circulating in China, but not from AIVs of other subtypes or other infectious avian viruses. The sensitivity of the dRT-PCR assay corresponding to H9 AIV, IBV and mixture of H9 AIV and IBV were at a concentration of 1×10(1), 1.5×10(1) and 1.5×10(1) 50% egg infective doses (EID(50)) mL(−1), respectively. The concordance rates between the dRT-PCR and virus isolation were 99.1 and 98.2%, respectively, for detection of samples from H9N2 AIV or IBV infected chickens, while the concordance rate was 99.1% for detection of samples from H9N2 AIV and IBV co-infected chickens. Thus, the dRT-PCR assay reported herein is specific and sensitive, and suitable for the differential diagnosis of clinical infections and surveillance of H9 AIVs and IBVs."
9264,324. DNA Vaccination To Generate Chikungunya Virus-Specific Immunity,
9265,Abstracts cont.,
9266,PIV-21 Respiratory viral infections in adult patients with hematologic malignancies,
9267,"Single-Agent High-Dose Melphalan as Conditioning Regimen in Autologous Hematopoietic Stem Cell Transplantation for Hodgkin's Lymphoma: Safety, and Long-Term Efficacy",
9268,"66 Incidence of Burkholderia cepacia complex infection in a Cystic Fibrosis Centre in Buenos Aires City, Argentina, from 2004 to 2014","Burkholderia cepacia complex (Bcc) is recognized as a significant respiratory pathogen in Cystic Fibrosis (CF) patients. The identification at species level among the 18 established Bcc members is an essential tool for epidemiological studies and infection control policies. In the early 2000s the epidemiology of Burkholderia cepacia (Bcc) in Argentina was characterized by the occurrence of a B. contaminans outbreak that took place in major CF centres. This situation was quite different from other countries where B. cenocepacia and B. multivorans have been the most frequent Bcc infecting species in CF patients. Although B. contaminans outbreak was studied, little is known about the evolution of Bcc epidemiology during the last years. The aim of this study was to analyse Bcc infections in CF patients (pt) attending Hospital de Niños “R. Gutiérrez” in 3 different periods between 2004 and 2014. Incidence and distribution of Bcc species have been described. 2004–2005: Incidence 13.5% (22/163 pt). B. contaminans 55.6% (10/18), B. cepacia 16.7% (3/18), B. cenocepacia and B. seminalis 11.1% (2/18), B. multivorans 5.6% (1/18), 4 nonviable strains. 2007–2009: Incidence 6.6% (12/181 pt). B. contaminans 72.7% (8/11), B. cepacia 27.3% (3/11), 1 nonviable strain. 2012–2014: Incidence 5.4% (10/184 pt). B. contaminans 90% (9/10), B. cepacia 10% (1/10). CONCLUSION: B. contaminans remains the most frequent isolated species among the new cases of infection. Although incidence values have decreased, these results suggest the situation with B. contaminans hasn't been solved yet. More studies specially focusing on the transmission of these bacteria and the possible sources of infection are needed."
9269,25 Chronic rhinoviral infection in lung transplant recipients,
9270,"Meeting report: Part III. Notes from the 20th Annual Clinical Virology Symposium, April 25–28, 2004, Clearwater Beach, FL, USA",
9271,Abstracts of the 2(nd) Global Congress on Molecular Pathology,
9272,Guidelines for the Diagnosis and Treatment of Community-Acquired Pneumonia. Spanish Society of Pulmonology and Thoracic Surgery (SEPAR),
9273,Impact Factors!,
9274,Free paper and oral poster abstracts,
9275,PIV-36 Performance of the Qiagen Resplex II ver. 2.0 & ver. 3.0 multiplex assays for the detection of (H1N1V) pandemic influenza A in a London teaching hospital,
9276,PIV-37 Do viral respiratory co-pathogens contribute to morbidity & mortality in an outbreak of parainfluenza type 3 in haematology-oncology patients?,
9277,Oral Presentation Abstracts,
9278,Infectious disease surveillance update,
9279,Environmental Risk and Assessment Management System of High-level Biosafety Laboratory,"How to avoid the potential risk from high-level biosafety laboratories (BSL-3, BSL-4) has been highly concerned by governments all over the world. Based on the study of construction status and environmental risk of high-level biosafety laboratories and on the study of the layout structure and bio risk measures of biosafety laboratory contaminants, this paper analyzed the key point of environmental risk, and proposed the risk management system of high-level biosafety laboratories. System framework and realization process is given in the paper in order to provide reference for domestic construction of high-level biosafety laboratories and the improvement of risk emergency system."
9280,OP3-3 Effect of rTGF-β on nitric oxide synthase (iNOS) AND dsRNA dependent protein kinase (PKR) during experimental influenza infection in mice,
9281,XXX Reunión de la Sociedad Española de Neumología Pediátrica,
9282,CS15-03 Prevention of HCC Related to Viral Hepatitis,
9283,Vaccines,
9284,PP-180 Elaboration of viral vaccine delivery,
9285,MERS CoV infection - ecological investigations,
9286,Acute care issues in internationally adopted children,"Over the past decade there has been a dramatic increase in international adoptions in the United States. While most adopted children will have common illnesses, others may have unique medical issues as a result of the conditions in their birth country requiring a broadened differential diagnosis. Knowledge of these issues is essential in the management of these patients. This review will predominately focus on infectious disease issues commonly seen in international adoptees but will also discuss other medical conditions and some of the psychosocial issues which may be encountered by caregivers in the emergency department."
9287,P176 Detection of respiratory viruses in cystic fibrosis: comparison of nasal FLOQ Swabs™ and sputum using the FilmArray® platform,
9288,Infectious disease surveillance update,
9289,Prospective Assessment of Diagnostic Infectious Disease Molecular PCR Testing with Early Fiberoptic Bronchoscopy (FOB) in the Evaluation of New Pulmonary Infiltrates in Hematopoietic Stem Cell Transplantation (HSCT) and Acute Leukemia (AL) Patients (pts),
9290,Effectiveness of masks and respirators against respiratory infections in healthcare workers: A systematic review and meta-analysis,
9291,SS7-3 A non-redundant role of IFN-λ in antiviral defense of the intestinal tract,
9292,China receives SARS warning,
9293,Inflammatory myofibroblastic tumor in the lung with feeding vessel: mimicking a congenital lung malformation,
9294,Persistence of SARS-CoV in bat feces (Rhinolophus ferrumequinum) and implications for the ecology of SARS-CoV related viruses in nature,
9295,Untangling Alzheimer's Therapy,
9296,Can homemade fit testing solutions be as effective as commercial products?,"BACKGROUND: Fit testing is used to determine whether a N95 mask will provide respiratory protection for the wearer by preventing inhalation of airborne transmitted microorganisms. National guidelines recommend that healthcare workers (HCW) who use N95 masks require fit testing. Quantitative fit testing requires the purchasing and use of fit testing solutions and associated equipment. In high volume, these solutions are expensive and may not be readily available, as was seen in the 2009 H1N1 influenza pandemic. The aim of this study was to determine how a homemade solution compared against a commercially available product and a placebo. METHODS: Afit test was performed on the same person, on three separate occasions, using three different solutions – commercial (45% sodium saccharin), homemade (to be disclosed) and placebo (water). The solution was double blinded and solutions were chosen and administered in a random order. RESULTS: Atotal of 48 people participated in this study.At the threshold testing stage, 8.3% did not taste any solution, 16.7% of people could taste the placebo, 89.6% could taste the commercial solution and 91.7% could taste the homemade solution. All persons who could taste the commercial solution could taste homemade solution. CONCLUSION: The findings of our study suggest that fit testing solutions could be made locally with a similar effect to that of commercial products, that quantitative fit testing is unreliable and that serious consideration should be given to the role of quantitative fit testing in future guidelines and standards. We recommend that this study be conducted on a larger scale to support our findings."
9297,Liquorice compound beats latent herpesvirus,
9298,65 Clinical outcomes of chronic “Prairie Epidemic Strain” Pseudomonas aeruginosa infection in adults with cystic fibrosis,"OBJECTIVES: Transmissible Pseudomonas aeruginosa (PA) strains have been described in CF and may be associated with a poorer prognosis. The “Prairie Epidemic Strain” (PES) has been recently identified in up to 30% of patients at prairie-based CF centres, however, its clinical impact remains to be determined. METHODS: A cohort study of adults with cystic fibrosis from 1981–2014 was conducted and all PA isolates from clinical visits were prospectively collected. PA strain typing at clinic enrolment, and most recent was conducted by PFGE. Patients were divided into one of four cohorts: no PA, transient PA, unique chronic PA, and chronic PES. Random effects and proportional Cox hazard models were conducted for outcome of death, transplantation and FEV1% decline. RESULTS: 204 patients (54% male) with CF were analysed: 38 no PA, 20 transient PA, 103 unique PA, 43 PES. Baseline FEV1% was lowest in the chronic PES group (p = 0.002). Overall rate of FEV1% decline was –1.19%/year (95% CI: –1.41 to –0.97, p<0.001); the chronic PES group had the greatest rate of decline at –1.24%/year (p<0.001). There were a total of 42 deaths and 37 transplants through 1862 and 2050 follow-up years, respectively. The age-adjusted hazard ratio (HR) for death was not different for the PA groups compared to the no PA group. Relative to the no PA group, risk of transplant was increased in those with chronic PES (HR 9.13, CI 1.29–69, p = 0.032) compared to the no PA group. CONCLUSION: Chronic PES infection is significantly associated with a greater rate of FEV1% decline and risk of lung transplantation but not with increased risk of death compared to no PA infection."
9299,Viral infections in solid transplant patients,
9300,PI-7 The measles in Poland in period 2004–2009,
9301,"Traditional Use, Pharmacology, Toxicology, and Quality Control of Species in Genus Bupleurum L.","Many species of genus Bupleurum L. have been pharmaceutically used mainly in Asia and Europe for thousand years. Their roots are the most popular ingredients in Chinese materia medica prescriptions for the treatment of inflammatory diseases and auto-immune diseases. A plenty of chemical constituents have been isolated and identified from the species in Bupleurum L., such as saikosaponins, polysaccharides, volatile oils, flavonoids, polyacetylenes, lignins, and coumarins, most of which possess a variety of biological activities, especially for the hepatoprotective effect, antitumor activity, immunoregulation, and febrifuge efficacy. Therefore, the species in genus Bupleurum L. could be potential herbs of immunomodulator, antineoplastic, anti-oxidant, etc. Meanwhile, as potential toxicities have been discovered in some constituents, it is urgent to establish a comprehensive quality evaluation system to ensure the safety and efficiency of herbs. This paper reviews on the phytochemical and pharmacological studies, especially for the toxicology and quality control of the species in Bupleurum L., which is a reference for the species in this genus for safe usage and further development."
9302,Immune surveillance-related genes are significantly over expressed in the breast epithelium of postmenopausal parous women(),
9303,OL-043 Mechanism and therapeutic efficacy of peroxisome proliferator activated receptor agonist for virus-associated hemophagocytic syndrome,
9304,Highlights from the fifth IMED,
9305,Gastroenteritis aguda,
9306,"Volume contents, author and keyword indices",
9307,I-57 Emerging Bartonella in animal and human in China,
9308,Large cash boost to combat avian influenza,
9309,SUBJECT INDEX FOR VOLUME 37,
9310,Media Watch,
9311,Infectious diseases surveillance update,
9312,Critical care nursing: Expanding beyond critical care,
9313,Drivers for MERS-CoV emergence in Qatar,
9314,TOC,
9315,A systematic review of healthcare associated outbreaks in Singapore post SARS: 2003-2016,
9316,OL-042 Specific T-cell responses to CFP-10 antigens of Mycobacterium tuberculosis in Chinese HIV positive individuals,
9317,Promotion of seasonal influenza vaccination among staff in residential care homes for elderly in Hong Kong,"Annual influenza epidemics continue to cause worldwide morbidity, mortality and societal disruption, especially among the aged residents of residential care homes for the elderly (RCHEs). Vaccination remains the most effective measure to prevent influenza and its associated complications. The seasonal influenza vaccine uptake rates among RCHE staff were much lower than that among residents. In order to increase uptake of influenza vaccination among RCHE staff in Hong Kong, this study developed and evaluated amultimodal vaccine promotion program (VPP) based on identified factors affecting vaccination acceptance or refusal within the Hong Kong Chinese context. Vaccine acceptance was found to be significantly associated with belief in vaccine efficacy, duration of service, staff group and providing direct care to residents. The focus group study revealed that RCHE staff's belief in the efficacy and safety of the vaccine played a major role in vaccine acceptance. VPP effectiveness was evaluated with a cluster randomised controlled trial among RCHEs with staff vaccination rates below 50%. Compared with 2008/09, the 2009/10 mean staff vaccination rates increased significantly in both the intervention (39.4% to 59.6% (P < 0.001)) and control groups (36.3% to 47.6% (P = 0.008)). RCHE staff in the intervention group had a higher vaccination rate than in the control group (59.6% versus 47.6%, P = 0.072). This program reinforces the importance of a comprehensive and culturally sensitive approach to promote influenza vaccination for RCHE staff."
9318,Communicable Disease Control Handbook second edition,
9319,"Scientific Program (as of June 21, 2010)",
9320,OP4-3 Molecular detection of respiratory viruses: routine application on 522 samples taken in children less than 2 year old,
9321,ABSTRACT BOOK,
9322,PP-086 Increase influenza virus yield by reverse genetics system through a strong RNA Polymerase II promoter,
9323,CS15-02 Current Japanese Strategies for Preventing HCC Development,
9324,Identification of respiratory viruses detected during three consecutive winter seasons,
9325,P.036 GeneXpert and TaqMan-PCR assay for the detection of enterovirus/parechovirus in cerebrospinal fluid,
9326,Common Cold Viruses Early After Hsct Are Associated With Life Threatening Alloimmune Lung Syndromes,
9327,Reflections on emergency preparedness level of selected Asian hospitals visited during Bali Fellowship study tour,
9328,Avian & Exotic News,
9329,Generation of Coronavirus-based multigene RNA vectors,
9330,PIV-1 Respifinderplus for the diagnostics of respiratory infections with a focus on the 2009 A/H1N1 pandemic,
9331,"Keyword Index, Volume 29 (2005)",
9332,Infectious disease surveillance update,
9333,Cause of Kawasaki syndrome uncertain again,
9334,P.035 Expression of the major capsid protein of JC and BK polyomavirus and herpes simplex and varicella zoster virus glycoproteins using a plasmid based system in insect cells,
9335,Ebola virus disease outbreak in West Africa and challenge of Hajj and Omrah in Saudi Arabia,
9336,Association for Molecular Pathology 2007 Annual Meeting Abstracts,
9337,Papers to Appear in Forthcoming Issues,
9338,"Use of a Multiplex RT-PCR Assay for Simultaneous Detection of the North American Genotype Porcine Reproductive and Respiratory Syndrome Virus, Swine Influenza Virus and Japanese Encephalitis Virus","A multiplex reverse transcriptase-polymerase chain reaction (multiplex RT-PCR) assay was developed and subsequently evaluated for its efficacy in the detection of multiple viral infections simultaneously, in swine. Specific primers for each of the 3 RNA viruses, North American genotype porcine reproductive and respiratory syndrome virus, Japanese encephalitis virus, and swine influenza virus, were used in the testing procedure. The assay was shown to be highly sensitive because it could detect as little as 10(−5) ng of each of the respective amplicons in a single sample containing a composite of all 3 viruses. The assay was also effective in detecting one or more of the same viruses in various combinations in specimens, including lymph nodes, lungs, spleens, and tonsils, collected from clinically ill pigs and in spleen specimens collected from aborted pig fetuses. The results from the multiplex RT-PCR were confirmed by virus isolation. The relative efficiency (compared to the efficiency of separate assays for each virus) and apparent sensitivity of the multiplex RT-PCR method show that this method has potential for application in routine molecular diagnostic procedures."
9339,P177 Characterisation of pathogens causing lung infection in people with cystic fibrosis by surface-enhanced Raman spectroscopy (SERS),
9340,I-47 Creative hand hygiene campaigns,
9341,The nucleocapsid protein of SARS CoV interacts with PIAS1 and affects the NFkappaB pathway,
9342,PIV-26 Human bocavirus-monoinfection and viremia are associated with airway infection in children,
9343,Diagnostic Challenge,
9344,Is SARS masking an influenza threat?,
9345,Sindbis Virus Targets Cancers in Mice,
9346,Miniaturized drug discovery and high throughput microarrays for biological discovery,
9347,236 SARS-coronavirus inhibits interferon induction both at pre- and post-transcriptional levels,
9348,P.039 Is replacement of tAN cells in routine viral culture possible?,
9349,Natural Compounds Potentially Suppressible Corona Virus Infection Disease,
9350,OP3-2 Spread and evolution of avian influenza virus in poultry and wild-birds in Africa,
9351,From SARS and avian flu to swine flu,
9352,New infectious diseases centre opens in China,
9353,Le réanimateur à l'interface des pathologies infectieuses émergentes,
9354,Inhibition of HCoV-NL63 infection at early stages of the replication cycle,
9355,135. Safety of Liver-Directed AAV2/8-Mediated Gene Transfer in a Large Animal Model of Lysosomal Storage Disease,
9356,"Index to Volume 6, 2004",
9357,Life threatening human metapneumovirus infections in the West of Scotland,
9358,27 Severe SARS coronavirus infection in aged macaques is associated with reduced expression of anti-inflammatory type-1 interferons,
9359,Diversity of Coronaviruses in Bats: Insights Into Origin of SARS Coronavirus,
9360,Facing the Global Challenges of Emerging and Re-emerging Infectious Diseases in Taiwan,
9361,Original research in The Lancet Infectious Diseases,
9362,"Epidemiology, pathogenesis, and treatment of the common cold","The common cold is an acute illness of the upper respiratory tract caused by a virus acquired from another person. Some viruses that produce colds are capable of infecting an individual repeatedly (eg, respiratory syncytial virus); others, with many serotypes (eg, rhinovirus), infect only once. The sustained epidemic of colds that occurs annually during September through April is explained by successive waves of different viruses moving through a community. The peak incidence of colds occurs in preschool children, who typically sustain at least one illness per month during the epidemic period. Clinical manifestations of colds are largely subjective in adults. Colds in preschoolers differ from those in adults as follows: (1) fever is common in children during the first 3 days; (2) colored nasal secretions may be the only indication of nasal involvement in children; and (3) colds in children last 10 to 14 days, as compared with a duration of less than a week in adults. The paranasal sinuses and the middle ear cavities are commonly involved during viral colds in adults (and presumably in children) in the absence of bacterial superinfection. Cold symptoms are due to the host's response to the virus rather than to destruction of the nasal mucosa. Viral infection of a very limited portion of the nasal epithelium results in an influx of polymorphonuclear leukocytes, cytokine release, and a vascular leak. Colds are self-limited illnesses. Therefore, in the absence of adequate blinding of controls, ineffective treatments erroneously may be considered efficacious. None of the medicines used for symptom relief in colds is curative."
9363,Epidemiology of respiratory coronaviruses (HCoV) in a Dutch university hospital,
9364,P.061 Clinical evaluation of pediatric viral acute respiratory tract infections detected by multiplex real-time PCR,
9365,Newsbytes,
9366,M-VI Laboratory tools for diagnosis and monitoring of hepatitis C virus infection,
9367,Covering the Cover - May 2020,
9368,OP4-5 Genetic variants of human parvovirus B19 in South Africa: co-circulation of three genotypes and identification of a novel subtype of genotype 1.,
9369,CS14-04 The Development of an AIDS Mucosal Vaccine,
9370,SARS-Coronavirus ancestor's foot-prints in Thai bat colonies and the refuge theory: A phylogeography perspective,
9371,K.02 Re-emerging epidemiology of hepatitis virus infections in Europe?,
9372,Prevalence of Feline Coronavirus Antibodies in Cats in Bursa (Turkey) by An Enzyme-Linked Immunosorbent Assay,
9373,Keyword Index,
9374,Resolution of undefined aetiology of respiratory infections in lung transplant patients with unbiased metagenomic sequencing,
9375,The detection of human papilloma virus in infant respiratory tract papillomas,
9376,I-58 More and more human and animal coronaviruses,
9377,The role of respiratory viruses in developing bronchiolitis obliterans and IPS in pediatric HCT patients,
9378,OL-045 Clinical significance of beta-herpesvirus infections in HIV/AIDS and chronic fatigue syndrome patients in Latvia,
9379,Creating young scientists through community science projects,"This research aimed to develop an STS-based learning unit on biological control to enhance scientific inquiry capability of secondary school students through community science projects. It was framed by the science-technology-society (STS) teaching approach, and focused on collaboration between individual students, peers, teachers, agriculturists, and local experts. Students were assessed for their scientific inquiry ability at the beginning and the end of the learning process using five instruments: experimental skill test, students’ laboratory reports, students’ science projects, semi-structured interview and classroom observation. The results showed that the STS-based learning unit on biological control helped students gain significant improvement in scientific inquiry. They were able to apply and integrate the scientific knowledge learned in both classroom and field studies to help solve agricultural problems in their own communities. Moreover, this learning unit encouraged students’ skills in solving problems in other situations."
9380,"From Taiwan's experience to global prevention and control of pandemic influenza - surveillance, epidemiology and public health policies",
9381,Nucleic acid amplification tests for detection of respiratory viruses,
9382,keyword index,
9383,Media Watch,
9384,Improved laboratory diagnosis of HTLV in corneal transplant donor specimens,
9385,"The hidden epidemic: MERS-CoV-related stigma observations from the field, Qatar 2012-2015",
9386,Chapter 1 discovery of the aquaporins and their impact on basic and clinical physiology,
9387,Multiplex RT-PCR for detecting nineteen respiratory viruses,
9388,WHO's avian influenza tsar takes Director-General post,
9389,"Retinal degenerations of hereditary, viral and autoimmune origins: Studies on opsin and IRBP",
9390,Mass screening for fever: A comparison of three infrared thermal dectection systems and selfreported fever,
9391,Human Coronavirus (HCOV) and Rhinovirus (HRHV) Infection among Hematopoietic Stem Cell Transplantation (HCT) Recipients,
9392,Community Acquired Pneumonia Etiology Study (CAPES): Experience of over 4000 cases from a single centre in India,
9393,Viral pneumonia in children,"Viral pneumonia causes a heavy burden on our society. In the United States, more than one million cases of pneumonias afflict children under the age of 5 years, costing hundreds of millions of dollars annually. The majority of these infections are caused by a handful of common viruses. Knowledge of the epidemiology of these viruses combined with new rapid diagnostic techniques will provide faster and more, reliable diagnoses in the future. Although the basic clinical epidemiology of these viruses has been carefully investigated over the last 30 years, new molecular techniques are greatly expanding our understanding of these agents and the diseases they cause. Antigenic and genetic variations are being discovered in many viruses previously thought to be homogeneous. The exact roles and the biological significance of these variations are just beginning to be explored, but already evidence of differences in pathogenicity and immunogenicity has been found in many of these substrains. All of this information clearly will impact the development of future vaccines and antiviral drugs. Effective drugs exist for prophylaxis against influenza A and respiratory syncytial virus, and specific therapy exists for influenza A. Ribarivin is approved for use in respiratory synctial virus infections, and it alone or in combination with other agents (eg, IGIV) may be effective in immunocompromised patients, either in preventing the development of pneumonia or in decreasing morbidity and mortality. Many new antiviral agents are being tested and developed, and several are in clinical trials."
9394,Atypical presentation and nosocomial spread - intensifying the MERS mystery and misery,
9395,Editor's Choice,
9396,OP3-9 Adenovirus DNA positivity in nasopharyngeal aspirate preceding stem cell transplantation: a very strong predictor for Adenovirus DNA-emia in pediatric patients,
9397,PP-084 Early virologic response predicts therapeutic outcomes in adefovir-treated HBeAg-positive chronic hepatitis B (CHB) patients,
9398,SARS—What is next and how do you know?,
9399,Interferon-lambda mediates resistance against various respiratory viruses,
9400,Major infectious diseases of children in developing countries: Challenges and opportunities of today and the future,
9401,Hemophagocytic lymphohistiocytosis associated with viral infections: Diagnostic challenge and therapeutic dilemma(),"Hemophagocytic lymphohistiocytosis is a frequently fatal clinicopathologic syndrome in which an uncontrolled and ineffective immune response leads to severe hyperinflammation. It may occur as either a familial disorder or a sporadic condition in association with a variety of triggers: infections, malignancies, autoimmune diseases, and acquired immune deficiencies. However, the most consistent association is with viral infections, especially Epstein–Barr virus. The main clinical features are fever, liver dysfunction, coagulation abnormalities and pancytopenia. Early diagnosis and treatment are important to reducing mortality, but the diagnosis is difficult because of the rarity of the syndrome and the lack of specificity of the clinical findings. Treatment should be directed toward treating the underlying disease and to suppressing the exaggerated inflammatory response through the use of immunosuppressive agents."
9402,Trent HCV study: mortality rates and ethnic differences in outcome,
9403,Infectious diseases high on agenda in WHO leadership race,
9404,Cumulative Index 2000,
9405,"Mosaic structure of human coronavirus NL63, one thousand years of evolution",
9406,RNA virus replication,
9407,Risque de récurrence à 1 an d’une population de nourrissons ayant présenté une bronchiolite aiguë : le poids de l’allergie familiale ?,
9408,"Summary Report of a Meeting on the Estimation of the Potency of Inactivated Poliovaccine: Institut Pasteur, Paris 12–13 February 1990",
9409,Keyword Index,
9410,Forthcoming topics,
9411,M-II Quality control in a molecular virology laboratory,
9412,CS15.2 Drug design and development against EV71 and other enteroviruses,
9413,Enteric virus detection and identification with a universal virus discovery assay,
9414,634: Clinical Outcome of Brazilian Lung Transplant Recipients after Respiratory Virus Infections,
9415,EPS4.6 Inherent differences in multiple breath washout (MBW) using N(2) and SF(6) demonstrated by simultaneous analysis with respiratory mass spectrometry (RMS),
9416,Viral burden in acute respiratory tract infections in hospitalized children in the wet and dry zones of Sri Lanka,
9417,EPS4.3 Differential sensitivity of outcome measures that assess progression of mild CF lung disease in school age children,
9418,The spread of filthy lucre and disease,
9419,Author/subject index,
9420,Infectious disease surveillance update,
9421,Spectre of SARS still looms,
9422,A Novel Therapeutic and Prophylactic Vaccine against Tuberculosis Using the Cynomolgus Monkey Model and Mouse Model,"We have developed a novel tuberculosis (TB) vaccine; a combination of the DNA vaccines expressing mycobacterial heat shock protein 65 (HSP65) and interleukin 12 (IL-12) delivered by the hemagglutinating virus of Japan (HVJ)-envelope and –liposome (HSP65 + IL-12/HVJ). This vaccine provided remarkable protective efficacy in mouse model compared to the BCG. This vaccine also provided therapeutic efficacy against multi-drug resistant TB (MDR-TB) and extremely drug resistant TB (XDR-TB) in murine models. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. This novel vaccine provided a higher level of the protective efficacy than BCG based upon the assessment of mortality. The BCG prime and HSP65 + IL-12/HVJ vaccine (boost) by the prime-boost method showed a synergistic prophylactic effect in the monkey. Furthermore, this vaccine exerted therapeutic efficacy (100% survival) and augmentation of immune responses in the TB-infected monkeys.HVJ-Envelope/HSP65 DNA + IL-12 DNA vaccine increased the body weight of TB-infected monkeys, improved the ESR, and augmented the immuneresponses (proliferation of PBL and IL-2 production). The enhancement of IL-2 production from monkeys treated with this vaccine was correlated with the therapeutic efficacy of the vaccine. These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis including XDR-TB and MDR-TB for human therapeutic clinical trials."
9423,Cytomegalovirus monitoring in allogeneic haemopoietic stem cell transplant recipients,
9424,P.059 Detection of Epstein–Barr Virus DNA in respiratory specimens from patients with chronic obstructive pulmonary disease by quantitative PCR,
9425,Family syndromes of cancer of female reproductive organs in Chernivtsi region,
9426,Rapid Recovery of Classical Swine Fever Virus Directly from Cloned cDNA,"The reverse genetics for classical swine fever virus (CSFV) is currently based on the transfection of in vitro transcribed RNA from a viral genomic cDNA clone, which is inefficient and time-consuming. This study was aimed to develop an improved method for rapid recovery of CSFV directly from cloned cDNA. Full-length genomic cDNA from the CSFV Shimen strain, which was flanked by a T7 promoter, the hepatitis delta virus ribozyme and T7 terminator sequences, was cloned into the low-copy vector pOK12, producing pOKShimen-RzTΦ. Direct transfection of pOKShimen-RzTΦ into PK/T7 cells, a PK-15-derived cell line stably expressing bacteriophage T7 RNA polymerase, allowed CSFV to be rescued rapidly and efficiently, i.e., at least 12 h faster and 31.6-fold greater viral titer when compared with the in vitro transcription-based rescue system. Furthermore, the progeny virus rescued from PK/T7 cells was indistinguishable, both in vitro and in vivo, from its parent virus and the virus rescued from classical reverse genetics. The reverse genetics based on intracellular transcription is efficient, convenient and cost-effective. The PK/T7 cell line can be used to rescue CSFV directly from cloned cDNA and it can also be used as an intracellular transcription and expression system for studying the structure and function of viral genes."
9427,Travellers' Vaccines (2004),
9428,Heterologous recombination in the segmented dsRNA genome of bacteriophage Φ6,"The genome of bacteriophage Φ6 is composed of three unique segments of double-stranded RNA packaged within a procapsid. One segment can recombine with another in regions that share little sequence similarity. Although the recombination is therefore heterologous, the crossover points usually consist of two to six identical nucleotides. The frequency of recombinants is enhanced by conditions that prevent or hinder the minus strand synthesis of a single plus strand segment. Recombination serves as a repair system as well as a means of changing the genetic structure of the virus. The reaction can be studied in an in-vitro packaging and replication system involving purified procapsids and ssRNA. Although there are striking differences in the mechanisms of recombination in RNA viruses, there are also strong similarities. All seem to use a copy-choice template switching action for recombination. The Φ6 system is a useful model for the recombination of other segmented double-stranded RNA viruses such as the Reoviridae."
9429,From SARS to MERS and Ebola,
9430,Editor's Choice,
9431,Abstracts cont.,
9432,"XXXI Reunión de la SOCIEDAD ESPAÑOLA DE NEUMOLOGÍA PEDIÁTRICA: Jaén, 7, 8 y 9 de Mayo de 2009",
9433,Association between influenza and pneumococcal carriage in patients with severe acute respiratory infection in Malawi,
9434,"Index to Volume 7, 2005",
9435,Using the Incidence Decay and Exponential Adjustment (IDEA) model to understand transmission dynamics of MERS-CoV in a camel herd,
9436,P941 – P1197,
9437,IF-02 Successful Control of Influenza Using Stockpile of Tamiflu® during 2003/2004 SARS Period,
9438,Le cardiologue et l’infection à Ebola virus,
9439,"Serological investigation of MERS-CoV in humans between 2011-2016, Jeddah, Saudi Arabia",
9440,"Phylogenetics, virus evolution and molecular epidemiology",
9441,US government (depository items),
9442,ABCD (who's who),
9443,27 Clinical features associated with Coronavirus infections: A prospective and hospital-based study,
9444,OP4-2 Timely diagnosis of respiratory tract infections: evaluation of the performance of the respifinder assay compared to the RVP assay,
9445,554. A Candidate SARS-Associated Coronavirus Vaccine Elicits Broad Immunity in Monkeys,
9446,PIV-23 Clinical usefulness of HMPV quantitative PCR in paediatric respiratory samples,
9447,EPS4.5 Epidemiology of viral respiratory tract infections in a paediatric CF centre,
9448,Forthcoming Articles,
9449,Neonatal Nursing: A Global Affair,
9450,PP-085 Large scale protein expressions for antigenomics studies of respiratory viruses,
9451,Infectious disease surveillance update,
9452,Research Update,
9453,Cumulative Keyword Index,
9454,India - National disaster and epidemic preparedness,
9455,JOGC Update Page,
9456,The gardner lecture: New respiratory viruses: from viral RNA to symptomatic patients,
9457,151* Sino-pulmonary pairs of mucoid and non-mucoid Pseudomonas aeruginosa isolates from cystic fibrosis patients with chronic airways infection have similar gene expression profiles,
9458,ProMED update,
9459,"Infectious diseases in the 21(st) century: increasing threats, fewer new treatments and a premium on prevention",
9460,Table of Contents / barcode,
9461,WHA adopts new International Health Regulations,
9462,PIII-1 Frequency and genotyping of human papillomavirus in pap smear samples,
9463,Abstracts cont.,
9464,"SARS survivors fail to recover by 1 year, say researchers",
9465,OP4-1 Surveillance and oseltamivir resistance of human influenza A virus in Turkey during the 2007–2008 season,
9466,Early evolution of hepatitis C virus (HCV) quasispecies after liver transplantation,
9467,Infectious disease surveillance update,
9468,Microbiology of the nasopharynx in children hospitalized with suspected pulmonary tuberculosis,
9469,I-46 Clinical management of severe respiratory infections in adult hospitalized patients,
9470,67 CF patients with a declining FEV(1): At risk for acquisition of Burkholderia cepacia complex infection?,"INTRODUCTION: Burkholderia cepacia complex (Bcc) infection is considered to be associated with worsening of CF lung disease. Patient to patient spread has been reported, however mechanisms of acquisition of Bcc are not well understood. Method: Data from the Belgian CF Registry (year 2000–2010) were collected. Inclusions: Bcc infected patients with entries on lung function in at least 1 y before and 3 y after Bcc acquisition. For each case, we included 2 controls, matched for age at the index year (year of first Bcc infection), pancreatic status, sex. Cumulative data up to 2 years before index year were compared to values obtained after infection using Rank sum test. Rate of decline in lung function was adjusted for baseline lung function, age, sex. RESULTS: Bcc prevalence in CF is low in Belgium (<3%). 183 patients were included: 61 cases, 122 controls. 59% were F508del homozygous. Mean age in cases was 20.9 y (SD 10.5) vs 20.3 y (SD 10.3) in controls. Among the Bcc, 54% were unspecified, 31% were B. multivorans. Mean FEV(1) at index year was 65.2% (SD 24.9) in cases vs 73.1 (SD 26.9) in controls (p = 0.07). FEV(1) decline before index year was significantly higher in cases (–1.7%, SD 0.5) compared to controls (–1.0%, SD 0.3) (p = 0.002). FEV(1) slopes were comparable in the period after index year (–1.1%, SD 0.5, in cases vs –0.99%, SD 0.4, p = 0.24). CONCLUSION: Our results suggest that a declining FEV(1) precedes acquisition of Bcc and may be a risk factor. After acquisition, lung function decline was comparable in Bcc infected and uninfected patients. These results should be interpreted with caution, since registry data are collected retrospectively and bear a risk of incompleteness or inaccuracy."
9471,Highlights from the 20th ECCMID,
9472,News in brief,
9473,The dictionary of virology,
9474,Infectious disease surveillance update,
9475,Cumulative Keyword Index for Volumes 114-117,
9476,"SARS in context: memory, history, policy",
9477,ProMED Update,
9478,149* 2009 H1N1 influenza A in cystic fibrosis patients. A French collaborative study,
9479,Coping with pain: The impact of SARS visitation restrictions on patients' perception of nursing support,
9480,Virus detection made easy: Nanotechnology,
9481,SARS source back on the menu,
9482,PIV-28 Detection of respiratory viruses by molecular methods – a way of improving conventional diagnosis,
9483,Travel Medicine,
9484,"EPS4.4 Correlation between long-term changes in LCI, FEV(1) and CFCT score in children with cystic fibrosis",
9485,Middle East respiratory syndrome (MERS 2012): roles of clinical pathology laboratory for screening and diagnosis,
9486,Effective Intervention and Vaccination Strategies Against Nosocomial Infection Based on Network Analysis,
9487,A novel coronavirus emerges,
9488,"Root growth and cyclin control: Doerner, P., Jørgensen, J-E., You, R., Steppuhn, J. and Lamb, C. (1996) Control of root growth and development by cyclin expression, Nature 380, 520–523",
9489,Bayer molecular: viral load testing today and tomorrow,
9490,Peter Salama,
9491,Middle East respiratory syndrome coronavirus conference,
9492,"Pathogen identification in travelling patients with severe acute respiratory infections from the Middle East to the Philippines, 2014–2016",
9493,IF-01 Rapid and Sensitive Detection of Various Influenza Virus Subtypes Using SAT,
9494,Author index volume 7 international journal of infectious diseases,
9495,Association for Molecular Pathology 2006 Annual Meeting Abstracts,
9496,Infectious disease surveillance update,
9497,Herpes simplex (HSV) viral load in bronchoalveolar lavage: risk factors and clinical outcome,
9498,TOC,
9499,Respiratory Pathogen Evaluation for Lipschütz Ulcer,
9500,Contents-cover detailsi,
9501,Posters,
9502,K.01 Emerging viruses: From clinical virology to virus ecology,
9503,PIN12 - HOSPITALIZATIONS RELATED TO RESPIRATORY VIRAL INFECTIONS DURING THE 2017/18 SEASON IN THE VALENCIA REGION OF SPAIN,
9504,PP-182 Systematic study the clinic characters of a local measles outbreak in East China,
9505,"Hepatobiliary & Pancreatic Diseases International (HBPD Int). Table of Contents Vol. 4, No. 1, 2005",
9506,Subject index (vol. 90),
9507,THE RETROSPECTIVE ANALYSIS OF GLUCOCORTICOSTEROIDS USE IN THE TREATMENT OF SARS IN BEIJING,
9508,"Coronaviruses and their diseases. Advances in experimental medicine and biology, Volume 276: Edited by D. Cavanagh & T. D. K. Brown. New York and London: Plenum Press. 1990. 676 pp. US$155.40",
9509,FEBS Letters,
9510,Infection precautions,
9511,Comparison of enzyme-linked immunosorbent assay and western blotting in the detection of anticryptosporidial antibodies in the investigation of a waterborne outbreak of cryptosporidiosis,
9512,"List of Contents, Author, and Keyword Indices, Vol 29, 2005",
9513,Contents of Volume 143,
9514,"Asian–Oceanian textbook of radiology: By W. C. G. Peh and Y. Hiramatsu. Hardcover, 1300 pp. TTG Asia Media, Singapore, 2003. Price US$120, €98",
9515,Pyogranulomatous Pleuropneumonia and Mediastinitis in Ferrets Associated with Chryseomonas-like Bacteria,
9516,Exercise Limitation in Survivors of Severe Acute Respiratory Syndrome (SARS),
9517,Community-Acquired Respiratory Virus Infections During the First Year After Lung Transplantation,
9518,Keyword Index,
9519,Respiratory Infection Routes of MERS-CoV in Rabbits,
9520,P241 Validation of APPS tool to predict mortality in moderate and severe acute respiratory distress syndrome,
9521,Keyword Index,
9522,To Disclose the Anti-Infection/Inflammatory Mechanism of Terpenoids From Houttuynia Cordata in Virtue of Molecular Simulation,
9523,Contents of Volume 151,
9524,CHARACTERISTICS AND OUTCOMES AMONG PATIENTS WITH RESPIRATORY VIRUS INFECTIONS DURING THE FIRST YEAR AFTER LUNG TRANSPLANTATION,
9525,The veterinary formulary. Handbook of medicines used in veterinary practice: Edited by Yolande Debuf London: The Pharmaceutical Press. 1991. 448 pp. £37.50 (hard),
9526,Pulmonary Function in Survivors of Severe Acute Respiratory Syndrome (SARS),
9527,PULSED METHYLPREDNISOLONE USAGE IN ARDS DUE TO VIRAL PNEUMONIA,
9528,The Use of Drotrecogin Alfa (activated) in a Patient With Severe Acute Respiratory Syndrom,
9529,Binding and entry of animal viruses,"Viruses are infectious agents capable of packaging and delivering nucleic acids and proteins to specific populations of cells. To initiate infection, viruses bind to sites, or receptors, on the cell surface and transfer their genome across the limiting membrane of the cell. The mechanisms underlying these events, and viral tropism for particular host cells, are becoming increasingly well understood. Several cell surface proteins have now been identified as viral receptors, and analyses of intact virus particles and sub-viral components are revealing the structures of the binding determinants on the viruses themselves. For many viruses, the events leading to penetration and delivery involve constitutive endocytic properties of the host cell, and the low pH environment in endocytic compartments is a crucial trigger in the penetration process. The knowledge of viral tropism, binding and entry suggests strategies which may be applied to the design of targeted therapeutic agents with appropriate specificities and effective delivery mechanisms."
9530,"Techniques for the Brucellosis laboratory: G. G. Alton, L. M. Jones, R. D. Angus & J. M. Verger Versailles Cedex: INRA Publications. 1988. 192pp. Ff 195",
9531,The role of Cryptosporidium parvum-derived phospholipase in mediating enteric host cell invasion in vitro,
9532,Author index to volume 87,
9533,Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus That Caused It,
9534,Infection and immunity in farm animals: Edited by R. Pandey Basel: S. Karger. 1985. 255 pp. SFr. 164,
9535,Subject Index: TO FOLLOW,
9536,"SUBJECT INDEX Volume 125 (JANUARY–JUNE, 2004)",
9537,Imaging in SARS,
9538,Viral Infections and Inflammatory Bowel Disease,
9539,Master Author Index,
9540,"Contents and index of volume 113, July to November 1995",
9541,"Comparison of the Mortality Prediction of Different ICU Scoring Systems (APACHE II and III, SAPS II, and SOFA) in Acute Respiratory Distress Syndrome Patients",
9542,DASATINIB-RELATED CHYLOTHORAX,
9543,Cumulative subject index volumes 24–25,
9544,Enteric viral infection in patients with the acquired immunodeficiency syndrome: A case of diarrhea?,
9545,Liquid column chromatography,
9546,Animal health 1984—Report of the chief veterinary officer: London: HMSO. 159 pp. £9.30,
9547,Anaesthesia and Intensive Care A-Z–An Encyclopaedia of Principles and Practice,
9548,IMAGINATION OF THE IMAGES WHEN VIRUSES ATTACK THE LUNGS,
9549,Abstracts of Papers Submitted to the American Gastroenterological Association,
9550,High Dose Intravenous Methylprednisolone in the Treatment of Severe Acute Respiratory Syndrome: A Case Repor,
9551,Cell Tropism of Middle East Respiratory Syndrome Coronavirus in Experimentally Infected Dromedaries,
9552,Anesthesia and Uncommon Diseases,
9553,AGA abstracts T1786–W1189,
9554,Primum Non Nocere,
9555,Corrigendum to “Individual and common inhibitors of coronavirus and picornavirus main proteases” [FEBS Lett. 583 (2009) 549–555],
9556,Tissue Distribution of the Mers-Coronavirus Receptor in Bats,
9557,Evolution and tumor pathology of the neuroendocrine system. Fernström foundation series,
9558,Master Subject Index,
9559,The Novel Human Coronavirus EMC Causes Disease in Macaques but not in Ferrets,
9560,Campylobacter infection in man and animals,
9561,"Toxicological evaluation of certain veterinary drug residues in food: Prepared by The 36th Meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA). WHO food additive series: 27 Geneva: WHO 1211 Geneva 27, Switzerland/London: HMSO Books. 1991. 227 pp. Sw.fr. 25. (paper)",
9562,Effect of human recombinant interferon-γ on Salmonella typhimurium invasion in cultured human intestinal cells,
9563,Nonbacterial respiratory infections,
9564,An Uncommon Cause of Adult Respiratory Distress Syndrome,
9565,"Horses in health and disease: J. L. Naviaux Philadelphia: Lea and Febiger/Beckenham, Kent: Quest-Meridien Ltd. 1985. 300 pp. $27",
9566,"THE LONG-TERM IMPACT OF SEVERE ACUTE RESPIRATORY SYNDROME (SARS) ON PULMONARY FUNCTION, EXERCISE CAPACITY, AND QUALITY OF LIFE IN A COHORT OF SURVIVORS",
9567,The First Outbreak of Porcine Epidemic Diarrhoea in Slovenia: A Signal of Emerging Disease?,
9568,"Contents and index of volume 119, july to november 1998",
9569,Imaging in SARS,
9570,In Brief,
9571,Contents of volume 87,
9572,Contents of Volume 138,
9573,Bovine Histophilosis in Southern Brazil,
9574,Mers Coronavirus Infection in Dromedary Camels,
9575,Subject index to volume 104,
9576,Subject index to volume 87,
9577,Contents of Volumes 166 to 173,
9578,Virus diseases in laboratory and captive animals: Edited by Gholamreza Darai Dordrecht: Martinus Nijhoff/Kluwer Academic Publishers. 1988. 568 pp. £96.50,
9579,Cumulative subject index volumes 52–53,
9580,RARE CASE OF MORTALITY FROM NON-CIRRHOTIC HYPERAMMONEMIA,
9581,The EMPOWER-SUSTAIN e-Health Intervention to improve patient activation and self-management behaviours among individuals with Metabolic Syndrome in primary care: study protocol for a pilot randomised controlled trial,"BACKGROUND: Epidemiological studies conducted in various parts of the world have clearly demonstrated that metabolic syndrome (MetS) is an increasing global health problem, not only in Western societies but also in Asian populations. Web-based and mobile phone-based self-management applications have been proven to be effective in improving self-management behaviour of patients with MetS components (i.e., diabetes or hypertension). However, evidence is lacking in terms of their effectiveness specifically for patients with MetS. The aim of this pilot study is to evaluate the feasibility and potential effectiveness of the EMPOWER-SUSTAIN Self-Management e-Health Intervention in improving activation and self-management behaviours among patients with MetS. This paper presents the study protocol. METHODS: A pilot randomised controlled trial will be conducted in a university primary care clinic. A total of 232 patients aged 18–60 years with MetS will be recruited; 116 will be randomised to receive the EMPOWER-SUSTAIN intervention for 6 months, and another 116 patients will continue with usual care. The EMPOWER-SUSTAIN intervention is a multifaceted chronic disease management strategy based on the Chronic Care Model and persuasive technology theory. It consists of training primary care physicians, nurses and patients to use the EMPOWER-SUSTAIN web-based self-management mobile app, strengthening the patient–physician relationship and reinforcing the use of relevant clinical practice guidelines to guide management and prescribing. The primary outcome is the mean change in patient activation score using the Patient Activation Measure short form Malay version (PAM-13-M) questionnaire. The secondary outcomes include the changes in waist circumference, body mass index, blood pressure, patient physical activity level, eating behaviour, perception of chronic illness care, satisfaction with patient–physician interaction, and perceived absolute 10-year cardiovascular disease risk. Feasibility of implementing the intervention will be evaluated. This includes acceptability of the intervention, estimating the likely rate of participant recruitment and retention, appropriateness of the outcome measures, calculation of sample size, and the intervention’s potential effectiveness. CONCLUSION: To our knowledge, this is the first study in Malaysia that aims to determine the feasibility of a multifaceted e-health intervention, as well as to indicate more useful aspects of this intervention for further exploration in a larger trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04120779. Registered on 9 October 2019, protocol version 1."
9582,Contents of volume 301 (2005),
9583,adr-type hepatitis B virus surface antigen for vaccine production obtained by culture of human hepatoma cell strain huGK-14,
9584,"New dengue virus Type-1 strain; recombinant DEN1 protein expression; potential in recombinant vaccine construction, virus detection and dengue fever diagnosis and therapy",
9585,"Recombinant DNA encoding hepatitis B virus polypeptide antigen is used in detection of infection and in vaccine production; production in prokaryotic or eukaryotic host; core antigen, surface antigen DNA sequence",
9586,"Genetically engineered vaccines for mycobacterial antigens comprising recombinant poxvirus, e.g. vaccinia virus, capable of expressing Mycobacterium leprae, Mycobacterium tuberculosis or Mycobacterium bovis antigens",
9587,Bordetella bronchiseptica vaccine production by fermentation under specified conditions,
9588,¿Qué ha cambiado en la neumonía adquirida en la comunidad en los últimos años?,
9589,Issue TOC,
9590,JINF – Posters,
9591,Cumulative subject index volumes 168–173,
9592,"Ribavirine : au revoir VHC, bonjour VHE",
9593,"Subject index: Volume 32, 1999",
9594,Enteric viruses in a cohort of rural costa rican children(),
9595,Pathology of the Fischer Rat — Reference and Atlas,
9596,Isolated specific epitope region of thyroid peroxidase; for use as a recombinant vaccine in thyroid tumour or Hashimoto disease immunotherapy,
9597,Subject index for volume 190,
9598,Cumulative subject index volumes 69–75,
9599,Lead level in edible macromycetes in NW spain as biomarker in ecotoxicology,
9600,"Esophageal function after cardiomyotomy for achalasia in children: A. Koch, M. Bettex, H. Tschäppeler, et al. Z Kinderchir 38:206–210, (August), 1983",
9601,Canine parvovirus vaccine preparation by growth of CPV-HP stem on dog tumour fibroblasts or renal cells,
9602,"Pharyngitis: When is aggressive treatment warranted?: Bonilla JA, Bluestone CD. Postgrad Med 97:61, 1995",
9603,Feedback,
9604,"Vulnerability to Poverty in South-East Asia: Drivers, Measurement, Responses, and Policy Issues",
9605,Vaccine against feline infectious peritonitis virus is prepared from virus FIPV 79-1146 serially passaged in non-oncogenic cell until nonvirulent,
9606,Subject Index of Papers Published in Volume 60 of the Journal of the American Dairy Science Association,
9607,Author index volume 85 (1989),
9608,Allergie respiratoire,
9609,Vaccine against Schistosoma mansoni containing soluble antigen from larvae or adults,
9610,"Pulsed low-energy infrared laser irradiation of human dentin, a SEM study",
9611,Infections respiratoires basses de l'adulte: pneumonie communautaire et bronchite aiguë,
9612,"Feline T-cell lymphotropic lentivirus proteins; cat FIV virus used for the specific detection of FIV antibodies, production of antibodies and in vaccine; DNA sequence",
9613,"Acute and chronic sinusitis: Ferguson BJ. Postgrad Med 97:45, 1995",
9614,"Cumulative Index 1981, 1982, and 1983 Index",
9615,Information for authors,
9616,"New DNA sequences of Epstein-Barr virus genome useful in protein expression for viral antibody detection in blood serum, for vaccine production and as DNA probe",
9617,60 Seconds,
9618,Subject index for volume 77,
9619,Antitumour vaccine containing major histocompatibility complex protein for metastase control; application in cancer therapy,
9620,Transmissible gastroenteritis (TGE): prophilactice with live homo- and heterovaccines,
9621,Environmental contaminations and immunosupression,
9622,Subject index for volume 174,
9623,Information for authors,
9624,Subject index for volume 112,
9625,Binge watching isn't as bad as we thought,"It has been said that streaming 30 minutes of Netflix releases as much carbon as a short car ride, but this isn't true, says Michael Le Page"
9626,Detection of rotavirus and “corona-like virus” in stool samples of infected pigs by solid phase immune electron microscopy (spiem). Comparison of spiem with direct electron microscopy and enzymelinked immunosorbent assay (elisa),
9627,"Age and susceptibility to toxic substances: Calabrese, E. J. New York: John Wiley (1900)",
9628,Borrelia burgdorferi gene encoding conserved 79 kDa antigen: DNA probe or DNA primer and polymerase chain reaction for Lyme disease diagnosis and recombinant vaccine; monoclonal antibody production,
9629,Cumulative subject index volumes 174–179,
9630,"Herpes virus recombinant pox virus recombinant vaccine; recombinant vaccinia virus, canary-pox virus, fowl-pox virus construction by insertion of glycoprotein gene from foreign herpes virus, pseudorabies virus, Epstein-Barr virus or cytomegalovirus",
9631,"Interaction of mouse hepatitis virus 3 with Kupffer cells explanted from susceptible and resistant mouse strains. Antiviral activity, interleukin-1 synthesis","The genetic sensitivity of mouse strains to mouse hepatitis virus 3 (MHV 3) has been related in vitro to a delay of virus replication in liver sinusoidal cells. In vivo immuno-histochemical studies of the liver from infected mice have demonstrated that mechanisms other than direct viral injury are in operation. To examine potential mechanisms, the interaction of lipopolysaccharide (LPS)-stimulated Kupffer cells with MHV 3 was studied. We first observed a dramatic inhibition in viral replication in LPS-treated Kupffer cells explanted from A/J resistant mice. Second, we demonstrated that MHV 3 induced a dose-dependent interleukin 1 (IL-1) activity in the supernatants of infected Kupffer cells of both strains. These results led us finally to examine the antigen-proceesing function of the Kupffer cellsof both strains of mice. No striking differences were observed in the ability of Kupffer cells from resistant or sensitive mice to collaborate with immunocompetent lymphocytes. Our data suggest that Kupffer cells play a double role which is crucial in the pathogenesis of MHV 3-induced hepatitis. First, they act directly as the genetically determined sensitivity of mice to MHV 3 infection is correlated with the efficiency of the antiviral activity induced in Kupffer cells by LPS. Second, they act indirectly through the synthesis of different amounts of IL-1 induced by MHV 3. This hypothesis is further borne out by the effects of indomethacin treatment on the course of MHV 3 infection in A/J resistant mice in vivo."
9632,New protein comprising at least one hepatitis A virus epitope; capsid protein expression in vaccinia virus vector for use as recombinant vaccine,
9633,Announcement,
9634,Preparation of a helicase region coded by hepatitis C virus; hepatitis C virus recombinant helicase production via gene cloning and expression in Spodoptera frugiperda insect cell culture using baculovirus vector : Soyaku Eng. Res. Inst. Jpn 06319 583; 22 November 1994,
9635,Contents List,
9636,Production of polypeptide for vaccine against malaria by cultivation of Escherichia coli transformed with vector coding for repeat unit circumsporozoite protein of Plasmodium falciparum,
9637,Vaccine against varicella-zoster virus (causative agent of chicken pox) using a DNA segment encoding the protective immunogenic gB glycoproteins,
9638,Cumulative subject index volumes 76–83,
9639,"SARS, Greater China, and the Pathologies of Globalization and Transition",
9640,Contents index,
9641,"Molecular biology of microbial pathogenicity: Adhesion, invasion and receptors: 17–20 June 1985 Umeå, Sweden organised by: S. Normark, B.E. Uhlin and H. Wolf-Watz on behalf of the Swedish Society for Microbiology and the University of Umeå",
9642,Cumulative subject index volumes 162–167,
9643,Author index to volumes 296–307 (2005),
9644,"Necrotising enterocolitis in small bowel atresia: K. Lafferty, R. J. Brereton, and V. M. Wright Z Kinderchir 38:224–227, (August), 1983",
9645,Contents List,
9646,Next month's highlights,
9647,The legacy of BSE,We have to remain vigilant so we can act at the first sign of an emerging disease
9648,Eimeria acervulina antigen isolation and use as a vaccine against fowl coccidiosis (US Equivalent),
9649,Genetic reassortment of rotaviruses for production of vaccines and vaccine precursors,
9650,Keyword Index,
9651,EM diagnostic determination of faecal viruses: Comparison of the direct staining method and the ultracentrifugation concentration method,
9652,"Oral vaccine production by inactivating virus in the presence of protective compounds from the culture medium, adding further stabilizer and then freeze-drying",
9653,Deadly MERS virus could hold the key to its own cure,"Recreating a small part of the MERS virus, which has killed 76 people so far, could block it from infecting cells and spreading disease"
9654,Malaria vaccine peptide Plasmodium falciparum circumsporozoite protein gene cloning in vaccinia virus,
9655,Patent report,
9656,Vaccine for immunizing cattle against lungworm comprising live immunogenic attenuated Dictyocaulus viviparus third stage larvae,
9657,Production of a vaccine against rotavirus disease; live attenuated strain containing the fourth rotavirus gene associated with attenuation,
9658,"Antigen specific to non-A, non-B hepatitis virus: application for vaccine production",
9659,"Vaccine comprising anti-idiotype antibody conjugate; induces production of neutralizing antibody (human monoclonal antibody, chimeric antibody or FAb, F(Ab′) 2 or Fv fragment) against HIV virus-1",
9660,index mots clés 2004,
9661,"Gastric manometric abnormalities in patients with dyspeptic symptoms after fundoplication: V. Stanghellini and J. R. Malagelada. Gut 24:790–797, (September), 1983",
9662,"Update on antimicrobial resistance: mechanisms, methods and practice","Antimicrobial resistance is a major problem for hospitals and the community. This interactive session developed for trainees will explore current antimicrobial resistance issues pertinent to the laboratory, including detection and importance in determining mechanisms of resistance, screening, therapeutic implications and consequences for infection control. Four trainees will present illustrative cases of antimicrobial resistance (MRSA, VRE, multi-resistant Gram-negative organisms and Candida) followed by expert panel discussion. Dr John Merlino will deliver an update on hot topics in antimicrobial susceptibility testing and resistance in a ‘show and tell session’. Finally trainees and the expert panel will have an opportunity to discuss prepared questions on antimicrobial resistance issues."
9663,Subject index volumes 126–135 1990,
9664,New glutathione-S-transferase of Schistosoma mansoni; DNA sequence; site-directed mutagenesis and expression in Escherichia coli for use as recombinant vaccine or in therapy of schistosomiasis,
9665,Subject index for volume 176,
9666,60 Seconds,
9667,Index des matieres 1980,
9668,New human recombinant cytomegalo virus containing foreign gene: DNA sequence encoding HIV virus antisense mRNA or malarial surface antigen,
9669,Keyword index to volumes 296–307 (2005),
9670,B-02 Efficacité en situation réelle de la stratégie thérapeutique initiale dans l’exacerbation aiguë de la bronchite chronique (EABC) en France,"INTRODUCTION ET OBJECTIFS: Évaluer l’efficacité de la stratégie thérapeutique dans la prise en charge de l’EABC en pratique courante. MATÉRIELS ET MÉTHODES: Cohorte prospective observationnelle auprès d’un échantillon aléatoire de médecins généralistes (MG) et pneumologues libéraux. L’efficacité était évaluée par le % de patients sans nouvelle consultation pour EABC à 3 mois. Le modèle de Cox a été utilisé pour la recherche de facteurs pronostiques. RÉSULTATS: 951 mg et 89 pneumologues ont inclus 4 994 patients. L’âge moyen était de 64,4 ans, avec 61,4 % d’hommes, 38,7 % d’anciens fumeurs, 35,7 % de fumeurs actuels. 2 ou 3 critères d’Anthonisen dont une expectoration muco-purulente étaient retrouvés chez 71,8 % des patients, 2 ou 3 critères hors expectoration mucopurulente chez 12,8 % et < 2 critères chez 15,4 %. Prescriptions : antibiothérapie (AB) à 91,9 % des patients, corticoïdes systémiques (41,5 %), mucolytiques (41,0 %) et bronchodilatateurs beta2-adrénergiques (30,7 %). L’absence d’une nouvelle consultation pour EABC à 3 mois concerne 63,8 % des patients. L’AB réduit le risque de survenue d’une nouvelle consultation (RR [IC 95 %] = 0,35 [0,13 ; 0,94]) chez les fumeurs actuels ayant au moins 2 critères dont une expectoration mucopurulente. Une corticothérapie systémique augmente le risque chez les patients ayant au moins 2 critères d’Anthonisen dont l’expectoration muco-purulente (1,16 [1,03 ; 1,30]) et chez les patients ayant deux critères d’Anthonisen hors expectoration muco-purulente ou moins de 2 critères (1,29 [1,06 ; 1,57]). CONCLUSION: Chez les fumeurs actuels ayant au moins deux critères d’Anthonisen dont l’expectoration muco-purulente, l’AB réduit de 65 % le risque de nouvelle consultation. La corticothérapie par voie générale augmente ce risque de 16 % à 29 % selon le groupe de patients."
9671,"Sonographic diagnosis of intussusception in childhood: E. Dinkel, M. Dittrich, G. Pistor, et al. Z Kinderchir 38:220–223, (August), 1983",
9672,Subject index for volume 182(),
9673,Preparation of cholera toxin subunit-B for use in vaccine preparation,
9674,VIRO-01 - Intérêt du test de diagnostic des virus respiratoires par PCR multiplex.,
9675,Chinese illness caused by a virus,
9676,Nematode protein complex; Haemonchus contortus immunogen and anthelmintic agent; protein sequence; recombinant vaccine production,
9677,Peptide capable of binding rubella immunoglobulin useful for rubella diagnosis and vaccine production; expression in Escherichia coli,
9678,"Monoclonal antibody recognizing nucleic acid bases — useful for DNA sequencing, e.g. vaccine quality control",
9679,Oral vaccine for prophylaxis of periodontitis using the whole cell pilus or extract of Bacterioides gingivalis etc.,
9680,Antigen composition comprising PEB1 and/or PEB3 antigen from Campylobacter jejuni; useful as vaccine and for diagnosis of C. jejuni and Campylobacter coli infections,
9681,"Orifice of ampulla of vater in duodenal web: M. Suga, K. Morita, I. Okabe, et al. J Jap Soc Pediatr Surg 19:919–923, (August), 1983",
9682,Combined enzyme-histochemistry and X-ray microanalysis on iron-containing organelles in hepatocytes of patients with hemosiderosis,
9683,"Vaccine for preventing or treating T-cell mediated pathology; comprises an effective amount of a T-lymphocyte receptor and a pharmaceutical medium; application in rheumatoid arthritis, multiple sclerosis therapy, diagnosis, prevention",
9684,Cumulative subject index volumes 186–191,
9685,Graphical abstracts,
9686,Effect of atrazine on glucocorticoid receptor binding in rat,
9687,"Recombinant pox virus expressing pseudorabies virus antigens used as live vaccines, for producing subunit vaccine and for diagnosis",
9688,Volume 22 Subject Index,
9689,Cumulative subject index volumes 148–155(),
9690,Envelope region nucleic acid fragment of type-C hepatitis virus and its detection; diagnosis using hepatitic C virus DNA probe or RNA probe; DNA sequence; potential recombinant vaccine preparation,
9691,Synthesis of dimeric Lex or difucosyl Y2 cancer antigen; useful as antitumor vaccine and to subside inflammatory processes of rheumatoid arthritis; preparation using α 1–3-fucosyltransferase,
9692,"Involvement of (Na(+) + K(+))-ATPase in binding and actions of palytoxin on human erythrocytes: Böttinger, H., Béress, L. and Habermann, E. (Buchheim-Institut Für Pharmakologie, Justus-Liebig-Universität Giessen, Frankfurter Strasse 107, D-6300 Giessen, F.R.G.) Biochim. biophys. Acta861, 165–176. (1986).",
9693,Subject index for volume 188,
9694,Subject index for volume 165,
9695,New avirulent Salmonella-Escherichia coli hybrid strains useful in live oral vaccine against enteric diseases including cholera,
9696,Subject index for volume 116,
9697,"Interpretive Summaries, March 2020",
9698,Cumulative subject index,
9699,"Gene encoding H-protein of sclerosing-panencephalitis virus, a potential vaccine",
9700,"Feline infectious-peritonitis virus vaccine; produced by serial passage in non-oncogenic e.g. FCWF, CrFK cell culture",
9701,Subject index for volume 128,
9702,Subject index*(),
9703,Viruses from animals,Infections that cross over from other species are a deadly problem
9704,Subject index for volume 175,
9705,"Vaccine comprising live attenuated or inactivated rotavirus strains; HRV 89-12C2, HRV 408, HRV 248 HRV 456 and/or CJN, for immunization against rotavirus illnesses",
9706,Appendixes,
9707,"Emerging viral illnesses – preparedness, testing and assuring safety",
9708,Vaccine against transmissible-gastroenteritis virus of pigs; antigen from non-pathogenic pig respiratory-corona virus,
9709,Peptide fragments immunoreactive with HTLV-III virus (HIV virus) antibody obtained by expressing cloned fragmented HTLV-II provirus nucleotide sequences; vaccine production etc.,
9710,The past and present of malaria diagnosis,"Within 30 years of Laveran’s discovery of human malaria parasites in 1880, four species, Plasmodium falciparum, P. vivax, P. malar-iae and P. ovale, had been described and their morphological distinguishing features clarified. Although other diagnostic techniques have been developed, 130 years later the gold standard is still examination of thick and thin blood films. Recently a fifth species, the monkey malaria Plasmodium knowlesi, has been found to infect humans in parts of Southeast Asia. With human activities continuing to impinge on the habitats of other primates, it is possible that other malaria species may cross over to humans as well."
9711,"Reduction rhinoplasty and nasal patency: Change in the cross-sectional area of the nose evaluated by acoustic rhinometry: Grymer LF. Laryngoscope 105:429, 1995",
9712,60 Seconds,
9713,Enhanced quinone-induced oxidative stress in erythrocytes of thalassemic patients,
9714,Canine corona virus vaccine production by infected cell culture; effective against dog corona virus and dog parvo virus infection,
9715,Feline T-lymphotropic lentivirus (FTLV); separated from cell culture and useful as vaccine; hybridoma construction and monoclonal antibody preparation for use in immunoassay; DNA probe construction; and HIV virus model system,
9716,Subject index for volume 114(),
9717,Cytotoxic activity in culture filtrates from the entomopathogenic fungus Beauveria sulfurescens,"The hyphomycete fungus Beauveria sulfurescens secretes into the culture medium several components toxic for Galleria mellonella larvae. Concentrated and dialyzed (cutoff 12,000) B. sulfurescens culture filtrate also contains a highmolecular-weight compound cytotoxic for the Mamestra brassicae cell line. A fractionation in two chromatographic steps separated a cytotoxic fraction (IC(50)= 1.15 ± 0.05 μg/ ml), which was poorly toxic to larvae (LC(50) = 150 ± 10 μg/ ml) and an insecticidal fraction (LC(50) = 2.1 ± 0.1 μg/ml) devoid of detectable cytotoxicity. The two kinds of activity, i.e., cytotoxicity in vitroand toxicity in vivo are thus independent. The cytotoxic activity, initially detected on a M. brassicae cell line, also affected two other insect cell lines (G. mellonella and Spodoptera frugiperda). The cytotoxic fraction provoked not only the inhibition of cell proliferation, but also cell death. Adhesive mammalian cell lines were not sensitive. Nonadhesive mammalian cell lines of murine myeloma and hybridomas were poorly sensitive."
9718,Identification of a pro-inhibitory region on the surface of human CYP1A2,
9719,"Antiviral Therapy: Respiratory Infections, Genital Herpes, and Herpetic Keratitis",
9720,"Advances in Penicillium and Aspergillus systematics: Samson, R. A. and Pitt, J. I. (Eds) Proceedings of the First International Penicillium and Aspergillus Workshop, 6 – 10 May 1985, Amsterdam (NATO Advanced Science Institute - ASI - Series, Series A: Life Sciences, Vol. 102), X + 483 pp. ISBN 0-306-42222-0. New York: Plenum Press. (1985)",
9721,Peptides from merozoite stage of malaria parasite and DNA sequence encoding them; Plasmodium falciparum merozoite thrombospondin-related anonymous protein expression in Spodoptera frugiperda insect cell transformed with nuclear-polyhedrosis virus vector; vaccine,
9722,Aspects infectieux de la diarrhée aiguë de l'enfant en France : Pourquoi ce sujet en 1991 ?(),
9723,Inactivated canine coronavirus vaccine,
9724,Subject index for volume 186,
9725,Authors response to Influence of country of study on student responsiveness to the H1N1 pandemic,
9726,"Ringworm vaccine; containing antigen from e.g. Microsporum canis, Microsporum gypsum or Trichophyton mentagrophytes",
9727,Keywords index,
9728,Working hypothesis,Sorting the week's supernovae from the absolute zeros
9729,"New epitope-bearing portions of Entamoeba histolytica; recombinant non-glycosylated epitope production and expression in prokaryote host cell, for application in a recombinant vaccine : Univ. Virginia Pat. Found. World 9500 849; 5 January 1995",
9730,Subject index for volume 166,
9731,"Hepatitis C virus asialoglycoprotein-E1 and -E2; useful as vaccine or for diagnosis of non-A non-B hepatitis virus infection, or for concentrating or reducing HCV proteins in biological samples, and obtained by gene expression in yeast",
9732,January highlights,
9733,"Recombinant feline corona virus-S protein; expressed as galactokinase fusion protein and useful as reconbinant vaccine, therapeutic and diagnostic agents for feline-infectious-peritonitis virus",
9734,"Mucocele of the pteryomaxillary space: Stack BC, Klotch DW. Ann Otol Rhinol Laryngol 104:246, 1995",
9735,Un cinquantenaire : La mort de charles nicolle et le “destin des maladies infectieuses”,
9736,Recombinant pox virus containing Morbilli virus DNA; expression of e.g. measles virus haemagglutinin glycoprotein in host for construction of a potential recombinant vaccine against dog distemper virus,
9737,Recombinant Pseudomonas exotoxin produced by cloning of Pseudomonas aeruginosa DNA in Escherichia coli having low toxicity to human or mice cells but retaining enzymatic activity giving cell-specific immunotoxin; vaccine application,
9738,"Mengo virus as a vector for expression of foreign polypeptides; hepatitis A virus, HIV virus, rabies virus, foot-and-mouth-disease virus, coronat virus, Rous sarcoma virus, herpes virus, etc., live attenuated recombinant vaccine : Inst. Pasteur Paris World 9429 472; 22 December 1994",
9739,Complex virus promoter; complex pox virus promoter construct; recombinant vaccinia virus construction,
9740,Threatwatch: Is the MERS virus spreading its wings?,"The Philippines and Malaysia have identified their first ever MERS cases, while infections in Saudi Arabia surge, particularly among health workers"
9741,Contents of volume 296 (2005),
9742,Intestinal protection against challenge with transmissible gastroenteritis virus of pigs immune after infection with the porcine respiratory coronavirus,
9743,"Necrotizing enterocolitis in full-term newborns: E. de Gamarra, P. Helardot, G. Moriette, et al. Biol Neonate 44:185–192, (September), 1983",
9744,Synthetic peptide antigen corresponding to the major sites of T-lymphocyte recognition within the HIV virus envelope protein: recombinant vaccine production,
9745,New gene fragment encoding rabies virus glycoprotein; DNA sequence expression in eukaryote cell culture and application to recombinant vaccine construction,
9746,index mots clés,
9747,Studies on immune responses and interference of oral polio vaccine (OPV) on seroconversion to rotavirus vaccine,
9748,Erratum to “Epitope mapping and biological function analysis of antibodies produced by immunization of mice with an inactivated Chinese isolate of severe acute respiratory syndrome-associated coronavirus (SARS-CoV)” [Virology 334 (2005) 134–143],
9749,Vient de paraître,
9750,"309 Quantitative tests (QLFTS) detect impaired hepatic function in a high proportion of chronic hepatitis C patients with fibrosis or compensated cirrhosis and may predict risk of cirrhosis, splenomegally, and varices",
9751,Subject index for volume 177,
9752,Vaccine for swine trichinosis comprising inert newborn Trichinella spiralis newborn larvae emulsified with an adjuvant,
9753,"Molecular organization of positive-strand RNA viruses: 24–26 June, 1985 Cambridge, England organised by: D.J. Rowlands (Wellcome Biotechnology Ltd.), M.A. Mayo (Scottish Crop Research Institute) and B.W.J. Mahy (Animal Virus Research Institute) on behalf of the Virus Group of the Society for General Microbiology",
9754,An attempt at measuring health in nucleus and multiplier pig farms,"A pilot epidemiological inquiry was undertaken in France in a group of 205 nucleus and multiplier pig farms. The aim was to find out a method for a quantitative evaluation of the health level in farms selling young breeders. An exhaustive protocol was prepared for data collection. The sources of information were clinical inspections on the farms, meat inspection data at slaughter and laboratory investigations. Data processing issued in the selection of a profile made of 14 prevailing health indicators. These were then associated so as to set up a health index with an overall score. In a second phase, the relevance of the method with respect to disease transmission was assessed. The principle was a contact challenge within totally controlled facilities between SPF pigs hysterectomy-derived and gilts taken from farms with different health scores as previously checked. The contact lasted for 28 days. Eleven farms were chosen and in every one of them 7 gilts were sampled and 10 SPF pigs were assigned to each of these farms. All the pigs were submitted to a detailed observation. At the end of it the pigs were euthanized at the laboratory and checked to find out any lesions and infectious agents. A wide range of symptoms appeared among the SPF pigs. Mortality rate was 14.6%. Pneumonia affected 23.7% of them. A relationship was found between the germ transfer and the severity of the troubles. The degree of illness in SPF pigs was clearly related to the score obtained previously in the corresponding farms. Consequently, the method was considered as valid with respect to health evaluation."
9755,Subject index for volume 151,
9756,Methods in Cartilage Research,
9757,2007 Subject index,
9758,Que reste-t-il de la pathologie liée au VIH ?,
9759,Vaccine containing cattle papilloma virus-2 and/or cattle papilloma virus-4 L2 protein; for use as recombinant vaccine or in tumour therapy,
9760,Subject index for volume 130,
9761,Serial killers,
9762,Volume 63 - 2007,
9763,Volume 23 (2005) Subject Index,
9764,Natural infection with bovine virus diarrhoea virus in a dairy herd: A spectrum of symptoms including early reproductive failure and retained placenta,"The consequences of natural infections by bovine virus diarrhoea virus (BVDV) in a dairy herd comprising approximately 60 cows were studied over a 3 year period. The outcome of 39 pregnancies after artificial insemination or natural service during a 4 month period of risk for contracting BVDV was nine abortions, one mummified foetus, one still-birth, three calves that died within 1 week of age, 12 calves persistently infected (PI) with BVDV (11 males and one female) and 13 non-PI calves. Retrospective studies showed that only two of the 13 dams (15.4%) of non-PI calves had been inseminated once, which is a significantly (P < 0.001) lower rate than for 192 other gestations (66.7%) during the 3 year period. The gestational duration of multiparous cows (but not of heifers) was longer (P < 0.01) for five cows with PI calves (mean ± SD 287.6 ± 9.5 days) than for 53 other gestations in 35 cows (280.6 ± 3.8 days). Five of the 12 dams of the PI calves had not expelled the foetal membranes within 2 days after calving, which is a higher (P < 0.001) incidence than the seven cases of retained placenta observed after 198 other calvings. Furthermore, there was a 4.4-fold higher risk (P < 0.01) of treatment for enteritis and/or pneumonia in calves and a 6.0-fold higher risk of calf mortality associated with the introduction of BVDV. The mean heart girth of the PI calves was less (P < 0.05) than that of non-PI calves, at both 80 and 180 days of age."
9765,Controverse : pour ou contre la PCR multiplexe dans les infections respiratoires,
9766,Announcement,
9767,Pathogen strain Borrelia burgdorferi ZS7 (DSM 5527); for the production of passive antibodies for the treatment of Lyme disease : Max Planck Soc; German Cancer Res. Inst. Eur 633 313; 11 January 1995,
9768,AIDS recombinant vaccine; recombinant HIV virus core protein cloning in vaccinia virus vector,
9769,Subject index for volume 180,
9770,Inactivated poultry plague vaccine from virus Newcastle disease culture in incubated hen egg,
9771,"Severity of rotavirus infection in relation to serotype, monotype and electropherotype",
9772,Pilgrims warned of MERS,
9773,Inactivated pigeon herpes virus vaccine from chicken fibroblast cell culture,
9774,"New vaccine against infectious viruses — e.g. feline infectious-peritonitis virus, providing cell-mediated immunity",
9775,"Interpretive Summaries, April 2010",
9776,Cumulative subject index volumes 92–99(),
9777,"Diphtheria recombinant vaccine; comprises Corynebacterium diphtheriae toxin-A fragment mutein, Gly158 DT-A, which is enzymatically inactive; DNA sequence",
9778,"Protecting against Bordetella pertussis or Bordetella bronchiseptica using native, recombinant vaccine consisting of 69 kDa outer membrane protein or filamentous hemagglutinin protein purified from B. pertussis, Bordetella parapertussis or B. bronchiseptica",
9779,"New recombinant adenovirus used as vaccine; dog adenovirus-2 vector; dog parvovirus, cat panleukopenia virus, cat or dog coronavirus, dog distemper virus, cat leukemia virus, rabies virus or FIV virus recombinant vaccine construction",
9780,Influenza virus inactivated vaccine for pig: virus culture in embryonated egg allantoin and preparation,
9781,Medical progress: recent progress in poliomyelitis research,
9782,Issue TOC,
9783,Keyword index to volumes 284-295 (2004),
9784,Cumulative subject index volumes 180–185,
9785,"Deactivated triple vaccine for abortus fever, Ibaraki disease and Akabane disease produced by incubation of the viruses in cell culture",
9786,Subject index for volume 78(),
9787,Protein homologous to Trypanosoma cruzi heat shock protein; used in vaccine and diagnosis of e.g. Mycoplasma or Mycobacterium,
9788,I16 Hemophilia,
9789,"Total volvulus with complete necrosis of the small bowel and pseudocystic tumor: K. J. Neis and H. Seeliger Z Kinderchir 38:249–252, (August), 1983",
9790,60 Seconds,
9791,Cumulative subject index volumes 156–161,
9792,"Pertussis: 22–24 April 1985 Potsdam, GDR. Postponed",
9793,Parasitic nematode vaccine for human and animal protection fusion protein expression,
9794,Advances in Nutrition and Management of Calves and Heifers,"Strides have been significant in the knowledge of calf and heifer rearing during the last 25 yr. Much information has been gathered on digestive enzymes, development of the digestive system, and metabolism. Investigations have clarified further the role of colostrum in immunity and nutrition of the young calf. Several sources of nutrients have been tested for their suitability in formulation of acceptable milk replacers and calf starters. Once-a-day feeding of milk, colostrum, or milk replacer and early weaning are practical management procedures. Labor and cost efficient methods of feeding and caring for young calves have developed. Extensive work on rearing rates and methods of rearing was published during these 25 yr. Successful schemes have evolved for feeding heifers to freshen at an optimal age and to occupy a respectful position in the milking line. Developments in housing have been phenomenal – from the calf hutch to environmentally controlled nurseries for calves. Heifer housing has ranged from relatively simple, but labor-efficient housing, to complete confinement systems. Herd health programs have developed to minimize many disease problems that can be particularly disastrous in large herds. Contract rearing of herd replacements has become a more frequently chosen option in this period. Budgets for rearing calves from birth to freshening have appeared in recommendations for raising heifers."
9795,INF-04 Nouvelles Infections : Gestion Pratique D'Une Épidémie Dans Un Service D'Infectiologie,
9796,Polypeptide derived from Plasmodium falciparum antigen GLURP; vector plasmid pRD15 expression in Escherichia coli or Bacillus subtilis; recombinant vaccine construction and malaria therapy; monoclonal antibody and hybridoma preparation,
9797,Wuhan virus spreads,"We now know the virus responsible for deaths and infections in China can pass between people, reports Jessica Hamzelou"
9798,Canine coronavirus vaccine,
9799,New nucleic acid encoding E2 protein of canine corona virus; dog corona virus recombinant E2 protein production; may be used in recombinant vaccine production,
9800,Plasmodium Duffy receptor protein; Plasmodium knowlesi or Plasmodium vivax gene cloning and expression; potential recombinant vaccine against malaria; DNA sequence,
9801,Generic names of viruses of vertebrates,
9802,Author index(),
9803,Volume 59 of the Journal by the American Dairy Science Association,
9804,Information for authors,
9805,Multivalent pneumococcal vaccine and its preparation from polysaccharide purified from Pneumococcus,
9806,"Candida guilliermondii immunobiological composition production by aerobic cultivation of the organism and extraction, used for diagnosis prophylaxis and treatment of infections, and as vaccine",
9807,"Heterologous virus peptide immunogen production: recombinant vaccine production in L-cell, Chinese hamster ovary, C127 cell culture",
9808,Bioterrorism: introduction,
9809,Nucleic acid encoding a T4 glycoprotein used for treatment of AIDS and producing antibodies for use as a vaccine for immunization against AIDS,
9810,Superoxide dismutase and catalase in ethanol treated rats,
9811,Strain-independent inactivated influenza vaccine production by removal of the hemagglutinin heavy HA1 chain,
9812,PhoE protein with an inserted antigenic determinant — at a region localized at Enterobacteriaceae cell surface for production of vaccine and diagnosis purposes,
9813,Live or inactivated canine coronavirus vaccine; new antigen dog coronavirus isolate,
9814,Prevention of Common Colds by Hydrotherapy: A Controlled Long-term Prospective Study,"In a search for an effective prophylaxis against common colds, 25 volunteers were treated regularly with a standardised hydrotherapy programme for half a year, while 25 matched untreated persons served as controls. The frequency, duration and strength of colds were recorded. Results show that there is a significant reduction in frequency of colds in the treated group. Similarly, this group seemed also to be affected less severely. The duration of common colds was shorter in the treated group which, however, failed to reach the level of significance. The prophylactic effects took about three months to become apparent. The underlying mechanism, by which the effect is mediated, is speculative at present. It is suggested that regular hydrotherapy represents an effective prophylaxis against common colds."
9815,New canine parvo virus strain 154 and use in vaccine effective in young animals in the presence of maternal antibodies,
9816,60 Seconds,
9817,Subject index for volume 183(),
9818,"Nucleic acid constructs, malaria polypeptides and vaccines; recombinant malaria serine-repeat antigen production in yeast for the construction of a recombinant vaccine",
9819,B-01 Évaluation des Pratiques Professionnelles (EPP) et Tableau de Bord (TB) : exemple du Traitement des Pneumonies Aigues Communautaires (PAC),"INTRODUCTION ET OBJECTIFS: L’EPP vise à améliorer nos pratiques médicales. Elle comporte 3 phases : la mise en évidence de dysfonctionnements, la proposition de mesures correctives puis l’évaluation des ajustements induits. L’EPP est difficile sans outil pertinent. Notre objectif est d’illustrer l’intérêt d’un TB pour réaliser une EPP. MATÉRIELS ET MÉTHODES: Notre TB existe depuis Juillet 2005, incluant 24 paramètres dont le diagnostic, l’antibiothérapie et la date d’hospitalisation. Lors de la 1(re) phase d’EPP, le TB a été utilisé pour étudier les modalités thérapeutiques des PAC, révélant une hétérogénéité d’antibiothérapie non justifiée (Med Mal Inf 2008;9:457-64). La 2(e) phase a consisté en l’écriture de notre protocole thérapeutique, visant à réduire les prescriptions de fluoroquinolones (FQ) et de céphalosporines de 3(e) génération (C3G). Nous rapportons ici la 3(e) phase d’EPP, utilisant le TB pour comparer l’application du protocole sur 2 périodes : avant (d’octobre à janvier 2005 et 2006) et après (d’octobre 2008 au 20 février 2009) sa mise en place. L’utilisation de plusieurs lignes thérapeutiques, suggérant l’inadéquation de l’antibiothérapie initiale, a été répertoriée. RÉSULTATS: Les PAC représentaient 178 hospitalisations avant l’application du protocole, et 81 après. Le taux de conformité avec le protocole était respectivement de 101/178 (57 %), et de 52/81 (64 %). Le nombre d’antibiothérapies contenant des FQ et/ou des C3G de manière inadéquate était de 45/178 (25 %) durant la première période, et de 19/81 (23 %) durant la seconde période. Plusieurs lignes thérapeutiques étaient utilisées 28/178 fois (16 %) et 12/81 fois (15 %). La durée d’hospitalisation était respectivement de 9 ± 5 et 8 ± 5 jours, une évolution défavorable étant observée dans 8/178 (5 %) et 1/81 cas (1,2 %). CONCLUSION: Un TB permet l’exécution rapide de 2 des 3 phases de l’EPP. Nos résultats suggèrent une appropriation partielle de notre protocole, la réduction des FQ et des C3G apparaissant sans impact sur la morbi-mortalité."
9820,A trial of the immunogenicity of inactivated hepatitis A vaccine administered with immune serum globulin,
9821,"Comparison of cytopathogenicity, immunofluorescence and In situ DNA hybridization as methods for the detection of adenoviruses","Three different methods were compared for their efficiency at detection of adenoviruses. The samples examined for viral analysis consisted of concentrates prepared from raw sewage, chosen as providing a representation of the spectrum of viruses being intestinally shed from a large population at any given time. When using one single cell line, HEp-2, the overall numbers of adenoviruses detected using cytopathogenicity and immunofluorescence were roughly equal. In situ hybridization was approx. 40% more sensitive than either of these other methods as determined by average virus titers for the different samples, and also proved to be better by means of a nonparametric comparison. The 293 cell line was approx. 5 times more sensitive for detecting adenoviruses by cytopathogenicity as compared with the HEp-2 cell line, but proved unsuitable in our hands for quantitatively detecting indigenous adenoviruses by immunofluorescence. The relative number of indigenous adenoviruses present in the sewage concentrates we examined was, on average, 94-fold greater than that of enteroviruses. Assay of enteroviruses was performed by plaque assay in the BGM cell line."
9822,Bordetella pertussis coding sequences used for producing polypeptides that retain immunogenicity but lack virulence for vaccine production,
9823,Immunologically active parvovirus B19 peptide; comprises capsid protein VP1 or VP2 fragment; application to recombinant vaccine construction and disease diagnosis; protein sequence,
9824,Rhinopharyngite aiguë,
9825,Vaccine for use in cases of sheep foot-rot comprising at least one protease of Bacteroides nodosus,
9826,Non-infective structural particle preparation containing flavivirus surface antigen protein; Japanese-encephalitis virus cDNA gene cloning in dengue virus-2-preinfected cell with a vaccinia virus vector and use of a non-infective structural particle as recombinant vaccine,
9827,Subject index for volume 134,
9828,Patent report,
9829,Working hypothesis,Sorting the week's supernovae from the absolute zeros
9830,Universal coronavirus vaccine; spike protein cloning and expression for use as a recombinant vaccine,
9831,Index des mots clés,
9832,Subject index for volume 169,
9833,Cumulative subject index volumes 132–139(),
9834,"Complications of viral and mycoplasmal infections in rodents to toxicology research and testing. Chemical Industry Institute of Toxicology Series: Hamm, T. E. London: Hemisphere. (1986)",
9835,"Antigens of Cysticercus cellulosae; used for antibody production, treatment of neurocysticercosis, diagnosis or vaccine production",
9836,Erratum,
9837,Síndrome respiratorio agudo severo en la UCI,
9838,Peptide blocking the binding of P. aeruginosa to buccal epithelial cells; Pseudomonas aeruginosa recombinant epitope peptide production for use as recombinant vaccine and as adjuvant in lung cancer therapy,
9839,Thème : Infections virales,
9840,Answer to Picture Quiz,
9841,"Tourism in China: A. Lew, L. Yu, J. Ap and Z. Guangrui (Eds.); The Haworth Hospitality Press, New York, 2003, pp. 325, (softback), ISBN: 0789012820",
9842,Técnicas microbiológicas en el estudio de las infecciones pulmonares en el paciente con SIDA,
9843,Subject index for volume 108,
9844,One slip up from a worldwide pandemic,"Do the risks of a lethal flu virus escaping the lab outweigh the benefits of the research, ask Peter Aldhous and Debora MacKenzie"
9845,Suppression of nonsense codon or frameshift mutation especially useful in vaccine production,
9846,60 Seconds,
9847,Cumulative subject index for volumes 108–115,
9848,Novel strain of influenza virus is useful in inactivated vaccine production,
9849,"Chronic intestinal pseudo-obstruction in children: W. Yanxia. Chin J Pediatr Surg 3:21–23, (March), 1982",
9850,"New peptides with immunological properties of HIV-2 envelope protein with the structure of simian immune deficiency virus proteins, useful in dignosis and as vaccine components",
9851,Subject index for volume 110,
9852,cDNA clone of non-A non-B hepatitis virus (NANB) post transfusion and its use — DNA sequence; potential application as recombinant vaccine; DNA probe application in disease diagnosis,
9853,"Endoscopic intranasal frontal sinusotomy: Har-El G, Lucente F. Laryngoscope 105:440, 1995",
9854,"Emerging viral illnesses – preparedness, testing and assuring safety",
9855,Subject index for volume 157,
9856,INF-01 Les Isolements : Actualites Et Perspectives,
9857,"Transgenic plant expressing antigen of pathogenic organism; e.g. using Escherichia coli or Streptococcus mutans, used for oral immunization to inhibit colonization or invasion by pathogens",
9858,"Cumulative Index: 1980, 1981, and 1982",
9859,Mitteilungen des Berufsverbandes der Deutschen Radiologen,
9860,Continuing Education and Meeting Calendar,
9861,"Now, more than ever, our community is needed: spinal cord injury care during a global pandemic",
9862,What is acute gastro-enteritis in young children?,
9863,Why Can't We Just Use PCR? The Role of Genotypic versus Phenotypic Testing for Antimicrobial Resistance Testing,"There is a need for phenotypic susceptibility testing that is expeditious and that can be performed directly from clinical specimens. While rapid pathogen identification is important, it is the susceptibility result that is essential for antimicrobial optimization. The options for rapid susceptibility testing are limited, with the majority of commercial tests available offering genotypic resistance detection only. In this article, a laboratorian and a clinician discuss the benefits and limitations of genotypic and phenotypic susceptibility testing and provide examples of how results should be interpreted to maximize the clinical utility."
9864,"On vous demande, sachez répondre",
9865,Coronavirus NL63 Illnesses in Infancy are a Risk Factor for Asthma at Age Six,
9866,Effect of farming environment on atopic diseases in mongolia(),
9867,Lung Features of Infection with Corona Virus in Wistar Rats,
9868,Effect Of Tobacco Smoke And Respiratory Virus Infection In Preschool-aged Children,
9869,"Contents of volumes 263, 264, 266–289",
9870,Analysis of the complete genome sequences of human rhinovirus,
9871,Respiratory Virus Detection in Nasal Lavage Fluid of Chronic Rhinosinusitis Patients During Acute Exacerbations,
9872,"Airway function during mild viral respiratory illnesses. The effect of rhinovirus infection in cigarette smokers: Fridy, W. W., Jr., Ingram, R. H., Jr. Heihdser, J. C., and Coleman, M. T.: Ann. Intern. Med. 80: 150, 1974",
9873,Scientific Abstract Sessions,
9874,Age-related maturation of the nasal immune system in children(),
9875,Viral Detection and Cytokine Profile in Early Transient Wheeze and Childhood Asthma,
9876,"1. Decreased urinary cyclic 3′,5′-vdenosine manophosphate (CAMPY after epinephrine? in asthmatic patients",
9877,Does the immune response to cat among children living with a cat influence the prevalence of IgE to dog and birch?(),
9878,Viral Etiology and Rhinovirus Serotypes of Recurrent Respiratory Illnesses during Infancy,
9879,Viral infections in relation to age and the atopic status of children hospitalized for wheezing(),
9880,Author Index to Volume 67,
9881,The contributions of allergic sensitization and respiratory pathogens to asthma inception,
9882,Viral Detection and Rhinovirus Strain Identification among Asthmatic Children During Peak Times of Asthma Exacerbations,
9883,Allergy is a negative prognostic factor for the outcome after sinus surgery(),
9884,Paradoxical effect of cow dung exposure on childhood atopy in rural and urban children in South India(),
9885,"The effect of frequent administration of sodium cromoglycate to asthmatic children who previously responded poorly: Konig, P., and Godfrey, S.: Clin. Allergy 3: 395, 1973",
9886,Validation of the classification of aria (Allergic rhinitis and its impact on asthma)(),
9887,Viral Infections and Their Impact on the Respiratory Microbiome in Pediatric Patients with Cystic Fibrosis,
9888,Asthma in the elderly: Diagnosis and management,
9889,Prevalence of Respiratory Viruses in Patients with Acute Respiratory Infections in Korea,
9890,Evaluation of an environmental exposure unit (EEU) for controlled inhalation studies with pollen allergens(),
9891,Exacerbation de l'asthme: le role declenchant des coronavirus humains n'est pas confirme,
9892,Lots in common,
9893,Evaluation de la technique d'utilisation de la chambre d'inhalation avec masque facial dans le traitement de l'asthme,
9894,Index to subjects,
9895,Insuffisance cardio-respiratoire reversible par hypoplasie de l'etage moyen de la face chez un enfant achondroplase,
9896,Graphical abstract TOC continued,
9897,Pneumopathie aigue bacterienne et infection vih chez l'enfant en milieu tropical,
9898,Graphical Abstract Contents Continued,
9899,Scientific Abstract Sessions,
9900,Cumulative index of reviews for 1980–1985,
9901,Proteins: stay tuned!,
9902,Response from Lane and Buchmeier,
9903,The aquaporin family of membrane water channels,"The rapid movement of water across the plasma membranes of certain cells has been a long-standing puzzle to membrane biophysicists and physiologists; the discovery of the red cell channel-forming integral protein has provided a molecular solution to this puzzle. The identification of this protein has led to the recognition of a family of related water-selective channels, the aquaporins, that are found in animals, plants and microbial organisms. In order to provide insight into the remarkable but simple function of these membrane proteins, their structures are being elucidated."
9904,Membrane proteins,
9905,Deep life,
9906,Cumulative Index 2004,
9907,Pyelonephrite aigue chez l'entant a propos de 79 cas,
9908,Diagnostic des infections respiratoires par amplification des acides nucléiques,
9909,Complications de la rougeole et facteurs de risque de deces,
9910,Current opinion in structural biology,
9911,Forthcoming Articles,
9912,Forthcoming articles page,
9913,Double dealing,
9914,Role pathogene des coronavirus humains chez l'enfant: analyse systematique de la litterature,
9915,"Subject index for research articles and reviews, 1989",
9916,Tolerance d'infanrix polio-Hib en rappel chez 950 nourrissons,
9917,Des vaisseux et des gènes,
9918,Proteins — discovery and detail,
9919,Digénisme : le retour,
9920,RNA pseudoknots,"Many new RNA pseudoknot structures have been detected and proposed in the past year. Although we are still waiting for the first detailed structure of a pseudoknot, their role in processes such as translational autoregulation or ribosomal frameshifting has been extensively studied and is now well established. Pseudoknot structures appear to play a pivotal role in small subunit ribosomal RNA and in the noncoding regions of viral RNAs. There are also strong indications that RNA pseudoknots are highly suitable structural motifs for the recognition and binding of proteins."
9921,Contents and Editorial Board,
9922,Editorial Board and Contents,
9923,Patent reports,
9924,Department of Error,
9925,Editorial Board and Contents,
9926,Patent reports,
9927,Contents and Editorial Board,
9928,Erratum,
9929,Index to volume 29,
9930,Sobre la necesidad de modernizar la vigilancia epidemiológica y de ampliar el uso del diagnóstico molecular para las enfermedades infecciosas en Colombia,
9931,Author indexes,
9932,Editorial Board and Contents,
9933,"New methodologies for the pathologic diagnosis of placental infections-immunohistochemistry, immunofluorescence, in situ nucleic acid hybridization and polymerase chain reaction: A review","A variety of highly sensitive laboratory techniques is now available for the detection and localization of infectious agents in the placenta. This communication discusses, the role of immunohistochemistry, immunofluorescence, in situ nucleic acid hybridization, and polymerase chain reaction for infectious disease diagnosis in formalinfixed placental tissues. These techniques, as well as other sophisticated molecular methods currently in development, will greatly facilitate characterizing the role of infectious agents in a variety of perinatal and pediatric conditions, including birth defects, intrauterine growth retardation, and stillbirth."
9934,Patent reports,
9935,Patent Reports,
9936,Recent research in infectious disease,
9937,Editorial Board and Contents,
9938,Contents of other veterinary journals from Elsivier,
9939,Recent research in infectious disease,
9940,Gastroenteritis in Auckland: An aetiological and clinical study,"Faecal specimens from 60 patients (under six years old), most of whom were Maoris and Pacific Islanders admitted to Auckland Hospital with gastroenteritis during the months of June and July 1977, were examined for the presence of faecal viruses, bacterial pathogens and parasites. Faecal specimens from 18 non-diarrhoeal control patients were also examined, of which three contained rotavirus. Forty-three (72 per cent) gastroenteritis patients had rotavirus detectable in stools by electron microscopy or immune electron microscopy. Of the remainder, 17 patients were regarded as having non-rotavirus diarrhoea. Enterotoxigenic Esch. coli. was isolated from seven patients of whom six yielded stable toxin producers (ST+), four labile toxin producers (LT+) and two dual toxigenic strains (ST+/LT+). All ST+ isolates appeared to be of low enterotoxigenicity as indicated by low gut weight/carcass weight ratios in the infant mouse assay. Rotavirus was the commonest aetiological agent (72 per cent), bacterial pathogens (alone) accounted for only five per cent and no enteric pathogens were found in 15 per cent of cases. Non-agglutinable rotavirus, presumably a different serotype, was seen in both gastroenteritis and control patients. Rotavirus ‘satellite’ particles previously undescribed were demonstrated in a number of stool samples."
9941,Volume Contents Index,
9942,ISAR News,
9943,"Contents of Veterinary Immunology and Immunopathology, Volume 112",
9944,ISAR News,
9945,Recent research in infectious disease(),
9946,Recent research in infectious disease,
9947,"Volume Contents, Author and Subject Index for Vol. 42",
9948,Author Index to Volume 31,
9949,Neonatal bacterial infection: A changing scene?,
9950,Antiviral activities of interferons,
9951,IFC - Editorial Board / Publication Info,
9952,Table of Contents from Journal of Psychosomatic Research,
9953,"A comparative analysis of the porcine, murine, and human immune systems",
9954,Viruses demonstrated in children in Tanzania: Studies in diarrhoea and measles,"Causes of diarrhoea with particular reference to viral agents were investigated in 123 infants and young children in Dar es Salaam, Tanzania. Twenty-six of the patients also had measles. Viruses were found in 52 of the 123 patients (43 per cent) and rotavirus occurred in 38 children (31 per cent). Enteroviruses were found in 10 patients, adenoviruses in nine and ‘small round virus’ in one (six patients had dual infection). Four patients died and only one of these children had viral particles in the stools. Breast milk formed part or all of the diet in 77 children (63 per cent) and virus isolation showed a similar pattern in breast fed infants and those not receiving breast milk. In 26 patients with measles only five were excreting viruses in their stools. Therefore no strong evidence was found to link the diarrhoea associated with measles in Tanzanian children to any particular virus. The pattern of virus infection causing infantile diarrhoea was similar in Dar es Salaam to other parts of the world."
9955,Recent research in infectious disease,
9956,Patent reports,
9957,SUBJECT INDEX,
9958,The Journal of Comparative Pathology Educational Trust and Petplan Charitable Trust Joint Research Award in Veterinary Pathology,
9959,Master subject index,
9960,Feedback,
9961,"Subject Index to Volume 65, issues 1 and 2",
9962,Ocular and central nervous system involvement in non-effusive form of feline infectious peritonitis,
9963,Related Elsevier virology titles contents alert,
9964,Contents of volume 39,
9965,Author index (vols. 2–3),
9966,Cumulative Subject Index for 2005,
9967,"Gene expression, virulence and vaccine development in coronaviruses",
9968,"V, 2.Ribosomal frameshifting in astroviruses","This chapter reviews ribosomal frameshifting with an emphasis on the frameshifting process in astroviruses. Frameshifting is a potential antiviral target. It is possible that the replication cycle of any virus that uses this process could be disrupted by modulation of frameshift efficiencies, but a better understanding of the occurrence and the molecular basis of frameshifting will be required before it can be considered a genuine target. To date, there are no confirmed examples of frameshift signals from conventional eukaryotic cellular genes, although computer-assisted database searches have identified a number of candidates. The frameshift allows the required ratio of viral proteins to be produced, but it may also serve to downregulate levels of viral replicases that may be toxic in high amounts."
9969,Development of a Cell-Based Assay for Identification of Viral Entry Inhibitors Against SARS-CoV by High Throughput Screening (HTS),
9970,Subject index (volume 5),
9971,Contents of volume 38,
9972,Contents of volume 3,
9973,4904391 Method and apparatus for removal of cells from bone marrow: Richard B Freeman,
9974,Viral etiology of multiple sclerosis: where does the truth lie?,
9975,"I, 3. The enteric nervous system and infectious diarrhea","This chapter discusses the background knowledge about the enteric nervous system (ENS) as well as the role of ENS in secretory states of the small intestine. The chapter describes the anatomy and physiology of the ENS. A description of the experimental evidence for the involvement of ENS in secretory states of the gut, primarily in cholera toxin-induced secretion that is the most thoroughly investigated secretory state, is presented in the chapter. The chapter focuses on the involvement of ENS in rotavirus (RV) diarrhea. The involvement of the ENS in diarrhea pathophysiology opens up new potential sites of action for drugs in the treatment of intestinal secretory states. The chapter concludes with a discussion of the sites of action for the pharmacological treatment of diarrhea."
9976,4904596 Hybridoma antibody (FH6) defining a human cancer-associated difucoganglioside: Sen-itiroh Hakomori assigned to Fred Hutchinson Cancer Research Center,
9977,4904481 Method of conferring immuno-tolerance to a specific antigen: C Garrison Fathman assigned to The Board of Trustess of Leland Stanford University,
9978,4902685 2-Amino-3-cyano-bicyclic pyridines/pyrazines as inhibitors of interleukin 1: Jerauld Skotnicki assigned to American Home Products Corporation,
9979,"Evaluation of Interferon Inducers, Ribavirin and Mouse Hyperimmune Serum in a Pathogenesis/Lethal Mouse Model Using a Mouse-adapted SARS-CoV",
9980,Contents of volume 12,
9981,Effects of the Addition of Hiltonol(®) (Poly-ICLC) to a SARS-CoV S Protein Vaccine in Lethal SARS-CoV Mouse Model,
9982,19th ICAR Abstracts:,
9983,"5420253 Method for purifying egg yolk immunoglobulins : Emery Daryll A; Straub Darren E Willmar, MN, United States Assigned to Willmar Poultry Company Inc",
9984,The role of pathogenic Escherichia coli in the etiology of veal calf hemorrhagic enteritis,"Veal calf hemorrhagic enteritis, a condition that has no identified specific etiology, is a fatal syndrome of veal calves and has recently become a major concern of the veal calf industry in the midwestern United States. To determine the possible role of common enteric pathogens in this disease, 40 veal calves with hemorrhagic enteritis (cases) and 25 dairy calves diagnosed with enteric infection (control) were investigated. The veal calves were negative for several known enteric pathogens except for pathogenic Escherichia coli isolates that expressed multiple virulence attributes. To determine whether such isolates have a significant association with hemorrhagic enteritis in veal calves, we compared the prevalence of pathogenic E. coli in the 40 veal calves with the prevalence of similar E. coli in the dairy calves that were diagnosed with colibacillosis within the same season of the year. Escherichia coli isolates from the two groups of calves were tested for several properties of E. coli related to pathogenicity, i.e. production of verotoxins, heat-stable enterotoxin (ST(a)), heat-labile enterotoxin, enterohemolysin, K99 fimbrial antigens, hemagglutination activity, and attachment to Hep-2 tissue culture cells. Escherichia coli that produces ST(a) were more commonly isolated from veal calves with hemorrhagic enteritis (45%) than from dairy calves with enteritis (12%) (P<0.05). Various patterns of attachment of E. coli to Hep-2 tissue culture cells were studied. The E. coli that demonstrated aggregative patterns of attachment were more commonly represented in veal calves (32%) than in dairy calves (8%). We observed that there was no correlation between ST(a) production and K99 pili expression among the enterotoxigenic E. coli (ETEC) isolates that were recovered from veal calves. This may indicate the emergence of K99-negative ETEC, probably as a result of the wide use of K99-based vaccines."
9985,Related elsevier virology titles contents alert,
9986,Scientific program,
9987,Epidemiologic approaches used in a herd health practice to investigate neonatal calf mortality,"Epidemiologic methods were applied in an investigation into causes of neonatal mortality on a 1400-cow dairy in the southern San Joaquin Valley of California. A format for collation of information on birthdate and date of death was assembled into a matrix which improved conceptualization of the data and which simplified procedures for estimation of mortality rates. Contemporary and birth cohort life table methods, mortality density estimations and relative risk assessment were used to ascertain if there were high-risk groups of calves that could be identified by age, day-of-the-week born, day-of-the-week died and sex. During the outbreak of neonatal diarrhea on this dairy, female calves were found to have experienced an atypically higher rate of mortality (10.7%) than did males (5.3%). Calves of both sexes died between the ages of 9 and 19 days. In addition, the risk of dying was 11 times greater for calves born on Wednesdays than for those born on Saturdays. These findings formed the basis for recommended changes in management of neonatal calves on the dairy."
9988,"P232 MOLECULAR PHYLOGENETICS OF HEPATITIS C VIRUS (HCV) AS A TOOL TO UNDERSTAND THE HCV EPIDEMIC IN BRITISH COLUMBIA (BC), CANADA",
9989,Author index of volume 178 Supplement 1,
9990,Cumulative Author Index for 2010,
9991,High Throughput Screening of Protease Inhibitor Libraries Using a Novel Dual Pseudotype-Based Assay for SARS-CoV Entry,
9992,"P233 THE NATURAL COMPOUND PENTA-O-GALLOYL-GLUCOSE, DERIVED FROM THE ROOT CORTEX MOUTAN, EFFICIENTLY INHIBITS HEPATITIS C-VIRUS ENTRY AND SHOWS EXCELLENT PHARMACOKINETIC PERFORMANCE IN VIVO",
9993,"5424065 Vaccines containing avirulent phop-type microorganisms : Curtiss Roy;Galan Jorge St Louis, MO, United States Assigned to Washington University",
9994,Contents of volume 71,
9995,Contents of volume 35,
9996,"5013542 Method to inhibit adhesion of disease-causing microorganisms to teeth: Donald I Hay, Ronald J Gibbons, Edgard G Moreno assigned to Forsyth Dental Infirmary for Children",
9997,The prevalence of some economically important swine diseases in farrowing units in southwestern Finland,"The prevalence and geographical distribution of some economically important swine diseases were surveyed in 114 randomly selected farrowing units which had a contract with Southwestern Finland's Cooperative Slaughterhouse (LSO) for producing feeder pigs to be delivered to the all in-all out finishing units. The focus was on infectious diseases which could be transmitted to the finishing units with delivered growers, and which might have some influence on partial carcass condemnations (PCC) in meat inspection. Farm visits were done by a veterinarian (senior author) assisted by a technician. Colostrum samples (average 22 per herd) were taken in 100 herds, and analyzed for Actinobacillus pleuropneumoniae (A. pleur) and Mycoplasma hyopneumoniae (M.hyo) antibodies by enzyme-linked immunosorbent assays (ELISAs). Only nine of 114 herds were judged to be free of mange. It was concluded that all finishing units received mange-infected feeder pigs each time the unit was filled. One or more acute erysipelas outbreaks had occurred in every fifth herd during the previous year. The risk of a finishing unit receiving feeder pigs carrying erysipelas was considered to be high. Swine dysentery (Serpulina hyodysenteriae) was not found to be a problem in the LSO area. Clostridium perfringens type C enteritis was found in eight (7%) herds. Seven of these herds were located in those supply areas where the PCC percentage of feeder pigs was high. In spite of statistical connection no causality between this disease and PCC was presumed. There were no previous diagnoses of respiratory diseases but spontaneous coughing was observed in 5% of the herds. Provocation testing induced coughing in 22% of herds but not serious coughing in any herd. Managers had observed coughing in 15% of herds. Ninety-one herds were positive in a colostrum ELISA for A. pleur antibodies, and eight herds were positive for M.hyo antibodies. A.pleur-positive herds had several positive or samples suspected of being positive in each herd bu M.hyo-positive herds had only one or two positive or suspected samples per herd. Six of the M.hyo herds were located in the high PCC area, two in the average PCC area and none in the low PCC area. M.hyo was suggested to be one of the possible explanations for geographical variation of PCC. Atrophic rhinitis was not considered to be of importance in LSO."
9998,"5017559 Agent for blocking nonspecific adsorption, process for preparing thereof and method of blocking nonspecific adsorption: Shunichi Dosako, Hiroshi Shinmoto, Saitamaken, Japan assigned to Snow Brand Milk Products Co Ltd",
9999,Detection of foot-and-mouth disease virus infection-associated antigen antibodies: comparison of the enzyme-linked immunosorbent assay and agar gel immunodiffusion tests,"A liquid-phase enzyme-linked immunosorbent assay (ELISA) was compared with the standard agar gel immunodiffusion test (AGID) to identify and quantify antibodies against foot-and-mouth disease (FMD) virus infection-associated (VIA) antigen. A total of 3181 cattle sera were tested. Of these sera, 1885 were from cattle which had not been exposed to FMD. A total of 1296 sera were either from cattle which were experimentally exposed to FMD virus or from cattle involved in field outbreaks. The results indicate that the ELISA has the same specificity as the AGID test, but is more efficient in detecting cattle exposed to FMD virus. The ELISA technique will probably prove to be a more satisfactory test in support of the prevention, control and eradication programs for the disease."